John C. Lucke

On-Pump versus Off-Pump Coronary-Artery Bypass Surgery

BACKGROUND Coronary-artery bypass grafting (CABG) has traditionally been performed with the use of cardiopulmonary bypass (on-pump CABG). CABG without cardiopulmonary bypass (off-pump CABG) might reduce the number of complications related to the heart-lung machine. METHODS We randomly assigned 2203 patients scheduled for urgent or elective CABG to either on-pump or off-pump procedures. The primary short-term end point was a composite of death or complications (reoperation, new mechanical support, cardiac arrest, coma, stroke, or renal failure) before discharge or within 30 days after surgery. The primary long-term end point was a composite of death from any cause, a repeat revascularization procedure, or a nonfatal myocardial infarction within 1 year after surgery. Secondary end points included the completeness of revascularization, graft patency at 1 year, neuropsychological outcomes, and the use of major resources. RESULTS There was no significant difference between off-pump and on-pump CABG in the rate of the 30-day composite outcome (7.0% and 5.6%, respectively; P=0.19). The rate of the 1-year composite outcome was higher for off-pump than for on-pump CABG (9.9% vs. 7.4%, P=0.04). The proportion of patients with fewer grafts completed than originally planned was higher with off-pump CABG than with on-pump CABG (17.8% vs. 11.1%, P<0.001). Follow-up angiograms in 1371 patients who underwent 4093 grafts revealed that the overall rate of graft patency was lower in the off-pump group than in the on-pump group (82.6% vs. 87.8%, P<0.01). There were no treatment-based differences in neuropsychological outcomes or short-term use of major resources. CONCLUSIONS At 1 year of follow-up, patients in the off-pump group had worse composite outcomes and poorer graft patency than did patients in the on-pump group. No significant differences between the techniques were found in neuropsychological outcomes or use of major resources. (ClinicalTrials.gov number, NCT00032630.).

Percutaneous Coronary Intervention Versus Coronary Artery Bypass Graft Surgery for Patients With Medically Refractory Myocardial Ischemia and Risk Factors for Adverse Outcomes With Bypass: A Multicenter, Randomized Trial

Abstract BACKGROUND Percutaneous coronary intervention (PCI) and coronary artery bypass graft surgery (CABG) are being applied to high-risk populations, but previous randomized trials comparing revascularization methods have excluded a number of important high-risk groups. OBJECTIVES This five-year, multicenter, randomized clinical trial was designed to compare long-term survival among patients with medically refractory myocardial ischemia and a high risk of adverse outcomes assigned to either a CABG or a PCI strategy, which could include stents. METHODS Patients from 16 Veterans Affairs Medical Centers were screened to identify myocardial ischemia refractory to medical management and the presence of one or more risk factors for adverse outcome with CABG, including prior open-heart surgery, age >70 years, left ventricular ejection fraction RESULTS A total of 232 patients was randomized to CABG and 222 to PCI. The 30-day survivals for CABG and PCI were 95% and 97%, respectively. Survival rates for CABG and PCI were 90% versus 94% at six months and 79% versus 80% at 36 months (log-rank test, p = 0.46). CONCLUSIONS Percutaneous coronary intervention is an alternative to CABG for patients with medically refractory myocardial ischemia and a high risk of adverse outcomes with CABG.

Percutaneous coronary intervention versus coronary bypass graft surgery for diabetic patients with unstable angina and risk factors for adverse outcomes with bypass: Outcome of diabetic patients in the AWESOME randomized trial and registry

OBJECTIVES This study compared survival after percutaneous coronary intervention (PCI) with survival after coronary artery bypass graft surgery (CABG) among diabetics in the Veterans Affairs AWESOME (Angina With Extremely Serious Operative Mortality Evaluation) study randomized trial and registry of high-risk patients. BACKGROUND Previous studies indicate that CABG may be superior to PCI for diabetics, but no comparisons have been made for diabetics at high risk for surgery. METHODS Over five years (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior CABG, myocardial infarction within seven days, left ventricular ejection fraction <0.35, age >70 years, or an intra-aortic balloon being required to stabilize) were identified. A total of 781 were acceptable for CABG and PCI, and 454 consented to be randomized. The 1,650 patients not acceptable for both CABG and PCI constitute the physician-directed registry, and the 327 who were acceptable but refused to be randomized constitute the patient-choice registry. Diabetes prevalence was 32% (144) among randomized patients, 27% (89) in the patient-choice registry, and 32% (525) in the physician-directed registry. The CABG and PCI survival rates were compared using Kaplan-Meier curves and log-rank tests. RESULTS The respective CABG and PCI 36-month survival rates for diabetic patients were 72% and 81% for randomized patients, 85% and 89% for patient-choice registry patients, and 73% and 71% for the physician-directed registry patients. None of the differences was statistically significant. CONCLUSIONS We conclude that PCI is a relatively safe alternative to CABG for diabetic patients with medically refractory unstable angina who are at high risk for CABG.

