The Best Bypass Surgery Trial: rationale and design of a randomized clinical trial with blinded outcome assessment of conventional versus off-pump coronary artery bypass grafting.

BACKGROUND: Recent trials suggest that off-pump coronary artery bypass grafting (OPCAB) reduces the risk of mortality and morbidity compared with conventional coronary artery bypass grafting (CCAB) using cardiopulmonary bypass. Patients with a moderate- to high-risk of complications after CCAB may have additional benefit from OPCAB. METHODS: The Best Bypass Surgery Trial is a randomized, single center trial comparing the effects of OPCAB versus CCAB. The inclusion criteria are 3 vessel coronary heart disease affecting one of the marginal arteries, age>54 years, and EuroSCORE>or=5. The primary composite outcome measure consists of all-cause mortality, myocardial infarction, stroke, cardiac arrest, cardiogenic shock, and cardiac revascularization procedure. Follow up involves collection of data of mortality and morbidity via linkage to public registers, quality of life assessment at 3 and 12 months postoperatively and angiographic control at 12 months. The sample size of 330 patients was based on an estimated 75% one-year event free rate of the primary outcome measure in the OPCAB arm and 60% in the control arm with alpha=.05 and beta=.20. Accordingly, the trial will be able to detect an absolute risk reduction of 15% or a relative risk reduction of 37.5%. The median follow-up time is scheduled to 3 years. RESULTS: Enrollment started in April 2002 and ended March 2006. CONCLUSION: The results may have implications on the treatment modality of moderate- to high-risk patients scheduled for coronary artery bypass grafting.

Off-pump versus on-pump CABG in high-risk patients: short- and mid-term outcome.

OBJECTIVE: During recent years Conventional Coronary Artery Bypass Grafting (cCABG) and Off-Pump Coronary Bypass (OPCAB) have been compared in several randomised and non-randomised studies. Focus has been on postoperative outcome with short-term follow-up in low-risk patients and therefore little is known of the effectiveness of OPCAB in high-risk patients. Furthermore, it is unknown if a potential beneficial short-term outcome is consistent over time. DESIGN: In 2001, 217 patients with a Euroscore > or =5 were included in an observational cohort study; 162 patients were operated by cCABG and 55 by OPCAB. Follow-up data were retrieved from the Danish national person registry. The study includes a mid-term follow-up, with a mean follow-up time of 3.97 years+/-0.32. RESULTS: No differences in mortality between OPCAB and cCABG were found. In-hospital mortality was 5.5% in the OPCAB group vs 5.6% in the cCABG group and mid-term mortality was 21.8% in the OPCAB group vs 24.7% in the cCABG group; p = 0.71. During the follow-up period 41.5% of patients with an EF < or =35% at the time of surgery and 43.3% of patients with a Euroscore >8 died. Seven percent in the cCABG group had a perioperative AMI vs none in the OPCAB group; p < 0.05. In 74.5% cCABG's allogenic transfusions of blood components was necessary vs only 55.6% OPCAB's (p < 0.05). No significant differences in CNS complications or atrial fibrillation could be demonstrated. CONCLUSION: A similar outcome between OPCAB in cCABG in high-risk patients with respect to mortality was found. OPCAB seems to have a beneficial effect on morbidity. A cautious approach to patients with a combined high Euroscore and low ejection fraction should be the strategy of choice.

Health-related quality of life following off-pump versus on-pump coronary artery bypass grafting in elderly moderate to high-risk patients: a randomized trial.

OBJECTIVE: Previous trials comparing coronary artery bypass grafting (CABG) with or without extracorporeal circulation have mainly enrolled selected patients at younger age and low risk. Patient-reported health-related quality of life has not been significantly different. We compared health-related quality of life in elderly moderate to high-risk patients randomized to either off-pump or on-pump surgery. METHODS: The study is a sub-study of the randomized Best Bypass Surgery Trial that compares off-pump to on-pump treatment, with respect to peri- and postoperative mortality and morbidity in patients with a moderate to high-predicted preoperative risk. After randomization and before heart surgery, 120 consecutive patients were asked to fill in the Medical Outcomes Study Short Form 36 (SF-36) and Major Depression Inventory (MDI) diagnostic scale for self-report of health-related quality of life. Three months after surgery, the same questionnaires were mailed to the patients. RESULTS: The response rate was 96.5%. At baseline, the groups were comparable except for a difference in educational level. Both groups improved in all eight SF-36 domains from baseline to 3 months. No statistical differences were seen between the groups except for changes in mean difference of role limitation due to emotional problems, which was significantly (P=.04) improved in favour of the on-pump group. Depression scores remained unchanged within and between the two surgical groups. CONCLUSIONS: Both on-pump and off-pump patients improved in health-related quality of life scores after CABG surgery. No clinically relevant difference between the groups could be demonstrated.

