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Original Article

Anaortic Techniques Reduce Neurological MorbidityAfter Off-Pump Coronary Artery Bypass SurgeryMichael P. Vallely, PhD, FRACS ∗, Kieron Potger, BSc, CCP, Darryl McMillan, CCP,

Jonathan M. Hemli, MB BS, MSc, Peter W. Brady, FRACS,R. John L. Brereton, FRACS, David Marshman, FRACS,Manu N. Mathur, FRACS and Donald E. Ross, FRACS

Department of Cardiothoracic Surgery, Royal North Shore Hospital, Sydney, NSW, Australia

Background: Stroke remains one of the most devastating complications of cardiac surgery. Advocates of off-pumpcoronary revascularisation (OPCAB) maintain that post-operative neurologic morbidity is reduced by avoiding aorticcannulation and cross-clamping, and by eliminating the systemic effects of cardiopulmonary bypass. We sought to deter-mine whether completing off-pump coronary surgery without any aortic manipulation (“anaortic” technique) affordedany additional neurological protection, as compared to off-pump grafting in which the aorta was utilised for graftinflow.

Methods: A comprehensive review of prospectively collected data was undertaken of all patients undergoing OPCAB inour institution between January 2002 and December 2006. Cases requiring intra-operative conversion to cardiopulmonarybtp

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ypass were excluded from further analysis. Patients having OPCAB surgery with aortic manipulation were comparedo those having OPCAB surgery without aortic manipulation. Multiple logistic regression was used to identify possibleredictors of post-operative neurologic morbidity, with particular focus on the role of aortic manipulation.Results: During the period of review, 1758 patients underwent OPCAB, of which 1201 (68.3%) were completed without

ortic manipulation, constituting the “anaortic” cohort. This group was compared with the remaining 557 patients, whichncluded fashioning at least one aorto-conduit anastomosis, utilising either a side-biting aortic clamp or a no-clamproximal anastomotic device. The two groups of patients were well-matched with respect to risk factors for adverseeurologic outcomes. Nine patients sustained focal neurological deficits (transient or permanent) in the peri-operativeeriod, constituting a stroke rate of 0.51% for the entire series. The incidence of peri-operative neurological deficit in thenaortic group was 0.25% compared with 1.1% in the aortic manipulation group (odds ratio (OR) 0.23, 95% confidencenterval (CI) 0.06–0.92, p = 0.037). Advanced age was also associated with peri-operative neurological injury (OR 1.1, 95%I 1.01–1.20, p = 0.017).Conclusions: Off-pump coronary artery surgery is associated with a low incidence of peri-operative stroke. Completing

he surgical procedure without manipulating the ascending aorta in any way (“anaortic” technique) offers additionaleurological protection and should be the goal in all suitable off-pump coronary cases.

(Heart, Lung and Circulation 2008;17:299–304)© 2007 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society of Australia and

New Zealand. Published by Elsevier Inc. All rights reserved.

eywords. CABG; OPCAB; Stroke

ackground

ff-pump coronary artery bypass surgery (OPCAB)is a well established technique for coronary revas-

ularisation, with at least equivalent, if not superioresults, when compared to coronary artery surgery utilis-ng cardiopulmonary bypass (CABG).1 OPCAB may havedditional benefits in sub-groups of patients who are con-

eceived 14 September 2007; accepted 21 November 2007;vailable online 21 February 2008

Corresponding author. Department of Cardiothoracic Surgery,oyal North Shore Hospital, St Leonards, NSW 2068, Australia.-mail address: michael.vallely@bigpond.com (M.P. Vallely).

sidered at higher risk of peri-operative neurological injury.These include patients 70 years of age or older, patientswith a history of cerebrovascular disease, those withperipheral vascular disease (including aortic atheroma),as well as those with diabetes mellitus and renal failure.2,3

These risk factors are not infrequently associatedwith increased atherosclerotic disease of the ascendingaorta.

Stroke after cardiac surgery is a devastating outcomefor the patient and their families. The economic cost tothe community is also very high.4 The incidence of strokewithin 30 days of on-pump coronary artery bypass surgery(CABG) is reported to be 2–4%.5–8 In a large multi-centreprospective study, Roach et al. reported a 3.1% incidence of

2007 Australasian Society of Cardiac and Thoracic Surgeons and the Cardiac Society ofustralia and New Zealand. Published by Elsevier Inc. All rights reserved.

