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Early and Midterm Results of Off-Pump Coronary Artery Bypass Grafting
Toshihiro Fukui, MD, Shuichiro Takanashi, MD, Yasuyuki Hosoda, MD, and Shigefumi Suehiro, MD Department of Cardiovascular Surgery, Osaka City University Graduate School of Medicine, Osaka, Department of Cardiovascular Surgery, Sakakibara Heart Institute, Tokyo, and Department of Cardiovascular Surgery, Shin-Tokyo Hospital, Chiba, Japan
Background. Early outcomes of off-pump coronary artery bypass grafting have been documented by numerous studies. However, there have been few reports concerning midterm outcomes after off-pump coronary artery bypass grafting. Methods. We retrospectively reviewed the records of 602 consecutive patients (24.8% female) who underwent isolated off-pump coronary artery bypass grafting between April 2001 and July 2004. Mean age was 66.7 ⴞ 9.3 years. Mean Canadian Cardiovascular Society score was 2.5 ⴞ 0.9. Early postoperative angiograms were evaluated during the same period of hospitalization. Midterm outcomes, including overall patient survival, freedom from cardiac death, and freedom from the combined endpoint of cardiac events, were evaluated. Results. The average number of distal anastomoses per patient was 3.6 ⴞ 1.4. The average operation time was
286.1 ⴞ 72.1 minutes. Long segmental reconstruction of the left anterior descending coronary artery was performed in 218 patients (36.2%). Total arterial grafting was performed in 466 patients (77.4%). Thirty-day mortality was 0.5%. Overall patency rate for all grafts and anastomoses was 97.5% and 97.6%, respectively. Mean follow-up time was 2.9 ⴞ 1.0 years. Cumulative patient survival at 5 years was 87.9% ⴞ 2.4%. Freedom from cardiac death was 97.7% ⴞ 0.6% at 5 years. Freedom from the combined endpoint of cardiac events was 83.8% ⴞ 2.3% at 5 years. Conclusions. Early and midterm outcomes after offpump coronary artery bypass grafting have acceptable mortality and cardiac events rates, with favorable early graft patency rates. (Ann Thorac Surg 2007;83:115–9) © 2007 by The Society of Thoracic Surgeons
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performed OPCAB whenever feasible in patients undergoing CABG; however, intramyocardial target vessels and severe left ventricular dysfunction were the main reasons for selecting conventional CABG. No age criteria were used in the selection of patients. The preoperative characteristics of the patients are summarized in Table 1. The study was approved by our institutional review committee, and informed consent was obtained from each patient with respect to the surgical method and postoperative angiography. Follow-up was achieved by direct communication with the patient, their family, attending physician, or a combination of these during a 3-month closing interval ending in March 2006. Complete revascularization was defined as “traditional” completeness in this study. “Traditional” completeness was defined as all diseased arterial systems (stenosis ⱖ50%) receiving at least one graft insertion [7]. Total arterial grafting was defined as no usage of saphenous vein graft (SVG) in the procedure. Perioperative myocardial infarction was defined as a positive result for new Q waves in the electrocardiogram, or a peak level of creatine kinase MB greater than 10% of total creatine kinase. Low-output syndrome was defined as the need for greater than 5 g · kg⫺1 · min⫺1 of inotropic agent (dopamine or dobutamine). Postoperative stroke was defined as a central neurologic deficit persisting for more than 72 hours, and was confirmed by computed tomography. In patients with preoperative stroke, postoperative stroke was defined as a worsening
umerous studies have demonstrated that off-pump coronary artery bypass grafting (OPCAB) has excellent early clinical outcomes superior or equal to conventional coronary artery bypass grafting (CABG) with cardiopulmonary bypass [1]. Avoiding the harmful effects of cardiopulmonary bypass is the main contribution to reducing the morbidity after surgical revascularization [2]. However, there is still skepticism about the quality of anastomoses and completeness of revascularization with OPCAB [3, 4]. This skepticism may be resolved with angiographic studies and long-term follow-up. There have been some reports about midterm outcomes after OPCAB [5, 6]; however, there have been none about combined assessment of early graft patency and midterm clinical outcomes. This study aimed to evaluate the early angiographic results and midterm outcomes after OPCAB.
Patients and Methods Patient Population Between April 2001 and July 2004, 669 patients underwent isolated CABG at the Shin-Tokyo Hospital, Japan. Of these patients, 602 (90.0%) underwent OPCAB. We Accepted for publication Aug 3, 2006. Address correspondence to Dr Fukui, Department of Cardiovascular Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka City, 545-8585, Japan; e-mail: tm-fukui@ gem.hi-ho.ne.jp.
© 2007 by The Society of Thoracic Surgeons Published by Elsevier Inc
0003-4975/07/$32.00 doi:10.1016/j.athoracsur.2006.08.009
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Table 1. Preoperative Patient Characteristics Variable
Value 66.7 ⫾ 9.3 149 (24.8%) 212 (35.2%) 278 (46.2%) 2.5 ⫾ 0.9 299 (49.7%) 0.561 ⫾ 0.105 2.6 ⫾ 0.6 168 (27.9%) 467 (77.6%) 304 (50.5%) 85 (28.0%) 219 (72.0%) 313 (52.0%) 234 (38.9%) 43 (7.1%) 75 (12.5%) 36 (6.0%) 23 (3.8%) 44 (7.3%) 10 (1.7%)
Age (y) Number of female patients Unstable angina Previous myocardial infarction Mean CCS score CCS score ⫽ 3 or 4 Left ventricular ejection fraction Number of diseased coronary arteries Left main coronary artery disease Hypertension Diabetes mellitus Insulin-dependent Non–insulin-dependent Hypercholesterolemia Smoking history Peripheral arterial disease Previous stroke Chronic renal failure Chronic obstructive lung disease Non elective surgery Repeat surgery CCS ⫽ Canadian Cardiovascular Society.
of neurologic deficit, with new radiologic findings. Postoperative renal insufficiency was defined as a new requirement for dialysis postoperatively. Patients who required blood transfusion in the present study included those who received not only red blood cells, but also platelets and fresh-frozen plasma.
