CD&D Contributing Writers

HOLLYWOOD, Florida – Doctors suggested that preliminary results indicate that treating acute strokes with Boston Scientific's (Natick, Massachusetts) WingSpan stent can make the difference as to whether a patient has to be institutionalized or can go to his or her home.

"Our preliminary data is very exciting," said L.N. "Nick" Hopkins, MD, professor and chairman of neurosurgery at the University at Buffalo in New York, and director of the Toshiba Stroke Research Center. "What these preliminary results tell us is that this treatment works."

He reported at the International Symposium on Endovascular Therapy (ISET) in January that of the 18 acute stroke patients treated – most of them long after the three-hour window of opportunity for lytic treatment – 12 of the patients survived, and lowered their NIH Stroke Scale scores by 6 to 8 points. "We are seeing pretty significant improvement," he said.

"If anyone comes in with a 9 or 10 in the NIH scale it is a bad stroke; it is a nursing home stroke," Hopkins said. "If we can drop that 6 to 8 points, the patient would probably look normal within a few months. That's the difference between going to a nursing home or going home."

He worked with a team of researchers and support staff led by the trial principal investigator Elad Levy, MD, also of the University at Buffalo. "We received FDA approval to use the WingSpan stent in 20 cases in a pilot study," Hopkins said.

"Previously we might be able to get half the arteries open and get improvement rates in the 30% range," he said. "In our small study we are getting more like 100% of the arteries open," he said – and getting a favorable outcome in about 70% of the cases.

Hopkins said that the procedure is rapid. "From the time we put a needle into the patient's groin until we place the stent and open the artery it takes about 15 minutes," he said. He noted that the brain arteries being treated are similar in size to coronary arteries, but the arteries in the brain are far more fragile than those in the heart.

While getting patients to treatment as soon as possible is still the goal of stroke therapy, Hopkins said time is no longer that critical if proper imaging is performed. "If the CT perfusion imaging shows that the brain is viable, I really don't care how late it is – it can even be done days later," he said. "That doesn't change the fact that there is urgency but what it speaks to it that in every person there is collateral flow. That flow isn't enough to allow the cell to function, but the cells won't die until the flow decreases even further."

The Dynamic Volume CT measurement gives doctors a clear idea of where blood flow warrants placing a stent, and where to avoid opening an arties as well.

"The FDA is excited about us expanding this study to other centers," he said. "That's our next step."

Hopkins said he and stroke team members deployed a number of devices available for removing clots. "They ought to be, theoretically, the way to go because stroke is usually an embolic event rather than a plaque rupture, thrombolic event," he explained. "But what appears to happen is that the clot becomes very adherent to the wall of the artery very quickly – within hours. And the clot retrieval devices don't work. Something is probably happening with the vascular wall.

"We would get frustrated working for hours to remove a clot without success," Hopkins said. "So we kicked around the idea of putting in a stent. We tried it and it worked. We started with a coronary stent, but they don't track very well in the brain. They are too stiff and they are balloon-expandable, so you run the risk of hurting things in getting them there. But when we got them there and popped them open, it worked. Then along came neural, self-expanding stents and that worked too," he said.

Among the patients treated in the series was a 27-year-old woman who, eight weeks after a Cesarean delivery, collapsed. Her initial deficits included upper extremity and slurred speech. She left the hospital nearly normal after having the stent placed.

Hopkins said intravenous tissue plasminogen activator (tPA) appears to work in mild strokes, but overall 50% of patients are dead or disabled after three months. As the U.S. population ages, strokes are increasing. He said that the 750,000 cases a year will reach 1.2 million by 2025.

He said that since 1991, his stroke center has used or adopted medical treatment of stroke with urokinase, prourokinase, tPA, abciximab, combinations of drugs, and, more recently angioplasty, clot retrieval and stenting to open the blood vessels that have remained blocked despite use of thrombolytic agents.

"The improvements in technologies – in the type of stent and the type of catheters – are making these advances possible," said James Benenati, MD, medical director of the noninvasive vascular laboratory at Baptist Cardiac & Vascular Institute (Miami).

What makes this study interesting is that the researchers and the device maker are working with the FDA under an Investigational Device Exemption procedure, which may make the off-label use of the stent an approved usage.

"I think the use of stents in the brain to treat an acute stroke is going to be the way we go," Benenati said. The symposium is sponsored by the vascular institute.

