Curr Cardiol Rep (2014) 16:455 DOI 10.1007/s11886-013-0455-2
ISCHEMIC HEART DISEASE (D MUKHERJEE, SECTION EDITOR)
Off-Pump Versus On-Pump Coronary Artery Bypass Grafting Christian H. Møller & Daniel A. Steinbrüchel
# Springer Science+Business Media New York 2014
Abstract Coronary artery bypass grafting (CABG) remains the preferred treatment in patients with complex coronary artery disease. However, whether the procedure should be performed with or without the use of cardiopulmonary bypass, referred to as off-pump and on-pump CABG, is still up for debate. Intuitively, avoidance of cardiopulmonary bypass seems beneficial as the systemic inflammatory response from extracorporeal circulation is omitted, but no single randomized trial has been able to prove off-pump CABG superior to on-pump CABG as regards the hard outcomes death, stroke or myocardial infarction. In contrast, off-pump CABG is technically more challenging and may be associated with increased risk of incomplete revascularization. The purpose of the review is to summarize the current literature comparing outcomes of off-pump versus on-pump coronary artery bypass surgery. Keywords Coronary artery bypass grafting . Off-pump . On-pump . Cardiopulmonary bypass
Introduction Coronary artery bypass grafting (CABG) remains the standard treatment for revascularization of patients with complex coronary artery disease [1]. However, over the last decades the use of percutaneous coronary intervention (PCI) has increased significantly and has challenged CABG in its role to be the most effective treatment for revascularization of the myocardium. Two recently This article is part of the Topical Collection on Ischemic Heart Disease C. H. Møller (*) : D. A. Steinbrüchel Department of Cardiothoracic Surgery, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark e-mail: [email protected]
published trials have shown CABG superior to PCI in patients with 3-vessel coronary disease and in patients with diabetes and coronary disease [2, 3]. In the SYNT AX trial, including 1800 patients with 3-vessel coronary disease and/or left main coronary stenosis, at both 1- and 5-years follow-up there was a significant difference in the primary endpoint (all-cause mortality, stroke, myocardial infarction, and repeat revascularization) in favor of CABG [3, 4]. The benefit of CABG was even more pronounced in the patients with higher SYNTAX scores. The FREEDOM trial included 1900 patients with diabetes and multivessel coronary disease [2]. The 5-year primary composite outcome (death, myocardial infarction, and stroke) occurred in 26.6 % in the PCI group versus 18.7 % in the CABG group (P = 0.005). Furthermore, there was a significant increased risk of death and myocardial infarction in the PCI group, but more strokes after CABG [2]. Coronary artery bypass grafting is routinely performed with cardiopulmonary bypass (CPB) and the heart arrested referred to as on-pump CABG [5]. During on-pump CABG, the coronary bypasses can be performed in a blood-free surgical field with the heart immobilized and empty. This gives excellent presentation of the coronaries and the anastomosis performed with high precision. In an attempt to reduce the postoperative complications seen after on-pump CABG, interest in performing CABG on the beating heart without CPB (off-pump CABG) gained increasing interest in the mid 1990s [6]. Several trials comparing off-pump versus on-pump have been published over the last decades [7•]. But still there is an ongoing debate whether off-pump CABG and the avoidance of CPB is beneficial for the patients [8, 9]. With the recent publication of two relatively large randomized clinical trials the CORONARY trial and GOPCABE trial this review re-evaluates the current knowledge of off-pump versus on-pump CABG [10••, 11••].
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Outcomes of Off-Pump Versus On-Pump CABG Since the renewed interest in off-pump CABG in the mid 1990s several randomized trials comparing off-pump with on-pump CABG have been published. The majority of these trials have been underpowered to show significant differences in mortality, myocardial infarction and stroke after CABG surgery [7•]. Furthermore, the methodological quality of these trials has been poor leaving ample room for bias. Since the publication of the Cochrane Systematic Review comparing off-pump versus on-pump CABG, new larger and welldesigned randomized trials have been conducted and published. The to date largest randomized trial of off-pump versus on-pump CABG is the CORONARY trial including 4752 patients enrolled from 79 centers in 19 countries. At both 30 days and 12 months there was no significant difference in the primary outcome (a composite of death, myocardial infarction, stroke, or new renal failure requiring dialysis) [11••, 12••]. At 30 days the primary outcome had occurred in 9.8 % in off-pump group compared with 10.3 % in the onpump group (hazard ratio, HR 0.95, 95 % confidence interval, CI, 0.79-1.14, P=0.59). After 12 months, the primary outcome was seen in 12.1 % of the patients in the off-pump group and in 13.3 % in the on-pump group (HR 0.91, 95 % CI 0.771.07, P =0.24). In the GOPCABE trial, elderly patients aged 75 years or older were randomized to off-pump versus onpump CABG at 12 German centers. The trial included 2539 patients and the primary outcome was a composite of death, stroke, myocardial infarction, repeat revascularization, or new renal replacement therapy. At both 30 days and 12 months after surgery no significant difference was observed between off-pump and on-pump CABG in the primary outcome (at 30 days; 7.8 % vs. 8.2 %, odds ratio, OR 0.95, 95 % CI 0.71-1.28, P=0.74, and at 12 months; 13.1 % vs. 14.0, HR 0.93, 95 % CI 0.76-1.16, P=0.48) [10••]. Therefore, neither of these trials have been able to end the discussion whether off-pump CABG or on-pump CABG should be the preferred approach for coronary revascularization. However, each procedure may have different advantages. Mortality Several randomized trials have shown similar in-hospital mortality between off-pump and on-pump mortality [10••, 12••, 13–18]. Depending on the risk profile of the patients, 30-day mortality was in the range between 0 % and 6.7 %. Only a single trial has demonstrated a significant reduction in hospital mortality with off-pump CABG compared with on-pump CABG. This result was found in a small trial including patients with ST-segment elevation myocardial infarction and cardiogenic shock, who underwent emergency CABG within 6 hours of onset of symptoms [19]. In contrast, several observational studies have shown a significant reduction in 30-day
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mortality after off-pump CABG. However, a Cochrane systematic review raised concern about increased long-term mortality after off-pump CABG [7•]. In a subgroup analysis of trials conducted with low risk of bias showed a risk ratio (RR) of 1.35 (95 % CI 1.07-1.70, P=0.01) in favor of on-pump CABG. With the 1-year mortality results from the CORONARY and GOPCABE trials this risk may be overestimated. One-year mortality in the CORONARY trial was 5.1 % in the off-pump group compared with 5.0 % in the on-pump group (HR 1.03; 95 % CI 0.80-1.32) [11••] and in the GOPCABE trial 7.0 % versus 8.0 % (HR 0.88; 95 % CI 0.65-1.18) [10]. An updated meta-analysis based on current RCT demonstrates no significant difference in survival (RR 1.04; 95 % CI 0.911.19, P=0.53) (Fig. 1). Based on the New York state’s Cardiac surgery Reporting System including 49,830 patients, an observational retrospective study showed no significant difference in adjusted HR for 30-day mortality (HR 1.01, 95%CI 0.92-1.10 P=0.89) and at 3 years follow-up 90.1 % of patients in the on-pump group versus 89.4 in the off-pump group were alive (P =0.20) [20]. In contrast, a study of 12,812 patients from The Society of Thoracic Surgeons National Adult Cardiac Database reported a significant reduction in 30-day mortality after off-pump CABG (adjusted odds ratio 0.68; 95 % CI 0.46-0.99, P=0.045), and with equivalent 10-years