Enhanced Release of Endothelin-1 and Angiopoietin-2 During Experimentally-Induced Peripheral Venous Congestion is Associated with Heart Failure-Related Clinical Events
Recommended Citation
Castagna F, Onat D, Wong K, Harxhi A, Hayashi Y, Pinsino A, Mebazaa A, Arrigo M, LeJemtel TH, Sabbah H, Schmidt A, Yuzefpolskaya M, Demmer R, and Colombo PC. Enhanced Release of Endothelin-1 and Angiopoietin-2 During Experimentally-Induced Peripheral Venous Congestion is Associated with Heart Failure-Related Clinical Events. J Heart Lung Transplant 2023; 42(4):S323-S324.
Document Type
Conference Proceeding
Publication Date
4-1-2023
Publication Title
J Heart Lung Transplant
Abstract
Purpose: Growing evidence suggests that venous congestion (VC) is a contributor to the pathophysiology of heart failure (HF) progression by causing inflammation, vasoconstriction, oxidative stress and endothelial activation. We hypothesized that: 1) euvolemic HF with reduced ejection fraction (HFrEF) pts with a recent history of HF hospitalization have more pronounced phenotypic response to VC compared to pts not hospitalized; 2) greater phenotypic response to VC is associated with subsequent HF-related events.
Methods: Two matched groups of euvolemic NYHA Class II-III HFrEF pts, with and without history of HF hospitalization within prior 6 months, were studied. We modeled acute VC by inflating a cuff around the dominant arm, targeting ∼30 mmHg increase in venous pressure. Blood was sampled before and after 90 min of VC (Fig A). HF-related events were recorded during 4-y follow up.
Results: 44 pts were studied (53±12 yo; 32% female). During follow up, 16 pts had a HF hospitalization, 6 LVAD implant, 3 heart transplant and 3 died. Circulating endothelin-1 (ET-1), tumor necrosis factor-α, interleukin-6, isoprostane, angiotensin II, angiopoietin-2 (Ang-2), vascular cell adhesion molecule-1 and soluble CD146 were significantly increased in the congested vs. control arm after 90 min of VC. Higher ET-1 and Ang-2 response to VC was present in pts with vs. without recent HF hospitalization, and prospectively associated with incident HF-related events (Fig B-C). These results were confirmed after adjustment for age, sex, and history of recent (<6 months) HF hospitalization: ET-1 (HR 1.70, 95% CI 1.05-2.73) and Ang-2 (HR 2.37, 95% CI 1.12 -4.98).
Conclusion: A greater ET-1 and Ang-2 response to VC is: 1) present in euvolemic pts with vs. without a recent history of HF hospitalization, and 2) prospectively associated with more HF-related events. A distinct and sustained biological sensitivity to VC occurs in pts at high-risk for HF progression.
Volume
42
Issue
4
First Page
S323
Last Page
S324
