CMR Imaging, NT-proBNP Improve Risk Prediction in Hypertrophic Cardiomyopathy

Cardiac magnetic resonance (CMR) imaging markers and blood biomarkers may significantly improve risk prediction in hypertrophic cardiomyopathy (HCM), potentially helping clinicians better identify patients at risk for adverse cardiovascular outcomes beyond current guideline-based tools, according to new research.¹

The findings, published in JAMA, stem from a large international registry-based study of 2698 patients with HCM followed for nearly 7 years across 44 specialized centers in North America and Europe. Investigators found that measures of left ventricular (LV) scar burden, LV structure and function, heart failure history, and levels of N-terminal pro–B-type natriuretic peptide (NT-proBNP) were among the strongest predictors of major adverse outcomes.

“These results provide prospective evidence for incorporating CMR and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy,” wrote the researchers of the study.

Current risk stratification guidelines for HCM largely focus on predicting sudden cardiac death (SCD), often to guide implantable cardioverter defibrillator (ICD) placement decisions. However, these tools remain imperfect and may lead to unnecessary ICD implantation in some patients while failing to identify others at elevated risk.

The study prospectively enrolled 2750 patients with HCM between 2014 and 2017. After excluding patients with HCM phenocopies and withdrawals, 2698 participants were included in the final analysis. The cohort was predominantly male (71%), with a mean (SD) age of 50 (11) years. Investigators collected baseline clinical histories, blood biomarkers, genotyping data, and contrast-enhanced CMR imaging results.

The predefined primary composite end point included HCM-related death, nonfatal sustained ventricular arrhythmias requiring cardioversion or defibrillation, LV assist device implantation, or heart transplantation. During a mean (SD) follow-up of 6.9 (2.1) years, 104 patients experienced a primary outcome event.

Among the strongest predictors of adverse outcomes was the percentage of LV scar detected by late gadolinium enhancement (LGE) on CMR imaging. Each 10-unit increase in LGE percentage was associated with an 86% increased risk of the primary composite outcome (HR, 1.86; 95% CI, 1.58-2.20; P < .001). Investigators also found that an LGE burden of at least 9% of LV mass substantially increased event rates.

Other significant predictors included LV mass index, LV end-systolic volume index, prior heart failure history, and elevated NT-proBNP levels. The resulting prediction model demonstrated strong discriminatory performance, with a C-index of 0.77.

For the secondary outcome of SCD and ventricular arrhythmias, predictors included LGE percentage, LV mass index, LV ejection fraction, and NT-proBNP levels.

Integrating Imaging and Biomarker Data Into Future Risk Prediction Strategies

The findings align with prior evidence supporting the prognostic value of myocardial fibrosis in HCM. A 2023 scientific statement from the American Heart Association noted that extensive LGE identified on CMR is increasingly recognized as an important marker of arrhythmic risk and disease progression in patients with HCM.²

Although genetic testing was included in the study, genetic variables did not emerge among the strongest independent predictors in the final risk models.¹ The authors suggested that phenotypic disease expression captured through imaging and biomarkers may currently provide greater prognostic utility.

The study has several implications for clinical practice, particularly as HCM management becomes increasingly personalized. Incorporating advanced imaging and biomarker assessment into routine evaluations may help clinicians identify patients who could benefit from closer surveillance, earlier intervention, or ICD placement.

Still, the investigators noted that additional validation studies will be needed before these findings are incorporated into future guideline recommendations.

“These results provide prospective evidence for incorporating cardiac magnetic resonance and NT-proBNP in the evaluation of patients with hypertrophic cardiomyopathy,” wrote the researchers.

References

1. The HCMR Investigators. Predictors of long-term outcomes in hypertrophic cardiomyopathy: the NHLBI HCM registry. JAMA. Published online May 11, 2026. doi:10.1001/jama.2026.5633

2. Ommen SR, Mital S, Burke MA, et al. 2023 AHA/ACC guideline for the diagnosis and treatment of hypertrophic cardiomyopathy. Circulation. 2023;148(5):e123-e245. doi:10.1161/CIR.0000000000001115