survival [21]. From a multicenter register in Japan (CREDO-Kyoto) adjusted 30-day mortality was not significantly different between off-pump and on-pump patients regardless of their predicted risk of operative mortality [22]. Myocardial Infarction Current randomized trials have not demonstrated significant differences in postoperative myocardial infarction (MI) after off-pump CABG compared with on-pump CABG. In the CORONARY trial MI was observed in 6.7 % in the offpump group and 7.2 % in the on-pump after 30 days. In the GOPCABE trial the event rate of MI within 30 days was only 1.5 % versus 1.7 %. In the Cochrane systematic review, the meta-analysis of 55 randomized trials encompassing 8547 patients found similar occurrence of MI after off-pump and on-pump CABG (RR 1.00, 95 % CI 0.79-1.26) [7•]. Interesting, several trials have reported a significant reduction in release on coronary enzymes after off-pump CABG, but without obvious clinical manifestation in MI [16, 18, 23]. Stroke Although postoperative stroke is seen relatively seldom after CABG, it is one of the most devastating and feared complications. Elimination of aortic cannulation, cardiopulmonary bypass, and aortic cross clamping was thought to reduce the incidence of postoperative stroke after off-pump CABG. However, no single randomized trial has revealed off-pump
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Fig. 1 Meta-analysis of all-cause mortality in randomized trials comparing off-pump versus onpump CABG. Updated version of the Cochrane Systematic Review. Trials without death in both the off-pump and on-pump group have been excluded as these trials do not generate a risk ratio
CABG superior to on-pump CABG in reducing stroke. To date in the largest RCT, the CORONARY trial, stroke was observed in 1 % in the off-pump group and 1.1 % in the onpump group within 30 days. Similar results were seen in the ROOBY trial including 2203 low-risk patients from 18 Veterans Affairs medical centers [17]. Within 30 days stroke was registered in 1.3 % off-pump patients compared with 0.7 % on-pump patients (P=0.2). Not even in RCTs including elderly patients or high-risk patients, have off-pump CABG been able to show a significant reduction in stroke. The DOORS trial randomized 900 patients aged >70 years to off-pump or on-pump CABG. After 30 days, stroke was seen in 2.2 % and 4 % (P=0.12), respectively [14]. In the BBS trial, 341 patients with 3-vessel coronary disease and EuroSCORE ≥5 were randomized. In the off-pump group 4.0 % had a stroke compared with 3.7 % in the on-pump group (P=1.0) [15]. In the recent Cochrane systematic review including 61 trials, the meta-analysis of stroke was not significantly different between off-pump and on-pump CABG (RR 0.76, 95 % CI 0.54 – 1.06, P=0.10) [7•]. However, updating this meta-
analysis with the recently published CORONARY and GOPCABE trials, this revealed a significant 20 % relative risk reduction in stroke with off-pump CABG (RR 0.80, 95 % CI 0.64 - 1.00, P=0.05) (Fig. 2). Likewise, several retrospective analyses have shown that off-pump CABG was associated with a reduced event rate of stroke compared with on-pump CABG [20, 22, 24]. To further reduce the incidence of stroke after off-pump CABG some surgeons advocate for an ‘aortic no-touch’ or ‘anaortic’ technique [25–27]. In a study comparing off-pump CABG with partial aortic cross clamping versus the HEARTSTRING device aortic proximal anastomosis, the no touch technique reduced the occurrence of stroke to 0.7 % vs 2.3 % (OR 0.39, 95 % CI 0.16-0.90, P=0.04) [25]. Acute Kidney Injury and Dialysis Cardiopulmonary bypass may have a detrimental effect on early postoperative kidney function due to the inflammatory response, non pulsative flow, hemodilution, and hypoperfusion of the kidney. Postoperative renal function has been
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Fig. 2 Meta-analysis of stroke in randomized trials comparing offpump versus on-pump CABG. Updated version of the Cochrane Systematic Review. Trials without stroke in both the offpump and on-pump group have been excluded as these trials do not generate a risk ratio
studied in several studies assessed by serum creatinine, creatinine clearance, N-acetylglucosaminidase activity, and urinary excretion of retinol binding protein and microalbumin [28–30]. Most of these trials have found off-pump CABG to be gentler to the kidney. In the CORONARY trial postoperative renal insufficiency was assessed by the RIFLE criteria and off-pump CABG significantly reduced the rate of acute kidney injury (17.0 % vs. 19.5 %, RR 0.87; 95 % CI 0.76-0.98, P =0.02), but the number of patients requiring dialysis was similar (1.2 % vs. 1.1 %, RR 1.04; 95 % CI 0.61-1.76) [12••]. In the GOPCABE trial, including patients aged≥75 years, the incidence of postoperative dialysis was higher but again without significant difference between off-pump and on-pump CABG (2.9 % vs. 3.5 %, HR 0.82; 95 % CI 0.521.28, P=0.37) [10••]. These findings are in accordance with a previously published meta-analysis of randomized trials [31]. Completeness of Revascularization and Graft Patency As off-pump CABG is technical more demanding than onpump CABG there seems to be a higher risk of incomplete revascularization after off-pump CABG. One of the major drawbacks with off-pump CABG is the difficulties to perform
the anastomosis on the lateral wall of the left ventricle and the marginal branches [32]. Several larger randomized trials have shown off-pump CABG associated with significantly fewer distal anastomosis performed [12••, 14, 17, 18]. In a recent meta-analysis of number of distal anastomosis found average mean differences of -0.28 (95 % CI -0.40 to -0.16) [7•]. However, the number of distal anastomosis may not directly mirror the degree of incomplete revascularization. In the ROOBY trial patients not receiving the number of planned grafts were significantly lower in the off-pump group (17.8 % vs. 11.1). The results for the ROOBY trial have been criticized for the use of inexperienced off-pump surgeons as residents were allowed to be primary surgeons [17]. But similar findings were seen in the GOPCABE trial in which participating surgeons were required to be established experts in the performance of either off-pump or on-pump CABG. In the offpump group 34 % of the patients received fewer grafts than anticipated versus 29 % in the on-pump group [10••]. Also in the CORONARY trial incomplete revascularization was more frequent in the off-pump group (10 % vs. 11.8 %, P=0.05) [12••]. Although, it may be difficult to prove the exact benefit of complete revascularization a recent study of 1606 patients undergoing off-pump CABG showed an increased risk of all-
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cause mortality after incomplete revascularization (propensity adjusted HR 1.75, 95 % CI 1.10-2.79) [33]. Another concern with off-pump CABG is the quality of the anastomosis performed on a beating heart. Graft patency has been studied in ten randomized trials [13, 17, 34–41]. In three trials graft patency was found significantly reduced with off-pump CABG [17, 35, 39]. In the PROMISS trial, including 150 patients randomized to off-pump or on-pump CABG, graft patency was evaluated with 16 slice multidetector computer tomography at 4-6 weeks. In the off-pump group 26.7 % of the patients had at least one occluded graft compared with 5.0 % in the on-pump group (P=0.04) [39]. In the ROOBY trial 64.5 % of the enrolled patients underwent 1-year coronary angiography. At least one occluded graft was found in 36.5 % of the patients in the off-pump group and 28.7 % in the on-pump group (P=0.002) [17]. Furthermore, observational studies have shown that off-pump CABG results in increased risk of repeat revascularization [20, 42], which has been confirmed in a recent meta-analysis of randomized trials [43]. The meta-analysis included 12 trials (11,594 patients) and found a 38 % increase in repeat revascularization rates with off-pump relative to on-pump CABG in a fixed-effects model (OR, 1.38; 95 % CI, 1.09–1.76; P=0.008) [43].
