Interaction between alveolar diffusing capacity and B lines in heart failure with preserved ejection fraction – A non-invasive exercise study

Background: Patients with heart failure and preserved ejection fraction (HFpEF) present with elevated left atrial pressures. The elevation in pulmonary venous pressures and lung interstitial fluid accumulation is exacerbated by exercise. An analysis on the lung extravascular fluid (lung B-lines) combined with lung diffusing capacity for carbon monoxide (DLCO) with his subcomponents, alveolar-capillary membrane conductance (Dm) and capillary volume (Vcap) has not been performed. Purpose: To assess the association between resting pulmonary diffusing capacity and exercise-induced pulmonary congestion in HFpEF patients. . Methods: DLCO, Dm and Vcap were measured in 40 stable HFpEF subjects (age = 73 ± 8; BMI = 27,1 ± 4,3 kg/m2) and in healthy controls at rest with parallel assessment of B-lines during combined Stress Echocardiography and Cardiopulmonary Exercise Test (ESE-CPET). B-lines evaluation of both hemithorax was performed at rest and at peak of exercise. Results: Compared to controls, HFpEF group exhibited lower DLCO and Dm at rest and a higher number of B-lines at peak of exercise with a significant correlation observed for HFpEF but not for controls (resting DLCO vs peak B-lines in HFpEF: R = - 0,66, P < 0,001; resting Dm vs peak B-lines in HFpEF: R = - 0,72, P <0,001). We found also a significant negative correlation between Dm at rest with VE/VCO2 slope at CPET (R = - 0,51, P < 0,001), and Dm at rest with E/e' at peak of stress test in HFpEF group (R = - 0,59, P < 0,001), reflecting a ventilatory/perfusion mismatch along with an elevation of left ventricular filling pressures exacerbated by exercise. Conclusions: In HFpEF altered pulmonary gas exchange capacity at rest, and an excessive lung extravascular water at rest and during effort are combinatory factors affecting exercise performance. The true cause-effect relationship between these variables needs to be tested by mechanicistic experimental studies.