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Ann Thorac Surg 2005;80:1353-1360
© 2005 The Society of Thoracic Surgeons

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Original article: Cardiovascular

Does Diabetes Affect the Postoperative Outcomes After Total Arterial Off-Pump Coronary Bypass Surgery in Multivessel Disease?

Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, Seoul, Korea

Accepted for publication April 21, 2005.

^_* Address reprint requests to Dr Kim K-B, Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, 28 Yeun-Kun Dong, Chong-Ro Ku, Seoul 110-744, Korea (Email: kimkb{at}snu.ac.kr).

	Abstract

Top Abstract Introduction Material and Methods Results Comment References

 
BACKGROUND: Previous studies have reported conflicting results regarding the adverse effects of diabetes on surgical outcomes after coronary artery bypass grafting (CABG). We reviewed our experience to determine the impact of diabetes on early and midterm surgical outcomes of patients with multivessel disease who underwent total arterial revascularization with avoidance of cardiopulmonary bypass.

METHODS: Between January 1998 and December 2003, 517 patients with multivessel disease underwent total arterial off-pump CABG; 214 were diabetic (DM group) and 303 were nondiabetic (NDM group). The DM group was sicker than the NDM group (more left ventricular dysfunction, postinfarction angina, previous myocardial infarction, and chronic renal failure). Mean follow-up period was 34 ± 17 months. The multivariate risk factors for operative mortality, one-year angiographic patency, and midterm survival were analyzed.

RESULTS: Mean numbers of distal anastomoses were not different between the two groups (DM, 3.1 ± 0.9; NDM, 3.0 ± 0.8). Operative mortality was 1.4% (DM, 1.4% vs NDM, 1.3%; p = not significant [ns]). No differences were found in the incidences of postoperative morbidities, including mediastinitis and superficial wound problems, between the two groups. In immediate postoperative angiography, the patency rates were 99.2% in the DM and 98.9% in the NDM group (p = ns). One-year patency rates in angiography were also similar between the two groups (DM, 96.0%; NDM, 95.4%; p = ns). Multivariate analysis indicated that diabetes was not an independent risk factor of steno-occlusion at one-year follow-up angiography. Five-year cumulative survival was 87.7 ± 4.1% in the DM, and 94.2 ± 1.4% in NDM (p = ns) group. Five-year freedom from cardiac death was 99.0 ± 0.7% in the DM, and 97.4 ± 1.0% in the NDM (p = ns) group. Old age (age >75 years) and chronic renal failure were independent risk factors for lower midterm survival. Our study failed to demonstrate that diabetes was an independent risk factor for lower midterm survival.

CONCLUSIONS: Diabetes mellitus did not affect the early postoperative and midterm results, including one-year graft patency, in patients with multivessel disease undergoing total arterial and off-pump CABG.

	Introduction

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Previous studies have reported conflicting results regarding the adverse effect of diabetes on surgical outcomes after coronary artery bypass grafting (CABG) [1–6]. These equivocal data may be because each study differed in the extent of coronary artery disease, adequacy of diabetic control, strategy of conduit selection, and surgical techniques including cardiopulmonary bypass, which have been considered as possible factors influencing surgical outcome in diabetic patients [2, 6–13].

Recent studies indicate that arterial conduit might have a positive effect on maintaining its biologic integrity and improving surgical outcome in diabetics [2, 14, 15] and that off-pump coronary artery bypass (OPCAB) technique would reduce surgical morbidities even in diabetic patients [12, 13]. The aim of this study was to evaluate whether diabetes influences the surgical outcome as a risk factor in patients with multivessel disease, undergoing total arterial revascularization with avoidance of cardiopulmonary bypass.

	Material and Methods

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Of the 825 patients who underwent isolated CABG (109 on-pump CABGs, 716 OPCABs) between January 1998 and December 2003, 517 patients, who had multivessel disease and underwent total arterial OPCAB with at least one internal thoracic artery (ITA) graft, were studied in a prospective nonrandomized manner. A computer-based patient database system was used for this prospective study. Patients were regularly followed up through the out patient clinic at 3 or 4 month intervals postoperatively, and telephone contact was performed to confirm a patient's condition if the last hospital visit was not conducted at the scheduled time. Five hundred and seven patients (98.1%) were followed up until December 2004 and the mean follow-up period was 34 ± 17 months. The 517 patients were divided into two groups for comparison; 214 were diabetic (DM group) and 303 were nondiabetic (NDM group). The operations were all performed by a single surgeon (Ki-Bong Kim).

