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Does preoperative carotid stenosis screening reduce perioperative stroke in patients undergoing coronary artery bypass grafting?

Open ArchivePublished:February 09, 2015DOI:https://doi.org/10.1016/j.jtcvs.2015.02.003

      Abstract

      A number of institutions routinely perform carotid artery ultrasound screening before coronary artery bypass grafting (CABG) to identify carotid artery disease requiring revascularization before or during CABG, with the expectation of reducing perioperative neurologic events. The assumptions are that carotid disease is causally related to perioperative stroke and that prophylactic carotid revascularization decreases the risk of post-CABG neurologic events. Although carotid artery stenosis is a known risk factor for perioperative stroke in patients undergoing CABG, it might be a surrogate marker for diffuse atherosclerotic disease rather than a direct etiologic factor. Moreover, the benefit of prophylactic carotid revascularization in patients with asymptomatic unilateral carotid disease is uncertain. Therefore, we have reviewed the literature for evidence that preoperative carotid artery screening, by identifying patients with significant carotid artery stenosis and altering their management, reduces perioperative neurologic events in those undergoing CABG.

      Abbreviation and Acronym:

      CABG (coronary artery bypass grafting)

      Key Words

      CTSNet classification

      A number of institutions routinely perform carotid artery ultrasound screening before coronary artery bypass grafting, with the expectation of decreasing perioperative neurologic events. However, carotid artery stenosis might simply be a surrogate marker for diffuse atherosclerotic disease, and the benefit of prophylactic carotid revascularization in asymptomatic patients with unilateral carotid disease is uncertain.
      A number of institutions routinely perform carotid artery ultrasound screening before coronary artery bypass grafting (CABG) to identify carotid artery disease that necessitates revascularization before or during CABG, with the expectation of reducing perioperative neurologic events. However, among patients undergoing CABG, clinical variables alone can identify those who have significant carotid artery disease, with as high a degree of sensitivity as ultrasound. Moreover, carotid duplex ultrasound screening, whether selective or nonselective, identifies only a minority of patients who will develop perioperative stroke, and intervening for those with carotid disease might not decrease the risk of these neurologic events.
      Stroke is a devastating complication of coronary artery bypass grafting (CABG).
      • Tarakji K.G.
      • Sabik III, J.F.
      • Bhudia S.K.
      • Batizy L.H.
      • Blackstone E.H.
      Temporal onset, risk factors, and outcomes associated with stroke after coronary artery bypass grafting.
      For this reason, a number of institutions routinely screen patients undergoing CABG (Table 1)
      • Salehiomran A.
      • Shirani S.
      • Karimi A.
      • Ahmadi H.
      • Marzban M.
      • Movahedi N.
      • et al.
      Screening of carotid artery stenosis in coronary artery bypass grafting patients.
      • Fukuda I.
      • Gomi S.
      • Watanabe K.
      • Seita J.
      Carotid and aortic screening for coronary artery bypass grafting.
      • Anastasiadis K.
      • Karamitsos T.D.
      • Velissaris I.
      • Makrygiannakis K.
      • Kiskinis D.
      Preoperative screening and management of carotid artery disease in patients undergoing cardiac surgery.
      • Durand D.J.
      • Perler B.A.
      • Roseborough G.S.
      • Grega M.A.
      • Borowicz Jr., L.M.
      • Baumgartner W.A.
      • et al.
      Mandatory versus selective preoperative carotid screening: a retrospective analysis.
      • Shirani S.
      • Boroumand M.A.
      • Abbasi S.H.
      • Maghsoodi N.
      • Shakiba M.
      • Karimi A.
      • et al.
      Preoperative carotid artery screening in patients undergoing coronary artery bypass graft surgery.
      • Lee E.J.
      • Choi K.H.
      • Ryu J.S.
      • Jeon S.B.
      • Lee S.W.
      • Park S.W.
      • et al.
      Stroke risk after coronary artery bypass graft surgery and extent of cerebral artery atherosclerosis.
      for severe carotid artery stenosis and potential carotid revascularization, with the expectation of reducing the risk of post-CABG stroke. This practice is contrary to guidelines recommending screening in selected patients only.
      • Hillis L.D.
      • Smith P.K.
      • Anderson J.L.
      • Bittl J.A.
      • Bridges C.R.
      • Byrne J.G.
      • et al.
      2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. Executive summary.

      The Society of Thoracic Surgeons. Five things physicians and patients should question. Choosing wisely. An initiative of the ABIM Foundation. Available at: http://www.choosingwisely.org/doctor-patient-lists/the-society-of-thoracic-surgeons/ Accessed September 4, 2013.

      The underlying assumptions are that carotid disease is causally related to perioperative stroke and that prophylactic carotid revascularization decreases its risk. However, if carotid artery stenosis is not a direct etiologic risk factor for perioperative stroke, routine nonselective screening may not be cost effective.
      • Anastasiadis K.
      • Karamitsos T.D.
      • Velissaris I.
      • Makrygiannakis K.
      • Kiskinis D.
      Preoperative screening and management of carotid artery disease in patients undergoing cardiac surgery.
      • Naylor A.R.
      Managing patients with symptomatic coronary and carotid artery disease.
      In addition, the benefit of prophylactic carotid revascularization in patients with asymptomatic unilateral carotid disease is controversial.
      • Gerraty R.P.
      • Gates P.C.
      • Doyle J.C.
      Carotid stenosis and perioperative stroke risk in symptomatic and asymptomatic patients undergoing vascular or coronary surgery.
      • Li Y.
      • Walicki D.
      • Mathiesen C.
      • Jenny D.
      • Li Q.
      • Isayev Y.
      • et al.
      Strokes after cardiac surgery and relationship to carotid stenosis.
      • Ghosh J.
      • Murray D.
      • Khwaja N.
      • Murphy M.O.
      • Walker M.G.
      The influence of asymptomatic significant carotid disease on mortality and morbidity in patients undergoing coronary artery bypass surgery.
      • Prasad S.M.
      • Li S.
      • Rankin J.S.
      • O'Brien S.M.
      • Gammie J.S.
      • Puskas J.D.
      • et al.
      Current outcomes of simultaneous carotid endarterectomy and coronary artery bypass graft surgery in North America.
      • Naylor A.R.
      Does the risk of post-CABG stroke merit staged or synchronous reconstruction in patients with symptomatic or asymptomatic carotid disease?.
      Therefore, we have reviewed the literature for evidence that preoperative carotid artery screening, by identifying patients with substantial carotid stenosis and altering their management, decreases perioperative neurologic events in patients undergoing CABG.
      Table 1Carotid artery screening in patients undergoing coronary artery bypass grafting
      First author and yearNo. of screened patientsPopulationRoutine screeningScreening methodDegree of internal carotid artery stenosis considered significant (%)Prevalence (%)
      Wanamaker
      • Wanamaker K.M.
      • Moraca R.J.
      • Nitzberg D.
      • Magovern Jr., G.J.
      Contemporary incidence and risk factors for carotid artery disease in patients referred for coronary artery bypass surgery.
      2012
      559CABGNoDUS>5036
      Ansari
      • Ansari S.
      • Tan J.Y.
      • Larcos G.S.
      • Paterson H.
      Low prevalence of significant carotid artery disease on ultrasound in patients proceeding to coronary artery bypass surgery.
      2011
      116CABG with/without valve surgeryNoDUS>706.6
      Drohomirecka
      • Drohomirecka A.
      • Koltowski L.
      • Kwinecki P.
      • Wronecki K.
      • Cichon R.
      Risk factors for carotid artery disease in patients scheduled for coronary artery bypass grafting.
      2010
      682CABGNoDUS≥5018
      Cornily
      • Cornily J.C.
      • Le Saux D.
      • Vinsonneau U.
      • Bezon E.
      • Le Ven F.
      • Le Gal G.
      • et al.
      Assessment of carotid artery stenosis before coronary artery bypass surgery. Is it always necessary?.
      2010
      205CABGNoDUS≥705.8
      Anastasiadis
      • Anastasiadis K.
      • Karamitsos T.D.
      • Velissaris I.
      • Makrygiannakis K.
      • Kiskinis D.
      Preoperative screening and management of carotid artery disease in patients undergoing cardiac surgery.
      2009
      307Cardiac surgeryYesDUS>706.5
      Kiernan
      • Kiernan T.J.
      • Taqueti V.
      • Crevensten G.
      • Yan B.P.
      • Slovut D.P.
      • Jaff M.R.
      Correlates of carotid stenosis in patients undergoing coronary artery bypass grafting–a case control study.
      2009
      643CABGNoDUS>707.7
      Sheiman
      • Sheiman R.G.
      Janne d'Othee B. Screening carotid sonography before elective coronary artery bypass graft surgery: who needs it.
      2007
      295CABGYesDUS≥5024
      Shirani
      • Shirani S.
      • Boroumand M.A.
      • Abbasi S.H.
      • Maghsoodi N.
      • Shakiba M.
      • Karimi A.
      • et al.
      Preoperative carotid artery screening in patients undergoing coronary artery bypass graft surgery.
      2006
      1045CABG with/without valve surgeryYesDUS>606.9
      Durand
      • Durand D.J.
      • Perler B.A.
      • Roseborough G.S.
      • Grega M.A.
      • Borowicz Jr., L.M.
      • Baumgartner W.A.
      • et al.
      Mandatory versus selective preoperative carotid screening: a retrospective analysis.
      2004
      1138CABGYesDUS and/or angiography≥7013.4
      Fukuda
      • Fukuda I.
      • Gomi S.
      • Watanabe K.
      • Seita J.
      Carotid and aortic screening for coronary artery bypass grafting.
      2000
      308CABGYesDUS>5014.3
      Salasidis
      • Salasidis G.C.
      • Latter D.A.
      • Steinmetz O.K.
      • Blair J.F.
      • Graham A.M.
      Carotid artery duplex scanning in preoperative assessment for coronary artery revascularization: the association between peripheral vascular disease, carotid artery stenosis, and stroke.
      1995
      387CABGNoDUS>808.5
      CABG, Coronary artery bypass grafting; DUS, duplex ultrasonography.

