Left Subclavian Artery Stenosis in Coronary Artery Bypass: Prevalence and Revascularization Strategies

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1 Left Subclavian Artery Stenosis in Coronary Artery Bypass: Prevalence and Revascularization Strategies Ho Young Hwang, MD, Jin Hyun Kim, MD, Whal Lee, MD, PhD, Jae Hyung Park, MD, PhD, and Ki-Bong Kim, MD, PhD Departments of Thoracic and Cardiovascular Surgery and Radiology, Seoul National University Hospital, and Department of Thoracic and Cardiovascular Surgery, Seoul Medical Center, Seoul, Korea Background. We examined the prevalence of significant proximal left subclavian artery (LSA) stenosis in patients referred for isolated coronary artery bypass grafting, and assessed management by percutaneous transluminal angioplasty (PTA) for LSA stenosis and revascularization using the left internal thoracic artery, or revascularization using grafts other than the left internal thoracic artery. Methods. Between 1998 and 2007, significant proximal LSA stenosis was identified in 38 of 1,498 patients who underwent isolated coronary revascularization. Percutaneous transluminal angioplasty was performed before or after surgery in 20 patients (PTA group). Revascularization using grafts other than the left internal thoracic artery was performed in 18 patients with LSA stenosis unamenable to PTA (non-pta group). Early, 1-year, and 5-year follow-up angiograms were performed to assess patency of both grafts and PTA. Computed tomographic angiography was also performed at 2 years in the PTA group. Results. Prevalence of significant LSA stenosis was 2.5%. Early, 1-year, and 5-year angiograms showed overall graft patency rates of 97.2% (105 of 108 distal anastomoses), 88% (81 of 92), and 92% (23 of 25), respectively. No differences were observed in graft patency rates between the two groups during the follow-up period. No intervention-related morbidities occurred in the PTA group. Estimated patency rates of PTA at 2 and 5 years were 100% and 85.7%, respectively. Conclusions. Percutaneous transluminal angioplasty for LSA and revascularization using the left internal thoracic artery may be an effective treatment for patients with significant LSA stenosis. In patients with LSA stenosis unamenable to PTA, revascularization using grafts other than the left internal thoracic artery may be another treatment option. (Ann Thorac Surg 2010;89: ) 2010 by The Society of Thoracic Surgeons Use of the left internal thoracic artery (ITA) with supplemental vein grafts has been the standard in coronary artery bypass grafting (CABG). However, the presence of significant proximal left subclavian artery (LSA) stenosis may result in reversal of ipsilateral ITA coronary graft flow and produce myocardial ischemia [1]. Prevalence of significant LSA stenosis in patients referred for CABG was reported to be 0.2% to 6.8% [1 4]. The aims of this study were (1) to evaluate the prevalence of significant LSA stenosis in patients who underwent isolated CABG and (2) to assess management strategies and mid-term results of endovascular treatment for LSA stenosis or revascularization using grafts other than the left ITA. Material and Methods The study protocol was reviewed by the institutional review board and approved as a minimal risk retrospective study (approval number: H ) that did Accepted for publication Jan 4, Address correspondence to Dr K-B Kim, Department of Thoracic and Cardiovascular Surgery, Seoul National University Hospital, 28 Yeongeon-dong, Jongno-gu, Seoul , Korea; kimkb@snu.ac.kr. not require individual consent based on the institutional guidelines for waiving consent. Patient Characteristics We defined significant proximal LSA stenosis as angiographic stenosis of at least 50% with a brachial systolic pressure difference of at least 20 mm Hg. Of the 1,498 patients who underwent isolated CABG between January 1998 and December 2007 (conventional CABG in 136 patients; off-pump