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eft Main Coronary Artery Disease Does Not Affecthe Outcome of Off-Pump Coronary Artery Bypassrafting
omoaki Suzuki, MD, PhD, Tohru Asai, MD, PhD, Keiji Matsubayashi, MD, PhD,tsushi Kambara, MD, Norihiko Hiramatsu, MD, Takeshi Kinoshita, MD, andsamu Nishimura, MD
epartment of Cardiovascular Surgery, Shiga University of Medical Science, Otsu City, Shiga, Japan
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Background. Left main coronary artery (LMCA) steno-is (>50%) has historically been recognized as a riskactor among patients undergoing coronary artery bypassrafting.Methods. From January 2002 to December 2008, a total
f 665 patients, 268 of whom had significant LMCAisease, underwent isolated off-pump coronary arteryypass surgery at Shiga Medical University Hospital. Weompared the clinical results in the 237 patients withMCA stenosis (LMCA group) with those in the propen-ity score-matched 237 patients without LMCA stenosisnon-LMCA group). We performed off-pump surgery inll coronary artery bypass grafting cases with no exclu-ion criteria.
Results. All procedures were performed by off-pumpechnique without conversion to on-pump. Two patientsn the LMCA group (2 of 237; 0.8%) and four in the
on-LMCA group (4 of 237; 1.7%) died within 30 dayswoltL
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urgery, Shiga University of Medical Science, Otsu City, Shiga, Japan;-mail: [email protected].
2010 by The Society of Thoracic Surgeonsublished by Elsevier Inc
fter surgery. Follow-up was completed in 96.2% of theatients. The rates of six-year freedom from all causeeath were 87.3% and 60.7% in the LMCA group andon-LMCA group, respectively (p � 0.17), and the corre-ponding rates for the combined endpoint of cardiaceath, myocardial infarction, angina pectoris, repeat cor-nary intervention, and heart failure were 80.4% and0.4% (p � 0.98). Multivariate Cox regression analysisevealed chronic renal failure as a statistically significantredictor for late cardiac event.Conclusions. Off-pump coronary artery bypass grafting
s feasible and safe in patients with critical LMCAtenosis and LMCA disease is not recognized as a riskactor after off-pump coronary artery bypass grafting inither the short or the long term.
(Ann Thorac Surg 2010;90:1501–6)
© 2010 by The Society of Thoracic Surgeonseft main coronary artery (LMCA) disease represents asignificant independent predictor of mortality in
atients with ischemic heart disease. Patients identifiedith LMCA stenosis are acknowledged to be at increased
isk when receiving medical therapy alone as comparedith surgical revascularization [1–3]. The standard ther-
py for patients with LMCA disease is coronary arteryypass grafting (CABG). Off-pump coronary artery bypassrafting (OPCAB) has recently become widespread inter-ationally, and has produced good clinical outcomes. How-ver, because of concern about the ability to tolerate beat-ng-heart surgery, patients with LMCA stenosis have beenxcluded from off-pump revascularization [4].
Left main coronary artery stenosis has historically beenecognized as a risk factor for early death among patientsndergoing CABG [5, 6]. A number of recent reports,owever, have indicated the safety and efficacy ofPCAB in patients with LMCA disease [7–10]. There are,oreover, reports [11, 12] of similar long-term survival
fter CABG regardless of LMCA disease status.
ccepted for publication June 7, 2010.
ddress correspondence to Dr Suzuki, Department of Cardiovascular
We became skeptical as to whether LMCA stenosisas still a significant risk factor after CABG. The purposef the present study was to compare short-term and
ong-term clinical outcome after OPCAB surgery be-ween propensity-matched groups with and withoutMCA disease.
atients and Methods
ll patients had previously granted permission for use ofheir medical records for research purposes. The Institu-ional Review Board approved this study.
