Experimentally-Induced Peripheral Venous Congestion Exacerbates Inflammation, Oxidative Stress, Neurohormonal and Endothelial Cell Activation in Systolic Heart Failure Patients
Colombo PC, Castagna F, Onat D, Wong KY, Harxhi A, Hayashi Y, Friedman RA, Pinsino A, Ladanyi A, Mebazaa A, Jelic S, Arrigo M, LeJemtel TH, Papapanou P, Sabbah HN, Schmidt AM, Yuzefpolskaya M, and Demmer RT. Experimentally-Induced Peripheral Venous Congestion Exacerbates Inflammation, Oxidative Stress, Neurohormonal and Endothelial Cell Activation in Systolic Heart Failure Patients. J Card Fail 2023.
Journal of cardiac failure
BACKGROUND: Venous congestion (VC) is a hallmark of symptomatic heart failure (HF) requiring hospitalization; however, its role in the pathogenesis of HF progression remains unclear. We investigated whether peripheral VC exacerbates inflammation, oxidative stress, neurohormonal and endothelial cell (EC) activation in HF with reduced ejection fraction (HFrEF) patients.
METHODS AND RESULTS: Two matched groups of HFrEF patients with no peripheral VC, with vs. without recent HF hospitalization were studied. We modeled peripheral VC by inflating a cuff around the dominant arm, targeting ∼30mmHg increase in venous pressure (venous stress test (VST)). Blood and ECs were sampled before and after 90 minutes of VST. Forty-four patients were studied (age 53±12 years, 32% female). Circulating endothelin-1, tumor necrosis factor-α, interleukin-6, isoprostane, angiotensin II, angiopoietin-2, vascular cell adhesion molecule-1 and CD146 significantly increased after VST. Enhanced endothelin-1 and angiopoietin-2 response to VST was present in patients with vs. without recent hospitalization, and prospectively associated with incident HF-related events. 6,698mRNA probe sets were differentially expressed in ECs after VST.
CONCLUSIONS: Experimental VC exacerbates inflammation, oxidative stress, neurohormonal and EC activation, and promotes unfavorable transcriptome remodeling in ECs of HFrEF patients. A distinct biological sensitivity to VC appears associated with high-risk for HF progression.
ePub ahead of print