Off-Pump Coronary Artery Bypass: Techniques, Pitfalls, and Results

Off-Pump Coronary Artery Bypass: Techniques, Pitfalls, and Results Steven J. Hoff, MD In an attempt to advance the surgical treatment of coronary artery disease, surgeons sought a way to offer the proven benefits of coronary revascularization and avoid the side effects of cardiopulmonary bypass by performing revascularization in the beating heart (off-pump coronary artery bypass). This review will describe the development and refinement of the technique, pitfalls to its widespread adoption, and an up-to-date assessment of current results. Semin Thorac Cardiovasc Surg 21:213-223 © 2009 Elsevier Inc. All rights reserved. KEYWORDS off-pump coronary artery bypass, OPCAB, technique

S

ince its first description in the 1960s, coronary artery bypass (CAB) has been one of the most scrutinized procedures in healthcare. As patients referred for CAB become more complex, off-pump CAB or off-pump coronary artery bypass (OPCAB) has gained increased attention. This review will describe the development and refinement of the technique, pitfalls to its widespread adoption, and an assessment of current results.

Development of OPCAB Technique Kolesov1 is credited with the first description of CAB in 1964, when he created a left internal mammary artery anastomosis to the left anterior descending (LAD) artery without cardiopulmonary bypass. Since then, the practice of performing CAB through a median sternotomy using cardiopulmonary bypass and cardioplegic arrest [on-pump coronary artery bypass (ONCAB)] has been the gold standard for surgical revascularization of the heart for decades.2-4 Extensive investigation over the years has resulted in a reduction of the negative physiological effects of cardiopulmonary bypass, and led to improved clinical outcomes. Despite these efforts, significant deleterious effects on the hematologic, pulmonary, renal, and neurologic systems remained. In an attempt to advance the surgical treatment of coronary

Department of Cardiac Surgery, Vanderbilt Heart and Vascular Institute, Nashville, Tennessee. Address reprint requests to Steven J. Hoff, MD, Department of Cardiac Surgery, Vanderbilt Heart and Vascular Institute, 1215 21st Avenue South, Nashville, TN 37232-8802. E-mail: [email protected]

1043-0679/09/$-see front matter © 2009 Elsevier Inc. All rights reserved. doi:10.1053/j.semtcvs.2009.09.002

artery disease, surgeons sought a way to offer the proven benefits of coronary revascularization, and yet avoid the side effects of cardiopulmonary bypass by performing revascularization on the beating heart off pump. Even as on-pump coronary surgery was developing, there were descriptions of the operation performed without the pump.5,6 Early reports in the USA began in the early 1990s.7,8 Early innovators in the field included Michael Mack and Jim Edgerton in Dallas, John Puskas in Atlanta, Jim Hart in Harrisburg, and Joe Sabik in Cleveland. Though techniques varied slightly, early results were generally favorable when compared with ONCAB, with similar graft patency and lower complication rates and shorter hospital stays.9-12 Improvements in results paralleled an increase in surgeon experience and the development of more effective technologies to allow improved stabilization and visualization. This refinement in techniques and enabling devices has allowed expansion of the application of OPCAB to a wider range of patients, and continued to improve results. Surgeons were able to perform OPCAB on more difficult to visualize lateral wall targets. OPCAB was offered not only on the sick patient with left ventricular dysfunction or diffuse coronary calcification, but also to the elective low-risk patient. In experienced hands it can now be universally applied, and in some centers it is an important part of the standard of care for surgical myocardial revascularization.

Technique of OPCAB Many descriptions of the techniques common to OPCAB procedures are available.13-15 These include technical aspects, such as incision, patient positioning and preparation, expo213

S.J. Hoff

214 sure and visualization of target vessels, conduit selection and harvest, anticoagulation protocols, and suture technique, and will be discussed here. Most of these revolve around the 3 main tenets of successful OPCAB: adequate exposure of the operative site without hemodynamic compromise, complete stabilization of the target vessel, and excellent visualization of the anastomotic area. Equally important topics related to patient factors and decision-making, including patient selection, anesthetic management, prevention of ischemia, grafting sequence, reoperative strategies, and medical management will be discussed later in this review under the section concerning pitfalls to adoption and their avoidance.

Adequate Exposure Without Hemodynamic Compromise Incision The vast majority of OPCAB cases are performed through standard median sternotomy. This provides excellent exposure to the entire heart and allows the mobility to create excellent hemodynamic stability and target vessel exposure and visualization. Later in this section, we will present an advanced alternative through a limited access, small left anterior thoracotomy that may be an attractive alternative for selected patients and highly experienced surgeons. Patient Positioning and Preparation Many target vessels can be adequately exposed with the patient in the supine position. Placing the patient in the Trendelenburg position and rotating the bed to the patient’s right (the “OPCAB position”), provides hemodynamic and exposure advantages. Trendelenburg position is known to increase preload and cardiac output, thereby improving hemodynamic stability as the heart is being manipulated for target vessel exposure.16,17 In this position, gravity helps move the right side of the heart under the right sternal table, allowing exposure of the lateral, posterior, and inferior walls of the left ventricle. This is enhanced by elevating the right side of the retractor with towels, dividing the musculofascial attachments to the distal portion of the right table of the sternum, and extending the pericardiotomy incision near the inferior portion of the right side of the sternum from the diaphragm toward the inferior vena cava. A pericardial retraction suture placed at the leftward limit of the standard inverted-T pericardiotomy and sewn to the skin just below the inferior end of the left side of the sternum will also elevate the heart and accentuate the visualization of the inferolateral portion of the left ventricle without hemodynamic consequence. These maneuvers should be performed in all patients. Additional maneuvers that may be considered to help improve hemodynamics and provide optimum positioning of the heart include opening the right pleural space in its entirety, and removal of the right pleuro-pericardial fat pad. Exposure of Target Vessels Excellent exposure of target vessels can be achieved in a variety of ways. Many off-pump surgeons have successfully used a series of deep pericardial sutures in a technique initially described by left internal mammarian artery (LIMA).

Heavy silk sutures are placed in the pericardium adjacent to the left superior pulmonary vein, a second directly posterior to the heart near the midline, and a third near the diaphragm just to the left of the inferior vena cava.18 These can be placed around the left side of the sternal retractor through a Rummel tourniquet, or placed in the pericardial suture stays of a standard sternal retractor. Differential tension on these sutures can expose the high lateral wall of the left ventricle, the lateral or posterolateral wall, and the inferoposterior portion of the heart.13 The advantage to this system is that it is very costeffective and can help support the heavy, hypertrophied heart often better than other methods. Care should be taken to avoid creating undo compression of lateral wall vessels by these sutures with positioning, particularly when they are relatively undiseased and collateralized, as this can lead to ischemic changes that are readily reversed by repositioning. A moist lap pad between the sutures and the heart may help to avoid coronary compression and aid in elevation of the heart. More commonly, commercially-available positioning devices are available to aid in cardiac positioning.19 Modern positioning devices are on the basis of suction application to the heart and can be positioned on the apex of the heart or off-apex. The key to maintaining hemodynamic stability with these devices is to maintain right ventricular geometry and output while avoiding compression of the right side of the heart with positioning. Constant attention to keeping the heart elongated as it is manipulated will avoid hemodynamic compromise. We advocate the use of these positioning devices in cases where the ventricular function is extremely poor, early in a surgeon’s learning curve, and while teaching residents, as extended periods of exposure are possible with minimal hemodynamic compromise.

