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Ann Thorac Surg 2008;85:508-512. doi:10.1016/j.athoracsur.2007.09.048
© 2008 The Society of Thoracic Surgeons
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Original Articles: Cardiovascular

Excellent Long-Term Clinical Outcome After Coronary Artery Bypass Surgery Using Three Pedicled Arterial Grafts in Patients With Three-Vessel Disease

Nic J.G.M. Veeger, MSa,b, Gerald F. Panday, MD, Adriaan A. Voors, MD, PhDc, Jan G. Grandjean, MD, PhDa, Jan van der Meer, MD, PhDd, Piet W. Boonstra, MD, PhDa,*

a Thoraxcenter, Department of Cardiothoracic Surgery, University Medical Center Groningen, University of Groningen, the Netherlands
b Thoraxcenter, Department of Epidemiology, University Medical Center Groningen, University of Groningen, the Netherlands
c Thoraxcenter, Department of Cardiology, University Medical Center Groningen, University of Groningen, the Netherlands
d Thoraxcenter, Department of Hematology, Division of Hemostasis, Thrombosis and Rheology, University Medical Center Groningen, University of Groningen, the Netherlands

Accepted for publication September 25, 2007.

* Address correspondence to Dr Boonstra, Thoraxcenter, University Medical Center Groningen, University of Groningen, Hanzeplein 1, PO Box 30,001, Groningen, 9700 RB, the Netherlands (Email: p.w.boonstra{at}thorax.umcg.nl).


   Abstract
Top
 Abstract
Introduction
 Patients and Methods
 Results
 Comment
 References
 
Background: Long-term clinical outcome of complete arterial grafting in three-vessel disease is unknown.

Methods: We studied 344 patients who underwent complete arterial revascularization using the internal thoracic arteries and the right gastroepiploic artery. Freedom from major adverse cardiac events (MACE) was evaluated by the Kaplan-Meier method, and homogeneity of outcome in strata of patients was assessed using Cox proportional hazards modeling.

Results: Median follow-up of survivors was 9.3 years (range, 0.01 to 12.8 years). The 12-year freedom from MACE was 75.5%. For the composite of MACE, this was 86.9% for cardiovascular death, 93.3% for myocardial infarction, and 89.4% for reintervention. In patients aged older than 65 years, MACE occurred significantly more frequent, with a freedom from MACE of 65.8% compared with 82.6% in younger patients (hazard ratio, 3.4; 95% confidence interval, 2.1 to 5.6, p < 0.001).

Conclusions: Complete arterial revascularization using both pedicled internal thoracic arteries and the gastroepiploic artery in patients with three-vessel disease resulted in an excellent long-term clinical outcome, especially in patients aged younger than 65 years.


   Introduction
Top
 Abstract
 Introduction
Patients and Methods
 Results
 Comment
 References
 
Venous grafts are used in most patients who have coronary artery bypass grafting (CABG), although it is well known that the use of at least one arterial graft to the left anterior descending coronary artery significantly reduces mortality and morbidity [1–3]. In addition, using both internal mammary arteries resulted in an even better clinical outcome [4–6]. However, two arteries often do not provide enough grafting material to obtain total arterial revascularization, especially in patients with three-vessel disease.

There are two possibilities for additional arterial grafting material. First, the radial artery provides enough material, it can be used safely, and its reported short- and mid-term clinical results are satisfactory [7]. Second, we and others demonstrated that the right gastroepiploic artery also can be used for complete arterial revascularization in three-vessel disease [8]. Our mid-term follow-up results of CABG using both internal mammary arteries combined with the right gastroepiploic artery appeared to be promising [9, 10]; however, the follow-up was too short to draw definite conclusions. In the present study, we therefore evaluated the long-term clinical outcome of patients with three-vessel disease who underwent CABG with both internal thoracic arteries and the right gastroepiploic artery.


   Patients and Methods
Top
 Abstract
 Introduction
 Patients and Methods
Results
 Comment
 References
 
Patients
Between 1989 and 1994, 344 patients underwent complete arterial revascularization using both internal thoracic arteries in combination with the right gastroepiploic artery for three-vessel coronary artery disease. All patients were operated on in the University Medical Center of Groningen. Long-term clinical outcome was retrospectively assessed up to June 2002 through telephone interviews of the patients using a standard questionnaire and by reviewing the medical files of their cardiologists or general practitioners, or both, when appropriate.

For this retrospective study approval from the local Ethics Committee was obtained. Individual patient data were collected without patient identification information. Owing to the retrospective nature of the study, the need for written informed consent was waived.

