**Meet the editor**

Dr P. Syamasundar Rao is Professor of Pediatrics and Medicine and Emeritus Chief of Pediatric Cardiology at the University of Texas-Houston Medical School and Professor of Pediatrics at the University Texas M.D. Anderson Cancer Center, Houston, Texas, USA. Dr. Rao received his medical degree from Andhra Medical College/University, Visakhapatnam. Following completion

of pediatric training in USA, he received training in Pediatric Cardiology at Stanford University, Case-Western Reserve University and University of California at Los Angeles. After training he joined the faculty at the Medical College of Georgia, Augusta, Georgia, USA, then rose to the rank of Professor of Pediatrics and Associate Director of Pediatric Cardiology. Dr. Rao authored 350 papers, eight monographs/books and 55 book chapters.

Contents

**Preface IX** 

**Section 1 General Review of Atrial Septal Defects 1** 

Chapter 2 **Pregnancy Issues in Women with Atrial Septal Defect 21** 

**Septal Defect and Associated Findings 31** 

Chapter 4 **Computer-Aided Automatic Delivery System of High-Intensity Focused Ultrasound for Creation of an Atrial Septal Defect 39**  Hiromasa Yamashita, Gontaro Kitazumi,

> **Occlusion of Atrial Septal Defects 57**  Srilatha Alapati and P. Syamasundar Rao

> **Echocardiography in Transcatheter Occlusion of Atrial Septal Defects 85**

Keri Kim and Toshio Chiba

**Section 4 Transcatheter Closure of ASD 55** 

Chapter 5 **Historical Aspects of Transcatheter** 

Gurur Biliciler-Denktas

Chapter 6 **Role of Transesophageal** 

Chapter 1 **Atrial Septal Defect – A Review 3**  P. Syamasundar Rao

Duraisamy Balaguru

Chapter 3 **Prevalence of Secundum Atrial** 

Mark D. Reller

**Section 3 Creation of ASDs 37** 

**Section 2 Natural History 29** 

### Contents

#### **Preface XI**


X Contents


Chapter 11 **Transcatheter Occlusion of Atrial Septal Defects for Prevention of** 

Mohammed Tawfiq Numan

**Recurrence of Paradoxical Embolism 167**  Nicoleta Daraban, Manuel Reyes and Richard W. Smalling

### Preface

Defects in the atrial septum are one the most common types of congenital heart defects (CHDs) in children and such a defect is the most common CHD in adults. Atrial septal defects (ASDs) cause left to right shunt because the left atrial pressure is higher than that in the right atrium. This causes volume overloading of the right ventricle. While this is generally well tolerated during infancy and childhood, development of exercise intolerance and arrhythmias in later childhood, adolescence and adulthood, and the risk for development of pulmonary vascular obstructive disease in adulthood make these defects important. The major types of atrial defects are ostium secundum, ostium primum, sinus venosus and coronary sinus ASDs and patent foramen ovale (PFO).

In the first chapter, I review the clinical features and management of ASDs. Patients with small defects are usually asymptomatic while moderate to large defects may present with symptoms. Physical findings include hyperdynamic precordium, widely split and fixed second heart sound, ejection systolic murmur at the left upper sternal border and a mid‐diastolic flow rumble at the left lower sternal border. In patients with ostium primum ASDs, an apical holosystolic murmur may also be heard. Clinical diagnosis is not difficult and the diagnosis can be confirmed and quantified by echocardiographic studies. While surgical intervention was used in the past, transcatheter methods are currently used for closure of ostium secundum ASDs. Surgical correction is necessary for the ostium primum, sinus venosus and coronary sinus defects. PFO is present in nearly one third of normal population and is likely to be a normal variant and such isolated PFOs do not need intervention. When associated with other CHDs, the PFO facilitates intra‐cardiac shunt to allow appropriate egress and/or mixing of blood flow. Hypoxemia in post‐surgical residual defects including Fontan fenestrations, right ventricular infarction and platypnea‐orthodexia syndrome may be secondary to right to left shunt across PFO and these defects may need closure. PFO, presumed to be the seat of paradoxical embolism resulting in stroke/transient ischemic attacks is the subject active investigation. Similarly the role of PFO in Caisson's disease and migraine is not well‐established. There is varying degrees of evidence for benefit of transcatheter occlusion of these PFOs.

