Respiratory exchange ratio overshoot during exercise recovery: a novel prognostic marker in heart failure

Abstract Funding Acknowledgements Type of funding sources: None. Background In recent years considerable new evidence has been added on the analysis of the recovery phase in patients with heart failure. Transient increases (overshoot) in respiratory gas variables have been observed during exercise recovery, but their clinical significance is not clearly understood. Respiratory Exchange Ratio (RER) at peak exercise (RER peak) is an objective index of exercise intensity. The overshoot phenomenon of the RER is commonly observed during recovery from maximal cardiopulmonary exercise testing (CPET) but initial studies have found a decreased RER-magnitude in patients with heart failure with reduced ejection fraction (HFrEF). Purpose To characterize the functional and prognostic significance of RER recovery kinetics in individuals with HFrEF. Methods This cross-sectional study included all patients with HFrEF who underwent functional evaluation with maximal CPET for the heart transplant checklist at the Sports and Exercise Medicine Division of the Padova University Hospital between January 2018 and December 2021. The presence of overshoot phenomena of different respiratory gas indices was evaluated during the recovery phase, focusing on the RER. The RER behaviour has been evaluated assessing the maximal value during recovery phase (RER max) and the magnitude of the RER overshoot (RER mag). Results 164 patients with HFrEF and 128 controls were included in the study. RER recovery parameters were significantly lower in patients with HFrEF compared to healthy subjects. The RER overshoot showed significant correlations with prognostically relevant CPET parameters and these RER metrics were significantly higher in patients presenting better ventilatory and Weber classes. 24 patients with HFrEF did not present a RER overshoot showing worse cardiorespiratory fitness and efficiency compared to patients with overshoot. Mean follow-up period was 2.57 years during which there were 55 first major cardiovascular events, 22 deaths, 21 heart transplants, and 9 ventricular assist device implantations. The absence of RER overshoot predicted major adverse cardiac events- and transplant-free survival in univariate and multivariate Cox regression analysis. Conclusions RER overshoot represents a new index to monitor respiratory gas kinetics during the recovery phase, since it is a feasible and reproducible parameter for clinical practice. A reduced overshoot or its absence are significantly associated with functional impairment, cardiorespiratory inefficiency and worse prognosis. Thus, the evaluation of the respiratory gas indices during recovery from maximal CPET should be included in routine test interpretation, particularly for patients with HFrEF.