Carotid Artery Stenosis, Carotid Endarterectomy

& Stroke Prevention

Joseph V. Lombardi, MD Professor & Chief, Division of Vascular Surgery

Director, Cooper Aortic Center Cooper University Hospital

• Stroke is the third leading cause of death in the Western world

• Principal cause of permanent neurological disability

• More than half of all stroke survivors remaining dependent on others for everyday activities

• Carotid-related ischemic strokes are perhaps the most amenable to treatment to prevent further major strokes or death

Transient Monocular Blindness Associated with Hemiplegia Charles Miller Fischer 1952 “a sort of warning that disaster threatened”

The link between carotid disease and stroke

Presenter

Presentation Notes

This year, 2017, sees the 65th anniversary of the publication of the classic paper by Fisher, “Transient Monocular Blindness Associated with Hemiplegia” (Figure 2), which was to usher in a new era in vascular neurology5 . In this clinical study, Fisher analyzed seven patients with transitory blindness and observed that this finding could be “a sort of warning that disaster threatened”2,5. At the time, he changed the term that he had used previously, transient unilateral blindness, to transient monocular blindness, to avoid confusion with unilateral loss of vision from hemianopsia2,5. He described his first patient diagnosed with this clinical condition in 1950, when he was at the Queen Mary Veterans’ Hospital, Montreal, Canada: “A patient with a left-sided paralysis reported that, before his stroke, he had several brief spells of blindness in his right eye”2,5,6. The patient himself commented, “Isn’t it funny, it was in the wrong eye? I went blind in the right eye and got paralyzed on the left side.” The patient had metastatic colorectal cancer and died soon afterward. The autopsy revealed occlusion of the right internal carotid artery in the neck (Figure 3)2,5,6. Fisher also described 150 cases in the literature in which transient monocular blindness was associated with different causes (arteriosclerosis, spasm, migraine, Raynaud’s disease, reflex amaurosis and arteritis) but not, at the time, with carotid artery disease2,7. Fisher initially believed that the basic mechanism involved vasospasm but said that “the exact relation of the carotid occlusion to the transient phenomena is far from clear”2,5.However, subsequent studies of carotid stenosis between 1954 and 1962 and the definition of TIA (transient ischemic attack, with brain ischemic lesions completely resolved in less than 24 hours) led Fisher to conclude in 1976, that the basic mechanism of transient monocular blindness was related to the presence of microembolism (“The microembolic theory of transient ischemic attacks”)2,8. He remarked, “It’s amazing how facts, that today are readily obvious, were ignored at that time”2 and, in 1989, he declared that he opposed the use of the term “amaurosis fugax”, preferring the term he had defined previously (transient monocular blindness)9 http://www.scielo.br/pdf/anp/v75n10/0004-282X-anp-75-10-0754.pdf

”one day surgeons may even devise a method to remove the offending plaque and thereby prevent stroke”

The link between carotid disease and stroke.

Stroke. 1995;26:188-201

Guidelines for Carotid Endarterectomy A Multidisciplinary Consensus Statement From the Ad Hoc Committee, American Heart Association

Degree of Carotid Stenosis as a Surrogate for Stroke Risk & Rate

The rupture prone atherosclerotic plaque has a thin fibrous cap overlaying a large necrotic core. shows a carotid plaque with a large necrotic core (block arrow) containing hemorrhage (red staining). The fibrous cap shows a dramatic thinning near the shoulder of the core (arrow in the lumen).

The Carotid Plaque & Rupture Risk • The rupture prone

atherosclerotic plaque has a thin fibrous cap overlaying a large necrotic core

• Block Arrow: carotid plaque with a large necrotic core containing hemorrhage (red staining)

• The fibrous cap shows a dramatic thinning near the shoulder of the core (arrow in the lumen).

