Outcome of Coronary Artery Bypass Grafting Strategies for Improvement

Transcription

1 Outcome of Coronary Artery Bypass Grafting Strategies for Improvement Ardawan J Rastan 1 and Volkmar Falk 2 1. Department of Cardiac Surgery, Heart Centre, University of Leipzig; 2. Department of Cardiac and Vascular Surgery, University Hospital Zurich Abstract During recent years, new conceptual, technical and drug strategies have led to improved early and late outcomes after coronary artery bypass surgery. These new strategies can be divided into the following three groups: optimisation of pre-operative patient selection and indications for and timing of the operation; peri-procedural refinements, including new techniques and instruments to avoid extracorporeal circulation, reduce aortic manipulation and minimise surgical access; and improvements to post-operative care, such as fast-track protocols and long-term drug therapy. In summary, the wide range of the surgical armamentarium available today allows cardiovascular surgeons to adapt the surgical strategy to individual patients and the given clinical scenario. This article aims to describe clinical rationales for the adoption of new concepts, provide an introduction to technical details and discuss clinical study results where appropriate. Keywords Off-pump coronary artery bypass (OPCAB), endoscopic graft harvesting, minimally invasive surgery, minimally invasive direct coronary artery bypass (MIDCAB), hybrid coronary revascularisation Disclosure: The authors have no conflicts of interest to declare. Received: 28 November 2010 Accepted: 7 January 2011 Citation: European Cardiology, 2011;7(1):55 61 Correspondence: Ardawan J Rastan, Department of Cardiac Surgery, University of Leipzig, Struempellstr. 39, Leipzig, Germany. E: rastan@rz.uni-leipzig.de Since the early 1980s, coronary artery bypass grafting (CABG) has been routinely performed with cardioplegic arrest and cardiopulmonary bypass (CPB) support as a first-choice revascularisation strategy to treat complex coronary artery disease (CAD). Despite intensive debate about the optimal cardioplegic solution and cardioplegic delivery route, CABG procedures became highly standardised, allowing short learning curves, widespread application and improved outcomes. With refinements to percutaneous coronary intervention (PCI) techniques and more aggressive PCI indications having taken place, even in elective patients presenting prognostic CAD pathologies surgeons were challenged to address the limitations of surgical coronary revascularisation. In addition, surgeons themselves admitted to limitations associated with conventional CABG (ccabg). As a result, a wide range of surgical CABG modifications were developed and have been creating controversy since the mid-1990s. These developments include efforts to reduce early morbidity and mortality by looking for safer alternatives to ccabg, including off-pump beating heart bypass surgery (off-pump coronary artery bypass [OPCAB]), hybrid concepts and endoscopic graft harvesting techniques and efforts to improve long-term outcome by choosing appropriate bypass grafts and offering the optimal post-operative medical treatment. In parallel, efforts were made to find the best revascularisation strategy (PCI versus CABG) for stable patients with different CAD pathologies and to optimise the surgical indication and timing of operations in a huge number of high-risk sub-populations. In this article we aim to describe clinical rationales for the adoption of several new surgical concepts, to provide an introduction to surgical details and to discuss potential advantages in the context of data from the relevant literature whenever appropriate. Pre-operative Patient Selection, Indication and Timing of the Operation Patient Selection and Coronary Artery Bypass Grafting Indication in Stable Patients Compared with PCI, CABG is undoubtably the more effective revascularisation concept, with better early and long-term target vessel patency rates and less recurrent angina; however, CABG is more invasive and is associated with a significantly higher rate of minor complications and longer hospitalisation. Regarding survival analyses, most comparative PCI versus CABG studies have been performed on patients with two-vessel disease (2-VD) excluding the left anterior descending (LAD) territory and left main stem or in highly selected patients with 3-VD presenting coronary lesions that were exceptionally suitable for PCI, and thus failed to demonstrate a survival benefit of CABG over PCI. By contrast, the SyNergy between percutaneous coronary intervention with Taxus and cardiac surgery (SYNTAX) study was designed to compare for the first time modern surgical and percutaneous techniques (drug-eluting stents) as a primary treatment strategy in 1,800 randomised patients with de novo 3-VD and/or left main disease in a real-world scenario. An important conclusion from the SYNTAX study was that the primary study end-point of the 12-month major adverse cardiac and cerebrovascular event (MACCE) rate significantly favoured CABG over PCI (12.1 versus 17.8%; p=0.0015), which was mostly based on a two-fold higher rate of repeat revascularisation in the PCI patients. 1 However, there was no difference between the two groups in terms of the safety end-point, which included all-cause death, cerebrovascular events and myocardial infarction after 12 months. The three-year followup data are now available, revealing a significantly lower incidence of TOUCH BRIEFINGS