Complete Stabilization of the Target Vessel Target vessel visualization is accomplished by mechanical aids to stabilization and commercially available aids to visualization. Mechanical stabilizers that relied on pressure on the myocardium have generally been replaced by devices that rely on suction to accomplish stabilization. These stabilizers typically have 2 arms that are placed on either side of the intended area of anastomosis to provide stabilization. Some devices are designed so the arms distract away from the area of anastomosis as they are tightened, thereby creating stabilization in an additional plane to provide further increase in visibility. Attention should be paid to take full advantage of the suction design of these devices. They are designed to provide stabilization in a “zero-displacement” mode. There should be not much, if any, downward pressure on the myocardium as the device is placed. Downward pressure on the heart will only serve to limit ventricular filling and therefore ejection and should be avoided.

Excellent Visualization of the Anastomotic Area Visualization of the target vessel is accomplished by assuring that the field is as close to bloodless as possible. This can be

Off-pump coronary artery bypass accomplished by blowing blood out of the field, interrupting blood flow to the field, or shunting blood around the field. The use of a humidified CO2 blower is common practice in OPCAB. They provide visualization by insufflating CO2 into the area of interest. Desiccation of tissue is avoided by a light spray of a pH-balanced solution. Care should be taken to avoid excessive CO2 flow as desiccation or intimal injury of the target vessel or conduit can occur. A more controversial topic in off-pump surgery is the achievement of a bloodless field by interruption of coronary flow to the anastomosis, or the placement of an intracoronary shunt to allow flow to bypass around the intended anastomotic area. Each has proponents and opponents. Those that advocate interruption of flow use a soft silastic suture placed around the proximal area of the coronary artery just proximal to the intended anastomotic site.20,21 Back bleeding from the opened coronary artery can be controlled with the aid of the humidified CO2 blower. Some advocate a period of test occlusion or myocardial preconditioning as a way to identify those vessels that will not tolerate prolonged interruption. In the target vessel that demonstrates a propensity for ischemic changes, selective shunting can be performed. Intracoronary shunts are also available to provide excellent target vessel visualization.22,23 When placed routinely, they can be placed quickly and atraumatically. If necessary, the vessel can be sized by placing a coronary dilator gently into the proximal portion of the vessel through the arteriotomy. To avoid trauma to the intima of the vessel, the shunt can be undersized to allow a small amount of bleeding around both the proximal and distal portions of the arteriotomy. This can easily be overcome by the humidified blower to achieve excellent visualization. A certain amount of arterial spasm around the shunt may also occur which will improve visualization. In our experience, this is transient and will not compromise graft patency or produce distal ischemia. By placing an intracoronary shunt and avoiding distal ischemia, the anastomosis can be performed in a calm, unhurried manner, avoiding instability, and reducing the need for urgent or emergent conversion to cardiopulmonary bypass. In cases where the inflow to the anastomotic area is so limited by proximal stenosis, distal perfusion devices are available and have been used successfully by some surgeons to help avoid ischemia in the target bed.

Additional Technical Issues Grafting Sequence Opinions vary regarding the conduct of an OPCAB procedure. Many experienced OPCAB surgeons successfully use the same grafting strategy that they were comfortable with when on-pump. Many experts believe that the operation, when fundamentally the same, must be accomplished with a different set of priorities. The following are general guidelines and must be individualized to the situation and the patient. Proximals Before Distals We believe that the performance of proximal anastomoses, by whatever means the surgeon is comfortable, is an impor-

215 tant first step in OPCAB. We typically use a side partial occlusion clamp on the proximal aorta and perform up to 4 hand-sewn anastomoses with a single application of the clamp. We ask our anesthesia colleagues for mild hypotension with a systolic blood pressure around 100-120 mm Hg. This allows a good perfusion pressure and avoids blood pressure spikes that could lead to aortic injury with the partial occlusion clamp placed just beyond the aortic valve in a beating heart. We place the patient in the Trendelenburg position before removing the cross clamp to allow de-airing of the aortas through the grafts. We believe much of the data generated about embolic phenomena are related to partial aortic cross clamps is a result of air embolism at the time of cross clamp release, which can be avoided in large part by careful de-airing of the aorta after proximal graft completion. We then leave the patient in the OPCAB position throughout the remainder of the performance of the distal anastomoses. The advantage to having created all proximals first is that in the unlikely event that the patient develops ischemia during the performance of any distal anastomosis (particularly when an intraluminal shunt is in place) that release of the bulldog clamp from the graft at the completion of the distal anastomosis provides immediate flow down that bed, generally with rapid resolution of ischemic changes. While assessing graft length using this technique is different than most surgeons are used to in an on-pump setting, we have found it easier to more accurately measure graft length in a full beating heart. Our intraoperative completion angiogram experience24 has shown us that the predominate problem observed after CAB is not anastomotic problems, but conduit problems, and when there is a problem with length, grafts are invariably too long. With the chest open, the graft length may look adequate, but with the chest closed they can kink and graft compromise occurs. Collateralized Vessels Before Collateralizing Vessels It has long been held in OPCAB that it is safer to graft a totally occluded or highly stenotic vessel with collaterals than one that provides collateral flow to another totally occluded bed. This is particularly important when the collateralized vessels are on the inferior or anterior wall, which can be accessed with minimal manipulation of the heart, even in the face of profound ventricular dysfunction, with minimal hemodynamic change. If proximal anastomoses can be performed first, improved flow in the totally occluded bed and may provide additional recruitment or stabilization of the myocardium to foster improved hemodynamic through the remainder of the case. The routine grafting of collateralizing vessels early may ultimately lead to intraoperative difficulties. LIMA Was First, Now Last In our early experience with OPCAB, we felt that grafting the LAD with the LIMA as the first step helped stabilize the myocardium and provided additional benefits in hemodynamic stability. Although this may be necessary in selected patients, we have found that it is in fact preferable to wait and graft the LIMA last. With careful attention to detail, we have not generally found it difficult to manipulate the heart using many of the tips discussed here and perform all other grafts first. It has

S.J. Hoff

216 been our experience with completion arteriography that has taught us that the LIMA graft itself, as well as the target LAD, are frequently prone to spasm, which we believe is exacerbated by manipulation of the heart and the graft once it is constructed. While this spasm is almost always temporary and clinically inapparent, it can occasionally be profound and persistent. Therefore, we now prefer to graft the LIMA to LAD last and avoid significant manipulation of the graft or the heart once it is performed. Summary Using the principles we have outlined, the typical grafting sequence for a routine 3 vessel OPCAB with a LIMA to LAD graft and vein grafts to obtuse marginal and posterior descending aorta would be: proximals first, followed by distal anastomoses to the posterior descending aorta, then the obtuse marginal, and finally creation of the LIMA graft to the LAD.

