1. Marvin D. Atkins, Jr., MD Division of Vascular Surgery Temple, Texas, USA April 2011 Marvin D. Atkins, Jr., MD Division of Vascular Surgery Temple, Texas, USA April 2011 Carotid Artery Occlusive Disease Update 2011 Carotid Artery Occlusive Disease Update 2011

2. Stroke in the United States Third leading cause of adult death and leading cause of Neurologic Disability in the United States.  Approximately 750,000 new cases per year.  Annual Cost ~$40,000,000,000  Framingham Study – 88% ischemic, 9% intracerebral hemorrhage, and 3% SAH  Estimated that 30% of ischemic strokes are related to carotid disease.

3. Carotid Surgery Carotid artery occlusive disease is the most readily treatable lesion leading to stroke. Carotid endarterectomy is the most common operative procedure in peripheral vascular surgery.

4. Carotid Occlusive Disease Atherosclerosis produces 90% of lesionsOther causes: Fibromuscular dysplasia carotid kinking/coils extrinsic compression Trauma intimal dissection vasculitis radiation

5. Other Causes

6. Distribution of atherosclerotic occlusive lesions

7. Carotid Plaque and Embolization

9. Carotid Plaque

10. PATIENT PRESENTATION Asymptomatic cervical bruit. Transient hemispheric neurologic deficit Transient monocular dysfunction (amaurosis fugax). Stroke with or without residual deficit. Acute stroke or stroke in evolution.

11. Carotid Bruits Present in 5% of the > 50 y/o population. Only 23% of bruits associated with >50% carotid artery stenosis. Less than half of hemodynamically significant lesions have a bruit. Stronger predictor of significant coronary artery disease.

12. Surgical Emergencies Crescendo TIA: escalating frequency with resolution between. Stroke in evolution: Waxing and waning symptoms without complete resolution between. Urgent surgical treatment: improved results with complete recovery in up to 70%.

13. Completed Stroke Decision to evaluate best determined by whether another stroke in same distribution would likely impair patient substantially beyond current level For small strokes and resolved deficits, surgery can be done sooner than has been recommended in past.

14. Most of these symptoms are more likely to be a manifestation of cardiac arrhythmias, seizures, migraine, or other non-vascular-related conditions

15. Screening Recommendations

16. Recently published intersociety guidelines JACC

17. Class I Known or suspected carotid disease – Ultrasound (US) recommended as first line screening test Class 2a US is reasonable in asymptomatic pts w/ bruit Annual US in those with >50% stenosis Class 2b US may be reasonable in those with CAD, AAA, or PVD Class 3 Not recommended in asymptomatic pts without risk factors

18. Medical Management: Recommendations

19. Smoking Cessation Statin is recommended for all pts with carotid dz to lower LDL < 100 (Class 1, level B), possibly even < 70 (Class 2A, level B) HTN – below 140/90 Control of Diabetes to Hba1C < 7 Antiplatelet recommendations :

21. Practical Recommendations: Aspirin as first line therapy - 325mg for larger patients, 81mg for small pts or those complaining of bleeding/bruising. Increase antiplatelet regimen if symptoms develop - Add Aggrenox (ASA 25mg/Dipyridamole 200mg) BID - or Plavix 75mg QD Do Not stop antiplatelet agents prior to CEA. - Add statin (Lipitor > Pravachol or Zocor) Ok to stop if asymptomatic prior to another procedure. Restart as soon as possible.

22. Surgical Management: Evaluation

23. History Symptoms Risk factors non-modifiable: age, gender, race, heredity. modifiable: HTN, tobacco, cholesterol, DM, cardiac disease. Physical Examination Neurologic exam Bilateral arm pressures Carotid bruit? Vascular disease in other territories Patient Evaluation

24. EVALUATION TECHNIQUES Search for arterial lesions, coagulopathy, sources for emboli. Duplex imaging. Brain imaging - CT or MRI to determine areas of cerebral damage or alternative pathology, i.e. tumors, aneurysms, vascular malformations, etc. CT Angiography MR Angiography Contrast angiography

25. EVALUATION TECHNIQUES Duplex Imaging B-mode ultrasound combined with spectral analysis of flow velocities determined by doppler identifies:  Degree of stenosis  Plaque morphology and surface characteristics *** Plaque surface characteristics may be more significant than degree of stenosis in determining risk for cerebral vascular events.

