Ann Thorac Surg 2001;71:1056-1061
© 2001 The Society of Thoracic Surgeons
Current review
Coronary revascularization without cardiopulmonary bypass in high-risk patients: a route to the future
Sotiris C. Stamou, MD, PhDa,
Paul J. Corso, MDa
a Section of Cardiac Surgery, Department of Surgery, Washington Hospital Center, Washington, DC, USA
Address reprint requests to Dr Corso, Section of Cardiac Surgery, Washington Hospital Center, 106 Irving St NW, Suite 316, South Tower, Washington, DC 20010
e-mail: pjc1{at}mhg.edu
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Abstract
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Previous reports have demonstrated that reoperative coronary revascularization, advanced age, female sex, and impaired left ventricular dysfunction are independent predictors of operative mortality after coronary artery bypass grafting (CABG). CABG without cardiopulmonary bypass (off-pump CABG) has been proposed as a potential therapeutic alternative in these high-risk patient groups. Despite the substantial learning curve associated with off-pump CABG, early outcomes of off-pump CABG in high-risk patients are better than those associated with the conventional on-pump CABG approach. These results suggest that off-pump CABG is a safe alternative to on-pump CABG in high-risk patients. Randomized prospective studies are needed to validate the results of these initial retrospective reports and to demonstrate the long-term benefits of this approach.
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Introduction
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Coronary artery bypass grafting (CABG) is the most frequently performed operative procedure in the United States and Canada. The safety, efficacy, and long-term durability of this procedure are well established. Coronary artery bypass grafting is a better treatment modality than medical therapy [1–3] or percutaneous transcatheter intervention in terms of completeness of revascularization and angina improvement [4, 5]. One of the most challenging aspects of CABG is optimum management of high-risk patients to achieve acceptable morbidity, mortality, and quality of life. Favorable short-term and long-term survival after CABG continue to be reported despite a subset of increasingly high-risk patients undergoing cardiovascular surgical procedures [6]. Previous reports have demonstrated that reoperative CABG, advanced age (>80 years), and severe left ventricular dysfunction (ejection fraction < 0.35; The Society of Thoracic Surgeons’ definition, www.ctsnet.org/doc/230) are the most important independent predictors of operative mortality after CABG [7]. Data from The Society of Thoracic Surgeons National Database confirm the results of these studies (www.ctsnet.org/doc/4314) [8].
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Inflammatory reactions after cardiopulmonary bypass and their effects on perioperative outcomes
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Minimally invasive techniques to perform CABG without cardiopulmonary bypass (off-pump CABG) may be of particular utility in high-risk patients. Compared with on-cardiopulmonary bypass (on-pump CABG) techniques, off-pump CABG has been associated with decreased foreign surface–blood interactions and shear response [9], lower rates of atrial fibrillation [9] and stroke [10], and improved perioperative outcomes. However, other studies [11–13] failed to reproduce these favorable outcomes. Despite their importance, these preliminary studies [9, 10] are significantly limited by small sample sizes (statistical type II error) and thus their results are not conclusive. Patients with arteriosclerosis of the ascending aorta, who are at higher risk for atheromatous embolization during aortic cannulation, may particularly benefit from off-pump CABG [14, 15]. Cross-clamping of the aorta poses an additional risk for cerebral embolization. Atheromatous embolization caused by partial clamping of the aorta in off-pump CABG may be prevented by avoiding proximal anastomoses and eliminating aortic side-clamping either by using all arterial conduits or sequential distal anastomoses (skip grafts), as suggested by Murkin and associates [15]. Arom and coworkers [16] have recently demonstrated significantly lower mortality for high-risk off-pump CABG patients than for high-risk on-pump patients (7.7% off-pump versus 28.8% on-pump, p = 0.008), whereas in risk-stratified medium-risk and low-risk groups, no significant differences were found in off-pump and on-pump CABG-associated mortality.
Neuropsychologic complications associated with cardiopulmonary bypass
Although previous studies failed to show any improvement in neurologic or neuropsychologic outcomes associated with off-pump CABG [17, 18], recent studies showed a lower rate of release of S100B protein (a marker of brain injury) [19] and a lower incidence of high intensive transient signals in transcranial Doppler ultrasound after off-pump versus on-pump CABG [20]. However, the validity of S100ß as a marker of cerebral injury has been questioned because it may originate from extracerebral sources. A significant amount of S100ß is found both in the blood from the surgical field and in shed postoperative mediastinal blood. Infusion of this blood results in infusion of S100ß into the circulation and interferes with interpretation of early systemic S100ß values favoring the off-pump group [21]. Indeed, the level of S100ß after on-pump CABG using a cell-saving device was the same as that after off-pump CABG [22]. Only prospective randomized multi-institutional studies will be able to resolve this contradiction in the current literature and definitively answer the question of whether off-pump CABG reduces the neuropsychologic dysfunction that is frequently observed after on-pump CABG.
