Abstract
Introduction: Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure with reduced ejection fraction (HFrEF). Women appear to respond differently to CRT, yet it remains unclear whether this is inherent to the female sex itself, or due to other patient characteristics. In this study, we aimed to investigate sex differences in response to CRT. Methods: This is a post-hoc analysis of a prospective, multicenter study (MARC) in the Netherlands, studying HFrEF patients with an indication for CRT according to the guidelines (n = 240). Primary outcome measures are left ventricular ejection fraction (LVEF) and left ventricular end systolic volume (LVESV) at 6 months follow-up. Results were validated in an independent retrospective Belgian cohort (n = 818). Results: In the MARC cohort 39% were women, and in the Belgian cohort 32% were women. In the MARC cohort, 70% of the women were responders (defined as >15% decrease in LVESV) at 6 months, compared to 55% of men (p = 0.040) (79% vs. 67% in the Belgian cohort, p = 0.002). Women showed a greater decrease in LVESV %, LVESV indexed to body surface area (BSA) %, and increase in LVEF (all p < 0.05). In regression analysis, after adjustment for BSA and etiology, female sex was no longer associated with change in LVESV % and LVESV indexed to BSA % and LVEF % (p > 0.05 for all). Results were comparable in the Belgian cohort. Conclusions: Women showed a greater echocardiographic response to CRT at 6 months follow-up. However, after adjustment for BSA and ischemic etiology, no differences were found in LV-function measures or survival, suggesting that non-ischemic etiology is responsible for greater response rates in women treated with CRT.
Highlights
Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure with reduced ejection fraction (HFrEF)
This sex difference in left ventricular (LV) remodeling response to CRT was lost after accounting for ischemic etiology, which confirms our hypothesis that the difference in response is mainly determined by HF etiology, where patients with non-ischemic etiology are more likely to respond to CRT
As this study shows this direct relationship between heart failure etiology and reverse remodeling response to CRT in a relatively large
Summary
Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure with reduced ejection fraction (HFrEF). Women appear to respond differently to CRT, yet it remains unclear whether this is inherent to the female sex itself, or due to other patient characteristics. We aimed to investigate sex differences in response to CRT. Results: In the MARC cohort 39% were women, and in the Belgian cohort 32%. Cardiac resynchronization therapy (CRT) is an established therapy for patients with heart failure with reduced ejection fraction (HFrEF) and ventricular conduction disturbance, which aims to improve cardiac function through resynchronizing electrical activation. Women generally have a smaller body surface area (BSA), which may be a driver for differences in response to heart failure therapy between women and men, reflected by different response to CRT treatment but for example differences in optimal CRT, including etiology of HF, QRS morphology, duration and area, and female sex [3,4,5,6,7].
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