The VeithSymposium: Five Presenters on Hot Topics

“EVAR is the preferred treatment for ruptured aneurysms.”

Frank J. Veith, MD, Professor of Surgery, The Cleveland Clinic and New York University, The William J. von Liebig Chair in Vascular Surgery, The Cleveland Clinic and New York University Medical Center Cleveland, Ohio and New York, New York. Dr. Veith is the Founder and VeithSymposium Chairman. Can you give us an overview of endovascular aneurysm repair (EVAR)? Endovascular aneurysm repair is a less invasive endoluminal repair of an aneurysm using an endovascular graft. There are now several commercial varieties of endograft. Access is gained through the groin, either open or percutaneously. There are two separate issues to consider. One is endovascular repair of an elective abdominal aortic aneurysm (AAA), which is gaining market share and is now well accepted. The number of patients treated by open aneurysm repair has reciprocally decreased. Dr. Juan Parodi did the first EVAR in 1990 in Argentina. We did the first EVAR in the U.S. in 1992, and since then, there has been a steady increase in acceptance of the endovascular procedure on the part of surgeons and others who deal with abdominal aortic aneurysms. In addition, there has been development of better and more versatile devices. I would estimate that currently 55-65% of electively treated aneurysms are treated by some form of endovascular graft. Those that are treated by open repair either have unsuitable anatomy or are treated by surgeons who are not in sync with what is happening in the world, i.e. they are practicing outdated medicine. The second issue is ruptured abdominal aortic aneurysms (RAAA). We did the first EVAR for a RAAA in 1994, and in 1994 and 1995, had surprisingly good results from the procedure. We had a number of patients who for a variety of reasons could not have survived an open operation, but who survived endovascular repair. In 1995, we started doing all ruptured aneurysms that were anatomically suitable, which is about 70-80%, also with very good results. Mortality was much lower than we had in the past with open repair, and as a result, we advocated treating all ruptured aneurysms by EVAR. However, there were some groups, notably in Europe, that didn’t notice any lowering of mortality with endovascular versus open repair, and there were published articles showing comparable mortality. We therefore reviewed the worldwide experience, and published “Collected world and single center experience with endovascular treatment of ruptured abdominal aortic aneurysms” in the November 2009 Annals of Surgery. What did your review of the data reveal? We reviewed the world experience in treatment of ruptured AAA in two groups of patients. The first group was all patients, which included 1,037 ruptured aneurysms (collected from 49 centers around the world) that were treated by EVAR. The mortality for this group was 21%, whereas the mortality for open repair, according to the literature, is 35-55%. Obviously 21% compares favorably with 35-55%. Still, that comparison is potentially flawed, since some of the 49 centers only used EVAR on more stable, less risky patients. This comparison is not a fair one, since the sicker patients got open repair. The second group included data from 13 centers, like our own, that did EVAR on all anatomically suitable patients with ruptured aneurysms. We compared the mortality from EVAR with the mortality from open repair in those 13 centers. EVAR mortality at 30 days was 19.7%, and the mortality after open repair was 36.3%, dramatically in favor of EVAR. This, in our opinion, proves EVAR is better. The criticism could be made that maybe we were comparing results in different risk groups of patients: those suitable for EVAR and those who did not have suitable anatomy. The patients with the bad anatomy may also have been higher risk. We do not think that is likely, but it can’t be ruled out. However, balanced against that unlikely possibility is the 10-15% of patients treated by EVAR that we felt were totally impossible to treat with open repair. These included patients with abdominal wall hernias or infection, or colostomies, that made an urgent open operation impossible or very risky. We therefore believe that our data proves that EVAR is better than open repair. However, there are still those who believe we need a randomized study, and there are three such studies being done in Europe: one in England, one in Holland and one in France. Those studies are going to be difficult to do for a variety of reasons. None of the surgeons in the 13 centers using EVAR as a first-choice therapy believe that a randomized trial is necessary. They are so convinced that EVAR is better that they would not participate in a randomized trial for ethical reasons. The analogy might be doing a randomized trial of the value of proximal control in arterial bleeding. It’s just not justified. However, there are those who believe such a randomized trial is warranted and we await the results with interest. Although it is still controversial, I believe more and more people are beginning to think that EVAR is the preferred treatment for ruptured aneurysms for a variety of reasons. How crucial is experience for improving outcomes with EVAR? We did a presentation at the conference looking at why some groups are able to get good results and other groups are not. Like everything else in this world, there are certain tricks, strategies and technical tips that make outcomes better with EVAR, and if they are not used, the results are poor. (These are covered in the Annals article as well.) First, one must have organization and supplies. There are a lot of logistical issues that make for better results, and it all starts with people trained and committed to doing EVAR. One has to have a system. Next, it is important to recognize and treat abdominal compartment syndrome (ACS), or increasing pressure in the abdomen, which can kill patients. All the blood outside the blood vessels causes swelling in the abdomen with resulting pressure. Patients cannot be ventilated and circulation to their organs is impaired. ACS has to be recognized and treated, and that is one of the key elements in getting good results. The other key element is the proper use of an aortic balloon to control bleeding. It is also important to limit fluid resuscitation, which can lead to increased bleeding. Allowing patients to exist with reduced blood pressure can diminish bleeding and may improve outcomes. Can you tell us more about the 10-15% of patients done at the 13 EVAR centers that were not eligible for open repair? These patients were either very sick, with heart failure, for example, or they have what we call a “hostile abdomen,” meaning large hernias, colostomies, and various other things that make it difficult to do an open operation. When such patients were treated endovascularly, the majority of them survived. In our original series, we had 12 patients ineligible for surgery. Of these 12 treated with EVAR, only two died. That is a 17% mortality in patients that otherwise would have died. Sometimes, it is a judgment call. Some surgeons may operate when a RAAA patient is very high risk and others may not. Our original 12 patients absolutely could not have been operated on. One such example was a Jehovah’s Witness who could not be given a blood transfusion and could not have been operated on without a transfusion at some point. She survived after EVAR and is still alive five years later. How do patients do long-term? In our study, 30-day mortality was the key parameter. We need to gather data on long-term survival after EVAR for RAAA. We are working in collaboration with Dr. Lachat and Dr. Mayer from Zurich. However, this study is not yet completed. Dr. Veith can be contacted at fjvmd@msn.com _____________________________

