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## **Meet the editor**

Dr. Umashankar Lakshmanadoss completed his training from Madras Medical College, India, and from University of Rochester, NY, USA. He served as director of inpatient medical consult service at Johns Hopkins University School of Medicine and then joined the Division of Cardiovascular Medicine at Guthrie Clinic, Sayre, PA, USA. Then he pursued training in cardiac electrophys-

iology at Oakland University William Beaumont School of Medicine and continued his advanced cardiac electrophysiology training at Mayo Clinic, Rochester, MN. Currently, he is an assistant professor of medicine in the Division of Cardiology, Louisiana State University Health Sciences Center, Shreveport, LA. He also serves as the director of complex arrhythmia ablation program. His research interest is in the field of clinical cardiac electrophysiology.

## Contents

**Preface XI**


Chapter 6 **Cardiac Imaging in Hypertrophic Cardiomyopathy 115** Dai-Yin Lu and Ming-Chong Hsiung


Tomoko Kato, Takashi Nishimura, Shunei Kyo, Kenji Kuwaki, Hiroyuki Dada and Atsushi Amano


## Preface

Chapter 7 **Noninvasive Measurement of Pulmonary Capillary Wedge Pressure by Speckle Tracking Echocardiography 133**

Chapter 8 **The Role of Echocardiography in the Management of Patients**

**Undergoing a Ventricular Assist Device Implantation and/or**

Gunjan Choudhary, Arushi A. Malik, Dwight Stapleton and Pratap

Tomoko Kato, Takashi Nishimura, Shunei Kyo, Kenji Kuwaki,

Masanori Kawasaki

**VI** Contents

**Transplantation 147**

Manivannan Veerasamy

C. Reddy

Hiroyuki Dada and Atsushi Amano

Chapter 9 **Assessment of Right Ventricle by Echocardiogram 169**

Chapter 10 **Role of Echocardiography in the Critically Ill Patients 191**

The world of echocardiography continues to be full of exciting new technological develop‐ ments with an ultimate goal of better patient care. In this book, titled "Echocardiography in Heart Failure and Cardiac Electrophysiology", authors from different parts of the world contributed to the advancement of the field. We have authors who describe the basics of speckle tracking echocardiography and its recent applications and estimating strain pattern. Clinically relevant topics such as multimodality imaging in the diagnosis and management of hypertrophic cardiomyopathy have been discussed very nicely. Despite improvements in medical therapy, the mortality rate in congestive heart failure is still unacceptably high. Ear‐ ly diagnosis and management would be the key in reducing the mortality rate. An entire chapter is dedicated to the noninvasive measurement of pulmonary capillary wedge pres‐ sure. By early identification of this increased wedge pressure, clinicians may be in a position to diagnose heart failure in the earlier phase. In patients who have advanced heart failure, the obvious options include a bridging therapy such as left ventricular assist device or a des‐ tination therapy such as a cardiac transplantation. We have included a chapter that is entire‐ ly dedicated to the role of echocardiography in the management of patients with left ventricular assist device and possible cardiac transplantation. When we talk about conges‐ tive heart failure, we typically think about left ventricular heart failure. However, the recent data clearly suggest that the right ventricle plays a major role and is often neglected, un‐ fortunately. Hence, we have included an excellent chapter describing the various modalities of processing the right ventricular function by echocardiography. Echocardiography could be very useful in critically ill patients and for early diagnosis, management, and possible differential diagnosis. One dedicated chapter describes the use of echocardiography in this sicker population. In patients with progressive heart failure and electromechanical distur‐ bances, cardiac resynchronization therapy could be very useful to improve their quality of life and reduce the mortality. One of the authors has a dedicated chapter about the various noninvasive imaging technologies involving cardiac resynchronization therapy. We clearly know that atrial fibrillation and congestive heart failure go hand in hand. We have included a basic chapter describing the role of electrocardiographic markers for atrial arrhythmias. The patient with patrons in relation could be a good candidate for atrial fibrillation ablation, which is a highly advanced and complex procedure. One of our authors put together an ex‐ cellent review about the multimodality echocardiographic assessment of patients undergo‐ ing atrial fibrillation. These topics would be of great interest to the clinicians whether they are trainees, physicians, advanced care providers, or anyone involved in patient care.

This work was made possible because of the contributors who have worked assiduously to help us produce an excellent book. I am indebted to Ms. Iva Lipović, publishing process manager at InTech, for the constant support. I dedicate this book to my mother Jana, my source of inspiration and encouragement, wife Gini and son Babboo, for their understand‐ ing, support, and unconditional love.

> **Umashankar Lakshmanadoss, MD, CCDS** Assistant Professor of Medicine, Director, Complex Arrhythmia Ablation Program, Louisiana State University Health Sciences Center, Shreveport, LA, USA

**Echocardiography in Electrophysiology**

manager at InTech, for the constant support. I dedicate this book to my mother Jana, my source of inspiration and encouragement, wife Gini and son Babboo, for their understand‐

**Umashankar Lakshmanadoss, MD, CCDS**

Director, Complex Arrhythmia Ablation Program, Louisiana State University Health Sciences Center,

Assistant Professor of Medicine,

Shreveport, LA, USA

ing, support, and unconditional love.

VIII Preface

## **Introductory Chapter: Practical Approach to the Use of Intracardiac Echocardiography in Invasive Electrophysiology Procedures Introductory Chapter: Practical Approach to the Use of Intracardiac Echocardiography in Invasive Electrophysiology Procedures**

Umashankar Lakshmanadoss Umashankar Lakshmanadoss

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/65243

## **1. Introduction**

Use of intracardiac echocardiography (ICE) has been significantly increased with the advent of invasive electrophysiology and interventional procedures. In this day and age, we as a clinician are focused more on efficient and safe procedures for the patient. Intracardiac echocardiography plays a major role in doing these interventional procedures in a safe and efficient way. In addition to this, the use of ICE significantly reduced the need for fluoroscopy and hence reduced the occupational hazards of radiation and lead aprons for the physicians. It changed the way of doing these interventional procedures and one could easily say that this is one of the paradigm shift for us. In this chapter, I intend to review the basics of intracardiac echocardiography and also describe the various views and applications of intracardiac echocardiography in invasive electrophysiological procedures.

Several types of ice catheters are available in the market currently. They could be broadly divided into two different modalities. One catheter is a mechanical non-steerable catheter, which utilizes a rotating element to create a video 360° imaging claim perpendicular to the long axis of the catheter (UltraICE® Boston Scientific). This is 9 Fr catheter using 9 MHz. The second group of the catheter is a 64 element phased array 4-way steerable catheter. AcuNav® catheter (Biosense – Webster) is one of the commonly available phased out a catheter with the frequency range of 5.5–10 MHz. This is available in 8 and 10 Fr sizes. The system uses gray scale and has the facility for performing color Doppler, tissue Doppler and 3-D localization with Cartosound®. The images from this catheter result in a 90° sector image in the form of pie. ClearICE® catheter (St. Jude Medical) is another form of 64 elements phased array site looking highly steerable catheter with two sets of electrodes for integration of 3-D localization

with NavX®. In addition to the gray scale and tissue Doppler, this can also do synchronization mapping which speckles tracking. In our electrophysiology laboratory, we commonly use the phased array 8 or 10 Fr AcuNav® catheter. Forthe purpose of this chapter, one the images from phased array system is included.

## **2. What are all the moments possible with the ICE catheter?**

There are totally eight movements possible with this steerable catheter. With these eight movements, an experienced operator should be able to navigate through the important structures of the heart.


## **3. How to advance the ICE catheter into the heart?**

In our laboratory, the imaging catheter is mostly advanced, either from the right or left femoral vein into the right atrium. This could be performed without the use of fluoroscopy. After getting a venous access, the ICE catheter is advanced through the sheath into the femoral vein. Once the catheter is out of the venous access sheath, one should be able to visualize the lumen of the venous system. We typically advance the catheter making sure that there is a sufficient lumen seen at the tip of the catheter. To negotiate the side branches and tortuous veins, we use the knob of the ice catheter to do the various possible movements as described above. While advancing the catheter, one could clearly visualize the structures including liver. Once we reached right atrium, we typically leave the catheter to get the home you as described below. Fluoroscopy guidance should be used by less experienced operators as the catheter tip is not soft.

## **4. What settings does one need to have to optimize the ice images?**

with NavX®. In addition to the gray scale and tissue Doppler, this can also do synchronization mapping which speckles tracking. In our electrophysiology laboratory, we commonly use the phased array 8 or 10 Fr AcuNav® catheter. Forthe purpose of this chapter, one the images from

There are totally eight movements possible with this steerable catheter. With these eight movements, an experienced operator should be able to navigate through the important

In our laboratory, the imaging catheter is mostly advanced, either from the right or left femoral vein into the right atrium. This could be performed without the use of fluoroscopy. After getting a venous access, the ICE catheter is advanced through the sheath into the femoral vein. Once the catheter is out of the venous access sheath, one should be able to visualize the lumen of the venous system. We typically advance the catheter making sure that there is a sufficient lumen seen at the tip of the catheter. To negotiate the side branches and tortuous veins, we use the knob of the ice catheter to do the various possible movements as described above. While advancing the catheter, one could clearly visualize the structures including liver. Once we reached right atrium, we typically leave the catheter to get the home you as described below. Fluoroscopy guidance should be used by less experienced operators as the

**2. What are all the moments possible with the ICE catheter?**

phased array system is included.

4 Echocardiography in Heart Failure and Cardiac Electrophysiology

**1.** Clockwise: rotation of the catheter away from the operator

**3.** Anterior flexion: catheter bends forward

**4.** Posterior flexion: catheter bends backward

**5.** Right tilt: catheter bends towards the right side

**6.** Left tilt: catheter bends towards the left side

**7.** Push: catheter is advanced in further

**8.** Pull: catheter is withdrawn

catheter tip is not soft.

**2.** Counterclockwise: rotation of the catheter towards the operator

**3. How to advance the ICE catheter into the heart?**

structures of the heart.

It is also important to understand the basics and physical principles of echocardiography to optimize the images obtained.


## **5. What are all the structures one could view using ICE catheter?**


Introductory Chapter: Practical Approach to the Use of Intracardiac Echocardiography In Invasive Electrophysiology... http://dx.doi.org/10.5772/65243 7

**7.** Tissue Doppler: tissue Doppler could be used to find the area of scar or fibrosis. This could

**8.** Color Doppler and continuous wave Doppler: this could be used in evaluating pulmonary

**5. What are all the structures one could view using ICE catheter?**

be of vital importance in ventricular tachycardia ablation.

6 Echocardiography in Heart Failure and Cardiac Electrophysiology

veins and valves.

**Right atrium:**

Superior vena cava

Eustachian valve

Crista terminalis

Tricuspid valve

**Right ventricle:**

Papillary muscle

Moderator band

Para Hisian region

Pulmonic valve

Inter atrial septum

Left atrial appendage

Left-sided pulmonary veins

Right-sided pulmonary veins

**Left atrium:**

Right ventricular outflow tract

Right atrium appendage

Ostium of the coronary sinus

Cavotricuspid isthmus

Right ventricular inflow

Tricuspid valve attachments

Right ventricular inferior wall, apex, and lateral wall

Left atrial posterior wall Mitral annulus Coronary sinus **Left ventricle:** Left ventricular inflow Anterolateral and posteromedial papillary muscle Left ventricle apex Left ventricular outflow tract Aortic valve Aorta **Miscellaneous:** Pericardial effusion Thrombus or mass attached to the intracardiac leads Adequate contact of the catheter with the tissue Echogenicity of the tissue during ablation Left atrial appendage closure device Atrial septal defect closure device Esophagus

## **6. How does one use the ICE catheter in atrial fibrillation ablation?**

While advancing the ice catheter from the femoral vein, one could visualize the liver. At this time, the catheter is slightly advanced into the mid-right atrium. When the catheter in this position, we could visualize most of the right atrium, tricuspid valve, and right ventricle. This is referred to "home position". The catheter is left over here in an unlocked are a neutral position. This whole meal allows the assessment of the tricuspid valve structure, function and estimation of pulmonary artery systolic pressure using tricuspid regurgitation. This view also gives a better sense about right atrium and the right ventricle leads. Whenever the operator feels that he is lost secondary to the unfamiliar imaging plane, he just needs to put on the catheter to the home view by removing all catheter deflections and gently rotating the ice catheter in the clockwise and counterclockwise rotation until the tricuspid valve is visualized (**Figure 1**).

**Figure 1.** Home position.

**Figure 2.** Left atrium and pulmonary veins.

From the home position, with the mild clockwise rotation, we can direct imaging plane posteriorly and left the ward. Initially, we can see the aortic valve, right ventricle inflow and right ventricle outflow just below the aortic valve. From this view, for the clockwise rotation of the catheter with about 45°, we can see the long axis of the aortic root. Here, we can analyze any atheroma of the aorta. This could be of vital importance when the operator is planning for a retrograde aortic approach. The aortic valve is also visualized well in this view. This is a good view to look for any regurgitation through the aortic valve. Just behind the aortic valve, one may be able to see the pulmonary artery and pulmonic valve. A continued clockwise rotation from this view will direct the image plane more posteriorly. This view is a good view to visualize left atrial appendage, mitral annulus and ostium of the coronary sinus. Many operators use this view to interrogating left atrial appendage for any thrombus. This view can also be used to help in cannulation of the coronary sinus in the case of any technical difficulties (**Figures 2** and **3**).

**Figure 3.** Continuous wave Doppler of the pulmonary veins.

**Figure 1.** Home position.

8 Echocardiography in Heart Failure and Cardiac Electrophysiology

**Figure 2.** Left atrium and pulmonary veins.

From the home position, with the mild clockwise rotation, we can direct imaging plane posteriorly and left the ward. Initially, we can see the aortic valve, right ventricle inflow and right ventricle outflow just below the aortic valve. From this view, for the clockwise rotation of the catheter with about 45°, we can see the long axis of the aortic root. Here, we can analyze any atheroma of the aorta. This could be of vital importance when the operator is planning for a retrograde aortic approach. The aortic valve is also visualized well in this view. This is a good

**Figure 4.** Tenting of the interatrial septum.

From this view, the catheter is slightly rotated clockwise. In this plane, one could visualize both left-sided pulmonary veins. The left superior pulmonary vein is usually visualized earlier and further clockwise rotation from that angle will bring left inferior pulmonary vein into visualization. This is a good view to measure the dimensions of the pulmonary vein, color Doppler of the pulmonary vein and continuous wave Doppler to evaluate the velocity of the pulmonary vein. During atrial fibrillation ablation, this view could be used to avoid ablation deep into the veins (**Figure 4**).

For the clockwise rotation of the ice catheter from this view will typically show the posterior wall of the left atrium. In this view, one could visualize esophagus and descend aorta. Esophageal temperature probe catheter can be visualized in the esophagus from the right atrium using this view. During ablation of the posterior wall of the right atrium, it would be easy to visualize the echogenicity of the lesion and proximity to the esophagus. Continued clockwise rotation of the ice catheter from this view will bring the right-sided pulmonary veins closer to the imaging surface of the ice catheter. The right-sided pulmonary veins will be visualized in a short axis. Using color Doppler, we could identify the pulmonary vein flow. Further advancement of the catheter into the right atrium and continued clockwise rotation from this level will bring up the right superior pulmonary vein in a better imaging plane. We will be able to see both right-sided pulmonary veins and pulmonary artery at this level. Usually, the right superior pulmonary vein is one of the most difficult veins to visualize. Sometimes the addition of a slight posterior tilt and right or left steering can further optimize this image to visualize the right superior pulmonary vein. Further clockwise rotation from this view will bring the catheter to the home view.

From the home position, ice catheter is advanced with a little bit of posterior flexion and rightward tilt. At this view, one could visualize the junction of the superior vena cava with right atrium. This view is commonly used to advance the guidewire into the superior vena cava before transseptal puncture. From here, the ice catheter is pulled down a little bit with continued posterior and right tilt. Now, they can clearly visualize interatrial septum including limbus and fossa ovalis. Typically, the operator advances the transseptal access needle in this view. One will be able to identify the tenting of the interatrial septum and further advancement of the transseptal needle into the left atrium. Slight clockwise rotation over here will help the operator to visualize and estimate the distance between the transseptal access site and posterior left atrial wall, thereby avoiding perforation into the left atrial posterior wall during transseptal access. Similarly, the distance between the transseptal access and left lateral wall can also be assessed in the previous imaging plane and hence avoiding left atrial perforation during transseptal access.

## **7. How does one use ICE catheter in ventricular tachycardia ablation?**

From the home view, the catheter is tilted anteriorly. Now, we can visualize the posterior tricuspid leaflet and inferior wall of the right ventricle. The catheter is further advanced through the tricuspid valve into the right ventricle with continuous monitoring of the ICE imaging. Once the catheter is just below the aortic valve in this view, further anterior tilt will make the catheter flex towards the inferior part of the right ventricle. This view is a good view to visualize the long axis of the posteromedial papillary muscle. From here, the anterior tilt is gently released in the catheter is further advanced towards the right ventricular apical region. Here, the catheter is brought to a neutral position with no tension on the knob. From here, clockwise rotation of the catheter will help us in visualizing the interventricular septum. This is also a good view of the epicardial axis as the right ventricular apical region is well visualized over here. With continuous clocking from here, we could visualize the posteromedial papillary muscle, and further clocking will bring the popular anterolateral muscle. The left ventricle cavity will be well visualized. Further clocking will also bring aortomitral continuity into the picture. Further advancement of the catheter into the right ventricle outflow tract with continued clockwise rotation will bring left ventricular outflow tract into the picture in a short axis view. We will be able to see all the three cusps of the aortic valve. Here noncoronary cusp will be adjacent to the inter-atrial septum; right coro-

**Figure 5.** Left ventricle.

From this view, the catheter is slightly rotated clockwise. In this plane, one could visualize both left-sided pulmonary veins. The left superior pulmonary vein is usually visualized earlier and further clockwise rotation from that angle will bring left inferior pulmonary vein into visualization. This is a good view to measure the dimensions of the pulmonary vein, color Doppler of the pulmonary vein and continuous wave Doppler to evaluate the velocity of the pulmonary vein. During atrial fibrillation ablation, this view could be used to avoid ablation deep into the

For the clockwise rotation of the ice catheter from this view will typically show the posterior wall of the left atrium. In this view, one could visualize esophagus and descend aorta. Esophageal temperature probe catheter can be visualized in the esophagus from the right atrium using this view. During ablation of the posterior wall of the right atrium, it would be easy to visualize the echogenicity of the lesion and proximity to the esophagus. Continued clockwise rotation of the ice catheter from this view will bring the right-sided pulmonary veins closer to the imaging surface of the ice catheter. The right-sided pulmonary veins will be visualized in a short axis. Using color Doppler, we could identify the pulmonary vein flow. Further advancement of the catheter into the right atrium and continued clockwise rotation from this level will bring up the right superior pulmonary vein in a better imaging plane. We will be able to see both right-sided pulmonary veins and pulmonary artery at this level. Usually, the right superior pulmonary vein is one of the most difficult veins to visualize. Sometimes the addition of a slight posterior tilt and right or left steering can further optimize this image to visualize the right superior pulmonary vein. Further clockwise rotation from this view will

From the home position, ice catheter is advanced with a little bit of posterior flexion and rightward tilt. At this view, one could visualize the junction of the superior vena cava with right atrium. This view is commonly used to advance the guidewire into the superior vena cava before transseptal puncture. From here, the ice catheter is pulled down a little bit with continued posterior and right tilt. Now, they can clearly visualize interatrial septum including limbus and fossa ovalis. Typically, the operator advances the transseptal access needle in this view. One will be able to identify the tenting of the interatrial septum and further advancement of the transseptal needle into the left atrium. Slight clockwise rotation over here will help the operator to visualize and estimate the distance between the transseptal access site and posterior left atrial wall, thereby avoiding perforation into the left atrial posterior wall during transseptal access. Similarly, the distance between the transseptal access and left lateral wall can also be assessed in the previous imaging plane and hence avoiding left atrial perforation during

**7. How does one use ICE catheter in ventricular tachycardia ablation?**

From the home view, the catheter is tilted anteriorly. Now, we can visualize the posterior tricuspid leaflet and inferior wall of the right ventricle. The catheter is further advanced through the tricuspid valve into the right ventricle with continuous monitoring of the ICE

veins (**Figure 4**).

bring the catheter to the home view.

10 Echocardiography in Heart Failure and Cardiac Electrophysiology

transseptal access.

**Figure 6.** Aortic cusps.

nary cusp will be adjacent to the right ventricular outflow tract and left coronary cusp will be adjacent to the left ventricular outflow tract. In this view, one can also visualize left atrial appendage. In between the left coronary cusp on the left atrial appendage, we may be able to see left main coronary artery or left anterior descending artery. Further clockwise rotation over here will bring the aortic valve and ascending aorta in long axis (**Figures 5** and **6**).

## **8. How does one use ICE catheter to avoid complications during electrophysiological procedures?**

Ice catheter can be used to monitor the catheter contact with the tissue. This helps us to make sure that they are ablating the right structure. It also helps us to maintain a better stability during respiration or with cardiac motion. With the help of the near field lesion visualization, one could avoid over ablating a region. Steam pops can happen during ablation secondary to high temperatures in the tissue. Impending signs of steam pop like increased echogenicity and microbubbles can be seen using ice catheter and hence avoiding imminent complications including perforation. Ice catheters also help us in negotiating through the valves safely without getting entangled in the valve apparatus. During ablation, continuous monitoring of the pericardial space can identify an early pericardial effusion thereby avoiding a less optimal outcome for the patient.

## **9. Conclusion**

Imaging using intracardiac echocardiography has led to significant improvement in the safety and efficacy of the complex local physiological procedures. In addition to this, less dependence on the fluoroscopy also produces the occupational hazards for the physicians and the patients.

## **Author details**

Umashankar Lakshmanadoss

Address all correspondence to: drlumashankar@gmail.com

Louisiana State University Health Science Center, Shreveport, USA

## **The Role of Electrocardiographic Markers in the Prevention of Atrial and Ventricular Arrhythmias The Role of Electrocardiographic Markers in the Prevention of Atrial and Ventricular Arrhythmias**

Veronika Sebestyén and Zoltán Szabó Veronika Sebestyén and Zoltán Szabó Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64460

## **Abstract**

nary cusp will be adjacent to the right ventricular outflow tract and left coronary cusp will be adjacent to the left ventricular outflow tract. In this view, one can also visualize left atrial appendage. In between the left coronary cusp on the left atrial appendage, we may be able to see left main coronary artery or left anterior descending artery. Further clockwise rotation over here will bring the aortic valve and ascending aorta in long axis (**Figures 5** and **6**).

Ice catheter can be used to monitor the catheter contact with the tissue. This helps us to make sure that they are ablating the right structure. It also helps us to maintain a better stability during respiration or with cardiac motion. With the help of the near field lesion visualization, one could avoid over ablating a region. Steam pops can happen during ablation secondary to high temperatures in the tissue. Impending signs of steam pop like increased echogenicity and microbubbles can be seen using ice catheter and hence avoiding imminent complications including perforation. Ice catheters also help us in negotiating through the valves safely without getting entangled in the valve apparatus. During ablation, continuous monitoring of the pericardial space can identify an early pericardial effusion thereby avoiding a less optimal

Imaging using intracardiac echocardiography has led to significant improvement in the safety and efficacy of the complex local physiological procedures. In addition to this, less dependence on the fluoroscopy also produces the occupational hazards for the physicians and the patients.

**8. How does one use ICE catheter to avoid complications during**

**electrophysiological procedures?**

12 Echocardiography in Heart Failure and Cardiac Electrophysiology

outcome for the patient.

**9. Conclusion**

**Author details**

Umashankar Lakshmanadoss

Address all correspondence to: drlumashankar@gmail.com

Louisiana State University Health Science Center, Shreveport, USA

In our chapter, we overview the main clinical conditions that increase arrhythmogenic‐ ity, and we present the surface electrocardiogram (ECG) markers that could be suitable for the prediction of atrial and ventricular arrhythmias. We highlight the clinical value of the prolongation of the P‐wave duration and P dispersion (Pd) in the prediction of atrial fibrillation, and we also expound the utility of QT interval, T‐wave peak‐to‐end interval (Tpe), and Tpe/QT ratio (known as arrhythmogenic index (AIX)) in the prediction of ventricular arrhythmias. Furthermore, we present the results of our clinical investigations with regard to surface ECG markers among patients with increased arrhythmia vulnerability. Moreover, we mention other, novel, effectively used ECG markers.

**Keywords:** atrial fibrillation, P dispersion, P‐wave interval, QT interval, T‐wave peak‐ to‐end interval, ECG markers, ventricular arrhythmias

## **1. Introduction**

There are several diseases which may affect the pulse generation and the conduction in the heart. Patients suffering from these clinical conditions have increased probability for the occurrence of atrial and ventricular arrhythmias [1–4]. Numerous studies have been dealing with certain surface electrocardiogram (ECG) markers which could be suitable for the prevention of various cardiac rhythm disturbances [5–7]. Previously, it has been shown that the prolongation of the P‐wave duration and P dispersion (Pd) can predict atrial arrhythmias [5, 8, 9]. Moreover, it has also been demonstrated that the prolongation of QT interval, T‐wave peak‐to‐end interval (Tpe) and Tpe/QT ratio (known as arrhythmogenic index—AIX) could

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

predict ventricular arrhythmias [6, 7]. In our chapter we would like to present the electrophy‐ siological substrates and pathogenetic factors taking part in arrhythmogenesis and to demonstrate ECG‐based diagnostic opportunities that can help in the prediction and preven‐ tion of arrhythmias. Furthermore, we present the results of our studies to demonstrate the clinical use of these ECG markers.

## **2. Non-invasive electrocardiographic markers in the prediction of atrial fibrillation**

## **2.1. Epidemiology and electrophysiological background of atrial fibrillation**

The most common form of rhythm disturbances is atrial fibrillation (AF). Its prevalence is 0.12–0.16% among people younger than 49 years, 3.7–4.2% with regard to people aged 60–70 years and 10–17% among people aged 80 years or older [10]. Age, gender, hypertension, dia‐ betes mellitus, heart failure and valvular heart disease are independent risk factors that may play a role in arrhythmogenesis. Moreover, AF may be caused by hyperthyroidism and ex‐ cessive alcohol consumption [11, 12] (**Table 1**).


**Table 1.** Cardiovascular causes of atrial fibrillation.

In patients with end‐stage renal failure, its prevalence is approximately 13%. Interestingly, 10% of subjects suffering from 'lone' AF have no comorbidity, detectable underlying structural or functional heart disease. Previous studies have also demonstrated that nearly 30% of patients with atrial fibrillation may have a positive family history. The predisposition for arrhythmia events was shown to be inherited in an autosomal dominant pattern. In a small proportion of familial AF, specific mutant genes were identified, and mutations were detected mainly in KCNE2, KCNJ2, and KCNQ1. While encoding the protein products of certain potassium channels, these are suggested to play a role in the maintenance of sinus rhythm [13–16].

Atrial anisotropy is thought to be one of the key points of increased atrial arrhythmia vulner‐ ability, where the inhomogeneous spreading of atrial impulses can be secondary to an altered histological structure of the atrial myocardium (hypertrophy, fibrosis, and fatty degeneration) [17–19]. Consequently, the dilation of both atria may appear representing an increased susceptibility for atrial arrhythmias [20]. Furthermore, increase in cardiac preload and afterload and electrolyte imbalances may also have an additive role in the increase of atrial arrhythmogenicity and reentry mechanism, where the latter is the electrophysiological substrate for atrial fibrillation.

## **2.2. Clinical consequences of atrial fibrillation**

predict ventricular arrhythmias [6, 7]. In our chapter we would like to present the electrophy‐ siological substrates and pathogenetic factors taking part in arrhythmogenesis and to demonstrate ECG‐based diagnostic opportunities that can help in the prediction and preven‐ tion of arrhythmias. Furthermore, we present the results of our studies to demonstrate the

**2. Non-invasive electrocardiographic markers in the prediction of atrial**

The most common form of rhythm disturbances is atrial fibrillation (AF). Its prevalence is 0.12–0.16% among people younger than 49 years, 3.7–4.2% with regard to people aged 60–70 years and 10–17% among people aged 80 years or older [10]. Age, gender, hypertension, dia‐ betes mellitus, heart failure and valvular heart disease are independent risk factors that may play a role in arrhythmogenesis. Moreover, AF may be caused by hyperthyroidism and ex‐

In patients with end‐stage renal failure, its prevalence is approximately 13%. Interestingly, 10% of subjects suffering from 'lone' AF have no comorbidity, detectable underlying structural or functional heart disease. Previous studies have also demonstrated that nearly 30% of patients with atrial fibrillation may have a positive family history. The predisposition for arrhythmia events was shown to be inherited in an autosomal dominant pattern. In a small proportion of familial AF, specific mutant genes were identified, and mutations were detected mainly in KCNE2, KCNJ2, and KCNQ1. While encoding the protein products of certain potassium channels, these are suggested to play a role in the maintenance of sinus rhythm [13–16].

Atrial anisotropy is thought to be one of the key points of increased atrial arrhythmia vulner‐ ability, where the inhomogeneous spreading of atrial impulses can be secondary to an altered histological structure of the atrial myocardium (hypertrophy, fibrosis, and fatty degeneration)

**2.1. Epidemiology and electrophysiological background of atrial fibrillation**

Ischemic heart disease 17 Hypertensive cardiomyopathy 21 Valvulopathies 15 Dilated cardiomyopathy 9 Hypertrophic cardiomyopathy 5 Other structural heart diseases 9 Non‐structural heart diseases 29

clinical use of these ECG markers.

14 Echocardiography in Heart Failure and Cardiac Electrophysiology

cessive alcohol consumption [11, 12] (**Table 1**).

**Cardiovascular causes of atrial fibrillation (%)**

**Table 1.** Cardiovascular causes of atrial fibrillation.

**fibrillation**

Irregular and high ventricular response due to AF, atrioventricular dissociation and the lack of atrial systole may contribute to low cardiac output syndrome. Patients usually complain about palpitation, fatigue, dyspnea, vertigo/dizziness, and chest pain. However, 11% of these patients are asymptomatic. Decrease in atrial blood flow velocity gives the chance for atrial thrombus formation. Mortality caused by atrial fibrillation is primarily connected with an increased risk for thromboembolic events and stroke (**Figure 1**) [10, 11, 21].

**Figure 1.** Pathomechanism and consequences of atrial fibrillation.

#### **2.3. Electrocardiographic prediction of AF**

## *2.3.1. P-wave duration and P dispersion*

Due to the structural and electrophysiological heterogeneity of the left atrium, unidirectional block can occur, which plays a role in the genesis of atrial microreentry and premature beats. In patients with paroxysmal atrial fibrillation during sinus rhythm, the intra‐ and interatrial conduction time of the sinus impulse were shown to lengthen, and the duration of the P wave measured on a surface electrocardiogram (ECG) is increased, where the prolongation of atrial conduction time is proportional with the duration of P‐wave interval. Previously, it has also been shown that the prolongation of P‐wave duration and P dispersion (Pd) can predict atrial arrhythmias. P‐wave duration of the surface electrocardiogram is specified as the section from the first electrical activity following the T wave (or the U wave) to the intersection of the P wave's descending branch and the isoelectric line. The investigator should analyze three consecutive P waves each lead and calculate their average duration, where the result is the P wave duration in the given lead (**Figure 2**). P dispersion (Pd) is determined as the difference between the longest and shortest P interval. P interval and Pd can be corrected to the heart rate (Pmaxc, Pdc) according to Bazett's formula (Pmaxc = Pmax/√RR (ms), Pdc = Pd/√RR (ms)) (**Figure 2**) [5, 8, 9].

**Figure 2.** Measurement of P‐wave duration on the surface ECG.

## *2.3.2. Alterations of P-wave duration and P dispersion among patients participating renal replacement therapy*

The incidence of atrial fibrillation is increased during hemodialysis (HD), and the prolongation of P‐wave duration has been shown to be a valuable indicator of atrial conduction disturbances. Based on the aforementioned, we analyzed the length of P‐wave interval and P dispersion on the surface ECG of 28 patients with end‐stage renal failure on extracorporeal renal replacement therapies. According to our results, P‐wave duration and P dispersion increased significantly at the end of the hemodialysis sessions compared to those measured at the beginning, and they remained lengthened 2 hours after the treatment [22]. Previously, a novel convective‐transport‐ based renal replacement method, the hemodiafiltration (HDF), has been introduced. Lately, convective treatment has been proven to reduce mortality of these particular patients with end‐ stage kidney disease. This favorable effect of HDF may be partly caused by the decreased occurrence of atrial and ventricular arrhythmias. We intended to examine whether these suggested differences between hemodialysis and hemodiafiltration with regard to arrhythmia vulnerability could be shown as alterations of P interval and P dispersion on the surface ECG. We obtained clinical data from 30 patients receiving HDF over a period of 3 months; and the same group of patients was then evaluated during treatment with conventional HD for at least another 3 months. The duration of the P wave and Pd increased significantly during HD, but no such significant prolongations were observed in the case of HDF (**Figure 3**) [23].

**Figure 3.** Changes in corrected P‐wave duration (P interval) and corrected P dispersion (Pd) during hemodialysis and hemodiafiltration.

## *2.3.3. Biphasic P wave*

measured on a surface electrocardiogram (ECG) is increased, where the prolongation of atrial conduction time is proportional with the duration of P‐wave interval. Previously, it has also been shown that the prolongation of P‐wave duration and P dispersion (Pd) can predict atrial arrhythmias. P‐wave duration of the surface electrocardiogram is specified as the section from the first electrical activity following the T wave (or the U wave) to the intersection of the P wave's descending branch and the isoelectric line. The investigator should analyze three consecutive P waves each lead and calculate their average duration, where the result is the P wave duration in the given lead (**Figure 2**). P dispersion (Pd) is determined as the difference between the longest and shortest P interval. P interval and Pd can be corrected to the heart rate (Pmaxc, Pdc) according to Bazett's formula (Pmaxc = Pmax/√RR (ms), Pdc = Pd/√RR (ms))

(**Figure 2**) [5, 8, 9].

*replacement therapy*

**Figure 2.** Measurement of P‐wave duration on the surface ECG.

16 Echocardiography in Heart Failure and Cardiac Electrophysiology

*2.3.2. Alterations of P-wave duration and P dispersion among patients participating renal*

The incidence of atrial fibrillation is increased during hemodialysis (HD), and the prolongation of P‐wave duration has been shown to be a valuable indicator of atrial conduction disturbances. Based on the aforementioned, we analyzed the length of P‐wave interval and P dispersion on the surface ECG of 28 patients with end‐stage renal failure on extracorporeal renal replacement therapies. According to our results, P‐wave duration and P dispersion increased significantly at the end of the hemodialysis sessions compared to those measured at the beginning, and they remained lengthened 2 hours after the treatment [22]. Previously, a novel convective‐transport‐ based renal replacement method, the hemodiafiltration (HDF), has been introduced. Lately, convective treatment has been proven to reduce mortality of these particular patients with end‐ stage kidney disease. This favorable effect of HDF may be partly caused by the decreased occurrence of atrial and ventricular arrhythmias. We intended to examine whether these suggested differences between hemodialysis and hemodiafiltration with regard to arrhythmia vulnerability could be shown as alterations of P interval and P dispersion on the surface ECG. We obtained clinical data from 30 patients receiving HDF over a period of 3 months; and the same group of patients was then evaluated during treatment with conventional HD for at least Slow and inhomogeneous atrial conduction, thus atrial anisotropy, can appear as biphasic P wave in the inferior electrocardiographic leads (leads II, III, and aVF). In nearly 75% of patients with paroxysmal, AF has an increased duration of the initial portion of P wave in lead III [24]. Various investigations have reported the clinical value of P‐wave measurements in the prediction of AF (**Table 2**) [22, 23, 25–30].


**Table 2.** Studies which investigated alterations of the atrial phase of surface ECG.

## *2.3.4. Investigation of Ta wave*

Inhomogeneous atrial repolarization may also play an additive role in the genesis of atrial arrhythmias and paroxysmal atrial fibrillation. Therefore, ECG analysis of atrial repolarization may provide further data on atrial arrhythmia vulnerability. Recently, a novel electrocardio‐ graphic marker the atrial T wave, also known Ta wave, has been shown to characterize atrial repolarization in patients with sinus rhythm. Due to its small amplitude within the PQ segment, signal averaging is necessary to soften the measurements. Moreover, in patients with physiologic atrioventricular conduction, it is generally localized in the subsequent QRS complex (name for the combination of three of the graphical deflections seen on a surface ECG which corresponds to the ventricular depolarization) holding the measurements to be impos‐ sible. Nevertheless, characteristics of the detectable atrial repolarization phase of the ECG have been compared between individuals with sinus rhythm and paroxysmal AF. However, no significant differences with regard to the morphology, amplitude and length of Ta wave have been clearly elucidated yet [31].

## **3. Ventricular arrhythmias and sudden cardiac death**

## **3.1. The role of electrocardiographic markers in the prevention of ventricular rhythm disturbances and sudden cardiac death**

Despite the improvement in statistical data, cardiovascular diseases are responsible for approximately 17 million deaths every year in the world, where approximately 25% is related to sudden cardiac death [32]. Malignant ventricular arrhythmias (e.g. ventricular tachycardia and ventricular fibrillation) are the most important underlying rhythm disturbances respon‐ sible for these unfavorable statistics. The incidence of these ventricular arrhythmias correlates with age primarily due to the higher prevalence of coronary artery disease [33]. Sudden cardiac death has an estimated incidence of 1100–9000 in Europe and 800–6200 in the United States every year [32].

#### **3.2. Pathomechanism of ventricular arrhythmias and sudden cardiac death**

Various factors have been shown to play a role in the genesis of ventricular arrhythmias. Both congenital factors and acquired pathophysiological mechanisms can provoke these cardiac rhythm disturbances [33]. Previously, it has been demonstrated that *genetic predisposition* can contribute to the genesis of sudden cardiac death. Fifty percent increase has been confirmed in the likelihood of the occurrence of malignant ventricular arrhythmias in the presence of a family history of sudden cardiac death [34]. Furthermore, it has been shown that familial sudden death appears more frequently in patients resuscitated from primary ventricular fibrillation [35]. Previously, single nucleotide polymorphisms located in the 21q21 and 2q24.2 loci have been also shown to increase the risk of sudden cardiac death [36, 37]. However, certain concerns were raised with regard to these results, and further investigations are needed. The risk of sudden cardiac death is higher in males [38, 39]. On the other hand, coronary artery disease, ischemic cardiomyopathy and heart failure, hypertensive heart disease, and lipid abnormalities are the most important *acquired* provoking factors with regard to ventricular arrhythmogenesis and sudden cardiac death [3, 38]. Interestingly, kidney disease and hemo‐ dialysis itself have been demonstrated to be significant underlying substrates for the genesis of ventricular arrhythmias. The incidence of sudden cardiac death in patients suffering from kidney diseases was shown to be approximately 1.4–25% [4]. Furthermore, physical inactivity, smoking, alcohol abuse, and inadequate alimentation are significant pathophysiologic factors that may contribute to ventricular arrhythmogenesis [39] (**Table 3**). Most importantly 50% of sudden death appears in patients without a previously known heart disease, but most of these individuals suffer from ischemic heart disease. Therefore, 40% of the reduction in sudden arrhythmia death is due to the effective management and prevention of coronary artery disease [38, 39]. Left ventricular systolic dysfunction has also been proven to be an important under‐ lying factor for ventricular arrhythmogenesis. Left ventricular ejection fraction, an echocar‐ diographic parameter, has been shown in association with increased probability for sudden cardiac death mainly in patients with myocardial infarction. Related to heart failure, certain biochemical indicators such as the B‐type natriuretic peptide and N‐terminal pro‐B‐type natriuretic peptide have also been shown to be useful in the risk stratification of sudden cardiac death [40, 41].

which corresponds to the ventricular depolarization) holding the measurements to be impos‐ sible. Nevertheless, characteristics of the detectable atrial repolarization phase of the ECG have been compared between individuals with sinus rhythm and paroxysmal AF. However, no significant differences with regard to the morphology, amplitude and length of Ta wave have

**3.1. The role of electrocardiographic markers in the prevention of ventricular rhythm**

**3.2. Pathomechanism of ventricular arrhythmias and sudden cardiac death**

Despite the improvement in statistical data, cardiovascular diseases are responsible for approximately 17 million deaths every year in the world, where approximately 25% is related to sudden cardiac death [32]. Malignant ventricular arrhythmias (e.g. ventricular tachycardia and ventricular fibrillation) are the most important underlying rhythm disturbances respon‐ sible for these unfavorable statistics. The incidence of these ventricular arrhythmias correlates with age primarily due to the higher prevalence of coronary artery disease [33]. Sudden cardiac death has an estimated incidence of 1100–9000 in Europe and 800–6200 in the United States

Various factors have been shown to play a role in the genesis of ventricular arrhythmias. Both congenital factors and acquired pathophysiological mechanisms can provoke these cardiac rhythm disturbances [33]. Previously, it has been demonstrated that *genetic predisposition* can contribute to the genesis of sudden cardiac death. Fifty percent increase has been confirmed in the likelihood of the occurrence of malignant ventricular arrhythmias in the presence of a family history of sudden cardiac death [34]. Furthermore, it has been shown that familial sudden death appears more frequently in patients resuscitated from primary ventricular fibrillation [35]. Previously, single nucleotide polymorphisms located in the 21q21 and 2q24.2 loci have been also shown to increase the risk of sudden cardiac death [36, 37]. However, certain concerns were raised with regard to these results, and further investigations are needed. The risk of sudden cardiac death is higher in males [38, 39]. On the other hand, coronary artery disease, ischemic cardiomyopathy and heart failure, hypertensive heart disease, and lipid abnormalities are the most important *acquired* provoking factors with regard to ventricular arrhythmogenesis and sudden cardiac death [3, 38]. Interestingly, kidney disease and hemo‐ dialysis itself have been demonstrated to be significant underlying substrates for the genesis of ventricular arrhythmias. The incidence of sudden cardiac death in patients suffering from kidney diseases was shown to be approximately 1.4–25% [4]. Furthermore, physical inactivity, smoking, alcohol abuse, and inadequate alimentation are significant pathophysiologic factors that may contribute to ventricular arrhythmogenesis [39] (**Table 3**). Most importantly 50% of sudden death appears in patients without a previously known heart disease, but most of these individuals suffer from ischemic heart disease. Therefore, 40% of the reduction in sudden

**3. Ventricular arrhythmias and sudden cardiac death**

been clearly elucidated yet [31].

every year [32].

**disturbances and sudden cardiac death**

18 Echocardiography in Heart Failure and Cardiac Electrophysiology


**Table 3.** Common causes of ventricular arrhythmias are shown. Congenital and acquired diseases may play a role in ventricular arrhythmogenesis; furthermore, temporary factors can additionally increase the susceptibility for rhythm disturbances.

**Figure 4.** The monophasic action potential of a ventricular myocardial cell is shown. The plateau phase largely de‐ pends on the potassium and the calcium ion channel activity. The longer the plateau phase, the more increased the myocardial cell's repolarization. M cells show a prominent prolongation in action potential diameter and develop early after depolarizations in response to rapidly activating delayed rectifier potassium current (IKr) blockers.

## **3.3. Ventricular repolarization and cardiac arrhythmias**

Secondary to the pathophysiologic factors, the electrophysiological properties of the myocar‐ dial cells can change, resulting in the modification of the duration and amplitude of the monophasic action potential featuring the myocardial cell's electrical properties (**Figure 4**) [42]. As a result, inhomogeneous ventricular repolarization and anisotropy may appear, which seem to be one of the electrophysiological key points in the genesis of ventricular arrhythmias. Previously, it has been shown that a mid‐myocardial population of cardiac myocytes (e.g. M cells) can play an important role in the prolongation of repolarizational dispersion [43, 44]. From an electrophysiologic point of view, these special cells have been shown to be between Purkinje and ventricular myocytes, while they show a significant prolongation in action potential diameter and develop early after depolarizations in response to rapidly activating delayed rectifier potassium current (IKr) blockers [45]. In the meantime epicardial and endocardial myocytes are less likely to do so. Accordingly, due to certain drug therapies (e.g. amiodarone and sotalol) or other provoking factors, an exaggerated dispersion in transmural action potential duration may come alive, resulting in an increased danger of transmural inhomogeneity of ventricular repolarization and an increased susceptibility for ventricular arrhythmias (**Figure 4**) [42, 46].

#### **3.4. QT interval and dispersion**

QT interval represents the electrical repolarization of the ventricular myocardium. Patients with increased susceptibility for the development of malignant ventricular dysrhythmias can be identified with the determination of QT interval [47]. Duration of the QT interval is changing in the different leads of the surface electrocardiogram. QT dispersion (QTd) is derived from the interlead alterations of QT intervals. This is a useful parameter to describe the differences in ventricular recovery times representing the prolongation of myocardial repolarization [48]. QT dispersion has also been proven to correlate with the duration of the monophasic action potential of the epicardial myocardial cells. Since these electrocardiographic markers have been introduced to predict ventricular arrhythmias and sudden cardiac death, they are considered to be among one of the non‐invasive parameters [49]. The prolongation of QT interval can be congenital (e.g. Romano‐Ward or Jervell and Lange‐Nielsen syndromes) or acquired. Congenital syndromes are caused by mutations in at least five different ion channel genes resulting in the defects in the sodium channel (SCN5A, LQT3), the rapidly activating delayed rectifier channel (IKr) (HERG, LQT2 or KCNE2, LQT6), and the slowly activating delayed rectifier channel (IKs) (KvLQT1, LQT1 or KCNE1, LQT5), respectively [50]. QT prolongation can be acquired and may occur after acute myocardial infarction, congestive heath failure, dyslipidemia, diabetes mellitus, sudden sympathetic autonomic activation (triggered activity) and renal failure [6, 51–55]. In individuals with liver cirrhosis, the length‐ ening of QT interval has not been shown to be related to the etiology of the liver disease and seems to appear both in alcoholic and nonalcoholic patients [46]. In addition, QT prolongation may be associated to certain drug interactions (e.g. haloperidol, methadone, amiodarone, sotalol, selective serotonin reuptake inhibitors, macrolide antibiotics, and antifungal agents) [56]. QT dispersion may also be affected by various diseases (amyloidosis, sarcoidosis, carcinoid, hemochromatosis, diabetes mellitus, thyroid dysfunction, or Parkinson's disease) [57–63].

## **3.5. QT measurements and their clinical use**

**Figure 4.** The monophasic action potential of a ventricular myocardial cell is shown. The plateau phase largely de‐ pends on the potassium and the calcium ion channel activity. The longer the plateau phase, the more increased the myocardial cell's repolarization. M cells show a prominent prolongation in action potential diameter and develop early

Secondary to the pathophysiologic factors, the electrophysiological properties of the myocar‐ dial cells can change, resulting in the modification of the duration and amplitude of the monophasic action potential featuring the myocardial cell's electrical properties (**Figure 4**) [42]. As a result, inhomogeneous ventricular repolarization and anisotropy may appear, which seem to be one of the electrophysiological key points in the genesis of ventricular arrhythmias. Previously, it has been shown that a mid‐myocardial population of cardiac myocytes (e.g. M cells) can play an important role in the prolongation of repolarizational dispersion [43, 44]. From an electrophysiologic point of view, these special cells have been shown to be between Purkinje and ventricular myocytes, while they show a significant prolongation in action potential diameter and develop early after depolarizations in response to rapidly activating delayed rectifier potassium current (IKr) blockers [45]. In the meantime epicardial and endocardial myocytes are less likely to do so. Accordingly, due to certain drug therapies (e.g. amiodarone and sotalol) or other provoking factors, an exaggerated dispersion in transmural action potential duration may come alive, resulting in an increased danger of transmural inhomogeneity of ventricular repolarization and an increased susceptibility for ventricular

QT interval represents the electrical repolarization of the ventricular myocardium. Patients with increased susceptibility for the development of malignant ventricular dysrhythmias can be identified with the determination of QT interval [47]. Duration of the QT interval is changing

after depolarizations in response to rapidly activating delayed rectifier potassium current (IKr) blockers.

**3.3. Ventricular repolarization and cardiac arrhythmias**

20 Echocardiography in Heart Failure and Cardiac Electrophysiology

arrhythmias (**Figure 4**) [42, 46].

**3.4. QT interval and dispersion**

Since these repolarizational variables are modified by numerous causes, the thorough inves‐ tigation of patient's history is one of the leading points during the determination of arrhythmia risk. Considering the required standards for precision, the measurement of QT interval still remains subjective as the terminal point of the T wave usually cannot be clearly defined. QT interval can be measured manually or automatically [49, 64]. During manual investigations, improvement in consistency of the results and the minimization of interobserver variability may be achieved by the measurements performed by one examiner. During the threshold method, the point where the T wave reaches the isoelectric line is determined as its end. According to the tangent method, the end of T wave is defined as the point where a given tangent line overtakes the isoelectric line, where the tangent line is the last part of the T wave at its maximum downslope. To get more accurate data, the average of three sequential periods in a given lead is calculated and defined as QT interval [47, 48] (**Figure 5**). QT measurements may also be performed by means of computers with the superimposed median beat method, where an electrocardiographic complex is constructed for each of the 12 leads. These medians are superimposed on each other. Afterwards, QT interval is determined from the earliest onset of the Q wave to the latest offset of the T wave. Moreover, QT interval can be measured from the point of maximum convergence for the Q‐wave onset to the T‐wave offset [48].

**Figure 5.** The manual measurement of the QT interval of the 12‐lead surface electrocardiogram. The calculation and averaging of three consecutive sections may provide a more accurate result in the given lead.

Ventricular rate has a significant influence on QT interval's duration. When heart rate acceler‐ ates, QT interval shortens. Therefore, QT interval has to be corrected to heart rate (QTc) using the Bazett's formula (QTc = QT/√RR) (borderline QTc, male 431–450 ms and female 451–470 ms; abnormal QTc, male ≥ 451 ms and female ≥471 ms). Normal values of QT dispersion vary in a very wide range from 10 to 71 ms. The QTc >450 ms value has been reported to have an increased risk for ventricular arrhythmias [49]. With regard to patients suffering from liver cirrhosis, a special relationship between QT interval duration and heart rate exists; thus, a specific 'cirrhosis formula'—similar to the Fridericia's—should be used. Measurement of QT interval and dispersion can help in the monitoring of antiarrhythmic therapy especially with the widely used antiarrhythmic drugs, amiodarone and sotalol [46, 56]. Previously, the prolongation of the QT dispersion has been shown to represent recurrent ischemia after percutaneous transluminal coronary angioplasty. Lately, the eligibility of QT dispersion in the evaluation of long‐term outcome of patients waiting for cardiac transplantation has also been discussed. Life‐threatening ventricular rhythm disturbances of patients with long QT syn‐ dromes often caused by a sudden increase in sympathetic activity, and beta‐blockers have been shown to significantly reduce these arrhythmic episodes. In patients who remain symptomatic despite treatment with beta‐blockers (mostly patients with LQT2 and LQT3), left cardiac sympathetic denervation may be a therapeutic solution. In the case of cardiac arrest, ICD should be implanted; however, there are controversial data regarding the ICD therapy in subjects with no such previous history [47, 49, 50].

#### *3.5.1. Changes in QT interval and QT dispersion in hyperlipidemia and kidney disease*

The susceptibility to malignant ventricular arrhythmias increases proportionally with the lengthening of QT interval. Progressive atherosclerosis is an independent risk factor of the occurrence of sudden cardiac death. In our study clinical data of 96 patients with hyperlipi‐ demia were compared to 103 controls. Serum LDL‐C (low density lipoprotein – cholesterol) and Tg levels were positively correlated with corrected QT interval and QT dispersion, so lipid parameters may affect these ECG markers [65]. Furthermore, we investigated the ECG parameters representing ventricular repolarization in the case of 30 patients receiving hemodiafiltration (HDF) over a period of 3 months, and we obtained data from the same patients after treatment with conventional hemodialysis (HD) for at least another 3 months. The duration of the QT interval and QT dispersion was only increased significantly in the case of HD, but no similar significant prolongations in the case of HDF could be observed (**Figure 6**) [66].

**Figure 6.** Prolongation of corrected QT interval and corrected QT dispersion (QTd) during different renal replacement therapies.

## **3.6. QT variability**

**Figure 5.** The manual measurement of the QT interval of the 12‐lead surface electrocardiogram. The calculation and

Ventricular rate has a significant influence on QT interval's duration. When heart rate acceler‐ ates, QT interval shortens. Therefore, QT interval has to be corrected to heart rate (QTc) using the Bazett's formula (QTc = QT/√RR) (borderline QTc, male 431–450 ms and female 451–470 ms; abnormal QTc, male ≥ 451 ms and female ≥471 ms). Normal values of QT dispersion vary in a very wide range from 10 to 71 ms. The QTc >450 ms value has been reported to have an increased risk for ventricular arrhythmias [49]. With regard to patients suffering from liver cirrhosis, a special relationship between QT interval duration and heart rate exists; thus, a specific 'cirrhosis formula'—similar to the Fridericia's—should be used. Measurement of QT interval and dispersion can help in the monitoring of antiarrhythmic therapy especially with the widely used antiarrhythmic drugs, amiodarone and sotalol [46, 56]. Previously, the prolongation of the QT dispersion has been shown to represent recurrent ischemia after percutaneous transluminal coronary angioplasty. Lately, the eligibility of QT dispersion in the evaluation of long‐term outcome of patients waiting for cardiac transplantation has also been discussed. Life‐threatening ventricular rhythm disturbances of patients with long QT syn‐ dromes often caused by a sudden increase in sympathetic activity, and beta‐blockers have been shown to significantly reduce these arrhythmic episodes. In patients who remain symptomatic despite treatment with beta‐blockers (mostly patients with LQT2 and LQT3), left cardiac sympathetic denervation may be a therapeutic solution. In the case of cardiac arrest, ICD should be implanted; however, there are controversial data regarding the ICD therapy in

averaging of three consecutive sections may provide a more accurate result in the given lead.

