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Ann Thorac Surg 1997;64:599-605
© 1997 The Society of Thoracic Surgeons

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Original Article: Cardiovascular

Single Versus Bilateral Internal Mammary Artery Grafts: 10-Year Outcome Analysis

Section of Cardiovascular Surgery, Mayo Clinic and Mayo Foundation, Rochester, Minnesota

	Abstract

Top Footnotes Abstract Introduction Patients and Methods Results Comments Appendix 1. Independent... References

 
Background. The superior long-term patency of the internal mammary artery (IMA) confers important short-term and late survival advantages when grafted to the left anterior descending coronary artery. However, it remains uncertain whether patients derive additional survival benefit when both IMAs are used in coronary revascularization.

Methods. Between June 1983 and May 1986, 160 patients (mean age 60 years) received bilateral IMA grafts for coronary artery bypass procedures, and in 93% of patients, the right IMA was used to bypass the left coronary system. During a similar interval, a group of 161 patients matched for symptomatic status and extent of disease (mean age, 62 years) received a single left IMA and saphenous vein grafts.

Results. The two groups were similar with respect to gender, preoperative angina class, priority status, extent of coronary artery disease, left ventricular function, and number of distal anastomoses. Diabetes was more prevalent in the patient group receiving a single IMA graft (27% versus 17.5%; p = 0.05). Early outcome was similar in the two groups; operative mortality was 0.6% for the patient group receiving single IMA grafts and 0% for those with bilateral IMA grafts. The mean follow-up of 320 hospital survivors was 10 years. Univariate analysis revealed significantly fewer overall deaths in the patients receiving bilateral IMA grafts (n = 30; p = 0.05), and less late cardiac mortality (n = 12; p = 0.016). Ten-year actuarial survival for patients dismissed from the hospital was 76% for those receiving single IMA graft versus 85% for those receiving bilateral IMA grafts. Multivariate analysis revealed diabetes (risk ratio = 1.73), advancing age (risk ratio = 1.08), and lower ejection fraction (risk ratio = 1.01) to be the only significant predictors of late cardiac death. Use of a single IMA graft was not significant (p = 0.138) despite a risk ratio of 1.78. Use of only a single IMA graft correlated with an increased risk of angina recurrence (p < 0.001), late myocardial infarction (p = 0.019), and risk of any cardiac event (p < 0.001).

Conclusions. Independent risk factors for late death were diabetes mellitus, older age, and reduced ejection fraction. Patients receiving bilateral IMA grafts had better long-term survival than those with a single IMA graft, but this was not independent of diabetes. Multivariate analysis, however, did confirm that compared with single arterial grafts, bilateral IMA grafting was an independent predictor of lower rates of angina recurrence, late myocardial infarction, and the composite end point of any cardiac event.

	Introduction

Top Footnotes Abstract Introduction Patients and Methods Results Comments Appendix 1. Independent... References

 
Use of the left internal mammary artery (IMA) to bypass the left anterior descending coronary artery (LAD) has become the standard of care based on reports of superior graft patency [1–3], reduced cardiac events [4–7], and enhanced survival when compared with patients receiving vein grafts alone [8–10]. Anticipating additional advantages with the use of a second arterial graft, many surgical groups have used both IMAs during revascularization, but confirmation of further benefit from a second IMA graft is lacking. Indeed, some centers have reported increased operative mortality [2] as well as higher rates of sternal infection, reoperation for bleeding, and the requirement for prolonged postoperative ventilation [11, 12]. In most series, longer follow-up has not demonstrated additional survival advantage over the use of a single IMA graft [1, 13–16], accounting for the procedure's failure to achieve widespread support.

