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Ann Thorac Surg 2001;71:180-186
© 2001 The Society of Thoracic Surgeons
a Division of Cardiovascular Surgery, Sunnybrook and Women’s College Health Sciences Centre, Toronto, Ontario, Canada
Address reprint requests to Dr Fremes, Division of Cardiovascular Surgery, Sunnybrook and Women’s College Health Sciences Centre, 2075 Bayview Ave, Room H410, Toronto, ON M4N 3M5, Canada
e-mail: stephen.fremes{at}swchsc.on.ca
Presented at the Thirty-sixth Annual Meeting of The Society of Thoracic Surgeons, Fort Lauderdale, FL, Jan 31–Feb 2, 2000.
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Abstract |
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Methods. Between March 1994 and March 1999, 2,847 patients underwent isolated coronary artery bypass grafting with a left internal thoracic artery graft, plus saphenous vein grafts (SVGs). Of these patients, 478 also received an RA graft (RA group). The RA patients were matched at a ratio of 1:2 with patients receiving only SVGs and a left internal thoracic artery graft (SVG group; n = 956) using six prognostic risk factors: age, sex, Canadian Cardiovascular Society class, left ventricular grade, number of diseased vessels, and timing of operation. Target vessels were graded according to quality and graftability and were similar between groups. Outcomes were evaluated by univariate and multivariate analyses.
Results. There was a significantly higher prevalence of diabetes, hypertension, and peripheral vascular disease in the RA group (p < 0.05). Although stay in the intensive care unit was shorter in the RA group (RA, 30 ± 2 hours, and SVG, 37 ± 2 hours; p = 0.0002), total hospital stay was similar between groups. The incidence of perioperative myocardial infarction was higher in the SVG group (SVG, 31 of 956 or 3.2%, and RA, 6 of 478 or 1.3%; p = 0.02). Multivariate analysis revealed RA grafting to be protective against early mortality and morbidity (odds ratio = 0.58; 95% confidence interval, 0.37 to 0.90; p = 0.015) and late mortality and morbidity including late reintervention (risk ratio = 0.60; 95% confidence interval, 0.37 to 0.93; p = 0.02). Actuarial freedom from events at 36 months postoperatively was greater in the RA group (RA, 95% ± 2%, and SVG, 86% ± 4%; p = 0.01).
Conclusions. Despite a higher prevalence of preoperative comorbidity, patients in the RA group demonstrated improved outcomes after coronary artery bypass grafting. The RA is a viable and beneficial conduit for this operation.
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Introduction |
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In view of the clear advantages of the internal thoracic artery (ITA) versus the saphenous vein for left anterior descending coronary artery bypass [6–9], expanded use of arterial conduits has long been advocated. However, for technical reasons as well as a lack of supportive data, multiple arterial grafting for CABG is not routinely performed [10].
Initially used as a bypass conduit in the early 1970s [11], the radial artery (RA) was reintroduced into clinical practice in 1989 [12]. Owing to various anatomical and practical characteristics, the RA represents a potential conduit that may be both technically and clinically advantageous compared with other arterial grafts. The following study summarizes our experiences using the RA as a conduit in combination with a left ITA (LITA) graft and SVGs in patients undergoing CABG. For completeness, comparison was made with patients receiving a LITA graft and SVGs only.
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Material and methods |
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Between March 1994 and March 1999, 2,847 patients underwent isolated CABG at our institution. Of these, 478 patients were identified as having received an RA graft in addition to a LITA graft with or without additional SVGs (RA group). These 478 patients constituted the case group and were assigned consecutive identification numbers and a group identification code (R). A printout of information was generated on these patients: identification number in the study, date of operation, age, sex, Canadian Cardiovascular Society angina class, left ventricular grade, number of diseased coronary arteries, and timing of operation (elective vs urgent). Four of the six surgeons accounted for 89% of the patients in the RA group, and 95% of the entire surgical population.
There were 2,369 patients in the 1994–1999 CABG database who received a single LITA graft plus SVGs but no additional arterial grafts (SVG group). During the matching procedure, only the matching variables were listed. There was no additional information screened by the analyst (M.G.T.) for any other prognostic, operative, or outcome data. Each individual RA group patient was matched on the basis of age (±1 year), sex, Canadian Cardiovascular Society angina class, left ventricular grade, number of diseased coronary arteries, and timing of operation to 2 SVG group patients. An attempt was made to match as closely as possible to the date of operation. The matched patients were assigned the same identification number as their RA group counterpart as well as a group identification code (S).
There were 956 patients in the SVG group (controls). The 1:2 matching ratio (RA:SVG) was successful for all 478 patients. Patients who received arterial grafts other than the LITA or RA were excluded.