22 Echocardiography in Heart Failure and Cardiac Electrophysiology

subjects with no such previous history [47, 49, 50].

*3.5.1. Changes in QT interval and QT dispersion in hyperlipidemia and kidney disease*

The susceptibility to malignant ventricular arrhythmias increases proportionally with the lengthening of QT interval. Progressive atherosclerosis is an independent risk factor of the occurrence of sudden cardiac death. In our study clinical data of 96 patients with hyperlipi‐ demia were compared to 103 controls. Serum LDL‐C (low density lipoprotein – cholesterol) and Tg levels were positively correlated with corrected QT interval and QT dispersion, so lipid parameters may affect these ECG markers [65]. Furthermore, we investigated the ECG

Previously, numerous studies have been dealing with the beat‐to‐beat variability in QT interval of the surface electrocardiogram in order to quantify temporal dispersion of ventricular repolarization [67]. Its increase has been associated to long QT syndrome, heart failure, myocardial ischemia, hypertrophic cardiomyopathy, and panic disorder [68–72]. Increased QT variability has also been shown to predict appropriate implantable cardioverter‐defibrillator shocks. Moreover, increased variability has been observed with regard to sudden cardiac death in patients with myocardial infarction without ICD therapy [73, 74]. QT variability may also increase in healthy people with postural change from the supine to standing position and after activities that increase beta‐adrenergic tone [75]. QT variability is measured by a special computer algorithm that is able to analyze QT‐interval signals that are derived from multiple channels [76].

#### **3.7. Short QT syndrome**

Short QT syndrome, an inherited disease, is characterized by QT interval <300 ms and an increased risk for paroxysmal atrial fibrillation and ventricular arrhythmias. Short QT syndrome is also related to an increased risk of sudden cardiac death, likely caused by ventricular fibrillation [77]. More genetic mutations of sodium and calcium channels have been reported to be an underlying substrate for this clinical entity (KCNH2, KCNQ1 and KCNJ2). Increased activity of outward potassium currents in phase 2 and phase 3 leads to the decreased duration of cardiac action potential, resulting in the shortening of refractory periods. This mechanism is thought to be responsible for the genesis of reentry mechanism and increased dispersion of ventricular repolarization [77, 78]. Besides ICD, antiarrhythmic drug therapy also has to be taken into consideration. Only quinidine, a sodium channel blocker, has been shown to normalize the QT interval at resting heart rates, while it restored the heart rate dependence of QT interval towards an adaptation range of healthy individuals by prolonging the duration of cardiac action potential [79, 80]. However its further effects remain to be elucidated.

## **3.8. Early repolarization**

Recently, a J‐point elevation of ≥0.1 mV in two adjacent leads occurring on the surface electro‐ cardiogram manifested as terminal QRS slurring (the transition from the QRS segment to the ST segment) or notching (a positive deflection inscribed on terminal QRS complex) associated with concave upward ST‐segment elevation and prominent T waves has been introduced as an early‐repolarization (ER) pattern [81, 82]. A transmural voltage gradient between the ventricular epicardium and endocardium may be responsible for this phenomenon [83, 84]. ER commonly occurs in the general population (approximately 10%) and often exists in athletes and youngsters and at slower heart rates in individuals without known cardiac diseases [85]. However, recently, studies have emphasized a possible link between ER and life‐threatening ventricular dysrhythmias [86]. The electrocardiographic signs of ER may be associated with a shorter QT interval and can display high dynamicity affected by ventricular rate and pauses, mediators of autonomic nervous system, androgen hormones and certain drugs (sodium channel blockers, beta‐blockers, quinidine and isoproterenol) [87–91]. Importantly, a distinc‐ tion between ER, short QT and Brugada syndromes sometimes proves to be difficult on the basis of electrocardiography, where genetic tests may be valuable in identifying the underlying ion channel defect [89, 92, 93]. Subjects with ECG signs of classic ER have minimal risk for ventricular arrhythmias, and the recognition of high‐risk patients is often a real challenge [93, 94]. The susceptibility for ventricular arrhythmias may increase when ER is associated with heart failure, hypokalemia or acute coronary syndrome [95, 96]. Furthermore, the family history of ERS or sudden death, the extension of electrocardiographic signs of ER into a Brugada syndrome pattern, the presence of horizontal ST segment following the J wave, ER signs localized in inferior or infero‐lateral leads, the presence of coupled ventricular premature beats, increase in parasympathetic tone, also the association of ER with short QT intervals, young age and male gender draw the attention to a higher arrhythmia risk [94, 97–99]. In high‐ risk patients with ER syndrome and a family history of sudden death, quinidine and/or ICD implantation can be a therapeutic solution. Furthermore, cilostazol, a phosphodiesterase III inhibitor, has been shown to normalize the aforementioned ECG changes. In the case of ER syndrome‐mediated electrical changes, a beta‐adrenergic agent (e.g. isoproterenol) may be a useful therapeutic solution [100].

## **3.9. T-wave alternans (TWA) and T-wave peak-to-end interval**

ventricular fibrillation [77]. More genetic mutations of sodium and calcium channels have been reported to be an underlying substrate for this clinical entity (KCNH2, KCNQ1 and KCNJ2). Increased activity of outward potassium currents in phase 2 and phase 3 leads to the decreased duration of cardiac action potential, resulting in the shortening of refractory periods. This mechanism is thought to be responsible for the genesis of reentry mechanism and increased dispersion of ventricular repolarization [77, 78]. Besides ICD, antiarrhythmic drug therapy also has to be taken into consideration. Only quinidine, a sodium channel blocker, has been shown to normalize the QT interval at resting heart rates, while it restored the heart rate dependence of QT interval towards an adaptation range of healthy individuals by prolonging the duration of cardiac action potential [79, 80]. However its further effects remain to be elucidated.

Recently, a J‐point elevation of ≥0.1 mV in two adjacent leads occurring on the surface electro‐ cardiogram manifested as terminal QRS slurring (the transition from the QRS segment to the ST segment) or notching (a positive deflection inscribed on terminal QRS complex) associated with concave upward ST‐segment elevation and prominent T waves has been introduced as an early‐repolarization (ER) pattern [81, 82]. A transmural voltage gradient between the ventricular epicardium and endocardium may be responsible for this phenomenon [83, 84]. ER commonly occurs in the general population (approximately 10%) and often exists in athletes and youngsters and at slower heart rates in individuals without known cardiac diseases [85]. However, recently, studies have emphasized a possible link between ER and life‐threatening ventricular dysrhythmias [86]. The electrocardiographic signs of ER may be associated with a shorter QT interval and can display high dynamicity affected by ventricular rate and pauses, mediators of autonomic nervous system, androgen hormones and certain drugs (sodium channel blockers, beta‐blockers, quinidine and isoproterenol) [87–91]. Importantly, a distinc‐ tion between ER, short QT and Brugada syndromes sometimes proves to be difficult on the basis of electrocardiography, where genetic tests may be valuable in identifying the underlying ion channel defect [89, 92, 93]. Subjects with ECG signs of classic ER have minimal risk for ventricular arrhythmias, and the recognition of high‐risk patients is often a real challenge [93, 94]. The susceptibility for ventricular arrhythmias may increase when ER is associated with heart failure, hypokalemia or acute coronary syndrome [95, 96]. Furthermore, the family history of ERS or sudden death, the extension of electrocardiographic signs of ER into a Brugada syndrome pattern, the presence of horizontal ST segment following the J wave, ER signs localized in inferior or infero‐lateral leads, the presence of coupled ventricular premature beats, increase in parasympathetic tone, also the association of ER with short QT intervals, young age and male gender draw the attention to a higher arrhythmia risk [94, 97–99]. In high‐ risk patients with ER syndrome and a family history of sudden death, quinidine and/or ICD implantation can be a therapeutic solution. Furthermore, cilostazol, a phosphodiesterase III inhibitor, has been shown to normalize the aforementioned ECG changes. In the case of ER syndrome‐mediated electrical changes, a beta‐adrenergic agent (e.g. isoproterenol) may be a

**3.8. Early repolarization**

24 Echocardiography in Heart Failure and Cardiac Electrophysiology

useful therapeutic solution [100].

T‐wave alternans is defined as an alteration in the morphology of the T wave in an AB‐AB or every‐other‐beat pattern (**Figure 7**). It has been introduced as a non‐invasive ECG marker for evaluating spatiotemporal heterogeneity of ventricular repolarization [101]. By reflecting the intracellular changes in calcium handling and showing beat‐to‐beat alternations of action potential duration of the ventricular cells, this electrocardiographic parameter seems to be capable for the prediction of ventricular repolarizational heterogeneity and the predisposition for ventricular arrhythmias [102].

**Figure 7.** Alternation in the morphology of T waves on the surface electrocardiogram. Based on Narayan [101].

The electronic filtering of the T wave on a 'microvolt level' (i.e. microvolt T‐wave alternans (MTWA)) creates even greater applicability of this non‐invasive electrocardiographic method [103]. Therefore, MTWA has also been introduced as a valuable tool for the risk stratification of sudden cardiac death. Importantly, MTWA seems to have a particular role in the risk stratification between patients who need implantable cardiac defibrillators and those who do not [103–105]. TWA test is usually conducted during treadmill or bicycle exercise or with the administration of chronotropic agents in order to achieve an optimal ventricular rate, since TWA may occur in normal individuals at heart rates >120 beats/min. Occasionally, pacemaker stimulation required to maintain stable ventricular frequency. A target ventricular rate range of 105–110/min was determined for pathologic alternans in adults. If ectopic or premature beats constitute >10% of beats, the affected portion of the electrocardiogram is not recommended for TWA examination [106–108]. MTWA tests' results can be positive, negative or indeterminate. Patients with indeterminate results have to be investigated again [109]. In the case of a negative test, the probability of malignant ventricular arrhythmias and sudden cardiac death are low (with 98% accuracy for follow‐up periods of 12–24 months in clinical studies) [110]. However, these patients have to undergo a repeated investigation every 12–24 months. Subjects with a negative MTWA test are not likely to require a defibrillator. Importantly, TWA testing may be equivalent to an electrophysiology study. Nevertheless, at present there is no definitive evidence available that can prove the real effectiveness of this method in guiding the antiar‐ rhythmic treatment [107]. Previously a novel electrocardiographic marker, T‐wave peak‐to‐ end interval (Tpe) has been reported to represent the transmural dispersion of repolarization of the left ventricle and the vulnerability to ventricular arrhythmias [6, 111]. The prolongation of Tpe has been shown to be associated with increased mortality rates in long QT syndrome, acute myocardial infarction, sleep apnea and hypertrophic cardiomyopathy [6, 111, 112]. Reference value of T‐wave peak‐to‐end interval is considered to be 94 ms in the case of male and 92 ms with regard to female subjects [113]. In addition, the Tpe/QT ratio is used as an arrhythmogenic index (AIX) of ventricular arrhythmogenesis [7, 114]. It has been demonstrat‐ ed that in patients with acquired QT syndrome, the Tpe/QT ratio is superior to QT interval and QT dispersion in the prediction of torsades de pointes ventricular tachycardia [115]. Also, Tpe/QT ratio was shown to be a valuable predictor of sudden cardiac death [116–118].

## **Author details**

Veronika Sebestyén and Zoltán Szabó\*

\*Address all correspondence to: szaboz.med@gmail.com

Division of Emergency Medicine, Faculty of Medicine, Clinical Centre, Institute of Medicine, University of Debrecen, Debrecen, Hungary

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Reference value of T‐wave peak‐to‐end interval is considered to be 94 ms in the case of male and 92 ms with regard to female subjects [113]. In addition, the Tpe/QT ratio is used as an arrhythmogenic index (AIX) of ventricular arrhythmogenesis [7, 114]. It has been demonstrat‐ ed that in patients with acquired QT syndrome, the Tpe/QT ratio is superior to QT interval and QT dispersion in the prediction of torsades de pointes ventricular tachycardia [115]. Also, Tpe/QT ratio was shown to be a valuable predictor of sudden cardiac death [116–118].

Division of Emergency Medicine, Faculty of Medicine, Clinical Centre, Institute of Medicine,

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#### **Echocardiography and Other Noninvasive Imaging Techniques in the Selection and Management of Patients with Cardiac Resynchronization Therapy Echocardiography and Other Noninvasive Imaging Techniques in the Selection and Management of Patients with Cardiac Resynchronization Therapy**

Silvia Lupu, Lucia Agoston-Coldea and Dan Dobreanu Silvia Lupu, Lucia Agoston-Coldea and Dan Dobreanu Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64594

## **Abstract**

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34 Echocardiography in Heart Failure and Cardiac Electrophysiology

2003;105:671‐676.

Cardiac resynchronization therapy has become a widely used procedure for the treatment of patients with heart failure and severely impaired systolic function who associate left bundle branch block and remain symptomatic, in New York Heart Association II to IV functional class, despite maximum tolerated medical therapy. Imaging evaluation of these patients is complex, aiming to provide an accurate and extensive assessment before and after implantation, although a standardized protocol is yet to be implemented. Extensive research has been conducted to assess the ability of different imaging techniques and parameters to identify and quantify mechanical dyssynchrony, assess myocardial remodeling, provide prognostic information, or help guide lead placement and pacing parameters optimization in this category of patients. For these purposes, ultrasound-based imaging techniques, as well as cardiac magnetic resonance imaging, multislice cardiac computed tomography and nuclear ventriculography have been and are currently used, for research, as well as for clinical purposes. The aim of the current paper was to provide some insights into the imaging assessment of candidates and patients who have undergone cardiac resynchronization therapy.

**Keywords:** cardiac resynchronization therapy, mechanical dyssynchrony, echocardiography, cardiac magnetic resonance imaging

## **1. The role of imaging techniques in assessing patients with cardiac resynchronization therapy: general considerations**

During the last two decades, cardiac resynchronization therapy (CRT) has become a valuable therapeutic procedure for patients with heart failure (HF) due to dilated cardiomyopathy (DCM),

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

improving prognosis, symptoms, quality of life, and ventricular function [1–6]. Current ESC guidelines on cardiac pacing and CRT recommend the procedure as a class I indication in HF patients with left bundle branch block (LBBB), QRS width ≥120 ms, and left ventricle ejection fraction (LVEF) ≤35%, who remain in New York Heart Association (NYHA) functional class II, III, and ambulatory IV despite optimal medical therapy [7].

According to these guidelines, patient selection mainly relies on clinical and electrocardiogram (ECG) characteristics, while the role of echocardiography is limited to determining LVEF. Despite this rather frugal approach, extensive research involving echocardiography and other imaging techniques has been conducted over the last few years, with the purpose of improving the selection and management of CRT candidates. Since CRT is still a rather expensive procedure [8–10], and not entirely risk-free [11], even if performed by experienced electrophysiologists, efforts were made to establish sound patient selection criteria, as well as to find accurate methods, techniques, algorithms, and tools for prognosis assessment and pacing optimization. As a consequence, a plethora of ultrasound imaging parameters for cardiac mechanics and dyssynchrony evaluation have been developed, and expert consensus statements were released [12, 13] in order to help clinicians choose the best therapeutic strategy.

Early studies on mechanical dyssynchrony parameters seemed somewhat promising. For instance, Yu et al. attempted to prove that CRT was beneficial in patients who had echocardiographic evidence of mechanical dyssynchrony, even if they had narrow QRS complexes. In their research, results were quite spectacular, raising hope that CRT indications might extend beyond the recommendations of the guidelines [14]. Regrettably, the results of the much larger Echocardiography Guided Cardiac Resynchronization Therapy (Echo-CRT) trial contradicted these findings, highlighting the deleterious effects of CRT in patients with evidence of mechanical dyssynchrony at echocardiography and narrow QRS complexes (QRS complex duration <130 ms) [15].

In addition to that, the Predictors of Response to CRT (PROSPECT) trial tested the sensitivity and specificity of 12 different echocardiography mechanical dyssynchrony parameters, yielding disappointing results. The sensitivity and specificity of the studied parameters were either too low or discordant, and, as consequence, none of them was acknowledged as being clinically useful [16]. Sanderson JE challenged the results of the PROSPECT trial, stating that this trial was rather a study of error and did not provide an accurate assessment of the reproducibility and clinical value of mechanical dyssynchrony parameters; according to this author, the results of the PROSPECT trial were justified by the fact that participating centers were more focused on electrophysiology and lacked the technical possibilities and/or the expertise for an appropriate echocardiographic assessment [17]. Bax and Gorcsan also found flaws in the PROSPECT study, pointing out that among selected patients, 20.2% had an LVEF >35% while 37.8% had end-diastolic dimensions <65 mm, and were therefore unlikely to develop spectacular reverse remodeling since there was little remodeling and systolic function impairment to begin with; in addition to that, they brought up technical issues, such as the fact that ultrasound machines that have been used for the study came from three different vendors, while also suggesting that the high interobserver variability in some parameters might have been justified by the lack of a systematic examination protocol [18].

As a consequence, there is currently not enough proof to either fully embrace or dismiss myocardial dyssynchrony parameters. In fact, some studies have suggested that the evaluation of cardiac mechanics by echocardiography may have quite an important role in optimizing pacing parameters [19], choosing the most appropriate site for lead placement [20], and assessing patient prognosis [21], particularly if advanced ultrasound imaging techniques, such as speckle tracking, are used.

improving prognosis, symptoms, quality of life, and ventricular function [1–6]. Current ESC guidelines on cardiac pacing and CRT recommend the procedure as a class I indication in HF patients with left bundle branch block (LBBB), QRS width ≥120 ms, and left ventricle ejection fraction (LVEF) ≤35%, who remain in New York Heart Association (NYHA) functional class II,

According to these guidelines, patient selection mainly relies on clinical and electrocardiogram (ECG) characteristics, while the role of echocardiography is limited to determining LVEF. Despite this rather frugal approach, extensive research involving echocardiography and other imaging techniques has been conducted over the last few years, with the purpose of improving the selection and management of CRT candidates. Since CRT is still a rather expensive procedure [8–10], and not entirely risk-free [11], even if performed by experienced electrophysiologists, efforts were made to establish sound patient selection criteria, as well as to find accurate methods, techniques, algorithms, and tools for prognosis assessment and pacing optimization. As a consequence, a plethora of ultrasound imaging parameters for cardiac mechanics and dyssynchrony evaluation have been developed, and expert consensus statements were released [12, 13] in order to help clinicians choose the best therapeutic strategy.

Early studies on mechanical dyssynchrony parameters seemed somewhat promising. For instance, Yu et al. attempted to prove that CRT was beneficial in patients who had echocardiographic evidence of mechanical dyssynchrony, even if they had narrow QRS complexes. In their research, results were quite spectacular, raising hope that CRT indications might extend beyond the recommendations of the guidelines [14]. Regrettably, the results of the much larger Echocardiography Guided Cardiac Resynchronization Therapy (Echo-CRT) trial contradicted these findings, highlighting the deleterious effects of CRT in patients with evidence of mechanical dyssynchrony at echocardiography and narrow QRS complexes (QRS complex

In addition to that, the Predictors of Response to CRT (PROSPECT) trial tested the sensitivity and specificity of 12 different echocardiography mechanical dyssynchrony parameters, yielding disappointing results. The sensitivity and specificity of the studied parameters were either too low or discordant, and, as consequence, none of them was acknowledged as being clinically useful [16]. Sanderson JE challenged the results of the PROSPECT trial, stating that this trial was rather a study of error and did not provide an accurate assessment of the reproducibility and clinical value of mechanical dyssynchrony parameters; according to this author, the results of the PROSPECT trial were justified by the fact that participating centers were more focused on electrophysiology and lacked the technical possibilities and/or the expertise for an appropriate echocardiographic assessment [17]. Bax and Gorcsan also found flaws in the PROSPECT study, pointing out that among selected patients, 20.2% had an LVEF >35% while 37.8% had end-diastolic dimensions <65 mm, and were therefore unlikely to develop spectacular reverse remodeling since there was little remodeling and systolic function impairment to begin with; in addition to that, they brought up technical issues, such as the fact that ultrasound machines that have been used for the study came from three different vendors, while also suggesting that the high interobserver variability in some parameters might have

been justified by the lack of a systematic examination protocol [18].

III, and ambulatory IV despite optimal medical therapy [7].

36 Echocardiography in Heart Failure and Cardiac Electrophysiology

duration <130 ms) [15].

Data on the preferences of clinical practitioners are currently scarce. In a relatively recent European survey, 68% of physicians in the responding centers declared that they only relied on guideline criteria for selecting CRT patients, but 66% acknowledged using echocardiography for pacing parameters optimization. Among these, 37% stated they used tissue Doppler imaging, 20% used speckle tracking-based techniques, and only 10% used three-dimensional echocardiography [22], with the latter two being less used, probably due to limited availability.

Besides that, it is important to remember that echocardiography examination of patients with CRT is not limited to mechanical dyssynchrony assessment and must include a thorough study of left ventricular (LV) systolic and diastolic dysfunction, mitral regurgitation, right chamber structure and function, or the possibility of pulmonary hypertension. All these topics will be further discussed in this chapter.

Beyond echocardiography, other imaging techniques, such as multislice detector computer tomography (MDCT) or cardiac magnetic resonance imaging (CMRI), can be very useful in the management of patients who are candidates for CRT. Evaluation by MDCT, for instance, can safely exclude significant coronary artery disease [23] and accurately describe coronary veins anatomy [24], which can facilitate lead placement. CMRI provides the advantages of very accurate LVEF determination, the ability to identify the extent and location of fibrosis by late gadolinium enhancement, and an extensive study of myocardial deformation and dyssynchrony by tagging techniques [25].

## **2. Echocardiography parameters for the assessment of patients with CRT**

## **2.1. Examination of the left chambers. LV size, systolic function and diastolic function. Left atrial size and function**

Echocardiographic assessment of left chamber dimensions and function in patients who are candidates for CRT or have already been submitted to the procedure is essential.

Conventional bidimensional echocardiography can be used for measuring LV end-diastolic (EDD) and end-systolic (ESD) diameters and, preferably, LV volumes, assessed by the biplane Simpson's modified method and indexed to body surface area [26]. To enhance the quality of endocardial delineation, contrast agents can also be used, particularly if an extremely accurate evaluation of regional myocardial motion is also desired [27, 28], while three-dimensional echocardiography increases the accuracy of volumetric measurements by reducing errors due to the foreshortening of the LV [26].

LV dimensions were previously shown to predict the response to CRT. In the Multicenter Automatic Defibrillator Trial-CRT (MADIT-CRT) for instance, an LV end-diastolic volume (LVEDV) indexed to body surface area (BSA) ≥125 mL/m2 was associated with a favorable response to CRT [29].

In a substudy of the Multisite Stimulation in Cardiomyopathies (MUSTIC) trial, EDD and EDS were shown to decrease 3 months after CRT (7.3 ± 0.8–6.8 ± 0.8 cm, p < 0.001, and 6.2 ± 0.8–5.9 ± 0.8 cm, p < 0.05, respectively), with further reduction after 12 months since device implantation (by 8.4 ± 7.8 and 8.8 ± 7.8 mm, respectively, both p < 0.001), with better results in patients with idiopathic DCM vs. patients with ischemic cardiomyopathy (8.9 and 9.8 mm, p < 0.01) [30]. The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) Study also yielded significant reductions in EDD and ESD, as well as in LV mass at 6-month follow-up [31]. By contrast, in the Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) trial, no significant changes were recorded in neither LV dimensions, nor in LVEF, despite improved quality of life scores and NYHA functional class [32]. However, most of the patients in this trial had ischemic cardiomyopathy (64% vs. 36% with idiopathic DCM in the CRT-D group and 75.8% vs. 26.4% in the implanted cardioverter-defibrillator group) [32], which is very likely to have confounded results, since ischemic etiology [29, 33, 34] and the presence of scar tissue [35] and non-viable myocardium [36] are known predictors of limited response to CRT and reverse remodeling.

As previously mentioned, LVEF is the single echocardiographic parameter that has been accepted as a CRT patients' selection criterion in current guidelines [7], and the cutoff value has been established at 35%. LVEF has proved to be one of the most important parameters for assessing the success of CRT in all major clinical trials, as well as smaller studies that addressed this issue [37–44]. In MADIT-CRT despite more reduction in LV dimensions in the LVEF >30% group, clinical outcomes were similar in patients with lower LVEF [45]. A subanalysis of data from the REVERSE trial revealed similar extents of reverse remodeling and clinical benefits in patients who had LVEF <30% vs. LVEF >30%, which may be justified by the fact that, unlike patients included in the MADIT-CRT trial, patients in REVERSE only had mild HF [38].

Interestingly, responders to CRT [38] and particularly super-responders in whom the LVEF becomes >50% [46] have an excellent prognosis, with a reduced number of ventricular tachyarrhythmias and good clinical progression at 2.2 years; the authors concluded that, in such patients, switching off the ICD function to prevent inadequate therapies from the device might be considered.

Highlighting regional kinetic abnormalities by echocardiography could also be an important issue, considering the fact that it may help identify patients with ischemic DCM, which is associated with poorer outcomes after CRT and less reverse remodeling [29–36, 47].

Moreover, diastolic function assessment is not less important in this category of patients, since it was shown to improve after CRT, in parallel with the LVEF [47] and particularly in responders [48]. Diastolic dysfunction has been previously assessed by either conventional echocardiography, including parameters such as transmitral flow waves velocities and E-wave deceleration time, diastolic myocardial velocities, the E/e' ratio, diastolic filling duration, or

isovolumic relaxation time, evaluated by pulsed wave and tissue Doppler imaging [48, 49], or advanced techniques, such as speckle tracking [50, 51].

LV dimensions were previously shown to predict the response to CRT. In the Multicenter Automatic Defibrillator Trial-CRT (MADIT-CRT) for instance, an LV end-diastolic volume

In a substudy of the Multisite Stimulation in Cardiomyopathies (MUSTIC) trial, EDD and EDS were shown to decrease 3 months after CRT (7.3 ± 0.8–6.8 ± 0.8 cm, p < 0.001, and 6.2 ± 0.8–5.9 ± 0.8 cm, p < 0.05, respectively), with further reduction after 12 months since device implantation (by 8.4 ± 7.8 and 8.8 ± 7.8 mm, respectively, both p < 0.001), with better results in patients with idiopathic DCM vs. patients with ischemic cardiomyopathy (8.9 and 9.8 mm, p < 0.01) [30]. The Multicenter InSync Randomized Clinical Evaluation (MIRACLE) Study also yielded significant reductions in EDD and ESD, as well as in LV mass at 6-month follow-up [31]. By contrast, in the Multicenter InSync ICD Randomized Clinical Evaluation (MIRACLE ICD) trial, no significant changes were recorded in neither LV dimensions, nor in LVEF, despite improved quality of life scores and NYHA functional class [32]. However, most of the patients in this trial had ischemic cardiomyopathy (64% vs. 36% with idiopathic DCM in the CRT-D group and 75.8% vs. 26.4% in the implanted cardioverter-defibrillator group) [32], which is very likely to have confounded results, since ischemic etiology [29, 33, 34] and the presence of scar tissue [35] and non-viable myocardium [36] are known predictors of limited response to CRT and

As previously mentioned, LVEF is the single echocardiographic parameter that has been accepted as a CRT patients' selection criterion in current guidelines [7], and the cutoff value has been established at 35%. LVEF has proved to be one of the most important parameters for assessing the success of CRT in all major clinical trials, as well as smaller studies that addressed this issue [37–44]. In MADIT-CRT despite more reduction in LV dimensions in the LVEF >30% group, clinical outcomes were similar in patients with lower LVEF [45]. A subanalysis of data from the REVERSE trial revealed similar extents of reverse remodeling and clinical benefits in patients who had LVEF <30% vs. LVEF >30%, which may be justified by the fact that, unlike patients included in the MADIT-CRT trial, patients in REVERSE only had mild HF [38].

Interestingly, responders to CRT [38] and particularly super-responders in whom the LVEF becomes >50% [46] have an excellent prognosis, with a reduced number of ventricular tachyarrhythmias and good clinical progression at 2.2 years; the authors concluded that, in such patients, switching off the ICD function to prevent inadequate therapies from the device

Highlighting regional kinetic abnormalities by echocardiography could also be an important issue, considering the fact that it may help identify patients with ischemic DCM, which is

Moreover, diastolic function assessment is not less important in this category of patients, since it was shown to improve after CRT, in parallel with the LVEF [47] and particularly in responders [48]. Diastolic dysfunction has been previously assessed by either conventional echocardiography, including parameters such as transmitral flow waves velocities and E-wave deceleration time, diastolic myocardial velocities, the E/e' ratio, diastolic filling duration, or

associated with poorer outcomes after CRT and less reverse remodeling [29–36, 47].

was associated with a favorable

(LVEDV) indexed to body surface area (BSA) ≥125 mL/m2

38 Echocardiography in Heart Failure and Cardiac Electrophysiology

response to CRT [29].

reverse remodeling.

might be considered.

During the last decade, left atrium (LA) dimensions, particularly LA indexed volume (LAVI) [52] and LA function, have become an important part of LV diastolic function assessment and studies exploring the use of these parameters in CRT patients have recently been published [53–59]. For instance, the MADIT-CRT trial showed significant reductions in LAVI in CRT-D vs. ICD-only patients [53]. Major improvements in LAVI 3–6 months after CRT have also been reported by Yu [54], Aksoy [55], and D'Andrea et al., the latter also showing better results in patients with idiopathic DCM, by comparison with ischemic DCM patients [56]. In addition to that, MADIT-CRT results highlighted the value of LAVI <40 ml/m2 as a predictor of clinical response [29], which is also endorsed by Yu et al. who reported lower LAVI in responders [54]. In both the MADIT-CRT trial [53] and in the research by Kloosterman et al., increased preimplantation LAVI was associated with increased risk of HF progression and death, independently of LV volumes [57]. Other studies approached LA myocardial strain assessment in patients with CRT, suggesting its prognostic value in assessing the risk for atrial fibrillation development [58] or the response to CRT [59].

## **2.2. Right ventricular size and function evaluation: pulmonary hypertension assessment by echocardiography**

Although the assessment of left chambers is essential in patients who are candidates for CRT or have undergone the procedure already, right chamber evaluation should not be overlooked. Echocardiography-based studies on the topic are scarce, since bidimensional ultrasound imaging has to overcome the obstacles posed by the complex anatomy of the right ventricle (RV). Volumetric measurements can be flawed due to gross geometrical assumptions, since the anatomic shape of the RV hardly resembles any geometric figure, and trabeculations of the RV free wall can hinder adequate tracings of myocardial borders. Also, normal values have not been firmly established for some right chamber parameters, such as the right atrium (RA) volume, which currently remains, however, the preferred parameter for assessing RA size [60], replacing RA area [26].

Despite these caveats, right chamber evaluation by echocardiography, as well as pulmonary artery pressure estimation following current guidelines [61], can and should be performed in CRT patients, as evidence regarding these parameters has started to accumulate, and right chamber dilatation has been shown to associate with higher mortality in HF patients [62].

Data from radionuclide ventriculography studies suggest that impaired RV systolic function, with RV ejection fraction ≤20%, is an independent predictor of mortality and hospitalization due to HF [63], and that poorer systolic function is associated with a lower response rate after CRT [65], accordingly, the evaluation of right chambers may have a certain role in selecting patients for CRT. Moreover, increased RA area and impaired myocardial deformation of the AD were proven to be negative predictors of response to CRT, as were ischemic DCM and low intraventricular asynchrony [65].

In the MADIT-CRT trial, RV ejection fraction was considerably improved, and patients with the highest values had the lowest rate of adverse events at one year [66].

## **2.3. Mitral regurgitation assessment**

Mitral regurgitation is another target for echocardiographic assessment in chronic HF patients, since it has been shown to alter prognosis [67, 68]. In DCM, mitral regurgitation is usually functional, developing as a consequence of mitral annulus dilatation, but mostly due to the change of balance between tethering forces, pulling the leaflets towards the LV, and the forces that favor normal closure of the mitral valve. Tethering forces are amplified by LV remodeling and dilatation which result in an increased sphericity index and papillary muscle displacement. In addition to that, the normal closure of the mitral valve is impaired by the reduction of myocardial contractility and by ventricular contraction dyssynchrony [69], particularly in the presence of LBBB [70].

Quantifying mitral regurgitation in these patients can be challenging, since the regurgitation jet is often eccentric and should include measurements of vena contracta, the tenting area, as well as of the area of regurgitant orifice and the regurgitation volume by the proximal isovelocity surface area (PISA) method, when it is feasible. The extensive evaluation of mitral regurgitation should be completed by a thorough evaluation of the ventricular function and the asynchrony of contraction [71].

One study by Kanzaki et al. revealed the significant reduction of mitral regurgitation immediately after CRT [70], which was most likely caused by contraction synchrony recovery. Similar results have been reported by Breithardt et al. [72]. Moreover, LV reverse remodeling and diminished tethering forces were shown to contribute to reducing mitral regurgitation on the long term [73]. As far as short-term evolution is concerned, more data emerged supporting mitral regurgitation dependency on ventricular dyssynchrony, as one study proved its reduction after CRT, but also highlighted the fact that switching off the CRT device aggravates the regurgitation even if the event occurs six months after implantation [74]. A similar, although smaller study, also reported the reversal of mitral regurgitation, suggesting that CRT should be continued indefinitely [75]. For these reasons, it is reasonable to take into account mitral regurgitation reduction as a criterion for procedure success, particularly since it is associated with clinical response [76–77].

Mitral regurgitation assessment should be done carefully and accurately in non-responders, since some of these might benefit from further interventional treatment by MitraClip, which was shown to reduce symptoms and promote LV reverse remodeling [78], or by surgical mitral annuloplasty [79].

## **2.4. Dyssynchrony parameters evaluation**

## *2.4.1. Clinical utility*

Cardiac mechanics assessment by echocardiography is currently considered a challenge, and research in the field has been extensive and endorsed by newly emerging techniques. However, despite all research efforts, none of the explored dyssynchrony parameters had proved to be solid and reproducible enough for predicting the response to CRT, and, thus, for helping in patients' selection. Data from the CARE-HF study supported the use of echocardiographic dyssynchrony parameters, showing that patients who had altered values responded better to CRT [80], and had more reverse remodeling [81, 82]. In addition to that, Penicka et al., for instance, proved that both the parameters for interventricular and intraventricular dyssynchrony, assessed by tissue Doppler, were predictors of reverse remodeling and functional recovery of the LV [83].

In the MADIT-CRT trial, RV ejection fraction was considerably improved, and patients with

Mitral regurgitation is another target for echocardiographic assessment in chronic HF patients, since it has been shown to alter prognosis [67, 68]. In DCM, mitral regurgitation is usually functional, developing as a consequence of mitral annulus dilatation, but mostly due to the change of balance between tethering forces, pulling the leaflets towards the LV, and the forces that favor normal closure of the mitral valve. Tethering forces are amplified by LV remodeling and dilatation which result in an increased sphericity index and papillary muscle displacement. In addition to that, the normal closure of the mitral valve is impaired by the reduction of myocardial contractility and by ventricular contraction dyssynchrony [69], particularly in

Quantifying mitral regurgitation in these patients can be challenging, since the regurgitation jet is often eccentric and should include measurements of vena contracta, the tenting area, as well as of the area of regurgitant orifice and the regurgitation volume by the proximal isovelocity surface area (PISA) method, when it is feasible. The extensive evaluation of mitral regurgitation should be completed by a thorough evaluation of the ventricular function and

One study by Kanzaki et al. revealed the significant reduction of mitral regurgitation immediately after CRT [70], which was most likely caused by contraction synchrony recovery. Similar results have been reported by Breithardt et al. [72]. Moreover, LV reverse remodeling and diminished tethering forces were shown to contribute to reducing mitral regurgitation on the long term [73]. As far as short-term evolution is concerned, more data emerged supporting mitral regurgitation dependency on ventricular dyssynchrony, as one study proved its reduction after CRT, but also highlighted the fact that switching off the CRT device aggravates the regurgitation even if the event occurs six months after implantation [74]. A similar, although smaller study, also reported the reversal of mitral regurgitation, suggesting that CRT should be continued indefinitely [75]. For these reasons, it is reasonable to take into account mitral regurgitation reduction as a criterion for procedure success, particularly since it is

Mitral regurgitation assessment should be done carefully and accurately in non-responders, since some of these might benefit from further interventional treatment by MitraClip, which was shown to reduce symptoms and promote LV reverse remodeling [78], or by surgical mitral

Cardiac mechanics assessment by echocardiography is currently considered a challenge, and research in the field has been extensive and endorsed by newly emerging techniques. However,

the highest values had the lowest rate of adverse events at one year [66].

**2.3. Mitral regurgitation assessment**

40 Echocardiography in Heart Failure and Cardiac Electrophysiology

the presence of LBBB [70].

the asynchrony of contraction [71].

associated with clinical response [76–77].

**2.4. Dyssynchrony parameters evaluation**

annuloplasty [79].

*2.4.1. Clinical utility*

As previously mentioned, the PROSPECT trial challenged the accuracy of echocardiographic dyssynchrony parameters [16] and was challenged in its turn by some authors [17, 18].

More recent and elaborate techniques motivated researchers to go further in the attempt to find the optimal parameters for dyssynchrony quantification. Suffoletto et al. explored the advantages of the speckle tracking technique, showing that radial dyssynchrony assessed by this method predicted the response to CRT on long and short term [84]. The evaluation of global strain [85], as well as the evaluation of longitudinal, circumferential, and radial strain by tissue Doppler, also provided encouraging results [86]. However, these methods are costly, not available in many clinical centers and time-consuming, requiring strenuous offline analysis.

More available methods, such as tissue Doppler, are, unfortunately, hindered by lower reproducibility in DCM patients, by comparison with normal individuals, probably due to the complex contraction movements of the dilated heart and the method's lack of standardization [87].

The controversy regarding the echocardiographic evaluation of ventricular dyssynchrony extends over their use for optimizing pacing parameters in CRT patients. Some electrophysiologists prefer out-of-the-box settings and only adjust delays if the patients are non-responders. This attitude is endorsed by the quite large SMART-AV (The SmartDelay Determined AV Optimization: A Comparison to Other AV Delay Methods Used in Cardiac Resynchronization Therapy) trial in which 1014 patients were enrolled; in this study, the ECG-based SmartDelay optimization algorithm, as well as echocardiography, did not show any benefit for optimization by comparison with the out-of-the box approach in which a standard atrio-ventricular delay of 120 msec was established [88]. Similar results emerged from smaller studies, such as the one by Sawhney et al. who compared the effects of pacing with out-of-the-box delays with those chosen after Doppler echocardiography, revealing quality of life and functional NYHA class improvement, without significant changes in LVEF and 6-minute walk test distance [89]. In a larger study, on 215 patients, delay adjustments only provided additional benefit in a low number of patients [90]. Vidal et al. also approached this issue, reporting minimal benefits in patients with optimized parameters [91]. A retrospective analysis of multicentric trials endorses the use of adaptive CRT, based on ambulatory measurements of intrinsic conduction, in addition to conventional echocardiographic assessment, for optimization [92].

Although there is no consensus regarding the correct approach on the necessity and benefit of optimization, or the appropriate means to perform it, American guidelines for the echocardiographic assessment of CRT patients released by the American Society of Echocardiography, endorsed by the Heart Rhythm Society, recommends considering echocardiography for pacing parameters adjustment [12]. Accordingly, for adjustment of atrio-ventricular delays, the guidelines suggest the evaluation of the transmitral flow by pulsed wave Doppler, based on the premises that a long delay can lead to E and A wave fusion, diastolic mitral regurgitation, and exposes the patient to the risk of native conduction that may lead to loss of resynchronization. On the other hand, an abnormally short atrio-ventricular delay can result in a truncated A wave, as a consequence of premature closure of the mitral valve [12]. The Ritter method and the iterative method are suggested as optimization algorithms [12, 92, 93]. For ventriculoventricular delay adjustment, the guidelines recommend measurements of the aortic velocity time integral after modifying the delay by 20 ms, starting with the maximal pre-excitation of the LV [12].

For adjusting both delays, a fast algorithm was suggested—QuickOpt—available on St Jude Medical devices, that was proved inferior to echocardiographic evaluation [94].

## *2.4.2. Cardiac mechanics evaluation parameters*

Echocardiographic dyssynchrony evaluation protocols may differ from center to center according to logistics, the available ultrasound machines and softwares, as well as the experience of the examiners and the number of hospitalized CRT patients. Since dyssynchrony evaluation methods are not perfectly standardized, the choice of assessment parameters can be influenced by the examiner's opinion or the particularities of the case.

**Figure 1.** Transmitral flow assessment. Measurements of diastole and cardiac cycle duration.

*Atrio-ventricular dyssynchrony criteria* [12, 13]:

**•** duration of diastole—duration of diastolic filling measured on the pulsed wave Doppler transmitral flow, from the onset of the E wave until the end of the A wave, at a sweep speed of 100 cm/s;


**Figure 2.** Septal-to-posterior wall motion delay measurement, using color M-mode imaging, from the parasternal short-axis view at papillary muscle level.

#### *Intraventricular dyssynchrony criteria*

diographic assessment of CRT patients released by the American Society of Echocardiography, endorsed by the Heart Rhythm Society, recommends considering echocardiography for pacing parameters adjustment [12]. Accordingly, for adjustment of atrio-ventricular delays, the guidelines suggest the evaluation of the transmitral flow by pulsed wave Doppler, based on the premises that a long delay can lead to E and A wave fusion, diastolic mitral regurgitation, and exposes the patient to the risk of native conduction that may lead to loss of resynchronization. On the other hand, an abnormally short atrio-ventricular delay can result in a truncated A wave, as a consequence of premature closure of the mitral valve [12]. The Ritter method and the iterative method are suggested as optimization algorithms [12, 92, 93]. For ventriculoventricular delay adjustment, the guidelines recommend measurements of the aortic velocity time integral after modifying the delay by 20 ms, starting with the maximal pre-excitation of

For adjusting both delays, a fast algorithm was suggested—QuickOpt—available on St Jude

Echocardiographic dyssynchrony evaluation protocols may differ from center to center according to logistics, the available ultrasound machines and softwares, as well as the experience of the examiners and the number of hospitalized CRT patients. Since dyssynchrony evaluation methods are not perfectly standardized, the choice of assessment parameters can

Medical devices, that was proved inferior to echocardiographic evaluation [94].

be influenced by the examiner's opinion or the particularities of the case.

**Figure 1.** Transmitral flow assessment. Measurements of diastole and cardiac cycle duration.

**•** duration of diastole—duration of diastolic filling measured on the pulsed wave Doppler transmitral flow, from the onset of the E wave until the end of the A wave, at a sweep speed

*Atrio-ventricular dyssynchrony criteria* [12, 13]:

of 100 cm/s;

the LV [12].

*2.4.2. Cardiac mechanics evaluation parameters*

42 Echocardiography in Heart Failure and Cardiac Electrophysiology


Tissue synchronization imaging is performed by the offline analysis of bidimensional images from the apical four-, three- and two-chambers views with overlaid color tissue Doppler, using specialized software. To acquire appropriate images, pulse repetition frequencies, color gain, and sector depth and width should be optimized, to ensure the highest frame rate frequency [100].

Tissue synchronization imaging allows the automatic and color-coded calculus of the time interval from QRS onset until maximum myocardial velocity in different points. The algorithm uses as reference points the onset of the QRS complex, either automatically identified by the echocardiograph, or manually adjusted by the examiner, as well as the onset and end point of the pulsed wave Doppler recording of the aortic flow, as surrogates of systole beginning and ending. The objective of the analysis is to assess post-systolic myocardial shortening in 2, 6, or 12 segments [101, 102]. The method requires a high degree of training, dedicated acquisition and analysis software, which is seldom available in many centers and is time-consuming. Yu et al. reported low interobserver and intra-observer variability of 5.9% and 4.2%, respectively [100]; however, in their study, measurements were most likely performed by highly skilled echocardiographers and might not be reproducible by less experienced examiners.

**•** Septal flash

In the presence of LBBB, the interventricular septum has a particular two-phase active contraction pattern, with a leftward motion occurring in the pre-ejection phase, followed by a second excursion later in ventricular systole [103]. This particular inward/outward movement called septal flash (**Figure 5**) is visible by conventional bidimensional imaging, but is better assessed by M-mode or, preferably, by color M-mode, from the parasternal longaxis view [104].

Although apparently simplistic, as it does not require elaborate measurements or advanced technology, septal flash assessment is reliable, reproducible, and a proven good predictor of response to CRT [104], even in patients with atrial fibrillation [105] in which other imaging mechanical dyssynchrony parameters may sometimes be difficult to assess.

**•** Apical rocking

**•** Measurements of delayed mechanical activity by tissue Doppler analysis of opposing walls motion (interventricular septum, lateral wall; anterior wall, inferior wall) using the apical two- and four-chamber views (**Figure 4**); measurements should be performed on minimum 3–5 cardiac cycles and in post-expiratory apnea; differences ≥65 ms predict the acute

**•** Spectral tissue Doppler assessment of contraction delay between opposing LV walls; images are acquired from the apical two- and four-chamber views; the sample volume is placed 1 cm below the mitral annular plane, guided by color tissue Doppler, with narrow sector; the time interval from the onset of the QRS complex until maximal systolic myocardial motion (peak of the S-wave) is measured, at a sweep speed of 100 cm/s; maximum differences ≥65 ms and the septum to lateral wall difference ≥65 ms suggest intraventricular dyssynchrony [98, 99]. Although the method is widely available, it is hindered by the fact that analysis of the delays is performed in different cardiac cycles and is strictly limited to the basal area of LV walls; moreover, the method is time-consuming and measurements are performed online, being, thus, dependant, on translational movements of the heart. All these

Tissue synchronization imaging is performed by the offline analysis of bidimensional images from the apical four-, three- and two-chambers views with overlaid color tissue Doppler, using specialized software. To acquire appropriate images, pulse repetition frequencies, color gain, and sector depth and width should be optimized, to ensure the

Tissue synchronization imaging allows the automatic and color-coded calculus of the time interval from QRS onset until maximum myocardial velocity in different points. The algorithm uses as reference points the onset of the QRS complex, either automatically identified by the echocardiograph, or manually adjusted by the examiner, as well as the onset and end point of the pulsed wave Doppler recording of the aortic flow, as surrogates of systole beginning and ending. The objective of the analysis is to assess post-systolic myocardial shortening in 2, 6, or 12 segments [101, 102]. The method requires a high degree of training, dedicated acquisition and analysis software, which is seldom available in many centers and is time-consuming. Yu et al. reported low interobserver and intra-observer variability of 5.9% and 4.2%, respectively [100]; however, in their study, measurements were most likely performed by highly skilled echocardiographers and might not be reproducible

In the presence of LBBB, the interventricular septum has a particular two-phase active contraction pattern, with a leftward motion occurring in the pre-ejection phase, followed by a second excursion later in ventricular systole [103]. This particular inward/outward movement called septal flash (**Figure 5**) is visible by conventional bidimensional imaging, but is better assessed by M-mode or, preferably, by color M-mode, from the parasternal long-

hemodynamic response post-CRT [83, 97, 98];

44 Echocardiography in Heart Failure and Cardiac Electrophysiology

obstacles may result in low accuracy measurements.

**•** Tissue synchronization imaging

highest frame rate frequency [100].

by less experienced examiners.

**•** Septal flash

axis view [104].

Apical rocking refers to the transverse movement of the apex, due to LV enlargement and asynchronous contraction of the interventricular septum and LV lateral wall. It can be visually assessed from the apical four-chamber view or can be quantified using specialized software and imaging techniques. The latter has proven superior to classical parameters of dyssynchrony quantification in terms of identifying dyssynchrony and predicting the response to CRT [106, 107].

**Figure 3.** Assessment of left intraventricular dyssynchrony. (a) Q-Mi measurement, on the pulsed wave Doppler transmitral flow. Q-PW measurement, using M-mode, from the parasternal long-axis view.

**Figure 4.** Assessment of left intraventricular dyssynchrony by color tissue Doppler, from the apical four-chamber view. Maximum contraction of the left ventricle lateral wall is significantly delayed by comparison with septal contraction.

**Figure 5.** Septal flash evaluation by color M-mode from the parasternal long-axis view.

#### *Interventricular dyssynchrony criteria*


short-axis view; for measuring both parameters, as well as all other time-related measurements, a sweep-speed of 100 cm/s should be used;

**•** Interventricular motion delay—the delay between the contraction of the RV and the LV, assessed by the difference in the two pre-ejection times; values ≥40 msec suggest interventricular dyssynchrony (**Figure 6**); Ghio et al. suggested an association between IVMD and ventricular remodeling after CRT [81].

**Figure 4.** Assessment of left intraventricular dyssynchrony by color tissue Doppler, from the apical four-chamber view. Maximum contraction of the left ventricle lateral wall is significantly delayed by comparison with septal contraction.

**•** A-PEP—aortic pre-ejection time, measured from QRS onset until the onset of the aortic flow analyzed by pulsed wave Doppler, with the sample volume placed in the LV outflow tract in the apical five-chamber view; values ≥140 ms are considered a criterion of intraventricu-

**•** P-PEP—pulmonary pre-ejection time, measured from the onset of the QRS complex to the onset on the pulmonary artery flow measured from the RV outflow tract, in the parasternal

**Figure 5.** Septal flash evaluation by color M-mode from the parasternal long-axis view.

*Interventricular dyssynchrony criteria*

46 Echocardiography in Heart Failure and Cardiac Electrophysiology

lar dyssynchrony [96].

**Figure 6.** Interventricular dyssynchrony evaluation. (a) A-PEP measurement by pulsed wave Doppler from the parasternal short-axis-view. (b) P-PEP measurement by pulsed wave Doppler from the apical five-chamber view.

## **3. Multimodality imaging in the assessment of CRT patients**

In CRT, procedural success depends on optimal lead placement, with reasonable stimulation thresholds and impedances in the absence of complications such as lead displacement, infection, coronary sinus dissection, or phrenic nerve stimulation.

The Resynchronization Reverse Remodeling in Systolic Left Ventricular Dysfunction (RE-VERSE) [108, 109] and SEPTAL-CRT [110] trials provided evidence that RV lead placement is not essential for procedure success, as similar results have been reported for both apical and mid-septal positions. However, when placing the coronary sinus lead, the optimal site for stimulation should be chosen, provided that venous anatomy is favorable. The importance of coronary sinus lead placement has been highlighted by several major trials. In the MADIT-CRT study, apical placement of the LV lead was associated with poorer outcomes [111], while in REVERSE, lead placement in the basal area of the LV posterolateral wall was associated with more LV reverse remodeling and longer intervals until either death or first hospitalization for HF [108].

Initially, the exact placement of the coronary sinus lead did not seem to be utterly important, as shown by the MADIT-CRT trial [111]. However, the Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy (TARGET) study presented evidence that survival was increased if LV pacing occurred in the area of maximum contraction delay, provided there was no scar tissue on site [112]. Similar results have been reported in a smaller study [113].

Considering the results of these large trials, imaging techniques for identifying the area of maximal delay, the presence and location of scar tissue, and for describing venous anatomy could be helpful. In both the TARGET trial and another smaller study, speckle tracking was used to identify the area of maximum mechanical delay [112, 113].

Beyond cardiac ultrasonography, other imaging techniques have proved their use for targeting the areas for optimal lead placement. CMRI, for instance, can help identify the area of maximum mechanical delay by myocardial tagging techniques [114, 115], while also providing data on scar location [116, 117] and scar burden [118] by late gadolinium enhancement imaging, as well as an accurate quantification of LV and RV dimensions and systolic function [119, 120]. Also, although MDCT is more widely used for this purpose, CMRI scans with ECG-triggered respiratory-navigated three-dimensional SSFP after the injection of dimeglumine gadobenate and ECG-triggered inversion recovery assessment can be used for venous sinus anatomy visualization [117] (**Figure 7**).

Cardiac magnetic resonance imaging has been compared against speckle tracking echocardiography, yielding reasonable limits of agreement [121]. Some authors suggest the additive value of echocardiographic assessment of myocardial delays by speckle tracking and CMRI for identifying scarred areas in order to identify the best area for lead placement [122].

Although the efficiency of CMRI in assessing the response to CRT has been proved in some studies [114, 118], its routine clinical use in patients who have already undergone the implant procedure is somewhat hindered by the fact that, in most cases, CMRI-safe leads and devices are not available. Also, patients with CRT-D are exposed to the risk of inappropriate shocks.

MDCT is also a reliable method in the assessment of candidates for CRT, by being able to safely exclude significant coronary artery lesions [123], and, implicitly, the ischemic etiology of the DCM, as well as by offering a detailed and accurate description of venus anatomy that can help electrophysiologists in preparing the implant procedure [124, 125]; a keen study of venous anatomy (**Figure 8**), combined with the identification of the area of maximum contraction delay by either echocardiography or CMRI, contributes to choosing the appropriate strategy before starting the implant procedure. As a consequence, during the intervention, the electrophysiologist can concentrate on the operation itself, rather than worrying over choosing the appropriate site for stimulation.

