Key result
Computer simulations accounting for smaller left ventricular size in females predicted female-specific QRS duration thresholds for CRT that are 9-13 ms lower than current guidelines.
Why the study?
Current CRT guidelines may be male-biased due to low female trial enrollment, while females respond at lower QRS duration thresholds potentially due to left ventricular size differences.
Do sex differences in left ventricular size explain the sex difference in QRS duration and predict sex-specific guidelines for CRT?
Do sex differences in left ventricular size explain the sex difference in QRS duration and predict sex-specific guidelines for CRT?
Computer modeling demonstrates that smaller left ventricular size in females accounts for sex differences in QRS duration, supporting a 9-13 ms lower QRS duration threshold for CRT in women.
LV size may explain female CRT benefit at lower QRSd; modeling extends mechanistic insight but leaves practice change open.
Cardiac resynchronization therapy (CRT) is an important treatment for heart failure. Low female enrollment in clinical trials means that current CRT guidelines may be biased toward males. However, females have higher response rates at lower QRS duration (QRSd) thresholds. Sex differences in the left ventricle (LV) size could provide an explanation for the improved female response at lower QRSd. We aimed to test if sex differences in CRT response at lower QRSd thresholds are explained by differences in LV size and hence predict sex-specific guidelines for CRT. We investigated the effect that LV size sex difference has on QRSd between male and females in 1093 healthy individuals and 50 CRT patients using electrophysiological computer models of the heart. Simulations on the healthy mean shape models show that LV size sex difference can account for 50-100% of the sex difference in baseline QRSd in healthy individuals. In the CRT patient cohort, model simulations predicted female-specific guidelines for CRT, which were 9-13 ms lower than current guidelines. Sex differences in the LV size are able to account for a significant proportion of the sex difference in QRSd and provide a mechanistic explanation for the sex difference in CRT response. Simulations accounting for the smaller LV size in female CRT patients predict 9-13 ms lower QRSd thresholds for female CRT guidelines.
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Lee et al. (2019) studied Heart failure (n=1,143). Female sex (smaller left ventricular size) vs. Male sex was evaluated on QRS duration (QRSd) thresholds for CRT. Computer simulations accounting for smaller left ventricular size in females predicted female-specific QRS duration thresholds for CRT that are 9-13 ms lower than current guidelines.
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