The DM group included all the patients who had been previously diagnosed as diabetic and requiring pharmacologic glycemic control. Nine patients without a previous diagnosis of diabetes mellitus but with elevated glucose levels at admission (fasting glucose level, 126 mg/dL; 2-h glucose level after a meal during glucose tolerance test, 200 mg/dL) were also included. In the DM group, there were 65 patients (30.4%) with insulin-treated diabetes and 149 patients (69.6%) with noninsulin-treated diabetes. Intravenous insulin, glucose, and potassium (GIK regimen) commenced before the operation for all diabetic patients. Usually, seven units of insulin in 500 mL 5% dextrose containing 15 mEq potassium was the starting solution, and was administered at 80 mL/h. The target glucose range was 90–180 mg/dL and serum potassium levels were maintained between 4.0 and 5.5 mmol/L. Blood glucose levels were monitored hourly intraoperatively and immediately after the operation. The infusion was stopped and the preoperative glucose control regimen resumed once oral intake was established, usually on the first postoperative day.

The patient's preoperative evaluation included clinical history, neurologic examination, and cardiac examination. The neurologic examination consisted of an interview and neurologic evaluation by a neurologist, carotid duplex ultrasonography, and transcranial Doppler or magnetic resonance angiography. The patients were reevaluated one week after the operation, or earlier if necessary. Stroke was defined as a new and sudden onset of neurologic deficits lasting more than 24 hours with no apparent nonvascular causes. Cardiac rhythm was continuously monitored postoperatively during the stay in the intensive care unit and in the general ward until the chest tubes were removed. A standard 12-lead electrocardiogram was checked daily thereafter during the postoperative hospital stay. Perioperative myocardial infarction was defined as positive results on at least two of the three different tests: the peak level in serial serum creatine kinase isoenzyme (>100 IU/L), appearance of a new Q wave on the electrocardiogram, or newly developed regional wall motion abnormalities on the postoperative echocardiogram. Postoperative acute renal failure was defined as a rise in serum creatinine of 1 mg/100 mL above baseline. In patients with a previous change in serum creatinine levels, postoperative acute renal failure was considered as an increase of 50% or more from the preoperative level.

Cardiac death was defined as any death related to cardiac events including sudden death. Operative mortalities and late mortalities were defined, respectively, as death rates within 30 days and after 30 days postoperatively. Preoperative data of this study showed that more patients in the DM group had left ventricular dysfunction, postinfarction angina, chronic renal failure, and a history of myocardial infarction than did those in the non-DM group (Table 1).

The patency after operation was evaluated by angiography and graded as described by FitzGibbon and colleagues [17]. Steno-occlusion was defined as occluded, or 75% or greater diameter stenosis. Early postoperative angiographies (postoperative 1.4 ± 1.2 days) were performed in 97.9% (506/517) of the patients (209/214 in the DM group, 297/303 in the NDM group), and postoperative one-year angiographies (12.1 ± 4.3 months postoperatively) were performed in 88.2% (456/517) of the patients (180/214 in the DM group, 276/303 in the NDM group), regardless of the patient's anginal symptom. Patients who died, refused angiographic evaluation, or had renal function impairment were excluded from the angiographic follow-up rate.

Target-lesion revascularization was defined as percutaneous coronary intervention of the target vessel because of the presence of 75% or greater diameter stenosis of the target lesion, as measured by the follow-up angiography. The target lesion was defined as the surgically bypassed segment. Target-vessel revascularization included the target lesion or another segment within the same vessel. Nontarget-vessel revascularization was defined as revascularization of a new lesion outside the target vessel.

Statistical analysis was performed with the SPSS software package (version 11.0, SPSS Inc, Chicago, IL). Comparison between the two groups was performed using the unpaired Student's t test, and using the ² test (Pearson ² and Fisher exact tests) for categoric variables. Follow-up losses were counted as missing data and excluded from the calculation of late mortality. Actuarial survival was calculated using the Kaplan-Meier method. Patient's variables associated with operative mortalities, graft steno-occlusion at postoperative 1-year, and midterm survival were assessed by univariate (², t test) and multivariate analysis (logistic or Cox regression analysis).

The univariate variables with p values less than 0.3 were entered into the logistic or Cox regression to detect significant independent risk factors. All results were expressed as mean ± standard deviation, and a p value of less than 0.05 was considered statistically significant.

