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

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.