Janet H. Baltz

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.).

Off-Pump Coronary Artery Bypass Surgery Is Associated With Worse Arterial and Saphenous Vein Graft Patency and Less Effective Revascularization Results From the Veterans Affairs Randomized On/Off Bypass (ROOBY) Trial

Background— The Department of Veterans Affairs Randomized On/Off Bypass (ROOBY) trial compared clinical and angiographic outcomes in off-pump versus on-pump coronary artery bypass graft (CABG) surgery to ascertain the relative efficacy of the 2 techniques. Methods and Results— From February 2002 to May 2007, the ROOBY trial randomized 2203 patients to off-pump versus on-pump CABG. Follow-up angiography was obtained in 685 off-pump (62%) and 685 on-pump (62%) patients. Angiograms were analyzed (blinded to treatment) for FitzGibbon classification (A=widely patent, B=flow limited, O=occluded) and effective revascularization. Effective revascularization was defined as follows: All 3 major coronary territories with significant disease were revascularized by a FitzGibbon A-quality graft to the major diseased artery, and there were no new postanastomotic lesions. Off-pump CABG resulted in lower FitzGibbon A patency rates than on-pump CABG for arterial conduits (85.8% versus 91.4%; P=0.003) and saphenous vein grafts (72.7% versus 80.4%; P<0.001). Fewer off-pump patients were effectively revascularized (50.1% versus 63.9% on-pump; P<0.001). Within each major coronary territory, effective revascularization was worse off pump than on pump (all P⩽0.001). The 1-year adverse cardiac event rate was 16.4% in patients with ineffective revascularization versus 5.9% in patients with effective revascularization (P<0.001). Conclusions— Off-pump CABG resulted in significantly lower FitzGibbon A patency for arterial and saphenous vein graft conduits and less effective revascularization than on-pump CABG. At 1 year, patients with less effective revascularization had higher adverse event rates. Clinical Trial Registration— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00032630.

Cognitive Outcomes After On- Versus Off-Pump Coronary Artery Bypass Surgery

BACKGROUND The Randomized On versus Off Bypass trial found no difference for a global cognitive outcome measure for patients receiving on-pump versus off-pump coronary artery bypass graft surgery (CABG). In this report, we present the baseline patient characteristics that were predictive of post-CABG cognitive decline as well as compare cognitive outcomes between treatment arms. METHODS A neuropsychological battery was administered preoperatively and at 1 year after undergoing CABG. Stepwise regression was used to identify demographic or clinical risk factors associated with cognitive decline. Neuropsychological data were converted to demographically corrected T scores to provide impairment levels. RESULTS Overall 1,156 patients (581 on-pump, 575 off-pump) completed match-paired neuropsychological assessments at baseline and 1-year follow-up. Baseline cognitive score, age, education level, and ethnicity predicted cognitive decline after CABG. Only 20% of either group had mild impairment at baseline on three of the test scores, and less than 10% had severe impairment on individual tests at either time. Few subjects in either group transitioned to clinically impaired levels at follow-up on individual tests. CONCLUSIONS At baseline, lower cognitive function, older age, lower education, and ethnicity other than white were predictive of cognitive decline after CABG. Patients in both groups demonstrated low frequencies of cognitive impairment on individual tests at baseline and follow- up, and few patients in either group were classified as impaired at 1-year follow-up on individual tests. In general, the Randomized On versus Off Bypass study documented that neither on-pump nor off-pump CABG adversely impacts long-term brain function.

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.

