Off-Pump Multivessel Coronary Artery Surgery inHigh-Risk PatientsZile Singh Meharwal, MCh, Yugal K. Mishra, PhD, Vijay Kohli, MCh,Ramesh Bapna, MCh, Sandeep Singh, MCh, and Naresh Trehan, MDDepartment of Cardiovascular Surgery, Escorts Heart Institute and Research Centre, New Delhi, India

Background. Coronary artery bypass surgery on cardio-pulmonary bypass is associated with significant morbid-ity and mortality, which may be more marked in high-risk patients. We evaluated our results of off-pumpcoronary artery bypass (OPCAB) in high-risk patientswith multivessel coronary artery disease and comparedthem with results in similar patients who underwentoperation on cardiopulmonary bypass.

Methods. A total of 1,075 patients who underwentOPCAB between October 1996 and June 2001 and whohad one or more of the following risk factors wereincluded in the study: poor left ventricular function (EF<30%), advanced age (>70 years), left main stenosis,acute myocardial infarction, and redo coronary arterysurgery. These patients were compared with 2,312 similarpatients who underwent coronary artery bypass graftingon cardiopulmonary bypass during the same period.Preoperative risk factors, intraoperative variables, andpostoperative results were analyzed and compared be-tween two groups.

Results. The average number of grafts was 3.0 � 0.4

and 3.2 � 0.3 in the off-pump (OPCAB) and on-pump(CCAB) groups, respectively. Hospital mortality was3.2% and 4.5% in OPCAB and CCAB groups respectively(p � 0.109). Perioperative myocardial infarction, require-ment of inotropic agents, stroke, and renal dysfunctionwere comparable in two groups. Intubation time (19 � 5vs 24 � 6 hours, p < 0.001), mean blood loss (362 � 53 vs580 � 66 mL, p < 0.001), atrial fibrillation (14.3 vs 19.7%,p < 0.001), and prolonged ventilation (4.6 vs 7.6%, p �0.002) were less in OPCAB group. Intensive care unit stay(20 � 8 hours) and hospital stay (6 � 3 days) weresignificantly less in the OPCAB group (p < 0.001).

Conclusions. Off-pump coronary artery surgery can besafely performed in high-risk patients with multivesselcoronary artery disease. Operative mortality is compara-ble to that associated with on-pump surgery, and avoid-ance of cardiopulmonary bypass is associated with re-duced postoperative morbidity in these patients.

(Ann Thorac Surg 2002;74:S1353–7)© 2002 by The Society of Thoracic Surgeons

Previous reports have demonstrated that advancedage, reoperative coronary artery bypass grafting

(CABG), and severe left ventricular dysfunction are themost important independent predictors of operativemortality after CABG [1, 2]. Cardiopulmonary bypass(CPB) is associated with diffuse systemic inflammatoryresponses during and after cardiac surgery [3, 4] and maycontribute to the morbidity associated with CABG [5].Off-pump coronary artery bypass grafting (OPCAB) hasemerged as an alternative technique allowing coronaryrevascularization without the risk associated with CPB[6]. The OPCAB approach has been shown to reduce theoverall systemic inflammatory response, including cyto-kine-mediated response [7, 8]. It also avoids physiologicderangement to the heart caused by cardioplegic arrestas shown by reduced troponin T release [7, 9]. Recentdevelopment of various tools and techniques, includingseveral stabilizers and intracoronary shunts, have madeOPCAB a safe procedure that is now being used for

treating multivessel coronary artery disease, even inpatients who are at high risk.

In this study, we analyzed our results of OPCAB inhigh-risk patients and compared them with results ofCABG on-pump (ie, conventional CABG) in a similargroup of patients.

