Interview with Ron Waksman, MD FACC

Angioplasty.Org recently talked with Dr. Ron Waksman, Associate Director, Division of Cardiology at the Washington Hospital Center (WHC) and Director of Experimental Angioplasty & Emerging Technologies for the Cardiovascular Research Institute(CRI) at WHC in Washington, DC. With over 25 years of experience in leading-edge medical technologies, Dr. Waksman is a world-renowned interventional cardiologist and is a highly sought after principal investigator for pre-clinical and clinical studies conducted in the United States and abroad. His current research interests include intravascular ultrasound, bioabsorbable and biodegradable stents, lipid sciences, and gene cell therapy.

Dr. Waksman has authored/co-authored 310 published manuscripts, over 230 abstracts, more than 20 book chapters and has been editor/co-editor of six books in the field of cardiology. He serves as the Editor-in-Chief of the journal Cardiovascular Revascularization Medicine (Including Molecular Interventions) and is on the editorial boards of numerous scientific journals including Circulation, Journal of American College of Cardiology, and American Journal of Cardiology.

Ron Waksman, MD, FACC

Co-Director of the Interventional Cardiology Fellowship Program at WHC, Dr. Waksman also runs the annual Cardiovascular Revascularization Therapies (CRT) meeting, an event that presents more than a dozen concurrent scientific meetings to medical and industry professionals in the field of cardiology.

CRT2009 will be held March 4-6, 2009 in Washington, DC.

Q: Your group authored a study, which was published online in the June 11 issue of the European Heart Journal. The paper is titled, “The potential clinical utility of intravascular ultrasound guidance in patients undergoing percutaneous coronary intervention with drug-eluting stents" (read abstract). To summarize, what were the major conclusions?

Dr. Waksman: We wanted to ask the question of whether systematic IVUS guidance of DES implantation results in better outcomes, meaning less stent thrombosis and perhaps also less repeat revascularization. The results of the study supported this hypothesis:

"if you do IVUS for most of your patients, you're probably going to end up with better results, as opposed to non-IVUS guided PCI with DES."

What prompted this whole research initiative was the fact that when we had been looking at patients with stent thrombosis initially and, when we tried to look at predictors for stent thrombosis, what always came up was the lack of IVUS use. So that actually prompted us to look at more comprehensive sets of patients, and to ask this as a direct question, rather than to bring it up as a predictor for stent thrombosis.

Q: So this was an observational study?
Dr. Waksman: It was observational. It was a retrospective analysis obviously, but there was a large cohort of patients initially entered into the database of the study to analyze and address this question -- our center uses IVUS in nearly 70% of our patients. We also recognized that there could be some limitations, because the potentially more difficult patients would undergo more IVUS than the simpler ones, or the simpler ones would not undergo IVUS at all.

So we did a very careful propensity-score matching analysis, which trimmed the 2,000 some patients to 800, split more or less evenly between the groups. The nice thing about it was that we got a very nice matching between the two groups: those who had IVUS versus those who did not have IVUS, in terms of baseline characteristics, in terms of angiographic characteristics, in terms of indication for use, in terms of the procedures that were done, everything was very well matched. And the only difference at the end of the day was the lack of IVUS in one group versus the use of IVUS-guided PCI in the other group. I think that's strengthened the results of the paper which do indicate that, with the broad use of IVUS, there is a reduction of stent thrombosis and also surprisingly, or maybe not surprisingly, also reduction in the need for repeat revascularization.

Washington Hospital
Center

Q: There have been previous studies, showing better results with bare metal stents, but I think this is the first study that looked at drug-eluting stents?
Dr. Waksman: Correct. This study was directed just for DES. Again, it's not a prospective study, but it's the largest retrospective observation. And it's a pretty large number, I mean if you're taking into account the amount of IVUS that is being used, and it's used so selectively. I think the difference in our center is that we use nearly 70% IVUS in our interventions. We can do this kind of analysis because we have enough patients, as opposed to centers that do only 12 or 15 or 20%, which is not sufficient numbers to do such a study.

Q: Based on your observations then, do you recommend greater IVUS use, generally speaking? And does every case need IVUS, or can IVUS really be targeted to more specific situations, such as more complex anatomy, etc.?
Dr. Waksman: I do think that it does help across the board, but obviously it is more helpful in more complex lesions. So, for example, there are some situations in which IVUS tells you a lot: for example, in-stent restenosis. If you want to know whether this is a mechanical issue versus a tissue issue, IVUS is very helpful.