CABG in 1,362 patients), significant proximal LSA stenosis was identified in 38 patients. None of the patients complained of symptomatic subclavian artery stenosis as characterized by vertebrobasilar insufficiency or upper limb ischemia. Myocardial revascularization was performed with off-pump CABG (OPCAB) in 35 patients and with on-pump CABG in 3 patients. All patients referred for CABG underwent invasive preoperative radiologic evaluation, including the coronary vessels, and LSA angiography or selective left ITA angiography. Since we began performing OPCAB at our institution in 1998, we have performed early postoperative graft angiography in almost all of our OPCAB patients to assess the accuracy of anastomosis and graft patency. Unnoticed significant LSA stenosis was demonstrated in postoperative graft angiograms in 3 patients who had received selective left ITA preoperative angiog by The Society of Thoracic Surgeons /10/$36.00 Published by Elsevier Inc doi: /j.athoracsur

2 Ann Thorac Surg HWANG ET AL 2010;89: LEFT SUBCLAVIAN ARTERY STENOSIS IN CABG 1147 Table 1. Preoperative Characteristics and Risk Factors of the Study Patients Variables Total (N 38) PTA Group (N 20) Non-PTA Group (N 18) p Value a Age (y) Male/female 25:13 14:6 11: Unstable/stable angina 33:5 17:3 16: Elective/emergent 35:3 20:0 15: Risk factors, n (%) Smoking 18 (47%) 11 (55%) 7 (39%) Hypertension 23 (61%) 12 (60%) 11 (61%) Diabetes mellitus 13 (34%) 7 (35%) 6 (33%) Other PVOD 16 (42%) 9 (35%) 7 (39%) Hyperlipidemia 11 (29%) 5 (25%) 6 (33%) History of stroke 6 (16%) 4 (20%) 2 (11%) Chronic renal failure 4 (11%) 2 (10%) 2 (11%) Angiographic diagnosis, n (%) Left main disease 17 (45%) 9 (45%) 8 (44%) Three-vessel disease 30 (79%) 18 (90%) 12 (67%) Causes of LSA stenosis Atherosclerosis 35 (92%) 19 (95%) 16 (89%) Takayasu arteritis 3 (8%) 1 (5%) 2 (11%) a p value between the groups PTA and non-pta. LSA left subclavian artery; PTA percutaneous transluminal angioplasty; PVOD peripheral vascular occlusive disease. raphy instead of LSA angiography. In 20 of 38 patients, percutaneous transluminal angioplasty (PTA) was performed days before surgery (n 16) or 5 3 days after surgery (n 4; collectively, PTA group). Of the 16 patients who underwent PTA before CABG, PTA was performed on the morning of surgery in 4 patients. Percutaneous transluminal angioplasty was performed with (n 18) or without (n 2) stent insertion. Another 5 patients showed total occlusion of LSA, which made PTA unfeasible and influenced the revascularization plan. Those 5 patients and the other 13 patients whose LSA stenosis was unamenable to PTA were excluded from using the in situ left ITA graft (non-pta group; n 18). Those 18 patients underwent revascularization using other in situ arterial grafts, such as the right ITA and right gastroepiploic artery, or free saphenous vein graft as a blood source. No differences were observed in patient characteristics between the two groups (Table 1). Percutaneous Transluminal Angioplasty Strategies and Techniques for Left Subclavian Artery Stenosis Left subclavian artery stenosis was considered significant when angiography showed stenosis of at least 50% with a brachial systolic pressure difference of at least 20 mm Hg. All patients received aspirin (100 mg/day) and clopidogrel (75 mg/day) before the procedure, and the dual antiplatelet regimen was continued postoperatively for 1 year. Percutaneous transluminal angioplasty procedures were performed in the endovascular operating room under local anesthesia. To maintain an activated clotting time of more than 180 seconds, patients were heparinized during the procedure. Using a 5F to 7F sheath through the common femoral artery, an angiographic catheter was inserted percutaneously. In patients with severely atherosclerotic narrowing of bilateral iliofemoral arteries, the catheter was inserted through the brachial artery. Once the angiographic catheter was advanced across