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(Chest. 2004;125:56-62.)
© 2004 American College of Chest Physicians

Long-term Beneficial Effect of Coronary Artery Bypass Grafting in Patients With COPD*

Benjamin Medalion, MD; Michael G. Katz, MD; Amram J. Cohen, MD, FCCP; Eli Hauptman, MD; Lior Sasson, MD and Arie Schachner, MD

* From the Department of Cardiothoracic Surgery, The Edith Wolfson Medical Center, Holon, Israel.

Correspondence to: Benjamin Medalion, MD, Department of Cardiothoracic Surgery, The Edith Wolfson Medical Center, POB 5, Holon, 58100, Israel; e-mail: medalion{at}wolfson.health.gov.il


   Abstract
TOP
 Abstract
Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
Objective: This study assesses the impact of COPD on the long-term outcome of patients undergoing coronary artery bypass grafting (CABG).

Methods: Between 1991 and 1993, 37 patients (5.68%) undergoing CABG had significant clinical COPD. They were compared to 37 matched control subjects.

Results: The patients in the COPD group had worse preoperative pulmonary function. More patients in this group were smokers, had more symptoms of shortness of breath, and had more preoperative arrhythmia. A total of 13 patients died in the COPD group compared with 3 subjects in the control group during 8.6 ± 2 years (mean ± SD) of follow-up with arrhythmia being the major cause of death (62%). Actuarial survival at 9 years was 92% for the control group vs 65% for the COPD group (p = 0.005). The rate of readmissions during mid-term follow-up (13.8 ± 7.2 months) was higher in the COPD group, and more patients in this group described their quality of life as worse than before the operation (37% vs 3%, p < 0.001). At late follow-up, all survivors in the COPD group had an improved quality of life. Cox regression analysis identified older age and lower FEV1 as independent predictors of late death. Pulmonary function returned to baseline in the control group and improved to above baseline in the patients with COPD.

Conclusions: Patients with significant COPD have a higher risk after CABG compared to patients without COPD. Nevertheless, when assessing the natural history of patients with COPD, it seems those who undergo CABG benefit from the operation.

Key Words: COPD • coronary artery bypass grafting • myocardial revascularization


   Introduction
TOP
 Abstract
 Introduction
Materials and Methods
 Results
 Discussion
 Conclusions
 References
 
COPD has been shown to be associated with both higher mortality and morbidity rates following coronary artery bypass grafting (CABG).1 2 3 4 5 6 7 In our previous studies, we have shown that clinical COPD was a significant factor for increased morbidity and mortality immediately after CABG and during the first postoperative year. The quality of life at that time was also reduced, and a significant proportion of the morbidity and mortality was due to postoperative arrhythmia.1 Patients who underwent CABG with reduced FEV1 were at risk for prolonged intubation, and early extubation followed by reintubation further increased morbidity and mortality in this cohort of patients.8

The purpose of this report is to describe the long-term follow-up of patients with significant COPD who underwent CABG, to compare them to matched control subjects, and to assess their survival relative to the natural history of patients with COPD who did not undergo CABG.


   Materials and Methods
TOP
 Abstract
 Introduction
 Materials and Methods
Results
 Discussion
 Conclusions
 References
 
Between June 1991 and June 1993, 37 of 651 patients undergoing CABG at our institution were defined as having significant COPD (COPD group). The definition of significant COPD included the following: (1) active treatment and follow-up in the pulmonary clinic for COPD, and (2) the symptomatology of the COPD had to be dominant or codominant to the symptomatology of the ischemic heart disease according to the referring physician. The 37 patients were compared to 37 control subjects matched for age, sex, ejection function, and date of operation (control group). For this study, heavy smoking was defined as > 15 cigarettes per day for > 5 years.

The groups were evaluated for preoperative, operative, and acute postoperative course. All patients or their families were contacted between July 1 1993, and August 1, 1993 (mid-term follow-up, 13.8 ± 7.2 months [mean ± SD]). All survivors were evaluated as to their clinical course, which included a history of readmissions and their causes, a questionnaire to assess their quality of life, chest radiographs, and pulmonary function tests where possible. The time of death and cause of death during early and mid-term follow-up were recorded, as previously reported.1

The surviving patients of both groups were analyzed again in our clinic at a mean late follow-up of 8.6 ± 2 years. For patients who died during follow-up, the date and cause of death were recorded. The data were analyzed for both long-term results of patients with significant COPD after CABG, as well as to identify predictors for their adverse outcomes.

