Background: Coronary artery spasm is an established cause for angina pectoris. Epicardial coronary spasm may occur in patients with obstructed as well as unobstructed coronary arteries. Previous studies have suggested that abnormal coronary morphology (i. e. epicardial atherosclerosis, myocardial bridging or coronary tortuosity) may be a prerequisite for the development of coronary spasm. The aim of the present study was to compare the results of intracoronary acetylcholine (ACh) testing in patients with signs and symptoms of myocardial ischemia with a comprehensive assessment of coronary morphology.

Methods: Between 2008 and 2016 a total number of 610 patients with signs and symptoms of myocardial ischemia yet unobstructed epicardial arteries (<50% epicardial stenosis) was included in the present study (mean age 61+/-11, 61% female). All patients underwent invasive diagnostic coronary angiography followed by intracoronary ACh testing according to a standardized protocol. The ACh-test was considered ‘positive’ in the presence of (a) angina, ischemic ECG shifts during the test and ≥75% focal or diffuse coronary diameter reduction (‘epicardial coronary artery spasm’) or (b) ischemic ST-shifts and angina in the absence of epicardial spasm (‘microvascular spasm’). In all angiograms coronary morphology was assessed in a blinded fashion using standardized definitions for epicardial atherosclerosis, myocardial bridging and coronary tortuosity.

Results: The analysis included 179 patients (29%) with epicardial spasm and 172 patients with microvascular spasm (28%). The remaining 259 patients (43%) had an uneventful or an inconclusive ACh-test result. There were 389 patients (64%) with completely smooth epicardial arteries. The remaining 221 patients (36%) had non-obstructive epicardial plaques <50%. On univariate analysis the presence of epicardial atherosclerosis was associated with epicardial spasm (p=0.006). Multivariate analysis revealed the presence of epicardial atherosclerosis (OR 1.921, CI 1.285-2.871, p=0.001) as well as female sex (OR 1.526, CI 1.024-2.274, p=0.038) as independent predictors for epicardial spasm. Muscular bridging was found in 83 patients (14%) without any correlation to the acetylcholine test results. Coronary tortuosity was absent in 6 patients (1%), mild in 306 patients (50%), moderate in 292 patients (48%) and severe in 6 patients (1%). Patients with microvascular spasm had significantly more often moderate/severe tortuosity compared to patients with other test results (p=0.024).

Conclusion: In patients with signs and symptoms of myocardial ischemia yet unobstructed coronary arteries the presence of epicardial atherosclerosis is an independent predictor for the occurrence of epicardial spasm. Moreover, the presence of at least moderate coronary tortuosity is associated with the occurrence of microvascular spasm.