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Ann Thorac Surg 2002;74:2106-2112
© 2002 The Society of Thoracic Surgeons

Original article: cardiovascular

Analysis of mortality within the first six months after coronary reoperation

Frans M. van Eck, MDa, Luc Noyez, MD, PhDa*, Freek W.A. Verheugt, MD, PhDb, Rene M.H.J. Brouwer, MD, PhDa

a Department of Thoracic and Cardiac Surgery, Heart Center, University Medical Center, St. Radboud, Nijmegen, The Netherlands
b Department of Cardiology, Heart Center, University of Nijmegen Medical Center, St. Radboud, Nijmegen, The Netherlands

Accepted for publication June 27, 2002.

* Address reprint requests to Dr Noyez, Department of Thoracic and Cardiac Surgery Heart Center, University of Nijmegen Medical Center, St. Radboud, P.O. Box 9101, 6500 HB Nijmegen, The Netherlands.
e-mail: l.noyez{at}thorax.umcn.nl


   Abstract
Top
 Abstract
Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 
BACKGROUND: Identify risk factors associated with mortality following repeat coronary revascularization (redoCABG) within the first 6 months following surgery.

METHODS: Five hundred forty-one redoCABG patients (1987 to 1998) were studied by univariant and multivariant analysis. Mortality was assessed at three different points: hospital mortality (A) (36/541, 6.7%); mortality at 6 months (C) (75/541, 13.9%); and outpatient perioperative mortality, which is a death occurring from the time of hospital discharge to 6 months postoperatively (B) (39/541, 7.2%).

RESULTS: Diabetes, hypertension, peripheral vascular disease, renal insufficiency, lung disease, myocardial infarction (MI) before the first operation, MI between the first and redoCABG, lack of sinus rhythm, no IMA graft, acute/emergency operation, perfusion time, and perioperative MI were all identified as risk factors related to early mortality. MI before the first operation, antegrade cardioplegia, and the time period 1987 to 1992 all influenced hospital mortality (A). Diabetes, hypertension, renal insufficiency, lung disease, and valvular heart disease all influenced the outpatient mortality up to 6 months. Independent predictive factors for early mortality were: age more than 69 years; diabetes; vascular insufficiency; chronic lung disease; MI between first and redoCABG; no IMA-graft; acute preoperative MI; emergency operation; perfusion time; perioperative MI; and the time period 1987 to 1992. Risk factors for in-hospital death included MI between the first and redoCABG, cardiopulmonary bypass time, and the time period 1987 to 1992. Diabetes is an important risk factor during the outpatient perioperative phase. Emergency surgery and perioperative MI predict mortality regardless of the time period (A, B, or C).

CONCLUSIONS: Early mortality after redoCABG is influenced by many variables during the first 6 months following surgery. Understanding these factors and their time course may better help to assess the true risk associated with reoperation for recurrent coronary insufficiency.


   Introduction
Top
 Abstract
 Introduction
Material and methods
 Results
 Comment
 Acknowledgments
 References
 
Mortality after coronary reoperations (redoCABG) is still higher than for the initial revascularization procedure (CABG). Several studies have attempted to analyze operative, 30-day, and hospital mortality following coronary reoperations [1–8]. In reviewing these studies, there is no consensus as to predictors of early mortality. The purpose of the present study is to identify risk factors for early mortality within the first 6 months following redoCABG, and also to analyze those risk factors and patient characteristics that may be associated with an increased risk following repeat revascularization.


   Material and methods
Top
 Abstract
 Introduction
 Material and methods
Results
 Comment
 Acknowledgments
 References
 
Patients
The Coronary Surgery Database at Radboud Hospital (CORRAD), a registry that stores pre-, peri-, and postoperative follow-up data on all patients undergoing isolated coronary bypass surgery at the University Medical Center St. Radboud, Nijmegen (UMC St. Radboud) was used to identify 541 patients undergoing a first coronary reoperation (redoCABG) from January 1987 to December 1998. All patients underwent isolated coronary revascularization. No patients with combined procedures were included. A number of different variables were analyzed and are presented in Table 1. A 6-month period of follow-up was selected. The information placed in our database is based on data from cardiologists, family doctors, and an annual survey sent directly to the patients. In addition a cross-sectional follow-up was performed in the first months of 2000. This follow-up was performed by a survey sent directly to the patients. If there was no response from the patient, the information was traced by telephone contact with the patient, family, doctor, or government records. The 6-month follow-up in this study was 100%. In case of death, the cardiologist, family doctor, or patient’s family was contacted to identify the cause of death.