Inflammatory reaction after cardiopulmonary bypass
Matata and colleagues [23] report significant increases from before anesthesia values of lipid hydroperoxides (190% at 4 hours), protein carbonyls (250% at 0.5 hours), and nitrotyrosine (510% at 0.5 hours) in on-pump CABG patients, but no or significantly reduced increases in off-pump CABG patients. Similarly, complement C3a and elastase levels were rapidly increased on institution of cardiopulmonary bypass, which was followed by increases in interleukin-8, tumor necrosis factor-
, and sE-selectin. In contrast, the rise of these factors was blunted in off-pump CABG patients [23]. In addition to elimination of cardiopulmonary bypass, use of minimal incisions may help to produce the lower inflammatory reaction observed after off-pump CABG compared with on-pump CABG [24, 25].
Myocardial injury after cardiopulmonary bypass
Recent studies focus on the lower degree of myocardial injury after off-pump versus on-pump CABG [26, 27]. Specifically, levels of troponin T and I and creatine kinase MB isoenzyme were lower in off-pump than in on-pump CABG patients, suggesting a higher degree of myocardial damage after on-pump CABG. These results echo those of Bouchard and Cartier [28], who reported a lower incidence of perioperative myocardial infarction after off-pump versus on-pump CABG in patients who had multivessel coronary artery disease and had complete revascularization.
Renal dysfunction and transfusion rates after cardiopulmonary bypass
On-pump coronary revascularization is associated with potential risk of renal dysfunction related to the systemic inflammatory response, hypoperfusion, and loss of pulsatile perfusion of cardiopulmonary bypass [29, 30]. Ascione and associates [30] reported significantly better glomerular filtration as assessed by creatinine clearance and urinary microalbumin to creatinine ratio in the off-pump than in on-pump patients (p < 0.0004 and p < 0.0083, respectively). Renal tubular function was also impaired in the on-pump group as assessed by increased N-acetyl glucosaminidase activity (p < 0.0272) [30]. Moreover, off-pump patients have less need for blood transfusions [31, 32].
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Selection criteria for off-pump coronary artery bypass grafting
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Indications for off-pump redo CABG at our institution included patients who were considered high risk for on-pump redo CABG because of medical comorbidities such as renal failure, diffuse cerebrovascular and peripheral vascular disease, aortic arteriosclerosis, chronic obstructive pulmonary disease, and religious convictions that precluded blood transfusions [33].
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Off-pump coronary artery bypass grafting in patients undergoing reoperation
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Off-pump redo CABG has been associated with relatively higher early mortality (3.4% to 12.5%) than first-time CABG surgical procedure [34–39]. To lower mortality rates after redo CABG surgical procedure, alternative surgical practices have evolved such as the "no-touch technique" or minimal dissection before bypass, routine femoral artery and vein cannulation, antegrade and retrograde blood cardioplegia, and performance of all vascular anastomoses with a single aortic cross-clamp [40]. Off-pump CABG has been of particular benefit in patients undergoing reoperation who have arteriosclerosis of the ascending aorta, because they are at higher risk for atheromatous embolization during aortic cannulation [41].
Surgical approaches for redo off-pump CABG include median sternotomy and minimally invasive direct CABG through left anterior thoracotomy (anterior MIDCAB) or left posterolateral thoracotomy (lateral MIDCAB). Major indications for anterior MIDCAB include isolated disease of the proximal or midleft anterior descending artery or first diagonal artery. Major indications for lateral MIDCAB include stenosis and regrafting of the circumflex system [42]. In multivessel (more than three) disease, a median sternotomy approach is usually favored.
The success of off-pump CABG in redo patients can be enhanced by minimally invasive incisions [42] so as to avoid the hazards of repeat sternotomy [42]. Adhesions from previous sternotomies, in addition to the use of an epicardial stabilizer, may have a local stabilizing effect, reducing the motion of the heart and thereby facilitating arteriotomy and anastomosis through a thoracotomy approach [43, 44]. Moreover, avoidance of the cardiac cannulation and dissection of adhesions required in sternotomy may eliminate the repeated lifting and manipulation of the heart that has been related to increased risk of embolization of the native coronary arteries because of dislodging atherosclerotic debris from the old but still patent grafts [45].
