Journal article
Deep-learning analysis of 3D microarchitectural remodeling in hypertrophic cardiomyopathy
Science (American Association for the Advancement of Science), Vol.391(6782), eady6443
01/15/2026
DOI: 10.1126/science.ady6443
PMCID: PMC12988831
PMID: 41538430
Abstract
Hypertrophic cardiomyopathy (HCM), a genetic heart disease defined by unexplained cardiac wall thickening, is a leading cause of sudden death worldwide. However, the three-dimensional organization of cardiac tissue underlying left ventricular hypertrophy remains poorly understood. We developed CaMVIA-3D, a deep-learning volumetric imaging and analysis pipeline to characterize cardiac microarchitecture. Analysis of tissues from HCM hearts revealed genotype-specific differences in cardiomyocyte volume, morphology, and extracellular volume, with pathogenic variants exhibiting greater concentric cellular hypertrophy and disarray and variant-negative cases showing predominant fibrosis. Longitudinal profiling of a pig HCM model revealed early-onset fibrosis preceding cardiomyocyte hypertrophy. Integrating transcriptomic and morphologic changes, we identified genes associated with cellular and extracellular remodeling. These findings define genotype-specific microstructural differences in HCM, offering insights to improve diagnostics and targeted therapies.
Details
- Title: Subtitle
- Deep-learning analysis of 3D microarchitectural remodeling in hypertrophic cardiomyopathy
- Creators
- Eric Q Wei - Brigham and Women's HospitalMartin Beyer - University Medical Center Hamburg-EppendorfKemar J Brown - Massachusetts General HospitalAlexander J Bansbach - Harvard UniversityJoshua M Gorham - Harvard UniversityBarbara McDonough - Harvard UniversityHuachen Chen - University of AlbertaMobin Khoramjoo - University of AlbertaAnran Zhang - University of AlbertaBrian Bishop - Exemplar Genetics (United States)Ferhaan Ahmad - University of IowaCarlos Del Rio - Bristol-Myers Squibb (United States)Ching-Pin Chang - Bristol-Myers Squibb (United States)David M Ryba - Bristol-Myers Squibb (United States)Sharlene M Day - University of PennsylvaniaDiane Fatkin - St Vincent's Hospital SydneyGavin Y Oudit - University of AlbertaChristine E Seidman - Brigham and Women's HospitalJonathan G Seidman - Harvard University
- Resource Type
- Journal article
- Publication Details
- Science (American Association for the Advancement of Science), Vol.391(6782), eady6443
- DOI
- 10.1126/science.ady6443
- PMID
- 41538430
- PMCID
- PMC12988831
- NLM abbreviation
- Science
- ISSN
- 0036-8075
- eISSN
- 1095-9203
- Publisher
- AAAS
- Grant note
- National Institutes of Health: T32HL007604 Harvard Medical School John S. Ladue Memorial FellowshipGerman Heart Foundation (Deutsche Herzstiftung e.V.)British Heart Foundation's Big Beat Challenge award: BBC/F/21/220106 National Science Foundation (NSF) Engineering Research Center on Cellular Metamaterials: EEC-1647837 Canadian Institutes of Health Research: PJT-462950 Australian-American Fulbright Commission Fulbright Future Scholarship
This work was supported by National Institutes of Health (NIH) grant T32HL007604 (E.Q.W.), Harvard Medical School John S. Ladue Memorial Fellowship (E.Q.W.), German Heart Foundation (Deutsche Herzstiftung e.V.) (M.B.), British Heart Foundation's Big Beat Challenge award to CureHeart (BBC/F/21/220106) (C.E.S. and J.G.S.), National Science Foundation (NSF) Engineering Research Center on Cellular Metamaterials EEC-1647837 (C.E.S. and J.G.S.), Canadian Institutes of Health Research Operating Grant PJT-462950 (G.Y.O.), and Australian-American Fulbright Commission Fulbright Future Scholarship (D.F.).
- Language
- English
- Date published
- 01/15/2026
- Academic Unit
- Radiology; Molecular Physiology and Biophysics; Cardiovascular Medicine; Fraternal Order of Eagles Diabetes Research Center; Internal Medicine
- Record Identifier
- 9985121595102771
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