The Resynchronization Reverse Remodeling in Systolic Left Ventricular Dysfunction (RE-VERSE) [108, 109] and SEPTAL-CRT [110] trials provided evidence that RV lead placement is not essential for procedure success, as similar results have been reported for both apical and mid-septal positions. However, when placing the coronary sinus lead, the optimal site for stimulation should be chosen, provided that venous anatomy is favorable. The importance of coronary sinus lead placement has been highlighted by several major trials. In the MADIT-CRT study, apical placement of the LV lead was associated with poorer outcomes [111], while in REVERSE, lead placement in the basal area of the LV posterolateral wall was associated with more LV reverse remodeling and longer intervals until either death or first hospitalization for

Initially, the exact placement of the coronary sinus lead did not seem to be utterly important, as shown by the MADIT-CRT trial [111]. However, the Targeted Left Ventricular Lead Placement to Guide Cardiac Resynchronization Therapy (TARGET) study presented evidence that survival was increased if LV pacing occurred in the area of maximum contraction delay, provided there was no scar tissue on site [112]. Similar results have been reported in a smaller

Considering the results of these large trials, imaging techniques for identifying the area of maximal delay, the presence and location of scar tissue, and for describing venous anatomy could be helpful. In both the TARGET trial and another smaller study, speckle tracking was

Beyond cardiac ultrasonography, other imaging techniques have proved their use for targeting the areas for optimal lead placement. CMRI, for instance, can help identify the area of maximum mechanical delay by myocardial tagging techniques [114, 115], while also providing data on scar location [116, 117] and scar burden [118] by late gadolinium enhancement imaging, as well as an accurate quantification of LV and RV dimensions and systolic function [119, 120]. Also, although MDCT is more widely used for this purpose, CMRI scans with ECG-triggered respiratory-navigated three-dimensional SSFP after the injection of dimeglumine gadobenate and ECG-triggered inversion recovery assessment can be used for venous sinus anatomy

Cardiac magnetic resonance imaging has been compared against speckle tracking echocardiography, yielding reasonable limits of agreement [121]. Some authors suggest the additive value of echocardiographic assessment of myocardial delays by speckle tracking and CMRI for identifying scarred areas in order to identify the best area for lead placement [122].

Although the efficiency of CMRI in assessing the response to CRT has been proved in some studies [114, 118], its routine clinical use in patients who have already undergone the implant procedure is somewhat hindered by the fact that, in most cases, CMRI-safe leads and devices are not available. Also, patients with CRT-D are exposed to the risk of inappropriate shocks. MDCT is also a reliable method in the assessment of candidates for CRT, by being able to safely exclude significant coronary artery lesions [123], and, implicitly, the ischemic etiology of the DCM, as well as by offering a detailed and accurate description of venus anatomy that can help electrophysiologists in preparing the implant procedure [124, 125]; a keen study of venous

used to identify the area of maximum mechanical delay [112, 113].

48 Echocardiography in Heart Failure and Cardiac Electrophysiology

HF [108].

study [113].

visualization [117] (**Figure 7**).

**Figure 7.** Late enhancement image in a patient with clinical presentation of myocarditis; midwall late gadolinium enhancement is present in the interventricular septum and diffuse subepicardial enhancement is visible on the lateral wall (arrows) in short-axis CMR views (a), four-chamber CMRI views (b) and two-chamber CMRI views (c).

**Figure 8.** Coronary venous anatomy using 3D volume rendered reconstructions.

The ongoing Imaging CRT trial aims to evaluate the benefits of multimodality imaging by speckle tracking echocardiography, single-photon emission computed tomography, and cardiac computed tomography in identifying the optimal positions for lead placement [126].

The extensive research conducted in this field proves the interest and necessity for developing evidence-based protocols in order to get optimum CRT results.

## **4. Conclusion**

Despite the fact that areas of controversy still exist regarding the imaging assessment of patients with CRT, it is undisputed that it will always have an essential role in this type of patients. The extensive research on the topic, the fast progress and development of new imaging techniques, as well as the possibility of skill improvement in interested examiners, are likely to contribute to a more and more accurate assessment of the patients, thus improving management.

## **Author details**

Silvia Lupu1\*, Lucia Agoston-Coldea2 and Dan Dobreanu1,3

\*Address all correspondence to: sil\_lupu@yahoo.com

1 University of Medicine and Pharmacy of Târgu Mureş, Târgu Mureş, Romania

2 2nd Department of Internal Medicine, Iuliu Hațieganu University of Medicine and Pharmacy, Cluj-Napoca, Romania

3 Cardiovascular Disease and Transplant Institute, University of Medicine and Pharmacy, Târgu Mureş, Romania

## **References**


failure [the Cardiac RE synchronization-Heart Failure (CARE-HF) trial extension phase. Eur Heart J. 2006;27:1928–32. DOI:10.1093/eurheartj/ehl141

The ongoing Imaging CRT trial aims to evaluate the benefits of multimodality imaging by speckle tracking echocardiography, single-photon emission computed tomography, and cardiac computed tomography in identifying the optimal positions for lead placement [126].

The extensive research conducted in this field proves the interest and necessity for developing

Despite the fact that areas of controversy still exist regarding the imaging assessment of patients with CRT, it is undisputed that it will always have an essential role in this type of patients. The extensive research on the topic, the fast progress and development of new imaging techniques, as well as the possibility of skill improvement in interested examiners, are likely to contribute to a more and more accurate assessment of the patients, thus improving

and Dan Dobreanu1,3

2 2nd Department of Internal Medicine, Iuliu Hațieganu University of Medicine and Phar-

3 Cardiovascular Disease and Transplant Institute, University of Medicine and Pharmacy,

[1] Cleland JGF, Freemantle N, Erdmann E, Gras D, Kappenberger L, Tavazzi L, Daubert JC. Long-term mortality with cardiac resynchronization therapy in the Cardiac Resynchronization-Heart Failure (CARE-HF) trial. Eur J Heart Fail. 2012;14:628–34.

[2] Cleland JGF, Freemantle N, Erdmann E, Gras D, Kappenberger L, Tavazzi L, Daubert JC. Longer-term effects of cardiac resynchronization therapy on mortality in heart

1 University of Medicine and Pharmacy of Târgu Mureş, Târgu Mureş, Romania

evidence-based protocols in order to get optimum CRT results.

50 Echocardiography in Heart Failure and Cardiac Electrophysiology

**4. Conclusion**

management.

**Author details**

Silvia Lupu1\*, Lucia Agoston-Coldea2

macy, Cluj-Napoca, Romania

DOI: 10.1093/eurjhf/hfs055

Târgu Mureş, Romania

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\*Address all correspondence to: sil\_lupu@yahoo.com


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## **Multimodality Echocardiographic Assessment of Patients Undergoing Atrial Fibrillation Ablation Multimodality Echocardiographic Assessment of Patients Undergoing Atrial Fibrillation Ablation**

Mariana Floria and Maria Daniela Tanase Mariana Floria and Maria Daniela Tanase

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64723

## **Abstract**

Atrial fibrillation (AF) is most common sustained arrhythmia in clinical practice. The new treatment standard in paroxysmal and persistent AF is the catheter ablation. Echocardiography plays a key role in risk stratification and management of patients with AF and is critical in the assessment of candidates for AF ablation, providing both anatomic and hemodynamic information. Echocardiography is crucial for patient selection, preprocedural left atrial appendage thrombus excluding, intraprocedural guidance, and detection and monitoring for early and late ablation related complica‐ tions. Transthoracic echocardiography allows rapid and comprehensive assessment of cardiac anatomical structure and function. Transoesophageal echocardiography also provides accurate information about the presence of a thrombus in the atria and thromboembolic risk, making safe the ablation procedure by immediately detection of the complications related procedure. Intracardiac echocardiography has emerged as a popular and useful tool in the everyday practice of interventional electrophysiology, being very useful only during the ablation procedure. This paper presents the role of echocardiography in all these steps concerning AF ablation procedure, and also (1) delineates the role of echocardiographic techniques in guiding the procedure, (2) discusses the critical echocardiographic aspects of this procedure, and (3) underlines the strengths and limitations of various echocardiographic modalities.

**Keywords:** atrial fibrillation, ablation, transthoracic echocardiography, transoesopha‐ geal echocardiography, intracardiac echocardiography

## **1. Introduction**

The most common sustained cardiac arrhythmia, nonvalvular atrial fibrillation (AF), has an increasing prevalence and incidence in association with increased age and medical comor‐

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

bidities. Nonvalvular AF is defined as AF in the absence of prosthetic mechanical heart valves, or haemodynamically significant mitral stenosis (moderate or severe) [1]. Evaluation of patients with AF requires an assessment of cardiac structure and function by echocardiogra‐ phy. Such an assessment complements the clinical evaluation and helps decision‐making regarding rhythm strategy (rhythm control vs. rate control), stroke risk stratification, and prognosis. Currently approved AF therapies are only partially effective and are associated with substantial morbidity and mortality. The new treatment standard in this arrhythmia, AF catheter ablation, requires a multidisciplinary team approach involving interventional cardiologists and imaging specialists. For AF ablation, there is a need to identify individual‐ ized mechanism‐based ablation targets (defined as mapping), located especially in left atrium (LA). Achieving durable pulmonary vein isolation as first step in AF ablation therapy remains technically challenging. AF substrate ablation (by targeting LA myocardium attaint by fibrosis due to the LA structural remodelling), in addition to pulmonary vein isolation, may prevent AF recurrence if pulmonary veins reconnect or nonpulmonary vein triggers emerge. Intrinsic cardiac autonomic nerve activity precedes the onset of AF. Autonomic activity is mediated by discrete ganglionated plexi localized on the LA posterior epicardium. It promotes LA electrical remodelling. Targeting these ganglionated plexi is another method for AF ablation. New approaches to mapping and ablation may targetregions of oscillating action potential duration (especially in the LA myocardium) that can cause wave breaks leading to AF [2]. Recently, European Association of Cardiovascular Imaging and the European Heart Rhythm Associa‐ tion published evidences available on the role of imaging techniques (including echocardiog‐ raphy) and their applications in patients with AF, and provided recommendations for their use in clinical practice [3]. Echocardiography is critical in the assessment of candidates for AF ablation, providing both anatomic and haemodynamic information; it offers the potential for improved safety of AF ablation. Echocardiography is very useful at each step of the procedure: before AF ablation (by patient selection and pre‐procedural LA appendage thrombus exclusion), intraprocedural guidance, and after AF ablation for detection and monitoring for early and late ablation‐related complications, and also atrial reverse remodelling occurrence after obtaining stable sinus rhythm.

## **2. Echocardiography before atrial fibrillation ablation**

Transthoracic echocardiography (TTE) allows rapid and comprehensive assessment of cardiac anatomical structure and function. It plays a central role in each of identifying comorbidities and identification of suitable candidates for AF catheter ablation. Pulmonary vein flow monitoring using echocardiography has the potential to an increasing role in the evaluation of cardiac diastolic function directly related to LA remodelling. Transoesophageal echocar‐ diography (TOE) also provides accurate information about the presence of a thrombus in the atria or LA appendage (which is an absolute contraindication for AF ablation) and throm‐ boembolic risk. The novel technique of intracardiac echocardiography (ICE) has emerged as a popular and useful tool in AF ablation during the procedure.

## **2.1. Echocardiography Assessment of Left Atrial Size, Anatomy and Function**

bidities. Nonvalvular AF is defined as AF in the absence of prosthetic mechanical heart valves, or haemodynamically significant mitral stenosis (moderate or severe) [1]. Evaluation of patients with AF requires an assessment of cardiac structure and function by echocardiogra‐ phy. Such an assessment complements the clinical evaluation and helps decision‐making regarding rhythm strategy (rhythm control vs. rate control), stroke risk stratification, and prognosis. Currently approved AF therapies are only partially effective and are associated with substantial morbidity and mortality. The new treatment standard in this arrhythmia, AF catheter ablation, requires a multidisciplinary team approach involving interventional cardiologists and imaging specialists. For AF ablation, there is a need to identify individual‐ ized mechanism‐based ablation targets (defined as mapping), located especially in left atrium (LA). Achieving durable pulmonary vein isolation as first step in AF ablation therapy remains technically challenging. AF substrate ablation (by targeting LA myocardium attaint by fibrosis due to the LA structural remodelling), in addition to pulmonary vein isolation, may prevent AF recurrence if pulmonary veins reconnect or nonpulmonary vein triggers emerge. Intrinsic cardiac autonomic nerve activity precedes the onset of AF. Autonomic activity is mediated by discrete ganglionated plexi localized on the LA posterior epicardium. It promotes LA electrical remodelling. Targeting these ganglionated plexi is another method for AF ablation. New approaches to mapping and ablation may targetregions of oscillating action potential duration (especially in the LA myocardium) that can cause wave breaks leading to AF [2]. Recently, European Association of Cardiovascular Imaging and the European Heart Rhythm Associa‐ tion published evidences available on the role of imaging techniques (including echocardiog‐ raphy) and their applications in patients with AF, and provided recommendations for their use in clinical practice [3]. Echocardiography is critical in the assessment of candidates for AF ablation, providing both anatomic and haemodynamic information; it offers the potential for improved safety of AF ablation. Echocardiography is very useful at each step of the procedure: before AF ablation (by patient selection and pre‐procedural LA appendage thrombus exclusion), intraprocedural guidance, and after AF ablation for detection and monitoring for early and late ablation‐related complications, and also atrial reverse remodelling occurrence

after obtaining stable sinus rhythm.

66 Echocardiography in Heart Failure and Cardiac Electrophysiology

**2. Echocardiography before atrial fibrillation ablation**

popular and useful tool in AF ablation during the procedure.

Transthoracic echocardiography (TTE) allows rapid and comprehensive assessment of cardiac anatomical structure and function. It plays a central role in each of identifying comorbidities and identification of suitable candidates for AF catheter ablation. Pulmonary vein flow monitoring using echocardiography has the potential to an increasing role in the evaluation of cardiac diastolic function directly related to LA remodelling. Transoesophageal echocar‐ diography (TOE) also provides accurate information about the presence of a thrombus in the atria or LA appendage (which is an absolute contraindication for AF ablation) and throm‐ boembolic risk. The novel technique of intracardiac echocardiography (ICE) has emerged as a LA dilatation (structural remodelling) can occur in a broad spectrum of cardiovascular diseases including hypertension, left ventricular dysfunction, mitral valve disease, and AF. In general, two major conditions are associated with LA dilatation: pressure overload and volume overload. TTE has an important role to diagnose all these diseases in patients with AF. The LA size has an incremental value of overconventional risk factors. However, LA size has also prognostic value for long‐term outcome. The current guidelines on management of patients with AF recommend a standard two‐dimensional (2D) TTE and Doppler echocardiogram, with assessment of LA *size and function*, in the clinical evaluation of all patients with AF (not only before AF ablation) [2].

LA size in addition to LA anatomy and function are the parameters mandatory to be assessed before deciding to include a patient for AF ablation procedure. The LA anterior‐posterior diameter was one of the first standardized echocardiographic parameters for assessment of *LA* size. LA enlargement may result in an asymmetrical geometry of the LA. LA anterior‐ posterior diameter assessed in the parasternal long‐axis view by 2D or M‐mode echocardiog‐ raphy may underestimate LA size [4]. Anterior‐posterior linear dimension should not be used as the sole measure of LA size [4]. Optimal assessment of LA size should include LA volume or LA area (preferably indexed) measurements [4]. LA dimensions can be assessed in the apical four‐ and two‐chamber views. LA dimensions should be measured at end‐ventricular systole, at maximal LA size. Each view must be optimized in order to avoid: an underestimation of LA size by foreshortening of the major length of the LA, inaccurate assumption of the mitral annulus boundary, loss of lateral resolution of the LA wall in the apical view, or dropout of the interatrial septum or anterior wall [4]. LA area is easy to assess and closer to LA size than anterior‐posterior diameter. Various methods for the assessment of LA volume with 2D echocardiography are available, including the cubical method, area‐length method, ellipsoid method, and modified Simpson's rule [4]. Because it is theoretically more accurate than the area‐length method, the biplane disk summation technique, which incorporates fewer geometric assumptions, should be the preferred method to measure LA volume in clinical practice. For LA volume assessment, the same views as LA area are indicated (**Figure 1**). In

**Figure 1.** Biplane left atrial volume measurement by disk summation method in apical 4‐chamber (A) and apical 2‐ chamber (B) views of bidimensional transthoracic echocardiography. LA: left atrium, LV: left ventricle, RA: right at‐ rium, RV: right ventricle.

addition, the same precautions must to be respected. LA appendage and pulmonary veins should be avoided to be included as LA cavity. LA long diameter is recommended to be considered the shorter value of this length assessed in the two views specified above. The measurement of LA length is considered appropriate if the difference between the two values (in apical two‐ and four‐chamber views) is not higher than 5 mm.

Alternatively, LA volume can be calculated using the disk summation technique by adding the volume of a stack of cylinders and area calculated by orthogonal minor and major transverse axes assuming an oval shape.

LA volume enables accurate assessment of the asymmetric structural remodelling of the LA and is a more robust predictor of cardiovascular events than linear or area measurements. However, the cornerstone of LA volume assessment is geometric assumptions about LA shape (as an ellipsoid shape).

The upper normal limit for 2D echocardiographic LA volume is 34 mL/m2 for both genders. Single‐plane apical four‐chamber indexed LA volumes are typically 1–2 mL/m2 smaller than apical two‐chamber volumes. Apical four‐ and two‐chamber linear measurements and nonindexed LA area and volume measurements are not recommended for routine clinical use [4].

In conclusion, TTE is the recommended approach for assessing LA size [4]. LA size should be measured at end‐ventricular systole, at maximal LA size, with precautions to not underesti‐ mate or overestimate LA dimensions [4]. TOE slightly underestimates LA size; it provides good correlation with TTE. Although TOE permits good views on the LA and the LA append‐ age, it should not be used to assess LA size [4].

Recently has been demonstrated the feasibility of three‐dimensional (3D) TTE for the assess‐ ment of LA volumes [5]. 3D echocardiography has the advantage that no geometrical assump‐ tion about LA shape has to be made and it seems to be more accurate when compared to 2D measurements. In addition, this echocardiographic method has a lower intraobserver and interobserver variability as compared to 2D echocardiography [5]. However, there still remain some technical limitations: The spatial and temporal resolution is low, depends on adequate image quality, and requires patient's cooperation; in addition, there are limited data on normal values [4].

LA size and volumes throughout the cardiac cycle can be acquired more precise with magnetic resonance image or computer tomography. Because the longitudinal axes of the left ventricle and LA frequently lie in different planes, dedicated acquisitions of the LA from the apical approach should be obtained for optimal LA volume measurements. However, these imaging methods are more expensive, sometimes with limited accessibility and more invasive (X‐ray irradiation for computer tomography and potential kidney complications for both image techniques).

ICE is only used during AF catheter ablation procedure [6]. Therefore, no standardized measurements of LA size or volume are available. Although ICE is limited by the monoplane character and the lack of standardized measurements of LA size, it is a valuable tool for guidance ablation procedure.

The assessment of *LA anatomy* is important in the setting of catheter ablation procedures for AF [6]. Because of the complex anatomy of the LA and the variability in pulmonary vein anatomy, a detailed roadmap is mandatory to be known before the ablation procedure. The various imaging modalities that are available for assessment of LA and pulmonary vein anatomy in catheter ablation procedures include multislice computed tomography, magnetic resonance imaging, ICE, and electroanatomical mapping systems. Patients referred for AF ablation often have highly variable pulmonary vein anatomy, which could influence the procedure technique [6]. Four discrete pulmonary veins are present in the minority of patients with paroxysmal AF undergoing pulmonary vein isolation [6]. Anatomical variations include a single insertion or common antrum of the ipsilateral pulmonary veins, and an additional pulmonary vein. Assessment of LA and pulmonary vein anatomy by cardiac magnetic resonance or computed tomography before AF ablation is mandatory before the procedure. Pulmonary vein anatomy may in part explain the variable outcome to electrical isolation in patients with paroxysmal AF, although there is still debate concerning the best ablation strategy and the optimal lesion set. This information might aid in planning procedural strategies, and reducing unexpected procedural complications in AF ablation [6]. Among echocardiographic methods, only ICE (not TTE and TOE) has the capacity to assess a detailed pulmonary vein anatomy and morphology [7–9]. The interest in LA anatomy increases with AF ablation techniques developing [7–9]. New image integration systems have become available for AF catheter ablation procedures [8].

addition, the same precautions must to be respected. LA appendage and pulmonary veins should be avoided to be included as LA cavity. LA long diameter is recommended to be considered the shorter value of this length assessed in the two views specified above. The measurement of LA length is considered appropriate if the difference between the two values

Alternatively, LA volume can be calculated using the disk summation technique by adding the volume of a stack of cylinders and area calculated by orthogonal minor and major

LA volume enables accurate assessment of the asymmetric structural remodelling of the LA and is a more robust predictor of cardiovascular events than linear or area measurements. However, the cornerstone of LA volume assessment is geometric assumptions about LA shape

apical two‐chamber volumes. Apical four‐ and two‐chamber linear measurements and nonindexed LA area and volume measurements are not recommended for routine clinical use

In conclusion, TTE is the recommended approach for assessing LA size [4]. LA size should be measured at end‐ventricular systole, at maximal LA size, with precautions to not underesti‐ mate or overestimate LA dimensions [4]. TOE slightly underestimates LA size; it provides good correlation with TTE. Although TOE permits good views on the LA and the LA append‐

Recently has been demonstrated the feasibility of three‐dimensional (3D) TTE for the assess‐ ment of LA volumes [5]. 3D echocardiography has the advantage that no geometrical assump‐ tion about LA shape has to be made and it seems to be more accurate when compared to 2D measurements. In addition, this echocardiographic method has a lower intraobserver and interobserver variability as compared to 2D echocardiography [5]. However, there still remain some technical limitations: The spatial and temporal resolution is low, depends on adequate image quality, and requires patient's cooperation; in addition, there are limited data on normal

LA size and volumes throughout the cardiac cycle can be acquired more precise with magnetic resonance image or computer tomography. Because the longitudinal axes of the left ventricle and LA frequently lie in different planes, dedicated acquisitions of the LA from the apical approach should be obtained for optimal LA volume measurements. However, these imaging methods are more expensive, sometimes with limited accessibility and more invasive (X‐ray irradiation for computer tomography and potential kidney complications for both image

ICE is only used during AF catheter ablation procedure [6]. Therefore, no standardized measurements of LA size or volume are available. Although ICE is limited by the monoplane character and the lack of standardized measurements of LA size, it is a valuable tool for

for both genders.

smaller than

(in apical two‐ and four‐chamber views) is not higher than 5 mm.

The upper normal limit for 2D echocardiographic LA volume is 34 mL/m2

Single‐plane apical four‐chamber indexed LA volumes are typically 1–2 mL/m2

transverse axes assuming an oval shape.

68 Echocardiography in Heart Failure and Cardiac Electrophysiology

age, it should not be used to assess LA size [4].

(as an ellipsoid shape).

[4].

values [4].

techniques).

guidance ablation procedure.

In patients in sinus rhythm LA has three important functions: the reservoir, the conduit, and the booster pump function. The change in the *LA function* in different phases can be evaluated noninvasively by echocardiography, utilizing not only usual methods including transmitral flow and changes in LA area and volume.

**Figure 2.** Tissue Doppler Imaging study (at the level of basal segment of septal interventricular wall) in apical four‐ chamber view of transmitral inflow in a patient with paroxysmal atrial fibrillation during sinus rhythm. Sa represents systolic myocardial velocity of left ventricle; Ea represents early diastolic filling myocardial velocity of left ventricle; Aa represents late diastolic filling myocardial velocity of left ventricle.

Pulsed‐wave Doppler permits the assessment of late diastolic filling wave (A) on transmitral inflow pattern as marker of LA mechanical function. Both peak velocity and time‐velocity integral of the mitral A wave could be used. However, in AF patients A wave is absent, so cannot be used for LA mechanical function assessment [5].

New echocardiographic techniques, such as Tissue Doppler Imaging (TDI) and speckle tracking (strain and strain rate) imaging, allow noninvasive measurement of regional function of the myocardium (including LA). TDI allows the quantification of the low‐velocity, high‐ amplitude, long‐axis intrinsic myocardial velocities in both systole and diastole, and provides a relatively load‐independent measure of both left ventricle systolic and diastolic function (**Figure 2**).

The similar parameter of peak A velocity measured by TDI (Aa) is a myocardial velocity (not flow velocity) and could be also used as an atrial function parameter. It correlates with other parameters of atrial function as atrial fraction and atrial ejection force. In addition, it seems that Aa velocity assessed by TDI correlates with LA fractional area and volume change [5].

However, regional LA function is not routinely assessed, and therefore, no standardized parameters for regional LA functions are yet available [5]. A strong limitation for current using of this parameter is LA walls, which are thin and therefore difficult to be measured during wall moving. Improvement of LA regional function as marker of atrial electromechanical remod‐ elling is an important outcome in patients that underwent AF catheter ablation.

Total electromechanical activity of the atria could be calculated by the interval between the onsets of the P‐wave on the electrocardiogram to the end of the Aa wave on the TDI. However, TDI evaluation of regional LA function is the angle dependent. Therefore, careful adjustment of the beam and gain settings should be made to avoid aliasing and to allow reliable meas‐ urement of tissue velocities of the LA.

Another brand new technique, namely speckle tracking, is based on myocardial deformation assessment. Strain and strain rate are the two parameters that measure myocardial tissue velocity gradient by speckle tracking. This technique has some major advantages comparing with TDI: It is independent of wall movements and could differentiate between active and passive motion [5].

All TDI‐derived parameters of the LA, including tissue velocities, strain and strain rate, were significantly reduced in patients with AF. Using TDI and/or strain imaging techniques, the decreased compliance of LA walls, the impairment of the reservoir and conduit function of LA, and the loss of the booster pump function in patients with AF were found.

After catheter ablation of AF, decreasing of these parameters means a possible criterion of do not interrupt the antiarrhythmic and anticoagulation treatment even in sinus rhythm due to the AF recurrences [5].

All changes in left ventricle diastolic function reflect on pulmonary venous flow morphology assessed by pulsed‐wave Doppler [5]. In patients with AF due to LA pressure and functions (mainly the reservoir function), the following changes are possible: The wave of atrial reverse flow is absent due to the active LA mechanical function disappearance; peak velocity of systolic flow decreases and is related to the LA appendage dysfunction and thromboembolic risk; peak diastolic velocity higher than peak systolic velocity; an early systolic reverse flow is present [5]. In patients with AF catheter ablation pulmonary venous flow monitoring is important to assess LA mechanical function recovering. Preserved reservoir function of LA during AF is predictive of satisfactory recovery of mechanical function after pulmonary vein isolation [4, 5].

Pulsed‐wave Doppler permits the assessment of late diastolic filling wave (A) on transmitral inflow pattern as marker of LA mechanical function. Both peak velocity and time‐velocity integral of the mitral A wave could be used. However, in AF patients A wave is absent, so

New echocardiographic techniques, such as Tissue Doppler Imaging (TDI) and speckle tracking (strain and strain rate) imaging, allow noninvasive measurement of regional function of the myocardium (including LA). TDI allows the quantification of the low‐velocity, high‐ amplitude, long‐axis intrinsic myocardial velocities in both systole and diastole, and provides a relatively load‐independent measure of both left ventricle systolic and diastolic function

The similar parameter of peak A velocity measured by TDI (Aa) is a myocardial velocity (not flow velocity) and could be also used as an atrial function parameter. It correlates with other parameters of atrial function as atrial fraction and atrial ejection force. In addition, it seems that Aa velocity assessed by TDI correlates with LA fractional area and volume change [5]. However, regional LA function is not routinely assessed, and therefore, no standardized parameters for regional LA functions are yet available [5]. A strong limitation for current using of this parameter is LA walls, which are thin and therefore difficult to be measured during wall moving. Improvement of LA regional function as marker of atrial electromechanical remod‐

Total electromechanical activity of the atria could be calculated by the interval between the onsets of the P‐wave on the electrocardiogram to the end of the Aa wave on the TDI. However, TDI evaluation of regional LA function is the angle dependent. Therefore, careful adjustment of the beam and gain settings should be made to avoid aliasing and to allow reliable meas‐

Another brand new technique, namely speckle tracking, is based on myocardial deformation assessment. Strain and strain rate are the two parameters that measure myocardial tissue velocity gradient by speckle tracking. This technique has some major advantages comparing with TDI: It is independent of wall movements and could differentiate between active and

All TDI‐derived parameters of the LA, including tissue velocities, strain and strain rate, were significantly reduced in patients with AF. Using TDI and/or strain imaging techniques, the decreased compliance of LA walls, the impairment of the reservoir and conduit function of

After catheter ablation of AF, decreasing of these parameters means a possible criterion of do not interrupt the antiarrhythmic and anticoagulation treatment even in sinus rhythm due to

All changes in left ventricle diastolic function reflect on pulmonary venous flow morphology assessed by pulsed‐wave Doppler [5]. In patients with AF due to LA pressure and functions (mainly the reservoir function), the following changes are possible: The wave of atrial reverse flow is absent due to the active LA mechanical function disappearance; peak velocity of systolic

LA, and the loss of the booster pump function in patients with AF were found.

elling is an important outcome in patients that underwent AF catheter ablation.

cannot be used for LA mechanical function assessment [5].

70 Echocardiography in Heart Failure and Cardiac Electrophysiology

(**Figure 2**).

urement of tissue velocities of the LA.

passive motion [5].

the AF recurrences [5].

Pulmonary venous diastolic deceleration time is very useful to predict diastolic left ventricle filling pressure, as estimated by pulmonary capillary wedged pressure in AF [9]. This param‐ eter is easy to be assessed after pulmonary venous flow registration by pulsed‐wave Doppler. It is defined as duration between peak diastolic velocity and the upper deceleration slope extrapolated to the baseline.

According to the current guidelines, all these measurements should be taken on 5–10 cardiac cycles during a heart rate of 60–80 beats/min.

It seems that pulmonary venous deceleration time correlates better with pulmonary capillary wedged pressure than transmitral deceleration time in patients with AF [10]. Pulmonary venous deceleration time ≤150 ms could predict pulmonary capillary wedged pressure ≥18 mm Hg with 100% sensitivity and 96% specificity in patients with AF [10].

Patients with larger LA size, reduced LA function, and increased LA fibrosis (as marker of advanced electrical and structural remodelling) content are more likely to experience AF recurrences after ablation. The new echocardiography techniques have an emerging role in assessment of atrial fibrosis in patients with AF [7]. The appropriate selection of patients is mandatory for better outcomes in AF ablation; less fibrosis (that means less structural remod‐ elling) seems to translate in better outcomes. Until now, there are not known imaging techni‐ ques able to predict AF ablation rate success tailored to each patient undergoing this treatment. However, there are some useful clinical tools (risk scores such as CHADS2, CHA2DS2‐VASc, or APPLE scores) to identify patients with low, intermediate, or high risk of AF recurrence after AF ablation. However, echocardiography is very useful to detect and monitor LA reverse remodelling and improvement in atrial or ventricular function after AF ablation.

Atrial cardiomyopathies may provide the basis for the development of atrial fibrillation. The molecular alterations may also contribute to the occurrence of atrial thrombi. Thus, the concept of thrombogenic endocardial remodelling was introduced. In the future, echocardiography might be useful in this new type of atrial remodelling assessment.

## **2.2. Echocardiography Assessment of Left Atrial or Left Atrial Appendage Thrombus**

The presence of LA appendage or LA thrombi is an absolute contraindication for AF ablation. Therefore, echocardiography assessment of thrombi presence is mandatory before AF ablation procedure. 2D TTE has a low sensitivity for detection of thrombi in LA and especially LA appendage. 2D or 3D TOE provides excellent visualization of posterior cardiac structures because of the anatomic relationship of these structures to the oesophagus. TOE is one of the modality of choice for detecting LA or LAA thrombi (**Figure 3A**).

**Figure 3.** Two‐dimensional transesophageal echocardiogram, midoesophageal view, allowing the identification of a left atrial appendage thrombus (A); zoom of the left atrial appendage illustrating the presence of a dense spontaneous echo contrast with swirling movements in the left atrial appendage (B).

**Figure 4.** (A) Two‐dimensional transesophageal echocardiogram, midoesophageal view, shows left atrial appendage with muscular ridge, namely coumadin ridge and pectinate muscles which could be misinterpreted as clots. (B) Pulsed‐wave Doppler of the left atrial appendage demonstrates the decreased emptying and filling velocities in pa‐ tients with atrial fibrillation.

It can detect thrombi with a high degree of sensitivity and specificity varying from 93% to 100% [5]. LA appendage has a very complex anatomy with variable shape, size, and orienta‐ tion, with the possibility of several lobes and branches; therefore, thrombi assessment can be challenging. The muscular ridges and pectinate muscles (**Figure 4A**) must be carefully observed, because they can be misinterpreted as clots. Also ICE is very useful during AF ablation procedure to make the difference between muscular ridges and pectinate muscles (**Figure 5**). However, 3D TOE could make a better distinction between the pectinate muscles and thrombi, comparing with 2D TOE [11]. In addition, TOE is helpful in assessment of LA appendage velocities by pulsed‐wave Doppler (**Figure 4B**). Usually, in patients in sinus rhythm without history of AF the average LA appendage filling velocity is 40–50 cm/s and correlates well with the LA appendage contraction velocity; the average LA appendage contraction velocity is 50–60 cm/s. Low LA appendage emptying flow velocities (defined as <20 cm/s) in AF correlate strongly with the presence of spontaneous echo contrast and thrombus formation. For patients with AF, TOE risk factors for thromboembolism associated with high risk of stroke include at least one of the following factors: LA appendage thrombus, severe spontaneous echo contrast, low flow velocities at LA appendage ostium, and complex aortic plaques [3].

**Figure 3.** Two‐dimensional transesophageal echocardiogram, midoesophageal view, allowing the identification of a left atrial appendage thrombus (A); zoom of the left atrial appendage illustrating the presence of a dense spontaneous echo

**Figure 4.** (A) Two‐dimensional transesophageal echocardiogram, midoesophageal view, shows left atrial appendage with muscular ridge, namely coumadin ridge and pectinate muscles which could be misinterpreted as clots. (B) Pulsed‐wave Doppler of the left atrial appendage demonstrates the decreased emptying and filling velocities in pa‐

It can detect thrombi with a high degree of sensitivity and specificity varying from 93% to 100% [5]. LA appendage has a very complex anatomy with variable shape, size, and orienta‐ tion, with the possibility of several lobes and branches; therefore, thrombi assessment can be challenging. The muscular ridges and pectinate muscles (**Figure 4A**) must be carefully observed, because they can be misinterpreted as clots. Also ICE is very useful during AF ablation procedure to make the difference between muscular ridges and pectinate muscles (**Figure 5**). However, 3D TOE could make a better distinction between the pectinate muscles and thrombi, comparing with 2D TOE [11]. In addition, TOE is helpful in assessment of LA appendage velocities by pulsed‐wave Doppler (**Figure 4B**). Usually, in patients in sinus rhythm without history of AF the average LA appendage filling velocity is 40–50 cm/s and correlates well with the LA appendage contraction velocity; the average LA appendage contraction velocity is 50–60 cm/s. Low LA appendage emptying flow velocities (defined as <20 cm/s) in AF correlate strongly with the presence of spontaneous echo contrast and thrombus formation. For patients with AF, TOE risk factors for thromboembolism associated with high risk of stroke

contrast with swirling movements in the left atrial appendage (B).

72 Echocardiography in Heart Failure and Cardiac Electrophysiology

tients with atrial fibrillation.

**Figure 5.** Intracardiac echocardiography shows very clearly anatomic structures during ablation procedure. This image was offered by courtesy of the editor. RVOT: right ventricle outflow tract; LSPV: left superior pulmonary vein.

Thrombus identification is also challenging even if the appendage is visualized adequately. In the absence of formed thrombi, a dense spontaneous echo contrast (**Figure 3B**) has been demonstrated to be strong a predictor of thromboembolism. Spontaneous echo contrast can be classified into four groups (1 to 4+), depending on the intensity, location, and presence of the swirling movement [12]. It seems that patients under anticoagulation and with throm‐ boembolic risk scores (CHADS2 and CHA2DS2‐VASc) <2 have a negative predictive value approaches to 100%; therefore, TOE before catheter ablation of AF might be avoided [13].

Sometimes it is difficult to distinguish small thrombi from artefacts, including prominent trabecular structures, duplication artefacts, and adipose tissue within the transverse sinus. It is necessary to attempt to differentiate any suspicious abnormalities from thrombus in multiple views. The mechanical function of LA appendage is best assessed with TOE utilizing pulsed‐ wave Doppler measurement of LA appendage emptying and filling velocities.

In addition to LA appendage Doppler assessment, measuring LA appendage area and ejection fraction (evaluated through vector velocity imaging), TDI, and 3D TOE are less validated and less frequently performed parameters associated with cerebrovascular events and the forma‐ tion of LA appendage thrombus [11]. Pre‐procedural multislice computed tomography may also identify the presence of thrombi in the LA appendage, but the gold standard is TOE [11]; in addition to the anatomy of the LA and pulmonary veins, it also provides detailed informa‐ tion on surrounding structures, such as the oesophagus and coronary arteries.

## **3. Echocardiography-Guided Ablation of Atrial Fibrillation**

According to the new theories of AF physiopathology, some ablation strategies were elabo‐ rated; however, none is known as golden standard of this therapy. Depending on ablation technique, LA anatomy and pulmonary vein morphology are of essential importance to be well known during the ablation procedure. The veno‐atrial junctions and anatomical structures of the LA, such as Coumadin ridge or the ridge between the left superior pulmonary vein and LA appendage, are critical for a safe and successful procedure.

**Figure 6.** Two‐dimensional transesophageal echocardiogram, midoesophageal view, shows (A) interatrial septum with left‐right shunt in colour Doppler through patent foramen oval and (B) lipomatous interatrial septum. Ao: aorta; IAS: interatrial septum; LA: left atrium; RA: right atrium.

For pulmonary vein isolation or LA substrate ablation, it is mandatory to puncture the interatrial septum to gain left atrial posterior wall and pulmonary veins. If the patient has a patent foramen oval (**Figure 6A**), some operators say that transseptal puncture could be avoided. However, this is arguable, because accessibility to LA to gain pulmonary veins is difficult through a patent foramen oval. During TOE, a microbubble test under Valsalva manoeuvre could unmask a patent foramen oval. Rarely, TTE in subxiphoid view could identify the presence of a patent foramen oval. However, TOE has better sensibility to diagnose patent foramen oval before AF ablation. In patients with the lipomatous hypertrophy of the interatrial septum (**Figure 6B**), transseptal puncture could be difficult, without echocardio‐ graphic guidance.

**3. Echocardiography-Guided Ablation of Atrial Fibrillation**

LA appendage, are critical for a safe and successful procedure.

74 Echocardiography in Heart Failure and Cardiac Electrophysiology

According to the new theories of AF physiopathology, some ablation strategies were elabo‐ rated; however, none is known as golden standard of this therapy. Depending on ablation technique, LA anatomy and pulmonary vein morphology are of essential importance to be well known during the ablation procedure. The veno‐atrial junctions and anatomical structures of the LA, such as Coumadin ridge or the ridge between the left superior pulmonary vein and

**Figure 6.** Two‐dimensional transesophageal echocardiogram, midoesophageal view, shows (A) interatrial septum with left‐right shunt in colour Doppler through patent foramen oval and (B) lipomatous interatrial septum. Ao: aorta; IAS:

For pulmonary vein isolation or LA substrate ablation, it is mandatory to puncture the interatrial septum to gain left atrial posterior wall and pulmonary veins. If the patient has a patent foramen oval (**Figure 6A**), some operators say that transseptal puncture could be avoided. However, this is arguable, because accessibility to LA to gain pulmonary veins is difficult through a patent foramen oval. During TOE, a microbubble test under Valsalva manoeuvre could unmask a patent foramen oval. Rarely, TTE in subxiphoid view could identify the presence of a patent foramen oval. However, TOE has better sensibility to diagnose patent foramen oval before AF ablation. In patients with the lipomatous hypertrophy of the

interatrial septum; LA: left atrium; RA: right atrium.

**Figure 7.** Transseptal puncture guided by bidimensional TOE shows direct visualization of the transseptal catheter and its relationship to the fossa ovalis and the ascending aorta. Ao: aorta; IAS: interatrial septum; LA: left atrium; RA: right atrium.

**Figure 8.** Uses of ICE for transseptal puncture guidance. LA: left atrium; RA: right atrium. This image was offered by courtesy of the editor.

Transseptal puncture allows procedural access to the LA. Anatomic structures are not directly visualized during transseptal puncture by fluoroscopic guidance. TTE and especially TOE may be helpful in performing this procedure by allowing direct visualization of the transseptal catheter and its relationship to the fossa ovalis. Anatomic variability in the position and orientation of the fossa ovalis and its surrounding structures may be challenging to even those interventional cardiologists with significant transseptal experience. However, echocardiogra‐ phy imaging offers increased safety to the operator, by avoiding the puncture of the intraper‐ icardial aorta, a serious complication of transseptal puncture. In addition, radiation minimizes the fluoroscopy time required for the procedure, being very important during the learning curve. It was shown that TOE is of great value in performing transseptal punctures in AF ablation procedures. TTE can delineate the aorta and interatrial septum, and the characteristic bulging (or tenting) of the fossa ovalis and saline contrast echocardiography with TTE may help confirm needle position in the right atrium before puncture and in the LA after puncture (**Figure 7**). Anatomical variations in interatrial septum such as aneurismal septum, double‐ membrane septum, patent foramen oval, and others make this process complicated. Because TTE does not always offer sufficient imaging resolution, TOE and more recently ICE are preferably (**Figure 8**).

ICE could be useful only during the ablation procedure. It enables visualization of anatomical particularities of LA, being mostly important in transseptal puncture guidance and circular Lasso catheter positioning [14]. ICE enables to visualize the tenting of the interatrial septum due to the transseptal sheath tip during the puncture. It is important to be correctly placed in the posterior region of the fossa ovalis to avoid potential life‐threatening complications such as aortic root perforation or LA lateral wall penetrating. For an appropriate mapping and ablation lesions, a good placement of Lasso catheter at the pulmonary vein antrum is manda‐ tory. It could avoid important complications such as acute thrombus formation or early or late pulmonary vein stenosis by power, impedance, and temperature monitoring during energy delivery. Impedance increasing could be proceeding by microbubbles due to tissue superheat‐ ing. ICE enables directly visualization of these microbubbles. In this case, immediate inter‐ ruption of lesion creation is recommended to prevent severe complications such as cardiac tamponade by LA perforation, oesophageal injury or pulmonary vein stenosis. ICE is a useful tool also for the placement of mapping/ablation catheter according to anatomic landmarks and morphologic lesion changes monitoring for a safety and efficacy AF ablation procedure [7]. ICE has becoming a gold standard in complex AF ablation procedures by replacing fluoro‐ scopy technique [14].

There has been a revival in the use of transseptal catheterization due to the increased use of radiofrequency ablation in the LA. Utilization of ICE in conjunction with fluoroscopy allows the electrophysiologist to clearly identify the interatrial septum and adjacent structures. ICE provides excellent views of the fossa ovalis and of the transseptal apparatus [7]. Life‐threat‐ ening complications following inadvertent puncture of anatomic structures can be avoided under direct visualization. For electrophysiologist is important a direct visualization of the Brockenbrough needle and the Mullins sheath during the transseptal puncture. Sheath position in the LA could be verified by saline microbubbles or intravenous contrast injection.

The location of the Marshall vein, relevant in AF ablation, can also be identified from imaging of the "Q‐tip" ridge, seen between the LA appendage and left pulmonary veins [7].

Transseptal puncture allows procedural access to the LA. Anatomic structures are not directly visualized during transseptal puncture by fluoroscopic guidance. TTE and especially TOE may be helpful in performing this procedure by allowing direct visualization of the transseptal catheter and its relationship to the fossa ovalis. Anatomic variability in the position and orientation of the fossa ovalis and its surrounding structures may be challenging to even those interventional cardiologists with significant transseptal experience. However, echocardiogra‐ phy imaging offers increased safety to the operator, by avoiding the puncture of the intraper‐ icardial aorta, a serious complication of transseptal puncture. In addition, radiation minimizes the fluoroscopy time required for the procedure, being very important during the learning curve. It was shown that TOE is of great value in performing transseptal punctures in AF ablation procedures. TTE can delineate the aorta and interatrial septum, and the characteristic bulging (or tenting) of the fossa ovalis and saline contrast echocardiography with TTE may help confirm needle position in the right atrium before puncture and in the LA after puncture (**Figure 7**). Anatomical variations in interatrial septum such as aneurismal septum, double‐ membrane septum, patent foramen oval, and others make this process complicated. Because TTE does not always offer sufficient imaging resolution, TOE and more recently ICE are

ICE could be useful only during the ablation procedure. It enables visualization of anatomical particularities of LA, being mostly important in transseptal puncture guidance and circular Lasso catheter positioning [14]. ICE enables to visualize the tenting of the interatrial septum due to the transseptal sheath tip during the puncture. It is important to be correctly placed in the posterior region of the fossa ovalis to avoid potential life‐threatening complications such as aortic root perforation or LA lateral wall penetrating. For an appropriate mapping and ablation lesions, a good placement of Lasso catheter at the pulmonary vein antrum is manda‐ tory. It could avoid important complications such as acute thrombus formation or early or late pulmonary vein stenosis by power, impedance, and temperature monitoring during energy delivery. Impedance increasing could be proceeding by microbubbles due to tissue superheat‐ ing. ICE enables directly visualization of these microbubbles. In this case, immediate inter‐ ruption of lesion creation is recommended to prevent severe complications such as cardiac tamponade by LA perforation, oesophageal injury or pulmonary vein stenosis. ICE is a useful tool also for the placement of mapping/ablation catheter according to anatomic landmarks and morphologic lesion changes monitoring for a safety and efficacy AF ablation procedure [7]. ICE has becoming a gold standard in complex AF ablation procedures by replacing fluoro‐

There has been a revival in the use of transseptal catheterization due to the increased use of radiofrequency ablation in the LA. Utilization of ICE in conjunction with fluoroscopy allows the electrophysiologist to clearly identify the interatrial septum and adjacent structures. ICE provides excellent views of the fossa ovalis and of the transseptal apparatus [7]. Life‐threat‐ ening complications following inadvertent puncture of anatomic structures can be avoided under direct visualization. For electrophysiologist is important a direct visualization of the Brockenbrough needle and the Mullins sheath during the transseptal puncture. Sheath position in the LA could be verified by saline microbubbles or intravenous contrast injection.

preferably (**Figure 8**).

76 Echocardiography in Heart Failure and Cardiac Electrophysiology

scopy technique [14].

During AF ablation procedure, the mapping is followed by energy applications and lesion creation. Atrial myocardium suffers some alterations after energy application such as thick‐ ening, dimpling, and hyper‐echogenicity. ICE enables identification of all myocardium sites transformed during ablation. The characteristics of lesions could be controlled by monitoring and titrating of energy parameters (temperature, impedance, and power). In addition, ICE allows identification of triggers sites such ligament of Marshall and to treat by applications under direct visualization. The applications on LA posterior wall could translate into fistula between anterior wall of the oesophagus and LA, a lethal complication of an extensive AF ablation procedure. Therefore, ICE is very useful during the procedure to titrate energy parameters to avoid this. In conclusion, ICE is used only during the ablation procedure; it allows better results of the procedure and lower risk of complications [15].

All echocardiography methods, TTE, TOE, or ICE, have the ability to detect early and avoid potential lethal complications during AF ablation [15]. Appropriate anticoagulation could prevent spontaneously thrombus formation and embolization during the procedure. Imme‐ diate detecting of thrombus by ICE allows prompting removal of catheters to avoid embolic complications.

Microbubbles visualization is most useful for prompting discontinuation of energy delivery when microbubbles are seen. Early detection of a pericardial effusion before cardiac tampo‐ nade (preferable before signs of haemodynamic compromise) and catheter‐based treatment of the effusion are two facilitations allowed by TTE, TOE, or ICE. Pulmonary vein stenosis is a serious complication that can be detected early by visual tissue swelling and assessing severity with peak velocity measurements and colour flow parameters or pulsed‐wave Doppler imaging, available with phased‐array imaging [14].

During ablation procedure, ICE can accurately visualize LA anatomy and related structures and may guide transseptal catheterization and it is helpful in monitoring potential complica‐ tions during catheter ablation procedures. In addition, it allows to establish a clear‐cut relationship between the catheter tip and underlying tissue and to visualize the lesion formation; it can be performed with minimal additional patient risk and discomfort, without additional sedation or general anaesthesia; it does not need prolonged oesophageal intubation, accompanying patient discomfort, or the risk for aspiration. ICE offers imaging that is comparable with or superior to TOE and is an alternative to TOE in selected patients with absolute contraindications to TOE (oesophagectomy). This technique is quite safe with a negligible rate of complications and good patient tolerance. It allows improvement in success rate and decrease in complication when compared to fluoroscopic approach. ICE has been shown to improve patient comfort, shorten both procedure and fluoroscopy times, and offer comparable cost with TEE‐guided interventions [5].

Comparing with TOE, ICE has some advantages: clearer image, reduced irradiation, and shorter duration of the procedure [16]. It has also some disadvantages such as: the shaft is thick without the possibility to have ports for pressure, therapeutic devices, and guide wires; the phased‐array catheters are cost‐ineffective (single use, higher costs); ICE offers only mono‐ plane image views being difficult to obtain some sections as for TOE [10]. In addition, there are not still standard views for ICE as for other echocardiographic imaging modality such as TTE or TOE. In addition, in the literature there are described some potential risks of vascular lesion, cardiac perforation, arrhythmias, thromboembolism, and cutaneous nerve palsy [5]. However, it is expected to be used widely in clinical practice and even to become the standard for the transseptal catheterization.

## **4. Echocardiography after Atrial Fibrillation Ablation**

Echocardiography is very useful after AF ablation for detection and monitoring for early and late related complications, and also for LA reverse remodelling assessment in patients with stable sinus rhythm.

Pulmonary veins flow monitoring is used to detect early pulmonary vein stenosis after AF ablation, which could occur in 1% to 3% of current series [17]. TOE allows the suspicion of a significant PV stenosis (**Figure 9**) by a combination of elevated peak pulmonary vein velocity (≥110 cm/s) with turbulence and little flow variation [17]. Although TOE has been used, it does not usually provide adequate assessment.

**Figure 9.** (A) Colour Doppler mode by transoesophageal echocardiography at the level of left superior pulmonary vein identify a significant pulmonary vein stenosis. (B) Pulsed‐wave Doppler of left superior pulmonary vein inflow con‐ firms haemodynamically significant stenosis. LA: left atrium, AO: aorta, LSPV: left superior pulmonary vein.

However, TTE or TOE are limited by its inability to image deeply into all four pulmonary veins and are less useful in establishing the extent and location of pulmonary vein stenosis. Diag‐ nostic tests of value include magnetic resonance angiography and computed tomography. Progression of stenosis is unpredictable and may be rapid. Recurrent restenosis after angio‐ plasty and stenting, as therapeutic solution of this complication, may occur in 30–50% of patients with pulmonary veins stenosis [17]. Follow‐up of these patients typically involves computed tomography imaging to document restenosis.

phased‐array catheters are cost‐ineffective (single use, higher costs); ICE offers only mono‐ plane image views being difficult to obtain some sections as for TOE [10]. In addition, there are not still standard views for ICE as for other echocardiographic imaging modality such as TTE or TOE. In addition, in the literature there are described some potential risks of vascular lesion, cardiac perforation, arrhythmias, thromboembolism, and cutaneous nerve palsy [5]. However, it is expected to be used widely in clinical practice and even to become the standard

Echocardiography is very useful after AF ablation for detection and monitoring for early and late related complications, and also for LA reverse remodelling assessment in patients with

Pulmonary veins flow monitoring is used to detect early pulmonary vein stenosis after AF ablation, which could occur in 1% to 3% of current series [17]. TOE allows the suspicion of a significant PV stenosis (**Figure 9**) by a combination of elevated peak pulmonary vein velocity (≥110 cm/s) with turbulence and little flow variation [17]. Although TOE has been used, it does

**Figure 9.** (A) Colour Doppler mode by transoesophageal echocardiography at the level of left superior pulmonary vein identify a significant pulmonary vein stenosis. (B) Pulsed‐wave Doppler of left superior pulmonary vein inflow con‐ firms haemodynamically significant stenosis. LA: left atrium, AO: aorta, LSPV: left superior pulmonary vein.

However, TTE or TOE are limited by its inability to image deeply into all four pulmonary veins and are less useful in establishing the extent and location of pulmonary vein stenosis. Diag‐ nostic tests of value include magnetic resonance angiography and computed tomography. Progression of stenosis is unpredictable and may be rapid. Recurrent restenosis after angio‐ plasty and stenting, as therapeutic solution of this complication, may occur in 30–50% of

**4. Echocardiography after Atrial Fibrillation Ablation**

for the transseptal catheterization.

78 Echocardiography in Heart Failure and Cardiac Electrophysiology

not usually provide adequate assessment.

stable sinus rhythm.

Pulmonary vein stenosis could occur late after AF ablation. TOE could raise the suspicion by detection of high pulmonary vein velocities. Follow‐up of these patients typically involves computed tomography or magnetic resonance imaging to document stenosis.

TOE and ICE allow early identification of complications related with procedure including damage to intracardiac structures, thrombus formation, pulmonary vein stenosis, and pericardial effusion during catheter ablation of AF.

A TOE performed 3–6 months after AF ablation can also evaluate thromboembolic risk and need for long‐term anticoagulation, as echocardiographic risk factors may be present even if restoration of sinus rhythm is successful.

Catheter ablation has been demonstrated to be successful in the restoration of sinus rhythm and is performed in an increasing number of patients with symptomatic drug‐refractory paroxysmal and persistent AF. It has been demonstrated that restoration and maintenance of sinus rhythm after catheter ablation is associated with a decrease in LA volumes (reverse structural LA remodelling), with subsequent improvement of LA function [5]. Using the new tissue Doppler‐derived parameters, it was shown that in parallel with the improvement in LA function, both left ventricle systolic and diastolic function improved in the patients who maintained sinus rhythm [5]. In addition to LA reverse remodelling, even the area of the pulmonary venous ostia may decrease after successful catheter ablation procedures [5]. Post‐ procedural imaging to evaluate the extent of reverse LA remodelling after catheter ablation is critical to appropriate decisions regarding ongoing anti‐arrhythmic therapy and long‐term anticoagulation.