Five-Year Outcomes after On-Pump and Off-Pump Coronary-Artery Bypass

Background Coronary‐artery bypass grafting (CABG) surgery may be performed either with cardiopulmonary bypass (on pump) or without cardiopulmonary bypass (off pump). We report the 5‐year clinical outcomes in patients who had been included in the Veterans Affairs trial of on‐pump versus off‐pump CABG. Methods From February 2002 through June 2007, we randomly assigned 2203 patients at 18 medical centers to undergo either on‐pump or off‐pump CABG, with 1‐year assessments completed by May 2008. The two primary 5‐year outcomes were death from any cause and a composite outcome of major adverse cardiovascular events, defined as death from any cause, repeat revascularization (CABG or percutaneous coronary intervention), or nonfatal myocardial infarction. Secondary 5‐year outcomes included death from cardiac causes, repeat revascularization, and nonfatal myocardial infarction. Primary outcomes were assessed at a P value of 0.05 or less, and secondary outcomes at a P value of 0.01 or less. Results The rate of death at 5 years was 15.2% in the off‐pump group versus 11.9% in the on‐pump group (relative risk, 1.28; 95% confidence interval [CI], 1.03 to 1.58; P=0.02). The rate of major adverse cardiovascular events at 5 years was 31.0% in the off‐pump group versus 27.1% in the on‐pump group (relative risk, 1.14; 95% CI, 1.00 to 1.30; P=0.046). For the 5‐year secondary outcomes, no significant differences were observed: for nonfatal myocardial infarction, the rate was 12.1% in the off‐pump group and 9.6% in the on‐pump group (P=0.05); for death from cardiac causes, the rate was 6.3% and 5.3%, respectively (P=0.29); for repeat revascularization, the rate was 13.1% and 11.9%, respectively (P=0.39); and for repeat CABG, the rate was 1.4% and 0.5%, respectively (P=0.02). Conclusions In this randomized trial, off‐pump CABG led to lower rates of 5‐year survival and event‐free survival than on‐pump CABG. (Funded by the Department of Veterans Affairs Office of Research and Development Cooperative Studies Program and others; ROOBY‐FS ClinicalTrials.gov number, NCT01924442.)

Effect of clopidogrel use post coronary artery bypass surgery on graft patency.

BACKGROUND Clopidogrel use post coronary artery bypass grafting (CABG) has become more popular under the assumption that it improves graft patency. The purpose of this sub-analysis from the Randomized On and Off-Pump Bypass (ROOBY) trial is to evaluate the role of clopidogrel use post CABG to improve graft patency when added to standard aspirin therapy. METHODS The ROOBY trial was a multi-center, randomized, controlled clinical trial that compared on-pump versus off-pump coronary artery bypass grafting (CABG). Clopidogrel use post CABG was left at the discretion of the operator. Detailed data regarding the use and timing of clopidogrel post CABG were collected prospectively, along with 1-year angiograms to evaluate graft status. RESULTS Of the 2,203 subjects undergoing CABG, 953 patient records had complete clopidogrel use and 1-year angiographic data. Of these, 345 (36.2%) received clopidogrel post CABG prior to discharge. Compared with patients with no post-CABG clopidogrel use, baseline characteristics were similar for the clopidogrel group except for the following: lower preoperative aspirin use (80.2% vs 86.7%, p = 0.009); higher preoperative clopidogrel use (23.5% vs 14.0%, p < 0.001), less on-pump (35.9% vs 55.9%, p < 0.0001); and lower endoscopic vein harvesting (30.8% vs 42.5%, p < 0.001) rates. Overall 1-year graft patency rates were not different between the clopidogrel and no-clopidogrel groups (86.5% vs 85.3%, p = 0.43). Multivariable analyses did not alter these findings. CONCLUSIONS This study suggests that routine post-CABG clopidogrel use may not translate to improved 1-year graft patency. Future studies appear warranted to better define the role of more aggressive antiplatelet therapy post CABG on graft patency and clinical outcomes.

Outcomes After Conversion in the Veterans Affairs Randomized On Versus Off Bypass Trial

