Asian Cardiovasc Thorac Ann 2004;12:379-386
© 2004 Asia Publishing EXchange Ltd
Off-Pump Coronary Artery Bypass Surgery
Edward A Black, FRCS,
Sudip Ghosh, PhD,
Kenny Sin, FRCS1,
Tom Spyt, MD,
Ravi Pillai, FRCS2
Department of Cardiothoracic Surgery Glenfield Hospital Leicester, UK
1 National Heart Centre Republic of Singapore
2 Oxford Heart Centre John Radcliffe Hospital Oxford, UK
For reprint information contact: Edward A Black, FRCS Tel: 44 116 287 1471 Fax: 44 116 232 2511 Email: edblackis{at}hotmail.com Department of Thoracic Surgery, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK.
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ABSTRACT
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Off-pump coronary artery bypass surgery has been adopted enthusiastically worldwide. However, despite more than 6 years’ experience and refinement, many surgeons use it only sporadically and some hardly at all. This reluctance persists despite support for the procedure because of the lack of properly designed risk models and/or randomized studies. Although it has not been overwhelmingly shown that off-pump surgery is superior to the conventional on-pump procedure, the technique has its place in our specialty. It has been shown to be better for noncritical end points in selected patients in the hands of selected surgeons. That there are differences in surgical skill among surgeons is something we all know but rarely discuss in public. Until now, disparities in skill have been most salient with uncommon and extraordinarily challenging operations. Perhaps the off-pump procedure should be regarded as the "challenging" aspect of coronary artery bypass surgery, and self-restraint may need to remain in force if we are to continue to achieve the highest level of clinical excellence.
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INTRODUCTION
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Coronary artery disease is one of the most common causes of death in the Western world. It accounts for almost 133,000 deaths per annum in the UK, causing the loss of 151,000 years of working life.1 Coronary artery bypass grafting (CABG) became a reality 40 years ago, heralding a new age of treatment for ischemic heart disease.2–4 The introduction of cardiopulmonary bypass (CPB)5 provided the means by which later surgeons could reliably revascularize the heart with reproducible results. Worldwide adoption of on-pump coronary artery bypass surgery (ONCAB) then took off. CABG is now the most commonly performed major operation in the world.
During the last decade, there have been 2 principal areas of innovation in surgical revascularization: arterial revascularization and off-pump coronary artery bypass surgery (OPCAB). Evidence suggests that complete arterial revascularization improves survival, extends the symptom-free interval, and reduces the need for reoperation.6,7 In contrast, the place of OPCAB has not been as decisively established, and debate continues about its role within the cardiothoracic world some 7 years after its reappearance in the world literature.8,9 The minority of surgeons who enthusiastically perform most or nearly all of their coronary artery operations without CPB have not persuaded the majority of surgeons who perform ONCAB that it is necessary to change their practice. Why has the technique not become more widespread? What is the evidence that supports it? Is the literature on OPCAB decisive? This review will attempt to outline the main areas where OPCAB has been suggested beneficial.
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DEVELOPMENT
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Concerns about the morbidity associated with extracorporeal circulation and the cost of CABG have led to the reintroduction of OPCAB around the world.10,11 As techniques and instruments were developed, OPCAB and minimally invasive techniques increased in popularity. Now virtually all cardiothoracic journals and meetings contain articles that support or caution against the adoption of OPCAB or minimally invasive direct coronary artery bypass (MIDCAB with left anterior small thoracotomy).12,13
Since the early description of CABG utilizing saphenous vein grafts sutured with silk,4 surgical revascularization has evolved significantly. Major advances have occurred and are ongoing in the areas of CPB, myocardial protection, sutured and sutureless anastomoses, stabilizers, robotics, anesthesia, and postoperative care. They have made CABG, for the most part, a reliable and reproducible operation in an ever sicker population.14 For some patients, however, CABG is associated with major complications, such as myocardial injury and neuropsychological, renal, and respiratory impairment. The development of OPCAB is driven by a desire to reduce this morbidity. However, it needs to have proven benefit to the patient. The areas of concern can be broken down into several categories. Firstly, can it be done?