Conversion of AF and atrial flutter to sinus rhythm could result in a transient mechanical dysfunction of LA and LA appendage, termed atrial stunning [17]. Atrial stunning has been reported including after radiofrequency ablation. This phenomenon is well recognized with peak A velocity of transmitral inflow (by a very low value or absence) as well as TDI or strain imaging. Atrial stunning is at maximum immediately after procedure and improves progres‐ sively with a complete resolution within a few minutes to 4–6 weeks depending on the duration of the preceding AF, atrial size, and structural heart disease [18]. This suggests that a dissoci‐ ation of electrical and mechanical recovery occurs after successful restoration of sinus rhythm, with a delay in gradual improvement of atrial mechanical function.

Stiff LA syndrome, defined as pulmonary hypertension with LA diastolic dysfunction, has regained attention in patients who had undergone catheter ablation for AF, especially after multiple ablation procedures [19]. This syndrome is a rare but potentially significant compli‐ cation of AF ablation. Severe LA scarring, LA ≤45 mm, diabetes mellitus, obstructive sleep apnoea, and high LA pressure are clinical variables that predict the development of this syndrome [19]. The main echocardiographic findings include pulmonary hypertension in the absence of pulmonary vein stenosis or LA pressure tracings in the absence of mitral regurgi‐ tation. Pulmonary vein diastolic flow velocity (assessed by TTE or TOE) and E/Ea (by TTE using pulse wave Doppler and TDI) can be used as a noninvasive parameter predicting high LA pressure peak (during sinus rhythm) in patients with AF [19]. Elevated LA pressure was closely associated with electroanatomical remodelling of the LA and was an independent predictor for recurrence after AF ablation [20, 21].

## **5. Conclusion**

Multimodality echocardiography is needed at each step of AF ablation procedure. LA size, morphology, and function together with other cardiac parameters are mandatory for patient selection. 2D TTE allows rapid and comprehensive assessment of cardiac anatomical structure and function. 2D or 3D TOE provides accurate information about preprocedural LA append‐ age thrombus in the atria and thromboembolic risk and is very useful for intraprocedural guidance. The novel technique of ICE has emerged also as a popular and useful tool in the guidance of AF ablation procedure. TTE or TOE is need for early and late ablation‐related complications detection and monitoring. In the future, echocardiography might be useful in thrombogenic endocardial remodelling assessment, a novel concept in atrial cardiomyopathies such as atrial fibrillation.

## **Author details**

Mariana Floria\* and Maria Daniela Tanase

\*Address all correspondence to: floria\_mariana@yahoo.com

Gr. T. Popa University of Medicine and Pharmacy, Iasi, Romania

## **References**


update of the 2010 ESC Guidelines for the management of atrial fibrillation. Europace 2012;14:1385–413.

LA pressure peak (during sinus rhythm) in patients with AF [19]. Elevated LA pressure was closely associated with electroanatomical remodelling of the LA and was an independent

Multimodality echocardiography is needed at each step of AF ablation procedure. LA size, morphology, and function together with other cardiac parameters are mandatory for patient selection. 2D TTE allows rapid and comprehensive assessment of cardiac anatomical structure and function. 2D or 3D TOE provides accurate information about preprocedural LA append‐ age thrombus in the atria and thromboembolic risk and is very useful for intraprocedural guidance. The novel technique of ICE has emerged also as a popular and useful tool in the guidance of AF ablation procedure. TTE or TOE is need for early and late ablation‐related complications detection and monitoring. In the future, echocardiography might be useful in thrombogenic endocardial remodelling assessment, a novel concept in atrial cardiomyopathies

[1] Van Wagoner DR, Piccini JP, Albert CM, Anderson ME, Benjamin EJ, Brundel B, Califf RM, Calkins H, Chen PS, Chiamvimonvat N, Darbar D, Eckhardt LL, Ellinor PT, Exner DV, Fogel RI, Gillis AM, Healey J, Hohnloser SH, Kamel H, Lathrop DA, Lip GY, Mehra R, Narayan SM, Olgin J, Packer D, Peters NS, Roden DM, Ross HM, Sheldon R, Wehrens XH: Progress toward the prevention and treatment of atrial fibrillation: a summary of the Heart Rhythm Society Research Forum on the Treatment and Prevention of Atrial Fibrillation, Washington, DC, 9–10 December 2013. Heart Rhythm 2015;12:e5–e29. doi:

[2] Camm AJ, Lip GY, De Caterina R, Savelieva I, Atar D, Hohnloser SH, Hindricks G, Kirchhof P: ESC committee for practice guidelines‐CPG; document reviewers: 2012 focused update of the ESC guidelines for the management of atrial fibrillation: an

predictor for recurrence after AF ablation [20, 21].

80 Echocardiography in Heart Failure and Cardiac Electrophysiology

and Maria Daniela Tanase

\*Address all correspondence to: floria\_mariana@yahoo.com

10.1016/j.hrthm.2014.11.011.

Gr. T. Popa University of Medicine and Pharmacy, Iasi, Romania

**5. Conclusion**

such as atrial fibrillation.

**Author details**

Mariana Floria\*

**References**


**Echocardiography in Heart Failure**

[11] Providência R, Trigo J, Paiva L, Barra S: The role of echocardiography in thromboem‐ bolic risk assessment of patients with nonvalvular atrial fibrillation. J Am Soc Echo‐

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[18] Khan IA: Atrial stunning: basics and clinical considerations. Int J Cardiol 2003;92:113–

[19] Gibson DN, Di Biase L, Mohanty P, Patel JD, Bai R, Sanchez J, Burkhardt JD, Heywood JT, Johnson AD, Rubenson DS, Horton R, Gallinghouse GJ, Beheiry S, Curtis GP, Cohen DN, Lee MY, Smith MR, Gopinath D, Lewis WR, Natale A: Stiff left atrial syndrome after catheter ablation for atrial fibrillation: clinical characterization, prevalence, and

predictors. Heart Rhythm 2011;8:1364–1371. doi:10.1016/j.hrthm.2011.02.026.

[20] Park J, Yang PS, Kim TH, Uhm JS, Kim JY, Joung B, Lee MH, Hwang C, Pak HN: Low left atrial compliance contributes to the clinical recurrence of atrial fibrillation after catheter ablation in patients with structurally and functionally normal heart. PLoS One

[21] Park J, Joung B, Uhm JS, Young Shim C, Hwang C, Hyoung Lee M, Pak HN: High left atrial pressures are associated with advanced electroanatomical remodeling of left atrium and independent predictors for clinical recurrence of atrial fibrillation after catheter ablation. Heart Rhythm 2014;11:953–60. doi:10.1016/j.hrthm.2014.03.009.

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28.

#### **Speckle-Tracking Imaging, Principles and Clinical Applications: A Review for Clinical Cardiologists Speckle-Tracking Imaging, Principles and Clinical Applications: A Review for Clinical Cardiologists**

Iacopo Fabiani, Nicola Riccardo Pugliese, Veronica Santini, Lorenzo Conte and Vitantonio Di Bello Iacopo Fabiani, Nicola Riccardo Pugliese, Veronica Santini, Lorenzo Conte and Vitantonio Di Bello Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64261

#### **Abstract**

Evaluation of myocardial mechanics, although complex, has now entered the clinical arena, thanks to the introduction of bedside imaging techniques, such as speckletracking echocardiography.

Overcoming the limitations of previous techniques, such as tissue Doppler Imaging (TDI), bi-dimensional (2D) and, only recently, three-dimensional (3D) speckle tracking, allows a fast, reproducible, and semi-automated description of myocardial deformation parameters, including strain, strain rate, velocity, displacement, torsion, and timing of contraction/relaxation. From research tool, speckle tracking has become a great help for clinicians, validated with respect to more complex, time-consuming, and expensive techniques.

Nowadays, further development in technology and image processing draws the attention of the cardiology community. This review intends to describe the fundamental aspects of the imaging technique, together with some recent innovations and clinical applications in this field.

**Keywords:** cardiac mechanics, deformation, strain, strain rate, speckle tracking

## **1. Introduction**

Speckle-tracking imaging (STI) is a non-invasive ultrasound technique that allows an objective and quantitative evaluation of global and regional myocardial function, independently from the angle of insonation and partly from cardiac translational movements [1–4].

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.


**Table 1.** Advantage and disadvantage of different techniques for myocardial deformation analysis.

Echocardiographic estimation of segmental left ventricular contractility is routinely accomplished through visual interpretation of endocardial motion and myocardial thickening. This method is subjective and requires a relatively experienced observer. Quantitative analysis based on tracing of the endocardial border may also be hampered by endocardial "dropout" and trabeculations.

Tissue Doppler imaging (TDI) has been previously used in deriving myocardial velocities and assessing fundamental parameters of myocardial deformation (strain and strain rate) [5]. Myocardial tissue velocities represent the net effect of the contractile and elastic properties of the area under investigation and the motion caused by traction and tethering from other regions. In contrast, strain is a dimensionless index reflecting the total deformation of the ventricular myocardium during a cardiac cycle, as a percentage of its initial length. Strain rate is the rate of deformation or stretch. Strain techniques are, in principle, the optimal modalities for the assessment of regional myocardial function. The major limitation of TDI has been its angle dependency [5], requiring alignment of the ultrasound beam parallel to the direction of tissue movement. Thus, deformation study was substantially limited to the analysis of the tissue moving toward or away from the probe (**Table 1**).

STI is based on bi-dimensional (2D) echocardiographic technology, not limited by Doppler analysis [6–8]. Segments of myocardial tissue show a pattern of gray values in the ultrasound. This pattern, resulting from the spatial distribution of gray values, is commonly referred to as speckle pattern, characterizes the underlying myocardial tissue acoustically and is unique for each myocardial segment. Speckle tracking allows the measure of all in-plane components of the velocity vector, in all pixels [9]. More recently, the addition of the third dimension (3D) has partly expanded the scope of this technology.

## **2. Human myocardium**

**Technique Advantage Disadvantage**

**•** Temporal resolution **•** Poor image quality **•** Myocardial curvature

**•** Lower frame rates in tachycardia

**•** Interobserver variability

**•** Technically demanding **•** Low signal-noise ratio **•** Poor spatial resolution

**•** Time-consuming

**•** Angle dependency

**•** Displacement in relation to transducer

**•** One dimension

**•** Tissue movement relative to adjacent segments

2D, bi-dimensional; STI, speckle-tracking imaging; TDI, tissue Doppler imaging

**Table 1.** Advantage and disadvantage of different techniques for myocardial deformation analysis.

Echocardiographic estimation of segmental left ventricular contractility is routinely accomplished through visual interpretation of endocardial motion and myocardial thickening. This method is subjective and requires a relatively experienced observer. Quantitative analysis based on tracing of the endocardial border may also be hampered by endocardial "dropout"

Tissue Doppler imaging (TDI) has been previously used in deriving myocardial velocities and assessing fundamental parameters of myocardial deformation (strain and strain rate) [5]. Myocardial tissue velocities represent the net effect of the contractile and elastic properties of the area under investigation and the motion caused by traction and tethering from other regions. In contrast, strain is a dimensionless index reflecting the total deformation of the ventricular myocardium during a cardiac cycle, as a percentage of its initial length. Strain rate is the rate of deformation or stretch. Strain techniques are, in principle, the optimal modalities for the assessment of regional myocardial function. The major limitation of TDI has been its angle dependency [5], requiring alignment of the ultrasound beam parallel

STI **•** Analysis in 2D

**•** Angle independency

**•** Automated tracking system

**•** Lower interobserver variability

86 Echocardiography in Heart Failure and Cardiac Electrophysiology

**•** Spatial resolution

**•** Low noise

TDI **•** Adequate image quality

and trabeculations.

**•** Temporal resolution

Human myocardium is made up of multiple layers [10–12]. According to the helical model described by Torrent-Guasp, a single myocardial muscle band folding upon itself creates varying orientations of fibers throughout the myocardium, with two principal loops, basal (transverse) and apical (oblique). Myocardium finally consists of three separate layers: transversely oriented circular fibers that wrap (around both ventricles), the inner oblique layer (clockwise rotation), and the outer oblique layer (counterclockwise rotation). Briefly, the myofiber geometry of the LV changes gradually from a right-handed helix in the subendocardium to a left-handed helix in the subepicardium.

The mechanics of the LV is complex, but three principal components contribute to systole: inward motion, longitudinal motion (base moving toward the apex), and differential rotation of the apex and base (twisting). Diastolic mechanics is the opposite of systolic motion. LV torsion (or twist) has an important role in cardiac systo-diastolic mechanics. During the cardiac cycle, there is a systolic twist and an early diastolic untwist around left ventricular long axis, due to opposite apical and basal rotations. Systolic apical rotation is counterclockwise and basal rotation is clockwise [13]. LV rotation is a sensitive indicator of changes in regional and global LV function.

## **2.1. Cardiac mechanics and limits of conventional indices**

Cardiac function is the result of force development (inotropism: opening of the cardiac valves) and deformation (shortening of the myocytes: volume ejection) and can be evaluated globally (pump performance) or regionally [14]. Correct evaluation of systolic function should focus on the intrinsic properties of the fibers and myocytes that represent the real actors behind heart function as well as a pathologic process. The deformation of a myocardial segment during the cardiac cycle is a complex phenomenon and consists of normal deformation (longitudinal shortening/lengthening, radial thickening/thinning, and circumferential shortening/lengthening) and shear deformation (base-apex twisting, epi-endo circumferential shear, and epiendo longitudinal shear). There is a clear gradient from base to apex in both velocity and displacement (stationary of the apex within the thorax while the base is moving toward it). In contrast, deformation is more or less homogenous throughout the (normal) myocardial wall. It is important to understand the relation between intrinsic function (contractility) and the resulting motion/deformation. A myocardial segment develops a force but it is also subject to the forces developed by near segments. The intrinsic contractile force of the myocardium (inotropism) is the most important determinant of myocardial performance, but any segment of myocardium is part of a ventricle, with external forces acting up on it (mostly in the opposite direction of the contractile force) and resulting from local wall stress, caused by the intracavitary pressure (related to local geometry of the ventricle) and the interaction with neighboring contracting segments ("pulling" the segment itself). The relationship between acting forces and the resultant deformation is influenced by regional elasticity, which by itself is not a constant; due to the structure of the tissue, the more the myocardium is stretched, the more difficult it becomes to stretch it even further.

Regional myocardial deformation is thus the result of:

## *Active forces:*

**•** Intrinsic contractility (influenced by tissue perfusion and electrical activation).

## *Passive forces:*


## *Tissue elasticity:*


Despite this pathophysiological insight, echocardiography is still mainly based on global and indirect indices such as ejection fraction, a volume-based parameter that does not reflect contractility, being based on geometric assumptions. For example, "supranormal" values of ejection fraction (EF) are often found in hypertrophied or volume-overloaded ventricles, thus not reflecting real changes in contractility. EF is also load dependent and, per se, is only a global index, without regional implications and not taking into account segmental interactions, which do not contribute to pump function. Moreover, indices for global functional assessment reflect mainly radial function, ignoring longitudinal function, which is usually altered long before changes occur in radial indices.

## **2.2. The concept of myocardial deformation**

When two neighboring points of the myocardium move at different velocities, myocardium changes its shape (deforming). Otherwise, myocardium is moving but not deforming. When the velocity of the tissue is known, several other parameters can be derived.

Displacement is the integral of the velocity over time (Eq. (1)).

Speckle-Tracking Imaging, Principles and Clinical Applications: A Review for Clinical Cardiologists http://dx.doi.org/10.5772/64261 89

$$d = \int\_{r\_0}^{r} \nu(t)dt\tag{1}$$

Strain and strain rate are measures of changes in shape, that is, deformation.

For mono-dimensional deformations, that is, shortening or lengthening, the simplest measurement is conventional or Lagrangian strain (Eq. (2)).

$$
\omega(t) = \frac{L(t) - L\_0}{L\_0} \tag{2}
$$

The Greek letter epsilon (ε) is commonly used as a symbol for conventional strain. The strain value is dimensionless and can be presented as a fractional number or as a percentage. For Lagrangian strain, a single reference length (*L*0) is defined, against which all subsequent deformation (*L(t)*) will be measured. Strain is positive if *L* is major than *L*<sup>0</sup> (an object has lengthened) and negative if *L* is smaller than *L*<sup>0</sup> (shortening). If *L* equals *L*0, the strain is thus zero.

Natural strain (*ε'*) is defined as [15]:

It is important to understand the relation between intrinsic function (contractility) and the resulting motion/deformation. A myocardial segment develops a force but it is also subject to the forces developed by near segments. The intrinsic contractile force of the myocardium (inotropism) is the most important determinant of myocardial performance, but any segment of myocardium is part of a ventricle, with external forces acting up on it (mostly in the opposite direction of the contractile force) and resulting from local wall stress, caused by the intracavitary pressure (related to local geometry of the ventricle) and the interaction with neighboring contracting segments ("pulling" the segment itself). The relationship between acting forces and the resultant deformation is influenced by regional elasticity, which by itself is not a constant; due to the structure of the tissue, the more the myocardium is stretched, the more

difficult it becomes to stretch it even further.

88 Echocardiography in Heart Failure and Cardiac Electrophysiology

*Active forces:*

*Passive forces:*

*Tissue elasticity:*

**•** Segment interaction.

**•** Myofibrillar architecture;

**•** Collagen amount (fibrosis).

changes occur in radial indices.

**2.2. The concept of myocardial deformation**

Regional myocardial deformation is thus the result of:

**•** Intrinsic contractility (influenced by tissue perfusion and electrical activation).

Despite this pathophysiological insight, echocardiography is still mainly based on global and indirect indices such as ejection fraction, a volume-based parameter that does not reflect contractility, being based on geometric assumptions. For example, "supranormal" values of ejection fraction (EF) are often found in hypertrophied or volume-overloaded ventricles, thus not reflecting real changes in contractility. EF is also load dependent and, per se, is only a global index, without regional implications and not taking into account segmental interactions, which do not contribute to pump function. Moreover, indices for global functional assessment reflect mainly radial function, ignoring longitudinal function, which is usually altered long before

When two neighboring points of the myocardium move at different velocities, myocardium changes its shape (deforming). Otherwise, myocardium is moving but not deforming. When

the velocity of the tissue is known, several other parameters can be derived.

Displacement is the integral of the velocity over time (Eq. (1)).

**•** Intracavitary pressure (afterload/preload; ventricular geometry);

$$
\varpi' = \ln(\frac{L}{L\_o}) \tag{3}
$$

Natural strain employs a reference length that changes as the object deforms. It therefore describes the instantaneous length change and it is independent of reference times. Compared to that of conventional strain, the natural strain amplitude is smaller for positive strains and larger for negative strains. This concept applies in principle to all three one-dimensional (longitudinal, circumferential, and radial) displacement and strain components.

In two or three dimensions, we should also consider shear strain, i.e., measurement of deformation in angle. It is also mandatory to specify directions and magnitudes of maximal and minimal strain.

The strain rate is the temporal derivative of the strain (Eq. (4)).

$$
\varepsilon' = \frac{d\varepsilon}{dt} \tag{4}
$$

Whereas strain indicates the amount of deformation, strain rate indicates the rate of the deformation. The spatial gradient in myocardial velocities represents the rate of myocardial deformation, that is, the strain rate. The unit of the strain rate is normally 1/s or s−1. Strain rate is more uniformly distributed along the different regions of the LV, whereas myocardial velocity decreases from base toward apical parts of the LV. Strain can subsequently be derived by temporal integration of the strain rate curve. Indeed, if the rate of deformation is known at each time instance during the cardiac cycle, the total amount of deformation can easily be calculated. A positive strain rate means that the length of the object is increasing, whereas a negative strain rate means that the length is decreasing. If the length is constant, the strain rate is zero. Therefore, whereas strain is a measurement of deformation relative to a reference state, strain rate is an instantaneous measurement. When the strain rate has been calculated for each time point during the deformation, the strain can be found as the temporal integral of the strain rate (Eq. (5)).

$$
\varepsilon' = \int\_{T\_0}^{T} \varepsilon'(t)dt
\tag{5}
$$

2D strain comprises four measurements: two natural strains and two shear strains [6].

A 3D model allows the evaluation of three natural strain and six shear strain measurements along *x*, *y*, and *z* or azimuthal axes.

## **2.3. Fundamentals of speckle tracking**

"Speckles" are small groups of myocardial pixels created by the interaction of ultrasonic beams and the myocardium, with specific gray scale characteristics. A speckle is commonly defined as the spatial distribution of gray values in the ultrasound image. The result of a speckletracking procedure (followed by regularization process) is an estimate of the in-plane velocity vector in all pixels in each of the frames of the ultrasound data set (dynamic velocity vector field). The spatial distribution of the gray values within the ultrasound image is due to constructive and destructive interference of reflections from the individual scatterers within the myocardium. Reflections occur at transitions between different types of tissues or at specific sites, and are much smaller than the wavelength. Constructive interference generates a highamplitude signal, destructive a low-amplitude one. The exact scatter positions determine the speckle characteristics. Speckle-tracking technology offers the ability to identify and track the same speckle throughout the cardiac cycle [4].

In the ultrasound image, we see the speckle pattern occurring at a position further away from the transducer. To correctly detect speckles, the motion of the tissue should be slower than the motion of the ultrasound beam (image lines). Sound waves propagate through tissues at an average velocity of 1530 m/s, while myocardial tissue moves at velocities in the order of centimeters per second: the basic condition is thus clearly met [16].

There are different algorithms used by different vendors in tracking these speckles. Some speckle-tracking methods are based on so-called block matching, where a region in the image is selected (the kernel) and is followed in the next image frame by subsequently trying out different positions and by determining the similarity between the kernel and the pattern observed in that position. The position where the similarity between the kernel ("fingerprint") and the observed pattern is maximal is assumed to be the new position of the speckle pattern [16]. Another common approach is based on conservation of gray value, that is, it is assumed that gray values do not change over time. Radio frequency (RF) speckle—used in blockmatching method—is a high-frequency signal, so that small between-frame motion can be detected, whereas its corresponding gray-scale speckle—used in gray-scale tracking—is derived from lower-frequency signals, being less sensitive to small displacements. Importantly, speckle tracking of gray-scale images does not necessarily perform well on high frame-rate data [16]. Then, RF-based methods allow to obtain a higher spatial, temporal, and velocity resolution because they use a signal with a higher-frequency content; at the same time, these methods are more sensitive to decorrelation and noise, requiring more severe regularization, which in turn might limit their resolution. Because both RF and gray-scale approaches offer advantages, a hybrid method was recently proposed.

by temporal integration of the strain rate curve. Indeed, if the rate of deformation is known at each time instance during the cardiac cycle, the total amount of deformation can easily be calculated. A positive strain rate means that the length of the object is increasing, whereas a negative strain rate means that the length is decreasing. If the length is constant, the strain rate is zero. Therefore, whereas strain is a measurement of deformation relative to a reference state, strain rate is an instantaneous measurement. When the strain rate has been calculated for each time point during the deformation, the strain can be found as the temporal integral of the strain

0

 e ¢= ¢( ) ò *T <sup>T</sup> t dt*

2D strain comprises four measurements: two natural strains and two shear strains [6].

A 3D model allows the evaluation of three natural strain and six shear strain measurements

"Speckles" are small groups of myocardial pixels created by the interaction of ultrasonic beams and the myocardium, with specific gray scale characteristics. A speckle is commonly defined as the spatial distribution of gray values in the ultrasound image. The result of a speckletracking procedure (followed by regularization process) is an estimate of the in-plane velocity vector in all pixels in each of the frames of the ultrasound data set (dynamic velocity vector field). The spatial distribution of the gray values within the ultrasound image is due to constructive and destructive interference of reflections from the individual scatterers within the myocardium. Reflections occur at transitions between different types of tissues or at specific sites, and are much smaller than the wavelength. Constructive interference generates a highamplitude signal, destructive a low-amplitude one. The exact scatter positions determine the speckle characteristics. Speckle-tracking technology offers the ability to identify and track the

In the ultrasound image, we see the speckle pattern occurring at a position further away from the transducer. To correctly detect speckles, the motion of the tissue should be slower than the motion of the ultrasound beam (image lines). Sound waves propagate through tissues at an average velocity of 1530 m/s, while myocardial tissue moves at velocities in the order of

There are different algorithms used by different vendors in tracking these speckles. Some speckle-tracking methods are based on so-called block matching, where a region in the image is selected (the kernel) and is followed in the next image frame by subsequently trying out different positions and by determining the similarity between the kernel and the pattern observed in that position. The position where the similarity between the kernel ("fingerprint") and the observed pattern is maximal is assumed to be the new position of the speckle pattern

(5)

e

rate (Eq. (5)).

along *x*, *y*, and *z* or azimuthal axes.

**2.3. Fundamentals of speckle tracking**

90 Echocardiography in Heart Failure and Cardiac Electrophysiology

same speckle throughout the cardiac cycle [4].

centimeters per second: the basic condition is thus clearly met [16].

So far, it is possible to evaluate the direction of movement, the speed of movement, and the distance of such movement at any point in the myocardium, independently from the transducer, relative to adjacent segments. The semi-automated nature of speckle-tracking echocardiography guarantees good intra-observer and inter-observer reproducibility [4].

Given that the velocity vector field is known for all pixels within the image, the axes are known with minimal user interaction. The radial, longitudinal, or circumferential velocity profiles throughout the cardiac cycle can be reconstructed, independent of the angle between the ultrasound image line and the direction of motion as in the conventional Doppler imaging [16]. The process of correcting the initial velocity vector estimates by applying additional boundary conditions based on a priori knowledge about the characteristics of the velocity field is called regularization. Regularization can consist of median filtering, weighted smoothing, elastic model, and myocardial boundaries definition.

Velocity vector imaging is partly analogous to 2D STI as it too tracks the speckles using 2D echocardiography, but utilizes additional physiological information to more robustly track the speckle kernels [17]. Each vector is an expression of direction and the magnitude of the velocity. The qualitative evaluation of the velocity is determined by comparing vectors along the tracked contour. Longitudinal strain is the percentage decrease in the length of the myocardium during systole (movement of the base toward the apex). It is expressed as a percent negative value (decrease in length in systole) [18]. Longitudinal strain may be calculated as an endocardial strain, midline strain, epicardial strain, or averaged over the entire cardiac wall. There is currently insufficient evidence to favor one way over another. Radial strain refers to the thickening of the myocardial wall during inward motion of the ventricle, measured in the shortaxis views. The value is traditionally defined as percent positive (thickening in systole). Circumferential strain represents the change in the length along the circular perimeter, by definition percent negative in systole. Strain parameters can be individualized for each myocardial segment or can be expressed as global strain (averaging of all segments). Strain rate (evaluated globally or for each segment) represents rate of longitudinal, radial, or circumferential deformation in time. It has a marked systolic negative peak (S) with two positive peak in early (E) and late diastole (A).

Relevant strain values along strain curves are, but are not limited to:


Modern software allows display of results in bull's eye (polar map) similar to single-photon emission computed tomography (SPECT). This is more familiar to cardiologists as it depicts single myocardial segments with relative values of strain, strain rate, and time to peak strain/ strain rate (synchronicity). A more unfamiliar method to display results in a monoplane view is the so-called curved anatomic M-mode (CAMM) which depicts timely variation of single parameters evaluated for a specific segment of interests from base to the apex and from septal to lateral wall. This offers a unique opportunity for timing and recognizing precise phases of a cardiac cycle (relaxation) and for the evaluation of AVC. End-systole coincides with AVC and can be visualized in the parasternal or apical long-axis view or by detecting the closure click on the spectral tracing of the pulsed-wave Doppler of aortic valve flow [19].

Rotation is the measure of the rotational movement of the myocardium in relation to an imaginary long-axis line from apex to base drawn through the middle of LV cavity 4]. Clockwise rotation is defined as negative, while counterclockwise rotation has a positive value. Twist is the algebraic difference in rotation between the apex and the base. Torsion is the twist normalized for the length of the LV cavity (degrees per centimeter). LV rotation or twisting motion has an important role in LV systolic and diastolic function. Normal values for LV rotation and twist angle have shown high variability (technique used, location of the region of interest, age, and loading hemodynamics of the ventricle). The increase in LV twist angle with age observed in literature can be explained by less opposed apical rotation, resulting from a gradual decrease in subendocardial function with aging. Worsening of diastolic relaxation and reduced diastolic suction is, however, associated with an early reduced and delayed diastolic untwisting.

Myocardial strain and Strain Rate (SR) are sensitive parameters for the quantification of diastolic function. Diastolic SR signals can be recorded during isovolumic relaxation, during early filling, and in late diastole. The hemodynamic determinants of protodiastolic strain rate include LV relaxation, regional diastolic stiffness, systolic function, end-systolic wall stress, and filling pressures. In addition, protodiastolic strain rate can assess interstitial fibrosis and can be used to identify viable myocardium after stunning and infarction. Measurement of diastolic strain and strain rate may be useful for research applications but is presently not recommended for routine clinical use.

The detection of myocardial fibrosis and viability depends on the evaluation of myocardial characteristics and shape during the cardiac cycle. Fibrotic tissue may be focal (as occurs in patients with myocardial infarction [MI]) or diffuse (systemic or metabolic disturbances). Fibrosis is actually accurately identified using myocardial late enhancement or T-weighted mapping with cardiac magnetic resonance imaging (MRI), but speckle tracking (especially systolic and protodiastolic strain rate) has a good correlation with tissue fibrosis, evaluated via cardiac magnetic resonance or biopsy.

All these parameters can be measured not only for the LV but also for the right ventricle (RV) and left and right atria (LA and RA, respectively), but have not been fully validated and, still together, commercial applications to process these chambers do not exist.

Timing peak strain is pivotal in defining dyssynchrony as well as for the evaluation of ischemia (post-systolic thickening or shortening).

## **2.4. Image acquisition**

**•** End-systolic strain: the value at end-systole;

92 Echocardiography in Heart Failure and Cardiac Electrophysiology

described as "post-systolic strain") [19].

**•** Positive peak systolic strain;

untwisting.

recommended for routine clinical use.

**•** Peak systolic strain: the peak value during systole;

**•** Peak strain: the peak value during the entire heart cycle. The peak strain may coincide with the systolic or end-systolic peak, or may appear after aortic valve closure (AVC) (it may be

Modern software allows display of results in bull's eye (polar map) similar to single-photon emission computed tomography (SPECT). This is more familiar to cardiologists as it depicts single myocardial segments with relative values of strain, strain rate, and time to peak strain/ strain rate (synchronicity). A more unfamiliar method to display results in a monoplane view is the so-called curved anatomic M-mode (CAMM) which depicts timely variation of single parameters evaluated for a specific segment of interests from base to the apex and from septal to lateral wall. This offers a unique opportunity for timing and recognizing precise phases of a cardiac cycle (relaxation) and for the evaluation of AVC. End-systole coincides with AVC and can be visualized in the parasternal or apical long-axis view or by detecting the closure click

Rotation is the measure of the rotational movement of the myocardium in relation to an imaginary long-axis line from apex to base drawn through the middle of LV cavity 4]. Clockwise rotation is defined as negative, while counterclockwise rotation has a positive value. Twist is the algebraic difference in rotation between the apex and the base. Torsion is the twist normalized for the length of the LV cavity (degrees per centimeter). LV rotation or twisting motion has an important role in LV systolic and diastolic function. Normal values for LV rotation and twist angle have shown high variability (technique used, location of the region of interest, age, and loading hemodynamics of the ventricle). The increase in LV twist angle with age observed in literature can be explained by less opposed apical rotation, resulting from a gradual decrease in subendocardial function with aging. Worsening of diastolic relaxation and reduced diastolic suction is, however, associated with an early reduced and delayed diastolic

Myocardial strain and Strain Rate (SR) are sensitive parameters for the quantification of diastolic function. Diastolic SR signals can be recorded during isovolumic relaxation, during early filling, and in late diastole. The hemodynamic determinants of protodiastolic strain rate include LV relaxation, regional diastolic stiffness, systolic function, end-systolic wall stress, and filling pressures. In addition, protodiastolic strain rate can assess interstitial fibrosis and can be used to identify viable myocardium after stunning and infarction. Measurement of diastolic strain and strain rate may be useful for research applications but is presently not

The detection of myocardial fibrosis and viability depends on the evaluation of myocardial characteristics and shape during the cardiac cycle. Fibrotic tissue may be focal (as occurs in patients with myocardial infarction [MI]) or diffuse (systemic or metabolic disturbances). Fibrosis is actually accurately identified using myocardial late enhancement or T-weighted

on the spectral tracing of the pulsed-wave Doppler of aortic valve flow [19].

Gated images are obtained during end-expiratory breath holding with stable electrocardiographic traces, avoiding foreshortening of the ventricle and proper visualization of endocardial border. Images acquired should be of high quality. Optimal frame rate should be 60–110 frames per second (FPS). The operator should keep the sector width and depth minimal to focus on the structure of interest. Usually, three consecutive cardiac cycles are obtained and the values averaged for the final processing. Low FPS limits tracking efficacy, while higher FPS "smooths" speckle pattern and the final quality of the analysis. Apical four-chamber, two-chamber, and three-chamber views are necessary for estimation of LV strain and strain rates by 2D STI. This finally offers global longitudinal strain (GLS) value, that is, the average of longitudinal strain for all segments in all views. Parasternal short-axis views (basal, papillary muscles, and apex) are necessary for radial and circumferential strains (finally averaged in global radial and circumferential strain) and strain rates as well as for rotation, twist, and torsion analysis. The ways myocardial segments are divided widely vary among vendors, but in general, a 16–18 segment LV model is used. Myocardium is divided into six segments: basal septal, mid septal, apical septal, apical lateral, mid lateral, and basal lateral. For the timing determination of cardiac events, mitral inflow and LV outflow velocities are recorded using pulsed-Doppler echocardiography and the aortic and mitral valve closure/opening (AVC/O and MVC/O, respectively) times are obtained, as well as visually (AVC in apical long-axis view) or semiautomatically (evaluation of CAMM). The recordings are analyzed offline using semiautomated computer software for estimation of strain and strain rate by 2D STI. A region of interest (ROI) has to be outlined manually, tracing the endocardium. The epicardium is automatically traced by the system, but the wall thickness can be manually adjusted.

The ROI is defined at end-diastole by [19]:


Each of these contours can be user defined or generated automatically.

Topographic definitions of the myocardial ROI in apical views are [19]:


Vendors have incorporated tools to help users identify tracking reliability. Various methods are utilized. Some vendors have introduced protocols that identify segments where tracking is suboptimal and is excluded from the final results. In addition, some vendors provide accuracy indices to guide the user in tracking performance estimates.

Longitudinal strain is more robust and reproducible than other parameters. The values tend to be partly different for different walls and segments. There is a gradient of longitudinal strain values from base to apex (higher values for apical segments) as well as from endo to epicardium (higher values of strain in the subendocardial region). **Table 2** depicts the recently published data on normal values for different strains of LV, while **Table 3** depicts the principal advantages and pitfalls of different strain imaging techniques [20].


**Table 2.** Mean percentage left ventricular strain values for strain in healthy adults.

A recent meta-analysis identified normal values for strain as (GLS) -19.7% (95% CI, −20.4 to −18.9%), global circumferential strain (GCS) −23.3% (95% CI, −24.6 to −22.1%), global radial strain (GRS) 47.3% (95% CI, 43.6–51.0%). Age, gender, body mass index, systolic blood pressure, frame rate, and equipment vendor were considered the variables most likely to influence GLS. In a general linear model, only mean blood pressure was independently associated with higher values of strain. The differences in each strain component are probably actually linked to technical motives: the superiority of longitudinal strain is linked to the reliability of measurements in the axial plane respective to azimuthal one; the variability of radial strain may reflect the limited amount of tissue to track in the short-axis view of the nonhypertrophied heart; the ROI, which is user defined, may affect the strain amplitude [21]. 2D strain parameters have been validated against tagged MRI studies and sonomicrometry studies [22–24]. 2D strain data correlate well with TDI-derived ones, although with higher strength and reproducibility [2].


2D, bi-dimensional; 3D, three-dimensional; STI, speckle-tracking imaging; TDI, tissue Doppler imaging.

**Table 3.** Tissue Doppler imaging, bi-dimensional and three-dimensional speckle-tracking imaging.

## **2.5. 3D strain**

**•** "Left/right base";

94 Echocardiography in Heart Failure and Cardiac Electrophysiology

**•** "Left/right ROIs."

Vendors have incorporated tools to help users identify tracking reliability. Various methods are utilized. Some vendors have introduced protocols that identify segments where tracking is suboptimal and is excluded from the final results. In addition, some vendors provide

Longitudinal strain is more robust and reproducible than other parameters. The values tend to be partly different for different walls and segments. There is a gradient of longitudinal strain values from base to apex (higher values for apical segments) as well as from endo to epicardium (higher values of strain in the subendocardial region). **Table 2** depicts the recently published data on normal values for different strains of LV, while **Table 3** depicts the principal advantages

> **Radial Strain**

Anterior 39 ± 16

Lateral 37 ± 18

Posterior 37 ± 17

Inferior 37 ± 17

Septal 37 ± 19

Anterospetal 39 ± 15

accuracy indices to guide the user in tracking performance estimates.

**Circumferential**

**Strain**

Anterior 24 ± 6

Lateral 22 ± 7

Posterior 21 ± 7

Inferior 22 ± 6

Septal 24 ± 6

**Table 2.** Mean percentage left ventricular strain values for strain in healthy adults.

Anteroseptal 26 ± 11

A recent meta-analysis identified normal values for strain as (GLS) -19.7% (95% CI, −20.4 to −18.9%), global circumferential strain (GCS) −23.3% (95% CI, −24.6 to −22.1%), global radial strain (GRS) 47.3% (95% CI, 43.6–51.0%). Age, gender, body mass index, systolic blood pressure, frame rate, and equipment vendor were considered the variables most likely to influence GLS. In a general linear model, only mean blood pressure was independently associated with higher values of strain. The differences in each strain component are probably actually linked to technical motives: the superiority of longitudinal strain is linked to the

and pitfalls of different strain imaging techniques [20].

**•** "Midbase";

**•** "Apex";

**Longitudinal Strain**

Apical septal 21 ± 4

Mid septal 19 ± 4

Basal septal 17 ± 4

Apical lateral 21 ± 7

Mid lateral 19 ± 6

Basal lateral 19 ± 6

With developments in ultrasound transducer technology and both hardware and software computing, systems capable of acquiring real-time volumetric LV data are now widely available. Reasonable spatial and temporal resolution of 3D data sets can now be achieved. The ability to estimate true 3D myocardial motion and deformation using various STI approaches may provide cardiologists with a better view of regional myocardial mechanics, which may be important for diagnosis, prognosis, and therapy. These 3D approaches can measure all strain components in all LV segments from a single acquisition [25–27]. Furthermore, they are angle independent, do not suffer from strain estimation errors associated with out-of-plane motion, and may in theory allow more precise calculations of LV twist and assessment of shear strain components [28–31]. This tool is promising for the evaluation of deformation parameters, although only preliminary data are available. A single apical fullvolume acquisition is performed, according to standard modalities, with an FPS between 18 and 25 (3D temporal resolution is lower than that obtained with 2D images) [32]. This avoids multiple acquisitions making readily and instantaneously available evaluation of strain parameters and torsion. The operator is able to limit foreshortening and properly identify walls and segments [33, 34]. 3D strain offers a combined assessment of longitudinal and circumferential strain [35]. To evaluate transmural (radial) deformation, due to image quality and tracking limitation, a derivative parameter, area strain, has been introduced. However, it is important to note that full volume is the result of a stitching process, which can limit tracking of speckles. Frame rate and lateral resolution can also limit good tracking.

#### **2.6. Recent advances and consensus: need for standardization**

Recognizing the critical need for standardization in strain imaging, in particular in order to derive a common standard for GLS, the most affordable parameter, in 2010, the European Association of Echocardiography and the American Society of Echocardiography (ASE) invited technical representatives from all interested vendors to participate in a concerted effort to reduce intervendor variability of strain measurement [36, 37]. In order to obtain a perfectly defined strain, synthetic ultrasound images simulated from mathematically modeled ventricles (phantoms) were developed. Jan D'hooge and colleagues from the University of Leuven generated cine loops mimicking normal, hypertrophied, and dysfunctional ventricles (**Figures 1**–**3**), and provided them to the vendors: after several attempts, results were similar for the principal vendors.

**Figure 1.** Global longitudinal strain calculation from phantom model (normal). AP4: apical four-chamber view; L. Strain: longitudinal strain.

parameters and torsion. The operator is able to limit foreshortening and properly identify walls and segments [33, 34]. 3D strain offers a combined assessment of longitudinal and circumferential strain [35]. To evaluate transmural (radial) deformation, due to image quality and tracking limitation, a derivative parameter, area strain, has been introduced. However, it is important to note that full volume is the result of a stitching process, which can limit tracking

Recognizing the critical need for standardization in strain imaging, in particular in order to derive a common standard for GLS, the most affordable parameter, in 2010, the European Association of Echocardiography and the American Society of Echocardiography (ASE) invited technical representatives from all interested vendors to participate in a concerted effort to reduce intervendor variability of strain measurement [36, 37]. In order to obtain a perfectly defined strain, synthetic ultrasound images simulated from mathematically modeled ventricles (phantoms) were developed. Jan D'hooge and colleagues from the University of Leuven generated cine loops mimicking normal, hypertrophied, and dysfunctional ventricles (**Figures 1**–**3**), and provided them to the vendors: after several attempts, results were similar

**Figure 1.** Global longitudinal strain calculation from phantom model (normal). AP4: apical four-chamber view; L.

of speckles. Frame rate and lateral resolution can also limit good tracking.

**2.6. Recent advances and consensus: need for standardization**

96 Echocardiography in Heart Failure and Cardiac Electrophysiology

for the principal vendors.

Strain: longitudinal strain.

**Figure 2.** Global longitudinal strain from phantom model (dilated cardiomyopathy). AP4: apical four-chamber view; Deform. Long.: longitudinal deformation.

**Figure 3.** Global longitudinal strain from phantom model (amyloid). AP4: apical four-chamber view; L. Strain: longitudinal strain.

Moreover, a great effort has been made to standardize, speedup, and automatize (less subjective approach) GLS calculation, in order to offer immediate results to clinicians (bedside) and avoid errors in calculations (heart rate variability).

## **2.7. Clinical applications**

2D STI has a wide field of clinical applications. We focus on main and novel fields of application (see also '**Table 4**') [38–48].


2D, bi-dimensional; 3D, three-dimensional; EF, ejection fraction; HFnEF, heart failure with normal ejection fraction; LV, left ventricle; STI, speckle-tracking imaging; TDI, tissue Doppler imaging; WMSI, wall motion score index.

**Table 4.** Principal clinical applications of speckle-tracking echocardiography.

Moreover, a recent meta-analysis presented the incremental value respective to EF retained by GLS [49]. It is essential to understand that technology development has today made available a fast, objective (automatized), and standardized definition of GLS, with final representation of bull's-eye plot of longitudinal strain value making it appealing, easily recognizable, and aligned with standardized segmentation of LV wall (**Figures 4** and **5**).

Speckle-Tracking Imaging, Principles and Clinical Applications: A Review for Clinical Cardiologists http://dx.doi.org/10.5772/64261 99

Moreover, a great effort has been made to standardize, speedup, and automatize (less subjective approach) GLS calculation, in order to offer immediate results to clinicians (bedside) and

2D STI has a wide field of clinical applications. We focus on main and novel fields of application

Longitudinal, radial, and circumferential strain reduction in ischemia.

Differentiation of active contraction from passive tethering.

Longitudinal strain from TDI velocity with 2D STI radial strain.

Systemic hypertension, diabetes mellitus, systemic sclerosis, amyloidosis, and

severe aortic stenosis despite normal EF. Septal strain and mitral regurgitation.

Myocardial ischemia Reduction in strain by 2D STI more objective than WMSI.

Myocardial viability Objective evaluation during stress echo.

Takotsubo cardiomyopathy Impaired longitudinal strain.

Cardiotoxicity Chemotherapy.

Restrictive cardiomyopathy Impaired longitudinal deformation and twist.

Constrictive pericarditis Impaired LV circumferential deformation and torsion.

Congenital heart disease Right ventricular longitudinal strain and strain rate.

aligned with standardized segmentation of LV wall (**Figures 4** and **5**).

**Table 4.** Principal clinical applications of speckle-tracking echocardiography.

Myocardial infarction Differentiation of transmural from subendocardial infarction. Remodeling.

Twisting/untwisting.

Longitudinal strain delay index. Radial strain and survival.

Duchenne's muscular dystrophy. Valvular heart disease Decreased radial, circumferential, and longitudinal strain in patients with

2D, bi-dimensional; 3D, three-dimensional; EF, ejection fraction; HFnEF, heart failure with normal ejection fraction; LV,

Moreover, a recent meta-analysis presented the incremental value respective to EF retained by GLS [49]. It is essential to understand that technology development has today made available a fast, objective (automatized), and standardized definition of GLS, with final representation of bull's-eye plot of longitudinal strain value making it appealing, easily recognizable, and

left ventricle; STI, speckle-tracking imaging; TDI, tissue Doppler imaging; WMSI, wall motion score index.

avoid errors in calculations (heart rate variability).

98 Echocardiography in Heart Failure and Cardiac Electrophysiology

**2.7. Clinical applications**

(see also '**Table 4**') [38–48].

Heart failure with normal LVEF

Cardiac resynchronization therapy

Detection of subclinical myocardial

(HFnEF)

(CRT)

disease

**Field of Application Explanation**

**Figure 4.** Global longitudinal strain calculation: on top showing tracking in four- (**B**) and two- (**A**) chamber view with strain curves; final bull's-eye plot (**C**) showing global results and superimposed regional values (Normal subject). AP2: apical two-chamber view; AP3: apical three-chamber view; AP4: apical four-chamber view; Deform. Long.: longitudinal deformation; EDV (bi-plane): end-diastolic volume (bi-plane); ESV (bi-plane): end-systolic volume (bi-plane); EF (bi-plane): ejection fraction (bi-plane); global Deform. Long. (GLS): global longitudinal strain; HR: heart rate.

**Figure 5.** Global longitudinal strain calculation: on top showing tracking in three- (**A**) and four- (**B**) chamber view with strain curves; final bull's-eye plot (**C**) showing global results and superimposed regional values (dysfunctioning patient). AP2: apical two-chamber view; AP3: apical three-chamber view; AP4: apical four-chamber view; Deform. Long.: longitudinal deformation; EDV (bi-plane): end-diastolic volume (bi-plane); ESV (bi-plane): end-systolic volume (biplane); EF (bi-plane): ejection fraction (bi-plane); global Deform. Long. (GLS): global longitudinal strain; HR: heart rate.

#### *2.7.1. Ischemic cardiomyopathy*

In coronary artery disease, an assessment of myocardial ischemia other than simple visual wall motion score estimation (high inter-observer variability) has been invoked from a long time. Regional velocities (TDI) as well as peak systolic strain rate and systolic strain (TDI and STI) reduce linearly with a reduction in regional perfusion, time-delay prolongation to treatment, and the presence of fibrosis [14, 50, 51]. Subendocardial longitudinal fibers are the most vulnerable ones, resulting in an early deterioration of longitudinal strain, followed by radial and circumferential strains. Anyway, it's rather improper to consider a "radial function," because there are no myocardial fibers going in the radial direction. Actually, wall thickening measured by radial strain is a function of wall shortening, as the heart muscle is incompressible. At the same time, circumferential strain does not reflect circumferential fiber contraction because circumferential shortening is mainly due to the inward movement of mid-wall circumference as the wall thickens (inwards—as described by the eggshell model) [52–54]. Briefly, there would have been circumferential shortening even without circumferential fibers. These aspects, together with less standardized values than GLS, make GRS and GCS considerably reliable.

Dobutamine stress echocardiography is an important area of interest because in normal tissues an increased deformation occurs (continuously increasing strain/strain rate) as long as filling is not reduced by increased heart rate. On the contrary, acutely ischemic tissue during stress test shows less deformation and post-systolic deformation (PSD, thickening/shortening with radial/longitudinal strain, respectively), that is, the continued contraction of the myocardium after AVC. PSD is a common finding in myocardial ischemia. All these alterations are proportional to the severity of ischemia and persist in the experimental setting for up to 2 h after the ischemic insult resolution, with a peculiar time decay [55–57]. A noteworthy fact is that the stunned myocardium is characterized by decreased systolic deformation and PSD at rest, but almost normal systolic deformation and disappearance of PSD with dobutamine [50]. This behavior could be secondary to the heterogeneous contractile properties of the myocardium, probably linked to myofibrillar edema reducing the effective force myocardium can develop [58]. Furthermore, interstitial myocardial edema results in a sudden and temporary increase in end-diastolic wall thickness (this behavior is observed also in infarcted segments at the moment of reperfusion) [59, 60]. In chronic infarction, dobutamine is associated with low or no deformation increase, depending on the fibrosis extension (from subendocardial to transmurality involvement) [50].

#### *2.7.2. Volume overload*

Deformation is also closely related to ventricular geometry. Dilation is the end stage of most of the cardiomyopathies and heart valve diseases because for a given volume, the object with the smallest surface area is the sphere. This means that the same deformation (determined by the contractile force) can generate a larger stroke volume in a dilated heart. Similarly, in a dilated heart the same amount of stroke volume can be generated with less contractility and less deformation, that we can directly evaluate with strain(-rate) [14]. Remodeling in the long term will lead to irreversible damage to the heart muscle and finally ventricular dysfunction, but there is no specific diagnostic method to detect subclinical changes in systolic function. STI and TDI might potentially be useful in detecting subclinical changes in cardiac function [60].

Mitral regurgitation (MR) is a typical volume overload condition. Primary MR leads to cardiac remodeling, increased left ventricular filling pressure, pulmonary arterial hypertension, and myocardial dysfunction. Conventional 2D, M-mode, and Doppler examination play a critical role in the initial and longitudinal assessment; anyway, most variables are load dependent and both afterload and preload are altered during the disease course. TDI and STI provide new parameters to assess regional and global myocardial performance and may help in identifying asymptomatic patients and choosing the optimal time for surgical correction. It is worthy to note that patients with severe primary degenerative MR may have near-normal left ventricle ejection fractions (LVEFs) because of disproportionately higher compensation in GLS. Moreover, the higher the GLS, the higher the risk of substantial reduction in LVEF (>10%) during the immediate postoperative period [61]. On the contrary, in patients tested at 6 months after surgery, when LV reverse remodeling has already settled, LVEF reductions >10% were associated with lower baseline strains [62]. Chronic ischemic MR instead is not a valvular disease per se but is rather a "ventricular disease." In particular, inferior MI has been recognized as the most frequent cause of ischemic MR because of the geometric distortion in the papillary muscle-bearing segments [63]. Therefore, the site of MI might be a more important determinant of MR degree in LV dysfunction than the extent of post-MI LV remodeling. Under normal conditions, the basal rotation, which is determined mainly by inferior and posterior myocardial segments [64], shortens the distance between the mitral valve and the head of the papillary muscles, contributing to MVC and counterbalancing the tethering forces. When local remodeling occurs, as in patients with inferior-posterior MIs, the basal strain and basal rotation are significantly lower and fail to shorten the distance between the papillary muscles and the mitral valve. Interestingly, Zito et al. demonstrated that basal rotation but not basal strain was an independent predictor of the severity of MR [65].

## *2.7.3. Pressure overload*

*2.7.1. Ischemic cardiomyopathy*

100 Echocardiography in Heart Failure and Cardiac Electrophysiology

erably reliable.

transmurality involvement) [50].

*2.7.2. Volume overload*

In coronary artery disease, an assessment of myocardial ischemia other than simple visual wall motion score estimation (high inter-observer variability) has been invoked from a long time. Regional velocities (TDI) as well as peak systolic strain rate and systolic strain (TDI and STI) reduce linearly with a reduction in regional perfusion, time-delay prolongation to treatment, and the presence of fibrosis [14, 50, 51]. Subendocardial longitudinal fibers are the most vulnerable ones, resulting in an early deterioration of longitudinal strain, followed by radial and circumferential strains. Anyway, it's rather improper to consider a "radial function," because there are no myocardial fibers going in the radial direction. Actually, wall thickening measured by radial strain is a function of wall shortening, as the heart muscle is incompressible. At the same time, circumferential strain does not reflect circumferential fiber contraction because circumferential shortening is mainly due to the inward movement of mid-wall circumference as the wall thickens (inwards—as described by the eggshell model) [52–54]. Briefly, there would have been circumferential shortening even without circumferential fibers. These aspects, together with less standardized values than GLS, make GRS and GCS consid-

Dobutamine stress echocardiography is an important area of interest because in normal tissues an increased deformation occurs (continuously increasing strain/strain rate) as long as filling is not reduced by increased heart rate. On the contrary, acutely ischemic tissue during stress test shows less deformation and post-systolic deformation (PSD, thickening/shortening with radial/longitudinal strain, respectively), that is, the continued contraction of the myocardium after AVC. PSD is a common finding in myocardial ischemia. All these alterations are proportional to the severity of ischemia and persist in the experimental setting for up to 2 h after the ischemic insult resolution, with a peculiar time decay [55–57]. A noteworthy fact is that the stunned myocardium is characterized by decreased systolic deformation and PSD at rest, but almost normal systolic deformation and disappearance of PSD with dobutamine [50]. This behavior could be secondary to the heterogeneous contractile properties of the myocardium, probably linked to myofibrillar edema reducing the effective force myocardium can develop [58]. Furthermore, interstitial myocardial edema results in a sudden and temporary increase in end-diastolic wall thickness (this behavior is observed also in infarcted segments at the moment of reperfusion) [59, 60]. In chronic infarction, dobutamine is associated with low or no deformation increase, depending on the fibrosis extension (from subendocardial to

Deformation is also closely related to ventricular geometry. Dilation is the end stage of most of the cardiomyopathies and heart valve diseases because for a given volume, the object with the smallest surface area is the sphere. This means that the same deformation (determined by the contractile force) can generate a larger stroke volume in a dilated heart. Similarly, in a dilated heart the same amount of stroke volume can be generated with less contractility and less deformation, that we can directly evaluate with strain(-rate) [14]. Remodeling in the long term will lead to irreversible damage to the heart muscle and finally ventricular dysfunction, Considering pressure overload pathology, aortic stenosis (AS) is the most common valve lesion causing chronic pressure overload on the LV. The development of symptoms in AS heralds a malignant phase of the condition and prompt aortic valve replacement results in a clear reduction in mortality [66]. In contrast, the management of patients with severe AS in the absence of symptoms remains one of the most controversial and debated areas in modern cardiology [67, 68].