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included. The primary composite outcome of death, myocardial infarction, and stroke was not different between patients randomized to off-pump or on-pump CABG (10.7 % vs. 10.2 %, P=0.83) [14]. In the recently published GOPCABE trial including 2539 patients aged ≥75 years, no benefit of off-pump CABG was demonstrated at 30-days in the primary outcome, a composite of death, stroke, myocardial infarction, new renal replacement therapy, or repeat revascularization (7.8 % vs. 8.2 %, OR 0.95, 95 % CI 0.71-1.28). However, off-pump CABG resulted in significantly fewer blood transfusions but increased risk of repeat revascularization [10••]. However, retrospective studies have demonstrated improved outcomes in patients with left ventricle dysfunction [46, 47]. In a very large cohort of 83,914 high-risk patients no difference operative mortality was documented, but off-pump CABG was associated with a small absolute reduction in the risk of postoperative stroke of 0.5-1.2 % [24]. Similar findings have been reported from the Japanese CREDO-Kyoto registry. No survival benefit of off-pump CABG was shown regardless of preoperative risk level, but in the cohort of patients with a EuroSCORE ≥6 offpump was associated with a decreased risk of stroke [22].
Conclusion High Risk Patients During the last decades, the preoperative risk profile of patients referred for CABG has changed, i.e., increased age, more severe coronary disease, and comorbidity. As these types of patients have an increased risk of postoperative complications, it seemed reasonable that this group of patients would benefit the most by avoiding aortic cannulation, cardiopulmonary bypass, and aortic cross clamping. Few randomized trials have focused on these high risk patients and the results have not shown a clear benefit. In BBS trial 341 patients with a EuroSCORE ≥5 were randomized to off-pump versus onpump CABG. No significant difference in the primary composite outcome (all-cause mortality, cardiac arrest with successful resuscitation, low cardiac output syndrome, myocardial infarction, stroke, or coronary reintervention) was found [15]. At 30-days there was a trend toward lower mortality in the off-pump group, but at long-term follow-up an increased all-cause mortality was seen in the off-pump group (HR 1.66; 95 % CI 1.02-2.73, P=0.04) [44•]. In an interim analysis of the randomized On-Off study, including 411 patients with a EuroSCORE ≥6, no significant difference in mortality, myocardial infarction or stroke was demonstrated, but the primary outcome (a composite of operative mortality, myocardial infarction, stroke, renal failure, reoperation for bleeding and adult respiratory distress syndrome within 30 days after surgery) was reduced after off-pump CABG (OR 2.51; 95 % CI 1.23-5.10, P=0.011) [45]. Two trials have focused on elderly patients. In the DOORS trial 900 patients aged 70 years or more were
Coronary artery bypass grafting can be performed with both low short-tem morbidity and mortality. Intuitively, off-pump CABG seems to be a more gentle approach but this technique is more challenging and demanding. Off-pump CABG reduces postoperative bleeding and the risk of blood transfusion. However, off-pump is associated with fewer grafts performed, especially to the lateral wall of the left ventricle and in an increased risk of incomplete revascularization. Based on the current literature, the potential harms of cardiopulmonary bypass during on-pump CABG seems to be minimal in lowrisk patients and compared to the higher degree of technical precision, anastomotic quality, and completeness of revascularization, this should not be jeopardized in order to avoid CPB. In patients with advanced ascending aortic disease offpump CABG is the preferred procedure for coronary revascularization and should be performed as a no-touch aortic technique. Furthermore, patients with increased preoperative risk of stroke and renal failure may benefit from off-pump CABG due to the reduced manipulation of the aorta and avoidance of the inflammatory response triggered by CPB. Compliance with Ethics Guidelines Conflict of Interest Christian H. Møller and Daniel A. Steinbrüchel declare that they have no conflict of interest. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
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References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
Montalescot G, Sechtem U, Achenbach S, et al. ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013. doi:10.1093/ eurheartj/eht296. 2. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367:2375–84. 3. Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381:629–38. 4. Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360:961–72. 5. Li Z, Yeo KK, Parker JP, et al. Off-pump coronary artery bypass graft surgery in California, 2003 to 2005. Am Heart J. 2008;156: 1095–102. 6. Borst C, Jansen EW, Tulleken CA, et al. Coronary artery bypass grafting without cardiopulmonary bypass and without interruption of native coronary flow using a novel anastomosis site restraining device ("Octopus"). J Am Coll Cardiol. 1996;27:1356–64. 7.• Møller CH, Penninga L, Wetterslev J, et al. Off-pump versus onpump coronary artery bypass grafting for ischaemic heart disease. Cochrane Database Syst Rev. 2012;3:CD007224. This study provides a systematic review, including quality assessment and meta-analysis, of randomized trials comparing off-pump and on-pump CABG. 8. Gardner TJ. On-pump versus off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2007;133:1. 9. Taggart DP, Altman DG. Off-pump vs. on-pump CABG: are we any closer to a resolution? Eur Heart J. 2012;33:1181–3. 10.•• Diegeler A, Borgermann J, Kappert U, et al. Off-pump versus onpump coronary-artery bypass grafting in elderly patients. N Engl J Med. 2013;368:1189–98. Randomized trial including more than 2200 elderly patients (> 75 years) undergoing off-pump versus on-pump CABG, the trial could not demonstrate significant differences in 30 day and 1 year composite outcome. However, incomplete revascularization and repeat revascularization were more often seen in the off-pump group. 11.•• Lamy A, Devereaux PJ, Prabhakaran D, et al. Effects of off-pump and on-pump coronary-artery bypass grafting at 1 year. N Engl J Med. 2013;368:1179–88. The 1-year results of the largest randomized trial between off-pump and on-pump CABG. The trial demonstrated equivalent 1-year outcomes between groups. 12.•• Lamy A, Devereaux PJ, Prabhakaran D, et al. Off-pump or onpump coronary-artery bypass grafting at 30 days. N Engl J Med. 2012;366:1489–97. This is the to date largest randomized trial comparing off-pump and on-pump CABG. The study found similar event rate in the primary outcome. However, off-pump CABG reduced the incidence of acute kidney injury, but increased repeat revascularization. 13. Angelini GD, Taylor FC, Reeves BC, Ascione R. Early and midterm outcome after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two randomised controlled trials. Lancet. 2002;359: 1194–9.
Curr Cardiol Rep (2014) 16:455 14.
