A rule-based method for predicting the electrical activation of the heart with cardiac resynchronization therapy from non-invasive clinical data:Medical Image Analysis

Aims: Cardiac Resynchronization Therapy (CRT) is an important treatment for heart failure. Low female enrolment in clinical trials means that current CRT guidelines may be biased towards males. However, females have higher response rates at lower QRS duration (QRSd) thresholds. Sex-differences in 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. Methods and Results: 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 9-13ms lower than current guidelines. Conclusion: Sex-difference 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 9-13ms lower QRSd thresholds for female CRT guidelines.