Abstract 16004: Clinical and Hemodynamic Correlates of Exaggerated Metabolic Cost of Exercise Initiation

Introduction: Exercise intolerance is common in cardiovascular disease and is a cardinal manifestation of heart failure with preserved ejection fraction (HFpEF). Decreased exercise capacity is often attributed to cardiac limitations, though HFpEF is increasingly recognized to be both a metabolic and a cardiovascular disorder. Hypothesis: Patients with HFpEF will have exaggerated metabolic cost of exercise initiation with associated high expenditure of hemodynamic reserve capacity. Methods: We quantified the workload-equivalent cost of initiating exercise using cardiopulmonary exercise testing in patients with HFpEF (N=184, age 62±13, 47% women, peak VO2 13.8±3.3 ml/kg/min). Individualized VO2-work rate relationships during loaded exercise were used to derive the work-equivalents required to move extremities with zero external resistance (0 watts)—termed “internal work” (IW). Standard linear regression techniques were used for comparisons. Results: In individuals with HFpEF, the internal work (42±28 W) was often a large portion of the total workload achieved. BMI accounted for the greatest variance in IW (23%), suggesting a metabolic basis for IW. Resting measures of myocardial function and biventricular filling pressures did not measurably contribute to explanatory variance in IW, suggesting a non-cardiac origin. Individuals with HFpEF in the fourth quartile of IW (76±28W) had a dramatic hemodynamic response to exercise in pulmonary capillary wedge and mean pulmonary arterial pressures. Changes in hemodynamic measurements were more modest between quartiles of IW in the submaximal ramp period following unloaded exercise. Conclusions: Internal work is a new measure that captures the metabolic cost of initiating movement. Internal work is associated with limitations in achievable external workload as well as steep early increases in cardiac filling pressures in HFpEF. Further investigation into the pathophysiology of elevated IW is needed.