Adverse clinical consequences associated with conventional coronary artery bypass (CCAB) surgery have largely been attributed to cardiopulmonary bypass circuit (CPB), hypothermic cardiac arrest, aortic cannulation and cross-clamping. Consequently, there has been a growing interest in safer alternatives to CCAB, including off-pump beating heart bypass surgery (OPCAB, see Figure 1). Since the introduction of OPCAB for coronary artery disease, numerous studies have been published to evaluate the impact of OPCAB surgery compared with CCAB. However, subsequent prospective randomised studies and meta-analyses comparing OPCAB and CCAB surgery were performed on low-risk patients or mixed-risk populations. Due to underpowered design for infrequent complications, they usually failed to demonstrate a significant benefit of OPCAB surgery on early mortality and peri-operative major cardiac and cerebrovascular events. In recent years, further efforts have been made to elucidate the meaning of beating-heart concepts for patients with specific extra-cardiac and cardiac risk factors for extracorporeal circulation and cardioplegic arrest. In this article current study evidence on varying subsets of patients is summarised.
Patients with Specific Extra-cardiac Morbidity
Advanced Age
In a meta-analysis including seven non-randomised studies and 1,672 patients with advanced age (mostly >80 years of age), 30-day mortality was 4.1% for OPCAB surgery compared with 5.6% for CCAB, without reaching statistical significance.1 However, in this analysis a significant reduction of peri-operative stroke rate (6.6% versus 1.0%), blood transfusion requirement (76.6% versus 47.8%), post-operative new onset of atrial fibrillation (45.9% versus 30.4%) and peri-operative intra-aortic balloon pump insertion (9.5% versus 1.5%) was demonstrated for the OPCAB approach.
Diabetes Mellitus
No early survival benefit could be found in three retrospective, risk-adjusted studies when using OPCAB in diabetic patients.2–4 In two of these studies the peri-operative stroke rate was significantly reduced. This was also shown by Puskas and co-workers in their meta-analysis on 2,478 diabetic patients, finding a stroke rate of 1.0% for OPCAB and 2.1% for CCAB surgery.1 In this meta-analysis post-operative atrial fibrillation was also reduced for OPCAB. In a propensity score-adjusted analysis on diabetic patients, Magee also found a significant lower rate of blood transfusion requirement and post-operative new onset of renal replacement therapy.3
Female Gender
In a retrospective analysis of 16,871 female patients from 78 cardiac surgery units in North America, Brown and colleagues quoted a reduced peri-operative mortality of 3.1% for OPCAB compared with 3.9% for CCAB surgery. In a risk-adjusted mortality analysis they found a 42% increase in mortality for CCAB operation, however, without finding other significant differences in peri-operative complications.5 Similar to these results, in a propensity score-matched study of 7,932 women, CCAB surgery was associated with a 73% increase in operative mortality and a 47% increased risk of post-operative bleeding.6
Chronic Obstructive Pulmonary Disease
Three randomised and non-randomised studies on a limited number of patients (n=37–76) with pre-operative chronic obstructive pulmonary disease (COPD) are now available. All of them demonstrate a trend towards reduced ventilation time and lower pulmonary complications when using OPCAB strategies.7–9 In a meta-analysis of these studies, no significant benefit on peri-operative mortality and severe morbidity was evident. However, pulmonary complications were 12.5% in the CCAB patients and thus more frequent than in the OPCAB patients, where no pulmonary complications were recognised.1
Pre-operative Renal Insufficiency
For patients with chronic renal insufficiency stage II and III, a meta-analysis of four observational studies including 643 patients could not give evidence for a survival benefit for OPCAB patients compared with cardioplegic arrest coronary artery bypass surgery.1 In contrast to these results, most of the studies on dialysis-dependent patients demonstrated a reduced peri-operative mortality for OPCAB surgery.10,11 In other single-centre studies on patients with pre-operatively impaired renal function a significantly reduced peri-operative stroke rate9,12,13 and blood transfusion rate9,12 was shown for OPCAB patients. It remains unclear whether or not the OPCAB approach is associated with a reduced incidence of post-operative dialysis in patients with pre-operatively compensated renal dysfunction. In most of the studies focusing on that problem, a lower rate of post-operative renal failure is reported when avoiding cardiopulmonary bypass circulation;1,9,12,13 however, these findings were not confirmed in a propensity score-adjusted analysis of 632 patients.14
Additive EuroSCORE >5 and Multi-risk Patients
No randomised studies are available comparing OPCAB and CCAB surgery in patients with generally increased peri-operative risk. The interpretation of the currently available observational studies is limited because of varying definitions of risk status. A EuroSCORE more than 5 additive points is a commonly used risk criterion, but other surgical risk scores as well as the presence of more than one cardiac or extracardiac risk factor are also commonly applied to classify multi-risk patients. In a meta-analysis of five studies including 2,545 patients with a EuroSCORE >5 and a further nine studies in 10,374 multi-risk patients, a significantly reduced mortality was found for OPCAB surgery. For patients with a EuroSCORE >5, 30-day mortality was 2.6% for OPCAB compared with 7.1% for CCAB, whereas for multirisk patients 30-day mortality was also 2.6% for CCAB but 3.8% for CCAB surgery.1 In the same meta-analysis, stroke rate (0.5% versus 1.6%), post-operative onset of atrial fibrillation (15.9% versus 21.9%), blood transfusion rate (34.5% versus 55.1%), incidence of intra-aortic balloon pump support (1.2% versus 3.4%), rethoracotomy (1.8% versus 2.8%) and pulmonary complication rate (4.6% versus 7.7%) were significantly lower for OPCAB than for CCAB.