What is Happening to the Relationship Between Physicians, Industry and CME: Are Government and the ACCME Going to Block Industry Support For CME Activities?

Barry Katzen, MD, FACR, FACC, Founder and Medical Director of Baptist Cardiac & Vascular Institute, a part of Baptist Health South Florida, and a Clinical Professor of Radiology at the University of Miami School of Medicine, Miami, Florida What is happening to medical education? There are potential changes in continuing medical education that are the result of the changing environment between industry and physicians, and government regulations. A hostile environment is developing that threatens the future of continuing medical education as we know it. Right now, much of continuing medical education is especially directed at specialty and sub-specialty education. We are working in fields that are rapidly changing due to new techniques and procedures, not simply a fund of knowledge. There is a constant need to maintain current education, much of which cannot be provided through Internet-based tools. What I would call a somewhat hostile environment has occurred for many reasons. One reason is the various attacks on the Accreditation Council for Continuing Medical Education (ACCME), which governs medical education, and their response to these attacks in regulating how money is spent by industry to support education. It is important to understand that most medical education is actually funded through industry support. The registration fees charged at various post graduate courses only cover a fraction of the costs necessary to actually present the continuing medical education. The second adverse change has come from the government, by which I mean some of the early sunshine laws in Massachusetts and Vermont. I have a photograph of a sign that is posted outside of a meeting exhibit area, which says that physicians from Vermont and Massachusetts are certainly welcome to come in and look, but they are not allowed to eat any food. That is symbolic of how ludicrous things have become and how we have gone to an extreme. The effect of industry on creating educational bias is valid, but I think there are ways to deal with it inside our existing structure and make sure that programs and speakers are unbiased. How can we eliminate bias? The most important step is to shine a light on the responsibility of the program directors to assess content in advance. Program directors also should make sure that speakers who do exhibit bias in their presentation, if it’s not detected in advance, be somehow reprimanded, recognized, not invited back, notified, etc. Rather than just ignoring these events, program directors need to step up. Physicians and healthcare professionals who are attending conferences also need to be very vocal when they perceive obvious conflicts of interest between physicians or biased presentations. Some of that may be difficult, because you may be challenging thought leaders in the field. We have to make it easy for attendees to do it, so they are not intimidated by the process. It doesn’t have to be one-on-one through a Q&A. It should be through evaluation forms. We have to make it easier for the registrants to identify and communicate when they think there is a bias or conflict of interest. Conflict of interest is another concern which sunshine laws were created to address. It’s not practical to think that medical technology can advance without input from physicians. In theory, divorcing physician industry involvement from product development would result in products physicians couldn’t use or products with no adequate medical benefit. There are extreme positions, such as accepting no outside funding and that those with a conflict of interest should not be allowed to get to the podium. I think that’s harsh. If you are an inventor, if you are someone who has done early first-in-man, if you are the physician who has treated the first 10 patients, you are the one with the knowledge and understanding of the rationale. To me, the issue is more of transparency, and managing conflict of interest rather than totally eliminating it. Finally, if we look at the amount of dollars being spent by industry on physician education, let’s also consider that the United States is the only country which allows pharma and to some extent, medical manufacturers, to advertise directly to patients who can’t use their products. It was estimated that all the revenue spent on advertising during last year’s Superbowl for prescription drugs was the equivalent of funding 5 to 6 NIH trials. Do you think direct consumer advertising by pharmacology and other medical companies will ever be eliminated? It’s not even on the table. But it is important to point out the inequity when you compare that type of advertising to what is being spent on medical education. Spending on advertising is much, much greater — yet what is more important? State-of-the-art, knowledgeable physicians at the top of their game? Or advertising to people who aren’t even the ones making the decision to use that particular drug or device? Lay people are certainly entitled to know this information. That’s not the argument. The use of advertising to get patients to influence their physicians is not a useful or appropriate way to allocate resources as compared to educating physicians on how to use the latest technology or appropriately manage their patients. Dr. Katzen can be contacted at barryk@baptisthealth.net _________________________________

