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(Circulation. 2001;103:507.)
© 2001 American Heart Association, Inc.

Clinical Investigation and Reports

Use of the Internal Mammary Artery Graft and In-Hospital Mortality and Other Adverse Outcomes Associated With Coronary Artery Bypass Surgery

Bruce J. Leavitt, MD; Gerald T. O’Connor, PhD, DSc; Elaine M. Olmstead, BA; Jeremy R. Morton, MD; Christopher T. Maloney, MD; Lawrence J. Dacey, MD; Felix Hernandez, MD; Stephen J. Lahey, MD; for the Northern New England Cardiovascular Disease Study Group

From Fletcher Allen Health Care, Burlington, Vt (B.J.L.); Dartmouth Medical School, Center for the Evaluative Clinical Sciences, Hanover, NH (G.T.O.); Dartmouth-Hitchcock Medical Center, Lebanon, NH (E.M.O., L.J.D.); Maine Medical Center, Portland, Maine (J.R.M.); Catholic Medical Center, Manchester, NH (C.T.M.); Eastern Maine Medical Center, Bangor, Maine (F.H.); and Beth-Israel Deaconess Medical Center, Boston, Mass (S.J.L.). Dr Lahey is now with Worchester Medical Center, Worchester, Mass.

Correspondence to Bruce Leavitt, MD, University of Vermont, 111 Colchester Ave, Fletcher House, 4th Floor, Burlington, VT 05401. E-mail Bruce.Leavitt{at}vtmednet.org

	Abstract

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Background—There is clear evidence that patients having coronary artery bypass graft surgeries with an internal mammary artery (IMA) have better long-term survival. Some studies have suggested a short-term protective effect as well but, because older and sicker patients are less likely to receive an IMA graft, there has been concern that the apparent protective effect of the IMA on short-term mortality has been confounded by other risk factors. This study was intended to examine the independent effect of IMA grafts on in-hospital mortality while adjusting for patient and disease factors.

Methods and Results—We studied the use of the left IMA (LIMA) in 21 873 consecutive, isolated, first-time coronary artery bypass graft procedures from 1992 through 1999. A total of 87% of the patients received a LIMA graft. LIMA graft use was associated with a significantly decreased risk of mortality. The crude odds ratio for death (LIMA versus no LIMA) was 0.26 (95% confidence intervals, 0.22, 0.31; P<0.001). LIMA grafts were protective across all major patient and disease subgroups. The odds ratios by subgroup ranged from 0.13 to 0.48. After adjustment for all major risk factors, the odds ratio for death was 0.40 (95% confidence intervals, 0.33, 0.48; P<0.001). Rates of cerebrovascular accident, return to cardiopulmonary bypass, return to the operating room for bleeding, and mediastinitis or sternal dehiscence requiring surgery were also less in the LIMA group, although not significantly so.

Conclusions—These data suggest that in addition to its well-documented patency and long-term beneficial effect, LIMA grafting has a strong protective effect on perioperative mortality.

Key Words: cardiovascular diseases • bypass • revasuclarization • arteries

	Introduction

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Since Green et al’s¹ introduction of the internal mammary artery (IMA) as a conduit for coronary bypass surgery (CABG), there have been numerous reports comparing the IMA to venous conduits. These studies have shown improved long-term patency^{2 3 4 5} and survival^{4 6 7 8} with IMA use. However, the short-term effects of IMA use as a conduit for CABG have only recently been evaluated. Using the Society of Thoracic Surgeons’ National Cardiac Surgical Database, Edwards et al⁹ studied the impact of IMA conduits on operative mortality in 38 578 patients undergoing CABG from 1987 to 1991. The operative mortality of patients receiving an IMA graft was significantly less than that of patients receiving venous conduits only. However, patients in the lowest quartile of risk did not seem to benefit from the presence of an IMA graft. Only 48% of patients in their study received an IMA graft. We reported in 1997 that there were widespread differences in IMA use in our region.¹⁰ Patients who were female, older, of smaller size, of urgent or emergent priority, and with decreased left ventricular ejection fractions received an IMA graft less often. Individual surgeon IMA use ranged from 42% to 95%. These data suggested that more patients could benefit from the use of an IMA as a conduit for CABG surgery. The Northern New England Cardiovascular Disease Study Group is a voluntary research consortium composed of clinicians, scientists, and hospital administrators from 6 medical centers in New England. The intent of the group is to foster continuous improvement in the quality of care of patients with cardiovascular disease. This is accomplished through the pooling of process and outcome data and the timely feedback of data to clinicians.¹¹ The purpose of this study was to investigate the association between the use of the left IMA (LIMA) graft and perioperative outcomes associated with CABG surgery, while adjusting for preoperative differences in patient and disease characteristics.