1443-9506/04/$30.00doi:10.1016/j.hlc.2007.11.138

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Type I neurological injury after CABG. The hospital stay (25days versus 10 days) and in-hospital mortality (21% versus2%) was dramatically increased in this group of patients.4

Subtle neurocognitive impairment after coronarysurgery is believed to result from cerebral micro-emboliand the untoward effects of the non-physiologic flow ofcardiopulmonary bypass.9 It is well known that up to 50%of patients have demonstrable cognitive impairment afterCABG, which persists at up to six months in 25% of cases.5

It has been suggested that OPCAB could minimise thesepost-operative changes.10,11

Atherosclerosis of the ascending aorta is the single mostsignificant risk factor for stroke after cardiac surgery.3

Even more importantly, ascending aortic cannulation andclamping-related injuries lead to post-operative strokemore than other types of lesions.12 The incidence of post-operative stroke in patients with atherosclerotic ascendingaortas has been reported as 8.7%.8 Several authors havepublished data demonstrating dramatic reductions in therate of adverse neurological outcome in elderly patientsand in patients at higher risk of stroke using off-pumptechniques that avoid manipulation of the ascendingaorta.13–17

We have been performing off-pump coronary bypasssurgery at our institution since 1999. Several of the sur-geons in the unit have a special interest in off-pump orbeating-heart on-pump surgery, with a view to avoid-

Methods

Study DesignProspectively collected data of 1758 consecutive patients,who underwent isolated primary OPCAB between January2002 and December 2006, were reviewed. Of these, 1201(68.3%) underwent OPCAB without aortic manipulation(the “anaortic” group). The rest of the patient cohort (557patients) had proximal graft anastomoses fashioned to theascending aorta, utilising an aortic partial occlusion clamp(“side-biting” clamp), a commercially available proximalanastomotic device, or an in-house version of the “Vettathobturator” device. Pre-operative patient characteristics forthe off-pump cohort are summarised in Table 1.

Definition of TermsOperative mortality was defined as death within 30 days ofthe operation. Neurological complications were defined asa new global or focal neurological deficit that was evidentafter the operation and categorised as either permanent orreversible. Permanent stroke was defined as a new centralneurological deficit that persisted for more than 72 h. Atransient neurological deficit was defined as a new centralneurological deficit that had resolved completely within72 h. Chronic renal failure was defined as a documentedhistory of renal failure and/or fasting creatinine >2 mg/dL(%).

1201

cant.

ing and/or reducing aortic manipulation, with the aimof eliminating post-operative neurological injury. All ofthe surgeons perform off-pump surgery in cases consid-ered high-risk for neurological complications. Currently,50–60% of coronary bypass procedures are performed off-pump in our unit.

We present one of the largest series of prospectivelycollected data comparing patients having OPCAB surgerywith and without aortic manipulation (anaortic) and com-pare this to a contemporary cohort of patients undergoingCABG with cardiopulmonary bypass and cardioplegicarrest.

Table 1. Pre-operative Characteristics

Variable Anaortic Group n =

Age (years) mean 67.6Range 30.7–91.1Age ≥80 years (%) 11.6Euroscore (%) 4.2Female gender (%) 24.3Hypertension (%) 69.1Diabetes (%) 25.0Obese (BMI > 30) (%) 30.2Chronic renal failure (%) 4.7Chronic lung disease (%) 8.4MI (<90 days) (%) 28.3Left main stenosis (>50%) (%) 60.4Three-vessel disease (%) 37.3Ejection fraction <30% (%) 4.6Elective operation (%) 56.1Pre-operative IABP (%) 0.9Prior cerebrovascular disease (%) 13.5Carotid disease (>50% stenosis) (%) 6.3

Chi-square test and Student’s t-test. p < 0.05 considered statistically signifi

Surgical TechniqueChoice of surgical technique (on-pump, off-pump, or“anaortic” off-pump) was based on individual surgeonpreference. All surgeons routinely perform off-pumpCABG when the patients are deemed to be high-risk can-didates for adverse neurological events. Therefore, therewas a bias towards performing off-pump surgery in theolder and more high-risk patients.

All OPCAB procedures were performed via a mediansternotomy (or lower hemi-sternotomy). Anticoagulationwas achieved using intravenous heparin (200–300 U/kg).

Aortic Manipulation Group n = 557 p-Value

67.6 NS22.1–90.711.3 NS

4.2 NS28.2 NS67.1 NS23.2 NS25.2 0.04

4.3 NS9.5 NS

23.5 NS56.0 NS35.2 NS

4.3 NS56.2 NS

0.4 NS14.5 NS

6.3 NS

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2008;17:299–304 Anaortic techniques reduce neurological morbidity after OPCAB surgery

The activated clotting time (ACT) was maintained above300 s. Partial or complete reversal of the heparin with pro-tamine was at the discretion of the surgeon and was judgedclinically and by progress ACT.

