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Ann Thorac Surg 2003;76:444-451
© 2003 The Society of Thoracic Surgeons

Original article: cardiovascular

Is the use of cardiopulmonary bypass for multivessel coronary artery bypass surgery an independent predictor of operative mortality in patients with ischemic left ventricular dysfunction?

Sharif Al-Ruzzeh, FRCSa, Thanos Athanasiou, PhDa, Shane George, FRCAa, Brian E. Glenville, FRCSa, Anthony C. DeSouza, FRCSa, John R. Pepper, FRCSa, Mohamed Amrani, FRCS*a

a The National Heart and Lung Institute, Imperial College of Science, Technology and Medicine, Harefield Hospital, Middlesex, United Kingdom

Accepted for publication February 14, 2003.

* Address reprint requests to Mr Amrani, Department of Cardiac Surgery, Harefield Hospital, Middlesex UB9 6JH, UK
e-mail: mr.amrani{at}rbh.nthames.nhs.uk


   Abstract
Top
 Abstract
Introduction
 Patients and methods
 Results
 Comment
 References
 
BACKGROUND: Coronary artery bypass grafting for patients with ischemic left ventricular dysfunction (ILVD) remains superior to medical therapy in terms of long-term survival. Recently, off-pump coronary artery bypass surgery has been shown to be very promising in achieving functional improvements with favorable operative mortality in this challenging group of patients. The aim of this study was to assess the risk factors responsible for operative mortality in this group of patients.

METHODS: The records of 305 consecutive ILVD patients, who underwent primary isolated coronary artery bypass grafting for multivessel disease at The National Heart and Lung Institute, Imperial College, University of London, between January 1999 and January 2002, were reviewed retrospectively. Patients were considered to have ILVD if they had a left ventricular ejection fraction of 0.30 or less on preoperative coronary angiography. One hundred six patients were operated on using the off-pump coronary artery bypass surgery technique, and 199 patients were operated on using the conventional coronary artery bypass grafting technique with cardiopulmonary bypass.

RESULTS: Seven (6.6%) patients died in the off-pump coronary artery bypass surgery group, whereas 28 (14.1%) patients died in the cardiopulmonary bypass group (p = 0.05). Univariate analysis of all the preoperative characteristics was performed to identify the potential predictors of mortality in the whole group of ILVD patients. Potential predictors of mortality included symptom status (stable/unstable), chronic obstructive airway disease, dyspnea grade III and IV on the New York Heart Association classification, intravenous nitrates, preoperative use of intraaortic balloon pump, ventricular tachycardia or ventricular fibrillation, body surface area less than 2, and cardiopulmonary bypass. Only ventricular tachycardia or ventricular fibrillation was proved to act as an independent predictor of operative mortality in this group of ILVD patients, with an odds ratio of 29.6 (95% confidence interval, 8.9 to 98).

CONCLUSIONS: This study showed that using cardiopulmonary bypass for multivessel coronary artery bypass grafting in patients with ILVD was not proved to act as an independent predictor of operative mortality.


   Introduction
Top
 Abstract
 Introduction
Patients and methods
 Results
 Comment
 References
 
Coronary artery bypass grafting (CABG) for patients with ischemic left ventricular dysfunction (ILVD) remains superior to medical therapy in terms of long-term survival [1–3]. Despite the previously reported high operative mortality in this group of patients [4], CABG still confers a significant reduction in longer-term mortality [5] and protects against future infarction and death even without postoperative improvement in ventricular function [6]. Cardiac transplantation is a valid option for end-stage ILVD but it is limited by a shortage of donor organs and the side effects of long-term immunosuppression [7, 8].

Recently, off-pump coronary artery bypass (OPCAB) surgery, by avoiding the deleterious effects of cardiopulmonary bypass (CPB), has been shown to be very promising in achieving functional improvements with favorable operative mortality in this challenging group of patients [9, 10]. The aim of this study was to assess the risk factors responsible for operative mortality in this group of patients.


   Patients and methods
Top
 Abstract
 Introduction
 Patients and methods
Results
 Comment
 References
 
Clinical data collection
The records of 305 consecutive ILVD patients, who underwent primary isolated CABG for multivessel disease at The National Heart and Lung Institute, Imperial College, University of London, between January 1999 and January 2002, were reviewed retrospectively. Patients were considered to have ILVD if they had a left ventricular ejection fraction of 0.30 or less on preoperative coronary angiography.

Registry database, medical notes, and charts were studied for preoperative and postoperative data of the patients. Analysis of the study patients was originally planned on the basis of intention to treat; however, there was no conversion from OPCAB to CPB in this group, which prevented the possibility of crossover between the two groups. One hundred six patients were operated on using the OPCAB technique, and 199 patients were operated on using the conventional CABG technique with CPB. Patients were selected for the surgical technique, whether OPCAB or CPB, by 4 individual surgeons.

