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Hypertrophic cardiomyopathy (HCM) is a genetic disorder of cardiac muscle with a prevalence of 1 in 500 of the general population.w1 In most adults, HCM is inherited as an autosomal dominant trait caused by mutations in genes encoding cardiac sarcomere proteins.1 The disease is clinically defined by left ventricular hypertrophy (LVH) unexplained by abnormal loading conditions,2 and is often associated with left ventricular outflow tract obstruction (LVOTO) caused by the systolic anterior movement of the mitral valve.w2 Histologically, HCM is characterised by cardiomyocyte hypertrophy and disarray, myocardial fibrosis, and small vessel disease.1 w3
Sudden cardiac death (SCD), heart failure, and thromboembolism are the main causes of death.3 Early studies of small HCM cohorts from tertiary referral centres reported cardiovascular mortality rates of ∼6%/year, but later less selected studies demonstrated a more favourable clinical course with an overall cardiovascular mortality of ∼2%/year.3 Nevertheless, SCD still occurs with an incidence of ∼0.8%/year, peaking in early adulthood.4 ,5 As observational data suggest that implantable cardioverter defibrillators (ICDs) can prevent SCD, there is a clinical need to identify accurately individual patients at high risk.
Causes of SCD
Numerous cardiac arrhythmias have been reported in association with SCD in HCM, including asystole,w4 atrioventricular block,w5 pulseless electrical activity,w6 w7 and supraventricular arrhythmias.w8 Data from chance electrocardiographic recordings and stored intracardiac electrograms from ICDs suggest that SCD in HCM is most commonly caused by ventricular fibrillation (VF).w9 w10 The characteristic cellular disarray and cardiac hypertrophy facilitate the development of re-entry arrhythmias,w11 and delayed after depolarisations caused by calcium (Ca2+) leak from the sarcoplasmic reticulum render the myocardium vulnerable to triggered activity.w12 Increased myofilament Ca2+ sensitivity also causes shorter effective refractory periods and increased dispersion of repolarisation, predisposing to functional re-entry.w13