The Ruptured Carotid Plaque • Large arrow: common

carotid cap disruption

• Asterisk: fibrous cap

• Small Arrow: cap overlaid with thrombus on the left

• Chevron: organizing thrombus

Major Studies Controversies Current Guidelines

• Symptomatic

• Asymptomatic

• CEA vs CAS

• MicroEmboli • “silent

stroke”

• AHA,ASA,ACCF, SVS Guidelines

• Take Away Message

Symptomatic Asymptomatic

Symptomatic

Symptomatic • NASCET trial (North American Symptomatic

Carotid Endartectomy Trial)

• 2 year stroke risk 70-99% Stenosis • 9% w/ CEA and 26% w/ medical

management

• 2 year stroke risk 50-69% stenosis • 9% w/ CEA and 15% with medical

management.

Asymptomatic

Asymptomatic • ACAS - asymptomatic carotid atherosclerosis

study • 5 year stroke risk >60 % Stenosis

• 5.1% risk w/ CEA and 11% w/ medial management.

STATINS and Antiplatelet Agents

Presenter

Presentation Notes

Medical management is imperative for the treatment of carotid disease https://onlinelibrary.wiley.com/doi/pdf/10.1111/eci.12340 The direct effects of statins on stabilization of human carotid plaques were also investigated [70–76]. We recently showed that an ongoing statin treatment might be associated with reduction in the systemic activation of the receptor activator of NF-kB ligand (RANKL)/osteoprotegerin (OPG) system in patients with severe carotid stenosis and asymptomatic for ischaemic stroke [77]. This beneficial improvement might be associated with a decrease in neutrophil activation and related vulnerability [77]. Table 2 summarizes the main studies evaluating the pleiotropic effects of statins on human carotid plaque structure and related vulnerability. Figure 1 Statin-mediated pleiotropic activities in atherogenesis. Independently of lowering cholesterol levels, statins were shown to reduce subclinical systemic inflammation (serum C-reactive protein [CRP] levels), endothelial activation, leucocyte intraplaque infiltration, and increase protective smooth muscle cell migration. The final result of these histological features is represented by an improvement in carotid plaque vulnerability Statins exert their pleiotropic effects by reducing subclinical systemic inflammation and promoting intraplaque stabilization indecently of lowering serum cholesterol levels. These benefi- cial effects were demonstrated by a variety of basic research and clinical studies [61–63]. Recently, our research group showed that pre-incubation with different statins was able to reduce chemokine release, upregulation of adhesion molecules and chemotaxis in vitro in human monocytes exposed to CRP (Fig. 1) [64]. Additional benefits were induced by statins on endothelial cell activation [65] and apoptosis [66] (Fig. 1). Although the effects mediated by statins on endothelial cell apoptosis are still controversial [67], these cells represent a critical target in different phases of atherogenesis and drugs (such as statins) potentially interfering with their dysfunction could be of particular interest. An indirect confirmation of the pleiotropic effects of statins is represented by the complex relationship between lipids and stroke. Whereas the association between cholesterol levels and stroke is less significantly consistent than that between cholesterol levels and coronary artery disease, statins were shown to be effective on both primary and secondary stroke prevention trials [68,69].

• Reduce: • C-RP • endothelial activation • leukocyte intraplaque infiltration especially

macrophages

• Increase: • Protective smooth muscle cell migration

• Net result is a more stable, less likely to embolize,

plaque

Presenter

Presentation Notes

Medical management is not enough

• Stroke 2007

• 1065 patients with any degree of carotid stenosis • 2 duplex studies 7 months apart • Followed for a median of 3 years

• ~10 % of patients had progression of disease in

the 7 month period

• Progression of disease was

associated with a 2 fold increase in stroke risk

• 70% of patients with progression of disease were being treated with statins

• Disease progressed despite medical management

CEA vs CAS

Carotid Endarterectomy

• Duplex US usually primary screening tool • Followed by CT or MRA • Look at Degree of stenosis and plaque morphology