Material and Methods

Data were prospectively collected on patients who wereundergoing off-pump coronary artery bypass surgery(OPCAB group) and who had one or more of the follow-ing risks factors: age greater than 70 years, poor leftventricular ejection fraction (EF �30%), significant leftmain coronary artery stenosis (�70%), redo surgery, andacute myocardial infarction operated within 48 hours.The decision for a patient to undergo operation on pumpor off pump was made by the operating surgeon. Allsurgeons in the department perform off-pump and on-pump procedures with nearly equal distribution. Preop-erative risk factors, intraoperative variables, and postop-erative results were analyzed and compared with thosefor patients with similar risk factors who were undergo-ing conventional coronary artery bypass (ie, CABG on

Presented at the Eighth Annual Cardiothoracic Techniques and Technol-ogies Meeting 2002, Miami Beach, FL, Jan 23–26, 2002.

Address reprint requests to Dr Meharwal, Senior Consultant CardiacSurgeon, Escorts Heart Institute and Research Centre, Okhla Road, NewDelhi 110, India; e-mail: meharwal@hotmail.com.

© 2002 by The Society of Thoracic Surgeons 0003-4975/02/$22.00Published by Elsevier Science Inc PII S0003-4975(02)03915-2

cardiopulmonary bypass; CCAB group) during the sameperiod.

Anesthetic and Anticoagulation ProtocolPatients were premedicated using morphine (0.1 mg/kg)and lorazepam (2 to 4 mg). Induction of anesthesia wasachieved with midazolam (15 to 20 �g/kg) and fentanyl(10 to 100 �g/kg). Muscle relaxation was achieved withvacuronium bromide (0.10 to 15 mg/kg). Anesthesia wasmaintained with oxygen, air, and incremental doses ofmidazolam and fentanyl. Heparin was injected in a doseof 2 mg/kg in patients who underwent operation withoutCPB and 3 mg/kg in patients with CPB. Activated clottingtime was measured initially and then every 30 minutes; itwas maintained for more than 300 seconds in patientswho underwent surgery off pump and more than 400seconds in those who had their surgery on pump. Prota-mine sulfate was used in 1:1 ratio to reverse the heparineffect after the procedure.

A femoral arterial line was used for insertion of anintraaortic balloon pump if a patient became unstableduring induction of anesthesia or at a later stage beforerevascularization

Hemodynamic MonitoringHemodynamic monitoring comprised of six-channelelectrocardiography with ST-segment trend analysis, ra-dial arterial pressure, and pulmonary artery measure-ments. Recorded variables were mean arterial pressure,central venous pressure, mean pulmonary pressure, pul-monary capillary wedge pressure, cardiac index, strokevolume, and systemic vascular resistance. Oxygen satu-ration was continuously monitored with a pulse oxime-ter. Arterial blood gases and activated clotting time ACTwere monitored every 30 minutes. Intraoperative trans-esophageal echocardiographic monitoring was done us-ing a multiplane transducer and Sonos 5500 imagingsystem (Hewlett Packard, Andover, MA). Variables mon-itored included: regional wall motion abnormalities,changes in global and regional LV function, LV filling,right atrial filling, mitral regurgitation, and right ventric-ular outflow tract obstruction.

Surgical Technique for Off-Pump Coronary ArteryBypass SurgeryAll patients underwent operation through a mediansternotomy. The left internal mammary artery (LIMA)was harvested by standard technique using hemoclips.The other conduits (saphenous veins and radial artery)were harvested simultaneously. Octopus 2, Octopus 2�,and Octopus 3 (Octopus tissue stabilization system,Medtronic Inc, Minneapolis, MN) or CTS MIDCAB ac-cess platform and stabilizer (Cardiothoracic Systems,Cupertino, CA) were used to stabilize the target coronaryvessel. Intracoronary shunts (Baxter AnastaFLO Intravas-cular shunt, Irvine, CA) were used for most of theanastomosis.