The analyzed preoperative and postoperative variables are defined in Appendix Tables 1 and 2.


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  		Table 1. Preoperative Characteristics

 
Operative technique
Anesthesia was induced using propofol 1 to 2 mg/kg, pancuronium 0.1 mg/kg, and fentanyl 8 to 15 µg/kg. It was maintained by air–oxygen and propofol 2 to 3 mg · kg-1 · h-1. Transesophageal echocardiography was used for additional monitoring as required. For cases performed by OPCAB technique, normothermia was maintained by using warm intravenous fluids, heating mattress, and a humidified airway, in addition to maintaining a warm operating theater. A standby perfusionist with primed bypass circuit was available for all OPCAB cases.

Approach and exposure
A standard midline sternotomy incision is used to expose the heart. The pericardium is opened using an inverted T-shaped incision after the harvest of the internal thoracic arteries. Opening the right pleural space creates a space for the rotated and vertically placed heart to minimize hemodynamic compromise when performing the operation off pump. This is followed by an evaluation of the status of the coronary arteries and the required lengths of the conduits.

Cardiopulmonary bypass technique
Anticoagulation was achieved using 250 U/kg of heparin. The activated clotting time was maintained greater than 480 seconds. Heparin was reversed by protamine at the end of the procedure. Cardiopulmonary bypass was instituted with a single right atrial cannula and an ascending aorta perfusion cannula. Standard bypass management included membrane oxygenators, arterial line filters, nonpulsatile flow of 2.4 L · min-1 · m-2 with a mean arterial blood pressure greater than 50 mm Hg. Myocardial protection was achieved mainly by intermittent antegrade cold blood cardioplegia (4:1 blood to crystalloid ratio). Retrograde blood cardioplegia was used occasionally in addition, particularly if there was left main stem disease with tight right coronary artery stenosis, which might cause inadequate delivery of the cardioplegia to the targeted myocardium and consequently incomplete myocardial protection.

Off-pump coronary artery bypass grafting technique
Anticoagulation was achieved using 150 U/kg of heparin. The activated clotting time was maintained greater than 250 seconds. The heart is stabilized using either the Octopus III (Medtronic, Minneapolis, MN) or CTS tissue stabilizer (Cardio-Thoracic Systems, Cupertino, CA). One deep pericardial retraction suture is placed at the posterior fibrous pericardium very close and medial to the most proximal part of the inferior vena cava. It acts as a lever that helps the surgeon manipulate and rotate the heart to vertical and lateral positions along with the stabilizer. The detailed technique of exposure and stabilization has been recently reported [11].

Statistical analysis
Patient preoperative characteristics and postoperative complications and mortality were compared using Fisher’s exact test or {chi}2 test when appropriate, and p values of equal to or less than 0.05 indicated a significant difference. Preoperative variables were compared by univariate analysis with regard to the effect on 30-day mortality, and those proved to be significant (ie, p <= 0.05) were included in the logistic regression multivariate analysis for 30-day mortality to determine the independent predictors of mortality in the whole group of ILVD patients. We performed a multivariate analysis for the calculation of the propensity score for mortality including all the risk factors. We also added the surgeon as a categorical variable (with the first surgeon as a reference) to cover for the difference among the 4 surgeons, and the year of the operation as another categorical variable (with the year 1999 as a reference) to account for the subtle improvements that are constantly being introduced into coronary surgical techniques and also for the learning curve phenomenon. The variable CPB was excluded from the propensity score analysis as previously practiced and recommended [12, 13]. After completion of the propensity model, a propensity score for mortality was calculated from the logistic equation for each patient. Then, on this basis, patients were sorted by propensity and compared within five quintiles [12].

The statistical analysis addressed confounding factors (patient selection) by use of a propensity score and heterogeneity (risk factors) by multivariate risk factor analysis.


   Results
Top
 Abstract
 Introduction
 Patients and methods
 Results
Comment
 References
 
Preoperative characteristics
The preoperative characteristics are presented in Table 1. The CPB group included significantly more female patients, whereas the OPCAB group included significantly more patients with hypertension and hypercholesterolemia. However, the two groups had similar percentage of patients with preoperative high-risk profiles, ie, Parsonnet score more than 10. The two groups had similar degrees of coronary disease (2.9 ± 0.48 vessels for OPCAB and 2.9 ± 0.36 vessels for CPB, p = 1) and similar degrees of left ventricular function impairment (left ventricular ejection fraction = 21.9% ± 1.2% for CPB and 21.6% ± 1.8% for OPCAB; p = 0.12). The mean age of the OPCAB patients was 59.4 ± 8.3 years, whereas the mean age for the CPB patients was 58.2 ± 6.2 years (p = 0.16). None of the study patients had significant valvular disease including mitral regurgitation on preoperative echocardiography or angiography.