Status of the TACIT Trial: Will We Ever Know the Truth About how Asymptomatic Patients With Carotid Stenosis Should be Treated?

John H. Rundback, MD, FSIR, FAHA, Associate Professor of Clinical Radiology. Columbia University College of Physicians and Surgeons; Director, Interventional Institute, Holy Name Hospital. Teaneck, New Jersey What is the TACIT trial? The TACIT trial, which has been in development for a number of years, stands for the Transatlantic Asymptomatic Carotid Intervention Trial. It is a 3-arm trial evaluating patients with asymptomatic carotid artery stenosis who are randomized in a 1:1.5:1.5 fashion to receive best medical therapy alone, best medical therapy and stenting of the carotid artery, or best medical therapy and endarterectomy. There are several reasons TACIT is such a critical trial. First, there are 125,000 carotid endarterectomies and about 30,000 carotid stents placed each year in the U.S. Eighty percent are for asymptomatic disease, which, in part, is based on the results of the ACST trial (Asymptomatic Carotid Surgery Trial) published a few years ago. However, some methodologic flaws in that trial have left tremendous doubt about whether asymptomatic patients are best served with revascularization. As a matter of fact, if you look at a New England Journal of Medicine worldwide survey done last year, 50% of physicians facing the scenario of a 70-year-old male with carotid stenosis and several cardiovascular risk factors would still treat medically. So the value of various treatment strategies for asymptomatic carotid stenosis is still an extraordinarily relevant topic. Stroke is the third leading cause of death in the U.S. and a leading cause of adult disability. About 25% are due to previously asymptomatic extracranial carotid disease, so it is a major public health concern. The ACST trial showed a 5.3% absolute difference over the course of 5 years, with benefit for endarterectomy compared to medical therapy. That’s essentially a 1% benefit per year, and it took two years from the onset of therapy to even see a benefit because of the initial risk of endarterectomy compared to medical therapy, i.e. the risk of procedure-related stroke. Still, ACST was deemed a statistically significant study and had an impact on practice. The problem is that if you look at the use of medical therapy in that trial, 17% of patients were on lipid-lowering therapy at the beginning, and at the end, 70% were on lipid-lowering therapy. While this may represent the best possible compliance, during the course of the trial, most patients did not get optimal lipid-lowering. Antiplatelet therapy was not mandated at all in the trial. ACE inhibitor use, clearly shown in recent studies to be an important preventative measure for stroke in patients with carotid disease, was not used routinely. Perhaps most importantly, while medications were given and monitored as to whether they were utilized, there was no targeted lipid-lowering or blood pressure lowering. ACST did not monitor whether patients achieved therapeutic targets according to accepted guidelines. TACIT will have targeted medical therapy. Right. Targeted medical therapy adhering to ACC/AHA recommendations. There was an article from Dr. Ross Naylor a few months ago in the European Journal of Vascular and Endovascular Surgery and another more recent publication by Dr. Anne Abbott in the journal Stroke, both of which suggest that medical non-operative therapy may be the best management for patients with asymptomatic severe carotid disease. These articles looked at 11 medical trials of patients with carotid disease over the course of the last 10 years, and showed that the risk of stroke with medical therapy is lower than the lowest risk of stroke seen in either the ACST or the earlier Asymptomatic Carotid Artery Surgery Trial (ACAS). I’m an interventionalist. Despite what most interventionalists and surgeons would like to believe, which is that revascularization is better in this population, the data suggests that it may not be the case. Both the public and referring physicians often think that medical therapy is as good or better, and are wary of the risk of revascularization, for which you get a 1% per year gain over the course of five years, which is not very dramatic or compelling to clinicians or patients. At noted earlier, ACST did not clearly compare surgery to BEST medical therapy. Even though the 70% antilipemic medication use at the end of the study may have been the best possible compliance (although I doubt this), patients weren’t monitored to see if they achieved the desired level of lipid-lowering, nor were ACE inhibitors or antiplatelets