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(Circulation. 2001;104:2152.)
© 2001 American Heart Association, Inc.

Editorials

Superiority of Bilateral Internal Thoracic Artery Grafting

It’s Been a Long Time Comin’

Bruce W. Lytle, MD; Floyd D. Loop, MD

From the Department of Thoracic and Cardiovascular Surgery, the Cleveland Clinic Foundation, Cleveland, Ohio.

Correspondence to Bruce W. Lytle, MD, Department of Thoracic and Cardiovascular Surgery, The Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk F-25, Cleveland, Ohio 44195. E-mail lytleb{at}ccf.org

Key Words: Editorials • grafting • bypass

A myriad of data have established the superiority of the left internal thoracic artery (LITA) graft to the left anterior descending (LAD) coronary artery.^1,2 Late patency rates of LITA-LAD grafts far exceed those of saphenous vein grafts (SVG) to the LAD, and ITA grafts avoid the late complications of vein graft atherosclerosis.³ Once an ITA graft is patent, late failure is extremely rare. These advantages are reflected in improved clinical outcomes. When compared with patients receiving only SVGs, patients receiving LITA-to-LAD grafts and SVGs to other vessels experience an improved long-term survival rate, fewer reoperations, and fewer cardiac hospital admissions.^1,2

See p 2164

If one ITA graft is good, might two be better? Even before the demonstration of the benefit of LITA-LAD grafts in the 1980s, a minority of coronary artery surgeons used bilateral ITA (BITA) grafts for selected patients based on the premise that more extensive ITA use might further improve outcomes. However, the incremental benefit of BITA grafts over the LITA-LAD plus SVG strategy has been difficult to document, despite its apparent logic.

Why has the benefit of BITA grafting been difficult to show? Probably for multiple reasons. First, the LITA-LAD plus SVG strategy produces very good outcomes during the first postoperative decade. Therefore, to show improved outcomes, a large sample size is needed and those patients must be followed for relatively long postoperative intervals. BITA grafting has not been a common operation at most institutions, and the length of follow-up has often been short. Also, if it is the case that only some patient subgroups benefit from BITA grafting, the sample size needed to produce a statistically significant difference becomes greater. Second, no randomized data exist comparing BITA and single ITA (SITA) surgical strategies and, in nonrandomized comparisons, patient and surgeon-related factors introduce potentially confounding variables that make statistical analyses difficult. Third, techniques of ITA use vary (in situ grafts or free grafts) and the choice of vessels grafted with the ITAs vary, and those factors may influence long-term outcomes. Fourth, BITA grafting is not necessarily total ITA revascularization, and events caused by vein graft failure may blunt the positive impact of ITA grafts.

In this issue of Circulation, Endo et al⁴ report on 1131 patients undergoing bypass surgery (443 receiving BITA grafts) who were followed for a median postoperative interval of 6 years. After using Cox regression analyses to identify variables that had a significant impact on outcomes in a multivariate setting, they concluded that, compared with SITA grafting, the BITA strategy decreased the likelihood of reoperation and decreased the risk of cardiac death for patients with an ejection fraction >40% and for patients with left main stenoses. In addition to concluding that BITA grafting produced some improved outcomes, they further noted that the full benefit of BITA grafting might not be appreciated during their relatively short follow-up interval. They are right on both counts.

Considerable data now exist that confirm and extend their observations concerning the benefit of BITA grafts. The largest patient cohort followed for the longest postoperative interval was the subject of a recent retrospective, nonrandomized study from the Cleveland Clinic Foundation; it involved 10 124 patients (2001 receiving BITA grafts) who were followed for a mean postoperative interval of 10 years.⁵ Multiple statistical strategies were used for risk adjustment, including propensity matching and parsimonious and nonparsimonious risk factor models. All comparisons demonstrated better survival rates and fewer reinterventions (reoperation or percutaneous transluminal coronary angioplasty [PTCA]) for patients receiving BITA grafts compared with those receiving only a SITA graft. Figure 1 depicts the survival and reoperation hazard function (percent reoperation per year) curves for propensity-matched SITA and BITA patients for 12 postoperative years; a higher survival rate and fewer reoperations are shown for the BITA group, and an increasing benefit of BITA grafting is seen with increasing follow-up interval.