	Methods

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Data Collection
All 6 member medical centers and all 34 member cardiothoracic surgeons participated in this study. The institutional review board of each participating hospital approved the data collection method. The data set included 21 873 consecutive patients undergoing first-time CABG surgery from 1992 through 1999. Patients undergoing repeat CABG and those undergoing CABG with valve or other significant surgery were excluded from the study. Patients who received bilateral IMA grafts or right IMA grafts were also excluded (4% of patients). Data were collected on the following variables: age, sex, body surface area, body mass index, significant comorbid conditions (diabetes mellitus, chronic obstructive pulmonary disease, peripheral vascular disease, dialysis-dependent renal failure, and congestive heart failure), ejection fraction, left ventricular end diastolic pressure, number of diseased coronary arteries, percentage stenosis of the left main coronary artery, priority at surgery, use of an IMA graft, return to cardiopulmonary bypass pump, intraoperative or postoperative stroke, bleeding requiring reoperation, sternal dehiscence/mediastinitis requiring surgery, and status at hospital discharge (alive or dead).

Priority at surgery was assessed by the surgeon using previously published definitions.¹² Briefly, "emergency" meant that medical factors relating to the patient’s cardiac disease dictated that surgery should be performed within hours to prevent morbidity or death; "urgent" meant that medical factors required the patient to stay in the hospital for an operation before discharge; and "elective" meant that medical factors indicated the need for operation, but the clinical situation allowed discharge from the hospital with readmission at a later date.

Statistical Methods
Standard statistical methods were used for the calculation of the univariate odds ratio (OR), relative risk, risk difference, and the ² test.¹³ Logistic regression analysis was used to calculate adjusted ORs and to generate summary predicted risk variables from multivariate statistical models.¹⁴ Direct standardization was used to adjust rates for all adverse outcomes. Analyses were performed using the Stata¹⁵ and SAS¹⁶ statistical programs. Statistical significance was defined as a 2-tailed P <0.05.

	Results

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LIMA Use and In-Hospital Mortality
Table 1 shows the relative size of each subgroup and the percentage of patients receiving a LIMA. The size of the patient subgroups examined ranged from 1.7% (those with preexisting renal failure) to 98.3% (those without renal failure) of the total sample, but most subgroups comprised at least a third of the sample. Of the 21 873 patients in our study, 19 016 (86.9%) received a LIMA graft. Among those not receiving a LIMA graft, 67% had significant left anterior descending coronary artery (LAD) disease and only 8% had isolated severe right coronary artery or posterior descending artery disease. Thus, the majority of these patients were likely eligible for LIMA grafting.

View this table: [in this window] [in a new window]   Table 1. Rates of Use and Relative Odds of In-Hospital Death for Those Receiving LIMA Grafts by Subgroup

Rates of LIMA graft use among patient subgroups ranged from 59.7% (among emergency patients) to 90.6% (among elective patients and those <60 years of age). Lower rates of LIMA use were seen among smaller patients (74.2% in those with a body surface area <1.6 m²), the elderly (81.9%), women (81.5%), patients with comorbid diseases (chronic obstructive pulmonary disease, 83.9%; congestive heart failure, 82.4%; and renal failure, 79.6%), and patients with a left main stenosis 90% (80.2%).

The overall in-hospital adjusted mortality rate among patients receiving a LIMA was 2.2%, and that for those patients who did not receive a LIMA was 4.9% (P<0.001; Table 2). The overall crude OR for in-hospital mortality was 0.26 (95% confidence intervals [CI], 0.22, 0.31; P<0.001). LIMA use was studied in all major subgroups of patients. The ORs of in-hospital mortality (with LIMA versus without LIMA) are shown for each patient group (Table 1). In all patient groups examined, those who received a LIMA graft had significantly decreased in-hospital mortality compared with those who did not. Patients 60 to 69 years of age showed an 80% reduced risk of mortality with a LIMA (OR, 0.20), but even patients 70 years benefited from a LIMA (OR, 0.41). Although women received a LIMA graft less often than men did, those who did had lower mortality rates (OR, 0.35) than those who did not. Patients with comorbid disease, poor ejection fractions (<40%), higher left ventricular end-diastolic pressures (20 mm Hg), left main stenosis 90%, or 3-vessel coronary disease all had lower mortality rates if a LIMA was used. Even patients who had urgent or emergency surgery had a reduced risk of death if a LIMA was used (for urgent patients, OR=0.36; for emergency patients, OR=0.30). The overall adjusted OR for mortality for LIMA versus no LIMA was 0.40 (95% CI, 0.33, 0.48; P<0.001), which is a 60% reduction in risk (Table 1).