Surgical Techniques
The surgical techniques are extensively described elsewhere [9, 10]. In brief, all patients were operated on with the use of extracorporeal circulation, using mild hypothermia (28° to 32°C nasopharyngeal temperature) and crystalloid-induced cardioplegic arrest. The right internal thoracic artery (ITA) was routed through the transverse sinus in 75% of the patients to reach the circumflex coronary artery; in 25%, it was routed directly to the left anterior descending coronary artery. The left ITA was routed under the mediastinal fat deep along the parietal left pleura to the left anterior descending coronary artery in 75% of patients and to the circumflex area in 25%. The right gastroepiploic artery was always routed anterior to the liver and through a hole in the diaphragm.

All patients received anticoagulant or antiplatelet drug therapy (mostly aspirin) for at least 1 year after CABG. In most patients, this was continued afterwards to maintain graft patency.

Clinical End Points
Major adverse cardiac events (MACE) were defined as cardiac mortality, myocardial infarction, and coronary revascularization. Cardiac mortality was defined as death due to acute myocardial infarction, acute cardiac arrest, sudden death, or progressive congestive heart failure. Unknown causes of death were classified as cardiac death. For myocardial infarction, pathologic Q-waves had to be present on the electrocardiogram (ECG) in combination with creatine phosphokinase (CPK) and CPK-MB serum levels that exceeded the upper limits of normal ranges. Revascularization was defined as percutaneous coronary intervention (PCI) or redo-CABG during follow-up.

Statistical Analysis
The objective of this study was to evaluate long-term clinical outcome in patients who underwent complete arterial revascularization using three arterial grafts. The primary composite end point was MACE. Event-free survival was graphically depicted using the Kaplan-Meier method. To evaluate the homogeneity of outcome in different categories of patients, Cox proportional hazards regression analysis was performed. Predefined risk factors for MACE included in univariate analyses were baseline data for age, sex, body mass index, left ventricle ejection fraction (LVEF) of 0.30 or less, hypertension, diabetes mellitus, smoking, hypercholesterolemia, history of myocardial infarction, PCI, and concomitant cardiovascular medication. Other factors included the number of distal anastomoses, perfusion duration, and year of surgery.

All tests performed to test the (null) hypothesis of no difference were two-sided. A value of p < 0.05 was considered statistically significant. For all analyses, SAS 9.1 software (SAS Institute, Cary, NC) was used.


   Results
Top
 Abstract
 Introduction
 Patients and Methods
 Results
Comment
 References
 
Patient Characteristics
The study included 344 consecutive patients (89% men) who underwent CABG from September 1989 to December 1994. The total follow-up time was 3055 patient-years. Mean age at time of operation was 59 years. Anginal complaints at inclusion were 62% at New York Heart Association (NYHA) functional class III and 33% at class IV. Left ventricular function was normal in 76%, moderate in 21%, and poor (LVEF <0.30) in 3% of the patients. All patients used cardiovascular drugs, as summarized in Table 1.


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  		Table 1 Baseline Characteristics of Patients With Total Arterial Revascularization
 
Death and Additional Procedures
Postoperative mortality (≤30 days) was 1.5%. During follow-up, 3 patients had abdominal surgery: twice for aneurysm of the abdominal aorta and once for a tumor of the stomach. These operations were completed without damage to the gastroepiploic artery.

Clinical Outcome
Median follow-up was 9.3 years (range, 0.01 to 12.8 years). During follow-up, MACE events occurred in 69 patients (20.1%). MACE-free survival is presented in Figure 1, indicating a 12-year freedom from MACE of 75.5%. The 12-year event-free survival for the components of MACE was 86.9% for cardiovascular death, 93.3% for myocardial infarction, and 89.4% for revascularization (also see Fig 1).


Figure 1
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  		Fig 1. Freedom from major adverse cardiac events (MACE, black line) during 12 years of follow-up as well as from the separate components of MACE, consisting of cardiac death (solid grey line), myocardial infarction (dash-dot line), and revascularization either by percutaneous coronary intervention or redo coronary artery bypass grafting (dash line).

 
Angina pectoris status was assessed in 279 patients (81%). Of these, 88% were in NYHA class I, 10% in class II, 1% in class III, and 1% in class IV. Anginal status was not assessed in 37 patients due to a fatal cardiovascular event.

Predictors of Major Adverse Cardiac Events
Cox proportional hazards regression analysis showed differences in the risk for MACE between various strata of known risk factors. Especially in elderly patients (≥65 years), the 12-year freedom from MACE was 65.8% compared with 82.6% for younger patients, resulting in a 3.4-fold (95% confidence interval [CI] 2.1 to 5.6, p < 0.001) higher risk (see Fig 2) in the elderly patients. In patients with a moderate to poor left ventricular function before operation, the risk was 1.9-fold higher (95% CI, 1.1 to 3.1; p = 0.02) compared with patients with a normal left ventricular function. A history of hypertension, myocardial infarction before CABG, the number of distal anastomoses, and diabetes mellitus was also associated with the occurrence of MACE. Multivariable analysis showed that myocardial infarction before CABG, the number of distal anastomoses, and diabetes mellitus were no longer independently associated with MACE, whereas age, a history of hypertension, and left ventricular function remained as important predictors for MACE (Fig 3).


