BackgroundAdenosine‐assisted transthoracic Doppler‐derived coronary flow reserve (TDE‐CFR) reflects coronary vascular function. The prognostic and incremental value of left anterior descending coronary artery TDE‐CFR above myocardial perfusion scintigraphy in patients with suspected myocardial ischemia has not yet been studied.Methods and ResultsThree hundred seventy‐one patients (mean age, 62.3±8.7 years; 46.8% males) referred to myocardial perfusion scintigraphy attributed to suspected myocardial ischemia were included in the study. The TDE‐CFR result was blinded to the referring physician. Patients were followed up regarding major cardiovascular events, defined as cardiovascular death, myocardial infarction, or acute revascularization during a median follow‐up time of 4.5 years. A TDE‐CFR value of ≤2.0 was considered reduced. Major cardiovascular events occurred during follow‐up in 60 patients (16.2%). A reduced TDE‐CFR was detected in 76 patients (20.5%). Patients with reduced TDE‐CFR had an event rate of 36.8% compared to 10.8% in patients with normal TDE‐CFR (unadjusted hazard ratio, 4.63; 95% CI, 2.78–7.69; P<0.001). In a multivariate model, TDE‐CFR remained a significant independent predictor of major cardiovascular events. The major cardiovascular events rate was 7.5% in patients without myocardial perfusion scintigraphy‐detected myocardial ischemia and normal TDE‐CFR (n=200), 24.2% in patients without ischemia but with reduced TDE‐CFR (n=33), and 46.5% in patients with both myocardial perfusion scintigraphy–detected myocardial ischemia and a reduced TDE‐CFR (n=43; P<0.001).ConclusionsCoronary microvascular dysfunction, as determined by TDE‐CFR, is a strong independent predictor of cardiovascular events and adds incremental prognostic value compared with myocardial perfusion scintigraphy. The current study supports routine assessment of CFR in patients with suspected ischemic heart disease.