Electrical optimization can overcome gender bias in CRT outcomes, JACC study.

Why women benefit more from cardiac resynchronization therapy (CRT) than men, is still an unexplained observation. Exploring this enigma, Lopez et al have hypothesized that the shorter intrinsic PR interval observed in women allows a greater degree of fusion with intrinsic conduction, achieving a shorter QRS interval duration accounting for a better response. Their recent study shows that the difference in QRS interval duration and response between men and women does not persist when CRT was optimized using fusion with intrinsic conduction. These findings were published in an online edition of JACC Clinical Electrophysiology this week.

Subanalyses of randomized clinical trials and meta-analyses have shown that women achieve better CRT outcomes than men. Previous findings in the BEST (Fusion Based optimization in resynchronization Therapy demonstrated that CRT optimization based on the fusion-optimized intervals (FOI) method resulted in a narrower QRS interval and greater LV remodeling compared to nominal settings.

Lopez et al hypothesized that women respond better to CRT because their shorter PR interval promotes better spontaneous fusion with intrinsic conduction, resulting in a narrower QRS interval and better resynchronization. Controlling this factor by optimizing CRT with the FOI method would eliminate sex differences in CRT outcomes.

A cohort of 180 patients included in the BEST study were retrospectively analyzed. Patients were initially randomized to either nonoptimized CRT (NON-OPT group; n = 89) or electrocardiographically optimized CRT based on the fusion-optimized intervals (FOI) method (FOI group; n = 91). Echocardiographic response was defined as a >15% decrease in left ventricular end-systolic volume at the 12-month follow-up.

The study showed that:

1. The basal PR interval was shorter in women as compared to men.

2. In the NON-OPT group, CRT resulted in a shorter paced QRS interval in women than in men and expected better response in women.

3. There were no differences in paced QRS interval duration or response between women and men in the FOI group.

4. FOI extended the atrioventricular interval to obtain the best fusion; the atrioventricular intervals tended to require greater extension in men than in women (22 ± 33 ms vs. 8 ± 28 ms, respectively; p = 0.07).

Therefore, longer PR intervals may be detrimental for the optimized delivery of CRT and could account for the relatively poorer outcomes in men. "Our results support the notion that electrical optimization may resolve sex differences in CRT response", noted the authors.

Optimal resynchronization is reached by the interplay of activation waves originating from pacing electrodes and from intrinsic conduction.(Figure) The FOI method achieved the narrowest QRS interval, adjusting the AV interval to obtain the maximum fusion with intrinsic conduction in both men and women.

To conclude, compared to men, women have more fusion and intrinsic conduction due to a shorter PR. As a result, if the CRT device is not optimized, women obtain a shorter QRS interval and consequently show greater response than men with the same nominal programming.

Source: JACC Clinical Electrophysiology: DOI: 10.1016/j.jacep.2021.03.023