Conduit Selection Conduit selection in experienced hands should be no different for operations performed on or off pump. This choice should rest with each individual surgeon, their comfort level and familiarity. In general, the smaller the vessels (conduits or target) and the more arterial anastomoses performed, the greater the technical challenge. Many descriptions exist of complex, all-arterial revascularization performed off-pump with excellent results.25,26

Anticoagulation Protocols and Prevention of Thrombotic Complications As some off-pump surgeons give a full dose of heparin before grafting (3-4 mg/kg), most experienced off-pump surgeons give a half dose of heparin (1.5-2 mg/kg) to maintain activated clotting times (ACT) at 300 seconds or greater.27 Heparin regimens can be run somewhat tighter in selected cases where systemic anticoagulation may be detrimental to the patient, such as recent gastrointestinal hemorrhage or cerebrovascular accident without significant sequelae. The ACT is repeated every 20-30 minutes until the last graft is completed and additional boluses of 2500-5000 U of heparin are administered as needed to achieve the target ACT. After all anastomoses are completed and checked for bleeding, protamine sulfate is administered at a dose approximately 1 mg/kg to achieve near-complete reversal of heparinization. The thrombotic complications after CAB (deep venous thrombosis, pulmonary embolism, etc.) are relatively rare. It has been proposed that these patients were relatively protected from these complications by the use of high dose heparin during the procedure and by the coagulopathy inherent in the use of cardiopulmonary bypass. This also likely provided some protection from early graft failure, which while uncommon, remains a potential barrier to adoption of an off-pump strategy. By avoiding the use of cardiopulmonary bypass, OPCAB patients may theoretically be more prone to thrombotic events.28-30 Whether this is due to a true hypercoagulable state or the lack of protection for these events that the pump afforded is not clear. In any event, most experience

OPCAB surgeons feel that these patients require additional considerations to prevent these events. Most use dual antiplatelet therapy similar to that used in intracoronary stent patients. Most surgeons continue aspirin therapy throughout the postoperative course without interruption. Many load patients with clopidogrel immediately postoperatively, and then continue patients on clopidogrel for 1-3 months postoperatively.31 Others begin clopidogrel when the patient is taking oral medication without a loading dose, or begin therapy at hospital discharge.

Suture Technique With excellent hemodynamics, stabilization, and visualization, standard suturing techniques can be used. The conduct of performing proximal and distal anastomoses can ensue in a calm, relaxed, and unhurried manner, assuring excellent technical results. No compromise in anastomotic precision should be accepted for anastomoses performed off-pump. If excellent conditions are not accomplished for the performance of a perfect anastomosis, adjustments should be made to optimize the situation. The presence of an intracoronary shunt can be of assistance in visualizing the intima of both the native vessel and the conduit vessel for every bite, as well as helping to avoid the inadvertent inclusion of the back wall of the native vessel in the suture line. There is no excuse to not visualize every bite of the anastomosis performed off the pump as well or better than those created on the pump. Multiple small bites and meticulous attention to detail will ensure a reproducible anastomosis and excellent clinical results.

Reoperation Performing OPCAB on a patient who has undergone previous bypass grafting presents unique opportunities and challenges. Candidates for reoperative coronary surgery face known increased morbidity and mortality rates. As with many other high risk groups, OPCAB may be a reasonable way to lower perioperative risk in experienced hands.32 Special considerations in reoperative patients with regard to patient selection, exposure, conduit choice, and conduct of the operation have been previously described.26 Many of these are similar in patients considered for an off pump approach.32 Because myocardial protection is not an issue in the off pump setting, only that part of the heart that allows adequate exposure of target vessels needs to be dissected. Similarly, a patent LIMA graft need only be dissected out enough to allow sufficient mobilization of the heart to expose all intended targets. If lateral wall targets are to be grafted, the entire heart as well as a patent LIMA graft will need to be mobilized. We have liberally used a cardiac positioning device to allow manipulation and mobilization of the heart during the dissection to maintain hemodynamic stability. Patience is important during this process, with small, slow changes in heart position being better tolerated. Handling the aorta during reoperative OPCAB may provide the biggest challenge. The presence of a more diseased aorta than during the primary procedure, or the presence of

Off-pump coronary artery bypass patent vein grafts may mean a clampless technique will be needed. Liberal use of epicardial ultrasound can help guide the surgeon in managing the aorta during reoperation. We have found the use of facilitated anastomotic devices to be particularly important in this patient population. Which device is used depends largely on the surgeon’s experience. Recently, we have taken a more aggressive approach to using a partial occlusion clamp more liberally in reoperation when previous vein grafts are occluded with excellent results. The use of the innominate artery as a site of proximal vein graft anastomosis can also be helpful when the aorta is too diseased to be used.

Alternative Incisions Our experience with a new approach to multivessel coronary revascularization through a small left anterior thoracotomy has been particularly rewarding. The concept of performing CAB through sternal sparing incisions was popularized in the early 1990s by Subramanian33 and Calafiore et al34 through a third interspace left anterior thoracotomy incision and described by him and others as a minimally invasive direct CAB or minimally invasive direct coronary artery bypass. It was generally limited to left internal mammary artery anastomosis to the LAD coronary artery. Initial excitement over the possibility of providing the benefits of surgical myocardial revascularization was overshadowed by questions regarding the precision, patency, and durability of the operation. Several years ago, in an attempt to continue the innovation cardiac surgeons have been known for and to offer multivessel revascularization options to patients through limited access, surgeons such a Dr. Joseph McGinn in Staten Island began to use a different incision to allow conduit harvest and coronary anastomoses. He used a fourth interspace thoracotomy incision (using a similar skin incision in men and a submammary skin incision in women) that provided superior visualization and reliability in left internal mammary artery harvest, as well as excellent exposure to the proximal ascending aorta for proximal inflow anastomoses, and exposure to most of the epicardial surface for multivessel grafting. He has performed hundreds of cases in this manner with excellent long-term clinical results (Dr. Joseph McGinn, personal communication, February 2009). With the help of commercially available retractors, positioners, and stabilizers designed particularly for this approach, excellent exposure of most distal targets is achievable. Ideal candidates for this approach are patients with left main coronary disease, those with complex left sided stenoses, and in patients with significant comorbidities where avoiding sternotomy may be preferable, such as patients with long-term steroid use, advanced age, need for other major operative procedures, severe de-conditioning, or with arthritic or orthopedic problems. This approach is not appropriate for emergency situations or in patients with hemodynamic instability. It should be avoided in the morbidly obese, patients with left ventricular ejection fractions less than 20%, patients with posterolateral disease, as this is the most difficult area to expose using this technique, and in patients with more than mild aortic valve insufficiency or who have severe

217 peripheral vascular disease. In experienced hands, it may be considered a viable alternative in patients requiring reoperation to the LAD territory when the left internal mammary artery has not previously been used.32 Patients are placed supine with a roll placed longitudinally between the left scapula and the spine. The left elbow is draped slightly away from the patient’s side to expose the left lateral thoracic wall. Placement of a double lumen endotracheal tube or bronchial blocker allows isolation of the left lung. The skin is made 5-7 cm in length. The intercostal muscles are divided generously laterally to avoid rib fracture. A soft tissue retractor can be placed to improve visualization in the field. This incision allows excellent visualization of the left internal mammary artery along its length. It can be taken down with standard electrocautery using an extended tip under direct vision along its entire length, which was not possible with previously described techniques. Proximal aortic anastomoses can often be performed with a side-biting aortic clamp using standard instruments under direct vision. Alternatively, facilitated anastomotic connectors can be used. Commercially, available positioning and stabilizing devices are placed through 2 cm counter incisions and provide excellent exposure while maintaining hemodynamic stability. Anastomoses can be performed with standard length instruments, standard suture and suturing techniques, and under direct vision. The use of intercostal nerve blocks and implantable pain pumps can help with postoperative pain management. McGinn advocates early use of pump assist when necessary. He uses femoral access either percutaneously or by cut down on the femoral vessels. He recommends its use early in a surgeon’s experience, as well as at the first sign of difficulty with either hemodynamic issues or inability to adequately visualize distal targets. We have used this approach in patients requiring multiple grafts off the pump or in a hybrid situation where a LIMA graft to the LAD may provide significant improvement for the patient, with disease in other territories treated medically or with stents. At our institution, we perform all these cases in a hybrid OR/Cath laboratory.