	Results

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Arterial Grafts Used and Distal Anastomoses
The right ITA, bilateral ITAs, and radial artery were used more frequently in NDM patients, whereas the right gastroepiploic artery was more common in DM patients (Table 2). The number of distal anastomoses per patient was not different between the two groups. The rates of constructing arterial Y grafts and sequential anastomoses were 68.2% and 39.2%, respectively, in the DM group, and 60.4% and 36.6%, respectively, in the NDM group (p = not significant [ns]).

Late Mortalities and Midterm Survival (Appendix)
Late mortality was 5.3% (27 of 507 patients). There were no significant differences in late mortalities between the DM and NDM groups (7.2%, 15/209 vs 4.0%, 12/298; p = ns). Late mortality of insulin-treated diabetics was not significantly different from that of noninsulin treated diabetics (9.8%, 6/61 vs 6.1%, 9/148; p = ns). Among the 27 late deaths, the number of cardiac deaths was four (14.8%). There were no significant differences in the incidence of late cardiac deaths between the DM and NDM groups (0.5%, 1/209 vs 1.0%, 3/298; p = ns). In terms of midterm actuarial survival, there were no significant differences between the DM and NDM groups (93.8 ± 1.7% vs 96.6 ± 1.0% at 1 yr, 87.7 ± 4.1% vs 94.2 ± 1.4% at 5 yr; p = 0.119) (Fig 1). There were no significant differences in freedom from cardiac deaths between the two groups (99.0 ± 0.7% vs 98.3 ± 0.8% at 1 yr, 99.0 ± 0.7% vs 97.4 ± 1.0% at 5 yr; p = 0.261).

View larger version (25K): [in this window] [in a new window]   Fig 1. Comparison of midterm survival: DM versus NDM groups. (DM = diabetes mellitus; F/U = follow-up; NDM = nondiabetes mellitus.)

Causes of Deaths and Risk Factor Analysis
Whereas 71.4% of early deaths were cardiac deaths, 14.8% of late deaths were cardiac deaths. Common causes of noncardiac late deaths were chronic renal failure, infection, and malignancy (Table 6). Univariate and logistic regression analysis for increased operative mortality demonstrated that left main disease was the only independent risk factor (p= 0.013) (Table 7). Diabetes and preoperative insulin treatment were not independent risk factors at either univariate or multivariate analysis.

	Comment

Top Abstract Introduction Material and Methods Results Comment References

Diabetes has been reported to have an adverse effect on surgical outcomes and most CABG series comprise 20% to 30% of the diabetic population [13, 18–21]. We controlled the bias associated with the extent of coronary disease involvement by limiting the study to patients with disease in more than two vessels because coronary artery disease tends to be more extensive, involving multiple vessels in diabetic patients [22, 23]. This study included a relatively high diabetic population (41.4 %), which might result from our inclusion criteria of multivessel disease, racial difference, and high percutaneous intervention rate in our country. Cardiopulmonary bypass was reported to be associated with more complications [13] and to induce a greater oxidative stress in diabetic patients than in those without diabetes [24]. We routinely performed OPCAB for isolated coronary artery disease in our institute.

Although there have been disappointing long-term results of saphenous vein grafts in CABG [17, 25–27], the superiority of the ITA, even in diabetic patients, has been reported [15, 28, 29]. In this study, we used at least one ITA for CABG. In diabetic patients, the right gastroepiploic artery was more frequently used and bilateral ITAs were less frequently used compared with nondiabetic patients. In the early period of this study, we tried to avoid bilateral ITAs and used the gastroepiploic artery as an alternative graft in diabetic patients. We rarely used the radial artery as a bypass graft because it is prone to arteriosclerosis, intimal hyperplasia, and medial calcification [29] as well as the requirement of additional incision. The radial artery was used less often in DM patients with impaired renal function, in preparation for the future need of arteriovenous fistula for hemodialysis, especially in insulin-treated patients. The less frequent use of bilateral ITAs in diabetic patients may have been related to the result of no differences in the incidences of mediastinitis and superficial wound infection between the DM and NDM groups. However, since August 1999, when a standard skeletonizing technique was used, we have felt that skeletonization of ITA lowers the risk of deep sternal and superficial wound infection, even in diabetic patients who used bilateral ITAs; this has already been noted by other authors [30].

