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Ann Thorac Surg 2008;86:1147-1152. doi:10.1016/j.athoracsur.2008.05.037
© 2008 The Society of Thoracic Surgeons
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Original Articles: Adult Cardiac

Immediate and Intermediate Outcome After Off-Pump and On-Pump Coronary Artery Bypass Surgery in Patients With Unstable Angina Pectoris

Fausto Biancari, MD, PhD*, Muhammad Ali Asim Mahar, MBBS, Martti Mosorin, MD, Jouni Heikkinen, MD, PhD, Matti Pokela, MD, PhD, Panu Taskinen, MD, PhD, Vesa Anttila, MD, PhD, Jarmo Lahtinen, MD, PhD, Martti Lepojärvi, MD, PhD

Division of Cardiothoracic and Vascular Surgery, Department of Surgery, Oulu University Hospital, Oulu, Finland

Accepted for publication May 15, 2008.

* Address correspondence to Dr Biancari, Division of Cardio-thoracic and Vascular Surgery, Department of Surgery, Oulu University Hospital, P.O. Box 21, Oulu, 90029, Finland (Email: faustobiancari{at}yahoo.it).


   Abstract
Top
 Abstract
Introduction
 Material and Methods
 Results
 Comment
 References
 
Background: We have evaluated the immediate and intermediate outcome after off-pump (OPCAB) and conventional on-pump coronary artery bypass surgery (CCAB) in patients with unstable angina pectoris requiring nitrates infusion until arrival in the operating room.

Methods: A consecutive series of 153 and 161 patients with unrelenting angina pectoris underwent CCAB and OPCAB, respectively. Conversion from OPCAB to beating heart surgery with perfusion occurred in 4 patients.

Results: The OPCAB patients had a significantly higher operative risk than CCAB patients (logistic European System for Cardiac Operative Risk Evaluation [EuroSCORE]: 13.8 ± 12.8% vs 10.5 ± 10.0%, p = 0.005). In the overall series, a lower 30-day postoperative mortality was observed among OPCAB patients (1.9% vs 3.9%, p = 0.33), the difference increased along the logistic EuroSCORE tertiles (upper tertile: 3.2% vs 9.5%, p = 0.14), but failed to reach statistical significance. Similar results have been observed among one-to-one propensity score matched pairs. The results of three surgeons who treated most of their patients (96.9%) with OPCAB were compared with those of three surgeons who used, in most of cases (97.1%), the CCAB technique. When adjusted for logistic EuroSCORE, patients operated on by CCAB surgeons had a significantly higher 30-day postoperative mortality (7.1% vs 2.1%, p = 0.04; odds ratio [OR] 10.143; 95% confidence interval [CI] 1.084 to 94.945) as well as a higher risk of combined adverse events (47.1% vs. 35.1%, p = 0.009; OR 2.586; 95% CI 1.274 to 5.250).

Conclusions: This study provided further evidence on the safety and efficacy of OPCAB in the treatment of high-risk patients. A dedicated approach to OPCAB seems to provide particularly good results. Such findings further support a more confident approach with OPCAB in these patients.


   Introduction
Top
 Abstract
 Introduction
Material and Methods
 Results
 Comment
 References
 
Controversies still exist whether off-pump coronary artery bypass surgery (OPCAB) provides better immediate and long-term results over conventional on-pump coronary artery surgery (CCAB). Beside possible relevant differences in technical aspects and surgeon and anesthesiologist approach to OPCAB, a comparative analysis of results of OPCAB and CCAB is complicated by possible heterogeneity in the study populations. There is some evidence showing that high-risk patients are those who may most benefit from OPCAB 1–4. Previously we have observed in our early experience with OPCAB that this technique can provide similar results to CCAB in patients with additive European System for Cardiac Operative Risk Evaluation (EuroSCORE) 6 or greater [5]. One of the major limitations of any comparative analysis is that patients with unstable hemodynamics possibly, and more likely, are treated with CCAB rather than with OPCAB. In order to compare these two techniques in patients with high operative risk, but with stable hemodynamics, we have reviewed our experience in the treatment of patients who required urgent or emergent coronary artery bypass surgery because of unstable, refractory angina pectoris requiring nitrates infusion upon arrival to the operating room.


