on behalf of the Multicenter InSync ICD II Study GroupBackground-The effects of cardiac resynchronization therapy (CRT) in patients with mildly symptomatic heart failure have not been fully elucidated. Methods and Results-The Multicenter InSync ICD Randomized Clinical Evaluation II (MIRACLE ICD II) was a randomized, double-blind, parallel-controlled clinical trial of CRT in NYHA class II heart failure patients on optimal medical therapy with a left ventricular (LV) ejection fraction Յ35%, a QRS Ն130 ms, and a class I indication for an ICD. One hundred eighty-six patients were randomized: 101 to the control group (ICD activated, CRT off) and 85 to the CRT group (ICD activated, CRT on). End points included peak V O 2 , V E/V CO 2 , NYHA class, quality of life, 6-minute walk distance, LV volumes and ejection fraction, and composite clinical response. Compared with the control group at 6 months, no significant improvement was noted in peak V O 2 , yet there were significant improvements in ventricular remodeling indexes, specifically LV diastolic and systolic volumes (Pϭ0.04 and Pϭ0.01, respectively), and LV ejection fraction (Pϭ0.02). CRT patients showed statistically significant improvement in V E/V CO 2 (Pϭ0.01), NYHA class (Pϭ0.05), and clinical composite response (Pϭ0.01). No significant differences were noted in 6-minute walk distance or quality of life scores. Conclusions-In patients with mild heart failure symptoms on optimal medical therapy with a wide QRS complex and an ICD indication, CRT did not alter exercise capacity but did result in significant improvement in cardiac structure and function and composite clinical response over 6 months.

N IMPORTANT SUBSET OF PAtients who have chronic heart failure (HF) also have cardiac dyssynchrony. Delays in interventricular or intraventricular electrical activation cause marked abnormalities in the sequence of global and segmental right and left ventricular (LV) activation and impair mechanical performance. 1-3 The ability of new methods of cardiac stimulation to resynchronize ventricular function, improve overall cardiac performance, and increase exercise capacity has been shown by the results of several observational and controlled studies. 4-10 The Multicenter InSync Randomized Clinical Evaluation (MIRACLE), the first ran-Author Affiliations and Financial Disclosures are listed at the end of this article.

Annual coronary arteriograms have been obtained from all heart transplant recipients at Stanford University Medical Center since 1969. Angiographic lesions in 81 transplant patients exhibiting coronary vascular disease were classified into three categories: type A, discrete or tubular stenoses; type B, diffuse concentric narrowing; and type C, narrowed irregular vessels with occluded branches. The 81 arteriograms showing transplant coronary vascular disease were contrasted with 32 from nontransplant patients with coronary artery disease analyzed in a similar fashion. The nontransplant angiograms showed 178 lesions, all of type A (discrete or tubular) morphology, 75% of which were located in primary epicardial coronary vessels and 25% in secondary branch vessels. In the patients with transplant coronary vascular disease, 349 (76%) of 461 lesions were type A: 57% in primary vessels, 42% in secondary branches and 1.4% in tertiary branches. Of the 112 type B and C lesions (diffuse narrowing, tapering and obliteration), 25% were in primary vessels, 44% in secondary vessels and 31% in tertiary branches (p less than 0.05 for patients with transplant coronary vascular disease versus patients with nontransplant coronary artery disease). Total vessel occlusion was found in proximal or middle vessel segments in 96% and distally in 4% of patients with "ordinary" coronary artery disease versus 49% distally in patients with transplant coronary disease (p less than 0.002). In the presence of total vessel occlusion, collateral vessels were poor or absent in 92% of transplant versus 7% of nontransplant patients with coronary disease (p less than 0.002). Therefore, coronary artery disease in transplant patients represents a mixture of typical atheromatous lesions and unique transplant-related progressive distal obliterative disease that occurs without collateral vessel development.

Background-The transmembrane sodium/hydrogen exchanger maintains myocardial cell pH integrity during myocardial ischemia but paradoxically may precipitate cell necrosis. The development of cariporide, a potent and specific inhibitor of the exchanger, prompted this investigation of the potential of the drug to prevent myocardial cell necrosis. Methods and Results-A total of 11 590 patients with unstable angina or non-ST-elevation myocardial infarction (MI) or undergoing high-risk percutaneous or surgical revascularization were randomized to receive placebo or 1 of 3 doses of cariporide for the period of risk. The trial failed to document benefit of cariporide over placebo on the primary end point of death or MI assessed after 36 days. Doses of 20 and 80 mg every 8 hours had no effect, whereas a dose of 120 mg was associated with a 10% risk reduction (98% CI 5.5% to 23.4%, Pϭ0.12). With this dose, benefit was limited to patients undergoing bypass surgery (risk reduction 25%, 95% CI 3.1% to 41.5%, Pϭ0.03) and was maintained after 6 months. No effect was seen on mortality. The rate of Q-wave MI was reduced by 32% across all entry diagnostic groups (2.6% versus 1.8%, Pϭ0.03), but the rate of non-Q-wave MI was reduced only in patients undergoing surgery (7.1% versus 3.8%, Pϭ0.005). There were no increases in clinically serious adverse events. Conclusions-No significant benefit of cariporide could be demonstrated across a wide range of clinical situations of risk.The trial documented safety of the drug and suggested that a high degree of inhibition of the exchanger could prevent cell necrosis in settings of ischemia-reperfusion. (Circulation. 2000;102:3032-3038.)

TxCAD incidence appears to be lower in patients treated with ganciclovir who are not treated with calcium blockers. Given the limitations imposed by post hoc analysis, a randomized clinical trial is required to address this issue.

The majority of patients 1 or more years after cardiac transplantation have ultrasound evidence of intimal thickening not apparent by angiography. Intracoronary ultrasound offers early detection and quantitation of transplant coronary disease and provides characterization of vessel wall morphology, which may prove to be a prognostic marker of disease.

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These findings confirm the prognostic importance of mean intimal thickening of > 0.3 mm in heart transplant recipients and suggest that these patients should be candidates for early interventional strategies.