Off-pump coronary artery bypass grafting: For the many or the few?

Abstract

Off-pump coronary artery bypass grafting (OPCAB) without cardiopulmonary bypass has evolved during the past 2 decades and has gained popularity in many centers. Despite favorable evidence from both prospective randomized trials and large observational studies, however, the adoption of OPCAB has been variable both worldwide and in the United Kingdom, where it has plateaued at approximately 17%.1Bridgewater B. Keogh B. Kinsman R. Walton P. Demonstrating quality: Sixth National Adult Cardiac Surgical Database Report 2008. Society for Cardiothoracic Surgery in Great Britain & Ireland. Dendrite Clinical Systems, Henley-on-Thames (UK)2009Google Scholar Moreover, recent studies suggest that OPCAB may be associated with adverse outcomes. The goals of this editorial are to evaluate critically the current status of OPCAB in the light of recent evidence and to suggest its future direction. The routine application of OPCAB is as safe as coronary artery bypass grafting with cardiopulmonary bypass (ONCAB). Meta-analyses of randomized controlled trials in low-risk patients demonstrate similar outcomes for both interventions in terms of mortality, myocardial infarction, and need for repeat revascularization at 1 and 2 years.2Feng Z.Z. Shi J. Zhao X.W. Xu Z.F. Meta-analysis of on-pump and off-pump coronary arterial revascularization.Ann Thorac Surg. 2009; 87 (Erratum in: Ann Thorac Surg. 2009;87:2008): 757-765Abstract Full Text Full Text PDF PubMed Scopus (60) Google Scholar, 3Møller C.H. Penninga L. Wetterslev J. Steinbrüchel D.A. Gluud C. Clinical outcomes in randomized trials of off- vs. on-pump coronary artery bypass surgery: systematic review with meta-analyses and trial sequential analyses.Eur Heart J. 2008; 29: 2601-2616Crossref PubMed Scopus (110) Google Scholar They also demonstrate that OPCAB is associated with reductions in the risks for stroke (50%), atrial fibrillation (30%), wound infection (48%), and acute kidney injury (70%).3Møller C.H. Penninga L. Wetterslev J. Steinbrüchel D.A. Gluud C. Clinical outcomes in randomized trials of off- vs. on-pump coronary artery bypass surgery: systematic review with meta-analyses and trial sequential analyses.Eur Heart J. 2008; 29: 2601-2616Crossref PubMed Scopus (110) Google Scholar, 4Sedrakyan A. Wu A.W. Parashar A. Bass E.B. Treasure T. Off-pump surgery is associated with reduced occurrence of stroke and other morbidity as compared with traditional coronary artery bypass grafting: a meta-analysis of systematically reviewed trials.Stroke. 2006; 37: 2759-2769Crossref PubMed Scopus (171) Google Scholar, 5Nigwekar S.U. Kandula P. Hix J.K. Thakar C.V. Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized and observational studies.Am J Kidney Dis. 2009; 54: 413-423Abstract Full Text Full Text PDF PubMed Scopus (108) Google Scholar OPCAB also reduces transfusion and inotrope requirements, ventilation time, intensive care unit and hospital stays, and in-hospital and 1-year direct costs.6Bainbridge D. Martin J. Cheng D. Off pump coronary artery bypass graft surgery versus conventional coronary artery bypass graft surgery: a systematic review of the literature.Semin Cardiothorac Vasc Anesth. 2005; 9: 105-111Crossref PubMed Scopus (28) Google Scholar, 7Cheng D.C. Bainbridge D. Martin J.E. Novick R.J. Evidence-Based Perioperative Clinical Outcomes Research GroupDoes off-pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A meta-analysis of randomized trials.Anesthesiology. 2005; 102: 188-203Crossref PubMed Scopus (384) Google Scholar Our group has recently reported long term follow-up at 6 to 8 years among survivors of the BHACS-1 and BHACS-2 trials.8Angelini G.D. Culliford L. Smith D.K. Hamilton M.C. Murphy G.J. Ascione R. et al.Effects of on- and off-pump coronary artery surgery on graft patency, survival, and health-related quality of life: long-term follow-up of 2 randomized controlled trials.J Thorac Cardiovasc Surg. 2009; 137: 295-303Abstract Full Text Full Text PDF PubMed Scopus (150) Google Scholar We found no difference in the likelihoods of graft occlusion (odds ratio [OR], 1.00; 95% confidence interval [CI], 0.55–1.81), death (hazard ratio [HR], 1.24; 95% CI, 0.72–2.15), major adverse cardiac-related events (HR, 0.84; 95% CI, 0.58–1.24) or