From January 2002 to December 2008, a total of 665atients, 268 of whom had significant LMCA disease,nderwent isolated OPCAB surgery under a single sur-eon (T.A.) at Shiga Medical University Hospital. Weave calculated a propensity score for LMCA disease toet one-to-one match pairs with similar clinical charac-eristics. Logistic regression with backward selection waserformed to calculate the propensity score. By matchingropensity score, 237 pairs were successfully matched inone-to-one manner. We compared the clinical results
etween these propensity-matched groups. We per-
ormed OPCAB in all CABG cases with no exclusion0003-4975/$36.00doi:10.1016/j.athoracsur.2010.06.023
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1502 SUZUKI ET AL Ann Thorac SurgOFF-PUMP CORONARY SURGERY FOR LMCA DISEASE 2010;90:1501–6A
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riteria. Patients with acute myocardial infarction werencluded, but patients who had undergone a salvagerocedure were excluded from the study. Postoperativeenal failure was defined as the requirement for hemo-ialysis. Postoperative stroke was defined as a new neu-ologic event persisting for more than 24 hours afternset and was confirmed by computed tomography.ollow-up was achieved by direct communication withhe patient, the patient’s family, or the attending physi-ian. Significant LMCA disease was defined as LMCAith stenosis greater than 50%, assessed visually by thehysician performing the coronary angiography.
nesthetic and Surgical Techniquesstandard anesthetic technique was used for all pa-
ients. The induction of anesthesia was achieved withentanyl citrate (5 to 10 �g/kg), thiopental (3 to 5 mg/kg),r propofol infusion (3 to 4 mg/kg/hour), and vecuroniumromide (0.1 mg/kg). Anesthesia was maintained with
entanyl, propofol (2 to 3 mg/kg), and low concentrationsf sevoflurane as necessary. Anticoagulation waschieved with heparin (1 mg/kg) after the conduits werearvested. The activated clotting time was maintained at50 seconds or greater. Heparin was reversed with pro-amine after completion of the anastomosis. Standardntraoperative monitoring techniques were used. Pulmo-ary artery flotation catheters were used routinely androvided continuous evaluation of cardiac output. Trans-sophageal echocardiography was used routinely.All procedures were performed through a median
ternotomy. The conduits (one or both internal thoracicrteries, the right gastroepiploic artery, and saphenousein) were harvested and skeletonized. We used bilateralnternal thoracic arteries routinely for two-vessel orhree-vessel disease patients who required grafting to theeft anterior descending artery and circumflex artery. Aommon combination for internal thoracic artery graftlacement was in situ grafting of the left internal thoracic
Abbreviations and Acronyms
BITA � bilateral internal thoracic arteriesCABG � coronary artery bypass graftingCHF � congestive heart failureCOPD � chronic obstructive pulmonary diseaseCre � serum creatinineCRF � chronic renal failureGEA � gastroepiploic arteryIABP � intraaortic balloon pumpICU � intensive care unitLMCA � left main coronary arteryLVEF � left ventricular ejection fractionNYHA � New York Heart AssociationOPCAB � off-pump coronary artery bypass
graftingPCI � percutaneous coronary interventionSD � standard deviation
rtery to the circumflex area and the right internal p
horacic artery to the left anterior descending area. Welso aggressively used the skeletonized right gastroepip-oic artery to reconstruct the distal right coronary arterys an in situ graft. We used a suction-type mechanicaltabilizer (Octopus 4.3; Medtronic, Minneapolis, MN) tommobilize the target coronary artery, but did not useeart positioning. An intracoronary shunt tube and car-on dioxide blower were used routinely. The distalnastomosis was constructed with 7-0 polypropylenesing a standard technique. A red blood cell savingevice was used in all cases.