To ensure minimal variability, a subgroup analysis was undertaken whereby target coronary arteries were graded according to quality and graftability in 50 randomly chosen patients from each group. A standardized scoring system based on the percentage of stenosis (0 = 30% to 49%, 1 = 50% to 69%, 2 = 70% to 89%, 3 = 90% to 99%, 4 = 100%), target coronary artery size (0 = 
2.00 mm, 1 = 1.50 to 1.99 mm, 2 = 1.00 to 1.49 mm, 3 = < 1.00 mm), target coronary artery quality (0 = normal, 1 = mildly diseased or irregular vessel, 2 = moderately diseased or noncritical stenosis, 3 = severely diseased or 50% stenosis), target coronary artery calcification (0 = none, 1 = mildly calcified, 2 = severely calcified), and target location (proximity to coronary sinus) was used for this purpose. Scoring was done by a single blinded observer (G.C.) according to the visual assessment of the coronary angiogram. Specified scores were tallied to determine graftability, and a comparison was made between groups.
Surgical methods
The Allen test was used to determine the adequacy of collateral circulation to the hand. The RA was not considered if any of the following conditions applied: the Allen test was positive; the patient had an abnormal upper-extremity Doppler study; a RA plaque was noted on ultrasound; or the patient had a history of vasculitis or Raynaud’s disease. The nondominant arm was used almost exclusively for RA harvesting, which was performed simultaneously with harvest of all other conduits. The RA was harvested as a pedicle with adjacent veins and surrounding fatty tissue. An atraumatic "no-touch" technique was used for harvesting. After heparinization, the artery was gently dilated in situ by a slow intraluminal injection of dilute papaverine hydrochloride and verapamil hydrochloride solution (5 mL: papaverine, 60 mg, and verapamil 5 mg, in 16 mL of Ringer’s lactate) [13–15]. Ex vivo, the artery was immersed in the same solution. The saphenous vein was harvested using conventional methods followed by immersion in papaverine solution. More often than not, the RA was used to graft a major coronary branch on the lateral or inferior wall of the heart. Single grafts (one distal anastomosis per graft) as opposed to sequential grafts (more than one distal anastomosis per graft) were constructed.
Postoperative management
Electrocardiograms were obtained preoperatively, on day 1 postoperatively, and either at the time of discharge or on day 5 postoperatively. Patients received intravenous nitroglycerin (1 to 4 ug · kg-1 · min-1) for the first 24 hours after operation provided the systolic blood pressure was greater than 100 mm Hg [15–17]. Oral nifedipine (Adalat XL, 20 to 30 mg daily) was continued for 6 months thereafter, beginning on the first postoperative day. For patients intolerant of nifedipine, diltiazem hydrochloride or amlodipine was substituted. Sublingual nifedipine (10 mg every 6 hours) was used in the intensive care unit only in instances of persistent hypertension (systolic blood pressure > 140 mm Hg) despite adequate doses of intravenous nitroglycerin or sodium nitroprusside. All patients were placed on a regimen of aspirin, 325 mg daily, beginning 6 hours postoperatively and were maintained indefinitely on cholesterol-lowering agents.
Statistical analyses
The SAS for PC [18] and BMD/PLR [19] programs were used for statistical analyses.
The baseline characteristics and hospital outcomes for the two groups of patients were compared using 
2 analysis or Fisher’s exact test for categorical data and t tests for continuous variables. Hospital outcomes were evaluated multivariately by stepwise logistic regression analysis. Odds ratios and their 95% confidence intervals for hospital events were calculated accordingly.
The differences between the SVG and RA groups for late survival and other longitudinal outcomes were evaluated by Kaplan-Meier univariate analyses. The Cox proportional hazards procedure was used to adjust the risk ratios for all prognostic variables including the matching variables using a stepwise procedure.
Results are reported as the mean ± the standard deviation in the text and the table and as the mean ± the standard error in the figures unless not applicable. Statistical significance was defined as a p value of less than 0.05. Multivariate procedures used an entry level p value of 0.15.
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Results |
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TopFootnotesAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsDiscussionReferences |
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Postoperative stay in the intensive care unit was shorter in the RA group (SVG, 37 ± 2 hours, and RA, 30 ± 2 hours; p = 0.0002), although total hospital stay was similar between groups (SVG, 8 ± 6 days, and RA, 8 ± 5 days; p = 0.32).
Perioperative mortality was identical in the two groups (SVG, 10 of 956 or 1%, and RA, 5 of 478 or 1%; p = 1.00). The incidence of perioperative MI was elevated in the SVG group (SVG, 31 of 956 or 3%, and RA, 6 of 478 or 1%; p 
0.02). The incidence of perioperative low-output syndrome (the requirement of inotropic or intraaortic balloon pump support for longer than 30 minutes to sustain a cardiac index greater than 2.2 L · min-1 · m2 and a systolic blood pressure greater than 90 mm Hg), however, was not significantly different between groups (SVG, 70 of 956 or 7%, and RA, 25 of 478 or 5%; p = 0.133) (Fig 1). Logistic regression analysis revealed RA grafting to be protective against early mortality or morbidity (MI, low-output syndrome, intraaortic balloon pump support, stroke) (odds ratio = 0.58; 95% confidence interval, 0.37 to 0.90; p = 0.015) (Fig 2).