The heart was stabilised using the Platypus (beating-heart.com) compression stabiliser or the Octopus suctionstabiliser (Medtronic®). Choice of stabiliser was individualsurgeon preference. Deep pericardial retraction sutureswere placed inferior to the left inferior pulmonary vein,and on the diaphragmatic surface adjacent to the infe-rior vena cava, to elevate and rotate the heart. The rightpleura was opened and right-sided pericardial incisionsdirected vertically towards the inferior vena cava, and (forone surgeon) the superior vena cava, to facilitate expo-sure of the lateral wall vessels whilst maintaining systemicvenous return. Silastic intracoronary shunts were usedroutinely by some surgeons and selectively by others.Silastic “snares” to encircle the target artery and provideproximal and/or distal control were used selectively.

In the anaortic group, graft inflow was establishedvia “T” grafts based on left internal mammary artery(LIMA) inflow (utilising the radial artery, the right inter-nal mammary artery (RIMA) or long saphenous vein), orvia composite grafts (RIMA – radial artery or saphenousvein extension grafts). In the aortic manipulation group,at least one aorto-conduit (saphenous vein, radial arteryor free-IMA) proximal anastomosis was performed usinga“d

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Table 2. Operative Data

Variable AnaorticGroupn = 1201

AorticManipulationGroup n = 557

p-Value

Grafts/patient ratioMean 2.5 2.6 0.003S.D. 1.2 0.9

Use of left IMA 94.0 84.2 <0.0001Use of right IMA 27.8 17.2 <0.0001Use of bilateral IMA 26.5 14.5 <0.0001Use of radial artery 77.1 22.9 <0.0001Use of SVG 13.7% 75.6% <0.0001

Chi-square test and Student’s t-test. p < 0.05 considered statisticallysignificant.

variate model. A backwards stepwise elimination processwas used to remove covariates from the maximum multi-variate model whose multivariate p-value was >0.05. Theterm anaortic OPCAB surgery was forced to remain inthe model. Operation type was a binary variable with 0indicating aortic manipulation and 1 indicating anaortic.

Results

Pre-operative (Table 1) and intra-operative (Table 2) vari-ables were compared using Chi-square and Student’st-test. The groups were well-matched for age. The anaor-tic group had significantly more male patients, obesepatients, patients with left main stem stenosis >50%, andmore patients who had sustained an acute myocardialinfarction within the preceding 90 days. The patients wereotherwise well-matched.

Pre-operative and intra-operative parameters wereassessed for their effects on survival and complicationsby using univariate analysis.

Operative Morbidity and MortalityThe 30-day morbidity and mortality data comparing theanaortic with aortic manipulation off-pump cohort is pre-sented in Table 3. The 30-day mortality for the anaorticgroup was 1.4% (17/1201) and for the aortic manipulationgroup was 1.3% (7/557). The adverse neurological eventrppfihwa(stlWwd

PMu

n aortic partial occlusion clamp or a modification of theVettath Obturator” (a no-clamp proximal anastomoticevice).Conversion to on-pump CABG was observed in 4.6% of

ases in the study (4.3% in the aortic manipulation groupnd 4.7% in the anaortic group). It was then surgeon pref-rence as to whether the procedure was completed withr without aortic cross-clamping and cardioplegic arrest.hese patients were excluded from further study.Post-operatively, all patients received anti-platelet ther-

py with aspirin and/or clopidogrel, as well as a lowose of subcutaneous heparin. If the patient was not

udged to have excessive loss from the chest drains, theseedications were administered within the first six hours

ost-operatively.

ata Analysisatients’ demographics, risk factors, clinical status, intra-perative and post-operative data were prospectivelyollected on a datasheet to be entered into a cus-omised Microsoft Access database. Statistical analysesere performed using StatView (StatView; Abacus Con-

epts, Berkeley, CA) with two-tailed tests performed andp < 0.05 considered significant. The two groups (anaor-

ic versus aortic manipulation) were compared using the2 statistic or Fisher exact test for categorical data, andnpaired t-tests.To determine if anaortic OPCAB surgery was an inde-

endent predictor of post-operative neurologic morbidityhe following analyses were performed. Multiple logisticegression was used to identify univariate predictors ofost-operative neurologic morbidity. A univariate p < 0.25ualified the variable for inclusion in the maximum multi-

ate in the anaortic group was 0.25% (3/1201), with twoatients having had a transient event (0.17%) and only oneatient (0.08%) having had a permanent stroke within therst 30 post-operative days. The aortic manipulation groupad an adverse neurological event rate of 1.1% (6/557),ith three patients having had a transient event (0.54%),

nd three patients having sustained a permanent stroke0.54%). The peri-operative myocardial infarction rate wasimilar between the two groups (anaortic 0.58% versus aor-ic manipulation 0.36%). Rates of new renal failure wereess than 1% in each group and not significantly different.