In the second chapter, Dr. Balaguru from the University of Texas Medical School, Houston, Texas discusses issues related to ASD in pregnant women. There are remarkable changes in cardiovascular physiology during pregnancy; the cardiac output increases, related to increased stroke volume and heart rate. The systemic vascular resistance decreases; however, concurrent increase in cardiac output keeps blood pressure stable. The blood volume increases (by 1.5 times) by raise in plasma volume; however, this is out of proportion to the increase in red cell mass with consequent relative anemia. These changes are tolerated well because the changes occur gradually. During the third trimester, enlarging uterus compresses the inferior vena cava (IVC) in supine posture leading to decrease in cardiac output and predisposes to deep vein thrombosis. In pregnant women with ASD, there is a greater increase in right atrial and right ventricular size (compared to pregnant women with no heart defect) and a higher incidence of supraventricular tachycardia. The probability of paradoxical embolism via the ASD is high given the predisposition to deep vein thrombosis and hypercoagulable state. If the diagnosis is known prior to pregnancy and the ASD is large and associated with moderate or severe right heart enlargement and is a potential candidate for supraventricular tachycardia and thromboembolic events during pregnancy, labor or postpartum, the ASD should be closed prior to planned‐pregnancy. Transcatheter or surgical closure could be performed based on the size of the ASD and adequacy of septal rims. When the ASD is diagnosed during pregnancy but, the patient is asymptomatic without functional compromise (NYHA Class I and II) and has no heart failure, atrial arrhythmia, pulmonary hypertension or history of stroke, the these women are likely to do well throughout pregnancy and do not require transcatheter or surgical closure. On the contrary, in the presence of any of these issues, transcatheter or surgical closure may be performed. If transcatheter is opted, second trimester (13‐28 weeks) is preferred instead of first trimester to avoid irradiation to the fetus. Local anesthesia with conscious sedation, intracardiac echocardiography to aid balloon sizing and device deployment and use of long venous sheath; the latter two to avoid or reduces radiation, may be appropriate. If the ASD is unsuitable for transcatheter closure, surgical closure of ASD may be performed in the second trimester with the following precautions: infusion of high‐concentration of glucose (to provide energy for fetus), fetal monitoring, maintenance of high‐flow, high mean arterial pressure (60 mmHg) and high hematocrit (> 25%) and hyper oxygenation. The author concludes that the need for closure of ASD during pregnancy is rare and if possible avoided. When closure is indicated transcatheter or surgical closure may be performed, taking appropriate precautions.

Preface XI

Holt‐Oram syndrome; chromosome 22q11 deletion in association with DiGeorge syndrome; velo‐cardio‐facial syndrome; Noonan syndrome and NKX2‐5 gene defect. Patients with secundum ASD are more likely to have a positive family history of congenital heart disease. There is higher prevalence of secundum ASD in girls. Secundum ASD is also associated with non‐cardiac malformations such as cleft palate and VACTERL association. Fetal alcohol syndrome, cytomegalovirus (CMV) and rubella infections during pregnancy and maternal diabetes are also associated with an increased prevalence of secundum ASD. Lower gestational age (low birth weight), small for gestational age, increased maternal age and multiple gestation pregnancy are also associated with higher prevalence of secundum ASD. With regard to natural history, the ASDs have a tendency to regress in size, including spontaneous closure. Small defects (between 4‐5 mm) at the time of initial diagnosis either spontaneously close or regress to a size considered to be insignificant (≤ 3 mm). Larger defects (> 10 mm) do not close spontaneously and 75% of these patients may require surgical or device closure. It may be concluded that secundum ASD is the third most common congenital cardiac defect with incidence similar to peri‐membranous VSD, the prevalence of secundum ASD is increasing, the cause of which remain speculative and there is a tendency for spontaneous closure or decreased size, especially in small

Yamashita and associates from National Centre for Child Health and Development, Japan, in the chapter 4, describe a new approach with an automatic delivery system of high intensity focused ultrasound (HIFU) with real‐time two dimensional‐ultrasound (2D‐US) imaging analysis to establish fetal interatrial communications. In the fetus with hypoplastic left heart syndrome (HLHS) and restrictive atrial septum leads to irreversible pulmonary vascular damage. The current approach of ultrasound‐guided percutaneous puncture through both the uterine wall and fetal chest wall to create interatrial communications is associated with serious complications such as profound bradycardia, bleeding and hemopericardium and intracardiac thrombus formation. In addition, closure of the in utero created atrial septal defects can also occur prior to delivery. They developed a new approach with HIFU to establish fetal interatrial communications with potential for minimal adverse effects. HIFU ablation requires highly accurate pinpoint delivery in real‐time based on computer‐aided auto‐tracking of atrial septum. Their system features automatic detection of rate of heart beat, automatic estimation of atrial septal position and automatic generation of HIFU delivery timing. They describe system configuration of computer‐aided automatic HIFU delivery, automatic detection of heartbeat rates, position of the atrial septum and other procedural details. They performed a feasibility study for creation of an atrial septal defect using the beating heart of four anesthetized adult rabbits, which appear not to satisfactory. But, the authors interpret that they were able to confirm pinpoint delivery of HIFU to the pulsating atrial septum within beating hearts of anesthetized adult rabbits. The above studies were performed with 2D‐US. Three‐ dimensional‐US to track movement of intrauterine fetus may make the procedure more accurate. In conclusion, these workers developed computer‐aided automatic

defects.

In the third chapter Reller from Oregon Health & Science University, Portland, Oregon reviews data on the prevalence, associated cardiac and non‐cardiac findings and natural history of secundum ASDs, defined as size greater than 4 mm. The prevalence of secundum ASD is estimated to be 10.3 per 10,000 births, prevalence comparable to that of peri‐membranous ventricular septal defects. The increase in the prevalence of secundum ASD was attributed to evaluation by color flow Doppler‐echocardiography. The association of secundumASD with peri‐membranous VSD and valvar pulmonary stenosis is well recognized. The cause(s) of secundum ASD remain largely unknown. Genetic syndromes associated with secundum ASD include Trisomy 21, 13 and 18; Holt‐Oram syndrome; chromosome 22q11 deletion in association with DiGeorge syndrome; velo‐cardio‐facial syndrome; Noonan syndrome and NKX2‐5 gene defect. Patients with secundum ASD are more likely to have a positive family history of congenital heart disease. There is higher prevalence of secundum ASD in girls. Secundum ASD is also associated with non‐cardiac malformations such as cleft palate and VACTERL association. Fetal alcohol syndrome, cytomegalovirus (CMV) and rubella infections during pregnancy and maternal diabetes are also associated with an increased prevalence of secundum ASD. Lower gestational age (low birth weight), small for gestational age, increased maternal age and multiple gestation pregnancy are also associated with higher prevalence of secundum ASD. With regard to natural history, the ASDs have a tendency to regress in size, including spontaneous closure. Small defects (between 4‐5 mm) at the time of initial diagnosis either spontaneously close or regress to a size considered to be insignificant (≤ 3 mm). Larger defects (> 10 mm) do not close spontaneously and 75% of these patients may require surgical or device closure. It may be concluded that secundum ASD is the third most common congenital cardiac defect with incidence similar to peri‐membranous VSD, the prevalence of secundum ASD is increasing, the cause of which remain speculative and there is a tendency for spontaneous closure or decreased size, especially in small defects.