      Perioperative Stroke in Patients Undergoing CABG

      Stroke is a serious complication of CABG that occurs in 1.3% to 2.0% of patients
      • Tarakji K.G.
      • Sabik III, J.F.
      • Bhudia S.K.
      • Batizy L.H.
      • Blackstone E.H.
      Temporal onset, risk factors, and outcomes associated with stroke after coronary artery bypass grafting.
      • Roach G.W.
      • Kanchuger M.
      • Mangano C.M.
      • Newman M.
      • Nussmeier N.
      • Wolman R.
      • et al.
      Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators.
      • Brown P.P.
      • Kugelmass A.D.
      • Cohen D.J.
      • Reynolds M.R.
      • Culler S.D.
      • Dee A.D.
      • et al.
      The frequency and cost of complications associated with coronary artery bypass grafting surgery: results from the United States Medicare program.
      • Frye R.L.
      • Kronmal R.
      • Schaff H.V.
      • Myers W.O.
      • Gersh B.J.
      Stroke in coronary artery bypass graft surgery: an analysis of the CASS experience. The participants in the Coronary Artery Surgery Study.
      and results in acute mortality of up to 38%.
      • McKhann G.M.
      • Grega M.A.
      • Borowicz Jr., L.M.
      • Bechamps M.
      • Selnes O.A.
      • Baumgartner W.A.
      • et al.
      Encephalopathy and stroke after coronary artery bypass grafting: incidence, consequences, and prediction.
      • Salazar J.D.
      • Wityk R.J.
      • Grega M.A.
      • Borowicz L.M.
      • Doty J.R.
      • Petrofski J.A.
      • et al.
      Stroke after cardiac surgery: short- and long-term outcomes.
      The cause of post-CABG stroke is multifactorial, but because most strokes occur ≥24 hours after surgery, embolic events are the most likely culprits.
      • Naylor A.R.
      Does the risk of post-CABG stroke merit staged or synchronous reconstruction in patients with symptomatic or asymptomatic carotid disease?.
      • Borger M.A.
      • Ivanov J.
      • Weisel R.D.
      • Rao V.
      • Peniston C.M.
      Stroke during coronary bypass surgery: principal role of cerebral macroemboli.
      • Schoof J.
      • Lubahn W.
      • Baeumer M.
      • Kross R.
      • Wallesch C.W.
      • Kozian A.
      • et al.
      Impaired cerebral autoregulation distal to carotid stenosis/occlusion is associated with increased risk of stroke at cardiac surgery with cardiopulmonary bypass.
      • Hise J.H.
      • Nipper M.L.
      • Schnitker J.C.
      Stroke associated with coronary artery bypass surgery.
      • Naylor A.R.
      • Mehta Z.
      • Rothwell P.M.
      • Bell P.R.
      Carotid artery disease and stroke during coronary artery bypass: a critical review of the literature.
      Macroembolization of atherothrombotic debris from the severely atherosclerotic aorta is strongly associated with postoperative stroke.
      • Roach G.W.
      • Kanchuger M.
      • Mangano C.M.
      • Newman M.
      • Nussmeier N.
      • Wolman R.
      • et al.
      Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators.
      • John R.
      • Choudhri A.F.
      • Weinberg A.D.
      • Ting W.
      • Rose E.A.
      • Smith C.R.
      • et al.
      Multicenter review of preoperative risk factors for stroke after coronary artery bypass grafting.
      • Mickleborough L.L.
      • Walker P.M.
      • Takagi Y.
      • Ohashi M.
      • Ivanov J.
      • Tamariz M.
      Risk factors for stroke in patients undergoing coronary artery bypass grafting.
      • Lynn G.M.
      • Stefanko K.
      • Reed III, J.F.
      • Gee W.
      • Nicholas G.
      Risk factors for stroke after coronary artery bypass.
      Shedding of emboli to the brain might be caused by manipulation of the ascending aorta during aortic clamping, cannulation, and proximal graft anastomosis.
      • Hise J.H.
      • Nipper M.L.
      • Schnitker J.C.
      Stroke associated with coronary artery bypass surgery.
      • Stamou S.C.
      • Hill P.C.
      • Dangas G.
      • Pfister A.J.
      • Boyce S.W.
      • Dullum M.K.
      • et al.
      Stroke after coronary artery bypass: incidence, predictors, and clinical outcome.
      • Blauth C.I.
      • Cosgrove D.M.
      • Webb B.W.
      • Ratliff N.B.
      • Boylan M.
      • Piedmonte M.R.
      • et al.
      Atheroembolism from the ascending aorta. An emerging problem in cardiac surgery.
      Dislodging of emboli from the heart due to manipulation by the surgeon or atrial fibrillation are other possible causes.
      • Roffi M.
      • Ribichini F.
      • Castriota F.
      • Cremonesi A.
      Management of combined severe carotid and coronary artery disease.
      Intraoperative hemodynamic abnormalities, such as hypotension during cardiopulmonary bypass, and pulmonary diastolic hypertension after cardiopulmonary bypass, are also associated with increased risk of post-CABG stroke.
      • Reich D.L.
      • Bodian C.A.
      • Krol M.
      • Kuroda M.
      • Osinski T.
      • Thys D.M.
      Intraoperative hemodynamic predictors of mortality, stroke, and myocardial infarction after coronary artery bypass surgery.
      Microembolization of platelet aggregates and turbulent blood flow during cardiopulmonary bypass are other possible causes.
      • Stamou S.C.
      • Hill P.C.
      • Dangas G.
      • Pfister A.J.
      • Boyce S.W.
      • Dullum M.K.
      • et al.
      Stroke after coronary artery bypass: incidence, predictors, and clinical outcome.
      • Tokuda Y.
      • Song M.H.
      • Ueda Y.
      • Usui A.
      • Akita T.
      • Yoneyama S.
      • et al.
      Three-dimensional numerical simulation of blood flow in the aortic arch during cardiopulmonary bypass.
      In addition, atherosclerotic disease of the cerebral arteries is an important mechanism of stroke in patients undergoing CABG.
      • Lee E.J.
      • Choi K.H.
      • Ryu J.S.
      • Jeon S.B.
      • Lee S.W.
      • Park S.W.
      • et al.
      Stroke risk after coronary artery bypass graft surgery and extent of cerebral artery atherosclerosis.
      Risk factors for perioperative stroke include older age, prior stroke or transient ischemic attack, peripheral artery disease, hypertension, left ventricular dysfunction, preoperative atrial fibrillation,
      • Tarakji K.G.
      • Sabik III, J.F.
      • Bhudia S.K.
      • Batizy L.H.
      • Blackstone E.H.
      Temporal onset, risk factors, and outcomes associated with stroke after coronary artery bypass grafting.
      • John R.
      • Choudhri A.F.
      • Weinberg A.D.
      • Ting W.
      • Rose E.A.
      • Smith C.R.
      • et al.
      Multicenter review of preoperative risk factors for stroke after coronary artery bypass grafting.
      • Stamou S.C.
      • Hill P.C.
      • Dangas G.
      • Pfister A.J.
      • Boyce S.W.
      • Dullum M.K.
      • et al.
      Stroke after coronary artery bypass: incidence, predictors, and clinical outcome.
      • Newman M.F.
      • Wolman R.
      • Kanchuger M.
      • Marschall K.
      • Mora-Mangano C.
      • Roach G.
      • et al.
      Multicenter preoperative stroke risk index for patients undergoing coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.
      • Hogue Jr., C.W.
      • Murphy S.F.
      • Schechtman K.B.
      • Davila-Roman V.G.
      Risk factors for early or delayed stroke after cardiac surgery.
      • Filsoufi F.
      • Rahmanian P.B.
      • Castillo J.G.
      • Bronster D.
      • Adams D.H.
      Incidence, topography, predictors and long-term survival after stroke in patients undergoing coronary artery bypass grafting.
      • Nishiyama K.
      • Horiguchi M.
      • Shizuta S.
      • Doi T.
      • Ehara N.
      • Tanuguchi R.
      • et al.
      Temporal pattern of strokes after on-pump and off-pump coronary artery bypass graft surgery.
      and carotid artery stenosis.
      • Gerraty R.P.
      • Gates P.C.
      • Doyle J.C.
      Carotid stenosis and perioperative stroke risk in symptomatic and asymptomatic patients undergoing vascular or coronary surgery.
      • Naylor A.R.
      • Mehta Z.
      • Rothwell P.M.
      • Bell P.R.
      Carotid artery disease and stroke during coronary artery bypass: a critical review of the literature.
      • Stamou S.C.
      • Hill P.C.
      • Dangas G.
      • Pfister A.J.
      • Boyce S.W.
      • Dullum M.K.
      • et al.
      Stroke after coronary artery bypass: incidence, predictors, and clinical outcome.
      • Hogue Jr., C.W.
      • Murphy S.F.
      • Schechtman K.B.
      • Davila-Roman V.G.
      Risk factors for early or delayed stroke after cardiac surgery.
      • D'Agostino R.S.
      • Svensson L.G.
      • Neumann D.J.
      • Balkhy H.H.
      • Williamson W.A.
      • Shahian D.M.
      Screening carotid ultrasonography and risk factors for stroke in coronary artery surgery patients.
      A carotid bruit has been found to be a preoperative predictor of severe aortic arch atheroma.
      • Katz E.S.
      • Tunick P.A.
      • Rusinek H.
      • Ribakove G.
      • Spencer F.C.
      • Kronzon I.
      Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass: experience with intraoperative transesophageal echocardiography.
      Therefore, some consider carotid artery disease to be an epiphenomenon, serving as a marker for diffuse systemic atherosclerotic disease, rather than being a causal factor.
      • Naylor A.R.
      Managing patients with symptomatic coronary and carotid artery disease.
      • Li Y.
      • Walicki D.
      • Mathiesen C.
      • Jenny D.
      • Li Q.
      • Isayev Y.
      • et al.
      Strokes after cardiac surgery and relationship to carotid stenosis.
      • Borger M.A.
      Preventing stroke during coronary bypass: are we focusing on the wrong culprit?.
      • Forbes T.L.
      • Ricco J.B.
      Trans-Atlantic debate: is carotid artery disease responsible for perioperative strokes after coronary artery bypass surgery?.
      Data from Cleveland Clinic patients undergoing noncardiac surgery demonstrated no association between carotid artery stenosis and stroke (odds ratio 1.0, with a 95% confidence interval of 0.99-1.02) for a 10-unit increase in internal carotid artery peak systolic velocity, the variable used to quantify carotid artery stenosis.
      • Sonny A.
      • Gornik H.L.
      • Yang D.
      • Mascha E.J.
      • Sessler D.I.
      Lack of association between carotid artery stenosis and stroke or myocardial injury after noncardiac surgery in high-risk patients.

