Cardiomyopathies

Cardiomyopathies are heterogeneous diseases of the myocardium associated with mechanical and/or electrical dysfunction, in the absence of coronary artery disease, hypertension, valvular disease, or congenital defects sufficient to explain the abnormality. For NEET PG, the morphology (gross + microscopic) and the haemodynamic signature of each type carry the highest yield — especially the myofibre disarray of hypertrophic cardiomyopathy, a perennial image-based favourite.

Definition & classification

A cardiomyopathy is defined as primary myocardial dysfunction not attributable to ischaemic, hypertensive, valvular, or congenital heart disease. The traditional functional/pathological classification (WHO/Robbins) recognises three principal patterns, plus arrhythmogenic right ventricular cardiomyopathy (ARVC).

Feature	Dilated (DCM)	Hypertrophic (HCM)	Restrictive (RCM)
Frequency	~90% (commonest)	~10%	Least common
Primary defect	Systolic (pump/contractile) failure	Diastolic dysfunction ± LVOT obstruction	Diastolic (filling/compliance) failure
Ventricular cavity	Dilated (all 4 chambers)	Small/normal, thick walls	Normal or small
Wall thickness	Thinned/normal	Markedly increased (asymmetric septal)	Normal/mildly increased
Ejection fraction	Markedly reduced (<40%)	Preserved or increased (>60%)	Preserved (until late)
Heart weight	Increased (heavy, flabby)	Markedly increased	Normal/mildly increased
Typical genetics	Cytoskeletal proteins	Sarcomeric (β-myosin heavy chain)	Variable; often infiltrative

High-yield: Dilated cardiomyopathy = SYSTOLIC dysfunction (poor contraction, low EF). Hypertrophic and restrictive = DIASTOLIC dysfunction (impaired relaxation/filling with preserved EF). This single distinction answers a large fraction of questions.

The genetic basis maps neatly onto the cellular compartment affected: Cytoskeleton → DCM; Sarcomere → HCM; Interstitium/infiltration → RCM; Desmosome → ARVC.

Dilated cardiomyopathy (DCM)

Etiology

DCM is the final common pathway of diverse myocardial insults. Causes are remembered by the mnemonic "ABCCD":

• A — Alcohol (most common identifiable toxic cause), Adriamycin (doxorubicin), Amyloid (overlap)
• B — Beriberi (wet, thiamine deficiency), pregnancy (peri-partum, last trimester to 6 months postpartum)
• C — Coxsackie B virus / viral myocarditis (commonest infective trigger), Chagas disease (Trypanosoma cruzi) — leading infective cause worldwide
• C — Cocaine, Cobalt ("beer-drinker's cardiomyopathy")
• D — Doxorubicin/Daunorubicin (dose-dependent, free-radical mediated), genetic (Dystrophin mutations — Duchenne/Becker)

Up to 30–50% are familial, most often autosomal dominant; mutations affect cytoskeletal/sarcomeric proteins (titin — commonest gene, lamin A/C, dystrophin, desmin).

Pathophysiology

Myocyte injury → loss of contractile units → progressive eccentric hypertrophy with chamber dilatation (sarcomeres added in series). Reduced stroke volume triggers neurohormonal activation (RAAS, sympathetic), causing further remodelling, mitral/tricuspid regurgitation from annular stretch, and stasis predisposing to mural thrombi and embolism.

Morphology

• Gross: Heavy (up to 2–3× normal weight), flabby, dilated all four chambers; wall thickness may be normal, less than, or greater than normal despite enlargement. Mural thrombi common (especially LV apex). Functional (stretch-induced) AV valve regurgitation; coronaries typically clean.
• Micro: Non-specific — myocyte hypertrophy with enlarged hyperchromatic nuclei, attenuated/stretched myocytes, and interstitial + endocardial fibrosis.

Clinical features & management

Presents as congestive (biventricular) heart failure at 20–50 years: dyspnoea, fatigue, S3 gallop, displaced apex, functional MR. ECG shows LBBB, LVH, arrhythmias. Echo confirms a dilated, globally hypokinetic LV with low EF.

Management: Standard HFrEF therapy — ARNI/ACEi, β-blockers, MRA (spironolactone), SGLT2 inhibitors, diuretics for congestion; anticoagulation if thrombus/AF; ICD for EF ≤35%; CRT if wide QRS; transplant is definitive in end-stage disease. Abstinence reverses alcoholic DCM if early.

High-yield: Peripartum cardiomyopathy → last month of pregnancy up to 5–6 months postpartum; recurrence risk in subsequent pregnancies. Doxorubicin cardiotoxicity is dose-dependent and free-radical mediated — limit cumulative dose; dexrazoxane (iron chelator) is cardioprotective.

Hypertrophic cardiomyopathy (HCM)

The most heavily tested cardiomyopathy in image-based questions.

Genetics & pathophysiology

HCM is the commonest monogenic cardiac disorder — autosomal dominant, caused by mutations in sarcomeric proteins. The two commonest genes:

• β-myosin heavy chain (MYH7) — classically cited "commonest"
• Myosin-binding protein C (MYBPC3) — most frequent in many population series

The result is massive myocardial hypertrophy without dilatation, a stiff non-compliant ventricle with diastolic dysfunction, a small/obliterated cavity, and in ~25% a dynamic left ventricular outflow tract obstruction (LVOTO).

