Asian Cardiovasc Thorac Ann 2007;15:106-112
© 2007 Asia Publishing EXchange Ltd
Radial Artery Graft Use and Off-Pump Coronary Artery Bypass Surgery Outcome
Ahmet T Gurbuz, MD,
Orhan Findik, MD,
Haiyan Cui, PhD1,
Aydin Aytac, MD
Department of Cardiothoracic Surgery, Tucson Medical Center
1 Department of Biostatistics and Biometrics, Arizona Cancer Center, University of Arizona, Tucson, USA
For reprint information contact: Ahmet T Gurbuz, MD, Tel: 1 520 631 3719, Fax: 1 520 544 8190, Email: atgurbuz{at}yahoo.com, 4729 East Sunrise Drive, Suite 153, Tucson, AZ 85718, USA.
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ABSTRACT
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Radial artery is commonly used as a conduit for surgical revascularization. There is scarce data on the effect of radial artery use on outcome following off-pump coronary artery bypass. We prospectively evaluated 591 patients undergoing off-pump coronary artery bypass. Radial artery grafts were used in 398 of these patients (mean age, 67.6 ± 10.4 years; mean follow-up, 37.7 ± 13.4 months). Symptom recurrence (angina, congestive heart failure), adverse cardiac events (myocardial infarction, coronary re-intervention, sudden cardiac death), and overall mortality were recorded. Multivariate Cox regression analysis was used to evaluate predictors of endpoints. Patients with and without radial artery grafts were similar with respect to preoperative risk factors. Recurrent angina developed in 29 patients, congestive heart failure in 5, and myocardial infarction in 9. Coronary arteriography was performed in 27 patients, and 23 underwent re-intervention. Radial artery graft was an independent predictor of increased symptom recurrence and adverse cardiac events. Patients with radial artery grafts also had a tendency towards more angina recurrence, coronary re-intervention, and sudden cardiac death.
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INTRODUCTION
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Conduit selection for coronary artery bypass surgery (CABG) has been a matter of debate since the early years of surgical revascularization. Internal thoracic artery (ITA) and the saphenous vein graft (SVG) remain the most commonly used conduits. Radial artery (RA) grafts were used in the 1970s, with a revival of interest in the last decade.1,2 The RA is relatively easy to harvest and has adequate graft length (18–22 cm) and diameter (2.5–3.0 mm), which makes it an attractive conduit for coronary grafting. It can be used as a composite graft with ITA or as an aortocoronary graft; therefore, it provides versatile grafting options. Radial artery may be used in off-pump coronary artery bypass (OPCAB). It may avoid manipulation of the ascending aorta and ensure immediate coronary perfusion when used as a composite graft.
There are several reports of excellent short- and long-term RA graft patency after CABG. Radial artery grafts were also found to improve survival compared to SVG 6 years after CABG.3 However, most of these studies were retrospective, lacked adequate control groups, and failed to demonstrate a clear benefit of RA grafting. Data on the performance of RA grafts after OPCAB and the effect of RA grafting on OPCAB outcome is very limited. Radial artery graft patency was found to be lower than that of ITA and SVG 3 months after OPCAB in one prospective randomized study.4
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PATIENTS AND METHODS
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Over a 4-year period (2000–2004), 591 consecutive patients underwent OPCAB at Tucson Heart Hospital and Tucson Medical Center, by one surgeon using the same technique, without any exclusion criteria. Preoperative patient characteristics are summarized in Table 1
. Mean age was 67.6 ± 10.7 years. All procedures were performed through a complete median sternotomy with full-dose unfractionated porcine heparin anticoagulation (4 mg·kg–1, target activated clotting time > 400 sec). The RA was not used in our early OPCAB patients. We adopted RA grafting in June 2001 after favorable results were reported, thus patients who received RA grafts and those who did not belong to different time periods in our OPCAB experience. All patients treated after June 2001 were considered as candidates for an RA graft unless there was poor ulnar collateral flow to the hand or no eligible target vessels. Radial artery grafts were not used in patients with stand-alone left main coronary artery stenosis. A preoperative Allen’s test was used to evaluate hand circulation. The RA was used only if the pulse oximetry signal on the thumb returned within 10 sec after manual RA occlusion. The RA was harvested from the non-dominant hand as a pedicled graft with full-exposure incisions, using sharp dissection and hemoclips. Diathermy was