      Possible Mechanisms by Which Carotid Artery Stenosis Could Lead to Perioperative Stroke

      It is thought that carotid intraplaque hemorrhage can result in plaque destabilization
      • Redgrave J.N.
      • Lovett J.K.
      • Gallagher P.J.
      • Rothwell P.M.
      Histological assessment of 526 symptomatic carotid plaques in relation to the nature and timing of ischemic symptoms: the Oxford plaque study.
      • Michel J.B.
      • Virmani R.
      • Arbustini E.
      • Pasterkamp G.
      Intraplaque haemorrhages as the trigger of plaque vulnerability.
      • Takaya N.
      • Yuan C.
      • Chu B.
      • Saam T.
      • Polissar N.L.
      • Jarvik G.P.
      • et al.
      Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study.
      • Singh N.
      • Moody A.R.
      • Gladstone D.J.
      • Leung G.
      • Ravikumar R.
      • Zhan J.
      • et al.
      Moderate carotid artery stenosis: MR imaging-depicted intraplaque hemorrhage predicts risk of cerebrovascular ischemic events in asymptomatic men.
      • Turc G.
      • Oppenheim C.
      • Naggara O.
      • Eker O.F.
      • Calvet D.
      • Lacour J.C.
      • et al.
      Relationships between recent intraplaque hemorrhage and stroke risk factors in patients with carotid stenosis: the HIRISC study.
      and intimal ulceration, creating a nidus for thromboembolism.
      • Cambria R.P.
      The endovascular revolution stopped at the carotid bifurcation… or did it?.
      • Jorgensen L.
      • Torvik A.
      Ischaemic cerebrovascular diseases in an autopsy series. I. Prevalence, location and predisposing factors in verified thrombo-embolic occlusions, and their significance in the pathogenesis of cerebral infarction.
      • Castaigne P.
      • Lhermitte F.
      • Gautier J.C.
      • Escourolle R.
      • Derouesne C.
      Internal carotid artery occlusion. A study of 61 instances in 50 patients with post-mortem data.
      • Pessin M.S.
      • Hinton R.C.
      • Davis K.R.
      • Duncan G.W.
      • Roberson G.H.
      • Ackerman R.H.
      • et al.
      Mechanisms of acute carotid stroke.
      • Jayasooriya G.
      • Thapar A.
      • Shalhoub J.
      • Davies A.H.
      Silent cerebral events in asymptomatic carotid stenosis.
      • Altaf N.
      • Goode S.D.
      • Beech A.
      • Gladman J.R.
      • Morgan P.S.
      • MacSweeney S.T.
      • et al.
      Plaque hemorrhage is a marker of thromboembolic activity in patients with symptomatic carotid disease.
      Intraplaque hemorrhage detected by magnetic resonance imaging is associated with increased risk of ipsilateral stroke in symptomatic and asymptomatic nonsurgical patients
      • Takaya N.
      • Yuan C.
      • Chu B.
      • Saam T.
      • Underhill H.
      • Cai J.
      • et al.
      Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events: a prospective assessment with MRI–initial results.
      • Altaf N.
      • Daniels L.
      • Morgan P.S.
      • Auer D.
      • MacSweeney S.T.
      • Moody A.R.
      • et al.
      Detection of intraplaque hemorrhage by magnetic resonance imaging in symptomatic patients with mild to moderate carotid stenosis predicts recurrent neurological events.
      and is strongly related to onset of symptoms.
      • Lusby R.J.
      • Ferrell L.D.
      • Ehrenfeld W.K.
      • Stoney R.J.
      • Wylie E.J.
      Carotid plaque hemorrhage. Its role in production of cerebral ischemia.
      We hypothesize that anticoagulating patients during CABG might be responsible for increased intraoperative risk of intraplaque hemorrhage. Mechanical causes can trigger intraplaque hemorrhage as well, such as turbulent blood flow and hypertension, both of which can occur during cardiac surgery.
      • Lusby R.J.
      • Ferrell L.D.
      • Ehrenfeld W.K.
      • Stoney R.J.
      • Wylie E.J.
      Carotid plaque hemorrhage. Its role in production of cerebral ischemia.
      Impaired cerebral hemodynamic function distal to carotid artery stenosis is another determinant of postoperative stroke.
      • Schoof J.
      • Lubahn W.
      • Baeumer M.
      • Kross R.
      • Wallesch C.W.
      • Kozian A.
      • et al.
      Impaired cerebral autoregulation distal to carotid stenosis/occlusion is associated with increased risk of stroke at cardiac surgery with cardiopulmonary bypass.
      • Silvestrini M.
      • Vernieri F.
      • Pasqualetti P.
      • Matteis M.
      • Passarelli F.
      • Troisi E.
      • et al.
      Impaired cerebral vasoreactivity and risk of stroke in patients with asymptomatic carotid artery stenosis.
      Maximally dilated vessels distal to carotid artery stenosis can no longer vasodilate in response to hemodynamic compromise. Therefore, perioperative reduction in blood pressure or cardiac output in this group of patients is hypothesized to lead to cerebral ischemia.
      • Forbes T.L.
      • Ricco J.B.
      Trans-Atlantic debate: is carotid artery disease responsible for perioperative strokes after coronary artery bypass surgery?.
      • Silvestrini M.
      • Vernieri F.
      • Pasqualetti P.
      • Matteis M.
      • Passarelli F.
      • Troisi E.
      • et al.
      Impaired cerebral vasoreactivity and risk of stroke in patients with asymptomatic carotid artery stenosis.
      Moreover, reduced cerebral blood flow might result in decreased washout of microemboli in patients undergoing CABG.
      • Nicolaides A.N.
      • Kakkos S.K.
      • Kyriacou E.
      • Griffin M.
      • Sabetai M.
      • Thomas D.J.
      • et al.
      Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification.

      Detecting Carotid Artery Disease

      Carotid artery duplex ultrasound, which is used to visualize plaque and measure flow velocity to quantify stenosis, is the screening test usually used to identify patients with carotid artery stenosis (see Central Image).
      • Grant E.G.
      • Benson C.B.
      • Moneta G.L.
      • Alexandrov A.V.
      • Baker J.D.
      • Bluth E.I.
      • et al.
      Carotid artery stenosis: gray-scale and Doppler US diagnosis–Society of Radiologists in Ultrasound Consensus Conference.
      The sensitivity of carotid ultrasound to detect carotid artery stenosis, of >70% is 86% to 90%, with a specificity of 87% to 94%.
      Screening for carotid artery stenosis: U.S. Preventive Services Task Force recommendation statement.
      Although ultrasound screening is currently used to determine the degree of carotid artery stenosis, other duplex-determined plaque characteristics are also associated with cerebrovascular symptoms, including hypoechoic lesions (low grayscale median, larger juxtaluminal black area), plaque heterogeneity (presence of noncalcified, discrete white areas without acoustic shadowing), plaque ulceration, and larger plaque area.
      • Nicolaides A.
      • Sabetai M.
      • Kakkos S.K.
      • Dhanjil S.
      • Tegos T.
      • Stevens J.M.
      • et al.
      The Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study. Aims and results of quality control.
      • Nicolaides A.N.
      • Kakkos S.K.
      • Griffin M.
      • Sabetai M.
      • Dhanjil S.
      • Tegos T.
      • et al.
      Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study.
      • Jmor S.
      • El-Atrozy T.
      • Griffin M.
      • Tegos T.
      • Dhanjil S.
      • Nicolaides A.
      Grading internal carotid artery stenosis using B-mode ultrasound (in vivo study).
      • Griffin M.
      • Nicolaides A.
      • Kyriacou E.
      Normalisation of ultrasonic images of atherosclerotic plaques and reproducibility of grey scale median using dedicated software.
      • Elatrozy T.
      • Nicolaides A.
      • Tegos T.
      • Zarka A.Z.
      • Griffin M.
      • Sabetai M.
      The effect of B-mode ultrasonic image standardisation on the echodensity of symptomatic and asymptomatic carotid bifurcation plaques.
      • Tegos T.J.
      • Sabetai M.M.
      • Nicolaides A.N.
      • Pare G.
      • Elatrozy T.S.
      • Dhanjil S.
      • et al.
      Comparability of the ultrasonic tissue characteristics of carotid plaques.
      • Sabetai M.M.
      • Tegos T.J.
      • Nicolaides A.N.
      • Dhanjil S.
      • Pare G.J.
      • Stevens J.M.
      Reproducibility of computer-quantified carotid plaque echogenicity: can we overcome the subjectivity?.
      • Geroulakos G.
      • Ramaswami G.
      • Nicolaides A.
      • James K.
      • Labropoulos N.
      • Belcaro G.
      • et al.
      Characterization of symptomatic and asymptomatic carotid plaques using high-resolution real-time ultrasonography.
      • Nicolaides A.N.
      • Kakkos S.K.
      • Griffin M.
      • Sabetai M.
      • Dhanjil S.
      • Thomas D.J.
      • et al.
      Effect of image normalization on carotid plaque classification and the risk of ipsilateral hemispheric ischemic events: results from the asymptomatic carotid stenosis and risk of stroke study.
      • Spence J.D.
      Technology Insight: ultrasound measurement of carotid plaque–patient management, genetic research, and therapy evaluation.
      • Golledge J.
      • Cuming R.
      • Ellis M.
      • Davies A.H.
      • Greenhalgh R.M.
      Carotid plaque characteristics and presenting symptom.
      • Bassiouny H.S.
      • Sakaguchi Y.
      • Mikucki S.A.
      • McKinsey J.F.
      • Piano G.
      • Gewertz B.L.
      • et al.
      Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis.
      • Griffin M.B.
      • Kyriacou E.
      • Pattichis C.
      • Bond D.
      • Kakkos S.K.
      • Sabetai M.
      • et al.
      Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms.
      • Pedro L.M.
      • Fernandes e Fernandes J.
      • Pedro M.M.
      • Goncalves I.
      • Dias N.V.
      • Fernandes e Fernandes R.
      • et al.
      Ultrasonographic risk score of carotid plaques.
      • Sztajzel R.
      • Momjian-Mayor I.
      • Comelli M.
      • Momjian S.
      Correlation of cerebrovascular symptoms and microembolic signals with the stratified gray-scale median analysis and color mapping of the carotid plaque.
      • Kakkos S.K.
      • Griffin M.B.
      • Nicolaides A.N.
      • Kyriacou E.
      • Sabetai M.M.
      • Tegos T.
      • et al.
      The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke.
      Therefore, both carotid artery flow velocity and plaque characterization could be used to identify patients who are at higher risk of developing perioperative neurologic events when undergoing CABG.
      • Nicolaides A.N.
      • Kakkos S.K.
      • Kyriacou E.
      • Griffin M.
      • Sabetai M.
      • Thomas D.J.
      • et al.
      Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification.
      Regardless of whether carotid artery stenosis is an etiologic factor for perioperative stroke, carotid artery ultrasound screening detects only a minority of patients who experience perioperative neurologic events. For example, by screening every patient undergoing CABG, Durand and colleagues
      • Durand D.J.
      • Perler B.A.
      • Roseborough G.S.
      • Grega M.A.
      • Borowicz Jr., L.M.
      • Baumgartner W.A.
      • et al.
      Mandatory versus selective preoperative carotid screening: a retrospective analysis.
      found that 13.4% had carotid artery stenosis of ≥70%. Among those who developed postoperative stroke after undergoing CABG, only 19% had carotid artery stenosis of ≥70% ipsilateral to the side of the stroke.
      An alternative to routine ultrasound screening is risk profiling. Several groups have identified risk factors associated with significant carotid artery stenosis in patients undergoing CABG (Table 2). Peripheral artery disease, cerebrovascular disease (prior stroke or transient ischemic attack), and old age were the risk factors most consistently identified in these studies.
      • Salehiomran A.
      • Shirani S.
      • Karimi A.
      • Ahmadi H.
      • Marzban M.
      • Movahedi N.
      • et al.
      Screening of carotid artery stenosis in coronary artery bypass grafting patients.
      • Fukuda I.
      • Gomi S.
      • Watanabe K.
      • Seita J.
      Carotid and aortic screening for coronary artery bypass grafting.
      • Anastasiadis K.
      • Karamitsos T.D.
      • Velissaris I.
      • Makrygiannakis K.
      • Kiskinis D.
      Preoperative screening and management of carotid artery disease in patients undergoing cardiac surgery.
      • Shirani S.
      • Boroumand M.A.
      • Abbasi S.H.
      • Maghsoodi N.
      • Shakiba M.
      • Karimi A.
      • et al.
      Preoperative carotid artery screening in patients undergoing coronary artery bypass graft surgery.
      • D'Agostino R.S.
      • Svensson L.G.
      • Neumann D.J.
      • Balkhy H.H.
      • Williamson W.A.
      • Shahian D.M.
      Screening carotid ultrasonography and risk factors for stroke in coronary artery surgery patients.
      • Berens E.S.
      • Kouchoukos N.T.
      • Murphy S.F.
      • Wareing T.H.
      Preoperative carotid artery screening in elderly patients undergoing cardiac surgery.
      • Sheiman R.G.
      Janne d'Othee B. Screening carotid sonography before elective coronary artery bypass graft surgery: who needs it.
      • Salasidis G.C.
      • Latter D.A.
      • Steinmetz O.K.
      • Blair J.F.
      • Graham A.M.
      Carotid artery duplex scanning in preoperative assessment for coronary artery revascularization: the association between peripheral vascular disease, carotid artery stenosis, and stroke.
      • Kiernan T.J.
      • Taqueti V.
      • Crevensten G.
      • Yan B.P.
      • Slovut D.P.
      • Jaff M.R.
      Correlates of carotid stenosis in patients undergoing coronary artery bypass grafting–a case control study.
      • Drohomirecka A.
      • Koltowski L.
      • Kwinecki P.
      • Wronecki K.
      • Cichon R.
      Risk factors for carotid artery disease in patients scheduled for coronary artery bypass grafting.
      • Ansari S.
      • Tan J.Y.
      • Larcos G.S.
      • Paterson H.
      Low prevalence of significant carotid artery disease on ultrasound in patients proceeding to coronary artery bypass surgery.
      Applying carotid disease–screening algorithms to cohorts of ultrasound-screened patients undergoing CABG showed that most who had significant carotid artery stenosis could be detected.
      • Durand D.J.
      • Perler B.A.
      • Roseborough G.S.
      • Grega M.A.
      • Borowicz Jr., L.M.
      • Baumgartner W.A.
      • et al.
      Mandatory versus selective preoperative carotid screening: a retrospective analysis.
      • Sheiman R.G.
      Janne d'Othee B. Screening carotid sonography before elective coronary artery bypass graft surgery: who needs it.
      • Cornily J.C.
      • Le Saux D.
      • Vinsonneau U.
      • Bezon E.
      • Le Ven F.
      • Le Gal G.
      • et al.
      Assessment of carotid artery stenosis before coronary artery bypass surgery. Is it always necessary?.
      Thus, Durand and colleagues
      • Durand D.J.
      • Perler B.A.
      • Roseborough G.S.
      • Grega M.A.
      • Borowicz Jr., L.M.
      • Baumgartner W.A.
      • et al.
      Mandatory versus selective preoperative carotid screening: a retrospective analysis.
      found that a risk-profiling algorithm based on a prior stroke or transient ischemic attack, carotid bruit on exam, or age >65 years would have missed significant carotid disease in only 2.3% of patients undergoing CABG (26 of 1138), although this represented 17% of 152 patients with significant carotid disease, and 582 had a false-positive result.
      • Durand D.J.
      • Perler B.A.
      • Roseborough G.S.
      • Grega M.A.
      • Borowicz Jr., L.M.
      • Baumgartner W.A.
      • et al.
      Mandatory versus selective preoperative carotid screening: a retrospective analysis.
      Thus, their selective screening algorithm had a sensitivity and specificity of 83% and 41%, respectively.
      Table 2Risk factors for significant carotid artery stenosis
      First author and yearOlder age (y)FemaleBruitSmokingDMHtnLMCAHistory of CVDPADOthers
      Wanamaker
      • Wanamaker K.M.
      • Moraca R.J.
      • Nitzberg D.
      • Magovern Jr., G.J.
      Contemporary incidence and risk factors for carotid artery disease in patients referred for coronary artery bypass surgery.
      2012
      YesYesNSNoNoYesYesYesYesRenal failure (dialysis)
      Ansari
      • Ansari S.
      • Tan J.Y.
      • Larcos G.S.
      • Paterson H.
      Low prevalence of significant carotid artery disease on ultrasound in patients proceeding to coronary artery bypass surgery.
      2011
      YesNSNSNoNoNoNSYesYesHypercholesterolemia/abnormal renal function
      Cornily
      • Cornily J.C.
      • Le Saux D.
      • Vinsonneau U.
      • Bezon E.
      • Le Ven F.
      • Le Gal G.
      • et al.
      Assessment of carotid artery stenosis before coronary artery bypass surgery. Is it always necessary?.
      2010
      NSNoYesNoYesNoNSNoYes
      Drohomirecka
      • Drohomirecka A.
      • Koltowski L.
      • Kwinecki P.
      • Wronecki K.
      • Cichon R.
      Risk factors for carotid artery disease in patients scheduled for coronary artery bypass grafting.
      2010
      YesNoNSNSNoNoNoYesYesUnstable angina
      Anastasiadis
      • Anastasiadis K.
      • Karamitsos T.D.
      • Velissaris I.
      • Makrygiannakis K.
      • Kiskinis D.
      Preoperative screening and management of carotid artery disease in patients undergoing cardiac surgery.
      2009
      NoNoYesNoNoNoNoYesNS
      Kiernan
      • Kiernan T.J.
      • Taqueti V.
      • Crevensten G.
      • Yan B.P.
      • Slovut D.P.
      • Jaff M.R.
      Correlates of carotid stenosis in patients undergoing coronary artery bypass grafting–a case control study.
      2009
      NSNSYesNSNSNSYesYesYes
      Sheiman
      • Sheiman R.G.
      Janne d'Othee B. Screening carotid sonography before elective coronary artery bypass graft surgery: who needs it.
      2007
      NSNoNSYesYesYesYesYesYesHistory of carotid disease
      Shirani
      • Shirani S.
      • Boroumand M.A.
      • Abbasi S.H.
      • Maghsoodi N.
      • Shakiba M.
      • Karimi A.
      • et al.
      Preoperative carotid artery screening in patients undergoing coronary artery bypass graft surgery.
      2006
      >50YesNSNoYesNSNSNSNSCholesterol >240

