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Domain

Cardiomyopathies

Modules

Hypertrophic Cardiomyopathy

Genetic sarcomere disease. SCD risk stratification and obstruction management.

Sarcomere Mutations and Hypercontractility

LVOT gradientThresholdMechanismAt rest≥30 mmHgSystolic anterior motion (SAM)With provocation≥50 mmHgof the mitral valve — Venturi effectBeta-blockers first-line; verapamil/disopyramide second-line; myosin inhibitor or SRT for refractory symptoms

Most HCM is caused by autosomal dominant mutations in sarcomeric protein genes (most commonly MYH7 and MYBPC3), which produce myocyte hypertrophy, disarray, and interstitial fibrosis. These mutations increase the number of actin-myosin cross-bridges available for force generation, producing a hypercontractile, hyperdynamic ventricle even before hypertrophy is apparent. In obstructive HCM, septal hypertrophy narrows the LVOT and generates a Venturi effect that pulls the mitral valve anteriorly (systolic anterior motion), further worsening obstruction and causing mitral regurgitation. Myocardial disarray and fibrosis also create the arrhythmogenic substrate underlying sudden cardiac death risk.

Diagnosis

Illustration of hypertrophic cardiomyopathy (Blausen Medical, Wikimedia Commons, CC BY 3.0)Unexplained LV wall thickness ≥15 mm (≥13 mm with family history or genetic mutation). Asymmetric septal hypertrophy is classic but variants exist (apical/Yamaguchi, mid-cavity, biventricular).

Obstruction

LVOT gradient ≥30 mmHg at rest or ≥50 mmHg with provocation. SAM of the mitral valve is the mechanism. Beta-blockers first-line; verapamil/disopyramide second-line.

Mavacamten

Cardiac myosin inhibitor. EXPLORER-HCM: improved exercise capacity and functional class. VALOR-HCM: reduced need for septal reduction. Requires echo monitoring for LVEF drop.

Septal Reduction Therapy

Surgical myectomy (procedure of choice at experienced centers, mortality <1%). Alcohol septal ablation for high-risk patients.

SCD Risk & ICD

HCM Risk-SCD inputsFamily history of sudden cardiac deathUnexplained syncopeMaximal LV wall thicknessLeft atrial sizeLVOT gradient at restNonsustained VT on HolterAHA/ACC adds: extensive LGE on CMR (>15% of LV mass), apical aneurysm, LVEF <50%HCM Risk-SCD calculator (ESC) integrates age, family history of SCD, unexplained syncope, LV thickness, LA size, LVOT gradient, NSVT. AHA/ACC uses risk factors + optional CMR (LGE >15% adds risk).

Septal Reduction Therapy and Sudden Death Risk

Septal myectomy or alcohol septal ablation is reserved for patients with severe outflow obstruction and symptoms refractory to negative inotropes; the HCM risk-SCD calculator, family history of sudden death, extreme LV hypertrophy, and unexplained syncope all factor into the ICD decision. Competitive high-intensity athletics are generally discouraged regardless of symptom status.
Clinical pearls
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Screen first-degree relatives with ECG + echo starting in childhood or at diagnosis. Genetic testing helps identify at-risk relatives.
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Athletic training can cause "athlete's heart" (LV wall thickness up to 13 mm) — differentiate from HCM by cavity size, diastolic function, and detraining response.
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Cardiac myosin inhibitors (e.g., mavacamten) reduce actin-myosin cross-bridge formation and are Class I add-on therapy for persistent symptoms despite beta-blocker or CCB.
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Genetic testing is Class I recommended in HCM to identify at-risk family members for cascade screening.
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Mavacamten is contraindicated in pregnancy (Class III) given teratogenic potential.
Related guidelines
TropOnTop — Cardiology Study Platform