• >50% symptomatic • >70-80 asymptomatic

• Antiplatelet agents are started or maintained for patients with critical disease

• General Anesthesia or Cervical Block • Duplex US

Carotid Endarterectomy

• General Anesthesia or Cervical Block • Duplex US identifies exact location of the carotid bifurcation

• Minimizes incision length

• Patient is monitored using EEG • MAP is brought above 90 mmHg prior to clamping • If EEG demonstrates decreased amplitudes or slowing of the wave

forms, a shunt is planned

• Endarterectomy (CEA) • Stenting (Stent)

Carotid Endarterectomy @ Cooper

• 2017 • 144 CEA’s • Symptomatic

• 27(18%)

• Asymptomatic • 117(82%)

• Cumulative Stroke • 3(2%)

Vascular, Vol. 20 No. 4, pp. 181–187, 2012

J Vasc Surg 2010;51:584-92.

J Vasc Surg 2010;51:584-92.

J Vasc Surg 2010;51:584-92.

• 21% of CAS patients had new DW-MRI lesions at 24 hours post op

• In CAS patients, new lesions at DW-MRI were significantly associated with a postoperative MMSE score decline >5 points (P .001).

Presenter

Presentation Notes

Increased biomarkers for neurologic stress and injury

\

Presenter

Presentation Notes

https://ac.els-cdn.com/S0741521411001935/1-s2.0-S0741521411001935-main.pdf?_tid=c20e1ae3-b755-4a9d-a47c-704bb7e6c507&acdnat=1523838106_4b8395ec99a8078d79aea6867494e60a

(Stroke. 2009;40:230-234.)

Presenter

Presentation Notes

Predictive value of HITS and subsequent ipsilateral ischemic event. Seven studies prospectively reported data on rates of ipsilateral ischemic stroke or TIA during a period of follow-up in patients who were asymptomatic at baseline. Six of these also provided data on risk of stroke alone (Table IV).29,50,57,73-76 The mean follow-up varied from 9 to 34 months. The percentage of patients experiencing a stroke or TIA during follow-up was higher in those positive for HITS compared with those negative for HITS (median 28% vs 2%; P .001) (Fig 4, A). The same was true for the end point of stroke alone (median 10% vs 1%; P .004) (Fig 4, B). Co https://ac.els-cdn.com/S0741521411001935/1-s2.0-S0741521411001935-main.pdf?_tid=c20e1ae3-b755-4a9d-a47c-704bb7e6c507&acdnat=1523838106_4b8395ec99a8078d79aea6867494e60a

Intense Medical Management

Endarterectomy

Stenting

Crest 2

Crest 2

Plan to assess: • treatment differences between IMM

alone compared to carotid endarterectomy (CEA) plus IMM

• treatment differences between IMM alone compared to carotid stenting (CAS) plus IMM

Crest 2

Goal to enroll 2480 participants 40% women and 12% minorities • ≥35 years, have narrowing (≥70%) of at least 1

of their carotid arteries, • no history of ipsilateral stroke or TIA within

180 days of randomization • carotid stenosis that is treatable with CEA or

CAS, and lack other serious medical conditions

Crest 2

• Primary outcome: proportion of patients who experience the composite end point of any stroke or death within 44 days of randomization or ipsilateral stroke ≤4 years thereafter

Crest 2

Secondary outcomes: • whether IMM differs from CEA and

from CAS in terms of cognitive function at 4 years

• if there are differences in major stroke, minor stroke, disabling stroke, non-disabling stroke, and tissue-based stroke at 4-years

• if the CEA or CAS versus IMM difference is affected by • age • sex • severity of carotid stenosis,

restenosis • risk factor level • duration of asymptomatic

period

Current Guidelines & Literature

Conclusion

• Carotid endarterectomy is the gold standard for stroke prevention in carotid disease

• Patients with symptomatic or asymptomatic carotid disease should be referred to a vascular surgeon for further workup, surveillance and treatment.