Statistical Analysis
Data were assessed by univariate analysis (t test, {chi}2, or Fisher exact test when appropriate). Receiver operating curve (ROC) analysis was used in order to ascertain the relation between low FEV1 and COPD. Cox multivariable analysis method was used for late events. Deaths from all causes were considered in the actuarial analysis and included early death. Statistical significance was defined as p < 0.05.


   Results
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
Discussion
 Conclusions
 References
 
Preoperative and operative characteristics of both groups were previously described.1 Selected preoperative and operative characteristics are presented in Table 1 . There were more smokers, more patients with symptoms of shortness of breath, and a higher prevalence of preoperative arrhythmia in the COPD group.


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  		Table 1.. Selected Preoperative and Operative Characteristics*

 
Survival
In the control group, there were a total of three deaths, all of them during the late follow-up period. One patient had a cardiac death, the second patient died of brain stroke, and the third patient died of cancer. In the COPD group, a total of 13 patients died after the operation. Two patients died in the early postoperative period, three patients died during mid-term follow-up, while another eight patients died during the late follow-up period. Arrhythmia or sudden death, assumed to be secondary to arrhythmia, was the major cause of death in 8 of 13 patients in the COPD group. In the remaining five patients, three patients died of respiratory complications and two patients died of other causes. Kaplan-Meyer survival curves are shown for the two groups in Figure 1 . The survival was significantly better for the control group compared to the COPD group (p = 0.005). Univariate analysis associated the following preoperative measures with death following surgery: age >= 70 years, hypertension, arrhythmia, shortness of breath, triple vessel or left main disease, COPD, and FEV1 <= 1.25 L (Table 2 ). Multivariable Cox regression analysis identified only older age and lower FEV1 as independent risk factors for death. These predictors appeared significant when used as continuous variables and when used as grouped variables in a separate model (Table 3 . Figures 2 , 3 show Kaplan-Meyer survival curves stratified by age and FEV1, respectively.



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  		Figure 1.. Overall survival for the COPD and control groups.

 

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  		Table 2.. Univariable Analysis of Death for Selected Preoperative Characteristics*

 

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  		Table 3.. Risk Factors for Death Identified by Multivariable Analysis

 


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  		Figure 2.. Overall survival for the study and control groups stratified by age.

 
Pulmonary Function
Since FEV1 turned to be an independent predictor for long-term survival, and since patients in the COPD group were not selected solely on the basis of low FEV1, a ROC analysis was performed to ascertain that in this study FEV1 indeed had the power to discriminate between patients in the COPD group and the control group. The area under the ROC was calculated to be 0.97 with a 95% confidence interval of 0.92 to 1. For FEV1 <= 1.77 L, the sensitivity and specificity of FEV1 as predictors of belonging to the COPD group were 90% and 100%, respectively.

Preoperative, mid-term, and late FEV1 and FVC are shown for the two groups in Figure 4 , top. Patients with COPD had significantly worse FEV1 and FVC at all time points measured. At mid-term follow-up, the control group showed mildly decreased pulmonary function compared to baseline, which returned to baseline at late follow-up. In contrast, compared to baseline, the COPD group showed a significant worsening of pulmonary function at mid-term, which improved at late follow-up to significantly above baseline. This pattern was also present when only survivors of the COPD group were analyzed (Fig 4 , bottom).



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  		Figure 4.. Preoperative (Preop), mid-term, and late FEV1 and FVC in all patients (top) and COPD survivors only (bottom) [n = 24].

 
Readmissions
During mid-term follow-up, 24 patients (65%) in the COPD group were readmitted to the hospital while only 11 patients (30%) were readmitted from the control group (p = 0.002). At late follow-up, the readmission rate was similar in both groups (83%), but the median number of readmissions per patient, although not significant, was higher in the COPD group compared to the control group (three vs one, p = 0.07). Most of the mid-term readmissions in the study group were due to respiratory problems followed by cardiac problems (51% and 19%, respectively), whereas in the control group the major cause of readmission was neither cardiac nor respiratory. In late follow-up, the major cause of readmission was cardiac in both groups (Fig 5 ).