X Preface

appropriate precautions.

output increases, related to increased stroke volume and heart rate. The systemic vascular resistance decreases; however, concurrent increase in cardiac output keeps blood pressure stable. The blood volume increases (by 1.5 times) by raise in plasma volume; however, this is out of proportion to the increase in red cell mass with consequent relative anemia. These changes are tolerated well because the changes occur gradually. During the third trimester, enlarging uterus compresses the inferior vena cava (IVC) in supine posture leading to decrease in cardiac output and predisposes to deep vein thrombosis. In pregnant women with ASD, there is a greater increase in right atrial and right ventricular size (compared to pregnant women with no heart defect) and a higher incidence of supraventricular tachycardia. The probability of paradoxical embolism via the ASD is high given the predisposition to deep vein thrombosis and hypercoagulable state. If the diagnosis is known prior to pregnancy and the ASD is large and associated with moderate or severe right heart enlargement and is a potential candidate for supraventricular tachycardia and thromboembolic events during pregnancy, labor or postpartum, the ASD should be closed prior to planned‐pregnancy. Transcatheter or surgical closure could be performed based on the size of the ASD and adequacy of septal rims. When the ASD is diagnosed during pregnancy but, the patient is asymptomatic without functional compromise (NYHA Class I and II) and has no heart failure, atrial arrhythmia, pulmonary hypertension or history of stroke, the these women are likely to do well throughout pregnancy and do not require transcatheter or surgical closure. On the contrary, in the presence of any of these issues, transcatheter or surgical closure may be performed. If transcatheter is opted, second trimester (13‐28 weeks) is preferred instead of first trimester to avoid irradiation to the fetus. Local anesthesia with conscious sedation, intracardiac echocardiography to aid balloon sizing and device deployment and use of long venous sheath; the latter two to avoid or reduces radiation, may be appropriate. If the ASD is unsuitable for transcatheter closure, surgical closure of ASD may be performed in the second trimester with the following precautions: infusion of high‐concentration of glucose (to provide energy for fetus), fetal monitoring, maintenance of high‐flow, high mean arterial pressure (60 mmHg) and high hematocrit (> 25%) and hyper oxygenation. The author concludes that the need for closure of ASD during pregnancy is rare and if possible avoided. When closure is indicated transcatheter or surgical closure may be performed, taking

In the third chapter Reller from Oregon Health & Science University, Portland, Oregon reviews data on the prevalence, associated cardiac and non‐cardiac findings and natural history of secundum ASDs, defined as size greater than 4 mm. The prevalence of secundum ASD is estimated to be 10.3 per 10,000 births, prevalence comparable to that of peri‐membranous ventricular septal defects. The increase in the prevalence of secundum ASD was attributed to evaluation by color flow Doppler‐echocardiography. The association of secundumASD with peri‐membranous VSD and valvar pulmonary stenosis is well recognized. The cause(s) of secundum ASD remain largely unknown. Genetic syndromes associated with secundum ASD include Trisomy 21, 13 and 18;

Yamashita and associates from National Centre for Child Health and Development, Japan, in the chapter 4, describe a new approach with an automatic delivery system of high intensity focused ultrasound (HIFU) with real‐time two dimensional‐ultrasound (2D‐US) imaging analysis to establish fetal interatrial communications. In the fetus with hypoplastic left heart syndrome (HLHS) and restrictive atrial septum leads to irreversible pulmonary vascular damage. The current approach of ultrasound‐guided percutaneous puncture through both the uterine wall and fetal chest wall to create interatrial communications is associated with serious complications such as profound bradycardia, bleeding and hemopericardium and intracardiac thrombus formation. In addition, closure of the in utero created atrial septal defects can also occur prior to delivery. They developed a new approach with HIFU to establish fetal interatrial communications with potential for minimal adverse effects. HIFU ablation requires highly accurate pinpoint delivery in real‐time based on computer‐aided auto‐tracking of atrial septum. Their system features automatic detection of rate of heart beat, automatic estimation of atrial septal position and automatic generation of HIFU delivery timing. They describe system configuration of computer‐aided automatic HIFU delivery, automatic detection of heartbeat rates, position of the atrial septum and other procedural details. They performed a feasibility study for creation of an atrial septal defect using the beating heart of four anesthetized adult rabbits, which appear not to satisfactory. But, the authors interpret that they were able to confirm pinpoint delivery of HIFU to the pulsating atrial septum within beating hearts of anesthetized adult rabbits. The above studies were performed with 2D‐US. Three‐ dimensional‐US to track movement of intrauterine fetus may make the procedure more accurate. In conclusion, these workers developed computer‐aided automatic

#### XII Preface

delivery system of HIFU for creation of an atrial septal defect and further work to improve precision of the focus positioning of HIFU delivery and improvement of HIFU energy efficiency to intracardiac tissue is in progress. The concept appears good as is the design of the system. While the current results are far from clinically applicable, the technique has good potential.