Percutaneous coronary intervention versus coronary bypass graft surgery for patients with medically refractory myocardial ischemia and risk factors for adverse outcomes with bypass: the VA AWESOME multicenter registry: comparison with the randomized clinical trial

OBJECTIVES This study was designed to compare the three-year survival after percutaneous coronary intervention (PCI) or coronary artery bypass graft surgery (CABG) in physician-directed and patient-choice registries with the Angina With Extremely Serious Operative Mortality Evaluation (AWESOME) randomized trial results. BACKGROUND The AWESOME multicenter randomized trial and registry compared the long-term survival after PCI and CABG for the treatment of patients with medically refractory myocardial ischemia and at least one additional risk factor for adverse outcome with CABG. The randomized trial demonstrated comparable three-year survival. METHODS Over a five-year period (1995 to 2000), 2,431 patients with medically refractory myocardial ischemia and at least one of five risk factors (prior heart surgery, myocardial infarction within seven days, left ventricular ejection fraction <0.35, age >70 years, intra-aortic balloon required to stabilize) were identified. By physician consensus, 1,650 patients formed a physician-directed registry assigned to CABG (692), PCI (651) or further medical therapy (307), and 781 were angiographically eligible for random allocation; 454 of these patients constitute the randomized trial, and the remaining 327 constitute a patient choice registry. Survival for CABG and PCI was compared using Kaplan-Meier curves and log-rank tests. RESULTS The CABG and PCI 36-month survival rates for randomized patients were 79% and 80%, respectively. The CABG and PCI 36-month survival rates were both 76% for the physician-directed subgroup; comparable survival rates for the patient-choice subgroup were 80% and 89%, respectively. None of the global log-rank tests for survival demonstrated significant differences. CONCLUSIONS Both registries support the randomized trial conclusion: PCI is an alternative to CABG for some medically refractory high-risk patients.

Results of Valve Replacement With Mechanical and Biological Prostheses in Chronic Renal Dialysis Patients

BACKGROUND Whether biological or mechanical valves should be used in patients on chronic dialysis therapy remains to be clearly defined. METHODS A retrospective review was performed on 19 consecutive patients from our institution with end-stage renal disease on chronic peritoneal or hemodialysis undergoing aortic (n = 12), mitral (n = 5), or aortic-mitral (n = 2) valve replacement. RESULTS The 9 biological and 10 mechanical valve patients had similar ages (56.5 versus 56.6 years) and cardiovascular risk factors. The overall estimated Kaplan-Meier survival was 60% +/- 12% at 12 months and 42% +/- 14% at 60 months. Mechanical valve patients had a significantly higher rate of postoperative cerebrovascular accidents or bleeding complications (10/10 versus 0/9; chi 2 = 17.0; p < 0.001). No subsequent reoperations were required for biological valve failure at a mean follow-up of 32 +/- 53 months. CONCLUSIONS These results demonstrate that in patients with end-stage renal disease, use of mechanical valves is associated with significant risk of complications, whereas biological valve failure from prosthetic dysfunction is unusual. Overall survival is poor in both groups of patients. Therefore, preference should be given to biological valve instead of mechanical valve prostheses in patients on chronic renal dialysis.

A study design to assess the safety and efficacy of on-pump versus off-pump coronary bypass grafting: the ROOBY trial.