Early outcomes
In a recent series in patients with single-vessel disease who underwent reoperation [46], off-pump CABG compared favorably with on-pump CABG, with a two-fold lower rate of postoperative transfusions (27% off-pump versus 58% on-pump, p = 0.001), less need for prolonged ventilatory support (4% off-pump versus 17% on-pump, p = 0.03), and a lower rate of postoperative atrial fibrillation (14% off-pump versus 29% on-pump, p = 0.04). Redo off-pump CABG was also associated with a shorter postoperative length of stay (5 ± 2 days off-pump versus 8 ± 4 days on-pump, p < 0.001), and a significantly lower rate of in-hospital mortality (1% off-pump versus 10% on-pump, p = 0.03). Similar results when comparing conventional on-pump redo CABG with off-pump CABG have been reported by previous authors [19, 38, 39, 47–50] (Table 1) ; half of these studies reflect single-vessel coronary artery disease [19, 39, 46, 47]
Long-term outcomes
In a recent study [41] investigating the long-term outcomes of redo off-pump CABG, actuarial survival at a mean follow-up of 2.5 ± 1 years (range, 1 month to 11 years) was 83%. Event-free survival in the same study (freedom from death, myocardial infarction, or repeat transcatheter percutaneous intervention or redo CABG) was 67%. Similarly, Mohr and associates [50] reported 1- and 4-year actuarial survival rates for off-pump CABG of 90% and 69%, respectively. In the same study, within a mean follow-up of 30 ± 15 months, there were 11 deaths, 2 (2.8%) nonfatal myocardial infarctions, and recurrent angina in 9 patients (12.8%). However, until the results of studies comparing long-term outcomes of off-pump with on-pump CABG in patients undergoing reoperation, no definitive conclusions can be made as to which approach is indicated in this subset of CABG patients.
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Off-pump coronary artery bypass grafting in octogenarians
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Perioperative morbidity and mortality rates rise with increasing age in patients undergoing CABG either with or without cardiopulmonary bypass [51, 52]. A rising trend has been documented in the number of octogenarians undergoing cardiac surgical procedures [53]. Less-invasive approaches have been favored in this subset of patients because of their advanced age and associated medical conditions [54–56]. Off-pump CABG may be a reasonable alternative in octogenarians because lower stroke rates and improved perioperative outcomes have been reported after off-pump CABG than after on-pump CABG in this subset of patients [57]. A possible mechanism may be the significantly higher rate of arteriosclerosis of the ascending aorta in octogenarians, which may potentiate migration of atheromatous microemboli to the brain during aortic cannulation and result in neurologic deterioration shortly after on-pump CABG [58].
In a recent series in octogenarians [59], off-pump CABG, compared with on-pump CABG, was associated with a substantially lower rate of intraoperative transfusions (0.4 ± 2 U packed red blood cells off-pump versus 2 ± 1 U on-pump, p < 0.001), a marked reduction in the need for prolonged ventilatory support (1% off-pump versus 12% on-pump, p = 0.01), and reduced postoperative length of stay (6 ± 2 days off-pump versus 9 ± 3 days on-pump, p = 0.01). Similarly, Boyd and associates [60] reported that in patients older than 70 years of age, off-pump CABG was associated with a lower rate of atrial fibrillation (10% off-pump versus 28% on-pump, p < 0.05). In the same study, off-pump CABG correlated with abbreviated length of stay and lower cost compared with on-pump CABG. Postoperative graft analysis after off-pump CABG also demonstrated a 100% patency rate [60]. Low mortality rates comparable with those after the conventional on-pump approach have also been reported after off-pump CABG in octogenarians [61, 62] (Table 2). However, comparative analysis on medium-term and long-term clinical outcomes of off-pump versus on-pump CABG has not yet been undertaken.
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Table 2. Published Series of In-Hospital Mortality Rates in Octogenarians Undergoing Coronary Artery Bypass Grafting
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Off-pump coronary artery bypass grafting in patients with impaired left ventricular function
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At least one previous report demonstrated increased perioperative mortality in CABG patients with impaired left ventricular function compared with patients with normal ventricular function [63]. Suboptimal outcomes in this subset of patients may be related to the damaging effect of cardiopulmonary bypass on the myocardium. These effects may be partially explained by the activation of various inflammatory mediators, which may significantly hinder the function of the already impaired myocardium, especially after prolonged pump runs [64]. Moreover, the change in left ventricular geometry of the empty heart during on-pump CABG has been shown to impede the coronary collateral flow that supplies potentially ischemic areas of the myocardium [65]. Akins and associates [66] have shown that normal septal movement is better preserved in patients after off-pump CABG, whereas on-pump CABG frequently results in paradoxical movement of the interventricular septum. Cardiomegaly, which is frequently encountered in this subset of high-risk patients, renders manipulation and rotation of the heart more difficult and potentially dangerous. An alternative treatment modality for these patients is to use left internal mammary artery to left anterior descending coronary artery off-pump CABG and complete the revascularization with percutaneous transcatheter intervention, ie, as a hybrid procedure. A useful adjunct to this treatment is preoperative or postoperative use of intraaortic balloon counterpulsation or a ventricular assist device (left, right, or BIVAD). In a recent study [67], circulatory support significantly improved myocyte contractile properties and increased ß-adrenergic responsiveness. Tasdemir and coworkers [68] suggest that even in patients with ventricular dysfunction, off-pump CABG is associated with low operative mortality and a low transfusion rate.
