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

Journal: Science (New York, N.Y.)
Published Date: Jan 15, 2026

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.

Authors

  • Eric Q Wei
    Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Martin Beyer
    Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Kemar J Brown
    Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Alexander J Bansbach
    Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Joshua M Gorham
    Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Barbara McDonough
    Department of Genetics, Harvard Medical School, Boston, MA, USA.
  • Huachen Chen
    Division of Cardiology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Mobin Khoramjoo
    Department of Physiology, University of Alberta, Edmonton, AB T6G 2H7, Canada; Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2S2, Canada.
  • Anran Zhang
    Division of Cardiology, Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, Alberta, Canada.
  • Brian Bishop
    Exemplar Genetics, North Liberty, IA, USA.
  • Ferhaan Ahmad
    Division of Cardiovascular Medicine, Department of Internal Medicine, University of Iowa, Iowa City, IA, USA.
  • Carlos Del Rio
    Bristol Myers Squibb, Princeton, NJ, USA.
  • Ching-Pin Chang
    Bristol Myers Squibb, Princeton, NJ, USA.
  • David M Ryba
    Bristol Myers Squibb, Princeton, NJ, USA.
  • Sharlene M Day
    Division of Cardiovascular Medicine, University of Pennsylvania, Philadelphia, PA, USA.
  • Diane Fatkin
    Victor Chang Cardiac Research Institute, Darlinghurst, New South Wales, Australia.
  • Gavin Y Oudit
    Mazankowski Alberta Heart Institute, University of Alberta, Edmonton, AB T6G 2S2, Canada; Division of Cardiology, Department of Medicine, University of Alberta, Edmonton, AB T6G 2G3, Canada. Electronic address: [email protected].
  • Christine E Seidman
    Departments of Genetics and Medicine, Harvard Medical School, Boston, MA, 02115, USA.
  • Jonathan G Seidman
    Departments of Genetics and Medicine, Harvard Medical School, Boston, MA, 02115, USA.

Keywords

External Resources

Popular Topics
Recent Journals