not used. Radial artery grafts were dilated topically but not intraluminally using dilute papaverine and heparin solution. The RA was only used to graft vessels with more then 80% stenosis. Proximal RA anastomoses were almost exclusively to the ITA as the source of inflow, unless the ITA was too small or had insufficient flow. Each RA graft had only one proximal and one distal anastomosis; sequential grafting was not performed. The RA was divided into two segments and each was anastomosed to the ITA separately when used for two different distal anastomoses. We performed the proximal anastomoses first when ITA was used as the source of inflow, and distal anastomoses were constructed before the proximal anastomoses when the aorta was used as inflow. Particular attention was paid to obtaining visible RA graft dilatation and free graft flow prior to distal anastomoses when proximal anastomoses were performed first. Either intraoperative diltiazem (0.25–0.50 µg·kg–1·min–1) or nitroglycerine was used in all patients with RA grafts. We tried to limit the use of perioperative alpha-agonist vasopressors to limit RA spasm induced by these agents. Diltiazem (180 mg·day–1) or a long-acting nitrate (30–60 mg·day–1) was continued orally for a minimum of 6 months after discharge. The grafting strategy was to use ITA for the LAD and to use the RA for the 2nd and 3rd targets, which were mostly circumflex branches and diagonal territories. Saphenous vein grafts were used for the remaining target vessels. The proximal anastomoses of all SVGs were performed on the ascending aorta. An Octopus stabilizing device (Medtronic, Inc., Minneapolis, MN, USA) was used for all distal anastomoses. Proximal coronary occlusion was obtained using soft silastic vessel loops. Distal occlusion was never used. Intraluminal shunts were utilized when deemed necessary by the surgical team. Heparin was partially reversed for a target activated clotting time in the range of 150–180 sec. Graft flows were evaluated using a handheld Doppler probe, and grafts lacking a prominent diastolic augmentation were immediately revised. There were 3 conversions to cardiopulmonary bypass early during the study period, all of these patients survived and were included in this study.
Aspirin (325 mg) was started in the first 6 hr after the procedure. Statin therapy was added if the preoperative low-density lipoprotein level was above 2.59 mmol·L–1 (100 mg·dL–1). Patients were followed prospectively. Data collected included recurrent angina, acute myocardial infarction, congestive heart failure, any repeat coronary intervention such as a percutaneous coronary intervention (PCI) and redo CABG, and any cardiac- and noncardiac-related deaths. Recurrent angina was defined as recurrent chest pain in Canadian Cardiovascular Society class II or higher, with demonstrable ischemia on the myocardial perfusion scan. Myocardial infarction was defined as an increase in cardiac-specific troponin T 
0.03 µg·L–1 with or without new ST- or T-segment changes. Congestive heart failure was defined as new onset shortness of breath, peripheral edema associated with new systolic or diastolic dysfunction on the echocardiogram, and/or the appearance of new pleural effusions. Data were available in all 591 patients. As there was a small number of overall symptom recurrences and adverse events, we grouped events together to facilitate statistical calculations. Angina recurrence and congestive heart failure were grouped under the heading of "symptom recurrence". Myocardial infarction, coronary re-intervention and any cardiac-related mortality including sudden cardiac death were grouped as "adverse cardiac events". Graft occlusion was defined as complete graft occlusion, and string sign was defined as uniform or segmental graft narrowing < 1 mm in diameter and delayed opacification in the target artery.
Hospital records and angiograms were reviewed in every patient who had any of the endpoints, as well as in all patients who died. The Social Security Death Registry Database was also searched for patients who could not be located and had no record of adverse events. Continuous variables are represented as mean ± standard deviation, and constant values are represented as absolute numbers. Predictors of symptom recurrence, adverse cardiac events, and mortality were determined using the chi-squared and Fisher’s exact tests. Statistical significance was set at a p value of 0.05. Risk factors that were associated with statistical significance were analyzed using multivariate stepwise Cox regression analysis. Hazard ratios and confidence intervals (CI) were calculated. All statistical analyses were performed using SPSS software for Windows 10.0 (SPSS Inc., Chicago, IL, USA). Survival curves were constructed using the Kaplan-Meier method and compared by log-rank analysis.