   Material and Methods
Top
 Abstract
 Introduction
 Material and Methods
Results
 Comment
 References
 
Off-pump coronary artery bypass surgery was introduced as an alternative to CCAB at our institution in 1996. Since 2003, OPCAB progressively has been used in a larger amount of patients with increased operative risk. From January 2003 to September 2007, 2,641 patients underwent isolated coronary artery bypass surgery. Of these, 315 patients (11.9%) had nitrates infusion until arrival in the operating room because of unrelenting angina pectoris with or without signs of myocardial infarction. One-hundred and fifty-three patients underwent CCAB and 161 underwent OPCAB. One patient, at the beginning of the study period, underwent planned beating-heart operation on perfusion without cardiac arrest and he was excluded from the analysis. The inclusion criteria of nitrates infusion at arrival have been chosen as this clearly indicates a high-risk status, but categorically excludes those patients with a markedly unstable hemodynamic status.

Clinical characteristics and operative data are summarized in Table 1. Clinical variables were defined according to the EuroSCORE criteria [6]. Stroke risk was assessed by the Northern New England Cardiovascular Disease Study Group scoring method [7]. The prevalence of OPCAB operations for unstable angina pectoris significantly increased along the years (2003: 34.9%; 2004: 48.4%; 2005: 54.1%; 2006: 56.9%; 2007: 63.0%, p = 0.026).


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  		Table 1 Clinical and Operative Data on Patients Who Underwent Isolated Off-Pump and On-Pump Coronary Artery Bypass Surgery
 
The decision to perform either OPCAB or CCAB was made by the surgeon based on his preferred technique and patient's conditions. Among the 13 surgeons who operated on these patients, 3 surgeons treated most of patients (96.9% of 97 patients: 3 patients have been operated by a junior surgeon, and CCAB approach at that time was suggested to him by an assisting senior surgeon) with the OPCAB technique and another 3 surgeons employing (in most of the patients) (97.1% of 70 patients) the CCAB technique. The other surgeons were variably using both techniques. The decision about the vessels to be revascularized was made by the operating surgeon, thus it might vary according to surgeon's revascularization philosophy. In all patients the revascularization was assumed to be complete according to angiographic and operative findings. During OPCAB, in case of target vessels considered not "reachable" by the standard technique, the procedure is always converted to heart beating surgery on perfusion without aortic cross-clamping.

Myocardial infarction was diagnosed preoperatively on the basis of electrocardiogram findings in addition to troponin I levels. Epiaortic ultrasound examination was performed based on surgeon's choice. Heparin (3.0 mg/kg) was administered intravenously after sternotomy to maintain an activated clotting time of more than 400 seconds, and it was neutralized at the end of the procedure by using protamine sulfate (3.0 mg/kg). Intermittent antegrade and retrograde cold blood cardioplegia was used during CCAB. Proximal anastomoses were sutured to the aorta during cross-clamping, when the latter was considered safe. Aortic side clamping was used only during OPCAB. Octopus and Starfish stabilizers (Medtronic, Minneapolis, MN) as well as intracoronary shunts were routinely used in patients who underwent OPCAB.

Hemodynamic instability during OPCAB was treated by changing the patient's position (Trendelenburg position) and by administering noradrenaline. ß-blockers were given only in case of tachycardia. Dobutamin and levosimendan are given in patients with severe hemodynamic instability. Since April 2004, enoxaparin (40 mg to 60 mg once-a-day) was administered postoperatively in patients with atrial fibrillation and progressively in all patients according to their weight.

