Abstract 17780: Pulmonary Arterial Aldosterone Levels Associate with Impaired Cardiac Reserve Capacity During Exercise in Left Ventricular Systolic Heart Failure Patients

Abstract

Elevated pulmonary arterial aldosterone levels (PA-ALDO) are associated with decreased exercise capacity in pulmonary hypertension patients despite normal left ventricular (LV) function. Pulmonary endothelial ALDO synthesis occurs in vitro under experimental conditions akin to LV systolic heart failure (HFrEF); however, the relevance of PA-ALDO to the clinical profile of HFrEF is not known. Therefore, we analyzed PA and radial arterial plasma in control and HFrEF patients to assess for transpulmonary ALDO release and determine if circulating ALDO is related to hemodynamic indices of cardiac reserve capacity during exercise. Data from 20 controls (51 ± 13 y, 13 females, LVEF=0.66 ± 0.9, volume of oxygen uptake at peak exercise [pVO2]=94.1 ± 11.5 % predicted) and 42 consecutive HFrEF patients (57 ± 13 y, 20 females, LVEF=0.36 ± 0.1, pVO2=47.1 ± 2.5 % predicted) undergoing invasive cardiopulmonary exercise testing were analyzed. At rest, HFrEF patients had increased PA-ALDO (714 ± 450 vs. 380 ± 187 ng/dl, P<0.001) and radial ALDO levels (796 ± 483 vs. 371 ± 175 ng/dl, P<0.001) compared to controls. Transpulmonary ALDO release (radial ALDO - PA-ALDO) was increased significantly in HFrEF at rest (+82 ± 20, P=0.02) and a trend was present with exercise (+62 ± 21, P=0.08). Although in controls, transpulmonary ALDO release levels were not significantly increased at rest (-9 ± 8, P=NS) or with exercise (+48 ± 13, P=NS), levels differed significantly between groups at rest and exercise (P<0.05 for both). By contrast, an incremental increase at peak exercise was present in PA-ALDO by 16.3% (P<0.01) and 9.2% (P<0.02) for controls and HFrEF patients, respectively, but there was no significant change in levels between groups. We next explored the relationship between ALDO and cardiovascular reserve capacity measures. After controlling for age and weight in the overall cohort, resting PA-ALDO levels correlated with pVO2 (Spearman coefficient -0.37, P<0.01), peak cardiac output (-0.36, P<0.01), and resting mean PA pressure (0.36, P<0.01). Collectively, these findings identify transpulmonary ALDO release as a novel characteristic of HFrEF and suggest that increased PA-ALDO in patients merits further investigation as a potential marker of impaired cardiac reserve capacity.