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

PLOS ONE, Dec 2019

Background 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. Methods 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. Results 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. Conclusion 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.

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

July Sex-specific mortality differences in heart failure patients with ischemia receiving cardiac resynchronization therapy Zhonglin Han 0 1 Zheng Chen 0 1 Rongfang Lan 0 1 Wencheng Di 0 1 Xiaohong Li 0 1 Hongsong Yu 0 1 Wenqing Ji 0 1 Xinlin Zhang 0 1 Biao Xu 0 1 Wei Xu 0 1 0 Editor: Doan TM Ngo, University of Adelaide , AUSTRALIA 1 Department of Cardiology, Nanjing University Medical School Affiliated Nanjing Drum Tower Hospital , Nanjing , China 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. Background Results OPEN ACCESS Data Availability Statement: All relevant data are within the paper and its Supporting Information files. Funding: This work was supported by National Natural Science Foundation of China (No. 81600267) to Zhonglin Han. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript. Competing interests: The authors have declared that no competing interests exist. 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. Conclusion 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. Introduction 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. The aim of this meta-analysis was to assess sex-specific differences in all-cause mortality in patients who received CRT. We also aimed to examine the effect of clinical factors on sexrelated outcomes. Methods 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. Literature search A computer-based literature search by two reviewers (Z.H. and Z.C.) was performed to iden tify English-language publications listed in the Medline (Pubmed source) and Embase electronic databases from January 1980 to September 2016. The search terms and algorithm for the literature search were as follows: cardiac resynchronization therapy OR CRT OR pace maker AND (female OR women OR gender). The detailed search strategy were uplo (...truncated)


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Zhonglin Han, Zheng Chen, Rongfang Lan, Wencheng Di, Xiaohong Li, Hongsong Yu, Wenqing Ji, Xinlin Zhang, Biao Xu, Wei Xu. Sex-specific mortality differences in heart failure patients with ischemia receiving cardiac resynchronization therapy, PLOS ONE, 2017, Volume 12, Issue 7, DOI: 10.1371/journal.pone.0180513