2 Figure 1: All-cause Death to Three Years After Allocation in Randomised SYNTAX Study Arm in the Subset of Patients Presenting Three-vessel Coronary Artery Disease Cumulative event rate (%) Before 1 year* 2.9% versus 4.5% p=0.18 CABG (n=549) p= years* 1.2% versus 2.1% p= Months since allocation 2 3 years* 1.7% versus 3.2% p=0.25 Taxus (n=546) Modified from the Transcatheter Cardiovascular Therapeutics (TCT) presentation by Professor Friedrich W Mohr, 2010, with permission. 2 CABG = coronary artery bypass graft. Figure 2: Incidence of Cumulative Two-year Major Adverse Cardiac and Cerebrovascular Event Rate in Randomised SYNTAX Study Patients PCI-RCT % 5.7% myocardial infarction (3.6 versus 7.1%) in the CABG patients compared with those receiving PCI. For the large subset of patients presenting 3- VD without left main disease, a significant survival benefit was found even for CABG patients (see Figure 1). By contrast, in the smaller cohort of patients with left main disease (isolated or in combination with 1-, 2- or 3-VD), there was a significant benefit of CABG over PCI only in patients with additional complex CAD (mostly 3-VD). However, in left main patients with less complex additional CAD, there were comparable results in the PCI group. The reasons for these findings are an unexpectedly high MACCE rate in this small number of surgical patients and a lower than average three-year incidence of repeat revascularisations in the PCI cohort. As a consequence, the recently published European Society of Cardiology (ESC) guidelines on myocardial revascularisation for the first time gave a class IIa recommendation for PCI for isolated ostial or midshaft lesion and only for left main with two or three vessel disease and a SYNTAX score of more than 33 left main stenting is still contraindicated. By combining the 897 patients randomised to CABG in the SYNTAX study with the 644 patients who were not randomised (owing to 14.3 all CABG The figure depicts the major adverse cardiac and cerebrovascular event (MACCE) rate of percutaneous coronary intervention versus coronary artery bypass graft patients according to the coronary complexity measured by the SYNTAX score. CABG = coronary artery bypass graft; PCI-RCT = percutaneous coronary interventionrandomised controlled trial coronary anatomy not suitable for PCI) but who were followed in a nested SYNTAX CABG registry, the largest CABG cohort to date from a single controlled multicentre clinical trial could be analysed. 4 These data revealed excellent contemporary CABG results with an overall early mortality rate of about 1%, which was not inferior to that seen with PCI. This low mortality rate was remarkable because only a few study exclusion criteria were defined in the SYNTAX study. A risk factor analysis of this entire SYNTAX CABG cohort revealed left main disease (p=0.049) and incomplete revascularisation (p=0.005) as coronary risk factors for adverse two-year MACCE rate. Other well-known extracardiac and cardiac predictors for two-year MACCE were arterial hypertension, EuroSCORE, peripheral vascular disease, advanced age, chronic obstructive lung disease, low ejection fraction, intra-aortic balloon pump and emergency indication. Medically treated diabetes was not a predictor. By contrast, complete surgical revascularisation was significantly protective against two-year MACCE, indicating that complete revascularisation should always be the aim whenever surgical revascularisation is performed. 5 The SYNTAX study also addressed differences in coronary complexity by using the SYNTAX score. The SYNTAX score was initially designed as a comprehensive angiographic scoring system to anticipate PCI complexity related to coronary pathology and to allow quantification of CAD beyond left main and three-major-vessel disease. 6,7 During the SYNTAX study, the SYNTAX score was calculated for all patients by a central core laboratory, with patients divided into tertiles of low (0 22), medium (23 32) and high ( 33) SYNTAX score. Interestingly, in contrast to the PCI results, it was demonstrated that for CABG patients the overall MACCE rates at two years were not influenced by differences in the complexity of CAD (see Figure 2). Surgical Indication and Timing in Patients with Acute Coronary Syndrome Compared with the options for patients with stabile angina pectoris (AP), there is a multitude of highly effective treatment options for acute coronary syndrome (ACS). Among these are new and refined treatment strategies using glycoprotein IIb/IIIa receptor antagonists, thienopyridines and antithrombin agents. 3,8 A timely coronary angiography and a prompt invasive revascularisation strategy play a significant role in patient outcomes. The revascularisation strategy today primarily follows catheter-based PCIs; however, depending on patient status and the complexity of CAD, and in cases of chronic total coronary artery occlusion or unsuccessful or complicated PCI, an urgent or emergency operative coronary bypass procedure may be indicated. In patients with unstable angina and non-st-segment myocardial infarction (NSTEMI), there is no reason why the choice of revascularisation modality should deviate from that used for stable angina Once a consensus has been reached for an operative indication, the timing of the operation must be determined based on the symptoms, the individual coronary pathology and the haemodynamic stability of the patient, as well as on the need for routine and additional diagnostics. Emergency indications are persistent or recurrent AP refractory to optimal medical treatment, sub-total non-collateralised coronary stenoses or impending or manifest cardiogenic shock. On the other hand, in patients with medically managed symptoms, chronically well collateralised coronary occlusions and stable haemodynamics, the operation may be postponed. However, the operation should still be carried out urgently within the same hospital stay or as an early elective operation. As shown recently by the 56 EUROPEAN CARDIOLOGY