the lesion, the pressure difference was measured and the lesion was dilated with an angioplasty balloon, followed by deployment of a balloon-expandable stent. Stent implantation was performed carefully to avoid covering the vertebral artery or left ITA (Table 2). For assessment of the patency of endovascular treatment as well as graft patency, early, 1-year, and 5-year follow-up coronary angiograms including LSA were performed, regardless of the patients anginal symptoms. For patients in the PTA group, 2-year follow-up computed tomographic angiogram was also performed to assess LSA patency. Table 2. Lesion Characteristics and Data on Angioplastic Procedure Variables N 20 Characteristics Discrepancy of blood pressure (mmhg) Degree of stenosis (%) Angioplastic procedures Anesthesia Local Approach Femoral 19 (95%) Brachial 1 (5%) Balloon diameter (mm) Stent length (mm) (n 18) Procedural success 20 (100%) Complications 0 (0%)

3 1148 HWANG ET AL Ann Thorac Surg LEFT SUBCLAVIAN ARTERY STENOSIS IN CABG 2010;89: Table 3. Early Mortality and Morbidities Variable PTA Group (N 20) Non-PTA Group (N 18) p Value Mortality 1 (5%) 2 (11%) Morbidities Atrial fibrillation 8 (40%) 5 (28%) Perioperative myocardial 1 (5%) 2 (11%) infarction Bleeding reoperation 2 (10%) 1 (6%) Prolonged ventilation 1 (5%) 1 (6%) Acute renal failure 0 (0%) 2 (11%) Stroke 1 (5%) 0 (0%) Mediastinitis 0 (0%) 0 (0%) Low cardiac output syndrome 0 (0%) 0 (0%) PTA percutaneous transluminal angioplasty. Statistical Analysis Statistical analysis was performed using the SPSS software package (version 12.0, SPSS Inc, Chicago, IL). Comparison of categorical variables was performed by 2 or Fisher s exact test. Continuous variables were analyzed using the Mann-Whitney U test. Two- and 5-year patency rates of PTA for LSA stenosis and 5-year patency rates of grafts to the left anterior descending artery (LAD) in the two groups were calculated using the Kaplan-Meier method. Kaplan-Meier curve was drawn using Prism software (version 5.0, GraphPad Software Inc, San Diego, CA). All results were expressed as mean standard deviation or as proportions. A probability value of less than 0.05 was considered statistically significant. Results Early Results Prevalence of significant LSA stenosis in patients referred for isolated CABG was 2.5% (38 of 1,498). Three in-hospital mortalities occurred (3 of 38; 7.9%): 1 death as a result of stroke that developed on the third postoperative day, 1 death as a result of sepsis, and 1 death as a result of acute myocardial infarction with severe right ventricular failure. Postoperative morbidities including atrial fibrillation (n 13; 34.2%), perioperative myocardial infarction (n 3; 7.9%), reoperation for bleeding (n 3; 7.9%), and acute renal failure (n 2; 5.3%) were not different between the two groups (Table 3). There was no low cardiac output syndrome, mediastinitis, or PTArelated complication. Among the survivors, no differences were observed in ventilator support time ( hours versus hours; p 0.446), intensive care unit stay ( hours versus hours; p 0.567), or hospital stay ( days versus days; p 0.789) between the two groups. The average number of distal anastomoses per patient was The average number of distal anastomoses per patient was larger in the PTA group than in the non-pta group ( versus ; p 0.02). Early postoperative ( days) angiograms including arch aortogram were performed in 35 patients. Overall graft patency rate was 97.2% (105 of 108 distal anastomoses), with no difference between the two groups (97.1% versus 97.5%). In the non-pta group, alternative in situ grafts used included the right ITA (n 15) and right gastroepiploic artery (n 1). Free saphenous veins anastomosed onto the ascending aorta were used in 2 patients. There was no difference in patency rate between grafts emanating from the left ITA in the PTA group and in situ grafts other than the left ITA in the non-pta group (96.7% versus 97.4%; Table 