In most cases, the left anterior descending coronaryartery was the first coronary artery to be grafted in mostcases. The right coronary artery was normally the second

artery, which was grafted. The vessels on the lateral andposterior wall were grafted last. However, the sequenceof grafting was individualized for a particular patient,depending on the severity of the lesions in differentcoronary arteries and patient’s hemodynamics. Both theleft anterior descending and right coronary arteries couldbe grafted without much displacement of the heart. Forexposure of the circumflex vessels, three pericardialtraction sutures were used to pull the heart vertically.The right pleura was opened wide and a vertical pericar-diotomy was performed to herniate the heart to the rightchest under the sternum. Other maneuvers such as theTrendlenberg position and tilting the table were per-formed as required. Inotropic agents were used as andwhen necessary during surgery. The distal anastomosiswas performed using 7-0 or 8-0 Prolene (Du Pont Phar-maceuticals, Wilmington, DE) suture.

Proximal anastomosis was performed using standardtechniques. The aorta was palpated before applyingpartial occlusion clamp for proximal anastomosis. Intra-operative transesophageal echocardiography was used toassess arteriosclerosis of the aorta. Recently we have alsostarted using epi-aortic scanning to assess the proximalaorta. If there was any evidence of significant aorticarteriosclerosis, clamping of the aorta was avoided andproximal anastomosis was performed to the LIMA pedi-cle. The proximal anastomosis was performed using 6-0Prolene suture.

Surgical Technique for On-Pump Coronary ArteryBypass SurgeryConventional coronary artery bypass procedures wereperformed using standard CPB, which was establishedusing ascending aortic and two-stage venous cannula-tion. The LIMA, radial artery, and saphenous veins wereharvested by standard techniques. The patient was notactively cooled but temperature was allowed to drift.Antegrade or combination of antegrade and retrogradewarm blood cardioplegia was used for myocardial pro-tection. Cardioplegia was repeated after every distalanastomosis. A total of 76 patients (3.3%) underwentoperation on CPB without arresting the heart (ie, with anempty beating heart). Hemodynamic monitoring wasperformed using a Swan-Ganz catheter (Edwards Life-sciences LLC, Irvine, CA) and transesophageal echocar-diography as in patients undergoing operation withoutCPB.

Study DefinitionsPerioperative MI was defined as development of new Qwaves on postoperative electrocardiography or loss of Rwave progression, new left bundle branch block, or newST and T wave changes in association with an increase increatine kinase (CK) level of more than 40 U/L or CK-MB/CK ratio of more than 5%. Blood loss was defined astotal chest tube drainage until chest tubes were removed.Prolonged ventilation was defined as ventilation for morethan 48 hours. Mediastinisis was defined as mediastinalcollection with positive culture. Acute renal failure wasdefined as requirement of peritoneal or hemodialysis.

S1354 CTT SUPPLEMENT MEHARWAL ET AL Ann Thorac SurgOPCAB IN HIGH-RISK PATIENTS 2002;74:S1353–7

Total operative time was defined as time from skinincision to closure of skin.

Urgent surgery was defined as surgery within 24 hoursof angiography. Surgery was considered as emergencysurgery when the patient was shifted directly to theoperating theater from the catheterization laboratory orthe surgery was required within a few hours of admissionor of performing angiography.

Statistical AnalysisData are reported as mean � SD. The �2 and Fisher’sexact tests were used to compare categorical variables.Unpaired Student’s t test was used to compare inter-group means. Intensive care unit and hospital stay arepresented as medians, with the Wilcoxon test used forcomparing the data in two groups. A p value of less than0.05 was accepted as significant. Variables that were notnormally distributed were compared using the Mann-Whitney test.

Results

Between October 1996 and June 2001, a total of 11,591patients underwent isolated CABG at our institute. Outof these, 3,387 patients had one or more of the risk factorsmentioned earlier. Of these patients in high-risk groups,a total of 1,075 underwent operation without CPB and

2,312 with CPB. The preoperative variables of the pa-tients are shown in Table 1. Patients in the OPCAB groupwere significantly older than those in the CCAB group,and there were more women in the OPCAB group.Incidence of left main stenosis was greater in the CCABthan in the OPCAB group. The other risk factors werecomparable in two groups except that there were moreredo operations and more patients with aortic arterio-sclerosis in the OPCAB group. The mean Parsonnet scorewas higher in the OPCAB group.