Houlind K, Kjeldsen BJ, Madsen SN, et al. On-pump versus offpump coronary artery bypass surgery in elderly patients: results from the Danish on-pump versus off-pump randomization study. Circulation. 2012;125:2431–9. 15. Møller CH, Perko MJ, Lund JT, et al. No major differences in 30day outcomes in high-risk patients randomized to off-pump versus on-pump coronary bypass surgery: the best bypass surgery trial. Circulation. 2010;121:498–504. 16. Puskas JD, Williams WH, Duke PG, et al. Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003;125: 797–808. 17. Shroyer AL, Grover FL, Hattler B, et al. On-pump versus off-pump coronary-artery bypass surgery. N Engl J Med. 2009;361:1827–37. 18. van Dijk D, Nierich AP, Jansen EW, et al. Early outcome after offpump versus on-pump coronary bypass surgery: results from a randomized study. Circulation. 2001;104:1761–6. 19. Fattouch K, Guccione F, Dioguardi P, et al. Off-pump versus onpump myocardial revascularization in patients with ST-segment elevation myocardial infarction: a randomized trial. J Thorac Cardiovasc Surg. 2009;137:650–6. 20. Hannan EL, Wu C, Smith CR, 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;116:1145–52. 21. Puskas JD, Kilgo PD, Lattouf OM, et al. Off-pump coronary bypass provides reduced mortality and morbidity and equivalent 10-year survival. Ann Thorac Surg. 2008;86:1139–46. 22. Marui A, Okabayashi H, Komiya T, et al. Benefits of off-pump coronary artery bypass grafting in high-risk patients. Circulation. 2012;126:S151–7. 23. Ascione R, Lloyd CT, Gomes WJ, et al. Beating versus arrested heart revascularization: evaluation of myocardial function in a prospective randomized study. Eur J Cardiothorac Surg. 1999;15: 685–90. 24. Cavallaro P, Itagaki S, Seigerman M, Chikwe J. Operative mortality and stroke after on-pump vs off-pump surgery in high-risk patients: an analysis of 83 914 coronary bypass operations. Eur J Cardiothorac Surg. 2013. doi:10.1093/ejcts/ezt221. 25. Emmert MY, Seifert B, Wilhelm M, et al. Aortic no-touch technique makes the difference in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2011;142:1499–506. 26. Edelman JJ, Sherrah AG, Wilson MK, et al. Anaortic, total-arterial, off-pump coronary artery bypass surgery: why bother? Heart Lung Circ. 2013;22:161–70. 27. Misfeld M, Brereton RJ, Sweetman EA, Doig GS. Neurologic complications after off-pump coronary artery bypass grafting with and without aortic manipulation: meta-analysis of 11,398 cases from 8 studies. J Thorac Cardiovasc Surg. 2011;142:e11–7. 28. Ascione R, Lloyd CT, Underwood MJ, et al. On-pump versus offpump coronary revascularization: evaluation of renal function. Ann Thorac Surg. 1999;68:493–8. 29. Caputo M, Yeatman M, Narayan P, et al. Effect of off-pump coronary surgery with right ventricular assist device on organ function and inflammatory response: a randomized controlled trial. Ann Thorac Surg. 2002;74:2088–95. 30. Tang AT, Knott J, Nanson J, et al. A prospective randomized study to evaluate the renoprotective action of beating heart coronary surgery in low risk patients. Eur J Cardiothorac Surg. 2002;22: 118–23. 31. Seabra VF, Alobaidi S, Balk EM, et al. Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized controlled trials. Clin J Am Soc Nephrol. 2010;5:1734–44.
Curr Cardiol Rep (2014) 16:455 32.
33.
34.
35.
36.
37.
38.
39.
40.
Robertson MW, Buth KJ, Stewart KM, et al. Complete revascularization is compromised in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2013;145:992–8. Nakano J, Okabayashi H, Noma H, et al. The impact of incomplete revascularization and angiographic patency on midterm results after off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2013. doi:10.1016/j.jtcvs.2013.03.026. Al Ruzzeh S, George S, Bustami M, et al. Effect of off-pump coronary artery bypass surgery on clinical, angiographic, neurocognitive, and quality of life outcomes: randomised controlled trial. BMJ. 2006;332:1365. Khan NE, De Souza A, Mister R, et al. A randomized comparison of off-pump and on-pump multivessel coronary-artery bypass surgery. N Engl J Med. 2004;350:21–8. Lingaas PS, Hol PK, Lundblad R, et al. Clinical and radiologic outcome of off-pump coronary surgery at 12 months follow-up: a prospective randomized trial. Ann Thorac Surg. 2006;81:2089–95. Møller CH, Perko MJ, Lund JT, et al. Graft patency after off-pump versus on-pump coronary artery surgery in high-risk patients. Scand Cardiovasc J. 2010;44:161–7. Puskas JD, Williams WH, Mahoney EM, et al. Off-pump vs conventional coronary artery bypass grafting: early and 1-year graft patency, cost, and quality-of-life outcomes: a randomized trial. JAMA. 2004;291:1841–9. Sousa UM, Cavaco S, Oliveira AG, et al. Early graft patency after off-pump and on-pump coronary bypass surgery: a prospective randomized study. Eur Heart J. 2010;31:2492–9. Widimsky P, Straka Z, Stros P, et al. One-year coronary bypass graft patency: a randomized comparison between off-pump and on-
Page 7 of 7, 455
41.
42.
43.
44.•
45.
46.
47.
pump surgery angiographic results of the PRAGUE-4 trial. Circulation. 2004;110:3418–23. Nathoe HM, van Dijk D, Jansen EW, et al. A comparison of onpump and off-pump coronary bypass surgery in low-risk patients. N Engl J Med. 2003;348:394–402. Hu S, Zheng Z, Yuan X, et al. Increasing long-term major vascular events and resource consumption in patients receiving off-pump coronary artery bypass: a single-center prospective observational study. Circulation. 2010;121:1800–8. Takagi H, Mizuno Y, Niwa M, et al. A meta-analysis of randomized trials for repeat revascularization following off-pump versus onpump coronary artery bypass grafting. Interact Cardiovasc Thorac Surg. 2013. doi:10.1093/icvts/ivt316. Møller CH, Perko MJ, Lund JT, et al. Three-year follow-up in a subset of high-risk patients randomly assigned to off-pump versus on-pump coronary artery bypass surgery: the Best Bypass Surgery trial. Heart. 2011;97:907–13. In this trial high-risk patients were randomized to off-pump versus on-pump CABG. Increased mortality was found in the off-pump group. Lemma MG, Coscioni E, Tritto FP, et al. On-pump versus off-pump coronary artery bypass surgery in high-risk patients: operative results of a prospective randomized trial (on-off study). J Thorac Cardiovasc Surg. 2012;143:625–31. Keeling WB, Williams ML, Slaughter MS, et al. Off-pump and onpump coronary revascularization in patients with low ejection fraction: a report from the society of thoracic surgeons national database. Ann Thorac Surg. 2013;96:83–8. Kunadian V, Zaman A, Qiu W. Revascularization among patients with severe left ventricular dysfunction: a meta-analysis of observational studies. Eur J Heart Fail. 2011;13:773–84.
