Breaking down the recovery of O2 pathway: Peripheral extraction recovery pattern defines exercise capacity and clinical outcomes

Abstract

Poor recovery pattern of oxygen consumption (V̇O2) post-exercise is associated with adverse clinical outcomes. However, it remains unknown which component of the O2 pathway (Fick principle) defines this prognostic risk, for example, peripheral extraction, stroke volume, heart rate. Retrospective cohort study included 120 participants (heart failure with preserved ejection fraction: HFpEF = 68, pre-capillary pulmonary hypertensio n = 31, non-cardiac dyspnea = 21). Percent recovery metrics were calculated as the percent reduction of each hemodynamic variable from peak exercise to recovery, for example, (exercise-recovery)/exercise ×100%. Overall, the mean age (standard deviation) was 62.6 (14.4) years and 54% were females. Among the three groups (HFpEF, pre-capillary pulmonary hypertension, non-cardiac dyspnea), recovery patterns of O2 pathway components were statistically non-significant. Peripheral extraction recovery (r2 = 0.43, p < 0.001) and heart rate recovery (r2 = 0.25, p < 0.001) correlated with peak V̇O2, but only peripheral extraction recovery remained significant in multivariate analysis (p = 0.01). Peripheral extraction recovery (<41%; median) demonstrated poor one-year survival from mortality and heart failure hospitalizations (HR 2.82; CI 95% 1.38–5.74, p = 0.003). Peripheral extraction recovery pattern is the most significant component of the O2 pathway and defines adverse outcomes. Physiologically, it elucidates the importance of skeletal muscle and peripheral vascular function.