The cardiomyopathies: hypertrophic, dilated, restrictive, and right ventricular

The term cardiomyopathy is used to describe heart muscle disease unexplained by abnormal loading conditions (hypertension, valve disease, etc.), congenital cardiac abnormalities, and ischaemic heart disease. The current classification is based on the predominant phenotype, i.e. hypertrophic, dilated, arrhythmogenic right ventricular, restrictive and unclassifiable (including left ventricular noncompaction), and—where possible—incorporating inheritance and genotype. Cardiomyopathies associated with systemic diseases are described in Chapter 16.7.3.

Hypertrophic cardiomyopathy

The diagnosis of hypertrophic cardiomyopathy is based upon the demonstration of unexplained myocardial hypertrophy, defined as a wall-thickness measurement exceeding two standard deviations above normal for gender and age. In practice, in an adult of normal size, the presence of a left ventricular myocardial segment of 1.5 cm or greater in thickness is diagnostic. Less stringent criteria should be applied to first-degree relatives of an unequivocally affected individual. Ninety per cent of patients have familial disease, usually with autosomal dominant inheritance. Mutations in genes encoding proteins of the cardiac sarcomere are most common (60% of cases).

Symptomatic presentation may be at any age, with breathlessness on exertion, chest pain, palpitation, syncope, or sudden death. In children and adolescents, the diagnosis is most often made during screening of siblings and offspring of affected family members. In most patients the physical examination is unremarkable, but characteristic features include a rapid upstroke arterial pulse, a forceful left ventricular cardiac impulse with palpable atrial beat, an ejection systolic murmur, and a fourth heart sound.

Investigation and diagnosis—the 12-lead ECG is the most sensitive diagnostic test, with ST-segment depression and T-wave changes being the most common abnormalities, usually associated with voltage changes of left ventricular hypertrophy and/or deep S waves in the anterior chest leads V1 to V3. Echocardiography reveals left ventricular hypertrophy that may be symmetric or asymmetric and localized to the septum or the free wall, but most commonly to both the septum and free wall with relative sparing of the posterior wall.

Management—β-adrenoceptor blockers and calcium antagonists (verapamil, diltiazem) are the mainstay of symptomatic pharmacological therapy. Surgery is considered for patients with obstruction (typically resting left ventricular outflow-tract gradient of more than 50 mmHg) and/or mitral valve abnormalities, with the commonest operation being removal of a segment of the upper anterior septum (myectomy) via a transaortic approach. Injection of alcohol into the septal artery that supplies the ‘obstructing’ septal muscle has been developed as a percutaneous, nonpharmacological approach to gradient reduction.

Prognosis—annual mortality is 0.5 to 1%, but the risk of death and other disease-related complications varies between individuals. Prevention of sudden death relies on risk factor stratification to identify high-risk individuals.

Dilated cardiomyopathy

Dilated cardiomyopathy is defined by dilatation and impaired systolic function of the left ventricle or both ventricles not attributable to coronary artery disease, valvular abnormalities, or pericardial disease. Up to 50% of cases are familial, with a large number of disease-causing gene mutations described.

Initial presentation is usually with symptoms of cardiac failure, but other presentations include arrhythmia, systemic embolism, or the incidental finding of an electrocardiographic or radiographic abnormality. Physical examination may reveal cardiac enlargement and signs of congestive heart failure.

Investigation and diagnosis—on echocardiography, the presence of ventricular end-diastolic dimensions greater than two standard deviations above the mean and fractional shortening less than 25% are generally sufficient to make the diagnosis.

Management—symptomatic therapy involves the treatment of heart failure with diuretics, angiotensin converting enzyme (ACE) inhibitors, and β-blockers. Anticoagulation with warfarin is advised in patients in whom an intracardiac thrombus is identified echocardiographically, or those with a history of thromboembolism. Internal cardioverter defibrillators are warranted if sustained or symptomatic ventricular arrhythmias are documented and for primary prophylaxis in selected high risk patients. Biventricular or left ventricular pacing can improve symptoms and prognosis in selected patients, and cardiac transplantation may be appropriate for those with progressive deterioration.

Restrictive cardiomyopathy

Restrictive cardiomyopathies are defined by restrictive ventricular physiology in the presence of normal or reduced diastolic volumes of one or both ventricles, normal or reduced systolic volumes, and normal ventricular wall thickness. In the Western world, amyloidosis is the commonest cause; in the tropics, endomyocardial fibrosis. Familial restrictive cardiomyopathy is usually caused by sarcomere mutations, with the full spectrum of restrictive cardiomyopathy and hypertrophic cardiomyopathy sometimes seen within individual families.

Presentation is usually insidious: left-sided disease may present with symptoms of pulmonary congestion and/or mitral regurgitation; right-sided disease with raised jugular venous pressure, hepatomegaly, ascites, and tricuspid regurgitation. Atrial fibrillation is uncommon. Echocardiography confirms the diagnosis, typically showing that ventricular dimensions and wall thickness are normal, but the atria are grossly enlarged.

Congestive symptoms from raised right atrial pressure can be improved with diuretics, though too great a reduction in ventricular filling pressure will lead to a reduction in cardiac output. Prognosis of advanced disease is poor.

Arrhythmogenic right ventricular cardiomyopathy

Arrhythmogenic right ventricular cardiomyopathy is a heart muscle disease characterized by progressive fibrofatty replacement of right ventricular myocardium, associated with ventricular arrhythmia, heart failure, and sudden cardiac death. It is inherited and caused by mutations in desmosomal genes in at least 50% of cases.

Symptomatic presentation is usually with palpitation and/or syncope from sustained ventricular arrhythmia, but the first presentation of the disease may be with sudden cardiac death. There is no single diagnostic test, and the diagnosis is based on the presence of major and minor criteria encompassing structural, histological, electrocardiographic, arrhythmic, and genetic factors. The most common electrocardiographic abnormality is T-wave inversion in leads V1 to V3 in the absence of right bundle branch block. Typical echocardiographic findings include right ventricular dilatation, regional hypokinesia or dyskinesia, and aneurysms.

Management—patients with symptomatic, non-life-threatening ventricular arrhythmias are treated empirically with β-blockers, amiodarone, or sotalol. Those with a history of sustained, haemodynamically compromising ventricular arrhythmia should be offered an implantable cardioverter–defibrillator.