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PATENCY
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Perhaps the most fundamental requirement of OPCAB is that it needs to be able to facilitate the creation of reliably accurate anastomoses with equal patency as current ONCAB (see Table 1
for comparisons). CABG requires anastomosis between 2 small (1.5 to 2.0 mm) vessels. Surgery of this sort is essentially microsurgery. A still and empty heart provides excellent conditions for effecting these anastomoses. The skill required to perform this microsurgery on a moving heart is obviously greater.15 The obvious marker of accuracy of creating the anastomoses is patency. The literature describing patency rates usually uses 2 methods of determining patency. Early, intraoperative flow assessment is advocated by some. This technique allows ready identification of anastomotic problems and prompt correction during the operation. Angiography, which is a more detailed, reliable, and reproducible technique, suffers from its invasiveness. It is more difficult to use and is associated with a morbidity risk; hence there are few large series using this technique.
The angiographic results of 617 ONCAB cases of left internal mammary artery (LIMA) to left anterior descending coronary artery (LAD) anastomoses have been published as a benchmark for comparing beating heart results.16 In this study, the LIMA was patent with 
50% stenosis anywhere in the graft or distal anastomosis (FitzGibbon grades A and B) in 91% of cases (561 patients). In 7.8% (48 patients), the LIMA was patent with a stenosis between 
50% and 99%. The LIMA was occluded ( 99% stenosis) in 8 patients (1.3%).
Compared with these results, the early OPCAB work may not be as good. From the early work done by Benetti’s10 and Buffolo’s11 groups dating back from the late 1970s and early 1980s to the early 1990s, patency rates of 93% for vein graft to LAD anastomoses and 88% for LIMA to LAD were achieved.
The MIDCAB procedure, by combining a small thoracotomy with beating heart surgery, is perhaps the most challenging.17,18 Reported patency of the LIMA–LAD graft is good (Table 1
). However, there is a low risk of incorrect vessel identification and perhaps difficulty in optimizing LIMA length.19 Technical adjuncts have helped improve patency particularly in these limited access procedures.13,20 Calafiore’s series13 of 434 patients who underwent MIDCAB demonstrated a high patency rate. Patency within the first year, determined by a combination of Doppler echocardiography (performed in all patients) and angiography (performed in 62.4% of patients within the first year) was 96.1%. In the last 190 patients of the series, the rate was 98.9% (confidence interval, 92.1% to 100%), and 97.4% showed no flow restriction (confidence interval, 94.3% to 100%), suggesting that a learning curve needs to be overcome before results are optimal. This learning curve involves the surgeon, equipment (blower-misters, stabilizers, shunts, and others), and support staff (anesthetists, assistants, nurses, and others). Subramanian’s series20 of MIDCAB cases from 1994 to 1996 had patency rates of 89% early after surgery using pharmacological stabilization but 97% when mechanical stabilization was used.
Diegeler and associates21 performed detailed angiographic studies in their single-center series of patients who had MIDCAB between 1996 and 1998. They were able to get angiograms early postoperatively in 81.5% of patients as well as at 6-month follow-up in 47.9% of patients. The patency rate was 96.8% early postoperatively and 95.4% at 6 months. They also reported no stenosis in 88.2% early postoperatively and 91.5% at 6 months. They suggested that these figures hint at a dynamic process whereby some anastomotic stenosis disappears with time.
With multivessel surgery, Puskas and colleagues22 demonstrated excellent early patency. Before hospital discharge, 421 arteries were assessed with angiography in 167 OPCAB patients, and 99% were patent (93% were FitzGibbon grade A, 6% grade B, 1% grade O).
