Clinical and genetic associations of deep learning-derived cardiac magnetic resonance-based left ventricular mass

Shaan Khurshid; Julieta Lazarte; James P Pirruccello; Lu-Chen Weng; Seung Hoan Choi; Amelia W Hall; Xin Wang; Samuel F Friedman; Victor Nauffal; Kiran J Biddinger; Krishna G Aragam; Puneet Batra; Jennifer E Ho; Anthony A Philippakis; Patrick T Ellinor; Steven A Lubitz

doi:10.1038/s41467-023-37173-w

Clinical and genetic associations of deep learning-derived cardiac magnetic resonance-based left ventricular mass

Nat Commun. 2023 Mar 21;14(1):1558. doi: 10.1038/s41467-023-37173-w.

Authors

Shaan Khurshid^{1

2

3}, Julieta Lazarte^{1

2

4}, James P Pirruccello^{1

2

5}, Lu-Chen Weng^{1

2}, Seung Hoan Choi^{1

2}, Amelia W Hall⁶, Xin Wang^{1

2}, Samuel F Friedman⁷, Victor Nauffal⁸, Kiran J Biddinger^{1

2}, Krishna G Aragam^{1

2

5}, Puneet Batra⁷, Jennifer E Ho^{2

9}, Anthony A Philippakis⁷, Patrick T Ellinor^{1

2

3}, Steven A Lubitz^{10

11

12}

Affiliations

¹ Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA.
² Cardiovascular Disease Initiative, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA, USA.
³ Demoulas Center for Cardiac Arrhythmias, Massachusetts General Hospital, Boston, MA, USA.
⁴ Department of Medicine, Schulich School of Medicine and Dentistry, Western University, London, ON, Canada.
⁵ Division of Cardiology, Massachusetts General Hospital, Boston, MA, USA.
⁶ Gene Regulation Observatory, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA, USA.
⁷ Data Sciences Platform, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA, USA.
⁸ Division of Cardiology, Brigham and Women's Hospital, Boston, MA, USA.
⁹ CardioVascular Institute and Division of Cardiology, Department of Medicine, Beth Israel Deaconess Medical Center, Boston, MA, USA.
¹⁰ Cardiovascular Research Center, Massachusetts General Hospital, Boston, MA, USA. slubitz@mgh.harvard.edu.
¹¹ Cardiovascular Disease Initiative, Broad Institute of Harvard and the Massachusetts Institute of Technology, Cambridge, MA, USA. slubitz@mgh.harvard.edu.
¹² Demoulas Center for Cardiac Arrhythmias, Massachusetts General Hospital, Boston, MA, USA. slubitz@mgh.harvard.edu.

Abstract

Left ventricular mass is a risk marker for cardiovascular events, and may indicate an underlying cardiomyopathy. Cardiac magnetic resonance is the gold-standard for left ventricular mass estimation, but is challenging to obtain at scale. Here, we use deep learning to enable genome-wide association study of cardiac magnetic resonance-derived left ventricular mass indexed to body surface area within 43,230 UK Biobank participants. We identify 12 genome-wide associations (1 known at TTN and 11 novel for left ventricular mass), implicating genes previously associated with cardiac contractility and cardiomyopathy. Cardiac magnetic resonance-derived indexed left ventricular mass is associated with incident dilated and hypertrophic cardiomyopathies, and implantable cardioverter-defibrillator implant. An indexed left ventricular mass polygenic risk score ≥90^th percentile is also associated with incident implantable cardioverter-defibrillator implant in separate UK Biobank (hazard ratio 1.22, 95% CI 1.05-1.44) and Mass General Brigham (hazard ratio 1.75, 95% CI 1.12-2.74) samples. Here, we perform a genome-wide association study of cardiac magnetic resonance-derived indexed left ventricular mass to identify 11 novel variants and demonstrate that cardiac magnetic resonance-derived and genetically predicted indexed left ventricular mass are associated with incident cardiomyopathy.

Publication types

Research Support, Non-U.S. Gov't
Research Support, N.I.H., Extramural

MeSH terms

Cardiomyopathies*
Deep Learning*
Genome-Wide Association Study
Humans
Magnetic Resonance Imaging, Cine
Magnetic Resonance Spectroscopy
Predictive Value of Tests

Abstract

Publication types

MeSH terms

Grants and funding