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

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.