To create suitable conditions to complete an anastomosis, there are different methods available, including slings or snares, blowers, and shunts. All of these techniques, to some extent, go against the principle of minimizing instrumentation during CABG, and there will be instances when these devices cause problems.23 Diseased blood vessels are fragile, so plaque rupture, vessel dissection, and reduced patency of bypass grafts may ensue. Blower-misters combining a source of gas (usually carbon dioxide) with saline to provide a mist that can be sprayed into the arteriotomy have been introduced, but their effect on the coronary endothelium has not been completely assessed. However, in terms of the "absolute" level of endothelial function, CPB may cause problems from a reduced endothelium-mediated vasomotor function.24
There are unresolved issues to explore more fully in the future. Vein grafts are well known to occlude faster than arterial grafts. How does omission of CPB affect these differences? Surgical trauma promotes a pro-coagulative state. Is there enough circulating heparin during OPCAB to prevent graft occlusion? Vein grafts are more susceptible than arterial grafts in this respect.25 Multiple arterial grafting confounds comparisons further, as anastomotic configurations change and more precise anastomoses are required.26
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CARDIAC RISKS
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Management of occlusion of a coronary vessel in a beating heart is a vital part of all types of OPCAB. In OPCAB, there is a combination of regional ischemia from vessel occlusion and hemodynamic disturbance from manipulation of the heart. In contrast, the use of CPB and cardioplegia causes (potentially) global ischemia (and myocardial edema and inflammation).
Lifting the heart while it is supporting the circulation can have profound effects on its function. The experienced OPCAB surgeon may be very comfortable managing this, but the OPCAB "beginner" perhaps less so. The surgical approach in the OPCAB patient differs from that with the ONCAB patient, where the perfusionist manipulates pressure and flow; in OPCAB, the surgeon (closely supported by an anesthetist) needs to be able to manipulate the heart, expose the vessels, and (at least currently) suture a small conduit to the diseased coronary artery. To expose the target artery, the pericardium is often lifted, possibly causing tension around the low-pressure inferior vena cava and pulmonary veins. Subsequent rotation of the heart can cause right ventricular compression during exposure of the circumflex vessels in particular.27,28 Even with short occlusion times, these maneuvers can cause significant changes in intracardiac pressures.29 Snaring of the coronaries and the resultant local ischemia produces temporary impairment of ventricular contraction30 and lactate accumulation in the coronary sinus.24 In ONCAB, the perfusionist and anesthetist can maintain blood pressure and flow during the various manipulations and periods of ventricular dysfunction. In OPCAB, this is obviously not available, and an initial impairment in fractional shortening might go on to reduce stroke volume and cardiac output, leading to more ischemia and more impairment.
The series of "short" periods of regional ischemia are punctuated by reperfusion with whole blood in OPCAB. This may better preserve myocardial energy than global ischemia (by crossclamping) with cardioplegia infusion and subsequent reperfusion. An early study reported that hypothermic CPB with either cold potassium cardioplegia or ventricular fibrillation and vessel occlusion was inferior to OPCAB in preserving or even improving interventricular septal function and ejection fraction.31 Perioperative biopsies showed that myocardial mitochondria can be preserved in OPCAB.10 Reducing myocardial reperfusion injury may account for shorter periods in intensive care and early hospital discharge of OPCAB patients.22,32,33
Attention to several "small" details when embarking on new techniques is important. In OPCAB, attention is directed towards a new paradigm to manage regional ischemia to avoid a spiral of worsening ischemia and function. Reducing regional ischemia with intracoronary shunts may provide a better alternative to snares for visualizing the anastomotic site.34,35 The degree and site of coronary stenosis are important in planning the order of revascularization. Less severely stenosed vessels produce greater impairment when occluded than more diseased ones.30 The grafting sequence needs to take into account collateral supply and whether the vessel is supplying other areas that have at-risk myocardium or is in an area being supplied by collaterals.
