Research Article: Sex-specific mortality differences in heart failure patients with ischemia receiving cardiac resynchronization therapy

Date Published: July 6, 2017

Publisher: Public Library of Science

Author(s): Zhonglin Han, Zheng Chen, Rongfang Lan, Wencheng Di, Xiaohong Li, Hongsong Yu, Wenqing Ji, Xinlin Zhang, Biao Xu, Wei Xu, Doan TM Ngo.


Recent studies have reported prognosis differences between male and female heart failure patients following cardiac resynchronization therapy (CRT). However, the potential clinical factors that underpin these differences remain to be elucidated.

A meta-analysis was performed to investigate the factors that characterize sex-specific differences following CRT. This analysis involved searching the Medline (Pubmed source) and Embase databases in the period from January 1980 to September 2016.

Fifty-eight studies involving 33445 patients (23.08% of whom were women) were analyzed as part of this study. Only patients receiving CRT with follow-up greater than six months were included in our analysis. Compared with males, females exhibited a reduction of 33% (hazard ratio, 0.67; 95% confidence interval, 0.62–0.73; P < 0.0001) and 42% (hazard ratio, 0.58; 95% confidence interval, 0.46–0.74; P = 0.003) in all-cause mortality and heart failure hospitalization or heart failure, respectively. Following a stratified analysis of all-cause mortality, we observed that ischemic causes (p = 0.03) were likely to account for most of the sex-specific differences in relation to CRT. These data suggest that women have a reduced risk of all-cause mortality and heart failure hospitalization or heart failure following CRT. Based on the results from the stratified analysis, we observed more optimal outcomes for females with ischemic heart disease. Thus, ischemia are likely to play a role in sex-related differences associated with CRT in heart failure patients. Further studies are required to determine other indications and the potential mechanisms that might be associated with sex-specific CRT outcomes.

Partial Text

Cardiac resynchronization therapy (CRT) is an effective treatment for heart failure patients exhibiting wide QRS complexes and reduced systolic left ventricular ejection fractions (LVEF). Although CRT devices are routinely implanted according to ACCF/AHA/HRS guidelines, approximately 20% of CRT patients fail to benefit from CRT [1]. Recently, sex-specific differences in relation to heart failure (HF) epidemiology, clinical presentation, response to CRT, and post-CRT prognosis have been reported. However, the mechanisms that underlie these differences are not well understood. An AHA Statistical Update from 2016 [2] reported that heart failure mortality was higher in women than men; however, no obvious sex-specific differences were observed in relation to the prevalence of heart failure. Therefore, these data suggest that sex-specific factors may cause differences in CRT response between males and females. Indeed, most studies and meta-analyses performed in this area report that women who received CRT experienced greater benefits and reduced mortality compared with men [3]. Studies evaluating the differential effects of clinical factors, including ischemic events, left bundle branch block (LBBB), age, LVEF, and atrial fibrillation on male and female clinical outcomes are limited. Thus, it is important that we attempt to identify and characterize factors that might help us to improve clinical responses to CRT for both male and female HF patients.

This meta-analysis was performed according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement [4]. No participation of human subjects were involved in this analysis.

The ACCF/AHA/HRS guidelines for CRT are based upon large clinical trials and meta-analyses of clinical trials. However, only 20% of the patients with HF that received CRT in these studies were female. This suggests that the current guidelines may be more applicable to male patients. In fact, clinical trial and meta-analysis data suggest that female patients respond better to CRT than male patients; however, there was no significant sex-related difference in relation to heart failure prevalence. More importantly, females exhibit higher mortality following HF, and were less likely to receive guideline-recommended treatment with medicine or CRT [66]. Data indicate that sex-related factors might influence the outcome of HF patients that receive CRT; however, this phenomenon has not yet been taken into account in the development of sex-specific diagnostic and treatment modalities, and we have yet to elucidate the potential clinical and molecular factors that underlie these sex-differences.




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