Statistical Analysis
Statistical analysis was performed using SPSS statistical software (SPSS v. 15.0.1; SPSS Inc, Chicago, IL). Continuous variables are reported as the mean ± standard deviation. The Pearson test, the Fisher exact test, Kruskall-Wallis test, and the Mann-Whitney test were used for univariate analysis. Logistic regression with the use of backward selection was performed to calculate the risk of these patients to be assigned either OPCAB or CCAB study group. Only variables with a p less than 0.20 have been included into the regression model. The receiver operating characteristic (ROC) curve analysis was used to estimate the area under the curve of the model predicting the probability of assignment to any of the study groups. The calculated propensity score was employed for one-to-one matching. Matching between OPCAB and CCAB pairs has been done according to a difference in the propensity score less than 0.005. Intermediate outcome was assessed by the Kaplan-Meier method. Logistic regression was used for multivariate analysis. A p value less than 0.05 was considered statistically significant.


   Results
Top
 Abstract
 Introduction
 Material and Methods
 Results
Comment
 References
 
Overall Results
Nine patients (2.9%) died during the 30-day postoperative period. Two patients died on the same operation day after CCAB of cardiac failure. In the other patients, low cardiac output syndrome (4 patients), pneumonia (4 patients), stroke (3 patients), sepsis (3 patients), and ventricular fibrillation (1 patient) were causes of immediate postoperative death. Other postoperative complications as well as intermediate outcome in the study groups are summarized in Table 2. It is worth noting the higher operative risk of patients who underwent OPCAB as indicated by significantly higher additive and logistic EuroSCOREs. Most of relevant preoperative variables, but cardiac index, were more frequently encountered among OPCAB patients. The higher preoperative cardiac indexes observed among OPCAB patients are, anyway, likely related to a more frequent use of inotropes before operation in this study group. The OPCAB patients had notably a higher prevalence of history of previous percutaneous coronary intervention, particularly during the same in-hospital stay-same day of coronary surgery.


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  		Table 2 Immediate and Late Outcome After Isolated Off-Pump and On-Pump Coronary Artery Bypass Surgery in Patients With Unstable Angina Pectoris
 
In 4 patients (2.5%) OPCAB was converted to heart beating surgery with perfusion without aortic cross-clamping because of hemodynamic instability. None of these patients died in the immediate postoperative period and they did not suffer major complications after surgery, except one patient who experienced postoperative sepsis.

In the overall series, a lower, but statistically nonsignificant 30-day postoperative mortality rate was observed among OPCAB patients. This difference increased along with logistic EuroSCORE tertiles, but failed to reach statistical significance (Fig 1).


Figure 1
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  		Fig 1. Thirty-day mortality rates per each tertile of logistic EuroSCORE after CCAB and OPCAB (p = 0.14). (Light grey column = CCAB; dark grey column = OPCAB; CCAB = conventional coronary artery bypass surgery; EuroSCORE = European System for Cardiac Operative Risk Evaluation; OPCAB = off-pump coronary artery bypass surgery.)

 
Similar outcomes were observed in the study groups. A significantly larger number of blood cell units were transfused to patients who underwent CCAB. A higher rate of postoperative stroke was observed among patients who underwent OPCAB, but they had a higher stroke risk (Table 1).

Postoperative stroke occurred in 9 patients. In 3 patients the day of occurrence of stroke was unclear because of unconsciousness. In one patient stroke occurred immediately after surgery, in another stroke occurred late on the first postoperative day, and in 4 patients later on (on the 3rd, 5th, 11th, and 16th postoperative day, respectively). Three of these patients died during the immediate postoperative period.

In one patient complete blindness of the right eye occurred on the 13th postoperative day and another developed partial blindness of the right eye on the 10th postoperative. Both patients had preoperatively atrial fibrillation and one of them suffered a massive myocardial infarction preoperatively. They had also, postoperatively, neuropsychologic disturbances.

Because not all surgeons performed epiaortic ultrasound in these patients, this prevented us from performing a more detailed analysis of this severe complication. Furthermore, only after April 2004 have we progressively administered heparin after surgery. This has led to a decrease of postoperative stroke rate (6.0% to 1.7%, p = 0.06), but has made the series even more heterogeneous for possible analysis. At 4-year follow-up, both CCAB and OPCAB patients had a similar, satisfactory overall survival rate approaching 90%.