Device a key aid in kidney injury cases

Doctors suggested that the use of the FlowMedica (Fremont, California) Benephit Intra-Renal Drug Delivery System can get enough drug into the kidneys to allow critically ill patients to recover function, which also has implications for cardiologists.

James Tumlin, MD, professor of medicine-nephrology at the University of Tennessee-Chattanooga, and director of clinical research at Southeast Renal Research Institute, said that the recovery is rapid, once the dual kidney catheter is placed and the vasodilator fenoldopam is administered.

"Over 61% of our patients in this study recovered renal function within four days after treatment with the catheter system," Tumlin said at the 21^st annual International Symposium on Endovascular Therapy (ISET) here this week. He enrolled 28 patients with acute kidney injury in the study, and 10.7% regained renal function – the ability to produce two times the baseline urine output – within two days; 36% additional patients recovered function within three days and another 14.3% recovery kidney function within four days.

"It is difficult for me to convey from the podium the severity of illness of these patients," said Tumlin as he delivered his report at the proffered papers session of the ISET meeting, which was attended by more than 1,200 doctors, scientists, clinicians and allied healthcare professionals.

Of the 28 patients enrolled in the study, 92% were diagnosed with oliguria and 90% were unresponsive to diuretic therapy. Unresponsiveness was defined as being unable to produce twice the baseline urine after an intravenous bolus of furosemide (80 mg to 120 mg).

He said that 14% of his patients had acute kidney injury as a result of a coronary artery bypass graft; 16% had undergone abdominal aorta aneurysm repair; 35% had reduced ejection fraction; 39% had developed sepsis and 61% had chronic kidney disease. The patients also had numerous co-morbid conditions, including respiratory distress among 57% of the patients; 46% were on mechanical ventilation.

Overall mortality at 28 days was 11%. "Although this is not a controlled trial, this is an unusually low mortality rate in our experience," Tumlin said. "The need for dialysis replacement therapy was 14% and none of the patients who required dialysis expired. The typical rate of death among this type of population is over 60%." Creatinine levers peaked at 2.5 mg/dl and decrease to about 2.05 at Day 7.

"Frankly, we would have expected 40% to 50% of these patients to have died within the 28 days we followed them," he said. "We would have thought that two of the three patients who had to go to dialysis would have died. But they all survived through at least 28 days."

The researchers, including his co-investigator David Allie, MD, director of the Cardiovascular Institute of the South (Lafayette, Louisiana), followed the patients through 28 days, so long-term outcomes were not available.

"The FlowMedica catheter system appears to be a safe and effective means for doing intra-renal fenoldopam infusion," Tumlin said. "We have successfully done this up to a dose of 0.8 micrograms/kg/minute. The standard dose is 0.4 mcg/kg/minute. High-dose intravenous fenoldopam responded with renal output in about 61% of patients within four days of treatment."

He noted that the incidence of acute kidney injury and dialysis-dependant renal failure is rising by the decade. Currently, he said 522 per 100,000 people will require some form of dialysis during their lifetimes. "It has become a very big deal," he said.

Development of acute kidney injury translates to a 22-fold higher post-operative mortality rate if the patients have a pre-operative glomerular filtration rate of less than 60 mm/minute. In coronary artery bypass graft surgery the risk of acute kidney injury is as high as 24%.

"High-dose vasodilator therapy has been attempted to correct the constriction that is inherent in acute kidney injury but its use has been controversial and somewhat disappointing," Tumlin said. Systemic treatment has not allowed for adequate medication to reach the kidney. We hypothesized that intra-renal delivery of fenoldopam would reduce hypotension and secondary renal hypoperfusion. Augmenting renal blood flow may reduce progression to dialysis-dependent acute kidney injury."

He said roadblocks to vasodilator therapy in acute kidney injury include lack of bedside access to reliable biomarkers for early identification of acute kidney injury; lack of the ability to deliver isolated vasodilator therapy to the renal circulation; the need to avoid systemic hypotension and the lack of infrastructure for the timely placement of a catheter.

Tumlin said that the use of the FlowMedica Benephit Intra-Renal Drug Delivery System could be placed by cardiologists, interventional radiologists and possibly even hospital intensives. He explained that the system is introduced into the aorta similarly to cardiac procedures. When the catheter passes above the junction of the kidney arteries, the "ears" of the Benephit system and deploys. As the catheter is pulled back, the ears float into the renal arteries.

