By CHRISTOPHER DELPORTE
CDU Washington Editor
and LARRY HAIMOVITCH
CDU Contributing Editor
NEW ORLEANS – Once thought of as a relatively boring cardiovascular sub-specialty, the field of electrophysiology (EP) has blossomed in the past decade, fueled primarily by the incredible clinical and commercial progress of implantable cardioverter-defibrillators (ICDs). The impressive growth in the EP field is best exemplified by the fact that the membership of the Heart Rhythm Society (HRS; Washington) has nearly quadrupled in the past 15 years.
While ICDs certainly were prominent at numerous sessions and posters at last month’s Heart Rhythm 2005, the 26th annual scientific sessions of HRS, other emerging technologies certainly enjoyed the limelight during the four-day meeting at the Ernest N. Morial Convention Center.
Although totally dwarfed in size by the $4 billion domestic ICD market (which also includes devices for cardiac resynchronization), catheter ablation nevertheless is an important aspect of the interventional EP market, as it addresses important arrhythmias that remain huge clinical problems.
Specifically, atrial fibrillation (AF) is an ongoing conundrum for patients and their physicians, as its prevalence and incidence not only continues to increase with the aging population, but its exact causes and, more importantly, successful therapies remain elusive.
Over the past five years, catheter ablation of AF has evolved from an experimental procedure to one that is commonly performed throughout the world. In the U.S., for example, an estimated 15,000 ablations to treat AF ablations are being done annually, with at least that many outside the U.S. The lion’s share of AF ablations are aimed at left atrial pulmonary vein (PV) ablation. EP experts generally agree that AF is triggered in most patients by arrhythomogenic tissue in the pulmonary vein.
Speaking at an evening symposium held during the HRS gathering, Hugh Calkins, MD, director of the EP lab at the Johns Hopkins Hospital (Baltimore), stated that the rapid growth of AFib ablation reflects “encouraging reports of the safety and efficacy of the procedure.”
Yet, much progress remains, since the clinical results are far from sterling. At an HRS session titled “Imaging, Mapping and Ablation from 2005 to 2010,” Riccardo Cappato. MD, of the Policlinico San Donato (Milan, Italy), reported on a worldwide survey of nearly 9,000 AF ablations that were performed at 100 centers between 1995 and 2002. Cappato noted that the reported success rate, defined as free of any medical management after six months, was a modest 52%, with another 24% experiencing reduced drug needs.
He noted that these results were probably even poorer, since hospitals that did few procedures did not even respond to the survey. “Clearly, we need to do better than this” to make ablation the procedure of choice, he said.
One of the EP community thought leaders, Karl Heinz Kuck, MD, of the Algemeines Krankenhaus St. Georg (Hamburg, Germany), delivered an excellent talk on how new energy sources, such as high-intensity focused ultrasound (HIFU) lasers and cryothermia will improve the results of AF ablation. Regarding HIFU, he cited the impressive technology of ProRhythm (Ronkonkoma, New York), which features a steerable catheter that is focused via a reflecting balloon configuration to deliver sufficient energy to achieve ablation to the pulmonary vein. ProRhythm’s technology is being evaluated in clinical trials in both Europe and the U.S
ProRhythm (formerly known as Transurgical) reported early this year that it had entered into a number of agreements with St. Jude Medical (St. Paul, Minnesota), providing, under certain conditions, for St. Jude to make two $12.5 million minority investments in ProRhythm, which the company anticipates will occur in 2005. The agreements also provide that St. Jude has the exclusive right to acquire ProRhythm for $125 million in cash, with additional cash payments payable to ProRhythm shareholders after completion of an acquisition if the company achieves certain milestones.
Citing several relatively recent innovations and developments now under way, Kuck concluded his HRS talk by saying that “the automation of mapping and ablation could become the standard of care by the year 2010.”
In a similar vein, renowned EP expert Douglas Packer, MD, of the Mayo Clinic (Rochester, Minnesota), indicated that “the integration of mapping, guidance and ablation will be commonplace by 2010.” He said he is particularly enthusiastic about 3-D MRI and computed tomography (CT), intracardiac echocardiography (ICE) and remote and image-guided robotic technologies.