Surgical Methods Operations were performed by two surgeons with the same strategy decided by one surgeon (T.S.). All arterial grafts were harvested in a skeletonized fashion using an ultrasonic scalpel (Harmonic Scalpel; Ethicon Endosurgery, Cincinnati, OH), and taken down after milrinone solution (50 mg/L) was injected at the distal end. In situ grafts were divided after heparinization (300 IU/kg).
Saphenous vein grafts were harvested using an open technique with fine scissors. The indication for performing bypass grafting was significant stenosis (ⱖ50% diameter reduction) in all coronary vessels larger than 1 mm in diameter. Composite and sequential grafting with arterial grafts is our preferred technique [8]. Saphenous vein grafts were used in vessels with nonsevere stenosis, and were not used in composite grafts. When an epiaortic echogram demonstrated ascending aortic atherosclerosis, an aortic no-touch technique was used. A commercially available heart positioner and stabilizer were applied to the heart (Starfish and Octopus; Medtronic, Minneapolis, MN). A deep pericardial stay suture was not used. A bloodless field was obtained using a proximal silicone elastomer snare suture and a carbon dioxide blower. An intraluminal shunt was sometimes used for grafting to the right coronary artery. Each anastomosis was performed with an 8-0 polypropylene running suture using the parachute technique. When sequential grafting was constructed, diamond-shaped side-to-side anastomosis and terminal T-shaped anastomosis (right-angled anastomosis) were our preferred approaches. Terminal anastomosis was performed first, followed by sequential anastomoses toward the proximal portion of the graft. When a composite graft was constructed, an anastomosis between the donor and branched arteries was performed after all distal anastomoses were completed. As required, long segmental reconstruction of diffusely diseased left anterior descending coronary artery using the left internal thoracic artery was performed [9]. Furthermore, we performed long segmental reconstruction with endarterectomy in a left anterior descending coronary artery that had a severely calcified, long hard fibrous, or long soft plaque. We performed endarterectomy using a long arteriotomy in the left anterior descending coronary artery and grafted an onlay patch of the left internal thoracic artery. Technical details of these methods have been described previously [10]. We did not assess graft patency during the operation. Anticoagulation was started on the first postoperative day. Patients who received SVGs were given low-dose aspirin (100 mg/day) and warfarin (maintained with a target international normalized ratio of 2.0). After 3 months, the administration of warfarin was stopped.
Table 2. Total Number of Grafts and Anastomoses Variable Inflow of other grafts One anastomosis Multiple anastomoses
Number of Distal Anastomoses
LITA
RITA
RA
GEA
IEA
SVG
5 451 118 6 0 0 0 580 705
54 231 40 24 1 0 0 350 387
0 142 92 51 34 6 3 328 663
27 115 47 4 1 0 0 194 225
0 5 0 0 0 0 0 5 5
1 86 39 8 2 0 0 136 196
0 1 2 3 4 5 6
Total grafts Total anastomoses GEA ⫽ gastroepiploic artery; IEA ⫽ inferior epigastric artery; internal mammary artery; SVG ⫽ saphenous vein graft.
LITA ⫽ left internal mammary artery;
RA ⫽ radial artery;
RITA ⫽ right
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Table 3. Postoperative Data Variable
No. (%)
30-day mortality Perioperative myocardial infarction Low output syndrome Atrial fibrillation Reexploration for bleeding Stroke Respiratory failure Renal insufficiency Mediastinitis
3 (0.5) 12 (2.0) 12 (2.0) 111 (18.4) 6 (1.0) 9 (1.5) 20 (3.3) 11 (1.8) 3 (0.5)
Angiographic Study
Fig 1. Actuarial survival rate including all deaths.
Postoperative angiography was performed to assess graft patency only in patients who gave informed consent, and before discharge at 7.5 ⫾ 2.5 days after surgery. When patients were symptomatic during follow-up, diagnostic angiography was performed at that time. If a new lesion of native coronary artery or graft occlusion was found, percutaneous coronary intervention was performed if possible. Angiographic studies were reviewed and evaluated by two cardiologists.
Statistical Analysis Continuous variables are reported as the mean ⫾ standard deviation. Continuous variables were compared by Student’s t test. Discrete variables were compared by the 2 test or Fisher’s exact test. A logistic regression model was used to determine significant predictors of postoperative stroke. Explanatory variables included all variables in Table 1 and intraoperative aortic manipulation. Actuarial survival and event-free survival curves were estimated by the Kaplan–Meier method. Differences were considered statistically significant at a probability less than 0.05. Statistical analyses were performed using the StatView 5.0 software package (SAS Institute, Cary, NC).