Before the seminal article by Loop and colleagues [9] confirming the benefit of an IMA graft to the LAD, there was conflicting opinion on clinical benefit of even a single IMA graft. In our early experience, we hypothesized that enhanced patency of only one arterial conduit might not be sufficient to reduce late ischemic events; thus, when arterial grafting was employed, we routinely attempted to use both IMAs to bypass branches of the left coronary system. This practice was standard on two surgical services (H.V.S. and T.A.O.) for a 2-year period beginning in January 1984. The present study analyzes late outcome of these patients compared with subsequent patients having revascularization with one IMA.

	Patients and Methods

Top Footnotes Abstract Introduction Patients and Methods Results Comments Appendix 1. Independent... References

 
Patients
During the 24-month period commencing in January 1984, 320 patients with multivessel disease underwent coronary revascularization with bilateral IMA grafts plus saphenous vein grafts (n = 160) or saphenous vein grafts alone (n = 160). Excluded from the review were patients having operation for single-vessel disease, those having reoperations, patients in whom alternate venous or arterial conduits were used, and patients requiring synchronous procedures or multiple endarterectomies. During an expanded time interval extending to May 1986, a matched group of 161 patients with a single IMA and supplementary vein grafts operated on by the same surgeons were identified. These 481 patients constituted 62% of all isolated coronary bypass procedures undertaken during this 3-year interval. The patient groups receiving single and bilateral IMA grafts form the study cohort for this report, and outcome of patients receiving only saphenous vein grafts is also presented.

Surgical Procedures
Indications for myocardial revascularization were based on standard clinical and angiographic criteria. All operations were undertaken through median sternotomy. Internal mammary arteries were dissected with electrocautery, and small side branches were clipped or cauterized; the artery was harvested with both accompanying veins as well as a generous surrounding pedicle of tissue. Generally, IMAs were prepared with dilute solution of papaverine applied topically, and considerable care was taken not to traumatize the endothelium. Cardiopulmonary bypass was conducted under moderate hypothermia (28° to 32°C) with antegrade crystalloid or blood cardioplegia. Distal anastomoses were performed during a single period of aortic occlusion with a running 7-0 polypropylene suture.

In patients receiving a single arterial graft, the left IMA was directed preferentially to the LAD (91%). In patients receiving bilateral IMA grafts, every effort was made to use the right IMA to bypass a branch of the left coronary system; in these patients, the right IMA was anastomosed to the LAD (45%), obtuse marginal artery (38%), right coronary artery (7%), first diagonal branch of LAD (6%), and intermediate coronary artery (4%).

Techniques and conduit routes for the patients receiving bilateral IMA grafts were: pedicled, anterior to the heart (49%); pedicled, through the transverse sinus (28%); free right IMA graft (14%); composite vein graft (6%); or composite arterial graft (3%).

Postoperative Follow-up
Clinical data were abstracted from patients' hospital records, and follow-up information was collected from the patients' most recent clinical visits, letters from home physicians, patient surveys, and telephone interviews. Cardiac-related events included in the calculation of an event-free survival were angina recurrence, cardiac death, sudden death, myocardial infarction (MI), percutaneous transluminal coronary angioplasty, and repeat coronary revascularization. Angina recurrence was defined as New York Heart Association class II or more. Survival analysis was also performed for all causes of death.

Data Analysis
Discrete variables were compared in the patients receiving single versus bilateral IMA grafts with ² tests. The distributions of continuous variables were compared in the two groups with Wilcoxon rank-sum tests. Survival curves were estimated with the Kaplan-Meier method. The relationships of discrete risk factors to survival were investigated with log-rank tests, and the Cox model was used to evaluate continuous risk factors.

Significant risk factors other than single versus bilateral IMA grafts were evaluated multivariately with Cox models (Appendix 1). Single versus bilateral IMA grafts was then added to the resulting multivariate model to determine if the number of IMA grafts was still significant after adjusting for other important risk factors. This analysis was carried out for seven separate late endpoints: all late deaths, late cardiac death, recurrence of angina, MI, percutaneous transluminal coronary angioplasty, reoperation, and any cardiac event.