Pitfalls to Successful Adoption of an Off-Pump Strategy Many pitfalls to the adoption of OPCAB exist. They include inappropriate patient selection, limited surgeon experience and training, difficulty maintaining hemodynamic stability, an unsuccessful grafting strategy, pessimistic assessment of currently available data, and lack of internal or external pressures to adopt this technology. When the surgeon or operating room team has early difficulties or clinical failures, lack of successful adoption is the inevitable outcome.

Adoption of OPCAB—National and Worldwide Trends In 2002, Hart et al13 estimated that OPCAB was performed in approximately 20% of all cases performed in the USA. By all

S.J. Hoff

218 accounts, this percentage had risen steadily and many predicted that it would continue to do so. The reality was that the penetrance of OPCAB became stagnant. A subsequent report by Mack and Brown12 in 2004 confirmed the penetrance of OPCAB had remained stable at 20%. In data presented at the STS in 2009, Puskas35 reported that 20.4% of all CAB performed in the US and reported to the STS database in 2007 were performed off-pump. Data from the Japanese Association of Thoracic Surgery25 suggests OPCAB is the standard method of surgical myocardial revascularization in Japan, where penetrance plateaued at 60% of all CAB cases performed in 2006. Conversely, the penetrance of OPCAB in Germany at the same time was estimated to be 5%.25

Patient Selection As with any operation, successful outcome depends upon appropriate patient selection. The selection of OPCAB for treatment of a particular patient will depend greatly on the experience of the surgeon and the surgical team. It is imperative for any team embarking on an OPCAB program that results are good early, not only for the surgeon’s peace of mind, the confidence of the rest of the operative and postoperative care team, including anesthesia colleagues, but also for the confidence of the referring physician. To this end, selecting patients and anatomy that are favorable is imperative. Severe proximal LAD, diagonal or posterior descending lesions with normal ventricular function are particularly amenable to off-pump revascularization in one’s early experience. As the team’s experience grows, target vessels in the proximal right coronary artery, ramus intermedius, and circumflex systems become more accessible. This is enhanced as the surgeon and their anesthesia colleagues more fully understand the maneuvers required to maintain hemodynamic stability during access of these target vessels. With experience it will become possible for the surgeon to safely and effectively work in a smaller area, perhaps with slightly less visualization, particularly where it will be more difficult for your first assistant to see to help you. Experienced OPCAB teams find it possible to avoid the pump in nearly all cases. These teams routinely perform OPCAB on patients with poor left ventricular or right ventricular function (even when the heart is enlarged), in need of reoperation, who have left main disease, valvular abnormalities, intramyocardial vessels, or small, diffusely calcified vessels. In selected cases, emergency operation can and often should be performed off-pump. The author has found this particularly true when the right ventricle is involved. The ability to perform OPCAB in this situation and avoid cross clamp and global ischemia on top of regional ischemia is extremely important. The reward will be an unexpectedly smooth postoperative course in an otherwise extremely challenging patient. In experienced hands the only time that it will not be feasible to perform beating heart surgery is when the heart is not beating. Profound hemodynamic instability or ischemia arrhythmias can rarely be dealt with off the pump. In those situations, however, an experienced team may choose a pump-assisted approach by full anticoagulation and cannu-

lation. By going on the pump but not cross clamping, while cooling minimally, the surgeon can provide hemodynamic support for only the time necessary to perform the most difficult anastomoses, and then turn the pump off when all grafts are completed.

Anesthetic Management As OPCAB has matured, the standard of care for anesthesia management has been well documented.36,37 The importance of close communication between the off-pump surgeon and the anesthesia team cannot be understated. This begins with a thorough understanding of each other’s role. Although full invasive monitoring is important, there is no substitute for a vigilant anesthesia team visually monitoring the conduct of the operation and the effect of various manipulations on the heart. Similarly, advanced knowledge of the surgeon’s operative plan and changes to it provide ample time for the anesthesia team to respond with measured changes in the medical regimen, avoiding the steep ups and downs that can lead to the need for conversion to an on-pump approach. Gradual regulation of continuous infusions rather than bolus administration of medication with the inevitable overcorrection can enhance the smooth conduct of the operation. For all team members involved in OPCAB, patience is a virtue. At our institution, we favor full invasive monitoring, including transesophageal echocardiography for all OPCAB cases. Subtle changes in pulmonary artery pressures alone may herald problems before they manifest in changes in cardiac output or wall motion abnormalities, allowing modification in techniques or grafting strategy. Adequate volume loading to ensure optimal hemodynamics, while avoiding excessive volume expansion will provide excellent operative stability, while avoiding postoperative problems with fluid overload with its sequelae. The maintenance of normothermia is also an important consideration. Although there are many strategies for warming patients and fluids that can be used successfully in the operating room, we have found maintaining normothermia in the preoperative holding room to be the most valuable. While it is possible to warm a cold patient in the operating room, this usually requires a very warm operating environment that makes the experience for the surgeon and staff grueling. We have found that when the patient comes into the operating room warm, and can be kept warm during the prepping and draping process that they will maintain their body temperature nicely even when the room is cooled to a very comfortable level for the operating team.

Negotiating the Learning Curve for OPCAB We have provided many suggestions to help surgeons with difficulties that may arise in the performance of OPCAB, whether it is a surgeon who is embarking on OPCAB for the first time, to 1 who performs selected cases routinely, but now wants to take their OPCAB experience to “the next level.” Table 1 outlines a list of methods designed to improve the adoption of OPCAB into any surgeon’s practice and have been previously discussed.38-40 We would emphasize starting

Off-pump coronary artery bypass Table 1 Methods to Improve Adoption of OPCAB Appropriate patient selection Individualized grafting stratety Peer-to-peer training of the entire team Graded clinical experience On-pump beating heart Cannulated OPCAB Wet pump Dry pump Minimally invasive/advanced OPCAB OPCAB, off-pump coronary artery bypass.

with carefully selected patients and anatomy, using sound grafting strategies to assure early success, taking advantage of peer-to-peer training opportunities often offered by institutions or industry, and a graded clinical experience. This may involve doing the first few patients on the pump but without a cross clamp or cardioplegia. On could then cannulate but not go on pump unless hemodynamic problems arose. The availability of a primed pump could then be used to assure swift conversion if one’s early experience. Finally, the presence a dry pump set up that can be primed quickly is useful. After thousands of OPCAB cases performed, we still set up a dry pump for each OPCAB case performed at our institution. Only after one has a breadth of experience with OPCAB, should they embark on advanced, minimally invasive techniques, such as those we have discussed above.