Propensity Score Analysis
According to logistic regression, patient age, preanesthesia induction cardiac index, and previous percutaneous coronary intervention were independent risk factors associated with assignment to OPCAB versus CCAB groups (Hosmer-Lemeshow: p = 0.308). The area under the ROC curve for the calculated propensity score (0.626, 95% CI 0.564 to 0.687, standard error 0.031, p < 0.0001) was significant, but not optimal. Despite several attempts, we did not achieve a better propensity score, probably because of the large imbalance in the operative risk, which was in favor of CCAB patients. Despite the imbalance in the operative risk persisted after one-to-one matching, the OPCAB patients had a somewhat lower 30-day postoperative mortality rate. They required a significantly less amount of red blood cell units. On the other hand OPCAB patients had significantly longer intensive care unit stay, likely because of a significantly higher prevalence of critical preoperative status (Table 1). Similarly, OPCAB had a higher stroke rate, which likely correlated with their increased Northern New England Cardiovascular Disease Study group stroke risk.

OPCAB Surgeons Versus CCAB Surgeons
In order to assess the impact of OPCAB surgery experience on the outcome of these patients, we have compared the results of three surgeons treating most of patients (96.9%) with OPCAB technique with those of three surgeons employing, in most of patients (97.1%), the CCAB technique.

The 30-day postoperative mortality (2.1% vs 7.1%, p = 0.13), the risk of resternotomy for bleeding (4.1% vs 11.4%, p = 0.13), the risk of stroke (3.1% vs 7.1%, p = 0.28), the amount of red blood cell units (1.9 ± 2.5 vs 3.7 ± 4.9, p = 0.004), length of stay in intensive care unit (3.5 ± 4.8 vs 3.9 ± 5.0, p = 0.25), and combined adverse postoperative events (30-day mortality, stroke, low cardiac-output, acute renal failure requiring dialysis,and intensive care unit stay ≥ 5 days) (35.1% vs 47.1%, p = 0.11) were in favor of OPCAB surgeons, but, with the exception of transfused red blood cells, failed to reach statistical significance. However, patients operated by OPCAB surgeons had a significantly higher operative risk (mean additive EuroSCORE: 8.5 ± 3.3 vs 7.5 ± 2.5, p = 0.043; mean logistic EuroSCORE: 14.3 ± 13.7% vs 9.9 ± 7.6%, p = 0.041). When adjusted for logistic EuroSCORE, patients operated on by CCAB surgeons had a significantly higher risk of 30-day postoperative mortality (p = 0.04; OR 10.143; 95% CI 1.084 to 94.945) as well as a higher risk of combined adverse events (p = 0.009, OR 2.586; 95% CI 1.274 to 5.250).


   Comment
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
References
 
An important finding of this study is the satisfactory outcome achieved by surgical revascularization among these patients with such a particularly high operative risk. The rather low postoperative mortality and morbidity rates herein observed certainly do not facilitate a comparative analysis of OPCAB and CCAB techniques and they prevent definitive conclusions on this controversial issue. This study confirms the findings of recent observations about the safety and efficacy of OPCAB, particularly in high-risk patients [1–4], and provides a background for further advances in beating heart surgery.

The main difficulty in analyzing these data was the heterogeneity of the OPCAB and CCAB population, as OPCAB patients had a markedly higher EuroSCORE. A propensity score analysis and matching had eliminated some, but not all, imbalances between these groups, and showed similar immediate and intermediate results. Indeed, of particular relevance is the finding of similar intermediate results despite higher operative risk among OPCAB patients. In fact, we have previously shown that EuroSCOREs significantly and markedly affect the long-term outcome [8].

Among the imbalances, we have observed a lower number of distal anastomoses in the OPCAB, which may speak against this technique and its value in achieving a complete revascularization. First, the OPCAB surgeon's revascularization strategy might have limited revascularization only to target vessels with hemodynamically significant stenoses. Second, the difference in the amount of distal anastomoses seems to be more statistical than clinical as most of the recent series [1, 4, 9] reports on the mean number of distal anastomoses in CCAB patients inferior (2.8 to 3.4) to the one herein reported in OPCAB patients (3.5). Third, in our institution we do not accept the concept of incomplete revascularization. The amount of distal anastomoses is based on angiographic and operative findings, and coronary arteries eventually "not graftable" during OPCAB, in our opinion, absolutely impose a conversion to heart beating surgery with perfusion or even to CCAB.

