Preface

**Section 3 Genetics 105**

**VI** Contents

Rodríguez

**Section 4 Sudden Death 165**

Chapter 9 **Sudden Cardiac Death 167**

and Uichi Ikeda

**2 (RyR2) 243** Jan Klimas

Chapter 14 **Pediatric Cardiomyopathies 281**

Chapter 7 **The Role of Genetics in Cardiomyopathy 107**

**Presentation and Treatment 133**

Prabhat Kumar and J Paul Mounsey

Chapter 10 **Role of Traditional Heart Failure Medications on Sudden Cardiac Death Prevention in Patients with**

Ann M. Anderson and M. Obadah Al Chekakie

Chapter 11 **Risk Stratification of Sudden Cardiac Death by Evaluating**

**Section 5 Cardiomyopathies in Special Populations 241**

Chapter 12 **Potential Target Molecules in Diabetic Cardiomyopathy:**

Chapter 13 **Cardiomyopathy in Women: Second Heart Failure 265** Kenneth J. McLeod and Carolyn Pierce

Aspazija Sofijanova and Olivera Jordanova

**Myocardial Sympathetic Nerve Activity Using Iodine-123 Metaiodobenzylguanidine Scintigraphy in Patients with Chronic Heart Failure and Dilated Cardiomyopathy 229** Yoshikazu Yazaki, Toshimasa Seki, Atsushi Izawa, Minoru Hongo

**Hepatocyte Growth Factor (HGF) and Ryanodine Receptor**

M. Obadah Al Chekakie

**Cardiomyopathy 213**

Chapter 8 **Specific Forms of Cardiomyopathy: Genetics, Clinical**

Luis Vernengo, Alain Lilienbaum, Onnik Agbulut and Maria-Mirta

More than 50 years ago, in 1957, Bridgen the word "cardiomyopathy" has been used for the first time. One year later, Teare described nine cases of interventricular septal hyper‐ trophy. In this book the broad aspects of cardiomyopathies are fully developed by re‐ nowned specialists. The book is divided in five sections – Cardiomyopathies - general aspects; pathophysiology and molecular mechanisms; genetics; sudden death and cardi‐ omyopathies in special populations.

The disease of the heart muscle may develop secondarily to other cardiac alterations, such as ischemic, hypertensive, valvular and systemic, among others. However, there is also a group of conditions with intrinsic myocardial involvement of genetic or multifac‐ torial etiology, characterized by high morbidity and mortality that represent a diagnos‐ tic and therapeutic challenge for the physician.

Cardiomyopathy (primary) is defined as a disease of the myocardium, which results in insufficient pumping of the heart. It is classified into four forms; dilated cardiomyop‐ athy, hypertrophic cardiomyopathy, restrictive cardiomyopathy, and arrhythmogenic right ventricular cardiomyopathy.

The book is focused on these forms, its features, its pathophysiology, and its relationship to sudden death. Mention is made also on general aspects, like ecocardiographic find‐ ings and myocardial contractile reserve, specific as pathophysiology and molecular mechanisms. Special attention is deserved to cardiomyopathies in special populations, like pediatrics, diabetic patients, and women, as well as to cases of chronic heart failure and dilated cardiomyopathy.

Cardiomyopathies are characterized by extensive remodeling of the myocardium mani‐ fested as hypertrophy, due to enlarged myocyte size and interstitial fibrosis. With the progression of the disease, the heart turns to a dilated state, with increase of the intra‐ ventricular volume and a mild increase in ventricular wall thickness. These changes, ap‐ parently compensatory, ultimately become maladaptive.

Dilated cardiomyopathy is one of the most common types of cardiomyopathy world‐ wide. It is characterized by progressive chamber dilatation and myocardial systolic dys‐ function and diagnosed by left ventricular enlargement and impaired systolic left ventricular function.

Regarding diagnosis, echocardiography is the most frequently used and readily availa‐ ble cardiac imaging technique. It has been established as the cardiac imaging modality of choice in diagnosis and longitudinal follow up of patients with cardiomyopathy.