View this table: [in this window] [in a new window]   Table 2. Use of LIMA and In-Hospital Outcomes: Risk-Adjusted1 Rates

Table 3 summarizes in-hospital mortality by LIMA use and patient risk groups. Risk groups were developed using multivariate analysis and included patient demographic characteristics, body size, the presence of comorbid conditions, the results of coronary catheterization, and the priority at surgery. A complete list of variables may be found in the footnote accompanying Table 3. Five mortality risk groups were developed (<1.5%, 1.5% to 2.9%, 3.0% to 4.9%, 5.0% to 9.9% and 10.0%). The majority of patients were in the lowest 2 risk groups, and the LIMA use percentage decreased monotonically as risk increased. The relative risk is the quotient of the mortality rate in the group receiving a LIMA and the group in which no LIMA was used. The relative risks varied from 0.37 to 0.59, indicating a protective effect of 63% to 41%. The risk difference shows the absolute difference in the mortality rates, that is, the subtrahend of the mortality rate with LIMA and without LIMA. A negative sign indicates a lower mortality rate with LIMA. The risk differences varied from -1.04% to -9.61% and increased across risk groups, with the largest differences found among the highest risk patients.

View this table: [in this window] [in a new window]   Table 3. In-Hospital Mortality by Use of LIMA and by Predicted Risk Category

LIMA Use and Other Adverse Outcomes
We examined the use of LIMA and its association with other adverse outcomes. Rates were adjusted for the following risk factors: age, sex, body surface area, body mass index >30 kg/m²; major medical comorbidities (chronic obstructive pulmonary disease, diabetes mellitus, congestive heart failure, and preoperative renal failure), preoperative left ventricular end-diastolic pressure, preoperative ejection fraction, left main coronary artery stenosis, 3-vessel disease, and priority at surgery. The adjusted mortality rate for the LIMA group was 2.2%; it was 4.9% in the group without LIMA (Table 2), which is a significant reduction in mortality rate (P<0.001). The use of the LIMA as a vascular conduit for CABG was associated with lower adjusted rates of intraoperative or postoperative cerebrovascular accident, return to cardiopulmonary bypass, return to the operating room for bleeding, and mediastinitis or sternal dehiscence. The cerebrovascular accident rate in the LIMA group was 1.6%; it was 1.9% in the non-LIMA group (P=0.096). Only 2.7% of patients in the LIMA group returned to the operating room for bleeding compared with 3.2% in the non-LIMA group (P=0.365). Infective mediastinitis or sternal dehiscence requiring reoperation occurred in 1.1% of the LIMA group and 1.3% of the non-LIMA group (P=0.810). Rates of return to bypass pump were 3.7% versus 4.3% (LIMA versus no LIMA). The differences observed in these rates of adverse outcomes, other than mortality, were not statistically significant.

	Discussion

Top Abstract Introduction Methods Results Discussion References

 
This regional, prospective study examined the effect of IMA grafts on in-hospital mortality while adjusting for patient and disease factors. We studied the use of the LIMA in 21 873 consecutive, isolated, first-time CABG procedures. A total of 87% of patients received a LIMA graft, and LIMA graft use was associated with a significantly decreased risk of in-hospital mortality. The crude OR for death (LIMA versus no LIMA) was 0.26 (95% CI, 0.22, 0.31; P<0.001). LIMA grafts were protective across all major patient subgroups, including age, sex, body surface area, obesity, comorbid conditions, ejection fraction, left ventricular end-diastolic pressure, left main coronary artery stenosis, number of diseased vessels, and priority at surgery. The OR by subgroup ranged from 0.13 to 0.48. After adjustment for all major risk factors, the OR for death was 0.40 (95% CI, 0.33, 0.48; P<0.001). Rates of cerebrovascular accident, return to cardiopulmonary bypass, return to the operating room for bleeding, and mediastinitis or sternal dehiscence requiring surgery were also less in the LIMA group, although not significantly so. These data suggest that in addition to its well-documented patency and long-term beneficial effect, LIMA grafting has a protective effect on perioperative mortality.

These results are consistent with those reported by Edwards et al⁹ and Cosgrove et al¹⁷ using observational data. A common criticism of observational studies such as theirs is that there is a patient selection bias in those patients who receive a LIMA. There is legitimate concern that the reason for the observed beneficial effect of IMA use is that patients receiving an IMA are not as sick or as high risk as those patients who do not receive a LIMA. However, in every patient subgroup in our study, there was a protective effect on in-hospital mortality in those patients who received a LIMA graft. Most surgeons would define higher risk patients as those >70 years of age with an elevated left ventricular end-diastolic pressure or diminished ejection fraction, serious comorbidity, small body size, or urgent or emergency presentation. In each of these patient higher risk subgroups, the use of an IMA graft at the time of surgery provided protection from in-hospital mortality. This consistency in protective effect of an IMA makes patient or disease characteristics an unlikely explanation for the findings. Of course, we could not rule out the possibility of confounding factors not measured by this study. This variable or variables would have to be unequally distributed between the patient groups, unknown to the surgeons (and to the database), and uncorrelated with the variables used in the adjustment models.