      Triglycerides >240
      Durand
      • Durand D.J.
      • Perler B.A.
      • Roseborough G.S.
      • Grega M.A.
      • Borowicz Jr., L.M.
      • Baumgartner W.A.
      • et al.
      Mandatory versus selective preoperative carotid screening: a retrospective analysis.
      2004
      >65YesYesNSNoYesYesYesYes
      Fukuda
      • Fukuda I.
      • Gomi S.
      • Watanabe K.
      • Seita J.
      Carotid and aortic screening for coronary artery bypass grafting.
      2000
      NoNSNSNoNoNoNoYesYesAtherosclerosis of ascending aorta
      D'Agostino
      • D'Agostino R.S.
      • Svensson L.G.
      • Neumann D.J.
      • Balkhy H.H.
      • Williamson W.A.
      • Shahian D.M.
      Screening carotid ultrasonography and risk factors for stroke in coronary artery surgery patients.
      1996
      YesYesNSYesYesNSYesYesYesPrior vascular operation
      Salasidis
      • Salasidis G.C.
      • Latter D.A.
      • Steinmetz O.K.
      • Blair J.F.
      • Graham A.M.
      Carotid artery duplex scanning in preoperative assessment for coronary artery revascularization: the association between peripheral vascular disease, carotid artery stenosis, and stroke.
      1995
      YesNSNSNoNoNoNSYesYesPrior carotid endarterectomy
      Berens
      • Berens E.S.
      • Kouchoukos N.T.
      • Murphy S.F.
      • Wareing T.H.
      Preoperative carotid artery screening in elderly patients undergoing cardiac surgery.
      1992
      NSYesNSYesNSNoYesYesYes
      Bruit, Carotid bruit; DM, diabetes mellitus; Htn, hypertension; LMCA, left main coronary artery; CVD, cerebrovascular disease; PAD, peripheral artery disease; NS, not studied.
      Sheiman and colleagues
      • Sheiman R.G.
      Janne d'Othee B. Screening carotid sonography before elective coronary artery bypass graft surgery: who needs it.
      used 7 risk factors (history of carotid artery disease, prior cerebrovascular event, hypertension, diabetes, peripheral artery disease, smoking, left main coronary disease, and female gender) to predict which patients have carotid artery disease. The presence of any 1 of these factors was 100% sensitive, but only 30% specific, in detecting patients with ≥50% carotid stenosis. Similarly, Cornily and colleagues
      • Cornily J.C.
      • Le Saux D.
      • Vinsonneau U.
      • Bezon E.
      • Le Ven F.
      • Le Gal G.
      • et al.
      Assessment of carotid artery stenosis before coronary artery bypass surgery. Is it always necessary?.
      found that risk factors including age >70 years, history of cerebrovascular disease, diabetes mellitus, peripheral artery disease, or carotid bruit on physical examination could have detected 11 of 12 patients with significant carotid artery stenosis. These studies suggest that clinical factors are sensitive in identifying patients with carotid disease, but that specificity is low, requiring more specific screening modalities, such as ultrasound, in more than half of patients.