tatistical Analysisata are presented as the mean � standard deviation.ategoric variables were analyzed using the �2 or Fish-r’s exact test. Continuous variables were examinedsing the t test or the Mann-Whitney U test.We have calculated a propensity score for LMCA
isease to get one-to-one match pairs with similar clinicalharacteristics. Logistic regression with backward selec-ion was performed to calculate the propensity score. The
statistic was calculated to assess the discriminatorybility of the model. Each patient with LMCA diseaseas then matched to one patient without LMCA diseasesing propensity scores identical to within 3%.Univariate and multivariate Cox proportional hazard
egression analyses were performed for the analysis ofate mortality and cardiac event. The multivariate analy-es were performed with a stepwise forward regressionodel in which each variable with a probability value of
ess than 0.20 in the univariate analysis was entered inhe model. Actuarial survival and event-free survivalurves were estimated using the Kaplan-Meier methodomparing differences between groups with the log-rankest. Calculated p values of less than 0.05 were consideredignificant. Data were analyzed using SPSS 11.5.1 (SPSSnc, Chicago, IL) for Windows (Microsoft Corp, Red-
ond, WA).
esults
he preoperative characteristics of the patients are sum-arized in Table 1. Preoperative patient comorbidities
nd cardiac characteristics were equally distributed inhe two matched groups. The discriminatory ability of theogistic model as measured by C statistic was 0.63 (p �.001) and the Hosmer-Lemeshow goodness-of-fit testas not statistically significant (p � 0.83), indicating goodiscriminative power and acceptable calibration of theodel, respectively.
hort-Term Resultsutcome after surgery is shown in Table 2. There wereo significant differences in the number of grafts peratient (3.34 � 1.0 vs 3.41 � 1.2; p � 0.22) or the rate ofchievement of complete revascularization (97% vs 98%;� 0.10). Bilateral internal thoracic artery use was higher
n the LMCA group (69% vs 56%; p � 0.01). The rates ofll arterial revascularization (60% vs 59%) and gastroepi-
loic artery use (39% vs 45%; p � 0.19) were equally
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1503Ann Thorac Surg SUZUKI ET AL2010;90:1501–6 OFF-PUMP CORONARY SURGERY FOR LMCA DISEASE
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istributed in the two groups. There was no significantifference in other morbidities: perioperative myocardial
nfarction (0.4% vs 0.8%), bleeding reoperation (2% vs%), cerebrovascular accident (0.4% vs 0.4%), acute renalailure (3% vs 2%), prolonged ventilator support forespiratory insufficiency (�24 hours) (3% vs 3%), andeep sternal infection (1.2% vs 0.4%). Two patients in theMCA group (2 of 237; 0.8%) died: one of low outputyndrome and one of multisystem organ failure. Fouratients in the non-LMCA group (4 of 237; 1.7%) died:
wo of ruptures of abdominal aortic aneurysms, one ofupture of a descending thoracic aortic aneurysm, andne of superior mesenteric artery thrombus.
ong-Term Resultsollow-up was completed in 96.2% (456 of 474) of theatients. The mean follow-up duration was 3.9 � 1.4ears. Six-year freedom from death from all causes was7.3% in the LMCA group and 60.7% in the non-LMCAroup (p � 0.17); the rates of freedom from the combinedndpoint of cardiac death, myocardial infarction, anginaectoris, repeat coronary intervention, and heart failureequiring treatment were 80.4% in the LMCA group and0.4% in the non-LMCA group (p � 0.98) (Figs 1; 2).ultivariate Cox proportional hazards regression analy-
is showed independent predictor of long-term cardiacvents (cardiac death, myocardial infarction, angina pec-oris, repeat coronary intervention, and heart failure) washronic renal failure (hazard ratio � 0.3, 95% confidence
able 1. Preoperative Patient Characteristics in Propensity-atched Groups
haracteristicsLMCA non-LMCA p
Value(n � 237) (n � 237)
ge (mean � SD) 68.9 � 9.2 67.8 � 10.5 0.07emale gender 38 (16%) 50 (21%) 0.28moking history 131 (55%) 128 (54%) 0.78ypertension 165 (70%) 177 (75%) 0.22yperlipidemia 123 (52%) 118 (50%) 0.65iabetes mellitus 106 (45%) 108 (46%) 0.85
nsulin-dependent 31 (13%) 40 (17%) 0.25OPD 39 (17%) 40 (17%) 0.90eripheral arterial disease 22 (9%) 24 (10%) 0.76revious stroke 27 (11%) 38 (16%) 0.14hronic renal failure(Cre �1.5)
41 (17%) 40 (17%) 0.90
emodialysis 22 (9%) 23 (10%) 0.88ongestive heart failure 30 (13%) 36 (15%) 0.78hree-vessel disease 158 (67%) 159 (67%) 0.92revious myocardialinfarction
97 (41%) 97 (41%) 1.0
VEF �0.40 27 (11%) 32 (14%) 0.49revious PCI 74 (31%) 67 (28%) 0.48mergency 61 (26%) 61 (26%) 1.0
OPD � chronic obstructive pulmonary disease; Cre � serum creat-nine; LMCA � left main coronary artery; LVEF � left ventricularjection fraction; PCI � percutaneous coronary intervention; SD �tandard deviation.
