Pellicori, P;
Cleland, JGF;
Borentain, M;
Taubel, J;
Graham, FJ;
Khan, J;
Bruzzese, D;
Kessler, P;
McMurray, JJV;
Voors, AA;
et al.
Pellicori, P; Cleland, JGF; Borentain, M; Taubel, J; Graham, FJ; Khan, J; Bruzzese, D; Kessler, P; McMurray, JJV; Voors, AA; O'Connor, CM; Teerlink, JR; Felker, GM
(2024)
Impact of vasodilators on diuretic response in patients with congestive heart failure: A mechanistic trial of cimlanod (BMS-986231).
Eur J Heart Fail, 26 (1).
pp. 142-151.
ISSN 1879-0844
https://doi.org/10.1002/ejhf.3077
SGUL Authors: Taubel, Jorg
Abstract
AIM: To investigate the effects of Cimlanod, a nitroxyl donor with vasodilator properties, on water and salt excretion after an administration of an intravenos bolus of furosemide. METHODS AND RESULTS: In this randomized, double-blind, mechanistic, crossover trial, 21 patients with left ventricular ejection fraction <45%, increased plasma concentrations of N-terminal pro-B-type natriuretic peptide (NT-proBNP) and receiving loop diuretics were given, on separate study days, either an 8 h intravenous (IV) infusion of cimlanod (12 μg/kg/min) or placebo. Furosemide was given as a 40 mg IV bolus four hours after the start of infusion. The primary endpoint was urine volume in the 4 h after the bolus of furosemide during infusion of cimlanod compared with placebo. Median NT-proBNP at baseline was 1487 (interquartile range: 847-2665) ng/L. Infusion of cimlanod increased cardiac output and reduced blood pressure without affecting cardiac power index consistent with its vasodilator effects. Urine volume in the 4 h post-furosemide was lower with cimlanod (1032 ± 393 ml) versus placebo (1481 ± 560 ml) (p = 0.002), as were total sodium excretion (p = 0.004), fractional sodium excretion (p = 0.016), systolic blood pressure (p < 0.001), estimated glomerular filtration rate (p = 0.012), and haemoglobin (p = 0.010), an index of plasma volume expansion. CONCLUSIONS: For patients with heart failure and congestion, vasodilatation with agents such as cimlanod reduces the response to diuretic agents, which may offset any benefit from acute reductions in cardiac preload and afterload.
Item Type: |
Article
|
Additional Information: |
© 2023 The Authors. European Journal of Heart Failure published by John Wiley & Sons Ltd on behalf of European Society of Cardiology.
This is an open access article under the terms of the Creative Commons Attribution-NonCommercial License (http://creativecommons.org/licenses/by-nc/4.0/), which permits use, distribution and reproduction in any medium, provided the original work is properly cited and is not used for commercial purposes. |
Keywords: |
Bioimpedance, Congestion, Diuretics, Heart failure, Natriuresis, Renal perfusion, Vasodilators, Humans, Diuretics, Furosemide, Heart Failure, Vasodilator Agents, Stroke Volume, Ventricular Function, Left, Sodium, Cardiotonic Agents, Humans, Sodium, Furosemide, Cardiotonic Agents, Vasodilator Agents, Diuretics, Stroke Volume, Ventricular Function, Left, Heart Failure, Heart failure, Congestion, Diuretics, Vasodilators, Renal perfusion, Bioimpedance, Natriuresis, 1102 Cardiorespiratory Medicine and Haematology, Cardiovascular System & Hematology |
Journal or Publication Title: |
Eur J Heart Fail |
ISSN: |
1879-0844 |
Language: |
eng |
Dates: |
Date | Event |
---|
18 February 2024 | Published | 28 December 2023 | Published Online | 24 October 2023 | Accepted |
|
Publisher License: |
Creative Commons: Attribution-Noncommercial 4.0 |
Projects: |
Project ID | Funder | Funder ID |
---|
UNSPECIFIED | Bristol-Myers Squibb | UNSPECIFIED |
|
PubMed ID: |
37990754 |
Web of Science ID: |
WOS:001133911000001 |
![](http://static.pubmed.gov/portal/portal3rc.fcgi/2745237/img/27842) |
Go to PubMed abstract |
URI: |
https://openaccess.sgul.ac.uk/id/eprint/116791 |
Publisher's version: |
https://doi.org/10.1002/ejhf.3077 |
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