The LVOTO mechanism: hypertrophied asymmetric septum narrows the outflow tract → high-velocity jet drags the anterior mitral leaflet toward the septum in systole (SAM — Systolic Anterior Motion), worsening obstruction and causing MR.

Morphology — the exam centrepiece

• Gross: Asymmetric septal hypertrophy — interventricular septum disproportionately thicker than free wall (septum:free-wall ratio >1.3). Banana-shaped, slit-like LV cavity. A subaortic endocardial mural plaque (fibrous, from septal contact with mitral leaflet) and thickened anterior mitral leaflet are characteristic.
• Micro: Myofibre (myocyte) disarray — the hallmark. Haphazardly arranged, branching, hypertrophied myocytes oriented at oblique/perpendicular angles instead of parallel, with interstitial fibrosis and enlarged "boxcar" nuclei.

High-yield (image): A histology slide showing whorled, haphazard, disorganised hypertrophied myocytes with interstitial fibrosis = myofibre disarray of HCM. This is the single most repeated image MCQ for cardiomyopathy.

Clinical features & dynamic murmur

• Young athlete with exertional dyspnoea, angina, syncope; leading cause of sudden cardiac death in young athletes (often the first manifestation).
• Harsh crescendo-decrescendo systolic murmur at left sternal border, ± murmur of MR.

Dynamic auscultation is a classic question — the LVOTO murmur behaves opposite to most murmurs:

Manoeuvre	Effect on preload/afterload	LVOTO murmur
Standing / Valsalva (strain)	↓ venous return (↓ preload)	Louder
Squatting / leg raise / handgrip	↑ preload / ↑ afterload	Softer
Amyl nitrite	↓ afterload	Louder

High-yield: Anything that decreases LV volume (↓ preload or ↓ afterload) increases the HCM/LVOTO murmur (and SAM). This is the reverse of aortic stenosis (which softens with reduced preload).

Echo findings: asymmetric septal hypertrophy, SAM of anterior mitral leaflet, small LV cavity, preserved/hyperdynamic EF, dynamic LVOT gradient.

Management

• Avoid dehydration, vasodilators (nitrates, ACEi), and intense competitive sport.
• First line: β-blockers (or non-dihydropyridine CCB — verapamil) to ↓ heart rate, prolong diastolic filling, and reduce contractility/gradient.
• Disopyramide (negative inotrope) for refractory symptoms.
• Mavacamten (cardiac myosin inhibitor) — newer targeted therapy reducing the LVOT gradient.
• Surgical septal myectomy or alcohol septal ablation for refractory severe LVOTO.
• ICD for sudden-death prevention in high-risk patients (prior cardiac arrest, family history of SCD, massive LVH ≥30 mm, unexplained syncope, NSVT).

Restrictive cardiomyopathy (RCM)

Mechanism

The least common type. Primary abnormality is decreased ventricular compliance → impaired diastolic filling with normal-to-near-normal systolic function and chamber size. Ventricular walls are stiff; atria dilate markedly.

Causes

• Idiopathic (interstitial fibrosis)
• Infiltrative: Amyloidosis (commonest cause of RCM in adults), sarcoidosis, haemochromatosis (iron), glycogen storage, Gaucher
• Endomyocardial: Endomyocardial fibrosis (children/young adults, tropical/Africa), Löffler endocarditis (eosinophilic, with hypereosinophilia), endocardial fibroelastosis (infants)
• Storage/other: radiation fibrosis, metastatic tumour

Cardiac amyloidosis (most tested)

• Deposition of β-pleated sheet protein in the interstitium.
• AL (light chain) type — plasma cell dyscrasia; ATTR type — transthyretin (senile/wild-type or hereditary).
• Micro: amorphous pink (eosinophilic) interstitial deposits; Congo red stain shows apple-green birefringence under polarised light.
• ECG: low voltage complexes despite thick walls on echo — a classic discordance clue.
• Echo: thickened myocardium with a "granular sparkling/speckled" texture, biatrial enlargement, thickened valves and interatrial septum.

High-yield: RCM with low-voltage ECG + thick "sparkling" myocardium on echo + Congo red apple-green birefringence = cardiac amyloidosis. Avoid digoxin (amyloid binds it → toxicity).

RCM vs Constrictive pericarditis

A favourite differential, since both present with right heart failure and preserved EF:

Feature	Restrictive CM	Constrictive pericarditis
Pathology	Myocardial stiffness	Rigid/calcified pericardium
Pericardial calcification	Absent	Often present (X-ray/CT)
Septal "bounce"	Absent	Present
Ventricular interdependence	Absent	Present (discordant pressures)
BNP	Markedly elevated	Mildly elevated
Equal diastolic pressures	LVEDP often > RVEDP (>5 mmHg)	Equalisation of all chambers
Endomyocardial biopsy	Abnormal (infiltrate)	Normal myocardium
Treatment	Treat cause; transplant	Pericardiectomy (curative)

Arrhythmogenic RV cardiomyopathy (ARVC)

• Autosomal dominant, mutations in desmosomal proteins (plakoglobin, desmoplakin, plakophilin-2). Naxos disease = ARVC + palmoplantar keratoderma + woolly hair (autosomal recessive plakoglobin).
• Morphology: RV myocardium replaced by fibrofatty tissue → RV dilatation/thinning.
• Clinical: ventricular arrhythmias of LBBB morphology, syncope, sudden death in young people/athletes.
• ECG: epsilon wave (terminal notch in QRS in V1) — classic.

