Rethinking “false positive” stress-induced ST changes in ANOCA: association with coronary flow velocity reserve

Background Stress-induced ST-segment depression (STD) is usually interpreted using obstructive coronary artery disease as the reference standard. Purpose To evaluate the relationship between STD and coronary flow velocity reserve (CFVR) during stress echocardiography (SE) in patients with angina and non-obstructive coronary arteries (ANOCA). Methods We examined 475 ANOCA patients (50% women, 59±13 years) with preserved left ventricular function. Obstructive coronary stenosis was ruled out by invasive angiography or coronary CT. All underwent SE (exercise 44.6%, dobutamine 28.0%, vasodilators 27.4%) with 12-lead EKG and no inducible wall motion abnormalities. B-lines were also assessed in 433 patients. STD (≥0.1 mV at 80 ms after the J point in at least two contiguous interpretable leads) was considered ischemic. CFVR was measured in the mid-distal LAD; impaired CFVR was defined as ≤2.0. Multivariable logistic regression included CFVR (continuous), peak heart rate, and sex. Results STD was observed in 47 patients (10%). CFVR was lower in patients with stress-induced STD compared to those without (1.81±0.53 vs 2.08±0.77, p=0.01). The sensitivity and specificity of STD for CFVR ≤2.0 were 13% and 93%, respectively, with positive and negative predictive values of 70% and 47%. In multivariable analysis, lower CFVR remained independently associated with stress-induced STD (OR per unit increase 0.54, 95% CI 0.31–0.89; p=0.014). Stress-induced B-lines were more common in patients with STD than those without (see Table). Conclusions In ANOCA patients without inducible wall motion abnormalities, stress-induced STD is independently linked to impaired CFVR and is highly specific for microvascular dysfunction. Physiological interpretation reduces false positives during SE.