Long-Term Outcomes Among Patients With Acetylcholine-Induced Coronary Spasm

Quick Takes

  • Overall prognosis of patients with stable angina and unobstructed coronary arteries is favorable with low event rates.
  • Recurrent angina is common among this cohort, especially among patients with presumed microvascular angina on acetylcholine (Ach) testing.
  • Clinical application of routine Ach testing of patients with stable angina and unobstructed coronary arteries requires further study.

Study Questions:

What are long-term outcomes among patients presenting with stable angina without obstructive coronary arteries and undergoing intracoronary acetylcholine (Ach) testing?


This is a single-center observational study of 847 patients with symptoms of myocardial ischemia without obstructive epicardial stenosis who underwent Ach testing at the time of angiography. Median follow-up time was 7.2 years and data were available in 736 patients. Primary outcomes were all-cause death and cardiac death. Secondary endpoints included nonfatal myocardial infarction (MI), stroke, recurrent angina, repeat angiography, revascularization, psychological disorders, Raynaud’s disease, and migraine headaches.


In total, 55 deaths (7.5%), eight nonfatal MIs (1.4%), and 12 strokes (2.2%) occurred during the follow-up period. Recurrent symptoms were reported by 64% of patients and repeated coronary angiography was performed in 12% of cases. Multivariate analysis revealed epicardial spasm as a predictor of nonfatal MI (hazard ratio [HR], 14.369; 95% confidence interval [CI], 1.727-119.528) and repeated angiography (HR, 1.699; 95% CI, 1.061-2.719), whereas patients with microvascular spasm more often had recurrent angina at follow-up (HR, 1.318; 95% CI, 1.004-1.730).


In this long-term follow-up study, overall prognosis of patients with coronary spasm was favorable. Patients with epicardial spasm were at increased risk of myocardial infarction and repeat angiography, while microvascular spasm was associated with recurrent angina.


Patients presenting with signs and symptoms of myocardial ischemia in the absence of obstructive epicardial coronary artery disease remain a challenging cohort to manage and treat. The current publication provides insight into long-term prognosis of this cohort. Consistent with other studies, overall prognosis with respect to mortality, specifically cardiac mortality, is low. The authors show increased risk of nonfatal MI (14-fold higher risk) among those with epicardial spasm in response to Ach; however, confidence in this finding is low given the very wide confidence intervals (HR, 14.369 [1.727-119.528]). This study re-confirms that presumed microvascular angina (indirectly measured in this study) is associated with recurrent angina on follow-up. Approximately 30% of patients had inconclusive Ach testing results. Whether routine use of Ach testing in this cohort can be considered requires further study.

Clinical Topics: Cardiac Surgery, Invasive Cardiovascular Angiography and Intervention, Noninvasive Imaging, Stable Ischemic Heart Disease, Atherosclerotic Disease (CAD/PAD), Cardiac Surgery and SIHD, Interventions and Coronary Artery Disease, Interventions and Imaging, Angiography, Nuclear Imaging, Chronic Angina

Keywords: Acetylcholine, Angina, Stable, Constriction, Pathologic, Coronary Angiography, Coronary Artery Disease, Coronary Vasospasm, Microvascular Angina, Migraine Disorders, Myocardial Infarction, Myocardial Ischemia, Myocardial Revascularization, Stroke

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