Predictors of Long-Term Outcomes in Hypertrophic Cardiomyopathy

Importance: Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. Objective: To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. Design, Setting, and Participants: A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. Exposures: Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. Main Outcomes and Measures: The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy-related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. Results: Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate (P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). Conclusions and Relevance: These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. Trial Registration: ClinicalTrials.gov Identifier: NCT01915615.

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Journal
JAMA
Published
2026-05-11
DOI
https://doi.org/10.1001/jama.2026.5633
Primary Topic
Cardiomyopathy and Myosin Studies
Type
article
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article

Predictors of Long-Term Outcomes in Hypertrophic Cardiomyopathy

Sherif F. Nagueh, Andrew Michael Crean, Bette Kim, Angus K. Nightingale et al.
JAMA
Cardiomyopathy and Myosin Studies
article

Predictors of Long-Term Outcomes in Hypertrophic Cardiomyopathy

Sherif F. Nagueh, Andrew Michael Crean, Bette Kim, Angus K. Nightingale, NANCY GELLER, Eleanor Elstein, Patrice Desvigne Nickens, Camillo Autore, William Bradlow, Eric E. Williamson, Andrew Flett, Betty Raman, Christopher M. Kramer, Amedeo Chiribiri, François‐Pierre Mongeon, Saidi Mohiddin, Han W. Kim, Heiko Mahrholdt, Mark S. Link, Sarahfaye Dolman, Lubna Choudhury, Eli V. Gelfand, Tjeerd Germans, Gary S. Francis, John P. DiMarco, Anjali T. Owens, C Bucciarelli-Ducci, S V E N Plein, M Y Desai, J White, C Berry, L Anderson, M G Friedrich, D Dawson, Stefan Piechnik, Sanjay K. Prasad, Daniel L. Jacoby, Albert van Rossum, Ornella Rimoldi, Allison G. Hays, Michael Salerno, Mark V. Sherrid, Dong-Yun Kim, Anna Woo, Hugh Watkins, William S. Weintraub, Martin S. Maron, Paul Kolm, Theodore P. Abraham, Lauren A. Baldassare, Ahmad Masri, Steven B. Heitner, The HCMR Investigators, Eric Larose, Jeanette Schulz-Menger, Carolyn Y. Ho, Masliza Mahmod, Elena Biagini, Barry Greenberg, Paolo Camici, Florian Andre, Michael Jerosch-Herold, Evan Appelbaum, Christopher Madias, Gerry P. McCann, Iacopo Olivotto, David E. Newby, Jonathan W. Weinsaft, Michelle Michels, Stefan Neubauer, Raymond Y. Kwong, Jeffrey B. Geske, Sanjay Sharma, Adam S. Helms
article en

Abstract

Importance: Current risk prediction guidelines for hypertrophic cardiomyopathy predict only sudden cardiac death and are imperfect, leading to avoidable deaths and unnecessary implantable cardioverter defibrillators. Objective: To combine prospectively collected clinical history, imaging, genetic, and biomarker data to improve risk prediction of adverse events in hypertrophic cardiomyopathy. Design, Setting, and Participants: A total of 2750 patients with hypertrophic cardiomyopathy were prospectively enrolled in the registry-based study from 44 sites in North America and Europe with expertise in hypertrophic cardiomyopathy and cardiac magnetic resonance (CMR) imaging. Participants were enrolled from April 1, 2014, to April 7, 2017. Exposures: Patients underwent a health history questionnaire, blood sampling for biomarkers and genotyping, and contrast-enhanced CMR. Patients were followed up yearly by telephone and through records review regarding event documentation. Main Outcomes and Measures: The predefined composite adjudicated primary end point was time to first event for hypertrophic cardiomyopathy-related deaths; nonfatal sustained ventricular arrhythmias (VAs) requiring cardioversion or defibrillation; and left ventricular (LV) assist device implant or heart transplant. A secondary end point was a composite of sudden cardiac death and nonfatal VA events. The elastic-net method identified the most important predictors. Cox proportional hazards regression assessed associations with time to the first end point. Results: Of the 2750 prospectively enrolled patients, 2698 (98%) had analyzable data after 9 were excluded because they had hypertrophic cardiomyopathy phenocopies and 43 withdrew. Of these remaining patients, 1919 (71%) were male, mean age was 50 years (SD, 11 years), and 423 (16%) were from underrepresented racial and minority groups. The mean follow-up was 6.9 years (SD, 2.1 years). The primary event model in 104 patients included LV scar as a percentage of LV mass by late gadolinium enhancement (LGE%; hazard ratio [HR], 1.86; 95% CI, 1.58-2.20; P < .001), LV mass index (HR, 1.09; 95% CI, 1.01-1.17; P = .03), LV end-systolic volume index (HR, 1.28; 95% CI, 1.12-1.46; P < .001 ), all per 10-unit increase, history of heart failure at study entry (HR, 2.89; 95% CI, 1.75-4.77; P < .001), and log N-terminal pro-B-type natriuretic peptide (NT-proBNP; HR, 1.41; 95% CI, 1.17-1.70; P < .001) level per log unit, (C index for all, 0.77). An LGE percentage of the LV mass of 9% or higher substantially increased the primary composite event rate (P = .001). The secondary sudden cardiac death and VA risk factor model (in 69 patients) included LGE%, LV mass index, LV ejection fraction, and log(NT-proBNP) (C index, 0.76). Conclusions and Relevance: These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy. Trial Registration: ClinicalTrials.gov Identifier: NCT01915615.

JAMA
Northwestern University (US), Brigham and Women's Hospital (US), Lahey Hospital and Medical Center (US), Tufts Medical Center (US), Houston Methodist (US), University of Leeds (GB), Beth Israel Deaconess Medical Center (US), Cleveland Clinic (US), Mayo Clinic (US), Johns Hopkins University (US), University of Leicester (GB), Oregon Health & Science University (US), St George's, University of London (GB), University of Calgary (CA), University of California, San Francisco (US), King's College London (GB), Georgetown University (US), University of Toronto (CA), University of Aberdeen (GB), Cornell University (US), Heidelberg University (DE), University of Michigan (US), Queen Elizabeth Hospital Birmingham (GB), Hospital of the University of Pennsylvania (US), Montreal Heart Institute (CA), University of Minnesota System (US), MedStar Georgetown University Hospital (US), Robert Bosch Hospital (DE), London Chest Hospital (GB), University Hospital Southampton NHS Foundation Trust (GB), University of Manchester (GB), Yale University (US), University of Bristol (GB), University of California San Diego (US), University of Oxford (GB), NYU Langone Health (US), Presbyterian Hospital (US), Royal Brompton Hospital (GB), National Heart, Lung, and Blood Institute (US), Azienda Ospedaliero-Universitaria Careggi (IT), NIHR Southampton Biomedical Research Centre (GB), Duke Medical Center (US), IRCCS Ospedale San Raffaele (IT), Cytokinetics (United States) (US), Men's Health Boston (US), Amsterdam University Medical Centers (NL), Helios Hospital Berlin-Buch (DE), Université Laval (CA), Istituto di Ricovero e Cura a Carattere Scientifico San Raffaele (IT), McGill University (CA), University of Virginia (US), University of Glasgow (GB), The University of Texas Southwestern Medical Center (US), Erasmus University Rotterdam (NL), University of Bologna (IT), University of Edinburgh (GB)
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Cardiomyopathy and Myosin Studies
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