Increasing serum soluble angiotensin-converting enzyme 2 activity after intensive medical therapy is associated with better prognosis in acute decompensated heart failure.
BACKGROUND
Angiotensin-converting enzyme 2 (ACE2) is an endogenous counterregulator of the renin-angiotensin system that has been recently identified in circulating form. We aimed to investigate the relationship among changes in soluble ACE2 (sACE2) activity, myocardial performance, and long-term clinical outcomes in patients with acute decompensated heart failure (ADHF). We hypothesized that increasing sACE2 activity levels during intensive medical treatment are associated with improved myocardial performance and long-term clinical outcomes.


RESULTS
In 70 patients admitted to the intensive care unit with ADHF, serum sACE2 activity levels, echocardiographic data, and hemodynamic variables were collected within 12 hours of admission (n = 70) and 48-72 hours after intensive medical treatment (n = 57). The median [interquartile range] baseline and 48-72-hour serum sACE2 activity levels were 32 [23-43] ng/mL and 40 [28-60] ng/mL, respectively. Baseline serum sACE2 activity levels correlated with surrogate measures of right ventricular diastolic dysfunction, including right atrial volume index (RAVi; r = 0.31; P = .010), tricuspid E/A ratio (r = 0.39; P = .007), and B-type natriuretic peptide (r = 0.32; P = .008). However, there were no correlations between serum sACE2 and left ventricular systolic or diastolic dysfunction. After intensive medical therapy, a 50% increase in baseline serum sACE2 levels predicted a significant reduction in risk of death, cardiac transplantation, or ADHF rehospitalization, including after adjustment for baseline age, RAVi, and BNP levels (hazard ratio 0.35, 95% confidence interval 0.12-0.84; P = .018).


CONCLUSIONS
In patients admitted with ADHF, increasing serum sACE2 activity levels during intensive medical therapy predict improved outcomes independently from underlying cardiac indices.
Center for Cardiovascular Diagnostics and Prevention, Department of Cell Biology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio.
Zhili
Z
Shao
Kevin
K
Shrestha
Allen G
AG
Borowski
David J
DJ
Kennedy
Slava
S
Epelman
James D
JD
Thomas
W H Wilson
WH
Tang
D000208:Acute Disease; D000328:Adult; D000368:Aged; D000085962:Angiotensin-Converting Enzyme 2; D015415:Biomarkers / Q000097:blood; D004789:Enzyme Activation / Q000502:physiology; D005260:Female; D006333:Heart Failure / Q000097:blood* / Q000175:diagnosis / Q000628:therapy*; D006801:Humans; D007362:Intensive Care Units / Q000639:trends; D008297:Male; D008875:Middle Aged; D007703:Peptidyl-Dipeptidase A / Q000097:blood*; D011379:Prognosis; D011446:Prospective Studies; D016896:Treatment Outcome
D015415:Biomarkers; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2
Soluble angiotensin-converting enzyme 2; acute decompensated heart failure; right ventricular diastolic dysfunction