In patients with hypertrophic cardiomyopathy (HCM), genotype, peak VO₂, log NT-proBNP and LVEF independently predict heart failure (HF) outcomes, and combining these measures identified patients at higher risk of HF-related death or transplant, according to a recent study published in JACC: Heart Failure.

Athanasios Bakalakos, MD, et al., included 505 patients with HCM (mean age 52 years, 33% women) who were stratified into gene-positive (G+) and gene-elusive (G–) groups and followed for a median follow-up of 10.6 years. The study's primary endpoint was HF-related death or cardiac transplantation.

Overall, 6.7% of patients experienced the primary endpoint, making up 12.8% of the G+ group and 2.4% of the G– group. G+ status (hazard ratio [HR], 5.86; 95% CI, 2.26-15.25; p < 0.001), peak VO₂ (HR, 0.90; 95% CI, 0.82-0.98; p<0.001), log NT-proBNP (HR, 2.46; 95% CI, 1.59-3.80; p<0.001), and LVEF (HR, 0.74 per 5% increment; 95% CI, 0.63-0.86; p<0.001) were all independently associated with HF outcomes.

Secondary analyzes looked at cardiac death, arrhythmic events and all-cause mortality, which occurred in 11.9%, 6.7% and 22.8% of patients, respectively.

"These findings suggest that integration of genotype with established clinical markers of hemodynamic stress, systolic performance, and functional capacity may help identify patients at higher risk of HF progression," note the authors. "However, the model should be viewed primarily as an exploratory framework for risk stratification, which will also inform larger studies, rather than a definitive clinical prediction tool."