Hypertrophic Cardiomyopathy

Hypertrophic cardiomyopathy (HCM) is unexplained left ventricular hypertrophy (wall thickness 15 mm or more, or 13 mm with family history) in the absence of loading conditions that explain it.

Prevalence about 1 in 500. Autosomal dominant sarcomere gene variants (MYH7, MYBPC3 most common) in 40 to 60%. Phenocopies: Fabry disease, amyloidosis, Danon disease, Noonan syndrome, Friedreich ataxia.

Pathophysiology: myocyte disarray, fibrosis, small vessel disease, diastolic dysfunction, dynamic left ventricular outflow tract obstruction (LVOTO) by systolic anterior motion of the mitral valve in about 70% (provocable).

It is the commonest cause of sudden cardiac death in athletes under 35 years.

Annual mortality about 1 to 2%.

• Often asymptomatic. Exertional dyspnoea, angina, presyncope, syncope, palpitations, fatigue.
• Harsh systolic ejection murmur at the left sternal border increased by Valsalva and standing, decreased by squatting; bisferiens carotid pulse; double apical impulse.
• Atrial fibrillation, ventricular arrhythmia, heart failure (end stage burnt out phase).

• ECG: left ventricular hypertrophy, deep T inversion, pathological Q waves.
• Echocardiography: asymmetric septal hypertrophy, LVOT gradient at rest and with Valsalva or exercise (obstruction is 30 mmHg or more, haemodynamically significant 50 mmHg or more), systolic anterior motion, diastolic function.
• Cardiac MRI: wall thickness, apical aneurysm, late gadolinium enhancement (over 15% of mass increases risk).
• Holter monitoring for non sustained ventricular tachycardia and atrial fibrillation.
• Genetic testing and cascade screening of relatives.
• Sudden death risk calculators (HCM Risk SCD). Major risk factors: family history of sudden death, unexplained syncope, massive hypertrophy (30 mm or more), non sustained VT, apical aneurysm, left ventricular systolic dysfunction.

Symptomatic obstructive HCM

• Beta blocker (metoprolol 50 to 200 mg daily, bisoprolol 5 to 10 mg) first line, or verapamil 120 to 480 mg daily.
• Disopyramide 250 to 500 mg twice daily added (monitor QT, anticholinergic effects).
• Cardiac myosin inhibitor mavacamten 2.5 mg daily titrated to 5, 10, 15 mg based on echo gradients and ejection fraction (monitor ejection fraction every 4 to 12 weeks; stop if below 50%; avoid strong CYP2C19 inhibitors). Aficamten is an alternative.
• Avoid vasodilators, high dose diuretics, digoxin and dehydration.
• Septal reduction for gradient 50 mmHg or more with refractory symptoms: surgical septal myectomy (preferred, mortality under 1% in experienced centres) or alcohol septal ablation.

Sudden death prevention

ICD for secondary prevention or for primary prevention based on risk score (5 year risk 6% or more).

Other

• Atrial fibrillation: anticoagulation regardless of CHA2DS2 VASc (apixaban 5 mg twice daily), rhythm control.
• Heart failure with preserved or reduced ejection fraction: standard therapy; transplantation for end stage.
• Avoid intense competitive sport after individual assessment, although moderate exercise is encouraged.
• Family screening every 1 to 2 years in children and young adults.