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

• Published in: Journal of cardiac failure Vol. 15; no. 7; pp. 565 - 571
• Main Authors: Epelman, Slava, MD, PhD, Shrestha, Kevin, BA, Troughton, Richard W., MBBS, Francis, Gary S., MD, Sen, Subha, PhD, DSc, Klein, Allan L., MD, Wilson Tang, W.H., MD
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01-09-2009
• Subjects: ACE2; Adult; Aged; angiotensin; Biomarkers - blood; Cardiovascular; Cohort Studies; Female; Follow-Up Studies; Heart failure; Heart Failure, Systolic - enzymology; Heart Failure, Systolic - mortality; Heart Failure, Systolic - physiopathology; Humans; Male; Middle Aged; Peptidyl-Dipeptidase A - biosynthesis; Peptidyl-Dipeptidase A - blood; Predictive Value of Tests; Prospective Studies; remodeling; Severity of Illness Index; Survival Rate - trends; Treatment Outcome; Ventricular Function - physiology; Heart failure; angiotensin; ACE2; remodeling
• ISSN: 1071-9164; 1532-8414
• DOI: 10.1016/j.cardfail.2009.01.014

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.