Background Since the late 1960s, coronary artery bypass graft (CABG-only) procedures were traditionally performed using a heart-lung machine on an arrested heart (on-pump). Over the past decade, an increasing number CABG-only procedures were performed on a beating heart (off-pump). Advocates of the off-pump approach expect to reduce many of the adverse side effects related to using the heart-lung machine, while advocates for the on-pump procedure raise concerns related to graft patency rates and long-term event-free survival for the off-pump technique. Purpose The U.S. Department of Veteran Affairs (VA) Cooperative Studies Program funded a randomized, multicenter clinical trial comparing the clinical and resourcerelated outcomes following on-pump versus off-pump techniques for veterans undergoing a non-emergent CABG-only procedure. The planning committee was faced with several critically important challenges to assure feasibility of study costs and required sample size; generalizability to non-VA surgical practices; and comparability of clinically meaningful results. These challenges are discussed. Methods This study is a prospective, randomized, multicenter, single blinded (patient) clinical trial that compares on-pump and off-pump techniques for veterans requiring non-emergent CABG-only procedures. There will be 2200 patients randomized at 17 VA Medical Centers when the five-year recruitment period ends on 15 April 2007. There are two primary objectives: a short-term objective to assess the immediate impact of the two techniques on 30-day mortality/morbidity and a long-term objective to assess one-year mortality/morbidity. Major secondary outcomes are one-year graft patency rates and change in neuropsychological assessments from baseline to one year. All patients are assessed at 30 days post-surgery or discharge from the hospital, whichever is latest, and at one-year post-surgery. Results During planning, several key issues had to be decided. These included 1) choosing primary objectives: a short-term (30-day) and a long-term (one-year) objective were chosen; 2) choosing primary outcome measures: composite measures were selected to ensure sufficient end-points; 3) standardization of surgical techniques: minimal standardization required but guidelines and continuing discussions on both techniques provided; 4) establishing criteria for surgeons and residents for participation: surgeons required to have completed 20 off-pump procedures prior to doing study procedures and residents, in presence of study surgeon, capable of doing either procedure; 5) identifying metrics of cognitive dysfunction sensitive to treatment: a neuropshychologist hired who centrally monitors cognitive functioning testing; and 6) blinding participants of surgical procedure: attempt to blind participants. Limitations Areas of concern are whether all surgeons sufficiently experienced on the off-pump procedure, should residents have been allowed to do study surgeries, should techniques have been standardized more and were the best neurocognitive tests selected. Conclusion The study design presented allows for a balanced and fair assessment of the on-pump and off-pump CABG procedures across a diversity of clinical outcomes and resource use metrics. Its results have the potential to influence clinical cardiac surgical practice in the future.

Mortality and need for reoperation in patients with mild-to-moderate asymptomatic aortic valve disease undergoing coronary artery bypass graft alone

BACKGROUND Patients presenting for coronary artery bypass graft (CABG) surgery may have concurrent asymptomatic aortic stenosis (AS) or aortic insufficiency (AI). This retrospective study was performed to evaluate outcomes in patients with aortic valve disease undergoing CABG with or without aortic valve replacement (AVR). METHODS Study groups included 414 patients undergoing combined AVR and CABG (AVR-CABG group) and 62 patients with asymptomatic mild-to-moderate AS, AI, or both undergoing CABG but not AVR (CABG group). End points included 30-day mortality rate, time to cardiac mortality, time to all-cause mortality, and time to aortic valve reoperation. Reoperation refers to surgery for replacement of the native aortic valve in the CABG group or replacement of the prosthetic aortic valve in the AVR-CABG group. Important patient characteristics affecting outcomes were determined by using Cox proportional-hazard analysis. These variables were then included in multivariable analyses by using logistic regression analysis and Cox proportional-hazard modeling to compare outcomes between each patient group. RESULTS No difference was seen in any of the mortality end points between the CABG group and the AVR-CABG group after controlling for significant differences between the groups. However, the need for reoperation for AVR was significantly higher for the CABG group than the AVR-CABG group. For patients followed for up to 6 years, the estimated need for aortic valve reoperation was 24.3% in the CABG group versus 3% in the AVR-CABG group. CONCLUSION On the basis of these results, patients with asymptomatic AS or AI should be considered for AVR at the time of CABG.

