Comparison of the Diagnostic Yield of Intracoronary Acetylcholine Infusion and Acetylcholine Bolus Injection Protocols During Invasive Coronary Function Testing

Coronary endothelial dysfunction (CED) and coronary artery spasm (CAS) are causes of angina in patients with no obstructive coronary arteries (ANOCA). Both can be diagnosed by invasive coronary function testing (ICFT) using Acetylcholine (ACh). This study aimed to evaluate the diagnostic yield of a 3-minute ACh infusion as compared to a 1-minute ACh bolus injection protocol in testing CED and CAS. In total 220 consecutive ANOCA patients underwent ICFT using continuous Doppler flow measurements. Per protocol, 110 patients were tested using 3-minute infusion and thereafter 110 patients using 1-minute bolus injections, due to a protocol change. CED was defined as a <50% increase in coronary blood flow or any epicardial vasoconstriction in reaction to low dose ACh and CAS according to the COVADIS criteria, both with and without T-wave abnormalities, in reaction to high dose ACh. The prevalence of CED was equal in both protocols (78% vs 79%; p=0.869). Regarding the endotypes of CAS according to COVADIS, the equivocal endotype was diagnosed less often in the 3-minutes vs 1-minute protocol (24% vs 44%; p=0.004). Including T-wave abnormalities to the COVADIS criteria resulted in a similar diagnostic yield of both protocols. Hemodynamic changes from baseline to the low or high ACh doses were comparable between the protocols for each endotype. In conclusion, ICFT using 3-minute infusion or 1-minute bolus injections of ACh showed a similar diagnostic yield of CED. When using the COVADIS criteria, a difference in the equivocal diagnosis was observed. Including T-wave abnormalities as diagnostic criterion reclassified equivocal test results into CAS and decreased this difference. For clinical practice, we recommend the inclusion of T-wave abnormalities as diagnostic criterion for CAS and the 1-minute bolus protocol for practicality.