health-related quality of life outcomes between the OPCAB and ONCAB groups. The recent ROOBY trial, however, a prospective, multicenter trial with 2000 patients randomly assigned to undergo OPCAB or ONCAB during a 6-year period, reported a 33% increase in the risk of the primary long-term composite end point of death from any cause, nonfatal myocardial infarction, or repeat revascularization within 1 year for patients undergoing OPCAB (relative risk, 1.33; 95% CI, 1.01–1.76; P = .04; number needed to cause 1 harmful event, 71).9Shroyer A.L. Grover F.L. Hattler B. Collins J.F. McDonald G.O. Kozora E. et al.On-pump versus off-pump coronary-artery bypass surgery.N Engl J Med. 2009; 361: 1827-1837Crossref PubMed Scopus (887) Google Scholar This study, however, had several major limitations. More than 70% of eligible patients (scheduled for urgent or elective coronary artery bypass grafting) were excluded because of clinical reservations of the surgical team or small target vessels. This suggests inexperience of surgeons in the trial, who were required to have performed just 20 OPCAB procedures to participate. Conversion to ONCAB, which is known to increase morbidity and mortality,10Jin R. Hiratzka L.F. Grunkemeier G.L. Krause A. Page 3rd, U.S. Aborted off-pump coronary artery bypass patients have much worse outcomes than on-pump or successful off-pump patients.Circulation. 2005; 112: I332-I337PubMed Google Scholar, 11Reeves B.C. Ascione R. Caputo M. Angelini G.D. Morbidity and mortality following acute conversion from off-pump to on-pump coronary surgery.Eur J Cardiothorac Surg. 2006; 29: 941-947Crossref PubMed Scopus (53) Google Scholar occurred in more than 12% of cases, much greater than the 1% to 3% reported by centers specializing in OPCAB.11Reeves B.C. Ascione R. Caputo M. Angelini G.D. Morbidity and mortality following acute conversion from off-pump to on-pump coronary surgery.Eur J Cardiothorac Surg. 2006; 29: 941-947Crossref PubMed Scopus (53) Google Scholar, 12Mack M. Bachand D. Acuff T. Edgerton J. Prince S. Dewey T. et al.Improved outcomes in coronary artery bypass grafting with beating-heart techniques.J Thorac Cardiovasc Surg. 2002; 124: 598-607Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar In the OPCAB group, more than 50% of patients received red blood cell transfusions, which contrasts with the 30% in previous randomized trials.7Cheng D.C. Bainbridge D. Martin J.E. Novick R.J. Evidence-Based Perioperative Clinical Outcomes Research GroupDoes off-pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A meta-analysis of randomized trials.Anesthesiology. 2005; 102: 188-203Crossref PubMed Scopus (384) Google Scholar Finally, only a small minority of the studied population were high-risk patients, a group more likely to benefit from OPCAB. Although data from randomized trials provide the most accurate evidence, they are underpowered to demonstrate a difference in hard end points. Several large propensity-matched retrospective series and meta-analyses from centers proficient in OPCAB have provided compelling evidence in favor of the technique. A retrospective analysis of 49,830 patients from the New York state registry reported lower 30-day mortality and incidences of postoperative stroke and respiratory failure for risk-adjusted isolated OPCAB versus ONCAB surgery.13Hannan E.L. Wu C. Smith C.R. Higgins R.S. Carlson R.E. Culliford A.T. et al.Off-pump versus on-pump coronary artery bypass graft surgery: differences in short-term outcomes and in long-term mortality and need for subsequent revascularization.Circulation. 2007; 116: 1145-1152Crossref PubMed Scopus (249) Google Scholar Three-year follow-up revealed that patients who had undergone OPCAB did have a higher rate of repeat revascularization; however, survival was equivalent between the groups.13Hannan E.L. Wu C. Smith C.R. Higgins R.S. Carlson R.E. Culliford A.T. et al.Off-pump versus on-pump coronary artery bypass graft surgery: differences in short-term outcomes and in long-term mortality and need for subsequent revascularization.Circulation. 