Abstract Background Impaired exercise capacity is a cardinal feature of heart failure (HF). Peak oxygen uptake (pVO2) and ventilatory efficiency (VE/VCO2 slope) during exercise are well-consolidated prognostic markers in patients with HF. A previous study suggested that abnormally prolonged VO2 recovery, specifically the failure to decrease VO2 from peak exercise by 10.5 mL/kg/min at 180 seconds of the recovery phase, predicts adverse outcomes in HF. However, it is unknown to what extent the recovery of VEqCO2, a marker of ventilation/perfusion mismatch, adds prognostic value to the already existing parameters. Purpose The aim of this study was to characterize the functional and prognostic significance of VEqCO2 kinetics following peak exercise in individuals with HF. Methods This retrospective single-center study included consecutive adult patients with chronic (>3 months) and stable HF with left ventricular ejection fraction (LVEF) <50% who underwent cardiopulmonary exercise testing (CPET) between 2015 and 2020. Following maximal exercise, patients recovered over a 3-minute period (walking 2km/h for 1 minute and sittng passively for 2 minutes). VO2 and VEqCO2 kinetics during recovery, described as the absolute difference to peak VO2 (difVO2) and VEqCO2 (difVEqCO2), were measured at 30, 60, 120, and 180 seconds. Outcomes were assessed as a composite of cardiovascular (CV) death, urgent cardiac transplant, or left ventricular assist device (LVAD) implantation at 1 year. Results A total of 238 patients were included (mean age 58 ± 12 years; 82% males; mean LVEF 34 ± 10%; 68% with ischemic HF; 75% in NYHA class II-III; mean pVO2 18 ± 6 mL/kg/min; mean VE/VCO2 slope 41 ± 12). During the 1-year follow-up, 19 patients met the endpoint (8 CV deaths, 8 urgent heart transplants, and 3 LVAD). ROC curve analysis showed that the best correlation between difVEqCO2 and outcomes was apparent at difVEqCO2 of 180 seconds (AUC 0.83) with a cut-off value of 1 (sensitivity 93%, specificity 58%). These patients, who had a decrease in VEqCO2 (difVEqCO2 >1) at 180 seconds, were significantly older (p=0.02), had a lower LVEF (p<0.001), and higher NYHA (p<0.001). They were at an increased risk of cardiovascular events compared to those with an increase in VEqCO2 (difVEqCO2 <1) at 180 seconds (event-free survival at 1 year 86% vs. 98%, log-rank p<0.001). In multivariate analysis, the statistical association between difVEqCO2 and outcomes remained significant, even after adjusting for difVO2 at 180 seconds (HR 4.315, CI95% (1.349-13.804), p=0.014). Conclusion Abnormal VEqCO2 kinetics in the recovery period of CPET is an easily recognizable non-invasively derived measurement that predicts outcomes in HF. VEqCO2 may complement the evaluation of VO2 and other parameters during recovery to further improve prognostic risk stratification in HF.
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