Figure 2
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  		Fig 2. Freedom from major adverse cardiac events (MACE) during 12 years of follow-up in patients younger than 65 years (black line) vs patients 65 years or older (dashed line) at the time of surgery.

 

Figure 3
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  		Fig 3. Multivariable analysis of the predictors of major adverse cardiac events (MACE) during long-term follow-up in patients with total arterial revascularization presented as hazard ratios (diamonds) and 95% confidence intervals (whiskers). (LVEF = left ventricular ejection fraction.)

 
When the components of MACE were considered separately, the hazard ratios for the respective risk factors of cardiovascular death, myocardial infarction, and reintervention, were comparable with those observed in the evaluation of the composite of MACE (data not shown).


   Comment
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
References
 
We evaluated a cohort of 344 patients who underwent complete arterial revascularization for triple-vessel disease using the internal thoracic arteries and right gastroepiploic artery. At 12 years, the freedom from MACE was 75.5%, and freedom from cardiovascular death was 86.9%, myocardial infarction was 93.3%, and revascularization was 89.4%.

The beneficial effects of arterial grafts were reported in 1986 [2, 3]. In a 15-year follow-up study of 748 CABG patients, the use of at least one ITA was associated with decreased death, risk of myocardial infarction, reoperations, and less recurrence of angina pectoris [3]. These findings were supported by those from a larger series of 5931 patients in whom the use of only vein grafts revealed a 1.6-fold increased death compared with the use of one ITA combined with vein grafts [2]. Using both left and right ITA resulted in an even better clinical outcome [5, 6]. A large retrospective study of 8123 patients who underwent CABG using both ITAs showed a small but significant reduction in the death rate compared with the use of one ITA [6]. In a 13-year follow-up study comparing bilateral with single ITA grafting, Berreklouw and colleagues [5] demonstrated a reduction of the combined end point of cardiac death, myocardial infarction, reintervention, or recurrent angina.

Despite these data, one arterial graft and a vein graft are still used in most patients. This can be explained by a lack of arterial graft material, especially in patients with three-vessel coronary artery disease. Another explanation might be that there is no evidence of superiority for three pedicled arterial grafts.

In combination with both left and right ITAs, there are several options to obtain additional arterial grafts. First, the radial artery is being used in an increasing number of CABG patients. Several authors reported beneficial angiographic and clinical short-term effects when this artery was used. Possati and colleagues [11] demonstrated a patency rate of 92% after a mean follow-up of 9 years compared with 98% for ITAs [11]; however, long-term angiographic graft patency varied widely.

Like other arterial grafts, the radial artery is very vulnerable to surgical trauma, hypotension, and early graft malfunction whenever {alpha}-adrenergic drugs are used. Recent improvements in surgical harvesting technique of the radial artery and in perioperative drug therapy have reduced these problems and consequently have increased the use of the radial artery [12–14].

Another option is the gastroepiploic artery. In contrast with the radial artery, this is a pedicled graft. Beneficial short-term effects, minimal operative risks, and good patency rates have been reported using the gastroepiploic artery [10, 15], and mid-term clinical outcome has also been promising [7, 16]. We previously reported the results of 7 years of follow-up in 256 patients with three-vessel disease who were grafted with the gastroepiploic artery together with both ITAs [7]. After 7 years, 85% were free from angina pectoris, a considerably better result than that reported from studies in patients in whom vein grafts, single ITA grafts, or double ITA grafts were used (59% to 77%) [7].

Other options for additional arterial grafts are the inferior epigastric artery [17] and, rarely used, bovine grafts [18]. However, their short-term patency rates do not warrant their use in routine CABG surgery [17, 18].

The benefit of complete arterial revascularization was less pronounced in elderly patients (≥65 years, see Fig 2). Moreover, the gastroepiploic artery should be considered in case of a calcified ascending aorta to avoid side clamping of the aorta for performing the proximal anastomosis. Previous studies suggested that the use of arterial grafts should be particularly preferred in patients with diabetes mellitus [12, 19]. We can neither confirm nor reject this hypothesis. Although hazard ratios indicated a higher risk in our patients with diabetes mellitus, their small number led to wide confidence limits.

Data published on results of patients with coronary revascularization are difficult to compare owing to the wide differences in used types of grafts and inclusion and exclusion criteria. We did, nevertheless, compare our results with those obtained from recently published studies (Table 2) [1, 3, 20–23] and concluded that actuarial survival and actuarial probability of remaining free from myocardial infarction or reintervention, or both, 10 years after the primary operation is excellent.