Patients with Atherosclerotic Thoracic Aorta
Atherosclerotic and calcified degeneration of the ascending thoracic aorta bears a high risk of aortic wall injury and plaque embolisation during aortic cannulation and cross-clamping. Thus, it is supposed that OPCAB approach strongly reduces these risks by reducing aortic manipulation. This theoretical advantage was confirmed in two Doppler studies demonstrating a dramatically higher cerebral microembolisation rate during CCAB operations compared with OPCAB surgery.15,16 In a case-control clinical study of patients with severely diseased atherosclerotic aorta, OPCAB was associated with a significantly reduced peri-operative mortality (3.8 versus 11.4%) and stroke rate (2.4 versus 4.7%) compared with conventional coronary artery bypass surgery.17
Patients with Specific Cardiac Morbidity
Patients with Severely Reduced Left Ventricular Function
Patients with pre-operatively reduced left ventricular function are at higher risk of post-operative low-cardiac output syndrome requiring inotropic or mechanical circulatory support. OPCAB advocates assumed that, particularly in poor ventricles, the preservation of global native myocardial perfusion during OPCAB surgery would help to minimise peri-operative myocardial injury and, consequently, low cardiac output syndrome.
In contrast, OPCAB antagonists expected an increased haemodynamic compromise during tilting these bad hearts leading to higher rate of OPCAB failure and conversion to heart-lung machine operations. Concerning the latter, it was recently shown that tilting the heart was comparably well tolerated in patients with reduced left ventricular function.18 In recent years several comparative studies on patients with reduced ejection fraction of 30–40% were published without reporting conversion rate in most of them. These studies demonstrated a trend towards lower peri-operative mortality for OPCAB compared with CCAB patients, but without reaching statistical significance.19–21 In a meta-analysis of nine studies and 3,223 patients with an ejection fraction of 30–40%, the 30-day mortality was 3.8% for OPCAB surgery and significantly lower than the 6.9% found for CCAB patients. This analysis also revealed an OPCAB benefit concerning post-operative renal failure, blood transfusion requirement and peri-operative inotropic support.1 Some other surgeons reported a reduced stay on intensive care unit (ICU) because of lower ventilation time for OPCAB patients.19,20 During long-term follow-up no difference was found between OPCAB and CCAB.21 In the authors’ centre a total of 364 patients with a severely reduced left ventricular ejection fraction ≤20% were operated on during a six-year study period. For these patients, significantly reduced peri-operative mortality and comparable long-term results were found.
Patients with Cardiac Reoperation
The value of OPCAB surgery for cardiac reoperations has not yet been well evaluated. Mack and co-workers reported a hospital mortality rate of 2.3% in 86 consecutive OPCAB patients.22 Conversion rate to cardiopulmonary bypass was 5.7%. Two of four non-randomised studies comparing OPCAB and CCAB surgery for this subset of patients demonstrated an early survival benefit for OPCAB patients;23,24 however, that could not be found in the others.25,26 In all four studies a lower rate of blood transfusion, reduced intensive care unit (ICU) stay and reduced ventilation time was found. It is of note that OPCAB revascularisation seems to be associated with a lower number of distal coronary anastomoses and thus to an increasing number of incomplete revascularisations compared with conventional bypass surgery.26 Although until now there has been no clear evidence that incomplete revascularisation is associated with impaired long-term survival in redo patients, it remains questionable whether OPCAB surgery is a meaningful alternative for redo coronary revascularisation.