4). In the PTA group, the patency rate of the left ITA to the LAD was 100% (18 of 18). In the non-pta group, the right ITA was used to revascularize the LAD in 13 patients, and the patency rate was 100% (13 of 13). Late Results Patients were followed up for months. There were 4 late noncardiac deaths (2 cases of lung cancer, 1 case of stroke, and 1 case of pneumonia). Thirty of 32 patients (93.8%) who were followed up for more than 1 year underwent 1-year ( months) angiograms (16 of 18 patients in the PTA group, 14 of 14 patients in the non-pta group; p 0.492). The overall patency rate was 88.0% (81 of 92 distal anastomoses), with no differences in patency rates between the two groups (88.9%, 48 of 54 versus 86.8%, 33 of 38; p 1.000). Between the two Table 4. Early, 1-Year, and 5-Year Angiographic Patency Rates Period Patency Total PTA Group Non-PTA Group p Value Early N 35 N 20 N 15 Total 105/108 (97.2%) 66/68 (97.1%) 39/40 (97.5%) Left ITA or other in situ grafts 96/99 (97.0%) 59/61 (96.7%) 37/38 (97.4%) year N 30 N 16 N 14 Total 81/92 (88.0%) 48/54 (88.9%) 33/38 (86.8%) Left ITA or other in situ grafts 75/84 (89.3%) 43/48 (89.6%) 32/36 (88.9%) year N 9 N 4 N 5 Total 23/25 (92%) 11/12 (91.7%) 12/13 (92.3%) Left ITA or other in situ grafts 18/18 (100%) 8/8 (100%) 10/10 (100%) ITA internal thoracic artery; PTA percutaneous transluminal angioplasty.

4 Ann Thorac Surg HWANG ET AL 2010;89: LEFT SUBCLAVIAN ARTERY STENOSIS IN CABG 1149 groups, no difference was observed in the patency rates of grafts emanating from the left ITA or other in situ grafts (89.6%, 43 of 48 versus 88.9%, 32 of 36; p 1.000). Patency rates of the left ITA (PTA group) and right ITA (non-pta group) for revascularization of the LAD were 93.3% (14 of 15) and 100% (10 of 10), respectively, at 1-year angiograms (p 1.000). Among 10 patients (PTA group, n 4; non-pta group, n 6) who were followed up for more than 5 years, 9 patients (PTA group, n 4; non-pta group, n 5) underwent 5-year (60 11 months) postoperative angiograms. Ninety-two percent (23 of 25 distal anastomoses) of anastomoses were patent without intergroup differences (91.7%, 11 of 12 versus 92.3%, 12 of 13; p 1.000). Distal anastomoses emanating from the left ITA or other in situ grafts were all patent (8 of 8 in the PTA group, 10 of 10 in the non-pta group; Table 4). The left ITA (PTA group) and right ITA (non-pta group) to revascularize the LAD were all patent at 5-year angiograms (3 of 3 and 4 of 4, respectively). Estimated 5-year patency rates of graft to the LAD were 91.7% and 100% in the PTA and non-pta groups, respectively (p 0.387; Fig 1). Among 13 patients who were followed up for more than 2 years in the PTA group, 2-year computed tomographic angiogram was performed in 11 patients. In 1 patient, computed tomographic angiography taken 26 months after PTA using a stent revealed a significant restenosis of more than 75%. The patient was treated with balloon angioplasty, and 5-year angiogram demonstrated a patent LSA. Mean duration of overall radiologic follow-up for PTA patency for LSA stenosis was months, and the PTA patency rate was 95% (19 of 20). Estimated 2-year and 5-year PTA patency rates for LSA stenosis were 100% and 85.7%, respectively (Fig 2). Fig 1. Patency rates of grafts anastomosed to the left anterior descending artery between the percutaneous transluminal angioplasty (PTA) and non-percutaneous transluminal angioplasty (non-pta) groups. Fig 2. Kaplan-Meier curve demonstrating 2-year and 5-year percutaneous transluminal angioplasty patency rates for left subclavian artery stenosis. Comment This study demonstrated three main findings. First, prevalence of significant LSA stenosis in patients referred for isolated CABG was 2.5%. Second, PTA for LSA stenosis and revascularization using the in situ left ITA could be an effective treatment option for patients with significant LSA stenosis. Third, in patients whose LSA stenosis was not amenable to