26. Duplex imaging is advocated as sole means of evaluating carotid disease by many: 7-10% error rate in “best of hands.” Positive predictive value > 90% identifying 70-99% internal carotid stenosis. No evaluation of distal ICA or intracranial stenosis. Carotid Duplex Imaging

27. Unstable Plaque Surfaces

28. Less than 50% Peak systolic:<130 cm/sec ICA:CCA ratio:< 1.8 50% to 69% Peak systolic:130 to 210 cm/sec ICA:CCA ratio:1.8 to 3.1 70% to 99% Peak systolic:> 210 cm/sec ICA:CCA ratio:> 3.1 Duplex Criteria for Native Carotid Lesions

29. *** Other high risk ultrasound findings include : ulcers, intraplaque hemorrhage, intraluminal thrombus or debris, intimal flaps or dissections. Ulcerative Plaque Characteristics

30. Ulcerative Plaque By Duplex Ultrasound

31. Intraplaque Hemorrhage: High risk for fibrous cap rupture, embolism and neurological symptoms.

32. Complex Irregular Plaque By Duplex Ultrasound

33. Contrast Angiography: “Gold Standard” for anatomical detail Provides information about tandem atherosclerotic disease, plaque morphology, and collateral circulation. Invasive procedure 0.1-1% stroke rate with angiogram alone during NASCET and ACAS trials.

34. MR Angiography:  Non invasive  MRI Contrast contraindicated with impaired renal function  Does not provide bony anatomical detail useful in surgical planning  No pacemakers, etc

35. CT Angiogram:  High resolution anatomical detail with good bone and calcium definition.  Iodinated contrast load can be similar to conventional angiography.  3-D imaging requires post scanning production to create images.

36. Estimating Stenosis

37. Endarterectomy Trials

38. 659 Pts, 50 centers: TIA, Afx, Non-Disabling CVA within 6 months: Best Med vs CEA + best Med Perioperative stroke/death rate = 5.8% Symptomatic Carotid Stenosis: NASCET Trial

39. 1662 Pts, 39 centers: Asymptomatic Carotid Stenosis > 60% Best Med vs. Best Med plus CEA. Outcomes: ipsilateral CVA or any CVA or death Over half periop events related to angiogram Conclusion: CEA for ASX stenosis > 60% justified with careful technique and patient selection. Asymptomatic Carotid Stenosis: ACAS Trial

40. Long-term Risk of Stroke

41. Operative Risk and Stroke Prevention

42. CREST Study Design Prospective, multicenter, randomized, controlled trial with blinded endpoint adjudication. Comparing CEA and CAS in participants with symptomatic and asymptomatic stenosis 108 US and 9 Canadian sites Team included neurologist, interventionalist, surgeon, and research coordinator at each center. NEJM May, 2010.

43. CAS (n=1262) CEA (n=1240) Age69 Female - %3634 Asymptomatic - %47 Hypertension - %86 Diabetes - %30 Dyslipidemia - %8285 Current smoker - %26 CREST: Patient Characteristics

44. Peri-procedural (a composite of):  any Clinical Stroke  Myocardial infarction  Death Post-procedural  Ipsilateral stroke up to 4 years CREST Primary Endpoint

45. An acute neurological ischemic event of at least 24 hours duration with focal signs and symptoms. Adjudicated by at least two neurologists blinded to treatment CREST: Stroke

46. Combination: Elevation of cardiac enzymes (CK-MB or troponin) to a value 2 or more times the individual clinical center's laboratory upper limit of normal. Plus Chest pain or equivalent symptoms consistent with myocardial ischemia, or, ECG evidence of ischemia including new ST segment depression or elevation > 1mm in 2 or more contiguous leads Not enzyme-only Adjudicated by two cardiologists blinded to treatment CREST: Myocardial Infarction

47. Primary Endpoint: peri-procedural components (any death, stroke, or MI within peri-procedural period) CAS vs. CEAHazard Ratio, 95% CIP-Value 5.24.5 5.2 vs. 4.5 % HR = 1.18; 95% CI: 0.82-1.680.38

48. Peri-procedural Stroke and MI CAS vs. CEAHazard Ratio 95% CI P- Value Stroke 4.12.3 4.1 vs. 2.3 % HR = 1.79; 95% CI: 1.14-2.820.01 MI 1.12.3 1.1 vs. 2.3 % HR = 0.50; 95% CI: 0.26-0.940.03

49. Peri-procedural Stroke CAS vs. CEAHazard Ratio 95% CI P- Value All Stroke 4.12.3 4.1 vs. 2.3 % HR = 1.79; 95% CI: 1.14-2.820.01 Major Stroke 0.90.6 0.9 vs. 0.6 % HR = 1.35; 95% CI: 0.54-3.360.52 “The quality of life analysis among survivors at one year in our trial indicate that stroke had a greater adverse effect on a broad range of health-status domains than did myocardial infarction”

50. Ipsilateral Stroke after Peri-procedural Period ≤ 4 years CAS vs. CEAHazard Ratio, 95% CI P- Value 2.02.4 2.0 vs. 2.4 % HR = 0.94; 95% CI: 0.50-1.760.85

51. CREST Conclusions CEA and CAS have similar net outcomes though the individual risks vary, lower stroke with CEA and lower MI with CAS.

