Safety of Acetylcholine in the Cath Lab

The concepts of ischemia with non-obstructive coronary artery disease (INOCA) and myocardial infarction with non-obstructive coronary artery disease (MINOCA) have been established, widely spread, accepted, and included in the different guidelines that support our clinical practice. Among INOCA and MINOCA we find vasospastic angina (VSA) caused by epicardial vessel spasms and angina caused by microvascular spasm (MVS), both described as syndrome etiology.

To establish the cause of MINOCA, coronary provocation testing with intracoronary acetylcholine is considered a IIA indication. Specific treatments for these cases might improve patient quality of life, since they often relapse. However, at present, physicians fear potential complications. 

The aim of this study was to assess, through a systematic review and meta-analysis, the safety of coronary provocation testing with intracoronary acetylcholine (ACh) for the contemporary diagnosis of epicardial and microvascular spasm. Major complication was defined as a composite of death, ventricular tachycardia/fibrillation, myocardial infarction, or shock requiring reanimation. Minor complications were paroxysmal atrial fibrillation, ventricular extrasystole, transient hypotension or bradycardia requiring pacemaker implantation. 

This meta-analysis included a total of 16 studies with 12585 patients, the administration of 100 to 200mcg acetylcholine to the left coronary and the assessment of endothelial function with a short 36mcg infusion.

Read also: Prognostic Value of Structural and Functional Microvascular Dysfunction in Patients with Nonobstructive Coronary Artery Disease.

Major complications incidence was 0.5% (CI 95% 0.0-1.3%). There were no deaths. Subgroup analysis showed accumulated incidence of major complications was higher in studies where spasm cutoff value was ≥90% obstruction vs. prior diagnostic cutoff value of ≥75% (1.0%; CI 95% 0.3-2.0%); the incidence was significantly lower in western populations vs. Asian (0.0%; CI 95% 0.0%-0.45%).

When comparing the safety of different doses, major and minor complications rates were similar when using different acetylcholine doses ranging 100 to 200mcg.


Provocation testing with intracoronary acetylcholine resulted safe. There were differences in subgroups, western populations being the least affected. 

Despite the fact that this meta-analysis showed great study heterogeneity, it shows promise towards advancing acetylcholine routine protocols in the cath lab, to better diagnose VSA and MVS as causes of INOCA and MINOCA. 

Dr. Omar Tupayachi

Dr. Omar Tupayachi.
Member of the Editorial Board of

Original Title: Safety of Provocative Testing With Intracoronary Acetylcholine and Implications for Standard Protocols.

Reference: Takahashi, Tatsunori et al. “Safety of Provocative Testing With Intracoronary Acetylcholine and Implications for Standard Protocols.” Journal of the American College of Cardiology vol. 79,24 (2022): 2367-2378. doi:10.1016/j.jacc.2022.03.385.

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