Arrhythmic burden and sudden cardiac death across cardiomyopathy phenotypes in the contemporary implantable cardioverter-defibrillator era

Background Inherited cardiomyopathies demonstrate heterogeneous arrhythmic burden. In the contemporary implantable cardioverter-defibrillator (ICD) era, both the overall burden of malignant ventricular arrhythmias (VA) and the proportion manifesting as sudden cardiac death (SCD) versus device-treated events remain incompletely characterised across cardiomyopathy subtypes. Purpose To describe patterns of major arrhythmic events (MAE), sudden cardiac death (SCD) and ICD utilisation across representative cardiomyopathy cohorts. Methods We conducted a quantitative synthesis of published data using aggregated cohort-level event counts and person-years (py) from representative studies of hypertrophic cardiomyopathy (HCM), dilated cardiomyopathy (DCM), and arrhythmogenic right ventricular cardiomyopathy (ARVC) in the contemporary ICD era. Data on MAE, aborted SCD, SCD, ICD implantation, and appropriate ICD therapies were extracted. MAE included sustained VA, appropriate ICD therapies, aborted SCD, or SCD according to study definitions. Appropriate ICD therapies included antitachycardia pacing and ICD shocks. Annualised incidence rates were calculated per 100 py. ICD use in cohorts where data was available was calculated as the total number of ICD implants divided by the total cohort size (ICD/n). The proportion of appropriate ICD therapies to implants was calculated among studies reporting both ICD implantation and therapy data. Results A total of 19 representative cohort studies were included. Marked phenotype-specific differences emerged in both arrhythmic incidence and fatal events as well as ICD utilisation (Figure 1). ARVC (n=1,199; 7066 py) demonstrated the highest arrhythmic incidence and the lowest relative proportion of fatal events among the three phenotypes (527 MAE and 19 SCD events; 7.46 MAE and 0.27 SCD per 100 py; SCD/MAE ratio 0.036), with an ICD implanted in 53% of the total population and appropriate therapies in 48% of ICD recipients. DCM (n=3,478; 8,231 py) showed an intermediate arrhythmic incidence (246 MAE and 28 SCD events; 2.99 and 0.34 per 100 py; SCD/MAE ratio 0.11), while an ICD was implanted in 32% of the patients, and 21% of ICD recipients experienced appropriate therapy. Notably, HCM (n= 21,747; 133,337 py) combined the lowest absolute arrhythmic incidence with the highest relative proportion of fatal events (1,152 MAE and 431 SCD events; 0.86 and 0.32 per 100 py; SCD/MAE ratio 0.37), while ICD use in HCM was substantially lower at 12% and appropriate therapy occurred in 20% of ICD recipients. Conclusions In the contemporary ICD era, cardiomyopathy subtypes demonstrate distinct patterns of arrhythmic burden, proportion of fatal events, and device utilisation. Our findings underscore significant differences in the management of arrhythmic risk across cardiomyopathies and highlight the need for continued refinement of phenotype-specific risk-stratification strategies to prevent SCD more effectively.