BACKGROUND The Randomized On versus Off Bypass trial reported conversion of 12.4% (n = 137) off-pump coronary artery bypass (OPCAB) patients and 3.6% (n = 40) on-pump cardiopulmonary bypass (CPB) patients. This paper explored outcomes after conversions. METHODS Elective and urgent CABG patients (n = 2,203) at 18 sites were studied. Randomization within 54 participating surgeons occurred preoperatively, after which conversion occurred if clinically indicated. Conversion reasons and outcomes were captured prospectively with additional details retrospectively extracted from patient records by a core clinical group. RESULTS Conversion rates varied considerably across participating surgeons. Converted OPCAB patients had more right coronary disease and coronary targets less than 1.5 mm. Conversions were elective in 49.3% of cases, urgent in 27.2%, or emergent in 23.5%. Elective conversions were mainly for poor exposure-intramyocardial vessel (35.8%). Urgent and emergent conversions were usually for hemodynamic instability (89.2% and 75.0%, respectively). Compared with CPB and OPCAB patients, OPCAB-converted patients had more 30-day complications and deaths (composite outcome rate of 5.7% and 5.5% vs 17.5% respectively, p < 0.001). Thirty-day outcomes for OPCAB-converted patients trended worse for emergent versus elective conversions (31.3% vs 13.4%, respectively, p = 0.05). One-year composite outcome rate (death, nonfatal myocardial infarction or revascularization) in OPCAB-converted patients was worse than in CPB patients (13.5% vs 7.1%, p = 0.02), but similar to OPCAB-nonconverted (9.4%). CONCLUSIONS The OPCAB patients requiring conversion had worse 30-day and 1-year outcomes. The OPCAB patients with right coronary artery disease or small targets were more often converted. The 30-day composite outcome trended worst for emergent OPCAB conversions.

Changes in Health-Related Quality of Life in Off-Pump Versus On-Pump Cardiac Surgery: Veterans Affairs Randomized On/Off Bypass Trial

BACKGROUND The relative benefits of performing coronary artery bypass graft surgery off-pump versus on-pump continue to be debated. A critical, patient-centered outcome is health-related quality of life; yet there has been limited evaluation in large-scale, multicenter trials of the off-pump versus on-pump impact upon quality of life. METHODS The Veterans Affairs Randomized On/Off Bypass trial randomized 2,203 nonemergent patients to off-pump or on-pump from February 2002 to May 2007. Patients completed a general quality of life survey (VR-36) and a disease-specific quality of life survey, the Seattle Angina Questionnaire (SAQ), prior to surgery, then again at 3 and 12 months post-bypass. RESULTS Of the 2,130 1-year survivors, 1,805 patients (85%) completed 1-year surveys. Randomization resulted in comparable baseline patient characteristics, including VR-36 and SAQ scores. At 3 months and 1-year post-procedure, there were no clinically relevant differences between off-pump and on-pump patients in any of the quality of life measures. Both groups had statistically significant, comparable improvements in the physical component scale of the VR-36, and in the SAQ scales. CONCLUSIONS For this trials male, low-to-moderate risk, veteran population, there were no significant differences between off-pump and on-pump with regard to 1-year general and disease-specific quality of life outcomes. Both treatment arms experienced some improvements by 3 months, with continued improvements through 1-year post-bypass.

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.

Impact of Lipid-Lowering Medications and Low-Density Lipoprotein Levels on 1-Year Clinical Outcomes after Coronary Artery Bypass Grafting

BACKGROUND Studies investigating lipid-lowering medication (LLM) use and LDL levels in coronary artery bypass grafting patients are limited. STUDY DESIGN The Veterans Affairs Randomized On/Off Bypass Trials patient records were analyzed for LLM use and 1-year LDL levels. Mortality, acute MI (AMI), and repeat revascularization rates were compared at 1 year between patients with and without LLM at discharge. In addition, AMI, repeat revascularization, and graft patency were compared between patients that did and did not achieve a 1-year LDL target level of <100 mg/dL. RESULTS The LLM data were available for 86.4% (1,904 of 2,203) of patients. Rates of LLM use were 83.4% (1,316 of 1,577) at discharge and 90.0% (1,713 of 1,904) at 1 year. Patients discharged after coronary artery bypass grafting on LLMs had a significantly lower 1-year mortality rate (1.9% vs 5.4%; p < 0.01) than those not discharged on LLM, and 1-year AMI and repeat revascularization rates were not significantly different. Of the patients with 1-year LDL measurements, 69.4% (1,200 of 1,729) achieved an LDL target level of <100 mg/dL. No differences were seen in AMI, revascularization, or graft occlusion rates between patients who achieved target LDL levels and those who did not. CONCLUSIONS Rates of LLM use among veterans post-coronary artery bypass grafting are high. Discharge on LLM might be associated with improved intermediate-term survival. Patients who achieved an LDL target of <100 mg/dL at 1-year did not experience improved 1-year clinical outcomes or graft patency. Longer-term follow-up might reveal differences in cardiac outcomes related to achievement of target LDL levels.