Discussion

Dr Ralph Dilley (LaJolla, Calif). President Andros, members and guests. The growing interest of using stents to treat carotid atherosclerosis is now well documented, and the modality is being used increasingly in many clinics and practices, often in patients who are asymptomatic and not in high-risk categories.

Unfortunately, we are beginning to learn of a number of potentially significant complications of carotid stenting, which might limit the application of this intervention. For instance, a number of recent reports have shown an increase in postprocedure stroke risk in patients over age 80. The incidence in these reports varies from 7% to 15%.

Second, almost all investigators agree it is important to use protection devices to decrease the frequency of atheroemboli during carotid stenting. These protection devices range from simple filters to the more complex flow reversal system as described by Parodi, but skepticism remains about their efficacy in capturing atherosclerotic particles.

In spite of these precautions, atheroemboli continue to occur during carotid angioplasty and stenting, and now we learn from this very nice presentation by Dr Rapp and his colleagues that atheroembolic showers occur not only during the procedure but continue at least up to 48 hours following the procedure when no protection device is in place.

Using diffusion-weighted MRI, analyzed both in coronal and axial planes, they demonstrated a 9% incidence of new lesions at 1 to 2 hours after the stent placement but also a highly significant 78% incidence at 48 hours. Most patients had multiple lesions, most often in the treated carotid distribution. All patients in their study had placement of a protection device during the intervention, and plaque fragments were present in the 44 submitted for analysis.

This is an excellent study and if you are concerned that these microembolic showers, although asymptomatic at the time, may ultimately cause problems, then the results of this study are indeed sobering and prompt many questions about the role of carotid stenting. I should hope the authors would comment on some of these questions.

Were you able to correlate the incidence of new lesions with the age of the patient? Is it likely that the embolic lesions, particularly those outside the carotid territory were related to arch atherosclerosis with embolic debris caused by catheter manipulation?

I noted that the evaluation of the arch was by MRI only in about 80% of the cases, and I wonder if this technique is sensitive enough to identify significant arch pathology, which if present, might alter the treatment plan?

Were you able to correlate the number of embolic lesions with any preintervention characteristics of the carotid plaque? For instance, how did patients with recurrent disease as an indication compare with de novo disease, and did you attempt to characterize the plaque by duplex as to its degree of instability or heterogeneity versus a stable or homogeneous plaque?

Should the workup prior to carotid stenting include transesophageal echo to exclude arch pathology or duplex to evaluate plaque characteristics, the findings of which might rule out stenting as an option?

Can you elaborate a little further on what the clinical significance of these lesions is? If they are a precursor to a dementia syndrome and continue to embolize up to 48 hours or more, they are very significant and a deterrent to expanding the indications for carotid stenting.

Finally, a number of your patients in the study were asymptomatic, and can you justify treating asymptomatic patients with a stent, particularly with the findings you report today?

Again, I enjoyed this presentation and congratulate the authors on an excellent study.

Dr Joseph Rapp. Thank you, Ralph. Ralph was very kind to not comment on the extremely rough draft that I sent him the first time around.

So do we know the timing of these lesions and could it happen that we are just missing it and they are embolizing at the end of the procedure and not during the procedure? Transcranial Doppler during the procedure I think is pretty well worked out, and I do not really understand why we do not have good data postprocedure because these people are monitored during the procedure in some of these studies. We do not do transcranial Doppler. Actually we now have a machine and we are going to start doing it for obvious reasons that I talked about. And so I don’t know actually the timing. My actual suspicion is that there is a lot more emboli in the postprocedure period than we appreciate, and I think we are going to look at that and hopefully work that out.

Does it correlate with age or the heterogeneity/homogeneity of the plaque? Well, I hate to admit to a group of vascular surgeons but I do not believe in homogeneity or heterogeneity of the plaque, so we do not get it. I never have been convinced that was worthwhile, but I know many of you do not share that opinion and so you are welcome to do that study and see. We looked at every parameter other than that that we could think of—degree of stenosis, length of the lesion. You know we have MRI. We look at all these lesions, and we could find nothing that correlated. We only had 3 or 4 recurrent lesions, so it really was not worth looking at whether they were recurrent or not. The recurrent lesions do actually shed particles, which I was interested to find out …

Unidentified speaker. … paper was appreciated very much. It was beautifully presented with good data, as usual. I have two questions and a couple of comments. You mentioned that we “don’t get emboli with carotid endarterectomy.” In fact, have you subjected a group of patients in your institution who have undergone carotid endarterectomy to the same rigorous examination with DWI as you did those undergoing angioplasty? Certainly if you do transcranial Doppler on people that undergo CEA you see a lot of hits in those patients, you just do not see them for long periods of time, and while this may have been studied, I am not aware of any literature right now to show that there are lesions DWI after CEA unless there is an obvious complication. I am just wondering if you happened to look at it because I think you are in an excellent position to do that and to compare it.

Dr Rapp. We have. We published that in the Journal of Neuroradiology in I think 2000-2001, and there is one from the neurosurgery group in Phoenix. We found one lesion in 25 and they found no lesions in 27 in diffusion-weighted imaging, so they are emboli. I misspoke. I said there were no emboli. There are no diffusion-weighted lesions after endarterectomy.