Is it plausible that the IMA confers a short-term protective effect in cardiac surgery? There are several studies that suggest this may be so. An important cause of short-term mortality after CABG surgery is graft failure. In 1972, Lesperance and colleagues¹⁸ reported that 21 of 105 grafts (20%) were occluded early after CABG surgery. In a review of saphenous vein graft (SVG) disease, Motwani and Topol¹⁹ summarized more recent studies showing SVG occlusion rates of 15% and showing that different pathogeneses are responsible for SVG closure at different time periods. During the first month after CABG surgery, graft failure is almost entirely due to thrombosis. Although SVG failure during the remainder of the first year was largely due to intimal hyperplasia, in subsequent years, it was primarily due to atherosclerosis. Lesperance and colleagues¹⁸ found that arterial runoff was the single most important determinant of short-term graft survival. Occluded vessels distal to the SVG anastomosis resulted in thrombosis and graft failures. The internal diameter of the mid-LAD is 1.7 mm, whereas that of a saphenous vein could be 4 to 5 mm.²⁰ This difference in diameter results in very different flow rates and the potential for much slower flow rates in the SVG than in the mid-LAD. This may result in the sludging of red blood cells and in SVG thrombosis. The internal diameter of the IMA is much more similar to that of the mid-LAD, and this may result in more similar flow rates and a decreased risk of graft thrombosis.

Important differences between the IMA and the SVG are found in the different biology of arteries and veins, as summarized by Motwani and Topol.¹⁹ There are several structural differences. In addition to its better size match with the grafted native vessel, the IMA also has no valves, fewer endothelial fenestrations, and a greater resistance to trauma during harvesting. Physiological differences include the higher flow reserve and shear stress of the IMA, higher nitric oxide and prostacyclin production, relaxation response to thrombin, low vasoconstrictor sensitivity and high vasodilator sensitivity, and fewer fibroblast growth factor receptors. Each of these structural and physiological differences between the IMA and SVG establish the plausibility of a protective effect of IMA use on short-term mortality, but none provide conclusive proof.

The LIMA graft has been associated with several postoperative complications after its use as a conduit for CABG surgery. There has been an association with increased mediastinitis in the diabetic population that receives bilateral IMA grafts, as was previously documented by Loop et al.⁸ Grover reported a significant OR increase in this problem in both single LIMA grafts and multiple arterial grafts.²¹ We did not study the effects of bilateral IMA grafts in our data set. However, our research shows a nonsignificant decrease in mediastinitis or sternal dehiscence among patients who receive a single LIMA graft. The percentage of patients with this complication is low; therefore, determinations regarding the direct effect of the presence of a LIMA graft on this complication are difficult to make. Our data, however, indicate that the presence of a single LIMA certainly does not increase the risk of mediastinitis or sternal dehiscence. Bleeding after CABG surgery is a concern to all practicing cardiac surgeons. Some surgeons believe that taking down the LIMA leaves a raw bed under the chest wall that has the potential to bleed after the chest is closed. In addition, there is the possibility of bleeding from intercostal branches off the LIMA itself. In our data set, there was a trend toward a diminished rate of return to the operating room for bleeding in those patients who received a LIMA. This difference was not statistically significant. Intraoperative and postoperative cerebrovascular accidents are a devastating complication to both the patient and his or her family. The causes of perioperative cerebral events are many, and most of the published series do not have a clear cause in any individual patient. There was certainly no increased risk of cerebrovascular accident in the patients who received a LIMA graft, and there seems to be a similar nonsignificant trend toward a lower cerebrovascular accident rate in those patients.

The constant evaluation of the process of cardiac surgery is essential for improving outcomes in this complicated procedure. The operative surgeon makes the choice of conduit for CABG surgery. Knowledge that the use of a LIMA graft has direct in-hospital survival benefits to the patient lying on the operative table may lead a surgeon to chose this conduit over another, even in a higher risk individual.

	Acknowledgments

 
This research was supported in part by a grant from the American Heart Association (9970047N).

Received July 7, 2000; revision received September 7, 2000; accepted September 15, 2000.

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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 Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Leavitt, B. J. Articles by Lahey, S. J. Search for Related Content PubMed PubMed Citation Articles by Leavitt, B. J. Articles by Lahey, S. J. Related Collections Health policy and outcome research CV surgery: coronary artery disease