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Comment |
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20 cm) makes it suitable for reaching all myocardial territories [16]. The diameter of the lumen is larger than that of other arterial grafts and corresponds well to most recipient coronary vessels [16]. The thick muscular wall is appropriate for both aortic and coronary anastomoses [16, 17], which are technically less demanding to construct than anastomoses fashioned using the ITAs, right gastroepiploic artery, or inferior epigastric artery. Contraindications to the use of other arterial conduits including advanced age, obesity, diabetes mellitus, obstructive pulmonary disease, and prior laparotomy do not generally apply to the RA. Moreover, relative to saphenous veins, RAs can be harvested without interfering with ambulation, and wound infection is less common. From a practical perspective, the RA can be harvested concurrently with other conduits, and the dissection can usually be accomplished by an assistant, thus preventing any undue prolongation of operative time. Finally, the versatility of the RA makes it well suited as a second arterial conduit. Introduced into clinical practice in the early 1970s [11], the RA graft was quickly abandoned because of high occlusion rates compared with contemporary saphenous vein or ITA grafts [20–22]. Carpentier [20], the original user of the RA graft, believed that such high occlusion rates were largely related to graft spasm. This concept was supported when follow-up angiography of patients in whom the RA graft had been thought to be totally or partially occluded revealed patent, angiographically normal RA grafts. In 1989, Carpentier’s group reintroduced the RA graft for CABG and reported their experiences in 1992 [12]. Among the 104 patients receiving an RA graft, there was one death (details not provided) and two perioperative MIs, neither of which was attributable to occlusion or spasm of the RA graft. Modifications in technique included harvesting the graft as a pedicle, intraluminal dilation with papaverine (as opposed to mechanical dilation), and postoperative administration of calcium-channel blockers to limit graft spasm. The early patency rate of the first 56 grafts studied within 2 weeks of operation was 100%. Late angiographic follow-up was obtained in 27 patients (31 grafts) at a mean of 9 months postoperatively. These results were better than those observed with SVGs or free ITA grafts. Twenty-nine grafts were patent, and none of them had any degree of narrowing. A later series by Calafiore and coworkers [23] involved 163 RA grafts. At an average of 3.6 months postoperatively, 75 (98.7%) of 76 grafts were patent, and 33 (94.3%) of 35 grafts studied 13 months or more postoperatively (mean time, 21.1 months) were patent.
In our series, despite a higher prevalence of preoperative comorbidity, the RA patients demonstrated a lower incidence of perioperative MI. Although the incidence of postoperative low-output syndrome was also slightly lower in the RA group, this difference did not reach significance. Nonetheless, such morbidity did translate into a significantly longer postoperative stay in the intensive care unit for the SVG group. These differences may be attributable to the superior early patency of RA grafts in comparison to SVGs. We have collated all available English-language publications and abstracted relevant data items evaluating the RA (unpublished observations). Cumulative totals suggest that an angiographic patency rate of approximately 97.5% (309 of 317 grafts) can be expected early (< 3 months) postoperatively and 93.0% (186 of 200 grafts) at 1 year. By comparison, in studies by Acar [12], Chen [24], and Affonso da Costa [25], and their associates, the early (< 3 months) patency rate of SVGs was reported as 88.9%, 92.3%, and 92.8%, respectively. Further, in a study by Manasse and colleagues [26], only 35 (76.1%) of 46 SVGs were patent at 1 year postoperatively.
In addition to the observed protective nature of RA grafting, one cannot overlook the role of surgeon-related variables to early outcome. The effect of the individual surgeon on the conclusions regarding the beneficial effects of RA grafting were analyzed, as the frequency of RA grafting differed significantly between surgeons. In stratified analyses, RA grafting was protective against early mortality and morbidity after controlling for the variable individual surgeon. In multivariate analyses for early or late events, RA grafting remained protective with minimal change in the odds or risk ratios when variables for individual surgeon were entered into the risk equations, findings suggesting that the RA effects were not a proxy for individual surgeon. Although certain surgeons used the RA more often than others, a consistent relationship could be demonstrated between RA grafting and patient outcome, thus indicating that the results were generalizable, at least within our institution.