The results of coronary angiography are shown inTable 2. The severity of coronary artery disease wascomparable in the two groups. Most patients (96.4% inthe OPCAB and 96.9% in the CCAB group) had double-vessel or triple-vessel disease. There were significantlymore patients in the CCAB group with left main stenosis.Ventricular function was comparable in the two groups.

The LIMA was used in 94.8% and 93.7% patients in theOPCAB and CCAB groups, respectively (Table 3). Only30.7% patients in the OPCAB and 28.7% patients in theCCAB group received radial artery grafts, because wetend not to use radial artery in elderly patients and forcoronary arteries, which do not have critical stenosis.

Table 1. Demographic Profile

Variable

OPCABGroup

(n � 1075)

CCABGroup

(n � 2312) p Value

Age (y) 63.9 � 11.0 60.3 � 9.9 �0.001Age �70 years (%) 398 (37.0) 689 (29.8) �0.001Male (%) 949 (88.3) 2106 (91.1) 0.012Female (%) 126 (11.7) 206 (8.9) 0.012NIDDM (%) 220 (20.5) 504 (21.8) 0.403IDDM (%) 30 (2.8) 48 (2.1) 0.243Hypertension (%) 435 (40.5) 946 (40.9) 0.832Smoker (%) 263 (24.5) 583 (25.2) 0.669COPD (%) 87 (8.1) 190 (8.2) 0.995History of CVA (%) 33 (3.1) 62 (2.7) 0.660Acute MI (%) 20 (1.9) 60 (2.6) 0.234NYHA class III or IV (%) 521 (48.5) 1080 (46.7) 0.360PVD (%) 83 (7.7) 187 (8.1) 0.759Obesity (%) 134 (12.5) 273 (11.8) 0.624Unstable angina (%) 398 (37.0) 846 (36.6) 0.838Redo CABG (%) 104 (9.7) 155 (6.7) 0.003Urgent surgery (%) 96 (8.9) 192 (8.3) 0.588Preoperative IABP (%) 89 (8.3) 176 (7.6) 0.546CHF (%) 115 (10.7) 222 (9.6) 0.352Aortic atherosclerosis (%) 138 (12.8) 150 (6.5) �0.001Parsonnet score 8.4 � 2.8 7.3 � 2.5 �0.001

CABG � coronary artery bypass grafting; CCAB � conventionalcoronary artery bypass; CHF � congestive heart failure; COPD �chronic obstructive pulmonary disease; CVA � cerebrovascular acci-dent; IABP � intra aortic balloon pump; IDDM � insulin-dependent diabetes mellitus; NIDDM � non–insulin-dependent dia-betes mellitus; NYHA � New York Heart Association; OPCAB �off-pump coronary artery bypass; PVD � peripheral vascular disease.

Table 2. Coronary Angiography Findings

Variable

OPCABGroup

(n � 1075)

CCABGroup

(n � 2312) p Value

Single-vessel disease (%) 38 (3.5) 72 (3.1) 0.560Double-vessel disease (%) 240 (22.3) 502 (21.7) 0.721Triple-vessel disease (%) 797 (74.1) 1738 (75.2) 0.546Left main stenosis (%) 242 (22.5) 700 (30.3) �0.001LVEF

�50% 224 (20.8) 476 (20.6) 0.90441–50% 207 (19.3) 400 (17.3) 0.18331–40% 156 (14.5) 347 (15.0) 0.744�30% 488 (45.4) 1089 (47.1) 0.374

LVEF � left ventricular ejection fraction; other abbreviations as inTable 1.

Table 3. Intraoperative Variables

Variable

OPCABGroup

(n � 1075)

CCABGroup

(n � 2312) p Value

LIMA (%) 1019 (94.8) 2166 (93.7) 0.235Radial artery (%) 330 (30.7) 664 (28.7) 0.256No. of grafts 3.0 � 0.4 3.2 � 0.3 �0.001CPB time (min) . . . 84 � 12 . . .ACC time (min) . . . 36 � 7 . . .Total operating time (min) 176 � 41 242 � 47 �0.001CPB with ACC (%) . . . 2236 (96.7) . . .CBP without ACC (%) . . . 76 (3.3) . . .Intraoperative inotropes (%) 234 (21.8) 264 (11.4) �0.001Intraoperative IABP (%) 39 (3.6) 95 (4.1) 0.566

A C C � a o r t i c c r o s s c l a m p ; C P B � c a r d i o p u l m o n a r ybypass; LIMA � left internal mammary artery; other abbrevia-tions as in Table 1.