3 Outcome of Coronary Artery Bypass Grafting Strategies for Improvement Assessment on the prevention of progression by rosiglitazone on atherosclerosis in type 2 diabetic patients with cardiac history (APPROACH) study, time from admission to CABG was not associated with an increased risk of short-term mortality. 12 For ST-segment myocardial infarction (STEMI), the contemporary guidelines suggest that for suitable coronary pathologies, PCI of left main stem lesions is equivalent to a coronary bypass operation for patients who have an elevated operative risk. 3,8 Surgical revascularisation in STEMI should always be considered when the infarct vessel cannot, or cannot sufficiently be interventionally revascularised, and is therefore indicated as an immediate procedure, analogous to PCI. Figure 3: Intraoperative Situs of a Sternotomy Off-pump Coronary Artery Bypass Procedure Not uncommonly, the infarct vessel can be acutely re-opened and unmasks an accompanying multivessel CAD during angiography, which per se represents a primary operative indication. In this setting an urgent operation is indicated, or sooner in the case of recurrent symptoms, haemodynamic instability or critical coronary anatomy. 1 cm Peri-procedural Refinements, Including Strategies for Avoiding Extracorporeal Circulation, Reducing Aortic Manipulation and Minimising Surgical Access In the mid-1990s, surgical strategies became available that allowed coronary artery bypass operations to be performed on the beating heart and without CPB. Since then, the number of OPCAB procedures has risen and they now account for about 30% of all coronary revascularisations worldwide, and in some countries with limited medical and financial resources the proportion exceeds 80%. In some units, OPCAB is used almost exclusively without patient selection. Off-pump Coronary Artery Bypass The major advantage of OPCAB procedures is the removal of the need for a heart lung machine, which avoids all of the adverse effects associated with extracorporeal circulation and cardioplegic arrest, such as systemic inflammatory response syndrome, aortic arteriosclerotic debris or air embolisation, laminar blood flow and global myocardial ischaemia. OPCAB procedures are performed on the beating heart with only local stabilisation of the relevant coronary segment with the aim of distal anastomosis. The anastomosis is performed by incising the coronary vessel and controlling the local bleeding using proximal vessel snares, intracoronary shunts and a CO 2 blower mister (see Figure 3). The evolution of OPCAB surgery is of course closely associated with the development of stabilisation arms, which first became available in the early 1990s. After early experiences it was obvious that exposure of the posterior wall would require vacuum-assisted stabilisers. It was also recognised that OPCAB requires more than just ccabg procedures: a team approach and optimal anaesthesiological management are also needed to support the procedure and to avoid haemodynamic compromise. During the last decade, several prospective randomised studies and meta-analyses comparing OPCAB and ccabg surgery have been published, focusing on low-risk or mixed-risk populations Most of the studies failed to demonstrate significant differences between the two surgical options regarding early mortality or peri-operative MACCE rates, but OPCAB was consistently superior regarding blood 1 = stabilisation arm; 2 = CO 2 blower; 3 = proximal snare; 4 = vacuum tube; 5 = bypass graft; 6 = pericardial stay sutures; 7 = distal anastomosis; 8 = intracoronary shunt. loss, transfusion requirements, ventilation time, intensive care unit (ICU) and length hospital of stay and, consequently, resource utilisation. Most of the large observational studies comparing OPCAB and ccabg strategies also revealed a benefit of OPCAB concerning early mortality, myocardial infarction and stroke rate. 16 In recent years, OPCAB revascularisation strategies have been evaluated on patients with specific cardiac and extracardiac risks. For most of these subsets of patients, single- and multicentre studies are now available. Although most of these studies were non-randomised, they demonstrated that multirisk patients and patients with severely reduced left ventricular function in particular benefit in terms of peri-operative mortality and major morbidity by avoiding CPB and cardioplegic arrest. However, because of the overall low incidence of MACCE in routine CABG surgery, large cohorts of patients which are available only in registry meta-analyses would be needed to demonstrate statistically significant differences in mortality, stroke and renal failure between the procedures. 14,17 In a thorough meta-analysis, the International Society for Minimally Invasive Cardiac Surgery Consensus Group published evidence supporting the use of OPCAB, 14 demonstrating that OPCAB reduces mortality, length of stay and the incidence of post-operative myocardial infarction, renal failure, atrial fibrillation and transfusion in mixed-risk and high-risk patients. During the early OPCAB period, concerns arose regarding incomplete surgical revascularisation and impaired graft patency owing to the more challenging OPCAB technique. 18,19 Two randomised controlled studies showed a significantly compromised graft patency in OPCAB compared with ccabg patients. 19,20 However, both studies came under severe fire in the surgical community because OPCAB was performed by inexperienced surgical trainees during the early learning curve, which was reflected in a conversion rate from OPCAB to on-pump of more than 12% fivefold higher than average in the US and Europe. Today, in experienced OPCAB centres, clinical data and graft patency are comparable between the two techniques, as shown in EUROPEAN CARDIOLOGY 57

4 Figure 4: Intraoperative Situs of a Minimally Invasive Direct Coronary Artery Bypass Procedure via Anterolateral Mini-thoracotomy reusable pressure stabilisers are then used to immobilise the target region before anastomosis (see Figure 4). MIDCAB modifications include an approach through a partial inferior sternotomy or a small anterolateral thoracotomy for multivessel bypass grafting. 33 Early angiographic patency rates reported for MIDCAB procedures are in the range of 94 98%, similar to those reported for sternotomy patients. 28,34 At six months, patency rates of 94% have been described. 35 Reported in-hospital mortality for MIDCAB is less than 1% and compares favourably with a rate of 1.4% for off-pump single-bypass and 3.6% for single bypass with CPB, as reported in the registry of the German Society for Thoracic and Cardiovascular Surgery, and is also lower than the 2.4% mortality rate seen in the Society of Thoracic Surgeons database. 