Unidentified speaker. The second question has to do with your anticoagulant and antiplatelet regimen periprocedure. Would you tell us a little bit about how much heparin you use, whether you use aspirin and Plavix, and when you start it and how long you continue it?

Dr. Rapp. We keep the ACT greater than 300 during the procedure and we continue heparin for 12 hours postop, and in the paper, one of the other alternatives that I mention is that maybe when you stop the heparin you are getting more emboli. We load the patients with Plavix either by 3 days before or, rarely, we load them the night before, depending on their proximity to us, etc. We continue Plavix for 6 weeks. Dr Pann and I have looked at antiplatelet agent anticoagulation in our rat model of emboli, and I can tell you even big doses of heparin make not a wit of difference in the incidence or the number of lesions that you get when you embolize cholesterol crystals.

Unidentified speaker. That is exactly the point. It suggested it is not platelet or thrombotic material that is embolizing; it is really plaque embolization that is really critical.

Obviously papers like this, for those who are interested in carotid endarterectomy, make our day, or at least seem to, and you are presenting this to a group of people who are very receptive obviously to the data that you are presenting. I would strongly encourage you to present this again at the stroke meetings, the American Heart Association, where you do have an eclectic audience of neurologists, neurosurgeons, vascular surgeons, etc, because they are the ones who need to hear this. There is a proposal up right now as a tag onto the CREST trial to do neuropsychiatric evaluations of patients in both the carotid endarterectomy as well as in the stenting group to see whether or not there is a difference in intellectual functioning and whether or not these DWI lesions in fact will be forerunners of dementia. I think it is terribly important. Whether it gets funded or not is another question. I enjoyed the paper and congratulations.

Dr Rapp. Thank you, and, Wes, I am only trying to continue the work that you started at the San Francisco VA.

Dr James Watson (Seattle, Wash). I, like you, do not believe in intervening in carotid stenosis that is less than 80% unless they are clearly symptomatic, so I would like to drill down a little more on your definition of asymptomatic.

Before coming down here I was presented with about a 60% carotid stenosis who had an asymptomatic Hollenhorst plaque discovered on retinal examination. How would you manage that patient? And as a follow-up question, what do you do with the asymptomatic carotid stenosis with a shown stroke by CT that shows up in your office and says they have no symptoms, but once again has a 50% to 79% carotid stenosis? Do you treat those patients as symptomatic or asymptomatic?

Dr Rapp. I think they are tough calls. Generally, we treat them as asymptomatic. We treat them that we do not know when the stroke occurred. We do not know when the Hollenhorst plaque occurred, and they weathered the storm and they have done well. As you know, if you have your clinical event, you are at your highest risk of recurrent event at that time, and that risk actually goes down and at 2 years joins the population with carotid stenosis that has never had an event. I think if you do not know when the event started, you are down here in this low-risk category and you have a 60% stenosis and you are not going to do anything.

Unlike our colleagues, I just went to a (Fox-Hollow) event and was told that we should be treating asymptomatic SFA stenoses, so I think there is a group of people out there who are truly scary in their indications to do these things. As our cardiologists have discovered that there is atherosclerosis outside the heart, this is a problem. It is a real problem when you have one standard to do interventions and the person down the hall has another.

Dr Jean-Pierre Becquemin (Paris, France). I really enjoyed your paper because I think it brings new clues that these may not be so innocuous that we all hoped for. I was interested to see that the majority of events occurred later on, after deployment of the stent. That means that you change stable plaque to unstable plaque. That means that all the debris goes through the strut of the stents, and my question is did you use different types of stent? Did you find a difference between open-cell stents versus closed-cell stents? Maybe you saw this paper at the last June meeting in Philadelphia from a Belgium group which showed that with a closed-cell stent, there were less emboli than with an open stent. Do you have the same experience?

Dr Rapp. I have no experience with that. What I am interested in actually is a covered stent and there is a study looking at covered stents in the carotid. Now that study was stopped because of their high rate of restenosis. I have the reference in my poring through Pub-Med to do this paper. I think that is very interesting, but I have no data on closed or open-cell stents.

Unidentified speaker. I enjoyed your paper very much. A couple of questions. There is some evidence experimentally at least that you can increase the number and size of emboli by using Dextran. Have you considered that?

Dr. Rapp. Increase?

Unidentified speaker. Decrease, size and number, by giving Dextran. The other question is, in light of all this then, should we be treating these people for 3 or 4 months with high-dose statins and antiplatelet therapy before we stent them?

Dr. Rapp. Two really great questions. I love Dextran. Using it for years and then in the last few, I don’t know, maybe 3 or 4 years collectively had two anaphylactic reactions to Dextran, my love of Dextran has been tempered, but Dextran is a very good drug, and there is a wonderful TCD paper showing that these postoperative embolizations actually stop when they put on Dextran. I think Dextran is exactly where we are going to go. I am concerned about the anaphylactic reaction to it.

In terms of statins and pretreatment with statins, that is a great idea. Certainly in our asymptomatic patients where it is unclear there is a rush to treatment that may well be a wonderful thing to try.