2007; 116: 1145-1152Crossref PubMed Scopus (249) Google Scholar A similar intention-to-treat analysis of 42,477 patients from the Society of Thoracic Surgeons National Adult Cardiac Surgery database showed reductions in risk-adjusted mortality, stroke, perioperative myocardial infarction, renal failure, mediastinitis, need for reoperation, atrial fibrillation, and prolonged ventilation for patients in the OPCAB group versus the ONCAB group.14Puskas J.D. Edwards F.H. Pappas P.A. O'Brien S. Peterson E.D. Kilgo P. et al.Off-pump techniques benefit men and women and narrow the disparity in mortality after coronary bypass grafting.Ann Thorac Surg. 2007; 84: 1447-1456Abstract Full Text Full Text PDF PubMed Scopus (119) Google Scholar A meta-analysis of 22 risk-adjusted (logistic regression or propensity-score) observational studies (n = 293,617) showed OPCAB to be associated with reduced 30-day mortality (OR, 0.72; 95% CI, 0.66–0.78), stroke (OR, 0.62; 95% CI, 0.55–0.69), myocardial infarction (OR, 0.66; 95% CI, 0.50–0.88), and atrial fibrillation (OR, 0.78; 95% CI, 0.74–0.82).15Wijeysundera D.N. Beattie W.S. Djaiani G. Rao V. Borger M.A. Karkouti K. et al.Off-pump coronary artery surgery for reducing mortality and morbidity: meta-analysis of randomized and observational studies.J Am Coll Cardiol. 2005; 46: 872-882Abstract Full Text Full Text PDF PubMed Scopus (248) Google Scholar At 1 to 2 years, OPCAB was associated with trends toward reduced mortality but also increased repeat revascularization (OR, 1.35; 95% CI, 0.76–2.39). These reports from large-volume centers suggest that OPCAB is a specialized technique requiring dedication, infrastructure, and expertise to achieve proficiency and good results. This in turn raises 2 important questions that relate to the future direction of OPCAB. First, how should OPCAB, a specialized technique, be safely introduced into routine clinical practice? Second, what group of patients will benefit most from OPCAB? The adoption of OPCAB has been highly variable. The reasons for this include the lack of established training programs, the perception that success with the technique is limited to more proficient surgeons, and a fear of deleterious patient outcomes, especially during the learning curve.16Murphy G.J. Rogers C.A. Caputo M. Angelini G.D. Acquiring proficiency in off-pump surgery: traversing the learning curve, reproducibility, and quality control.Ann Thorac Surg. 2005; 80: 1965-1970Abstract Full Text Full Text PDF PubMed Scopus (25) Google Scholar In the largest review of the incorporation of OPCAB into a surgical practice (12,540 patients undergoing coronary artery bypass grafting, including 1915 OPCAB procedures), Mack and colleagues12Mack M. Bachand D. Acuff T. Edgerton J. Prince S. Dewey T. et al.Improved outcomes in coronary artery bypass grafting with beating-heart techniques.J Thorac Cardiovasc Surg. 2002; 124: 598-607Abstract Full Text Full Text PDF PubMed Scopus (100) Google Scholar reported an increase in OPCAB from 1.2% of cases in 1995 to 34.1% of cases in 2000 (individual surgeon adoption rates ranged from 1% to 96% by 2000). Initially, OPCAB case selection considered only elective cases requiring a limited number of grafts (2 or 3) to the anterior surface of the heart, with patients in an unstable condition, those undergoing reoperation, and those requiring multiple bypasses on the lateral surface generally considered unsuitable. As surgeon experience increased along with developments in stabilizer technology, however, all patients were considered for OPCAB. The OPCAB to ONCAB conversion rate in this series was 2.9%. The increased use of OPCAB was associated with a reduction in hospital mortality from 4% to 3.2% and a reduction in procedural morbidity. In our unit, between 1997 and 2001, the proportion of OPCAB cases increased from 8% to 68% without any increase in procedural morbidity. This change was accompanied by gradual increases in the complexity of cases, number of distal anastomoses, use of multiple arterial conduits, and lateral wall revascularization.17Caputo M. Bryan A.J. Capoun R. Mahesh B. Ciulli F. Hutter J. et al.The evolution of training in off-pump coronary surgery in a single institution.Ann Thorac Surg. 2002; 74: S1403-S1407Abstract Full Text Full Text PDF PubMed Google Scholar, 18Caputo M. Chamberlain M.H. Ozalp F. Underwood M.J. Ciulli F. Angelini G.D. Off-pump coronary operations can be safely taught to cardiothoracic trainees.Ann Thorac Surg. 2001; 71: 1215-1219Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar Key elements