Patients with Significant Left Main Stem Stenosis
Based on haemodynamic and functional considerations, it is less reasonable to identify coronary left main stenosis as a special risk factor for OPCAB surgery. Nevertheless, only six non-controlled comparative studies, including a total of 1,126 left main patients, are published to date. In five of these, perio-perative mortality and long-term survival were comparable between OPCAB and CCAB surgery.27–31 One study demonstrated a peri-operative mortality of 1.9% for OPCAB that was significantly lower than the 6.4% found for CCAB patients.32 All of six studies revealed a lower rate of blood transfusion and peri-operative inotropic support. For OPCAB surgery a benefit concerning ventilation time29,30,32 and hospital stay was also reported.29,31
Emergency Patients with Acute Coronary Syndrome
Peri-operative mortality and morbidity in patients with acute coronary syndrome (ACS) requiring emergency operation within the first hours after admission is increased several-fold compared with elective coronary bypass surgery. Particularly in patients with acute coronary events, the preservation of native coronary perfusion and avoidance of ischaemic cardioplegic cardiac arrest could be helpful to reduce myocardial oedema, no-reflow phenomenon and myocardial necrosis. Thus, in the late 1990s two small OPCAB series on patients with acute myocardial infarction (MI) were reported.33,34 Nevertheless, only a few non-randomised, retrospective OPCAB/CCAB studies on these challenging patients are available so far and data interpretation is limited because of varying definitions of emergency status.35–40 In most of these studies hospital mortality was comparable between OPCAB and conventional bypass surgery,35,36,38–40 although there was a trend to reduced mortality for OPCAB surgery. Locker and colleagues reported a significantly lower hospital mortality in a total of 225 patients with acute MI when operating on the beating heart.37 Regarding peri-operative morbidity, OPCAB compared with CCAB was advantageous regarding peri-operative MI,38 peri-operative intra-aortic balloon pump,35,40 rethoracotomy,39,40 peri-operative inotropic support,38,39 acute renal failure,1,35,40 stroke rate,39 ICU and total hospital stay.35,36,38–40
Between January 2000 and September 2005 a total of 531 patients (374 CCAB and 157 OPCAB) with haemodynamically stable ACS were operated on at the Heart Center Leipzig within 12 hours of onset of symptoms. Peri-operative mortality and major cardiac and cerebrovascular event rate as well as long-term results were comparable between both operative strategies. However, a benefit for OPCAB patients concerning post-operative inotropic support, drainage loss, re-exploration rate, blood transfusion rate, total ventilation time, stroke rate and ICU and hospital stay was demonstrated.39
Patients with Cardiogenic Shock
For patients with ischaemic cardiogenic shock, Hochman and co-workers demonstrated a significant survival benefit for early myocardial revascularisation.41 If surgical revascularisation is indicated, additional myocardial injury cannot be fully avoided when using cardioplegic arrest. In contrast, beating heart coronary artery bypass strategies preserve native coronary blood flow and thus avoid additional cardioplegic arrest injury in these hearts. Besides, beating heart revascularisation allows faster revascularisation of the culprit lesion vessel.39 However, in the majority of cardiogenic shock patients connection of cardiopulmonary bypass is indicated to guarantee adequate organ perfusion and to support cardiac recovery on the deloaded heart.39 However, an on-pump beating heart coronary revascularisation strategy for the highest risk patients is a new concept and experiences are limited so far.42,43 Between January 2000 and September 2005 a total of 107 cardiogenic shock patients were operated on at the Leipzig Heart Center, 83 on the beating heart. For beating heart surgery patients, a significantly reduced hospital mortality, as well as a significant reduction of inotropic support, post-operative atrial fibrillation, acute renal failure and sternal wound complications, was found. Long-term follow-up demonstrated a trend to longer survival in beating heart surgery patients.39 Based on these results, on-pump beating heart coronary revascularisation today is the routine approach for emergency revascularisation of cardiogenic shock patients at the authors’ institution.
Conclusion
Several mono- and multicentre studies are currently available for patients with specific cardiac or extra-cardiac co-morbidities. Even if most of them were non-randomised and thus failed to reach American Heart Association (AHA)/American College of Cardiology (ACC) evidence level A, they still allow analysis of interim results for each specific peri-operative risk factor. Particularly multi-risk patients and patients with severely reduced left ventricular function seem to benefit in terms of peri-operative mortality and major morbidity by avoiding cardiopulmonary bypass and cardioplegic arrest. Moreover, for most patients with significant extra-cardiac risk factors the incidence of peri-operative stroke was reduced. In patients with pre-operative renal and pulmonary dysfunction a decrease of corresponding organ failure can be assumed for OPCAB strategy. For most risk populations, transfusion requirements were significantly lower in OPCAB compared with CCAB surgery. In none of the patient subsets could an unfavourable early outcome of beating heart surgery compared with CCAB be shown. For emergency patients with ACS presenting stable and unstable haemodynamics, a clinical benefit was found by using beating heart strategies. However, these patients seemed to profit by avoiding global cardiac ischaemia and maintaining native coronary blood flow. Follow-up results were comparable for these patients. In conclusion, beating heart coronary artery bypass grafting seems to be advantageous in various risk populations and should be considered for patients with more than average risks for cardiopulmonary bypass and cardioplegic arrest.