Comparison of Baseline and Post-Nitrate Exercise Testing in Patients with Angina but Non-Obstructed Coronary Arteries with Different Acetylcholine Test Results

Background: Intracoronary acetylcholine testing may induce epicardial coronary artery spasm (CAS) or coronary microvascular spasm (CMVS) in patients with angina syndromes but non-obstructive coronary artery disease, but their causal role in individual patients is not always clear. In this prospective, observational single-center study, we aimed to assess whether (1) the induction of myocardial ischemia/angina by electrocardiogram (ECG) exercise stress test (EST) differs between patients showing different results in response to acetylcholine testing (i.e., CAS, CMVS, or no spasm); (2) the preventive administration of short-acting nitrates has any different effects on the EST of those patients who showed a positive basal EST. We expected that if exercise-induced angina and/or ischemic ECG changes are related to CAS, they should improve after nitrates administration, whereas they should not significantly improve if they are caused by CMVS. Methods: We enrolled 81 patients with angina syndromes and non-obstructive coronary artery disease, who were divided into three groups according to acetylcholine testing: 40 patients with CAS (CAS-group), 14 with CMVS (CMVS-groups), and 27 with a negative test (NEG-group). All patients underwent a basal EST (B-EST). Patients with a positive B-EST repeated the test 24-48 h later, 5 min after the administration of short-acting nitrates (N-EST). Results: There were no significant differences among the groups in terms of the B-EST results. B-EST was positive in eight (20%) patients in the CAS-group, seven (50%) in the CMVS-group, and six (22%) in the NEG-group (p = 0.076). N-EST, performed in eight, six, and five of these patients, also showed similar results in the three groups. Furthermore, the N-EST results also did not significantly differ compared to B-EST in any group, remaining positive in seven (87.5%), four (66.7%), and four (80%) patients in the CAS-group, CMVS-group, and NEG-group, respectively (p = 0.78). Conclusions: Our data show that patients with angina and non-obstructive coronary artery disease show largely comparable results of the ECG exercise stress test and similar poor effects of short-acting nitrates on abnormal ECG exercise stress test results. On the whole, our findings suggest caution in attributing to the results of Ach testing a definite causal role for the clinical syndrome in individual patients.