In all statistical tests, a p value less than 0.05 was considered to be statistically significant.

	Results

Top Footnotes Abstract Introduction Patients and Methods Results Comments Appendix 1. Independent... References

 
Overall survival analysis for the 481-patient cohort demonstrated a clear survival advantage for both patient groups receiving IMA grafts compared with patients receiving only saphenous vein grafts (Fig 1). Patients receiving single or bilateral IMA grafts were then compared with respect to preoperative variables, risk factors for coronary artery disease, and operative parameters. The two groups were generally similar except that average age of patients receiving bilateral IMA grafts was 2 years less than patients with single IMA grafts (p = 0.05), and diabetes was less prevalent in the patients receiving bilateral IMA grafts compared with patients with only one IMA graft (p = 0.05) (Table 1). Cross-clamp and total bypass time for the bilateral IMA patients were slightly prolonged.

View larger version (15K): [in this window] [in a new window]   Fig 1. . Overall survival for patients revascularized with bilateral internal mammary artery (BIMA), single internal mammary artery (SIMA), and vein grafts.

Late follow-up was obtained in all patients (100%), and the mean interval of follow-up (9.8 ± 2.8 years, maximum 12.9 years) was similar in both groups. There were 50 late deaths among patients receiving a single IMA graft, and 29 of these deaths were related to cardiac causes. Patients receiving bilateral IMA grafts experienced an equivalent noncardiac mortality (18 versus 21) but significantly fewer late cardiac-related deaths (12 versus 29; p = 0.016) (Table 3).

View larger version (19K): [in this window] [in a new window]   Fig 2. . Late cardiac survival for patients receiving single (SIMA) versus bilateral internal mammary artery (BIMA) grafts.

View larger version (17K): [in this window] [in a new window]   Fig 3. . Overall survival for diabetic versus nondiabetic patients.

View larger version (19K): [in this window] [in a new window]   Fig 4. . Cumulative incidence of angina recurrence for patients receiving single (SIMA) versus bilateral internal mammary artery (BIMA) grafts.

View larger version (21K): [in this window] [in a new window]   Fig 5. . Freedom from occurrence of any cardiac event for single (SIMA) versus bilateral internal mammary artery (BIMA) grafts.

Eighty-four patients underwent repeat angiography at a mean of 6.9 years follow-up. A total of 124 IMA grafts were studied, revealing an 84% overall patency rate, better for the left IMA (88%) than for the right IMA (75%). Vein graft patency was 54% for these patients who had catheterization because of return of symptoms.

	Comments

Top Footnotes Abstract Introduction Patients and Methods Results Comments Appendix 1. Independent... References

 
Long-term survival and freedom from cardiac-related events after coronary artery bypass grafting are related to the completeness of revascularization, subsequent progression of native vessel disease, and late attrition of bypass conduits [17, 18]. The relative resistance of the IMA to arteriosclerosis is well known [19], and 10-year patency of 80% to 90% is almost twice that expected with saphenous vein grafts [4, 9]. Internal mammary arteries have other advantages including ideal coronary-to-conduit size match, functioning endothelium [20], and the capacity for flow regulation in response to varying myocardial demand [21].

Although early reports suggested use of the IMA increased operative time and perioperative complications, experience has shown that arterial bypass grafts add little, if any, morbidity or mortality [22, 23]. Studies of single IMA grafting from several centers have also confirmed improved cardiac event-free survival at 10 years compared with revascularization with vein grafts only [24, 25].