ISCHEMIC HEART DISEASE (D MUKHERJEE, SECTION EDITOR)
Off-Pump Versus On-Pump Coronary Artery Bypass Grafting Christian H. Møller & Daniel A. Steinbrüchel
# Springer Science+Business Media New York 2014
Abstract Coronary artery bypass grafting (CABG) remains the preferred treatment in patients with complex coronary artery disease. However, whether the procedure should be performed with or without the use of cardiopulmonary bypass, referred to as off-pump and on-pump CABG, is still up for debate. Intuitively, avoidance of cardiopulmonary bypass seems beneficial as the systemic inflammatory response from extracorporeal circulation is omitted, but no single randomized trial has been able to prove off-pump CABG superior to on-pump CABG as regards the hard outcomes death, stroke or myocardial infarction. In contrast, off-pump CABG is technically more challenging and may be associated with increased risk of incomplete revascularization. The purpose of the review is to summarize the current literature comparing outcomes of off-pump versus on-pump coronary artery bypass surgery. Keywords Coronary artery bypass grafting . Off-pump . On-pump . Cardiopulmonary bypass
Introduction Coronary artery bypass grafting (CABG) remains the standard treatment for revascularization of patients with complex coronary artery disease [1]. However, over the last decades the use of percutaneous coronary intervention (PCI) has increased significantly and has challenged CABG in its role to be the most effective treatment for revascularization of the myocardium. Two recently This article is part of the Topical Collection on Ischemic Heart Disease C. H. Møller (*) : D. A. Steinbrüchel Department of Cardiothoracic Surgery, Rigshospitalet, Copenhagen University Hospital, Blegdamsvej 9, 2100 Copenhagen, Denmark e-mail: [email protected]
published trials have shown CABG superior to PCI in patients with 3-vessel coronary disease and in patients with diabetes and coronary disease [2, 3]. In the SYNT AX trial, including 1800 patients with 3-vessel coronary disease and/or left main coronary stenosis, at both 1- and 5-years follow-up there was a significant difference in the primary endpoint (all-cause mortality, stroke, myocardial infarction, and repeat revascularization) in favor of CABG [3, 4]. The benefit of CABG was even more pronounced in the patients with higher SYNTAX scores. The FREEDOM trial included 1900 patients with diabetes and multivessel coronary disease [2]. The 5-year primary composite outcome (death, myocardial infarction, and stroke) occurred in 26.6 % in the PCI group versus 18.7 % in the CABG group (P = 0.005). Furthermore, there was a significant increased risk of death and myocardial infarction in the PCI group, but more strokes after CABG [2]. Coronary artery bypass grafting is routinely performed with cardiopulmonary bypass (CPB) and the heart arrested referred to as on-pump CABG [5]. During on-pump CABG, the coronary bypasses can be performed in a blood-free surgical field with the heart immobilized and empty. This gives excellent presentation of the coronaries and the anastomosis performed with high precision. In an attempt to reduce the postoperative complications seen after on-pump CABG, interest in performing CABG on the beating heart without CPB (off-pump CABG) gained increasing interest in the mid 1990s [6]. Several trials comparing off-pump versus on-pump have been published over the last decades [7•]. But still there is an ongoing debate whether off-pump CABG and the avoidance of CPB is beneficial for the patients [8, 9]. With the recent publication of two relatively large randomized clinical trials the CORONARY trial and GOPCABE trial this review re-evaluates the current knowledge of off-pump versus on-pump CABG [10••, 11••].
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Outcomes of Off-Pump Versus On-Pump CABG Since the renewed interest in off-pump CABG in the mid 1990s several randomized trials comparing off-pump with on-pump CABG have been published. The majority of these trials have been underpowered to show significant differences in mortality, myocardial infarction and stroke after CABG surgery [7•]. Furthermore, the methodological quality of these trials has been poor leaving ample room for bias. Since the publication of the Cochrane Systematic Review comparing off-pump versus on-pump CABG, new larger and welldesigned randomized trials have been conducted and published. The to date largest randomized trial of off-pump versus on-pump CABG is the CORONARY trial including 4752 patients enrolled from 79 centers in 19 countries. At both 30 days and 12 months there was no significant difference in the primary outcome (a composite of death, myocardial infarction, stroke, or new renal failure requiring dialysis) [11••, 12••]. At 30 days the primary outcome had occurred in 9.8 % in off-pump group compared with 10.3 % in the onpump group (hazard ratio, HR 0.95, 95 % confidence interval, CI, 0.79-1.14, P=0.59). After 12 months, the primary outcome was seen in 12.1 % of the patients in the off-pump group and in 13.3 % in the on-pump group (HR 0.91, 95 % CI 0.771.07, P =0.24). In the GOPCABE trial, elderly patients aged 75 years or older were randomized to off-pump versus onpump CABG at 12 German centers. The trial included 2539 patients and the primary outcome was a composite of death, stroke, myocardial infarction, repeat revascularization, or new renal replacement therapy. At both 30 days and 12 months after surgery no significant difference was observed between off-pump and on-pump CABG in the primary outcome (at 30 days; 7.8 % vs. 8.2 %, odds ratio, OR 0.95, 95 % CI 0.71-1.28, P=0.74, and at 12 months; 13.1 % vs. 14.0, HR 0.93, 95 % CI 0.76-1.16, P=0.48) [10••]. Therefore, neither of these trials have been able to end the discussion whether off-pump CABG or on-pump CABG should be the preferred approach for coronary revascularization. However, each procedure may have different advantages. Mortality Several randomized trials have shown similar in-hospital mortality between off-pump and on-pump mortality [10••, 12••, 13–18]. Depending on the risk profile of the patients, 30-day mortality was in the range between 0 % and 6.7 %. Only a single trial has demonstrated a significant reduction in hospital mortality with off-pump CABG compared with on-pump CABG. This result was found in a small trial including patients with ST-segment elevation myocardial infarction and cardiogenic shock, who underwent emergency CABG within 6 hours of onset of symptoms [19]. In contrast, several observational studies have shown a significant reduction in 30-day
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mortality after off-pump CABG. However, a Cochrane systematic review raised concern about increased long-term mortality after off-pump CABG [7•]. In a subgroup analysis of trials conducted with low risk of bias showed a risk ratio (RR) of 1.35 (95 % CI 1.07-1.70, P=0.01) in favor of on-pump CABG. With the 1-year mortality results from the CORONARY and GOPCABE trials this risk may be overestimated. One-year mortality in the CORONARY trial was 5.1 % in the off-pump group compared with 5.0 % in the on-pump group (HR 1.03; 95 % CI 0.80-1.32) [11••] and in the GOPCABE trial 7.0 % versus 8.0 % (HR 0.88; 95 % CI 0.65-1.18) [10]. An updated meta-analysis based on current RCT demonstrates no significant difference in survival (RR 1.04; 95 % CI 0.911.19, P=0.53) (Fig. 1). Based on the New York state’s Cardiac surgery Reporting System including 49,830 patients, an observational retrospective study showed no significant difference in adjusted HR for 30-day mortality (HR 1.01, 95%CI 0.92-1.10 P=0.89) and at 3 years follow-up 90.1 % of patients in the on-pump group versus 89.4 in the off-pump group were alive (P =0.20) [20]. In contrast, a study of 12,812 patients from The Society of Thoracic Surgeons National Adult Cardiac Database reported a significant reduction in 30-day mortality after off-pump CABG (adjusted odds ratio 0.68; 95 % CI 0.46-0.99, P=0.045), and with equivalent 10-years survival [21]. From