Cardiomyopathy - 10 Mark Notes

1. Definition

• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 515

2. Classification (3 Major Types)

• Dilated Cardiomyopathy (DCM) - most common (90% of cases) - systolic dysfunction
• Hypertrophic Cardiomyopathy (HCM) - diastolic dysfunction
• Restrictive Cardiomyopathy - least common - diastolic dysfunction
• Robbins & Kumar Basic Pathology, p. 334

3. Dilated Cardiomyopathy (DCM) - Pathogenesis

• Genetic: 20-50% of cases; autosomal dominant loss-of-function mutations in cytoskeletal/sarcomeric proteins. Titin (TTN) truncating mutations account for ~20-25% of familial cases. X-linked forms involve dystrophin (Duchenne/Becker muscular dystrophy).
• Viral myocarditis: Coxsackievirus B, parvovirus B19, HHV-6; viral injury can progress to end-stage DCM.
• Toxic: Alcohol and acetaldehyde have direct myocardial toxicity.
• Pregnancy: Peripartum cardiomyopathy.
• Robbins & Kumar Basic Pathology, p. 334

4. DCM - Morphology

• Heart is enlarged and heavy; all four chambers dilated
• Ventricular wall may be normal, thickened, or thinned
• Mural thrombi may form in dilated chambers (risk of embolism)
• Microscopically: myocyte hypertrophy, interstitial fibrosis, occasional myocyte dropout - but these are non-specific end-stage changes
• Robbins & Kumar Basic Pathology, p. 334

5. Hypertrophic Cardiomyopathy (HCM) - Pathogenesis

• Virtually ALL cases are autosomal dominant gain-of-function mutations in sarcomere proteins (contractile apparatus)
• Most common mutations: beta-myosin heavy chain and myosin-binding protein C
• Results in diastolic dysfunction (impaired relaxation/filling), NOT systolic dysfunction
• ~60-70% have asymmetric septal hypertrophy causing left ventricular outflow tract (LVOT) obstruction
• Goldman-Cecil Medicine, block 6

6. HCM - Morphology & Histology

• Massive ventricular hypertrophy, especially the interventricular septum (asymmetric)
• Small ventricular cavity
• Histological hallmark: myocyte disarray (haphazard arrangement of myocytes), interstitial fibrosis, and thickened small intramural coronary arteries
• LVOT obstruction leads to systolic anterior motion (SAM) of the mitral valve
• Robbins & Kumar Basic Pathology, p. 336

7. HCM - Clinical Features & Complications

• Often asymptomatic; may present with exertional dyspnea, angina, syncope
• Most common cause of sudden cardiac death (SCD) in young athletes
• Atrial fibrillation with risk of systemic thromboembolism
• Risk stratification for ICD implantation is key in management
• Goldman-Cecil Medicine

8. Restrictive Cardiomyopathy

• Least common type; characterized by a stiff, non-compliant myocardium that restricts ventricular filling (diastolic dysfunction)
• Ventricular systolic function is preserved early
• Causes:
  • Amyloidosis (most common in developed countries)
  • Sarcoidosis
  • Radiation-induced interstitial fibrosis
  • Endomyocardial fibrosis (eosinophilia-associated)
  • Loeffler endocarditis
• Clinically mimics constrictive pericarditis
• Robbins, Cotran & Kumar Pathologic Basis of Disease, p. 521

9. Arrhythmogenic Right Ventricular Cardiomyopathy (ARVC)

• Progressive replacement of RV myocardium with fibrofatty tissue
• Caused by mutations in desmosomal proteins (e.g., plakophilin-2, desmoplakin)
• Autosomal dominant with variable penetrance
• Clinical features: RV dysfunction, ventricular arrhythmias, sudden death in young adults/athletes
• ECG may show epsilon waves; MRI demonstrates fibrofatty replacement
• Robbins & Kumar Basic Pathology, p. 336

10. Myocarditis (Inflammatory Cardiomyopathy)

• Myocardial damage due to inflammatory infiltrates secondary to infection or immune reactions
• Most common cause in the US: viral infections (Coxsackievirus B, parvovirus B19)
• Clinically: can be asymptomatic, cause acute heart failure, or evolve into DCM
• Biopsy (Dallas Criteria): lymphocytic infiltrate with adjacent myocyte necrosis
• Special form: Giant cell myocarditis - rare, rapidly fatal without transplantation; can be stabilized with early immunosuppression
• Long-term mortality of biopsy-proven viral myocarditis: ~20% at 4.7 years
• Robbins, Cotran & Kumar, p. 523; Goldman-Cecil Medicine