In most patients suffering from cardiomyopathy and heart failure, symptoms are not present at rest but become evident with exercise. As said, the test universally used is echocardiography, but it is generally performed under resting conditions and left ven‐ tricular contractile function at rest is not reliable for the evaluation of the reversibility of myocardial contraction, that is contractile reserve. For this reason, it is important to eval‐ uate functional response also under dynamic conditions by the use of pharmacological and/or exercise stress. Also, the prognostic value of dobutamine- and pacing- induced mechanical alterations in outpatients with idiopathic dilated cardiomyopathy and se‐ vere heart failure is discussed, with respect to clinical conditions and mechanisms of de‐ velopment.

ease. In many women, an important event in heart failure is due to poor venous return resulting from inadequate calf muscle pump activity during upright posture. This ex‐ plains that while women survival rate with heart failure is better, their quality of life

As shown, the broad spectrum of new aspects of "Cardiomyopathies" are developed in

**Prof. Dr. José Milei**

Preface IX

**Prof. Giuseppe Ambrosio** Director of Cardiology

University of Perugia School of Medicine

Director del Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini"- UBA- CONICET (ININCA)

with heart failure is far worse.

this book, with the hope to be useful to cardiologists.

In this connection, left ventricular twist is indispensable for proper left ventricular func‐ tion. It originates from the dynamic interaction between oppositely wound subepicar‐ dial and subendocardial myocardial fibers. The direction of left ventricular twist is governed by the subepicardial fibers, mainly owing to their longer arm of movement. Measurement of left ventricular rotation by echocardiography has only recently become clinically feasible with the development of speckle tracking echocardiography. It has be‐ come clear that increased left ventricular twist, for example in hypertrophic cardiomy‐ opathy, diabetes, and in healthy ageing population, may serve as a compensatory mechanism to preserve ejection fraction.

Also, it is emphasized that measurement of left ventricular untwisting may become an important element of diastolic function evaluation in cardiomyopathies.

Since 20 years, several mutations in genes encoding sarcomeric proteins have been cau‐ sally linked to cardiomyopathies. There is a long list of affected sarcomeric proteins of striated muscles. Some selected proteins are described as to the molecular structure of their genes, as well as a comprehensive and up-to-date listing of the mutations that have been identified and directly linked to the development of cardiomyopathies is provided.

Most cardiomyopathies with primary myocardial pathology predispose to sudden car‐ diac death, especially in younger subjects. Although they account for a small fraction of population, a subset of these patients are at high risk and this justifies an aggressive pre‐ ventive strategy. These include dilated cardiomyopathy, hypertrophic cardiomyopathy, left ventricular non-compaction and arrhythmogenic right ventricular cardiomyopathy. Sarcoidosis is a rare form of cardiomyopathy that affects young patients and put them at risk of sudden cardiac death. Early recognition and treatment of all these disease is man‐ datory. Regarding diagnosis, 123I-MIBG scintigraphy to evaluate myocardial sympa‐ thetic nerve activity may be useful in risk stratification of the risk of sudden death in heart failure patients without sustained VT and a history of ventricular fibrillation and dilated cardiomyopathy.

Implantable defibrillator therapy has emerged as the most important management strat‐ egy for prevention of sudden death in patients with cardiomyopathy. Whilst the use of beta-blocker therapy, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, as well as aldosterone antagonists have been shown to decrease the risk of sud‐ den cardiac death especially in in patients with congestive heart failure.

Heart failure in women has a distinct phenotype; develops later in life, generally presents with preserved systolic function and it is less attributable to ischemic heart dis‐

ease. In many women, an important event in heart failure is due to poor venous return resulting from inadequate calf muscle pump activity during upright posture. This ex‐ plains that while women survival rate with heart failure is better, their quality of life with heart failure is far worse.

In most patients suffering from cardiomyopathy and heart failure, symptoms are not present at rest but become evident with exercise. As said, the test universally used is echocardiography, but it is generally performed under resting conditions and left ven‐ tricular contractile function at rest is not reliable for the evaluation of the reversibility of myocardial contraction, that is contractile reserve. For this reason, it is important to eval‐ uate functional response also under dynamic conditions by the use of pharmacological and/or exercise stress. Also, the prognostic value of dobutamine- and pacing- induced mechanical alterations in outpatients with idiopathic dilated cardiomyopathy and se‐ vere heart failure is discussed, with respect to clinical conditions and mechanisms of de‐

In this connection, left ventricular twist is indispensable for proper left ventricular func‐ tion. It originates from the dynamic interaction between oppositely wound subepicar‐ dial and subendocardial myocardial fibers. The direction of left ventricular twist is governed by the subepicardial fibers, mainly owing to their longer arm of movement. Measurement of left ventricular rotation by echocardiography has only recently become clinically feasible with the development of speckle tracking echocardiography. It has be‐ come clear that increased left ventricular twist, for example in hypertrophic cardiomy‐ opathy, diabetes, and in healthy ageing population, may serve as a compensatory

