Related Experiment Video
Updated: Nov 16, 2025
Percutaneous Contrast Echocardiography-guided Intramyocardial Injection and Cell Delivery in a Large Preclinical Model
Published on: January 21, 2018
Haemodynamic effects of the nitroxyl donor cimlanod (BMS-986231) in chronic heart failure: a randomized trial
Ninian N Lang1, Faheem A Ahmad1, John G Cleland2,3
1BHF Glasgow Cardiovascular Research Centre, Institute of Cardiovascular & Medical Sciences, University of Glasgow, Glasgow, UK.
Insights
Cimlanod and nitroglycerin show similar effects on cardiac function in patients with heart failure with reduced ejection fraction (HFrEF). Both reduced stroke volume index and blood pressure compared to placebo, indicating potential for managing HFrEF.
Area of Science:
- Cardiology
- Pharmacology
- Biochemistry
Background:
- Nitroxyl mediates vasodilatory and inotropic effects through thiol modification in animal models.
- Chronic heart failure with reduced ejection fraction (HFrEF) remains a significant clinical challenge.
- Nitroxyl donors are being investigated for their therapeutic potential in cardiovascular diseases.
Purpose of the Study:
- To compare the effects of the nitroxyl donor cimlanod (BMS-986231) with nitroglycerin (NTG) and placebo on cardiac function in patients with HFrEF.
- To evaluate the hemodynamic profile of cimlanod in a human clinical setting.
Main Methods:
- A randomized, multicenter, double-blind, crossover trial involving 45 patients with stable HFrEF.
- Intravenous infusions of cimlanod, NTG, or placebo were administered over 5 hours on separate days.
- Echocardiography was performed to assess cardiac function, with stroke volume index as the primary endpoint.
Main Results:
- Stroke volume index was significantly reduced with both cimlanod (P=0.03) and NTG (P=0.02) compared to placebo.
- Transmitral E-wave Doppler velocity, E/e', and E/A ratio were lower with cimlanod and NTG than with placebo, indicating reduced diastolic function.
- Blood pressure reduction was comparable between cimlanod and NTG, and greater than with placebo.
Conclusions:
- Cimlanod and NTG exert similar hemodynamic effects in patients with chronic HFrEF.
- Cimlanod's effects are likely attributable to venodilation and preload reduction, without significant additional inotropic or lusitropic actions.
- Further clinical trials are warranted to define the role of cimlanod in heart failure management.
Aims:
Nitroxyl provokes vasodilatation and inotropic and lusitropic effects in animals via post-translational modification of thiols. We aimed to compare effects of the nitroxyl donor cimlanod (BMS-986231) with those of nitroglycerin (NTG) or placebo on cardiac function in patients with chronic heart failure with reduced ejection fraction (HFrEF).
Methods And Results:
In a randomized, multicentre, double-blind, crossover trial, 45 patients with stable HFrEF were given a 5 h intravenous infusion of cimlanod, NTG, or placebo on separate days. Echocardiograms were done at the start and end of each infusion period and read in a core laboratory. The primary endpoint was stroke volume index derived from the left ventricular outflow tract at the end of each infusion period. Stroke volume index with placebo was 30 ± 7 mL/m2 and was lower with cimlanod (29 ± 9 mL/m2 ; P = 0.03) and NTG (28 ± 8 mL/m2 ; P = 0.02). Transmitral E-wave Doppler velocity on cimlanod or NTG was lower than on placebo and, consequently, E/e' (P = 0.006) and E/A ratio (P = 0.003) were also lower. NTG had similar effects to cimlanod on these measurements. Blood pressure reduction was similar with cimlanod and NTG and greater than with placebo.
Conclusion:
In patients with chronic HFrEF, the haemodynamic effects of cimlanod and NTG are similar. The effects of cimlanod may be explained by venodilatation and preload reduction without additional inotropic or lusitropic effects. Ongoing trials of cimlanod will further define its potential role in the treatment of heart failure.
Related Concept Videos
01:26Heart Failure Drugs: Inhibitors of Renin-Angiotensin System
01:22Heart Failure Drugs: β-Blockers
01:26Heart Failure Drugs: Inotropic Agents
01:30Heart Failure V: Medical Management
01:16Antianginal Drugs: Nitrates and β-Blockers
Organic nitrates, such as nitroglycerin, play a pivotal role. Once metabolized, they liberate nitric oxide, a molecular marvel. Nitric oxide triggers guanylyl cyclase and augments cGMP production. This biochemical cascade orchestrates the relaxation of vascular smooth muscles, ushering in vasodilation and enhancing coronary blood flow....
01:29Heart Failure II: Pathophysiology