to the adoption of OPCAB are appropriate patient selection, individualized grafting strategy, peer-to-peer training of the entire team, and graded clinical experience (preoperative planning, adequate exposure, proximal anastomoses to the aorta, distal anastomoses initially to anterior wall vessels, followed by inferior wall vessels and then lateral wall vessels).19Halkos M.E. Puskas J.D. Teaching off-pump coronary artery bypass surgery.Semin Thorac Cardiovasc Surg. 2009; 21: 224-228Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar In our experience, the surgeon's learning curve is around 50 to 75 cases, and good proficiency with the technique is usually associated with a low 1% to 2% conversion rate.20Rogers C.A. Reeves B.C. Caputo M. Ganesh J.S. Bonser R.S. Angelini G.D. Control chart methods for monitoring cardiac surgical performance and their interpretation.J Thorac Cardiovasc Surg. 2004; 128: 811-819Abstract Full Text Full Text PDF PubMed Scopus (143) Google Scholar, 21Caputo M. Reeves B.C. Rogers C.A. Ascione R. Angelini G.D. Monitoring the performance of residents during training in off-pump coronary surgery.J Thorac Cardiovasc Surg. 2004; 128: 907-915Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar Where senior surgeons are experienced with the technique, OPCAB can be safely and reproducibly taught to trainees.17Caputo M. Bryan A.J. Capoun R. Mahesh B. Ciulli F. Hutter J. et al.The evolution of training in off-pump coronary surgery in a single institution.Ann Thorac Surg. 2002; 74: S1403-S1407Abstract Full Text Full Text PDF PubMed Google Scholar, 18Caputo M. Chamberlain M.H. Ozalp F. Underwood M.J. Ciulli F. Angelini G.D. Off-pump coronary operations can be safely taught to cardiothoracic trainees.Ann Thorac Surg. 2001; 71: 1215-1219Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar, 21Caputo M. Reeves B.C. Rogers C.A. Ascione R. Angelini G.D. Monitoring the performance of residents during training in off-pump coronary surgery.J Thorac Cardiovasc Surg. 2004; 128: 907-915Abstract Full Text Full Text PDF PubMed Scopus (49) Google Scholar Careful early case selection with later progression to more complex procedures under the tutelage of experienced trainers has been shown to permit effective training without increased morbidity, even among high-risk patients.17Caputo M. Bryan A.J. Capoun R. Mahesh B. Ciulli F. Hutter J. et al.The evolution of training in off-pump coronary surgery in a single institution.Ann Thorac Surg. 2002; 74: S1403-S1407Abstract Full Text Full Text PDF PubMed Google Scholar, 22Ascione R. Reeves B.C. Pano M. Angelini G.D. Trainees operating on high-risk patients without cardiopulmonary bypass: a high-risk strategy?.Ann Thorac Surg. 2004; 78: 26-33Abstract Full Text Full Text PDF PubMed Scopus (40) Google Scholar OPCAB has been an integral part of our unit training program since the early days, with the proportion of OPCAB procedures performed by trainees increasing from 18% to 62% between the years 1999 to 2001.17Caputo M. Bryan A.J. Capoun R. Mahesh B. Ciulli F. Hutter J. et al.The evolution of training in off-pump coronary surgery in a single institution.Ann Thorac Surg. 2002; 74: S1403-S1407Abstract Full Text Full Text PDF PubMed Google Scholar, 18Caputo M. Chamberlain M.H. Ozalp F. Underwood M.J. Ciulli F. Angelini G.D. Off-pump coronary operations can be safely taught to cardiothoracic trainees.Ann Thorac Surg. 2001; 71: 1215-1219Abstract Full Text Full Text PDF PubMed Scopus (58) Google Scholar By the end of their 3rd year, residents have performed 40 to 50 multivessel OPCAB revascularizations as first surgeons under direct senior surgeon supervision. An early comparison of outcomes demonstrated no difference between patients operated on by senior surgeons or supervised trainees.17Caputo M. Bryan A.J. Capoun R. Mahesh B. Ciulli F. Hutter J. et al.The evolution of training in off-pump coronary surgery in a single institution.Ann Thorac Surg. 2002; 74: S1403-S1407Abstract Full Text Full Text PDF PubMed Google Scholar During the last 2 years of the training program, and after satisfying the senior surgeons that they are proficient in OPCAB techniques, residents are then permitted to perform OPCAB cases without direct supervision. When the results of these unsupervised cases were reviewed, again there was no increase