Introduction: Long- and short-acting nitrates are a mainstay treatment in patients with coronary artery spasm. While the efficacy of nitroglycerine in patients with epicardial spasm is clinically well-established, its role in patients with microvascular spasm remains unknown.

Aim: To assess the efficacy of intracoronary nitroglycerine in preventing coronary epicardial and microvascular spasm during acetylcholine re-challenge.

Methods: In this multi-center study, 95 consecutive symptomatic patients undergoing acetylcholine re-challenge after intracoronary nitroglycerine pre-treatment were included. According to the inclusion criteria, all patients had unobstructed coronary arteries (<50% stenosis) and a positive acetylcholine spasm test revealing epicardial or microvascular coronary spasm. After the initial acetylcholine test, 200µg nitroglycerine was administered intracoronarily and acetylcholine provocation was repeated after 3 minutes using the same acetylcholine dose that previously induced spasm. Epicardial and microvascular spasm were defined according to the COVADIS criteria based on symptom reproduction, ischemic ECG changes and the presence/absence of ≥90% epicardial vasoconstriction (epicardial/microvascular spasm).

Results: Patients in this study were 61 (Q1-Q3: 54-69) years old, predominantly female (70%) and had a preserved left ventricular ejection fraction (65±10%). Fifty-five patients (58%) had microvascular spasm during initial acetylcholine spasm testing and 40 patients (42%) had epicardial spasm. Epicardial spasm was diffuse in most patients (31/40; 78%), and focal in the remaining patients (9/40; 22%). Nitroglycerine prevented diffuse epicardial spasm in 24/31 (77%) of patients at re-challenge. In patients with microvascular spasm nitroglycerine prevented the inducibility of spasm by acetylcholine in only 31%. Furthermore, in 14/40 (35%) of patients with diffuse or focal epicardial spasm acetylcholine re-challenge revealed concomitant nitroglycerine-refractory microvascular spasm. Notably, nitroglycerine prevented the re-occurrence of all focal epicardial spasms when re-challenged with acetylcholine.

Conclusion: Our study demonstrates that intracoronary nitroglycerine is effective in preventing acetylcholine-induced coronary spasm in the cath lab. It was most effective in preventing focal epicardial spasm (100%) followed by diffuse epicardial spasm (77%), whereas it prevented microvascular spasm in only 31%. These observations suggest that 1) nitroglycerine treatment may be less effective in microvascular spasm than in epicardial spasm, but could still be helpful in a subset of patients with microvascular spasm, and 2) acetylcholine re-challenge may be a novel method to directly evaluate a patient’s response to anti-vasospastic medication.