The aim of this study was to evaluate the prognostic value of Doppler echocardiographically derived coronary flow reserve (CFR) in assessing inotropic response in patients with idiopathic dilated cardiomyopathy (IDC). One hundred thirty-two patients with IDC (90 men; mean age 62 +/- 11 years) were evaluated by transthoracic dipyridamole (0.84 mg/kg in 10 minutes) stress echocardiography. All patients had ejection fractions <40% (mean 33 +/- 7%) and angiographically normal coronary arteries, with New York Heart Association class <or=III. CFR was assessed in the left anterior descending coronary artery by pulsed Doppler as the ratio of maximal peak vasodilation (dipyridamole) to rest diastolic flow velocity. Inotropic reserve was identified as rest-stress variation in wall motion score index >0.25. All patients were followed for a median of 24 months. Mean CFR was 2.0 +/- 0.5. On individual patient analysis, 48 patients had normal CFR (>2), and 84 had abnormal CFR. The mean wall motion score index at rest was 2.0 +/- 0.33 and decreased to 1.8 +/- 0.4 at peak dipyridamole dose (p <0.000). Forty-two patients (32%) had inotropic reserve. During follow-up, 19 patients died, and 34 showed worsening of New York Heart Association class. The worst outcomes were observed in those patients with abnormal CFR and no inotropic reserve with high-dose dipyridamole. In a Cox model, mitral insufficiency (hazard ratio [HR] 1.7, 95% confidence interval [CI] 1.1 to 2.8), New York Heart Association class (HR 2.0, 95% CI 1.1 to 3.7), abnormal CFR (HR 2.8, 95% CI 1.0 to 8.5), wall motion score index at rest (HR 3.5, 95% CI 1.3 to 9.8), and the absence of inotropic reserve with high-dose dipyridamole (HR 2.3, 95% CI 1.06 to 5.1) were independent predictors of survival. In conclusion, in patients with IDC, CFR is often impaired. Reduced CFR and the absence of an inotropic response during vasodilator stress are additive in predicting a worse prognosis.