Improved imaging technologies and more precise navigation devices were clearly on display at this year’s HRS meeting. Both EP MedSystems (West Berlin, New Jersey) and Siemens Medical Solutions (Malvern, Pennsylvania) prominently featured their ICE product lines. The latter pioneered this technology and is the undisputed market leader, which is now increasingly being used in PV ablations. The former, which entered the market in 2004, recently initiated a multi-center, randomized U.S. study called Intra-Cardiac Echocardiography Guided Cardioversion to Help Interventional Procedures (ICE-CHIP), which will investigate the potential role of ICE in the cardioversion of AF patients.
EP Medsystems and Philips Medical Systems (Andover, Massachusetts) have recently concluded a multi-platform joint development agreement, to provide the most technologically advanced EP products. An initial collaboration has already occurred in the area of EP recording systems and this will likely evolve to a joint effort in the ICE area.
Innovative mapping technologies that have appeared in the last few years have clearly improved the safety and efficacy of catheter ablation. These include the CARTO, a 3-D, color-coded cardiac mapping and navigation system from Biosense Webster (Diamond Bar, California), a division of Johnson & Johnson (New Brunswick, New Jersey), the EnSite non-contact cardiac anatomical mapping technology from St. Jude Medical (St. Paul, Minnesota) and the Realtime Position Management (RPM) ultrasound catheter-based technology from Boston Scientific (Natick, Massachusetts). Many EP labs have acquired one of these technologies in recent years.
While 3-D MRI and CT will enhance these technologies, an exciting new area in interventional EP is in catheter navigation systems. A recently new public company, Stereotaxis (St. Louis) is the most prominent player at the moment. Its magnetic assisted intervention system consists of proprietary catheters, guidewires and stent delivery devices along with a computer-controlled, externally applied magnetic field that precisely and directly govern the motion of these devices. The goal is to bring precise remote digital instrument control and programmability to interventional procedures.
The range of procedures is enormous, spanning EP, cardiology and other interventional disciplines. Clinical results to date are positive and appear to validate the technology. For example, in a series of relatively simple supraventicular tachycardia ablations, both the procedural time and fluoroscopic time were cut significantly. In a study of left ventricular lead implants comparing conventional navigation to magnetic navigation, the procedure time again was reduced significantly, with a further benefit that the number of disposable supplies was reduced.
Speaking at a company-sponsored evening symposium, Ruchir Sehra, MD, Stereotaxis’ chief technology officer, indicated that his company has sold 30 systems worldwide (including 20 in the U.S.) and that about 1,600 cardiology procedures have been performed to date. The company has important strategic alliances with Siemens, Philips and Biosense Webster.
Warren Jackman, MD, director of clinical electrophysiology at the University of Oklahoma Medical Center (Oklahoma City), recently said that the Stereotaxis system “defines a new era in interventional medicine, one where computers and software provide an opportunity to help physicians navigate devices more precisely and efficiently.”
Debuting at HRS, privately owned, venture capital-backed Hansen Medical (Mountain View, California) was clearly one of the highlights of the meeting. The company was founded in 2002 by Frederic Moll, MD, who also was a founder of the enormously successful Intuitive Surgical (Sunnyvale, California), and Rob Younge, a co-founder of Intuitive. Hansen’s goal is to provide safe, accurate and efficient control over catheter movement during interventional procedures. Ideally, this precision will lead to faster procedures as well.
The basis of the system is an electromechanical robot, which the physician controls from a workstation that integrates visualization, guidance, and patient physiologic data. Once seated at the workstation the physician is able to instinctively guide the movement of diagnostic or therapeutic catheters with a “joystick” to the desired anatomic location.
Hansen’s exhibit, its first at HRS, was consistently buzzing with activity the entire show. In ad-dition, several talks during the conference were highly favorable, as physicians extolled its ease of use, instinctive operation and simplicity. At an evening symposia, Andrea Natale, MD, of the Cleveland Clinic (Cleveland), said that in his feasibility trial, the system performed very well, reducing procedural time and demonstrating safety and efficacy.