Emergency Conversion to On-Pump Conversion from OPCAB to on-pump CAB is an expected and reasonable alternative in some cases. Most studies have shown emergency conversion to be associated with increased morbidity and mortality.41,42 The incidence of stroke, need for inotropic support, transfusion requirements, ventilation time, intensive care unit, and hospitals stays have variably been shown to be higher in converted patients compared with patients who underwent successful OPCAB. These studies reproducibly demonstrate a reduction in the need for conversion as their experience improves, a clear indicator that surgeon and team experience play a role in the need for conversion from OPCAB. The refinement and increased use of positioning devices has also been shown to improve conversion rates.41 Elective conversion to a pump-assisted or on-pump approach should not be considered a sign of failure, but rather of sound clinical judgment. It should be performed sooner rather than later if needed. Emergency conversion from OPCAB should be rare in experienced hands. The calm, routine conversion into an on-pump beating heart or arrested technique is preferred to the hurried, emergent “crash on pump” scenario that is certain to lead to inferior outcomes. Early identification of trouble and sound clinical judgment will avoid experiences bound to frustrate the entire surgical team.

Other Barriers to Adoption There are certainly many other factors that could create barriers to adoption of OPCAB that may never be able to be

219 overcome. As cardiac surgeons, we all identify the fact that what we do daily is highly complex and can come with significant benefit as well as serious consequences for our patients. As such, the confidence a surgeon places in the routine performance of their practice is vital. Confidence is not some thing that can be turned on and off and comes from carefully consideration of all factors important to the patient’s “surgical experience.” According to local referral politics, economic or geography, there may be not much pressure to adopt new strategies when the current strategies work so well. There is still significant variability in the interpretation of the body of data that has accrued in the literature with regard to OPCAB. One could find data in the literature to support a vigorous defense or rejection of OPCAB. A review of the available literature follows.

Results Early Results The body of literature that has accumulated over the last decade or two on OPCAB seems to favor the thought that avoiding the pump results in at least equivalent early and late graft patency with excellent clinical outcomes, including an overall reduction in operative mortality, major perioperative complication rates, hospital length of stay, and cost. The literature on OPCAB has matured in parallel to the technique. In its early days, nonrandomized, small, single center reports confirmed good clinical outcomes and proved that the concept was valid.9,10 They also suggest that, particularly in highrisk patient populations, OPCAB provides superior results.43-48 These high risk groups have included the elderly people, women, reoperation, and patients with renal and preoperative pulmonary dysfunction.

Randomized Trials As experience grew so did the sophistication of the literature related to OPCAB. Many randomized trials have critically evaluated OPCAB.49-59 Some showed superiority of OPCAB in many respects, others showed equivalency. Care must be taken in interpretation of these early randomized trials.60-62 Many received significant criticism for inadequate study design. Results were often generalized on the basis of very small sample sizes, often in the hands of frankly inexperienced OPCAB surgeons early in the development of the operation. Most enrolled patients with only single and 2 vessel disease, normal left ventricular function, and not much comorbidity and clearly were not representative of “real world scenarios.” Expected morbidity and mortality would have been so low in these patients irrespective of the surgical approach that important differences between groups could not have resulted. Subsequent metanalyses of these studies added not much to the overall argument, as raw numbers were still small and valid statistical comparisons are still suspect.63-67 Taken in context, they provide limited useful information regarding the benefits of the procedure.

S.J. Hoff

220 Table 2 Risk-Adjusted Outcomes of OPCAB vs ONCAB

Operative mortality MACE Stroke Dialysis Reoperation Prolonged vent Renal failure Sternal failure PLOS > 14 d

OPCAB

ONCAB

P

Risk-Adjusted Odds Ratio (95% CI)

1.52 2.84 0.85 0.87 4.52 7.18 2.78 0.29 4.59

1.69 3.82 1.35 1.09 5.29 8.98 3.44 0.42 5.64

0.0439 <0.0001 <0.0001 0.0007 <0.0001 <0.0001 <0.0001 0.0001 <0.0001

0.80 (0.73, 0.87) 0.68 (0.64, 0.73) 0.62 (0.55, 0.68)

CI, confidence interval; MACE, major adverse cardiac events; ONCAB, on-pump coronary artery bypass; OPCAB, off-pump coronary artery bypass; PLOS, postoperative length of stay. Courtesy of John D. Puskas, MD.

Analysis of Large Databases Perhaps of more benefit are reviews of large regional or national databases that have emerged.68-75 Although these studies are not randomized, their sheer size allowed more sophisticated statistical analysis and more valid comparisons to on-pump surgery. Fortunately, the expected adverse event rate for either procedure is very low. As such, these larger studies provided superior statistical power to more effectively answer questions about the safety and efficacy of the 2 procedures. Cleveland68 reported the experience of the STS National Database from 1998 and 1999. Although this was early in OPCAB experience, the sample size was large. In that analysis, 106,423 patients underwent ONCAB and 11,717 patients underwent OPCAB. OPCAB patients were more likely to be older, female, and have more chronic obstructive pulmonary disease and renal failure. ONCAB patients were more likely to be diabetic, have 3-vessel or left main disease, or require emergency operation. Risk-adjusted mortality favored OPCAB (2.31% vs 2.93% ONCAB, P ⬍ 0.0001). OPBAB patients has fewer strokes (2.5% vs 4.6%, P ⬍ 0.0001), less prolonged mechanical ventilation (8.9% vs 11.3%), less reexploration for bleeding (2.1% vs 2.8%), and shorter postoperative length of stays (6.1 vs 7.0 days). A report of the New York State Database69 from 1997 to 2000 analyzed 59,044 ONCAB patients and 9135 patients in the OPCAB cohort. As with the STS data there was significantly greater proportion of older patients and women in the OPCAB group, which also contained a higher proportion of patients with previous stroke and cerebrovascular disease as well as renal failure. Even though the risk-adjusted operative mortality rate for OPCAB was lower (2.02% vs 2.16%) in this smaller study, it did not reach statistical significance. OPCAB patients did have significantly lower rates of stroke (1.6% vs 2.0%, P ⬍ 0.0003), and reoperation for bleeding (1.6% vs 2.2%, P ⬍ 0.0001), as well as shorter postoperative length of stay (5 vs 6 days, P ⬍ 0.0001). Improved survival at 3-year follow-up in the ONCAB group (89.5% vs 88.8%, P ⬍ 0.022) may have been affected by the older, sicker OPCAB profile. A subsequent analysis of the New York State database was published by Hannan et al75 in 2007. In that study, 49,830 patients (35,941 ONCAB, 13,889 OPCAB) were evaluated.