36,37 The rates of major peri-operative complications such as myocardial infarction and the need for target-vessel re-intervention are low and also comparable to those seen for standard CABG procedures. In addition, owing to anaortic surgery, peri-operative stroke is rare and the rate is considerably lower than that seen for conventional techniques (see below). randomised controlled trials such as the SMART, OCTOPUS and PRAQUE-4 studies In a recent meta-analysis of 10 trials including 4,821 patients, of whom 3,450 underwent PCI and 1,371 underwent OPCAB, the rates of stroke, myocardial infarction, cardiac mortality and all-cause mortality were similar between the two groups. The 12-month MACCE rate and need for repeat revascularisation were significantly lower in the OPCAB group compared with PCI patients. 25 Minimally Invasive Direct Coronary Artery Bypass A less invasive approach is to combine OPCAB strategies with the avoidance of a full median sternotomy; this reduces surgical trauma and wound complications. The minimally invasive direct coronary artery bypass (MIDCAB) concept was introduced for patients with isolated disease of the LAD in the mid-1990s and since then has found widespread application In some centres MIDCAB is the method of choice for surgical revascularisation of isolated LAD disease. In addition, MIDCAB is a valuable alternative to standard CABG or OPCAB in selected high-risk patients with multivessel disease and extensive co-morbidities, who are at a prohibitively high risk for sternotomy. 30 Standard MIDCAB is usually performed through a left anterolateral mini-thoracotomy in a right lateral position. After a 5 6cm skin incision above the fifth intercostal space or in the inframammary fold, take-down of the left internal mammary artery (LIMA) is usually performed under direct vision using special retractor systems. Alternatively, endoscopic LIMA takedown using a harmonic scalpel or telemanipulation system has been reported. 31,32 The pericardium should be opened above the course of the LAD and extended to the groove between the aorta and the pulmonary artery to facilitate the identification of the LAD. To enhance exposure, one or two pericardial stay sutures may be used to position the heart. Standard In our series of 1,918 patients who underwent MIDCAB between 1996 and 2009, the in-hospital mortality rate was 0.8% (predicted mortality by EuroSCORE 3.8%) and the stroke rate was 0.3%. Conversion to sternotomy was necessary in 1.6% of patients. A total of 745 patients received a routine post-operative angiogram, demonstrating a 96.3% early patency rate. Five-year survival was 91.5%. Freedom from MACCE and angina after five years was 88.6%. 38 These results are in accordance with the findings of other groups. However, MIDCAB is a highly demanding procedure that should be attempted only by surgeons who have sufficient experience in conventional and off-pump surgery. It has been shown that the complication rate of MIDCAB is significantly lowered after MIDCAB procedures. 39 Therefore, it is recommended that only dedicated and experienced surgeons use this procedure. Total endoscopic CABG (TECAB) is performed in a few centres. With the evolution of robotic surgery the results of off-pump TECAB have substantially improved, but larger trials are needed to determine the added benefit of this approach over MIDCAB. Hybrid Coronary Revascularisation Concepts The hybrid approach for patients with multivessel CAD combines the excellent long-term results of grafting a mammary artery to the LAD with the advantages of PCI to achieve complete revascularisation. The principle was first described by Angelini in The basal hypothesis of this concept is that in non-lad territories PCI can potentially achieve similar long-term results to CABG with a somewhat higher rate of re-intervention. However, combining the benefits of two different procedures also means adding the different risks inherent to each type of procedure. The risks of a surgical procedure such as general anaesthesia, mechanical ventilation, bleeding and wound healing complications are combined with the risks of PCI, which include dual antiplatelet therapy (DAPT) and the necessity of re-interventions for in-stent restenosis or acute stent thrombosis. Usually, a hybrid myocardial revascularisation strategy means combining a MIDCAB operation with PCI of the non-lad territories in multivessel CAD during the same hospital stay. 41 However, whether PCI should be performed immediately before, during or soon after the 58 EUROPEAN CARDIOLOGY

5 Outcome of Coronary Artery Bypass Grafting Strategies for Improvement MIDCAB procedure in this scenario is unclear so far, and there are arguments for each approach. Other general hybrid strategies include sternotomy CABG after emergency PCI of a culprit lesion or PCI before minimally invasive valve surgery. in situ, free graft) means it is difficult to carry out well-founded scientific analyses as a basis for general recommendations. Thus, in the current guidelines no recommendations are given except for the preference of LIMA-to-LAD. 10 Hybrid concepts for coronary artery revascularisation were considered for the first time in the recently published ESC guidelines on revascularisation and were defined as a planned, intentional combination of CABG with a catheter-based intervention to other coronary arteries during the same hospital stay. 3 It is recommended that indications for hybrid revascularisation be selected by a heart team combining surgical and PCI expertise. The limited availability of outcome data and a lack of randomised trials mean that the ESC guidelines focus only on potential clinical scenarios when hybrid revascularisation might be considered. Complete Arterial Revascularisation In the last 20 years there has been increasing concern about the long-term patency of vein grafts utilised for CABG compared with arterial grafts. It was thus suggested that revascularisation with arterial grafts rather than vein grafts may result in improved outcomes following CABG. In particular, the Cleveland Clinic group reported superior survival in patients receiving bilateral mammary artery bypass grafting to the left coronary territories. 