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J Thorac Cardiovasc Surg 2003;126:7-10
© 2003 The American Association for Thoracic Surgery
Editorial |
a Miami Heart Research Institute, Miami Beach, Fla, USA.
Received for publication September 18, 2002; accepted for publication September 23, 2002.
* Address for reprints: Paul A. Kurlansky, MD, Miami Heart Research Institute, 801 Arthur Godfrey Rd, 5th Floor, Miami Beach, FL 33140, USA
doctorwu18{at}aol.com
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Coronary artery bypass graft (CABG) surgery on a beating heart was introduced with suture techniques and local stabilization by Kolessov in 1967.1 However, cardiopulmonary bypass and cardioplegic arrest, with their ability to provide a quiet bloodless field for the construction of precise and delicate surgical anastomoses, offered compelling advantages compared with the off-pump approach and rapidly became more widely accepted.2 With the dramatic reduction of operative mortality throughout the ensuing decades, surgeons began to focus their attention on decreasing operative morbidity, especially conditions associated with neurologic and systemic inflammatory influences after CABG surgery. Traditionally, many of these sequelae have been ascribed to the use of cardiopulmonary bypass.
During the past decade, there has been a dramatic resurgence in the application of off-pump technology in CABG surgery. This has inspired remarkable advances in the techniques of localized tissue stabilization and a greater understanding of the physiology of beating heart mobilization and exposure. An avalanche of reports in the literature has demonstrated the early safety and efficacy of the procedure.3 More than 20% of CABG procedures performed nationwide apply off-pump technology. However, considerable controversy remains regarding the relative merits and long-term outcomes of this approach to coronary revascularization.4
One area of concern, and even greater uncertainty, surrounds the issue of the existence of a hypercoagulable state after off-pump CABG surgery. Are patients undergoing off-pump CABG surgery relatively more hypercoagulable postoperatively than their counterparts undergoing on-pump CABG surgery? Such a hypothesis is indeed reasonable in view of the acute phase activation of clotting factors that follow off-pump CABG surgery (as well as surgery in general) and the lack of platelet, fibrinolytic, and other abnormalities related to the heart-lung machine. However, there was no evidence to indicate a clinical problem associated with the procedure until Mariani and colleagues5 awakened our concern with their report in 1999. They reviewed 22 consecutive off-pump cases and found a postoperative increase in procoagulant activity, represented by prothrombin factor 1 and 2, which was also accompanied by an increase in von Willebrand factor (endothelial activation) and fibrinolysis. Although Mariani and colleagues5 demonstrated no clinical sequelae during their brief follow-up of this limited series of patients with internal thoracic artery (ITA) grafts, they recommended the institution of an aggressive perioperative anticoagulant regimen in all off-pump CABG cases.
What is the major concern? Clearly, a pattern of deep venous thrombosis, pulmonary embolism, or arterial thrombosis would be a source of serious concern to the cardiac surgeon. However, the already extensive clinical experience fails to demonstrate such a pattern. Perhaps a less apparent concern would be the occurrence of acute graft closure. Careful evaluation of the current body of knowledge would indicate just the opposite, with acute graft patency rates exceeding 90% in virtually all cases reviewed. The information in Table 1 summarizes the results of a series of angiographic patency studies after off-pump CABG surgery.6-15 Even accounting for extensive variability in patient selection, operative technique, and heparin and antiplatelet regimens in these studies, it does not seem that acute graft closure secondary to a hypercoagulable state is a valid clinical concern.
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It has been learned from multiple pathologic and clinical studies that vein graft disease takes many forms: thrombosis (acute), intimal hyperplasia (subacute), and graft atherosclerosis (chronic).16 Although intimal hyperplasia may take months to occur, and atherosclerosis 1 year or more to develop, the initiating events (intimal injury, platelet activation, thrombus formation, macrophage infiltration, and smooth muscle cell activation) all occur in the acute postoperative period of SVG (but not during ITA) healing. Therefore, during the early postoperative period, even in the absence of any clinically manifest adverse events, the groundwork may be laid for the occurrence of multiple late events, thus adversely impairing long-term graft patency. In short, have we, in our enthusiasm to reduce perioperative morbidity, created a sleeping giant of late graft closure?
Casati and colleagues17 compared multiple hematologic variables in patients undergoing off-pump versus on-pump CABG surgery. They documented that a decrease in platelet count and activation of fibrinolysis were more profound in on-pump surgery, whereas the activation of fibrinogen and other acute phase reactants (consistent with the deposition of thrombus at surgical sites of injury) seemed to be more evident during the first postoperative day in patients undergoing off-pump CABG surgery. Therefore, patients undergoing off-pump coronary artery bypass surgery might well be expected to be more prone to graft closure. As disconcerting as these findings may seem, a comparative analysis of perioperative hemostatic function in patients who did and did not experience SVG occlusion within 3 months of surgery found an increase in plasma plasminogen activator inhibitor-1 activity to be the only postoperative hemostatic measurement predictive of subsequent SVG closure.18 Notably, the classic atherosclerotic risk factors were found to be more powerful predictors than the hemostatic factors, a finding corroborated by the Cleveland Clinic experience.19
The emergence of long-term comparative studies demonstrating the clinical equivalence of on-pump and off-pump CABG surgery has been most encouraging.20 However, in the absence of convincing data, there is currently extreme variability in the management of anticoagulation and antiplatelet agents in off-pump CABG surgery.21
In the presence of a well-founded concern for the impact of a relatively hypercoagulable state after off-pump CABG surgery on long-term graft patency, and in the absence of valid data indicating appropriate guidelines, what reasonable recommendations can be offered at this time? First, arterial conduits, especially in situ ITA grafts, have been demonstrated to be less prone to the pathogenesis of late graft closure than SVG grafts and are considered to be the conduit of choice in myocardial revascularization. As a result, off-pump CABG surgery may prove to be an even stronger indication for the use of arterial grafting than conventional on-pump surgery.
