Vecchiato M; University Hospital of Padova,  Padova, Italy
Neunhaeuserer D; Zanardo E; Quinto G; Battista F; Aghi A;
Palermi S; Babuin L; Tessari C; Guazzi M; Gasperetti A; Ermolao A

Clinical Research in Cardiology. 115(3):412-423, 2026 Mar.

BACKGROUND AND AIMS: Transient increases (overshoot) in respiratory gas
analyses have been observed during exercise recovery, but their clinical
significance is not clearly understood. An overshoot phenomenon of the
respiratory exchange ratio (RER) is commonly observed during recovery from
maximal cardiopulmonary exercise testing (CPET), but it has been found
reduced in patients with heart failure with reduced ejection fraction
(HFrEF). The aim of the study was to analyze the clinical significance of
these RER recovery parameters and to understand if these may improve the
risk stratification of patients with HFrEF.

METHODS: This cross-sectional study includes HFrEF patients who underwent
functional evaluation with maximal CPET for the heart transplant checklist
at our Sports and Exercise Medicine Division. RER recovery parameters,
including RER overshoot as the percentual increase of RER during recovery
(RER mag), have been evaluated after CPET with assessment of hard clinical
long-term endpoints (MACEs/deaths and transplant/LVAD-free survival).

RESULTS: A total of 190 patients with HFrEF and 103 controls were
included (54.6 +/- 11.9 years; 73% male). RER recovery parameters were
significantly lower in patients with HFrEF compared to healthy subjects
(RER mag 24.8 +/- 14.5% vs 31.4 +/- 13.0%), and they showed significant
correlations with prognostically relevant CPET parameters. Thirty-three
patients with HFrEF did not present a RER overshoot, showing worse
cardiorespiratory fitness and efficiency when compared with those patients
who showed a detectable overshoot (VO2 peak: 11.0 +/- 3.1 vs 15.9 +/- 5.1
ml/kg/min; VE/VCO2 slope: 41.5 +/- 8.7 vs 32.9 +/- 7.9; DELTAPETCO2: 2.75
+/- 1.83 vs 4.45 +/- 2.69 mmHg, respectively). The presence of RER
overshoot was associated with a lower risk of cardiovascular events and
longer transplant-free survival.

CONCLUSION: RER overshoot represents a meaningful cardiorespiratory index
to monitor during exercise gas exchange evaluation; it is an easily
detectable parameter that could support clinicians to comprehensively
interpreting patients’ functional impairment and prognosis. CPET recovery
analyses should be implemented in the clinical decision-making of advanced
HF.