If you go to selection of length and size, that applies to every lesion. Even if you think that you know the size, you may be surprised that you are not exactly accurate just by doing angiography alone. And also it does help you if you need to make a decision whether to do plaque modification versus direct stenting, for example.

So there are a lot of helpful hints that you can get from IVUS. But perhaps the most important one applying to the drug-eluting stent is to obtain sufficient cross-sectional area after deployment of the stent.

So, not only verifying by angio that you got a good result, but to see that indeed the stent is well-expanded, and also well-apposed to the vessel wall. But I think the emphasis is on expansion, because sometimes you can miss on the expansion of the stent without an IVUS. Again, I think systematic use of IVUS post-stenting, enabling you to ensure expansion, to get the ideal cross-sectional area, probably will you get you out of trouble or may in the future.

Intravascular ultrasound image,
courtesy Volcano Corporation

Q: Your paper concluded that IVUS guidance has the potential to influence treatment strategies. What I found interesting was that the IVUS group had less direct stenting, more post-dilatation, and more cutting balloons and Rotablators were used. Were these tools and strategies called into play because of what IVUS showed?
Dr. Waksman: Absolutely. Absolutely, because if, for example, you see that this is not a very calcified lesion and you can go with direct stenting, you can save a predilation balloon, you can save any ablative devices. Contrary if you see that you have calcification, but if you can not even cross with an IVUS catheter, you would direct yourself more towards rotational atherectomy, and you may end with better expansion of the stent because of the plaque modification with rotational atherectomy. So these are two examples where IVUS can change your decision.

Also, I think in terms of strategizing the length of the stent, the positioning of the stent, and there's of course branching. For example, in bifurcation lesions, it would be almost essential to have IVUS, if not before, definitely post, primarily when you're dealing with two stents. You want to make sure that they're very well-apposed. It also can determine whether you need to do post-dilatation or you were happy with the cross sectional area that was obtained at a high pressure. It's also taught us to go with high pressure with drug-eluting stents more than we have used before bare metal stents. So there are many hints that even an experienced operator can be getting from the use of IVUS to optimize the outcome.

Q: The drug-eluting stents used in your study were mostly either Cypher or Taxus. Now second-generation stents, like the Endeavor and, when it’s approved, the XIENCE stent, are becoming available. Do you see less of a need for IVUS with these newer stents?
Dr. Waksman: I don't think so. It's true that this study was done with only Cypher and Taxus, and the other stents have maybe better profile and they also have different compliance curves. We would need to learn exactly how to handle them in the lab, and in terms of the assessment of the lesion before, I think you still need to have it. We don't have much experience with IVUS on the new stents, but you'd like to make sure that you get good expansion and apposition with also a second generation. So I think the role of IVUS will be there to stay: it's still very helpful to give you more confidence in what you're doing, what you're obtaining at the end of the procedure.

Q: Regarding the second-generation stents, we recently interviewed Dr. Shigeru Saito, the principal investigator for the Japanese arms of both Endeavor and XIENCE stent trials, and his results were better than the other arms of the studies, something he attributed to the fact that in Japan, IVUS is fully reimbursed and used on almost every case.
Dr. Waksman: Yes. I think there is one more study that's coming from Asia in which they looked at the left main, whether it was assisted with IVUS or not assisted with IVUS and I think they reported a sub-study that demonstrated that use of IVUS for the left main was associated with improved results when compared with those who underwent stenting without the use of IVUS.

Q: I was surprised to see that there was a three-fold reduction in stent thrombosis at both 30 days and 12 months with the IVUS group. The non-IVUS patients had three times the thrombosis. Is this correct?
Dr. Waksman: Yes, that's true. I think that again, it was unexpected to see because the rate of stent thrombosis is generally not so huge, yet it was a difference which was very impressive. And I think it's for real.

Q: There was no significant difference in late stent thrombosis, so we’re talking about the type of thrombosis that occurs in the earlier stages?
Dr. Waksman: Yes, and this applies to the mechanism of stent thrombosis. I think we better understand that the 30 day stent thrombosis, which is more mechanical and related to the apposition of the stent, as opposed to the very late that is maybe more related to healing, inflammation, and perhaps also to issues related to responsiveness to Plavix. So I think since the majority of the stent thrombosis in the first year occurs within the first 30 days. This is the most important part that we can influence and reduce further. But I would still question whether the very late stent thrombosis would be impacted by the use of IVUS. Maybe, but we couldn't prove it in this study.