      Role of Carotid Revascularization in Decreasing the Risk of Neurologic Events

      Carotid revascularization by staged or synchronous carotid endarterectomy or carotid artery stenting is considered acceptable in patients with symptomatic carotid disease, bilateral 70% to 99% carotid stenosis, or a unilateral 70% to 99% carotid stenosis with a contralateral occlusion.
      • Naylor A.R.
      Managing patients with symptomatic coronary and carotid artery disease.
      • Venkatachalam S.
      • Gray B.H.
      • Mukherjee D.
      • Shishehbor M.H.
      Contemporary management of concomitant carotid and coronary artery disease.
      • Venkatachalam S.
      • Shishehbor M.H.
      Management of carotid disease in patients undergoing coronary artery bypass surgery: is it time to change our approach?.
      • Augoustides J.G.
      Advances in the management of carotid artery disease: focus on recent evidence and guidelines.
      However, most carotid revascularization procedures are performed prophylactically in patients with asymptomatic unilateral carotid artery stenosis,
      • Gerraty R.P.
      • Gates P.C.
      • Doyle J.C.
      Carotid stenosis and perioperative stroke risk in symptomatic and asymptomatic patients undergoing vascular or coronary surgery.
      • McKhann G.M.
      • Grega M.A.
      • Borowicz Jr., L.M.
      • Bechamps M.
      • Selnes O.A.
      • Baumgartner W.A.
      • et al.
      Encephalopathy and stroke after coronary artery bypass grafting: incidence, consequences, and prediction.
      • Salazar J.D.
      • Wityk R.J.
      • Grega M.A.
      • Borowicz L.M.
      • Doty J.R.
      • Petrofski J.A.
      • et al.
      Stroke after cardiac surgery: short- and long-term outcomes.
      • Naylor A.R.
      • Mehta Z.
      • Rothwell P.M.
      • Bell P.R.
      Carotid artery disease and stroke during coronary artery bypass: a critical review of the literature.
      • D'Agostino R.S.
      • Svensson L.G.
      • Neumann D.J.
      • Balkhy H.H.
      • Williamson W.A.
      • Shahian D.M.
      Screening carotid ultrasonography and risk factors for stroke in coronary artery surgery patients.
      and the value of such interventions is uncertain.
      The assumed benefit of treating asymptomatic patients is extrapolated from the Asymptomatic Carotid Atherosclerosis Study and Asymptomatic Carotid Surgery Trial, which concluded that carotid endarterectomy decreases the 5-year risk of ipsilateral stroke in patients with asymptomatic isolated carotid disease.
      • Halliday A.
      • Mansfield A.
      • Marro J.
      • Peto C.
      • Peto R.
      • Potter J.
      • et al.
      Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
      Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
      However, the purpose of prophylactic carotid revascularization in patients undergoing CABG is to reduce perioperative neurologic events. Thus, long-term risk reduction of stroke should not be used as a justification to perform carotid revascularization in these patients, especially if operative morbidity from the combined procedures is higher than the added risks of the procedures performed separately.
      • Li Y.
      • Walicki D.
      • Mathiesen C.
      • Jenny D.
      • Li Q.
      • Isayev Y.
      • et al.
      Strokes after cardiac surgery and relationship to carotid stenosis.
      Results of the ongoing Coronary Artery Bypass graft surgery in patients with Asymptomatic Carotid Stenosis (CABACS) randomized clinical trial comparing the safety and efficacy of isolated CABG versus synchronous CABG and carotid endarterectomy in patients with asymptomatic high-grade carotid artery stenosis will elucidate whether surgical carotid revascularization helps to reduce the risk of perioperative stroke in patients undergoing CABG.
      • Knipp S.C.
      • Scherag A.
      • Beyersdorf F.
      • Cremer J.
      • Diener H.C.
      • Haverich J.A.
      • et al.
      Randomized comparison of synchronous CABG and carotid endarterectomy vs. isolated CABG in patients with asymptomatic carotid stenosis: the CABACS trial.
      However, the trial does not have a staged carotid artery stenting arm, so the best approach to managing these patients might remain unclear.
      • Shishehbor M.H.
      • Venkatachalam S.
      • Sun Z.
      • Rajeswaran J.
      • Kapadia S.R.
      • Bajzer C.
      • et al.
      A direct comparison of early and late outcomes with three approaches to carotid revascularization and open heart surgery.
      Currently, several findings argue against the usefulness of carotid revascularization in patients undergoing CABG. First, no direct causal relationship has been found between carotid artery stenosis and postoperative ipsilateral stroke,
      • Li Y.
      • Walicki D.
      • Mathiesen C.
      • Jenny D.
      • Li Q.
      • Isayev Y.
      • et al.
      Strokes after cardiac surgery and relationship to carotid stenosis.
      and most strokes occur outside the territory supplied by the carotid artery.
      • Barbut D.
      • Grassineau D.
      • Lis E.
      • Heier L.
      • Hartman G.S.
      • Isom O.W.
      Posterior distribution of infarcts in strokes related to cardiac operations.
      Second, the risk of perioperative stroke in patients with carotid disease is low.
      • Li Y.
      • Walicki D.
      • Mathiesen C.
      • Jenny D.
      • Li Q.
      • Isayev Y.
      • et al.
      Strokes after cardiac surgery and relationship to carotid stenosis.
      • Ghosh J.
      • Murray D.
      • Khwaja N.
      • Murphy M.O.
      • Walker M.G.
      The influence of asymptomatic significant carotid disease on mortality and morbidity in patients undergoing coronary artery bypass surgery.
      • Manabe S.
      • Shimokawa T.
      • Fukui T.
      • Fumimoto K.U.
      • Ozawa N.
      • Seki H.
      • et al.
      Influence of carotid artery stenosis on stroke in patients undergoing off-pump coronary artery bypass grafting.
      • Baiou D.
      • Karageorge A.
      • Spyt T.
      • Naylor A.R.
      Patients undergoing cardiac surgery with asymptomatic unilateral carotid stenoses have a low risk of peri-operative stroke.
      • Mahmoudi M.
      • Hill P.C.
      • Xue Z.
      • Torguson R.
      • Ali G.
      • Boyce S.W.
      • et al.
      Patients with severe asymptomatic carotid artery stenosis do not have a higher risk of stroke and mortality after coronary artery bypass surgery.
      In a meta-analysis by Naylor and Bown,
      • Naylor A.R.
      • Bown M.J.
      Stroke after cardiac surgery and its association with asymptomatic carotid disease: an updated systematic review and meta-analysis.
      the risk of ipsilateral stroke in patients with a unilateral, asymptomatic 50% to 99% stenosis was found to be only 2%.
      Third, if carotid disease is truly an important risk factor for post-CABG stroke, then patients with bilateral, severe carotid disease undergoing unilateral carotid revascularization should have a high rate of stroke ipsilateral to the “nonrevascularized” artery. However, studies show that the risk of perioperative neurologic events ipsilateral to the nonrevascularized artery is low.
      • Naylor A.R.
      • Bown M.J.
      Stroke after cardiac surgery and its association with asymptomatic carotid disease: an updated systematic review and meta-analysis.
      • Naylor A.R.
      Synchronous cardiac and carotid revascularisation: the devil is in the detail.
      Fourth, combined CABG and carotid revascularization is associated with higher risk than isolated CABG. Thus, Ghosh and colleagues
      • Ghosh J.
      • Murray D.
      • Khwaja N.
      • Murphy M.O.
      • Walker M.G.
      The influence of asymptomatic significant carotid disease on mortality and morbidity in patients undergoing coronary artery bypass surgery.
      found that occurrence of death, cerebrovascular events, and myocardial infarction within 30 days of CABG without prophylactic revascularization in asymptomatic patients with carotid artery stenosis of ≥70% was 4%, but Naylor
      • Naylor A.R.
      Managing patients with symptomatic coronary and carotid artery disease.
      reported that the composite risk of death, stroke, or myocardial infarction within 30 days of combined CABG and carotid revascularization was 9% to 11%.
      Surgeons can consider several other strategies to reduce the risk of perioperative neurologic events. First, monitoring of blood pressure throughout the procedure and postoperatively; avoiding extremes of blood pressure during surgery is important, because both hypertension, when it leads to carotid artery plaque rupture, and hypotension, when it leads to cerebral ischemia, can initiate neurologic damage. Second, postoperative antiplatelet therapy should be considered,
      • Hillis L.D.
      • Smith P.K.
      • Anderson J.L.
      • Bittl J.A.
      • Bridges C.R.
      • Byrne J.G.
      • et al.
      2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. Executive summary.
      Antithrombotic Trialists' Collaboration
      Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
      because most strokes result from thromboembolic events.
      Third, because these patients are likely to have aortic arch atheroma as part of their diffuse atherosclerotic disease, intraoperative assessment of the aorta should be done before clamping, and strategies should be used to decrease the shedding of emboli from the aorta during surgery, such as off-pump CABG without a partial occlusion clamp, or on-pump CABG with continuous perfusion without aortic clamping. Monitoring brain oxygen saturation during CABG through cerebral oximetry, to avoid profound cerebral desaturation, is also associated with better outcomes.
      • Murkin J.M.
      • Adams S.J.
      • Novick R.J.
      • Quantz M.
      • Bainbridge D.
      • Iglesias I.
      • et al.
      Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study.
      Moreover, dynamic bubble trap and arterial line filters may be considered to reduce the occurrence of stroke in patients undergoing CABG.
      • Gerriets T.
      • Schwarz N.
      • Sammer G.
      • Baehr J.
      • Stolz E.
      • Kaps M.
      • et al.
      Protecting the brain from gaseous and solid micro-emboli during coronary artery bypass grafting: a randomized controlled trial.
      • Whitaker D.C.
      • Stygall J.
      • Newman S.P.
      Neuroprotection during cardiac surgery: strategies to reduce cognitive decline.

      Value of Routine Carotid Screening

      The Society of Thoracic Surgeons and the American College of Cardiology/American Heart Association recommend ultrasound screening for carotid artery stenosis in selected patients only (class IIa recommendation, level of evidence C).
      • Hillis L.D.
      • Smith P.K.
      • Anderson J.L.
      • Bittl J.A.
      • Bridges C.R.
      • Byrne J.G.
      • et al.
      2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. Executive summary.

      The Society of Thoracic Surgeons. Five things physicians and patients should question. Choosing wisely. An initiative of the ABIM Foundation. Available at: http://www.choosingwisely.org/doctor-patient-lists/the-society-of-thoracic-surgeons/ Accessed September 4, 2013.

      • Brott T.G.
      • Halperin J.L.
      • Abbara S.
      • Bacharach J.M.
      • Barr J.D.
      • Bush R.L.
      • et al.
      2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery.
      The guidelines document
      • Gerraty R.P.
      • Gates P.C.
      • Doyle J.C.
      Carotid stenosis and perioperative stroke risk in symptomatic and asymptomatic patients undergoing vascular or coronary surgery.
      “2012 Appropriate Use Criteria for Peripheral Vascular Ultrasound and Physiological Testing” rated all clinical scenarios for cerebrovascular duplex scanning before cardiac surgery as uncertain (or “may be appropriate”).
      • Mohler III, E.R.
      • Gornik H.L.
      • Gerhard-Herman M.
      • Misra S.
      • Olin J.W.
      • Zierler R.E.
      • et al.
      ACCF/ACR/AIUM/ASE/ASN/ICAVL/SCAI/SCCT/SIR/SVM/SVS/SVU [corrected] 2012 appropriate use criteria for peripheral vascular ultrasound and physiological testing part I: arterial ultrasound and physiological testing: a report of the American College of Cardiology Foundation appropriate use criteria task force, American College of Radiology, American Institute of Ultrasound in Medicine, American Society of Echocardiography, American Society of Nephrology, Intersocietal Commission for the Accreditation of Vascular Laboratories, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Interventional Radiology, Society for Vascular Medicine, Society for Vascular Surgery, [corrected] and Society for Vascular Ultrasound. [corrected].
      The Society of Vascular and Interventional Neurology recommends screening of selected patients undergoing CABG (grade B), but screening of all patients was considered a grade D recommendation.
      • Qureshi A.I.
      • Alexandrov A.V.
      • Tegeler C.H.
      • Hobson II, R.W.
      • Dennis Baker J.
      • Hopkins L.N.
      Guidelines for screening of extracranial carotid artery disease: a statement for healthcare professionals from the multidisciplinary practice guidelines committee of the American Society of Neuroimaging; cosponsored by the Society of Vascular and Interventional Neurology.
      Because carotid artery stenosis is common in patients with coronary artery disease and is a marker of increased risk of cardiovascular events, detecting it is thought by some to be important for preoperative risk stratification.
      • Komorovsky R.
      • Desideri A.
      Carotid ultrasound assessment of patients with coronary artery disease: a useful index for risk stratification.
      However, the cost effectiveness of such nonselective screening in patients undergoing cardiac surgery is unknown. Indeed, the first research priority identified by the writing committee of the “2012 Appropriate Use Criteria for Peripheral Vascular Ultrasound and Physiologic Testing” document was to determine the clinical and cost effectiveness of carotid screening in patients undergoing cardiac surgery.
      • Mohler III, E.R.
      • Gornik H.L.
      • Gerhard-Herman M.
      • Misra S.
      • Olin J.W.
      • Zierler R.E.
      • et al.
      ACCF/ACR/AIUM/ASE/ASN/ICAVL/SCAI/SCCT/SIR/SVM/SVS/SVU [corrected] 2012 appropriate use criteria for peripheral vascular ultrasound and physiological testing part I: arterial ultrasound and physiological testing: a report of the American College of Cardiology Foundation appropriate use criteria task force, American College of Radiology, American Institute of Ultrasound in Medicine, American Society of Echocardiography, American Society of Nephrology, Intersocietal Commission for the Accreditation of Vascular Laboratories, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Interventional Radiology, Society for Vascular Medicine, Society for Vascular Surgery, [corrected] and Society for Vascular Ultrasound. [corrected].

