Studies in patients without coronary artery disease have shown the restoration of glucose metabolism by cardiac resynchronization therapy (CRT) without changes in myocardial perfusion. We report on the long-term outcome of CRT in 24 patients with severe heart failure (HF) and advanced coronary artery disease not amenable for revascularization. All patients had documented myocardial ischemia on stress (99)Tc-sestamibi single-photon emission computed tomography, and all underwent successful implantations of CRT systems. The mean left ventricular ejection fraction was 21%+/- 4%, 19 patients (79%) had anginal complaints and 20 (83%) had diffuse three-vessel disease. During a follow-up of 13 +/- 0.7 months, two patients died suddenly and one died of progressive HF. Among survivors, functional capacity decreased from New York Heart Association class 3.2 +/- 1.4 to 2.1 +/- 1.0 (P < 0.01), and the Minnesota questionnaire quality-of-life scores decreased from 43 +/- 15 to 28 +/- 13 (P < 0.01). Despite an increase from 264 +/- 104 to 385 +/- 121 m in distance walked in 6 minutes (P < 0.01), the number of anginal attacks/week remained unchanged (4.7 +/- 0.7 to 4.5 +/- 0.6). Patients with advanced HF, stable angina, and documented myocardial ischemia may undergo safe and successful implantations of CRT systems.