42 This is particularly important when considering that graft occlusion can result in recurrence of angina, re-hospitalisation and re-intervention. However, to date, neither multiple arterial grafting nor complete arterial revascularisation has become the standard approach for patients undergoing CABG. This is supported by reports from large contemporary multicentre studies suggesting that the use of multiple arterial grafting is limited to approximately 10 20% of all patients undergoing CABG. 1 There are several potential reasons why the use of complete arterial revascularisation has not appeared to increase significantly during the last two decades. Besides the fact that the procedures are longer and more technically demanding, there are two major arguments that might explain this phenomenon. First, the benefit of an additional arterial graft to the non-lad territories is not as scientifically well proven as it is in the LAD territory and that non-lad territories per se do not have the same impact on survival. For example, data from the Radial Artery Patency and Clinical Outcome Trial failed to demonstrate a significant difference in graft patency between the radial artery, the right mammary artery and a venous graft for the second largest territory in the presence of a LIMA-to-LAD bypass, 43,44 which is in stark contrast to recent data from the Cleveland Clinic. 45 Moreover, the patency of bypass grafts to the non-lad territories depends to a greater degree on the pathology of the target artery, the grade of native vessel stenosis and the conduit quality than grafts to the LAD. Interestingly, analysis of the entire SYNTAX CABG population revealed no significant advantage of arterial grafting over venous bypass surgery in the presence of an IMA-to-LAD anastomosis after two years. 4 It is hoped that long-term data from the randomised Arterial revascularisation trial (ART) will provide more evidence on this issue. 46 The use of different arterial grafts (second mammary, radial, gastroepiploic artery), different target vessel anatomy and the variety of options for arterial graft construction (sequential, Y-graft, T-graft, Second, the advantages of arterial bypass conduits become more evident over time and thus arterial revascularisation might be more important for prognosis in patients under 65 years of age. However, contemporary bypass surgery is confronted with an increasingly ageing patient population who probably do not benefit to the same degree as younger patients. Moreover, some surgeons also fear an increased risk of sternal wound complications and a prolonged hospital stay when the second mammary artery is used. However, using the skeletonised mammary harvesting technique, it has been shown that, even in patients with diabetes, the use of a bilateral mammary artery is not associated with a significantly increased risk of wound healing problems. 47,48 In summary, the selection of bypass graft material today is more demanding than in recent decades, with surgeons able to offer a flexible bypass graft concept adapted to patient age, risk profile and coronary anatomy. Anaortic Surgery The Achilles heel of contemporary CABG surgery remains the higher incidence of early neurological events compared with PCI; a cumulative rate of 2% after the first year was reported in the SYNTAX trial. OPCAB surgery offers the potential to reduce the incidence of peri-operative stroke by avoiding aortic cannulation and reducing aortic manipulation. However, most of the OPCAB studies include patients receiving partial occlusion clamping of the aorta for proximal bypass anastomosis, with the potential residual risk of cerebral debris embolisation from the arteriosclerotic ascending aorta. Anaortic surgery is defined as a CABG procedure that avoids any aortic manipulation by performing OPCAB surgery and constructing T-shaped or Y-shaped conduits that are centrally supplied by an in situ arterial graft. Usually, the in situ LIMA serves as a central conduit that delivers a second graft for the posterior and inferior coronary segments. Recently, it was demonstrated that anaortic surgery was associated with improved neurological outcome in about 2,000 OPCAB patients and reduced the 30-day stroke risk from 0.5 to 0.1%. 49 Anaortic surgery is thus an important option, especially for patients with an increased risk of cerebral adverse events owing to severe general arteriosclerosis including porcelain aorta. For those patients in whom at least one proximal aortic anastomosis seems appropriate, new proximal anastomotic devices are now available that are designed to offer a complete haemostatic seal without the need for an aortic side-clamp. 50 Endoscopic Graft Harvest There is overwhelming and consistent evidence from meta-analyses that endoscopic graft harvesting of the saphenous vein and the radial artery is significantly beneficial with regard to non-infective wound healing problems, septic wound complications, length of hospital stay, need for surgical wound intervention, pain, neuralgia and patient satisfaction. Thus, conduit harvest should be performed routinely through limited incisions, or endoscopically. A variety of techniques and device options for minimally invasive saphenous vein and radial artery harvesting have been described over time, and can be divided into three main groups: minimally invasive EUROPEAN CARDIOLOGY 59

