Deep-learning analysis of 3D microarchitectural remodeling in hypertrophic cardiomyopathy

Eric Q Wei; Martin Beyer; Kemar J Brown; Alexander J Bansbach; Joshua M Gorham; Barbara McDonough; Huachen Chen; Mobin Khoramjoo; Anran Zhang; Brian Bishop; Ferhaan Ahmad; Carlos Del Rio; Ching-Pin Chang; David M Ryba; Sharlene M Day; Diane Fatkin; Gavin Y Oudit; Christine E Seidman; Jonathan G Seidman

doi:10.1126/science.ady6443

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Deep-learning analysis of 3D microarchitectural remodeling in hypertrophic cardiomyopathy

Journal article

Peer reviewed

Deep-learning analysis of 3D microarchitectural remodeling in hypertrophic cardiomyopathy

Eric Q Wei, Martin Beyer, Kemar J Brown, Alexander J Bansbach, Joshua M Gorham, Barbara McDonough, Huachen Chen, Mobin Khoramjoo, Anran Zhang, Brian Bishop, …

Science (American Association for the Advancement of Science), Vol.391(6782), eady6443

01/15/2026

DOI: 10.1126/science.ady6443

PMID: 41538430

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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.

Animals

Cardiomyopathy, Hypertrophic - diagnostic imaging

Cardiomyopathy, Hypertrophic - genetics

Cardiomyopathy, Hypertrophic - pathology

Deep Learning

Disease Models, Animal

Fibrosis

Genotype

Humans

Hypertrophy, Left Ventricular - diagnostic imaging

Hypertrophy, Left Ventricular - genetics

Hypertrophy, Left Ventricular - pathology

Imaging, Three-Dimensional - methods

Myocardium - pathology

Myocytes, Cardiac - pathology

Swine

Transcriptome

Ventricular Remodeling - genetics

Details

Title: Subtitle: Deep-learning analysis of 3D microarchitectural remodeling in hypertrophic cardiomyopathy
Creators: Eric Q Wei - Brigham and Women's Hospital
Martin Beyer - University Medical Center Hamburg-Eppendorf
Kemar J Brown - Massachusetts General Hospital
Alexander J Bansbach - Harvard University
Joshua M Gorham - Harvard University
Barbara McDonough - Harvard University
Huachen Chen - University of Alberta
Mobin Khoramjoo - University of Alberta
Anran Zhang - University of Alberta
Brian Bishop - Exemplar Genetics
Ferhaan Ahmad - University of Iowa
Carlos Del Rio - Bristol-Myers Squibb
Ching-Pin Chang - Bristol-Myers Squibb
David M Ryba - Bristol-Myers Squibb
Sharlene M Day - University of Pennsylvania
Diane Fatkin - St Vincent's Hospital Sydney
Gavin Y Oudit - University of Alberta
Christine E Seidman - Brigham and Women's Hospital
Jonathan 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
NLM abbreviation: Science
ISSN: 0036-8075
eISSN: 1095-9203
Publisher: AAAS
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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