Diagnosis & investigation of choice

Stepwise approach: History/exam → ECG → Transthoracic ECHOCARDIOGRAPHY (investigation of choice) → Cardiac MRI (tissue characterisation/late gadolinium) → Endomyocardial biopsy (gold standard for infiltrative/specific diagnosis) → Genetic testing (familial)

• Echocardiography is the first-line, single best initial test — defines chamber size, wall thickness, EF, SAM, gradient.
• Cardiac MRI with late gadolinium enhancement characterises fibrosis/infiltration and is best for ARVC and amyloid patterns.
• Endomyocardial biopsy — definitive for amyloid, sarcoid, haemochromatosis, myocarditis.
• B-type natriuretic peptide elevated in all; markedly so in RCM.

Complications

• DCM: progressive CHF, mural thrombi → systemic/pulmonary emboli, arrhythmias, sudden death, functional MR.
• HCM: sudden cardiac death (ventricular arrhythmia — leading cause in young athletes), atrial fibrillation, infective endocarditis, progressive heart failure, stroke.
• RCM: refractory right heart failure, atrial fibrillation, conduction blocks (esp. amyloid/sarcoid), thromboembolism.

Key differentials

• HCM vs aortic stenosis vs hypertensive heart disease: HCM murmur increases with Valsalva; AS murmur decreases; AS has carotid radiation with parvus et tardus, HCM has brisk bifid pulse.
• Athlete's heart vs HCM: athlete's = symmetric mild LVH, large cavity, normal diastolic function, regresses with detraining; HCM = asymmetric, small cavity, diastolic dysfunction, family history.
• RCM vs constrictive pericarditis (table above).
• DCM vs ischaemic cardiomyopathy: the latter has obstructive CAD and regional wall-motion abnormalities.

Recently asked / exam angle

• Image of myofibre disarray → diagnosis is HCM (recurring NEET PG photomicrograph).
• Commonest cardiomyopathy? → Dilated.
• Cardiomyopathy with systolic dysfunction / low EF? → Dilated.
• Asymmetric septal hypertrophy + SAM + banana-shaped cavity? → HCM.
• Murmur that increases on standing/Valsalva? → HCM (LVOTO).
• Sudden death in a young athlete on the field? → HCM (commonest), ARVC.
• Congo red apple-green birefringence in myocardium + low-voltage ECG? → Cardiac amyloid (RCM).
• Epsilon wave + fibrofatty RV? → ARVC.
• Doxorubicin cardiotoxicity protective agent? → Dexrazoxane.
• Commonest gene in HCM? → β-myosin heavy chain (MYH7) / MYBPC3.
• Drug of choice for symptomatic HCM? → β-blocker (verapamil alternative); disopyramide / mavacamten for refractory.
• Curative treatment of constrictive pericarditis? → Pericardiectomy (distinguishing it from RCM).

Rapid revision

1. Dilated = systolic failure, low EF, four-chamber dilatation, heavy flabby heart, mural thrombi — commonest cardiomyopathy.
2. Commonest infective cause of DCM worldwide = Chagas disease; commonest toxic = alcohol; commonest viral = Coxsackie B.
3. Peripartum cardiomyopathy = last month of pregnancy to 5–6 months postpartum.
4. HCM = autosomal dominant, sarcomeric (β-MHC / MYBPC3), asymmetric septal hypertrophy, diastolic dysfunction, preserved/high EF.
5. Myofibre disarray = histologic hallmark of HCM (image MCQ).
6. SAM of the anterior mitral leaflet → dynamic LVOTO + MR; murmur louder with Valsalva/standing, softer with squatting/handgrip.
7. HCM is the commonest cause of sudden cardiac death in young athletes; β-blocker is drug of choice; avoid nitrates/diuretics/vasodilators.
8. Restrictive = diastolic failure, normal cavity, stiff walls, biatrial enlargement, preserved EF.
9. Amyloidosis = commonest RCM cause; low-voltage ECG, sparkling myocardium, Congo red apple-green birefringence; avoid digoxin.
10. RCM vs constrictive pericarditis: pericardial calcification, septal bounce, ventricular interdependence, and curative pericardiectomy favour constriction.
11. ARVC = desmosomal, fibrofatty RV, epsilon wave, LBBB-type VT; Naxos disease = ARVC + woolly hair + palmoplantar keratoderma.
12. Investigation of choice = echocardiography; gold standard for infiltration = endomyocardial biopsy; dexrazoxane protects against anthracycline cardiotoxicity.