In a study by Moshkovitz and associates [64], 1-year and 4-year actuarial survival after off-pump CABG in patients with an ejection fraction less than 0.34 was 96% and 73%, respectively. The same authors reported angina recurrence and the need for repeat CABG in 11% and 3% of these patients, respectively. Event-free survival at a mean follow-up of 28 months was 68%. In a similar study, Sternik and colleagues [69] reported a 2-year survival after off-pump versus on-pump CABG of 86% and 63%, respectively.
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Considerations of off-pump coronary revascularization and the impact of the learning curve
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Despite encouraging reports [70, 71], off-pump CABG has raised concerns regarding technical limitations and the accuracy of the anastomoses, particularly when minimal incisions are used [42, 72–75]. Inadequate patient selection (ie, those with small, calcified, or intramyocardial vessels) and inadequate exposure or stabilization of the anastomotic site are major causes of dismal results. Gundry and associates [74], in their initial experience with off-pump CABG, found that twice as many off-pump patients required recatheterization (20% off-pump versus 7% on-pump), and they attributed this difference to the limited revascularization obtained at the initial period of using off-pump CABG. In our initial experience in 274 off-pump CABG patients who had minimally invasive direct CABG and who received mostly one or two grafts, the reintervention rate (redo CABG or percutaneous transcatheter intervention) was 4% for the first year after operation [76]. The learning curve of this technically demanding novel approach may account for this rate of graft failure.
Significant improvement in technical and operative variables during the course of this study accentuated the existence of the learning curve. Comparison of the first 100 patients with the subsequent 174 patients revealed improved vessel occlusion time for creation of the anastomosis (14 ± 6 minutes in the first group versus 10 ± 5 minutes in the second group, p = 0.009) and reduced total procedural time (138 ± 24 minutes versus 132 ± 20 minutes, p = 0.04). However, operative mortality (1% in the first group versus 0% in the second group, p = 0.5) postoperative myocardial infarction (2% in the first group versus 2% in the second group, p = 1.00), length of postoperative stay (4 ± 3 days in the first group versus 4 ± 2 days in the second group, p = 0.8), and conversion to on-pump CABG (1% in the first group versus 0% in the second group, p = 0.6) were not significantly different between groups [76].
The technical aspects limit the wide application of off-pump CABG in high-risk patients who need multiple revascularizations. However, as experience accumulates, off-pump CABG becomes a reasonable approach to accomplishing complete revascularization. Technical improvements and better stabilization have also facilitated an increase in multivessel revascularization procedures on the beating heart. In our series, multivessel bypass became more routine over time, and the mean number of grafts performed increased substantially over time (Table 3).
Although complete revascularization is the optimal approach for high-risk patients, this goal may sometimes be relinquished to benefit from avoiding cardiopulmonary bypass. Arom and colleagues [16] recently demonstrated a higher rate of angina at 1-year follow-up in off-pump versus on-pump patients (40% off-pump versus 21% on-pump, p < 0.001). In the same study, off-pump patients had a higher rate of readmissions for angina in the first year after surgery than did on-pump patients (24% off-pump versus 9% on-pump, p < 0.001). These results have been attributed to the degree of complete versus incomplete revascularization, particularly during the earlier years of the study [16].
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Conclusions
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Coronary revascularization without cardiopulmonary bypass is a safe alternative to conventional on-pump CABG in high-risk patients. However, comparative data on long-term outcomes need to be obtained before the superiority of one approach over the other can be firmly established. Thorough scientific analysis in a prospective randomized setting should ideally be performed for all surgical management paradigms.
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Acknowledgments
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We are indebted to Ellen Shair, MA, Research Writer/Editor, MedStar Research Institute, for her editorial contribution to this manuscript.
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Abstract
Introduction
