Sex-specific differences in left ventricular reverse remodeling response to cardiac resynchronization
A B Curtis, C Linde, F Z Ahmed, S Feigofsky, L Gravelin, M Gwechenberger, M Pachon, K K M Chia, C Frazier-Mills, E Kotschet, L Lambrakos, K Soejima, Y Zhang, R Waxman, A M RussoAbstract
Introduction
Cardiac resynchronization therapy (CRT) is underutilized in women despite well-known clinical benefits. Several analyses have demonstrated sex differences in CRT response. In 2023, the Heart Rhythm Society upgraded CRT indications for women with left bundle branch block (LBBB) and QRS 120-149 ms from class 2a to class 1 but more studies are needed to understand sex differences in CRT response particularly in such patients.
Purpose
To compare 6-month post-implant left ventricular (LV) end-systolic volume (LVESV) changes in male and female patients with CRT devices in relation to QRS morphology and QRS width.
Methods
Individual patient level data were pooled from 5 randomized CRT trials (MIRACLE, MIRACLE ICD, REVERSE, Adaptive CRT, and ECG Belt). LVESV change was calculated as (LVESV at 6-month post implant - LVESV at baseline) / LVESV at baseline (%). LVESV change analysis using linear mixed models for 2 cohorts (Figure 1) were conducted to evaluate: (1) sex differences in LVESV change in CRT and No CRT patients from 3 studies; (2) sex differences in LVESV change among CRT patients from all 5 studies [a] by clear CRT indication class (per 2022 AHA/ACC/HFSA heart failure guidelines) based on QRS morphology, LV ejection fraction (LVEF), New York Heart Association (NYHA) class, and QRS width without adjustment, and [b] by QRS morphology, LVEF, NYHA class and QRS width adjusting for other covariates.
Results
Among the 2521 patients from 5 studies, 1840 were eligible (479 women) – met inclusion criteria (LBBB/non-LBBB, LVEF ≤50%, QRS ≥120 ms, NYHA I–IV), had CRT indication classified, and LVESV data. Of 1840 patients, 1230 (698 CRT, 532 No CRT) from 3 studies showed that female CRT patients had a greater reduction in LVESV compared to males (-22.9 % vs -9.1%, p<0.0001), while no significant sex difference in % LVESV change was seen in the No CRT group. Data from 1308 eligible CRT patients across all 5 studies showed that:[a] Female LBBB patients experienced greater reduction in LVESV than males for both QRS >150 ms (-25.6% vs -18.7%, p=0.0035) and QRS 120-149 ms (-13.7% vs -2.6%, p=0.0068), and the LVESV change in female LBBB patients with QRS 120-149 ms was comparable to that of male LBBB patients with QRS >150 ms; [b] Sex differences in LVESV change varied significantly by QRS morphology, NYHA class, and body mass index (BMI) - after adjusting for covariates, women showed a greater LVESV reduction than men in those with LBBB, NYHA I/II and lower BMI but this did not hold in non-LBBB, NYHA III/IV and higher BMI patients (Table 1).
Conclusion
Female CRT patients exhibit more reverse LV remodeling than males. Females with LBBB had greater LVESV reduction than men even with only moderately prolonged baseline QRS (120-149ms). Our findings reinforce the indications for CRT use, and improved outcomes in women, particularly those with symptomatic HF, LVEF ≤35%, LBBB and QRS 120-149ms highlighting the need for sex-specific QRS duration criteria.Figure 1For image description, please refer to the figure legend and surrounding text.Table 1 For image description, please refer to the figure legend and surrounding text.