Where saphenous vein grafts are used, proximal anastomoses could be performed first, minimizing ischemic time. Mechanical assistance with an intraaortic balloon pump is another method of protecting against deterioration in cardiac function during OPCAB.36 Active perfusion, furthermore, provides a mechanism whereby perfusion at systemic or supra-systemic pressures to the distal bed can be achieved down the conduit, independent of aortic pressure.37 With this technique, reperfusion injury can be modulated by substrate modification of the perfusate.38 Unfortunately, it is likely that some of the inflammatory responses arising from extracorporeal circulation will occur with this technique. Another technique of mechanical assistance "creeping" into the OPCAB arena is the utilization of right ventricular assist devices.39,40 Although it might be easy to state that these mechanically assisted OPCABs are basically ONCAB operations, they do of course avoid aortic cannulation and crossclamping.
In a large series of patients retrospectively analyzed to compare the results from OPCAB and ONCAB, a Significantly reduced myocardial infarction rate in the OPCAB group was found.33 Avoiding CPB, even in the absence of a perioperative myocardial infarction, also reduces the incidence of surrogate markers of myocardial injury, such as dysrhythmia, though the clinical significance of these observations is still uncertain. Myocardial ischemia and inadequate protection of the atria have previously been implicated as causes of atrial fibrillation (AF).41 It has also been suggested that there is a lower incidence of AF with OPCAB.11 A prospective randomized trial has more recently demonstrated that OPCAB was associated with a lower incidence of AF than CABG with cardioplegic arrest.42 In this study, 11% of OPCAB patients had AF, which was Significantly less than the 45% in the ONCAB group. Others have failed to demonstrate a significant difference between on- and off-pump patients, perhaps because the causes of postoperative AF are multifactorial.43,44
The still heart can be readily manipulated to expose almost all areas of the coronary arterial tree, thus enabling complete revascularization, which is an important factor in terms of late survival. Although there were some studies comparing OPCAB with ONCAB that had equal numbers of anastomoses in both groups,45 there were others that had fewer anastomoses in the OPCAB group.46 Clearly, it can be difficult to expose all the coronary arteries on a beating heart. Indeed, a major part of the skill of the surgical team is managing exposure and cardiac output.
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NEUROLOGICAL INJURY
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An estimated 6% of patients show serious neurological damage (stroke, prolonged unconsciousness, seizures, or encephalopathy) after CABG, resulting in an approximately tenfold increase in mortality.47 Evidence suggests that a much greater proportion of patients have new neurological signs, cognitive dysfunction, and behavioral change.48–50 These changes may be evident in 70% to 80% of patients before discharge, and they could be permanent in almost half of these patients.51,52 The risk of neurological injury has been directly correlated with the patient’s age and duration of CPB.47,53 The mechanisms of injury include embolism, hydrostatic changes (both arterial and venous), and inflammation. The sources of emboli include macroemboli from aortic manipulation and jet lesions during perfusion and microemboli from particulate materials passing through the CPB circuit (gas, fat, and platelets).51,52 Omitting CPB should eliminate the injury associated with embolism from aortic cannulation and microembolism from the pump, besides reducing the inflammatory process.
Exposure of target vessels can cause adverse hemodynamic changes.29 The use of the Trendelenburg position and increasing preload before manipulation are sometimes necessary to counteract these changes.28 The effect on cerebral perfusion of the resultant increase in right atrial pressure for several minutes is not clear.
While some groups have found a reduced incidence of cerebrovascular accidents (CVA) in OPCAB compared with ONCAB, others have not.22,32,45 An explanation for the different results might be related to the practice of avoiding any aortic manipulation versus avoiding only aortic cannulation. Calafiore and coworkers54 analyzed 4,823 patients to assess the risk factors for peri- and postoperative stroke. They determined that the strongest risk factor for CVA was a low cardiac output state, followed by any aortic manipulation, conversion of OPCAB to ONCAB, and then extracoronary arterial disease. Separating the different degrees of aortic manipulation revealed that side-clamping the aorta was a risk factor for CVA over and above the risk from cannulation and crossclamping. The authors suggested that a strategy of maximizing the myocardial function in the perioperative period and avoiding aortic manipulation is more important than omission of CPB alone in terms of CVA incidence.