6 techniques with direct vision, or bridging techniques; endoscopic harvesting using closed CO 2 systems; and endoscopic harvesting using open or no CO 2 systems. Irrespective of the device used, a short skin incision of 2 3cm is enough to harvest the vein (two- to three-vein conduit segments and the radial artery). Several groups have reported a fast learning curve with the endoscopic technique, with procedure duration reducing to an acceptable minutes after the first few cases. 51 In an International Society for Minimally Invasive Cardiothoracic Surgery (ISMICS) Consensus Group meta-analysis, the risk of wound complications from endoscopic vein harvesting techniques was reduced significantly by 69% compared with the open technique. 52 The need for surgical intervention for wound infection was also reduced significantly. With regard to the incidence of moderate to severe post-operative pain, a reduction of 74% was evident, and the incidence of mobility disturbance at discharge was reduced by 69%. extubation and sufficient analgesic management. 60 This potentially allows for the patient to be transferred to an intermediate care unit within the first three hours. It has been shown that this protocol, used in 421 consecutive patients, allowed patients to be extubated significantly earlier and led to a significantly shorter length of stay in the intermediate care unit and the hospital compared with standard ICU fast-track management. 60 A well-functioning fast-track protocol not only leads to faster recovery of routine cardiac surgery patients, but also allows ICU resources to be concentrated on the increasing number of critically ill patients. Post-operative Cardiac Medication Despite improvements in post-operative stabilisation of patients on cardiac medication, the SYNTAX trial revealed significant differences between PCI and CABG patients regarding the use of cardioprotective drugs at one year in favour of PCI patients. This had to be addressed by the surgeons to optimise long-term surgical outcome. 1 There are only a few trials focusing on cardiac outcomes and providing angiographic data on patency rates. A secondary analysis of the Project of ex-vivo vein graft engineering via transfection (PREVENT) IV trial demonstrated inferior patency rates for endoscopic versus open vein graft harvest after months: the vein graft failure rate was 46.7% in the endoscopic versus 38.0% in the open group (p<0.001). Endoscopic harvesting was also associated with higher rates of death, myocardial infarction and repeat revascularisation. 53 However, most studies found no differences in myocardial infarction, recurrent angina, coronary re-intervention and death over the short and medium term. 52,54 The few trials focusing on vascular integrity and vessel wall trauma found no difference for the endoscopic versus the open technique. 55 With regard to wound infections in endoscopic radial artery harvest, a lower rate was found (0 2.7%) compared with the open radial artery harvest technique. 56,57 Graft patency, clinical outcome, histological integrity and in vitro vasoreactivity are equal between open and endoscopic techniques. 58 Thus, endoscopic radial artery harvest should always be considered owing to better patient satisfaction and fewer wound healing complications. Improvements in Post-operative Care, Including Fast-track Protocol and Cardiac Medication Alongside pre- and intra-operative decisions and strategies, optimal post-operative care also significantly influences early and mid-term outcomes after CABG surgery. Fast-track Protocol Numerous studies have shown that early extubation or fast-track treatment of routine cardiac surgery patients results in a decrease in ICU and hospital length of stay and, subsequently, a reduction of hospitalisation costs. 59 There are various options for the implementation of a fast-track protocol and the choice depends on local hospital conditions. Two options that allow fast recovery and transfer of the patient to the intermediate care unit within the first hours post-operatively are fast-track protocols with extubation in the operation room followed by transfer to the ICU or extubation of the patient in the ICU early after admission. However, another fast-track protocol allows the patient to be transferred from the operation room directly to a post-anaesthetic care unit, where specally trained anaesthetic nurses and anaesthetists ensure early Although not well supported by large randomised studies, there is a wide consensus that CABG patients should receive lifetime acetylsalicylic acid (ASA) medication to prevent early and long-term graft failure. 10 Recently published data also support an additional intravenous ASA bolus application ( mg) a few hours (six to eight hours) after CABG surgery to prevent ASA resistance during the post-operative phase. 61 The additional protective value of clopidogrel in routine CABG patients is as yet unclear; however, a recently published randomised single-centre study revealed a significant benefit of DAPT on the venous bypass graft patency rate after three months compared with ASA alone. 62 In patients with previous stent implantation, the post-operative antiplatelet regime has to follow the recommendation for patients who have undergone PCI; this is of utmost importance in patients with functioning drug-eluting stents. 3 Whether surgical patients with ACS should also be managed with DAPT in a similar way to PCI patients needs to be evaluated in the future. Other long-term medical therapies with class I recommendation after CABG, unless contraindicated, include: 3 angiotensin-converting enzyme (ACE) inhibitors for patients with a left ventricular ejection fraction under 40% and in those with arterial hypertension, diabetes or chronic kidney disease. Angiotensin receptor blockers should be used as an alternative in patients who are intolerant of ACE inhibitors; beta-blockers in all patients after myocardial infarction, ACS or left ventricular dysfunction; and lipid-lowering drugs in a high dose are indicated in all patients regardless of lipid levels. Conclusions There is clear evidence that CABG remains the revascularisation strategy of choice in patients with three-vessel coronary artery disease including left main stenosis. Further analyses are required to understand suboptimal surgical results in less complex left main disease; these analyses should include measurements of competitive flow phenomena and coronary flow reserve. Arterial bypass grafting should be used liberally on an individual basis considering the patient s age, risk profile and coronary artery pathology and there is growing evidence in favour of OPCAB in high-risk patients. 60 EUROPEAN CARDIOLOGY