View larger version (23K): [in this window] [in a new window]   Figure 1. Comparison of survival and reoperation hazard function curves in propensity-matched patients (both P<0.0001; BITA, n=1989; SITA, n=4147). CABG indicates coronary artery bypass grafting. Reproduced with permission from Reference 5.

The demonstration that the entire patient population had better outcomes with the BITA strategy does not necessarily mean that every subset of patients will have better outcomes or identify the magnitude of that benefit. Figure 2 addresses these issues. By 12 postoperative years, half of the patient population would have a risk of death decreased by at least 6.3%, a risk of PTCA decreased by at least 3.9%, and a risk of reoperation decreased by at least 8.3% if they received BITA grafts rather than a SITA graft. Not every subgroup of patients benefits equally, and the greatest advantage of BITA grafts accrue to those patients with the longest life expectancy. The risk of death competes with the risk of reoperation and PTCA.⁶ However, despite a variable benefit, no patient subset was predicted to have worse outcomes with BITA grafting.

View larger version (26K): [in this window] [in a new window]   Figure 2. Nonproportional hazard equations were solved twice for each propensity-matched patient, once as if the patient had SITA grafting and once as if the patient had BITA grafting. The distribution of the percentage differences in outcomes for all patients based on BITA vs SITA grafting are shown. All patients had better predicted outcomes with BITA grafting. The percentage of the patient population is expressed vertically, and the percent difference in the occurrence of each event is expressed horizontally. The table details percent differences at selected percentages of the entire patient population. Reproduced with permission from Reference 5.

Other studies comparing BITA and SITA strategies have produced mixed results regarding any survival benefit of BITA grafting.^7–10 However, the studies showing no benefit have contained smaller numbers of patients followed for shorter intervals,^7–9 and those studies that have shown a survival benefit have tended to be larger.¹⁰ Even smaller studies have shown trends toward an advantage of the BITA strategy in avoiding reoperation or decreasing the risk of cardiac events.

With all these apparent benefits, why has BITA grafting not become more widely used? First, it is a technically demanding operation and may take more time. Multiple studies, however, have shown that in experienced hands, in-hospital mortality is not increased. Second, the use of bilateral in situ grafts has some limitations regarding the coronary vessels that can be grafted, and for some patients, the coronary anatomy does not lend itself well to the BITA strategy. However, the recent use of composite ITA grafts where the right ITA is anastomosed to the LITA as a Y or T graft allows the surgeon much more flexibility in grafting lateral wall and posterior vessels and also creates fewer problems if repeat cardiac surgery is ever needed.¹¹ Third, there has been a justified concern about the potential for increased morbidity associated with BITA grafting, most specifically the risk of sternal wound complications. Most studies have noted that wound complications are more frequent in diabetic patients.¹² Changing techniques of ITA preparation, in particular skeletonization of the ITA, seem to have decreased those risks, but obese diabetic patients make up a group that is still at an increased risk and has a relative contraindication to the use of BITA grafts.¹³

Finally, surgeons may be influenced in their choice of operation by the emphasis on short-term outcomes (in-hospital risks, costs, and length of stay) by other doctors, hospitals, governmental agencies, the insurance industry, and even the media. There is less emphasis on long-term outcomes. Often 5-year follow-up is considered long-term, and the 10- to 20-year outcomes after intervention are thought to exist in a foggy and rather nebulous future and to be unimportant. However, for a population of patients undergoing invasive treatment of coronary artery disease, that is the time when differences in the effectiveness of treatment begin to become clear. In the Cleveland Clinic study cited above, >70% of patients receiving either SITA or BITA grafts were still alive 12 years after the operation. Choosing a more complex surgical strategy because of better patient outcomes that will occur 10 to 20 years after the operation requires a long-term perspective and data to support that policy. Those data are now much more convincing than they have been in the past.

Have advances in alternative strategies reduced the advantage of ITA grafts? There is evidence that vein graft patency rates will be better today than noted in previous decades. Treating patients with platelet inhibitors and statin drugs seem to increase vein graft patency rates and to lower the rate of the development of vein graft atherosclerosis.^14,15 However, these improvements are only relative. Vein graft atherosclerosis continues to be the factor most commonly compromising the long-term effectiveness of bypass surgery. The use of the radial artery as a bypass graft (often a conduit easier to obtain and more technically forgiving to work with than the ITA) may offer some long-term advantages over vein grafts. However, with only 5-year angiographic data currently available, radial artery patency is not clearly superior to that for vein grafts, and it seems to be inferior to that for ITA grafts. Furthermore, whether radial artery grafts will have the ITA’s ability to resist the development of atherosclerosis is unknown.

