CDU

ANAHEIM, California – With the nearly endless list of events offered at the American Heart Association's (AHA; Dallas, Texas) annual Scientific Sessions here last month, an early morning session might be considered low on an attendee's things-to-do list. But a 6:30 a.m. breakfast focused on the use of radiofrequency (RF) to treat atrial fibrillation (AF) drew a full house to the San Simeon room of the Hilton Hotel, the crowd obviously hungering for more than breakfast pastries.The host was Cardima (Fremont, California), a developer of microcatheter-based systems for mapping and ablation of cardiac arrhythmias. The panel, moderated by Warren Jackman, MD, professor of medicine and director of clinical electrophysiology at the University of Oklahoma Health Sciences Center (Oklahoma City, Oklahoma), discussed several new technologies to treat AF, one of the large ongoing needs in the cardiovascular sector and still largely unmet.

Angelo de Pola, MD, director of cardiology at the Federal University of Sao Paulo (Sao Paulo, Brazil), focused on the mapping techniques required in catheter ablation, saying that magnetic resonance imaging (MRI) provides good images, "but you need information immediately when you are performing a procedure." MRIs can take too long to process when information is needed a rapid fashion, he said. "You need immediate information to make a clinical decision and the best way to do this is to monitor the positioning of a catheter ... with a detailed angiographic definition."

Acknowledging that MRI or computed tomography could be helpful prior to surgery for initial placement, he said the intravascular ultrasound probe is the most helpful for instantaneous results.

Thorston Lewalter, MD, of the University of Bonn (Bonn, Germany), discussed Cardima's Revelation Helix microcatheter, a new linear ablation device providing circumferential mapping and ablation of the pulmonary vein, laying out early results of the randomized multicenter BITMAP (Breakthrough and Isolation Trial Mapping and Ablation of Pulmonary Veins). Study objectives were the safety of the procedure and patient improvement.

"This approach was very helpful because we often tried to get a very ostial position, and this also indicated that we had large big left atrial far-field signaling to use program stimulation in order to more clearly separate signals," he said.

Thus far, eight patients been investigated, and 25 patients have been mapped and treated, with three-month, six-month and one-year follow-up yet to come. Lewalter said that the catheter is very flexible, and with the assistance of a reflective guide, "You can nicely position it without tension."

Hugh Calkins, MD, professor of medicine and director of electrophysiology services at Johns Hopkins University (Baltimore, Maryland), reported on the current results of the U.S. right-sided linear ablation trial of the Revelation ablating catheter, a study now in its third year. His discussion encompassed the design of the catheter and the current status of right atrial linear ablation in the overall picture of catheter ablation of AF.

He noted the need for an atrial catheter, adding a call to industry to develop one that would work properly. There have been many attempts to make such a device, Calkins said, but "the only one still standing right now is the Cardima Revelation." He noted that he was initially skeptical of the device's ability to make decent lesions. "I told them [Cardima] that I wanted to do animal studies myself," he said, adding that he was "pleasantly surprised" with the results.

Getting the device into the hands of his colleagues was a difficult endeavor, Calkins said, with the comment that the FDA "never makes things easy here in the U.S."

He first did a 10-patient feasibility study, then a Phase II trial, and finally a pivotal trial, currently in progress. Calkins said that the results of the first 48 patients can be interpreted based on "what type of person you are – an optimist or a pessimist. If you're a pessimist, you'd probably say, 47 out of 48 patients had atrial fibrillation again, and it doesn't work.' But if you're an optimist, you'd say, my goodness, look at this tremendous reduction in afib burden.'" He cited the example of a patient with more than 50 AF episodes a month, now down to just four per month.

Additionally, data from six-month follow-up demonstrated more than a 100% reduction of episodes in half the patients and a 50% reduction in episodes in 87% of the patients. The real issue here, he said, is quality of life, "since afib doesn't kill you."

Calkins said that he personally called some of the patients who had participated in the trial from one to three years previously, and asked about their condition. A total of 21 patients responded and said they were now minimally symptomatic.

Summarizing these preliminary results, he told his breakfast audience that radiation ablation using the Cardima system "demonstrates that it's safe, it seems to reduce the afib burden results in long-term elimination of afib in up to half the patients and improves [their] quality of life."

Abraham Kocheril, MD, head of cardiac electrophysiology at the University of Illinois (Champaign-Urbana, Illinois), discussed mapping guided linear ablation of atrial fibrillation. "Albert Einstein said to create you must first destroy,' and I think this is applicable to ablation of all types."