OPCAB was associated with significantly lower inpatient 30day mortality, stroke and respiratory failure, though a higher rate of unexplained operation in the same admission. There was no difference between groups in 3-year mortality. The findings of lower mortality differed from the previous study. Also, the late mortality at 3 years was no different in this study, a difference from the previous study that suggested OPCAB had a higher late mortality rate. The most recent and perhaps most powerful of these large nonrandomized trials was recently reported by Puskas35 at the Society of Thoracic Surgeons meeting in January of 2009. These authors used the power of the STS database to provide direct comparison between on-pump (ONCAB) and offpump (OPCAB) surgery. To remove the bias of low-volume center or surgeons and allow a critical look at the results of each technique in relatively experienced hands, they limited the analysis to centers that performed at least 150 OPCAB and 150 ONCAB over a 3-year period. This resulted in a study group of 186,458 patients who underwent CAB over that period in 1 of 160 centers. Of that group, 65,864 underwent OPCAB, whereas 120,594 underwent ONCAB. They further analyzed patients by coronary anatomy, grouping patients with 1 or 2 diseased vessels (45,969 patients), 3 diseased vessels without left main stenosis (97,997 patients), and 3 diseased vessels with left main stenosis (42, 492 patients). A multivariate logistic analysis 32 risk factors was used to risk-adjust outcomes. Importantly, crossovers from OPCAB to ONCAB were analyzed on an intention-to-treat basis. The OPCAB group was more likely to be elderly people, women, and have suffered a preoperative stroke or renal failure, whereas the ONCAB group were more likely to be diabetic, have a low ejection fraction congestive heart failure, or a previous myocardial infarction. OPCAB patients tended to have more single and 2 vessel disease (34% vs 19.6%, P ⬍ 0.001), therefore requiring fewer grafts (3.04 vs 3.58, P ⬍ 0.001). They show a significant reduction in operative mortality in the OPCAB group, as well as a highly significant reduction in overall adverse cardiac events, permanent stroke, dialysis, reoperation, prolonged ventilation, sternal wound infection, renal failure, and prolonged length of stay (Table 2). These results were consistent across anatomic

Off-pump coronary artery bypass

221

Table 3 Risk-Adjusted Outcomes of OPCAB vs ONCAB by Anatomic Group 1-2 Vessel Adjusted Odds Ratio Operative mortality Permanent stroke MI MACE

0.80 (0.66, 0.95) 0.47 (0.37, 0.59) 0.59 (0.46, 0.75) 0.63 (0.55, 0.71)

3 Vessel w/o LM

Adjusted P

Adjusted Odds Ratio

0.013 <0.001 <0.001 <0.001

0.85 (0.66, 0.95) 0.72 (0.62, 0.82) 0.63 (0.54, 0.74) 0.74 (0.69, 0.81)

Adjusted P 0.006 <0.001 <0.001 <0.001

3 Vessel w/LM Adjusted Odds Ratio 0.81 (0.70, 0.94) 0.64 (0.53, 0.77) 0.69 (0.56, 0.85) 0.72 (0.64, 0.80)

Adjusted P 0.006 <0.001 <0.001 <0.001

LM, left main disease; MACE, major adverse cardiac events; MI, myocardial infarction; ONCAB, on-pump coronary artery bypass; OPCAB, off-pump coronary artery bypass. Courtesy of John D. Puskas, MD.

groups, whether patients had 1-2 vessels diseased, or 3 diseased vessels with or without left main stenosis (Table 3).

Graft Patency The general assessment of graft patency has been discussed by other authors in this publication. Early assessment of graft patency in OPCAB anastomoses was provided by Poirier et al76 and Calafiore et al77 in 1999, and later by Puskas49 and Al-Ruzzeh et al.78 These studies described separate predischarge angiographic studies and when no immediate changes could be made other than catheter-based intervention, they provided valuable insight into the technical feasibility of the operation and helped validate the technique. In a recent meta-analysis, Raja and Dreyfus79 documented that the best available data from randomized controlled trials published in 2003 and 2004 suggest comparable graft patency rates after OPCAB and ONCAB. Small samples sizes should again be taken into account when making judgments about this conclusion. Our experience with graft assessment by intraoperative completion arteriography in a hybrid cath laboratory/OR at the time of surgery has recently been reported.24 We recently reviewed our experience with completion arteriography in our cohort of patients who have undergone a minimally invasive OPCAB to validate the technique (Hoff SJ, Ball SK, Petracek MR, et al, unpublished data). Twenty-eight patients underwent on-table completion arteriography after minimally invasive CAB grafting through a left thoracotomy without cardiopulmonary bypass. Thirty-three grafts in these 28 patients were performed, (average 1.2 grafts per patient, range 1-3). There were 3 findings on arteriogram leading to further intervention (11%). These included 1 patient who had limited dissection in the LIMA graft and underwent placement of an addition vein graft, and 2 grafts with anastomotic stenoses requiring stent placement. The remainder of the studies showed no significant abnormalities. There were no deaths in the study group and no serious complications. Patients were discharged home an average of 3.9 days postoperatively; (range 2-6). There were no instances of renal dysfunction postoperatively attributable to catheterization. We found that the results of completion arteriography after

minimally invasive OPCAB through left thoracotomy compare favorably to our published experience in patients undergoing CAB with cardiopulmonary bypass through sternotomy.

Future of OPCAB In summary, the experience to date with OPCAB would suggest that compared with an on-pump alternative, it remains more technically challenging, though the gap may be narrowing given improvements in technique and growing experience. Penetrance of OPCAB has remained stable in the USA over the last several years. Although many surgeons perform virtually all of their coronary bypass cases off-pump, many more do not perform OPCAB at all. A large number of surgeons will use OPCAB in those patients with 1 or 2 vessel disease who need 1-3 grafts, when performing more complex cases needing 4 or more grafts on-pump. The bulk of the available literature suggests that OPCAB is at least equivalent, and probably superior to an on-pump approach, particularly in certain high-risk patient subgroups. This is particularly true in the hands of experienced OPCAB surgeons.80,81 Innovation certainly has been important in the refinement of OPCAB techniques. New and innovative strategies will continue to be a part of its future. Perhaps this means an increased adoption of routine trans-sternal OPCAB. It may involve a hybrid approach using the best that cardiac surgery and interventional cardiology have to offer. The role of minimally invasive, limited access options discussed in this review may grow in the future. Technological innovation, such as improved facilitated anastomoses and advances in endoscopy and robotics may affect the future of myocardial revascularization as well. Economic realities may shape the future of surgical revascularization as well as catheter-based intervention. It remains unclear what effect the government or third party payers will have on medical care as economic pressors and national priorities for health care reform mount, how they will effect the surgical treatment of coronary artery disease, and what role OPCAB will play in that future. It is equally unclear how the increasing transparency of medical outcomes and evidencebased medicine will effect pressure to adopt OPCAB.