nterval � 0.2 to 0.6, p � 0.001) (Table 3).au
omment
ast studies comparing medical therapy alone with sur-ical revascularization document a significant survivalenefit for patients with critical left main coronary arteryisease who undergo surgery [1–3, 13, 14]. Even now,ABG is recommended for patients with critical LMCA
tenosis [15, 16]. However, significant LMCA stenosis haseen regarded as a risk factor for patients undergoingABG [5, 6]. Although these patients are high risk, the
ong-term prognosis is improved by CABG comparedith medical therapy alone.Following the development of technology, pioneering
ardiologists have recently performed percutaneous cor-nary intervention in patients with LMCA disease andeported good results compared with CABG [17–21].owever, the use of percutaneous coronary intervention
or these patients is still controversial and requires addi-ional supporting evidence.
Numerous studies [5, 6] have identified the presence ofMCA disease as an independent predictor of postoper-tive morbidity and mortality in patients undergoingABG. Such reports were based upon data presented in
he 1970s to 1990s, when the techniques of surgery,nesthesia, and medical management were less ad-anced than now. During the last two decades, thereave been major improvements in almost all fields relat-
ng to the perioperative management of patients under-oing CABG. Coronary artery bypass grafting has alsorogressed thanks to better management, with options
ncluding more frequent use of arterial graft, more use ofnternal thoracic arteries, and improved techniques inff-pump surgery.
able 2. Operative and Postoperative Data
ariablesLMCA non-LMCA p
Value(n � 237) (n � 237)
ABP use 29 (12%) 31 (13%) 0.78o. distal anastomoses 3.34 � 23.0 3.41 � 22.2 0.22omplete revascularization 239 (97%) 233 (98%) 0.21ITA use 164 (69%) 132 (56%) 0.002EA use 92 (39%) 106 (45%) 0.19ll arterial reconstruction 142 (60%) 140 (59%) 0.85rolonged ventilation (�24hours)
6 (3%) 7 (3%) 0.78
CU stay (hours) 22.1 � 23.3 22.2 � 22.8 0.78eoperation for bleeding 5 (2%) 5 (2%) 1.0eep sternal infection 2 (0.8%) 1 (0.4%) 0.62ermanent stroke 1 (0.4%) 1 (0.4%) 1.0erioperative myocardialinfarction
1 (0.4%) 2 (0.8%) 0.62
trial fibrillation 49 (21%) 50 (21%) 0.91enal failure requiringdialysis
6 (3%) 5 (2%) 0.76
ortality (30 days) 2 (0.8%) 4 (2%) 0.45
ITA � bilateral internal thoracic arteries; GEA � gastroepiploic
rtery; IABP � intraaortic balloon pump; ICU � intensive carenit; LMCA � left main coronary artery.
