Rethinking False Positive Exercise ECG Tests in ANOCA

Quick Takes

  • The presence of ischemia during exercise electrocardiogram stress testing was 100% specific for coronary microvascular dysfunction.
  • A significant difference in coronary microvascular dysfunction was noted with all patients in the ischemic group having coronary microvascular dysfunction.
  • Acetylcholine flow reserve was the strongest predictor of ischemia during exercise.

Study Questions:

What is the specificity of exercise electrocardiogram stress testing (EST) in detecting ischemic substrate in patients with angina and nonobstructive coronary arteries (ANOCA)?


Consecutive patients with ANOCA who underwent invasive coronary physiology assessment using adenosine and acetylcholine, who were referred for assessment, were enrolled in the present study. Patients with a left ventricular ejection fraction <50%, or chronic kidney disease, valvular disease, history of acute coronary syndrome, prior revascularization, noninterpretable electrocardiogram (ECG) (e.g., bundle branch block), or paced rhythm were excluded. Coronary microvascular dysfunction was defined as impaired endothelium-independent and/or endothelium-dependent function. EST was performed using a standard Bruce treadmill protocol. Ischemia was defined as the appearance of ≥0.1 mV ST-segment depression 80 milliseconds from the J-point on ECG.


A total of 102 patients were enrolled (mean age 60 ± 8 years old, 65% female), of which 32 developed ischemia during EST. No differences in gender, age, body mass index, or cardiovascular risk factors were noted between patients with ischemia and those without on EST. Patients with ischemia were more likely to have typical angina and lower hemoglobin levels than those without ischemia. No differences were noted in epicardial coronary physiology metrics, exercise time, or rates of exercise-induced angina. All 32 patients in the ischemic group had coronary microvascular dysfunction, compared to 66% of patients in the nonischemic group (p < 0.001). There were no differences in the coronary flow reserve or hyperemic microvascular resistance between the two groups. However, patients in the ischemic group had lower acetylcholine flow reserve (p < 0.001). The presence of ischemia during EST was 100% specific for coronary microvascular dysfunction. Using endothelium-independent and endothelium-dependent microvascular dysfunction as the reference standard, the false positive rate of ESTs dropped to 0%.


The authors conclude that in patients with ANOCA, ischemia on EST is highly specific of an underlying ischemic substrate. These findings challenge the traditional belief that EST has a high false positive rate.


Exercise stress testing has long been considered to have a high false positive rate. These data suggest a high sensitivity of EST among adults with angina and ANOCA. Given the prevalence of microvascular dysfunction, these data support the use of EST in evaluation of angina when coronary microvascular dysfunction is suspected.

Clinical Topics: Stable Ischemic Heart Disease, Chronic Angina

Keywords: Electrocardiography, Exercise Test, Microvascular Angina

< Back to Listings