Preface XIII

dimensions of the septal rims and measurement of balloon stretched diameter of the defect (when a sizing balloon is used) and identification of other defects while balloon occluding the defect. The echo and the interventional physicians work as a team to decide on the device size to be used for closure of ASD/PFO. Monitoring of the device deployment and verifying for correct position of the device prior to device release are germane. Post‐implantation study will follow to detect impingement on valves, obstruction to venous return and residual shunting. TEE is also useful in the detection of complications of device closure such as device dislodgement and pericardial effusion/tamponade. The author concludes that TEE is of utmost value during percutaneous closure of ASDs and PFOs and is the preferred imaging modality in

In Chapter 7, Gonzalez and Hijazi of Rush University Medical Center, Chicago, Illinois, review the role of ICE in transcatheter closure of ASDs. Accurate and precise knowledge of the anatomy of the secundum ASD and the nearby structures is essential for safely performing ASD closure. While the conventional imaging method has been TEE, the authors advocate ICE to guide device closure of ASDs and PFOs because general anesthesia is not needed, risks of anesthesia are avoided and patient discomfort after the procedure is reduced. Ultrasound tipped catheters became available during the 1950s and 1960s and progressed thru' the current state of the art ICE catheters. several types of ICE catheters from different manufacturers are currently available and include, *UltraICE* mechanical single‐element system (Boston Scientific Corp), *AcuNav* system (Siemens from Biosense‐Webster), *ClearICE* system (St Jude Medical), *SoundStar* Catheter system (Biosense‐Webster) and *ViewMate Z* Intracardiac Ultrasound System and *ViewFlex Plus* ICE Catheter (St Jude Medical). The authors opine that *AcuNav* catheter is the most popular ICE catheter currently in use. The AcuNav catheter should be carefully advanced from the groin to the heart under continuous fluoroscopic guidance to prevent inadvertent advancement of the catheter into side branches with potential vessel injury before reaching the right atrium. Their ICE protocol involves obtaining different views (home view, septal view, long axis view and short axis view) along with fluoroscopic images. Then ICE imaging during each step, namely, balloon sizing, deployment of left and then right disks and after releasing the device, is undertaken to ensure appropriate positioning of the device. The authors believe that ICE is more accurate in evaluation ASDs when compared to TEE, apart from avoiding general anesthesia, usually required for TEE. They mention limitations of ICE, which include large shaft size, complications related to ICE catheter placement, cost and non availability of real time three‐dimensional (3D) imaging. They conclude that ICE along with fluoroscopy will improve the safety and outcome of

In the next chapter, Sullebarger from Tampa, Florida, describes approaches to patients with technically challenging issues for transcatheter occlusion of ASDs and these include patients with poor femoral venous access, large defects and multiple defects. They also discuss minimally invasive, hybrid, transthoracic approach when

most catheterization laboratories.

percutaneous closure of ASDs.

percutaneous delivery of a device is not possible.

In the fifth chapter from our institution, Alapati and I review the historical aspects of transcatheter closure of ASDs. Since the initial description of ASD occluding devices by King, Rashkind and their associates, a large number of single disc and double disc devices have been designed and tested in animal models followed by clinical trials in human subjects. Feasibility, safety and effectiveness have been demonstrated with most devices. However, design, redesign, testing and re‐testing have been the typical path with most devices. Currently, only two devices are approved by the FDA in the US and these are: Amplatzer septal occluder and HELEX septal occluder. Several other devices are in development, some at the stage of animal experimentation and some in clinical trials in Europe or US. We will await for additional devices to be approved for general clinical use so that the practicing interventional cardiologist will have several devices at his/her disposal so that an appropriate device that suits best for a given patient and his/her defect is available. A brief review of historical aspects of PFO closure was also included. Majority of the ASD devices described in the ASD section, as and when they became available, have also been used to close PFOs; these include King's, clamshell, buttoned, Das‐Angel‐Wing and CardioSEAL devices. Existing devices were modified to address the anatomic features of the foramen ovale or new devices were designed to specifically address the PFOs and the latter include, Amplatzer PFO occluder, Cardia devices (PFO‐Star and several of its subsequent generations), Premere occluder, Coherex Flat stent, PFx Closure System (not a device but employs monopolar radio frequency energy to effect closure of a PFO by welding the tissues of the septum primum with the septum secundum), pfm PFO‐R, Solysafe PFO occluder and others. Amplatzer cribriform device was also used on off‐label basis to close PFOs.

