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 (VO 2 ) kinetics following peak exercise in individuals with heart failure (HF). Background It is unknown to what extent patterns of VO 2 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, VO 2 recovery delay (VO 2 RD), defined as time until post-exercise VO 2 falls permanently below peak VO 2 , was measured to characterize VO 2 recovery kinetics. Results VO 2 RD 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  2 RD was inversely related to cardiac output augmentation during exercise in HFpEF (ρ = −0.70) and HFrEF (ρ = −0.73, both p  2 RD predicted transplant-free survival in univariate and multivariable Cox regression analysis (Cox hazard ratios: 1.49 and 1.37 per 10-s increase in VO 2 RD, respectively; both p  Conclusions Post-exercise VO 2 RD 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 VO 2 RD may complement established exercise measurements for assessment of cardiac reserve capacity.