Second, risk factor modification is known to affect the course of both graft and native coronary disease in all patients undergoing CABG surgery, and patients undergoing off-pump CABG surgery are no exception. Therefore, careful attention to risk factor modification may prove critical in maintaining graft patency and improving long-term clinical results.
Third, in view of the lower incidence of bleeding complications after off-pump CABG surgery, consideration should be given to limiting the reversal of heparin intraoperatively.22
Fourth, in view of the well-documented and common unresponsiveness to aspirin,23 as well as the considerable effectiveness of thienopyridines (ticlopidine and its safer successor clopidogrel) reported in both the cardiology24and cardiac surgical literature,25 serious consideration should be given to the perioperative (and perhaps the prolonged postoperative) use of clopidogrel.
Fifth, the recent success of drug-eluting stents26 raises serious concerns regarding the use of SVGs in stentable vessels. These data, although still early, pose a theoretical issue in the use of combined procedures for patients unable to receive all-arterial conduits.
Sixth, gene therapy may have a dramatic impact on arresting the progression of SVG disease,27 and advances in this area may have particular relevance to patients undergoing off-pump coronary artery bypass surgery.
Perhaps the most helpful recommendation would be to direct research efforts toward managing the perioperative hypercoagulable state and its long-term impact on graft patency in patients undergoing off-pump coronary revascularization.
Footnotes
Presented at The Evolution of Facilitated Anastomoses, Four Seasons Resort, Aviara, North San Diego, Calif, April 5–7, 2002.
References
This article has been cited by other articles:
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  F. Bednar, P. Osmancik, T. Vanek, H. Mocikova, M. Jares, Z. Straka, and P. Widimsky Platelet activity and aspirin efficacy after off-pump compared with on-pump coronary artery bypass surgery: results from the prospective randomized trial PRAGUE 11-Coronary Artery Bypass and REactivity of Thrombocytes (CABARET). J. Thorac. Cardiovasc. Surg., October 1, 2008; 136(4): 1054 - 1060. [Abstract] [Full Text] [PDF]
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 B. R. Untch, W. P. Jeske, J. Schwartz, S. Botkin, M. Prechel, J. M. Walenga, and M. Bakhos Inflammatory and Hemostatic Activation in Patients Undergoing Off-Pump Coronary Artery Bypass Grafting Clinical and Applied Thrombosis/Hemostasis, April 1, 2008; 14(2): 141 - 148. [Abstract] [PDF]
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 M. E. Halkos, W. A. Cooper, R. Petersen, J. D. Puskas, O. M. Lattouf, J. M. Craver, and R. A. Guyton Early Administration of Clopidogrel Is Safe After Off-Pump Coronary Artery Bypass Surgery Ann. Thorac. Surg., March 1, 2006; 81(3): 815 - 819. [Abstract] [Full Text] [PDF]
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D. Paparella, A. Galeone, M. T. Venneri, M. Coviello, G. Scrascia, N. Marraudino, M. Quaranta, L. de Luca Tupputi Schinosa, and S. J. Brister Activation of the coagulation system during coronary artery bypass grafting: Comparison between on-pump and off-pump techniques J. Thorac. Cardiovasc. Surg., February 1, 2006; 131(2): 290 - 297. [Abstract] [Full Text] [PDF]
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A. Parolari, F. Alamanni, G. Polvani, M. Agrifoglio, Y. B. Chen, S. Kassem, F. Veglia, E. Tremoli, and P. Biglioli Meta-Analysis of Randomized Trials Comparing Off-Pump With On-Pump Coronary Artery Bypass Graft Patency Ann. Thorac. Surg., December 1, 2005; 80(6): 2121 - 2125. [Abstract] [Full Text] [PDF]
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A. Parolari, L. Mussoni, M. Frigerio, M. Naliato, F. Alamanni, A. Galanti, G. Fiore, F. Veglia, E. Tremoli, P. Biglioli, et al. Increased prothrombotic state lasting as long as one month after on-pump and off-pump coronary surgery J. Thorac. Cardiovasc. Surg., August 1, 2005; 130(2): 303 - 308. [Abstract] [Full Text] [PDF]
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 J. Pepper Controversies in Off-pump Coronary Artery Surgery Clin. Med. Res., February 1, 2005; 3(1): 27 - 33. [Abstract] [Full Text] [PDF]
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 V. Casati, S. Benussi, L. Sandrelli, M. A. Grasso, S. Spagnolo, and A. D'Angelo Intraoperative Moderate Acute Normovolemic Hemodilution Associated with a Comprehensive Blood-Sparing Protocol in Off-Pump Coronary Surgery Anesth. Analg., May 1, 2004; 98(5): 1217 - 1223. [Abstract] [Full Text] [PDF]
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 J. D. Puskas, W. H. Williams, E. M. Mahoney, P. R. Huber, P. C. Block, P. G. Duke, J. R. Staples, K. E. Glas, J. J. Marshall, M. E. Leimbach, 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, April 21, 2004; 291(15): 1841 - 1849. [Abstract] [Full Text] [PDF]
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