Ventricular Tachyarrhythmia Risk Differs Between Men, Women

Ilan Goldenberg, MD

New findings suggest that women have a significantly lower risk of first and recurrent life-threatening ventricular tachyarrhythmia events compared with male patients, but no difference in the risk of all-cause mortality.

The sex differences in VTA risk were found to be significantly higher in nonischemic cardiomyopathy than in ischemic cardiomyopathy patients, highlighting the need for sex-specific risk assessment for primary prevention implantable cardioverter-defibrillation (ICD) therapy, according to the investigators.

“Nevertheless, in women, the risk for VTA remains higher than the risk of nonarrhythmic mortality, suggesting that women with both ICM and NICM derive benefit from primary prevention ICD implantation,” wrote corresponding author Ilan Goldenberg, MD, Clinical Cardiovascular Research Center, Division of Cardiology, Department of Medicine, University of Rochester Medical Center.

Sex differences often have correlations between development and progression of disease in patients with heart failure. Previous findings have suggested a lower risk of mortality among women and a smaller ICD benefit compared with men. However, investigators noted these findings may be attributed to the underrepresentation of women in all major ICD randomized clinical trials, at less than 30% of enrolled patients.

The current study evaluated the association between sex and the risk of first occurrence of sustained VTA, total VTA and shock burden during follow-up in a recurrent event analysis and nonarrhythmic mortality among patients enrolled in the landmark Multicenter Automatic Defibrillator Implantation Trials (MADIT) from July 1997 - December 2011.

Primary end points consisted of the first occurrence of VTA, defined as ICD-recorded, treated or monitored, sustained ventricular tachycardia ≥170/min or ventricular fibrillation. Investigators used multivariable Cox proportional hazards regression analysis to identify and evaluate the association between sex and the risk of VTA.

From a total of 4506 study participants, 1075 were women (24%) with a mean age of 64 years. When comparing women and men, the left ventricular ejection fraction (24% vs 25%) were similar, but women had a lower frequency of ischemic cardiomyopathy (454 of 1075 women [42%] vs 2535 of 3431 men [74%]).

Over a mean follow-up of 3 years, investigators found women had significantly lower 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).

Moreover, the multiviariable Cox modeling showed a significantly lower risk of first VTA event associated with female sex (P <.001 for all):

• 40% lower risk of sustained VTA
• 45% lower risk of fast VTA ≥200/min
• 44% lower risk of appropriate ICD shock
• 39% lower risk of antitachycardia pacing

Investigators further observed the lower VTA risk associated with female sex was consistent in risk subsets. However, it was significantly more pronounced in patients with nonischemic cardiomyopathy (female vs male in the ischemic group: hazard ratio [HR}, 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).

“To our knowledge, this is the first study to examine sex differences in not only initial occurrence of VTA or first appropriate ICD therapy but also the overall burden of each of these end points among patients with primary prevention ICD implantation,” Goldenberg noted.

The study, “Sex Differences in the Risk of First and Recurrent Ventricular Tachyarrhythmias Among Patients Receiving an Implantable Cardioverter-Defibrillator for Primary Prevention,” was published in JAMA Network Open.