Cardiomyopathies — Dilated, Hypertrophic, Restrictive and Arrhythmogenic Right Ventricular

A cardiomyopathy is a primary disease of the myocardium that is not explained by valvular, hypertensive or coronary disease alone. The three classic phenotypes are dilated (DCM), hypertrophic (HCM) and restrictive (RCM), with arrhythmogenic right ventricular cardiomyopathy (ARVC) as an important fourth. Restrictive cardiomyopathy is the least common of the three major types, accounting for roughly 5% of cardiomyopathies.

HCM is the most common inherited cardiomyopathy, affecting about 1 in 500 adults. It is an autosomal dominant disease of the sarcomere; about 60% of cases are familial, and the two commonest genes are MYH7 (β-myosin heavy chain) and MYBPC3 (myosin-binding protein C3). Histology shows myocyte disarray, enlarged cardiomyocytes with box-shaped nuclei and interstitial fibrosis. Diagnosis in adults needs a left ventricular wall thickness of 15 mm or more (13 to 14 mm if there is a family history or other supportive features), with a septal to posterior wall ratio above 1.3 in normotensive patients.

Obstruction arises when the thickened septum narrows the outflow tract and the anterior mitral leaflet moves into it (systolic anterior motion, SAM). A resting or provoked gradient of 30 mm Hg or more is clinically significant, and 50 mm Hg or more is the usual threshold for septal reduction in symptomatic patients. Many patients have preserved or hyperdynamic ejection fraction (often above 65%); thickening and disarray stiffen the ventricle and impair relaxation. SAM has about 99% specificity for HCM on echocardiography.

• Examination: a 'jerky' pulse with rapid upstroke and downstroke and a harsh midsystolic ejection murmur at the left sternal border; coexisting mitral regurgitation gives an apical holosystolic murmur.
• Non-sustained VT is present in about 20 to 30% of patients; ventricular fibrillation is the commonest cause of sudden death.
• HCM is a leading cause of sudden cardiac death in athletes younger than 35 years; guidelines advise against strenuous competitive sport.
• Treatment: first-line beta-blockers, non-dihydropyridine calcium channel blockers (verapamil) or disopyramide; septal myectomy or alcohol septal ablation for refractory obstruction (ablation carries a higher risk of heart block); mavacamten, a cardiac myosin inhibitor, for symptomatic obstructive HCM; ICD for selected high-risk patients.

DCM is dilatation of one or both ventricles with impaired contractility, defined by a left ventricular ejection fraction below 40%. The commonest cause is idiopathic; genetic mutations (for example in desmin, lamin and myosin genes) can be familial. Secondary causes include infectious myocarditis (viral, Chagas disease, Lyme disease), alcohol abuse, anthracyclines, HIV, peripartum cardiomyopathy and infiltrative disease. Ischaemic cardiomyopathy is classified separately, and Takotsubo (transient left ventricular ballooning) is usually regarded as a distinct entity.

• Most patients present between 20 and 60 years, often with a long asymptomatic period; men are more commonly affected.
• Symptoms are those of heart failure: orthopnoea, paroxysmal nocturnal dyspnoea, oedema, fatigue.
• Signs: displaced apex, S3 gallop, raised JVP, crackles, functional mitral and tricuspid regurgitation from annular dilatation.
• Work-up looks for reversible causes: TSH, HIV, electrolytes, iron studies (haemochromatosis), alcohol and toxicology screen, and coronary angiography if no known coronary disease. Echocardiography is the key test; biopsy is rarely needed because idiopathic DCM histology is non-specific.

Management follows heart failure guidelines: loop diuretics for congestion, ACE inhibitor or ARB (with other guideline therapy), salt and water restriction and cardiac rehabilitation. Anticoagulation is recommended only for atrial fibrillation, prosthetic valves or a known mural thrombus — not routinely. ICD for primary prevention of sudden death and cardiac resynchronisation therapy are considered, and refractory disease may need transplantation or an LVAD.

RCM is diastolic dysfunction of a non-dilated ventricle: the myocardium is stiff, so filling pressures rise sharply while systolic function stays normal or near normal. Most causes are acquired, through infiltration between myocytes, storage of abnormal products within myocytes, or fibrosis. The three leading causes are cardiac amyloidosis, sarcoidosis and haemochromatosis; amyloidosis is the commonest in developed countries. In the tropics, endomyocardial fibrosis and Löffler endocarditis are important — up to 20% of heart failure in sub-Saharan Africa is attributed to endomyocardial fibrosis.

• Clinical: JVP with rapid Y descent, Kussmaul sign (JVP rises on inspiration), a fourth heart sound in sinus rhythm; atrial fibrillation is common.
• Diuretics are the mainstay for congestion, used carefully because these patients depend on high filling pressures.
• Advanced disease may need transplantation or an LVAD.

ARVC (also called arrhythmogenic right ventricular dysplasia) is a genetic disease in which myocardium, chiefly of the right ventricle, is replaced by fibrofatty tissue, producing arrhythmia. It is usually autosomal dominant with variable penetrance. About two-thirds of patients have a positive genetic test, mostly in desmosomal genes — PKP2, DSP, DSG2, DSC2 and JUP; non-desmosomal genes include TMEM43, DES and PLN. Naxos disease (autosomal recessive, JUP mutation; plakoglobin) combines ARVC with woolly hair (and sometimes alopecia). Estimated prevalence is about 1 in 5,000 to 1 in 2,000 in some European countries, and symptoms usually begin between the second and fourth decades.

• Presentation: palpitations or syncope on exertion; sudden cardiac death may be the first manifestation (including in young athletes).
• ECG: T-wave inversion in right precordial leads V1 to V4; the epsilon wave (small post-excitation deflection at the end of the QRS) is seen in about 50% and is now a minor criterion in the 2020 criteria.
• Ventricular tachycardia with a left bundle branch block pattern, often exercise-triggered.
• Histology: fibrofatty replacement beginning in the subepicardium and progressing to transmural; cardiac MRI with late gadolinium enhancement increasingly replaces biopsy.
• Management: restrict strenuous exercise; beta-blockers and antiarrhythmics; catheter ablation for refractory VT; ICD is the most effective measure to prevent sudden death in selected patients; transplantation for end-stage heart failure.

• Pattern recognition — matching vignette plus echo to dilated, hypertrophic or restrictive.
• HCM manoeuvres — Valsalva and standing increase the murmur; squatting and handgrip decrease it.
• Genetics — HCM autosomal dominant sarcomere mutations (MYH7, MYBPC3); ARVC desmosomal genes; Naxos disease.
• Causes of DCM — alcohol, doxorubicin, peripartum, Chagas and viral myocarditis.
• RCM causes and the constrictive pericarditis comparison — amyloid, sarcoid, haemochromatosis (phlebotomy), endomyocardial fibrosis.
• Sudden death in the young athlete — HCM and ARVC.