routinely utilized. So ACST doesn’t reflect best medical therapy. We understand that compliance is a problem in real life, and that medical therapy, for what it is worth, may have its own set of complications, risks and problems. Of course, medical therapy does not include a risk for stroke or death from the procedure. Our belief is — and it certainly needs to be studied — that if you have better medical compliance, better targets, routine use of all three classes of risk prevention strategies, that you’ve got to see better results, which we feel may obviate the small statistically significant benefit observed in ACST for endarterectomy. Because patients are required to be eligible for both stenting and for surgery, what kind of population will be excluded? Patients with anatomy preventing randomization either to surgery or stenting will be excluded. There will be a proportion of patients who have, for instance, very severe thoracic aortic arch disease, or type 3 arches who would not be stent candidates. On the other hand, we’ll have some patients with very high bifurcations near the mandible or near the arch which would not be candidates for surgery. We anticipate this will be less than 10% or certainly less than 20% of patients. What are the study endpoints? Traditional endpoints for prior carotid studies have been 30-day, all-cause mortality and stroke, and 5-year ipsilateral stroke. (As a side note, in ACST, the 1%/year improvement difference included all strokes. If you just look at ipsilateral stroke, it was not statistically different.) In TACIT, we have a 5-year endpoint, which is risk of stroke and neurocognitive decline. This is important because it’s increasingly recognized that what may be seen as asymptomatic may actually be associated with symptomatic declines in cognitive speed and function. Revascularization can be associated with improvements in cognitive performance, which can be notable. There are some very rigorous and reproducibly measurable parameters that have been reported by Dr. Rod Raabe’s group in Washington showing improvements in neurocognitive function after carotid stenting. TACIT will also look at carotid plaque characterization. Data, particularly out of the ICAROS substudy by Dr. Giorgio Biasi in Europe, suggest that some plaques are higher risk than others. TACIT may allow us, for the first time, to clearly identify a subset of patients in whom revascularization might be better, compared to medical therapy, based upon characteristics of the carotid stenosis. It will also be able to tell us the natural history of plaque in a large group of patients, about 1,100, treated with medical therapy alone. Additionally, important more so from a socioeconomic standpoint than from a medical one, is that TACIT will include cost analysis. Obviously, in today’s world, the relative cost of these therapies and the quality of adjusted life-year gained is a critical analysis. As physicians, we like to overlook that. Where does TACIT stand right now? The trial is not yet enrolling. We went to the NIH for funding; we had industry support, but that’s on hold pending the results of the CREST trial. No one is going to invest in a carotid trial that has a stent arm if CREST shows that stents are inferior to surgery. CREST will be reported in February 2010. If there is indeed noninferiority, we’re very eager and ready to push forward with the trial, and it actually may allow a redesign of the TACIT trial. If CREST shows there is no difference between stenting and surgery, we can perhaps now make TACIT a two-arm trial: medical therapy alone compared with best medical therapy plus revascularization at the operator’s discretion. We would then choose sites so there is relatively equal distribution of stenting and surgery. This version of the trial would be easier to enroll and would reduce our sample size down from 3,700 to almost 2,400, and reduce the cost down from about $60 million to $40 million over the course of five years. In a sense, this is one of the greatest travesties in medical history. Stroke cost in the U.S. alone is close to $60 billion a year. Consider the estimate that 1 in 4 of these strokes is due to extracranial carotid disease, of which 8 out of 10 are asymptomatic prior to the event, then you are talking about a $20 billion a year cost, as well as the associated disability. TACIT, which potentially will find the best therapy for a $20 billion a year healthcare problem in the U.S. alone, will cost a tiny fraction of that total — $20 million to begin, and $40-50 million to complete over 5 years. Dr. Rundback can be contacted at jr2041@columbia.edu ________________________________