Results Operative Results The average operation time was 286.1 ⫾ 72.1 minutes. The number of distal anastomoses per patient was 3.6 ⫾ 1.4. Complete revascularization was achieved in 99.2% of patients. The left internal thoracic artery was the most commonly used graft, in a total of 580 patients (96.3%). The right internal thoracic artery, the radial artery, the
gastroepiploic artery, and the inferior epigastric artery were used in 350 (58.1%), 328 (54.5%), 194 (32.2%), and 5 (0.8%) patients, respectively. The SVG was used in 136 (22.6%) patients. Total arterial grafting was achieved in 466 patients (77.4%). The total number of grafts and anastomoses is presented in Table 2. Long segmental reconstruction of the left anterior descending coronary artery was performed in 218 patients (36.2%). Of these patients, additional endarterectomy was carried out in 49 (22.5%). Mean length of the anastomosis was 4.1 ⫾ 1.5 cm. Blood transfusions were undertaken in 35.4% of cases.
Early Outcome Three patients died within 30 days (0.5%). One patient with multiple risk factors (hypertension, diabetes, hyperlipidemia, obesity, and Canadian Cardiovascular Society score 4) died of stroke 23 days after surgery. One patient who underwent repeat surgical revascularization with OPCAB died of sepsis 12 days after the second operation. One patient with chronic renal failure died of ventricular arrhythmia 12 days after surgery. Postoperative morbidity is shown in Table 3. The incidence of stroke was 1.5%. When the stroke rate was compared between patients with and without aortic manipulation, it was no different (1.4% versus 1.6%; p ⫽ 0.82). Furthermore, no factor was found to be a significant predictor of stroke when a logistic regression model was used. The mean intubation time was 10.7 ⫾ 9.4 hours. Mean intensive care unit and postoperative hospital stays were 1.5 ⫾ 1.2 and 13.6 ⫾ 12.0 days, respectively. Postoperative ejection fraction was 0.561 ⫾ 0.091.
Table 4. Patency of Both Grafts and Anastomoses Variable Patency of grafts Patency of distal anastomoses
LITA
RITA
RA
GEA
IEA
434/440 (98.6%) 265/267 (99.3%) 247/262 (94.3%) 151/156 (96.8%) 4/4 (100%)
SVG
Total
87/89 (97.8%) 1,188/1,218 (97.5%)
520/526 (98.9%) 293/295 (99.3%) 520/542 (95.9%) 171/177 (96.6%) 4/4 (100%) 122/126 (96.8%) 1,630/1,670 (97.6%)
GEA ⫽ gastroepiploic artery; IEA ⫽ inferior epigastric artery; internal mammary artery; SVG ⫽ saphenous vein graft.
LITA ⫽ left internal mammary artery;
RA ⫽ radial artery;
RITA ⫽ right
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Fig 2. Deaths and cardiac event-free rates.
Postoperative angiography was performed in 457 patients (75.9%). A total of 1,218 grafts (2.7 per patient) with 1,670 distal anastomoses (3.7 per patient) were evaluated. Overall patency rates for all grafts and all anastomoses were 97.5% and 97.6%, respectively. Patency rates for each graft and anastomosis are summarized in Table 4.
Midterm Outcome Follow-up was complete in 94.0% (566 of 602 patients) of the patients. During the follow-up period (2.9 ⫾ 1.0 years), there were 49 deaths (8.1%), including operative mortality. Cumulative patient survival at 5 years was 87.9% ⫾ 2.4% (Fig 1). Of these 49 patients, 13 died of cardiac causes. Freedom from cardiac death was 97.7% ⫾ 0.6% at 5 years (Fig 2). There were 2 patients who had a myocardial infarction during the follow-up period. There were 47 patients who underwent percutaneous coronary intervention after surgery. No patient required repeat CABG during the follow-up period. Freedom from the combined endpoint of cardiac death and myocardial infarction, including perioperative myocardial infarction, repeat percutaneous coronary intervention, and repeat CABG, was 83.8% ⫾ 2.3% at 5 years (Fig 3). At the end of the follow-up period, the mean Canadian Cardiovascular Society score was 1.3 ⫾ 0.6.
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leagues [5] demonstrated the equivalent midterm outcomes after off-pump and on-pump CABG. In their report, 4-year survival after OPCAB was 87.5%. The results of the present study, with a 5-year survival rate of 87.9% ⫾ 4% and freedom from cardiac death of 97.7% ⫾ 0.6%, are almost identical to those of previous studies. To achieve complete myocardial revascularization is one of the important goals of CABG, although the definition of completeness differs among studies. Kleisli and colleagues [13] demonstrated that the 5-year survival rate of complete revascularization was superior to that of incomplete revascularization (82.4% versus 52.6%). In their report, the anatomic reasons for incompleteness were small, such as severely diseased, arteries, nondominant right coronary artery, the presence of prior infarcted tissue, significant collateral circulation, and lack of conduit availability. Many studies have revealed that offpump surgery itself can be one of the reasons for incomplete revascularization [13–15]. Sabik and colleagues [15] reported that the mean number of bypass grafts in offpump patients (2.8 ⫾ 1.0) was significantly smaller than that in on-pump patients (3.5 ⫾ 1.1). Because we have adopted the definition of “traditional” completeness, the number of distal anastomoses per patient (3.6 ⫾ 1.4) in the present study was similar to that in the on-pump patients of Sabik and associates [15], and complete revascularization was achieved in 99.2% of patients. We indicate that complete myocardial revascularization using an off-pump technique can be safely performed, and we believe that complete revascularization, using the traditional definition, will improve long-term cardiac survival. Long-term follow-up is necessary to elucidate the detrimental effects of incomplete revascularization with OPCAB. The use of arterial grafts has been widely accepted for myocardial revascularization on the basis of the clinical advantage of using the left internal thoracic artery as a bypass conduit [16]. A decreased risk of cardiac death was associated with arterial grafting in a long-term follow-up study [13]. More recently, use of two or three arterial grafts was shown to improve survival and reduce the need for readmission for
Comment Coronary artery bypass grafting with cardiopulmonary bypass has been a standard procedure in multiple CABG. Off-pump CABG has been developed to avoid the morbidity associated with cardiopulmonary bypass, which can lead to severe systemic inflammatory responses [11]. Numerous studies have demonstrated the safety and effectiveness of OPCAB with favorable early outcomes. A recent meta-analysis has revealed that OPCAB may be a safe alternative to conventional CABG with respect to mortality, and it is recommended to reduce perioperative morbidity [1]. Even though early outcome shows excellent results, information on the midterm and long-term outcomes is necessary to evaluate the effectiveness of OPCAB. Nevertheless, there are a few reports about the midterm results of OPCAB [4 – 6, 12]. Sabik and col-
Fig 3. Freedom from combined endpoint of cardiac-cause mortality, myocardial infarction, repeat percutaneous coronary intervention, and repeat coronary artery bypass grafting.