The increased afterload leads to left ventricular hypertrophy and the basal septal is the first to show changes, due to increased wall stress according to the Laplace law [69]. It first shows a decrease in strain(-rate) and the development of PSD is observed, as well as the development of localized hypertrophy (septal bulge) [70]. Recently, GLS has been shown to be an independent predictor of outcomes in patients with severe asymptomatic AS, incremental to other echocardiographic markers [71]. Not to forget, the role of exercise testing in asymptomatic AS is well established, and recommended by guidelines in equivocal cases [72].

## *2.7.4. Mechanical dyssynchrony*

Searching for the presence of mechanical dyssynchrony to identify potentially recruitable function, rather than looking only for electrocardiogram (ECG) manifestations of ventricular conduction delay, could increase the rate of cardiac resynchronization therapy (CRT) responders [73]. Mitigation of intraventricular dyssynchrony is currently thought to be the primary mechanism of improved myocardial performance with CRT. Anyway, many patients eligible for CRT have dilated ventricles with complex motion, especially if infarcted areas are present. Moreover, in dilated hearts local motion is importantly influenced by other myocardial segments and even by right ventricular motion [74]. That's why to this day, M-mode, 2D e TDI analyses have expressed modest sensitivity and specificity in measuring dyssynchrony and improving patient selection for CRT [73].

STI-based methods, mostly assessing the time difference between maximal values form different myocardial segments (e.g. septal to posterior wall motion delay [75], septal rebound stretch [76], wasted work ratio) [77, 78], are promising, but they must be validated in multicenter randomized trials.

## *2.7.5. Diabetic cardiomyopathy*

Another field of interest is represented by diabetes mellitus because studies showed that myocardial damage occurred in at least 30% diabetic patients when LV diameter and LVEF were normal [79]. Diabetic myocardial diastolic dysfunction seems to precede systolic dysfunction, but this might be explained by the insensitivity of techniques for detecting LV systolic function. In many but small studies, longitudinal dysfunction (segmental GLS) occurred in early stages of diabetes, while LV torsion increased compensatively [80–84].

## *2.7.6. Cancer therapeutics-related cardiac dysfunction*

Cardiotoxicity from cancer therapy has become a leading cause of morbidity and mortality in survivors [85, 86]. A careful consideration of potential cardiotoxicity during therapy and a focus on early detection and intervention are developing. Echocardiography is the cornerstone in the cardiac imaging evaluation of patients in preparation for, during, and after cancer therapy because of its wide availability, repeatability, versatility, lack of radiation exposure, and safety. The most commonly used parameter for monitoring LV function with echocardiography is LVEF. In addition, the calculation of LVEF should be combined with assessment of the wall motion score index [87]. Anyway, 2D echocardiography appears to be reliable in the detection of differences close to 10% in LVEF [88]. Because this is the same magnitude of change used to adjudicate cancer therapeutics-related cardiac dysfunction, the sensitivity of LVEF has been questioned. Moreover, detecting a decreased LVEF after anthracyclines may be too late for treatment [89], suggesting that more sensitive parameters of LV dysfunction could be helpful. The prognostic value of early measurement of systolic deformation indices (above all ΔGLS) measured in the prediction of subsequent LV systolic function has been evaluated in several studies, both in animals [90] and in humans [91–94].

## *2.7.7. Left atrium*

*2.7.4. Mechanical dyssynchrony*

102 Echocardiography in Heart Failure and Cardiac Electrophysiology

improving patient selection for CRT [73].

*2.7.6. Cancer therapeutics-related cardiac dysfunction*

in several studies, both in animals [90] and in humans [91–94].

center randomized trials.

*2.7.5. Diabetic cardiomyopathy*

Searching for the presence of mechanical dyssynchrony to identify potentially recruitable function, rather than looking only for electrocardiogram (ECG) manifestations of ventricular conduction delay, could increase the rate of cardiac resynchronization therapy (CRT) responders [73]. Mitigation of intraventricular dyssynchrony is currently thought to be the primary mechanism of improved myocardial performance with CRT. Anyway, many patients eligible for CRT have dilated ventricles with complex motion, especially if infarcted areas are present. Moreover, in dilated hearts local motion is importantly influenced by other myocardial segments and even by right ventricular motion [74]. That's why to this day, M-mode, 2D e TDI analyses have expressed modest sensitivity and specificity in measuring dyssynchrony and

STI-based methods, mostly assessing the time difference between maximal values form different myocardial segments (e.g. septal to posterior wall motion delay [75], septal rebound stretch [76], wasted work ratio) [77, 78], are promising, but they must be validated in multi-

Another field of interest is represented by diabetes mellitus because studies showed that myocardial damage occurred in at least 30% diabetic patients when LV diameter and LVEF were normal [79]. Diabetic myocardial diastolic dysfunction seems to precede systolic dysfunction, but this might be explained by the insensitivity of techniques for detecting LV systolic function. In many but small studies, longitudinal dysfunction (segmental GLS) occurred in early stages of diabetes, while LV torsion increased compensatively [80–84].

Cardiotoxicity from cancer therapy has become a leading cause of morbidity and mortality in survivors [85, 86]. A careful consideration of potential cardiotoxicity during therapy and a focus on early detection and intervention are developing. Echocardiography is the cornerstone in the cardiac imaging evaluation of patients in preparation for, during, and after cancer therapy because of its wide availability, repeatability, versatility, lack of radiation exposure, and safety. The most commonly used parameter for monitoring LV function with echocardiography is LVEF. In addition, the calculation of LVEF should be combined with assessment of the wall motion score index [87]. Anyway, 2D echocardiography appears to be reliable in the detection of differences close to 10% in LVEF [88]. Because this is the same magnitude of change used to adjudicate cancer therapeutics-related cardiac dysfunction, the sensitivity of LVEF has been questioned. Moreover, detecting a decreased LVEF after anthracyclines may be too late for treatment [89], suggesting that more sensitive parameters of LV dysfunction could be helpful. The prognostic value of early measurement of systolic deformation indices (above all ΔGLS) measured in the prediction of subsequent LV systolic function has been evaluated

Speckle tracking was recently applied to study the myocardial mechanics of a thin-walled structure such as the LA [95–98]. For the analysis, apical views are obtained using conventional 2D gray-scale echocardiography, during a breath-hold, with a stable electrocardiographic recording. The frame rate is set between 60 and 80 frames/s, and recordings are processed using acoustic-tracking software. The LA mechanical indices are calculated by averaging values observed in all LA segments (global strain) with a 15-segment or a 12-segment model. The software generates longitudinal strain and strain rate curves for each atrial segment. The radial deformation cannot be calculated because the LA wall is thin and the spatial resolution is limited [99].

## *2.7.8. Right ventricle*

A recent methodological study has reported the feasibility, the reference values, and the reproducibility of right ventricular longitudinal strain measured by STI in normal patients and in patients with RV dysfunction [100]. The technique is similar as for LV: global strain is the average of six single segments (ROI) traced semi-automatically and processed by software packages (today, a dedicated software for RV does not exist). The evaluation of right ventricular function with STI, considering the important limitations of other parameters and methods, could offer more detailed information about regional and global RV mechanics with important clinical implications for non-invasive evaluation of RV systolic function (subclinical RV dysfunction). Further prospective studies are necessary to define its role in the management of patients.

## **3. Limitations**

Rotation, deformation, and out-of-plane motion can cause speckle patterns to change between acquisitions (decorrelation). Loss of tracking can be limited acquiring at a proper frame rate. Image artifacts should be avoided. In general, high-quality acquisition is a prerequisite for optimal speckle-tracking results [16].

Among limitations of the method, we should include:


tion and depth; depth dependence of transverse tracking; out-of-plane motion in short axis limiting tracking of the same ROI; noise.

Evaluation of radial strain poses important technical challenges compared to longitudinal one.

This is due to:


## **4. Conclusions**

Speckle tracking is actually a reality in echocardiography. Simple protocols of acquisition and novel processing packages have made available deformation analysis in daily clinical arena.

Overcoming many of the previous limitations, thanks to technological development, including 3D introduction and STI, offers to the cardiologists the potential benefit of a solid, fast, easy, and reproducible quantization of myocardial mechanics [37].

## **Author details**

Iacopo Fabiani1\*, Nicola Riccardo Pugliese2 , Veronica Santini1 , Lorenzo Conte1 and Vitantonio Di Bello1

\*Address all correspondence to: iacopofabiani@gmail.com

1 Dept. Section Universitary Cardio-Angiology, Surgical, Medical, Molecular and Critical Area Pathology Department, Pisa Univeristy, Pisa, Italy

2 Operative Unit Cardio-Vascular Disease Univ., Surgical, Medical, Molecular and Critical Area Pathology Department, Pisa Univeristy, Pisa, Italy

## **References**

[1] Perk G, Tunick PA, Kronzon I. Non-Doppler two-dimensional strain imaging by echocardiography – from technical considerations to clinical applications. J Am Soc Echocardiogr. 2007;20:234–243. DOI: 10.1016/j.echo.2006.08.023

[2] Dandel M, Lehmkuhl H, Knosalla C, Suramelashvili N, Hetzer R. Strain and strain rate imaging by echocardiography – basic concepts and clinical applicability. Curr Cardiol Rev. 2009;5:133–148. DOI: 10.2174/157340309788166642

tion and depth; depth dependence of transverse tracking; out-of-plane motion in short axis

Evaluation of radial strain poses important technical challenges compared to longitudinal one.

**•** Measurements in the axial plane are more reliable than those that depend on lateral and

**•** Limited amount of tissue to track in the short-axis view of the non-hypertrophied heart;

Speckle tracking is actually a reality in echocardiography. Simple protocols of acquisition and novel processing packages have made available deformation analysis in daily clinical arena. Overcoming many of the previous limitations, thanks to technological development, including 3D introduction and STI, offers to the cardiologists the potential benefit of a solid, fast, easy,

, Veronica Santini1

1 Dept. Section Universitary Cardio-Angiology, Surgical, Medical, Molecular and Critical Area

2 Operative Unit Cardio-Vascular Disease Univ., Surgical, Medical, Molecular and Critical

[1] Perk G, Tunick PA, Kronzon I. Non-Doppler two-dimensional strain imaging by echocardiography – from technical considerations to clinical applications. J Am Soc

Echocardiogr. 2007;20:234–243. DOI: 10.1016/j.echo.2006.08.023

, Lorenzo Conte1

and

limiting tracking of the same ROI; noise.

104 Echocardiography in Heart Failure and Cardiac Electrophysiology

elevation (or azimuthal) resolution;

**•** Placement of the ROI is user defined;

Iacopo Fabiani1\*, Nicola Riccardo Pugliese2

and reproducible quantization of myocardial mechanics [37].

\*Address all correspondence to: iacopofabiani@gmail.com

Pathology Department, Pisa Univeristy, Pisa, Italy

Area Pathology Department, Pisa Univeristy, Pisa, Italy

**•** Intervendors' differences.

**4. Conclusions**

**Author details**

Vitantonio Di Bello1

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This is due to:


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s00059-014-4138-6


## **Cardiac Imaging in Hypertrophic Cardiomyopathy Cardiac Imaging in Hypertrophic Cardiomyopathy**

Dai-Yin Lu and Ming-Chong Hsiung Dai-Yin Lu and Ming-Chong Hsiung

Additional information is available at the end of the chapter Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64364

## **Abstract**

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[102] Gayat E, Ahmad H, Weinert L, Lang RM, Mor-Avi V. Reproducibility and inter-vendor variability of left ventricular deformation measurements by three-dimensional speckletracking echocardiography. J Am Soc Echocardiogr. 2011;24:878–885. DOI: 10.1016/

2005.06.001

114 Echocardiography in Heart Failure and Cardiac Electrophysiology

ejechocard/jer174

j.echo.2011.04.016

Hypertrophic cardiomyopathy (HCM) is a relatively common inherited cardiomyop‐ athy, which is occasionally challenging to differentiate from hypertensive heart disease and athlete hearts on the basis of morphologic or functional abnormalities alone. Imaging studies provide solutions for most clinical needs, from diagnosis, anatomical and functional assessment, family screening, risk stratification, to monitoring of treatment response. Generally, transthoracic echocardiography is used as first‐line imaging tool to establish the diagnosis. A multimodality imaging approach (cardiac magnetic resonance, cardiac computed tomography, and cardiac nuclear imaging) is also encouraged in the assessment of these patients. The choice of imaging tool should be based on a broad perspective and expert knowledge of what each technique has to offer, including its specific advantages and disadvantages. In this chapter, we discuss the utility and pitfalls of established imaging modalities and discuss the evolving role of novel echocardiographic imaging modalities.

**Keywords:** cardiac computed tomography, cardiovascular magnetic resonance, echo‐ cardiography, hypertrophic cardiomyopathy, nuclear imaging

## **1. Introduction**

## **1.1. Definition and prevalence**

Hypertrophic cardiomyopathy (HCM) is the most common inherited cardiac disease presented with exercise intolerance, heart failure, cardiac arrhythmias and sudden cardiac death [1]. Across different ethnicities, the prevalence is approximately 0.2% [2]. This estimated frequency in the general population appears to exceed the relatively low visit of HCM in cardiology practices, implying that the most affected individuals remain undiagnosed, probably in most cases without symptoms or shortened life expectancy [3]. The clinical

diagnosis of HCM is based on the demonstration of asymmetric left ventricular hypertrophy (LVH) with maximal wall thickness ≥15 mm, in the absence of other cardiac or systemic cause that would produce such magnitude of hypertrophy.

## **1.2. Natural history and clinical course**

The natural history is generally benign in vast majority of patients, with a life span close to general population [4]. However, hemodynamic‐related symptoms secondary to dynamic left ventricular outflow tract (LVOT) obstruction as well as myopathy‐related complications may happen. Although symptoms may occur at any age, they are more common between young adult and middle age. Development of symptoms at older age is generally associated with less severe forms of the disease.

Although HCM presents primarily with ventricular septal hypertrophy, a key recognizable feature has been dynamic LVOT obstruction and HCM has been regarded as a predominantly obstructive disease [5]. Left ventricular outflow tract (LVOT) obstruction may be noted at rest or during physiological exercise in 50–70% of the HCM patients [6]. LVOT obstruction at rest, defined as ≥30 mmHg, is a strong, independent predictor for progression of heart failure and death [7, 8]. Accordingly, current AHA/ACC/ESC guidelines classify HCM patients based on their LVOT gradients into obstructive (resting and provoked gradients ≥30 mmHg); latent obstructive (resting <30 and provoked ≥30 mmHg); non‐obstructive (resting and provoked gradients <30 mmHg) [3, 4].

HCM also represents the most frequent cause of sudden cardiac death (SCD), one of the most serious complications, in young athletes in countries without systematic sport screening programs. Dynamic LVOT obstruction and disarrayed myocardial fiber impair diastolic function of left ventricle, followed by enlargement of left atrium and heart failure with preserved ejection fraction (EF). Atrial fibrillation (AF) is also a clinical presentation secondary to left atrial enlargement, which may later cause cardioembolic events and the following disability in the middle and older age groups.

## **2. The role of imaging in HCM**

Multimodality imaging—echocardiography, cardiac magnetic resonance, cardiac computed tomography, and cardiac nuclear imaging—provide comprehensive information. Patients with HCM usually require long‐term follow‐up. It is suggested that transthoracic echocardiography be performed every 1–2 years and cardiac magnetic resonance at least once after the diagnosis is made, yet the strategy needs to be individualized (**Table 1**).

## **2.1. Role of echocardiography in evaluation of HCM (Table 2) [9]**

## *2.1.1. Anatomical evaluation*

HCM presents primarily with LVH, which progresses with time (**Figure 1**). The presentation is rare when in childhood, and the growth of LVH becomes more obvious during adolescence. Other systemic causes of LVH (obesity, athlete heart, systemic hypertension, aortic stenosis, or infiltrative disease) should be ruled out first before the diagnosis is confirmed. The pattern of hypertrophy and LV volume can be analyzed by echocardiography. Ventricular volumes are generally normal or slightly lower, and the biplane Simpson's method has been applied to the measurement of LV volumes and EF [10]. Three‐dimensional (3D) echocardiography has also been shown to provide more accurate means of quantification, [11] yet the references for HCM are limited.


**Table 1.** Imaging tools in HCM.

diagnosis of HCM is based on the demonstration of asymmetric left ventricular hypertrophy (LVH) with maximal wall thickness ≥15 mm, in the absence of other cardiac or systemic cause

The natural history is generally benign in vast majority of patients, with a life span close to general population [4]. However, hemodynamic‐related symptoms secondary to dynamic left ventricular outflow tract (LVOT) obstruction as well as myopathy‐related complications may happen. Although symptoms may occur at any age, they are more common between young adult and middle age. Development of symptoms at older age is generally associated with less

Although HCM presents primarily with ventricular septal hypertrophy, a key recognizable feature has been dynamic LVOT obstruction and HCM has been regarded as a predominantly obstructive disease [5]. Left ventricular outflow tract (LVOT) obstruction may be noted at rest or during physiological exercise in 50–70% of the HCM patients [6]. LVOT obstruction at rest, defined as ≥30 mmHg, is a strong, independent predictor for progression of heart failure and death [7, 8]. Accordingly, current AHA/ACC/ESC guidelines classify HCM patients based on their LVOT gradients into obstructive (resting and provoked gradients ≥30 mmHg); latent obstructive (resting <30 and provoked ≥30 mmHg); non‐obstructive (resting and provoked

HCM also represents the most frequent cause of sudden cardiac death (SCD), one of the most serious complications, in young athletes in countries without systematic sport screening programs. Dynamic LVOT obstruction and disarrayed myocardial fiber impair diastolic function of left ventricle, followed by enlargement of left atrium and heart failure with preserved ejection fraction (EF). Atrial fibrillation (AF) is also a clinical presentation secondary to left atrial enlargement, which may later cause cardioembolic events and the following

Multimodality imaging—echocardiography, cardiac magnetic resonance, cardiac computed tomography, and cardiac nuclear imaging—provide comprehensive information. Patients with HCM usually require long‐term follow‐up. It is suggested that transthoracic echocardiography be performed every 1–2 years and cardiac magnetic resonance at least once after the diagnosis

HCM presents primarily with LVH, which progresses with time (**Figure 1**). The presentation is rare when in childhood, and the growth of LVH becomes more obvious during adolescence.

that would produce such magnitude of hypertrophy.

116 Echocardiography in Heart Failure and Cardiac Electrophysiology

**1.2. Natural history and clinical course**

severe forms of the disease.

gradients <30 mmHg) [3, 4].

disability in the middle and older age groups.

is made, yet the strategy needs to be individualized (**Table 1**).

**2.1. Role of echocardiography in evaluation of HCM (Table 2) [9]**

**2. The role of imaging in HCM**

*2.1.1. Anatomical evaluation*


LA = left atrium; LV = left ventricle; MV = mitral valve; PA = pulmonary artery; RV = right ventricle; TEE = transesophageal echocardiography (Adapted with permission from Nagueh et al. [9]).

**Table 2.** Echocardiogrophic evaluations of patients with HCM.

**Figure 1.** Left ventricular thickness, evaluated at septum and free wall level, is considered abnormal when ≥ 15 mm, and defined asymmetrical in presence of a septal to free wall thickness ratio between 1.3 and 1.5.

#### *2.1.2. Hemodynamic evaluation*

A key recognizable feature has been dynamic LVOT obstruction, and HCM has been regarded as a predominantly obstructive disease [5]. Patients with LVOT obstruction, defined by the presence of a peak gradient higher than 30 mmHg at rest or after provocative maneuvers (Valsalva, standing, and exercise) is a strong, independent predictor for progression of heart failure and death [7, 8] (**Figure 2**). Structural abnormalities of the mitral valve apparatus in HCM include hypertrophy of the papillary muscles, resulting in anterior displacement of papillary muscles, and mitral valve elongation [12, 13]. Systolic anterior motion (SAM) is defined as the systolic motion of the mitral leaflet, mainly anterior leaflet, or chordae into LVOT, resulting in outlet narrowing and flow disturbance. SAM also impairs the mitral leaflet coaptation, followed by regurgitation (**Figure 3**). The anterior leaflet motion is greater than that of the posterior leaflet during SAM and an interleaflet gap occurs, resulting in a typically posteriorly directed jet of mitral regurgitation. The anterior leaflet has a greater surface area and hence greater redundancy and mobility. If a concentric regurgitation jet is found in HCM patients, concomitant mitral valvulopathy should be carefully evaluated.

#### *2.1.3. Assessment of LV systolic function*

The ejection fraction of left ventricle in HCM patients is generally normal or even increased. However, patients with significant hypertrophy may have small LV end‐diastolic volumes and the following lower stroke volumes despite a normal LVEF. LV systolic dysfunction is usually defined as LVEF < 50%. When present, the prognosis is markedly worse. In addition to 2D imaging, Doppler echocardiography has been used to assess subclinical LV systolic dysfunc‐ tion. Tissue Doppler imaging measures the velocity of myocardial motion. A lower systolic (Sa) or reduced early diastolic (Ea or e′) velocities can occur before overt hypertrophy devel‐ ops [14].

**Figure 2.** (A) Asymmetric septal hypertrophy may cause narrowing of the left ventricular outflow tract, resulting in turbulent flow. (B) Doppler analysis across the LVOT in dynamic obstructive HCM results in a characteristic signal with a late‐peaking dagger‐shaped appearance.

#### *2.1.4. Assessment of LV diastolic function*

**Figure 1.** Left ventricular thickness, evaluated at septum and free wall level, is considered abnormal when ≥ 15 mm,

A key recognizable feature has been dynamic LVOT obstruction, and HCM has been regarded as a predominantly obstructive disease [5]. Patients with LVOT obstruction, defined by the presence of a peak gradient higher than 30 mmHg at rest or after provocative maneuvers (Valsalva, standing, and exercise) is a strong, independent predictor for progression of heart failure and death [7, 8] (**Figure 2**). Structural abnormalities of the mitral valve apparatus in HCM include hypertrophy of the papillary muscles, resulting in anterior displacement of papillary muscles, and mitral valve elongation [12, 13]. Systolic anterior motion (SAM) is defined as the systolic motion of the mitral leaflet, mainly anterior leaflet, or chordae into LVOT, resulting in outlet narrowing and flow disturbance. SAM also impairs the mitral leaflet coaptation, followed by regurgitation (**Figure 3**). The anterior leaflet motion is greater than that of the posterior leaflet during SAM and an interleaflet gap occurs, resulting in a typically posteriorly directed jet of mitral regurgitation. The anterior leaflet has a greater surface area and hence greater redundancy and mobility. If a concentric regurgitation jet is found in HCM

The ejection fraction of left ventricle in HCM patients is generally normal or even increased. However, patients with significant hypertrophy may have small LV end‐diastolic volumes and the following lower stroke volumes despite a normal LVEF. LV systolic dysfunction is usually

and defined asymmetrical in presence of a septal to free wall thickness ratio between 1.3 and 1.5.

patients, concomitant mitral valvulopathy should be carefully evaluated.

*2.1.2. Hemodynamic evaluation*

118 Echocardiography in Heart Failure and Cardiac Electrophysiology

*2.1.3. Assessment of LV systolic function*

Reduction in ventricular compliance and increased stiffness due to myocardial fibrosis coupled with a reduction of chamber volume and suction play a role in the pathophysiol‐ ogy of diastolic dysfunction in patients with HCM. LV and left atrial (LA) filling abnor‐ malities have been reported in patients with HCM, irrespective of the presence and extent of LV hypertrophy. Tissue Doppler echocardiography indicates impaired myocardial relax‐ ation regardless of symptoms or severity of LVOT obstruction [15]. Although tissue Dop‐ pler echocardiography has been successfully used to estimate filling pressures in a variety of cardiac disorders [16, 17], it is not as reliable in patients with hypertrophic cardiomy‐ opathy as in patients with left ventricular systolic dysfunction [18]. In a study consisting of 35 patients, LV filling pressures can be estimated with reasonable accuracy in HCM patients by measuring mitral early diastolic inflow/flow propagation velocity or ratio of early diastolic mitral flow velocity to the early diastolic mitral septal annulus motion ve‐ locity (E/e′) [19]. Whereas a later report with symptomatic HCM patients concluded Dop‐ pler echocardiographic estimates of left ventricular filling pressure with the use of transmitral flow and mitral annular velocities correlated modestly with direct measure‐ ment of left atrial pressure [20]. Despite of this inconsistency in filling pressure estima‐ tion, tissue Doppler imaging remains a useful tool for risk stratification of patients with HCM [21]. A higher septal E/e′ predicts patients with HCM who are at risk of sustained ventricular tachycardia (VT), implantable cardioverter defibrillator (ICD) discharge, car‐ diac arrest or sudden cardiac death [22, 23].

**Figure 3.** Systolic anterior motion (SAM) of anterior mitral leaflet at mid to late systolic phase (A) parasternal long axis view, 2D; (B) parasternal long axis view, M‐mode.

LA volume is mainly secondary to diastolic dysfunction, mitral regurgitation and atrial myopathy. LA enlargement is generally assessed by 2D or M‐mode linear dimensions. However, it is important to recognize that linear dimensions, particularly anteroposterior measurements of the LA, may not measure true LA size, as LA remodeling frequently happens asymmetrically [24]. Increased LA volume is an independent indicator of functional capacity [25] and an LA volume index of >34 ml/m2 has been shown to be predictive of a more severe LVH, diastolic dysfunction, and adverse cardiovascular outcomes [26].

## **2.2. Role of deformation imaging in HCM**

#### *2.2.1. TDI-derived strain*

of 35 patients, LV filling pressures can be estimated with reasonable accuracy in HCM patients by measuring mitral early diastolic inflow/flow propagation velocity or ratio of early diastolic mitral flow velocity to the early diastolic mitral septal annulus motion ve‐ locity (E/e′) [19]. Whereas a later report with symptomatic HCM patients concluded Dop‐ pler echocardiographic estimates of left ventricular filling pressure with the use of transmitral flow and mitral annular velocities correlated modestly with direct measure‐ ment of left atrial pressure [20]. Despite of this inconsistency in filling pressure estima‐ tion, tissue Doppler imaging remains a useful tool for risk stratification of patients with HCM [21]. A higher septal E/e′ predicts patients with HCM who are at risk of sustained ventricular tachycardia (VT), implantable cardioverter defibrillator (ICD) discharge, car‐

**Figure 3.** Systolic anterior motion (SAM) of anterior mitral leaflet at mid to late systolic phase (A) parasternal long axis

LA volume is mainly secondary to diastolic dysfunction, mitral regurgitation and atrial myopathy. LA enlargement is generally assessed by 2D or M‐mode linear dimensions. However, it is important to recognize that linear dimensions, particularly anteroposterior measurements of the LA, may not measure true LA size, as LA remodeling frequently happens

(A)

(B)

diac arrest or sudden cardiac death [22, 23].

120 Echocardiography in Heart Failure and Cardiac Electrophysiology

view, 2D; (B) parasternal long axis view, M‐mode.

Although tissue Doppler velocity was considered as a technique for evaluation of regional myocardial performance, the utility is limited in distinguishing myocardial contractility from passive motion. Such restriction later leads to the development of strain imaging. Strain is a measure of tissue deformation and is defined as the change in length normalized to the original length. The rate at which this change occurs is called strain rate (SR). In contrast to tissue Doppler velocity, which examines myocardial motion relative to the transducer, strain measures myocardial motion relative to the adjacent myocardium [27]. When the left ventricle contracts, the myocardium shortens in longitudinal and circumferential direction (negative value in strain) and thickens in the radial direction (positive value in strain) (**Figure 4**) [28]. Strain rate (SR) represents the local rate of myocardial deformation (**Figure 5**) [29]. Weidemann et al. (30) firstly described the use of TDI‐derived strain for the evaluation of HCM in a case report of a child with non‐obstructive HCM. Tissue Doppler velocities were found to be normal in all the septal segments interrogated. However, systolic longitudinal strain SR was signifi‐ cantly decreased in the mid septal region with no significant changes in the basal regions when compared with healthy children [30]. Later reports also confirmed similar findings in adults with HCM [31, 32].

**Figure 4.** Graphic representation of the principal myocardial deformations: longitudinal (A), radial and circumferential (B), and torsion (C). The direction of deformation in systole is shown as solid lines and that in diastole is shown as dashed lines. LONG indicates longitudinal; RAD, radial; and CIRC, circumferential. (Reprinted with permission from Abraham et al. [28]).

**Figure 5.** Strain analysis from tissue Doppler imaging from three representative regions of interest (ROIs) in LV septal wall.

## *2.2.2. 2D strain or speckle tracking imaging*

The interaction of ultrasound with the myocardium produces unique acoustic patterns, also known as "speckles." These speckles can be tracked over time and speckle displacement can be used to calculate the tissue velocity and strain [33]. This method is not based on the Doppler principle and relatively angle independent [34]. Deformation is calculated with frame‐by‐ frame speckle displacement, yielding angle independent parameters of myocardial contrac‐ tion, and gives longitudinal, transverse strain and strain rate in long‐axis images (**Figure 6**). Similarly, radial and circumferential strain or strain rate may be analyzed by the short‐axis images. In a study for patients with familial non‐obstructive HCM, average longitudinal was reduced in affected individuals compared with healthy controls, despite apparently normal systolic function. In addition, no significant difference in the values obtained by TDI versus 2D strain echocardiography was observed [35]. A recent study of patients with HCM and preserved systolic function demonstrated attenuated longitudinal strain, increased circum‐ ferential strain, and normal overall systolic LV twist or torsion [36].

**Figure 6.** Strain analysis from two‐dimensional speckle tracking from apical four chamber view.

## **2.3. Application of interventional echocardiography in HCM**

## *2.3.1. Alcohol septal ablation (ASA)*

**Figure 5.** Strain analysis from tissue Doppler imaging from three representative regions of interest (ROIs) in LV septal

The interaction of ultrasound with the myocardium produces unique acoustic patterns, also known as "speckles." These speckles can be tracked over time and speckle displacement can be used to calculate the tissue velocity and strain [33]. This method is not based on the Doppler principle and relatively angle independent [34]. Deformation is calculated with frame‐by‐ frame speckle displacement, yielding angle independent parameters of myocardial contrac‐ tion, and gives longitudinal, transverse strain and strain rate in long‐axis images (**Figure 6**). Similarly, radial and circumferential strain or strain rate may be analyzed by the short‐axis images. In a study for patients with familial non‐obstructive HCM, average longitudinal was reduced in affected individuals compared with healthy controls, despite apparently normal systolic function. In addition, no significant difference in the values obtained by TDI versus 2D strain echocardiography was observed [35]. A recent study of patients with HCM and preserved systolic function demonstrated attenuated longitudinal strain, increased circum‐

ferential strain, and normal overall systolic LV twist or torsion [36].

**Figure 6.** Strain analysis from two‐dimensional speckle tracking from apical four chamber view.

wall.

*2.2.2. 2D strain or speckle tracking imaging*

122 Echocardiography in Heart Failure and Cardiac Electrophysiology

2D echo is useful in search of suitable patients for ASA. During the procedure under trans‐ thoracic echocardiographic guidance, injection of echo contrast into a septal perforator branch of the left anterior descending artery helps determine whether the selected branch to occlude supplies the appropriate myocardium where SAM contacts interventricular septum (**Fig‐ ure 7**) [37]. For patients with suboptimal transthoracic echo window, transesophageal echo imaging may be another option.

**Figure 7.** Myocardial contrast echocardiography of the hypertrophied septum after injection of sonicated albumin (Contrast) and ethanol (Reprinted wth permission from Nagueh et al. [37]).

## *2.3.2. Surgical myectomy and mitral surgery*

It is important to have a real‐time imaging analysis in the peri‐procedural assessment of HCM patients undergoing myectomy, with or without mitral surgery. Intraoperative Transesopha‐ geal echocardiography (TEE) plays a key role in surgery, assessing mechanisms of LVOTO, mechanism of MR, extension of myocardial region that need to be removed and other possible intra‐operative complications.

## **2.4. Other imaging modality**

## *2.4.1. Cardiac magnetic resonance (Table 3) [38]*

#### *2.4.1.1. Anatomical evaluation*

Cardiac magnetic resonance (CMR) should be considered in the initial evaluation of all patients with HCM when clinic resources are available [4]. It provides comprehensive evaluation of both the ventricle, including assessment of wall thickness [39–41] and the chamber volumes, with high quality of spatial and temporal resolution (**Figure 8**) [38]. CMR may be more sensitive than echocardiography in detecting LVH [40]. The extension of LVH can be defined using CMR as focal (1–2 hypertrophic segments), intermediate (3–7 segments), and diffuse (8–16 hyper‐ trophic segments). CMR can also give more precise measurement in maximal diastolic wall thickness [42].

Left ventricle volumes, mass and ejection fraction Location, type, distribution of hypertrophy, maximal wall thickness and diastolic wall thickness to volume ratio Degree of asymmetry LVOT or mid‐cavity obstruction LGE: presence or absence; pattern and extension Evidence of MR Description of mitral valve apparatus (leaflets, chordae, papillary muscles) and its relation to obstruction or MR

LGE = late gadolinium enhancement; LVOT = left ventricular outlet tract; MR = mitral regurgitation. (Adapted with permission from Cardim et al. [38].)

**Table 3.** CMR evaluations of patients with HCM.

**Figure 8.** Cardiac MR in HCM patients. Cine CMR‐SSFP in different HCM patients. (A) Basal short‐axis view, asym‐ metric LVH with lateral wall sparing. (B) Three‐chamber view, mid‐ventricular hypertrophy of the medial segments of the posterior wall and anterior interventricular septum. (C) short‐axis view, LVH localized in the anteroseptal wall (18 mm), undetected by echocardiography. (D) Three‐chamber view, systolic phase. (Reprinted with permission from Car‐ dim et al. [38]).

#### *2.4.1.2. Tissue characterization*

CMR is the most important technique in tissue characterization. The principle of late gadoli‐ nium enhancement (LGE) in CMR is based on those tissues, with an expanded extracellular space that provides a larger distribution volume for the conventional CMR contrast agents, which occupy extravascular and extracellular space. Within 30 minutes, differences between the tissue with normal and expanded extracellular volumes are large and LGE imaging is acquired (**Figure 9**) [43]. Current LGE protocols provide a very high spatial resolution (≤1 mm) and also provide a very high contrast to noise ratio, allowing to delineate small amounts of myocardial fibrosis. In HCM patients, there is frequent [44] and progressive [45] fibrosis. Two major patterns of LGE distribution are demonstrated: Intramural LGE was seen within the hypertrophied segments, which are thought to be reflective of replacement fibrosis [46]. RV insertion points LGE corresponds to interstitial fibrosis and myocyte disarray [47].

**Figure 9.** Pre‐ and post‐contrast CMR images demonstrating enhancement. The pre‐contrast images are the diastolic frames of fast imaging with steady‐state precession cine loops. In the post‐contrast images, normal myocardium ap‐ pears dark. There is a large area of septal enhancement, with additional papillary muscle enhancement and subendo‐ cardial enhancement of the lateral wall. The total extent of enhancement was 25% of the left ventricular mass. (Reprinted with permission from Moon et al. [43]).

## *2.4.2. Cardiac nuclear imaging*

as focal (1–2 hypertrophic segments), intermediate (3–7 segments), and diffuse (8–16 hyper‐ trophic segments). CMR can also give more precise measurement in maximal diastolic wall

Location, type, distribution of hypertrophy, maximal wall thickness and diastolic wall thickness to volume ratio

Description of mitral valve apparatus (leaflets, chordae, papillary muscles) and its relation to obstruction or MR LGE = late gadolinium enhancement; LVOT = left ventricular outlet tract; MR = mitral regurgitation. (Adapted with

**Figure 8.** Cardiac MR in HCM patients. Cine CMR‐SSFP in different HCM patients. (A) Basal short‐axis view, asym‐ metric LVH with lateral wall sparing. (B) Three‐chamber view, mid‐ventricular hypertrophy of the medial segments of the posterior wall and anterior interventricular septum. (C) short‐axis view, LVH localized in the anteroseptal wall (18 mm), undetected by echocardiography. (D) Three‐chamber view, systolic phase. (Reprinted with permission from Car‐

CMR is the most important technique in tissue characterization. The principle of late gadoli‐ nium enhancement (LGE) in CMR is based on those tissues, with an expanded extracellular space that provides a larger distribution volume for the conventional CMR contrast agents, which occupy extravascular and extracellular space. Within 30 minutes, differences between the tissue with normal and expanded extracellular volumes are large and LGE imaging is

thickness [42].

Degree of asymmetry

Evidence of MR

dim et al. [38]).

*2.4.1.2. Tissue characterization*

LVOT or mid‐cavity obstruction

permission from Cardim et al. [38].)

Left ventricle volumes, mass and ejection fraction

124 Echocardiography in Heart Failure and Cardiac Electrophysiology

LGE: presence or absence; pattern and extension

**Table 3.** CMR evaluations of patients with HCM.

Single photon‐emission computed tomography (SPECT) myocardial perfusion imaging with Thallium‐201 and Tc‐99 m labelled tracers often demonstrate reversible (suggestive of ische‐ mia) and fixed defects (scar), even when there is no obvious epicardial coronary artery disease [48]. The positive predictive value for SPECT study in HCM is relatively low for epicardial coronary artery disease compared to a high negative predictive value. Ischemic and scarring have been demonstrated a predictor of worse outcome, including adverse remodeling, systolic dysfunction and sudden cardiac death [49]. In obstructive HCM patients, improvement of perfusion may be observed when the obstruction is relieved after myectomy (**Figure 10**) [38, 50].

**Figure 10.** Functional imaging of ischemia with single photon‐emission computed tomography (SPECT) with Tc‐99m‐ Sestamibi in a 34‐year‐old male patient with HCM with history of chest pain in the absence of epicardial coronary ar‐ tery disease). Stress (upper row) and rest (lower row). A fixed, non‐reversible defect (scar) in the basal segments of the LV was found, with a non‐coronary artery distribution. The apical perfusion is normal. However, this pattern may be a false perfusion defect due to increased hypertrophic mid‐ventricular and apical uptake of the radiotracer. (Reprinted with permission from Cardim et al. [38]).

Using N‐13‐labelled ammonia and O‐15‐labelled water, proton emission tomography (PET) imaging detects absolute myocardial blood flow in patients with HCM. In contrast to SPECT, PET allows the direct quantification of myocardial blood flow (**Figure 11**) [38]. PET imaging

**Figure 11.** Functional imaging of ischemia with nuclear proton emission tomography (PET). Stress dipyridamole (up‐ per row) and rest (lower row) 13NH3 perfusion images in an 14‐year‐old girl diagnosed with HCM with interventricu‐ lar septum (IVS) 29 mm. Stress: LV dilation and subendocardial hypoperfusion (IVS and antero‐lateral wall). Rest: increased IVS 13NH3 uptake is seen, indicative of IVS hypertrophy. (Reprinted with permission from Cardim et al. [38]).

is the most reliable noninvasive quantitative method for assessing myocardial ischemia in HCM [51].

## **3. Summary**

Echocardiography remains the first-line imaging tool in the assessment of HCM patients, while the role of cardiac MR and nuclear imaging is getting more and more important, providing specific clinical information, which echocardiography is unable to give. The assessment of fibrosis, tissue characterization, and myocardial function, represents imaging future priorities of HCM imaging.

## **Author details**

**Figure 10.** Functional imaging of ischemia with single photon‐emission computed tomography (SPECT) with Tc‐99m‐ Sestamibi in a 34‐year‐old male patient with HCM with history of chest pain in the absence of epicardial coronary ar‐ tery disease). Stress (upper row) and rest (lower row). A fixed, non‐reversible defect (scar) in the basal segments of the LV was found, with a non‐coronary artery distribution. The apical perfusion is normal. However, this pattern may be a false perfusion defect due to increased hypertrophic mid‐ventricular and apical uptake of the radiotracer. (Reprinted

Using N‐13‐labelled ammonia and O‐15‐labelled water, proton emission tomography (PET) imaging detects absolute myocardial blood flow in patients with HCM. In contrast to SPECT, PET allows the direct quantification of myocardial blood flow (**Figure 11**) [38]. PET imaging

**Figure 11.** Functional imaging of ischemia with nuclear proton emission tomography (PET). Stress dipyridamole (up‐ per row) and rest (lower row) 13NH3 perfusion images in an 14‐year‐old girl diagnosed with HCM with interventricu‐ lar septum (IVS) 29 mm. Stress: LV dilation and subendocardial hypoperfusion (IVS and antero‐lateral wall). Rest: increased IVS 13NH3 uptake is seen, indicative of IVS hypertrophy. (Reprinted with permission from Cardim et al. [38]).

with permission from Cardim et al. [38]).

126 Echocardiography in Heart Failure and Cardiac Electrophysiology

Dai-Yin Lu1,2 and Ming-Chong Hsiung3\*

\*Address all correspondence to: hsiungmc@gmail.com

1 Division of Cardiology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan

2 Department of Medicine, National Yang-Ming University, Taipei, Taiwan

3 Division of Cardiology, Heart Center, Chen-Hsin General Hospital, Taipei, Taiwan

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## **Noninvasive Measurement of Pulmonary Capillary Wedge Pressure by Speckle Tracking Echocardiography Noninvasive Measurement of Pulmonary Capillary Wedge Pressure by Speckle Tracking Echocardiography**

Masanori Kawasaki Masanori Kawasaki

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Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64864

### **Abstract**

The severity of left-sided heart failure can be evaluated by pulmonary capillary wedge pressure (PCWP) because PCWP reflects left ventricular (LV) filling pressure. Owing to developments in echocardiographic technology, speckle tracking echocardiography (STE) has allowed automatic construction of time-left atrial (LA) volume (LAV) curves. Thus, we developed a novel index based on a combination of LAV and LA function that would estimate PCWP using STE. The following regression equation described the relationship between PCWP that was obtained by right-heart catheterization and active LAEF/minimum LAV index (volume was indexed to body surface area: LAVI) in the patients with sinus rhythm: PCWP = 10.8–12.4 [log10 (active LAEF/minimum LAVI)] (r = −0.86, p <0.001) (measurements from the apical 4-chamber view). We defined this index [log10 (active LAEF/minimum LAVI)] as the kinetics-tracking index (KT index). The PCWP estimated by the KT index (ePCWP) had a strong correlation with PCWP obtained by right-heart catheterization (r = 0.92, p <0.001). The ePCWP measured by STE could be a useful parameter to improve clinical outcomes in patients with heart failure.

**Keywords:** speckle tracking echocardiography, heart failure, pulmonary capillary wedge pressure

## **1. Noninvasive assessment of PCWP**

#### **1.1. Introduction**

Regardless of the presence of abnormal left ventricular (LV) systolic fraction, chronic heart failure (HF) causes cardiac disease or cardiac death. The physiological cause in patients with

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

HF with preserved ejection fraction (HFPEF) is a diastolic dysfunction [1]. Evaluation of left atrial (LA) pressure is a useful parameter for the diagnosis and treatment of HF. However, measurement of pulmonary capillary wedge pressure (PCWP) or LV filling pressure is an invasive method, and there have been few noninvasive indices that can precisely estimate PCWP or LV filling pressure. Therefore, the establishment of a noninvasive parameterto easily and accurately predict PCWP is important for the clinical diagnosis of HF.

LA volume (LAV) has been thought to reflect elevated LV filling pressure and serves as a parameter to evaluate prognosis of cardiac disease [2–4]. LV filling pressure and LV diastolic function can be estimated by the regional tissue velocity of the mitral annulus measured during early filling (e′) or the ratio of peak early transmitral flow velocity (E) to regional tissue velocity of the mitral annulus measured during early filling (E/e′) [5–8]. However, these parameters do not necessarily reflect the conditions of myocardial expansion during mid and late diastole [8].

Speckle tracking echocardiography (STE) has allowed the automatic construction of time-left atrial (LA) volume curves due to developments in echocardiographic technology [9]. STE has also permitted the evaluation of phasic LA function and volume [10, 11]. LA function and volume are directly influenced by LV diastolic function. Therefore, the combined parameter of LA function and volume would be useful to estimate PCWP. A novel index based on the combination of LA function and volume evaluated by the time-LA volume curve using STE would be more accurate to evaluate PCWP than conventional parameters such as E/e′ and LAV.

## **1.2. Methods**

## *1.2.1. Subjects and study protocol*

The study group consisted of a training study and a testing study. Patients in normal sinus rhythm (NSR), patients with chronic atrial fibrillation (AF) and patients with moderate-tosevere mitral valve regurgitation (MR), who were referred for clinically-indicated right-heart catheterization, were evaluated. In the training study, we measured LAV and LA emptying function (LAEF) in patients in sinus rhythm without chronic AF or moderate-to-severe MR to derive a novel index that gave the best estimate of PCWP. Four parameters based on various combinations of active or total LAEF and minimum or maximum LAV were used to estimate PCWP. In the testing study, we evaluated the reliability and accuracy of the novel index in patients in sinus rhythm, patients with chronic AF and patients with moderate-to-severe MR. Volume was indexed to body surface area (LAV index: LAVI). Transthoracic echocardiography was performed in the left lateral decubitus position by two experienced sonographers just before right-heart catheterization (within 1 hour). As recommended by the American Society of Echocardiography, measurements of phasic LAV were made from the apical 2- and 4 chamber views [12].

#### *1.2.2. Echocardiographic studies and invasive measurements of PCWP*

Total LAEF (reservoir function), active LAEF (booster pump function) and passive LAEF (conduit function) were measured to estimate phasic LA function (**Figure 1**). Total, active and passive LAEF were defined as (maximum LAV – minimum LAV)/maximum LAV × 100%, (preatrial contraction LAV – minimum LAV)/pre-atrial contraction LAV × 100% and (maximum LAV – pre-atrial contraction LAV)/maximum LAV × 100%, respectively. The measurements of LAV and LA function were averaged from three consecutive beats. The reliability of the quantification of phasic LAV and LA function by STE has been established in previous studies [10, 11].

**Figure 1.** Representative time-left atrial volume curves in two patients. The patient on the left had a PCWP measured by right-heart catheterization of 5 mmHg, whereas the one on the right had a PCWP of 20 mmHg. Red lines are the time-left atrial volume curves, and blue lines are the d*V*/d*t* curves. PCWP: pulmonary capillary wedge pressure; LVEF: left ventricular ejection fraction.

A pulmonary artery balloon-occlusion catheter was connected to a fluid-filled transducer that was balanced before the study with the transducer located at the mid-axillary line. By the use of fluoroscopy, the wedge position was verified and the mean PCWP was measured.

## **1.3. Results**

HF with preserved ejection fraction (HFPEF) is a diastolic dysfunction [1]. Evaluation of left atrial (LA) pressure is a useful parameter for the diagnosis and treatment of HF. However, measurement of pulmonary capillary wedge pressure (PCWP) or LV filling pressure is an invasive method, and there have been few noninvasive indices that can precisely estimate PCWP or LV filling pressure. Therefore, the establishment of a noninvasive parameterto easily

LA volume (LAV) has been thought to reflect elevated LV filling pressure and serves as a parameter to evaluate prognosis of cardiac disease [2–4]. LV filling pressure and LV diastolic function can be estimated by the regional tissue velocity of the mitral annulus measured during early filling (e′) or the ratio of peak early transmitral flow velocity (E) to regional tissue velocity of the mitral annulus measured during early filling (E/e′) [5–8]. However, these parameters do not necessarily reflect the conditions of myocardial expansion during mid and late diastole [8].

Speckle tracking echocardiography (STE) has allowed the automatic construction of time-left atrial (LA) volume curves due to developments in echocardiographic technology [9]. STE has also permitted the evaluation of phasic LA function and volume [10, 11]. LA function and volume are directly influenced by LV diastolic function. Therefore, the combined parameter of LA function and volume would be useful to estimate PCWP. A novel index based on the combination of LA function and volume evaluated by the time-LA volume curve using STE would be more accurate to evaluate PCWP than conventional parameters such as E/e′ and LAV.

The study group consisted of a training study and a testing study. Patients in normal sinus rhythm (NSR), patients with chronic atrial fibrillation (AF) and patients with moderate-tosevere mitral valve regurgitation (MR), who were referred for clinically-indicated right-heart catheterization, were evaluated. In the training study, we measured LAV and LA emptying function (LAEF) in patients in sinus rhythm without chronic AF or moderate-to-severe MR to derive a novel index that gave the best estimate of PCWP. Four parameters based on various combinations of active or total LAEF and minimum or maximum LAV were used to estimate PCWP. In the testing study, we evaluated the reliability and accuracy of the novel index in patients in sinus rhythm, patients with chronic AF and patients with moderate-to-severe MR. Volume was indexed to body surface area (LAV index: LAVI). Transthoracic echocardiography was performed in the left lateral decubitus position by two experienced sonographers just before right-heart catheterization (within 1 hour). As recommended by the American Society of Echocardiography, measurements of phasic LAV were made from the apical 2- and 4-

Total LAEF (reservoir function), active LAEF (booster pump function) and passive LAEF (conduit function) were measured to estimate phasic LA function (**Figure 1**). Total, active and

and accurately predict PCWP is important for the clinical diagnosis of HF.

134 Echocardiography in Heart Failure and Cardiac Electrophysiology

**1.2. Methods**

chamber views [12].

*1.2.2. Echocardiographic studies and invasive measurements of PCWP*

*1.2.1. Subjects and study protocol*

## *1.3.1. Association between PCWP and echocardiographic parameters in the training and testing studies*

From the combination of LV function and volume, the following four parameters were calculated in the training study to predict PCWP:


In the training study, all of these indices were found to be logarithmically correlated with PCWP obtained by right-heart catheterization (**Figure 2**). Therefore, we used the logarithm of these parameters in linear regression analyses. E/e′ and the logarithm of these four indices along with phasic LAVI and phasic LA function were linearly correlated with PCWP measured by right-heart catheterization (**Figure 3**). The logarithm of active LAEF/minimum LAVI had the strongest correlation with PCWP obtained by right-heart catheterization among all of the echocardiographic parameters (**Figure 3**). We defined this novel index [log10 (active LAEF/ minimum LAVI)] as the kinetics-tracking index (KT index).

**Figure 2.** Relationship between pulmonary capillary wedge pressure measured by right-heart catheterization and the combined parameters of left atrial function and volume in the training study (n=50). The logarithm of each index was used in linear regression analysis. PCWP: pulmonary capillary wedge pressure; LAEF: left atrial emptying function; LAVI: left atrial volume index.

The following regression equation described the relationship between PCWP and active LAEF/ minimum LAVI in patients with sinus rhythm:

PCWP = 10.8–12.4 [log10 (active LAEF/minimum LAVI)] (r = −0.86, p <0.001) (measurements from the apical four-chamber view);

PCWP = 11.5–12.1 [log10 (active LAEF/minimum LAVI)] (r = −0.87, p <0.001) (measurements from the apical two- and four-chamber view).

In patients with chronic AF, total LAEF was substituted for active LAEF because pre-atrial contraction LAV was not present during AF. Only the KT index was found to be an independent predictor of PCWP among the various echocardiographic parameters by multiple regression analysis.

There was a strong correlation between the PCWP estimated by the KT index and PCWP obtained by right-heart catheterization (r = 0.92, p <0.001). **Figure 4** showed the relationship between PCWP estimated by the KT index and PCWP obtained by right-heart catheterization in the testing study.

Noninvasive Measurement of Pulmonary Capillary Wedge Pressure by Speckle Tracking Echocardiography http://dx.doi.org/10.5772/64864 137

echocardiographic parameters (**Figure 3**). We defined this novel index [log10 (active LAEF/

**Figure 2.** Relationship between pulmonary capillary wedge pressure measured by right-heart catheterization and the combined parameters of left atrial function and volume in the training study (n=50). The logarithm of each index was used in linear regression analysis. PCWP: pulmonary capillary wedge pressure; LAEF: left atrial emptying function;

The following regression equation described the relationship between PCWP and active LAEF/

PCWP = 10.8–12.4 [log10 (active LAEF/minimum LAVI)] (r = −0.86, p <0.001) (measurements

PCWP = 11.5–12.1 [log10 (active LAEF/minimum LAVI)] (r = −0.87, p <0.001) (measurements

In patients with chronic AF, total LAEF was substituted for active LAEF because pre-atrial contraction LAV was not present during AF. Only the KT index was found to be an independent predictor of PCWP among the various echocardiographic parameters by multiple regression

There was a strong correlation between the PCWP estimated by the KT index and PCWP obtained by right-heart catheterization (r = 0.92, p <0.001). **Figure 4** showed the relationship between PCWP estimated by the KT index and PCWP obtained by right-heart catheterization

minimum LAVI)] as the kinetics-tracking index (KT index).

136 Echocardiography in Heart Failure and Cardiac Electrophysiology

LAVI: left atrial volume index.

analysis.

in the testing study.

minimum LAVI in patients with sinus rhythm:

from the apical two- and four-chamber view).

from the apical four-chamber view);

**Figure 3.** Relationship between pulmonary capillary wedge pressure measured by right-heart catheterization and echocardiographic parameters in the training study (n=50). PCWP: pulmonary capillary wedge pressure; LAEF: left atrial emptying function; LAVI: left atrial volume index. Note that the KT index was better than LAV alone and E/e′ for estimation of PCWP.

**Figure 4.** (**A**) Relationship between pulmonary capillary wedge pressure measured by right-heart catheterization and estimated by the KT index in patients in the testing study and in the subgroups with left ventricular ejection fraction (LVEF) ≥50% and LVEF <50%. The relationships were evaluated by simple linear regression analysis. (**B**) Relationship between pulmonary capillary wedge pressure measured by right-heart catheterization and estimated by the KT index in patients in the testing study, in the subgroups with (CHF+) or without (CHF−) symptoms of congestive heart failure and in the subgroup with chronic atrial fibrillation (AF+). The relationships were evaluated by simple linear regression analysis.

