Friedrich, M G

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

Abstract Introduction Cardiovascular magnetic resonance (CMR) imaging enables precise, non-invasive assessment of cardiac structure and function, yet the clinical utility of CMR metrics is limited by the lack of comprehensive, population-specific reference values. By directly reanalyzing data from a large, multi-ethnic cohort rather than relying solely on pooled literature, could enable the establishment of standardized reference ranges and severity grading thresholds. Aim To provide comprehensive, age-, sex-, and ethnicity-stratified CMR reference ranges and severity grading thresholds for key ventricular and atrial parameters. Methods We analyzed over 9,000 CMR scans from the Healthy Hearts Consortium (HHC), comprising six international cohorts. All individuals were free from overt cardiovascular disease and major comorbidities, ensuring a verified healthy sample. Two automated segmentation software solutions—cvi42 (Circle Cardiovascular Imaging) and suiteHEART (Neosoft)—were used to quantify left and right ventricular volumes, myocardial mass, and atrial volumes in standard cine stacks. All endorsed segmentation modes were applied. Quality control protocol combined expert visual review and statistical outlier analysis. We derived 95% prediction intervals (PI) to define the normal range, with additional severity thresholds for mild (95–99.73% PI), moderate (99.73–99.99% PI), and severe (>99.99% PI) deviation from the reference range. Results The final dataset comprised of 9,059 verified healthy adults aged 18–83 years (mean 61 ± 13 years), with a near-equal sex distribution (51% women). Demographics included White (81.6%), South Asian (5.6%), Mixed/Other (5.3%), Black (3.8%), and Chinese (3.7%) participants. Results demonstrated that sex, age, and ethnicity strongly influenced cardiac indices. Men had higher indexed LV and RV volumes and greater myocardial mass than women. Black participants presented the highest indexed LV myocardial mass across age groups, whereas Chinese participants had comparatively lower myocardial mass values (Figure 1). In contrast, atrial volumes remained relatively stable across age categories. Comparative analysis showed minor differences between the two software tools, particularly for atrial parameters; however, derived ejection fractions remained consistent. We established age-, sex-, and ethnicity-stratified reference ranges for key CMR parameters. To facilitate clinical interpretation, we defined severity thresholds corresponding to mild, moderate, and severe abnormalities. Conclusion This large-scale, international effort addresses prior limitations in CMR interpretation by offering robust, contemporary reference ranges and severity grading applicable to diverse populations and imaging protocols. Our severity grading thresholds support consistency in clinical reporting and decision-making, enabling clearer identification of early subclinical changes and more accurate monitoring of disease progression.Subset of CMR value ranges in females