treatment of heart disease [17]. We prefer using arterial grafts with the OPCAB technique. Thus, total arterial grafting was performed in 77.4% of patients in the present study. Off-pump CABG is a suitable method for patients in whom proximal anastomoses of conduits cannot be performed because of diseased aorta. In these patients, composite and sequential grafting using arterial grafts can be safely performed [8]. The reduced patency of bypass grafts increases the need for repeat revascularization with time. Puskas and coworkers [18] demonstrated that graft patency in OPCAB patients is similar to that in conventional CABG patients at 30 days (99.0% versus 97.7%) and 1 year (93.6% versus 95.8%) after surgery. Our finding that overall early graft patency rate was 97.5% is almost identical to their results. We believe that the same early graft patency rate can be obtained in patients treated with OPCAB as compared with those undergoing conventional CABG. Some investigators have demonstrated a reduced patency rate for SVG in patients undergoing OPCAB [19]. Hypercoagulability may exist after OPCAB, and prophylactic postoperative anticoagulation therapy may be indicated for these patients [20]. More recently, Halkos and colleagues [21] reported that OPCAB patients could safely receive clopidogrel in the early postoperative period without increased risk for mediastinal bleeding. We have routinely used warfarin in addition to low-dose aspirin in patients with SVG. In the present study, the patency rate of SVG was 97.8%, which is similar to that of arterial grafts. Clopidogrel may be more effective than warfarin with low-dose aspirin to reduce graft occlusion rate. There are still some patients who cannot be treated with OPCAB, such as those with a large heart and impaired left ventricular function or intramyocardial coronary arteries. The rate of performing OPCAB in our isolated CABG patients was 90%. A recent meta-analysis clearly revealed the favorable outcomes of OPCAB [1], and concluded that OPCAB should be considered a safe alternative to conventional CABG with respect to mortality risk. Similar completeness of myocardial revascularization and graft patency can be achieved by OPCAB procedures using modern technology and techniques. Thus, we suggest that OPCAB should be performed whenever possible in patients undergoing isolated CABG. The limitations of our clinical study are that the number of patients was small and the length of clinical follow-up was relatively short. Postoperative angiographic data and clinical outcome could not be obtained from all patients. Furthermore, this was a retrospective observational study and was not randomized. It is possible that there are subtle selection biases in patients selected for OPCAB. Because there was no control group, we cannot conclude that the midterm outcomes after OPCAB were superior to those of conventional CABG.
References 1. Puskas J, Cheng D, Knight J, et al. Off-pump versus conventional coronary artery bypass grafting: a meta-analysis and
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12. 13. 14. 15. 16.
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consensus statement from The 2004 ISMICS Consensus Conference. Innovations 2005;1:3–27. Angelini GD, Taylor FC, Reeves BC, Ascione R. Early and midterm outcome after off-pump and on-pump surgery in Beating Heart Against Cardioplegic Arrest Studies (BHACAS 1 and 2): a pooled analysis of two randomized controlled trials. Lancet 2002;359:1194 –9. Khan NE, De Souza A, Mister R, et al. A randomized comparison of off-pump and on-pump multivessel coronary-artery bypass surgery. N Engl J Med 2004;350:21– 8. Gundry SR, Romano MA, Shattuck OH, Razzouk AJ, Bailey LL. Seven-year follow-up of coronary artery bypasses performed with and without cardiopulmonary bypass. J Thorac Cardiovasc Surg 1998;115:1273–7. Sabik JF, Nemeh H, Lytle BW, et al. Equivalent midterm outcomes after off-pump and on-pump coronary surgery. J Thorac Cardiovasc Surg 2004;127:142– 8. Gurbuz AT, Zia AA, Cui H, Sasmazel A, Ates G, Aytac A. Predictors of mid-term symptom recurrence, adverse cardiac events and mortality in 591 unselected off-pump coronary artery bypass graft patients. J Card Surg 2006;21:28 –34. Vander Salm TJ, Kip KE, Jones RH, et al. What constitutes optimal surgical revascularization? Answers from the Bypass Angioplasty Revascularization Investigation (BARI). J Am Coll Cardiol 2002;39:565–72. Fukui T, Takanashi S, Hosoda Y, Suehiro S. Total arterial myocardial revascularization using composite and sequential grafting with the off-pump technique. Ann Thorac Surg 2005;80:579 – 85. Takanashi S, Fukui T, Hosoda Y, Shimizu Y. Off-pump long onlay bypass grafting using left internal mammary artery for diffusely diseased coronary artery. Ann Thorac Surg 2003;76: 635–7. Fukui T, Takanashi S, Hosoda Y. Long segmental reconstruction of diffusely diseased left anterior descending coronary artery with left internal thoracic artery with or without endarterectomy. Ann Thorac Surg 2005;80:2098 –105. Larmann J, Theilmeier G. Inflammatory response to cardiac surgery: cardiopulmonary bypass versus noncardiopulmonary bypass surgery. Best Pract Res Clin Anaesthesiol 2004;18:425–38. Massoudy P, Thielmann M, Kienbaum P, et al. Off pump coronary artery bypass grafting—midterm results. Eur J Med Res 2006;11:38 – 42. Kleisli T, Cheng W, Jacobs MJ, et al. In the current era, complete revascularization improves survival after coronary artery bypass surgery. J Thorac Cardiovasc Surg 2005;129:1283–91. Czerny M, Baumer H, Kilo J, et al. Complete revascularization in coronary artery bypass grafting with and without cardiopulmonary bypass. Ann Thorac Surg 2001;71:165–9. Sabik JF, Gillinov AM, Blackstone EH, et al. Does off-pump coronary surgery reduce morbidity and mortality? J Thorac Cardiovasc Surg 2002;124:698 –707. 