Our findings at follow-up are not surprising in view of the published long-term patency rates of the RA in comparison to SVGs. Two groups [27, 28] have published RA graft patency results at 5 years postoperatively. In these studies, 111 (88.1%) of 126 RA grafts were demonstrated to be patent at 5 years compared with only 74.1% of vein grafts. In our series, although actuarial survival at 60 months was not significantly different between groups, multivariate analysis revealed RA grafting to be protective against late MI, late readmission, and late reintervention.
There was only one late death in the RA group, and it involved a patient with end-stage heart failure. Postmortem examination revealed all grafts to be patent. Of the 20 late readmissions in the RA group, only three were related to recurrence of angina. All 3 patients underwent diagnostic angiography. In 1 patient, the RA graft to the first obtuse marginal artery was found to be occluded. The patient was treated medically. In another patient, 95% stenosis of an RA graft to the right coronary artery was identified, which was treated by angioplasty and stenting of the native coronary artery. In the third patient, occlusion of an SVG to the right coronary artery was identified and was treated by angioplasty of the SVG.
Two RA harvest site complications were documented. In 1 patient, a 50-year-old man, a postoperative radial nerve palsy with weakness of extension at the wrist and fingers developed. Although improvement with time has been noted, a return to baseline function had not been achieved up to 5 years postoperatively. The second patient, a 67-year-old man, required readmission to the hospital for management of superficial cellulitis at the site of RA harvesting. The treatment, consisting of intravenous antibiotics, was successful, and no long-term sequelae were experienced.
The primary limitation of the study is its retrospective nature along with the potential for bias in the selection of patients for RA grafting. The study design did attempt to control for bias by using matched controls and by employing a semiquantitative scoring method for target vessels in a subset of patients. To alleviate such limitations, our group [29] has organized a multicenter randomized clinical trial comparing the 8- to 12-month angiographic patency of the RA graft versus the SVG for bypass of targets other than the left anterior descending coronary artery. This study should provide an unbiased estimate of the relative patency of RA grafts while controlling for patient variables and recipient vessel variables.
Despite a higher prevalence of preoperative comorbidity, patients receiving an RA graft during CABG demonstrated improved early and late outcomes. In summary, our findings, in combination with previously published reports, suggest that RA grafting (mainly to targets other than the left anterior descending coronary artery) is better than saphenous vein grafting for CABG and may be comparable to right ITA grafting.
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Footnotes |
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TopFootnotesAbstractIntroductionMaterial and methodsResultsCommentAcknowledgmentsDiscussionReferences |
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Discussion |
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DR COHEN: Thank you for your question. The degree of inherent stenosis within the bypassed coronary vessels was, in fact, analyzed, but this was not included in the scoring system applied to each target vessel. Indeed, there was a tendency towards the use of radial artery grafts to bypass only those vessels with high-grade stenoses. This has been the policy at our institution, and it continues to serve as a prerequisite for radial artery grafting in our ongoing prospective, randomized trial. At this point, I cannot comment on the fate of the radial artery when applied to vessels with low-grade stenoses because of the relatively small numbers of patients in this category. After having reviewed selected postoperative angiograms, I believe that excessive competitive flow within the native coronary artery may contribute to the characteristic string-sign effect often identified in failed radial artery bypass grafts. However, I do not have any objective data with which to confirm or refute this belief.
DR BUXTON: My second query pertains to the long-term outcome of the study. You had 3-year clinical end points. Do you have any late graft patency studies on these patients?
DR COHEN: Yes, we do. As I mentioned, we currently are undertaking a multicenter prospective, randomized trial in which the radial artery is being compared with the saphenous vein for coronary revascularization, with each patient acting as his or her own internal control. The primary end point of this study is angiographic patency. We hope to publicize the results of this trial in the near future.
DR JOHN PUSKAS (Atlanta, GA): Dr Cohen, would you please clarify the following points: the technique used to harvest the radial arteries, the pharmacologic maneuvers used to dilate the artery before implantation, and the therapy you apply in the postoperative period for patients who have received radial arteries.
I enjoyed your presentation.
DR COHEN: Thank you for your questions. We use a "no-touch" technique to harvest the radial artery. The saphenous vein is harvested using conventional methods.
After mobilization of its distal aspect, the radial artery is gently dilated using a solution comprising 60 mg of papaverine hydrochloride and 5 mg of verapamil hydrochloride. The radial artery is then immersed in the same solution until final use. In situations where radial anastomosis may be delayed, the vessel is attached to a manifold off the main arterial line for continuous infusion off the bypass circuit.
Postoperatively, if tolerated, all patients receive intravenous nitroglycerin at a dosage of 1 to 4 ug · kg-1 · min-1 during their stay in the intensive care unit. On the first postoperative day, patients are routinely placed on a calcium-channel blocker. At our institution, we use nifedipine, 20 to 30 mg orally once a day. This regimen is maintained for a period of 6 months postoperatively.
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