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  		Table 1. Preoperative Characteristics

 
Operative data
There was no significant difference in the number of grafts between both groups. The OPCAB patients received 2.96 ± 1.1 grafts whereas the CPB patients received 3.13 ± 0.76 grafts (p = 0.1). For the CPB patients the cumulative bypass time was 70.15 ± 26.01 minutes and the cumulative aortic cross-clamp time 29.89 ± 21.88 minutes. The grafts used included left internal thoracic artery in 89.2%, right internal thoracic artery in 37.4%, radial artery in 24.7%, and saphenous vein in 48.5%. There were no sequential grafts constructed, and no endarterectomy was performed on the grafted coronary arteries. The distribution of distal anastomoses to the various vascular territories of the heart was not significantly different between the two groups and is presented in Table 2.


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  		Table 2. Distribution of Distal Anastomoses Among the Various Vascular Territories of the Hearta

 
Postoperative outcome
Postoperative morbidity and mortality are presented in Table 3. Seven (6.6%) patients died in the OPCAB group, whereas 28 (14.1%) patients died in the CPB group (p = 0.05). The 7 OPCAB deaths included 5 cardiac and 2 neurologic deaths. The 28 CPB deaths included 20 cardiac, 3 neurologic, 2 respiratory failure, and 3 septicemia leading to multiorgan failure. The 5 OPCAB cardiac deaths included 1 caused by confirmed myocardial infarction and 4 caused by worsening heart failure with development of pulmonary edema, whereas the 20 CPB cardiac deaths included 4 caused by confirmed myocardial infarction and 16 caused by worsening heart failure with the development of pulmonary edema. All mortality figures represent 30-day mortality. None of the postoperative complications showed a significant difference in direct comparison between the two groups. The mortality data for each of the surgeons are presented in Table 4.


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  		Table 3. Postoperative Morbidity and Mortality

 

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  		Table 4. Surgeon-Specific Mortality

 
Univariate analysis of all the preoperative characteristics was performed (Table 5), to identify the potential predictors of mortality in the whole group of ILVD patients. Any of the preoperative factors that showed a significant p value equal to or less than 0.05 was considered a potential predictor of mortality, and these included symptom status (stable/unstable), chronic obstructive airway disease (COAD), dyspnea grade III and IV on New York Heart Association classification, intravenous nitrates, the preoperative use of intraaortic balloon pump, body surface area less than 2, ventricular tachycardia or ventricular fibrillation, and CPB. Of the eight factors, only ventricular tachycardia or ventricular fibrillation was proved to act as independent predictor of mortality in this group of ILVD patients and accounted for a 29-fold increase in the odds of operative mortality (Table 6).


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  		Table 5. Univariate Analysis of All Preoperative Characteristics With Regard to 30-Day Mortality

 

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  		Table 6. Logistic Regression Analysis of Potential Predictors of 30-Day Mortality

 
The regression model to calculate the propensity score was created (Table 7) and was validated by Hosmer and Lemeshow test ({chi}2=5.72, degrees of freedom, 8, p = 0.68). The risk-adjusted mortality, according to the calculated propensity score, did not reach statistical significance in any of the five quintiles (Table 8).


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  		Table 7. Variables Used To Develop the Propensity Score for 30-Day Mortality

 

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  		Table 8. Propensity Score Analysis

 

   Comment
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
References
 
This study shows that the occurrence of ventricular tachycardia or ventricular fibrillation in the perioperative period of multivessel CABG in patients with ILVD is associated with an almost 29-fold increase in the odds of operative mortality. Furthermore, it shows that the preoperative presence of COAD and unstable symptom status and the use of CPB may increase the odds of operative mortality, but none of the three was proved to act as an independent predictor of mortality in this data set as their confidence intervals straddle the value [1].

There is an increasing prevalence of moderate to severe ILVD in patients referred for CABG because of widespread use of thrombolysis, increased operations in patients with recent acute myocardial infarction, and angioplasty, which may delay surgical intervention until coronary arteriosclerosis is more extensive and ILVD more severe, which means these surgical patients are at much higher risk than before [14]. A significant risk factor for mortality in ILVD patients is the arrhythmic death, in which ventricular tachycardia occurs first and then degenerates into fatal ventricular fibrillation. Coronary artery bypass grafting appears to abolish this almost completely by reperfusing the ischemic myocardial areas that are the prime triggers of this fatal arrhythmia [5].