in patient morbidity relative to trainees operating under direct supervision.17Caputo M. Bryan A.J. Capoun R. Mahesh B. Ciulli F. Hutter J. et al.The evolution of training in off-pump coronary surgery in a single institution.Ann Thorac Surg. 2002; 74: S1403-S1407Abstract Full Text Full Text PDF PubMed Google Scholar A major criticism of the ROOBY trial was that 55% of OPCAB cases were performed primarily by residents.9Shroyer A.L. Grover F.L. Hattler B. Collins J.F. McDonald G.O. Kozora E. et al.On-pump versus off-pump coronary-artery bypass surgery.N Engl J Med. 2009; 361: 1827-1837Crossref PubMed Scopus (887) Google Scholar Evidence seems strongly to suggest, however, that it is not the residents but instead the lack of experienced trainers that resulted in poor outcomes. To date, all prospective randomized trials evaluating OPCAB have focused on low-risk patients or a mixed group of patients, demonstrating OPCAB to be as effective and safe as ONCAB. Observational studies, however, suggest that the greatest benefits of OPCAB, in terms of reductions in mortality and morbidity, may be seen among high-risk patients.23Al-Ruzzeh S. Nakamura K. Athanasiou T. Modine T. George S. Yacoub M. et al.Does off-pump coronary artery bypass (OPCAB) surgery improve the outcome in high-risk patients?: a comparative study of 1398 high-risk patients.Eur J Cardiothorac Surg. 2003; 23: 50-55Crossref PubMed Scopus (173) Google Scholar, 24Puskas J.D. Thourani V.H. Kilgo P. Cooper W. Vassiliades T. Vega J.D. et al.Off-pump coronary artery bypass disproportionately benefits high-risk patients.Ann Thorac Surg. 2009; 88: 1142-1147Abstract Full Text Full Text PDF PubMed Scopus (208) Google Scholar These include women in general and patients with a EuroSCORE greater than 5, left ventricle dysfunction, atherosclerotic aortic disease, age older than 75 years, diabetes, renal failure, left main stem disease, reoperations, chronic lung disease, emergency coronary artery bypass grafting, acute myocardial infarction, and preoperative cerebrovascular disease (see online bibliography). Currently, there are no published prospective randomized comparisons of OPCAB versus ONCAB for the treatment of high-risk patients. The recently published Best Bypass Surgery Trial claimed to evaluate 30-day outcomes in 341 high-risk patients randomly allocated to undergo either OPCAB or ONCAB.25Møller C.H. Perko M.J. Lund J.T. Andersen L.W. Kelbaek H. Madsen J.K. et al.No major differences in 30-day outcomes in high-risk patients randomized to off-pump versus on-pump coronary bypass surgery: the best bypass surgery trial.Circulation. 2010; 121: 498-504Crossref PubMed Scopus (124) Google Scholar The investigators reported no significant difference in their composite primary outcome of adverse cardiac and cerebrovascular events. This trial, however, did not truly recruit high-risk patients. The exclusion criteria were previous heart surgery, left ventricular ejection fraction less than 30%, unstable preoperative condition, and emergency surgery. There are currently 2 prospective randomized trials underway evaluating the efficacy of OPCAB in high-risk patients. The CRISP trial run by our and the Oxford unit (ISRCTN 29161170) is an international multicenter trial randomly assigning more than 5000 high-risk patients to OPCAB or ONCAB. The inclusion criterion is a EuroSCORE greater than 5. The design of this trial is “expertise based,” with patients randomly allocated to previously specified surgeons in the same unit who favor and practice primarily OPCAB or ONCAB. The other is the German Off Pump Coronary Artery Bypass in Elderly Study (GOPCABE, NCT00719667), a multicenter trial randomly allocating 2000 patients older than 75 years (but excluding patients undergoing reoperative surgery) to undergo either OPCAB or ONCAB. An overwhelming wealth of evidence demonstrates that OPCAB is a safe alternative to ONCAB, with similar outcomes for low risk patients, and that it can be safely incorporated into routine surgical practice. It is an obviously technically demanding procedure that should be performed in high-volume OPCAB centers to obtain proficiency and optimal outcomes. The greatest benefit of OPCAB is likely to be seen in high risk patients, and the results of ongoing prospective clinical trials are eagerly awaited.