We are not on the threshold of witnessing a widespread change to routine BITA grafting. It is a more complex operation and, in each situation, surgeons must choose the operation on the basis of what they believe they can best accomplish for that specific patient at that specific time. It has been suggested that women derive less benefit from BITA grafting, and there may be other patient subsets that benefit relatively little.¹⁶ However, until recently, it has been possible to ignore categorically the consideration of BITA grafting with the justification that there was no evidence for its efficacy. It is no longer possible to hold that position. For patients with a life expectancy greater than a decade, the extension of ITA grafting to the circumflex and/or right coronary system produces better long-term outcomes, and the longer the follow-up is extended, the larger the benefit seems to be. It has taken a long time to show that BITA grafting is better, but it is.

Footnotes

The opinions expressed in this editorial are not necessarily those of the editors or of the American Heart Association.

References

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3. Lytle BW, Loop FD, Cosgrove DM, et al. Long-term (5–12 years) serial studies of internal mammary artery and saphenous vein coronary bypass grafts. J Thorac Cardiovasc Surg. 1985; 89: 248–258.[Abstract]
   
4. Endo M, Nishida H, Tomizawa Y, et al. Benefit of bilateral internal mammary artery grafts over single IMA graft for multiple coronary artery bypass grafting. Circulation. 2001; 104: 2164–2170.[Abstract/Free Full Text]
   
5. 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]
   
6. Blackstone EH, Lytle BW. Competing risks after coronary bypass surgery: the influence of death on reintervention. J Thorac Cardiovasc Surg. 2000; 119: 1221–1132.[Abstract/Free Full Text]
   
7. Pick AW, Orszulak TA, Anderson BJ, et al. Single versus bilateral internal mammary artery grafts: 10-year outcome analysis. Ann Thorac Surg. 1997; 64: 599–605.[Abstract/Free Full Text]
   
8. Naunheim KS, Barner HB, Fiore AC. Results of internal thoracic artery grafting over 15 years: single versus double grafts: 1991 update. Ann Thorac Surg. 1992; 53: 716–718.[Medline] [Order article via Infotrieve]
   
9. Sergeant P, Blackstone E, Meyns B. Validation and interdependence with patient-variables of the influence of procedural variables on early and late survival after CABG: K U Leuven Coronary Surgery Program. Eur J Cardiothorac Surg. 1997; 12: 1–19.[Abstract]
   
10. Buxton BF, Komeda M, Fuller JA, et al. Bilateral internal thoracic artery grafting may improve outcome of coronary artery surgery: risk-adjusted survival. Circulation. 1998; 98: III-1–III-6.
    
11. Tector AJ, McDonald ML, Kress DC, et al. Purely internal thoracic artery grafts: outcomes. Ann Thorac Surg. 2001; 72: 450–455;discussion 455.[Abstract/Free Full Text]
    
12. Loop FD, Lytle BW, Cosgrove DM, et al. Sternal wound complications after isolated coronary bypass grafting: early and late mortality, morbidity and cost of care. Ann Thorac Surg. 1990; 49: 179–187.[Abstract]
    
13. Matsa M, Paz Y, Gurevitch J, et al. Bilateral skeletonized internal thoracic artery grafts in patients with diabetes. J Thorac Cardiovasc Surg. 2001; 121: 668–674.[Abstract/Free Full Text]
    
14. Goldman S, Copeland J, Moritz T, et al. Starting aspirin therapy after operation. Effects on early graft patency. Circulation. 1991; 84: 520–526.[Abstract/Free Full Text]
    
15. The Post Coronary Artery Bypass Graft Trial Investigators. The effect of aggressive lowering of low-density lipoprotein cholesterol levels and low-dose anticoagulation on obstructive changes in saphenous-vein coronary-artery bypass grafts. N Engl J Med. 1997; 336: 153–162.[Abstract/Free Full Text]
    
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