52. CREST and Octagenarians The risk of stroke with CAS was 13 x higher in those past the age of 80. Thought to be due to plaque within the aortic arch that is disrupted with catheter / wire manipulation. CAS not recommended in those >80 except in the most extenuating of circumstances. (High lesions, radiation to neck, tracheostomy, high cardiac risk, etc)

53. Center for Medicare/Medicaid Services (CMS) criteria for Carotid Artery Stent (CAS) reimbursement 2011: 1.Symptomatic patient 2.>70% stenosis 3.“High Risk” patient All three criteria must be met, and a distal embolic protection device must be used. At present, CMS has no plans to expand CAS coverage following the results of the CREST trial.

54. Surgical Management: Patient Selection

55. Less than 50% carotid stenosis regardless of plaque morphology 50-69% stenoses with low risk or stable plaques Treatment centers on preventing platelet aggregation and embolization Recommended drugs: Aspirin 160-325mg./day Clopidogeral (Plavix) 75 mg/day Ticlopidine (Ticlid) 250mg. b.i.d. Aggressive lipid control MEDICAL MANAGEMENT

56. FOLLOW-UP GUIDELINES Nonsurgical patients with significant disease: Duplex imaging every 6-12 months depending upon plaque morphology and rate of stenosis progression Immediate re-evaluation if new symptoms develop

57. Carotid Endarterectomy: Indications Symptomatic Disease Carotid Stenosis > 70% stenosis Acceptable > 50% stenosis* Unacceptable if stroke/death > 5% Asymptomatic Disease Carotid Stenosis > 60% stenosis Unacceptable if stroke/death > 3% * Look for other causes of stroke – TEE, Holter, Hypercoagulable work-up

58. So why are you watching my asymptomatic patient with a 70-99% carotid stenosis by Ultrasound? ACAS and other trials would suggest a surgeon has to do ~ 17 uncomplicated CEA’s to prevent one stroke. A 70-99% US stenosis may not be equivalent to a 60% or greater angiographic stenosis (which was used in the trials). I agree, very confusing. Several studies suggest, elevated EDV >100 or 125 cm/s and spectral broadening confer hemodynamic significance. The individual patients comorbidities, age, and ultrasound plaque characteristics are all taken into account.

59. Carotid Endarterectomy: Technique

60. Neck Incision Carotid Endarterectomy Endarterectomy Ouriel and Rutherford

61. Carotid Endarterectomy

63. Carotid Endarterectomy: Shunt insertion

64. Carotid Endarterectomy: Plaque Removal

67. Carotid Endarterectomy: Vein Patch

68. Carotid Endarterectomy: Complications

69. Asymptomatic Lesions 3%TIA 5%Ischemic Stroke 7%Recurrent disease 10%30 Day Mortality 2% Combined Stroke and Death Rate *** Leading cause of death is myocardial infarction ***

70. Postoperative carotid artery thrombosisCerebral ischemia during carotid clampingIntraoperative embolizationReperfusion edemaIntra-cerebral hemorrhage Causes of Perioperative Stroke

71. Recurrent laryngeal nerve 1.5-15%Hypoglossal nerve 4-6%Marginal mandibular nerve 1-3%Superior laryngeal nerve 1-3% Spinal accessory nerve 0.5-1% Complications: Nerve Injury *** most are transient ***

72. Recurrent laryngeal nerve Hypoglossal nerve Cranial Nerve Injury

73. Surgical Management: Follow-up Guidelines

74. Incidence 5-22% (1.5 to 4.5% annual) Pathology < 2 mos :residual atherosclerosis < 24 mos:neointimal hyperplasia > 36 mos :recurrent atherosclerosis Recurrent Stenosis Diabetes mellitus Hyperlipidemia Hypertension Smoking Young patient Women Risk Factors Recurrent Stenosis

75. Summary Recommendations

76. SURGICAL MANAGEMENT Asymptomatic 80 to 99% in surgically fit patient Consider in >60% range if unfavorable plaque. Symptomatic 50% or higher Implies ideal surgical results and optimum surgical risk. Recurrent Disease If symptomatic Stent v. Surgical Reconstruction Patient Selection

77. Summary Carotid artery occlusive disease is the most readily treatable lesion leading to stroke. In appropriately selected patients, Carotid endarterectomy remains a safe and effective treatment of cervical carotid occlusive disease.