## **1.4 Discussion**

## *1.4.1. Establishment of the KT index*

A previous experimental study reported that the LA pressure-volume relationship consists of two loops arranged in a horizontal figure-of-eight pattern that incorporates both the active (A loop) and passive (V loop) components of LA function [13]. Dernellis et al. [14] reported that there was a linear correlation between minimum LAVI and LA pressure in subjects with normal atrial function, patients with acute myocardial infarction and patients with chronic HF. LA volume increases in proportion to the deterioration of LV diastolic function [15, 16]. Therefore, we employed LAV as the denominator in the KT index to evaluate PCWP. Likewise, active LAEF decreases in proportion to the deterioration of LV diastolic function [17]. Therefore, we employed active LAEF as the numerator in the KT index to evaluate PCWP. Moreover, the logarithmic correlation between LV filling pressure and LA distensibility [(max LAVI – min LAVI)/min LAVI] that is similar to the total LAEF [(max LAVI –min LAVI)/max LAVI] is reported [16]. Therefore, we determined the logarithmic association between ePCWP and LA function. Based on our equation, the KT index decreased in proportion to the increase of PCWP.

In the patients with chronic AF, we calculated the regression equation using the data in the testing study and obtained the following regression equation: PCWP (measured by catheterization) = 10.5–12.5 KT index (r = 0.76). Intriguingly, PCWP obtained by the KT index in patients with chronic AF had good agreement with PCWP obtained by right-heart catheterization, even using the same regression equation as in patients in NSR. A possible explanation that the ratio of pre-AC LAVI to min LAVI (1.191) (similar ratio to active LAEF) in patients in NSR was similar to the ratio of max LAVI to min LAVI (1.213) (similar ratio to total LAEF) in the patients with chronic AF.

#### *1.4.2. Diagnostic accuracy of KT index and E/e′ for the prediction of PCWP*

It was reported that e′ represents regional tissue velocity and e′ reflects LV relaxation and has a good correlation with PCWP [7, 18]. However, e′ is associated not only with active relaxation but also with lengthening load and elastic recoil of left ventricle [19]. Thus, e′ does not directly reflect intrinsic LV relaxation. The E wave is also associated with loading conditions (afterload and preload) [20, 21]. Therefore, E/e′ does not directly reflect atrial active function that is associated with LV stiffness or the condition of diastasis that occurs during mid and late diastole. Therefore, E/e′ is an index that evaluates only early diastole. In the present study, there was a significant but moderate correlation between E/e′ and PCWP obtained by rightheart catheterization (r = 0.50), as well as in a previous study (r = 0.47) [17]. Several parameters (LAEF [17] and isovolumetric myocardial acceleration obtained by tissue Doppler imaging [22]) were reported to predict LV filling pressure or PCWP. However, the correlation coefficient (r = −0.63 and r = 0.74) between LV filling pressure and PCWP was less than that in the present study (r = −0.87). In addition, the prediction by isovolumetric myocardial acceleration was limited to patients with left ventricular ejection fraction (LVEF) <55% and E/e′ <8 or >15 [22]. In healthy subjects or in patients with acute decompensated HF, the correlation between E/e′ and LV filling pressure was not significant [23, 24]. We proposed a combination of minimum LAVI and active LAEF (KT index) that evaluates LA features throughout diastole to estimate LV filling pressure to overcome the limitations of E/e′.

## **2. Impacts of gender and healthy aging on PCWP**

## **2.1. Introduction**

**1.4 Discussion**

chronic AF.

*1.4.1. Establishment of the KT index*

138 Echocardiography in Heart Failure and Cardiac Electrophysiology

in proportion to the increase of PCWP.

A previous experimental study reported that the LA pressure-volume relationship consists of two loops arranged in a horizontal figure-of-eight pattern that incorporates both the active (A loop) and passive (V loop) components of LA function [13]. Dernellis et al. [14] reported that there was a linear correlation between minimum LAVI and LA pressure in subjects with normal atrial function, patients with acute myocardial infarction and patients with chronic HF. LA volume increases in proportion to the deterioration of LV diastolic function [15, 16]. Therefore, we employed LAV as the denominator in the KT index to evaluate PCWP. Likewise, active LAEF decreases in proportion to the deterioration of LV diastolic function [17]. Therefore, we employed active LAEF as the numerator in the KT index to evaluate PCWP. Moreover, the logarithmic correlation between LV filling pressure and LA distensibility [(max LAVI – min LAVI)/min LAVI] that is similar to the total LAEF [(max LAVI –min LAVI)/max LAVI] is reported [16]. Therefore, we determined the logarithmic association between ePCWP and LA function. Based on our equation, the KT index decreased

In the patients with chronic AF, we calculated the regression equation using the data in the testing study and obtained the following regression equation: PCWP (measured by catheterization) = 10.5–12.5 KT index (r = 0.76). Intriguingly, PCWP obtained by the KT index in patients with chronic AF had good agreement with PCWP obtained by right-heart catheterization, even using the same regression equation as in patients in NSR. A possible explanation that the ratio of pre-AC LAVI to min LAVI (1.191) (similar ratio to active LAEF) in patients in NSR was similar to the ratio of max LAVI to min LAVI (1.213) (similar ratio to total LAEF) in the patients with

It was reported that e′ represents regional tissue velocity and e′ reflects LV relaxation and has a good correlation with PCWP [7, 18]. However, e′ is associated not only with active relaxation but also with lengthening load and elastic recoil of left ventricle [19]. Thus, e′ does not directly reflect intrinsic LV relaxation. The E wave is also associated with loading conditions (afterload and preload) [20, 21]. Therefore, E/e′ does not directly reflect atrial active function that is associated with LV stiffness or the condition of diastasis that occurs during mid and late diastole. Therefore, E/e′ is an index that evaluates only early diastole. In the present study, there was a significant but moderate correlation between E/e′ and PCWP obtained by rightheart catheterization (r = 0.50), as well as in a previous study (r = 0.47) [17]. Several parameters (LAEF [17] and isovolumetric myocardial acceleration obtained by tissue Doppler imaging [22]) were reported to predict LV filling pressure or PCWP. However, the correlation coefficient (r = −0.63 and r = 0.74) between LV filling pressure and PCWP was less than that in the present study (r = −0.87). In addition, the prediction by isovolumetric myocardial acceleration was limited to patients with left ventricular ejection fraction (LVEF) <55% and E/e′ <8 or >15 [22]. In healthy subjects or in patients with acute decompensated HF, the correlation between E/e′

*1.4.2. Diagnostic accuracy of KT index and E/e′ for the prediction of PCWP*

Measurement of intracardiac pressure such as PCWP or LV filling pressure is useful for the stratification of LV diastolic dysfunction that can lead to HF due to hypertension and aging [25, 26]. However, measurement of PCWP or LV filling pressure is an invasive method, and there have been few noninvasive indices that can precisely estimate PCWP or LV filling pressure. The KT index was a more accurate and useful predictor of PCWP than E/e′ [27].

There have been no previous reports that evaluated PCWP in healthy subjects in a relatively large population because there has been no noninvasive method to measure PCWP in healthy subjects. Therefore, the aim of the present study was to evaluate the impact of gender and healthy aging without hypertension on ePCWP and other echocardiographic parameters.

## **2.2. Methods**

## *2.2.1. Subjects and study protocol*

Healthy subjects, who were free of cardiovascular or other systemic disease and not taking any medications, were included in the study. All the subjects had to have normal findings based on a physical checkup once every year or school physical checkup once every 3 years. We included subjects who were more than 40 years old with a normal electrocardiogram (ECG), but with chest discomfort or pain and shown to be free from cardiovascular disease evaluated by multidetector computed tomography, myocardial scintigraphy or left heart catheterization. We also included subjects more than 40 years old with a normal ECG, but with chest discomfort or pain and shown to be free from cardiovascular disease evaluated by exercise stress ECG. Although we included subjects who had a normal chest x-ray and echocardiographic findings according to the recommendations of the American Society of Echocardiography [12], we also included patients who had trivial valvular regurgitation and those with abnormal values of diastolic function parameters such as E/A and E/e′. Measurements of echocardiography were made according to the criteria of the American Society of Echocardiography [12]. Doppler measurements of mitral inflow E-wave and A-wave velocity were obtained, and tissue Doppler measurements of mitral e′ wave velocity were made at the septal annulus. Total, passive, active LAEF and KT index were also measured.

#### **2.3. Results**

#### *2.3.1. Impacts of healthy aging and gender on echocardiographic parameters*

The LVEF was not significantly different among the eight age groups of both males and females. The minimum, maximum and pre-atrial contraction LAVI significantly increased with advancing age, resulting in a deterioration of passive and total LAEF. E/e′ and E/A (indicators of LV diastolic function) with advancing age. However, ePCWP was maintained due to compensation by an increase in active LAEF. As shown in **Figure 5**, maximum and minimum LAVI in octogenarians were greater than those in subjects in their thirties, forties and fifties in both males and females.

**Figure 5.** Left atrial volume and function in each decade. Solid blue line: male; broken red line: female. LAVI: left atrial volume index, LAEF: left atrial emptying function, PCWP: pulmonary capillary wedge pressure, ANOVA: one-way analysis of variance. \*p<0.05 vs. twenties; †p<0.05 vs. thirties, forties and fifties;

#### *2.3.2. Relationship between age and LV diastolic dysfunction*

The relationships between age and the echocardiographic parameters that indicated LV diastolic dysfunction are shown in **Figure 6**. As age increased, the echocardiographic parameters, such as E/A and E/e′ (indicators of LV diastolic function) deteriorated to the same extent in males and females (slope of E/A: −0.021 in females and −0.021 in males) (slope of E/e′: 0.039 in females and 0.041 in males). However, there was no significant relationship between age and ePCWP. This suggested that ePCWP was maintained around 8 mmHg due to compensation by an increase in active LAEF in subjects without cardiovascular disease. Contrary, the compensation for LV diastolic dysfunction by an increase in active LAEF was more efficient in males than in females (slope=0.11) (slope=0.18, p=0.060 vs. females).

Noninvasive Measurement of Pulmonary Capillary Wedge Pressure by Speckle Tracking Echocardiography http://dx.doi.org/10.5772/64864 141

**Figure 6.** Relationships between age and the echocardiographic parameters. LAEF: left atrial emptying function, PCWP: pulmonary capillary wedge pressure. Center line indicates regression line. Inner lines indicate 95% confidence interval of the regression line. Outer lines indicate 95% confidence interval of the raw data.

## **2.4. Discussion**

**2.3. Results**

both males and females.

*2.3.1. Impacts of healthy aging and gender on echocardiographic parameters*

140 Echocardiography in Heart Failure and Cardiac Electrophysiology

The LVEF was not significantly different among the eight age groups of both males and females. The minimum, maximum and pre-atrial contraction LAVI significantly increased with advancing age, resulting in a deterioration of passive and total LAEF. E/e′ and E/A (indicators of LV diastolic function) with advancing age. However, ePCWP was maintained due to compensation by an increase in active LAEF. As shown in **Figure 5**, maximum and minimum LAVI in octogenarians were greater than those in subjects in their thirties, forties and fifties in

**Figure 5.** Left atrial volume and function in each decade. Solid blue line: male; broken red line: female. LAVI: left atrial volume index, LAEF: left atrial emptying function, PCWP: pulmonary capillary wedge pressure, ANOVA: one-way

The relationships between age and the echocardiographic parameters that indicated LV diastolic dysfunction are shown in **Figure 6**. As age increased, the echocardiographic parameters, such as E/A and E/e′ (indicators of LV diastolic function) deteriorated to the same extent in males and females (slope of E/A: −0.021 in females and −0.021 in males) (slope of E/e′: 0.039 in females and 0.041 in males). However, there was no significant relationship between age and ePCWP. This suggested that ePCWP was maintained around 8 mmHg due to compensation by an increase in active LAEF in subjects without cardiovascular disease. Contrary, the compensation for LV diastolic dysfunction by an increase in active LAEF was more efficient in

analysis of variance. \*p<0.05 vs. twenties; †p<0.05 vs. thirties, forties and fifties;

males than in females (slope=0.11) (slope=0.18, p=0.060 vs. females).

*2.3.2. Relationship between age and LV diastolic dysfunction*

## *2.4.1. The clinical value of estimated PCWP in healthy subjects*

HF affects many conditions of LV fluid volume and pressure status. The noninvasive measurement of PCWP in healthy subjects as well as patients with HF is useful for the quantitative stratification of intravascular fluid pressure and volume status to predict prognosis of HF. However, there have been few studies that evaluated PCWP in healthy subjects in a relatively large population because the measurement of PCWP requires an invasive method such as right-heart catheterization. PCWP in healthy subjects was maintained regardless of deterioration of LV diastolic function due to compensation by an increase in active LAEF in the present study. A previous study demonstrated that LV diastolic dysfunction, evaluated by E/A and E/ e′, deteriorated with advancing age in healthy subjects [28]. However, that report did not evaluate PCWP. Another study also demonstrated echocardiographic parameters using threedimensional echocardiography in healthy subjects [29]. That study focused only on volumetric parameters in the left atrium. However, the present study focused on ePCWP and LA function as well as LAV and demonstrated that the deterioration of LV diastolic function due to aging was compensated by LA function; thus, PCWP was maintained.

## *2.4.2. Estimated PCWP in healthy subjects*

A few studies that elucidated PCWP in the healthy subjects in small populations have been performed. In a previous study, PCWP was evaluated by right-heart catheterization in 70 healthy volunteers. The PCWP in these healthy volunteers was around 12 mmHg and did not differ among seniors (50% men, 70 ± 3 years old), late middle age (48% men, 57 ± 4 years old), early middle age (32% men, 42 ± 5 years old) and young (57% men, 28 ± 4 years old) [30], whereas E/A deteriorated from 1.9 to 0.8. PCWP measured by right-heart catheterization (12 mmHg) was slightly higher than that in the present study (8 mmHg), whereas this finding that did not differ with advancing age reinforced the present results. This discrepancy of PCWP (12 and 8 mmHg) may be due to the fact that evaluation of PCWP measured by right-heart catheterization was performed by an invasive method that imposed a physical burden on the healthy volunteers, whereas ePCWP measurement by STE did not impose a physical burden on the healthy subjects. Previous study reported PCWP that was measured by right-heart catheterization in 50 healthy, elderly, nonsedentary volunteers who had a normal echocardiographic and ECG findings and was free of pulmonary, cardiovascular, systemic disease, shortness of breath and chest pain. The PCWP in these subjects was around 9 mmHg (65 ± 10 years old, 74% men) [31]. This value was similar to ePCWP in the present study.

#### *2.4.3. Atrial function of males and females*

The maximum LAVI in octogenarians was greater than the values in subjects in their thirties, forties and fifties regardless of gender, whereas deterioration of passive LAEF developed almost two decades earlier in both males and females. These results were the same as the results of a previous study [32]. In the present study, however, there was compensation by an increase of active LAEF only in male septuagenarians and octogenarians. Another intriguing finding in the present study was that as age increases, the echocardiographic parameters that reflect LV diastolic dysfunction deteriorated to the same extent in both males and females. However, compensation for deterioration of LV diastolic function by an increase in active LAEF was more pronounced in males (slope = 0.18) than females (slope = 0.11). In males, there was a stronger correlation between E/A and active LAEF, and between E/e′ and active LAEF than in females. The slopes of these two regression lines indicate that the strength of the compensation for deterioration of LV diastolic function was also lesser in females than males. Compensation by an increase in active LAEF was less prominent in females than males. The Framingham Heart Study demonstrated that the prevalence of congestive HF in septuagenarians was higher in males than females [33]. However, the prevalence of congestive HF in octogenarians was lower in males than in females. The 11-year follow-up study reported that female gender was associated with new onset of HFPEF, whereas male gender was associated with new onset of HFPEF, after adjusting for age [34]. In the present study, compensation for deterioration of LV diastolic function by an increase in active LAEF was more increased only in male octogenarians than female octogenarians. This may explain why HFPEF occurs more frequently in females than in males.

## *2.4.4. Clinical implications*

The potential clinical application of the present methods and findings is broad. Noninvasive measurement of ePCWP is useful for the evaluation for intravascular fluid volume and pressure status to identify the onset of HF. Stratification of the risk of HF in patients as well as healthy subjects using PCWP is important for understanding when and why HF develops. The ePCWP that is measured by KT index also may be applicable for the determination of appropriate dry weight during dialysis and prediction of the onset of AF.

## **Author details**

did not differ with advancing age reinforced the present results. This discrepancy of PCWP (12 and 8 mmHg) may be due to the fact that evaluation of PCWP measured by right-heart catheterization was performed by an invasive method that imposed a physical burden on the healthy volunteers, whereas ePCWP measurement by STE did not impose a physical burden on the healthy subjects. Previous study reported PCWP that was measured by right-heart catheterization in 50 healthy, elderly, nonsedentary volunteers who had a normal echocardiographic and ECG findings and was free of pulmonary, cardiovascular, systemic disease, shortness of breath and chest pain. The PCWP in these subjects was around 9 mmHg (65 ± 10

The maximum LAVI in octogenarians was greater than the values in subjects in their thirties, forties and fifties regardless of gender, whereas deterioration of passive LAEF developed almost two decades earlier in both males and females. These results were the same as the results of a previous study [32]. In the present study, however, there was compensation by an increase of active LAEF only in male septuagenarians and octogenarians. Another intriguing finding in the present study was that as age increases, the echocardiographic parameters that reflect LV diastolic dysfunction deteriorated to the same extent in both males and females. However, compensation for deterioration of LV diastolic function by an increase in active LAEF was more pronounced in males (slope = 0.18) than females (slope = 0.11). In males, there was a stronger correlation between E/A and active LAEF, and between E/e′ and active LAEF than in females. The slopes of these two regression lines indicate that the strength of the compensation for deterioration of LV diastolic function was also lesser in females than males. Compensation by an increase in active LAEF was less prominent in females than males. The Framingham Heart Study demonstrated that the prevalence of congestive HF in septuagenarians was higher in males than females [33]. However, the prevalence of congestive HF in octogenarians was lower in males than in females. The 11-year follow-up study reported that female gender was associated with new onset of HFPEF, whereas male gender was associated with new onset of HFPEF, after adjusting for age [34]. In the present study, compensation for deterioration of LV diastolic function by an increase in active LAEF was more increased only in male octogenarians than female octogenarians. This may explain why HFPEF occurs more frequently in females

The potential clinical application of the present methods and findings is broad. Noninvasive measurement of ePCWP is useful for the evaluation for intravascular fluid volume and pressure status to identify the onset of HF. Stratification of the risk of HF in patients as well as healthy subjects using PCWP is important for understanding when and why HF develops. The ePCWP that is measured by KT index also may be applicable for the determination of appro-

priate dry weight during dialysis and prediction of the onset of AF.

years old, 74% men) [31]. This value was similar to ePCWP in the present study.

*2.4.3. Atrial function of males and females*

142 Echocardiography in Heart Failure and Cardiac Electrophysiology

than in males.

*2.4.4. Clinical implications*

Masanori Kawasaki

Address all correspondence to: masanori@ya2.so-net.ne.jp

Department of Cardiology, Gifu University Graduate School of Medicine, Gifu, Japan

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## **The Role of Echocardiography in the Management of Patients Undergoing a Ventricular Assist Device Implantation and/or Transplantation The Role of Echocardiography in the Management of Patients Undergoing a Ventricular Assist Device Implantation and/or Transplantation**

Tomoko Kato, Takashi Nishimura, Shunei Kyo, Kenji Kuwaki, Hiroyuki Dada and Atsushi Amano Tomoko Kato, Takashi Nishimura, Shunei Kyo, Kenji Kuwaki, Hiroyuki Dada and Atsushi Amano Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/65095

#### **Abstract**

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146 Echocardiography in Heart Failure and Cardiac Electrophysiology

J Am Coll Cardiol 1993;22:6A-13A.

Heart transplantation (HTx) is a curative treatment for patients with advanced heart failure (HF); however, since transplant opportunities are severely limited due to donor shortage, the left ventricular assist device (LVAD) has become a standard therapy for patients awaiting HTx. The role of echocardiography as a primary imaging modality to monitor the allograft function in transplant recipients as well as to optimize LVAD settings in LVAD recipients has been expanding. The purpose of this review is to highlight the clinical role of echocardiography in the management of patients under‐ going LVAD implantation and/or HTx. In particular, we overview (1) how to detect LVAD malfunction and device‐associated complication in LVAD recipients and (2) echocardiographic assessments of cardiac allograft rejection in transplant recipients.

**Keywords:** heart failure, transplant, rejection, ventricular assist device, echocardiogra‐ phy

## **1. Introduction**

Heart transplantation (HTx) provides considerable survival benefits for patients with end‐ stage heart failure, but it is available for only a small fraction of such patients all over the world due to donor shortage [1]. Therefore, many heart transplant candidates require long‐ term support by a left ventricular assist device (LVAD) while they await transplantation [1, 2]. More recently, mechanical circulatory support has evolved into a standard therapy for

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

patients with advanced heart failure, not only as a bridge to cardiac transplantation but also as a destination therapy or a bridge to myocardial recovery [3].

Echocardiography is a primary imaging modality in the assessment of cardiac structure and function in patients with advanced HF. In addition, echocardiography can be performed at the patient's bedside, and results are immediately available. In this review, we highlight the effectiveness of echocardiography in the management of patients undergoing LVAD implan‐ tation and/or HTx.

## **2. Echocardiography in LVAD recipients**

A growing number of heart transplant candidates require long‐term support by an LVAD while they await cardiac transplantation. Further, LVAD therapy has become a standard therapy for patients with advanced HF, not only as a bridge to cardiac transplantation but also as a destination therapy or a bridge to myocardial recovery. Here, we focused on the usefulness of echocardiography in patients undergoing LVAD implantation.

## **2.1. Preoperative assessment**

It is important to assess the LVAD eligibility and rule out any contraindications against LVAD surgery prior to an operation. Several structural issues that can be surgically corrected at the time of LVAD implantation should be carefully evaluated prior to the LVAD surgery. The presence of clots, especially at the apex, should be carefully assessed because it will increase the risk of inflow cannula obstructions and/or perioperative stroke. Intracardiac shunts, including patent foramen ovale, should also be carefully assessed before and during surgery. Intracardiac shunts must be closed at the time of LVAD surgery. Further, coexisting valvular heart disease should be assessed prior to the LVAD procedure. Concomitant valvular surgery can be performed at the time of LVAD implantation; however, although such an additional approach can provide possible benefits, data regarding its long‐term effect are limited, and the indications are still controversial. Another important issue to be carefully evaluated preoperatively includes right ventricular (RV) function because right ventricular failure (RVF) after LVAD placement is associated with increased morbidity and mortality.

## *2.1.1. Preoperative valvular assessment*

Regarding tricuspid regurgitation (TR), several previous papers have revealed that tricuspid annular dilatation is highly associated with post‐LVAD right ventricular failure [4]. Kukucka M et al. reviewed 122 patients without significant TR at the time of VAD implant and found that a tricuspid annulus diameter >43 mm was an independent predictor of survival after LVAD (**Figure 1**). On the other hand, whether the TR should be surgically managed at the time of LVAD surgery is controversial. Dunlay et al. performed a literature search of randomized controlled trials and observational studies (including 3249 patients) that compared the outcome of concomitant tricuspid valve surgery at the time of LVAD with that of LVAD alone [5]. They found that the addition of valvular surgery at the time of the LVAD procedure prolonged cardiopulmonary bypass times by an average of 31 minutes, but no differences were found between the groups for acute renal failure, early mortality, or the need for a right ventricular assist device. Having said that, a recent paper from Columbia University suggested that concomitant tricuspid valve procedures at the time of LVAD surgery can be performed safely and protect against worsening tricuspid regurgitation during the first two years of support [6]. In either case, the severity of TR and annular size need to be assessed preopera‐ tively. Surgeons should also bear in mind that preexisting severe TR, especially with annular size >43 mm, is at higher risk of adverse events after surgery.

patients with advanced heart failure, not only as a bridge to cardiac transplantation but also

Echocardiography is a primary imaging modality in the assessment of cardiac structure and function in patients with advanced HF. In addition, echocardiography can be performed at the patient's bedside, and results are immediately available. In this review, we highlight the effectiveness of echocardiography in the management of patients undergoing LVAD implan‐

A growing number of heart transplant candidates require long‐term support by an LVAD while they await cardiac transplantation. Further, LVAD therapy has become a standard therapy for patients with advanced HF, not only as a bridge to cardiac transplantation but also as a destination therapy or a bridge to myocardial recovery. Here, we focused on the usefulness of

It is important to assess the LVAD eligibility and rule out any contraindications against LVAD surgery prior to an operation. Several structural issues that can be surgically corrected at the time of LVAD implantation should be carefully evaluated prior to the LVAD surgery. The presence of clots, especially at the apex, should be carefully assessed because it will increase the risk of inflow cannula obstructions and/or perioperative stroke. Intracardiac shunts, including patent foramen ovale, should also be carefully assessed before and during surgery. Intracardiac shunts must be closed at the time of LVAD surgery. Further, coexisting valvular heart disease should be assessed prior to the LVAD procedure. Concomitant valvular surgery can be performed at the time of LVAD implantation; however, although such an additional approach can provide possible benefits, data regarding its long‐term effect are limited, and the indications are still controversial. Another important issue to be carefully evaluated preoperatively includes right ventricular (RV) function because right ventricular failure (RVF)

Regarding tricuspid regurgitation (TR), several previous papers have revealed that tricuspid annular dilatation is highly associated with post‐LVAD right ventricular failure [4]. Kukucka M et al. reviewed 122 patients without significant TR at the time of VAD implant and found that a tricuspid annulus diameter >43 mm was an independent predictor of survival after LVAD (**Figure 1**). On the other hand, whether the TR should be surgically managed at the time of LVAD surgery is controversial. Dunlay et al. performed a literature search of randomized controlled trials and observational studies (including 3249 patients) that compared the outcome of concomitant tricuspid valve surgery at the time of LVAD with that of LVAD alone [5]. They found that the addition of valvular surgery at the time of the LVAD procedure

after LVAD placement is associated with increased morbidity and mortality.

as a destination therapy or a bridge to myocardial recovery [3].

**2. Echocardiography in LVAD recipients**

148 Echocardiography in Heart Failure and Cardiac Electrophysiology

echocardiography in patients undergoing LVAD implantation.

tation and/or HTx.

**2.1. Preoperative assessment**

*2.1.1. Preoperative valvular assessment*

**Figure 1.** The impact on tricuspid valve annulus dilation on post‐LVAD survival (quoted from Ref. [4]). Kaplan‐Meier survival curves of patients with tricuspid valve (TV) annulus diameter <43 mm (blue) and >43 mm (red). Censored patients are represented by vertical marks. Numbers of patients at risk at 0, 12, 24, and 36 months of follow‐up are presented above the x‐axis (log‐rank test, p = 0.007).

Aortic insufficiency (AI) occurs in up to 50% of patients within 1 year after continuous flow LVAD implantation. Although de novo AI can be commonly seen postoperatively, the presence of more than mild AI as well as any structural abnormality, as detected by transthoracic echocardiography (TTE), should be reported to the LVAD surgery team. In cases with poor TTE images, the results derived from intraoperative transesophageal echocardiography (TEE) should be carefully discussed. The valvular morphology, valvular calcification, possible fusion, and myxomatous changes should also be reported to the surgeons. The recently published comprehensive review of AI post‐LVAD by Cowger et al. suggested the importance of intraoperative TEE to detect unmasked AI [7]. During the initiation of continuous flow LVAD support, as LV filling pressures drop with early unloading, the gradient between the aortic root and the LV increases, potentially exposing significant AI that was previously unrecog‐ nized. Because AI severity can be associated with an increase in pump speeds, we can quantitatively assess AI severity at different pump speeds to consider the necessity of con‐ comitant aortic valve surgery in an operating room. This review summarized the risk and benefits of aortic valve surgery at the time of LVAD (**Table 1**).


**Table 1.** Pros and cons of surgical management strategies of the native aortic valve (quoted from Ref. [7]).

Mitral valve insufficiency has fewer effects on postoperative outcome compared with aortic and tricuspid valve insufficiency. Indeed, a significant number of patients who had severe mitral regurgitation due to annulus dilatation and tethered pupillary muscle preoperatively showed a remarkable decrease in mitral regurgitation flow under LVAD support [8]. Although mitral valve surgery at the time of LVAD implant to correct severe mitral regurgitation does not affect postoperative mortality or cause other adverse events, the procedure can be consid‐ ered in cases undergoing an LVAD procedure as a bridge to recovery. In addition, concomitant mitral valve repair can decrease pulmonary vascular resistance [9]. Kitada et al. investigated preoperative echocardiographic features associated with persistent mitral regurgitation after LVAD implantation (**Figure 2**) [10]. They found that the posterior displacement of the coapta‐

tion point of a mitral leaflet (30 vs. 24 mm), papillary muscle distance (49 vs. 43 mm), and tethering area (353 vs. 299 mm2 ) before surgery were greater in patients who had persistent moderate to severe mitral regurgitation post‐LVAD than those in patients who did not have significant MR postoperatively. A multivariate analysis showed that the posterior displace‐ ment was the only independent predictor for persistent MR.

nized. Because AI severity can be associated with an increase in pump speeds, we can quantitatively assess AI severity at different pump speeds to consider the necessity of con‐ comitant aortic valve surgery in an operating room. This review summarized the risk and

**•** Questionable durability

LVAD explant

LVAD explant

aortic valve

**•** Questionable durability

**•** Need for AVR in the event of myocardial recovery leading to

**•** Need for AVR in the event of myocardial recovery leading to

**•** No blood ejection through the

**•** Risk of thrombus formation

stoppage or failure

**•** Risk of leaflet fusion

**•** Risk of death in the case of pump

**•** Increase CPB and cross‐clamp time

**•** Risk of valvular and subvalvular thrombus formation due to fresh suture lines combined with decreased

flow across the new valve

**•** Risk of progression to aortic stenosis

**•** Risk of progression to aortic stenosis

benefits of aortic valve surgery at the time of LVAD (**Table 1**).

150 Echocardiography in Heart Failure and Cardiac Electrophysiology

**Strategy Pros Cons**

the aortic valve

central stitch

**•** Simple with relatively fast repair time **•** Long‐term durability

**•** Relatively simple and can

**•** Permits blood ejection through the aortic valve but could be reduced compared to single

**•** Maintenance of valve opening in the postoperative period **•** Testing for cardiac recovery

**Table 1.** Pros and cons of surgical management strategies of the native aortic valve (quoted from Ref. [7]).

Mitral valve insufficiency has fewer effects on postoperative outcome compared with aortic and tricuspid valve insufficiency. Indeed, a significant number of patients who had severe mitral regurgitation due to annulus dilatation and tethered pupillary muscle preoperatively showed a remarkable decrease in mitral regurgitation flow under LVAD support [8]. Although mitral valve surgery at the time of LVAD implant to correct severe mitral regurgitation does not affect postoperative mortality or cause other adverse events, the procedure can be consid‐ ered in cases undergoing an LVAD procedure as a bridge to recovery. In addition, concomitant mitral valve repair can decrease pulmonary vascular resistance [9]. Kitada et al. investigated preoperative echocardiographic features associated with persistent mitral regurgitation after LVAD implantation (**Figure 2**) [10]. They found that the posterior displacement of the coapta‐

**•** Tolerance to exercise

be effective, even if leaflets are thin

**•** Simple and effective when the leaflet tissue has adequate tensile strength to hold sutures **•** Permit blood ejection through

Partial closure with a single central stitch (Park's stitch)

Modified Park's stitch additional pledgeted mattress suture

between the central stitch and each commissure

Complete closure of the ventriculo‐aortic juncture with a circular patch

Replacement of incompetent aortic valve with bioprosthetic

valve

**Figure 2.** The measurements of echocardiographic parameters to quantify the mitral leaflet configurations in 2D echo‐ cardiography (quoted from Ref. [10]). DA, apical displacement; DP, posterior displacement; LVEDD, left ventricular end diastolic dimension.

## *2.1.2. Preoperative and perioperative right ventricular assessment*

Right ventricular failure (RVF) remains a major cause of morbidity and mortality following LVAD surgery. The incidence of RVF post‐LVAD is 10–30% despite the recent improvements in device technology and postoperative patient management. Under LVAD support, right ventricular (RV) preload increases as a result of increased circulatory volume, whereas RV afterload is expected to decrease, secondary to improvement in pulmonary vascular resist‐ ance [11]. A sepal wall shift induced by LVAD alters the RV structure, which may worsen RV contractile and relaxation abnormalities. Therefore, when considering RV systolic and diastolic reserve before and also after surgery, it is important to identify which patients may need RV‐ specific mechanical and medical support post‐LVAD [12].


ACEI, angiotensin‐converting enzyme inhibitor; ALT, alanine aminotransferase; ARB, angiotensin receptor blocker; AST, aspartate aminotransferase; BiVAD, biventricular assist device; BP, blood pressure; BTT, bridge to transplantation; BUN, blood urea nitrogen; CF, continuous flow; CRITT, central venous pressure‐RV dysfunction‐preoperative intubation‐severe tricuspid regurgitation‐tachycardia; CVP, central venous pressure; DT, destination therapy; IABP; intra‐aortic balloon pump; INR, international normalized ratio; ITT, intention to treat; LVAD, left ventricular assist device; NO, nitric oxide; OR, odds ratio; PCWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; RV, right ventricle; RVAD, right ventricular assist device; RVF, right ventricular failure; RVSWI, right ventricular stroke work index; and TR, tricuspid regurgitation.

The data were obtained from the following papers: (a) Matthews JC, et al. J Am Coll Cardiol. 2008;51:2163–2172; (b) Fitzpatrick JR III, et al. J Heart Lung Transplant. 2008;27:1286–1292; (c) Drakos SG, et al. Am J Cardiol. 2010;105:1030– 1035; (d) Kormos RL, et al; HeartMate II Clinical Investigators. J Thorac Cardiovasc Surg. 2010;139:1316–1324; (e) Wang Y, et al. J Heart Lung Transplant. 2012;31:140–149; (f) Atluri P, et al. Ann Thorac Surg. 2013;96:857–863.

**Table 2.** Clinical risk prediction scores for right ventricular failure in left ventricular assist device recipients (quoted from Ref. [13]).

**Study Patients RVF definition**

152 Echocardiography in Heart Failure and Cardiac Electrophysiology

197 LVADs 28 CF‐LVAD 94% BTT

266 LVADs 6 CF‐LVAD BTT vs. DT not reported

175 LVADs 25 CF‐LVAD 58% BTT, 42% DT

All CF‐LVAD BTT 100%

183 LVADs 40 CF‐LVAD BTT vs. DT not reported

 (2013) 167 LVADs, all CF‐LVAD 51 BiVADsBTT vs. DT not reported

ventricular stroke work index; and TR, tricuspid regurgitation.

Michigan RV failure risk score (2008)a

Penn RVAD risk scoreb (2008)

Utah RV risk scorec

Pittsburgh Decision Treee (2012)

CRITTf

from Ref. [13]).

(2010)

Kormosd (2010)484 LVADs

**and rate**

Need for RVAD/ inotropes RVF rate: 35%

Need for RVAD RVF rate: 37%

Need for RVAD/ inotropes/ inhaled NO RVF rate: 44%

Need for RVAD/ inotropes RVF rate: 20.2%

Need for RVAD RVF rate: 15%

Need for BiVAD RVF rate: 23%

**Multivariable predictors Echocardiographic RV**

Preoperative vasopressors (4 pts)

Cardiac index ≤2.2 L/min/m2 RVSWI ≤0.25 mm Hg × L/m2 Severe RV dysfunction Creatinine ≥1.9 mg/dL Prior cardiac surgery Systolic BP ≤96 mm Hg

DT indication (3.5 pts)

Inotrope dependency (2.5 pts)

ACEI or ARB use (−2.5 pts) β‐blocker use (2 pts)

CVP/PCWP >0.63 (OR, 2.3) Need for preoperative ventilator support (OR, 5.5)BUN >39 mg/dL

Age, heart rate, transpulmonary gradient; right atrial pressure; INR, white blood cell count, ALT, number

Heart rate >100 (tachycardia [T])

IABP (4 pts) PVR (1–4 pts)

Obesity (2 pts)

(OR, 2.1)

of inotropic agents

Severe TR (T)

ACEI, angiotensin‐converting enzyme inhibitor; ALT, alanine aminotransferase; ARB, angiotensin receptor blocker; AST, aspartate aminotransferase; BiVAD, biventricular assist device; BP, blood pressure; BTT, bridge to transplantation; BUN, blood urea nitrogen; CF, continuous flow; CRITT, central venous pressure‐RV dysfunction‐preoperative intubation‐severe tricuspid regurgitation‐tachycardia; CVP, central venous pressure; DT, destination therapy; IABP; intra‐aortic balloon pump; INR, international normalized ratio; ITT, intention to treat; LVAD, left ventricular assist device; NO, nitric oxide; OR, odds ratio; PCWP, pulmonary capillary wedge pressure; PVR, pulmonary vascular resistance; RV, right ventricle; RVAD, right ventricular assist device; RVF, right ventricular failure; RVSWI, right

The data were obtained from the following papers: (a) Matthews JC, et al. J Am Coll Cardiol. 2008;51:2163–2172; (b) Fitzpatrick JR III, et al. J Heart Lung Transplant. 2008;27:1286–1292; (c) Drakos SG, et al. Am J Cardiol. 2010;105:1030– 1035; (d) Kormos RL, et al; HeartMate II Clinical Investigators. J Thorac Cardiovasc Surg. 2010;139:1316–1324; (e) Wang

**Table 2.** Clinical risk prediction scores for right ventricular failure in left ventricular assist device recipients (quoted

Y, et al. J Heart Lung Transplant. 2012;31:140–149; (f) Atluri P, et al. Ann Thorac Surg. 2013;96:857–863.

CVP >15 mm Hg (C) Severe RV dysfunction (R) Preoperative intubation (I)

AST ≥80 IU/L (2 pts) Bilirubin ≥2.0 mg/dL (2.5 pts) Creatinine ≥2.3 mg/dL (3 pts) **parameters considered**

RV systolic function

semiquantitative) TR (visual semiquantitative)

RV systolic function

semiquantitative)

Right atrial area

(visual

(visual

None

None

(visual

RV systolic function

semiquantitative) Severe TR (visual semiquantitative) **Table 2** summarizes the clinical risk prediction scores that have been cited in the recently published review literature [13]. In addition to these risk scores, serial echocardiographic assessments are helpful in evaluating RV functional reserve prior to surgery. Previously reported echocardiographic parameters associated with the risk for developing RVF after LVAD implantation have included tricuspid annular dilation (>43 mm) [4], tricuspid annular motion (8 vs. 15 mm) [14], and RV‐to‐LV end‐diastolic diameter ratio (>0.72) [15]. However, it is sometimes technically difficult to obtain ideal RV images that allow quantitative assessments of patients with advanced heart failure, particularly if the patients are severely congested, intubated, and/or have a markedly enlarged left ventricle (LV) that obscures the right ventricle (RV) [16]. Kato et al. focused only on left‐sided 2D echo parameters that can predict RVF post‐ LVAD. They showed that patients with relatively small LV size, preserved LV contraction, and a dilated left atrium were at higher risk for RVF after LVAD surgery (**Figure 3**) [16]. In addition to the conventional echo parameters, Grant et al. reported that the incremental role of RV strain to predict RVF [17]. More recently, Kato et al. reported that serial echocardiograms using tissue Doppler imaging (TDI) and speckle tracking echocardiography (STE) before and soon after (within 72 hours) LVAD surgery may aid in identifying the need to initiate targeted RVF‐ specific therapy [12]. In this study, RV stiffness (as reflected by TDI‐derived E/E′) and decreased RV contractility (as reflected by TDI‐derived S′ and RV longitudinal strain) before and soon after LVAD surgery were found to be useful parameters to include in the perioperative management of LVAD patients (**Figure 4**).

**Figure 3.** Left ventricular echocardiographic right ventricular failure score (LV‐for‐Echo‐RVF) based on two‐dimension‐ al echocardiographic left‐sided heart parameters (quoted from Ref. [16]). (A) Points associated with value of each vari‐ able. (B) Sensitivity and specificity of sum of points associated with right ventricular failure development after left ventricular assist device placement. (C) Representative 2D echo images in patients developing RVF post‐LVAD. (D) Re‐ ceiver operating characteristics curve for LV echocardiographic RVF score. AUC, area under the curve.

**Figure 4.** Representative global RV longitudinal strain and TDI obtained before surgery from a patient without RVF after LVAD and from a patient with RVF after LVAD (quoted from Ref. [18]). (A) The right ventricular (RV) global lon‐ gitudinal strain; tissue Doppler image (TDI)‐derived S′ and E′ for patient A was −14.3%, 7.8 cm/s and −10.8 cm/s, re‐ spectively. (B) These parameters were −6.2%, 4.6 cm/s and −5.3 cm/s, respectively. LVAD, left ventricular assist device; RVF, right ventricular failure.

## **2.2. Perioperative assessment**

Other than the speed adjustment to avoid RV failure due to excessive RV preload by LVAD support, several important points should be evaluated by intraoperative TEE. First, de‐airing of the heart chamber should be confirmed. Careful observation of trapped air at the site of anastomosis sites and around the LVAD inflow/outflow cannula is required [18]. Second, adjusting LV speed to maintain appropriate LV unloading without a septal shift under TEE guidance is required. The positioning of the inflow cannula at the apex should be monitored by TEE as well. Third, as mentioned above, the existence of valvular diseases and intracardiac shunts, which can be corrected simultaneously at the time of LVAD implantation, should be communicated to the surgeons. Finally, pericardial effusion and its amount should also be carefully observed by TEE. Cardiac tamponade can occur relatively often because patients under LVAD support require sufficient anticoagulation soon after surgery to prevent clot formation at the cannula and inside the device.

## **2.3. Postoperative assessment**

**Table 3** illustrates the checklist that will help sonographers/echocardiologists to perform an LVAD echo. In general, we can simply summarize the purposes of echo in LVAD recipients as follows: (1) to carefully monitor device malfunction, (2) to adjust appropriate LVAD setting/ speed (appropriate peripheral perfusion and RV preload), and (3) to evaluate myocardial recovery and to seek optimal timing for LVAD weaning.

The points to be evaluated by TEE on a periodic basis are as follows: the location and thrombus at the inflow cannula; LV cavity diameters; septal position; RV function; valvular regurgitation, especially about the aortic valve opening/intervals and regurgitation.


**Table 3.** Echo LVAD checklist.

**Figure 4.** Representative global RV longitudinal strain and TDI obtained before surgery from a patient without RVF after LVAD and from a patient with RVF after LVAD (quoted from Ref. [18]). (A) The right ventricular (RV) global lon‐ gitudinal strain; tissue Doppler image (TDI)‐derived S′ and E′ for patient A was −14.3%, 7.8 cm/s and −10.8 cm/s, re‐ spectively. (B) These parameters were −6.2%, 4.6 cm/s and −5.3 cm/s, respectively. LVAD, left ventricular assist device;

Other than the speed adjustment to avoid RV failure due to excessive RV preload by LVAD support, several important points should be evaluated by intraoperative TEE. First, de‐airing of the heart chamber should be confirmed. Careful observation of trapped air at the site of anastomosis sites and around the LVAD inflow/outflow cannula is required [18]. Second, adjusting LV speed to maintain appropriate LV unloading without a septal shift under TEE guidance is required. The positioning of the inflow cannula at the apex should be monitored by TEE as well. Third, as mentioned above, the existence of valvular diseases and intracardiac shunts, which can be corrected simultaneously at the time of LVAD implantation, should be communicated to the surgeons. Finally, pericardial effusion and its amount should also be carefully observed by TEE. Cardiac tamponade can occur relatively often because patients under LVAD support require sufficient anticoagulation soon after surgery to prevent clot

**Table 3** illustrates the checklist that will help sonographers/echocardiologists to perform an LVAD echo. In general, we can simply summarize the purposes of echo in LVAD recipients as follows: (1) to carefully monitor device malfunction, (2) to adjust appropriate LVAD setting/ speed (appropriate peripheral perfusion and RV preload), and (3) to evaluate myocardial

RVF, right ventricular failure.

**2.2. Perioperative assessment**

154 Echocardiography in Heart Failure and Cardiac Electrophysiology

**2.3. Postoperative assessment**

formation at the cannula and inside the device.

recovery and to seek optimal timing for LVAD weaning.

## *2.3.1. General postoperative assessment in LVAD recipients*

Recommendations for device speed adjustment include the target measures of mean arterial pressure above 65 mmHg, maintaining the position of interventricular septum and shape, and intermittent aortic valve opening, under the condition of no more than mild mitral regurgita‐ tion to ensure appropriate unloading of the LV. Optimization of speed settings is extremely important to prevent several of the key complications associated with chronic LVAD support. The importance of ensuring the middle septal position for optimal RV function has been well established [19, 20].

Serially monitoring the timing and its interval of aortic valve opening in all LVAD recipients are necessary. Also, adjusting the LVAD speed to maintain the aortic valve opening is important to prevent the development of aortic valve regurgitation. At least 10 cardiac cycles should be recorded to evaluate the aortic valve opening. Because the interval of aortic valve opening, LV diameter, and grade of MR entirely depend on the degree of LV unloading, the LVAD setting together with the echo report needs to be recorded (**Figure 5**). Aortic regurgitation is sometimes seen with atypical timing (**Figure 6**) or continuously, both during the diastolic and systolic phases [21].

Cardiac output using RV outflow‐derived Doppler estimation can be calculated as follows: cardiac output = stroke volume × heart rate, stroke volume = π × (RV outflow diameter/2)2 × time velocity integral at RV outflow. In patients who have at least an intermittent aortic valve opening, RV cardiac output minus LV outflow-derived cardiac output is equivalent to the estimated pump flow.

**Figure 5.** Representative images in a LVAD recipient with different LVAD speeds. This patient received HeartMate II (Thoratec Corp) implantation. Under 8400 rpm, the aortic valve opened intermittently, and the ejection time was only 75 ms. When we set the speed down to 8200, the aortic valve opened every beat, but due to less unloading, the LV diameter increased and the amount of mitral regurgitation also increased.

**Figure 6.** Aortic regurgitation during systolic phase accompanied by mitral regurgitation in patients with a continuous-flow left ventricular assist device (quoted from Ref. [22]). Echo images obtained from a patient undergoing LVAD implantation who showed systolic-phase aortic regurgitation (AR). The timing of the regurgitation jet started at the mid-systolic phase and ended at the early diastolic phase (A). The AR occurred slightly after the onset of mitral regurgitation (MR) (B), and both MR and AR timings were consistent with the systolic phase. No remarkable AR jet was documented during the diastolic phase. The AV was mostly closed throughout the cycles, which opens once every 8–10 beats (C). The mean pressure gradients of the trans-AV and trans-mitral valve based on the continuous wave Doppler measurements of AR (D) and MR flow (E) were 3.7 and 24.3 mmHg, respectively. The morphology of AV annulus changes through the cycles irrespective of the AV opening, with the AV annulus abnormally distorted and dilated during early mid-systole (F), whereas the septum wall as well as the AV annulus edge slightly pushed toward the LV during diastole (G).

Serial assessments of pulmonary artery pressure by Doppler‐derived TR pressure gradients are also important. In general, LVAD support can successfully unload LV, which results in the correction of pulmonary hypertension due to left‐sided heart failure. However, some patients have showed residual pulmonary vascular resistance post‐LVAD; therefore, echo‐guided optimal medical therapy, including the necessity of pulmonary dilators such as PDE5 inhibitors (sildenafil®, etc.), is required.

## *2.3.2. Detection of LVAD malfunction*

time velocity integral at RV outflow. In patients who have at least an intermittent aortic valve opening, RV cardiac output minus LV outflow-derived cardiac output is equivalent to the

**Figure 5.** Representative images in a LVAD recipient with different LVAD speeds. This patient received HeartMate II (Thoratec Corp) implantation. Under 8400 rpm, the aortic valve opened intermittently, and the ejection time was only 75 ms. When we set the speed down to 8200, the aortic valve opened every beat, but due to less unloading, the LV

**Figure 6.** Aortic regurgitation during systolic phase accompanied by mitral regurgitation in patients with a continuous-flow left ventricular assist device (quoted from Ref. [22]). Echo images obtained from a patient undergoing LVAD implantation who showed systolic-phase aortic regurgitation (AR). The timing of the regurgitation jet started at the mid-systolic phase and ended at the early diastolic phase (A). The AR occurred slightly after the onset of mitral regurgitation (MR) (B), and both MR and AR timings were consistent with the systolic phase. No remarkable AR jet was documented during the diastolic phase. The AV was mostly closed throughout the cycles, which opens once every 8–10 beats (C). The mean pressure gradients of the trans-AV and trans-mitral valve based on the continuous wave Doppler measurements of AR (D) and MR flow (E) were 3.7 and 24.3 mmHg, respectively. The morphology of AV annulus changes through the cycles irrespective of the AV opening, with the AV annulus abnormally distorted and dilated during early mid-systole (F), whereas the septum wall as well as the AV annulus edge slightly pushed toward the LV dur-

diameter increased and the amount of mitral regurgitation also increased.

estimated pump flow.

156 Echocardiography in Heart Failure and Cardiac Electrophysiology

ing diastole (G).

The careful observation of the inflow cannula is critically important. By using multiple views, including nonstandard ones, the thrombus or other causes of obstruction should be ruled out. The direction of the inflow cannula should also be reported. The direction may sometimes change after the surgery and direct toward the lateral wall, which may cause suctioning or inadequate LVAD support. Contrast echocardiography can provide additional information. Detecting the outflow cannula obstruction by echocardiography is difficult, but practitioners should try to find a good echo window and investigate any abnormality, including kinking (**Figure 7**) [22, 23].

**Figure 7.** Cases of LVAD malfunction detected by echocardiography (quoted from Refs. [23, 24]). Left: A 29‐year‐old male developed low output syndrome 5 months after LVAD implantation. Echocardiography revealed pendulating ob‐ stacles at the inflow cannula of the LVAD. The obstacle was removed surgically, which histologically turned out to be myocardium with fibrous tissue and thrombi. Right: A 53‐year‐old man undergoing LVAD implantation developed low output syndrome. Echocardiography indicated distortion of the outflow cannula of the LVAD. A 3D CT also showed the kinking of the cannula. The autopsy revealed thrombus at the kinking site.

The protocol for a ramp study was established by Uriel N [20]. It is useful in optimizing LVAD settings and in diagnosing device malfunctions. Ramp test echocardiography can be per‐ formed at the time of discharge for speed optimization and/or if device malfunction is suspected (**Figure 8**) [24]. The patient's left ventricular size, the frequency of the aortic valve opening, valvular insufficiency, blood pressure, and continuous flow-LVAD parameters should be recorded according to the increments of the device speed. Serial assessments of ramp tests are also helpful to detect LVAD clots [24].

**Figure 8.** A representative case with device thrombosis was detected by a ramp echocardiography device (quoted from Ref. [24]). A case of a 29-year-old woman undergoing HeartMate II LVAD implantation; serial ramp studies were used to diagnose intradevice thrombus after device implantation. The first ramp study on postoperative day (POD) 26 revealed an adequate reduction in ventricular size according to the increase in LVAD. The patient was discharged home and received routine anticoagulation maintenance therapy. However, a second ramp test was performed on POD 56 due to increased lactase dehydrogenase and brain natriuretic peptide levels and showed a marked increase in the LV chamber size without an adequate response to the LVAD speed changes. Given the suspicion for partial pump thrombosis, the patient was immediately hospitalized and received intravenous heparin infusion. The patient eventually underwent cardiac transplant successfully, and the partial clot was found inside of the pump (lower panel).

#### *2.3.3. Assessment of native cardiac function*

It is important to assess native LV function, especially in patients receiving LVAD as a bridge to recovery. We cannot assess LV function without turning off the LVAD because it drastically affects preload and afterload; therefore, we need to reduce the LVAD speed under adequate anticoagulation during weaning test echocardiography. Strain assessment has been reported to be more sensitive in evaluating the myocardial systolic and diastolic reserve, and 2D speckle tracing echocardiography for the assessment of myocardial recovery in LVAD recipients may be useful [25].

## **3. Echocardiography in transplant recipients**

## **3.1. Donor heart evaluation**

suspected (**Figure 8**) [24]. The patient's left ventricular size, the frequency of the aortic valve opening, valvular insufficiency, blood pressure, and continuous flow-LVAD parameters should be recorded according to the increments of the device speed. Serial assessments of ramp

**Figure 8.** A representative case with device thrombosis was detected by a ramp echocardiography device (quoted from Ref. [24]). A case of a 29-year-old woman undergoing HeartMate II LVAD implantation; serial ramp studies were used to diagnose intradevice thrombus after device implantation. The first ramp study on postoperative day (POD) 26 revealed an adequate reduction in ventricular size according to the increase in LVAD. The patient was discharged home and received routine anticoagulation maintenance therapy. However, a second ramp test was performed on POD 56 due to increased lactase dehydrogenase and brain natriuretic peptide levels and showed a marked increase in the LV chamber size without an adequate response to the LVAD speed changes. Given the suspicion for partial pump thrombosis, the patient was immediately hospitalized and received intravenous heparin infusion. The patient eventually un-

It is important to assess native LV function, especially in patients receiving LVAD as a bridge to recovery. We cannot assess LV function without turning off the LVAD because it drastically affects preload and afterload; therefore, we need to reduce the LVAD speed under adequate anticoagulation during weaning test echocardiography. Strain assessment has been reported

derwent cardiac transplant successfully, and the partial clot was found inside of the pump (lower panel).

*2.3.3. Assessment of native cardiac function*

tests are also helpful to detect LVAD clots [24].

