hypertrophic cardiomyopathy

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pathophysiology

• genetic: autosomal dominant, sarcomere protein variants (MYH7, MYBPC3 most common)
• asymmetric septal hypertrophy → dynamic LVOT obstruction (LVOTO) in ~70%
• systolic anterior motion (SAM) of the mitral valve → LVOTO + mitral regurgitation
• diastolic dysfunction → elevated filling pressures → exertional dyspnoea
• myocardial fibrosis → arrhythmia substrate → VT/VF risk

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diagnosis

• echo: wall thickness ≥15 mm (or ≥13 mm with family history or positive genotype) not explained by loading conditions
• cardiac MRI: characterise hypertrophy pattern, detect apical variants (missed on echo), quantify LGE (fibrosis = arrhythmia risk)
• genetic testing: offered to all patients; guides family screening
• provocative testing: Valsalva, standing, exercise echo — unmask latent LVOTO (resting gradient may be <30 mmHg)

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screening first-degree relatives

• clinical screening (echo + ECG) every 1–2 years from age 12 (or earlier if competitive athlete or family history of early SCD)
• if gene-positive / phenotype-negative: annual echo + ECG
• genetic cascade screening if pathogenic variant identified in proband

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LVOT obstruction management

provocation and avoidance

LVOTO worsens with anything that reduces preload, reduces afterload, or increases contractility:

Worsen obstruction	Improve obstruction
dehydration, Valsalva, standing	volume loading, squatting, leg elevation
vasodilators (nitrates, dihydropyridines)	phenylephrine (acute)
exercise, post-prandial	—
positive inotropes (digoxin, dobutamine)	negative inotropes (BB, non-DHP CCB)

pharmacotherapy

Line	Agent	Notes
1st	beta-blocker (non-vasodilating)	reduce HR, contractility, and gradient; titrate to effect
1st	non-DHP CCB (verapamil)	alternative or add-on to BB; avoid if resting gradient >100 mmHg or severe HF
2nd	disopyramide	potent negative inotrope; must combine with BB or CCB (disopyramide has vagolytic effect → may increase AV conduction)
2nd	mavacamten	cardiac myosin inhibitor — EXPLORER-HCM (2020); reduces gradient, improves symptoms; monitor LVEF (hold if <50%); alternative to septal reduction

septal reduction therapy

• if refractory symptoms despite maximal medical therapy + resting or provoked gradient ≥50 mmHg
• surgical myectomy (gold standard) or alcohol septal ablation (if not surgical candidate)
• mavacamten may defer or avoid septal reduction — VALOR-HCM (2023)

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atrial fibrillation

• DOACs preferred over warfarin
• rhythm control often pursued (AF poorly tolerated due to loss of atrial kick in stiff ventricle)

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sudden cardiac death risk stratification

class I indication for ICD

• prior cardiac arrest or sustained ventricular tachycardia

class IIa — consider ICD (≥1 major risk factor)

Risk factor
maximal wall thickness ≥30 mm
family history of SCD from HCM
unexplained syncope
apical aneurysm
LVEF <50% (end-stage / burnt-out HCM)

• use the HCM Risk-SCD calculator (ESC) to guide 5-year SCD risk estimation
• exercise stress testing can unmask arrhythmias (NSVT on Holter is an additional risk factor)