a multicenter register in Japan (CREDO-Kyoto) adjusted 30-day mortality was not significantly different between off-pump and on-pump patients regardless of their predicted risk of operative mortality [22]. Myocardial Infarction Current randomized trials have not demonstrated significant differences in postoperative myocardial infarction (MI) after off-pump CABG compared with on-pump CABG. In the CORONARY trial MI was observed in 6.7 % in the offpump group and 7.2 % in the on-pump after 30 days. In the GOPCABE trial the event rate of MI within 30 days was only 1.5 % versus 1.7 %. In the Cochrane systematic review, the meta-analysis of 55 randomized trials encompassing 8547 patients found similar occurrence of MI after off-pump and on-pump CABG (RR 1.00, 95 % CI 0.79-1.26) [7•]. Interesting, several trials have reported a significant reduction in release on coronary enzymes after off-pump CABG, but without obvious clinical manifestation in MI [16, 18, 23]. Stroke Although postoperative stroke is seen relatively seldom after CABG, it is one of the most devastating and feared complications. Elimination of aortic cannulation, cardiopulmonary bypass, and aortic cross clamping was thought to reduce the incidence of postoperative stroke after off-pump CABG. However, no single randomized trial has revealed off-pump
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Fig. 1 Meta-analysis of all-cause mortality in randomized trials comparing off-pump versus onpump CABG. Updated version of the Cochrane Systematic Review. Trials without death in both the off-pump and on-pump group have been excluded as these trials do not generate a risk ratio
CABG superior to on-pump CABG in reducing stroke. To date in the largest RCT, the CORONARY trial, stroke was observed in 1 % in the off-pump group and 1.1 % in the onpump group within 30 days. Similar results were seen in the ROOBY trial including 2203 low-risk patients from 18 Veterans Affairs medical centers [17]. Within 30 days stroke was registered in 1.3 % off-pump patients compared with 0.7 % on-pump patients (P=0.2). Not even in RCTs including elderly patients or high-risk patients, have off-pump CABG been able to show a significant reduction in stroke. The DOORS trial randomized 900 patients aged >70 years to off-pump or on-pump CABG. After 30 days, stroke was seen in 2.2 % and 4 % (P=0.12), respectively [14]. In the BBS trial, 341 patients with 3-vessel coronary disease and EuroSCORE ≥5 were randomized. In the off-pump group 4.0 % had a stroke compared with 3.7 % in the on-pump group (P=1.0) [15]. In the recent Cochrane systematic review including 61 trials, the meta-analysis of stroke was not significantly different between off-pump and on-pump CABG (RR 0.76, 95 % CI 0.54 – 1.06, P=0.10) [7•]. However, updating this meta-
analysis with the recently published CORONARY and GOPCABE trials, this revealed a significant 20 % relative risk reduction in stroke with off-pump CABG (RR 0.80, 95 % CI 0.64 - 1.00, P=0.05) (Fig. 2). Likewise, several retrospective analyses have shown that off-pump CABG was associated with a reduced event rate of stroke compared with on-pump CABG [20, 22, 24]. To further reduce the incidence of stroke after off-pump CABG some surgeons advocate for an ‘aortic no-touch’ or ‘anaortic’ technique [25–27]. In a study comparing off-pump CABG with partial aortic cross clamping versus the HEARTSTRING device aortic proximal anastomosis, the no touch technique reduced the occurrence of stroke to 0.7 % vs 2.3 % (OR 0.39, 95 % CI 0.16-0.90, P=0.04) [25]. Acute Kidney Injury and Dialysis Cardiopulmonary bypass may have a detrimental effect on early postoperative kidney function due to the inflammatory response, non pulsative flow, hemodilution, and hypoperfusion of the kidney. Postoperative renal function has been
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Fig. 2 Meta-analysis of stroke in randomized trials comparing offpump versus on-pump CABG. Updated version of the Cochrane Systematic Review. Trials without stroke in both the offpump and on-pump group have been excluded as these trials do not generate a risk ratio
studied in several studies assessed by serum creatinine, creatinine clearance, N-acetylglucosaminidase activity, and urinary excretion of retinol binding protein and microalbumin [28–30]. Most of these trials have found off-pump CABG to be gentler to the kidney. In the CORONARY trial postoperative renal insufficiency was assessed by the RIFLE criteria and off-pump CABG significantly reduced the rate of acute kidney injury (17.0 % vs. 19.5 %, RR 0.87; 95 % CI 0.76-0.98, P =0.02), but the number of patients requiring dialysis was similar (1.2 % vs. 1.1 %, RR 1.04; 95 % CI 0.61-1.76) [12••]. In the GOPCABE trial, including patients aged≥75 years, the incidence of postoperative dialysis was higher but again without significant difference between off-pump and on-pump CABG (2.9 % vs. 3.5 %, HR 0.82; 95 % CI 0.521.28, P=0.37) [10••]. These findings are in accordance with a previously published meta-analysis of randomized trials [31]. Completeness of Revascularization and Graft Patency As off-pump CABG is technical more demanding than onpump CABG there seems to be a higher risk of incomplete revascularization after off-pump CABG. One of the major drawbacks with off-pump CABG is the difficulties to perform
the anastomosis on the lateral wall of the left ventricle and the marginal branches [32]. Several larger randomized trials have shown off-pump CABG associated with significantly fewer distal anastomosis performed [12••, 14, 17, 18]. In a recent meta-analysis of number of distal anastomosis found average mean differences of -0.28 (95 % CI -0.40 to -0.16) [7•]. However, the number of distal anastomosis may not directly mirror the degree of incomplete revascularization. In the ROOBY trial patients not receiving the number of planned grafts were significantly lower in the off-pump group (17.8 % vs. 11.1). The results for the ROOBY trial have been criticized for the use of inexperienced off-pump surgeons as residents were allowed to be primary surgeons [17]. But similar findings were seen in the GOPCABE trial in which participating surgeons were required to be established experts in the performance of either off-pump or on-pump CABG. In the offpump group 34 % of the patients received fewer grafts than anticipated versus 29 % in the on-pump group [10••]. Also in the CORONARY trial incomplete revascularization was more frequent in the off-pump group (10 % vs. 11.8 %, P=0.05) [12••]. Although, it may be difficult to prove the exact benefit of complete revascularization a recent study of 1606 patients undergoing off-pump CABG showed an increased risk of all-
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cause mortality after incomplete revascularization (propensity adjusted HR 1.75, 95 % CI 1.10-2.79) [33]. Another concern with off-pump CABG is the quality of the anastomosis performed on a beating heart. Graft patency has been studied in ten randomized trials [13, 17, 34–41]. In three trials graft patency was found significantly reduced with off-pump CABG [17, 35, 39]. In the PROMISS trial, including 150 patients randomized to off-pump or on-pump CABG, graft patency was evaluated with 16 slice multidetector computer tomography at 4-6 weeks. In the off-pump group 26.7 % of the patients had at least one occluded graft compared with 5.0 % in the on-pump group (P=0.04) [39]. In the ROOBY trial 64.5 % of the enrolled patients underwent 1-year coronary angiography. At least one occluded graft was found in 36.5 % of the patients in the off-pump group and 28.7 % in the on-pump group (P=0.002) [17]. Furthermore, observational studies have shown that off-pump CABG results in increased risk of repeat revascularization [20, 42], which has been confirmed in a recent meta-analysis of randomized trials [43]. The meta-analysis included 12 trials (11,594 patients) and found a 38 % increase in repeat revascularization rates with off-pump relative to on-pump CABG in a fixed-effects model (OR, 1.38; 95 % CI, 1.09–1.76; P=0.008) [43].
