Long-Term Prognostic Value of Cardiopulmonary Exercise Testing in Patients with Hypertrophic Cardiomyopathy

Abstract Aims Hypertrophic cardiomyopathy (HCM) is a heterogeneous myocardial disorder characterized by left ventricular (LV) 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 and Results We longitudinally studied 154 HCM patients (age 43±16 years; 27% female), who underwent symptom-limited CPET. At baseline, 98 patients were in 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. 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 (HR 4.16, 95%CI 1.89–9.14; p 0.001), and NYHA class I (HR 2.27, 95%CI 1.06–4.89; p=0.036). 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=0.002). 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 0.006), with risk divergence evident after nearly 15 years of follow-up. The result was also confirmed in the competing risk analysis. Conclusions 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.