      Conclusions

      Among patients undergoing CABG, clinical variables alone can identify those who have significant carotid artery disease with as high a degree of sensitivity as ultrasound. However, low specificity would seem to dictate ultrasound screening, and possibly additional confirmatory testing
      • Anastasiadis K.
      • Karamitsos T.D.
      • Velissaris I.
      • Makrygiannakis K.
      • Kiskinis D.
      Preoperative screening and management of carotid artery disease in patients undergoing cardiac surgery.
      of a large proportion of these patients, to alleviate a false-positive diagnosis. On the other hand, carotid duplex ultrasound screening, whether selective or nonselective, identifies only a minority of patients who will develop perioperative stroke, and intervening for those with carotid disease might not decrease the risk of these neurologic events. Absence of a direct causal relationship between carotid artery stenosis and ipsilateral stroke, and the increased morbidity associated with carotid revascularization, support the argument that prophylactic carotid revascularization might be of no benefit in asymptomatic patients undergoing CABG. This area, then, is clearly in great need of further research.

      Conflict of Interest Statement

      Authors have nothing to disclose with regard to commercial support.

      References

        • Tarakji K.G.
        • Sabik III, J.F.
        • Bhudia S.K.
        • Batizy L.H.
        • Blackstone E.H.
        Temporal onset, risk factors, and outcomes associated with stroke after coronary artery bypass grafting.
        JAMA. 2011; 305: 381-390
        • Salehiomran A.
        • Shirani S.
        • Karimi A.
        • Ahmadi H.
        • Marzban M.
        • Movahedi N.
        • et al.
        Screening of carotid artery stenosis in coronary artery bypass grafting patients.
        J Tehran Heart Cent. 2010; 5: 25-28
        • Fukuda I.
        • Gomi S.
        • Watanabe K.
        • Seita J.
        Carotid and aortic screening for coronary artery bypass grafting.
        Ann Thorac Surg. 2000; 70: 2034-2039
        • Anastasiadis K.
        • Karamitsos T.D.
        • Velissaris I.
        • Makrygiannakis K.
        • Kiskinis D.
        Preoperative screening and management of carotid artery disease in patients undergoing cardiac surgery.
        Perfusion. 2009; 24: 257-262
        • Durand D.J.
        • Perler B.A.
        • Roseborough G.S.
        • Grega M.A.
        • Borowicz Jr., L.M.
        • Baumgartner W.A.
        • et al.
        Mandatory versus selective preoperative carotid screening: a retrospective analysis.
        Ann Thorac Surg. 2004; 78 (discussion 159-66): 159-166
        • Shirani S.
        • Boroumand M.A.
        • Abbasi S.H.
        • Maghsoodi N.
        • Shakiba M.
        • Karimi A.
        • et al.
        Preoperative carotid artery screening in patients undergoing coronary artery bypass graft surgery.
        Arch Med Res. 2006; 37: 987-990
        • Lee E.J.
        • Choi K.H.
        • Ryu J.S.
        • Jeon S.B.
        • Lee S.W.
        • Park S.W.
        • et al.
        Stroke risk after coronary artery bypass graft surgery and extent of cerebral artery atherosclerosis.
        J Am Coll Cardiol. 2011; 57: 1811-1818
        • Hillis L.D.
        • Smith P.K.
        • Anderson J.L.
        • Bittl J.A.
        • Bridges C.R.
        • Byrne J.G.
        • et al.
        2011 ACCF/AHA Guideline for Coronary Artery Bypass Graft Surgery. A report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines. Developed in collaboration with the American Association for Thoracic Surgery, Society of Cardiovascular Anesthesiologists, and Society of Thoracic Surgeons. Executive summary.
        J Am Coll Cardiol. 2011; 58: 2584-2614
      1. The Society of Thoracic Surgeons. Five things physicians and patients should question. Choosing wisely. An initiative of the ABIM Foundation. Available at: http://www.choosingwisely.org/doctor-patient-lists/the-society-of-thoracic-surgeons/ Accessed September 4, 2013.

