Willixhofer R; Centro Cardiologico Monzino, IRCCS Milan Italy.
Mapelli M; Baracchini N; Campana N; Capovilla TM; Nava A;
Salvioni E; Vignati C; Rubbo FM; Magri D; Fiori E; Pezzuto B; Mattavelli
I; Apostolo A; Palermo P; Campodonico J; Contini M; Costantino S; Carriere
C; Tavcar I; Rossi M; Cadeddu Dessalvi C; Merlo M; Sinagra G; Agostoni P

Journal of the American Heart Association. 15(8):e046438, 2026 Apr 21.

BACKGROUND: The RoMa classification, based on peak heart rate and oxygen
pulse derived from cardiopulmonary exercise testing, was recently proposed
to stratify patients with hypertrophic cardiomyopathy by physiological
reserve during exercise. We aimed to externally validate RoMa in an
independent multicenter cohort with hypertrophic cardiomyopathy and assess
its association with long-term clinical outcomes.

METHODS: In this retrospective multicenter cohort study patients with
hypertrophic cardiomyopathy, undergoing cardiopulmonary exercise testing,
were consecutively enrolled. Patients were enrolled regardless of left
ventricular outflow tract obstruction and were naive to disease-specific
therapy (eg, mavacamten). Patients were categorized into RoMa I to IV
based on percentage of predicted heart rate and oxygen pulse. The primary
end point was a composite of all-cause and cardiovascular death, sudden
cardiac death, or aborted sudden cardiac death, heart failure-related
hospitalization, stroke, systemic embolism, surgical myectomy, and heart
transplantation.

RESULTS: The study included 292 patients (age 51 [36-63] years, 70% male
sex, 30% with obstructive left ventricular outflow tract). Functional
capacity declined hierarchically across RoMa groups (peak oxygen uptake
29.2 to 17.9 mL/kg/min; P-trend <0.001). During follow-up (=6 years), 68
composite events occurred. Kaplan-Meier analysis showed significant
differences in event-free survival across groups (log-rank P=0.019). In
multivariable analysis, RoMa II to IV compared with RoMa I were
independently associated with higher hazard ratios (HRs) for the composite
outcome (HRs, 3.89-5.37; all P<0.05), whereas genotype, LVEF <50%, male
sex, and left ventricular outflow tract obstruction were not predictive.

CONCLUSIONS: The RoMa classification independently predicts long-term,
clinically relevant outcomes in hypertrophic cardiomyopathy regardless of
left ventricular outflow tract obstruction and may provide a novel
approach to risk stratification.