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Multicenter Study
. 2022 Jun 1;5(6):e2217153.
doi: 10.1001/jamanetworkopen.2022.17153.

Sex Differences in the Risk of First and Recurrent Ventricular Tachyarrhythmias Among Patients Receiving an Implantable Cardioverter-Defibrillator for Primary Prevention

Shireen Saxena  1 , Ilan Goldenberg  1 , Scott McNitt  1 , Eileen Hsich  2 , Valentina Kutyifa  1 , Nicola Luigi Bragazzi  3 , Bronislava Polonsky  1 , Mehmet K Aktas  1 , David T Huang  1 , Spencer Rosero  1 , Helmut Klein  1 , Wojciech Zareba  1 , Arwa Younis  1   2
Affiliations
Multicenter Study

Sex Differences in the Risk of First and Recurrent Ventricular Tachyarrhythmias Among Patients Receiving an Implantable Cardioverter-Defibrillator for Primary Prevention

Shireen Saxena et al. JAMA Netw Open. .

Abstract

Importance: Current guidelines for primary implantable cardioverter-defibrillator (ICD) therapy do not account for sex differences in arrhythmic risk in ICD candidates.

Objective: To evaluate the association between sex and risk of ventricular tachyarrhythmia (VTA) and mortality.

Design, setting, and participants: This cohort study compared differences in the risk of VTA and mortality between 4506 men and women enrolled in the 4 Multicenter Automatic Defibrillator Implantation Trials (MADIT) between July 1, 1997, and December 31, 2011. Data from prospective randomized controlled multicenter studies were analyzed retrospectively. Men and women with an ICD or cardiac resynchronization therapy defibrillator who were enrolled in all MADIT studies were included. Data were analyzed between January 10 and June 10, 2021.

Exposures: ICD implant.

Main outcomes and measures: The primary end point was sustained VTA, defined as ICD-recorded, treated or monitored VTA at least 170/min or ventricular fibrillation. Secondary VTA end points included VTA at least 200/min, appropriate ICD shocks, and appropriate antitachycardia pacing. All end points were included in a first and recurrent event analysis.

Results: Of the 4506 study participants, 3431 were men (76%). Mean (SD) age of the cohort was 64 (12) years. For women vs men, the mean (SD) age (64 [12] years vs 64 [11] years) and left ventricular ejection fraction (24% vs 25%) were similar, but women exhibited a higher frequency of nonischemic cardiomyopathy (454 of 1075 women [42%] vs 2535 of 3431 men [74%]). Women had significantly lower 3-year cumulative probability of sustained VTA (16% vs 26%), fast VTA (9% vs 17%), and appropriate ICD shocks (7% vs 15%) compared with men (P < .001 for all). Multivariable analysis showed that female sex was independently associated with at least 40% lower risk of all first and recurrent VTA end points (P < .001 for all), including the primary end point (first event, HR = 60 [95% CI, 50-73], P < .001; recurrent event, HR = 49 [95% CI, 43-55], P < .001), after accounting for the competing risk of all-cause mortality and nonarrhythmic mortality. The lower VTA risk associated with female sex was consistent in risk subsets but was significantly more pronounced in patients with nonischemic cardiomyopathy (female vs male in the ischemic group: hazard ratio, 0.73 [95% CI, 0.56-0.95], P = .02; nonischemic group: hazard ratio, 0.50 [95% CI, 0.38-0.66], P < .001; P = .03 for interaction between female sex and cardiomyopathy).

Conclusions and relevance: Findings suggest that women display a significantly lower risk of first and recurrent life-threatening VTA events than men, and that it is more pronounced in patients with nonischemic cardiomyopathy, suggesting a need for sex-specific risk assessment for primary prevention ICD therapy.

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Conflict of interest statement

Conflict of Interest Disclosures: Ms Saxena reported receiving grants from the National Center for Advancing Translational Sciences of the National Institutes of Health (NIH) (University of Rochester CTSA award TL1 TR002000) during the conduct of the study. Dr Goldenberg reported receiving grants from Abbott, AstraZeneca, Boston Scientific, ZOLL, Medtronic, Biosense Webster, and Biotronik outside the submitted work. Dr Kutyifa reported receiving grants from Boston Scientific, Biotronik, NIH, ZOLL, and Spire; reported receiving personal fees from Medtronic and Abbott; and has consultant agreements with ZOLL and Biotronik outside the submitted work. Dr Aktas reported receiving grants from Boston Scientific and Medtronic. Dr Rosero reported receiving grants from Boston Scientific (unrestricted grant to the University of Rochester) during the conduct of the study. Dr Klein reported receiving grants from Boston Scientific and ZOLL and personal fees from ZOLL. Dr Zareba reported receiving research grants from Boston Scientific. No other disclosures were reported.

Figures

Figure 1.
Figure 1.. Association of Sex With Risk of Ventricular Tachyarrhythmia in Subgroups
Forest plot with multivariable Cox regression evaluating the association of female vs male sex with the development of sustained VTA, according to preselected subgroups. CRTD indicates cardiac resynchronization therapy defibrillator; EF, ejection fraction; HR, hazard ratio; ICD, implantable cardioverter-defibrillator; and VTA, ventricular tachyarrhythmia.
Figure 2.
Figure 2.. Cumulative Probability of Ventricular Arrhythmia by Sex and Cardiomyopathy
Three-year Kaplan-Meier cumulative probability by sex for sustained VTA and fast VTA at least 200/min in nonischemic patients (panels A and B, respectively) and ischemic patients (panels C and D, respectively). HR indicates heart rate; VTA, ventricular tachyarrhythmia.
Figure 3.
Figure 3.. Risk of Ventricular Tachyarrhythmic Burden by Sex and Cardiomyopathy
Mean cumulative rate for recurrent events per patient, stratified by sex for sustained ventricular tachyarrhythmia and fast ventricular tachyarrhythmia at least 200/min in nonischemic patients (panels A and B, respectively) and ischemic patients (panels C and D, respectively).
See this image and copyright information in PMC

Comment in

References

    1. Aimo A, Vergaro G, Barison A, et al. . Sex-related differences in chronic heart failure. Int J Cardiol. 2018;255:145-151. doi:10.1016/j.ijcard.2017.10.068 - DOI - PubMed
    1. Lam CSP, Arnott C, Beale AL, et al. . Sex differences in heart failure. Eur Heart J. 2019;40(47):3859-3868. doi:10.1093/eurheartj/ehz835 - DOI - PubMed
    1. Conen D, Arendacká B, Röver C, et al. . Gender differences in appropriate shocks and mortality among patients with primary prophylactic implantable cardioverter-defibrillators: systematic review and meta-analysis. PLoS One. 2016;11(9):e0162756. doi:10.1371/journal.pone.0162756 - DOI - PMC - PubMed
    1. MacFadden DR, Crystal E, Krahn AD, et al. . Sex differences in implantable cardioverter-defibrillator outcomes: findings from a prospective defibrillator database. Ann Intern Med. 2012;156(3):195-203. doi:10.7326/0003-4819-156-3-201202070-00007 - DOI - PubMed
    1. Zaman S, Deshmukh T, Aslam A, Martin C, Kovoor P. Sex differences in electrophysiology, ventricular tachyarrhythmia, cardiac arrest and sudden cardiac death following acute myocardial infarction. Heart Lung Circ. 2020;29(7):1025-1031. doi:10.1016/j.hlc.2019.07.017 - DOI - PubMed

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