Coronary flow reserve (CFR) is impaired in non-ischemic dilated cardiomyopathy (DCM). Mechanisms by which such impairment occurs are still unknown, but cofactors such as diastolic compressive force, left ventricular hypertrophy, and microvascular disease have been implied. In order to characterize the determinants of CFR in non-ischemic DCM, we evaluated 110 non-ischemic DCM patients (58 men; age=61+/-12 years) and 21 age- and gender-matched control patients (14 men; age=59+/-13 years) by transthoracic (n=88) or transesophageal (n=22) dipyridamole (0.84 mg/ kg in 10') stress echocardiography. All patients showed angiographically normal coronary arteries. Non-ischemic DCM patients had an ejection fraction <45% while control patients had normal left ventricular systolic function. CFR was assessed on LAD by pulsed Doppler as the ratio of maximal vasodilation (dipyridamole) to rest peak diastolic coronary flow velocity. Mean CFR value was 2.0+/-0.6 for DCM patients and 3.2+/-0.5 for controls (p<0.01). At individual non-ischemic DCM patient analysis, 46 patients had normal CFR> or =2 (Group 1) and 64 patients had abnormal CFR<2 (Group 2). On univariate analysis, CFR reduction correlated with NYHA functional class (r=-0.33, p=0.001), left ventricular ejection fraction ( r=0.23, p=0.02), end-systolic volume (r=-0.23, p=0.02), systolic pulmonary artery pressure (r=-0.42, p=0.0001), deceleration time (r=0.24, p=0.02). Logistic multiregression analysis showed that only NYHA functional class significantly and negatively correlated with CFR (odds ratio=0.9; 95% confidence intervals: 0.03-.35, p=0.0001). In patients with non-ischemic DCM, CFR is reduced but with substantial individual variability, only partially accounted for by level of systolic and diastolic dysfunction. The clinical functional class is the strongest predictor of CFR reduction in these patients, with lowest flow reserve found in more advanced NYHA class.