In the next chapter, Biliciler‐Denktas, also from our institution, describes the role of transesophageal echocardiography (TEE) in percutaneous closure of ASDs. Initially the embryologic development of the atrial septum was reviewed. Currently used imaging techniques during device implantation, namely, transthoracic echocardiography, TEE, intracardiac echocardiography (ICE) and real time three‐ dimensional transesophageal echocardiography (3D TEE) were reviewed and relative advantages and disadvantages of each of these techniques were discussed; TEE and ICE are the two most commonly employed techniques. The importance of defined protocols to evaluate the heart, the atrial septal defect and the septal rims is stressed. Evaluation prior to device implantation include, examination of the entire atrial septum and its surrounding structures and exclusion of additional defects that may render the defect unsuitable for closure; measurement of the number and size of the defect(s); color Doppler imaging to define the shunt, left to right or right to left; dimensions of the septal rims and measurement of balloon stretched diameter of the defect (when a sizing balloon is used) and identification of other defects while balloon occluding the defect. The echo and the interventional physicians work as a team to decide on the device size to be used for closure of ASD/PFO. Monitoring of the device deployment and verifying for correct position of the device prior to device release are germane. Post‐implantation study will follow to detect impingement on valves, obstruction to venous return and residual shunting. TEE is also useful in the detection of complications of device closure such as device dislodgement and pericardial effusion/tamponade. The author concludes that TEE is of utmost value during percutaneous closure of ASDs and PFOs and is the preferred imaging modality in most catheterization laboratories.

XII Preface

to close PFOs.

delivery system of HIFU for creation of an atrial septal defect and further work to improve precision of the focus positioning of HIFU delivery and improvement of HIFU energy efficiency to intracardiac tissue is in progress. The concept appears good as is the design of the system. While the current results are far from clinically

In the fifth chapter from our institution, Alapati and I review the historical aspects of transcatheter closure of ASDs. Since the initial description of ASD occluding devices by King, Rashkind and their associates, a large number of single disc and double disc devices have been designed and tested in animal models followed by clinical trials in human subjects. Feasibility, safety and effectiveness have been demonstrated with most devices. However, design, redesign, testing and re‐testing have been the typical path with most devices. Currently, only two devices are approved by the FDA in the US and these are: Amplatzer septal occluder and HELEX septal occluder. Several other devices are in development, some at the stage of animal experimentation and some in clinical trials in Europe or US. We will await for additional devices to be approved for general clinical use so that the practicing interventional cardiologist will have several devices at his/her disposal so that an appropriate device that suits best for a given patient and his/her defect is available. A brief review of historical aspects of PFO closure was also included. Majority of the ASD devices described in the ASD section, as and when they became available, have also been used to close PFOs; these include King's, clamshell, buttoned, Das‐Angel‐Wing and CardioSEAL devices. Existing devices were modified to address the anatomic features of the foramen ovale or new devices were designed to specifically address the PFOs and the latter include, Amplatzer PFO occluder, Cardia devices (PFO‐Star and several of its subsequent generations), Premere occluder, Coherex Flat stent, PFx Closure System (not a device but employs monopolar radio frequency energy to effect closure of a PFO by welding the tissues of the septum primum with the septum secundum), pfm PFO‐R, Solysafe PFO occluder and others. Amplatzer cribriform device was also used on off‐label basis

In the next chapter, Biliciler‐Denktas, also from our institution, describes the role of transesophageal echocardiography (TEE) in percutaneous closure of ASDs. Initially the embryologic development of the atrial septum was reviewed. Currently used imaging techniques during device implantation, namely, transthoracic echocardiography, TEE, intracardiac echocardiography (ICE) and real time three‐ dimensional transesophageal echocardiography (3D TEE) were reviewed and relative advantages and disadvantages of each of these techniques were discussed; TEE and ICE are the two most commonly employed techniques. The importance of defined protocols to evaluate the heart, the atrial septal defect and the septal rims is stressed. Evaluation prior to device implantation include, examination of the entire atrial septum and its surrounding structures and exclusion of additional defects that may render the defect unsuitable for closure; measurement of the number and size of the defect(s); color Doppler imaging to define the shunt, left to right or right to left;

applicable, the technique has good potential.

In Chapter 7, Gonzalez and Hijazi of Rush University Medical Center, Chicago, Illinois, review the role of ICE in transcatheter closure of ASDs. Accurate and precise knowledge of the anatomy of the secundum ASD and the nearby structures is essential for safely performing ASD closure. While the conventional imaging method has been TEE, the authors advocate ICE to guide device closure of ASDs and PFOs because general anesthesia is not needed, risks of anesthesia are avoided and patient discomfort after the procedure is reduced. Ultrasound tipped catheters became available during the 1950s and 1960s and progressed thru' the current state of the art ICE catheters. several types of ICE catheters from different manufacturers are currently available and include, *UltraICE* mechanical single‐element system (Boston Scientific Corp), *AcuNav* system (Siemens from Biosense‐Webster), *ClearICE* system (St Jude Medical), *SoundStar* Catheter system (Biosense‐Webster) and *ViewMate Z* Intracardiac Ultrasound System and *ViewFlex Plus* ICE Catheter (St Jude Medical). The authors opine that *AcuNav* catheter is the most popular ICE catheter currently in use. The AcuNav catheter should be carefully advanced from the groin to the heart under continuous fluoroscopic guidance to prevent inadvertent advancement of the catheter into side branches with potential vessel injury before reaching the right atrium. Their ICE protocol involves obtaining different views (home view, septal view, long axis view and short axis view) along with fluoroscopic images. Then ICE imaging during each step, namely, balloon sizing, deployment of left and then right disks and after releasing the device, is undertaken to ensure appropriate positioning of the device. The authors believe that ICE is more accurate in evaluation ASDs when compared to TEE, apart from avoiding general anesthesia, usually required for TEE. They mention limitations of ICE, which include large shaft size, complications related to ICE catheter placement, cost and non availability of real time three‐dimensional (3D) imaging. They conclude that ICE along with fluoroscopy will improve the safety and outcome of percutaneous closure of ASDs.