Also, it is emphasized that measurement of left ventricular untwisting may become an

Since 20 years, several mutations in genes encoding sarcomeric proteins have been cau‐ sally linked to cardiomyopathies. There is a long list of affected sarcomeric proteins of striated muscles. Some selected proteins are described as to the molecular structure of their genes, as well as a comprehensive and up-to-date listing of the mutations that have been identified and directly linked to the development of cardiomyopathies is provided. Most cardiomyopathies with primary myocardial pathology predispose to sudden car‐ diac death, especially in younger subjects. Although they account for a small fraction of population, a subset of these patients are at high risk and this justifies an aggressive pre‐ ventive strategy. These include dilated cardiomyopathy, hypertrophic cardiomyopathy, left ventricular non-compaction and arrhythmogenic right ventricular cardiomyopathy. Sarcoidosis is a rare form of cardiomyopathy that affects young patients and put them at risk of sudden cardiac death. Early recognition and treatment of all these disease is man‐ datory. Regarding diagnosis, 123I-MIBG scintigraphy to evaluate myocardial sympa‐ thetic nerve activity may be useful in risk stratification of the risk of sudden death in heart failure patients without sustained VT and a history of ventricular fibrillation and

Implantable defibrillator therapy has emerged as the most important management strat‐ egy for prevention of sudden death in patients with cardiomyopathy. Whilst the use of beta-blocker therapy, angiotensin-converting enzyme inhibitors, angiotensin receptor blockers, as well as aldosterone antagonists have been shown to decrease the risk of sud‐

Heart failure in women has a distinct phenotype; develops later in life, generally presents with preserved systolic function and it is less attributable to ischemic heart dis‐

den cardiac death especially in in patients with congestive heart failure.

important element of diastolic function evaluation in cardiomyopathies.

velopment.

VIII Preface

mechanism to preserve ejection fraction.

dilated cardiomyopathy.

As shown, the broad spectrum of new aspects of "Cardiomyopathies" are developed in this book, with the hope to be useful to cardiologists.

### **Prof. Dr. José Milei**

Director del Instituto de Investigaciones Cardiológicas "Prof. Dr. Alberto C. Taquini"- UBA- CONICET (ININCA)

> **Prof. Giuseppe Ambrosio** Director of Cardiology University of Perugia School of Medicine

**Section 1**

**Cardiomyopathies - General Aspects**

**Cardiomyopathies - General Aspects**

**Chapter 1**

**Echocardiography Findings in Common Primary and**

Cardiomyopathy is a heterogeneous group of disorders of varying etiology. Heart failure from systolic and/or diastolic cardiac dysfunction is common to all. Certain disorders are distin‐ guished by life threatening arrhythmia. Onset of symptoms may be acute or progress from preclinical to symptomatic state over time and at a variable rate. Early recognition permits therapeutic intervention thereby retarding clinical progression and in some reversal or arrest of pathologic state. Echocardiography being the most frequently used and readily available cardiac imaging technique has established itself as the cardiac imaging modality of choice in diagnosis and longitudinal follow up of patients with cardiomyopathy. Complementary information from other imaging techniques, e.g., tissue characterization with cardiac MRI in iron overload states and evaluation of coronary anatomy with cardiac CT as in some cases of dilated cardiomyopathy, usually follows recognition of cardiomyopathy on echocardiogram. An understanding of conventional echocardiogram and knowledge of novel applications of existing methods and emerging imaging echo techniques is important for effective clinical use

Standard echocardiogram includes analysis of myocardial and valvular structure, chamber quantification and estimation of function based on qualitative assessment and quantification by 2-D and M-mode echocardiography. Blood flow dynamics through different cardiac chambers and heart valves is assessed using spectral and color Doppler methods. Through prior work, pressure gradient across heart valves can be derived from measured flow velocity

> © 2013 Jamil et al.; licensee InTech. This is an open access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/3.0), which permits unrestricted use,

© 2013 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,

distribution, and reproduction in any medium, provided the original work is properly cited.

and reproduction in any medium, provided the original work is properly cited.

); flow velocity is directly measured from

**Secondary Cardiomyopathies**

Anwer Qureshi

**1. Introduction**

of echocardiography.

**1.1. Standard 2-D and M-mode echocardiogram**

by using the modified Bernoulli equation (4V2

http://dx.doi.org/10.5772/55036

Gohar Jamil, Ahmed Abbas, Abdullah Shehab and

Additional information is available at the end of the chapter
