Clinical profile of patients with hypertrophic cardiomyopathy and recurrent ventricular arrhythmias

Background Hypertrophic cardiomyopathy (HCM) is a common inherited cardiac disorder. While most patients remain free of ventricular arrhythmia events (VAEs), a small subset experiences recurrent episodes. The clinical profile of these patients remains poorly characterized. Objective This longitudinal, long-term follow-up study aimed to describe clinical characteristics of HCM patients with recurrent VAEs. Methods We conducted a retrospective review of a large HCM cohort evaluated at a single tertiary centre between July 2003 and December 2018. Deaths at follow-up were obtained by review of medical records and information from National Death Index. VAEs were defined as ventricular tachycardia, ventricular fibrillation, cardiac arrest, appropriate anti-tachycardia pacing or ICD shock, and sudden cardiac death. Results Among 5,234 patients with HCM, 246 experienced at least 1 VAE. 42 patients had recurrent VAEs; 36 male (86%), with mean age at diagnosis 48.5 ± 12 years. Mean follow-up of patients with recurrent VAEs was 9.8 ± 6 years; with time to first VAE 3.8 ± 4 years, and time to subsequent events 1.7 ± 3 years. 23/42 patients were genotyped, with 65% positive for HCM pathogenic variants, most commonly MYBPC3 (60%) and MYH7 (27%). Twelve patients (29%) had two events, 12 (29%) had 3 to 5, and 18 (42.9%) had more than 5, totalling 365 recurrent events: 82% VT, 17% VF, and 1% cardiac arrest. A positive family history of HCM was present in 48%, with atrial fibrillation (29%) and hypertension (21%) as most common comorbidities. Baseline median LVEF was 68% with LV outflow obstruction (at rest or with provocation) present in 40%. Median maximum LV wall thickness was 20 ± 6 mm with LV mass of 363g (SD 125) and LA volume index of 53.9 mL/m² (SD 24). Septal myectomy was performed in 43%. At first VAE, 76% were on beta-blockers and 88% had an ICD. Post-event interventions included medication adjustment (37%), ICD implantation (12%), and VT ablation (10%). Five patients (11.9%) underwent heart transplantation and 2 (4.8%) had cardiac sympathetic denervation. There were 7 deaths (16.7%), 4 of which were cardiac (2 VAE-related, 1 heart failure, 1 unspecified). Conclusions Recurrent VAEs are uncommon in HCM. Patients with multiple VAEs were predominantly male, had minimal comorbidities, commonly had a family history of HCM, and had low rates of LV outflow tract obstruction. These findings help define the phenotype of HCM patients at highest risk and provide insights for targeted management strategies.