Genotype-Phenotype Taxonomy of Hypertrophic Cardiomyopathy.

genotype hypertension hypertrophy magnetic resonance imaging phenotype

Journal

Circulation. Genomic and precision medicine
ISSN: 2574-8300
Titre abrégé: Circ Genom Precis Med
Pays: United States
ID NLM: 101714113

Informations de publication

Date de publication:
28 Nov 2023
Historique:
medline: 28 11 2023
pubmed: 28 11 2023
entrez: 28 11 2023
Statut: aheadofprint

Résumé

Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes, but there is no systematic framework for classifying morphology or assessing associated risks. Here, we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression. We enrolled 436 patients with HCM (median age, 60 years; 28.8% women) with clinical, genetic, and imaging data. An independent cohort of 60 patients with HCM from Singapore (median age, 59 years; 11% women) and a reference population from the UK Biobank (n=16 691; mean age, 55 years; 52.5% women) were also recruited. We used machine learning to analyze the 3-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree. Carriers of pathogenic or likely pathogenic variants for HCM had lower left ventricular mass, but greater basal septal hypertrophy, with reduced life span (mean follow-up, 9.9 years) compared with genotype negative individuals (hazard ratio, 2.66 [95% CI, 1.42-4.96]; We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severity, genetic risk, and outcomes. This approach will be of value in understanding the causes and consequences of disease diversity.

Sections du résumé

BACKGROUND UNASSIGNED
Hypertrophic cardiomyopathy (HCM) is an important cause of sudden cardiac death associated with heterogeneous phenotypes, but there is no systematic framework for classifying morphology or assessing associated risks. Here, we quantitatively survey genotype-phenotype associations in HCM to derive a data-driven taxonomy of disease expression.
METHODS UNASSIGNED
We enrolled 436 patients with HCM (median age, 60 years; 28.8% women) with clinical, genetic, and imaging data. An independent cohort of 60 patients with HCM from Singapore (median age, 59 years; 11% women) and a reference population from the UK Biobank (n=16 691; mean age, 55 years; 52.5% women) were also recruited. We used machine learning to analyze the 3-dimensional structure of the left ventricle from cardiac magnetic resonance imaging and build a tree-based classification of HCM phenotypes. Genotype and mortality risk distributions were projected on the tree.
RESULTS UNASSIGNED
Carriers of pathogenic or likely pathogenic variants for HCM had lower left ventricular mass, but greater basal septal hypertrophy, with reduced life span (mean follow-up, 9.9 years) compared with genotype negative individuals (hazard ratio, 2.66 [95% CI, 1.42-4.96];
CONCLUSIONS UNASSIGNED
We report a data-driven taxonomy of HCM for identifying groups of patients with similar morphology while preserving a continuum of disease severity, genetic risk, and outcomes. This approach will be of value in understanding the causes and consequences of disease diversity.

Identifiants

DOI: 10.1161/CIRCGEN.123.004200 PMID: 38014537
pubmed: 38014537
doi: 10.1161/CIRCGEN.123.004200
doi:

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

e004200

Auteurs

Lara Curran (L)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
ORCID: 0000-0003-1260-3741

Antonio de Marvao (A)

MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
Department of Women and Children's Health (A.d.M.).
British Heart Foundation Centre of Research Excellence, School of Cardiovascular & Metabolic Medicine and Sciences, King's College London, United Kingdom (A.d.M.).
ORCID: 0000-0001-9095-5887

Paolo Inglese (P)

MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
ORCID: 0000-0001-6179-9643

Kathryn A McGurk (KA)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
ORCID: 0000-0002-5445-6906

Pierre-Raphaël Schiratti (PR)

MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
ORCID: 0000-0002-6620-4888

Adam Clement (A)

MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
ORCID: 0000-0001-6073-1831

Sean L Zheng (SL)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
ORCID: 0000-0002-5762-6392

Surui Li (S)

Biomedical Image Analysis Group, Department of Computing (S.L., W.B.).
MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).

Chee Jian Pua (CJ)

National Heart Research Institute Singapore (C.J.P., C.W.L.C., S.A.C.).
ORCID: 0000-0003-4683-3043

Mit Shah (M)

MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).

Mina Jafari (M)

MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
ORCID: 0000-0003-0755-5562

Pantazis Theotokis (P)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
ORCID: 0000-0001-8718-230X

Rachel J Buchan (RJ)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
ORCID: 0000-0003-2490-9289

Sean J Jurgens (SJ)

Department of Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, the Netherlands (S.J.J., C.R.B.).
Cardiovascular Disease Initiative, Broad Institute of MIT and Harvard, Cambridge, MA (S.J.J.).
ORCID: 0000-0002-1605-9782

Claire E Raphael (CE)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
Mayo Clinic Rochester, MN (C.E.R.).
ORCID: 0000-0002-2206-0413

Arun John Baksi (AJ)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
ORCID: 0000-0001-5492-1743

Antonis Pantazis (A)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).

Brian P Halliday (BP)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
ORCID: 0000-0002-5876-1748

Dudley J Pennell (DJ)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
ORCID: 0000-0001-5523-1314

Wenjia Bai (W)

Biomedical Image Analysis Group, Department of Computing (S.L., W.B.).
Department of Brain Sciences, Imperial College London (W.B.).
ORCID: 0000-0003-2943-7698

Calvin W L Chin (CWL)

National Heart Research Institute Singapore (C.J.P., C.W.L.C., S.A.C.).
Department of Cardiology, National Heart Center Singapore (C.W.L.C.).
Cardiovascular Sciences ACP, Duke NUS Medical School, Singapore (C.W.L.C.).
ORCID: 0000-0002-9867-4390

Rafik Tadros (R)

Cardiovascular Genetics Centre, Montreal Heart Institute (R.T.).
Faculty of Medicine, Université de Montréal, QC, Canada (R.T.).
ORCID: 0000-0002-1472-0258

Connie R Bezzina (CR)

Department of Experimental Cardiology, Heart Center, Amsterdam Cardiovascular Sciences, Amsterdam UMC, University of Amsterdam, the Netherlands (S.J.J., C.R.B.).
ORCID: 0000-0002-0633-3514

Hugh Watkins (H)

Radcliffe Department of Medicine, University of Oxford, United Kingdom (H.W.).
ORCID: 0000-0002-5287-9016

Stuart A Cook (SA)

MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
National Heart Research Institute Singapore (C.J.P., C.W.L.C., S.A.C.).
ORCID: 0000-0001-6628-194X

Sanjay K Prasad (SK)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
ORCID: 0000-0002-5637-0727

James S Ware (JS)

National Heart and Lung Institute (L.C., K.A.M., S.L.Z., P.T., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
Royal Brompton and Harefield Hospitals, Guy's and St. Thomas' NHS Foundation Trust (L.C., R.J.B., C.E.R., A.J.B., A.P., B.P.H., D.J.P., S.K.P., J.S.W.).
MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
ORCID: 0000-0002-6110-5880

Declan P O'Regan (DP)

MRC London Institute of Medical Sciences, Imperial College London, Hammersmith Hospital Campus (A.d.M., P.I., K.A.M., P.-R.S., A.C., S.L.Z., S.L., M.S., M.J., P.T., R.J.B., S.A.C., J.S.W., D.P.O.).
ORCID: 0000-0002-0691-0270

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