Cardiopulmonary bypass was a significant variable in the univariate analysis but was not proved to be an independent predictor of mortality in the multivariate analysis. Although OPCAB produces local or regional ischemia, CBP with cross-clamping produces global ischemia that proves to be detrimental in ILVD patients who have minimal cardiac reserve to rely on. Indeed, left ventricular segmental wall motion has been found to be better in patients who underwent beating heart operations, compared with CPB [15]. Furthermore, the noncardioplegic fibrillating heart on CPB without cross-clamping was shown to have a better blood supply to the subendocardium and interventricular septum [16], leading to improved myocardial preservation [17], and this concept appears more in OPCAB in terms of more preservation of the septal wall motion [18].

Interestingly, in our study there was no difference in the average number of total grafts between the two groups, which denies the possibility of incomplete revascularization in the OPCAB patients that was previously suggested by others and allows for better matching and comparison of the two patient groups [19]. Furthermore, the absence of difference in the distribution of distal anastomoses to the various vascular territories of the heart reduces possible bias that could be involved in the selection of the procedure.

There were no rigid set criteria for the use of intraaortic balloon pump, and they were generally used in patients demanding high doses of inotropic agents preoperatively or those who had a failed attempt of angioplasty. The use of intraaortic balloon pump in our study patients, 14%, is less than half the rate of use of intraaortic balloon pump in another study, 30%, where it was found to be very rewarding in terms of reducing operative mortality significantly [20]. In our study it was a significant risk factor of mortality in the univariate analysis, but we think that this is an indication of probably having a high threshold of using intraaortic balloon pump late when the patient condition has irreversibly deteriorated, because it was shown before that a more liberal preoperative use reduced the 30-day mortality [21].

In contrast to previous studies on the possible risk factors for mortality in ILVD patients operated on using CPB [22, 23], demonstrating that congestive heart failure as represented by grade III/IV New York Heart Association class was responsible for a twofold increase in the odds of mortality, we could not demonstrate a similar result in our logistic regression model built on one third being OPCAB patients and two thirds being CPB patients. However, New York Heart Association grade III/IV was still significantly more prevalent in the patients who died as shown in the univariate analysis.

Interestingly, COAD showed up as significant variable in the univariate but not the multivariate analysis. One explanation for this finding is the immediate intraoperative swelling of impaired edematous left ventricle, particularly when CPB is used, which becomes compressed mechanically by the emphysematous COAD lungs and consequently fails acutely when the chest is closed at the end of the operation.

This probably explains the exceptionally excellent results that others achieved when they followed a systematic protocol that included, among other things, delayed sternal closure to the second or third postoperative day, when the heart has become less edematous and can accommodate chest closure [20]. Another possible explanation, at a cellular level, would be the impaired oxygenation in the COAD lungs, leading to a critical level of hypoxia that might cause more damage to myocardial muscle cells in an edematous impaired heart with limited or no reserve.

We do not routinely perform preoperative viability studies on ILVD patients to decide on their operability. We are rather more concerned with the practicality of operating on these patients, in terms of finding graftable coronary vessels that can be targeted. This is owing to several reasons: first, the previously suggested principle of the importance of flow–metabolism mismatch [24] in decision making was partially antagonized by finding a lesser degree of functional improvement when there was no such mismatch present [25]. Second, even patients who did not experience functional improvement in their left ventricular ejection fraction as predicted by their preoperative viability studies still experienced less risk of infarction and death [6]. Finally, cardiac transplantation remains a valid option and can be offered at a later stage if clinical improvement does not occur after CABG [26]. However, the lack of availability of these preoperative viability data on this group of patients is a limitation of this study.

The apparent high overall mortality in this ILVD patient group (11%) could be explained by the fact that almost 40% of the patients underwent nonelective surgery with an average Parsonnet score of 11% and average ejection fraction of 0.21. In addition, other relatively highly prevalent comorbid conditions in the study group included a high percentage of female patients, diabetic patients, and patients with COAD. Despite all these factors the overall mortality still compared favorably to previously reported series including those of Kaul and associates (24%) and Milano and colleagues (11%) [3, 27]. Furthermore, the OPCAB subgroup mortality (6.6%) compared more favorably to other studies, including Christakis and coworkers (9.8%) and Baumgartner and colleagues (8%) [4, 28].

Indeed, the study is limited by its retrospective nonrandomized, nonblinded design, although every effort was made to minimize the potential selection bias by applying the concepts of multivariate and propensity score analyses.


   Appendix
 


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  		Table 2. Postoperative Morbidity

 

   References
Top
 Abstract
 Introduction
 Patients and methods
 Results
 Comment
 References
 
  1. [No authors listed] Effect of enalapril on survival in patients with reduced left ventricular ejection fraction and congestive heart failure. The SOLVD Investigators. N Engl J Med 1991;325:293–302
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