Evaluation of myocardial metabolism with microdialysis after protection with cold blood- or cold crystalloid cardioplegia. A porcine model.

OBJECTIVES: There has been a considerable change in the patient population referred for cardiac surgery in the last decade. More complex and marginal patients require optimized myocardial protection. An insufficient cardioplegic procedure results in anaerobic metabolism during cardiac arrest with subsequent lactate accumulation. Increased lactate level is regarded as a predictor for low cardiac output syndrome. In an acute porcine model we examined two standard cardioplegic methods. Myocardial microdialysis was used to investigate the metabolism during cardioplegic arrest and in the reperfusion period. METHODS: Twelve domestic pigs were randomly chosen to receive either cold blood-or cold crystalloid cardioplegia. After midline sternotomy two microdialysis probes were implanted in two different regions of the heart. Cardiopulmonary bypass was initiated, aorta was clamped, and antegrade cardioplegia was delivered. These conditions were maintained for 90 min. Subsequent to myocardial reperfusion the animals were observed for 180 min. Microdialysis and plasma markers to characterize myocardial metabolism, and plasma markers for myocardial failure and necrosis were obtained every 30 min. RESULTS: Lactate concentrations were significantly increased in the cold crystalloid cardioplegia group compared to the cold blood cardioplegia group, in tissue dialysate (p < 0.001) as well as in serum (p = 0.018). Pyruvate concentrations in the dialysate were significantly increased in the cold crystalloid cardioplegia group compared to the cold blood cardioplegia group (p = 0.008). There were no significant differences in dialysate concentrations of glycerol. Plasma markers for myocardial failure (Brain Natriuretic Peptide) and for myocardial necrosis (Cardiac Troponin T) showed no differences between the groups. CONCLUSION: The results indicate that cold blood cardioplegia offers superior protection of the heart, in terms of more rapid normalization of myocardial metabolism. The microdialysis technique seems to have a high sensitivity and ability to detect even minor metabolic changes. This enhances the possibility of designing a myocardial protection, which might lower morbidity and mortality risk.

Cognitive outcomes in elderly high-risk patients after off-pump versus conventional coronary artery bypass grafting: a randomized trial.

BACKGROUND: It has been suggested that the risk of cerebral dysfunction is less with off-pump coronary artery bypass grafting (OPCAB) than with conventional coronary artery bypass grafting (CCAB). However, evidence for this statement is preliminary, and additional insight is needed. METHODS AND RESULTS: The study was a substudy of the randomized Best Bypass Surgery trial that compared OPCAB with CCAB treatment with respect to intraoperative and postoperative mortality and morbidity in patients with a moderate to high level of predicted preoperative risk. The outcome was cognitive function. A total of 120 elderly patients (mean age 76 years, SD 4.5 years) underwent psychometric testing before surgery and at a mean of 103 (SD 15) days postoperatively with a neuropsychological test battery that included 7 parameters from 4 tests. Cognitive dysfunction was defined as the occurrence of at least 2 of the 7 possible deficits. Secondary analysis was performed on the basis of the definition of a 20% decline in cognitive scores compared with baseline, and with z score analysis. Cognitive dysfunction was identified in 4 of the 54 patients (7.4%, 95% confidence interval [CI] 2.1% to 17.9%) in the OPCAB group and 5 of the 51 patients (9.8%, 95% CI 3.3% to 21.4%) in the CCAB group. We found no difference in incidence of cognitive dysfunction between the groups regardless of the definition applied. CONCLUSIONS: In elderly high-risk patients, no significant difference was found in the incidence of cognitive dysfunction 3 months after either OPCAB or CCAB.

Antithrombotic- and anticoagulation regimens in OPCAB surgery. A Nordic survey.

OBJECTIVES: The aim of the survey was to determine current practices for antiplatelet- and heparin therapy in OPCAB surgery in the Nordic countries. DESIGN: A postal survey questionnaire was sent to all 26 departments of Cardiothoracic Surgery in Norway, Sweden, Iceland, Finland, and Denmark. RESULTS: The overall response rate was 100%. The respondents performed between 130 and 1000 CABG procedures per year. Between 0.3% and 42.0% of these procedures were performed as OPCAB. Preoperative antiplatelet therapy was administered by 48%, while 96% routinely administer postoperative antiplatelet therapy. In the postoperative antiplatelet therapy there was a trend toward a combination of aspirin and low molecular weight heparin. Perioperative anticoagulation practices with heparin varied among departments as well as reversal with protamine. Eighty percent of the respondents register postoperative complications. CONCLUSION: In the Nordic countries there is no uniform practice regarding antiplatelet therapy pre- and postoperatively as well as heparin therapy perioperatively. Dose regimens are highly variable and standard protocols have not yet been developed.