Prognostic value of symptom-limited cardiopulmonary exercise testing outcomes on composite clinical outcomes and echocardiographic remodeling in patients with heart failure: a prospective cohort study
W Chengyi, Y ZhangAbstract
Background
Cardiopulmonary exercise testing (CPET) is a versatile tool for risk stratification in heart failure (HF). While peak oxygen uptake (peakVO2) is a well-established prognostic marker in maximal effort tests, its predictive utility may be diminished in patients limited by symptoms. The prognostic value of different CPET parameters in this population requires further investigation.
Purpose
This study aimed to investigate the predictive value of symptom-limited CPET parameters for adverse composite clinical outcomes and echocardiographic cardiac remodeling in patients with HF.
Methods
This prospective cohort study enrolled 209 patients with NYHA class III or IV. All patients underwent symptom-limited cycle ergometer CPET. Echocardiographic assessments were performed at baseline and at 6-month follow-up. The primary outcome was a hierarchical composite endpoint comprising six ordinal levels: all-cause death or heart transplantation, hospitalization for worsening HF, echocardiographic deterioration, persistent abnormality, improvement without normalization, and maintained or restored normal echocardiographic parameters. Multivariable competing risk models were constructed using oxygen uptake at anaerobic threshold (ATVO2), peakVO2, and the percentage of predicted peakVO2 (peakVO2%pred). Four models were developed with progressive adjustment for demographics, biomarkers, and clinical covariates, with Model 4 based on COX-LASSO variable selection. CPET parameters were also dichotomized by median for win ratio analysis. Model performance was assessed using C-index or win probability (Wp). Restricted cubic spline (RCS) regression was used to examine non-linear relationships.
Results
Over a median follow-up of 458 days, ATVO2, peakVO2, and peakVO2%pred were significant independent predictors of the primary outcome (all p < 0.001). In win ratio analysis, all three dichotomized parameters demonstrated significant predictive ability (Wp: 0.731–0.821). In the optimal COX-LASSO model (Model 4), peakVO2%pred (HR: 0.962; C-index: 0.738) showed the highest predictive value, followed by ATVO2 (HR: 0.778; C-index: 0.735). Continuous peakVO2 (HR: 0.859; C-index: 0.732) exhibited relatively lower predictive performance (Figure1) but, when dichotomized, demonstrated enhanced prognostic value, suggesting a threshold effect. RCS analysis revealed no non-linear relationships (Figure2).
Conclusions
In patients with advanced HF undergoing symptom-limited CPET, ATVO2 is a robust predictor of adverse outcomes and cardiac remodeling, outperforming continuous peakVO2. PeakVO2%pred offers superior prognostic value compared to absolute peakVO2. These findings suggest that for patients with severe HF, exhaustive maximal effort may not be essential for risk stratification; the identification of the anaerobic threshold alone provides sufficient prognostic information. ATVO2 and peakVO2%pred should be prioritized in this population.