Vascular Dysfunction in Heart Failure with Preserved Ejection Fraction

Abstract

Heart failure (HF) with preserved ejection fraction (HFPEF) is the fastest growing form of HF and is nearly exclusively found in older persons, particularly women, in whom 90% of new HF cases are HFPEF. Although these patients often have frequent episodes of acute decompensation, even when stable and compensated, the primary symptom in chronic HFPEF is severe exercise intolerance, which can be measured objectively as decreased pulmonary oxygen uptake during peak aerobic exercise (peak VO2), and is associated with their severely reduced quality of life. In accordance with the Fick principle (VO2 = cardiac output [CO] × arterial venous oxygen content difference [a-vO2diff]), the reduced peak VO2 in HFPEF patients may be due to impairments in cardiac, vascular, and/ or skeletal muscle function that result in decreased oxygen delivery to and/or utilization by the active skeletal muscles. Understanding the relative contributions of these factors to reduced exercise capacity requires their measurement during exercise along with VO2. Using upright exercise with expired gas analysis and simultaneous echocardiographic measurement of left ventricular volumes, our group reported that the lower peak VO2 in older HFPEF patients vs age-matched healthy subjects was due not only to reduced exercise cardiac output, but also to an equal contribution of reduced systemic a-vO2diff. Moreover, the rest to peak exercise change in a-vO2diff was the strongest independent predictor of peak VO2