In patients with non-obstructive coronary arteries undergoing acetylcholine testing, endothelial dysfunction and a MINOCA presentation were independently associated with adverse events, whereas classical spasm endotypes were not.
MINOCA was diagnosed in 9.4% of patients undergoing acetylcholine testing in the combined cohort.
Endothelial dysfunction was found in 57.4% of the overall cohort, with epicardial spasm in 7.05% and microvascular spasm in 1.94%.
MINOCA was independently associated with resting chest pain, previous myocardial infarction, and active smoking in multivariable regression.
Over a median follow-up of 3.0 years, major adverse cardiovascular events (MACE) occurred in 7.5% of patients.
MINOCA was independently associated with a nearly threefold higher risk of MACE compared to ANOCA.
Endothelial dysfunction was independently associated with a significantly higher risk of MACE.
Male sex was independently associated with increased MACE risk.
Patients with both MINOCA and endothelial dysfunction had the highest event rate at 19.4%.
This research suggests that among patients who have had a heart attack but whose coronary arteries are not significantly blocked (a condition called MINOCA), testing with a drug called acetylcholine can reveal important information about future cardiovascular risk. The study combined data from 723 patients across two registries in Spain and found that more than half of all patients tested had endothelial dysfunction — a condition where the inner lining of coronary arteries does not function normally. Importantly, MINOCA patients were more likely to have a history of prior heart attacks, resting chest pain, and active smoking, but they did not differ from patients with stable angina and non-obstructive arteries in terms of the specific type of coronary dysfunction detected. The study followed patients for a median of three years and found that 7.5% experienced major adverse cardiovascular events (MACE), such as further heart attacks or cardiovascular death. Two key factors independently predicted these bad outcomes: having had a MINOCA presentation (nearly tripling the risk) and having endothelial dysfunction (increasing risk by about 2.6-fold). Notably, the classical patterns of coronary spasm — epicardial and microvascular — were not independently linked to worse outcomes, suggesting that endothelial dysfunction as a broader category is the more clinically meaningful finding. Patients who had both MINOCA and endothelial dysfunction faced the worst prognosis, with an event rate of nearly 20%. This research suggests that acetylcholine testing, which can identify endothelial dysfunction in patients with non-obstructive coronary arteries, may help clinicians identify which patients are at highest risk for future cardiovascular events. The findings highlight that MINOCA is not a benign condition and that endothelial dysfunction — even beyond identifiable spasm — carries important prognostic significance, potentially informing how these patients are monitored and managed after their initial presentation.
Gabaldón-Badiola &, Ruiz Esquivel J, Rumiz E, Oteo J, Gutiérrez-Barrios A, Perez-Guerrero A, et al.. (2026). Endothelial dysfunction and long-term outcomes in patients with myocardial infarction and non-obstructive coronary arteries.. International journal of cardiology. https://doi.org/10.1016/j.ijcard.2026.134750