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;334:216 –9. Guru V, Fremes SE, Tu JV. How many arterial grafts are enough? A population-based study of midterm outcomes. J Thorac Cardiovasc Surg 2006;131:1021– 8. Puskas JD, Williams WH, Mahoney EM, et al. Off-pump vs conventional coronary artery bypass grafting: early and 1-year graft patency, cost, and quality-of-life outcomes: a randomized trial. JAMA 2004;291:1841–9. Omeroglu SN, Kirali K, Guler M, et al. Midterm angiographic assessment of coronary artery bypass grafting without cardiopulmonary bypass. Ann Thorac Surg 2000;70:844 –9. Kim KB, Lim C, Lee C, et al. Off-pump coronary artery bypass may decrease the patency of saphenous vein grafts. Ann Thorac Surg 2001;72(Suppl):S1033–7. Halkos ME, Cooper WA, Petersen R, et al. Early administration of clopidogrel is safe after off-pump coronary artery bypass surgery. Ann Thorac Surg 2006;81:815–9.
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Background. Early outcomes of off-pump coronary artery bypass grafting have been documented by numerous studies. However, there have been few reports concerning midterm outcomes after off-pump coronary artery bypass grafting. Methods. We retrospectively reviewed the records of 602 consecutive patients (24.8% female) who underwent isolated off-pump coronary artery bypass grafting between April 2001 and July 2004. Mean age was 66.7 ⴞ 9.3 years. Mean Canadian Cardiovascular Society score was 2.5 ⴞ 0.9. Early postoperative angiograms were evaluated during the same period of hospitalization. Midterm outcomes, including overall patient survival, freedom from cardiac death, and freedom from the combined endpoint of cardiac events, were evaluated. Results. The average number of distal anastomoses per patient was 3.6 ⴞ 1.4. The average operation time was
286.1 ⴞ 72.1 minutes. Long segmental reconstruction of the left anterior descending coronary artery was performed in 218 patients (36.2%). Total arterial grafting was performed in 466 patients (77.4%). Thirty-day mortality was 0.5%. Overall patency rate for all grafts and anastomoses was 97.5% and 97.6%, respectively. Mean follow-up time was 2.9 ⴞ 1.0 years. Cumulative patient survival at 5 years was 87.9% ⴞ 2.4%. Freedom from cardiac death was 97.7% ⴞ 0.6% at 5 years. Freedom from the combined endpoint of cardiac events was 83.8% ⴞ 2.3% at 5 years. Conclusions. Early and midterm outcomes after offpump coronary artery bypass grafting have acceptable mortality and cardiac events rates, with favorable early graft patency rates. (Ann Thorac Surg 2007;83:115–9) © 2007 by The Society of Thoracic Surgeons
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performed OPCAB whenever feasible in patients undergoing CABG; however, intramyocardial target vessels and severe left ventricular dysfunction were the main reasons for selecting conventional CABG. No age criteria were used in the selection of patients. The preoperative characteristics of the patients are summarized in Table 1. The study was approved by our institutional review committee, and informed consent was obtained from each patient with respect to the surgical method and postoperative angiography. Follow-up was achieved by direct communication with the patient, their family, attending physician, or a combination of these during a 3-month closing interval ending in March 2006. Complete revascularization was defined as “traditional” completeness in this study. “Traditional” completeness was defined as all diseased arterial systems (stenosis ⱖ50%) receiving at least one graft insertion [7]. Total arterial grafting was defined as no usage of saphenous vein graft (SVG) in the procedure. Perioperative myocardial infarction was defined as a positive result for new Q waves in the electrocardiogram, or a peak level of creatine kinase MB greater than 10% of total creatine kinase. Low-output syndrome was defined as the need for greater than 5 g · kg⫺1 · min⫺1 of inotropic agent (dopamine or dobutamine). Postoperative stroke was defined as a central neurologic deficit persisting for more than 72 hours, and was confirmed by computed tomography. In patients with preoperative stroke, postoperative stroke was defined as a worsening
umerous studies have demonstrated that off-pump coronary artery bypass grafting (OPCAB) has excellent early clinical outcomes superior or equal to conventional coronary artery bypass grafting (CABG) with cardiopulmonary bypass [1]. Avoiding the harmful effects of cardiopulmonary bypass is the main contribution to reducing the morbidity after surgical revascularization [2]. However, there is still skepticism about the quality of anastomoses and completeness of revascularization with OPCAB [3, 4]. This skepticism may be resolved with angiographic studies and long-term follow-up. There have been some reports about midterm outcomes after OPCAB [5, 6]; however, there have been none about combined assessment of early graft patency and midterm clinical outcomes. This study aimed to evaluate the early angiographic results and midterm outcomes after OPCAB.