PTA, revascularization using grafts other than the left ITA might be another treatment option. Use of the left ITA with supplemental arterial or vein grafts has been the standard treatment for CABG throughout the world because reduction in cardiac events and enhanced long-term survival have been shown when the left ITA is grafted to the LAD [5, 6]. However, the presence of significant proximal LSA stenosis may result in reversal of ipsilateral ITA coronary graft flow and produce myocardial ischemia [1]. Reported prevalence of significant LSA stenosis in patients referred for CABG is 0.2% to 6.8% [1 4]. In the present study, all patients referred for CABG underwent invasive preoperative radiologic evaluation, including cineangiography of the coronary vessels, and LSA angiography or selective left ITA angiography. Significant LSA stenosis was demonstrated during preoperative evaluation in 35 of the 1,498 patients who underwent isolated CABG. Additionally, significant LSA stenosis was diagnosed on the basis of the early postoperative angiograms in another 3 patients. These LSA stenoses were not recognized preoperatively because cardiologists missed the presence of LSA stenosis and performed selective left ITA angiography instead of LSA angiography. During the last 10 years, our prevalence of significant LSA stenosis in patients referred for isolated CABG was 2.5% (38 of 1,498 patients). The presence of significant proximal LSA stenosis in patients referred for CABG has been managed by operative reconstruction or endovascular intervention of LSA stenosis followed by revascularization using the left ITA

5 1150 HWANG ET AL Ann Thorac Surg LEFT SUBCLAVIAN ARTERY STENOSIS IN CABG 2010;89: or by revascularization using grafts other than the left ITA [1, 3, 4, 7, 8]. Although operative reconstruction was previously considered to be the procedure of choice for LSA stenosis [9], recent studies [7, 8] have suggested endovascular intervention as the first-line therapy owing to equal effectiveness and fewer complications. Furthermore, patients who have already had CABG and present subsequently with coronary-subclavian steal syndrome have been considered as good candidates for endovascular intervention [7]. Endovascular intervention on the LSA before CABG is becoming prevalent in patients who do not require emergent CABG. However, there are no published data with regard to timing of CABG after endovascular intervention including stenting. Given the large caliber of the LSA and low thrombosis rates, CABG can theoretically be performed safely soon after intervention, even within the first few days [8]. In the present study, most PTA (16 of 20 patients) was performed before surgery, and in 4 patients, PTA was performed on the same day, before surgery. We did not experience periprocedural complications after PTA. Although subacute stent thrombosis or occlusion appears to be an exceptionally rare event, aspirin should be given after stenting and can be continued through CABG [8]. The role of dual antiplatelet therapy in subclavian artery stenting has not been studied [10]. Previous studies demonstrated a 5-year patency rate of 89% to 95% after PTA [10, 11]. The present study demonstrated that estimated 2-year and 5-year PTA patency rates for LSA stenosis were 100% and 85.7%, respectively. The estimated 5-year patency rate of 85.7%, however, might result from the fact that only 7 patients underwent follow-up angiography more than 26 months after PTA and 1 patient had restenosis of the LSA. The lesion was treated with balloon angioplasty, and a 5-year angiogram demonstrated a patent LSA. In the present study, because of lesion complexities or total occlusion of the LSA, LSA stenosis was not amenable to endovascular intervention in half of the patients. For those patients, revascularization using grafts other than the left ITA had to be considered, and revascularization using the in situ right ITA was preferred because