“This is a very promising approach to EP catheter navigation,” he told a packed room. Natale did caution, however, that because of the lack of tactile feel of conventional catheter manipulation, it would take time to get used to using this robotic system. “It is very different than what we are used to” he concluded.
Hansen said it hopes to attain FDA clearance via a 510(k) in the second half of this year. Final pricing of the system has not yet been determined, but CEO Moll told Cardiovascular Device Update that he expects it will be priced at about half that of the Stereotaxis system, or somewhere in the neighborhood of $1 million.
Fast pace of change for HF docs
Just in the last few years, the approach to heart failure treatment has gone through dramatic change, and the pace – pardon the pun – is not slowing.
That was the main message from Robin Germany, MD, cardiologist at University of Oklahoma Health Sciences Center (Oklahoma City), during the Heart Rhythm 2005 gathering.
Germany offered her thoughts on changes in heart failure treatment from a physician’s perspective. “Only a few years ago, most heart failure treatment programs in the U.S. were focused on getting patients to transplantation,” she said. “If you look today, biventricular pacing and ICDs [implantable cardioverter defibrillators] are really where we’re at. Now where do we go from here?”
When heart failure drug therapies such as ACE inhibitors and beta-blockers became available, the beginning of a culture change emerged, resulting in decreased mortality by 40% to 45% in the last 10 years. “But now with studies such as MADIT I and MADIT II showing that these devices are really benefiting patients,” she said, “we now have to look at the whole disease process differently. Perhaps devices actually may be the key to our chronic management.”
Transplants aren’t needed as often, and patients are living longer, Germany said. But that encouraging news still comes with many challenges. “Part of the culture change means we’re not looking at transplantation as the end all or be all, but if you look at the incidents of sudden cardiac death in this country, we are will missing a tremendous amount of these patients,” she added.
Germany suggested that heart disease is something that must be approached with more of a long-term focus, saying that it will have to be managed more as a “diabetes-type chronic condition.” She said, “I have several patients in their 30s, and they could live another 50 years with biventricular ICDs. How many devices am I going to have to implant and pull out?”
As patients live longer, the management of their devices and their care come into question. More clinical trials showing longer-term data will be helpful, she noted.
Devices, while helping patients lead longer and fuller lives, also are providing insight into better treatment options. “Devices and Internet-based technology can provide us so much information we can use to help our patients,” Germany said.
One of the slides she used during her presentation showed the heart rate variability in one of her patients. The graph showed heart rate during a fight with a child and then during a period when the patient (a little binge eating because of the stress, Germany said) had eaten pizza. The monitoring device also was able to show the recuperative effects drugs had on the trauma wrought during both the dispute with the child and gustatory struggle with the pizza.
The care for these patients is going to have to be a joint effort among cardiologists, electrophysiologists and internists, she said. “Now that patients are living forever,” Germany said, doctors in different areas will have access to a wealth of data from one patient, and they will all have to communicate regarding the patient’s care. She added: “That’ll require a change in mindsets.”
Better management can trim AF costs
In addition to breakthrough scientific data, organizers of this year’s Heart Rhythm Society (Washington) scientific sessions said there needs to be an increased focus on the financial side of heart rhythm management. As the most common heart rhythm disturbance, atrial fibrillation (AF) – given its financial impact on the healthcare system – is a pretty good place to start that greater examination.
During last month’s conference, Peter Zimetbaum, MD, assistant professor of medicine at Beth Israel Deaconess Medical Center and Harvard Medical School (Boston), presented information on the large socioeconomic implications of the disease.
“I think trying to get a clear sense for the cost of the management of atrial fibrillation is an incredibly difficult task,” Zimetbaum said, because the condition is interwoven with so many others ailments. “The rise in rates of atrial fibrillation of course is going to lead to a significant increase in healthcare expenditures,” he said
But Zimetbaum said that the rise in spending could be somewhat curbed – if not drastically reduced – through implementation of better disease management and reduction of hospital admissions, especially given the fact that most people deal with AF for 10 to 15 years.