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  		Table 1. Variables Analyzed in Patients Undergoing Reoperative Coronary Artery Bypass

 
Perioperative and six-month mortality
Hospital mortality (A) was defined as an operative death or mortality at the University Hospital anytime during the hospitalization for the redo coronary artery bypass. Six-month mortality (C) was defined as all mortality within the first 6 months from the time of surgery. This is consistent with the early phase mortality described by Blackstone [9]. Blackstone’s study only describes mortality up to 6 months following the operation. In addition, we defined outpatient perioperative mortality as the difference between the hospital- and 6-month mortality (B).

Discharge policy
Patients are either sent home or transferred to the referring cardiac center from UMC. St. Radboud Nijmegen. Patients are not discharged or transferred unless they are ambulatory and require minimal levels of care. The mean hospital stay the UMC St. Radboud for redoCABG is 10 days. Patients with postoperative complications such as wound problems remain at UMC St. Radboud until they are ambulatory and require minimal care. Thus patients who died in the perioperative period were all in good condition and functioning at the time they were discharged from the UMC St. Radboud center. In the 541 patients studied, all hospital deaths occurred within the first 5 months after surgery. None of the deaths occurring during the postdischarge perioperative period died after transfer to their referring cardiac center and thus would not be considered a hospital death directly related to the surgery.

Surgical technique
Our surgical technique has been described previously [7, 8]. It is important to note that since 1993 cardioplegia has been delivered using retrograde techniques in redoCABG procedures. Of the 541 patients, 230 (42%) patients had antegrade, and 305 patients (67%) had retrograde delivery of their cardioplegia. Six other patients (1%) were operated without cardioplegic arrest (intermittent aortic cross-clamping; two patients, off-pump, four patients).

The mean bypass time was 140 ± 60.8 minutes (range 25 to 485), and the mean duration of aortic cross-clamping was 70 ± 33.6 minutes (range 10 to 227). There were 2.4 ± 0.8 grafts (range 1 to 5), per patient, and 3.2 ± 1.2 (range 1 to 7) distal anastomoses. On average, 1.0 ± 0.6 (range 1 to 2) arterial grafts were used in the patients, and resulted in 1.2 ± 0.9 (range 1 to 5) distal anastomoses. 428 patients (79.1%) received at least one new arterial graft.

Statistical analysis
To test which variables were associated with increased perioperative risk and six-month mortality, a Fischer’s exact test (univariant analysis) was used. Multiple logistic regression analysis was used to identify risk factors that independently predicted an increased or decreased risk of death. A p value of 0.05 or less was considered significant. All mortality data are presented with 95% confidence interval (CI).


   Results
Top
 Abstract
 Introduction
 Material and methods
 Results
Comment
 Acknowledgments
 References
 
The overall risk for hospital, perioperative, and 6-month mortality is 36/541 (6.7%, 95% CI 4.6 to 6.8), 39/541 (7.2%, 95% CI 5.1 to 9.3), and 75/541 (13.9%, 95% CI 11.0 to 16.8 respectively). Cardiovascular causes were the reasons for mortality at 6 months in 64 patients (85%) [10].

Univariant analysis
The results of the univariant analysis are presented in Table 2. Risk factors for hospital mortality (A) include: peripheral vascular pathology (p = 0.04) myocardial infarction (p = 0.02) myocardial infarction between initial CABG and redoCABG (p = 10-4) no IMA graft (p = 0.05) operative status (p = 0.003) perfusion time >= 120 minutes (p = 0.001) antegrade delivery of cardioplagia (p = 0.008) perioperative myocardial infarction (p = 7.10-6) and the earlier time period 1987 to 1992 (p = 0.003).


