Endothelial Dysfunction and Long-Term Prognosis of Variant Angina

Purpose. Variant angina is a broad clinical diagnosis that includes patients at different levels of coronary artery disease (CAD) and risk for an unfavorable outcome. Methods. We followed for a mean of 13 years (range 2 to 23) 117 consecutive patients admitted to coronary care unit with chest pain and transient ST elevation. At recruitment, all patients underwent intracoronary acetylcholine testing. Patients with obstructive CAD underwent coronary revascularization within 6 months from admission. Treatment with calcium antagonists was kept constant during follow-up. Results. Intracoronary acetylcholine provoked endothelial dysfunction in 39 patients (group 1). It caused focal coronary spasm in 17 patients and diffusely severe vasoconstriction (coronary diameters changes of –35+/-11%; range---) in 22 patients. The remaining 20 patients (group 2) showed mild to normal endothelial function (vasodilatation or mild vasoconstriction with coronary diameters changes of 5+/-1%; range---). At the end of follow-up, cardiac death occurred in 20 patients and non-fatal myocardial infarction in 24. The Cox analysis selected left ventricular function, duration of angina, age, and endothelial dysfunction as multivariate independent predictors of survival and nonfatal myocardial infarction. Endothelial dysfunction was the strongest predictor (p < .0001) of major coronary events. Survival of group 1 and 2 was 82% and 95% respectively; survival without infarction was 62% and 83%, respectively. The extent of obstructive CAD at admission was a predictor of revascularization, but not of survival and nonfatal myocardial infarction. Myocardial infarction and death occurred most commonly late (4 to 7 years) after diagnosis in patients previously found with non-obstructive CAD. Recurrent episodes of angina rarely preceded late coronary events. Conclusions. Although, as in other categories of CAD, the state of left ventricular function and the age are major determinants of long-term prognosis, recognition of clinical markers of endothelial dysfunction predicts an unfavorable course in patients with variant angina. The extent of CAD does not correlate with endothelial dysfunction. Intra-coronary acetylcholine may be of value in defining future management strategies in such patients.