Kocheril said that the current model in treating afib is an attempt "to limit the amount of continuous myocardium available for palpitation of atrial fibrillation," but that such an approach may not be correct for what needs to be accomplished.He has developed what he called an "unconventional method" to induce atrial fibrillation in patients by putting lesions in the most optimal sites. "What I'm doing," Kocheril said, "is trying to individualize the linear lesions to the patient."

His first patient was ablated in May 1998. That patient hasn't suffered from atrial fibrillation since and is off all medications, according to Kocheril. "You have to have a case like this to want to do more of a study, and he was a good case to start off with," he said, noting that the results of a 29-patient study of this novel treatment will be issued this month.

Elsewhere during the AHA gathering:

A large study probing the issue of stents vs. balloon angioplasty alone was presented by researchers from the Mayo Clinic (Rochester, Minnesota), comparing the use of stents following balloon angioplasty and angioplasty alone and attempting to assess the impact of coronary stents on mortality. Rather than resolving the question, the study may simply fuel further debate. Peter Berger, MD, said that stenting reduces target vessel revascularization (TVR) by 50% compared with balloon angioplasty alone. "We did an extensive search and tried to identify all published and unpublished randomized control trials carrying a strategy of stenting vs. a strategy of balloon angioplasty alone. We think we got all of these at the time that we put this presentation together."

In all, a total of 22 trials were studied, including trials that studied de novo lesions, small vessels, chronic occlusions and myocardial infarction. Patients were followed-up from 6 months to 36 months, with only the longest follow-up from each trial analyzed. The trials included a total of 8,520 patients, fairly evenly divided between the two cohorts – 4,203 randomized to stent and 4,317 to balloon angioplasty alone. Surprisingly, no significant difference in mortality was observed with 2.5% reported for stenting and 2.3% for balloon angioplasty. However, crossover, or the additional use of stenting, was required in 14% of balloon angioplasty patients. Also of note, however, was the fact that there was no apparent reduction in mortality with stents compared with balloon angioplasty, despite the nearly 50% reduction in TVR with stents. "It's only when you look at the combined endpoint of any major events that you get a distinct difference with a low frequency of adverse events among those patients treated with a strategy of initial stenting," Berger said. He added that this favorable finding was present in nearly every study.

Berger cautioned that these results are not necessarily a pure head-to-head comparison of stents and angioplasty, saying, "We're talking about a strategy of stent placement vs. a strategy of balloon and crossover to stent if needed." However, even Berger was impressed with the significant number of crossovers. "I believe it's clear that the ability to achieve excellent results with a stent in 14% of balloon patients in whom balloon alone could not achieve an excellent result undoubtedly improved the outcome of these angioplasty patients."

In a version of the drug-coated stent strategy that is all the rage in the interventional cardiology sector, Angiogene (Montreal, Canada) presented six abstracts, three of them related to its study involving the coating of the BiodivYsio stent with the radioactive drug Oliglow. Oliglow is described as a Beta-emitter source shown to have optimal retention properties in the arterial wall as well as effectiveness in inhibiting smooth muscle cell proliferation. Results of an animal study showed a significant reduction of tissue growth in arteries using the coated BiodivYsio stents in adult farm pigs, a research effort being conducted with Biocompatibles (Farnham, United Kingdom), maker of the BiodivYsio stent. Also observed was improvement in lumen internal vessel size, ranging from 33% for a low-dose group to 54% for a high-dose group.

Advanced Tissue Sciences (ATS; La Jolla, California) presented new research on its tissue-engineered epicardial patch, called Anginera, showing its ability to improve the overall function of damaged heart tissue in mice while exhibiting no adverse effects on normal heart tissue. The study advances earlier research from ATS, published in the Oct. 23 issue of Circulation, showing that Anginera therapy stimulated the growth of mature blood vessels in damaged heart tissue. Anginera is a bioengineered living human tissue derived from ATS's core technology for developing biological materials for wound healing. Gail Naughton, PhD, president of ATS, said that while the first stage of research showed Anginera's ability to build new blood vessels in the damaged heart tissue of mice, the second-stage study "was designed to determine whether these new blood vessels would make any difference to the function of the heart." And the second study "showed that when applied to damaged heart tissue, Anginera significantly improved overall cardiac function and strengthened structural integrity, without negatively affecting healthy tissue." ATS announced in early October a collaboration with Medtronic (Minneapolis, Minnesota) to explore the application of its technology in areas of interest to that company.