ound infection rates (sternal and conduit harvest sites)ere less than 4.5% in each group and not significantlyifferent.

redictors of Adverse Neurological Outcomeultiple logistic regression and univariate analysis were

sed to assess the effects of confounding factors on adverse

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Table 3. Thirty-day Morbidity and Mortality

Variable Anaortic Group n = 1201 Aortic Manipulation Group n = 557 p-Value

Thirty-day mortality 17 (1.4%) 7 (1.3%) NS

Length of hospital stay (days)Mean 7.9 8.0 NSS.D. 3.7 3.9

Length of ICU stay (h)Mean 62.3 61.8 NSS.D. 63.2 62.1

Myocardial infarction 7 (0.58%) 2 (0.36%) NSCoronary artery re-intervention 4 (0.3%) 5 (0.9%) NSTake-back for bleeding 56 (4.7%) 14 (2.5%) 0.03New renal failure 11 (0.92%) 5 (0.90%) NSInfection 52 (4.33%) 23 (4.13%) NS

Major neurologic event 3 (0.25%) 6 (1.08)% 0.024Transient 2 (0.17%) 3 (0.54%) NSPermanent 1 (0.08%) 3 (0.54%) NS

Chi-square test. p < 0.05 considered statistically significant.

Table 4. Independent Risk Factors for Adverse NeurologicEvents

Variable OR 95% CI p-Value

Age 1.11 1.02–1.20 0.017Anaortic 0.23 0.06–0.92 0.037

OR, odds ratio; CI, confidence interval.

neurological events after off-pump CABG. These resultsare shown in Table 4 (p < 0.05 was considered statisticallysignificant). Aortic manipulation and advanced age wereidentified as independent predictors of an adverse neuro-logical event.

Comparisons with Contemporary On-pump CABGCohortIn a contemporary cohort of 1599 patients undergoingcoronary artery bypass grafting with cardiopulmonarybypass, an adverse neurological event occurred in 30patients (1.81%). Eighteen patients (1.13%) suffered a per-manent stroke, and 11 patients (0.69%) had a transientneurological event.

The post-operative myocardial infarction rate was 0.44%(7/1592), which is similar to the off-pump cohort, suggest-ing similar short-term graft patency rates between the twotechniques.

Follow-up StatusThirty-day follow-up was 100% complete. Certain sub-groups of this cohort are subject to longer term studiesusing non-invasive assessment of coronary arteries andgrafts, with particular emphasis on studying patency ofLIMA/radial artery and LIMA/RIMA ‘T’ grafts.

Discussion

be number of underlying factors. The study groups areoften too small to detect a significant difference in out-comes, which are already relatively infrequent in theirown right (Type 2 error). The study groups may some-times be heterogenous, or have low-risk profiles for pooroutcomes, and hence it is difficult to demonstrate a dif-ference between the two techniques. However, there areseveral good retrospective and prospective studies thatclearly demonstrate a benefit of off-pump over on-pumpcoronary artery surgery.16,17,19,20

Recent data highlighting the survival benefits andreduced coronary re-intervention rates when comparingsurgical revascularisaton to percutaneous coronary inter-vention (PCI) (bare-metal and drug-eluting stents) meansthat more patients are likely to be referred for coronarysurgery.21–23 The cost of stroke, both to the patient and tothe community, mandates that the cardiac surgical frater-nity endeavours to reduce the peri-operative stroke rateas much as possible.

It is well known that the stroke rate after percuta-neous coronary intervention (0.3%) 24 is significantly lessthan that observed after on-pump CABG (2–4%).4 How-ever, several studies of aortic no-touch (anaortic) OPCABsurgery,2,16,17,25 including ours, have demonstrated anadverse neurological event rate which is the same as thatobserved after percutaneous coronary intervention.3,24

Patients referred for surgical myocardial revascularisa-

It has been difficult to prove conclusively that there arebenefits of off-pump over on-pump coronary surgery, andmany surgeons have used this to support their decisionnot to pursue off-pump techniques.18 There are likely to

tion are older and have more medical comorbidities thana comparable cohort a decade ago, and hence their inher-ent risk of peri-operative stroke is higher. Age-adjustedrates of stroke after conventional on-pump CABG havebeen reported as high as 9%.26 There have been reportsof no strokes in elderly patients undergoing off-pumprevascularisation.15,27

