Relationship between sex, body size, and cardiac resynchronization therapy benefit: A patient-level meta-analysis of
Daniel J Friedman1, Antonio Olivas-Martinez2, Frederik Dalgaard3
1Division of Cardiology, Duke University School of Medicine, Durham, North Carolina; Duke Clinical Research Institute, Duke University School of Medicine, Durham, North Carolina.
Insights
Women may experience greater benefits from cardiac resynchronization therapy (CRT) than men, especially with shorter QRS durations. Body size partially explains these differences, suggesting improved patient selection for CRT.
Area of Science:
- Cardiology
- Medical Devices
- Biomedical Engineering
Background:
- Cardiac resynchronization therapy (CRT) is a treatment for heart failure.
- Previous studies suggest women may benefit more from CRT than men.
- Sex-based differences in CRT effectiveness require further investigation.
Purpose of the Study:
- To determine if height, body surface area (BSA), or left ventricular end-diastolic dimension (LVEDD) better account for sex-based differences in CRT effects.
- To analyze patient-level data from multiple CRT trials.
Main Methods:
- Bayesian hierarchical Weibull regression models were used to analyze data from seven major CRT trials.
- QRS duration and CRT effects were examined overall and stratified by sex.
- QRS duration was indexed by height, BSA, or LVEDD to assess its impact on CRT outcomes.
Main Results:
- Women (n=1439) were shorter and had smaller BSAs than men (n=5628).
- The reduction in heart failure hospitalization (HFH) or death was significantly greater for women (HR, 0.54) than for men (HR, 0.77).
- CRT effects were observed at shorter QRS durations in women (126 ms) compared to men (145 ms), particularly in nonischemic cardiomyopathy.
Conclusions:
- Body size partially explains sex-specific QRS duration thresholds for CRT benefit.
- Indexing QRS duration for body size may enhance patient selection for CRT, especially for those with borderline QRS durations.
- While body size influences thresholds, it does not appear to affect the magnitude of CRT benefit.
Background:
Women might benefit more than men from cardiac resynchronization therapy (CRT) and do so at shorter QRS durations.
Objective:
This meta-analysis was performed to determine whether sex-based differences in CRT effects are better accounted for by height, body surface area (BSA), or left ventricular end-diastolic dimension (LVEDD).
Methods:
We analyzed patient-level data from CRT trials (MIRACLE, MIRACLE ICD, MIRACLE ICD II, REVERSE, RAFT, COMPANION, and MADIT-CRT) using bayesian hierarchical Weibull regression models. Relationships between QRS duration and CRT effects were examined overall and in sex-stratified cohorts; additional analyses indexed QRS duration by height, BSA, or LVEDD. End points were heart failure hospitalization (HFH) or death and all-cause mortality.
Results:
Compared with men (n = 5628), women (n = 1439) were shorter (1.62 [interquartile range, 1.57-1.65] m vs 1.75 [1.70-1.80] m; P < .001), with smaller BSAs (1.76 [1.62-1.90] m2 vs 2.02 [1.89-2.16] m2; P < .001). In adjusted sex-stratified analyses, the reduction in HFH or death was greater for women (hazard ratio, 0.54; credible interval, 0.42-0.70) than for men (hazard ratio, 0.77; credible interval, 0.66-0.89; Pinteraction = .009); results were similar for all-cause mortality even after adjustment for height, BSA, and LVEDD. Sex-specific differences were observed only in nonischemic cardiomyopathy. The effect of CRT on HFH or death was observed at a shorter QRS duration for women (126 ms) than for men (145 ms). Indexing QRS duration by height, BSA, or LVEDD attenuated sex-specific QRS duration thresholds for the effects of CRT on HFH or death but not on mortality.
Conclusion:
Although body size partially explains sex-specific QRS duration thresholds for CRT benefit, it is not associated with the magnitude of CRT benefit. Indexing QRS duration for body size might improve selection of patients for CRT, particularly with a "borderline" QRS duration.
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