Impact of Nitroglycerin Administration on Acetylcholine Provocation Testing in Angina With Nonobstructive Coronary Arteries

Abstract

Background: Invasive coronary function testing, using acetylcholine (ACh) to diagnose coronary artery spasm (CAS) and coronary microvascular dysfunction assessment, is considered the gold standard for evaluating patients suffering from angina with nonobstructive coronary arteries. Notably, equipoise remains regarding the optimal sequence for coronary function testing, and no global consensus exists. Although nitroglycerin (NTG) is routinely administered post–radial access and prior to coronary microvascular dysfunction testing, its effect on subsequent ACh testing remains unclear. This study aimed to evaluate the diagnostic impact of preceding intravascular NTG on ACh provocation testing. Methods: Multivessel ACh provocation testing was systematically performed in patients with suspected CAS. To assess the reinducibility of epicardial spasm, an ACh rechallenge was performed in patients who tested positive by readministering the spasm provocation dose into the affected coronary artery at different time intervals following the administration of intravascular NTG. Results: This multicenter study enrolled 102 patients (mean age 59.3 ± 10.0 years; 55% female), of whom 40 were diagnosed with epicardial CAS and underwent ACh rechallenge. Among these, 25 patients (62.5%) exhibited a diffuse spasm pattern, whereas 15 patients (37.5%) demonstrated focal spasm. After the ACh rechallenge, epicardial spasm was reinduced in 22 patients (55%), microvascular spasm in 6 patients (15%), and no spasm in 12 patients (30%). The sensitivity of ACh provocation testing declined to 55% at the end of the rechallenge. Conclusions: Nitroglycerin administration reduces the diagnostic accuracy of ACh provocation testing for CAS in angina with nonobstructive coronary arteries patients. Findings from this study indicate that clinicians should avoid NTG administration prior to ACh testing or significantly delay ACh testing after NTG exposure to preserve diagnostic sensitivity.