Aggressive Interventional Treatment of Chronic DVT: A New Method to Decrease the Symptoms of the Post-Thrombotic Syndrome

Mark Garcia, MD, Medical Director, Peripheral and Vascular Laboratories, Christiana Care Center for Heart and Vascular Disease, Christiana Hospital, Newark, Delaware Your data showed intervention can help patients with chronic deep venous thrombosis (DVT). We pulled out a cohort of 50 patients from our registry of chronic DVT patients, defined as patients with clot or symptoms for greater than one month. Quite a few actually had symptoms years out from their DVT and had very hard chronic occlusions that led to post-thrombotic syndrome. Essentially, we found that most people who had developed these extensive, chronic and old clots also developed some form of post-thrombotic syndrome, which can be a compilation and a continuum of symptoms from pain and swelling all the way through to skin changes, ulcers and gangrene. Amputation is rare. Once a clot develops, the gold standard of therapy is to put these DVT patients on anticoagulation and compression stockings. We looked at an aggressive treatment methodology to take care of these patients with chronic DVT, and discovered that if we take the time to chisel our way through this very hard, concrete-like clot, we can make a difference. We can improve their quality of life and help restore patient activity levels. Although we presented a small series with short, early outcomes, we are finding that in the long term, patients are significantly improved. They have the ability to return to a more normal activity. To work our way through the occlusion, we use standard endovascular techniques, but because the chronic clot is very hard, we have to be patient and persistent with our catheters and Glidewires. Once we get to the other side, standard angioplasty technique creates some space in the very hard, atretic vein, which then allows us to use ultrasound-assisted thrombolysis. The combination of ultrasound and tPA appears to help soften and dissolve the clot, and create a larger space. The ultrasound aids in creating a channel of flow, restoring patency in the vein and improving quality of life. At least in the short term, patients have seen a benefit. What lengths of clot are typical for chronic DVT patients? A smaller portion of our patients had clot from the groin down the leg, but the majority went from the upper pelvis or iliac vein all the way down the leg. Eight of our 50-patient cohort had clot involving the inferior vena cava. We have treated patients, in the worst case scenario, from the hepatic veins all the way down the IVC and into the leg, to a smaller population of patients with clot from the groin down. Regardless, all patients were symptomatically affected by the sequelae from their chronic DVT. How long is an average procedure? The more extensive and complex the case, the longer it may take, and can ultimately last up to several days. The first day is typically the longest, evaluating the anatomy and then trying to work your way through the clot. This can usually take two to three hours on the first day. Depending on the situation and case, there may be follow up afterwards, for perhaps another hour and a half to two hours. Total procedure length, on average, is anywhere from two to six hours time, and sometimes longer. The patients with inferior vena cava (IVC) involvement have taken work over several days to reestablish the flow. But, with patience and persistence, we are capable of doing it. The beauty of treating patients in the acute phase, where the clot is soft (less than 14 days), is that you can take patients who have extensive, large volume DVT, that may even involve the IVC and bilateral legs, and have these patients in and out of the hospital in 3-4 days, with no DVT remaining. That’s the beauty of the rapid lysis technique. Will the chronic DVT patient population increase or decrease in the future? I wish I had that data. I just came back from the American Venous Forum and asked that question. The problem is, getting that data is extremely difficult. If you look at the population in general, nearly a million people a year are diagnosed with DVT, with the standard still being anticoagulation and compression stockings. We’re trying to change that by getting rid of the clot burden at an earlier stage. If you compile the number of patients who have gone on to develop post-thrombotic syndrome and chronic DVT over the years, it is probably millions of patients in the U.S alone. It would be reasonable to assume that there may be several million patients with chronic DVT and post-thrombotic syndrome. The standard of care is to treat these patients with anticoagulation and compression stockings, but many patients have to live and deal with the sequelae. You mentioned that your data is short-term thus far. Some of our patients have been out several years, but for the most part, these are early results. We’re trying to help these patients and develop the best treatment method. In our series, we only failed in getting across the occlusion in one patient, so it is possible to cross these old occlusions. Doctors just have to take their time and persevere. Once you get across, you can make a difference. In those patients completing follow-up quality of life questionnaires, 100% of them reported an improvement. Not one person stayed the same or got worse. The message is that patients that have chronic DVT do not necessarily have to suffer. Our role is to educate the patient population and stimulate the medical community to further their techniques and ability to take these patients on and treat them. We hope to communicate to doctors and patients, that it may be worth taking these patients on, because you may be able to make a huge difference. But, as I said, you have to be patient and persistent, because the procedure does take time. It is not a quick, in-and-out procedure. You have to work hard with these patients, but the outcomes make it well worth the time. Dr. Garcia can be contacted at magarcia@christianacare.org ________________________________

