Post-Exercise Oxygen Uptake Recovery Delay: A Novel Index of Impaired Cardiac Reserve Capacity in Heart Failure

Abstract

Objectives: This study sought to characterize the functional and prognostic significance of oxygen uptake (VO₂) kinetics following peak exercise in individuals with heart failure (HF).

Background: It is unknown to what extent patterns of VO₂ recovery following exercise reflect circulatory response during exercise in HF with preserved ejection fraction (HFpEF) and HF with reduced ejection fraction (HFrEF).

Methods: We investigated patients (30 HFpEF, 20 HFrEF, and 22 control subjects) who underwent cardiopulmonary exercise testing with invasive hemodynamic monitoring and a second distinct HF cohort (n = 106) who underwent noninvasive cardiopulmonary exercise testing with assessment of long-term outcomes. Fick cardiac output (CO) and cardiac filling pressures were measured at rest and throughout exercise in the initial cohort. A novel metric, VO₂ recovery delay (VO₂RD), defined as time until post-exercise VO₂ falls permanently below peak VO₂, was measured to characterize VO₂ recovery kinetics.

Results: VO₂RD in patients with HFpEF (median 25 s [interquartile range (IQR): 9 to 39 s]) and HFrEF (28 s [IQR: 2 to 52 s]) was in excess of control subjects (5 s [IQR: 0 to 7 s]; p < 0.0001 and p = 0.003, respectively). VO₂RD was inversely related to cardiac output augmentation during exercise in HFpEF (ρ = -0.70) and HFrEF (ρ = -0.73, both p < 0.001). In the second cohort, VO₂RD predicted transplant-free survival in univariate and multivariable Cox regression analysis (Cox hazard ratios: 1.49 and 1.37 per 10-s increase in VO₂RD, respectively; both p < 0.005).

Conclusions: Post-exercise VO₂RD is an easily recognizable, noninvasively derived pattern that signals impaired cardiac output augmentation during exercise and predicts outcomes in HF. The presence and duration of VO₂RD may complement established exercise measurements for assessment of cardiac reserve capacity.

Keywords: cardiopulmonary exercise testing; exercise hemodynamics; heart failure; recovery kinetics.