As for direct comparisons, neurocognitive changes have been compared in 2 randomized trials. One (a relatively small study) demonstrated a reduction in adverse neurocognitive events when CPB was avoided,55 while the other did not.56
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RESPIRATORY COMPLICATIONS
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Traditional texts alert us to the adverse effects of CPB on the lungs. The Society of Thoracic Surgeons database has recorded such complications as endotracheal ventilation for > 24 hours in 5.4% of patients who had first-time ONCAB, pneumonia in 2.2%, and pulmonary edema in 1.9%. Can taking CPB out of the equation produce measurable benefit to patients? A combination of altered mechanics, altered blood flow, pain, and activation of inflammatory processes all have a role in producing lung injury during ONCAB. Clinical studies have tended to show a reduction in ventilation time and in respiratory infections without CPB.33,57,58 Others have found no difference. In small nonrandomized studies looking in more detail at respiratory functions, MIDCAB has been shown to produce less alteration in respiratory mechanics but no significant difference in gas exchange.59 And despite increases in inflammation in ONCAB, there is perhaps little effect on gas exchange too.60
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INFLAMMATION
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Avoiding the inflammatory response to CPB is one of the strongest reasons for the interest in OPCAB. The process of inflammation during CPB involves many factors. Complement activation leads to the activation of neutrophils. These in turn produce more adhesion molecules and cytokines. The result is neutrophil adhesion to the endothelium, migration from the vasculature, and tissue injury from proteolytic enzymes and oxygen free radicals.61 The inflammatory process that ensues may be responsible for much of the myocardial, renal, respiratory, and neurological problems associated with ONCAB. It is controlled in part by the balance between the pro-inflammatory cytokines interleukin-6 (IL-6) and IL-8 and the anti-inflammatory IL-10. We know that surgery itself induces inflammatory responses. It increases the level of IL-6.62 A median sternotomy produces relatively more tissue injury and complement factors C3a and C5b-9 than does a small anterolateral thoracotomy.63
Comparing OPCAB and ONCAB is difficult, as there are few randomized trials with large numbers of patients receiving multivessel revascularization through a median sternotomy on and off pump. Two randomized studies exist that show a reduction in cytokines after OPCAB but different results for complement activation. The study by the Bristol Heart Group found Significantly less leukocyte activation (cell count and elastase activity), less IL-8, and a subsequent lower incidence of infections in the OPCAB group.58 They did not find a difference in C3a and C5a levels. Matata and colleagues64 showed lower levels of C3a and elastase as well as IL-8 and tumor necrosis factor-
in OPCAB patients. The reduction in cytokine release with OPCAB may also explain the reduction in myocardial injury.62,65 Importantly, however, it has been demonstrated that CPB causes a huge early increase in IL-10, which is anti-inflammatory and thus may neutralize the harmful effects of CPB.66
The clinical relevance in most patients of reduction in inflammatory markers may be unclear. However, patients with advanced left ventricular dysfunction and elderly patients show increased cytokine response to CPB.67,68 It is interesting, therefore, to note that these groups in particular seem to benefit from OPCAB.69,70
The development of OPCAB surgery has encouraged further refinement of CPB to reduce its harmful effects. Steroids, heparin-coated circuits, aprotinin, elimination of cardiotomy suction, small circuits, and temperature management all have a role in reducing inflammation.
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RENAL IMPAIRMENT
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Measuring the effects on the kidneys, as in other areas, is confounded by a relatively small number of randomized studies and differences in assessment methods. Gerritsen and coworkers71 found that, compared with ONCAB, OPCAB was associated with less oxidative stress, less ischemic reperfusion injury, and better-preserved glomerular function. Ascione and colleagues,72 who randomized 50 low-risk patients to either OPCAB or ONCAB, also suggested that ONCAB causes Significantly greater impairment of glomerular and tubular function than does OPCAB. Both of these studies demonstrated, perhaps not unexpectedly, that even in OPCAB there is a reduction in renal function. The significance of this finding in clinical practice, therefore, might be that we should not expect OPCAB to prevent renal impairment but to reduce its risk in patients who still have "renal reserve" preoperatively.