Ultrasound-Accelerated Thrombolysis for the Treatment of Massive Pulmonary Embolism

Peter H. Lin, MD, Chief of Vascular Surgery & Endovascular Therapy of the Michael E. DeBakey Department of Surgery at Baylor College of Medicine, Chief of Vascular Surgery at St. Joseph Medical Center, Houston, Texas How prevalent is pulmonary embolism (PE)? PE is one of the more common causes of mortality in the U.S., accounting for 10% of all in-hospital mortality in this country. In September 2008, Acting Surgeon General Steven K. Galson, MD issued a national call for action for the prevention of DVT and PE. It is estimated there are 300,000 patients that die each year in the U.S. because of a pulmonary embolism. Ninety percent develop PE because of lower leg deep venous thrombosis (DVT). DVT and PE are considered under a set entity called venous thromboembolism. Each year, more than 900,000 patients in the U.S. suffer from venous thromboembolism. Traditionally, massive pulmonary embolism is associated with a very high mortality rate. It is important to emphasize that these are very sick patients. All have classic signs of heart failure secondary to this massive pulmonary embolism. All have significant hemodynamic instability — their pressures are low, their heart rates are extremely high, and they all have difficulty breathing, along with chest pain. There is a new, endovascular treatment strategy that may present a life-saving option for these very sick patients. The technique involves placing a catheter emitting ultrasound energy along with thrombolysis. The combination of thrombolytic agents (typically tPA, retivase, retiplase, tenecteplase or urokinase) along with ultrasound energy will break up the PE. What is the standard treatment for PE? The traditional treatment option is peripheral anticoagulation using heparin. The literature has explored giving the thrombolytic therapy directly into the lung, into the pulmonary artery and into the clot itself. These treatments resulted in varying degrees of success. What’s different today is that we can add the benefit of ultrasound energy, which actually enhances the efficacy of thrombolytic medication. The concept of using ultrasound energy to break up clot has been around for five or six years, but more specifically, use of this technology in patients with massive pulmonary embolism is relatively new. Are there any potential complications? If excessive or prolonged administration of thrombolytic therapy is given, there may be an increased risk of bleeding. However, with ultrasound-accelerated technology, clot is broken down much more quickly than with thrombolytic use alone. Not only is the infusion duration of the thrombolytic therapy minimized, but the overall dosage of the thrombolytic therapy is decreased. From a bleeding standpoint, complications from using this new technology are actually less. Is there a time difference in terms of treatment length (heparin versus ultrasound-assisted thrombolysis)? With heparin, typically given through a peripheral IV in the upper extremity, the benefit of dissolving the clot in the lung is very prolonged. The improvement in symptoms, which include respiratory discomfort and right heart failure, can be as long as months, if not years, because heparin alone does not actively break down the clot in the lung. Heparin simply minimizes worsening of the clot progression. With catheter-directed thrombolysis, we can see symptom improvement in days to weeks. In our experience, we have seen dramatic improvement within 12 to 24 hours. These patients have difficulty breathing and signs of right heart failure because stress on the lung and pressure is so high. We see improvement typically within 12 to 24 hours once we initiate the ultrasound-assisted therapy. How many patients have you treated so far? We have treated over 20 patients and now followed them out from 3 months to 18 months. Nearly all have experienced dramatic improvement with successful outcome. Dr. Lin can be contacted at plin@bcm.edu

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