7 Outcome of Coronary Artery Bypass Grafting Strategies for Improvement OPCAB is already the preferred method of bypass grafting in many centres and offers the option of anaortic surgery, especially in patients with a specific risk of stroke. MIDCAB is a valuable option for patients with single-vessel disease of the LAD. Excellent long-term data confirm the efficacy of this approach. The MIDCAB strategy in combination, hybrid or multivessel surgical revascularisation concepts has not been well analysed and thus has to be individually indicated by a specialised heart team. The benefits of endoscopic graft harvesting in terms of wound healing may come at the cost of inferior patency results. Larger randomised trials are needed before endoscopic harvesting can be recommended for routine application. Post-operative transfer of patients after CABG to highly specialised staff experienced in fast-track protocols allows ICU resources to be concentrated on the increasing number of critically ill patients. Optimal long-term medical therapy, unless contraindicated, includes ASA and lipid-lowering drugs in all patients. In all patients with previous cardiovascular events, beta-blockers and ACE inhibitors are strongly recommended. DAPT potentially has an additional benefit on the venous bypass patency rate. n 1. Serruys PW, Morice MC, Kappetein AP, et al., Percutaneous coronary intervention versus coronary-artery bypass grafting for severe coronary artery disease, N Engl J Med, 2009;360: Friedrich W Mohr, Three-year Outcomes of the SYNTAX Trial: 3VD Subgroup, presentation at Transcatheter Cardiovascular Therapeutics, Sept 21, Task Force on Myocardial Revascularization of the European Society of Cardiology (ESC) and the European Association for Cardio-Thoracic Surgery (EACTS); European Association for Percutaneous Cardiovascular Interventions, Guidelines on myocardial revascularization, Eur J Cardiothorac Surg, 2010;38:S Mohr FW, Rastan AJ, Serruys PW, et al., Impact of complex coronary anatomy in modern bypass surgery? Lessons learned from the SYNTAX trial after two years, J Thorac Cardiovasc Surg, 2011;141(1): Rastan AJ, Walther T, Falk V, et al., Does reasonable incomplete surgical revascularization affect early or long-term survival in patients with multi-vessel coronary artery disease receiving left internal mammary artery to left anterior descending artery bypass?, Circulation, 2009;120:S Sianos G, Morel MA, Kappetein AP, et al., The SYNTAX Score: an angiographic tool grading the complexity of coronary artery disease, EuroIntervention, 2005;1: Valgimigli M, Serruys PW, Tsuchida K, et al., Cyphering the complexity of coronary artery disease using the SYNTAX Score to predict clinical outcome in patients with three-vessel lumen obstruction undergoing percutaneous coronary intervention, Am J Cardiol, 2007;99: Kushner FG, Hand M, Smith SC Jr, et al., 2009 focused updates: ACC/AHA guidelines for the management of patients with ST-elevation myocardial infarction, Circulation, 2009;120: Silber S, Albertsson P, Avilés FF, et al., Guidelines for percutaneous coronary interventions. The Task Force for Percutaneous Coronary Interventions of the European Society of Cardiology, Eur Heart J, 2005;26: Eagle KA, Guyton RA, Davidoff R, et al., ACC/AHA 2004 guideline update for coronary artery bypass graft surgery: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines (Committee to Update the 1999 Guidelines for Coronary Artery Bypass Graft Surgery), Circulation, 2004;110:e Patel MR, Dehmer GJ, Hirshfeld JW, et al., ACCF/SCAI/STS/ AATS/AHA/ASNC 2009 appropriateness criteria for coronary revascularization, J Am Coll Cardiol, 2009;53: Deyell MW, Ghali WA, Ross DB, et al., Alberta Provincial Project for Outcome Assessment in Coronary Heart Disease (APPROACH) Investigators. Timing of nonemergent coronary artery bypass grafting and mortality after non-st elevation acute coronary syndrome, Am Heart J, 2010;159: Cheng DC, Bainbridge D, Martin JE, et al., Evidence-Based Perioperative Clinical Outcomes Research Group, Does off-pump coronary artery bypass reduce mortality, morbidity, and resource utilization when compared with conventional coronary artery bypass? A meta-analysis of randomized trials, Anesthesiology, 2005;102: 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, Innovation, 2005;1: Wijeysundera DN, Beattie WS, 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, 2005;46: Hannan EL, Wu C, Smith CR, et al., Off-pump versus on-pump coronary artery bypass graft surgery: differences in short-term outcomes and in long-term mortality and need for subsequent revascularization, Circulation, 2007;116: Sergeant P, Wouters P, Meyns B, et al., OPCAB versus early mortality and morbidity: an issue between clinical relevance and statistical significance, Eur J Cardiothorac Surg, 2004;25: Sabik JF, Blackstone EH, Lytle BW, et al., Equivalent midterm outcomes after off-pump and on-pump coronary surgery, J Thorac Cardiovasc Surg, 2004;127: Khan NE, De Souza A, Mister R, et al., A randomized comparison of off-pump and on-pump multivessel coronary artery bypass surgery, N Engl J Med, 2004;350: Shroyer AL, Grover FL, Hattler B, et al., Veterans Affairs Randomized On/Off Bypass (ROOBY) Study Group, On-pump versus off-pump coronary-artery bypass surgery, N Engl J Med, 2009;361: Puskas JD, Williams WH, Mahoney EM, et al., Off-pump versus conventional coronary artery bypass grafting: Early and 1-year graft patency rate, cost, and quality-of-life outcomes: A randomized trial, JAMA, 2004;291: Nathoe HM, vandijk D, Jansen EW, et al., A comparison of on-pump and off-pump coronary bypass surgery in low-risk patients, N Engl J Med, 2003;348: 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, 2009;137: 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, 2004;110: Edelman JJ, Yan TD, Padang R, et al., Off-pump coronary artery bypass surgery versus percutaneous coronary intervention: a meta-analysis of randomized and nonrandomized studies, Ann Thorac Surg, 2010;90: Calafiore AM, Giammarco GD, Teodori G, et al., Left anterior descending coronary artery grafting via left anterior small thoracotomy without cardiopulmonary bypass, Ann Thorac Surg, 1996;61: Cremer J, Strueber M, Wittwer T, et al., Off-bypass coronary bypass grafting via minithoracotomy using mechanical epicardial stabilization, Ann Thorac Surg, 1997;63:S Diegeler A, Matin M, Kayser S, et al., Angiographic results after minimally invasive coronary bypass grafting using the minimally