Abstract 15597: Acute Venous Congestion Causes Angiotensin II formation via Angiotensin-Converting Enzyme Activation in Compensated Ambulatory Patients with Systolic Heart Failure
Background: Plasma levels of angiotensin II (AII) are increased in congestive states such as heart failure (HF). The current study examined i) whether venous congestion (VC) itself promotes AII formation, and ii) the contributions of angiotensin-converting enzyme (ACE) vs. other enzymes such as chymases to AII generation in patients with systolic HF.
Methods: 42 ambulatory patients with NYHA functional class II or III, an LVEF <40%, no evidence of VC on physical exam and on stable medical therapy were studied. To experimentally model VC, venous arm pressure was increased to 30 mmHg above baseline by inflating a pressure cuff around the dominant arm. Blood was sampled from test and control arm (lacking an inflated cuff) before and after 90 minutes of VC. Radioimmunoassay was used for plasma AII measurements.The effect of ACE inhibitor (ACEI) based therapy (N=29) vs. non-ACEI (N=13) was compared.
Results: The age of the study cohort was 53±12 years, 29% were female, 31% had an ischemic etiology and the LVEF was 22±8%. Baseline AII levels were 3-times lower in the ACEI vs. non-ACEI group (24±10 vs. 76±40 pg/mL, P<0.001). Plasma AII was significantly higher in the congested over control arm only in non-ACEI group after 90 minutes of VC (figure). No adverse event was observed during the test.
Conclusions: Our study provides the first direct evidence that VC is sufficient to cause AII formation in compensated ambulatory HF patients on non-ACEI based therapy. ACEI treatment completely abolished this increase suggesting activation of ACE, rather than other enzymes such as chymases, to be the cause of volume-dependent AII formation in response to peripheral VC.
Author Disclosures: K. Wong: None. Y. Hayashi: None. D. Onat: None. A. Harxhi: None. M. Wakabayashi: None. M.M. Ahmad: None. N. Uriel: Honoraria; Modest; Thoratec, heartware. U.P. Jorde: None. R.T. Demmer: None. P.C. Colombo: None.
- © 2014 by American Heart Association, Inc.