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  		Table 2. Univariant Analysis of Variables

 
Risks for perioperative outpatient mortality (B) include: diabetes (p = 10-7) hypertension (p = 0.002) peripheral vascular disease (p = 10-5) renal insufficiency (p = 0.01), pulmonary disease (p = 3.10-6) infarction between initial CABG and redoCABG (p = 0.04) no IMA graft (p = 0.03) operative status (p = 10-7) mild valvular disease (p = 0.04) perfusion time >= 120 minutes (p = 0.04), and perioperative myocardial infarction (p = 2.10-8).

Risk factors for six-month mortality (C) include: diabetes (p = 10-4) hypertension (p = 0.03) peripheral vascular disease (p = 10-5) renal insufficiency (p = 0.02) pulmonary disease (p = 3.10-5) myocardial infarction (p = 0.003) myocardial infarction between initial CABG and redoCABG (p = 2.10-5) cardiac rhythm other than sinus (p = 0.03) occluded IMA graft (p = 0.003) operative status (p = 8.10-12) mild valvular heart disease (p = 0.02) perfusion time >= 120 minutes (p = 6.10-5) and perioperative myocardial infarction (p = 2.10-14).

Multivariant analysis
Table 3 illustrates the results of the multiple logistic regression analysis. For hospital mortality (A) a myocardial infarction (p = 0.003), the time period of surgery 1987 to 1992 (p = 0.002), emergency operation (p = 10-4), perfusion time >= 120 minutes (p = 0.03), a perioperative myocardial infarction (p = 0.003) are all identified as independent variables predicting hospital death. For patients, their outpatient perioperative mortality (B) was predicted by diabetes (p = 0.0005), pulmonary disease (p = 0.02), emergency operation (p = 0.001), and perioperative myocardial infarction (p = 10-4).


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  		Table 3. Multivariant Risk Analysis

 
Predictors for 6-month mortality (C) include: age more than 69 years (p = 0.05) diabetes mellitus (p = 0.008) peripheral vascular disease (p = 0.02) pulmonary disease (p = 0.02) myocardial infarction between initial CABG and redoCABG (p = 0.002) occluded IMA graft (p = 0.04) and also the time period of surgery 1987 to 1992 (p = 0.007). Independent perioperative variables include: acute MI (p = 0.05) emergency operation (p = 10-4), perfusion time 120 minutes (p = 0.007) and perioperative myocardial infarction (p = 10-4).


   Comment
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
Acknowledgments
 References
 
Redo coronary bypass surgery is known to be high-risk surgery. High mortality and morbidity rates are described in several reports [1–8]. This study is focused on mortality within the first 6 months following operation. The choice for this time interval is based on the work of Blackstone [9], who describes a prolonged early phase in high-risk patients. Several clinical studies have also highlighted the importance of analysis of this period [11, 12]. Hospital mortality is defined as any death occurring during their hospitalization at the UMC St. Radboud where the patient underwent redoCABG. Thus hospital mortality included not only surgical deaths, but also patients who died after a complicated postoperative recovery. All hospital deaths are included. The perioperative outpatient mortality is the period between hospitalization and 6 months. This includes all patients who died after discharge from the UMC St. Radboud. All of these patients were in good condition at the time of discharge from the UMC St. Radboud. An event then occurred within the first 6 months after their redoCABG that lead to their death. It is important to note that none of these patients died after transfer to their referring cardiac center, which would have to have been considered as part of their hospitalization. A number of variables were selected for study, but the list was not all-inclusive. Certain variables such as left ventricular function, identified as a predictor for hospital and late mortality in several reports [1, 3, 4] were not included because the data were not available in our database. Ejection fraction is not routinely calculated for all patients, except for those with severe decrease in their left ventricular function. Seven patients had a documented ejection fraction lower than 30%. Because of the limited number of patients with documented, impaired left ventricular function, we excluded this variable in our analysis. Myocardial infarction may influence left ventricular function and survival, thus infarction before the initial CABG and infarction occurring between the initial procedure and the reoperation are included. The presence of a patent IMA graft is included in our analysis however, the patency and the degree of disease in old vein grafts is not. Perioperative variables such as lack of graft material and completeness of revascularization during redoCABG are also not included in this analysis.