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  		Figure 5.. Number and causes of readmissions during mid-term and late follow-up for the COPD and control groups.

 
Quality of Life
Quality of life for the survivors was defined as better than, the same as, or worse than preoperative status based on an identical questionnaire asked at mid-term and late follow-up. All surviving patients with COPD had improved quality of life on late follow-up. At mid-term follow-up, less than half of the surviving patients with COPD believed they had improved their quality of life. However, on late follow-up, all patients with COPD who survived believed they had a significantly improved quality of life compared to preoperative status (Fig 6 ).



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  		Figure 6.. Quality of life during mid-term (mid) and late follow-up for the COPD and control groups.

 

   Discussion
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
Conclusions
 References
 
COPD has been shown to be associated with both higher mortality and morbidity rates following CABG.1 2 3 4 5 6 7 We previously presented the mid-term results of patients with COPD who underwent CABG.1 In this study, we present the long-term (8.6 ± 2 years) outcome of both COPD and control groups.

Detailed analysis of the influence of COPD on patients undergoing CABG is sparse and deals only with short-term and mid-term results.1 5 Part of the problem is defining significant COPD. Whereas the definition of severe COPD is well established with the use of laboratory parameters, these patients are clearly too ill to undergo CABG.9 In an attempt to overcome this problem, we choose to define our population on the basis of clinical criteria, namely patients actively treated and followed up in the pulmonary clinic, who had symptomatology of COPD that is dominant or codominant to their coronary artery disease. Further discussion regarding our criteria can be found elsewhere.1 Samuels and colleagues,5 in a later study, used the Summit Database definition for COPD.

Over a mean of 8.6 ± 2 years of follow-up, there was a significant difference in the mortality between groups. The patients in the COPD group had a higher mortality rate that started immediately after the operation, and increased continuously during the follow-up period. A Veterans Administration study2 showed patients undergoing CABG with an FEV1 < 1.25 L to have a significantly higher acute mortality rate. Samuels and colleagues5 found that in patients with severe COPD who were receiving steroids and were > 75 years old, the hospital mortality was exceptionally high.5 Canver and colleagues10 identified preoperative FEV1 as a significant predictor of 5-year survival in patients with COPD undergoing CABG. In our study, there were not enough perioperative deaths to identify independent risk factors for early postoperative death. However, older age and lower preoperative FEV1 have been clearly identified as independent predictors for late death. Patients > 70 years old had a four times higher chance of dying with actuarial 9-year survival of 50% compared to those who were < 70 years who had actuarial 9-year survival of 85%. A preoperative FEV1 of < 1.25 L carried a seven times higher chance of death during follow-up with actuarial 9-year survival of 42%, compared to those with FEV1 > 1.25 L who had actuarial 9-year survival of 76%.

The calculated area under the ROC of 0.97 with sensitivity of 90% and specificity of 100% for FEV1 <= 1.77 L determines that FEV1 is a good predictor for COPD in this study. Therefore, it can be stated that patients with significant COPD, assessed by low FEV1, who undergo CABG are less likely to survive during long-term follow-up compared to patients without COPD who undergo CABG.

In view of this higher risk, it is of great interest to know whether patients with COPD who undergo CABG benefit from the operation. To answer this question, we compared the results from this study with historical natural history studies of patients with COPD. Although performed years ago, the classical studies by Burrows and Earle,11 Boushy et al,12 and the Veterans Administration cooperative study of pulmonary function13 are among the few studies to document the natural history and actuarial survival in patients with COPD. We elected to concentrate on the patients with more severe COPD in our study, those with FEV1 <= 1.25 L, and compare them to patients with relatively similar FEV1 from the natural history studies. The actuarial survival for different time intervals as presented in those studies and the survival of patients with FEV1 <= 1.25 L from the current study for the same time intervals are summarized in Table 4 ). Although this is an indirect comparison to historical analyses, it seems that the long-term survival of patients with COPD after CABG is at least as good as the natural history of an isolated patient with COPD. This finding may reflect a better care for current patients with COPD relative to the time these historical studies were performed or, more importantly, it may demonstrate that CABG for patients with COPD brings the patients to the same survival curve as for patients with COPD who did not require CABG, reflecting a beneficial long-term effect of CABG.