AVI BioPharma (Portland, Oregon) presented strong positive results on the use of its proprietary NeuGene antisense compound, Resten-NG (AVI-4126), as a stent coating in preclinical studies, comparing use of the drug both with uncoated stents and three other compounds currently in clinical trials. AVI's data showed that arteries treated with AVI-4126-coated stents healed almost as quickly as those treated with uncoated stents. Arteries treated with stents coated with dactinomycin (Cosmegen or actinomycin-D) and paclitaxel (Taxol) healed much more slowly. No significant difference in healing time was found between AVI-4126 and the use of sirolimus (Rapamune) was detected. In addition, unlike these three comparison drugs, AVI-4126 was also found to be cytotoxic, unlike the three comparison drugs. AVI and Medtronic, through an agreement announced in May, are developing a coated stent using the NeuGene antisense technology described in this study. AVI Chairman and CEO Denis Burger, PhD, said the company will use the Resten-NG coated stents next year in Phase III human trials.

Cambridge Heart (Bedford, Massachusetts) rolled out results of an independent multicenter study conducted in seven Japanese medical centers demonstrating the ability of its Microvolt T-Wave Alternans Test to identify those patients who have experienced one heart attack and are at greatest risk for another. Presented by Takanori Ikeda, MD, of Toho University (Tokyo), the study concluded that Microvolt T-Wave Alternans is a strong risk stratifier for sudden cardiac death (SCD) after myocardial infarction. The test measures subtle fluctuations in the beat-to-beat patterns of the heart, called T-wave alternans, with these variations – measured at one millionth of a volt – detected during a typical treadmill or bicycle exercise stress test by sensors placed on a patient's chest, with previous research having shown the test's ability to detect life-threatening arrhythmias. The study evaluated 834 consecutive heart attack patients with follow up for an average of 25 months, with those who tested positive for Microvolt T-Wave Alternans being 11.4 times more likely to have a cardiac arrest or to become a victim of SCD than patients who had a negative test. None of the other available risk stratifiers evaluated were able to achieve statistical significance for this primary endpoint, researchers said.

Two technical abstracts released at the meeting supported the use of the Freezor technology from CryoCath Technologies (Kirkland, Quebec) over radiofrequency (RF) treatments to reduce both clot formation, known as thrombogenicity, and closing of the coronary artery, known as stenosis, which commonly lead to cardiac arrhythmias. The animal studies were conducted at the Montreal Heart Institute (Montreal, Quebec) and the University of Oklahoma Health Sciences Center. Steven Arless, president and CEO of CryoCath, said the papers underscored cryoablation's advantages in "an expanding ablation market opportunity of approximately $1 billion." CryoCath is projecting product launches in Canada and the U.S. over the next two years. The company said it expects to complete its pivotal investigation device exemption study, now under way, by Q101. Enrollment is that study is now more than 50% complete.

Point Biomedical (San Carlos, California) reported positive results for Phase II trials of its lead product PB127, an ultrasound imaging agent for assessing myocardial perfusion. In the trial, 54 patients with suspected coronary artery disease underwent simultaneous stress Myocardial Contrast Echocardiography (MCE) using PB127 and nuclear myocardial perfusion (SPECT) studies using 99mTc sestamibi. The investigators concluded that PB127 MCE demonstrated good concordance with SPECT sestamibi. Additionally, a subset of the patients underwent angiography, revealing that SPECT sestamibi had missed five cases of significant coronary disease that were correctly identified by PB127 MCE, and that PB127 only missed one case of significant coronary artery disease that was correctly identified by SPECT. When incorporated into a final clinical diagnosis, the sensitivity for detecting perfusion defects with PB127 was 97%, with a specificity of 83%, and an overall accuracy of 93%.

Radiant Medical (Redwood City, California) reported promising data from the COOL MI feasibility trial (COOLing as an Adjunctive Therapy to Percutaneous Intervention in Patients with Acute Myocardial Infarction) using the SetPoint Endovascular Temperature Management System. The SetPoint System is designed to cool a patient via endovascular heat exchange catheter. Researchers reported on treatment in 42 acute myocardial infarction (AMI),or heart attack, patients, receiving either cooling with the SetPoint System or no cooling therapy and all were treated with percutaneous interventions.

In the area of radiation treatment, Radiance Medical Systems (Irvine, California) held a BRITE II (Beta Radiation to Reduce In-Stent Restenosis) Study Clinical Investigators Meeting in conjunction with the AHA sessions. A multicenter, randomized study conducted in approximately 30 clinical centers in the U.S. and enrolling more than 400 patients, BRITE will determine the safety and effectiveness of the RDX Coronary Radiation Delivery System in patients who have had a coronary stent implanted and have returned to the hospital with restenosis in the coronary artery at the stent site. Radiance said that the preliminary data "may show the lowest restenosis rates of any vascular brachytherapy clinical trial conducted thus far."

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