Over the study period, the percentage of redoCABG’s increased from 10% in 1987 to 12% in 1998. In this study, only patients who had isolated myocardial revascularization at both operations were included. Our hospital mortality of 6.7% and 6-month mortality of 12.9% is comparable with other reports [1–6]. The finding of an additional 7.2% perioperative outpatient mortality is alarming and confirms for the first time the importance of a longer follow-up period for the evaluation of early mortality in high-risk patients [9, 11, 12]. Simply looking at hospital mortality may not give an accurate picture as to a patient’s true risk after a complicated procedure.

Looking at the univariant analysis of these patients, we have found that their hospital mortality is influenced by the presence of peripheral vascular disease, myocardial infarction between the initial operation and redo, and occluded IMA grafts, operative status (emergency vs elective), ECC time >= 120 minutes, antegrade delivery of cardioplegia, occurrence of perioperative myocardial infarction, and also the time period of their surgery 1987 to 1992.

Several factors also help define the mortality at 6 months. The presence of diabetes, hypertension, peripheral vascular disease, renal insufficiency, pulmonary disease myocardial infarction between operations, lack of sinus rhythm, no IMA grafts, operative status (emergency vs elective), mild valvular disease, time on cardiopulmonary bypass, perioperative myocardial infarction, and the time period 1987 to 1992 all were associated with increased mortality.

Most of these same variables have been identified as risk factors for mortality in previous reports [1–6]. In these reports, however, there are different definitions of mortality as it relates to the procedure. With our distinction between hospital and six-month mortality, we see the importance of different risk factors during the first 6 months. By looking at perioperative mortality, we have been able to look at three distinct time periods within the first 6 months. The importance of the identified risk factors is demonstrated in Table 4. Vascular disease, as a mirror of the extent of arteriosclerosis for the patient, myocardial infarction and subsequent myocardial infarction after the first CABG, as well as the influence of ventricular function, are all important predictors of hospital mortality. The presence of a patent IMA graft has been shown to decrease the mortality and morbidity of redo surgery [8, 13, 14]. The importance of a patent IMA graft is further illustrated by reports that show that an injury to a patent IMA graft increases mortality [13]. The importance of retrograde cardioplegia is well known [6], and it seems logical that the influence of operative myocardial protection is reflected in the hospital mortality. The effect of a prolonged period of cardiopulmonary bypass (>= 120 minutes) may be relative; a technically difficult operation often leads to a longer pump time. Patients with difficulty in coming off of bypass may also have a longer pump time. Thus, the influence of prolonged extracorporeal circulation time may be related to other factors that increase extracorporeal circulation time and not the time per se. The fact that patients operated on before 1992 had an increased risk is likely due to improved myocardial protection and retrograde cardioplegia, as well as more experience with redo operations by our group. The influence of an emergency operation, and the presence of a perioperative myocardial infarction are both important risks, and have been confirmed by several others [1–7]. This report, however, also demonstrates that the influence is not only on hospital mortality, but also for the early six-month mortality (emergency/acute operations, perioperative myocardial infarction) and is balanced over the whole first 6 months (early postdischarge mortality for emergency procedures and perioperative myocardial infarction). In coronary artery bypass graft surgery, unstable angina is an incremental risk factor for death during the early hazard phase [11]. No IMA grafts have a balanced influence, however, of lesser importance. The influence of initial myocardial infarction and perioperative myocardial infarction between operations, cardiopulmonary bypass time (>= 120 minutes, on the 6-month mortality seems to be a consequence of their importance on the hospital mortality. On the other hand, the influence of vascular disease, mild valvular heart disease, on the 6-month mortality is related to the early perioperative mortality. Diabetes, hypertension, renal insufficiency, and pulmonary disease are indicated as risk factors for 6-month mortality, but their influence is mainly in the early discharge perioperative mortality. The way of delivery of cardioplegia, and the time the operation was performed does not seem to be related to the 6-month mortality. The absence of sinus rhythm, however, is a significant risk factor for the 6-month mortality, but not for the hospital mortality, and for early discharge perioperative mortality; however, there is a trend toward significance. The limited number of patients without sinus rhythm undergoing a redo operation (6%) is probably a reason that significance is not reached in the outpatient perioperative mortality.


