Deep-learning analysis of 3D microarchitectural remodeling in hypertrophic cardiomyopathy
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.
Authors
- Anran Zhang (ORCID: https://orcid.org/0000-0002-9286-453X)
- Joshua Gorham (ORCID: https://orcid.org/0000-0001-5969-4690)
- Carlos L. del Rio (ORCID: https://orcid.org/0000-0002-9761-7888)
- Martin Beyer (ORCID: https://orcid.org/0000-0003-0925-7067)
- Ferhaan Ahmad
- D Fatkin
- Brian L. Bishop (ORCID: https://orcid.org/0000-0002-8098-119X)
- SC Day
- David M. Ryba (ORCID: https://orcid.org/0000-0002-5994-5581)
- J G Seidman
- Barbara McDonough (ORCID: https://orcid.org/0000-0002-4257-8623)
- Mobin Khoramjoo
- Huachen Chen (ORCID: https://orcid.org/0000-0003-3542-0884)
- Ching-Pin Chang
- K A Brown
- Alexander Bansbach
- Gavin Y. Oudit
- Eric Q. Wei
- Christine E. Seidman
Institutions
- University of Iowa (US)
- Brigham and Women's Hospital (US)
- Harvard University (US)
- University of Alberta (CA)
- Universität Hamburg (DE)
- Victor Chang Cardiac Research Institute (AU)
- UNSW Sydney (AU)
- St Vincent's Hospital Sydney (AU)
- Massachusetts General Hospital (US)
- Bristol-Myers Squibb (United States) (US)
- University Medical Center Hamburg-Eppendorf (DE)
- German Centre for Cardiovascular Research (DE)
- Exemplar Genetics (United States) (US)
- University of Pennsylvania (US)
Publication Details
- Journal
- Science
- Published
- 2026-01-15
- DOI
- https://doi.org/10.1126/science.ady6443
- Primary Topic
- Cardiomyopathy and Myosin Studies
- Type
- article
- Field-Weighted Citation Impact
- 0.00