Patients and Methods Patient Population Between April 2001 and July 2004, 669 patients underwent isolated CABG at the Shin-Tokyo Hospital, Japan. Of these patients, 602 (90.0%) underwent OPCAB. We Accepted for publication Aug 3, 2006. Address correspondence to Dr Fukui, Department of Cardiovascular Surgery, Osaka City University Graduate School of Medicine, 1-4-3 Asahimachi, Abeno-ku, Osaka City, 545-8585, Japan; e-mail: tm-fukui@ gem.hi-ho.ne.jp.
© 2007 by The Society of Thoracic Surgeons Published by Elsevier Inc
0003-4975/07/$32.00 doi:10.1016/j.athoracsur.2006.08.009
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Table 1. Preoperative Patient Characteristics Variable
Value 66.7 ⫾ 9.3 149 (24.8%) 212 (35.2%) 278 (46.2%) 2.5 ⫾ 0.9 299 (49.7%) 0.561 ⫾ 0.105 2.6 ⫾ 0.6 168 (27.9%) 467 (77.6%) 304 (50.5%) 85 (28.0%) 219 (72.0%) 313 (52.0%) 234 (38.9%) 43 (7.1%) 75 (12.5%) 36 (6.0%) 23 (3.8%) 44 (7.3%) 10 (1.7%)
Age (y) Number of female patients Unstable angina Previous myocardial infarction Mean CCS score CCS score ⫽ 3 or 4 Left ventricular ejection fraction Number of diseased coronary arteries Left main coronary artery disease Hypertension Diabetes mellitus Insulin-dependent Non–insulin-dependent Hypercholesterolemia Smoking history Peripheral arterial disease Previous stroke Chronic renal failure Chronic obstructive lung disease Non elective surgery Repeat surgery CCS ⫽ Canadian Cardiovascular Society.
of neurologic deficit, with new radiologic findings. Postoperative renal insufficiency was defined as a new requirement for dialysis postoperatively. Patients who required blood transfusion in the present study included those who received not only red blood cells, but also platelets and fresh-frozen plasma.
Surgical Methods Operations were performed by two surgeons with the same strategy decided by one surgeon (T.S.). All arterial grafts were harvested in a skeletonized fashion using an ultrasonic scalpel (Harmonic Scalpel; Ethicon Endosurgery, Cincinnati, OH), and taken down after milrinone solution (50 mg/L) was injected at the distal end. In situ grafts were divided after heparinization (300 IU/kg).
Saphenous vein grafts were harvested using an open technique with fine scissors. The indication for performing bypass grafting was significant stenosis (ⱖ50% diameter reduction) in all coronary vessels larger than 1 mm in diameter. Composite and sequential grafting with arterial grafts is our preferred technique [8]. Saphenous vein grafts were used in vessels with nonsevere stenosis, and were not used in composite grafts. When an epiaortic echogram demonstrated ascending aortic atherosclerosis, an aortic no-touch technique was used. A commercially available heart positioner and stabilizer were applied to the heart (Starfish and Octopus; Medtronic, Minneapolis, MN). A deep pericardial stay suture was not used. A bloodless field was obtained using a proximal silicone elastomer snare suture and a carbon dioxide blower. An intraluminal shunt was sometimes used for grafting to the right coronary artery. Each anastomosis was performed with an 8-0 polypropylene running suture using the parachute technique. When sequential grafting was constructed, diamond-shaped side-to-side anastomosis and terminal T-shaped anastomosis (right-angled anastomosis) were our preferred approaches. Terminal anastomosis was performed first, followed by sequential anastomoses toward the proximal portion of the graft. When a composite graft was constructed, an anastomosis between the donor and branched arteries was performed after all distal anastomoses were completed. As required, long segmental reconstruction of diffusely diseased left anterior descending coronary artery using the left internal thoracic artery was performed [9]. Furthermore, we performed long segmental reconstruction with endarterectomy in a left anterior descending coronary artery that had a severely calcified, long hard fibrous, or long soft plaque. We performed endarterectomy using a long arteriotomy in the left anterior descending coronary artery and grafted an onlay patch of the left internal thoracic artery. Technical details of these methods have been described previously [10]. We did not assess graft patency during the operation. Anticoagulation was started on the first postoperative day. Patients who received SVGs were given low-dose aspirin (100 mg/day) and warfarin (maintained with a target international normalized ratio of 2.0). After 3 months, the administration of warfarin was stopped.
Table 2. Total Number of Grafts and Anastomoses Variable Inflow of other grafts One anastomosis Multiple anastomoses
Number of Distal Anastomoses
LITA
RITA
RA
GEA
IEA
SVG
5 451 118 6 0 0 0 580 705
54 231 40 24 1 0 0 350 387
0 142 92 51 34 6 3 328 663
27 115 47 4 1 0 0 194 225
0 5 0 0 0 0 0 5 5
1 86 39 8 2 0 0 136 196
0 1 2 3 4 5 6
Total grafts Total anastomoses GEA ⫽ gastroepiploic artery; IEA ⫽ inferior epigastric artery; internal mammary artery; SVG ⫽ saphenous vein graft.
