In silico trials for sex-specific patient inclusion criteria in cardiac resynchronization therapy

Q: What are the key findings of this study?

Height-indexed QRS duration criteria effectively resolved sex differences in left bundle branch block detection and maintained low non-LBBB selection rates, demonstrating superior performance for equitable CRT selection.

Q: What is the clinical evidence from this study?

Population: Cardiac Resynchronization Therapy (CRT) candidate evaluation (n=3039). Intervention: Height-indexed QRS duration criteria vs. Conventional QRS duration criteria. Primary outcome: Diagnostic performance (sensitivity and specificity) for detecting true left bundle branch block.

Q: What does this research mean for the field?

Height-indexed QRS duration criteria effectively resolve sex differences in left bundle branch block detection and maintain low non-LBBB selection rates, demonstrating superior performance for equitable cardiac resynchronization therapy selection. Novelty: ClaimNovelty.NOVEL_FINDING. Consensus alignment: ConsensusAlignment.CHALLENGES_CONSENSUS.

Shuang Qian; Devran Uğurlu; 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

doi:10.1038/s41746-026-03139-7

Key result

Height-indexed QRS criteria resolve sex differences in LBBB detection to enable equitable CRT selection.

n=3,039

Why the study?

CRT guidelines rely on trials with limited female representation, and conventional QRSd criteria show variable diagnostic accuracy between sexes due to differences in heart size and remodelling.

Key Points

To assess how sex, cardiac anatomy, left bundle branch block, and conduction delay affect QRS duration, and determine whether indexing QRS duration improves patient selection for cardiac resynchronization therapy.
Conducted population-based electrophysiological simulations using anatomical models from 2627 UK Biobank healthy participants and 359 patients with ischaemic heart disease.
Simulated four pathological states across all anatomical models: normal activation and left bundle branch block (LBBB), each with normal or slowed myocardial conduction.
Assessed diagnostic classification performance comparing conventional fixed QRS duration thresholds against criteria indexed to left ventricular end-diastolic volume, left ventricular mass, and height.
Conventional 150 ms threshold under-selected LBBB females with slow conduction, identifying 71% of males vs 53% of females with ischaemic heart disease and 58% of males vs 11% of females with healthy anatomies (both P < 0.03).
Indexing QRS duration to left ventricular end-diastolic volume or mass reduced sex disparities in LBBB detection (rates 73.2–100%) but markedly increased false-positive selection among non-LBBB patients (rates 49.7–100%).
Height-indexed QRS duration resolved sex differences across most scenarios, achieving 83.1% and 82.2% selection in female ischaemic heart disease models at 0.8 ms/cm with low non-LBBB false-positive rates (5.6% and 2.2%).

PICO

P

Population

3,039 virtual patient models derived from healthy volunteers, ischemic heart disease patients, and CRT recipients to evaluate sex-specific QRS duration criteria for left bundle branch block detection.

E

Exposure / Comparator

Height-indexed QRS duration criteria vs Conventional QRS duration criteria

O

Primary Outcome

Diagnostic performance (sensitivity and specificity) for detecting true left bundle branch block

Limitations

Cohorts analyzed are modest in size and enriched for ischemic heart diseases.
Healthy and IHD cohorts have mid-range LVEF (~45-57%), differing from severely reduced LVEF (<35%) required for Class IA CRT indication.
Slow conduction scenarios were implemented as a generic representation of impaired propagation, not considering specific etiology of fibrosis or scar.
Uncertainty in the placement and orientation of the patient-specific heart model within the representative torso affecting precordial lead morphology.

Implication

May reduce sex disparities in CRT eligibility; leaves open prospective outcome validation.

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.

Discussion

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Cite This Study

Qian et al. (2026) studied Cardiac Resynchronization Therapy (CRT) candidate evaluation (n=3,039). Height-indexed QRS duration criteria vs. Conventional QRS duration criteria was evaluated on Diagnostic performance (sensitivity and specificity) for detecting true left bundle branch block. Height-indexed QRS duration criteria effectively resolved sex differences in left bundle branch block detection and maintained low non-LBBB selection rates, demonstrating superior performance for equitable CRT selection.

synapsesocial.com/papers/6a895eeeca7ade938187d2b0 https://doi.org/10.1038/s41746-026-03139-7

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In silico trials for sex-specific patient inclusion criteria in cardiac resynchronization therapy

Key Points

PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

In silico trials for sex-specific patient inclusion criteria in cardiac resynchronization therapy

Key Points

PICO

Limitations

Implication

Abstract

Discussion

Cite This Study

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