Prognostic significance of individual COVADIS criteria in patients undergoing acetylcholine provocation testing

Background: The prognostic significance of the Coronary Vasomotor Disorders International Study Group (COVADIS) criteria during acetylcholine (ACh) provocation testing is uncertain. Aims: The aim of this study was to assess the prognostic impact of COVADIS criteria in patients with myocardial ischaemia (INOCA) or myocardial infarction (MINOCA) and non-obstructive coronary arteries undergoing ACh provocation testing. Methods: We enrolled consecutive INOCA and MINOCA patients undergoing ACh provocation testing. The occurrence of each COVADIS criterion was recorded. The primary outcome was the incidence of major adverse cardiovascular and cerebrovascular events (MACCE) at follow-up. Results: Among 519 patients (346 [66.7%] INOCA and 173 [33.3%] MINOCA), 274 (52.8%) exhibited a positive ACh test. Over a median 22-month follow-up, the highest incidence of MACCE occurred in patients with 3 positive criteria (15.4%), followed by those with 2 (10.3%) and 1 (9.2%), while the lowest incidence occurred in patients with 0 (3.1%; p=0.004). Patients with ≥1 positive criteria had significantly higher MACCE rates than those with 0 (12.5% vs 3.1%; p=0.003). MACCE-free survival differed significantly among the four groups, with the best survival for 0 criteria and the worst for 3 (p=0.004). Epicardial coronary diameter reduction ≥90% and MINOCA were independent MACCE predictors. Among patients with a negative test, an epicardial coronary diameter reduction ≥90% was the only independent predictor of MACCE, and the presence of ≥1 criteria in this group was associated with a significantly higher MACCE rate compared to patients without any criteria. Conclusions: Our findings challenge the binary stratification (positive vs negative) of COVADIS criteria, suggesting an added value of a comprehensive analysis of their components to provide prognostic stratification and personalised treatment.