Soluble Angiotensin-Converting Enzyme 2 in Human Heart Failure: Relation With Myocardial Function and Clinical Outcomes

Slava Epelman, Kevin Shrestha, Richard W. Troughton, Gary S. Francis, Subha Sen, Allan L. Klein, W. H. Wilson Tang

Research output: Contribution to journalArticlepeer-review

101 Scopus citations

Abstract

Background: Angiotensin-converting enzyme 2 (ACE2) is an endogenous counterregulator of the renin-angiotensin system. The relationship between soluble ACE2 (sACE2), myocardial function, and clinical outcomes in patients with chronic systolic heart failure is not well established. Methods and Results: We measured sACE2 activity in 113 patients with chronic systolic heart failure (left ventricular ejection fraction [LVEF] ≤35%, New York Heart Association Class II-IV). Comprehensive echocardiography was performed at the time of blood sampling. We prospectively examined adverse clinical events (death, cardiac transplant, and heart failure hospitalizations) over 34 ± 17 months. Patients who had higher sACE2 plasma activity were more likely to have a lower LVEF (Spearman's r = -0.36, P < .001), greater right ventricular systolic dysfunction (r = 0.33, P < .001), higher estimated pulmonary artery systolic pressure (r = 0.35, P = .002), larger left ventricular end-diastolic diameter (r = 0.23, P = .02), and higher plasma NT-proBNP levels (r = 0.35, P < .001). sACE2 was less associated with diastolic dysfunction (r = 0.19, P = .05), and was similar between patients with ischemic and nonischemic cardiomyopathies. There was no relationship between sACE2 activity and markers of systemic inflammation. After adjusting for NT-proBNP and LVEF, sACE2 activity remained an independent predictor of adverse clinical events (HR = 1.7 [95% CI: 1.1-2.6], P = .018). Conclusions: Elevated plasma sACE2 activity was associated with greater severity of myocardial dysfunction and was an independent predictor of adverse clinical events.

Original languageEnglish (US)
Pages (from-to)565-571
Number of pages7
JournalJournal of cardiac failure
Volume15
Issue number7
DOIs
StatePublished - Sep 2009

Bibliographical note

Funding Information:
The original Assessment of Doppler Echocardiography in Prognosis and Therapy study was supported by the 2003 American Society of Echocardiography Outcomes Research Award (Drs. Troughton and Klein), GlaxoSmithKline Pharmaceuticals, and Roche Diagnostics Inc.

Copyright:
Copyright 2010 Elsevier B.V., All rights reserved.

Keywords

  • ACE2
  • Heart failure
  • angiotensin
  • remodeling

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