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  		Table 4. Risk Factors Related to Mortality (Univariant and Multivariant Analysis), After First Redo-Coronary Artery Bypass, and the Phase in Which They Exert Their Effect

 
Multivariant analysis
Multivariant analysis identified age more than 69 years, diabetes, peripheral vascular disease, pulmonary disease, myocardial infarction between operations, no IMA grafts, time period 1987 to 1992, emergency operations, cardiopulmonary bypass time >= 120 minutes, and perioperative myocardial infarction as independent risk factors for early six-month mortality. As in the univariant analysis, there are differences in these factors during the first 6 months following surgery (Tables 2 and 3). Age more than 69 years, peripheral vascular disease, no IMA grafts, and emergency surgery were all significant predictors for six-month mortality, with a spread risk over the whole time period. Diabetes and pulmonary disease, however, were important in the early outpatient perioperative period, and did not appear to influence mortality in the immediate postoperative period. Acute myocardial infarction between operations, the time period 1987 to 1992, and the ECC time influenced the inpatient mortality. The same factors that may have affected the prolonged extracorporeal circulation time that were discussed in the univariant analysis also apply to the multivariant analysis as well. Emergency operations and a perioperative myocardial infarction are, however, the strongest independent risk factors for early mortality for both the hospital and the outpatient perioperative mortality. It seems strange that the way of delivery of cardioplegia is not identified as an independent predictor of hospital mortality. This is of interest because of the time period 1987 to 1992 was significant. The use of retrograde cardioplegia has increased since 1992 and since 1993, cardioplegia is delivered in a retrograde fashion predominantly. Since the time period 1987 to 1992 appears to be an independent predictor for early six-month mortality, especially for hospital mortality, means that factors not incorporated in this risk analysis, related to the time cohort, are important. Growing surgical experiences in period 1993 to 1998 may be part of the explanation. Most of the redoCABG’s were performed by one surgeon (LN), the changing profile of the patient population [15], and completeness of revascularization are all possible variables. Another possibility is that retrograde delivery of cardioplegia alters the occurrence of a perioperative myocardial infarction, which is an independent predictor of hospital outpatient perioperative and six-month mortality. Renal disease, identified in several reports as an independent predictor [4, 5], was not identified as an independent risk factor in our analysis. However, renal disease has an odds ratio of 2.8 for early mortality, indicating a higher risk for these patients. That we did not reach statistical significance is probably related to the limited number of patients with renal disease (6.6%) in our series.

The aim of this study was to identify risk factors for early 6-month mortality. Therefore, statistical analysis in this study is limited to a univariant and multivariant analysis. The finding that different variables, or the same variables, have a different importance at different times as a risk factor for early six-month mortality is the conclusion of the study. At the same time there is also the confirmation of the mortality rates when the early outpatient perioperative mortality is superimposed on the hospital mortality. This fact may be helpful in counseling surgeons and patients about the true risk of redo coronary bypass surgery, and eventually allow the construction of models that may allow for a reduction of mortality. These models, however, would be limited to preoperative variables and will not likely include perioperative ones, such as cardiopulmonary bypass times, or completeness of revascularization during the reoperations [10].

In conclusion, the present study emphasizes that early mortality after a redo coronary artery surgery is influenced by several variables at different times. Insight into this time-related influence of variables associated with an increased risk may explain the different results of risk analysis in several reports and help point out factors that contribute to death soon after surgery, and death that occurs after hospital discharge. Emergency operation and the occurrence of a perioperative myocardial infarction, however, are the crucial independent risk factors for early mortality after redo surgery.


   Acknowledgments
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
References
 
The authors thank Johannes A. M. van Druten, PhD, Department of Medical Informatics, Epidemiology and Statistics at the University of Nijmegen, for the statistical analysis; Dr Eric N. Robertson, Anesthesiologist, for his correction of the English text; and Dr David M. Follette for language editing this manuscript.


   References
Top
 Abstract
 Introduction
 Material and methods
 Results
 Comment
 Acknowledgments
 References
 

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