In the next chapter, Sullebarger from Tampa, Florida, describes approaches to patients with technically challenging issues for transcatheter occlusion of ASDs and these include patients with poor femoral venous access, large defects and multiple defects. They also discuss minimally invasive, hybrid, transthoracic approach when percutaneous delivery of a device is not possible.

In the chapter 9, I address issues related why, when and how should ASDs be closed in adults. ASDs in adult subjects should be closed at presentation, electively, irrespective of their age. Evidence was presented to indicate that untreated ASD patients tend to have decreased event‐free survival rates when compared to normal population and surgical closure is safe and effective with high event‐free survival rates. ASD closure also prevents functional deterioration, improves cardiac function and increases functional capacity. Consequently hemodynamically significant (right ventricular volume overload) ASDs in adults should be occluded irrespective of symptomatology. When the effect of age at closure of ASD was examined, the Mayo Clinic data indicated that the actuarial survival rates are lower in patients who had surgery after 24 years of age; the earlier the surgery was performed the better were the 27‐year survival rates. Since there is no advantage in waiting beyond 24 years of age, the closure should be performed at the time of identification of the case. While surgical closure is safe and effective, device closure has less morbidity, lower number of complications, requires less hospital stay and is less expensive than surgery. Multiple devices have been investigated over the last few decades, but only Amplatzer and HELEX devices received FDA approval as of this time. The Amplatzer is useful in most ASDs while the HELEX device is useful in small and medium‐sized defects. Surgical repair is largely reserved for ASDs with poor septal rims. ASDs could also be closed surgically when intra‐cardiac repair of other defects is contemplated. Some procedural details were mentioned with particular emphasis on the need for test occlusion of ASD in the elderly and testing with vasodilator agents in patients with associated pulmonary hypertension. Approaches taken to occlude ASDs with complex anatomy were also reviewed. Amplatzer device appears to be best available option for closure of ASDs at the present time. Careful attention to the details of the technique is mandatory to achieve successful outcomes.

Preface XV

of pulmonary arterial wedge pressure was performed in only 7 of 30 cases. Device implantation was successful in 28 (93%) of the 30 patients. Significant improvement of NYHA functional class in 20 (74%) of the 27 patients, significant improvement in plasma BNP level, decreased resting heart rate, improvement of tricuspid regurgitation in 11 of 17 patients (65%) and cardiac remodeling with improvement in RVEDD/LVEDD ratio at follow‐up were observed. The author concludes that their experience in the elderly patients, while small, indicates that transcatheter closure of ASD can be performed safely and contributes to improvement of NYHA functional

In the Chapter 11, Numan from the University of Texas Medical School, Houston discusses the role of ASD/PFO in migraine. The incidence of migraine is 13% and has adverse affect on social life and potential for development of neurological complications. The age of migraine attacks is said to 20 to 64 years with the majority occurring prior to the age of 30 years. Migraine with aura, also known as "classic migraine" is seen in only 25% cases. There is an increased prevalence of PFOs in patients with migraine, but no causal relationship between these two is established. Such association appears to more convincing in patients with migraine with aura. The author then describes the pathologic anatomy and echocardiographic features of PFO. Transcranial Doppler has higher sensitivity than Echo (TTE, TEE or ICE) in detecting the right to left shunt across the PFO. The author reviews several studies examining the effect of occlusion of PFOs with devices; most single institutional, non‐randomized studies show improvement in migraine; this improvement is greater in patients with aura. However, Migraine Intervention With STARFlex Technology (MIST), a randomized prospective study with patients blinded for PFO closure did not demonstrate statistical difference between the two groups. The author offers several objections to the interpretation of the study, but concludes that the MIST study raises questions to be addressed in future studies. However, it may be concluded that the majority of the studies show benefit to patients suffering from migraine with aura.

In the last chapter, Daraban and her associates, also from the University of Texas Medical School, Houston discusses transcatheter occlusion of atrial defects for prevention of recurrence of paradoxical embolism. Stroke is the third most common cause of death in the United States. Cryptogenic stroke, consisting of 40% of stroke population may be related paradoxical embolism via PFO or ASD. Therapeutic measures for secondary prevention in this patient population include medical treatment or surgical/percutaneous closure of the PFO/ASD. The authors describe embryology, fetal and postnatal changes of PFO. The authors then describe the anatomy and associated anomalies such as atrial septal aneurysms (ASA), Chiari network and fenestrated atrial septum. TEE with or without contrast injection and Valsalva maneuver and transcranial Doppler (TCD) are important diagnostic tools in the identification of right‐to‐left shunt across the PFO. They then go on to describe the rationale for PFO and ASD closure treatment in patients with paradoxical embolism. The authors briefly describe the devices used for occlusion of PFO and describe in

class and encourages positive cardiac remodeling.

