title: Elevated pulmonary arterial and systemic plasma aldosterone levels associate with impaired cardiac reserve capacity during exercise in left ventricular systolic heart failure patients: A pilot study.
abstract: BACKGROUND
  Elevated levels of aldosterone are a modifiable contributor to clinical worsening in heart failure with reduced ejection fraction (HFrEF). Endothelin-1 (ET-1), which is increased in HFrEF, induces pulmonary endothelial aldosterone synthesis in vitro. However, whether transpulmonary aldosterone release occurs in humans or aldosterone relates to functional capacity in HFrEF is not known. Therefore, we aimed to characterize ET-1 and transpulmonary aldosterone levels in HFrEF and determine if aldosterone levels relate to peak volume of oxygen uptake (pVO2).
  
  
  METHODS
  Data from 42 consecutive HFrEF patients and 18 controls referred for invasive cardiopulmonary exercise testing were analyzed retrospectively.
  
  
  RESULTS
  Radial ET-1 levels (median [interquartile range]) were higher in HFrEF patients compared with controls (17.5 [11.5-31.4] vs 11.5 [4.4-19.0] pg/ml, p = 0.04). A significant ET-1 transpulmonary gradient (pulmonary arterial [PA] - radial arterial levels) was present in HFrEF (p < 0.001) but not in controls (p = 0.24). Compared with controls, aldosterone levels (median [interquartile range]) were increased in HFrEF patients in the PA (364 [250-489] vs 581 [400-914] ng/dl, p < 0.01) and radial compartments (366 [273-466] vs 702 [443-1223] ng/dl, p < 0.001). Akin to ET-1, a transpulmonary increase (median [interquartile range]) in aldosterone concentration was also observed between controls and HFrEF patients at rest (7.5 [-54 to 40] vs 61.6 [-13.6 to 165] ng/dl, p = 0.01) and peak exercise (-20.7 [-39.6 to 79.1] vs 25.8 [-29.2 to 109.3] ng/dl, p = 0.02). The adjusted pVO2 correlated inversely with aldosterone levels at peak activity in the PA (r = -0.31, p = 0.01) and radial artery (r = -0.32, p = 0.01).
  
  
  CONCLUSIONS
  These data provide preliminary evidence in support of increased transpulmonary aldosterone levels in HFrEF and suggest an inverse relationship between circulating aldosterone and pVO2. Future prospective studies are needed to characterize the functional effects of transpulmonary and circulating aldosterone on cardiac reserve capacity in HFrEF.
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts; Department of Cardiology, Veterans Affairs Boston Healthcare System, West Roxbury, Massachusetts.
authors.forename: Bradley A
authors.initials: BA
authors.lastname: Maron
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Thomas E
authors.initials: TE
authors.lastname: Stephens
authors.affiliation: Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Laurie A
authors.initials: LA
authors.lastname: Farrell
authors.affiliation: Division of Pulmonary and Critical Care Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: William M
authors.initials: WM
authors.lastname: Oldham
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Joseph
authors.initials: J
authors.lastname: Loscalzo
authors.affiliation: Division of Cardiovascular Medicine, Department of Medicine, Brigham and Women's Hospital and Harvard Medical School, Boston, Massachusetts.
authors.forename: Jane A
authors.initials: JA
authors.lastname: Leopold
authors.affiliation: Division of Cardiology, Massachusetts General Hospital and Harvard Medical School, Boston, Massachusetts. Electronic address: glewis@partners.orrg.
authors.forename: Gregory D
authors.initials: GD
authors.lastname: Lewis
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000450:Aldosterone / Q000097:blood*; D019332:Endothelin-1 / Q000097:blood; D015444:Exercise; D005260:Female; D053805:Fractional Flow Reserve, Myocardial; D054143:Heart Failure, Systolic / Q000097:blood* / Q000503:physiopathology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D010865:Pilot Projects; D011651:Pulmonary Artery; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D019332:Endothelin-1; D000450:Aldosterone
keywords: aldosterone; cardiac reserve; exercise; heart failure; reduced ejection fraction