Cardiomyopathy

Echocardiographic Comparison

Classification by Functional Pattern

1. Dilated Cardiomyopathy (DCM)

Definition & Epidemiology

Pathogenesis

• Genetic (20–50% of cases): >50 genes implicated; autosomal dominant predominant. Key mutations:
  • Titin (TTN) truncation — up to 20% of cases; titin is critical for sarcomeric force generation
  • Cytoskeletal/sarcolemmal proteins: β-myosin heavy chain, α-myosin heavy chain, cardiac troponin T
  • LMNA (nuclear lamins A/C) — often with conduction disease
  • Dystrophin (X-linked DCM) — couples cytoskeleton to extracellular matrix
  • Desmin — principal intermediate filament protein in cardiac myocytes
• Viral myocarditis: Adenovirus, enterovirus, parvovirus B-19, human herpesvirus 6; coxsackievirus B can progress to chronic DCM
• Toxic: Alcohol and its metabolite acetaldehyde have direct myocardial toxicity; also doxorubicin (anthracycline), cobalt
• Peripartum cardiomyopathy: Occurs in last month of pregnancy or within 5 months postpartum
• Other: Hemochromatosis, sarcoidosis, chronic anemia, idiopathic

Gain-of-function mutations in some of the same sarcomere genes (e.g., MYH7) instead cause hypertrophic cardiomyopathy. — Robbins & Kumar Basic Pathology

Pathology

• Dilated, flabby heart (often >900 g); all four chambers affected
• Microscopy: myocyte hypertrophy, interstitial fibrosis, variable inflammatory infiltrates
• Mural thrombi common → risk of systemic and pulmonary embolism
• Tricuspid and mitral regurgitation due to annular dilation

Clinical Features

• Heart failure symptoms (dyspnea, orthopnea, edema, fatigue)
• Atrial and ventricular arrhythmias in up to 50% → significant SCD risk
• S3 gallop, displaced apical impulse, functional MR murmur

Diagnosis

• Echo/cardiac MRI: Confirms LV dilation and reduced EF
• Endomyocardial biopsy: Not routine; indicated when biopsy result would change management (e.g., new HF <2 weeks + hemodynamic compromise; new HF 2 weeks–3 months + high-grade AVB or ventricular arrhythmias failing usual therapy)

Treatment

• Pharmacologic (same as HFrEF): β-blockers, ARNI (sacubitril/valsartan) or ACEi/ARB, mineralocorticoid receptor antagonists (MRA), SGLT2 inhibitors
• Device therapy: ICD (if EF ≤35% despite optimal therapy), cardiac resynchronization therapy (CRT) for LBBB + reduced EF
• Cardiac transplantation for refractory disease
• Immunosuppression (prednisone, azathioprine) for proven myocarditis has not shown consistent benefit — exception: giant cell myocarditis

2. Hypertrophic Cardiomyopathy (HCM)

Definition & Epidemiology

Pathogenesis

• Autosomal dominant gain-of-function mutations in sarcomere proteins
• Most common mutations: MYBPC3 (myosin binding protein C) and MYH7 (myosin heavy chain 7) — together account for >50% of identified mutations
• Histology: hypertrophied myocytes in disorganized ("whorled") arrangement with interstitial fibrosis — the pathognomonic myocyte disarray
• Results in asymmetric septal hypertrophy (though any segment can be involved)

Pathophysiology

• Diastolic dysfunction: Delayed relaxation and reduced compliance → elevated filling pressures → pulmonary congestion
• LVOT obstruction (~70% at rest or with provocation): due to systolic anterior motion (SAM) of the mitral valve anterior leaflet → worsened by ↑ contractility (exercise), ↓ preload (Valsalva, dehydration), ↓ afterload (vasodilators)
• Myocardial ischemia: Supply-demand mismatch (hypertrophied myocardium + compressed intramural vessels)
• Mitral regurgitation from SAM

