JAMA
Cardiac MRI, blood test sharpen risk prediction in hypertrophic cardiomyopathy
Clinical Takeaway: Routine cardiac MRI and a common blood biomarker may identify patients headed not just for sudden death but for heart failure, sustained arrhythmias, and transplant, outcomes current calculators miss entirely.
Hypertrophic cardiomyopathy (HCM) affects roughly 1 in 500 people and is a leading cause of sudden cardiac death in young adults, but the narrow focus of existing risk tools leaves clinicians without good ways to anticipate other serious events. This prospective study tested whether adding imaging, blood biomarkers, and genotyping to clinical history could give a fuller picture of who is most at risk.
Myocardial scar visible on cardiac MRI emerged as the strongest single predictor of negative outcomes. Late gadolinium enhancement, the imaging signal for scarred heart muscle, was tied to nearly doubled risk of the primary composite (HCM-related death, sustained ventricular arrhythmias, and LV assist device or transplant) for each 10-percentage-point rise in scar burden. A scar burden of 9% or more of left ventricular mass marked a sharp jump in event rates.
A history of heart failure at enrollment nearly tripled risk, and higher NT-proBNP independently predicted events. Left ventricular mass and end-systolic volume also added incremental value. NT-proBNP rises when heart muscle is stretched or working against elevated pressure, reflecting the diastolic dysfunction and outflow obstruction that drive much of the harm in HCM but may not be fully visible on a structural scan.
The same tools also outperformed for sudden cardiac death and ventricular arrhythmias. Genotype, despite being part of the assessment battery, did not emerge as an independent predictor in the final models, suggesting that imaging and biomarkers may carry more practical risk information.
The Hypertrophic Cardiomyopathy Registry enrolled 2,750 patients across 44 sites in North America and Europe with expertise in HCM and cardiac imaging, with analyzable data on 2,698. Mean age was 50 years, 71% were male, and 16% were from underrepresented racial and minority groups. Patients underwent a health history questionnaire, blood sampling, genotyping, and contrast-enhanced cardiac MRI, then were followed for a mean of 6.9 years.
The findings argue for routine integration of cardiac MRI and NT-proBNP into HCM evaluation, both to flag patients headed for heart failure or transplant and to refine decisions about implantable defibrillators, where current guidelines can lead to avoidable deaths from both under-implantation and unnecessary device placements.
Next steps include validating the model in independent cohorts and translating it into a usable bedside risk calculator that incorporates cardiac MRI and NT-proBNP alongside clinical history.
"Current risk prediction guidelines for hypertrophic cardiomyopathy are imperfect, as they predict only sudden cardiac death, and not heart failure or other fatal and nonfatal cardiac adverse events," said principal investigator Christopher Kramer, MD, cardiologist at the Heart and Vascular Center of the University of Virginia Health System. "This study is a major advance in that it provides evidence that incorporating these additional assessment methods better predicts risk of adverse outcomes."
Source: Kramer C. JAMA. 2026 May 11. Predictors of Long-Term Outcomes in Hypertrophic Cardiomyopathy: The NHLBI HCM Registry