A Multicenter, Randomized Trial of Percutaneous Coronary Intervention Versus Bypass Surgery in High-Risk Unstable Angina Patients

This multicenter, prospective randomized trial was designed to test the hypotheses that percutaneous coronary intervention (PCI) is a safe and effective alternative to coronary artery bypass grafting (CABG) for patients with refractory ischemia and high risk of adverse outcomes. As a comparison of revascularization strategies, the trial specifically allows surgeons and interventionists to use new techniques as they become clinically available. After 42 months of this 72-month trial, 17,624 patients have been screened and 2022 met eligibility requirements: 341 have been randomized to either CABG or PCI, and the remaining 1681 are being prospectively followed in a registry. The 3-year overall survival of patients in the registry and randomized trial is comparable. To enhance accrual into the randomized trial, site visits were conducted, a few low-accruing hospitals were put on probation and/or replaced, eligibility criteria were reviewed at annual meetings of investigators, and the accrual period was extended by 1 year. These data demonstrate that a prospective randomized trial and registry of coronary revascularization for medically refractory high-risk patients is feasible.

Mechanical determinants of myocardial oxygen consumption in conscious dogs

A new practical descriptor of metabolic to mechanical myocardial energy transfer (MET), termed the virtual work model, was evaluated in 32 conscious dogs and in 8 isolated canine hearts. An index of total mechanical energy expenditure (TME) was calculated as the sum of external energy (stroke work) and an internal energy index of heat (left ventricular end-diastolic volume times left ventricular mean ejection pressure). Physiological comparison of TME (x-axis) and myocardial oxygen consumption (MVO2; y-axis) yielded highly linear MET relationships (mean r = 0.93 +/- 0.07), with an average slope of 0.86 +/- 0.39 (SD) and a y-intercept of 9.1 +/- 6.4 mW/ml myocardium. The linear MVO2-TME relationship did not vary under steady-state vs. dynamic vena caval occlusion, increased heart rate, increased afterload, or increased inotropic state with calcium infusion. Compared with five other indexes of myocardial energetics, the virtual work model of MET was the most linear, the most practical in not requiring determination of the end-systolic pressure-volume relationship, and the most accurate predictor of MVO2 under normal and altered hemodynamic conditions.

Surgeon Judgment and Utility of Transit Time Flow Probes in Coronary Artery Bypass Grafting Surgery

IMPORTANCE Transit time flow (TTF) probes may be useful for predicting long-term graft patency and assessing grafts intraoperatively in patients undergoing coronary artery bypass grafting (CABG); however, studies of TTF probe use are limited. OBJECTIVE To examine 1-year graft patency and intraoperative revision rates in patients undergoing CABG based on intraoperative TTF assessment. DESIGN, SETTING, AND PARTICIPANTS Retrospective analysis of a multicenter randomized clinical trial conducted at 18 Veterans Affairs hospitals using the Randomized On/Off Bypass (ROOBY) Trial data set. Of the original 2203 patients undergoing CABG surgery with or without cardiopulmonary bypass from February 1, 2002, through May 31, 2008, we studied a subset of 1607 who underwent TTF probe analysis of 1 or more grafts during surgery. EXPOSURES Use of TTF probes to assess graft flow and pulsatility index (PI) values. The decision to revise a graft was based on the judgment of the attending surgeon. MAIN OUTCOMES AND MEASURES Rates of 1-year FitzGibbon grade A patency and intraoperative revision were compared based on TTF measurements (<20 [low flow] vs ≥20 mL/min [normal flow]) and PI values (<3, 3-5, and >5). RESULTS We measured TTF and/or PI in 2738 grafts, and 1-year patency was determined in 1710 (62.5%) of these grafts. FitzGibbon grade A patency occurred significantly less often in grafts with a TTF with low flow (259 of 363 [71.3%]) than in those with normal flow (1174 of 1347 [87.2%]; P < .01). FitzGibbon grade A patency was also inversely correlated with increasing PI values, as found in 936 of 1093 grafts (85.6%) with a PI less than 3, 136 of 182 grafts (74.7%) with a PI of 3 to 5, and 91 of 134 grafts (67.9%) with a PI greater than 5 (P ≤ .01). Intraoperative graft revision was more frequent in grafts with low flow (44 of 568 [7.7%]) than in those with normal flow (8 of 2170 [0.4%]; P < .01). Graft revision was also more frequent as PI increased (12 of 1827 [0.7%] with a PI <3, 9 of 307 [2.9%] with a PI 3-5, and 9 of 155 [5.8%] with a PI >5; P < .01). CONCLUSIONS AND RELEVANCE Intraoperative TTF probe data may be helpful in predicting long-term patency and in the decision of whether to revise a questionable graft for patients undergoing CABG surgery.