Background: In patients with Hypertrophic Cardiomyopathy (HCM) S-ICD is usually the preferred option as pacing is generally not indicated. However, limited data are available on its current practice adoption and long term follow-up. Purpose: The present study was designed to examine in a multicenter, open-label, long-term study, the patient’s selection process for S-ICD implantation, the short and long term complications, the appropriate shock (AS) rates, shock efficacy and outcome. Methods: Consecutive HCM patients with an S-ICD implanted between 2013 and 2021 in 3 international centers were enrolled in this prospective observational study. Baseline, procedural and follow-up data together with clinical evaluation, ECG, echocardiography, and telemetry checks of the S-ICD were regularly collected. Results: Seventy patients (64% males) were enrolled, implanted at 41±15 years, 62 (89%) in primary prevention with a mean ESC SCD risk score of 4,5±1.9%: 25 (40%) at low risk, 17 (27%) at intermediate and 20 (33%) at high risk. Patients were followed-up for 5.1±2.3 years (327 person-years). Notably, 25 (36%) were followed for more than 6 years up to 10 years. Two patients (3%) received an appropriate shock on ventricular fibrillation and 17 (24%) were diagnosed with a de-novo atrial fibrillation, sub-clinical in 6 (9%). One TIA and 2 strokes were reported. Inappropriate shocks occurred in 4 patients (6%), all before Smart-Pass algorithm implementation. Eight patients experienced device related adverse events (11%). Conclusions: S-ICDs in HCM patients followed for over 5 years showed to be effective in the conversion of VF in 2 ESC SCD high risk patients (3%) and useful in the detection of sub-clinical AF in 6 (9%). S-ICDs are implanted in patients with an overall low-intermediate ESC SCD risk, probably reflecting both the inclusion of additional risk markers (i.e extensive LGE, reduced EF and apical aneurism) and the physician perception of low device-related complications S-ICD is generally safe, but greater scrutiny may be required to avoid overtreatment in HCM patients with milder risk profiles.Real world use and candidacy of S-ICDAppropriate and inappropriate shocks

In hypertrophic cardiomyopathy (HCM), the presence of pathogenic/likely pathogenic (P/LP) disease-causing genetic variants may indicate a worse prognosis. Few data exist on the effects of these genetic variants on cardiopulmonary exercise test (CPET) performance in HCM patients. We analysed asymptomatic and slightly symptomatic HCM patients (NYHA I-II) whose genetic analysis and CPET were available; at baseline, left ventricular function was normal and severe left ventricular outflow trait obstruction was excluded. Out of 120 HCM patients, we excluded 13 carrying variants of uncertain significance; of the remaining 107 patients, 54 were genotype negative [gene (−)], and 53 had a P/LP variant in sarcomeric genes [gene (+)]. Patients in the two groups had similar NYHA class, cardiovascular risk factors and echocardiographic characteristics. Gene (+) patients showed a lower peak VO₂% and O₂ pulse % (p < 0.05). Moreover, among gene (+), patients with P/LP variants in the so called “thin-filament” genes (TNNT2, TPM1 and MYL3) had the poorest CPET results. In asymptomatic or slightly symptomatic HCM patients with similar echocardiographic characteristics, exercise tolerance is affected by the genetic background. Indeed, exercise capacity is poorer in gene (+) compared to gene (−) patients and those carrying P/LP variants in “thin-filament” genes show the worst performance.