LITA ⫽ left internal mammary artery;
RA ⫽ radial artery;
RITA ⫽ right
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Table 3. Postoperative Data Variable
No. (%)
30-day mortality Perioperative myocardial infarction Low output syndrome Atrial fibrillation Reexploration for bleeding Stroke Respiratory failure Renal insufficiency Mediastinitis
3 (0.5) 12 (2.0) 12 (2.0) 111 (18.4) 6 (1.0) 9 (1.5) 20 (3.3) 11 (1.8) 3 (0.5)
Angiographic Study
Fig 1. Actuarial survival rate including all deaths.
Postoperative angiography was performed to assess graft patency only in patients who gave informed consent, and before discharge at 7.5 ⫾ 2.5 days after surgery. When patients were symptomatic during follow-up, diagnostic angiography was performed at that time. If a new lesion of native coronary artery or graft occlusion was found, percutaneous coronary intervention was performed if possible. Angiographic studies were reviewed and evaluated by two cardiologists.
Statistical Analysis Continuous variables are reported as the mean ⫾ standard deviation. Continuous variables were compared by Student’s t test. Discrete variables were compared by the 2 test or Fisher’s exact test. A logistic regression model was used to determine significant predictors of postoperative stroke. Explanatory variables included all variables in Table 1 and intraoperative aortic manipulation. Actuarial survival and event-free survival curves were estimated by the Kaplan–Meier method. Differences were considered statistically significant at a probability less than 0.05. Statistical analyses were performed using the StatView 5.0 software package (SAS Institute, Cary, NC).
Results Operative Results The average operation time was 286.1 ⫾ 72.1 minutes. The number of distal anastomoses per patient was 3.6 ⫾ 1.4. Complete revascularization was achieved in 99.2% of patients. The left internal thoracic artery was the most commonly used graft, in a total of 580 patients (96.3%). The right internal thoracic artery, the radial artery, the
gastroepiploic artery, and the inferior epigastric artery were used in 350 (58.1%), 328 (54.5%), 194 (32.2%), and 5 (0.8%) patients, respectively. The SVG was used in 136 (22.6%) patients. Total arterial grafting was achieved in 466 patients (77.4%). The total number of grafts and anastomoses is presented in Table 2. Long segmental reconstruction of the left anterior descending coronary artery was performed in 218 patients (36.2%). Of these patients, additional endarterectomy was carried out in 49 (22.5%). Mean length of the anastomosis was 4.1 ⫾ 1.5 cm. Blood transfusions were undertaken in 35.4% of cases.
Early Outcome Three patients died within 30 days (0.5%). One patient with multiple risk factors (hypertension, diabetes, hyperlipidemia, obesity, and Canadian Cardiovascular Society score 4) died of stroke 23 days after surgery. One patient who underwent repeat surgical revascularization with OPCAB died of sepsis 12 days after the second operation. One patient with chronic renal failure died of ventricular arrhythmia 12 days after surgery. Postoperative morbidity is shown in Table 3. The incidence of stroke was 1.5%. When the stroke rate was compared between patients with and without aortic manipulation, it was no different (1.4% versus 1.6%; p ⫽ 0.82). Furthermore, no factor was found to be a significant predictor of stroke when a logistic regression model was used. The mean intubation time was 10.7 ⫾ 9.4 hours. Mean intensive care unit and postoperative hospital stays were 1.5 ⫾ 1.2 and 13.6 ⫾ 12.0 days, respectively. Postoperative ejection fraction was 0.561 ⫾ 0.091.
Table 4. Patency of Both Grafts and Anastomoses Variable Patency of grafts Patency of distal anastomoses
LITA
RITA
RA
GEA
IEA
434/440 (98.6%) 265/267 (99.3%) 247/262 (94.3%) 151/156 (96.8%) 4/4 (100%)
SVG
Total
87/89 (97.8%) 1,188/1,218 (97.5%)
520/526 (98.9%) 293/295 (99.3%) 520/542 (95.9%) 171/177 (96.6%) 4/4 (100%) 122/126 (96.8%) 1,630/1,670 (97.6%)
GEA ⫽ gastroepiploic artery; IEA ⫽ inferior epigastric artery; internal mammary artery; SVG ⫽ saphenous vein graft.
LITA ⫽ left internal mammary artery;
RA ⫽ radial artery;
RITA ⫽ right
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FUKUI ET AL MID-TERM OUTCOMES AFTER OPCAB
Fig 2. Deaths and cardiac event-free rates.
Postoperative angiography was performed in 457 patients (75.9%). A total of 1,218 grafts (2.7 per patient) with 1,670 distal anastomoses (3.7 per patient) were evaluated. Overall patency rates for all grafts and all anastomoses were 97.5% and 97.6%, respectively. Patency rates for each graft and anastomosis are summarized in Table 4.
Midterm Outcome Follow-up was complete in 94.0% (566 of 602 patients) of the patients. During the follow-up period (2.9 ⫾ 1.0 years), there were 49 deaths (8.1%), including operative mortality. Cumulative patient survival at 5 years was 87.9% ⫾ 2.4% (Fig 1). Of these 49 patients, 13 died of cardiac causes. Freedom from cardiac death was 97.7% ⫾ 0.6% at 5 years (Fig 2). There were 2 patients who had a myocardial infarction during the follow-up period. There were 47 patients who underwent percutaneous coronary intervention after surgery. No patient required repeat CABG during the follow-up period. Freedom from the combined endpoint of cardiac death and myocardial infarction, including perioperative myocardial infarction, repeat percutaneous coronary intervention, and repeat CABG, was 83.8% ⫾ 2.3% at 5 years (Fig 3). At the end of the follow-up period, the mean Canadian Cardiovascular Society score was 1.3 ⫾ 0.6.