S1355Ann Thorac Surg CTT SUPPLEMENT MEHARWAL ET AL2002;74:S1353–7 OPCAB IN HIGH-RISK PATIENTS

Patients in the CCAB group received more grafts than theOPCAB group. Intraoperatively, more patients in theOPCAB group required inotropic agents than those inthe CCAB group. Total operating time was significantlyless in the OPCAB group.

Table 4 shows postoperative outcome data for the twogroups of patients. Hospital mortality was 3.3% (35/1,075)and 4.5% (104/2,312) in the OPCAB and CCAB groups,respectively (p � 0.124). When the different subgroupswere compared separately, the mortality was not signif-icantly different in the two groups (Table 5). The inci-dence of postoperative MI, stroke, renal dysfunction,pulmonary infection, and sternal infection were compa-rable between the two groups (Table 4). The intubationtime, blood loss, number of patients requiring blood andblood products, reoperation for bleeding and atrial fibril-lation were significantly less in the OPCAB group. Thenumber of patients who required intraaortic balloonpump postoperatively was also less in the OPCAB group.The mean intensive care unit and hospital stays weresignificantly less in the OPCAB group.

Comment

Off-pump coronary artery surgery has been shown to bea feasible, safe alternative to on-pump coronary arterysurgery. Complete revascularization can now be accom-plished in the majority of patients with excellent short-term results [10, 11]. This technique is now being used forhigh-risk patients including patients with poor ventricu-lar function, advanced age, renal dysfunction, and previ-ous history of stroke; morbidity and mortality have beenreported to be lower than in patients undergoing opera-tion on CPB [12, 13].

In our study, the mortality of OPCAB was comparableto that of CCAB patients, although there were moreelderly patients in the OPCAB group and there weremore redo operations in this group. The mean Parsonnetscore was also higher in the OPCAB than in the CCABgroup. When compared between different subgroups, themortality was not statistically significantly different.

Perioperative morbidity and mortality rates rise withincreasing age in patients undergoing CABG [14]. TheOPCAB approach has been shown to reduce periopera-tive complications and resource use in elderly patients[13]. The incidence of postoperative complications wasless in the OPCAB than in the CCAB group in our studyalso. The stroke rate in our study was comparable in thetwo groups, though there were more elderly patients inthe OPCAB than in the CCAB group, and more patientsin the OPCAB group (12.8%) had arteriosclerosis of theaorta than those in the CCAB group. Ricci and colleagues[15] have also shown reduced incidence of stroke inoctogenarians undergoing OPCAB. A possible mecha-nism may be the significantly higher rate of arterioscle-rosis of the ascending aorta in octogenarians, which maypotentiate migration of atheromatous microemboli to thebrain during aortic cannulation and result in neurologicinjury after on-pump CABG.

Patients with left main stenosis have been consideredto be a relative contraindication to OPCAB surgery.However, with the development of exposure and stabili-zation techniques and the introduction of intracoronaryshunts, even patients with critical left main disease canundergo off-pump surgery with good results, as recentlyreported by us [16] and by Yeatman and colleagues [17].

Other groups of patients who are at high risk withregard to surgery are those with severely impaired LVfunction. Most of these patients have a combination ofrisk factors, and expected mortality may reach 10% orhigher [18, 19]. In our study, mortality in patients withpoor LV function in the OPCAB group was comparable tothat in the CCAB group. Many studies [12, 20] havereported excellent results for CABG on the beating heartin this group of patients. The relatively low mortality andmorbidity observed after off-pump surgery in this groupof patients may be explained by the favorable effect of thebeating heart on the blood supply to the subendocar-dium [21], the reportedly better preservation of interven-tricular septal contractility after OPCAB [5, 22], and theavoidance of damaging effects of CPB and aorticcrossclamping.

