Background Information

The Arterial Revascularisation Trial (ART) is sponsored by the British Heart Foundation and the Medical Research Council.  The aim of ART is to determine if the use of both internal mammary arteries (BIMA) during coronary artery bypass grafting (CABG) improves survival and the need for further intervention over that observed with a single internal mammary artery (SIMA).

CABG is the optimal therapy, prognostically and symptomatically, for multi-vessel ischaemic heart disease [1]. Worldwide, around 800,000 CABG are performed annually. Recognising the under provision of CABG in the UK, the National Service Framework (NSF) aims to increase numbers from 500 [2] to 750 per million of population. The requirement for CABG is also likely to increase because of a growing elderly population with coronary disease and because percutaneous interventions ultimately lead to an increased requirement for CABG [3].

Most CABG patients require three grafts and the standard operation uses a single IMA (SIMA) and supplemental vein or radial artery grafts.  CABG provides excellent short and intermediate term outcomes but its long-term efficacy is limited by vein graft failure. Ten years after CABG around 1/2 of vein grafts are blocked and of the remaining 50% half are severely diseased [6] whereas up to 95% of IMA conduits remain disease free. In addition to reducing long-term survival, vein graft failure significantly increases the risk of recurrent angina, late myocardial infarction and the need for further intervention [4-7]. Indeed, by 10 years after CABG >50% of patients have recurrent angina and up to 1/3 may eventually require redo CABG [8-11].  Aspirin and statins [10,11] may improve vein graft patency but are unlikely to achieve the patency rates of IMA grafts.

As discussed below, bilateral IMA (BIMA) in comparison to SIMA grafts, may improve survival and reduce the need for redo CABG.  However while BIMA grafting is common in some centres in Europe, America, Australia and Japan, it still not widely used. For example, in 1998 15% of UK CABG patients received two arterial grafts (and a significant proportion of these would have used a radial artery rather than a second IMA graft) [2].  The major reasons for not using BIMA grafts is because of no definitive evidence of benefits (there are no randomised trials) and the perceptions that it is technically more challenging, more prolonged and increases the risk of impaired wound healing. Given the number of CABG procedures currently performed in the UK and the aim of the NSF to increase these numbers, it is also important to obtain accurate information on the costs and cost-effectiveness of using BIMA versus SIMA grafts.

Nine studies, reviewed extensively in reference 12, have compared the influence of SIMA and BIMA grafts on survival and the need for redo surgery. Interpretation of individual studies is, however, complicated by lack of randomisation, small patient numbers and inadequate length or completeness of follow-up. Furthermore, as the use of BIMA grafts was initially confined to younger, lower risk patients, any long-term benefits were attributed to the inherently more favourable characteristics of these patients, obscuring any benefit of BIMA.

A recent systematic review was performed of those studies, meeting pre-specified criteria relating to patient selection, comparability of groups, outcome assessment, and completeness of follow-up, to determine if there are differences in survival, expressed as a pooled hazard ratio (HR), in patients receiving SIMA or BIMA [12] (Figure1). The analysis included 15962 patients comprising 11269 SIMA and 4693 BIMA patients from seven studies that either matched or adjusted for age, sex, ventricular function and diabetes. The results suggested a survival advantage for BIMA grafts (HR for death=0.81, 95%CI: 0.70 to 0.94) without any evidence of a detrimental effect, however there was very limited evidence relating to secondary endpoints including possible adverse consequences.

 Figure 1. Effects of bilateral IMA compared with single IMA

  

In the largest single study [13], of 8000 SIMA and 2000 BIMA patients, Lytle et al reported that the HR for death was decreased by 23% in the BIMA group at 12 years and the need for redo CABG reduced from 40% in the SIMA to 10% in the BIMA group.

In another observational study, published after the systematic review, Endo et al reported outcome in 688 SIMA and 443 BIMA patients [14]. The groups were similar regarding age and ventricular function but there were more diabetics in the BIMA group (18% vs 13%) and females in the SIMA group  (19% vs 10%). At six years the combined incidence of death, myocardial infarction and redo CABG was lower in the BIMA group (p=0.06) and particularly in the 782 patients below 71 years and with an ejection fraction > 0.4 (HR: 0.61; 95%CI, 0.38 to 0.98:p=0.04). As vein graft failure increases markedly beyond seven years after CABG the authors suggest that the benefits of BIMA grafts are likely to increase with further follow-up.

Two studies reported no benefit of BIMA grafting [15,16]. Sergeant’s study, however, had fewer than 100 BIMA patients with 10-year follow up and use of the second IMA was frequently suboptimal [15]. Kurlansky et al reported no survival difference at ten years in 261 women with BIMA grafts and a matched cohort with SIMA grafts [16]. However, 81% of the BIMA group vs 66% of the SIMA group had triple vessel disease (p<0.001) and only 120 patients in each group were available for comparison at ten years.

For optimal patency both IMA should be placed to the left sided arteries  [17-19]. Patency of the right IMA is reduced if used as a free aortic graft [18] or placed to the right coronary artery [19] due to size discrepancy and eventual disease development at the crux.

Angiographic studies demonstrate markedly superior patency of BIMA grafts,compared to vein grafts, refuting the assertion that the superior patency of IMA grafts is due to better ‘run-off’ in the LAD territory. Patency rates for BIMA to various coronary arteries, are 98% at 7 days [14] and 95% at two [20] and seven years [21]. Furthermore, off-pump CABG (OPCAB) now makes CABG feasible in patients whose advanced age previously precluded CABG using cardiopulmonary bypass. A composite radial artery from one or both IMA, allows up to four grafts as an ‘off-pump’ CABG, eliminating both cardiopulmonary bypass and aortic manipulation and minimizing the risk of cerebral injury [22].

Opposition to BIMA grafting is largely based on the perception of increased perioperative risk and especially sternal wound morbidity. There is consistent evidence, however, that the operative mortality of BIMA grafting at 1%-2% [12,13] is no higher, and may, in fact, be less than that of the standard operation because of a reduced risk of early graft failure.

Sternal dehiscence is a potential complication of BIMA grafts and particularly in diabetics. In reality, there is only a minimal increase in the risk of impaired wound healing in both non-diabetics [13, 23-27] and diabetics [23-27] unless the patient is morbidly obese and/or has marked respiratory impairment [24]. The risk of impaired wound healing can be minimized with judicious patient selection and modification of the IMA harvesting method whereby a ‘skeletonized’ rather than ‘pedicled’ fashion preserves collaterals and sternal blood supply [25] and improves wound healing, particularly in diabetics.  No difference has been found in myocardial enzymes [28], parameters of respiratory exchange [29] or in respiratory injury between SIMA and BIMA patients.  BIMA harvesting adds around 30 minutes to a three-hour operation.  

Uncertainty remains because there is no randomised evidence, so we have designed a randomised trial - the Arterial Revascularisation Trial (ART) - to compare SIMA versus BIMA grafting in coronary revascularisation.  ART will compare survival rates, need for redo CABG, recurrent angina, myocardial infarction, quality of life and cost effectiveness of SIMA versus BIMA grafting.

References

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