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RESULTS
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Of the 591 patients, 113 had 1 or 2 bypass grafts (19.1%) and 478 (80.9%) had 3 or more grafts. At least one ITA graft was used in 564 patients (95.4%) and at least one SVG in 489 (82.7%). Radial artery was used primarily as the 2nd arterial graft. Right ITA grafts were used only when RA grafts were not available; 12 patients received bilateral ITA grafts. The distributions of various graft types according to coronary territory in patients with and without RA grafts are shown in Table 2. At least one RA graft was used in 398 patients (67.3%); 388 had unilateral RA harvest, and 10 had bilateral RA harvest. Of these, 155 had one RA graft, 216 had 2 RA grafts, and 27 had 3 RA grafts; there was a total of 668 RA grafts. Radial artery grafts were not used after harvesting in 5 patients due to severe calcification. The RA grafts were anastomosed to the ITA in a T- or Y-configuration (ITA-RA group) in 385 patients (655 grafts). The RA grafts in the other 13 patients were anastomosed to the ascending aorta (Ao-RA group). Intraoperative graft revision was performed in 9 patients (12 grafts): these comprised ITA in 2 patients (2 grafts), RA in 3 (3 grafts), and SVG in 4 (7 grafts).
Comparison of preoperative risk factors and perioperative variables in patients with and without RA grafts showed similar characteristics, except for a higher percentage of patients with > 3 grafts and greater postoperative statin use in the RA group (Table 3). Major early postoperative complications were re-operation for bleeding in 8 patients, renal failure requiring dialysis in 3, respiratory failure in 5, myocardial infarction in 2, deep sternal wound infections in 5, and permanent neurological deficits in 4 patients. Both incidences of myocardial infarction occurred in RA graft territories. Twelve patients died in the perioperative period.
Mean follow-up was 37.7 ± 13.4 months and it was complete in all 591 patients. Recurrent angina developed in 29 patients at 2 to 38 months after the procedure; cardiac catheterization was performed in 15 of these patients (2 had all grafts patent and 13 required re-intervention). Congestive heart failure developed in 5 patients over the follow-up period, of whom 4 underwent repeat cardiac catheterization (2 had all grafts patent and 2 needed re-intervention). There were 9 cases of myocardial infarction; coronary angiography was carried out in 8 of them (8 re-interventions). Repeat coronary angiography was performed in 27 patients at 16 ± 9 months after the procedure. Of 82 grafts studied (Table 4), 32 had occlusion or string sign, of which 21 were RA grafts (16 occluded, 5 string sign). There were 50 patent grafts of which 8 were RA ( p < 0.001).
Repeat revascularization was performed in 23 patients; 21 had a PCI, 2 had redo CABG. Target vessels for PCI were bypass grafts in 4 patients (2 SVG and 2 RA grafts) and native coronary arteries that were supplied by the occluded/string sign grafts in 12 patients (2 had SVG and 10 had RA grafts). A primary PCI was performed in 5 patients (2 circumflex arteries and 3 right coronary arteries) in vessels that were not bypassed previously. None of these vessels had significant stenosis at the time of OPCAB. Two patients underwent re-operation. There was occlusion or string sign in 3 of the 4 grafts in one patient (2 RA grafts with string sign and one occluded SVG), and string sign in the single RA graft in another patient. There was no mortality in those needing re-intervention.
Twenty-nine patients died during follow-up. The cause of death was cardiac in 9 patients (sudden cardiac death in 5, end-stage ischemic cardiomyopathy in 1, in-hospital arrhythmic death in 1, and end-stage congestive heart failure in 2 patients). Radial artery grafts were used in 6 of these patients, whereas 3 did not have any RA grafts ( p > 0.5). The cause of death was noncardiac in 20 patients: 1 metastatic prostate cancer, 1 lung cancer, 1 colon cancer, 4 cerebrovascular accidents, 1 traffic accident, 2 sepsis, 3 end-stage lung disease, 2 end-stage renal disease, 1 pulmonary embolus, 1 upper gastrointestinal bleeding, 1 pancreatitis, and 2 pneumonia.
