Sex-specific differences in risk stratification of ventricular arrhythmias among implantable cardioverter defibrillator patients: do women differ from men?

Abstract

Abstract Background Implantable cardioverter defibrillator (ICD) guidelines and risk stratification models of sudden cardiac death (SCD) are applied without differentiation between men and women, based on the assumption that the incidence of ventricular arrhythmias and risk factors of SCD are similar in both sexes. Sex-specific risk factors of SCD may influence studies evaluating the benefit of ICD therapy, for both men and women. Purpose Aim of the study is to assess sex-specific differences in occurrence and predictors of appropriate device therapy (ADT) for ventricular arrhythmias. Methods A multicenter retrospective cohort of 2300 consecutive patients was evaluated, including patients referred for ICD implantation between the years 2009–2018 (age 62±13 years, LVEF 32±12%, 53% ischemic cardiomyopathy [CMP], 28% resynchronization therapy, 65% primary prevention). Exclusion criteria were: (1) patients with hypertrophic CMP, arrhythmogenic right ventricular CMP, systemic infiltrative cardiac disease or channelopathy; (2) lost to follow-up immediately after ICD implantation. Primary endpoint was ADT, defined as anti-tachycardia pacing or shock for ventricular tachyarrhythmia. Secondary endpoints were mortality and inappropriate ICD therapy. Univariable and multivariable Cox regression analyses, stratified by sex, were performed to assess predictors of ADT. Results The cohort primarily consisted of men (75%). After a mean follow-up of 4.8±3.0 years, men experienced more ADT compared to women (25% versus 16%, HR 1.71, p<0.001) and men displayed a higher mortality compared to women (25% versus 19%, HR 1.37, p<0.01). No difference in inappropriate ICD therapy was observed (9% versus 10%, HR 1.01, p=0.94). In the total study cohort, male sex (HR 1.55, p<0.001), higher age (HR 1.15 per 10 years, p<0.0019), left bundle branch block (LBBB, HR 0.74, p=0.01) and secondary prevention indication (HR 1.89, p<0.001) were independently associated with ADT. In male patients, independent predictors of ADT were comparable with the total study cohort: higher age (HR 1.20 per 10 years, p<0.001), LBBB (HR 0.72, p=0.01) and secondary prevention therapy (HR 1.80, p<0.001). In contrast, age (p=0.54) or LBBB (p=0.29) were not associated with ADT in women. In women, only paroxysmal atrial fibrillation (HR 1.76, p=0.03) and secondary prevention therapy (HR 1.78, p<0.01) were independently associated with ADT. Conclusion This study showed that men were at higher risk of ADT compared to women and that risk factors associated with SCD differ between both sexes. The results strongly suggests that SCD risk stratification models are primarily driven by male patients and sex-specific risk models of SCD are needed to identify those women at high risk of SCD. Figure 1 Funding Acknowledgement Type of funding source: None