        • Naylor A.R.
        Managing patients with symptomatic coronary and carotid artery disease.
        Perspect Vasc Surg Endovasc Ther. 2010; 22: 70-76
        • Gerraty R.P.
        • Gates P.C.
        • Doyle J.C.
        Carotid stenosis and perioperative stroke risk in symptomatic and asymptomatic patients undergoing vascular or coronary surgery.
        Stroke. 1993; 24: 1115-1118
        • Li Y.
        • Walicki D.
        • Mathiesen C.
        • Jenny D.
        • Li Q.
        • Isayev Y.
        • et al.
        Strokes after cardiac surgery and relationship to carotid stenosis.
        Arch Neurol. 2009; 66: 1091-1096
        • Ghosh J.
        • Murray D.
        • Khwaja N.
        • Murphy M.O.
        • Walker M.G.
        The influence of asymptomatic significant carotid disease on mortality and morbidity in patients undergoing coronary artery bypass surgery.
        Eur J Vasc Endovasc Surg. 2005; 29: 88-90
        • Prasad S.M.
        • Li S.
        • Rankin J.S.
        • O'Brien S.M.
        • Gammie J.S.
        • Puskas J.D.
        • et al.
        Current outcomes of simultaneous carotid endarterectomy and coronary artery bypass graft surgery in North America.
        World J Surg. 2010; 34: 2292-2298
        • Naylor A.R.
        Does the risk of post-CABG stroke merit staged or synchronous reconstruction in patients with symptomatic or asymptomatic carotid disease?.
        J Cardiovasc Surg (Torino). 2009; 50: 71-81
        • Roach G.W.
        • Kanchuger M.
        • Mangano C.M.
        • Newman M.
        • Nussmeier N.
        • Wolman R.
        • et al.
        Adverse cerebral outcomes after coronary bypass surgery. Multicenter Study of Perioperative Ischemia Research Group and the Ischemia Research and Education Foundation Investigators.
        N Engl J Med. 1996; 335: 1857-1863
        • Brown P.P.
        • Kugelmass A.D.
        • Cohen D.J.
        • Reynolds M.R.
        • Culler S.D.
        • Dee A.D.
        • et al.
        The frequency and cost of complications associated with coronary artery bypass grafting surgery: results from the United States Medicare program.
        Ann Thorac Surg. 2008; 85: 1980-1986
        • Frye R.L.
        • Kronmal R.
        • Schaff H.V.
        • Myers W.O.
        • Gersh B.J.
        Stroke in coronary artery bypass graft surgery: an analysis of the CASS experience. The participants in the Coronary Artery Surgery Study.
        Int J Cardiol. 1992; 36: 213-221
        • McKhann G.M.
        • Grega M.A.
        • Borowicz Jr., L.M.
        • Bechamps M.
        • Selnes O.A.
        • Baumgartner W.A.
        • et al.
        Encephalopathy and stroke after coronary artery bypass grafting: incidence, consequences, and prediction.
        Arch Neurol. 2002; 59: 1422-1428
        • Salazar J.D.
        • Wityk R.J.
        • Grega M.A.
        • Borowicz L.M.
        • Doty J.R.
        • Petrofski J.A.
        • et al.
        Stroke after cardiac surgery: short- and long-term outcomes.
        Ann Thorac Surg. 2001; 72 (1195-201; discussion 1201-2)
        • Borger M.A.
        • Ivanov J.
        • Weisel R.D.
        • Rao V.
        • Peniston C.M.
        Stroke during coronary bypass surgery: principal role of cerebral macroemboli.
        Eur J Cardiothorac Surg. 2001; 19: 627-632
        • Schoof J.
        • Lubahn W.
        • Baeumer M.
        • Kross R.
        • Wallesch C.W.
        • Kozian A.
        • et al.
        Impaired cerebral autoregulation distal to carotid stenosis/occlusion is associated with increased risk of stroke at cardiac surgery with cardiopulmonary bypass.
        J Thorac Cardiovasc Surg. 2007; 134: 690-696
        • Hise J.H.
        • Nipper M.L.
        • Schnitker J.C.
        Stroke associated with coronary artery bypass surgery.
        AJNR Am J Neuroradiol. 1991; 12: 811-814
        • Naylor A.R.
        • Mehta Z.
        • Rothwell P.M.
        • Bell P.R.
        Carotid artery disease and stroke during coronary artery bypass: a critical review of the literature.
        Eur J Vasc Endovasc Surg. 2002; 23: 283-294
        • John R.
        • Choudhri A.F.
        • Weinberg A.D.
        • Ting W.
        • Rose E.A.
        • Smith C.R.
        • et al.
        Multicenter review of preoperative risk factors for stroke after coronary artery bypass grafting.
        Ann Thorac Surg. 2000; 69 (discussion 5-6): 30-35
        • Mickleborough L.L.
        • Walker P.M.
        • Takagi Y.
        • Ohashi M.
        • Ivanov J.
        • Tamariz M.
        Risk factors for stroke in patients undergoing coronary artery bypass grafting.
        J Thorac Cardiovasc Surg. 1996; 112 (discussion 8-9): 1250-1258
        • Lynn G.M.
        • Stefanko K.
        • Reed III, J.F.
        • Gee W.
        • Nicholas G.
        Risk factors for stroke after coronary artery bypass.
        J Thorac Cardiovasc Surg. 1992; 104: 1518-1523
        • Stamou S.C.
        • Hill P.C.
        • Dangas G.
        • Pfister A.J.
        • Boyce S.W.
        • Dullum M.K.
        • et al.
        Stroke after coronary artery bypass: incidence, predictors, and clinical outcome.
        Stroke. 2001; 32: 1508-1513
        • Blauth C.I.
        • Cosgrove D.M.
        • Webb B.W.
        • Ratliff N.B.
        • Boylan M.
        • Piedmonte M.R.
        • et al.
        Atheroembolism from the ascending aorta. An emerging problem in cardiac surgery.
        J Thorac Cardiovasc Surg. 1992; 103 (discussion 11-2): 1104-1111
        • Roffi M.
        • Ribichini F.
        • Castriota F.
        • Cremonesi A.
        Management of combined severe carotid and coronary artery disease.
        Curr Cardiol Rep. 2012; 14: 125-134
        • Reich D.L.
        • Bodian C.A.
        • Krol M.
        • Kuroda M.
        • Osinski T.
        • Thys D.M.
        Intraoperative hemodynamic predictors of mortality, stroke, and myocardial infarction after coronary artery bypass surgery.
        Anesth Analg. 1999; 89: 814-822
        • Tokuda Y.
        • Song M.H.
        • Ueda Y.
        • Usui A.
        • Akita T.
        • Yoneyama S.
        • et al.
        Three-dimensional numerical simulation of blood flow in the aortic arch during cardiopulmonary bypass.
        Eur J Cardiothorac Surg. 2008; 33: 164-167
        • Newman M.F.
        • Wolman R.
        • Kanchuger M.
        • Marschall K.
        • Mora-Mangano C.
        • Roach G.
        • et al.
        Multicenter preoperative stroke risk index for patients undergoing coronary artery bypass graft surgery. Multicenter Study of Perioperative Ischemia (McSPI) Research Group.
        Circulation. 1996; 94: II74-80
        • Hogue Jr., C.W.
        • Murphy S.F.
        • Schechtman K.B.
        • Davila-Roman V.G.
        Risk factors for early or delayed stroke after cardiac surgery.
        Circulation. 1999; 100: 642-647
        • Filsoufi F.
        • Rahmanian P.B.
        • Castillo J.G.
        • Bronster D.
        • Adams D.H.
        Incidence, topography, predictors and long-term survival after stroke in patients undergoing coronary artery bypass grafting.
        Ann Thorac Surg. 2008; 85: 862-870
        • Nishiyama K.
        • Horiguchi M.
        • Shizuta S.
        • Doi T.
        • Ehara N.
        • Tanuguchi R.
        • et al.
        Temporal pattern of strokes after on-pump and off-pump coronary artery bypass graft surgery.
        Ann Thorac Surg. 2009; 87: 1839-1844
        • D'Agostino R.S.
        • Svensson L.G.
        • Neumann D.J.
        • Balkhy H.H.
        • Williamson W.A.
        • Shahian D.M.
        Screening carotid ultrasonography and risk factors for stroke in coronary artery surgery patients.
        Ann Thorac Surg. 1996; 62: 1714-1723
        • Katz E.S.
        • Tunick P.A.
        • Rusinek H.
        • Ribakove G.
        • Spencer F.C.
        • Kronzon I.
        Protruding aortic atheromas predict stroke in elderly patients undergoing cardiopulmonary bypass: experience with intraoperative transesophageal echocardiography.
        J Am Coll Cardiol. 1992; 20: 70-77
        • Borger M.A.
        Preventing stroke during coronary bypass: are we focusing on the wrong culprit?.
        J Card Surg. 2005; 20: 58-59
        • Forbes T.L.
        • Ricco J.B.
        Trans-Atlantic debate: is carotid artery disease responsible for perioperative strokes after coronary artery bypass surgery?.
        Eur J Vasc Endovasc Surg. 2010; 40: 695
        • Sonny A.
        • Gornik H.L.
        • Yang D.
        • Mascha E.J.
        • Sessler D.I.
        Lack of association between carotid artery stenosis and stroke or myocardial injury after noncardiac surgery in high-risk patients.
        Anesthesiology. 2014; 121: 922-929
        • Redgrave J.N.
        • Lovett J.K.
        • Gallagher P.J.
        • Rothwell P.M.
        Histological assessment of 526 symptomatic carotid plaques in relation to the nature and timing of ischemic symptoms: the Oxford plaque study.
        Circulation. 2006; 113: 2320-2328
        • Michel J.B.
        • Virmani R.
        • Arbustini E.
        • Pasterkamp G.
        Intraplaque haemorrhages as the trigger of plaque vulnerability.
        Eur Heart J. 2011; 32 (85a, 85b, 85c): 1977-1985
        • Takaya N.
        • Yuan C.
        • Chu B.
        • Saam T.
        • Polissar N.L.
        • Jarvik G.P.
        • et al.
        Presence of intraplaque hemorrhage stimulates progression of carotid atherosclerotic plaques: a high-resolution magnetic resonance imaging study.
        Circulation. 2005; 111: 2768-2775
        • Singh N.
        • Moody A.R.
        • Gladstone D.J.
        • Leung G.
        • Ravikumar R.
        • Zhan J.
        • et al.
        Moderate carotid artery stenosis: MR imaging-depicted intraplaque hemorrhage predicts risk of cerebrovascular ischemic events in asymptomatic men.
        Radiology. 2009; 252: 502-508
        • Turc G.
        • Oppenheim C.
        • Naggara O.
        • Eker O.F.
        • Calvet D.
        • Lacour J.C.
        • et al.
        Relationships between recent intraplaque hemorrhage and stroke risk factors in patients with carotid stenosis: the HIRISC study.
        Arterioscler Thromb Vasc Biol. 2012; 32: 492-499
        • Cambria R.P.
        The endovascular revolution stopped at the carotid bifurcation… or did it?.
        J Vasc Surg. 2012; 56: 1748-1760
        • Jorgensen L.
        • Torvik A.
        Ischaemic cerebrovascular diseases in an autopsy series. I. Prevalence, location and predisposing factors in verified thrombo-embolic occlusions, and their significance in the pathogenesis of cerebral infarction.
        J Neurol Sci. 1966; 3: 490-509
        • Castaigne P.
        • Lhermitte F.
        • Gautier J.C.
        • Escourolle R.
        • Derouesne C.
        Internal carotid artery occlusion. A study of 61 instances in 50 patients with post-mortem data.
        Brain. 1970; 93: 231-258
        • Pessin M.S.
        • Hinton R.C.
        • Davis K.R.
        • Duncan G.W.
        • Roberson G.H.
        • Ackerman R.H.
        • et al.
        Mechanisms of acute carotid stroke.
        Ann Neurol. 1979; 6: 245-252
        • Jayasooriya G.
        • Thapar A.
        • Shalhoub J.
        • Davies A.H.
        Silent cerebral events in asymptomatic carotid stenosis.
        J Vasc Surg. 2011; 54: 227-236
        • Altaf N.
        • Goode S.D.
        • Beech A.
        • Gladman J.R.
        • Morgan P.S.
        • MacSweeney S.T.
        • et al.
        Plaque hemorrhage is a marker of thromboembolic activity in patients with symptomatic carotid disease.
        Radiology. 2011; 258: 538-545
        • Takaya N.
        • Yuan C.
        • Chu B.
        • Saam T.
        • Underhill H.
        • Cai J.
        • et al.
        Association between carotid plaque characteristics and subsequent ischemic cerebrovascular events: a prospective assessment with MRI–initial results.
        Stroke. 2006; 37: 818-823
        • Altaf N.
        • Daniels L.
        • Morgan P.S.
        • Auer D.
        • MacSweeney S.T.
        • Moody A.R.
        • et al.
        Detection of intraplaque hemorrhage by magnetic resonance imaging in symptomatic patients with mild to moderate carotid stenosis predicts recurrent neurological events.
        J Vasc Surg. 2008; 47: 337-342
        • Lusby R.J.
        • Ferrell L.D.
        • Ehrenfeld W.K.
        • Stoney R.J.
        • Wylie E.J.
        Carotid plaque hemorrhage. Its role in production of cerebral ischemia.
        Arch Surg. 1982; 117: 1479-1488
        • Silvestrini M.
        • Vernieri F.
        • Pasqualetti P.
        • Matteis M.
        • Passarelli F.
        • Troisi E.
        • et al.
        Impaired cerebral vasoreactivity and risk of stroke in patients with asymptomatic carotid artery stenosis.
        Jama. 2000; 283: 2122-2127
        • Nicolaides A.N.
        • Kakkos S.K.
        • Kyriacou E.
        • Griffin M.
        • Sabetai M.
        • Thomas D.J.
        • et al.
        Asymptomatic internal carotid artery stenosis and cerebrovascular risk stratification.
        J Vasc Surg. 2010; 52: 1486-1496.e1-5
        • Grant E.G.
        • Benson C.B.
        • Moneta G.L.
        • Alexandrov A.V.
        • Baker J.D.
        • Bluth E.I.
        • et al.
        Carotid artery stenosis: gray-scale and Doppler US diagnosis–Society of Radiologists in Ultrasound Consensus Conference.
        Radiology. 2003; 229: 340-346
      2. Screening for carotid artery stenosis: U.S. Preventive Services Task Force recommendation statement.
        Ann Intern Med. 2007; 147: 854-859
        • Nicolaides A.
        • Sabetai M.
