Impaired Pulmonary Diffusion in Heart Failure With Preserved Ejection Fraction

Objectives: The purpose of this study was to compare measures of gas exchange at rest and during exercise in patients with heart failure and preserved ejection fraction (HFpEF) with age- and sex-matched control subjects. Background: Patients with HFpEF display elevation in left heart pressures, but it is unclear how this affects pulmonary gas transfer or its determinants at rest and during exercise. Methods: Patients with HFpEF (n = 20) and control subjects (n = 26) completed a recumbent cycle ergometry exercise test with simultaneous measurement of ventilation and gas exchange. Diffusion of the lungs for carbon monoxide (DL_CO) and its subcomponents, pulmonary capillary blood volume (V_C) and alveolar-capillary membrane conductance (D_M), were measured at rest, and matched for low-intensity (20 W) and peak exercise. Stroke volume was measured by transthoracic echocardiography to calculate cardiac output. Results: Compared with control subjects, patients with HFpEF displayed impaired diastolic function and reduced exercise capacity. Patients with HFpEF demonstrated a 24% lower DL_CO at rest (11.0 ± 2.3 ml/mm Hg/min vs. 14.4 ± 3.3 ml/mm Hg/min; p < 0.01) related to reductions in both D_M (18.1 ± 4.9 ml/mm Hg/min vs. 23.1 ± 9.1 ml/mm Hg/min; p = 0.04), and V_C (45.9 ± 15.2. ml vs. 58.9 ± 16.2 ml; p = 0.01). DL_CO was lower in patients with HFpEF compared with control subjects in all stages of exercise, yet its determinants showed variable responses. With low-level exercise, patients with HFpEF demonstrated greater relative increases in V_C, coupled with heightened ventilatory drive and more severe symptoms of dyspnea compared with control subjects. At 20-W exercise, D_M was markedly reduced in patients with HFpEF compared with control subjects. From 20 W to peak exercise, there was no further increase in V_C in patients with HFpEF, which in tandem with reduced D_M, led to a 30% reduction in DL_CO at peak exercise (17.3 ± 4.2 ml/mm Hg/min vs. 24.7 ± 7.1 ml/mm Hg/min; p < 0.01). Conclusions: Subjects with HFpEF display altered pulmonary function and gas exchange at rest and especially during exercise, which contributes to exercise intolerance. Novel therapies that improve gas diffusion may be effective to improve exercise tolerance in patients with HFpEF.