The potential survival benefit of using a second IMA for coronary artery bypass grafting has been difficult to establish, and there are reports of increased operative mortality [2, 19] and perioperative morbidity [11] with bilateral IMA grafts; major sternal infection was reported in up to 4% of patients having bilateral IMA grafts, especially in diabetic females or patients with postcardiotomy low output states [12]. These reports also suggested that reoperation for bleeding occurred two to three times more frequently as a consequence of the enlarged endothoracic wound, prolonged operative time, and increased platelet dysfunction after bypass; prolonged postoperative ventilatory support has also been reported in patients receiving two IMA grafts [11, 22, 26]. For these reasons, most surgeons have reserved use of bilateral IMA grafts to younger, nondiabetic male patients, and late studies of outcome of bilateral IMA grafts are thus influenced by this selection bias. In the present study, durations of aortic occlusion and cardiopulmonary bypass were slightly prolonged with use of bilateral IMA grafts, but there were no important differences in perioperative mortality or morbidity comparing the two groups.

Also, investigations of late survival after bilateral IMA grafting are confounded by different strategies in use of the right IMA graft and variable periods of observation. In the study of Fiore and associates [2], who evaluated outcome of 100 patients with bilateral IMA grafts and a matched group receiving a single IMA conduit and additional vein grafts, multivariate analysis at 15 years' follow-up failed to show any survival benefit for bilateral IMA grafts despite significantly improved freedom from MI (75% versus 59%; p = 0.025) and recurrent angina (36% versus 27%; p < 0.025) [13]. However, the second mammary was directed in all patients to the right coronary artery. In the series reported by Sargeant and colleagues [27], the right IMA was directed to the diagonal branch of the LAD. Studies by Galbut and coworkers [1], Morris and associates [14], and Dewer and colleagues [15] each included more than 1,000 patients with bilateral IMA grafts, and no significant difference in late mortality was found compared with groups with single arterial grafts; mean follow-up intervals were 3.3, 4, and 5 years, respectively.

The present study differs from most other investigations of bilateral IMA grafting because of the extended follow-up and our protocol whereby every effort was made to use both arterial grafts for bypass of the left coronary system. Both overall survival and survival from cardiac-related deaths were better in patients having two IMA grafts, but multivariate analysis showed that this difference was the result in large part of the greater prevalence of diabetes in patients having only one IMA graft. Nevertheless, there remained an important trend toward fewer late cardiac deaths among patients having bilateral IMA grafts even with adjustment for the difference in prevalence of diabetes.

Patients receiving bypass grafts with both IMAs also had significantly fewer complications of ischemic heart disease during follow-up compared with those having only one IMA graft. This finding of a reduction in late ischemic events [2, 10, 13, 16, 20] gives further support to the observation that use of both IMAs may decrease late cardiac deaths compared with revascularization with one IMA.

Many techniques have been described for bypassing multiple coronary arteries with IMAs [28]. Length of the right IMA may be limited when the pedicle is left intact; however, as demonstrated in the review, pedicled right IMA grafts can reach proximal branches of the circumflex coronary artery through the transverse sinus. Another option is to disconnect the right IMA graft proximally and anastomose it directly to the aorta or use it as a composite arterial or venous conduit, allowing the second IMA to be directed to any vessel in the left coronary circulation. Comparative long-term patency appears to be slightly less for grafts using the right IMA than for those using the left IMA, but when stratified according to the vessel bypassed, patency rates of the right and left IMA are similar [29]. When used as a free graft, IMA patency is approximately 80% at 10 years [30]. We believe that in order to show additional survival benefits from the use of a second arterial conduit, it must be preferentially directed to the left coronary circulation using one of these methods. In our series, this was achieved in 95% of patients.

Diabetes mellitus, older age, and reduced ejection fraction are known risk factors for mortality in prior series and have been demonstrated to predict reduced survival after primary as well as reoperative coronary surgery [31, 32]. A review of 674 patients undergoing bilateral IMA grafting from Emory demonstrated diabetes and reoperative surgery to be the only significant multivariate correlates of poor long-term survival [33].

Late MI occurred more frequently among patients with diabetes in whom its often silent presentation can cause delay in diagnosis and may well explain the survival disadvantage experienced in the non-coronary artery bypass grafting arm of the BARI trial. In our study, use of only a single IMA graft also correlated with an increased risk of late MI independent of diabetes, constituting our second significant finding in favor of bilateral IMA grafts.

