BACKGROUND Cardiac resynchronization therapy (CRT) improves functional outcomes in patients with severe systolic heart failure. Whether the effects of CRT on left ventricular (LV) diastolic function and clinical outcomes are influenced by the cause as either ischemic or nonischemic cardiomyopathy (CM) has not been well established. METHODS A total of 57 patients (age 60 +/- 11 years; 25% women; LV ejection fraction 25 +/- 5%) were studied before and 4 +/- 2 months after CRT by echocardiography. Heart failure cause was ischemic CM in 19 and nonischemic CM in 38. Measurements of LV systolic and diastolic function were determined by 2-dimensional and Doppler echocardiography with Doppler tissue imaging of regional myocardial velocities. Clinical outcome events were assessed at long-term follow-up and included hospitalization for heart failure exacerbation, heart transplantation, or cardiac-related death. RESULTS There were significant increases in LV ejection fraction, reductions in end-systolic volumes, and improved LV systolic dyssynchrony in both groups. However, significant improvements in LV diastolic function were observed only in the patients with nonischemic CM. Clinical events occurred in 53% of the ischemic group versus 26% of the nonischemic group (P < .05) after 20 +/- 11 months of CRT. Univariate and multivariate analysis revealed that Doppler-estimated LV filling pressures were predictors of clinical outcome events. CONCLUSIONS After CRT patients with ischemic CM exhibit lack of improvement in LV diastolic function despite favorable effects on LV systolic performance. The Doppler-derived LV filling indices may be an important predictor of long-term clinical outcomes after CRT.