Multivariate Cox regression analysis was performed to identify the effect of preoperative risk factors, intraoperative, and postoperative variables on symptom recurrence, adverse cardiac events, and mortality. Radial artery use was an independent predictor of symptom recurrence ( p = 0.002, OR 3.92, 95% CI 1.64–9.3), as was chronic obstructive pulmonary disease ( p < 0.0001, OR 6.78, 95% CI 3.59–12.79), and age > 70 years ( p= 0.02, OR 0.96, 95% CI 0.94–0.99). Postoperative use of a statin ( p= 0.001, OR 0.23, 95% CI 0.10–0.55) or clopidogrel ( p = 0.04, OR 0.39, 95% CI 0.15–0.99) independently decreased symptom recurrence. Freedom from symptom recurrence was 89.6% in those with RA grafts and 96.5% in patients with no RA grafts (Figure 1); log rank 5.85, p = 0.015.
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Figure 1. Freedom from symptom recurrence in patients with and without radial artery grafts. Comparison of survival curves with log rank analysis, p = 0.015.
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Combined adverse cardiac events independently increased with RA use ( p = 0.005, OR 2.96, 95% CI 1.37–6.36) as well as chronic obstructive pulmonary disease ( p < 0.0001, OR 3.35, 95% CI 1.75–6.40), left ventricular dysfunction ( p < 0.0001, OR 4.0, 95% CI 2.22–7.19), active smoking ( p < 0.0001, OR 4.22, 95% CI 1.93–9.23), and marginally with diabetes ( p = 0.04, OR 1.84, 95% CI 1.02–3.31). Postoperative clopidogrel was an independent predictor of decreased adverse cardiac events ( p = 0.0001, OR, 95% CI 0.21 0.10–0.45). Freedom from adverse cardiac events was significantly less in patients with RA grafts (Figure 2): 89.4% vs. 95.8% in those with no RA grafts (log rank 7.19, p = 0.0073). Although RA grafts increased mortality in univariate analysis ( p = 0.026), this was not significant in multivariate analysis. However, Kaplan-Meier survival curves comparing overall mortality showed significantly worse survival in patients with RA grafts (Figure 3): 93.7% vs 97.0% in patients with no RA grafts (log rank 5.61, p = 0.017). There was a tendency for those with RA grafts to have more individual endpoints (angina recurrence, congestive heart failure, myocardial infarction, and coronary re-intervention); however, these did not reach statistical significance. There was a slightly increased incidence of overall mortality in patients with RA grafts (Table 5).
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Figure 2. Freedom from adverse cardiac events in patients with and without radial artery grafts. Comparison of survival curves with log rank analysis: p = 0.0073.
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Figure 3. Overall survival in patients with and without radial artery grafts. Comparison of survival curves with log rank analysis: p = 0.017.
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We also looked at the site of proximal RA anastomoses in relation to symptom recurrence, adverse cardiac events, and graft patency. Of the 29 patients with RA grafts who experienced symptom recurrence, 22 had ITA-RA grafts and 7 had Ao-RA grafts ( p > 0.05). Of the 30 patients with RA grafts who had adverse cardiac events, 20 had ITA-RA grafts and 10 had Ao-RA grafts ( p > 0.05). As for graft patency, 17 of the 21 occluded RA grafts were in the ITA-RA group and 4 of the 8 patent grafts were in the Ao-RA group. The degree of native coronary artery stenosis was also evaluated in patients with RA angiographic data. A smaller proportion of RA grafts used for coronary arteries with > 90% stenosis had string sign or occlusion (4/11) compared to RA grafted to coronary arteries with < 90% stenosis (17/18). The effect of intraoperative graft revision on adverse midterm outcome was also analyzed. Only one of the 9 patients with graft revision had symptom recurrence, and no patient with graft revision had any adverse cardiac events or cardiac death.