S.J. Hoff

222

References 1. Kolesov VI: Mammary artery-coronary artery anastomosis as a method for treatment of angina pectoris. J Thorac Cardiovasc Surg 54:535-544, 1967 2. Coronary Artery Surgery Study (CASS): A randomized trial of coronary artery bypass surgery. Survival data. Circulation 68:939, 1983 3. Eleven-year survival in the veteran’s administration randomized trial of coronary bypass surgery for stable angina. The Veteran’s Administration Coronary Artery Bypass Surgery Cooperative Study Group. N Engl J Med 311:1333, 1984 4. Varnauskas E: Twelve-year follow-up of survival in the randomized European Coronary Surgery Study. N Engl J Med 319:332, 1988 5. Bennetti FJ, Naselli G, Wood M, et al: Direct myocardial revascularization without extracorporeal circulation: Experience in 700 patients. Chest 100:312-316, 1991 6. Buffolo E, de Andrade CS, Branco JN, et al: Coronary artery bypass grafting without cardiopulmonary bypass. Ann Thorac Surg 61:63-66, 1996 7. Pfister AJ, Zaki S, Garcia JM, et al: Coronary artery bypass without cardiopulmonary bypass. Ann Thorac Surg 54:1085-1092, 1992 8. Puskas JD, Wright CE, Ronson RS, et al: Off-pump multivessel coronary bypass via sternotomy is safe and effective. Ann Thorac Surg 66:1068-1072, 1998 9. Puskas JD, Wright CE, Ronson RS, et al: Clinical outcomes and angiographic patency in 125 consecutive off-pump coronary bypass patients. Heart Surg Forum 2:216-221, 1999 10. Puskas JD, Thourani VH, Marshall JJ, et al: Clinical outcomes, angiographic patency, and resource utilization in 200 consecutive off-pump coronary bypass patients. Ann Thorac Surg 71:1477-1483, 2001; discussion 1483-1484 11. Hart JC: A review of 140 octopus off-pump bypass patients over the age of seventy: Procedure of choice? Heart Surg Forum 4:S24-S29, 2001 12. Mack MJ, Brown PP, Kugelmass AD, et al: Current status and outcomes of coronary revascularization 1999-2002: 148,396 surgical and percutaneous procedures. Ann Thorac Surg 77:761-768, 2004 13. Hart JC, Puskas JD, Sabik JF III: Off-pump coronary revascularization: Current state of the art. Semin Thorac Cardiovasc Surg 14:70-81, 2002 14. Puskas JD: Tips and techniques for multivessel OPCAB. A comparative atlas. Oper Tech Thorac Cardiovasc Surg 11:78-89, 2006 15. Sabik JF III: Off-pump coronary revascularization: Operative technique. A comparative atlas. Oper Tech Thorac Cardiovasc Surg 11:90104, 2006 16. Couture P, Denault A, Limoges P, et al: Mechanisms of hemodynamic changes during off-pump coronary artery bypass surgery. Can J Anesth 49:835-849, 2002 17. Nierich AP, Diephuis KJ, Jansen EWL, et al: Heart displacement during off-pump CABG: How well is it tolerated? Ann Thorac Surg 70:466472, 2000 18. Lima R: Surgical techniques of coronary artery exposure, in Solerno TA, Ricci M, Karamanoukian HL, et al (eds): Beating Heart Coronary Surgery. Armonk, NY, Futura, 2001, pp 21-34 19. Borst C, Jansen EWL, 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 27:1356-1364, 1996 20. Hangler H, Mueller L, Ruttmann E, et al: Shunt or snare: Coronary endothelial damage due to hemostatic devices for beating heart coronary surgery. Ann Thorac Surg 86:1873-1877, 2008 21. Emmiler M, Kocogullari CU, Ela Y, et al: Influence of intracoronary shunt on myocardial damage: A prospective randomized study. Eur J Cardio Thorac Surg 34:1000-1004, 2008 22. Bergsland J, Lingaas PS, Skulstad H, et al: Intracoronary shunt prevents ischemia in off-pump coronary artery bypass surgery. Ann Thorac Surg 87:54-60, 2009 23. Tok M, Ucar HI, Dogan OF, et al: Protective role of intracoronary shunt in off-pump coronary bypass operations. Saudi Med J 29:573-579, 2008 24. Zhao DX, Leacche M, Balaguer JM, et al: Routine intraoperative completion angiography after coronary artery bypass grafting and 1-stop

25. 26. 27.

28.

29.

30.

31.

32. 33. 34.

35. 36.

37.

38.

39.

40.

41.

42.

43.

44.

45.

46.

47.

hybrid revascularization, results from a fully integrated hybrid catheterization laboratory/operating room. J Am Coll Cardiol 53:232241, 2009 Kobayyashi J: Current status of coronary artery bypass grafting. J Gen Thorac Cardiovasc Surg 56:260-267, 2008 Barner HB: Operative treatment of coronary atherosclerosis. Ann Thorac Surg 85:1473-1482, 2008 Tanaka KA, Thourani VH, Williams WH, et al: Heparin anticoagulation in patients undergoing off-pump and on-pump coronary bypass surgery. J Anesth 21:297-303, 2007 Mishra YK, Mishra M, Malhotra R, et al: Evolution of off-pump coronary artery bypass grafting over 15 years—A single-institution experience of 14,030 cases. Innovations 1:88-91, 2005 Quigley RL, Fried DW, Pym J, et al: Off-pump coronary artery bypass surgery may produce a hypercoagulable patient. Heart Surg Forum 6:94-98, 2003 Serna DL, Thourani VH, Puskas JD: Antifibrinolytic agents in cardiac surgery: Current controversies. Semin Thorac Cardiovasc Surg 17:5258, 2005 Halkos ME, Cooper WA, Petersen R, et al: Early administration of clopidogrel is safe after off-pump coronary artery bypass surgery. Ann Thorac Surg 81:815-819, 2006 Mack MJ: Off-pump surgery and alternatives to standard operation in redo coronary surgery. J Cardiovasc Surg 19:313-319, 2004 Subramanian VA: Less invasive arterial CABG on a beating heart. Ann Thorac Surg 63:S68-S71, 1997 Calafiore AM, Giammarco GD, Teodori G, et al: Midterm results after minimally invasive coronary surgery (LAST operation). J Thorac Cardiovasc Surg 115:763-771, 1998 Puskas JD: OPCAB: Is it a better strategy? Presented at STS/AATS Tech Con 2009. San Francisco, California, January 24, 2009 Bainbridge D, Cheng DC: Minimally invasive direct coronary artery bypass and off-pump coronary artery bypass surgery: Anesthetic considerations. Anesthesiol Clin 26:437-452, 2008 Morganstern J, Kanchuger MJ: Pro: All off-pump coronary artery bypass graft surgeries should include intraoperative transesophageal echocardiography assessment. J Cardiothorac Vasc Anesth 22:625628, 2008 Song HK, Petersen RJ, Sharoni E, et al: Safe evolution towards routine off-pump coronary artery bypass: Negotiating the learning curve. Eur J Cardio Thorac Surg 24:947-952, 2003 Murphy GJ, Rogers CA, Caputo M, et al: Acquiring proficiency in off-pump surgery: Traversing the learning curve, reproducibility, and quality control. Ann Thorac Surg 80:1965-1970, 2005 Mariani MA, Gu YJ, Boonstra PW, et al: Procoagulant activity after off-pump coronary operation: Is the current anticoagulation adequate? Ann Thorac Surg 67:1370-1375, 1999 Hovakimyan A, Manukyan V, Ghazaryan S, et al: Predictors of emergency conversion to on-pump during off-pump coronary surgery. Asian Cardiovasc Thorac Ann 16:226-230, 2008 Patel NC, Patel NU, Loulmet DF, et al: Emergency conversion to cardiopulmonary bypass during attempted off-pump revascularization results in increased morbidity and mortality. J Thorac Cardiovasc Surg 128:655-661, 2004 Al-Ruzzeh S, George S, Yacoub M, et al: The clinical outcome of offpump coronary artery bypass surgery in the elderly patients. Eur J Cardio Thorac Surg 20:1152-1156, 2001 Hoff SJ, Ball SK, Coltharp WH, et al: Coronary artery bypass in patients 80 years and over: Is off-pump the operation of choice? Ann Thorac Surg 74:S1340-S1343, 2002 Beauford RB, Saunders CR, Niemeier LA, et al: Is off-pump revascularization better for patients with non– dialysis-dependent renal insufficiency? Heart Surg Forum 7:141-146, 2003 Dewey TM, Herbert MA, Prince S, et al: Does coronary artery bypass graft surgery improve survival among patients with end-stage renal disease? Ann Thorac Surg 81:591-598, 2006 Sharoni E, Song HK, Peterson RJ, et al: Off pump coronary artery bypass surgery for significant left ventricular dysfunction: Safety, feasi-

Off-pump coronary artery bypass

48.

