In silico trials for sex-specific patient inclusion criteria in cardiac resynchronization therapy
File(s)
Accepted version
Author(s)
Type
Journal Article
Abstract
Cardiac resynchronization therapy (CRT) guidelines are based on clinical trials with limited female representation and inconsistent le bundle branch block (LBBB) definitions. Conventional QRS duration (QRSd) criteria show variable diagnostic accuracy between sexes, partly due to differences in heart size and remodeling. We evaluated the influence of sex, heart size, LBBB, and conduction delay on QRSd and assessed the diagnostic performance of conventional and indexed QRSd criteria using a population-based modelling approach. Simulated QRSd were derived from electrophysiological simulations conducted in 2627 UK Biobank healthy participants and 359 patients with ischemic heart disease, by modelling LBBB and normal activation combined with/without conduction delay. QRSd criteria under-selected LBBB females and over-selected non-LBBB patients. Indexing by LVEDV and LV mass reduced sex disparities but increased the over-selection in non-LBBB patients. Height-indexed QRSd effectively resolved sex differences and maintained low non-LBBB selection rates, demonstrating superior performance and potential for more equitable CRT selection. These results uncover a key mechanistic driver of sex differences in LBBB detection that may contribute to CRT outcomes and underscore the importance of incorporating sex-specific considerations into updated CRT guidelines to ensure equitable and effective treatment.
Date Acceptance
2026-08-05
Citation
npj Digital Medicine
ISSN
2398-6352
Publisher
Nature Portfolio
Journal / Book Title
npj Digital Medicine
Copyright Statement
© The Author(s) 2026. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproductionin any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyrightholder.To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/.
License URL
Publication Status
Published online
Date Publish Online
2026-08-19