Hemodynamic assessment of coronary vasomotor responses to acetylcholine complements standard clinical criteria: insights from the MICRO-SNAPE registry

Abstract Background Coronary spasm is an important differential diagnosis for patients with angina and non-obstructive coronary artery disease. Current COVADIS (Coronary Vasomotor Disorders International Study Group) and EAPCI (European Association for Percutaneous Coronary Interventions) guidelines for the diagnosis of vasospasm leverage clinical symptoms (reproduction of angina) and ECG changes induced by acetylcholine infusions. We investigate whether the inclusion of hemodynamic measures improves the diagnostic yield of these assessments. Methods Patients experiencing recurrent angina (CCS II-IV) with no relevant epicardial stenosis were enrolled in an international, multicenter registry (MICRO-SNAPE). Based on guideline criteria, epicardial spasm was defined as >90% angiographic vasoconstriction of an epicardial coronary with angina and ECG changes; microvascular spasm was diagnosed in the presence of ischemia without epicardial spasm. Hemodynamic epicardial obstruction (Pd/Pa<0.80, ratio of distal to aortic mean blood pressure) and microvascular spasm (increased microvascular resistance during acetylcholine compared to rest) were assessed using the bolus thermodilution technique and intracoronary acetylcholine (2, 20 and 100microgr). Results 818 patients (mean age 62,7 ± 11,2 years, 53,8% female) were recruited. The prevalence of epicardial spasm was 11,2% (92 patients), that of microvascular spasm was 21,1% (173 patients). Hemodynamic evidence of spasm, i.e. a Pd/Pa(Ach)<0.80, was found in additional 44 (6,1%) patients, in whom the diagnosis would have been missed using traditional criteria. Similarly, a diagnosis based on hemodynamic changes allowed the identification of 37 (5,7%) patients who would have not been diagnosed as suffering from microvascular spasm. The overall diagnosis of epicardial spasm was therefore present in 136 (16,6%) patients, that of microvascular spasm was made in 210 (25,7%). Of note, 148 (85,5%) patients satisfying traditional criteria for microvascular spasm had no hemodynamic evidence of increased resistances, suggesting that the mechanism of ischemia might be different than traditionally assumed. Of those fulfilling the guideline criteria for epicardial spasm, only 37 (40,2%) had a hemodynamically significant epicardial obstruction (Pd/Pa<0.80) induced by acetylcholine (P<0.001). Conclusion A diagnosis of epicardial and microvascular spasm based on the standard guideline criteria can be enriched by the introduction of quantitative hemodynamic parameters, increasing the yield of acetylcholine testing.