158 Echocardiography in Heart Failure and Cardiac Electrophysiology

Evaluating a donor heart as accurately as possible at the time of procurement provides essential information to a recipient team leading the delicate posttransplant management of the heart [26]. If an organ procurement team has a cardiologist or sonographer who knows which patient is going to receive the heart, the team can gather detailed information by bedside echocar‐ diography on the donor in light of the potential recipient's conditions at the organ procure‐ ment.

Measuring the heart size of the donor from bedside echocardiography at the time of organ procurement can provide useful information for judging the appropriateness of proceeding with the heart transplant in the case of a donor‐recipient size mismatch. The wall thickness of the donor heart may also be useful information for optimizing the medical therapy after transplantation, as well as for deciding whether or not to use the organ. Information regarding the presence or absence of a septal defect would be of help to surgeons planning the additional procedure of septal closure at the time of transplantation. Information about the coronary flow in the left anterior descending artery of the donor heart, especially in cases with coronary risk factors, is useful for judging the availability of the heart, as well as for considering issues related to posttransplant medical management. Finally, information about preexisting localized wall motion abnormalities from bedside echocardiography is useful for speculating on the possi‐ bility of rejection or other reasons for wall motion abnormality after transplant surgery.

According to such information, the team can make a final decision whether or not to harvest the heart. For example, the donor heart may be relatively small for the potential recipient. If a donor heart with a lower limit of normal systolic function shows decreased coronary flow and localized right heart wall motion abnormality, the heart should be declined in cases where the potential recipients have moderately high pulmonary vascular resistance. Such recipients need to receive a donor heart with good right ventricular function.

## **3.2. A noninvasive rejection diagnosis**

Advances in immunosuppressive therapy have resulted in a marked decrease in the incidence of acute allograft rejection in heart transplant recipients; however, acute rejection still remains an important determinant factor for long‐term morbidity and mortality. Acute rejection can result in not only the immediate risk of graft loss or heart failure but also of subsequent allograft vasculopathy [27]. Therefore, early diagnosis of rejection and consequent timely treatment are crucial for the early and long‐term care in heart transplant recipients. Detection of allograft rejection based on the findings derived from endomyocardial biopsy (EMB) is still a gold standard; however, EMB is invasive, cost and time consuming, and may have a possibility of sampling error and interobserver variability. Although many noninvasive modalities, includ‐ ing radionuclide imaging, MRI, and gene expression profiling, have been investigated for their potential to detect rejection, none of them have been found to be sufficient for replacing EMB. Echocardiography has been routinely used in the management of cardiac transplant recipients. Indeed, it is an easily applicable, repeatable, and powerful noninvasive tool in the management of posttransplant recipients [28].


A, late diastolic mitral inflow velocity; DcT, deceleration time; E, early diastolic mitral inflow velocity; EF, ejection fraction; FS, fractional shortening; LV, left ventricle, left ventricular; IVRT, isovolumic relaxation time; IMP, myocardial performance index. \*MPI = (isovolumic contraction time – IVRT)/ejection time.

**Table 4.** Conventional echocardiographic variables associated with rejections (quoted from Ref. [29]).

#### *3.2.1. Conventional echocardiography*

**Table 4** summarizes the conventional echocardiographic parameters associated with acute cellular rejection [28]. Conventional echocardiography soon after the surgery can provide information about global systolic and diastolic functions, wall motion abnormality, and the hemodynamics of the transplanted hearts. Any apparent abnormal findings such as remark‐ able systolic and/or diastolic impairment may acute or hyperacute rejection, including antibody‐mediated rejection, although primary graft failure, donor‐related graft dysfunction, and any perioperative accidents should also be considered. The ability of conventional echo parameters to detect rejection is still limited to severe clinically detectable rejection. However, the findings are still useful for assessing responsiveness to treatment. In general, patients with rejection develop restrictive physiology accompanied by various degrees of systolic dysfunc‐ tion. Valantine HA et al. reported that a 15% decrease in mitral deceleration time or isovolumic relaxation time (IVRT) is associated with biopsy proven rejection [29]. More recently, Sun et al. reported that a combination of IVRT less than 90 ms, a mitral E/A ratio more than 1.7, and other clinical parameters is independently associated with rejection [30]. However, because transplant recipients usually have higher resting heart rates than the nontransplant population due to denervation, their mitral E and A waves can be fused. Indeed, it is difficult to obtain clear Doppler waves from transplant recipients. They frequently have extended adhesion of the transplanted heart to the chest cavity, which hinders the acquisition of an appropriate Doppler angle. The TEI index or myocardial performance index (MPI), which is a parameter of a Doppler‐derived combination of systolic and diastolic time intervals, is a useful parameter in patients with E‐A fusion and high heart rate; therefore, the MPI has the potential to detect rejection more accurately than traditional Doppler indices [31]. Representative conventional 2D echo images associated with and without rejection are shown in **Figure 9**.

standard; however, EMB is invasive, cost and time consuming, and may have a possibility of sampling error and interobserver variability. Although many noninvasive modalities, includ‐ ing radionuclide imaging, MRI, and gene expression profiling, have been investigated for their potential to detect rejection, none of them have been found to be sufficient for replacing EMB. Echocardiography has been routinely used in the management of cardiac transplant recipients. Indeed, it is an easily applicable, repeatable, and powerful noninvasive tool in the management

**•** Myocardial edema/preoperative ischemia also cause increase in LV wall thickness; so difficult

**•** Abnormal filling pattern/restrictive physiology is associated with rejection

**•** Heart rate dependent (not appropriate for patients with tachycardia)

Pericardial effusion↑ **•** May be related to the inflammatory process of rejection, but can have many causes, especially

**Table 4** summarizes the conventional echocardiographic parameters associated with acute cellular rejection [28]. Conventional echocardiography soon after the surgery can provide information about global systolic and diastolic functions, wall motion abnormality, and the hemodynamics of the transplanted hearts. Any apparent abnormal findings such as remark‐ able systolic and/or diastolic impairment may acute or hyperacute rejection, including antibody‐mediated rejection, although primary graft failure, donor‐related graft dysfunction, and any perioperative accidents should also be considered. The ability of conventional echo parameters to detect rejection is still limited to severe clinically detectable rejection. However,

A, late diastolic mitral inflow velocity; DcT, deceleration time; E, early diastolic mitral inflow velocity; EF, ejection fraction; FS, fractional shortening; LV, left ventricle, left ventricular; IVRT, isovolumic relaxation time; IMP, myocardial

**Table 4.** Conventional echocardiographic variables associated with rejections (quoted from Ref. [29]).

**•** Occurs in the late phase of the rejection process

**•** May be related to inflammatory cell infiltration

to interpret during early postoperative periods

TEI Index\* (MPI) ↑ **•** Can evaluate global ventricular performance (both systolic and diastolic)

**•** Derived from Doppler‐derived time intervals

during the early postoperative phase

performance index. \*MPI = (isovolumic contraction time – IVRT)/ejection time.

**•** Mild/moderate rejection cannot be detected

**•** Relatively pre/after‐load dependent

**•** Doppler angle dependent

**•** HR independent

*3.2.1. Conventional echocardiography*

of posttransplant recipients [28].

LVEF ↓ LV %FS ↓

LV wall thickness ↑ LV mass ↑

Mitral E/A ratio ↑ Mitral DcT ↓ IVRT ↓

**Variables Characteristics and pitfalls**

160 Echocardiography in Heart Failure and Cardiac Electrophysiology

**Figure 9.** Representative 2D echocardiography in a patient with and without cellular rejection. Representative conven‐ tional 2D echocardiograms obtained from a 26‐year‐old female transplant recipient at the time when her EMB showed conventional ISHLT grade 0 (left) and ISHLT grade 3a rejection (right). The posterior wall thickness of LV and the LV mass index without rejection (left) were 9 mm and 88 g/m2 , respectively. The same parameters associated with rejection (right) were 13 mm and 112 g/m2 . The arrow in the right lower panel indicates a pericardial effusion. EMB, endomyo‐ cardial biopsies; ISHLT, International Society for Heart and Lung Transplantation; LV, left ventricular and left ventricle.


**Table 5.** Tissue‐Doppler imaging and 2D‐speckle‐tracking echocardiography‐derived variables associated with rejections (quoted from Ref. [29]).

#### *3.2.2. Tissue Doppler imaging and speckle tracking echocardiography*

systolic rotation) – (basal end‐systolic rotation).

Tissue Doppler imaging (TDI) enables the measurements of systolic and diastolic velocities within the myocardium. Several studies have evaluated the usefulness of TDI‐derived mitral annular velocities to detect allograft rejection, which are summarized in **Table 5** [28]. Strain rate analysis has a potential to detect even mild rejection. Kato TS et al. reported that the attenuation of LV longitudinal strain and the diastolic strain rate derived from TDI were associated with conventional ISHLT (International Society for Heart and Lung Transplanta‐ tion) grade 1b or higher rejection without hemodynamic alterations (**Figure 10**) [32]. Marciniak et al. found significantly lower LV longitudinal and radial peak systolic strain and strain rate values in patients with conventional ISHLT grade 1b or higher rejection. TDI‐derived strain and strain rate potentially reflect abnormalities [33].

**Variables Characteristics and pitfalls**

162 Echocardiography in Heart Failure and Cardiac Electrophysiology

**•** Angle dependent

**•** Angle dependent **•** Frame rate limitations

**•** Angle dependent **•** Frame rate limitations

**•** Angle independent

**•** Angle independent

diastolic global strains **•** Angle independent

A′, late diastolic mitral annular velocity, E′, early diastolic mitral annular tissue velocity. \* LV torsion = (apical end‐

**Table 5.** Tissue‐Doppler imaging and 2D‐speckle‐tracking echocardiography‐derived variables associated with

Tissue Doppler imaging (TDI) enables the measurements of systolic and diastolic velocities within the myocardium. Several studies have evaluated the usefulness of TDI‐derived mitral annular velocities to detect allograft rejection, which are summarized in **Table 5** [28]. Strain rate analysis has a potential to detect even mild rejection. Kato TS et al. reported that the attenuation of LV longitudinal strain and the diastolic strain rate derived from TDI were associated with conventional ISHLT (International Society for Heart and Lung Transplanta‐ tion) grade 1b or higher rejection without hemodynamic alterations (**Figure 10**) [32]. Marciniak et al. found significantly lower LV longitudinal and radial peak systolic strain and strain rate

*3.2.2. Tissue Doppler imaging and speckle tracking echocardiography*

TDI‐derived diastolic strain rate ↓ **•** Reflecting relaxation abnormalities

2D‐STE‐derived LV torsion ↓ **•** Reflecting relaxation abnormalities

**•** Reflecting increased LV filling pressure/relaxation abnormalities

**•** Possibility of reflecting heterogeneous myocardial abnormalities

**•** Reflecting both systolic and diastolic abnormalities

**•** Ability to detect subclinical rejection

**•** Ability to detect subclinical rejection

**•** Ability to detect subclinical rejection

**•** Ability to detect subclinical rejection

**•** Values can be calculated offline using stored 2D images

**•** Values can be calculated offline using stored 2D images

**•** Values can be calculated offline using stored 2D images

**•** Possibility of reflecting heterogeneous myocardial abnormalities

**•** May be more sensitive for the early detection of rejection than systolic and early

**•** Reflecting both systolic and diastolic abnormalities

TDI derived E′ ↓ A′ ↓

TDI‐derived longitudinal systolic

TDI‐derived radial systolic strain ↓

2D‐STE‐derived global radial

2D‐STE‐derived systolic and diastolic global strain rate ↓

rejections (quoted from Ref. [29]).

systolic rotation) – (basal end‐systolic rotation).

systolic strain ↓

E/E′ ↑

strain ↓

**Figure 10.** Representative TDI‐derived strain analysis in a patient with and without rejection (quoted from Ref. [33]). Representative pathological findings for EMB specimens (a, b) and strain analysis (c, d) of HTx with ISHLT grade 0 (a, c) or 3a (b, d) rejection. Sections in (a) and (b) were stained with hematoxylin‐eosin; scale bars, 100 mm. EMB, endo‐ myocardial biopsies; HTx, heart transplant recipients; ISHLT, International Society for Heart and Lung Transplanta‐ tion.

Two‐dimensional speckle‐tracking echocardiography (2D‐STE) was developed as an angle‐ independent echocardiographic modality to evaluate cardiac mechanical function. The 2D‐ STE‐derived parameters associated with rejection are also shown in **Table 5** [28]. The association between LV torsional deformation and rejection in transplant recipients has been reported since the 1980s. Sato et al. reported that 2D‐STE‐derived LV torsion values are decreased in patients with rejection, and the serial assessments of an intra‐patients comparison showed that a cut‐off value of a 25% reduction of LV torsion from the baseline is associated with ISHLT grade 2 or higher rejection, which returns to the baseline after adequate rejection treatment (**Figure 11**) [34]. LV global strains are also calculated using 2D‐STE in an angle‐ independent manner. Sera F et al. reported that 2D‐STE‐derived LV global longitudinal strain was associated with treatment‐requiring rejection [35] (**Figure 12**). In addition to its major advantage of angle independency, 2D‐STE has other advantages over TDI, such as spatial resolution, translational artifacts, the sensitivity to signal noise, the time needed for data acquisition, and the necessity of employing expert readers. Three‐dimensional (3D) STEs are useful echocardiographic modalities to assess various strain and rotation parameters more accurately than 2D‐STE by tracking the same speckle throughout the cardiac cycle. However, it will take several years for the validation studies of 3D‐STE to be performed to verify the value of rejection‐detecting tools in heart transplant recipients.

**Figure 11.** Representative 2D speckle‐tracking echocardiogram and analysis of torsion in a patient with and without rejection. (quoted from Ref. [35]). Representative 2D‐STE imaging with rotation curves obtained from the same recipi‐ ent (a 32‐year‐old man) at LV short‐axis views of the apex (a, c) and the base (b, d). Each color of the deformational curve represents one segment of the LV, and the dashed white curve depicts the mean rotation of six segments. The LV‐ tor, defined as the difference between apical basal end‐systolic rotation when the patient had ISHLT grade 2 rejection, was 10.9 degrees (a, b). The LV torsion accompanied with ISHLT grade 0 after rejection treatment was 15.6 degrees (c, d). The % change of LV torsion in this patient at the time of rejection was approximately 30% decreased from his base‐ line. ISHLT, International Society for Heart and Lung Transplantation; LV, left ventricular; 2D‐STE, 2D speckle‐tracking echocardiography; EMB, endomyocardial biopsies; HTx, heart transplant recipients.

**Figure 12.** Representative 2D speckle tracking echocardiogram and analysis of global longitudinal strain in a patient with and without rejection (quoted from Ref. [36]). LS curves obtained from a patient without rejection (grade 0) (A) and another patient with grade 3a rejection (B). LS, longitudinal strain.

## *3.2.3. Transplant vasculopathy and echocardiography*

Echocardiography is a helpful and an ideal noninvasive tool to detect transplant vasculopathy or chronic rejection as well. Dobutamine or/and exercise stress echocardiography has been used to detect allograft vasculopathy, especially for pediatric patients or those with renal insufficiency [36]. Decreases in strain and strain rates at rest and with dobutamine stress are also useful to detect significant transplant vasculopathy. Contrast echocardiography is another useful method.

## **Author details**

**Figure 11.** Representative 2D speckle‐tracking echocardiogram and analysis of torsion in a patient with and without rejection. (quoted from Ref. [35]). Representative 2D‐STE imaging with rotation curves obtained from the same recipi‐ ent (a 32‐year‐old man) at LV short‐axis views of the apex (a, c) and the base (b, d). Each color of the deformational curve represents one segment of the LV, and the dashed white curve depicts the mean rotation of six segments. The LV‐ tor, defined as the difference between apical basal end‐systolic rotation when the patient had ISHLT grade 2 rejection, was 10.9 degrees (a, b). The LV torsion accompanied with ISHLT grade 0 after rejection treatment was 15.6 degrees (c, d). The % change of LV torsion in this patient at the time of rejection was approximately 30% decreased from his base‐ line. ISHLT, International Society for Heart and Lung Transplantation; LV, left ventricular; 2D‐STE, 2D speckle‐tracking

**Figure 12.** Representative 2D speckle tracking echocardiogram and analysis of global longitudinal strain in a patient with and without rejection (quoted from Ref. [36]). LS curves obtained from a patient without rejection (grade 0) (A)

echocardiography; EMB, endomyocardial biopsies; HTx, heart transplant recipients.

164 Echocardiography in Heart Failure and Cardiac Electrophysiology

and another patient with grade 3a rejection (B). LS, longitudinal strain.

Tomoko Kato1,2\*, Takashi Nishimura1,2, Shunei Kyo1,2, Kenji Kuwaki1,2, Hiroyuki Dada1,2 and Atsushi Amano1,2


## **References**


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#### **Assessment of Right Ventricle by Echocardiogram Assessment of Right Ventricle by Echocardiogram**

Gunjan Choudhary, Arushi A. Malik, Gunjan Choudhary, Arushi A. Malik, Dwight Stapleton and Pratap C. Reddy

Dwight Stapleton and Pratap C. Reddy Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/64781

## **Abstract**

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Assessment of right ventricular (RV) function is important to ascertain clinical outcome in patients with symptoms of right ventricular failure manifested as lower extremity swelling and abdominal congestion. RV function is not routinely assessed and reported in clinical practice. Unlike the bullet‐shaped left ventricle (LV), RV has a complex geometry with a triangular shape. RV is further divided into the inlet, trabecular apex, and infundibulum or conus. RV evaluation involves quantifying afterload and preload, assessing the mechanism and severity of tricuspid regurgitation (TR), and quantitative evaluation of RV performance. For quantification of RV size and function, we can use intravenous contrast for endocardial tracing of RV border to measure RV dimensions, tricuspid annular plane systolic excursion (TAPSE), fractional area change (FAC), Doppler index of myocardial performance (Tei index or myocardial performance index), pulsed wave or color Doppler tissue imaging systolic velocity [s'], or strain imaging. For qualitative evaluation of RV, the RV size is compared to the LV size in parasternal, short axis, and subcostal projections.

**Keywords:** right ventricle, functional evaluation, right heart hemodynamics, echocar‐ diography, clinical significance

## **1. Introduction**

Historically, the importance of right ventricle (RV) has been underestimated and overlooked in clinical practice and literature. Usually, left ventricle (LV) function is most commonly reported and signified. Only in recent years, the importance of assessment of RV size and function in clinical management and treatment of cardiopulmonary disorders has been recognized [1]. RV dysfunction is associated with adverse clinical outcome [2–8] in patients with LV dysfunction,

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

acute myocardial infarction, pulmonary embolism, pulmonary arterial hypertension, and congenitalheartdisease[9–11].Hence,thishasgeneratedinterestintheevaluationofRVfunction. RV dysfunction could be secondary to pressure or volume overload; from primary right heart disease or secondary to left heartdiseases such as cardiomyopathy or valvular heartdisease [12, 13] (**Tables 1** and **2**). RV dysfunction may affect by way of interventricular septal motion (ventricular interdependence) and by affecting LV preload.


**Table 1.** Causes of RV contractile dysfunction.


**Table 2.** Causes of right ventricular overload.

Of all the noninvasive imaging modalities, echocardiography remains a mainstay in the evaluation of RV. Moreover, with advances in echocardiography the pathophysiology of RV has been better understood. In this chapter, we aim to review various methods to assess RV anatomy, function, and hemodynamics using two‐dimensional (2D) echocardiography, color Doppler echocardiography, tissue Doppler imaging (TDI), three‐dimensional (3D) echocar‐ diography, and strain imaging echocardiography [12]. To identify RV pathology, guidelines have been published by the American Society of Echocardiography (ASE) on parameters and normal reference values (**Table 5**).

## **2. Location and anatomy of RV**

acute myocardial infarction, pulmonary embolism, pulmonary arterial hypertension, and congenitalheartdisease[9–11].Hence,thishasgeneratedinterestintheevaluationofRVfunction. RV dysfunction could be secondary to pressure or volume overload; from primary right heart disease or secondary to left heartdiseases such as cardiomyopathy or valvular heartdisease [12, 13] (**Tables 1** and **2**). RV dysfunction may affect by way of interventricular septal motion

(ventricular interdependence) and by affecting LV preload.

Arrhythmogenic right ventricular cardiomyopathy (ARVC)

170 Echocardiography in Heart Failure and Cardiac Electrophysiology

**Table 1.** Causes of RV contractile dysfunction.

(Tetralogy of Fallot, hypertrophic cardiomyopathy)

Secondary to tricuspid annular dilation from RV Dilation

**Table 2.** Causes of right ventricular overload.

Anomalous pulmonary venous drainage

All groups of pulmonary hypertension Massive pulmonary embolism

**RV cardiomyopathy**

Uhl's anomaly Sepsis

Viral myocarditis Coronary artery disease

**RV pressure overload**

Eisenmenger syndrome RV outflow obstruction Pulmonic valve stenosis Infundibular stenosis

Mechanical ventilation Hypoventilation **RV volume overload** Left to right shunt Atrial septal defect

Pulmonary regurgitation Tricuspid regurgitation

Infective endocarditis Carcinoid syndrome Rheumatic heart disease Ebstein's anomaly

Primary

ARDS

Dilated cardiomyopathy Endomyocardial fibrosis Cirrhotic cardiomyopathy Eosinophilic myocarditis Peripartum cardiomyopathy

> The RV in the normal heart is the most anteriorly situated cardiac chamber located immediately behind the sternum and anterior to LV. It forms the majority of the anterior as well as the inferior border of the cardiac silhouette. Due to this unique anatomical location, assessment of RV size and function by transthoracic echocardiogram (TTE) may appear easy but assessment of RV function is challenging given the odd geometry of the crescent‐shaped RV that wraps around conical LV. Furthermore, heavily trabeculated myocardium also limits the delineation of RV endocardial surface.

**Figure 1.** RV anatomy and myocardial fibers. The RV structure: illustrates the inlet, trabecular, and outlet components.

Unlike the LV that is ellipsoid or conical, the RV is crescent shaped or pyramidal, and its cavity has three components [14]: **Figure 1**


The RV is formed by free (anterior and posterior) wall and interventricular septum. Blood supply to the RV is by right coronary artery (equal in systole and diastole except in pressure overload and hypertrophy). The moderator band is supplied by the left anterior descending artery. The tricuspid valve has three papillary muscles and three cusps (anterior, posterior, and septal). The tricuspid valve is 2 mm more apical to the mitral valve. It is very important to be able to differentiate left ventricle from right ventricle based on morphology seen on an echocardiogram (**Table 3**).

Right ventricle is characterized by:


of the left ventricle)

**Table 3.** Morphological differences between the right ventricle from the left ventricle.

## **2.1. Musculature of ventricular wall**

The RV has one‐sixth the muscle mass of LV as it pumps against approximately one‐sixth the resistance the LV encounters. However, the RV pumps equal cardiac output as LV. The RV ejection fraction (EF) is lower as RV end‐diastolic volume is slightly larger than that of the left ventricle. Appropriately, the RV is adaptable as a volume pump but is likely to fail when subjected to acute pressure overload. The muscular wall of the RV excluding trabeculations is 3–5 mm thick [16]. RV is relatively thin walled having superficial subepicardial circumferential myofibers parallel to the atrioventricular groove that encircles the subpulmonary infundibu‐ lum and deeper subendocardial longitudinal myofibers. Unlike the relatively thick‐walled LV, the RV lacks the third layer of spiral/oblique myofibers. Longitudinal fibers contract to result in inward/radial thickening. The septal motion is considered to contribute to both LV and RV function [17, 18] and is a major determinant of overall RV performance [17–19].

## **2.2. RV area**

Unlike the LV that is ellipsoid or conical, the RV is crescent shaped or pyramidal, and its cavity

**1.** The muscular inlet comprising of the tricuspid valve, chordae tendineae, and three papillary muscles, which originate in ventricular wall and attach to anterior, posterior,

**2.** Immobile apex with heavy, coarse trabeculations; two thick intracavitary muscle bands, the crista supraventricularis [15], and the moderator band attached to the right ventricular outflow tract (RVOT) extending from the interventricular septum (IVS) to the anterior RV wall. The apical part of the RV is heavily trabeculated and virtually an immobile part of

The RV is formed by free (anterior and posterior) wall and interventricular septum. Blood supply to the RV is by right coronary artery (equal in systole and diastole except in pressure overload and hypertrophy). The moderator band is supplied by the left anterior descending artery. The tricuspid valve has three papillary muscles and three cusps (anterior, posterior, and septal). The tricuspid valve is 2 mm more apical to the mitral valve. It is very important to be able to differentiate left ventricle from right ventricle based on morphology seen on an

**•** Presence of trabeculations (trabeculations can also be seen in the left ventricle in case of pathological noncompaction

The RV has one‐sixth the muscle mass of LV as it pumps against approximately one‐sixth the resistance the LV encounters. However, the RV pumps equal cardiac output as LV. The RV ejection fraction (EF) is lower as RV end‐diastolic volume is slightly larger than that of the left ventricle. Appropriately, the RV is adaptable as a volume pump but is likely to fail when subjected to acute pressure overload. The muscular wall of the RV excluding trabeculations is

and septal leaflets of the tricuspid valve via chordae tendineae.

**3.** Smooth funnel‐shaped myocardial outflow tract called infundibulum [14].

**•** More *apical position* of the tricuspid valve as compared to the mitral valve

**•** Three leaflets of the tricuspid valve with *septal* papillary attachments

**Table 3.** Morphological differences between the right ventricle from the left ventricle.

has three components [14]: **Figure 1**

172 Echocardiography in Heart Failure and Cardiac Electrophysiology

the ventricle.

echocardiogram (**Table 3**).

Right ventricle is characterized by:

**•** Presence of a moderator band

of the left ventricle)

**•** Presence of more than three papillary muscles

**2.1. Musculature of ventricular wall**

The RV area is measured in the apical four‐chamber window at end‐diastole by planimetry of the RV cavity. Delineation of the RV endocardium is challenging and should exclude tra‐ beculations or moderator band; however, one should include the apex of the RV to avoid erroneous estimation. The normal reference limit for RV end‐diastolic area is *≤*24 cm2 in men and *≤*20 cm2 in women [14].

## **2.3. RV wall thickness**

The RV wall thickness can be measured by M‐mode or 2D echocardiography from either the left parasternal window or subcostal window at the level of the tip of the anterior tricuspid leaflet. RV hypertrophy is seen in infiltrative and hypertrophic cardiomyopathy, whereas RV wall thinning is seen in Uhl anomaly and arrhythmogenic RV cardiomyopathy. When meas‐ uring the RV wall thickness, it is essential to exclude RV trabeculations, papillary muscle, thickened pericardium, and epicardial fat. The normal cutoff is 0.5 cm from either parasternal long axis (PLAX) or subcostal windows.

## **2.4. RV linear dimensions**

RV size can be measured from the apical four‐chamber view at end‐diastole wherein RV should appear almost two‐thirds of the size of LV on qualitative assessment. The RV is enlarged in acute pressure and volume overload. The absence of standard reference points in RV imaging serves as a limitation in using transthoracic echocardiogram. The RV may appear viable in size when RV imaging is done through various cut planes depending on the probe rotation [20]. In the four‐chamber view, the focus should be on the right ventricular chamber "RV Focused view" for better imaging of the RV lateral wall and to maximize the RV size. One should adjust the transducer to attain maximal plane to avert underestimation and to avoid overestimation by positioning the transducer over the cardiac apex with the plane through the left ventricle in the center of the cavity. The basal diameter is the maximal short‐axis dimension in the basal, one‐third of the right ventricle. The mid‐cavity diameter is measured at the level of the LV papillary muscles in mid‐third of the RV, and the longitudinal dimension is measured from the plane of the tricuspid annulus to the RV apex. ASE guidelines for the right heart assessment recommend measurement of the following dimensions: RV basal‐apical four‐chamber view, RV wall thickness (subcostal long axis view), proximal RVOT PSAX (parasternal short axis) view at the great vessels level, and distal RVOT PLAX view (**Figure 2**).

**Figure 2. (A) RV basal apical four‐chamber view**: illustrating the plane of the tricuspid valve and RV endocardial bor‐ der. **(B) RV wall thickness** (subcostal long axis view): illustrates the LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; and RV lateral wall. **(C) Proximal RVOT** (parasternal short‐axis view PSAX at the great vessels lev‐ el): illustrates the Ao, aorta; PA, pulmonary artery; LV, left ventricle; RVOT, right ventricular outflow tract; and RV an‐ terior wall. **(D) Distal RVOT** (parasternal long axis view PLAX): illustrates the Ao, aorta; LA, left atrium; LV, left ventricle; RVOT, right ventricular outflow tract, RV anterior wall.

## **2.5. Right ventricular outflow tract**

(A)

174 Echocardiography in Heart Failure and Cardiac Electrophysiology

(B)

(D)

ventricle; RVOT, right ventricular outflow tract, RV anterior wall.

**Figure 2. (A) RV basal apical four‐chamber view**: illustrating the plane of the tricuspid valve and RV endocardial bor‐ der. **(B) RV wall thickness** (subcostal long axis view): illustrates the LA, left atrium; LV, left ventricle; RA, right atrium; RV, right ventricle; and RV lateral wall. **(C) Proximal RVOT** (parasternal short‐axis view PSAX at the great vessels lev‐ el): illustrates the Ao, aorta; PA, pulmonary artery; LV, left ventricle; RVOT, right ventricular outflow tract; and RV an‐ terior wall. **(D) Distal RVOT** (parasternal long axis view PLAX): illustrates the Ao, aorta; LA, left atrium; LV, left The RVOT includes the pulmonic valve and subpulmonary infundibulum or conus that extends from the crista supraventricularis to the pulmonary valve [21, 22]. RVOT is usually imaged from the left parasternal short axis view. In patients with congenital heart disease and arrhythmogenic RV dysplasia, parasternal long axis view may be added to assess the proximal and distal diameter of RVOT. There is no standard window for measurement of RVOT size; oblique imaging may interfere in the accurate estimation of its size. The upper reference limit for the PSAX distal RVOT diameter is 27 mm and for PLAX is 33 mm (**Table 5**).

## **2.6. Interventricular septal morphology**

Normally the LV has circular shape throughout the cardiac cycle. During systole, the LV protrudes into the RV. Compliance of one ventricle can modify the other through diastolic ventricular interaction. However, interventricular septum gets flattened and curved into LV cavity secondary to volume and pressure overload of the RV. The LV cavity, therefore, appears D‐shaped at end‐systole and end‐diastole in RV pressure overload and RV volume overload (e.g., tricuspid regurgitation), respectively [17, 19] (**Figure 3**).

## **2.7. Volumetric assessment of RV**

Two‐dimensional TTE approximates complex RV geometry and underestimates MRI‐derived RV volume. Assessment of RV volume using 3D TTE is superior and more accurate because 3D echo uses disc summation and apical rotational methods for RV volume and EF assessment [20]. However, the accuracy of RV volume assessment is less definite when the RV is dilated.

**Figure 3.** Example of RV with D‐shaped LV cavity. RV, right ventricle; LV, left ventricle.

## **3. Intracardiac pressure measurement**

Echocardiography can provide an estimate of right heart hemodynamics.

## **3.1. Estimated right atrial (RA) pressure**

Estimation of right atrial pressure can be derived from the size of the inferior vena cava (IVC) and its response to changes in spontaneous respiration [23, 24]. Using a dilated IVC to assess elevated RA pressures is not accurate in mechanically ventilated patients. However, a small IVC of less than 1.2 cm in mechanically ventilated patient is 100% specific for an RA pressure of less than 10 mm Hg. Normal IVC is <2 cm in diameter, approximately 1 cm from RA‐IVC junction and collapses by at least 50% with inspiration or sniff. A flat IVC indicates low RA pressure [0–5 mm Hg]. IVC <2 cm with normal inspiratory collapse indicates RA pressure of 5 mm Hg, and an IVC of >2 cm with normal inspiratory collapse suggests an RA pressure of 10 mm Hg. IVC <2 cm but without inspiratory collapse suggests 15 mm Hg RA pressure; IVC >2 cm but without inspiratory collapse suggests an RA pressure of 20 mm Hg. The normal RA pressure is 0–5 mm Hg.

## **3.2. Pulmonary artery systolic pressure (PASP)**

Pulmonary artery (PA) systolic pressure can be determined from tricuspid regurgitation peak velocity. Provided there is no tricuspid valve obstruction, peak TR velocity depends on the pressure gradient between the right ventricle and right atrium [the difference between peak right ventricular systolic pressure (RVSP) and RA pressure] (**Table 4**). Therefore, estimated RVSP is equal to pressure difference (determined from peak TR velocity using Bernoulli equation) and estimated RA pressure [25]. (**Figure 4**) When there is no obstruction across the pulmonic valve, RVSP will be similar to PASP. PASP = 4 × peak TR velocity2 + estimated RA pressure. For example, if TR velocity is 2.5 m/sec and IVC is normal in size and collapses with inspiration the estimated PASP would be 33 mm Hg [4(2.5)2 mm Hg = 25 mm Hg + 5 mm Hg (estimated RA pressure)]. If the estimated PASP is >35 to 40 mm Hg, pulmonary HTN is considered to be present.

#### **3.3. Pulmonary artery diastolic pressure (PADP)**

Pulmonary regurgitation (PR) represents the pressure difference between pulmonary artery and right ventricle. Hence, the end‐diastolic pulmonary regurgitation velocity can be utilized to measure the end‐diastolic pressure difference between PA and right ventricle. PA diastolic pressure can be estimated from the spectral Doppler signal of pulmonary regurgitation. The right ventricular end‐diastolic pressure is the same as RA pressure; therefore, PADP can be estimated by addition of the estimated RA pressure to the end‐diastolic pressure difference between PA and right ventricle. Thus, PADP = 4 × (end‐diastolic pulmonary regurgitation velocity)2 + estimated RA pressure.

Color flow regurgitant jet area of 30% or more of RA area Annulus dilation (≥4 cm) or inadequate cusp coaptation Late systolic concave configuration of the continuous‐wave signal Late systolic flow reversals in the hepatic vein ERO of 0.4 cm2 or larger Regurgitant volume of 45 mL or more Width of vena contracta of 6.5 mm or more

**3. Intracardiac pressure measurement**

176 Echocardiography in Heart Failure and Cardiac Electrophysiology

**3.2. Pulmonary artery systolic pressure (PASP)**

**3.3. Pulmonary artery diastolic pressure (PADP)**

+ estimated RA pressure.

**3.1. Estimated right atrial (RA) pressure**

pressure is 0–5 mm Hg.

considered to be present.

velocity)2

Echocardiography can provide an estimate of right heart hemodynamics.

Estimation of right atrial pressure can be derived from the size of the inferior vena cava (IVC) and its response to changes in spontaneous respiration [23, 24]. Using a dilated IVC to assess elevated RA pressures is not accurate in mechanically ventilated patients. However, a small IVC of less than 1.2 cm in mechanically ventilated patient is 100% specific for an RA pressure of less than 10 mm Hg. Normal IVC is <2 cm in diameter, approximately 1 cm from RA‐IVC junction and collapses by at least 50% with inspiration or sniff. A flat IVC indicates low RA pressure [0–5 mm Hg]. IVC <2 cm with normal inspiratory collapse indicates RA pressure of 5 mm Hg, and an IVC of >2 cm with normal inspiratory collapse suggests an RA pressure of 10 mm Hg. IVC <2 cm but without inspiratory collapse suggests 15 mm Hg RA pressure; IVC >2 cm but without inspiratory collapse suggests an RA pressure of 20 mm Hg. The normal RA

Pulmonary artery (PA) systolic pressure can be determined from tricuspid regurgitation peak velocity. Provided there is no tricuspid valve obstruction, peak TR velocity depends on the pressure gradient between the right ventricle and right atrium [the difference between peak right ventricular systolic pressure (RVSP) and RA pressure] (**Table 4**). Therefore, estimated RVSP is equal to pressure difference (determined from peak TR velocity using Bernoulli equation) and estimated RA pressure [25]. (**Figure 4**) When there is no obstruction across the

pressure. For example, if TR velocity is 2.5 m/sec and IVC is normal in size and collapses with inspiration the estimated PASP would be 33 mm Hg [4(2.5)2 mm Hg = 25 mm Hg + 5 mm Hg (estimated RA pressure)]. If the estimated PASP is >35 to 40 mm Hg, pulmonary HTN is

Pulmonary regurgitation (PR) represents the pressure difference between pulmonary artery and right ventricle. Hence, the end‐diastolic pulmonary regurgitation velocity can be utilized to measure the end‐diastolic pressure difference between PA and right ventricle. PA diastolic pressure can be estimated from the spectral Doppler signal of pulmonary regurgitation. The right ventricular end‐diastolic pressure is the same as RA pressure; therefore, PADP can be estimated by addition of the estimated RA pressure to the end‐diastolic pressure difference between PA and right ventricle. Thus, PADP = 4 × (end‐diastolic pulmonary regurgitation

+ estimated RA

pulmonic valve, RVSP will be similar to PASP. PASP = 4 × peak TR velocity2

*Abbreviations*: ERO, effective regurgitant orifice; RA, right atrium.

**Table 4.** Severe TR is defined by echocardiography on the basis of the following criteria.

**Figure 4.** Peak TR velocity. RVSP = 4(*V*max) 2 + RAP. In the absence of pulmonic stenosis: RVSP = PASP. Peak TR velocity depends on pressure gradient between right ventricle and right atrium [difference between peak RVSP and RA pres‐ sure] provided there is no tricuspid valve obstruction. TR, tricuspid regurgitation; RAP, right atrium pressure; RVSP, right ventricle systolic pressure; *V*max, peak TR velocity.

#### **3.4. Mean pulmonary artery pressure**

There are various formulae to estimate mean PA pressure [26–28]. Mean PA pressure = 1/3(PASP) + 2/3 (PADP). Mean PA pressure can be estimated by pulmonary acceleration time (AT) measured by pulsed Doppler of the pulmonary artery in systole. Mean PA pressure = 79 × (0.45 × AT) or if AT <120 ms, mean PA pressure = 90 – (0.62 × AT). Mean PA pressure = 4 × (early PR velocity)2 + estimated RA pressure. Mean PA pressure = estimated RA pressure + velocity‐time integral of the TR jet to calculate a mean systolic pressure.

## **3.5. Pulmonary vascular resistance (PVR)**

As per the formula *P* = *QR*, where pressure (*P*) equals the product of flow (*Q*) and resistance (*R*), PASP can be elevated in the setting of increased stroke volume without PVR being elevated. PVR can be calculated by the ratio of peak TR velocity (m/s) to RVOT VTI (velocity time integral) (cm) [29, 30]. PVR = [(TR velocity/RVOT VTI) × 10] + 0.16. PVR value is in Woods units (WU) and correlates well with invasively measured PVR up to approximately 8 WU [30]. However, when PVR is >8 WU by invasive hemodynamic measurement the relationship is not reliable. This method is not validated and should not be used for routine clinical purposes in place of invasive hemodynamic measurements. It can be used when PASP is elevated from increased stroke volume or PASP is low (despite increased PVR) from decreased stroke volume.

## **4. Assessment of RV function**

Most of the RV contraction occurs longitudinally from base to apex (contributing to most of the RV stroke volume), along with radial thickening/inward motion. The following techniques are used to assess RV function [15, 16, 31, 32].

## **4.1. Tricuspid annular planar systolic excursion (TAPSE)**

TAPSE is a diagnostic and prognostic tool of mortality and morbidity in patients with preca‐ pillary pulmonary hypertension, RV infarction associated with inferior myocardial infarction, and chronic left‐sided heart failure [33, 34]. TAPSE is assessed in an apical four‐chamber view by placing the M‐mode on the lateral tricuspid annulus; maximum systolic excursion of the lateral annulus along its longitudinal plane toward the apex is recorded [33, 35]. The displace‐ ment of the basal segment from the reference point reflects longitudinal contraction of the RV. Normal reference limit is TAPSE of >1.6 cm [36, 37]. This is the most commonly used method as it is a simple, easily obtainable, reproducible with a low interobserver variability. For accurate estimation of TAPSE, one should place M‐mode cursor parallel to the plane of longitudinal motion carefully measuring the magnitude of displacement from the M‐mode image. The limitations of this method are that TAPSE estimates only the longitudinal contrac‐ tion within one segment of RV and hypothesizes that the function of a single RV segment reflects the entire RV function which is not true in conditions like RV infarction and pulmonary embolism (**Figure 5**).

(AT) measured by pulsed Doppler of the pulmonary artery in systole. Mean PA pressure = 79 × (0.45 × AT) or if AT <120 ms, mean PA pressure = 90 – (0.62 × AT). Mean PA pressure = 4 ×

As per the formula *P* = *QR*, where pressure (*P*) equals the product of flow (*Q*) and resistance (*R*), PASP can be elevated in the setting of increased stroke volume without PVR being elevated. PVR can be calculated by the ratio of peak TR velocity (m/s) to RVOT VTI (velocity time integral) (cm) [29, 30]. PVR = [(TR velocity/RVOT VTI) × 10] + 0.16. PVR value is in Woods units (WU) and correlates well with invasively measured PVR up to approximately 8 WU [30]. However, when PVR is >8 WU by invasive hemodynamic measurement the relationship is not reliable. This method is not validated and should not be used for routine clinical purposes in place of invasive hemodynamic measurements. It can be used when PASP is elevated from increased stroke volume or PASP is low (despite increased PVR) from decreased stroke

Most of the RV contraction occurs longitudinally from base to apex (contributing to most of the RV stroke volume), along with radial thickening/inward motion. The following techniques

TAPSE is a diagnostic and prognostic tool of mortality and morbidity in patients with preca‐ pillary pulmonary hypertension, RV infarction associated with inferior myocardial infarction, and chronic left‐sided heart failure [33, 34]. TAPSE is assessed in an apical four‐chamber view by placing the M‐mode on the lateral tricuspid annulus; maximum systolic excursion of the lateral annulus along its longitudinal plane toward the apex is recorded [33, 35]. The displace‐ ment of the basal segment from the reference point reflects longitudinal contraction of the RV. Normal reference limit is TAPSE of >1.6 cm [36, 37]. This is the most commonly used method as it is a simple, easily obtainable, reproducible with a low interobserver variability. For accurate estimation of TAPSE, one should place M‐mode cursor parallel to the plane of longitudinal motion carefully measuring the magnitude of displacement from the M‐mode image. The limitations of this method are that TAPSE estimates only the longitudinal contrac‐ tion within one segment of RV and hypothesizes that the function of a single RV segment reflects the entire RV function which is not true in conditions like RV infarction and pulmonary

velocity‐time integral of the TR jet to calculate a mean systolic pressure.

+ estimated RA pressure. Mean PA pressure = estimated RA pressure +

(early PR velocity)2

volume.

**3.5. Pulmonary vascular resistance (PVR)**

178 Echocardiography in Heart Failure and Cardiac Electrophysiology

**4. Assessment of RV function**

embolism (**Figure 5**).

are used to assess RV function [15, 16, 31, 32].

**4.1. Tricuspid annular planar systolic excursion (TAPSE)**

**Figure 5.** A: Example of a normal TAPSE (tricuspid annular planar systolic excursion) value >1.6 cm; B: normal TAPSE; C: reduced TAPSE.

C

## **4.2. Tricuspid annular velocity S'**

The tricuspid annular velocity is also known as systolic excursion velocity S'. In an apical four‐ chamber view, the cursor of pulsed tissue Doppler or color‐coded tissue Doppler is placed on the lateral tricuspid annulus to measure the longitudinal velocity of excursion of basal‐free wall segment and tricuspid annulus in systole. Normal reference limit (**Table 5**) of S' is *>*9.5 cm/s. Color‐coded tissue Doppler yields lower velocities and is analyzed off‐line on specific platforms. The advantages and disadvantages are similar to TAPSE.


*Abbreviations*: 2D, two‐dimensional; 3D, three‐dimensional ; FAC, fractional area change; MPI, myocardial performance index; PLAX, parasternal long‐axis; PSAX, parasternal short‐axis; RA, right atrium; RV, right ventricle; RVOT, right ventricular outflow tract; TAPSE, tricuspid annular plane systolic excursion; RIMP, right ventricular index of myocardial performance.

**Table 5.** Echocardiographic parameters for assessment of right ventricle based on ASE recommendations.

#### **4.3. Myocardial performance index (MPI)**

The myocardial performance index is also denoted as the right ventricular index of myocardial performance (RIMP) or right ventricular Tei index. It is an index of global ventricular function and is independent of the geometry of the ventricle [38]. The MPI is calculated by the ratio of isovolumetric time interval over ventricular ejection time as follows: MPI = (isovolumetric relaxation time + isovolumetric contraction time)/ventricular ejection time = (tricuspid closure to opening time – ejection time)/ejection time. Lower MPI values indicate healthy RV function as less time is utilized in isovolumetric state and more time is consumed in ejecting blood. MPI can be measured through pulsed Doppler or tissue Doppler methods (**Figure 6**).

**Figure 6.** Pulse Doppler MPI. Calculation of RIMP by pulse tissue Doppler imaging RIMP = (TCO ‐ ET)/ET or IVRT + IVCT/ET. RIMP, right ventricular index of myocardial performance; TCO, tricuspid valve closure to opening time; IVCT, isovolumetric contraction time; IVRT, isovolumetric relaxation time; ET, ejection time.

## *4.3.1. Pulsed Doppler method*

**4.2. Tricuspid annular velocity S'**

180 Echocardiography in Heart Failure and Cardiac Electrophysiology

**RV systolic dysfunction**

TAPSE ≤ 1.6 cm

2D RV FAC <35%

RVEF 3D ≤44%

**RV diastolic dysfunction** E/A <0.8 by tissue Doppler E/A >2.1 by tissue Doppler **Dilated RV chamber** Basal RV diameter >4.2 cm Mid‐level diameter >3.5 cm Longitudinal dimension >8.6 cm

**Abnormal RVOT value**

performance.

RVOT in PSAX distal diameter >2.7 cm RVOT in PLAX proximal diameter >3.3 cm Increased RV subcostal wall thickness >0.5 cm

**4.3. Myocardial performance index (MPI)**

The tricuspid annular velocity is also known as systolic excursion velocity S'. In an apical four‐ chamber view, the cursor of pulsed tissue Doppler or color‐coded tissue Doppler is placed on the lateral tricuspid annulus to measure the longitudinal velocity of excursion of basal‐free wall segment and tricuspid annulus in systole. Normal reference limit (**Table 5**) of S' is *>*9.5 cm/s. Color‐coded tissue Doppler yields lower velocities and is analyzed off‐line on specific

*Abbreviations*: 2D, two‐dimensional; 3D, three‐dimensional ; FAC, fractional area change; MPI, myocardial performance index; PLAX, parasternal long‐axis; PSAX, parasternal short‐axis; RA, right atrium; RV, right ventricle; RVOT, right ventricular outflow tract; TAPSE, tricuspid annular plane systolic excursion; RIMP, right ventricular index of myocardial

The myocardial performance index is also denoted as the right ventricular index of myocardial performance (RIMP) or right ventricular Tei index. It is an index of global ventricular function and is independent of the geometry of the ventricle [38]. The MPI is calculated by the ratio of isovolumetric time interval over ventricular ejection time as follows: MPI = (isovolumetric

**Table 5.** Echocardiographic parameters for assessment of right ventricle based on ASE recommendations.

platforms. The advantages and disadvantages are similar to TAPSE.

Pulse Doppler peak annular velocity at tricuspid annulus S' <9.5 cm/s

Tei index/RIMP >0.40 by pulsed Doppler and >0.55 by tissue Doppler

In the pulsed Doppler method, pulsed wave Doppler tracing of the distal RVOT is used to obtain ejection time, while the tricuspid‐closure‐opening time is calculated from the pulsed wave Doppler tracing of the tricuspid inflow (time from end of the A wave to the onset of the following E wave) or the continuous wave Doppler tracing of the tricuspid regurgitation jet. The total isovolumetric time is calculated from the difference between the tricuspid‐closure‐ opening time and the ejection time. The normal reference limit for the pulsed Doppler MPI is *<*0.40.

## *4.3.2. Tissue Doppler method*

Tissue Doppler method obtains the ejection time, tricuspid‐closure‐opening time, and total isovolumetric time from the pulsed tissue Doppler tracing of the lateral tricuspid annulus. The normal reference limit for the tissue Doppler MPI is *<*0.54.

MPI is a sensitive parameter to evaluate subclinical or early RV dysfunction even in poorly visualized RV because it depends on time intervals [39]. However, MPI is observer dependent as delineating time intervals can be challenging [40].

## **4.4. Fractional area change (FAC)**

FAC is the percent change in RV area from diastole to systole.

FAC = [(end‐diastolic RV area – end‐systolic RV area)/end‐diastolic RV area] × 100. FAC is best correlated with MRI‐derived RVEF. RV endocardium is traced both in systole and diastole from the annulus, along the free wall to the apex and then back to the annulus, along the interventricular septum. The RV wall should be carefully traced under the trabeculations. FAC has prognostic value and is an independent predictor of all‐cause mortality in patients with acute myocardial infarction and low left ventricular ejection fraction. The reference value for normal RV systolic function is *>*35%.

## **5. Pulse Doppler MPI**

## **5.1. Three‐dimensional echocardiogram**

3D echo combined with intravenous contrast agents can improve endocardial border delin‐ eation and RV end‐diastolic and end‐systolic volumes.

$$\begin{aligned} \text{RVEF} &= \begin{bmatrix} \text{end} - \text{diastolic RV volume} \ - \text{ end} - \text{systolic RV volume} \end{bmatrix} / \\ \text{end} &- \text{diastolic RV volume} \end{aligned} \tag{1}$$

The RV volumes measured by 3D echo use disk summation or surface modeling method. Although 3D echo‐derived RVEF correlates well with MRI‐derived RVEF, the method is complex, time‐consuming, and very much dependent on image quality [20]. The normal reference limit for 3D‐derived RVEF is *>*45%.

## **5.2. Strain imaging by 2D**

The strain is the degree of myocardial deformation, while strain rate represents the rate of myocardial deformation over time [38]. In echocardiography, RV longitudinal strain can be assessed reliably from apical views, whereas the assessment of radial strain is challenging from the parasternal views because of near‐field artifacts and extremely small computational distance. The crescent shape of thin‐walled RV contributes to inhomogeneous strain rate and values with the highest values in the apical segments and outflow tract. One‐dimensional strain is measured using a tissue Doppler (angle‐dependent) [18], while 2D strain is measured by speckle tracking (non‐angle‐dependent). 2D strain imaging estimates global and regional RV function, reflects intrinsic contractility of the RV (with contractility defined as the less stress‐ strain interplay), and evaluates diastolic properties [39, 41].

Disadvantages are a dearth of normative data, challenges in the adequate image acquisition and analysis requiring high frame rates, high signal‐to‐noise ratio, minimal image dropout, and most notably the need for experienced observers for reproducible measurements. As it is not highly reproducible, this technique is not recommended for routine use. Given high variability, no reference limits are available [40].

## **6. Clinical and prognostic significance of assessment of right ventricle**

Quantitative assessment of RV size and function has prognostic value regarding exercise tolerance and outcome in various cardiac and pulmonary diseases [3, 36, 42, 43]. RV pump function depends on contractility, afterload, preload, heart rate, rhythm, and valve function. Being a thin‐walled chamber, it is not suited to sustain high pressure (**Tables 1** and **2**). RV dysfunction can be acute or chronic, secondary to RV volume overload, pressure overload, or decreased contractility.

## **6.1. RV overload**

**4.4. Fractional area change (FAC)**

182 Echocardiography in Heart Failure and Cardiac Electrophysiology

normal RV systolic function is *>*35%.

**5.1. Three‐dimensional echocardiogram**

reference limit for 3D‐derived RVEF is *>*45%.

eation and RV end‐diastolic and end‐systolic volumes.

end diastolic RV volu e

strain interplay), and evaluates diastolic properties [39, 41].

= - -

**5. Pulse Doppler MPI**

**5.2. Strain imaging by 2D**

FAC is the percent change in RV area from diastole to systole.

FAC = [(end‐diastolic RV area – end‐systolic RV area)/end‐diastolic RV area] × 100. FAC is best correlated with MRI‐derived RVEF. RV endocardium is traced both in systole and diastole from the annulus, along the free wall to the apex and then back to the annulus, along the interventricular septum. The RV wall should be carefully traced under the trabeculations. FAC has prognostic value and is an independent predictor of all‐cause mortality in patients with acute myocardial infarction and low left ventricular ejection fraction. The reference value for

3D echo combined with intravenous contrast agents can improve endocardial border delin‐


/

RVEF end diastolic RV volume – end systolic RV volume [ ]

m .

The RV volumes measured by 3D echo use disk summation or surface modeling method. Although 3D echo‐derived RVEF correlates well with MRI‐derived RVEF, the method is complex, time‐consuming, and very much dependent on image quality [20]. The normal

The strain is the degree of myocardial deformation, while strain rate represents the rate of myocardial deformation over time [38]. In echocardiography, RV longitudinal strain can be assessed reliably from apical views, whereas the assessment of radial strain is challenging from the parasternal views because of near‐field artifacts and extremely small computational distance. The crescent shape of thin‐walled RV contributes to inhomogeneous strain rate and values with the highest values in the apical segments and outflow tract. One‐dimensional strain is measured using a tissue Doppler (angle‐dependent) [18], while 2D strain is measured by speckle tracking (non‐angle‐dependent). 2D strain imaging estimates global and regional RV function, reflects intrinsic contractility of the RV (with contractility defined as the less stress‐

Disadvantages are a dearth of normative data, challenges in the adequate image acquisition and analysis requiring high frame rates, high signal‐to‐noise ratio, minimal image dropout, and most notably the need for experienced observers for reproducible measurements. As it is RV overload can be related to pressure overload or volume overload. RV overload, in turn, reduces LV diastolic function and causes higher filling pressures.