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leagues [5] demonstrated the equivalent midterm outcomes after off-pump and on-pump CABG. In their report, 4-year survival after OPCAB was 87.5%. The results of the present study, with a 5-year survival rate of 87.9% ⫾ 4% and freedom from cardiac death of 97.7% ⫾ 0.6%, are almost identical to those of previous studies. To achieve complete myocardial revascularization is one of the important goals of CABG, although the definition of completeness differs among studies. Kleisli and colleagues [13] demonstrated that the 5-year survival rate of complete revascularization was superior to that of incomplete revascularization (82.4% versus 52.6%). In their report, the anatomic reasons for incompleteness were small, such as severely diseased, arteries, nondominant right coronary artery, the presence of prior infarcted tissue, significant collateral circulation, and lack of conduit availability. Many studies have revealed that offpump surgery itself can be one of the reasons for incomplete revascularization [13–15]. Sabik and colleagues [15] reported that the mean number of bypass grafts in offpump patients (2.8 ⫾ 1.0) was significantly smaller than that in on-pump patients (3.5 ⫾ 1.1). Because we have adopted the definition of “traditional” completeness, the number of distal anastomoses per patient (3.6 ⫾ 1.4) in the present study was similar to that in the on-pump patients of Sabik and associates [15], and complete revascularization was achieved in 99.2% of patients. We indicate that complete myocardial revascularization using an off-pump technique can be safely performed, and we believe that complete revascularization, using the traditional definition, will improve long-term cardiac survival. Long-term follow-up is necessary to elucidate the detrimental effects of incomplete revascularization with OPCAB. The use of arterial grafts has been widely accepted for myocardial revascularization on the basis of the clinical advantage of using the left internal thoracic artery as a bypass conduit [16]. A decreased risk of cardiac death was associated with arterial grafting in a long-term follow-up study [13]. More recently, use of two or three arterial grafts was shown to improve survival and reduce the need for readmission for
Comment Coronary artery bypass grafting with cardiopulmonary bypass has been a standard procedure in multiple CABG. Off-pump CABG has been developed to avoid the morbidity associated with cardiopulmonary bypass, which can lead to severe systemic inflammatory responses [11]. Numerous studies have demonstrated the safety and effectiveness of OPCAB with favorable early outcomes. A recent meta-analysis has revealed that OPCAB may be a safe alternative to conventional CABG with respect to mortality, and it is recommended to reduce perioperative morbidity [1]. Even though early outcome shows excellent results, information on the midterm and long-term outcomes is necessary to evaluate the effectiveness of OPCAB. Nevertheless, there are a few reports about the midterm results of OPCAB [4 – 6, 12]. Sabik and col-
Fig 3. Freedom from combined endpoint of cardiac-cause mortality, myocardial infarction, repeat percutaneous coronary intervention, and repeat coronary artery bypass grafting.
treatment of heart disease [17]. We prefer using arterial grafts with the OPCAB technique. Thus, total arterial grafting was performed in 77.4% of patients in the present study. Off-pump CABG is a suitable method for patients in whom proximal anastomoses of conduits cannot be performed because of diseased aorta. In these patients, composite and sequential grafting using arterial grafts can be safely performed [8]. The reduced patency of bypass grafts increases the need for repeat revascularization with time. Puskas and coworkers [18] demonstrated that graft patency in OPCAB patients is similar to that in conventional CABG patients at 30 days (99.0% versus 97.7%) and 1 year (93.6% versus 95.8%) after surgery. Our finding that overall early graft patency rate was 97.5% is almost identical to their results. We believe that the same early graft patency rate can be obtained in patients treated with OPCAB as compared with those undergoing conventional CABG. Some investigators have demonstrated a reduced patency rate for SVG in patients undergoing OPCAB [19]. Hypercoagulability may exist after OPCAB, and prophylactic postoperative anticoagulation therapy may be indicated for these patients [20]. More recently, Halkos and colleagues [21] reported that OPCAB patients could safely receive clopidogrel in the early postoperative period without increased risk for mediastinal bleeding. We have routinely used warfarin in addition to low-dose aspirin in patients with SVG. In the present study, the patency rate of SVG was 97.8%, which is similar to that of arterial grafts. Clopidogrel may be more effective than warfarin with low-dose aspirin to reduce graft occlusion rate. There are still some patients who cannot be treated with OPCAB, such as those with a large heart and impaired left ventricular function or intramyocardial coronary arteries. The rate of performing OPCAB in our isolated CABG patients was 90%. A recent meta-analysis clearly revealed the favorable outcomes of OPCAB [1], and concluded that OPCAB should be considered a safe alternative to conventional CABG with respect to mortality risk. Similar completeness of myocardial revascularization and graft patency can be achieved by OPCAB procedures using modern technology and techniques. Thus, we suggest that OPCAB should be performed whenever possible in patients undergoing isolated CABG. The limitations of our clinical study are that the number of patients was small and the length of clinical follow-up was relatively short. Postoperative angiographic data and clinical outcome could not be obtained from all patients. Furthermore, this was a retrospective observational study and was not randomized. It is possible that there are subtle selection biases in patients selected for OPCAB. Because there was no control group, we cannot conclude that the midterm outcomes after OPCAB were superior to those of conventional CABG.
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