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  		Table 2 Literature Review a
 
In conclusion, we demonstrated that the use of complete arterial revascularization using both pedicled ITAs and the gastroepiploic artery in patients with three-vessel disease resulted in excellent long-term clinical outcome. These long-term results confirm our earlier mid-term findings of excellent results with complete arterial grafting in these patients.


   References
Top
 Abstract
 Introduction
 Patients and Methods
 Results
 Comment
 References
 

  1. Sergeant PT, Blackstone EH, Meyns BP. Does arterial revascularization decrease the risk of infarction after coronary artery bypass grafting? Ann Thorac Surg 1998;66:1-10.[Abstract/Free Full Text]
  2. Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events N Engl J Med 1986;314:1-6.[Abstract]
  3. Cameron A, Kemp HG, Green GE. Bypass surgery with the internal mammary artery graft: 15 year follow up Circulation 1986;74(suppl III):III-30-III-36.[Medline]
  4. Endo M, Nishida H, Tomizawa Y, Kasanuki H. Benefit of bilateral over single internal mammary artery grafts for multiple coronary artery bypass grafting Circulation 2001;104:2164-2170.[Abstract/Free Full Text]
  5. Berreklouw E, Rademakers P, Koster J, van Leur L, van der Wielen B, Westers P. Better ischemic event-free survival after two internal thoracic artery grafts: 13 years of follow-up Ann Thorac Surg 2001;72:1535-1541.[Abstract/Free Full Text]
  6. Lytle BW, Blackstone EH, Loop FD, et al. Two internal thoracic artery grafts are better than one J Thorac Cardiovasc Surg 1999;117:855-872.[Abstract/Free Full Text]
  7. Bergsma TM, Grandjean JG, Voors AA, Boonstra PW, den Heyer P, Ebels T. Low recurrence of angina pectoris after coronary artery bypass graft surgery with bilateral internal thoracic and right gastroepiploic arteries Circulation 1998;97:2402-2405.[Abstract/Free Full Text]
  8. Hirose H, Amano A, Takanashi S, Takahashi A. Coronary artery bypass grafting using the gastroepiploic artery in 1,000 patients Ann Thorac Surg 2002;73:1371-1379.[Abstract/Free Full Text]
  9. Grandjean JG, Boonstra PW, den Heyer P, Ebels T. Arterial revascularization with the right gastroepiploic artery and internal mammary arteries in 300 patients J Thorac Cardiovasc Surg 1994;107:1309-1316.[Abstract/Free Full Text]
  10. Grandjean JG, Voors AA, Boonstra PW, den Heyer P, Ebels T. Exclusive use of arterial grafts in coronary artery bypass operations for three-vessel disease: use of both thoracic arteries and the gastroepiploic artery in 256 consecutive patients J Thorac Cardiovasc Surg 1996;112:935-942.[Abstract/Free Full Text]
  11. Possati G, Gaudino M, Prati F, et al. Long-term results of the radial artery used for myocardial revascularization Circulation 2003;108:1350-1354.[Abstract/Free Full Text]
  12. Tatoulis J, Buxton BF, Fuller JA, Royse AG. Total arterial coronary revascularization: techniques and results in 3,220 patients Ann Thorac Surg 1999;68:2093-2099.[Abstract/Free Full Text]
  13. Tatoulis J, Buxton BF, Fuller JA. Patencies of 2127 arterial to coronary conduits over 15 years Ann Thorac Surg 2004;77:93-101.[Abstract/Free Full Text]
  14. He GW. Nitric oxide and endothelium-derived hyperpolarizing factor in human arteries and veins J Card Surg 2002;17317–3.
  15. Suma H, Isomura T, Horii T, Sato T. Late angiographic result of using the right gastroepiploic artery as a graft J Thorac Cardiovasc Surg 2000;120:496-498.[Abstract/Free Full Text]
  16. Nishida H, Tomizawa Y, Endo M, Konyanagi H, Kasanuki H. Coronary artery bypass with only in situ bilateral internal thoracic arteries and right gastroepiploic artery Circulation 2001;104(12 suppl 1):176-180.
  17. Cremer J, Mugge A, Schulze M, et al. The inferior epigastric artery for coronary bypass graftingFunctional assessment and clinical results. Eur J Cardiothorac Surg 1993;7:423-427.[Abstract]
  18. Suma H, Wanibuchi Y, Takeuchi A. Bovine internal thoracic artery graft for myocardial revascularization: late results Ann Thorac Surg 1994;57:704-707.[Abstract]
  19. Thourani VH, Weintraub WS, Stein B, et al. Influence of diabetes mellitus on early and late outcome after coronary artery bypass grafting Ann Thorac Surg 1999;67:1045-1052.[Abstract/Free Full Text]
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