In the next chapter Akagi of Okayama University Hospital, Okayama, Japan reviews ASD closure in geriatric population. He introduces the subject of ASDs in the elderly (≥ 70 years) by pointing out increasing prevalence of congenital heart disease in general and ASDs in particular in this age group. He also states that mortality of congenital heart disease in the aged is increasing during past few decades. The clinical features of ASD in the elderly are different from those in children and young adults because they present with hemodynamic abnormalities such as pulmonary hypertension, valvar regurgitation, congestive heart failure and left ventricular diastolic dysfunction, atrial arrhythmias and co‐morbidities, such as hypertension, chronic obstructive lung disease, coronary artery disease, kidney disease and others. The author emphasizes that there are only a few studies in the aged population re functional results of catheter and surgical closure of ASD and reviews his experience with catheter closure of ASD in geriatric patients as well as long‐term outcome. Of the 420 patients who had attempted transcatheter closure of ASD at their institution, 30 patients were older than 70 years. Their mean age was 75.8 ± 3.8 years with a range of 70 and 85 years. Mean ASD diameter was 20.3 ± 6.4 mm and mean pulmonary‐ systemic flow (Qp/Qs) was 2.4 ± 0.7. Test balloon occlusion of ASD with measurement of pulmonary arterial wedge pressure was performed in only 7 of 30 cases. Device implantation was successful in 28 (93%) of the 30 patients. Significant improvement of NYHA functional class in 20 (74%) of the 27 patients, significant improvement in plasma BNP level, decreased resting heart rate, improvement of tricuspid regurgitation in 11 of 17 patients (65%) and cardiac remodeling with improvement in RVEDD/LVEDD ratio at follow‐up were observed. The author concludes that their experience in the elderly patients, while small, indicates that transcatheter closure of ASD can be performed safely and contributes to improvement of NYHA functional class and encourages positive cardiac remodeling.

XIV Preface

mandatory to achieve successful outcomes.

In the chapter 9, I address issues related why, when and how should ASDs be closed in adults. ASDs in adult subjects should be closed at presentation, electively, irrespective of their age. Evidence was presented to indicate that untreated ASD patients tend to have decreased event‐free survival rates when compared to normal population and surgical closure is safe and effective with high event‐free survival rates. ASD closure also prevents functional deterioration, improves cardiac function and increases functional capacity. Consequently hemodynamically significant (right ventricular volume overload) ASDs in adults should be occluded irrespective of symptomatology. When the effect of age at closure of ASD was examined, the Mayo Clinic data indicated that the actuarial survival rates are lower in patients who had surgery after 24 years of age; the earlier the surgery was performed the better were the 27‐year survival rates. Since there is no advantage in waiting beyond 24 years of age, the closure should be performed at the time of identification of the case. While surgical closure is safe and effective, device closure has less morbidity, lower number of complications, requires less hospital stay and is less expensive than surgery. Multiple devices have been investigated over the last few decades, but only Amplatzer and HELEX devices received FDA approval as of this time. The Amplatzer is useful in most ASDs while the HELEX device is useful in small and medium‐sized defects. Surgical repair is largely reserved for ASDs with poor septal rims. ASDs could also be closed surgically when intra‐cardiac repair of other defects is contemplated. Some procedural details were mentioned with particular emphasis on the need for test occlusion of ASD in the elderly and testing with vasodilator agents in patients with associated pulmonary hypertension. Approaches taken to occlude ASDs with complex anatomy were also reviewed. Amplatzer device appears to be best available option for closure of ASDs at the present time. Careful attention to the details of the technique is

In the next chapter Akagi of Okayama University Hospital, Okayama, Japan reviews ASD closure in geriatric population. He introduces the subject of ASDs in the elderly (≥ 70 years) by pointing out increasing prevalence of congenital heart disease in general and ASDs in particular in this age group. He also states that mortality of congenital heart disease in the aged is increasing during past few decades. The clinical features of ASD in the elderly are different from those in children and young adults because they present with hemodynamic abnormalities such as pulmonary hypertension, valvar regurgitation, congestive heart failure and left ventricular diastolic dysfunction, atrial arrhythmias and co‐morbidities, such as hypertension, chronic obstructive lung disease, coronary artery disease, kidney disease and others. The author emphasizes that there are only a few studies in the aged population re functional results of catheter and surgical closure of ASD and reviews his experience with catheter closure of ASD in geriatric patients as well as long‐term outcome. Of the 420 patients who had attempted transcatheter closure of ASD at their institution, 30 patients were older than 70 years. Their mean age was 75.8 ± 3.8 years with a range of 70 and 85 years. Mean ASD diameter was 20.3 ± 6.4 mm and mean pulmonary‐ systemic flow (Qp/Qs) was 2.4 ± 0.7. Test balloon occlusion of ASD with measurement

In the Chapter 11, Numan from the University of Texas Medical School, Houston discusses the role of ASD/PFO in migraine. The incidence of migraine is 13% and has adverse affect on social life and potential for development of neurological complications. The age of migraine attacks is said to 20 to 64 years with the majority occurring prior to the age of 30 years. Migraine with aura, also known as "classic migraine" is seen in only 25% cases. There is an increased prevalence of PFOs in patients with migraine, but no causal relationship between these two is established. Such association appears to more convincing in patients with migraine with aura. The author then describes the pathologic anatomy and echocardiographic features of PFO. Transcranial Doppler has higher sensitivity than Echo (TTE, TEE or ICE) in detecting the right to left shunt across the PFO. The author reviews several studies examining the effect of occlusion of PFOs with devices; most single institutional, non‐randomized studies show improvement in migraine; this improvement is greater in patients with aura. However, Migraine Intervention With STARFlex Technology (MIST), a randomized prospective study with patients blinded for PFO closure did not demonstrate statistical difference between the two groups. The author offers several objections to the interpretation of the study, but concludes that the MIST study raises questions to be addressed in future studies. However, it may be concluded that the majority of the studies show benefit to patients suffering from migraine with aura.