We have herein observed that the immediate outcome may significantly differ when patients are treated by surgeons employing mostly OPCAB or CCAB. We do not believe that the reason for this resides in differences between surgeon's skills, but rather in the technique employed. In fact, in our institution surgeons devoted almost exclusively to CCAB are very experienced, senior surgeons with recognized excellent results in all adult cardiac operations. On the contrary, among OPCAB surgeons there was a junior cardiac surgeon. However, it seems that the approach to operate on all patients requiring coronary artery bypass surgery using beating heart technique may pay off by the continuous experience in employing this technique. This may eventually lead to the development of the individual approach of the surgeon in dealing with technical aspects unique to beating heart surgery. Indeed, contrary to CCAB, OPCAB is far from being a standardized technique. Beyond the controversy about the use and type of stabilizers, coronary shunts and pericardial sutures, the approach in handling the beating heart clearly differs from surgeon to surgeon. Patience and gentleness in manipulating the beating heart are not strictly synonymous of the technical skills of the cardiac surgeon, but are of fundamental importance during OPCAB. Similarly, also the anesthesiologist's approach and her/his interaction and cooperation with the surgeon during OPCAB greatly contribute to optimize the results of OPCAB. However, these aspects are not easily quantifiable and this may account for the lack of a univocally "statistically significant" evidence of the benefits of avoiding cardiopulmonary bypass in coronary surgery.

In conclusion, this study provided further evidence on the safety and efficacy of OPCAB in the treatment of high-risk patients. A dedicated approach to OPCAB seems to provide particularly good results. Such findings further support a more confident approach with OPCAB in these patients.


   References
Top
 Abstract
 Introduction
 Material and Methods
 Results
 Comment
 References
 

  1. 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;116:1145-1152.[Abstract/Free Full Text]
  2. Oo AY, Grayson AD, Patel NC, Pullan DM, Dihmis WC, Fabri BM. Is off-pump coronary surgery justified in EuroSCORE high-risk cases. A propensity score analysis. Interact Cardiovasc Thorac Surg 2003;2:660-664.[Abstract/Free Full Text]
  3. Darwazah AK, Abu Sham'a RA, Hussein E, Hawari MH, Ismail H. Myocardial revascularization in patients with low ejection fraction ≤ 35%: effect of pump technique on early morbidity and mortality J Card Surg 2006;21:22-27.[Medline]
  4. Rastan AJ, Eckenstein JI, Hentschel B, et al. Emergency coronary artery bypass graft surgery for acute coronary syndrome: beating heart versus conventional cardioplegic cardiac arrest strategies Circulation 2006;114(1 suppl):I477-I485.[Medline]
  5. Lahtinen J, Biancari F, Rimpiläinen J, et al. Off-pump versus on-pump coronary artery bypass surgery in high-risk patients (EuroSCORE ≥ 6) Thorac Cardiovasc Surg 2007;55:13-18.[Medline]
  6. Roques F, Nashef SA, Michel P, et al. Risk factors and outcome in European cardiac surgery: analysis of the EuroSCORE multinational database of 19030 patients Eur J Cardiothorac Surg 1999;15:816-823.[Abstract/Free Full Text]
  7. Charlesworth DC, Likosky DS, Marrin CA, et al. Development and validation of a prediction model for strokes after coronary artery bypass grafting Ann Thorac Surg 2003;76:436-443.[Abstract/Free Full Text]
  8. Biancari F, Kangasniemi OP, Luukkonen J, et al. EuroSCORE predicts immediate and late outcome after coronary artery bypass surgery Ann Thorac Surg 2006;82:57-61.[Abstract/Free Full Text]
  9. Cheng DC, Bainbridge D, Martin JE, Novick RJ. 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;102:188-203.[Medline]



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