Table 4. Postoperative Results

Variable

OPCABGroup

(n � 1075)

CCABGroup

(n � 2312) p Value

Intubation time (h) 19 � 5 24 � 6 �0.001Postoperative inotropes (%) 70 (6.5) 139 (6.0) 0.627Blood loss (mL) 362 � 53 580 � 66 �0.001Blood and blood product

transfusion (%)331 (30.8) 1047 (45.3) �0.001

Postoperative IABP (%) 14 (1.3) 76 (3.3) 0.001Perioperative MI (%) 18 (1.7) 42 (1.8) 0.879Reoperation for bleeding (%) 10 (0.9) 66 (2.9) �0.001Atrial fibrillation (%) 154 (14.3) 455 (19.7) �0.001Stroke (%) 6 (0.6) 25 (1.1) 0.196Prolonged ventilation (%) 50 (4.6) 176 (7.6) 0.002Renal dysfunction (%) 15 (1.4) 49 (2.1) 0.192ICU stay (h) 18 33 �0.001Pulmonary infection (%) 31 (2.9) 83 (3.6) 0.338Sternal infection (%) 12 (1.1) 32 (1.4) 0.633Operative mortality (%) 35 (3.3) 104 (4.5) 0.109Hospital stay (days) 6 8 �0.001

IABP � intra aortic balloon pump; ICU � intensive care unit; MI� myocardial infarction; other abbreviations as in Table 1.

Table 5. Mortality in Different Subgroups

Subgroup

OPCABGroup

Mortality

CCABGroup

Mortality p Value

Left main stenosis 4/242 (1.7%) 18/700 (2.6%) 0.570Redo surgery 4/104 (3.8%) 6/155 (4.1%) 0.750Ejection fraction �30% 20/448 (4.1%) 61/1089 (5.6%) 0.260Acute MI 1/20 (5.0%) 7/60 (11.7%) 0.672Age �70 years 9/398 (2.3%) 24/689 (3.5%) 0.343

MI � myocardial infarction; other abbreviations as in Table 1.

S1356 CTT SUPPLEMENT MEHARWAL ET AL Ann Thorac SurgOPCAB IN HIGH-RISK PATIENTS 2002;74:S1353–7

Exposure and stabilization of the vessels on the poste-rior and lateral walls present an occasional challenge inthese patients, especially in the presence of significantcardiomegaly. Deep pericardial sutures, deep verticalright pericardiotomy, and extensive right pleurotomyhelp in maintaining hemodynamic stability during anas-tomosis on these vessels in these patients.

Redo CABG has been reported to be associated withrelatively higher mortality and morbidity, and long CPBtime has been identified as the most powerful indepen-dent predictor of mortality after reoperative CABG [23].In this regard, avoidance of CPB may be considered avaluable alternative in these patients. The mortality ofredo surgery in our study was not significantly differentfrom that in the CCAB group.

Emergency CABG in patients with acute MI has poorresults because the ischemic myocardium cannot endurethe side effects of CPB and cardiac arrest; several authorshave reported a mortality of 20% to 30% in patientsundergoing conventional CABG with CPB [24]. The OP-CAB approach may be a viable alternative in thesepatients [25]. During off-pump coronary revasculariza-tion in these patients, myocardial perfusion starts as soonas first distal anastomosis has been completed. This helpsto stabilize the patient, and the other anastomosis can beperformed in a relatively stable patient. We did not findsignificant difference in mortality in the OPCAB andCCAB groups.

In conclusion, off-pump coronary artery bypass is asafe alternative to conventional CABG in high-risk pa-tients with multivessel coronary artery disease. Thistechnique significantly reduces postoperative morbidityin these patients. However, prospective randomizedstudies with long-term results comparing these two tech-niques are required.

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