TY - JOUR

T1 - Effects of Acute GLP-1 Infusion on Pulmonary and Systemic Hemodynamics in Patients With Heart Failure

T2 - A Pilot Study

AU - Clarke, Sophie J.

AU - Pettit, Stephen

AU - Giblett, Joel P.

AU - Zhao, Tian

AU - Kydd, Anna C.

AU - Albrechtsen, Nicolai J. W.

AU - Deacon, Carolyn F.

AU - Parameshwar, Jayan

AU - Hoole, Stephen P.

PY - 2019

Y1 - 2019

N2 - Purpose: Cardiovascular-safety studies assessing glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have provided inconsistent data on the risk for developing heart failure. Animal studies have shown that GLP-1 is a vasodilator; if confirmed in humans, this may ameliorate heart failure symptoms. Methods: In a single-center, observational pilot study, we recruited 10 patients with advanced heart failure undergoing right heart catheterization, and we recorded pulmonary hemodynamic measures, including cardiac output calculated by thermodilution and the indirect Fick method before and after a 15-minute continuous infusion of native GLP-1 (7-36) NH2. Findings: There was a neutral effect of GLP-1 on all pressure and hemodynamics indices as derived by cardiac output calculated by thermodilution. However, there was a small but consistent reduction in cardiac output as calculated by the indirect Fick method after GLP-1 infusion (baseline, 4.0 [1.1] L/min vs GLP-1, 3.6 [0.9] L/min; P = 0.003), driven by a consistent reduction in mixed venous oxygen saturation after GLP-1 infusion (baseline, 62.2% [7.0%] vs GLP-1, 59.3 % [6.8 %]; P < 0.001), whereas arterial saturation remained constant (baseline, 96.8% [3.3%] vs GLP-1, 97.0% [3.2%]; P = 0.34). This resulted in an increase in systemic vascular resistance by Fick (baseline, 1285 [228] dyn . s/cm(5) vs GLP-1, 1562 [247] dyn . s/cm(5); P = 0.001). (C) 2018 Elsevier Inc. All rights reserved.

AB - Purpose: Cardiovascular-safety studies assessing glucagon-like peptide (GLP)-1 receptor agonists and dipeptidyl peptidase 4 inhibitors have provided inconsistent data on the risk for developing heart failure. Animal studies have shown that GLP-1 is a vasodilator; if confirmed in humans, this may ameliorate heart failure symptoms. Methods: In a single-center, observational pilot study, we recruited 10 patients with advanced heart failure undergoing right heart catheterization, and we recorded pulmonary hemodynamic measures, including cardiac output calculated by thermodilution and the indirect Fick method before and after a 15-minute continuous infusion of native GLP-1 (7-36) NH2. Findings: There was a neutral effect of GLP-1 on all pressure and hemodynamics indices as derived by cardiac output calculated by thermodilution. However, there was a small but consistent reduction in cardiac output as calculated by the indirect Fick method after GLP-1 infusion (baseline, 4.0 [1.1] L/min vs GLP-1, 3.6 [0.9] L/min; P = 0.003), driven by a consistent reduction in mixed venous oxygen saturation after GLP-1 infusion (baseline, 62.2% [7.0%] vs GLP-1, 59.3 % [6.8 %]; P < 0.001), whereas arterial saturation remained constant (baseline, 96.8% [3.3%] vs GLP-1, 97.0% [3.2%]; P = 0.34). This resulted in an increase in systemic vascular resistance by Fick (baseline, 1285 [228] dyn . s/cm(5) vs GLP-1, 1562 [247] dyn . s/cm(5); P = 0.001). (C) 2018 Elsevier Inc. All rights reserved.

KW - GLP-1

KW - heart failure

KW - hemodynamics

KW - right heart catheterization

U2 - 10.1016/j.clinthera.2018.11.013

DO - 10.1016/j.clinthera.2018.11.013

M3 - Journal article

C2 - 30598343

VL - 41

SP - 118

EP - 127

JO - Clinical Therapeutics

JF - Clinical Therapeutics

SN - 0149-2918

IS - 1

ER -