| Title: | In silico trials for sex-specific patient inclusion criteria in cardiac resynchronization therapy |
| Journal: | npj Digital Medicine |
| Published: | 19 Aug 2026 |
| DOI: | https://doi.org/10.1038/s41746-026-03139-7 |
| URL: | http://dx.doi.org/10.1038/s41746-026-03139-7 |
Publication 20961
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Abstract
Cardiac resynchronization therapy (CRT) guidelines are based on clinical trials with limited female representation and inconsistent left bundle branch block (LBBB) definitions. Conventional QRS duration (QRSd) criteria show variable diagnostic accuracy between sexes, partly due to differences in heart size and remodelling. 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 ischaemic 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.</p>
19 Authors
- Shuang Qian
- Devran Ugurlu
- Elliot Fairweather
- Richard E. Jones
- Hassan Zaidi
- Sanjay Prasad
- Brian P. Halliday
- Daniel Hammersley
- Gernot Plank
- Edward Vigmond
- Cristobal Rodero
- Abdul Qayyum
- Derek Bivona
- Kenneth C. Bilchick
- Christopher A. Rinaldi
- Alistair Young
- Pablo Lamata
- Martin Bishop
- Steven Niederer
1 Application
| Application ID | Title |
|---|---|
| 88878 | The cardiovascular digital twin of the adult population: defining the population ranges. |
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