Development and Validation of Imaging-Free Myocardial Fibrosis Prediction Models, Association with Outcomes, and
Nicholas Black1,2, Joshua Bradley1,2, Gavin Lewis3
1Division of Cardiovascular Sciences, School of Medical Sciences, Faculty of Biology, Medicine and Health, Manchester Academic Health Science Centre University of Manchester UK.
Journal of the American Heart Association
|April 3, 2025
Summary
Predicted extracellular volume (ECV) can identify patients with myocardial fibrosis without imaging. This approach simplifies clinical trials for antifibrotic therapies, increasing participant numbers while avoiding complex imaging requirements.
Area of Science:
- Cardiology
- Medical Imaging
- Clinical Trials
Background:
- Phase 3 trials for myocardial fibrosis treatments need non-imaging-based measurement methods.
- Current methods often rely on tomographic imaging with intravenous contrast, posing limitations.
Purpose of the Study:
- To develop and validate models for predicting extracellular volume (ECV) using readily available clinical data.
- To assess the association between predicted ECV and adverse cardiovascular outcomes.
- To estimate sample size requirements for clinical trials using predicted versus measured ECV.
Main Methods:
- Developed and validated ECV prediction models using comorbidity and natriuretic peptide data, excluding imaging variables.
- Utilized survival analysis to test associations between predicted ECV and outcomes (death or heart failure hospitalization).
- Calculated sample size estimates for hypothetical antifibrotic therapy trials based on predicted ECV, measured ECV, or no ECV.
Main Results:
- Prediction models showed good discrimination (C-statistic 0.78 in derivation, 0.74 in validation) and calibration.
- Predicted ECV ≥27% was associated with a 2.21-fold increased risk of adverse outcomes.
- Using predicted ECV in a hypothetical trial (ECV ≥27%) could reduce cardiac MRI scans by 3940, with a manageable increase in screened/enrolled participants.
Conclusions:
- Predicted ECV, derived without imaging, effectively identifies patients at risk for adverse outcomes.
- This method can facilitate the design of larger Phase 3 trials for myocardial fibrosis, simplifying eligibility criteria.
- Predicted ECV offers a practical approach to advance antifibrotic therapy development by avoiding complex imaging procedures.