Neurological injury after cardiac surgery can take oneof two forms: gross injury, such as stroke (Type 1 injury),and subtle neurocognitive changes (Type 2 injury).9 Mech-anisms leading to neurological injury are multifactorialand include cerebral hypoperfusion, systemic inflamma-tory response syndrome and embolism. Type 1 injuries

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are generally believed to result from emboli after aorticmanipulation, such as cannulation and clamping (includ-ing the aortic “side-biting” clamp).3,5,9 However, thepathophysiological effects of extracorporeal circulation,such as contact activation and the systemic inflammatoryresponse syndrome, may contribute to adverse neurolog-ical outcomes and type 2 neurological injuries.

The majority of strokes (62%) after on-pump CABG areembolic.28 Reducing aortic manipulation by avoiding can-nulation for cardiopulmonary bypass and clamping forcardioplegic arrest or for fashioning inflow anastomosessignificantly reduces the release of emboli.11,29

Extracardiac arteriopathy and manipulation of the aortahave been shown to be independent risk factors for neu-rological injury after CABG.17 Off-pump surgery providesan opportunity to perform coronary revascularisationusing an “aortic no-touch” technique. In a large risk-adjusted retrospective study (4269 on-pump and 2527off-pump), Kapetanakis et al. demonstrated that patientswho had their aorta extensively manipulated were 1.8times more likely to have a stroke than those patients whodid not have their aorta handled (2.2% versus 0.8%).25

In a similar prospective study of patients having off-pump surgery, Lev-Ran et al. demonstrated that theincidence of stroke was significantly lower in patients whohad an “aortic no-touch” technique 0.2% versus 2.2%,p = 0.01).14 Kim et al. demonstrated a 0% stroke rate inp0a

asKcCrodietCoa

noptioisiecccd

Limitations of the StudyThe patients were studied prospectively, but were not ran-domised. The patient selection for on-pump, off-pumpwith aortic manipulation or anaortic off-pump revascu-larisation was not randomised and was surgeon specific.Surgical techniques differed between surgeons.

Conclusions

The reduction in neurological injury in the anaorticoff-pump surgery group when compared to the aorticmanipulation off-pump surgery group in this series is sig-nificant (0.25% versus 1.1%). However, the neurologicalbenefits of “anaortic” OPCAB surgery when compared tothe on-pump surgery cohort are even more interesting(0.25% versus 1.8%). There was a 7.2-fold increase in therate of adverse neurological events in the on-pump CABGgroup when compared with the anaortic OPCAB group.

Our data adds significantly to the literature on this sub-ject and highlights the significant reduction in adverseneurological events that can be achieved when coronaryartery bypass surgery is performed without cardiopul-monary bypass and without manipulating the ascendingaorta.

As the age and complexity of patients presenting forsurgical revascularisation increases, it is important that allsurgeons (or all surgical units) have the expertise to per-form full surgical revascularisation without manipulatingt

R

atients (n = 222) undergoing anaortic OPCAB versus a.8% stroke rate in patients (n = 123) having OPCAB withortic manipulation.16

Patients with known peripheral vascular disease aret higher risk from adverse cerebrovascular events afterurgery.30,31 In a recent risk-adjusted retrospective study,arthik et al. demonstrated that patients with signifi-

ant peripheral vascular disease undergoing off-pumpABG had a stroke rate of 1.0% compared to a stroke

ate of 5.6% in the on-pump group.13 In a meta-analysisf published trials from 1990 to 2002, Parolari et al.emonstrated a trend in the reduction of strokes favour-

ng off-pump over on-pump CABG (p = 0.08).32 Sharonyt al. compared outcomes for patients with atheroma-ous ascending aortas undergoing on-pump or off-pumpABG. The authors demonstrated a benefit of off-pumpver on-pump with reduced death, stroke and morbiditynd improved medium term survival.33

To summarise the data from our series: The adverseeurological event rate of 0.25% (permanent stroke ratef 0.08%) observed in 1201 patients undergoing off-ump coronary artery surgery without manipulation of

he aorta is equivalent to or less than that observedn patients undergoing general surgical (0.08–0.7%) 34

r peripheral vascular procedures (0.8–3.0%).35 Signif-cantly, the stroke rate after anaortic OPCAB is theame as that seen after percutaneous coronary arteryntervention.24 Coupled with the proven long-term ben-fits of surgical revascularisation over percutaneousoronary intervention, off-pump anaortic/no-touch revas-ularisation would appear to be the procedure ofhoice for the treatment of multi-vessel coronary arteryisease.

he ascending aorta.

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