## *6.1.1. Volume overload*

Volume overload can result from tricuspid regurgitation, pulmonary regurgitation, ASD, and VSD and is assessed through the movement of IVS. Normally during systole, IVS thickens and moves into the left ventricle and during diastole, it moves into the RV cavity. In RV volume overload, RA and RV are enlarged, and IVS is pushed into the LV during end‐systole and early diastole as RV pressure exceeds LV pressure. This leads to IVS flattening and a D‐shaped LV only during early diastole. At the outset of systole, LV contraction increases LV pressure pushing the IVS in the direction of RV cavity [12].

## *6.1.2. Pressure overload*

Pressure overload can be acute or chronic. Acute pressure overload can be from adult respi‐ ratory distress syndrome (ARDS) or massive pulmonary embolism. Echocardiographic findings of RV pressure overload are the same as volume overload. RA and RV are enlarged with no hypertrophy of RV‐free wall; there is a flattening of the IVS in diastole. The peak RV systolic pressures rarely exceed 50 mm Hg in acute pressure overload. Chronic pressure overload is secondary to chronic lung diseases, chronic thromboembolism, or chronic pulmo‐ nary venous hypertension from left heart pathology. RV is enlarged with thickening of the RV‐ free wall and increased trabeculation. The RV can generate higher peak systolic pressures, usually exceeding 50 mm Hg. The IVS remains flattened into the LV cavity during the entire cardiac cycle.

## **6.2. Right ventricular diastolic function**

RV diastolic dysfunction has prognostic value and has been associated with both acute and chronic conditions. RV diastolic function is assessed like that of the left ventricle. Techniques used are Doppler velocities of the trans tricuspid flow (E, A, E/A), tissue Doppler velocities of the tricuspid annulus (E', A', and E'/A'), deceleration time, and isovolumetric relaxation time [20, 40]. Estimation of RA pressure by measurement of IVC diameter and collapse with inspiration is to be considered while determining the RV diastolic function.

## **6.3. Cardiac rhythm and the RV**

RV function is dependent on cardiac rhythm. RV function is compromised by atrial fibrillation and ventricular tachycardia originating from the RV examples of which are arrhythmogenic RV dysplasia, RV myocardial infarction, idiopathic ventricular tachycardia, or ventricular tachycardia occurring after surgical repair of congenital heart disease [44].

## **6.4. Cardiac markers**

The elevated B‐type natriuretic peptide is associated with RV failure secondary to pulmonary hypertension, congenital heart disease, or pulmonary disease [45–47]. Elevated troponin levels indicate poor prognosis in pulmonary embolism and pulmonary hypertension [48].

## **6.5. Evaluation of pulmonary arterial hypertension**

Pulmonary arterial hypertension is a clinical entity that is seen as a consequence of both left heart disease and pulmonary pathology, as well as occurring without an underlying etiology such as primary pulmonary arterial hypertension. Estimation of pulmonary artery pressure can be performed by TTE in the majority of patients [37, 49].

## **6.6. Evaluation of patients with pulmonary embolism**

Pulmonary embolism is associated with high mortality and morbidity; hence, prompt diag‐ nosis and treatment is imperative. When a patient has had a large pulmonary embolism, this may place acute pressure overload on the right ventricle. The right ventricle handles pressure poorly and may undergo acute dilation with decreased right ventricular systolic function as a result of an acute increase in afterload. Usually, peak systolic pressures in the pulmonary artery do not exceed 50 mm Hg unless there is a baseline chronic RV pressure overload. The size and function of the RV are among the most important factors in determining the initiation of either thrombolysis or referral for surgical embolectomy. A classic pattern of RV systolic dysfunction in acute pulmonary embolism has been described. This is known as McConnell sign and is characterized by akinesis of the free wall of the right ventricle with sparing of the apical segment. This phenomenon has 77% sensitivity and 94% specificity for the diagnosis of acute pulmonary embolism (**Figure 7**).

## **6.7. Evaluation of RV dyssynchrony**

Echocardiographic indices of dyssynchrony are assessed by measuring time delay in mechan‐ ical activity between segments. Tissue Doppler imaging is limited to the assessment of the septum‐RV free wall.

**Figure 7.** McConnell sign. McConnell sign: akinesis of the free wall of the right ventricle with sparing of the apical segment seen in acute pulmonary embolism causing right ventricle systolic dysfunction.

## **7. Conclusion**

used are Doppler velocities of the trans tricuspid flow (E, A, E/A), tissue Doppler velocities of the tricuspid annulus (E', A', and E'/A'), deceleration time, and isovolumetric relaxation time [20, 40]. Estimation of RA pressure by measurement of IVC diameter and collapse with

RV function is dependent on cardiac rhythm. RV function is compromised by atrial fibrillation and ventricular tachycardia originating from the RV examples of which are arrhythmogenic RV dysplasia, RV myocardial infarction, idiopathic ventricular tachycardia, or ventricular

The elevated B‐type natriuretic peptide is associated with RV failure secondary to pulmonary hypertension, congenital heart disease, or pulmonary disease [45–47]. Elevated troponin levels

Pulmonary arterial hypertension is a clinical entity that is seen as a consequence of both left heart disease and pulmonary pathology, as well as occurring without an underlying etiology such as primary pulmonary arterial hypertension. Estimation of pulmonary artery pressure

Pulmonary embolism is associated with high mortality and morbidity; hence, prompt diag‐ nosis and treatment is imperative. When a patient has had a large pulmonary embolism, this may place acute pressure overload on the right ventricle. The right ventricle handles pressure poorly and may undergo acute dilation with decreased right ventricular systolic function as a result of an acute increase in afterload. Usually, peak systolic pressures in the pulmonary artery do not exceed 50 mm Hg unless there is a baseline chronic RV pressure overload. The size and function of the RV are among the most important factors in determining the initiation of either thrombolysis or referral for surgical embolectomy. A classic pattern of RV systolic dysfunction in acute pulmonary embolism has been described. This is known as McConnell sign and is characterized by akinesis of the free wall of the right ventricle with sparing of the apical segment. This phenomenon has 77% sensitivity and 94% specificity for the diagnosis of acute

Echocardiographic indices of dyssynchrony are assessed by measuring time delay in mechan‐ ical activity between segments. Tissue Doppler imaging is limited to the assessment of the

indicate poor prognosis in pulmonary embolism and pulmonary hypertension [48].

inspiration is to be considered while determining the RV diastolic function.

tachycardia occurring after surgical repair of congenital heart disease [44].

**6.5. Evaluation of pulmonary arterial hypertension**

can be performed by TTE in the majority of patients [37, 49].

**6.6. Evaluation of patients with pulmonary embolism**

pulmonary embolism (**Figure 7**).

septum‐RV free wall.

**6.7. Evaluation of RV dyssynchrony**

**6.3. Cardiac rhythm and the RV**

184 Echocardiography in Heart Failure and Cardiac Electrophysiology

**6.4. Cardiac markers**

Accurate quantitative assessment of right ventricular size and function remains difficult given its unique shape despite significant advances in echocardiography. RV dysfunction is an important diagnostic and prognostic indicator in many cardiac and pulmonary diseases [42, 43, 50, 51]. Qualitative evaluation of RV systolic function is through visual assessment. For quantitative assessment of RV, FAC, TAPSE, pulsed tissue Doppler S', and MPI are available and at least one of them should be routinely performed and reported as recommended by the ASE. If more than one of these measurements is used in conjunction, RV function can be more reliably and accurately assessed [36, 40, 52].

## **Author details**

Gunjan Choudhary1\*, Arushi A. Malik2 , Dwight Stapleton1 and Pratap C. Reddy3


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#### **Role of Echocardiography in the Critically Ill Patients Role of Echocardiography in the Critically Ill Patients**

Manivannan Veerasamy Manivannan Veerasamy

Additional information is available at the end of the chapter

Additional information is available at the end of the chapter

http://dx.doi.org/10.5772/65068

#### **Abstract**

Since its inception in 1950s, echocardiography has evolved significantly. Its role has expanded beyond cardiology into operating theaters, intensive care units, and emergency departments. It is an easy, inexpensive, noninvasive, and portable technique, which can be rapidly performed at bedside. It is devoid of complications and, for the most part, universally available. This review focuses on growing importance of echocardiography for critically ill patients in the intensive care and high dependency unit settings including indications, modalities, measurements, and therapeutic impact. Literature review of echocardiography use for the cardiovascular assessment of the critically ill patients was done and various indications are discussed including appropriate use scores. Methods being used include transthoracic and transesophageal echo with various modes. This does include assessment of volume status of the hemodynamically unstable patients, myocardial function, global left ventricular systolic function, regional wall motion abnormalities, cardiac output, cardiac tamponade, valvular function, left ventricular outflow obstruction, and right ventricular function. Other diagnostic assessments include aortic dissection, thromboembolisms, pleural effusions, and septal defects. Echocardiography is now considered as an indispensable tool for diagnosis and management including hemodynamic monitoring in critically ill patients. It provides advantages including noninvasiveness and real-time anatomical and functional assessment of the cardiovascular system.

**Keywords:** echocardiography, critically ill, ventricular function, hemodynamics

## **1. Introduction**

Echocardiography (echo) is one of the most powerful diagnostic and monitoring tools available to the modern emergency/critical care practitioner. The provision of echo is fundamental to the management of patients with acute cardiovascular disease. Since its inception

© 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited. © 2016 The Author(s). Licensee InTech. This chapter is distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

in 1950s, echocardiography has evolved significantly. Its role has expanded beyond cardiology into operating theaters, intensive care units, and emergency departments [1]. It is an easy, inexpensive, noninvasive, and portable technique, which can be rapidly performed at bedside. It is devoid of complications and, for the most part, universally available. This review focuses on growing importance of echocardiography for critically ill patients in the intensive care and high dependency unit settings including indications, modalities, measurements, and therapeutic impact.

Echocardiography has been included in international guidelines regarding the management of cardiac arrest and in the universal definition of acute myocardial infarction (AMI). In the acutely ill and critical care settings, echocardiography can be used to measure/monitor cardiac output (CO) and to determine abnormalities of cardiac physiology and coronary perfusion, as well as providing more standard anatomical information related to diagnosis.

This chapter is not intended to be a comprehensive review of echocardiographic techniques. Instead, it focuses on the indications, therapeutic impact, and some of the most common scenarios (**Table 1**) where dilemmas can be answered using echocardiography in critically ill patients.


**Table 1.** General indications for echocardiographic examination in the intensive care unit.

## **2. Types of echo**

The challenges of imaging in the acute settings are well studied and may influence echocardiographic findings and interpretation in critically ill patients. These include a number of factors such as filling status, metabolic status, patient habitus and positioning, positive pressure ventilation, intubation/mechanical ventilation, different ventilation modalities, weaning inotropic status, lung injury, the presence of lines/dressings and/or drains, and extracorporeal support. The echocardiographic data should be interpreted in the case scenario of the acutely/critically ill patient, particularly when time-specific factors further challenge the echocardiographer (i.e., cardiac arrest).

## **2.1. Transthoracic echocardiography**

in 1950s, echocardiography has evolved significantly. Its role has expanded beyond cardiology into operating theaters, intensive care units, and emergency departments [1]. It is an easy, inexpensive, noninvasive, and portable technique, which can be rapidly performed at bedside. It is devoid of complications and, for the most part, universally available. This review focuses on growing importance of echocardiography for critically ill patients in the intensive care and high dependency unit settings including indications, modalities, measurements, and thera-

Echocardiography has been included in international guidelines regarding the management of cardiac arrest and in the universal definition of acute myocardial infarction (AMI). In the acutely ill and critical care settings, echocardiography can be used to measure/monitor cardiac output (CO) and to determine abnormalities of cardiac physiology and coronary perfusion, as

This chapter is not intended to be a comprehensive review of echocardiographic techniques. Instead, it focuses on the indications, therapeutic impact, and some of the most common scenarios (**Table 1**) where dilemmas can be answered using echocardiography in critically ill

The challenges of imaging in the acute settings are well studied and may influence echocardiographic findings and interpretation in critically ill patients. These include a number of factors such as filling status, metabolic status, patient habitus and positioning, positive pressure ventilation, intubation/mechanical ventilation, different ventilation modalities, weaning inotropic status, lung injury, the presence of lines/dressings and/or drains, and extracorporeal support. The echocardiographic data should be interpreted in the case scenario of the acutely/critically ill patient, particularly when time-specific factors further challenge the

well as providing more standard anatomical information related to diagnosis.

peutic impact.

patients.

Hypovolemia/hypotension Hemodynamic instability Ventricular dysfunction

Acute valvular regurgitations

Acute aortic syndromes

**2. Types of echo**

Evaluation of cardiac thrombus or embolus Pulmonary embolism infective endocarditis

Pericardial effusions/cardiac tamponade

echocardiographer (i.e., cardiac arrest).

Complications after cardiac procedures/cardiothoracic surgery

192 Echocardiography in Heart Failure and Cardiac Electrophysiology

**Table 1.** General indications for echocardiographic examination in the intensive care unit.

Transthoracic echocardiography (TTE) is a widely available, inexpensive tool, which is generally the initial imaging modality in the assessment of acute cardiac conditions (**Table 2**). It is used in the majority of clinical scenarios associated with cardiac emergencies. Findings can be overlooked if the study is restricted to standard imaging only. The study should be comprehensive and undertaken with a fully equipped echocardiographic machine. The easiest and least invasive way to image cardiac structures is echocardiography using the transthoracic approach [2]. This noninvasive imaging modality is of great value in the critical care settings because of its portability, widespread availability, and rapid diagnostic capability.


*Note:* I: inappropriate test for that indication (not generally acceptable and not a reasonable approach. Score 1–3 out of 9); U: uncertain for specific indication (may be acceptable and may be a reasonable approach. Also implies that further patient information/research needed to classify indication definitively. Score 4–6 out of 9); A: appropriate test for that indication. (Test is generally acceptable and is a reasonable approach for the indication. Score 7–9 out of 9.) MI: myocardial infarction, PE: pulmonary embolism, RV: right ventricle, PAP: pulmonary arterial pressure.

**Table 2.** Indications for echocardiography in acute care settings, evaluated using appropriate use scores (AUS).

## **2.2. Transesophageal echocardiography**

A nondiagnostic TTE usually requires a transesophageal echocardiography (TEE). TEE allows better imaging of the posterior structures and heart in general, due to the position of the probe and better acoustic transmission. Certain situations that warrant TEE include acute aortic syndromes, unexplained hypotension, trauma, morbid obesity, prosthetic valve dysfunction, valvular regurgitations/vegetation, and mechanical ventilation with high-level positive endexpiratory pressure and source of cardiac emboli. TEE should be done cautiously in patients with coagulopathy, potential trauma to airway or esophagus, and in patients who are unable to protect their own airways or severely hypoxic without mechanical ventilation. During the study, the airway and hemodynamics should be monitored. In the ICU, transthoracic echocardiography (TTE) may, in certain cases, fail to provide adequate image quality because of different factors that can potentially hinder the quality of the ultrasound signal, be it air, bone, calcium, a foreign body, or any other type of interposed structure.

Other imaging modalities include contrast echocardiography, 3D-echo, lung ultrasound examination, focused cardiac ultrasound, and pocket imaging devices.

## **3. Hemodynamic evaluation**

## **3.1. Ventricular function**

#### *3.1.1. Left ventricular systolic function*

Patients may present with a spectrum of conditions ranging from cardiogenic shock, acute pulmonary edema, isolated RV dysfunction, or heart failure (HF) complicating an ACS. Since HF is not a diagnosis *per se*, but rather a syndrome, additional investigations are required to determine the underlying cause. Rapid diagnosis of the underlying cause, and distinction between HF due to systolic versus isolated diastolic dysfunction, should be obtained since identification of these features determines immediate treatment in the acute settings.

Assessment of the left ventricular (LV) systolic function is an integral part of the medical management of hemodynamically unstable critically ill patients. Assessment of the global LV function can be quickly obtained by "eyeballing" from the parasternal long- and shortaxis, apical two- and four-chamber, and subcostal views and real-time visualization of the kinetics and size of the cardiac cavities, a combination of ejection fraction/fractional shortening, Doppler patterns of ventricular filling and tissue. Doppler imaging supplements to the information from the echocardiogram. Assessment of the chamber size and LV wall thickness is also done. Findings may include increase in the left ventricular end-systolic and diastolic volume, increase in end-systolic and diastolic diameter and abnormal wall motion. Two other modes of imaging that are relatively easy to obtain for the assessment of the LV function are the atrioventricular plane displacement (AVPD) and systolic tissue Doppler velocities (sTD) [3].

TTE was shown to be an excellent diagnostic tool for assessment of the LV function in the ICU, even when positive end expiratory pressure was present [4]. However, if the TTE provides suboptimal imaging for evaluation of ventricular function, TEE can be obtained for better assessment. It is important to remember that significant LV dysfunction is common in critically ill patients and the "normal" values quoted from noncritical care studies may not be valid.

## *3.1.1.1. Sepsis-related cardiomyopathy*

expiratory pressure and source of cardiac emboli. TEE should be done cautiously in patients with coagulopathy, potential trauma to airway or esophagus, and in patients who are unable to protect their own airways or severely hypoxic without mechanical ventilation. During the study, the airway and hemodynamics should be monitored. In the ICU, transthoracic echocardiography (TTE) may, in certain cases, fail to provide adequate image quality because of different factors that can potentially hinder the quality of the ultrasound signal, be it air, bone,

Other imaging modalities include contrast echocardiography, 3D-echo, lung ultrasound

Patients may present with a spectrum of conditions ranging from cardiogenic shock, acute pulmonary edema, isolated RV dysfunction, or heart failure (HF) complicating an ACS. Since HF is not a diagnosis *per se*, but rather a syndrome, additional investigations are required to determine the underlying cause. Rapid diagnosis of the underlying cause, and distinction between HF due to systolic versus isolated diastolic dysfunction, should be obtained since

Assessment of the left ventricular (LV) systolic function is an integral part of the medical management of hemodynamically unstable critically ill patients. Assessment of the global LV function can be quickly obtained by "eyeballing" from the parasternal long- and shortaxis, apical two- and four-chamber, and subcostal views and real-time visualization of the kinetics and size of the cardiac cavities, a combination of ejection fraction/fractional shortening, Doppler patterns of ventricular filling and tissue. Doppler imaging supplements to the information from the echocardiogram. Assessment of the chamber size and LV wall thickness is also done. Findings may include increase in the left ventricular end-systolic and diastolic volume, increase in end-systolic and diastolic diameter and abnormal wall motion. Two other modes of imaging that are relatively easy to obtain for the assessment of the LV function are the atrioventricular plane displacement (AVPD) and systolic tissue Doppler

TTE was shown to be an excellent diagnostic tool for assessment of the LV function in the ICU, even when positive end expiratory pressure was present [4]. However, if the TTE provides suboptimal imaging for evaluation of ventricular function, TEE can be obtained for better assessment. It is important to remember that significant LV dysfunction is common in critically ill patients and the "normal" values quoted from noncritical care studies may not be valid.

identification of these features determines immediate treatment in the acute settings.

calcium, a foreign body, or any other type of interposed structure.

**3. Hemodynamic evaluation**

194 Echocardiography in Heart Failure and Cardiac Electrophysiology

*3.1.1. Left ventricular systolic function*

**3.1. Ventricular function**

velocities (sTD) [3].

examination, focused cardiac ultrasound, and pocket imaging devices.

Bedside echocardiography is an important tool for identification of the cause of hemodynamic instability (which may be of cardiogenic, hypovolemic, or distributive origin) and for the further management (i.e., administration of fluid, vasoactive, or inotropic agent infusion). Classically, septic shock has been considered to be a hyperdynamic state characterized by normal or high cardiac output (CO). But echocardiographic studies indicate that ventricular performance is often diminished in those patients. LVEF might not be a reliable index of LV systolic function in patients with early septic shock.

## *3.1.1.2. Stress-induced cardiomyopathy (Takotsubo syndrome)*

Defined as a transient, stress-induced dysfunction of the LV apex, it predominantly affects female patients (90%). Takotsubo cardiomyopathy mimics an ACS, echo findings show a reversible LV dysfunction with regional wall motion abnormalities, but these patients have no angiographic evidence of ACS. Akinesia has also been demonstrated in the LV mid-cavity, LV base, and RV, with or without sparing of the other LV segments (**Figure 1**). Echo is a useful tool for the follow-up as the LV function must completely recover over time to confirm the diagnosis.

LV measurements also provide data on myocardial injury, cardiomyopathies, and fluid status. The left atrial size is evaluated as an enlarged Left atrium (LA) may indicate significant valvular disease, intra-atrial shunting and atrial fibrillation, all of which may in turn cause hemodynamic instability. Finally, the aortic and mitral valves are assessed to complete the examination of left ventricular function. Two-dimensional speckle tracking echocardiography (STE) offers potentially useful information in acute HF patients with underlying cardiomyopathies.

## *3.1.2. LV diastolic function*

In the ICU, when EF is normal or supernormal and ventricular filling pressure (pulmonary artery occlusion pressure) is elevated, diastolic dysfunction should be suspected. The filling patterns related to the diastolic function can be influenced by different factors such as heart rate, ischemia, left atrial pressure, ventricular hypertrophy, and valvular pathologies. In patients with an abnormal relaxation pattern (E/A < 1), and peak E velocity <50 cm/s, LV filling pressures are usually normal [5]. With restrictive filling (E/A ≥ 2, mitral E deceleration time <150 ms), mean LA pressure is often increased. Patients with heart failure with preserved LV ejection fraction (HFpEF) present with signs and/or symptoms of HF and several echocardiographic findings.

In both acute systolic and diastolic HF, interstitial edema may be diagnosed at the bedside by the demonstration of an abnormally high number of bilateral sonographic B-lines (also called ultrasound lung comets). Two-dimensional speckle tracking echocardiography offers diagnostic data in acute heart failure associated with cardiomyopathies, specifically when ejection fraction appears preserved [5].

## *3.1.3. Cardiac arrest*

Echo is a very useful tool in the management of critically ill patients with cardiac arrest. The use of echo in an advanced cardiac life support (ACLS) is supported by international evidencebased recommendations. Peri-resuscitation echocardiography does not impact upon highquality cardiopulmonary resuscitation (CPR) when appropriately applied and requires special training in advanced cardiac life support (ACLS) compliant manner. Images should be obtained only during the pulse/rhythm check. It can provide data to diagnose or exclude certain potential reversible causes of cardiac arrest (including severe LV/RV dysfunction, myocardial infarction, hypovolemia, pulmonary embolism (PE), tension pneumothorax, or tamponade). Echo is particularly useful in situations of pulseless electrical activity (electromechanical dissociation—EMD) to differentiate between pseudo-EMD and true EMD. Though there is extensive data, we need further recommendations regarding how to use echo during a code situation and specific guidelines for termination of resuscitation.

## **3.2. Right ventricular function**

Right ventricular (RV) function can be altered by massive pulmonary embolism and acute respiratory distress syndrome (ARDS), the two main causes of acute cor pulmonale, in the critical care settings [6]. Other causes of acute RV dysfunction include RV infarction associated with inferior myocardial infarction, myocardial contusion, fat or air embolism, acute sicklecell crisis, and sepsis. In unstable critically ill patients, specifically those with massive PE and acute respiratory distress syndrome, a diagnosis of RV dysfunction may guide therapy (e.g., use of thrombolytics, vasopressors, volume resuscitation, and catheter-directed interventional therapy). RV size and function are frequently evaluated by visual comparison with the left ventricle. RV kinetics of the cavity and septum, and diastolic dimensions are also measured, using either TTE or TEE. Measuring the ratio between the RV and LV end diastolic areas from apical four-chamber view is one of the best ways to evaluate RV dilation [7]. The diastolic ventricular ratio of 0.6–1.0 is consistent with moderate RV dilation and a ratio of 1 is consistent with severe RV dilation. Tricuspid regurgitation, right atrial dilation, and inferior vena caval dilation are commonly associated with RV diastolic enlargement.

## *3.2.1. Pulmonary embolism*

*3.1.2. LV diastolic function*

196 Echocardiography in Heart Failure and Cardiac Electrophysiology

graphic findings.

*3.1.3. Cardiac arrest*

fraction appears preserved [5].

**3.2. Right ventricular function**

In the ICU, when EF is normal or supernormal and ventricular filling pressure (pulmonary artery occlusion pressure) is elevated, diastolic dysfunction should be suspected. The filling patterns related to the diastolic function can be influenced by different factors such as heart rate, ischemia, left atrial pressure, ventricular hypertrophy, and valvular pathologies. In patients with an abnormal relaxation pattern (E/A < 1), and peak E velocity <50 cm/s, LV filling pressures are usually normal [5]. With restrictive filling (E/A ≥ 2, mitral E deceleration time <150 ms), mean LA pressure is often increased. Patients with heart failure with preserved LV ejection fraction (HFpEF) present with signs and/or symptoms of HF and several echocardio-

In both acute systolic and diastolic HF, interstitial edema may be diagnosed at the bedside by the demonstration of an abnormally high number of bilateral sonographic B-lines (also called ultrasound lung comets). Two-dimensional speckle tracking echocardiography offers diagnostic data in acute heart failure associated with cardiomyopathies, specifically when ejection

Echo is a very useful tool in the management of critically ill patients with cardiac arrest. The use of echo in an advanced cardiac life support (ACLS) is supported by international evidencebased recommendations. Peri-resuscitation echocardiography does not impact upon highquality cardiopulmonary resuscitation (CPR) when appropriately applied and requires special training in advanced cardiac life support (ACLS) compliant manner. Images should be obtained only during the pulse/rhythm check. It can provide data to diagnose or exclude certain potential reversible causes of cardiac arrest (including severe LV/RV dysfunction, myocardial infarction, hypovolemia, pulmonary embolism (PE), tension pneumothorax, or tamponade). Echo is particularly useful in situations of pulseless electrical activity (electromechanical dissociation—EMD) to differentiate between pseudo-EMD and true EMD. Though there is extensive data, we need further recommendations regarding how to use echo during

Right ventricular (RV) function can be altered by massive pulmonary embolism and acute respiratory distress syndrome (ARDS), the two main causes of acute cor pulmonale, in the critical care settings [6]. Other causes of acute RV dysfunction include RV infarction associated with inferior myocardial infarction, myocardial contusion, fat or air embolism, acute sicklecell crisis, and sepsis. In unstable critically ill patients, specifically those with massive PE and acute respiratory distress syndrome, a diagnosis of RV dysfunction may guide therapy (e.g., use of thrombolytics, vasopressors, volume resuscitation, and catheter-directed interventional therapy). RV size and function are frequently evaluated by visual comparison with the left ventricle. RV kinetics of the cavity and septum, and diastolic dimensions are also measured, using either TTE or TEE. Measuring the ratio between the RV and LV end diastolic areas from

a code situation and specific guidelines for termination of resuscitation.

Though pulmonary angiography remains the gold standard for diagnosis of pulmonary embolism (PE), other available imaging modalities include ventilation-perfusion scanning, spiral computed tomography (CT), and magnetic resonance imaging (MRI) angiography. TTE can help to establish a prompt diagnosis to identify patients with high-risk features, especially if the patient is hemodynamically unstable. Overall, the sensitivity of TTE for the diagnosis of pulmonary embolism is about 50–60% while the specificity is around 80–90%. In some situations, that is, in critically ill patients, TEE may improve the sensitivity.

The main indirect findings for pulmonary embolism (**Table 3**) are the consequences of acutely increased pulmonary artery/right heart pressures [5]. In pulmonary embolism, RV hypokinesia is not necessarily global but can be limited to the mid-RV free wall while the contraction of the RV apex may be normal or hyperdynamic (McConnell sign) (**Figure 2**).

Thrombus into right chambers RV systolic dysfunction/global RV hypokinesia Dilatation RA, RV (end-diastolic RV/LV diameter.0.6 or area.1.0) Mild to severe TR Pulmonary arterial dilatation Abnormal septal motion toward LV McConnell sign—mid-RV wall hypokinesia with apical sparing Pulmonary hypertension around 40–50 mm Hg (60 mm Hg in the case of pre-existing pulmonary hypertension) Lack of respiratory variation of the inferior vena cava

**Table 3.** Echocardiographic finding in pulmonary embolism.

As other clinical conditions can produce acute cor pulmonale in the ICU, better visualization of the pulmonary arteries is needed to achieve high accuracy for the diagnosis of PE. This goal can be achieved by using TEE. TEE helps to achieve a better visualization of the pulmonary arteries and detecting emboli that are lodged in the main and right pulmonary arteries. The diagnosis is made when an embolus is visualized. When the index of suspicion for PE is high and TEE is negative, then pulmonary angiography or helical computed tomography should be considered as the next step. The demonstration of acute cor pulmonale with echocardiography has important prognostic and therapeutic implications. The presence of cor pulmonale with massive PE is associated with increased mortality, whereas the absence of RV dysfunction is associated with a better prognosis.

**Figure 2.** Thrombus in the right ventricle.

## **3.3. Assessment of cardiac output (CO)**

Measurement of CO is an important data in the assessment of critically ill patients with unstable hemodynamics. Cardiac output and stroke volume can be established by combining Doppler data derived from blood flow velocity through a conduit and the cross-sectional area of the conduit. The most common and most reliable technique is using the left ventricular outflow tract and aortic valve. Another method using an esophageal probe inserted in sedated patients, to measure blood flow velocity waveforms in the descending aorta combined with a nomogram, is particularly useful in adult patients to provide continuous monitoring of cardiac function.

#### **3.4. Assessment of filling pressures and volume status**

Accurate measurement of volume status and LV preload is important for management of critically ill patients. Besides, invasive pressure measurements to assess LV filling may not correlate well with LV volume. Echo can be very useful in adequately evaluating preload. Measurements from two-dimensional and Doppler echo include LV end-diastolic volume (EDV), LV end-diastolic area (EDA), transmitral diastolic filling pattern, and mitral and pulmonary venous flow.

"Eyeballing" LV end-diastolic (LVED) and end-systolic (LVES) areas provide a quick assessment of intracardiac volume status. Findings in hypovolemic patients include hyperdynamic LV with a reduced end-diastolic volume and "kissing" papillary muscles in systole, suggesting an increased ejection fraction with an empty ventricle at end-systole. Septic patients tend to have a reduced afterload, which is usually demonstrated by a normal LVED area, but a reduced LVES area. Patients with chronic cardiac failure have a dilated LV and may be hypovolemic even with a higher LVED area.

Right atrial pressure measurement is also helpful in the evaluation of the circulating volume status and often measured by the diameter and change in caliber with inspiration of the inferior vena cava. A dilated vena cava (diameter of 20 mm) without a normal inspiratory decrease in caliber (50% with gentle sniffing) usually indicates elevated right atrial pressure. Available data suggest inferior vena cava diameter variation with inspiration can be used a guide to fluid therapy [8]. A small vena cava in mechanically ventilated patient excludes the presence of elevated right atrial pressure, as these patients usually have dilation of the inferior vena cava [9].

## **3.5. Assessment of pulmonary artery pressure**

Pulmonary hypertension is usually diagnosed when systolic pulmonary pressure is ~35 mm Hg, diastolic pulmonary pressure is ~15 mm Hg, and mean pulmonary pressure is ~25 mm Hg. Critically ill patients commonly have pulmonary arterial hypertension, possibly from various cardiac, pulmonary, and systemic processes. Several echocardiographic methods have been validated for noninvasive estimation of pulmonary artery pressure [10], which are useful in critically ill patients. A large number of ICU patients have some degree of tricuspid and pulmonary regurgitation, which are needed to measure pulmonary arterial pressure. The tricuspid and pulmonary regurgitation velocities determine systolic and diastolic pulmonary artery pressures.

## **3.6. Assessment of valvular function**

**Figure 2.** Thrombus in the right ventricle.

function.

pulmonary venous flow.

**3.3. Assessment of cardiac output (CO)**

198 Echocardiography in Heart Failure and Cardiac Electrophysiology

**3.4. Assessment of filling pressures and volume status**

Measurement of CO is an important data in the assessment of critically ill patients with unstable hemodynamics. Cardiac output and stroke volume can be established by combining Doppler data derived from blood flow velocity through a conduit and the cross-sectional area of the conduit. The most common and most reliable technique is using the left ventricular outflow tract and aortic valve. Another method using an esophageal probe inserted in sedated patients, to measure blood flow velocity waveforms in the descending aorta combined with a nomogram, is particularly useful in adult patients to provide continuous monitoring of cardiac

Accurate measurement of volume status and LV preload is important for management of critically ill patients. Besides, invasive pressure measurements to assess LV filling may not correlate well with LV volume. Echo can be very useful in adequately evaluating preload. Measurements from two-dimensional and Doppler echo include LV end-diastolic volume (EDV), LV end-diastolic area (EDA), transmitral diastolic filling pattern, and mitral and

"Eyeballing" LV end-diastolic (LVED) and end-systolic (LVES) areas provide a quick assessment of intracardiac volume status. Findings in hypovolemic patients include hyperdynamic LV with a reduced end-diastolic volume and "kissing" papillary muscles in systole, suggesting an increased ejection fraction with an empty ventricle at end-systole. Septic patients tend to

Significant valvular abnormalities can be present in the critically ill patient without being clinically recognized. In the ICU, TTE can provide valuable information concerning valvular integrity and function [11] but may be suboptimal and TEE may be indicated. Adequate and accurate evaluation of the valvular structures may often be required in the critically ill patients. The most common indications for bedside echocardiography for evaluation of the valvular apparatus in this population are for suspected endocarditis, acute valvular stenosis or regurgitation, critical aortic stenosis, significant mitral stenosis, or prosthetic valve dysfunction including regurgitation and obstruction. Information regarding etiology, pathogenesis, and severity of the valvular lesions, valvular anatomy and function, chamber size, function, and wall thickness of the ventricles can be readily obtained by echo. Abnormalities such as vegetation, thrombus, fibrosis, calcification, immobile, or prolapsing leaflets or prosthetic valve dehiscence can be detected by echo [5].

## **3.7. Evaluation of the pericardial space**

Suspected tamponade is the most common indication for assessment of the pericardium in the critically ill patient. The pericardial space can be filled with a variety of substances including fluid, pus, blood, or air. Presence of fluid in this space is detected as an echo-free space. TTE easily detects pericardial effusion (**Figure 3**), usually in the parasternal long and short-axis and the apical views. But, given higher chances of suboptimal TTE in critically ill patients, TEE may be warranted, particularly in patients with poor acoustic windows or post cardiothoracic surgical patients.

**Figure 3.** Pericardial effusion.

Echocardiography is also useful in the management of pericardial effusion, as pericardiocentesis can be performed safely under echocardiographic guidance [12]. Echocardiography also can be used to accurately place the needle during the drainage, immediately monitor the results of the pericardiocentesis, and serially monitor to evaluate the reaccumulation of the effusion.

#### *3.7.1. Cardiac tamponade in the ICU*

The most common causes of cardiac tamponade in the ICU are listed in **Table 4**.

Complication of myocardial infarction (e.g., ventricular rupture)

Blunt or penetrating chest trauma

Proximal ascending aortic dissection

Myocardial or coronary perforation secondary to catheter-based interventions (i.e., after

intravenous pacemaker lead insertion, central catheter placement, or percutaneous coronary interventions)

Uremic or infectious pericarditis

Compressive hematoma after cardiac surgery

Pericardial involvement by metastatic disease or other systemic processes

**Table 4.** Common causes of cardiac tamponade in intensive care unit.

There are several 2D-echo findings that suggest a hemodynamically significant pericardial fluid collection (**Table 5**). The rate of accumulation of the pericardial fluid, and collection and size of the collection determine the intrapericardial pressure. Although diastolic RV collapse (inward diastolic motion of the RV free wall) occurs later, it is a more specific sign and is best appreciated from the parasternal or subcostal long-axis views [13] (**Figure 4**).

Usually large pericardial effusion

Swinging heart

easily detects pericardial effusion (**Figure 3**), usually in the parasternal long and short-axis and the apical views. But, given higher chances of suboptimal TTE in critically ill patients, TEE may be warranted, particularly in patients with poor acoustic windows or post cardiothoracic

Echocardiography is also useful in the management of pericardial effusion, as pericardiocentesis can be performed safely under echocardiographic guidance [12]. Echocardiography also can be used to accurately place the needle during the drainage, immediately monitor the results of the pericardiocentesis, and serially monitor to evaluate the reaccumulation of the effusion.

The most common causes of cardiac tamponade in the ICU are listed in **Table 4**.

intravenous pacemaker lead insertion, central catheter placement, or percutaneous coronary interventions)

Myocardial or coronary perforation secondary to catheter-based interventions (i.e., after

Pericardial involvement by metastatic disease or other systemic processes

**Table 4.** Common causes of cardiac tamponade in intensive care unit.

surgical patients.

200 Echocardiography in Heart Failure and Cardiac Electrophysiology

**Figure 3.** Pericardial effusion.

*3.7.1. Cardiac tamponade in the ICU*

Blunt or penetrating chest trauma Proximal ascending aortic dissection

Uremic or infectious pericarditis

Compressive hematoma after cardiac surgery

Complication of myocardial infarction (e.g., ventricular rupture)

RA collapse (rarely LA)

Diastolic collapse of the anterior RV-free wall (rarely LV)

IVC dilatation (no collapse with inspiration)

TV flow increases and MV flow decreases during inspiration (reverse in expiration)

Systolic and diastolic flows are reduced in systemic veins in expiration and reverse flow with atrial contraction is increased

**Table 5.** Echo findings of hemodynamically significant pericardial effusion.

**Figure 4.** Cardiac tamponade.

If the patient's condition requires urgent pericardiocentesis, the procedure may be echocardiographically guided, as this has been shown to reduce complications. Echocardiography can additionally be used to verify whether the collection has been completely drained. TEE is rarely indicated in this setting.

## **4. Some other common conditions/scenarios**

## **4.1. LVOT obstruction**

In patients who develop dynamic Left Ventricular Outflow Tract (LVOT) obstruction with resultant decrease in cardiac output, particularly the ones who fail to respond to inotropic support, echo is a valuable diagnostic tool. In these patients, right heart catheterization can often be misleading, resulting in inappropriate management.

## **4.2. Cardiogenic shock**

The commonest cause of cardiogenic shock is severe systolic dysfunction from acute myocardial infarction and echo remains an excellent initial diagnostic tool. Shock due to LV dysfunction remains the leading cause of mortality in AMI (50–70%) [14]. Other etiologies include mechanical complications of AMI, myocarditis, cardiomyopathy, valvular heart disease, RV dysfunction, myocardial contusion, and acute aortic dissection. TTE should be obtained first in this set of patients and TEE may be warranted when TTE is suboptimal. Common findings of cardiogenic shock complicating acute myocardial infarction are shown in **Table 6**.


**Table 6.** Echo findings in cardiogenic shock complicating acute myocardial infarction.

## **4.3. Complications after cardiac surgery/procedures**

In patients with hemodynamic instability after cardiothoracic operations, bedside echocardiography has been shown as a valuable tool in the critical care management [15]. TTE is often suboptimal and TEE is warranted as it obtains information that can help determine the etiology of hypotension in this set of patients. Most frequently encountered echocardiographic findings of LV dysfunction, cardiac tamponade, RV failure, hypovolemia, and valvular dysfunction have been described in earlier sections of this chapter.

Echo is useful in other situations such as evaluation of coronary arteries in suspected coronary disruption, RV dysfunction, and TAPSE (pre-, intra-, and postoperative TAPSE) evaluation, immediately after heart transplant (to rule out early rejection, early RV dysfunction, tamponade, or other causes of instability). Echo is an initial modality of imaging in patients who underwent catheterization/electrophysiology procedures presenting with potential acute complications include ventricular failure, cardiogenic shock, tamponade, displacement of implanted devices, and occlusion of coronary stents.

## **4.4. Extracorporeal support**

**4. Some other common conditions/scenarios**

202 Echocardiography in Heart Failure and Cardiac Electrophysiology

often be misleading, resulting in inappropriate management.

In patients who develop dynamic Left Ventricular Outflow Tract (LVOT) obstruction with resultant decrease in cardiac output, particularly the ones who fail to respond to inotropic support, echo is a valuable diagnostic tool. In these patients, right heart catheterization can

The commonest cause of cardiogenic shock is severe systolic dysfunction from acute myocardial infarction and echo remains an excellent initial diagnostic tool. Shock due to LV dysfunction remains the leading cause of mortality in AMI (50–70%) [14]. Other etiologies include mechanical complications of AMI, myocarditis, cardiomyopathy, valvular heart disease, RV dysfunction, myocardial contusion, and acute aortic dissection. TTE should be obtained first in this set of patients and TEE may be warranted when TTE is suboptimal. Common findings

**LV dysfunction** Depressed EF, regional wall motion abnormalities, decrease in stroke volume, CO, elevated LV

In patients with hemodynamic instability after cardiothoracic operations, bedside echocardiography has been shown as a valuable tool in the critical care management [15]. TTE is often suboptimal and TEE is warranted as it obtains information that can help determine the etiology of hypotension in this set of patients. Most frequently encountered echocardiographic findings of LV dysfunction, cardiac tamponade, RV failure, hypovolemia, and valvular dysfunction

Echo is useful in other situations such as evaluation of coronary arteries in suspected coronary disruption, RV dysfunction, and TAPSE (pre-, intra-, and postoperative TAPSE) evaluation, immediately after heart transplant (to rule out early rejection, early RV dysfunction, tamponade, or other causes of instability). Echo is an initial modality of imaging in patients who

Obvious cardiac tamponade or only pericardial collection in subacute free wall rupture (30%

Complete or partial rupture of the posterior papillary muscle with partial or complete flail of the mitral valve. Also from acute systolic anterior motion of the mitral valve secondary to

of cardiogenic shock complicating acute myocardial infarction are shown in **Table 6**.

**RV infarction** RV dilatation, dyssynergy, paradoxical septal motion, and McConnell sign, decrease of

pressures, mitral regurgitation infarction

of rupture)

dynamic LVOT obstruction

**4.3. Complications after cardiac surgery/procedures**

have been described in earlier sections of this chapter.

**Table 6.** Echo findings in cardiogenic shock complicating acute myocardial infarction.

tricuspid annulus systolic excursion (TAPSE)

**4.1. LVOT obstruction**

**4.2. Cardiogenic shock**

**Free ventricular wall**

**rupture**

**Acute mitral regurgitation** Extracorporeal support is increasingly used to support critically ill patients with severe cardiac and/or respiratory failure. Echocardiography for extracorporeal support is highly specialized. Thus echocardiography has a vital role in excluding any potentially treatable underlying cause for cardiorespiratory failure, essential to determine the requirement for the RV and/or LV support and level of support required, mandatory to exclude cardiovascular contraindications for initiation of the support. Echocardiography subsequently has a vital role in its successful implementation, including confirming/guiding correct cannula placement, ensuring the goals of support are met, detecting complications, and assessing tolerance to assistance. Finally, in patients requiring extracorporeal cardiac support, various echocardiographic parameters have been proposed to be used in conjunction with clinical and hemodynamic assessment in order to attempt to predict those patients who can be successfully weaned.

## **4.5. Cardiac arrhythmias**

In the critically ill patient population, heart rates of 100–120/min may be required to maintain adequate cardiac output.

## *4.5.1. Atrial arrhythmias*

Atrial arrhythmias, common in the acute settings, present challenging conditions for assessing cardiac function and hemodynamics, especially when irregular (as in atrial fibrillation). Use of echo in critically ill patients is done with caution. In atrial fibrillation, measurements are obtained from an average of about 10 consecutive heartbeats, to permit the use of echocardiographic parameters usually used in sinus rhythm, to predict elevated filling pressures. The "index beat" method using the measurement performed on the cardiac cycle following a pair of equal preceding cardiac cycles, is also being used in practice.

## *4.5.2. Ventricular arrhythmias*

Echocardiography is one of the first investigations to be performed as soon as the arrhythmia is successfully terminated. Etiologies include ischemic and nonischemic causes that require echocardiographic evaluation.

#### **4.6. Assessment of the aorta**

TTE is a good initial investigation tool for evaluation of the proximal aorta (ascending aorta and arch). Because of the close anatomic relationship between the thoracic aorta and the esophagus, TEE allows optimal visualization of the entire thoracic aorta.

## *4.6.1. Aortic dissection and rupture*

Diagnosis and management of aortic dissection is an emergency and these patients are often critically ill. Of the various available imaging modalities, echo, particularly TEE has been recommended for evaluation of suspected aortic dissection (**Figure 5**). TEE has the ability to assess the following, including extension of dissection into the proximal coronary arteries, the point of entry and exit between the true and false lumens, the presence of thrombus in the false lumen, the presence of pericardial or mediastinal hematoma or effusion, severity, and mechanism of associated aortic valve regurgitation, and ventricular function.

**Figure 5.** Ascending aortic dissection on TEE.

## *4.6.2. Intraaortic balloon pump*

TEE is useful in various phases of management including evaluation of aortic regurgitation as a contraindication prior to insertion, to confirm the position of the catheter, to ensure correct functioning of the balloon, and to rule out complications such as aortic dissection.

#### *4.6.3. Traumatic injuries of the heart and aorta*

Blunt or penetrating chest trauma may cause severe injury to the heart and great vessels. A rapid, focused assessment with echocardiography can detect pericardial collection, myocardial contusion, mediastinal hematomas, aortic intramural hematomas, aortic dissection or transection, and pleural collections. Both TTE and TEE play an important role in the assessment of patients with chest trauma, and TEE may be indicated in patients with polytrauma and/or on mechanical ventilation or when a traumatic, acute aortic syndrome is suspected. It is important to distinguish aortic from cardiac injuries. Also, traumatic pseudoaneurysms must be differentiated from true aneurysms. Trauma may cause aortic rupture, dissection, or intramural hematoma. Partial disruption of the aortic wall may lead to pseudoaneurysm. Once pericardial tamponade is excluded, a standard echocardiogram is useful in other conditions, like cardiac contusion/dysfunction, myocardial rupture, septal and valvular injury. Acute MI from coronary artery dissection and arrhythmias in acute trauma patients warrant echocardiographic evaluation.

## **4.7. Infective endocarditis**

*4.6.1. Aortic dissection and rupture*

204 Echocardiography in Heart Failure and Cardiac Electrophysiology

**Figure 5.** Ascending aortic dissection on TEE.

*4.6.3. Traumatic injuries of the heart and aorta*

*4.6.2. Intraaortic balloon pump*

Diagnosis and management of aortic dissection is an emergency and these patients are often critically ill. Of the various available imaging modalities, echo, particularly TEE has been recommended for evaluation of suspected aortic dissection (**Figure 5**). TEE has the ability to assess the following, including extension of dissection into the proximal coronary arteries, the point of entry and exit between the true and false lumens, the presence of thrombus in the false lumen, the presence of pericardial or mediastinal hematoma or effusion, severity, and mech-

TEE is useful in various phases of management including evaluation of aortic regurgitation as a contraindication prior to insertion, to confirm the position of the catheter, to ensure correct

Blunt or penetrating chest trauma may cause severe injury to the heart and great vessels. A rapid, focused assessment with echocardiography can detect pericardial collection, myocardial contusion, mediastinal hematomas, aortic intramural hematomas, aortic dissection or

functioning of the balloon, and to rule out complications such as aortic dissection.

anism of associated aortic valve regurgitation, and ventricular function.

Febrile illness in critically ill patients warrants evaluation including infective endocarditis. See section on valvular lesions evaluations. Echocardiography is the test of choice for the noninvasive diagnosis of endocarditis. The echocardiographic findings may include new valvular regurgitation, an oscillating intracardiac mass on a valve or supporting structure or in the path of a regurgitant jet or an iatrogenic device, valve abscesses and new partial dehiscence or vegetation of a prosthetic valve. TEE has also been clearly shown to be superior to TTE for diagnosing complications of endocarditis, such as aortic root abscess, fistulas, and ruptured chordae tendineae of the mitral valve.

**Figure 6.** Pleural effusion on echo.

## **4.8. Pleural effusions**

Echocardiogram often finds the presence of pleural effusions (**Figure 6**) and can be used as a diagnostic tool while evaluating the cardiovascular system, especially in patients with acute dyspnea and decompensated heart failure.

## **4.9. Assessment for intracardiac and intrapulmonary shunts**

In critically ill patients with unexplained embolic stroke or refractory hypoxemia, the presence of a right-to-left shunt needs to be excluded. Common positions of right-to-left shunt are atrial septal defect or patent foramen ovale at the cardiac level, arteriovenous fistula at the pulmonary level and pulmonary arteriovenous fistulas. Bubble study, color Doppler studies, and contrast-enhanced studies are done to increase the detection rate of intracardiac shunt.

## **4.10. Source of embolus**

Patients presenting with acute unexplained embolic stroke and arterial occlusions, echocardiography should be obtained to investigate a potential embolic source of cardiac origin. In this situation, TEE is the preferred imaging of choice. Possible cardiac sources of emboli include thrombus in the left atrial or appendage, LV thrombus, valvular vegetation, right-sided clots (right atrium, right ventricle, vena cava) combined with a right-to-left intracardiac shunt (leading to a paradoxical embolus), thoracic atheromatosis, and cardiac tumors. TEE is a valuable tool in evaluating the left atrium and appendage for the presence of thrombus, for patients with atrial fibrillation or flutter in whom cardioversion is considered.

## **5. Conclusion**

Echocardiography is now considered as an indispensable tool and primary imaging modality for diagnosis and management of hemodynamic monitoring in critically ill patients. However, echocardiography is subject to variations in interpretation, which can potentially lead to errors, as with any diagnostic and monitoring tool and caution need to be undertaken during interpretation. Nevertheless, it provides advantages including noninvasiveness and rapid and accurate real-time anatomical and functional assessment of the cardiovascular system under stressful situations and is very useful in assisting therapeutic procedures.

## **Author details**

Manivannan Veerasamy

Address all correspondence to: manivannan22@gmail.com

Spectrum Health, GRMEP/Michigan State University, Grand Rapids, MI, USA

## **References**

**4.8. Pleural effusions**

**4.10. Source of embolus**

**5. Conclusion**

**Author details**

Manivannan Veerasamy

dyspnea and decompensated heart failure.

206 Echocardiography in Heart Failure and Cardiac Electrophysiology

**4.9. Assessment for intracardiac and intrapulmonary shunts**

Echocardiogram often finds the presence of pleural effusions (**Figure 6**) and can be used as a diagnostic tool while evaluating the cardiovascular system, especially in patients with acute

In critically ill patients with unexplained embolic stroke or refractory hypoxemia, the presence of a right-to-left shunt needs to be excluded. Common positions of right-to-left shunt are atrial septal defect or patent foramen ovale at the cardiac level, arteriovenous fistula at the pulmonary level and pulmonary arteriovenous fistulas. Bubble study, color Doppler studies, and contrast-enhanced studies are done to increase the detection rate of intracardiac shunt.

Patients presenting with acute unexplained embolic stroke and arterial occlusions, echocardiography should be obtained to investigate a potential embolic source of cardiac origin. In this situation, TEE is the preferred imaging of choice. Possible cardiac sources of emboli include thrombus in the left atrial or appendage, LV thrombus, valvular vegetation, right-sided clots (right atrium, right ventricle, vena cava) combined with a right-to-left intracardiac shunt (leading to a paradoxical embolus), thoracic atheromatosis, and cardiac tumors. TEE is a valuable tool in evaluating the left atrium and appendage for the presence of thrombus, for

Echocardiography is now considered as an indispensable tool and primary imaging modality for diagnosis and management of hemodynamic monitoring in critically ill patients. However, echocardiography is subject to variations in interpretation, which can potentially lead to errors, as with any diagnostic and monitoring tool and caution need to be undertaken during interpretation. Nevertheless, it provides advantages including noninvasiveness and rapid and accurate real-time anatomical and functional assessment of the cardiovascular system under

patients with atrial fibrillation or flutter in whom cardioversion is considered.

stressful situations and is very useful in assisting therapeutic procedures.

Spectrum Health, GRMEP/Michigan State University, Grand Rapids, MI, USA

Address all correspondence to: manivannan22@gmail.com


[12] Callahan, J. A., Seward, J. B. (1997). Pericardiocentesis guided by two-dimensional echocardiography. *Echocardiography (Mount Kisco, N.Y.), 14*(5), 497–504. doi/10.1111/j.

[13] Troianos, C.A., Porembka, D.T. (1996). Assessment of left ventricular function and hemodynamics with transesophageal echocardiography. *Critical Care Clinics, 12*(2),

[14] Klein, T., Ramani, G.V. (2012). Assessment and management of cardiogenic shock in the emergency department. *Cardiology Clinics, 30*(4), 651–664. doi:10.1016/j.ccl.

[15] Wake, P.J., Ali, M., Carroll, J., Siu, S.C., Cheng, D.C. (2001). Clinical and echocardiographic diagnoses disagree in patients with unexplained hemodynamic instability after cardiac surgery. *Canadian Journal of Anaesthesia, 48*(8), 778–783. doi:10.1007/BF03016694

1540-8175. 1997.tb00757

208 Echocardiography in Heart Failure and Cardiac Electrophysiology

2012.07.004

253–272. doi :10.1016/S0749-0704(05)70248-7

## *Edited by Umashankar Lakshmanadoss*

The world of echocardiography continues to be full of exciting new technological developments with an ultimate goal of better patient care. In this book, titled "Echocardiography in Heart Failure and Cardiac Electrophysiology", authors from various parts of the world contributed to the advancement of the field. We have included various chapters about the use of echocardiography and modalities of imaging in various common clinical scenarios—ranging from evaluation of commonly ignored right ventricle, imaging in congestive heart failure, to echocardiographic evaluation of critically ill patients. We have also included topics describing the use of echocardiography in cardiac electrophysiology with special interest to cardiac resynchronization therapy and atrial fibrillation ablation. These topics would be of great interest to the clinicians whether they are trainees, physicians, advanced care providers, or anyone involved in the patient care.

Echocardiography in Heart Failure and Cardiac Electrophysiology

Echocardiography in

Heart Failure and Cardiac

Electrophysiology

*Edited by Umashankar Lakshmanadoss*

Photo by m63085 / iStock