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CONCLUSION
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OPCAB has been adopted enthusiastically by many surgeons throughout the world; but despite more than 6 years’ experience and progressive refinement of techniques and equipment, many surgeons use it only sporadically and some hardly at all. This reluctance persists despite advocacy of OPCAB because of the lack of properly designed risk models and/or randomized studies demonstrating that OPCAB offers benefits to patients in the hands of all surgeons. With regard to the former issue, which in itself is complex, the question remains whether the risk models within the cardiac database in Britain and North America, which are derived from experience with ONCAB, are valid for assessing risk for patients undergoing OPCAB.
No risk-adjustment model can identify all confounding variables, and there are always some unidentified confounders in any model; it can only be hoped that they are unimportant. The model of the Society of Thoracic Surgeons was developed in 1994–95 for ONCAB, and it is reasonable to suggest that it missed confounding variables that are unique to OPCAB and could affect mortality, morbidity, and the selection of patients for OPCAB. These variables include the presence of intramyocardial coronaries; diffuse coronary artery disease with poor targets; aortic atherosclerosis, which precludes the use of side-biting clamps for proximal anastomosis; left ventricular hypertrophy, which makes heart placement much more difficult; and other factors. The role of the surgeon’s experience and expertise must also be analyzed. Most of the necessary data are not being collected and, more importantly, would be very difficult to collect because they are highly subjective and are impossible to compare between different institutions. Even if the data were available, it would take years to weight properly. Any new risk-adjustment model for OPCAB would require adequate validation.
Randomized studies are therefore essential because the conclusions of nonrandomized, experimental reports will always be suspect. Randomized studies should eliminate the problems of risk adjustment and can be designed so that all operations are done by the same surgeons. It must be mentioned that randomized trials are not a panacea; they still rely on subjective surgical interpretation, which may not be generalized to all institutions. The first such study, carried out at 3 hospitals in the Netherlands by pioneers in OPCAB, reported the early outcomes of 281 patients randomly allocated after they had been judged suitable for either technique and after all the surgeons were "experienced in both procedures".73 The only drawback to the randomization was that the patients and cardiologists were not blinded to the treatment. At 30-day follow-up, there were no differences in mortality, duration in intensive care, incidence of stroke, AF rate, myocardial infarction rate, use of blood products, quality of life, and hospital costs – parameters that one would have expected to benefit from OPCAB. The only significant improvements with OPCAB were less release of the creatine kinase MB isoenzyme and shorter postoperative hospital stay, results that have been reproduced by studies done by the authors of this review.74 More recently, the Bristol Heart Group published their results of 200 patients randomly allocated to OPCAB and 201 to ONCAB.75 Their findings were essentially no different from those of the Dutch study, with reasonable midterm (3-year) outcome.
These studies should not be misinterpreted as an argument against OPCAB. Although thus far the technique has not been overwhelmingly shown to be superior to ONCAB, it has its place in our specialty. It has been shown to be better than ONCAB for noncritical end points in selected patients in the hands of selected surgeons. That there are differences in surgical skill among surgeons is something we all know but rarely discuss in public. Until now, disparities in skill have been most conspicuous with uncommon and extraordinarily challenging operations, such as the Ross procedures and repair of thoracoabdominal aneurysm. It is possible that OPCAB should be regarded as the "challenging" aspect of the "bread and butter" procedure – CABG – of all adult cardiac surgeons and that self-restraint may need to remain in force if we are to continue to achieve the highest level of clinical excellence.
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ABSTRACT
INTRODUCTION
