Beyond peak VO2: prognostic utility of cardiopulmonary exercise testing in ambulatory heart failure
L Lorenzo Alves, J Silva Cardoso, R Rodrigues, S AmorimAbstract
Background
Cardiopulmonary exercise testing (CPET) plays a central role in the functional and prognostic assessment of patients with heart failure (HF). While peak oxygen uptake (VO₂ peak) is the most commonly used parameter, its prognostic utility may be attenuated in patients unable to achieve maximal effort, and the role of complementary CPET-derived indices remains incompletely defined.
Objectives
To evaluate the prognostic value of CPET-derived parameters and their association with clinical severity and outcomes in ambulatory HF patients.
Methods
We conducted a single-centre retrospective cohort study of patients with HF, NYHA (New York Heart Association) class I–IV, INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) profile 4–7, who underwent CPET between January 2023 and September 2025. Patients with prior heart transplantation, LVAD (left ventricular assist device), isolated pulmonary hypertension, hypertrophic or infiltrative cardiomyopathy were excluded. Clinical, laboratory, echocardiographic data and Seattle Heart Failure Model (SHFM) scores were collected from the closest assessment to CPET. The primary outcome was a composite of all-cause mortality, heart transplantation or LVAD implantation.
Results
Eighty-one patients were included (mean age 51.5 ± 13.0 years; 74% male); 41 (50.6%) achieved a maximal CPET. Over a mean follow-up of 577 ± 433 days, 17 patients (21.0%) experienced the primary outcome, including death in 5 patients (6.2%), heart transplantation in 10 (12.3%) and LVAD implantation in 2 (2.5%). Patients with events showed lower VO₂ peak (14.1 ± 3.2 vs 17.9 ± 5.3 mL/kg/min, p = 0.006), circulatory power (1844 ± 553 vs 2569 ± 983, p = 0.005) and peak PetCO₂ (29.4 ± 5.7 vs 36.5 ± 5.6 mmHg, p < 0.001), and higher VE/VCO₂ slope (40.6 ± 8.8 vs 30.9 ± 6.8, p < 0.001). These associations were preserved in patients undergoing submaximal CPET. In multivariable Cox regression, VE/VCO₂ slope emerged as the sole independent CPET-derived predictor of adverse outcomes (HR 1.09 per unit, 95% CI 1.03–1.15; p = 0.002), with no significant interaction with exercise maximality. Overall discriminative performance was good (AUC = 0.78).
Conclusions
CPET provides robust prognostic information in ambulatory HF patients regardless of exercise maximality. Multiple CPET-derived variables, including peak VO₂, circulatory power and PetCO₂, were associated with adverse outcomes; however, ventilatory inefficiency, quantified by VE/VCO₂ slope, emerged as the strongest independent prognostic marker, retaining its predictive value even in submaximal exercise tests. These findings support the use of comprehensive CPET-based risk stratification in routine HF assessment, even when maximal effort is not achieved.ROC curvesFor image description, please refer to the figure legend and surrounding text.