Safety of Provocative Testing With Intracoronary Acetylcholine and Implications for Standard Protocols

Background: Heterogeneity in diagnostic criteria and provocation protocols has posed challenges in understanding the safety of coronary provocation testing with intracoronary acetylcholine (ACh) for the contemporary diagnosis of epicardial and microvascular spasm. Objectives: We examined the safety of testing and subgroup differences in procedural risks based on ethnicity, diagnostic criteria, and provocation protocols. Methods: PubMed and Embase were searched in November 2021 to identify original articles reporting procedural complications associated with intracoronary ACh administration. The primary outcome was the pooled estimate of the incidence of major complications including death, myocardial infarction, ventricular tachycardia/fibrillation, and shock. Results: A total of 16 studies with 12,585 patients were included in the meta-analysis. The overall pooled estimate of the incidence of major complications was 0.5% (95% CI: 0.0%-1.3%) without any reports of death. Exploratory subgroup analyses revealed that the pooled incidence of major complications was significantly higher in the studies that followed the contemporary diagnosis criteria for epicardial spasm defined as ≥90% diameter reduction (1.0%; 95% CI: 0.3%-2.0%) but significantly lower in Western populations (0.0%; 95% CI: 0.0%-0.45%). The rate of positive epicardial spasm and the incidence of major complications were similar between provocation protocols using the maximum ACh doses of 100 μg and 200 μg. Conclusions: Intracoronary ACh administration for the contemporary diagnosis of epicardial and microvascular spasm is a safe procedure. Moreover, excellent safety records are observed in Western populations primarily presenting with myocardial ischemia and/or infarction with nonobstructive coronary arteries. This study will help standardize ACh testing to improve clinical diagnosis and ensure procedural safety.