"It is a very simple, easy to perform maneuver," Tumlin said. "We think it can be performed at bedside and cause less problems for already critically ill patients who will be spared a trip to the radiology department or the catheter laboratory."

The Benephit Infusion Systems are FDA-cleared and are indicated for the "infusion of physician-specified agents in the peripheral vasculature including, but not limited to, the renal arteries."

FlowMedica was purchased by AngioDynamics (Queensbury, New York) earlier in January.

Abele predicts boost for learning

Serving as the leadoff speaker for the conference, man helped set the tone for innovation early in the ISET meeting. John Abele, founder and chairman of Boston Scientific (Natick, Massachusetts), helped set the tone for innovation.

As reported in the conference newspaper, Abele addressed what he considers the forces most likely to affect medical education during the next 10 years, citing two influences in particular that promise to boost learning in the near future:

* Technology. Abele said there is a great deal of effort being put into virtual, simulated medical systems. He said that digital human projects not only have anatomical definitions of humans, but also thermal, electrical, mechanical and chemical definitions.

He cited software applications such as Photosynth and Multi-Touch that allow easy integration and interface with massive amounts of data. This type of simulation-based training should make learning efficient and compelling, Abele said.

"I think you're going to be quite amazed at the tools you're going to have in short order," he told his audience of physicians and researchers.

* Culture. "This is perhaps the most significant influence from my point of view: the whole concept of working together in large groups – the Wikinomics phenomenon, if you will," Abele said. "There are many physicians who are playing these massive, multiplayer online games, and they are going to have a role in education and learning."

Video games and virtual online communities such as Second Life are popular with physicians, he said, and there has already been a study on the impact of video games on surgeon training.

In the future, "I could see something like massive multi-player online case analyses," Abele said. "It is that cultural willingness to collaborate at that massive scale that we will be looking forward to."

Wrist access safer, easier

Data presented at ISET indicates that use of a radial artery (wrist) approach to unblock coronary arteries instead of the usual femoral artery procedure can mean less bleeding, less down time, lower costs and less risk overall, particularly for obese patients.

A study involving more than 5,000 procedures performed at Baptist Cardiac & Vascular Institute (Miami) suggests that accessing the blocked blood vessels through the radial artery significantly reduces the risk of bleeding and nerve damage.

The radial approach also is easier on patients, the study said, because they can sit up after the procedure and walk away almost immediately.

Currently, only about 2% of all minimally invasive heart treatments in the U.S. are performed through the wrist.

"I believe 75% of patients would be candidates for the radial approach if it were an option," said Ramon Quesada, MD, medical director of interventional cardiology at Baptist Cardiac & Vascular Institute and ISET course director. "The radial approach is a bit more technically challenging for physicians, but once they master it, I think most would prefer it."

When the femoral access approach is used, there is a 2.8% risk of bleeding or nerve damage, according to studies. At Baptist Cardiac & Vascular Institute, the complication rates for the radial approach are very low, with just 0.3% of patients having bleeding complications and none suffering nerve damage.

The radial approach isn't appropriate for all patients, including those who have very small or twisted arteries or are extremely thin, said Quesada. "Using the radial approach results in lower cost, less time before the patient can get up and walk around and fewer complications," he said. "Patients who are ideal candidates for the radial approach are those who are obese or have severe peripheral arterial disease."

Ultrasound can reduce drug need

Discussions surrounding a live case demonstration at the conference indicated that delivering clot-busting drugs with an ultrasound-enhanced delivery system could reduce the amount of drugs needed to break up blood clots in the legs and pelvis.

In a live case viewed by hundreds of endovacular specialists, Constantino Peña, MD, an interventional radiologist at Baptist Cardiac & Vascular Institute, treated a 74-year-old male with a blocked leg artery. Peña delivered the drug Tenecteplase (TNK) to the clot via ultrasound-accelerated catheter-directed thrombolysis, and the clot was completely dissolved upon examination 12 hours later.

Peña said that the amount of TNK used to dissolve the clot was half what is typically used.

Lowering the amount of drug needed to dissolve clots can significantly reduce the risk of major bleeding, according to Barry Katzen, MD, founder and medical director of Baptist Cardiac & Vascular Institute.

Ekos' (Bothell, Washington) EkoSonic Mach 4 is the only catheter that uses ultrasound to open clots. "It speeds up the process and can resolve deep-vein thrombosis in less than 12 hours," said Ekos President/CEO Robert Hubert.