Key Facts

Hypertrophic cardiomyopathy (HCM) is characterised by unexplained left ventricular hypertrophy (wall thickness ≥15 mm, or ≥13 mm with family history/positive genotype) not explained by abnormal loading conditions. It is the most common inherited cardiac disease.

Epidemiology

• Prevalence: ~1 in 500 (0.2%); one of the most common inherited heart conditions
• Equal sex distribution genotypically, but male predominance in clinical phenotype
• Most commonly diagnosed in adolescence/young adulthood
• Leading cause of SCD in young athletes (<35 years)

Aetiology

• Autosomal dominant with variable penetrance and expressivity
• Sarcomeric gene mutations (~60% of cases): MYH7, MYBPC3, TNNT2, TNNI3, TPM1, ACTC1, MYL2, MYL3
• ~40% are genotype-negative (may be polygenic or undiscovered genes)
• Phenocopies: Fabry disease, Danon disease, PRKAG2, Noonan syndrome, amyloidosis

Pathophysiology

• Sarcomeric mutations → myocyte disarray, fibrosis, small vessel disease
• Asymmetric septal hypertrophy (most common pattern): predominantly involves interventricular septum
• LVOTO (~70%): systolic anterior motion (SAM) of the mitral valve → septal contact → dynamic obstruction
  • Gradient increases with reduced preload (Valsalva, standing, dehydration) and increased contractility (exercise)
  • SAM also causes mitral regurgitation
• Diastolic dysfunction: stiff, non-compliant LV → elevated filling pressures
• Myocardial ischaemia: small vessel disease, supply-demand mismatch from hypertrophy
• Arrhythmias: from myocyte disarray and fibrosis → VT/VF → sudden death; AF common

Typical Presentation

• Many patients are asymptomatic (diagnosed on screening)
• Exertional dyspnoea (most common symptom)
• Exertional chest pain (myocardial ischaemia from supply-demand mismatch)
• Syncope/presyncope (LVOTO, arrhythmias)
• Palpitations (AF, VT)
• Sudden cardiac death (may be first manifestation, especially in young athletes)

Examination Findings

• Ejection systolic murmur at left lower sternal edge (LVOTO)
  • Increases with Valsalva and standing (reduced preload worsens obstruction)
  • Decreases with squatting and leg elevation (increased preload reduces obstruction)
• Jerky pulse (bifid — rapid upstroke then obstruction)
• Double apex beat (palpable a wave + systolic impulse)
• S4 (atrial contraction against stiff ventricle)
• Systolic murmur of mitral regurgitation (from SAM)

Red Flags

• Syncope during exercise
• Family history of sudden cardiac death
• NSVT on Holter monitoring
• Massive LVH (≥30 mm)
• Abnormal exercise BP response (failure to rise >20 mmHg)
• Late gadolinium enhancement on MRI (fibrosis)

Bedside

• ECG: LVH (Sokolow-Lyon criteria), deep T-wave inversions (lateral/inferior), pathological Q waves (septal), AF, pre-excitation (consider PRKAG2)
• CXR: normal cardiac silhouette (concentric hypertrophy) or mildly enlarged

Bloods

• BNP/NT-proBNP: may be elevated; useful for monitoring
• Genetic testing: first-line for sarcomeric mutations (MYH7, MYBPC3 etc.)
• Alpha-galactosidase A: if Fabry disease suspected (males)
• Troponin: if chest pain or acute presentation

Imaging

• Echocardiography: wall thickness measurement (≥15 mm), SAM of mitral valve, LVOT gradient (resting and provoked with Valsalva), diastolic function, MR severity
• Cardiac MRI: gold standard for wall thickness, fibrosis (LGE — extent correlates with SCD risk), apical HCM (may be missed on echo)
• Coronary angiography: if angina symptoms to exclude concomitant CAD

Special Tests

• Holter monitor (48 hours): detect NSVT (SCD risk factor)
• Exercise testing: assess symptoms, BP response (failure to rise is SCD risk factor), exercise-induced LVOT gradient
• HCM Risk-SCD calculator (ESC): estimates 5-year SCD risk based on age, LV wall thickness, LA size, LVOT gradient, FH of SCD, NSVT, unexplained syncope
  • ≥6%: ICD recommended
  • 4-<6%: ICD should be considered
  • <4%: ICD generally not indicated
• Family screening: ECG + echo for all first-degree relatives; repeat periodically (adolescence through adulthood)
• Genetic cascade testing: if proband has identified mutation

Non-pharmacological

• Avoid competitive/strenuous exercise: ESC recommends against high-intensity competitive sports
• Adequate hydration: avoid dehydration (worsens LVOTO)
• Avoid vasodilators, excessive diuretics, digoxin (worsen obstruction)
• Family screening and genetic counselling

Pharmacological

Symptomatic obstructive HCM:

• Beta-blockers (first-line): bisoprolol 2.5-10mg OD or propranolol 80-320mg/day (non-selective may be more effective)
• Verapamil 120-480mg/day: if beta-blocker intolerant or ineffective (caution: avoid with severe obstruction or HF)
• Disopyramide 300-600mg/day: negative inotrope; reduces LVOT gradient (add to beta-blocker)
• Mavacamten (cardiac myosin inhibitor): novel therapy; reduces LVOT gradient; NICE approved for symptomatic obstructive HCM (EXPLORER-HCM trial)
  • 15mg OD starting dose; monitor LVEF closely (risk of excessive reduction)

Non-obstructive HCM:

• Beta-blockers or verapamil for symptomatic relief
• Standard HF therapy if systolic dysfunction develops (burned-out phase)

AF management:

• Anticoagulation for ALL HCM patients with AF (high stroke risk regardless of CHA₂DS₂-VASc)
• Amiodarone or dronedarone for rhythm control (avoid flecainide)

Surgical/Interventional

• Septal myectomy (Morrow procedure): gold standard surgical treatment for refractory obstructive HCM
  • Resection of hypertrophied septum; reduces LVOTO by >90%
  • Operative mortality ~1-2% in experienced centres
• Alcohol septal ablation: percutaneous alternative; injection of alcohol into septal perforator artery
  • Creates controlled septal infarction; reduces LVOTO
  • Higher rate of AV block requiring pacemaker (~10-20%)
• ICD: for sudden death prevention based on HCM Risk-SCD calculator (≥6% 5-year risk)
• Heart transplantation: for end-stage (burned-out) HCM with systolic failure

Referral Criteria

• All suspected HCM: specialist HCM centre referral
• SCD risk stratification: electrophysiology/inherited cardiac conditions clinic
• Family screening: genetics clinic
• Refractory symptoms: surgical assessment (myectomy/ablation)

• Annual mortality: ~1% with modern management (previously quoted as 3-5%)
• Most patients have a normal or near-normal life expectancy
• SCD risk highest in adolescence/young adulthood; decreases with age
• ICD effectively prevents SCD; appropriate shock rate ~5% per year in high-risk patients
• ~5% develop end-stage (burned-out) phase with systolic dysfunction and DCM phenotype
• AF occurs in ~25% of HCM patients; increases stroke and HF risk
• Septal myectomy: excellent long-term outcomes; 10-year survival >90% in experienced centres

HCM Risk-SCD Calculator Variables

Dynamic Auscultation in HCM