Sex differences among S-ICD recipients: a propensity-matched, multicenter, international analysis from the i-SUSI project

Abstract

Abstract Background Women have been historically underrepresented in implantable cardioverter defibrillator (ICD) trials, despite sex differences in the epidemiology and clinical presentation of ventricular arrhythmias (VAs). So far, no data on sex differences among subcutaneous-ICD (S-ICD) recipients have ever been described. Purpose To investigate sex-related differences in patients undergoing S-ICD implantation. Methods Consecutive patients enrolled in the multicenter i-SUSI project were analyzed. The iSUSI (International SUbcutaneouS Implantable cardioverter defibrillator) is a multi-center, open-label, independent, and physician-initiated observational project, involving 22 Public and Private Healthcare Institutions from 5 different countries in Europe and in the US. Comparisons between sexes were performed using an adjusted analysis with 1:1 propensity matching for age, body mass index (BMI), left ventricular function (LVEF) and underlying myocardial substrate (ischemic vs non-ischemic cardiomyopathy). The primary outcome was the rate of appropriate shocks during follow-up. Inappropriate shocks and other device-related complications were deemed secondary outcomes. Results A total of 1698 patients were enrolled in the current project. Females represented the 23.5% (n=399) of the study cohort. After propensity matching, two cohorts of 374 matched patients with similar baseline characteristics served as the study cohort for this analysis (Figure 1, panel A). Despite similar procedural characteristics and a matched BMI, female S-ICD recipients had a lower calculated risk of ventricular arrhythmias conversion failure as per PRAETORIAN score (females at low-risk 73.4% vs males 81.3%, p=0.049). Over a median follow-up time of 26.5 [12.7–42.5] months (without differences between the two cohorts), n=68 (9.1%) patients experienced appropriate shocks and n=105 (14.0%) patients suffered from a device-related complication, including 75 (10.3%) cases of inappropriate shock therapy (Figure 1). Appropriate shocks were more common in the male cohort (rate/y 3.4% vs 1.7%; log-rank p=0.049), while no significant differences in device-related complications (rate/y: 6.3% vs 5.8%; log-rank p=0.595) and inappropriate shocks (rate/y: 4.3% vs 3.1% log-rank p=0.375) were observed among groups. Survival analysis for primary and secondary outcomes has been reported in Figure 1, panel B-C-D. At multivariate analysis, male sex remained significantly associated with the primary outcome of interest (aHR 1.591 CI 0.975–2.595, p=0.063). Conclusion In a large S-ICD registry, females were overall underrepresented. In a propensity-matched cohort of S-ICD recipients, women were less likely to experience appropriate ICD therapy, while not showing higher risk of device related-complications and inappropriate shocks. Despite similar BMI and peri-procedural characteristics, women showed a lower risk of conversion failure according to PRAETORIAN score.Figure 1