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included. The primary composite outcome of death, myocardial infarction, and stroke was not different between patients randomized to off-pump or on-pump CABG (10.7 % vs. 10.2 %, P=0.83) [14]. In the recently published GOPCABE trial including 2539 patients aged ≥75 years, no benefit of off-pump CABG was demonstrated at 30-days in the primary outcome, a composite of death, stroke, myocardial infarction, new renal replacement therapy, or repeat revascularization (7.8 % vs. 8.2 %, OR 0.95, 95 % CI 0.71-1.28). However, off-pump CABG resulted in significantly fewer blood transfusions but increased risk of repeat revascularization [10••]. However, retrospective studies have demonstrated improved outcomes in patients with left ventricle dysfunction [46, 47]. In a very large cohort of 83,914 high-risk patients no difference operative mortality was documented, but off-pump CABG was associated with a small absolute reduction in the risk of postoperative stroke of 0.5-1.2 % [24]. Similar findings have been reported from the Japanese CREDO-Kyoto registry. No survival benefit of off-pump CABG was shown regardless of preoperative risk level, but in the cohort of patients with a EuroSCORE ≥6 offpump was associated with a decreased risk of stroke [22].
Conclusion High Risk Patients During the last decades, the preoperative risk profile of patients referred for CABG has changed, i.e., increased age, more severe coronary disease, and comorbidity. As these types of patients have an increased risk of postoperative complications, it seemed reasonable that this group of patients would benefit the most by avoiding aortic cannulation, cardiopulmonary bypass, and aortic cross clamping. Few randomized trials have focused on these high risk patients and the results have not shown a clear benefit. In BBS trial 341 patients with a EuroSCORE ≥5 were randomized to off-pump versus onpump CABG. No significant difference in the primary composite outcome (all-cause mortality, cardiac arrest with successful resuscitation, low cardiac output syndrome, myocardial infarction, stroke, or coronary reintervention) was found [15]. At 30-days there was a trend toward lower mortality in the off-pump group, but at long-term follow-up an increased all-cause mortality was seen in the off-pump group (HR 1.66; 95 % CI 1.02-2.73, P=0.04) [44•]. In an interim analysis of the randomized On-Off study, including 411 patients with a EuroSCORE ≥6, no significant difference in mortality, myocardial infarction or stroke was demonstrated, but the primary outcome (a composite of operative mortality, myocardial infarction, stroke, renal failure, reoperation for bleeding and adult respiratory distress syndrome within 30 days after surgery) was reduced after off-pump CABG (OR 2.51; 95 % CI 1.23-5.10, P=0.011) [45]. Two trials have focused on elderly patients. In the DOORS trial 900 patients aged 70 years or more were
Coronary artery bypass grafting can be performed with both low short-tem morbidity and mortality. Intuitively, off-pump CABG seems to be a more gentle approach but this technique is more challenging and demanding. Off-pump CABG reduces postoperative bleeding and the risk of blood transfusion. However, off-pump is associated with fewer grafts performed, especially to the lateral wall of the left ventricle and in an increased risk of incomplete revascularization. Based on the current literature, the potential harms of cardiopulmonary bypass during on-pump CABG seems to be minimal in lowrisk patients and compared to the higher degree of technical precision, anastomotic quality, and completeness of revascularization, this should not be jeopardized in order to avoid CPB. In patients with advanced ascending aortic disease offpump CABG is the preferred procedure for coronary revascularization and should be performed as a no-touch aortic technique. Furthermore, patients with increased preoperative risk of stroke and renal failure may benefit from off-pump CABG due to the reduced manipulation of the aorta and avoidance of the inflammatory response triggered by CPB. Compliance with Ethics Guidelines Conflict of Interest Christian H. Møller and Daniel A. Steinbrüchel declare that they have no conflict of interest. Human and Animal Rights and Informed Consent This article does not contain any studies with human or animal subjects performed by any of the authors.
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References Papers of particular interest, published recently, have been highlighted as: • Of importance •• Of major importance 1.
Montalescot G, Sechtem U, Achenbach S, et al. ESC guidelines on the management of stable coronary artery disease: The Task Force on the management of stable coronary artery disease of the European Society of Cardiology. Eur Heart J. 2013. doi:10.1093/ eurheartj/eht296. 2. Farkouh ME, Domanski M, Sleeper LA, et al. Strategies for multivessel revascularization in patients with diabetes. N Engl J Med. 2012;367:2375–84. 3. Mohr FW, Morice MC, Kappetein AP, et al. Coronary artery bypass graft surgery versus percutaneous coronary intervention in patients with three-vessel disease and left main coronary disease: 5-year follow-up of the randomised, clinical SYNTAX trial. Lancet. 2013;381:629–38. 4. Serruys PW, Morice MC, Kappetein AP, et al. Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease. N Engl J Med. 2009;360:961–72. 5. Li Z, Yeo KK, Parker JP, et al. Off-pump coronary artery bypass graft surgery in California, 2003 to 2005. Am Heart J. 2008;156: 1095–102. 6. Borst C, Jansen EW, Tulleken CA, et al. Coronary artery bypass grafting without cardiopulmonary bypass and without interruption of native coronary flow using a novel anastomosis site restraining device ("Octopus"). J Am Coll Cardiol. 1996;27:1356–64. 7.• Møller CH, Penninga L, Wetterslev J, et al. Off-pump versus onpump coronary artery bypass grafting for ischaemic heart disease. Cochrane Database Syst Rev. 2012;3:CD007224. This study provides a systematic review, including quality assessment and meta-analysis, of randomized trials comparing off-pump and on-pump CABG. 8. Gardner TJ. On-pump versus off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2007;133:1. 9. Taggart DP, Altman DG. Off-pump vs. on-pump CABG: are we any closer to a resolution? Eur Heart J. 2012;33:1181–3. 10.•• Diegeler A, Borgermann J, Kappert U, et al. Off-pump versus onpump coronary-artery bypass grafting in elderly patients. N Engl J Med. 2013;368:1189–98. Randomized trial including more than 2200 elderly patients (> 75 years) undergoing off-pump versus on-pump CABG, the trial could not demonstrate significant differences in 30 day and 1 year composite outcome. However, incomplete revascularization and repeat revascularization were more often seen in the off-pump group. 11.•• Lamy A, Devereaux PJ, Prabhakaran D, et al. Effects of off-pump and on-pump coronary-artery bypass grafting at 1 year. N Engl J Med. 2013;368:1179–88. The 1-year results of the largest randomized trial between off-pump and on-pump CABG. The trial demonstrated equivalent 1-year outcomes between groups. 12.•• Lamy A, Devereaux PJ, Prabhakaran D, et al. Off-pump or onpump coronary-artery bypass grafting at 30 days. N Engl J Med. 2012;366:1489–97. This is the to date largest randomized trial comparing off-pump and on-pump CABG. The study found similar event rate in the primary outcome. However, off-pump CABG reduced the incidence of acute kidney injury, but increased repeat revascularization. 13. Angelini GD, Taylor FC, Reeves BC, Ascione R. Early and midterm outcome after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two randomised controlled trials. Lancet. 2002;359: 1194–9.
Curr Cardiol Rep (2014) 16:455 14.
