Servier – Phlebolymphology

Cerebrovascular diseases

Beyond endarterectomy, is there a better option for management of carotid disease?
Lecture by J Fernandes e Fernandes (Portugal)

In the first part of his lecture, Professor Fernandes presented the results of several trials analyzing medical treatment versus open surgery in the treatment of carotid artery stenosis. He listed the indications for open surgery in symptomatic and asymptomatic patients, and recommended the use of carotid ultrasound as a test of choice. If ultrasound does not produce a clear-cut result, the preoperative study should be completed by angio computed tomography (aCT) and nuclear magnetic resonance (MR) and, only in selected cases, by digital arteriography.

Professor Fernandes e Fernandes emphasized the importance of disabling strokes in previously asymptomatic patients with carotid stenosis. The stability of the carotid plaque will be one of the most important criteria in deciding on the best treatment in the near future. There is evidence that, in asymptomatic carotid disease, the risk of stroke is 2% per year, and these patients also have increased cardiovascular risk and mortality. Plaque structure and activity index, measured by high-definition ultrasonography with power Doppler and computer-assisted analysis, will establish new indications in the treatment of carotid stenosis. Higher activity index reflects and unstable plaque which can produce symptoms proximally. Plaque echolucency, measured by grey scale median (GSM) values, indicates plaque stability. The author presented the ACSRS study where 112 carotid plaques were studied by a double-blind analysis to determine the activity index in asymptomatic patients. The absolute risk of cerebrovascular events was 2.9% per year. A high activity index (more than 65) is very frequent when plaque is unstable, and surgery in 5 such patients is needed to prevent one event in four years.

In the second part of his lecture, Professor Fernandes e Fernandes analyzed the choice between carotid artery stenting (CAS) and carotid endarterectomy (CEA). He performed a review of published trials and emphasized the importance of microembolization during CAS determined by transcranial Doppler. Microembolization is more frequent during CAS in the presence of echolucent plaques. Some issues concerning CAS must be resolved before it can be selected as a first-choice therapeutic option. There is a need for studies with adequate analysis of patients, patient registries, standardization of CAS procedures and analyses of plaque structure (pre-procedural, quantification of heparin-induced thrombocytopenia, brain imaging pre- and post-procedure and cognitive function analysis). Surgery is highly effective in the treatment of carotid stenosis. It is nonselective, low-risk, has a low restenosis rate, and is cost effective.

Professor Fernandes e Fernandes concluded that there is no balanced decision between CAS and CEA. Current evidence does not support a shift away from CEA as standard treatment of carotid stenosis. CAS is an attractive treatment and potentially useful in selected patients (neck radiation, restenosis after CEA, very high-risk patients and ostial disease in supra-aortic trunks). For these reasons, CEA continues to be the first option in the treatment of carotid stenosis. We need properly designed randomized trials to define the indications of CAS.

Moderators: J Fernandes e Fernandes (Portugal), M Lazaridis (Greece)
Participants: Sir P Bell (UK), J Fernandes e Fernandes (Portugal), C Liapis (Greece), D Palumbo (Italy)

Carotid stenting – what went wrong? The procedure or the trials?
Sir P. Bell (UK)

The author started his presentation by commenting on the low scientific quality of the majority of studies designed to evaluate carotid artery stenting (CAS). Most studies are nonrandomized or series without follow-up. Sir P Bell outlined the principal problems with the majority of trials, such as failure to include sufficient patients in both arms, exclusion of females or elderly patients, exclusion of difficult cases, protocol violations, industry funding and involvement in the trials, use of biased end points, poor training of operators, crossover of patients, etc.

In the majority of trials, carotid stenting gave worse results than open surgery. CAS is probably indicated only in very specific cases (neck radiation, restenosis)and so Professor Bell avoids recommending CAS to most of his patients.

There are several unresolved questions in the field of carotid stenosis, such as the best timing of treatment of symptomatic patients with unstable plaque, with recent studies demonstrating the benefit of very early surgery. Another question is the use of statins and antiplatelet drugs in the acute phase to stabilize the plaque before surgery after one non-disabling stroke.

In conclusion, Sir P Bell highlighted the importance of analyzing plaque characteristics and of correct medical therapy, and the need to wait for new welldesigned trials.

Moderators: Sir P Bell (UK), C Klonaris (Greece)
Participants: E Bastounis (Greece), B Van Bellen (Brazil), G Torsello (Germany), G Biasi (Italy), MF Giannoni (Italy)

Carotid endarterectomy: is it still the gold standard?
E Bastounis (Greece)

The results of a personal series including 1271 carotid endarterectomy (CEA) were presented. The study was performed in 1083 patients (260 females, 130 high-risk patients, 120 older than 80 years, 89 redo operations, 127 with high cervical lesions, 59% symptomatic). All underwent conventional endarterectomy, with shunt and vein patch. The speaker reported a rate of major morbidity and mortality of 1.02%. He considered that high-risk patients may be as well served by CEA as low-risk patients, but should be referred in specialized centers with skilled personnel in order to lower the risk of stroke.