In conclusion, our experience confirms clear advantages for the use of bilateral IMA grafts in coronary revascularization by virtue of reduction in the late risk of MI and recurrent angina. We were unable to demonstrate an overall late survival benefit, but there was an important trend toward improvement in late survival free of cardiac death. It seems reasonable, therefore, to expand use of bilateral IMA grafting, especially when the right IMA can be used to bypass a major branch of the left coronary system. For obese and diabetic patients, the radial artery may be a better choice as a second arterial graft, thus minimizing the risk of sternal infection. Final clarification of the long-term survival benefits for patients receiving more than one arterial graft will need to await the results of larger patient series, after possibly longer follow-up. Meanwhile, patients can be offered bilateral IMA grafts with the expectation of improved freedom from recurrence of angina, late MI, and other late cardiac events.

	Appendix 1. Independent Variables Considered in the Multivariate Analysis

Top Footnotes Abstract Introduction Patients and Methods Results Comments Appendix 1. Independent... References

 
Age Sex Diabetes Smoking Hypercholesterolemia Hypertension Obesity Prior acute myocardial infarction Angina New York Heart Association class III and IV Urgent emergency status Left main >50% Ejection fraction (continuous) Performance of a sequential graft Number of coronary anastomoses Number of coronary grafts Internal mammary artery anastomoses Number of vein anastomoses

	Footnotes

Top Footnotes Abstract Introduction Patients and Methods Results Comments Appendix 1. Independent... References

 
Presented at the Poster Session of the Thirty-third Annual Meeting of The Society of Thoracic Surgeons, San Diego, CA, Feb 3–5, 1997.

Address reprint requests to Dr Schaff, Mayo Clinic, 200 First Street, SW, Rochester, MN 55905 (e-mail: schaff{at}mayo.edu).

	References

Top Footnotes Abstract Introduction Patients and Methods Results Comments Appendix 1. Independent... References

 

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				P. J. Shah, K. Bui, S. Blackmore, I. Gordon, D. L. Hare, J. Fuller, S. Seevanayagam, and B. F. Buxton Has the in situ right internal thoracic artery been overlooked? An angiographic study of the radial artery, internal thoracic arteries and saphenous vein graft patencies in symptomatic patients Eur. J. Cardiothorac. Surg., May 1, 2005; 27(5): 870 - 875. [Abstract] [Full Text] [PDF]

				M Bonacchi, F Battaglia, E Prifti, M Leacche, N S Nathan, G Sani, and G Popoff Early and late outcome of skeletonised bilateral internal mammary arteries anastomosed to the left coronary system Heart, February 1, 2005; 91(2): 195 - 202. [Abstract] [Full Text] [PDF]

				M. Tabata, S. Takanashi, T. Fukui, T. Horai, T. Uchimuro, K. Kitabayashi, and Y. Hosoda Off-Pump Coronary Artery Bypass Grafting in Patients With Renal Dysfunction Ann. Thorac. Surg., December 1, 2004; 78(6): 2044 - 2049. [Abstract] [Full Text] [PDF]

				O. M. Bical, W. Khoury, Y. Fromes, M. Fischer, M. Sousa Uva, G. Boccara, and P. H. Deleuze Routine Use of Bilateral Skeletonized Internal Thoracic Artery Grafts in Middle-Aged Diabetic Patients Ann. Thorac. Surg., December 1, 2004; 78(6): 2050 - 2053. [Abstract] [Full Text] [PDF]

				F. Formica, O. Ferro, P. Greco, A. Martino, D. Gastaldi, and G. Paolini Long-term follow-up of total arterial myocardial revascularization using exclusively pedicle bilateral internal thoracic artery and right gastroepiploic artery Eur. J. Cardiothorac. Surg., December 1, 2004; 26(6): 1141 - 1148. [Abstract] [Full Text] [PDF]