Impaired Pulmonary Diffusion in Heart Failure With Preserved Ejection Fraction

Abstract

Background Patients with heart failure and preserved ejection fraction (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. Objectives Compare measures of gas exchange at rest and during exercise in subjects with HFpEF to age and gender-matched controls. Methods HFpEF patients (n=20) and controls (n=26) completed a recumbent cycle ergometry exercise test with simultaneous measurement of ventilation and gas exchange. Diffusion of the lungs for carbon monoxide (DLCO) and subcomponents, pulmonary capillary blood volume (VC) and alveolar-capillary membrane conductance (DM), were measured at rest, matched low-intensity (20W), and peak exercise. Stroke volume was measured by transthoracic echocardiography to calculate cardiac output. Results Compared to controls, HFpEF subjects displayed impaired diastolic function and reduced exercise capacity. HFpEF subjects demonstrated 24% lower DLCO at rest (11.0±2.3 vs 14.4±3.3 mL/mmHg/min, p<0.01), related to reductions in both DM (18.1±4.9 vs 23.1±9.1 mL/mmHg/min, p=0.04), and VC (45.9±15.2. vs 58.9±16.2 mL, p=0.01). DLCO was lower in HFpEF compared to controls in all stages of exercise, yet its determinants showed variable responses. With low-level exercise, HFpEF subjects demonstrated greater relative increases in VC, coupled with heightened ventilatory drive and more severe symptoms of dyspnea compared to controls. At 20W exercise, DM was markedly reduced in HFpEF compared to controls. From 20W to peak exercise, there was no further increase in VC in HFpEF subjects, which in tandem with reduced DM, led to 30% reduction in DLCO at peak exercise (17.3±4.2 vs 24.7±7.1 mL/mmHg/min, p<0.01). Conclusion Patients 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.

Targeting Endothelial Function to Treat Heart Failure with Preserved Ejection Fraction: The Promise of Exercise Training

“…At exercise, diffusion abnormalities are exacerbated in HFpEF patients compared to healthy individuals [98]. These findings provide further evidence that exercise capacity is limited by O 2 diffusion in both the systemic and the pulmonary microcirculation.…”

Phenotype-Specific Treatment of Heart Failure With Preserved Ejection Fraction

“…These impairments become more dramatic during exercise owing to high LV filling pressures during stress 141 . HFpEF patients with increased interstitial pulmonary edema display greater pulmonary vascular abnormalities and RV dysfunction, supporting aggressive therapies to reduce left heart filling pressures chronically in patients with HFpEF 142 .…”

“…Impairments in pulmonary function predict incident development of HFpEF independent of cardiac function 140 . Patients with HFpEF display gas exchange abnormalities manifest by reduced alveolar capillary membrane conductance 141,142 . These impairments become more dramatic during exercise owing to high LV filling pressures during stress 141 .…”

Comparisons of Noninvasive Methods Used to Assess Exercise Stroke Volume in Heart Failure with Preserved Ejection Fraction

“…By contrast, perfusion sensitive inert gas pulmonary uptake techniques involving for example, acetylene (C 2 H 2 ) (Bunsen solubility coefficient in blood is 0.740, ~two times that of carbon dioxide [CO 2 , 0.470] or nitrous oxide [N 2 O, 0.405] (8, 15, 16, 36)) have demonstrated utility for objectively measuring Q and SV at rest and/or exercise in adults across the health spectrum (2, 13, 16, 33). Nevertheless, while observations from validation studies support the usefulness of inert gas uptake methods for measuring Q and SV in patients demonstrating overt cardiac and/or pulmonary limitations (2, 13, 16, 33), we acknowledge that marked perturbations in specific factors (e.g., low lung diffusing capacity (17, 30)) affecting ventilation-perfusion (V A /Q ) matching could render results from these approaches open to question. Likewise, any factor disturbing V A /Q matching influential to inert gas uptake methods would affect interpretability of oxygen pulse (O 2 pulse), which has been validated for predicting exercise SV given invariability in AVO 2 and heart rate (HR) (37, 40).…”