There was no difference in operative mortality between the DM and NDM groups in this study, which is in agreement with other reports [1, 4]. Most of our operative mortalities were related with cardiac death, and diabetes was not a risk factor for operative mortality at multivariate analysis. Calafiore and colleagues [18] also suggested that the 30-day mortality was influenced by the technical details of the surgery more than by the disease itself.

Overall and late mortalities during this study period were also similar between the two groups (8.4% and 7.2% in the DM, 5.3% and 4.0% in the NDM group, p = ns). In contrast to some reports [3, 6, 24, 30–32], diabetes did not appear as an independent risk factor for midterm survival in the Cox analysis and 5-year freedom from cardiac deaths was 99.0 ± 0.7% in diabetic patients (Fig 2) . Another study [1] a lso came to a conclusion similar to ours by showing that diabetes was not recognized as an independent risk factor for late survival. Our study showed more encouraging results, when considering that the DM group was sicker than the NDM group (more left ventricular dysfunction, postinfarction angina, previous myocardial infarction, and chronic renal failure).

View larger version (22K): [in this window] [in a new window]   Fig 2. Freedom from cardiac death: DM versus NDM groups. (DM = diabetes mellitus; F/U = follow-up; NDM = nondiabetes mellitus.)

Chronic renal failure (CRF) and old age (>75 years) were independent risk factors for midterm survival in our study. Although there were more patients with chronic renal failure in the DM group, the comparison of late deaths with CRF did not demonstrate any significant difference between the two groups. Six of 22 (27.3%) diabetic CRF patients and 2 of 7 (28.6%) nondiabetic CRF patients died during the follow-up period.

Hirotani and colleagues [2] showed that, from their angiographic results obtained three weeks after surgery in 395 patients, there was no difference in the graft patency rate between the diabetic and nondiabetic patients. Our one-year angiographic patency rates in both groups were higher than 95% without statistical difference, and preoperative insulin treatment did not influence the 1-year angiographic outcome.

There are limitations to the present study that must be recognized. First, this study had a relatively small sample size and a small number of postoperative events. These resulted in high confidence intervals and reduced statistical power, particularly in the multivariate risk factor analysis for operative and late mortalities. In this regard, further subgroup analyses (DM vs NDM groups, insulin-treated vs noninsulin-treated diabetes groups) were not performed adequately. Second, we focused on the patients undergoing total arterial OPCAB for multivessel disease and did not compare with other patient populations because we performed total arterial OPCAB in most of our patients. The results of this study might not be extrapolated to the patients with on-pump CABG, single-vessel disease, or saphenous vein grafting.

In conclusion, diabetes mellitus did not affect the early postoperative and midterm results, including one-year graft patency in patients with multivessel disease undergoing total arterial and off-pump CABG.

	Appendix

 
Variables Used in Risk Factor Analysis for Operative Mortality and Midterm Survival

Preoperative Variables

Female

Age >75 yr

BMI (body mass index) > 30

Smoking

Hypertension

Diabetes mellitus

Preoperative insulin treatment

Hyperlipidemia

Stroke history

CRF (chronic renal failure)

ARF (acute renal failure)

COPD (chronic obstructive pulmonary disease)

AMI (acute myocardial infarction) history

Postinfarction angina

Left main disease

PTCA (percutaneous coronary angioplasty) history

LV (left ventricular) dysfunction

Unstable angina

Intraoperative Variables

Intraoperative IABP (intraaortic balloon pump) insertion

Y-anastomosis

RGEA (right gastroepiploic artery)

RA (radial artery)

Bilateral ITAs (internal thoracic arteries)

Sequential anastomosis

Anterior vessels

Posterior vessels

Inferior vessels

Postoperative Variables

Steno-occlusion at immediate postoperative angiogram

Postoperative atrial fibrillation

Postoperative ARF

Respiratory complication

Mediastinitis

Reopen sternum d/t postoperative bleeding

Steno-occlusion at 1-yr angiography

TVR (target vessel revascularization) or non-TVR

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Top Abstract Introduction Material and Methods Results Comment References

 

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This Article Abstract Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Add to Personal Folders Download to citation manager Author home page(s): Kwang Ree Cho Ki-Bong Kim Permission Requests Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Choi, J.-S. Articles by Kim, K.-B. Search for Related Content PubMed PubMed Citation Articles by Choi, J.-S. Articles by Kim, K.-B.