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DISCUSSION
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In this study, having an RA graft was an independent predictor of symptom recurrence and adverse cardiac events following OPCAB. In the limited number of patients who underwent repeat angiography, there were more RA grafts with occlusion/string sign compared to SVGs. The 3-year freedom from adverse cardiac events and overall survival (89% vs 95% and 93% vs 97%, respectively) for patients with RA grafts vs. those with no RA graft, were similar to previously reported OPCAB series.5 A large amount of data have accumulated on RA grafting during the last decade. Most of these studies are retrospective and their main focus has been on graft patency. Although most demonstrate excellent early and late patency rates, diminished RA patency has been shown in recent retrospective on-pump CABG studies as well as in prospective studies comparing on-pump and OPCAB patients.2,4,6–8 The effect of RA use on the outcome after CABG is limited to retrospective studies that show improved survival with the use of RA without a difference in patency between RA grafts and SVGs.3,9 There are very few studies evaluating patency according to graft type in OPCAB patients. Radial artery grafts were found to be more vulnerable to occlusion than ITA grafts and SVGs in the only prospective randomized trial comparing off-pump and on-pump multivessel CABG.4
The etiology of the worse then expected performance of OPCAB patients receiving RA grafts may be several-fold. It may be related to the absence of cardiopulmonary bypass or to intrinsic factors associated with the RA, independent of surgical technique. A major difference between OPCAB and on-pump CABG is the absence of platelet dysfunction associated with the extracorporeal bypass circuit. This might produce a hypercoagulable state following OPCAB and decrease graft patency. Although earlier reports claimed that there might be an increased incidence of thrombotic events after OPCAB, others did not find a difference in the coagulability between on-pump CABG and OPCAB.10,11 Recently, an increase in platelet activation was reported after OPCAB.12 This would affect all conduit types and does not by itself explain unfavorable outcomes with RA grafts. Another important issue in OPCAB is the maintenance of physiological hemodynamic parameters and normothermia throughout the procedure. Avoiding hypothermia and hypotension would actually help to improve arterial graft performance and limit graft spasm; thus, it should positively affect RA performance.
Radial artery grafts were used as T- or Y-grafts from the left ITA in the majority of patients in this study, but we do not believe this strategy contributed significantly to the outcome. Others also reported no difference in RA graft patency between aortocoronary and composite grafting techniques.13 Intrinsic factors that may affect RA graft performance are increased vasoreactivity or spasm, and intimal hyperplasia, which might decrease graft patency.14,15 Radial artery spasm was once considered to be a significant contributor to RA occlusion, but it may not be such an important factor in RA graft patency.2 Anti-spasm prophylaxis is still widely employed, but treatment with calcium channel blockers was found to have no additional effect on graft patency during the first year or later after CABG.16,17 We administered long-acting nitrates or calcium channel blockers for 6 months postoperatively to all patients receiving RA grafts. We have since modified our practice and no longer use these medications.
The patency of RA grafts is being evaluated in several prospective randomized trials. Interim results of one study showed that RA grafts did not have superior patency and were not associated with fewer clinical events compared to the free right ITA and SVGs at 5-year follow-up.18 The disease-free patency rates of RA grafts were found to be similar to other graft types in another study.19 A multicenter prospective randomized study reported RA grafts to have a similar combined occlusion and string sign rate (15.2%) compared to SVGs (14.5%) after 1 year.20 None of these studies included OPCAB patients. The midterm and long-term outcome of these studies will define the role of RA grafts in CABG and specify the patients who will benefit most from this conduit.
This study was prospective but not randomized. Although there were more RA grafts with string sign and occlusion compared to other conduits, a limited number of patients underwent cardiac catheterization. Other limitations were that follow-up was relatively short, the sample size was not large, and the numbers of patients with symptom recurrence and adverse events were low. Nevertheless, it was concluded that a RA graft was a predictor of increased symptom recurrence and adverse cardiac events midterm after OPCAB.
Presented at the 52nd Annual Meeting of the Southern Thoracic Surgical Association, Orlando, FL, USA, November 10–12, 2005.
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REFERENCES
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- Gaudino M, Glieca F, Luciani N, Alessandrini F, Possati G. Clinical and angiographic effects of chronic calcium channel blocker therapy continued beyond first postoperative year in patients with radial artery grafts: results of a prospective randomized investigation. Circulation 2001;104(12 Suppl 1):I64–7.
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ABSTRACT
INTRODUCTION