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1504 SUZUKI ET AL Ann Thorac SurgOFF-PUMP CORONARY SURGERY FOR LMCA DISEASE 2010;90:1501–6A
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There have been many recent reports of completeevascularization achieved safely through OPCAB withxcellent early-stage clinical outcomes, superior or equalo those of conventional CABG with cardiopulmonaryypass. However, there are still some patients who can-ot be treated with OPCAB, such as those with a severeisk factor. While OPCAB for patients with LMCA steno-is remains challenging [4], a number of recent reportsave indicated the safety and efficacy of the technique inMCA stenosis patients [7–10]. Yeatman and colleagues
9] reported the safety and efficacy of OPCAB for criticalMCA disease in a comparison of 75 OPCAB cases and12 conventional CABG procedures. Lu and colleagues10] also evaluated OPCAB surgery in a comparison ofn-pump surgery using a risk-adjusted model. In ourPCAB series, the number of distal anastomoses per
ig 1. Six-year actuarial freedom from deathf any cause after off-pump coronary surgeryccording to LMCA (black line) or non-MCA (grey line). (LMCA � left main coro-ary artery.)
ig 2. Six-year actuarial freedom from anyardiac event (cardiac death, myocardial in-arction, angina pectoris, coronary reinterven-ion, and heart failure) according to LMCAblack line) or non-LMCA (grey line).LMCA � left main coronary artery.)
atient was 3.34 in the LMCA group and 3.41 in theon-LMCA group, with complete revascularizationchieved in 96.6% and 98.3%, respectively. There werehus no significant differences between the two groups.o patient in either group was converted from off-pump
o on-pump. Operative mortality was 0.8% in the LMCAroup and 1.7% in the non-LMCA group and postoper-tive morbidity was equally frequent in the two groupsith no significant differences. These early-stage resultsf the study also indicated the feasibility and effective-ess of the OPCAB approach for patients with significantMCA disease.In contrast to previous studies, Cosgrove and col-
eagues [11] report that LMCA disease is not an indepen-ent risk factor for operative mortality after CABG. Since
heir report, several studies [11, 12, 22] have recorded
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qual early-stage survival in patients with LMCA steno-is compared with other patients and similar long-termurvival after CABG. Jönsson and colleagues [22] dem-nstrated an improvement in surgical results over threeecades (1970s to 1990) and the neutralization of LMCAtenosis as a risk factor for both early and late deathuring the 1990s. Indeed, there was a pronounced de-rease over time in the risk of both early and late death inatients with LMCA undergoing CABG. Contributory to
his improvement were technical advances in surgery,nesthesia, and intensive care management. Improve-ent in medical management, including the use of
tatins, an effective antithrombotic drug, and �-blocker,as also a factor.Patients with LMCA stenosis have been recognized as
able 3. Univariate and Multivariate Cox Proportionalazard Regression Analyses of Late Cardiac Events (Cardiaceath, Myocardial Infarction, Angina Pectoris, Repeatoronary Intervention, and Heart Failure)
ariableHazardRatio
95%Confidence
Intervalp
Value
nivariate model:Age 0.7 0.4–1.3 0.26Female gender 0.7 0.4–1.6 0.45Smoking history 1.3 0.7–2.2 0.37Hypertension 1.6 0.8–3.2 0.15Hyperlipidemia 0.7 0.4–1.1 0.13Diabetes mellitus 0.8 0.5–1.4 0.39Insulin dependent 0.7 0.3–1.7 0.44COPD 1.3 0.7–2.6 0.46Peripheral arterial disease 1.5 0.7–3.4 0.31Previous stroke 1.5 0.7–3.1 0.27Chronic renal failure
(Cre �1.5)2.6 1.4–4.8 �0.01
LMCA 0.7 0.4–1.3 0.27Congestive heart failure 1.5 0.7–3.0 0.29Three-vessel disease 0.8 0.4–1.3 0.36Previous myocardial infarction 0.9 0.5–1.5 0.66LVEF �0.40 1.2 0.5–2.5 0.72Previous PCI 1.2 0.7–2.2 0.52Emergency 0.9 0.5–1.8 0.89IABP use 1.5 0.7–3.1 0.32Complete revascularization 0.3 0.1–0.9 0.03BITA use 0.9 0.6–1.7 0.81Atrial fibrillation 1.4 0.8–2.7 0.25ultivariate model:Chronic renal failure 0.3 0.2–0.6 �0.001Hypertension NSHyperlipidemia NSComplete revascularization NS
ITA � bilateral internal thoracic arteries; COPD � chronic obstruc-ive pulmonary disease; Cre � serum creatinine; IABP � intraaor-ic balloon pump; LMCA � left main coronary artery; LVEF � leftentricular ejection fraction; NS � not significant; PCI � percuta-eous coronary intervention.
