Cardiomyopathies Pathology
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Direct answer
A primary disorder of heart muscle — dilated, hypertrophic, restrictive or arrhythmogenic — defines the cardiomyopathies: myocardial disease occurring without coronary, valvular, hypertensive or congenital cause. Dilated cardiomyopathy, the commonest form, produces eccentric hypertrophy with a globular, poorly contracting ventricle; hypertrophic cardiomyopathy is an autosomal-dominant sarcomere disease with asymmetrical septal hypertrophy, myofibre disarray and a risk of sudden death; restrictive disease stiffens the ventricle through infiltrates such as amyloid or through endomyocardial fibrosis; arrhythmogenic right ventricular cardiomyopathy replaces right ventricular muscle with fibrofatty tissue. Each carries a gene list, a gross appearance and a treatment logic that examinations reward.
What you must remember
- Dilated cardiomyopathy: commonest form; causes include familial titin (TTN) mutations, alcohol, viral myocarditis, doxorubicin, thiamine deficiency (beriberi) and the peripartum period; all four chambers dilate, the wall thins, mural thrombi line the apex.
- Hypertrophic cardiomyopathy genetics: autosomal dominant with variable penetrance; MYH7 and MYBPC3 sarcomere genes account for most genotype-positive cases; septum exceeds 15 mm asymmetrically.
- HCM histology: disordered whorls of myofibre disarray, interstitial fibrosis and thickened intramural coronary arterioles — the microscopic triad.
- HCM mechanics and risk: systolic anterior motion of the mitral leaflet creates dynamic outflow obstruction; sudden-death markers include wall thickness over 30 mm, family history of sudden death, non-sustained ventricular tachycardia, unexplained syncope and a flat blood-pressure response to exercise.
- Treatment logic: beta-blockers and disopyramide reduce the gradient; digoxin, vasodilators and vigorous dehydration worsen it — a contraindication question in every series.
- Restrictive causes: cardiac amyloidosis leads in the West; endomyocardial fibrosis — endemic in Kerala and tropical Africa — plaques the ventricular apex and inflow tract; Loeffler eosinophilic endocarditis is its temperate counterpart.
- Arrhythmogenic right ventricular cardiomyopathy: desmosomal mutations (plakophilin-2 classical), fibrofatty replacement, exercise-triggered arrhythmia in the young; competitive sport is prohibited.
The athlete with a thick septum
A 22-year-old cricketer collapses briefly during training; echocardiography shows a 16 mm septum. Is this athlete's heart or hypertrophic cardiomyopathy? Reason it through. Athlete's heart gives a modest, symmetrical septum (rarely beyond 12-14 mm) with a large cavity, normal diastolic filling, a physiologically slow heart rate and a bland electrocardiogram that deconditions within weeks of stopping training. Hypertrophic cardiomyopathy gives asymmetrical thickening, a small hyperdynamic cavity, left atrial enlargement, diastolic dysfunction, bizarre electrocardiographic voltages, and — the decisive step — a first-degree relative with the same picture or a documented sudden death. Where the numbers straddle the grey zone, a period of detraining and family screening resolves more cases than any single test, and a positive genetic panel settles the rest. Missing the diagnosis kills a young person; overcalling it ends a career for no reason.
Restrictive versus constrictive
The classic bedside trap is the wet, stiff patient: restrictive cardiomyopathy or constrictive pericarditis? Both equalise diastolic pressures and both raise the jugular venous pulse. Constriction, the commonest cause of which is tuberculosis in India, adds a pericardial knock, a Kussmaul sign, septal bounce on imaging and often visible pericardial calcification on the lateral chest film; brain natriuretic peptide tends to be lower than in myocardial disease. Amyloid restriction gives a thick, speckled, grainy ventricular wall on echocardiography and a telling mismatch between a small-voltage electrocardiogram and a thick wall on imaging. The distinction matters because constrictive pericarditis is cured by pericardiectomy, while restrictive cardiomyopathy is treated medically — operating on the wrong patient is catastrophic.
Frequently asked questions
Which genes are most often mutated in hypertrophic cardiomyopathy?
MYH7 (beta-myosin heavy chain) and MYBPC3 (myosin-binding protein C), inherited as autosomal dominant with variable penetrance.
Why is digoxin contraindicated in hypertrophic cardiomyopathy?
Increased contractility enlarges the dynamic left ventricular outflow gradient generated by systolic anterior motion of the mitral leaflet; vasodilators and dehydration act in the same wrong direction.
What is the histological hallmark of hypertrophic cardiomyopathy?
Myofibre disarray — obliquely cut, whorled, hypertrophied myocytes in disordered bundles — accompanied by interstitial fibrosis and thickened intramural arterioles.
Where is endomyocardial fibrosis endemic?
Kerala and tropical Africa; fibrous endocardial plaques obliterate the ventricular apex and inflow tract, producing a restrictive picture with atrioventricular regurgitation.
Which structural protein is most often mutated in familial dilated cardiomyopathy?
Titin (TTN), the giant sarcomeric scaffold protein; other causes include alcohol, viral myocarditis, doxorubicin and the peripartum period.