TY - JOUR
T1 - Predictors of Long-Term Outcomes in Hypertrophic Cardiomyopathy
T2 - The NHLBI HCM Registry
AU - Kramer, Christopher M.
AU - Kolm, Paul
AU - Dimarco, John P.
AU - Desai, Milind Y.
AU - Ho, Carolyn Y.
AU - Kwong, Raymond Y.
AU - Dolman, Sarahfaye F.
AU - Desvigne-Nickens, Patrice
AU - Geller, Nancy
AU - Kim, Dong-Yun
AU - Schulz-Menger, Jeanette
AU - Friedrich, Matthias G.
AU - Maron, Martin S.
AU - Appelbaum, Evan
AU - Link, Mark S.
AU - Francis, Gary S.
AU - Greenberg, Barry
AU - Jerosch-Herold, Michael
AU - Piechnik, Stefan
AU - Mahmod, Masliza
AU - Raman, Betty
AU - Jacoby, Daniel L.
AU - Baldassare, Lauren A.
AU - White, James A.
AU - Chiribiri, Amedeo
AU - Helms, Adam S.
AU - Choudhury, Lubna
AU - Michels, Michelle
AU - Bradlow, William M.
AU - Salerno, Michael
AU - Heitner, Steven B.
AU - Masri, Ahmad
AU - Prasad, Sanjay K.
AU - Mohiddin, Saidi A.
AU - Plein, Sven
AU - Madias, Christopher
AU - Mahrholdt, Heiko
AU - Bucciarelli-Ducci, Chiara
AU - Nightingale, Angus K.
AU - Weinsaft, Jonathan W.
AU - Kim, Han W.
AU - McCann, Gerry P.
AU - van Rossum, Albert
AU - Germans, Tjeerd
AU - Williamson, Eric E.
AU - Geske, Jeffrey B.
AU - Flett, Andrew S.
AU - Dawson, Dana
AU - Mongeon, Francois-Pierre
AU - Olivotto, Iacopo
AU - Crean, Andrew M.
AU - Woo, Anna
AU - Owens, Anjali T.
AU - Anderson, Lisa
AU - Sharma, Sanjay
AU - Biagini, Elena
AU - Newby, David E.
AU - Andre, Florian
AU - Berry, Colin
AU - Kim, Bette
AU - Larose, Eric
AU - Abraham, Theodore P.
AU - Hays, Allison G.
AU - Sherrid, Mark V.
AU - Gelfand, Eli V.
AU - Nagueh, Sherif F.
AU - Rimoldi, Ornella
AU - Camici, Paolo
AU - Elstein, Eleanor
AU - Autore, Camillo
AU - Watkins, Hugh
AU - Weintraub, William S.
AU - Neubauer, Stefan
N1 - Publisher Copyright:
© 2026 American Medical Association.
PY - 2026/6/9
Y1 - 2026/6/9
N2 - 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
AB - 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
UR - https://www.scopus.com/pages/publications/105038816708
U2 - 10.1001/jama.2026.5633
DO - 10.1001/jama.2026.5633
M3 - Article
C2 - 42113540
SN - 0098-7484
VL - 335
SP - 1959
EP - 1969
JO - JAMA
JF - JAMA
IS - 22
ER -