Neurological dysfunction following carotid artery stenting: is it predictable?
B Van Bellen (Brazil)

The possible important risk factors involved in poor outcome following carotid artery stenting (CAS) was discussed. According to the speaker, the more symptomatic the patient, the higher the risk of the procedure (x7 with stroke and x6 with transient ischemic attack), as in carotid endarterectomy (CEA). CAS did not increase risk in females, although sex is a known risk factor in CEA. Age, on the other hand, was an important risk factor, but it is possible that the cause of complications is only indirectly related to age since aortic arch calcification and ulcerated plaques, which have a higher prevalence in elderly patients, are closely related to a higher incidence of new ischemic cerebral lesions. Diabetes was not considered to be a risk factor for CAS, and so for contralateral carotid occlusion. A possible explanation for this is the fact that carotid occlusion time during angioplasty is very short, and so there is little ischemia of the brain during the procedure. A significant increase in periprocedural complications was observed in patients with long lesions (>15 mm) and ostial lesions. Considering >85% stenosis as an increased risk for CAS is still controversial. Plaque calcification was also unrelated to periprocedural complications, but hypercholesterolemia can be considered as an additional risk factor. The observation that statins diminish the incidence of intraprocedural complications can possibly be related to the instability of symptomatic plaques, which result in a higher incidence of stroke during CAS. The speaker concluded that the answers to the majority of these issues may be provided by the ongoing trials.

Cerebral protection: myth or reality?
BG Torsello (Germany)

Embolization during carotid stenting (CAS) may occur at predilation, stenting, or postdilation, due to the manipulation of sheaths/guiding catheters, carotid plaque, or aortic arch. Proximal protection systems may be limited by the need for larger femoral sheaths and intolerance of clamping, limitations of filter devices with increased embolic events, internal carotid spasm, technical mishaps in attempts to retrieve the filters after stent deployment, and by filter pore size (100-150 µm). According to the results of a meta-analysis by Kastrup, the CAS registry in Germany, and a recently published randomized trial (Barbato et al, JVS 2008), the use of filters during CAS does not demonstrably reduce microemboli, and also filters cannot prevent embolic events in the aortic arch. He concluded that there is no level-1 evidence that cerebral protection improves outcomes. Filter-type devices may increase microemboli but can also trap macroemboli and because of this we should routinely use cerebral protection to prevent one major stroke by the capture of a large macroembolus.

Carotid plaque echostructure: its predictive role in future neurological events
G Biasi (Italy)

The ICAROS study pointed out the importance of echolucent carotid plaques with low gray-scale median (GSM) values as an increased risk factor for stroke during carotid artery stenting (CAS). The speaker considered that the analysis of carotid plaque morphology also has the potential to indicate the best brain protection device (echolucent plaques with proximal device and hyperechoic plaques with distal filter). He also noted that change in GSM scores can be a marker of the efficacy of statins and can predict future coronary events in patients with clinically stable coronary artery disease (OR 7.0, p<0.001). The speaker also presented the results of his personal experience (1996-2007) including 1151 cases of carotid endarterectomy (CEA) and 193 of CAS, with a rate of major morbidity and mortality of 2% in both groups, assuming that CEA is always the first choice and CAS only for high-risk patients.

Carotid artery stenting under protection. Limitations and new developments
M F Giannoni (Italy)

The new concept of silent cerebral ischemia detected with diffusion-weighted imaging in patients treated with protected and unprotected carotid artery stenting (CAS) was presented. This was done through a review of the characteristics and criteria for choice of different embolic protection devices (EPDs). This showed that embolism can occur during each step of the procedure, although most emboli do not produce clinical sequelae. The conclusion was that there is no ideal EPD (or stent), that CAS planning with EPD is mandatory, and also that skilled operators can make a difference because CAS is not an easy procedure.

Disease of the thoracic aorta

Thoracic aortic disease
Moderators: W. Sandman (Germani)-D. Kiskinis (Greece)
Participants: J. Brunkwall (Germany), E. Verhoeven (The Netherlands), K. Papazoglou (Greece)

Thoracoabdominal aortic aneurysm (TAAA) is one of the most severe conditions in vascular surgery. There are two basic surgical treatments of TAAA: thoracic open aneurysm repair (TOAR) and thoracic endovascular aneurysm repair (TEVAR). Each of these methods has advantages and disadvantages. TOAR has a clinical history of 50 years and can be applicable in most cases. However, TOAR is a long time surgical procedure (6-8 hours) accompanied by serious operational trauma, blood loss, frequent paraplegia (3-15%), renal insufficiency (5-10%), and high mortality rate (15-30%). Paraplegia is bound to damage the spinal cord arteries dissected during TAAA preparation. Artificial circulation, cardioplegia, and intraoperation perfusion are useful for protection of the brain, kidneys, and intestine. For these purposes, Sadmann et al used temporary ilio-subclavian or ilio-bi-subclavian shunting. Also, the authors have applied constant monitoring of the spinal cord conduction during surgery. Sadmann et al underline that restoration of the spinal cord blood circulation is possible during TOAR only. TEVAR has proven to be a useful alternative to TOAR in selected cases. There are fenestrated and branched endovascular techniques. The Achilles’ heel of the fenestrated technique is stability and durability of the seal between the nitinol ring and the covered stent. So, high-accuracy positioning of the fenestrated stent is necessary. Branched grafts are a better choice for most cases of TAAA. Branches are easier to position and to fix for the bridging stent-graft. Disadvantages include the required cranial approach to catheterize the branches and target vessels (E. Verhoeven et al.). Great variability in the anatomy of TAAA often requires a combination of both fenestrations and branches. The serious limitation of TEVAR is its very high cost and long-term manufacturing of the stent-graft. TEVAR is characterized by low mortality (20%) and paraplegia rates (5%). K. Papazoglou et al used TEVAR for treatment of a chronic dissection of the TAAA. The common contraindications to TEVAR are extreme tortuosity, narrow diameter, and calcification of the access vessels. The hybrid technique is a compromise between TOAR and TEVAR. Open visceral debranching is done before implantation of a thoracoaortic stent-graft. According to J. Brunkwall, hybrid operations use the advantages of TEVAR and decrease the disadvantages of TOAR. At the end of the discussion all participants agreed that randomized clinical studies are necessary to define the indications for and contraindications to open or endovascular repair of TAAA.