of well-established clinical and angiographic superiority of the in situ right ITA graft [12 14]. Patency rates of the right ITA (non-pta group) for revascularization of the LAD were similar to those of the left ITA (PTA group). The present study also demonstrated that there was no difference in patency rates between grafts emanating from the left ITA and other in situ grafts at early, 1-year, and 5-year angiography. The average number of distal anastomoses per patient was larger in the PTA group than in the non-pta group, probably related to the higher incidence of three-vessel disease in the PTA group. There are limitations to the present study that must be recognized. First, the present study was a retrospective observational study in a single institution, although a computer-based patient database system was used. Second, no data were available for comparison of results from patients in the PTA group with those of patients who underwent surgical reconstruction of the LSA. A randomized controlled trial will be needed to determine whether or not endovascular management of this uncommon problem provides durability and effectiveness comparable to that of surgical bypass. Third, because the number of enrolled patients is relatively small and only a few patients underwent 5-year follow-up angiograms, it is insufficient to reach a definite conclusion. References 1. Takach TJ, Reul GJ, Cooley DA, et al. Myocardial thievery: the coronary-subclavian steal syndrome. Ann Thorac Surg 2006;81: Osborn LA, Vernon SM, Reynolds B, Timm TC, Allen K. Screening for subclavian artery stenosis in patients who are candidates for coronary bypass surgery. Catheter Cardiovasc Interv 2002;56: Takach TJ, Reul GJ, Duncan JM, et al. Concomitant brachiocephalic and coronary artery disease: outcome and decision analysis. Ann Thorac Surg 2005;80: Prasad A, Prasad A, Varghese I, Roesle M, Banerjee S, Brilakis ES. Prevalence and treatment of proximal left subclavian artery stenosis in patients referred for coronary artery bypass surgery. Int J Cardiol 2009;133: Loop FD, Lytle BW, Cosgrove DM, et al. Influence of the internal-mammary-artery graft on 10-year survival and other cardiac events. N Engl J Med 1986;314: Cameron A, Davis KB, Green G, Schaff HV. Coronary bypass surgery with internal-thoracic-artery grafts effects on survival over a 15-year period. N Engl J Med 1996;334: Westerband A, Rodriguez JA, Ramaiah VG, Diethrich EB. Endovascular therapy in prevention and management of coronary-subclavian steal. J Vasc Surg 2003;38: Rogers JH, Calhoun RF 2nd. Diagnosis and management of subclavian artery stenosis prior to coronary artery bypass grafting in the current era. J Card Surg 2007;22: Takach TJ, Reul GJ, Gregoric I, et al. Concomitant subclavian and coronary artery disease. Ann Thorac Surg 2001;71: Linni K, Ugurluoglu A, Mader N, Hitzl W, Magometschnigg H, Hölzenbein TJ. Endovascular management versus surgery for proximal subclavian artery lesions. Ann Vasc Surg 2008;22: de Vries JPM, Jager LC, van den Berg JC, et al. Durability of percutaneous transluminal angioplasty for obstructive lesions of proximal subclavian artery: long-term results. J Vasc Surg 2005;41: Al-Ruzzeh S, George S, Bustami M, Nakamura K, Ilsley C, Amrani M. Early clinical and angiographic outcome of the pedicled right internal thoracic artery graft to the left anterior descending artery. Ann Thorac Surg 2002;73: Kim K-B, Cho KR, Chang W-I, Lim C, Ham BM, Kim YL. Bilateral skeletonized internal thoracic artery graftings in off-pump coronary artery bypass: early result of Y versus in situ grafts. Ann Thorac Surg 2002;74(Suppl):S Shah PJ, Bui K, Blackmore S, et al. Has the in situ right internal thoracic artery been overlooked? An angiographic study of the radial artery, internal thoracic arteries and saphenous vein graft patencies in symptomatic patients. Eur J Cardiothorac Surg 2005;27:870 5.

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