Houlind K, Kjeldsen BJ, Madsen SN, et al. On-pump versus offpump coronary artery bypass surgery in elderly patients: results from the Danish on-pump versus off-pump randomization study. Circulation. 2012;125:2431–9. 15. Møller CH, Perko MJ, Lund JT, et al. No major differences in 30day outcomes in high-risk patients randomized to off-pump versus on-pump coronary bypass surgery: the best bypass surgery trial. Circulation. 2010;121:498–504. 16. Puskas JD, Williams WH, Duke PG, et al. Off-pump coronary artery bypass grafting provides complete revascularization with reduced myocardial injury, transfusion requirements, and length of stay: a prospective randomized comparison of two hundred unselected patients undergoing off-pump versus conventional coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2003;125: 797–808. 17. Shroyer AL, Grover FL, Hattler B, et al. On-pump versus off-pump coronary-artery bypass surgery. N Engl J Med. 2009;361:1827–37. 18. van Dijk D, Nierich AP, Jansen EW, et al. Early outcome after offpump versus on-pump coronary bypass surgery: results from a randomized study. Circulation. 2001;104:1761–6. 19. Fattouch K, Guccione F, Dioguardi P, et al. Off-pump versus onpump myocardial revascularization in patients with ST-segment elevation myocardial infarction: a randomized trial. J Thorac Cardiovasc Surg. 2009;137:650–6. 20. Hannan EL, Wu C, Smith CR, 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;116:1145–52. 21. Puskas JD, Kilgo PD, Lattouf OM, et al. Off-pump coronary bypass provides reduced mortality and morbidity and equivalent 10-year survival. Ann Thorac Surg. 2008;86:1139–46. 22. Marui A, Okabayashi H, Komiya T, et al. Benefits of off-pump coronary artery bypass grafting in high-risk patients. Circulation. 2012;126:S151–7. 23. Ascione R, Lloyd CT, Gomes WJ, et al. Beating versus arrested heart revascularization: evaluation of myocardial function in a prospective randomized study. Eur J Cardiothorac Surg. 1999;15: 685–90. 24. Cavallaro P, Itagaki S, Seigerman M, Chikwe J. Operative mortality and stroke after on-pump vs off-pump surgery in high-risk patients: an analysis of 83 914 coronary bypass operations. Eur J Cardiothorac Surg. 2013. doi:10.1093/ejcts/ezt221. 25. Emmert MY, Seifert B, Wilhelm M, et al. Aortic no-touch technique makes the difference in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2011;142:1499–506. 26. Edelman JJ, Sherrah AG, Wilson MK, et al. Anaortic, total-arterial, off-pump coronary artery bypass surgery: why bother? Heart Lung Circ. 2013;22:161–70. 27. Misfeld M, Brereton RJ, Sweetman EA, Doig GS. Neurologic complications after off-pump coronary artery bypass grafting with and without aortic manipulation: meta-analysis of 11,398 cases from 8 studies. J Thorac Cardiovasc Surg. 2011;142:e11–7. 28. Ascione R, Lloyd CT, Underwood MJ, et al. On-pump versus offpump coronary revascularization: evaluation of renal function. Ann Thorac Surg. 1999;68:493–8. 29. Caputo M, Yeatman M, Narayan P, et al. Effect of off-pump coronary surgery with right ventricular assist device on organ function and inflammatory response: a randomized controlled trial. Ann Thorac Surg. 2002;74:2088–95. 30. Tang AT, Knott J, Nanson J, et al. A prospective randomized study to evaluate the renoprotective action of beating heart coronary surgery in low risk patients. Eur J Cardiothorac Surg. 2002;22: 118–23. 31. Seabra VF, Alobaidi S, Balk EM, et al. Off-pump coronary artery bypass surgery and acute kidney injury: a meta-analysis of randomized controlled trials. Clin J Am Soc Nephrol. 2010;5:1734–44.
Curr Cardiol Rep (2014) 16:455 32.
33.
34.
35.
36.
37.
38.
39.
40.
Robertson MW, Buth KJ, Stewart KM, et al. Complete revascularization is compromised in off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2013;145:992–8. Nakano J, Okabayashi H, Noma H, et al. The impact of incomplete revascularization and angiographic patency on midterm results after off-pump coronary artery bypass grafting. J Thorac Cardiovasc Surg. 2013. doi:10.1016/j.jtcvs.2013.03.026. Al Ruzzeh S, George S, Bustami M, et al. Effect of off-pump coronary artery bypass surgery on clinical, angiographic, neurocognitive, and quality of life outcomes: randomised controlled trial. BMJ. 2006;332:1365. Khan NE, De Souza A, Mister R, et al. A randomized comparison of off-pump and on-pump multivessel coronary-artery bypass surgery. N Engl J Med. 2004;350:21–8. Lingaas PS, Hol PK, Lundblad R, et al. Clinical and radiologic outcome of off-pump coronary surgery at 12 months follow-up: a prospective randomized trial. Ann Thorac Surg. 2006;81:2089–95. Møller CH, Perko MJ, Lund JT, et al. Graft patency after off-pump versus on-pump coronary artery surgery in high-risk patients. Scand Cardiovasc J. 2010;44:161–7. Puskas JD, Williams WH, Mahoney EM, et al. Off-pump vs conventional coronary artery bypass grafting: early and 1-year graft patency, cost, and quality-of-life outcomes: a randomized trial. JAMA. 2004;291:1841–9. Sousa UM, Cavaco S, Oliveira AG, et al. Early graft patency after off-pump and on-pump coronary bypass surgery: a prospective randomized study. Eur Heart J. 2010;31:2492–9. Widimsky P, Straka Z, Stros P, et al. One-year coronary bypass graft patency: a randomized comparison between off-pump and on-
Page 7 of 7, 455
41.
42.
43.
44.•
45.
46.
47.
pump surgery angiographic results of the PRAGUE-4 trial. Circulation. 2004;110:3418–23. Nathoe HM, van Dijk D, Jansen EW, et al. A comparison of onpump and off-pump coronary bypass surgery in low-risk patients. N Engl J Med. 2003;348:394–402. Hu S, Zheng Z, Yuan X, et al. Increasing long-term major vascular events and resource consumption in patients receiving off-pump coronary artery bypass: a single-center prospective observational study. Circulation. 2010;121:1800–8. Takagi H, Mizuno Y, Niwa M, et al. A meta-analysis of randomized trials for repeat revascularization following off-pump versus onpump coronary artery bypass grafting. Interact Cardiovasc Thorac Surg. 2013. doi:10.1093/icvts/ivt316. Møller CH, Perko MJ, Lund JT, et al. Three-year follow-up in a subset of high-risk patients randomly assigned to off-pump versus on-pump coronary artery bypass surgery: the Best Bypass Surgery trial. Heart. 2011;97:907–13. In this trial high-risk patients were randomized to off-pump versus on-pump CABG. Increased mortality was found in the off-pump group. Lemma MG, Coscioni E, Tritto FP, et al. On-pump versus off-pump coronary artery bypass surgery in high-risk patients: operative results of a prospective randomized trial (on-off study). J Thorac Cardiovasc Surg. 2012;143:625–31. Keeling WB, Williams ML, Slaughter MS, et al. Off-pump and onpump coronary revascularization in patients with low ejection fraction: a report from the society of thoracic surgeons national database. Ann Thorac Surg. 2013;96:83–8. Kunadian V, Zaman A, Qiu W. Revascularization among patients with severe left ventricular dysfunction: a meta-analysis of observational studies. Eur J Heart Fail. 2011;13:773–84.