In the last chapter, Daraban and her associates, also from the University of Texas Medical School, Houston discusses transcatheter occlusion of atrial defects for prevention of recurrence of paradoxical embolism. Stroke is the third most common cause of death in the United States. Cryptogenic stroke, consisting of 40% of stroke population may be related paradoxical embolism via PFO or ASD. Therapeutic measures for secondary prevention in this patient population include medical treatment or surgical/percutaneous closure of the PFO/ASD. The authors describe embryology, fetal and postnatal changes of PFO. The authors then describe the anatomy and associated anomalies such as atrial septal aneurysms (ASA), Chiari network and fenestrated atrial septum. TEE with or without contrast injection and Valsalva maneuver and transcranial Doppler (TCD) are important diagnostic tools in the identification of right‐to‐left shunt across the PFO. They then go on to describe the rationale for PFO and ASD closure treatment in patients with paradoxical embolism. The authors briefly describe the devices used for occlusion of PFO and describe in detail the procedure of closure using Amplatzer PFO Occluder. A number of randomized clinical studies comparing medical treatment with closure of atrial defect are underway. The authors describe the CLOSURE I, REDUCE and RESPECT trials. CLOSURE I, a randomized trial compared the safety and efficacy of percutaneous PFO closure with STARFlex device versus best medical therapy. During a two year follow‐ up, the rates of stroke or transient ischemic attack (TIA) were no different between groups. REDUCE is a FDA approved prospective, randomized, multicenter trial designed to demonstrate the safety and effectiveness of the HELEX Septal Occluder for PFO closure in patients with a history of cryptogenic stroke or TIA. The RESPECT trial is a randomized, multi‐center study investigating whether closure of PFOs using the Amplatzer PFO Occluder device is safer and more effective than current standard‐of‐ care treatment in the prevention of a cryptogenic stroke. If the results of these clinical trials, favor device closure, it is likely that percutaneous PFO closure can be used to prevent recurrence of paradoxical embolism and stroke.

Of the major types of atrial defects, namely ostium secundum, ostium primum, sinus venosus and coronary sinus ASDs and PFO, ostium primum, sinus venosus and coronary sinus defects usually require surgical closure. Such surgery may be performed at about 3 to 4 years of age or if they present later, at the time of presentation. Earlier surgery is not necessary unless heart failure is present. Ostium secundum ASDs can be successfully closed with transcatheter methodology and the majority of the book addresses the issues related such technology. PFOs are ordinarily considered as normal variants, although, sometimes they become the seat of right left shunting, requiring closure. The evidence for closure PFO with potential right to left shunt in situations related to paradoxical embolism, migraine and others is equivocal. The studies currently in progress may throw light on this subject. While the majority of the book addresses closure of atrial septal defects, one chapter in particular focuses on creating atrial defects in the fetus with HLHS. I hope that the fund of information provided in this book will be use to the practicing physician caring for infants, children and adults with suspected or known ASDs which may aid them in providing optimal care for their patients.

> **Dr. P. Syamasundar Rao** University of Texas at Houston Medical School Houston, Texas, USA

XVI Preface

detail the procedure of closure using Amplatzer PFO Occluder. A number of randomized clinical studies comparing medical treatment with closure of atrial defect are underway. The authors describe the CLOSURE I, REDUCE and RESPECT trials. CLOSURE I, a randomized trial compared the safety and efficacy of percutaneous PFO closure with STARFlex device versus best medical therapy. During a two year follow‐ up, the rates of stroke or transient ischemic attack (TIA) were no different between groups. REDUCE is a FDA approved prospective, randomized, multicenter trial designed to demonstrate the safety and effectiveness of the HELEX Septal Occluder for PFO closure in patients with a history of cryptogenic stroke or TIA. The RESPECT trial is a randomized, multi‐center study investigating whether closure of PFOs using the Amplatzer PFO Occluder device is safer and more effective than current standard‐of‐ care treatment in the prevention of a cryptogenic stroke. If the results of these clinical trials, favor device closure, it is likely that percutaneous PFO closure can be used to

Of the major types of atrial defects, namely ostium secundum, ostium primum, sinus venosus and coronary sinus ASDs and PFO, ostium primum, sinus venosus and coronary sinus defects usually require surgical closure. Such surgery may be performed at about 3 to 4 years of age or if they present later, at the time of presentation. Earlier surgery is not necessary unless heart failure is present. Ostium secundum ASDs can be successfully closed with transcatheter methodology and the majority of the book addresses the issues related such technology. PFOs are ordinarily considered as normal variants, although, sometimes they become the seat of right left shunting, requiring closure. The evidence for closure PFO with potential right to left shunt in situations related to paradoxical embolism, migraine and others is equivocal. The studies currently in progress may throw light on this subject. While the majority of the book addresses closure of atrial septal defects, one chapter in particular focuses on creating atrial defects in the fetus with HLHS. I hope that the fund of information provided in this book will be use to the practicing physician caring for infants, children and adults with suspected or known ASDs which may aid them in providing

**Dr. P. Syamasundar Rao**

Houston, Texas,

USA

University of Texas at Houston Medical School

prevent recurrence of paradoxical embolism and stroke.

optimal care for their patients.

**Section 1** 

**General Review of Atrial Septal Defects** 