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  		Table 4.. Natural History of COPD Relative to the Current Study

 
The association of COPD with an increased incidence of ventricular and supraventricular arrhythmias is well established.14 15 We have previously demonstrated the association of death in patients with COPD who undergo CABG with arrhythmias during mid-term follow-up.1 In long-term follow-up of the same group of patients, arrhythmias continued to be a major contributor to death.

At mid-term follow-up, both the COPD and the control groups showed mildly decreased pulmonary function compared to baseline. Pulmonary function returned to baseline at late follow-up in the control group. In the COPD group there was a dramatic improvement of pulmonary function to above baseline. To exclude the possibility that only those who had better preoperative pulmonary function survived to long term, the long-term survivors in the COPD group were analyzed separately (Fig 4 , bottom) and demonstrated the same temporal pattern. We believe that this improvement is related to multiple factors. First, the patients in the COPD group who survived may have changed their lifestyle, reflected by the fact that 67% of them smoked preoperatively while only 29% of them smoked at last follow-up. Second, these patients with significant COPD and significant cardiac pathology had most probably a combined cardiorespiratory detrimental effect on their pulmonary function. After the operation, the pulmonary function of the patients deteriorated, most probably due to the surgical insult. After a period of recovery from the operation, the pulmonary function of the control group returned to baseline. In the COPD group, however, the improvement in the cardiac status was most probably the leading cause for improved pulmonary function to above baseline in late follow-up.

At mid-term follow-up, less than half of the surviving patients in the COPD group, in contrast to most patients in the control group, believed they had improved quality of life. However, on late follow-up, all the patients who survived believed they had significantly improved quality of life for preoperative status in both groups. During mid-term follow-up, 65% of patients with COPD were readmitted to the hospital while only 30% of patients were readmitted from the control group. At late follow-up, the prevalence of readmissions was similar in both groups. While most of the mid-term readmissions in the COPD group were due to respiratory problems, the major cause of readmission in late follow-up was cardiac in both groups. This finding may be explained by the change in lifestyle, cessation of smoking, and improvement in pulmonary function.

It is of great interest whether performing CABG without the use of cardiopulmonary bypass would prove beneficial to these difficult patients. Guler and colleagues16 performed CABG on patients with COPD with and without the use of cardiopulmonary bypass. FEV1 obtained in the second postoperative month was significantly lower than preoperative values only in the group who was operated on with the use of cardiopulmonary bypass. They suggest that off-pump bypass surgical procedures are more advantageous than on-pump methods for patients with COPD. Further studies comparing different CABG techniques should be performed before such a conclusion can be made.


   Conclusions
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
References
 
Clinical COPD is a significant risk factor for mortality after CABG. Lower FEV1 and older age are independent risk factors for death during long-term follow-up. Nevertheless, since the long-term survival of patients with COPD after CABG is as good as the natural history of isolated patients with COPD, and since quality of life tends to improve as well, CABG seems to carry a beneficial long-term effect for patients with COPD.



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  		Figure 3.. Overall survival of the study group stratified by FEV1.

 

   Footnotes
 
Abbreviations: CABG = coronary artery bypass grafting; ROC = receiver operating curve

Affiliated with the Sackler School of Medicine, Tel Aviv University, Tel Aviv, Israel.

Received for publication February 26, 2003. Accepted for publication July 9, 2003.


   References
TOP
 Abstract
 Introduction
 Materials and Methods
 Results
 Discussion
 Conclusions
 References
 

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  4. Naunheim, KS, Fiore, AC, Wadley, JJ, et al The changing profile of the patient undergoing coronary artery bypass surgery. J Am Coll Cardiol 1988;11,494-498[Abstract]
  5. Samuels, LE, Kaufman, MS, Morris, RJ, et al Coronary artery bypass grafting in patients with COPD. Chest 1998;113,878-882[Abstract/Free Full Text]
  6. Loop, FD, Higgins, TL, Panda, R, et al Myocardial protection during cardiac operations: decreased morbidity and lower cost with blood cardioplegia and coronary sinus perfusion. J Thorac Cardiovasc Surg 1992;104,608-618[Abstract]
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