aving a poorer prognosis after CABG than those with-
ut. The present study showed a 6-year survival rate forll causes of death: 87.3% in the LMCA group and 60.7%n the non-LMCA group with no significant difference.reedom from any cardiac event (cardiac death, myocar-ial infarction, angina pectoris, percutaneous coronary
ntervention, cardiac failure) was 80.4% in the LMCAroup and 70.4% in the non-LMCA group. We found noignificant difference in long-term clinical outcome be-ween the two groups. In the present study, LMCAtenosis was thus not recognized as a risk factor afterABG in either short-term or long-term outcomes.A limitation of the present study is that it is non-
andomized and is a retrospective study comparing out-ome in patients with and without LMCA disease under-oing OPCAB. Our study population was small, resulting
n insufficient statistical power. However, all of the pro-edures were consecutive and conducted within a singlenstitute by a single surgeon. Additionally, comparison ofreoperative demographic and risk factors demonstrated
hat the two cohorts were well-matched. We concludedhat OPCAB is feasible and safe in patients with criticalMCA stenosis and that LMCA disease is not a risk factorfter OPCAB surgery in either the short- or long-term.
eferences
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1. Takagi T, Stankovic G, Finci L, et al. Results and long-termpredictors of adverse clinical events after elective percuta-neous interventions on unprotected left main coronary ar-tery. Circulation 2002;106:698–702.
2. Jönsson A, Hammar N, Nordquist T, Ivert T. Left main coro-nary artery stenosis no longer a risk factor for early and latedeath after coronary artery bypass surgery- an experience
covering three decades. Eur J Cardiothorac Surg 2006;30:311–7.NVITED COMMENTARY
uzuki and colleagues [1] provide early and late clinicalutcomes after off-pump coronary artery bypass graftingOPCAB) in patients with left main coronary arteryLMCA) stenosis. The LMCA stenosis has been identifieds a risk factor for mortality among patients undergoingoronary artery bypass grafting and also as a well-stablished risk factor for cardiac-related adverse events.he authors conclude that LMCA stenosis is not a risk
actor in early outcomes after OPCAB or late outcomesfter surgical revascularization when compared withhose outcomes in patients without LMCA stenosis. Al-hough the presence of critical LMCA stenosis ofteneters a surgeon from performing OPCAB, continuously
mproving surgical techniques and well-established in-raoperative strategies have demonstrated the feasibilityf complete revascularization and safety in OPCAB.Intra-aortic balloon pump (IABP) therapy is an effec-
ive tool in OPCAB patient with a high-risk factor, such asignificant LMCA stenosis; however, the incidence ofABP therapy was relatively high in the present study,onsidering the invasiveness of IABP therapy. A greaterumber of patients in the LMCA group received bilateral
nternal thoracic artery grafts, which might affect lateutcomes after surgery. The authors showed univariatend multivariate analyses of late cardiac events; however,he data showing cardiac deaths, myocardial infarction,ngina pectoris, repeat coronary intervention, and heartailure were not presented in detail in the article. The
hen attempting to draw long-term outcomes. Althoughropensity score matching was performed to correct theffect of nonrandomization of this retrospective studynd selection bias, the c-statistic of 0.63 is lower thansually expected. The McNemar test and paired t-test areenerally recommended when comparing matched data.n addition, multivariate regression analysis showed thathe hazard ratio of chronic renal failure was 0.3 (95%onfidence interval, 0.2 to 0.3), which suggested a protec-ive effect from long-term cardiac events rather than aisk factor.
Despite several limitations in this article, I agree withhe authors’ conclusion, based on my experience, thatPCAB is feasible and safe in patients with significantMCA stenosis.
i-Bong Kim, MD, PhD
epartment of Thoracic and Cardiovascular Surgeryeoul National University Hospital8, Yeongeon-dong, Jongno-gueoul, 110-744, Korea-mail: [email protected]
eference
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