Cardiomyopathies — pathophysiology, aetiology, clinical features, diagnosis and treatment

Cardiomyopathy = myocardial disorder in which the heart muscle is structurally and functionally abnormal, in the absence of coronary disease, hypertension, valvular disease or congenital disease sufficient to explain the abnormality.

Morphofunctional classification: dilated (DCM), hypertrophic (HCM), restrictive (RCM), arrhythmogenic right ventricular cardiomyopathy (ARVC), and non-dilated left ventricular cardiomyopathy (NDLVC) — the last added by the 2023 ESC cardiomyopathy guideline.

Aetiological classification: genetic (familial) versus acquired (mixed forms exist).

Dilated: ventricular dilatation with systolic dysfunction → reduced stroke volume → neurohormonal activation (RAAS, sympathetic) → adverse remodelling, mitral annular dilatation with functional regurgitation, mural thrombus and arrhythmia.

Hypertrophic: sarcomere protein mutations → myocyte hypertrophy and disarray with interstitial fibrosis → impaired relaxation, dynamic left ventricular outflow tract obstruction with systolic anterior motion of the mitral valve, microvascular ischaemia and arrhythmogenic substrate.

Restrictive: stiff, non-compliant ventricles with normal or near-normal systolic function and normal chamber size → severe diastolic impairment with biatrial enlargement and high filling pressures.

Arrhythmogenic: desmosomal mutations → fibrofatty replacement of myocardium → ventricular arrhythmia and sudden death.

Dilated: idiopathic/familial (titin, lamin A/C), ischaemic, alcohol, chemotherapy (anthracyclines, trastuzumab), viral myocarditis, thyroid disease, tachycardia-induced, peripartum, iron overload, nutritional (thiamine).

Hypertrophic: autosomal dominant sarcomere gene mutations (MYH7, MYBPC3); phenocopies include Fabry disease and amyloidosis.

Restrictive (most relevant to geriatrics): cardiac amyloidosis (transthyretin wild-type in the elderly, AL in plasma cell dyscrasia), sarcoidosis, haemochromatosis, endomyocardial fibrosis (important in tropical/Indian practice), radiation and hypereosinophilic syndrome.

Indian context: endomyocardial fibrosis, rheumatic heart disease as a differential, nutritional and alcoholic cardiomyopathy, and a relatively higher prevalence of idiopathic dilated cardiomyopathy than in the West.

Common to all: exertional dyspnoea, fatigue, palpitations, syncope, embolic events, arrhythmia and sudden cardiac death.

Dilated: features of congestive failure with a displaced diffuse apex, S3, functional mitral regurgitation.

Hypertrophic: ejection systolic murmur that increases with Valsalva and standing and decreases with squatting; jerky/bisferiens pulse; murmur does not radiate to the carotids (contrast with aortic stenosis). Essentials warns that in older adults this may be misdiagnosed as aortic stenosis or mitral regurgitation, and that digoxin and diuretics may worsen symptoms.

Restrictive/amyloid: right-sided failure predominates with raised JVP, Kussmaul's sign, hepatomegaly, ascites, peripheral oedema; extracardiac clues of transthyretin amyloidosis include bilateral carpal tunnel syndrome, lumbar spinal stenosis, biceps tendon rupture, and intolerance of standard heart failure drugs because of hypotension.

ECG: DCM — LBBB, poor R progression; HCM — LV hypertrophy with deep T inversion; amyloidosis — the classic mismatch of low QRS voltages with echocardiographic LV thickening, plus pseudo-infarct patterns and conduction block. Echocardiography defines the phenotype: chamber size, wall thickness, ejection fraction, outflow gradient, diastolic parameters and granular sparkling myocardium in amyloid; global longitudinal strain shows apical sparing ("cherry-on-top") in amyloidosis.

Advanced tests: cardiac MRI with late gadolinium enhancement and T1/extracellular volume mapping; 99mTc-PYP/DPD bone scintigraphy (Perugini grade ≥2) for transthyretin amyloidosis; serum free light chains with serum and urine immunofixation to exclude AL amyloidosis; genetic testing and family screening; endomyocardial biopsy where non-invasive tests are inconclusive; coronary angiography to exclude ischaemic disease.

DCM: full guideline-directed HFrEF therapy (four pillars), device therapy (CRT/ICD), anticoagulation if AF or mural thrombus, and removal of the cause (alcohol, tachycardia, thyroid). HCM: beta blockers or verapamil; disopyramide for obstruction; avoid dehydration, vasodilators, digoxin and diuretic excess; septal reduction (myectomy or alcohol ablation) for refractory obstruction; ICD for high sudden-death risk. RCM/amyloid: cautious diuretics for congestion, treat arrhythmia, anticoagulate for AF regardless of risk score, and use disease-modifying therapy for transthyretin amyloidosis. Avoid digoxin and calcium channel blockers in amyloidosis (binding to amyloid fibrils increases toxicity).