49.

50.

51.

52.

53.

54.

55.

56.

57.

58.

59.

60.

61. 62.

63.

64.

bility, and trends in methodology over time—An early experience. Heart 92:499-502, 2006 Kerendi F, Puskas JD, Craver JM, et al: Emergency coronary artery bypass grafting can be performed safely without cardiopulmonary bypass in selected patients. Ann Thorac Surg 79:801-806, 2005 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 125:797-808, 2003 Angelini GD, Culliford L, Smith DK, et al: Effects of on- and off-pump coronary artery surgery on graft patency, survival, and health-related quality of life: Long-term follow-up of 2 randomized controlled trials. J Thorac Cardiovasc Surg 137:295-303, 2009 Hueb W, Lopes NH, Gersh BJ, et al: A randomized comparative study of patients undergoing myocardial revascularization with or without cardiopulmonary bypass surgery: The mass III trial. Trials 9:52, 2008 Magee MJ, Alexander JH, Hafley G, et al; PREVENT IV Investigators. Coronary artery bypass graft failure after on-pump and off-pump coronary artery bypass: Findings from PREVENT IV. Ann Thorac Surg 85:494-499, 2008 Angelini GD, Taylor FC, Reeves BC, et al: 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 randomized controlled trials. Lancet 359:1194-1199, 2002 van Dijk D, Nierich AP, Jansen EW, et al; Octopus Study Group: Early outcome after off-pump versus on-pump coronary bypass surgery: Results from a randomized study. Circulation 104:1761-1766, 2001 Nathoe HM, van Dijk D, Jansen EW, et al; Octopus Study Group: A comparison of on-pump and off-pump coronary bypass surgery in low-risk patients. N Engl J Med 348:394-402, 2003 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 291: 1841-1849, 2004 Légaré JF, Buth KJ, King S, et al: Coronary bypass surgery performed off pump does not result in lower in-hospital morbidity than coronary artery bypass grafting performed on pump. Circulation 109:887-892, 2004 Muneretto C, Bisleri G, Negri A, et al: Off-pump coronary artery bypass surgery technique for total arterial myocardial revascularization: A prospective randomized study. Ann Thorac Surg 76:778-783, 2003 Widimsky P, Straka Z, Stros P, et al: One-year coronary bypass graft patency: A randomized comparison between off-pump and on-pump surgery angiographic results of the PRAGUE-4 trial. Circulation 110: 3418-3423, 2004 Küss O, Gummert JF, Börgermann J: Meta-analyses with rare events should use adequate methods. J Thorac Cardiovasc Surg 136:241, 2008 Benson K, Hartz AJ: A comparison of observational studies and randomized, controlled trials. N Engl J Med 342:1878-1886, 2000 Concato J, Shah N, Horwitz RI: Randomized, controlled trials, observational studies, and the hierarchy of research designs. N Engl J Med 342:1887-1892, 2000 Feng ZZ, Shi J, Zhao XW, et al: Meta-analysis of on-pump and offpump coronary arterial revascularization. Ann Thorac Surg 87:757765, 2009 Moller CH, Penninga L, Wetterslev J, et al: Clinical outcomes in ran-

223

65.

66.

67.

68.

69.

70.

71.

72.

73.

74.

75.

76.

77.

78.

79.

80. 81.

domized trials of off-vs. on-pump coronary artery bypass surgery: Systematic review with meta-analyses and trial sequential analyses. Eur Heart J 29:2601-2616, 2008 Wijeysundera DN, Beattie SW, Djaiani G, et al: Off-pump coronary artery surgery for reducing mortality and morbidity: Meta-analysis of randomized and observational studies. J Am Coll Cardiol 46:872-882, 2005 Cheng DC, Bainbridge D, Martin JE, et al: Does off-pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A metaanalysis of randomized trials. Anesthesiology 102:188-203, 2005 Puskas J, Cheng D, Knight J, et al: Off-pump versus conventional coronary artery bypass grafting: A meta-analysis and consensus statement from the 2004 ISMICS Consensus Conference. Innovations 1:3-27, 2005 Cleveland JC Jr, Shroyer AL, Chen AY, et al: Off-pump coronary artery bypass grafting decreases risk-adjusted mortality and morbidity. Ann Thorac Surg 72:1282-1288, 2001 Racz MJ, Hannan EL, Isom OW, et al: A comparison of short- and long-term outcomes after off-pump and on-pump coronary artery bypass graft surgery with sternotomy. J Am Coll Cardiol 43:557-564, 2004 Mack MJ, Pfister A, Bachand D, et al: Comparison of coronary bypass surgery with and without cardiopulmonary bypass in patients with multivessel disease. J Thorac Cardiovasc Surg 127:167-173, 2004 Hernandez F, Cohn WE, Baribeau YR, et al; Northern New England Cardiovascular Disease Study Group: In-hospital outcomes of offpump versus on-pump coronary artery bypass procedures: A multicenter experience. Ann Thorac Surg 72:1528-1534, 2001 Sabik JF, Blackstone EJ, Lytle BW, et al: Equivalent midterm outcomes after off-pump and on-pump coronary surgery. J Thorac Cardiovasc Surg 127:142-148, 2004 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 86:1139-1146, 2008 Puskas JD, Edwards FH, Pappas PA, et al: Off-pump techniques benefit men and women and narrow the disparity in mortality after coronary bypass grafting. Ann Thorac Surg 84:1447-1454, 2007 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 116:1145-1152, 2007 Poirier NC, Carrier M, Lesperance J, et al: Quantitative angiographic assessment of coronary anastomoses performed without cardiopulmonary bypass. J Thorac Cardiovasc Surg 117:292-297, 1999 Calafiore AM, Teodri G, Di Giammarco G, et al: Multiple arterial conduits without cardiopulmonary bypass: Early angiographic results. Ann Thorac Surg 67:450-456, 1999 Al-Ruzzeh S, George S, Bustami M, et al: Effect of off-pump coronary artery bypass on clinical, angiographic, neurocognitive, and quality of life outcomes: Randomised controlled trial. BMJ 332:1365-1372, 2006 Raja SG, Dreyfus GD: Impact of off-pump coronary artery bypass on graft patency: Current best available evidence. J Cardiovasc Surg 22: 165-169, 2007 Bonchek LI: Off-pump coronary bypass: Is it for everyone? J Thorac Cardiovasc Surg 124:431-434, 2002 Kerendi F, Morris CD, Puskas JD: Off-pump coronary bypass surgery for high-risk patients: Only in expert centers? Curr Opin Cardiol 23: 573-578, 2008