Clinical Features

• Exertional dyspnea, angina, syncope, palpitations
• SCD most common ages 10–35, often during or immediately after strenuous exertion
• Murmur: Coarse systolic murmur at left sternal border, louder with Valsalva/standing (↓ preload) and softer with squatting (↑ preload) — distinguishes HCM from aortic stenosis
• Bisferiens pulse (double-peak carotid pulse) in obstruction
• Double or triple apical impulse

Diagnosis

• Echo: LV wall thickness ≥15 mm not explained by loading conditions; SAM; LVOT gradient ≥30 mmHg at rest or with provocation
• ECG: ST-T changes, LVH; apical variant → giant negative T-waves across precordial leads (Yamaguchi pattern)
• Genetic testing recommended for patients and first-degree relatives

Treatment

• Asymptomatic: Activity restriction, avoid volume depletion; genetic counseling
• Symptomatic with obstruction:
  • β-blockers (first-line) — reduce HR, improve diastolic filling, reduce obstruction
  • Non-dihydropyridine CCBs (verapamil) — alternative to β-blockers
  • Mavacamten — novel cardiac myosin inhibitor (FDA approved 2022), reduces contractility and LVOT gradient
  • Disopyramide — negative inotrope, added to β-blocker for refractory obstruction
  • Avoid: Digoxin, dihydropyridine CCBs, nitrates, diuretics in obstructive HCM (worsen obstruction)
• Septal reduction therapy (surgical myectomy or alcohol septal ablation) for refractory LVOT obstruction
• ICD for SCD prevention in high-risk patients (prior cardiac arrest, sustained VT, family history of SCD, massive LVH ≥30 mm, unexplained syncope, LVEF <50%, abnormal BP response to exercise)

3. Restrictive Cardiomyopathy (RCM)

Definition

Causes

Pathophysiology

• Ventricular walls are rigid and noncompliant but systolic contraction relatively preserved
• Massive biatrial dilation from chronically elevated filling pressures (characteristic echo finding)
• Hemodynamics mimic constrictive pericarditis but cannot be relieved by pericardial surgery

Key Clinical Features

• Progressive exertional dyspnea, peripheral edema, ascites
• Elevated JVP with Kussmaul sign (paradoxical rise in JVP with inspiration)
• Distinguishing from constrictive pericarditis is clinically challenging (requires cardiac catheterization ± CMR)

Amyloid Cardiomyopathy (Special Emphasis)

• AL amyloidosis (plasma cell dyscrasia) and ATTR amyloidosis (transthyretin, wild-type or hereditary)
• Echo: "sparkling" myocardium, increased wall thickness, granular texture, small LV cavity, diastolic dysfunction
• CMR: global subendocardial late gadolinium enhancement
• Tafamidis (transthyretin stabilizer) is approved for wild-type and hereditary ATTR cardiomyopathy — reduces mortality and hospitalizations

4. Arrhythmogenic Cardiomyopathy (ACM / ARVC)

• Previously called arrhythmogenic right ventricular cardiomyopathy (ARVC); now recognized to affect both ventricles
• Genetic: Desmosomal protein mutations (PKP2, DSP, DSG2, DSC2, JUP) — autosomal dominant
• Fibro-fatty replacement of myocardium → ventricular arrhythmias, SCD, progressive heart failure
• ECG: epsilon waves, T-wave inversions in V1–V3
• Diagnosis: Task Force Criteria (major/minor from ECG, imaging, histology, genetics, family history)
• Treatment: ICD, antiarrhythmics, activity restriction, transplantation for end-stage disease

Myocarditis (Precursor to DCM)

• Viral (most common in US): Lymphocytic infiltrate; coxsackievirus B, parvovirus B-19, HHV-6
• Giant cell myocarditis: Multinucleate giant cells, widespread necrosis, poor prognosis — may respond to immunosuppression
• Hypersensitivity myocarditis: Eosinophil-rich infiltrate, drug reaction
• Chagas myocarditis (T. cruzi): Trypanosomes in myofibers; chronic phase → progressive CHF

Summary: Key Distinguishing Features