        • Kakkos S.K.
        • Dhanjil S.
        • Tegos T.
        • Stevens J.M.
        • et al.
        The Asymptomatic Carotid Stenosis and Risk of Stroke (ACSRS) study. Aims and results of quality control.
        Int Angiol. 2003; 22: 263-272
        • Nicolaides A.N.
        • Kakkos S.K.
        • Griffin M.
        • Sabetai M.
        • Dhanjil S.
        • Tegos T.
        • et al.
        Severity of asymptomatic carotid stenosis and risk of ipsilateral hemispheric ischaemic events: results from the ACSRS study.
        Eur J Vasc Endovasc Surg. 2005; 30: 275-284
        • Jmor S.
        • El-Atrozy T.
        • Griffin M.
        • Tegos T.
        • Dhanjil S.
        • Nicolaides A.
        Grading internal carotid artery stenosis using B-mode ultrasound (in vivo study).
        Eur J Vasc Endovasc Surg. 1999; 18: 315-322
        • Griffin M.
        • Nicolaides A.
        • Kyriacou E.
        Normalisation of ultrasonic images of atherosclerotic plaques and reproducibility of grey scale median using dedicated software.
        Int Angiol. 2007; 26: 372-377
        • Elatrozy T.
        • Nicolaides A.
        • Tegos T.
        • Zarka A.Z.
        • Griffin M.
        • Sabetai M.
        The effect of B-mode ultrasonic image standardisation on the echodensity of symptomatic and asymptomatic carotid bifurcation plaques.
        Int Angiol. 1998; 17: 179-186
        • Tegos T.J.
        • Sabetai M.M.
        • Nicolaides A.N.
        • Pare G.
        • Elatrozy T.S.
        • Dhanjil S.
        • et al.
        Comparability of the ultrasonic tissue characteristics of carotid plaques.
        J Ultrasound Med. 2000; 19: 399-407
        • Sabetai M.M.
        • Tegos T.J.
        • Nicolaides A.N.
        • Dhanjil S.
        • Pare G.J.
        • Stevens J.M.
        Reproducibility of computer-quantified carotid plaque echogenicity: can we overcome the subjectivity?.
        Stroke. 2000; 31: 2189-2196
        • Geroulakos G.
        • Ramaswami G.
        • Nicolaides A.
        • James K.
        • Labropoulos N.
        • Belcaro G.
        • et al.
        Characterization of symptomatic and asymptomatic carotid plaques using high-resolution real-time ultrasonography.
        Br J Surg. 1993; 80: 1274-1277
        • Nicolaides A.N.
        • Kakkos S.K.
        • Griffin M.
        • Sabetai M.
        • Dhanjil S.
        • Thomas D.J.
        • et al.
        Effect of image normalization on carotid plaque classification and the risk of ipsilateral hemispheric ischemic events: results from the asymptomatic carotid stenosis and risk of stroke study.
        Vascular. 2005; 13: 211-221
        • Spence J.D.
        Technology Insight: ultrasound measurement of carotid plaque–patient management, genetic research, and therapy evaluation.
        Nat Clin Pract Neurol. 2006; 2: 611-619
        • Golledge J.
        • Cuming R.
        • Ellis M.
        • Davies A.H.
        • Greenhalgh R.M.
        Carotid plaque characteristics and presenting symptom.
        Br J Surg. 1997; 84: 1697-1701
        • Bassiouny H.S.
        • Sakaguchi Y.
        • Mikucki S.A.
        • McKinsey J.F.
        • Piano G.
        • Gewertz B.L.
        • et al.
        Juxtalumenal location of plaque necrosis and neoformation in symptomatic carotid stenosis.
        J Vasc Surg. 1997; 26: 585-594
        • Griffin M.B.
        • Kyriacou E.
        • Pattichis C.
        • Bond D.
        • Kakkos S.K.
        • Sabetai M.
        • et al.
        Juxtaluminal hypoechoic area in ultrasonic images of carotid plaques and hemispheric symptoms.
        J Vasc Surg. 2010; 52: 69-76
        • Pedro L.M.
        • Fernandes e Fernandes J.
        • Pedro M.M.
        • Goncalves I.
        • Dias N.V.
        • Fernandes e Fernandes R.
        • et al.
        Ultrasonographic risk score of carotid plaques.
        Eur J Vasc Endovasc Surg. 2002; 24: 492-498
        • Sztajzel R.
        • Momjian-Mayor I.
        • Comelli M.
        • Momjian S.
        Correlation of cerebrovascular symptoms and microembolic signals with the stratified gray-scale median analysis and color mapping of the carotid plaque.
        Stroke. 2006; 37: 824-829
        • Kakkos S.K.
        • Griffin M.B.
        • Nicolaides A.N.
        • Kyriacou E.
        • Sabetai M.M.
        • Tegos T.
        • et al.
        The size of juxtaluminal hypoechoic area in ultrasound images of asymptomatic carotid plaques predicts the occurrence of stroke.
        J Vasc Surg. 2013; 57 (discussion 17-8): 609-618.e1
        • Berens E.S.
        • Kouchoukos N.T.
        • Murphy S.F.
        • Wareing T.H.
        Preoperative carotid artery screening in elderly patients undergoing cardiac surgery.
        J Vasc Surg. 1992; 15 (discussion 22-3): 313-321
        • Sheiman R.G.
        Janne d'Othee B. Screening carotid sonography before elective coronary artery bypass graft surgery: who needs it.
        AJR Am J Roentgenol. 2007; 188: W475-W479
        • Salasidis G.C.
        • Latter D.A.
        • Steinmetz O.K.
        • Blair J.F.
        • Graham A.M.
        Carotid artery duplex scanning in preoperative assessment for coronary artery revascularization: the association between peripheral vascular disease, carotid artery stenosis, and stroke.
        J Vasc Surg. 1995; 21 (discussion 61-2): 154-160
        • Kiernan T.J.
        • Taqueti V.
        • Crevensten G.
        • Yan B.P.
        • Slovut D.P.
        • Jaff M.R.
        Correlates of carotid stenosis in patients undergoing coronary artery bypass grafting–a case control study.
        Vasc Med. 2009; 14: 233-237
        • Drohomirecka A.
        • Koltowski L.
        • Kwinecki P.
        • Wronecki K.
        • Cichon R.
        Risk factors for carotid artery disease in patients scheduled for coronary artery bypass grafting.
        Kardiol Pol. 2010; 68: 789-794
        • Ansari S.
        • Tan J.Y.
        • Larcos G.S.
        • Paterson H.
        Low prevalence of significant carotid artery disease on ultrasound in patients proceeding to coronary artery bypass surgery.
        Intern Med J. 2011; 41: 658-661
        • Cornily J.C.
        • Le Saux D.
        • Vinsonneau U.
        • Bezon E.
        • Le Ven F.
        • Le Gal G.
        • et al.
        Assessment of carotid artery stenosis before coronary artery bypass surgery. Is it always necessary?.
        Arch Cardiovasc Dis. 2011; 104: 77-83
        • Venkatachalam S.
        • Gray B.H.
        • Mukherjee D.
        • Shishehbor M.H.
        Contemporary management of concomitant carotid and coronary artery disease.
        Heart. 2011; 97: 175-180
        • Venkatachalam S.
        • Shishehbor M.H.
        Management of carotid disease in patients undergoing coronary artery bypass surgery: is it time to change our approach?.
        Curr Opin Cardiol. 2011; 26: 480-487
        • Augoustides J.G.
        Advances in the management of carotid artery disease: focus on recent evidence and guidelines.
        J Cardiothorac Vasc Anesth. 2012; 26: 166-171
        • Halliday A.
        • Mansfield A.
        • Marro J.
        • Peto C.
        • Peto R.
        • Potter J.
        • et al.
        Prevention of disabling and fatal strokes by successful carotid endarterectomy in patients without recent neurological symptoms: randomised controlled trial.
        Lancet. 2004; 363: 1491-1502
      3. Endarterectomy for asymptomatic carotid artery stenosis. Executive Committee for the Asymptomatic Carotid Atherosclerosis Study.
        JAMA. 1995; 273: 1421-1428
        • Knipp S.C.
        • Scherag A.
        • Beyersdorf F.
        • Cremer J.
        • Diener H.C.
        • Haverich J.A.
        • et al.
        Randomized comparison of synchronous CABG and carotid endarterectomy vs. isolated CABG in patients with asymptomatic carotid stenosis: the CABACS trial.
        Int J Stroke. 2012; 7: 354-360
        • Shishehbor M.H.
        • Venkatachalam S.
        • Sun Z.
        • Rajeswaran J.
        • Kapadia S.R.
        • Bajzer C.
        • et al.
        A direct comparison of early and late outcomes with three approaches to carotid revascularization and open heart surgery.
        J Am Coll Cardiol. 2013; 62: 1948-1956
        • Barbut D.
        • Grassineau D.
        • Lis E.
        • Heier L.
        • Hartman G.S.
        • Isom O.W.
        Posterior distribution of infarcts in strokes related to cardiac operations.
        Ann Thorac Surg. 1998; 65: 1656-1659
        • Manabe S.
        • Shimokawa T.
        • Fukui T.
        • Fumimoto K.U.
        • Ozawa N.
        • Seki H.
        • et al.
        Influence of carotid artery stenosis on stroke in patients undergoing off-pump coronary artery bypass grafting.
        Eur J Cardiothorac Surg. 2008; 34: 1005-1008
        • Baiou D.
        • Karageorge A.
        • Spyt T.
        • Naylor A.R.
        Patients undergoing cardiac surgery with asymptomatic unilateral carotid stenoses have a low risk of peri-operative stroke.
        Eur J Vasc Endovasc Surg. 2009; 38: 556-559
        • Mahmoudi M.
        • Hill P.C.
        • Xue Z.
        • Torguson R.
        • Ali G.
        • Boyce S.W.
        • et al.
        Patients with severe asymptomatic carotid artery stenosis do not have a higher risk of stroke and mortality after coronary artery bypass surgery.
        Stroke. 2011; 42: 2801-2805
        • Naylor A.R.
        • Bown M.J.
        Stroke after cardiac surgery and its association with asymptomatic carotid disease: an updated systematic review and meta-analysis.
        Eur J Vasc Endovasc Surg. 2011; 41: 607-624
        • Naylor A.R.
        Synchronous cardiac and carotid revascularisation: the devil is in the detail.
        Eur J Vasc Endovasc Surg. 2010; 40: 303-308
        • Antithrombotic Trialists' Collaboration
        Collaborative meta-analysis of randomised trials of antiplatelet therapy for prevention of death, myocardial infarction, and stroke in high risk patients.
        BMJ. 2002; 324: 71-86
        • Murkin J.M.
        • Adams S.J.
        • Novick R.J.
        • Quantz M.
        • Bainbridge D.
        • Iglesias I.
        • et al.
        Monitoring brain oxygen saturation during coronary bypass surgery: a randomized, prospective study.
        Anesth Analg. 2007; 104: 51-58
        • Gerriets T.
        • Schwarz N.
        • Sammer G.
        • Baehr J.
        • Stolz E.
        • Kaps M.
        • et al.
        Protecting the brain from gaseous and solid micro-emboli during coronary artery bypass grafting: a randomized controlled trial.
        Eur Heart J. 2010; 31: 360-368
        • Whitaker D.C.
        • Stygall J.
        • Newman S.P.
        Neuroprotection during cardiac surgery: strategies to reduce cognitive decline.
        Perfusion. 2002; 17: 69-75
        • Brott T.G.
        • Halperin J.L.
        • Abbara S.
        • Bacharach J.M.
        • Barr J.D.
        • Bush R.L.
        • et al.
        2011 ASA/ACCF/AHA/AANN/AANS/ACR/ASNR/CNS/SAIP/SCAI/SIR/SNIS/SVM/SVS guideline on the management of patients with extracranial carotid and vertebral artery disease: executive summary: a report of the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines, and the American Stroke Association, American Association of Neuroscience Nurses, American Association of Neurological Surgeons, American College of Radiology, American Society of Neuroradiology, Congress of Neurological Surgeons, Society of Atherosclerosis Imaging and Prevention, Society for Cardiovascular Angiography and Interventions, Society of Interventional Radiology, Society of NeuroInterventional Surgery, Society for Vascular Medicine, and Society for Vascular Surgery.
        J Am Coll Cardiol. 2011; 57: 1002-1044
        • Mohler III, E.R.
        • Gornik H.L.
        • Gerhard-Herman M.
        • Misra S.
        • Olin J.W.
        • Zierler R.E.
        • et al.
        ACCF/ACR/AIUM/ASE/ASN/ICAVL/SCAI/SCCT/SIR/SVM/SVS/SVU [corrected] 2012 appropriate use criteria for peripheral vascular ultrasound and physiological testing part I: arterial ultrasound and physiological testing: a report of the American College of Cardiology Foundation appropriate use criteria task force, American College of Radiology, American Institute of Ultrasound in Medicine, American Society of Echocardiography, American Society of Nephrology, Intersocietal Commission for the Accreditation of Vascular Laboratories, Society for Cardiovascular Angiography and Interventions, Society of Cardiovascular Computed Tomography, Society for Interventional Radiology, Society for Vascular Medicine, Society for Vascular Surgery, [corrected] and Society for Vascular Ultrasound. [corrected].
        J Am Coll Cardiol. 2012; 60: 242-276
        • Qureshi A.I.
        • Alexandrov A.V.
        • Tegeler C.H.
        • Hobson II, R.W.
        • Dennis Baker J.
        • Hopkins L.N.
        Guidelines for screening of extracranial carotid artery disease: a statement for healthcare professionals from the multidisciplinary practice guidelines committee of the American Society of Neuroimaging; cosponsored by the Society of Vascular and Interventional Neurology.
        J Neuroimaging. 2007; 17: 19-47
        • Komorovsky R.
        • Desideri A.
        Carotid ultrasound assessment of patients with coronary artery disease: a useful index for risk stratification.
        Vasc Health Risk Manag. 2005; 1: 131-136
        • Wanamaker K.M.
        • Moraca R.J.
        • Nitzberg D.
        • Magovern Jr., G.J.
        Contemporary incidence and risk factors for carotid artery disease in patients referred for coronary artery bypass surgery.
        J Cardiothorac Surg. 2012; 7: 78