Q: What about tissue characterization? There’s been a lot of talk recently, unfortunately brought about by journalist Tim Russert’s untimely death, about vulnerable plaque and plaque rupture. Can IVUS help in this area?
Dr. Waksman: I think there is still a controversy about the ability to detect a vulnerable plaque with the current system, because with IVUS you can see multiple plaques that would be under the category of vulnerable, but we don't know if any of those are really going to be turned to a ruptured plaque, and that has not been proven yet. And yet, should you have this information, what type of therapy can you do? Let's assume you see 15 or 20 of those, which potentially you can see with IVUS tissue characterization, does that mean you're going to treat 20 spots with stenting?

It is important that it has raised this interest in continuation of exploring how to diagnose or to treat or to prevent vulnerable plaques to erupt. I'm not sure how much IVUS can help us alone, but I would say that there are an array of other devices that would be adjunct to IVUS that would tell us a little bit more about say, for example, the lipid composition within the plaque, the amount of inflammation, the necrotic core, the TCFA, the thin cap fibroatheroma, so all those may be features that may put the patients more at high risk vs. low risk. What we're missing now is the completion of the natural history study; we're missing the therapy right now that we can advocate to make a change in this. So it's the next step to see a little bit more. But I'm not sure at this stage we can state anything that could have prevented tragedies the like one that we had with Mr. Russert.

Q: What about other intravascular imaging technologies that can see lipid cores and such? For example, Optical Coherence Tomography (OCT) has been talked about.
Dr. Waksman: In terms of the imaging, there is a new infrared system that has just recently gotten 510k approval from the FDA and it's going to be commercially available soon. And that device can allow you to detect the amount of lipids within the plaque, so that's an interesting approach. Again, I don't know what to do with it, but it's there. OCT is being now moving to a more user-friendly system, and it has capabilities again to detect areas of necrotic core, and there's a lot of progress in that. There is also IVMRI which also can help detect lipid content within the plaque, and it has completed the clinical trial. And there are some other modalities that are being developed right now to enable us to get a little bit more information on plaque composition in potentially more high-risk patients. So I think it’s a dynamic field and we should look forward carefully on other modalities, but I would caution that those have to be integrated all in one catheter, because, as an interventionalist, you don't have the time to pull two or three catheters to get all the modalities systematically in every patient -- that's going to be almost impossible.

OCT image just proximal to a stent in Right Coronary Artery

OCT image just proximal to a stent in an RCA,
courtesy of the First in Man Volcano OCT
performed at ThoraxCenter in Rotterdam by Prof. Patrick Serruys and Dr. Evelyn Regar

Q: In the U.S. and other places, IVUS usage is only in the teens. Would your recommendation be that interventionalists start thinking about using IVUS more?
Dr. Waksman: I would think that 13% is not sufficient, so there is room to be more liberal with the use of IVUS. The excuse that it's cumbersome is fading slowly because we have now integrated systems, so I think that at this point this is becoming a more essential tool and there are really not many complications associated with it. As to it being time-consuming, it's also becoming relatively simple to use. So I would encourage cardiologists to use it more, just based on those results because, now that we've been published, I think that this is an opportunity for even good operators to end with better outcomes. And if that's the case, then it's definitely important also for those who feel less comfortable in the cath lab with complex angioplasty. Here we have a tool that can optimize your result and you should not spare it on the patient.

I think that this is kind of a wake-up call to people to look again. I think that's the message from the paper: maybe there's something there that we can do better and maybe we should give it a try. From my own experience, and this is more anecdotal, those who use IVUS a lot don't usually want to give it up, they continue to do IVUS. And it's just a question of passing the barrier to start to do it, or a learning curve, or confidence in the device. But once you start to do IVUS it's kind of something that you like, it's not an addiction, but I don't know many of those individuals that used to do a lot of IVUS and stopped doing it.

Q: Thank you, Dr. Waksman. We look forward to your CRT2009 meeting. Will you be running training sessions for IVUS?
Dr. Waksman: You're welcome. And yes, there is an IVUS workshop at CRT. It’s also in other courses, and also from time to time we have a group of technicians and physicians that come to the cath lab for training.

This interview was conducted in June 2008 by Burt Cohen of Angioplasty.Org.