invasive direct coronary bypass grafting (MIDCAB) approach, Eur J Cardiothorac Surg, 1999;15: Subramanian VA, McCabe JC, Geller CM., Minimally invasive direct coronary artery bypass grafting: two-year clinical experience, Ann Thorac Surg, 1997;64: Jacobs S, Holzhey D, Falk V, et al., High-risk patients with multivessel disease is there a role for incomplete myocardial revascularization via minimally invasive direct coronary artery bypass grafting?, Heart Surg Forum, 2007;10: Wolf RK, Ohtsuka T, Flege JB Jr, Early results of thoracoscopic internal mammary artery harvest using an ultrasonic scalpel, Eur J Cardiothorac Surg, 1998;14:S Duhaylongsod FG, Mayfield WR, Wolf RK, Thoracoscopic harvest of the internal thoracic artery: a multicenter experience in 218 cases, Ann Thorac Surg, 1998;66: McGinn JT Jr, Usman S, Lapierre H, et al., Minimally invasive coronary artery bypass grafting: dual-center experience in 450 consecutive patients, Circulation, 2009;120:S Mack MJ, Magovern JA, Acuff TA, et al., Results of graft patency by immediate angiography in minimally invasive coronary artery surgery, Ann Thorac Surg, 1999;68: Kettering K, Dapunt O, Baer FM, Minimally invasive direct coronary artery bypass grafting: a systematic review, J Cardiovasc Surg, 2004;45: Gummert JF, Funkat A, Krian A, Cardiac surgery in Germany during 2004: a report on behalf of the German Society for Thoracic and Cardiovascular Surgery, Thoracic Cardiovasc Surg, 2005;53: de Canniere D, Wimmer-Greinecker G, Cichon R, et al., Feasibility, safety, and efficacy of totally endoscopic coronary artery bypass grafting: multicenter European experience, J Thorac Cardiovasc Surg, 2007;134: Holzhey DM, Jacobs S, Mochalski M, et al., Seven-year follow-up after minimally invasive direct coronary artery bypass: experience with more than 1300 patients, Ann Thorac Surg, 2007;83: Holzhey DM, Jacobs S, Walther T et al., Cumulative sum failure analysis for eight surgeons performing minimally invasive direct coronary artery bypass, J Thorac Cardiovasc Surg, 2007;134: Angelini GD, Wilde P, Salerno TA, et al., Integrated left small thoracotomy and angioplasty for multivessel coronary artery revascularisation, Lancet, 1996;347: Holzhey DM, Jacobs S, Mochalski M, et al., Minimally invasive hybrid coronary artery revascularization, Ann Thorac Surg, 2008;86: Lytle BW, Blackstone EH, Sabik JF, et al., The effect of bilateral internal thoracic artery grafting on survival during 20 postoperative years, Ann Thorac Surg, 2004;78: Hayward PA, Gordon IR, Hare DL, et al., Comparable patencies of the radial artery and right internal thoracic artery or saphenous vein beyond 5 years: results from the Radial Artery Patency and Clinical Outcomes trial, J Thorac Cardiovasc Surg, 2010;139: Buxton BF, Hayward PA, Newcomb AE, et al., Choice of conduits for coronary artery bypass grafting: craft or science?, Eur J Cardiothorac Surg, 2009;35: Sabik JF, Stockins A, Nowicki ER, et al., Does location of the second internal thoracic artery graft influence outcome of coronary artery bypass grafting?, Circulation, 2008;118:S Taggart DP, Altman DG, Gray AM, et al., Randomized trial to compare bilateral vs. single internal mammary coronary artery bypass grafting: 1-year results of the Arterial Revascularisation Trial (ART), Eur Heart J, 2010;31: Saso S, James D, Vecht JA, et al., Effect of skeletonization of the internal thoracic artery for coronary revascularization on the incidence of sternal wound infection, Ann Thorac Surg, 2010;89: Svensson LG, Mumtaz MA, Blackstone EH, et al., Does use of a right internal thoracic artery increase deep wound infection and risk after previous use of a left internal thoracic artery?, J Thorac Cardiovasc Surg, 2006;131: Misfeld M, Potger K, Ross DE, et al., Anaortic off-pump coronary artery bypass grafting significantly reduces neurological complications compared to off-pump and conventional on-pump surgery with aortic manipulation, Thorac Cardiovasc Surg, 2010;58: Hilker M, Arlt M, Keyser A, et al., Minimizing the risk of perioperative stroke by clampless off-pump bypass surgery: a retrospective observational analysis, J Cardiothorac Surg, 2010;5: Chiu KM, Chen CL, Chu SH, Lin TY, Endoscopic harvest of saphenous vein: a lesson learned from 1,348 cases, Surg Endosc, 2008;22: Cheng D, Allen K, Cohn W, et al., Endoscopic vascular harvest in coronary artery bypass grafting surgery: a meta-analysis of randomized trials and controlled trials, Innovations, 2005;1: Lopes RD, Hafley GE, Allen KB, et al., Endoscopic versus open vein-graft harvesting in coronary-artery bypass surgery, N Engl J Med, 2009;361: Ouzounian M, Hassan A, Buth KJ, et al., Impact of endoscopic versus open saphenous vein harvest techniques on outcomes after coronary artery bypass grafting, Ann Thorac Surg, 2010;89: Crouch JD, O Hair DP, Keuler JP, et al., Open versus endoscopic saphenous vein harvesting: wound complications and vein quality, Ann Thorac Surg, 1999;68: Patel AN, Henry AC, Hunnicutt C, et al., Endoscopic radial artery harvesting is better than the open technique, Ann Thorac Surg, 2004;78: Aziz O, Athanasiou T, Darzi A, Minimally invasive conduit harvesting: a systematic review, Eur J Cardiothorac Surg, 2006;29: Bleiziffer S, Hettich I, Eisenhauer B, et al., Patency rates of endoscopically harvested radial arteries one year after coronary artery bypass grafting, J Thorac Cardiovasc Surg, 2007;134: Cheng DC, Wall C, Djaiani G, et al., Randomized assessment of resource use in fast-track cardiac surgery 1-year after hospital discharge, Anesthesiology, 2003;98: Ender J, Borger MA, Scholz M, et al., Cardiac surgery fast-track treatment in a postanesthetic care unit: six-month results of the Leipzig fast-track concept, Anesthesiology, 2008;109: Bach J, Kammerer I, Isgro F, et al., The impact of intravenous aspirin administration on platelet aspirin resistance after on-pump coronary artery bypass surgery, Platelets, 2009;20: Gao G, Zheng Z, Pi Y, et al., Aspirin plus clopidogrel therapy increases early venous graft patency after coronary artery bypass surgery a single-center, randomized, controlled trial, J Am Coll Cardiol, 2010;56: EUROPEAN CARDIOLOGY 61