Ordine L; School of Medicine, Naples, Italy.
Canciello G; Di Napoli S; Polizzi R; Pacella D; Lombardi R;
Esposito G; Losi MA

ESC heart failure. 13(1), 2026 Feb 03.

INTRODUCTION: Hypertrophic cardiomyopathy (HCM) is a heterogeneous
myocardial disorder characterized by left ventricular hypertrophy. The
role of cardiopulmonary exercise testing (CPET) in predicting major
adverse cardiac events (MACE) remains incompletely understood,
particularly over long-term follow-up and independently of baseline
symptoms.

METHODS: We longitudinally studied 154 HCM patients (age 43 +/- 16 years;
27% female), who underwent symptom-limited CPET. At baseline, 98 patients
were in New York Heart Association (NYHA) Class I, 48 in Class II, and 8
in Class III. Septal reduction therapies (SRT), progression to end-stage
HCM (ES-HCM), sudden cardiac death (SCD), heart failure-related death
(HF), and heart transplantation (HT) represented a composite MACE
endpoint.

RESULTS: Over a mean follow-up of 12 +/- 9 years, 38 patients experienced
MACE (SRT = 9; ES-HCM = 11; SCD = 10; HF/HT = 8). In multivariable
analysis, independent predictors of MACE were percentage predicted peak
VO2 (PVO2%) < 60 [hazard ratio (HR) 4.16, 95% confidence interval (CI)
1.89-9.14; P < .001], and NYHA Class >I (HR 2.27, 95% CI 1.06-4.89; P =
.036). By using SRT as a competing risk, the only predictor of MACE became
PVO2% < 60 (HR 3.966, 95% CI 1.626-9.670; P = .002). Among asymptomatic
patients (i.e. NYHA Class I), only PVO2% < 60 remained a significant
predictor of MACE (HR 5.611, 95% CI 1.635-19.253; P = .006), with risk
divergence evident after nearly 15 years of follow-up. The result was also
confirmed in the competing risk analysis.

CONCLUSION: In this long follow-up study, CPET is a powerful prognostic
tool in HCM. A reduced peak VO2 identifies those at higher risk,
highlighting the potential for CPET to improve risk stratification, even
among patients classified as NYHA Class I.