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AIM: To determine the impact of previous coronary artery revascularization by percutaneous transluminal coronary angioplasty and/or stenting (PCI) on outcome after subsequent coronary artery bypass grafting (CABG). METHODS AND RESULTS: The ischaemia management with Accupril post-bypass Graft via Inhibition of the coNverting Enzyme (IMAGINE) trial, conducted between November 1999 and September 2004, tested whether early initiation of an angiotensin-converting enzyme inhibitor post-CABG, in stable patients with LVEF >or=40%, would reduce cardiovascular events. Of the 2489 patients included in the IMAGINE trial, undergoing their first operation, 430 had a history of PCI prior to surgery (PCI group), and 2059 were referred to surgery without previous PCI (non-PCI group). There was a significant increase in the primary IMAGINE endpoint in the PCI group, HR = 1.53 [1.17-1.98], P = 0.0016. Coronary revascularization, HR = 1.80 [1.13-2.87], P = 0.014, unstable angina requiring hospitalization, HR = 2.43 [1.52-3.89], P = 0.0002, were the two individual components that significantly increased in the PCI group, even when adjusted for baseline characteristics (age, sex, history of myocardial infarction or stroke, diabetes, treatment group, or off-pump surgery). CONCLUSION: Patients with left ventricular ejection fraction >or=40% having a history of PCI prior to surgery had a worse outcome post-CABG than those with no prior PCI. Further studies are needed to investigate whether these results apply for drug eluting stents.

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BACKGROUND: Early after coronary artery bypass surgery (CABG), activation of numerous neurohumoral and endogenous vasodilator systems occurs that could be influenced favorably by angiotensin-converting enzyme inhibitors. METHODS AND RESULTS: The Ischemia Management with Accupril post-bypass Graft via Inhibition of the coNverting Enzyme (IMAGINE) trial tested whether early initiation (< or = 7 days) of an angiotensin-converting enzyme inhibitor after CABG reduced cardiovascular events in stable patients with left ventricular ejection fraction > or = 40%. The trial was a double-blind, placebo-controlled study of 2553 patients randomly assigned to quinapril, target dose 40 mg/d, or placebo, who were followed up to a maximum of 43 months. The mean (SD) age was 61 (10) years. The incidence of the primary composite end point (cardiovascular death, resuscitated cardiac arrest, nonfatal myocardial infarction, coronary revascularization, unstable angina or heart failure requiring hospitalization, documented angina, and stroke) was 13.7% in the quinapril group and 12.2% in the placebo group (hazard ratio 1.15, 95% confidence interval 0.92 to 1.42, P=0.212) over a median follow-up of 2.95 years. The incidence of the primary composite end point increased significantly in the first 3 months after CABG in the quinapril group (hazard ratio 1.52, 95% confidence interval 1.03 to 2.26, P=0.0356). Adverse events also increased in the quinapril group, particularly during the first 3 months after CABG. CONCLUSIONS: In patients at low risk of cardiovascular events after CABG, routine early initiation of angiotensin-converting enzyme inhibitor therapy does not appear to improve clinical outcome up to 3 years after CABG; however, it increases the incidence of adverse events, particularly early after CABG. Thus, early after CABG, initiation of angiotensin-converting enzyme inhibitor therapy should be individualized and continually reassessed over time according to risk.

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It has been hypothesized that angiotensin-converting enzyme (ACE) inhibition, independent from its effect on ventricular function and blood pressure, could affect the atherosclerotic process and reduce the incidence of ischemic events and its complications. Several large clinical outcome trials were designed to test this hypothesis: QUIET, HOPE, EUROPA, PEACE, and IMAGINE. The results of the PEACE study were recently reported, leaving the IMAGINE study as the last chapter in our efforts to evaluate the role of ACE inhibition in coronary artery disease with preserved left ventricular function. In this report, we compare these studies with respect to their methodology and patient population and analyze the unique nature of the last ongoing study, IMAGINE. The reported studies show that patients with coronary artery disease who are at low-to-moderate or high risk should receive an ACE inhibitor if tolerated. However, when the absolute risk of a patient decreases, and intensive contemporary management is given, with good control of risk factors, the absolute and perhaps relative benefits of an ACE inhibitor decrease and their routine use in these patients may not be warranted. The role of ACE inhibition started early post-coronary artery bypass graft in patients with preserved left ventricular function, and intensive contemporary management remains to be determined and should get answered by the IMAGINE study. Moreover, the IMAGINE population is not only a lower risk population than those enrolled in HOPE or EUROPA, but also the risk for this population is bimodal in nature (early post-revascularization inflammation and thrombosis vs long-term atherosclerosis progression) and may provide further insight into underlying mechanisms.

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OBJECTIVE: Nitrate-stimulated tilt testing may be used to diagnose vasovagal syncope or to guide therapy. To date, the reproducibility of the test in patients with clinically suspected vasovagal syncope and healthy controls is undetermined. A high reproducibility is a prerequisite for correct interpretation of the test result. This study investigates the reproducibility of a nitrate-stimulated tilt test in patients with clinically suspected vasovagal syncope and a healthy control group. METHODS AND RESULTS: We studied 43 patients (24 women, 19 men) with a typical history of vasovagal syncope and 18 healthy controls (3 women, 15 men). We used a combined tilt protocol with a 30-minute passive and 15-minute nitrate-stimulated phase. The second tilt test was performed 16 +/- 12 days after the first. In both patients and controls, overall positive tilt responses were reproduced in the second test in 100%. In contrast to this, the reproducibility of an overall negative test was 50% in patients but 93% in controls. Overall hemodynamic responses to tilt were reproducible in 80%. CONCLUSION: Nitrate-stimulated tilt testing in both patients with suspected vasovagal syncope and controls has an excellent reproducibility of positive results but a moderate reproducibility of negative results. Importantly, these results are still valid at a repeat interval of 2 weeks and longer. These data suggest that in patients with suspected vasovagal syncope, a nitrate-stimulated tilt test may provide a suitable tool to evaluate the efficacy of a therapeutic approach.

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BACKGROUND: Coronary artery bypass grafting (CABG) remains the revascularization treatment of choice for patients with severely symptomatic or life-threatening coronary artery disease (CAD). However, 9% to 25% of the patients undergoing CABG will suffer a recurrent ischemic event such as death, recurrent infarction, angina or repeat revascularization. The pathophysiological processes particular to the CABG procedure that may affect graft endothelial function are most active in the early phase after surgery. Angiotensin-converting enzyme (ACE) inhibition has been shown to be effective in reducing or preventing ischemic events in patients with and without left ventricular dysfunction, and in those at high risk for CAD. Nonetheless, no large clinical trail has investigated this role of ACE inhibition in preventing ischemic events early after CABG. OBJECTIVE: The Ischemia Management with Accupril post bypass Graft via Inhibition of angiotensin coNverting Enzyme (IMAGINE) study addressed whether ACE inhibition initiated early after CABG improves short and long term outcomes in patients after CABG. PATIENTS AND METHODS: This multicentre, multinational trial recruited 2204 patients with an uncomplicated course early after CABG from 55 to 65 medical care facilities in Canada, The Netherlands, Belgium and France. Eligible patients with normal left ventricular function were randomly assigned to placebo or quinapril (titrated up to 40 mg daily where possible) within seven to 10 days after CABG. All patients were followed up closely for a minimum of 12 months after random placement. The median treatment period is expected to be approximately 27 months.

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