Most of the costs come from the routine management of AF, he said, while costs from related complications, such as stroke, are harder to measure. AF can cause blood to pool inside the heart and form clots, which leads to stroke. According to the American Heart Association (Dallas), AF is the cause of 10% to 15% of all strokes.
Despite the increased availability of anti-arrhythmic drugs, the rate of hospital admissions for AF has increased over the last 10 years, Zimetbaum said. When AF is examined as the principal discharge diagnosis, the total cost is about $2.7 billion per year in the U.S. And when it is measured as a co-morbid diagnosis, the cost is $1.8 billion, which Zimetbaum termed most likely an “underestimate.” The cost of AF on an outpatient basis also is roughly $1.8 billion.
Compared to other cardiovascular disorders, the numbers are low, according to Zimetbaum. But when cost implications are examined in the light of AF as a cause of other cardiovascular conditions, the impact is greater.
In the case of stroke, he said there is little information on the cost of AF’s impact. In the U.S., an estimated $51 billion in productivity is lost as a result of strokes. And nursing home costs produce another $12 billion in expenses, much of that related directly to AF. Emergency department visits in this country are a primary source of AF-related hospital admissions, and AF accounts for more than 50% of all arrhythmia-related hospital admissions, he said.
Through doctor and patient education efforts, his institution has been trying to create ways to make AF “an entirely outpatient disorder,” Zimetbaum said.
“Interestingly, there is a bit of disparity in the U.S. with regard to hospital admissions and discharges related to AF, with lower admissions on the West Coast, where there is greater managed care, compared to the East Coast,” he said. Such efforts are leading to the implementation of more precise guidelines for AF discharge, he said.
Beth Israel estimates, Zimetbaum said, that “a simple, more common-sense approach in the emergency department” could reduce admissions to the hospital by 150,000 to 200,000 annually and save up to $500 million. “Improved measure to education physicians and patients will improve the compliance with anticoagulation guidelines,” he said. “Tremendous resources are being devoted for a potential cure, but efforts need to be made to improve the safety and efficiency of the every day routine management of these patients.”
‘Relative risk reduction’ seen for some
Cardiologists shouldn’t be in such a rush to use implantable cardioverter defibrillators (ICDs) as a cure-all, without better identification of at-risk patients. That was the take-away message of a presentation sponsored by GE Healthcare (Waukesha, Wisconsin) at the HRS scientific sessions. Mark Josephson, MD, Herman Dana professor of medicine at Harvard Medical School and cardiologist at Beth Israel Deaconess Medical Center (Boston) said that the technology may have reached “a point of diminishing returns.”
“Everyone in this country has jumped on this device as a primary therapy to treat those on a path to cardiac arrest and to prevent cardiac arrest,” he said. “The problem is that there has been only a relative risk reduction.”
Implantation of ICDs has increased logarithmically, according to Josephson. “That’s why we need to think about cost, especially when you consider that 90% of people may not benefit from the device,” he said. Roughly 150,000 ICDs were implanted in 2002 at a cost of $5 billion, according to Josephson’s numbers. He predicted 200,000 device implantations in 2006. “And that’s just the tip of what might happen unless the reimbursement structure changes and our risk stratification changes,” he added.
The CMS expanded ICD coverage in January, based on data from the results of the Sudden Cardiac Death in Heart Failure Trial (SCD-HeFT), sponsored by the National Institutes of Health (Bethesda, Maryland) and funded by ICD manufacturer Medtronic (Minneapolis) and drug maker Wyeth Pharmaceuticals (Madison, New Jersey).
Results of the 2,500-patient trial found that ICDs cut the risk of death in heart failure patients by 23%. Short follow-up from recent studies, such as SCD-HeFT, is “good news and bad news,” Josephson said, because short-term studies showed adequate efficacy but not long-term benefit after only a two-year follow up.
Josephson said the coverage decision was a good move but that now the challenge will be to save billions of dollars rather than spending them. “Let me say that I do believe that ICDs are the most effective way for preventing sudden death from a ventricular arrhythmia if you have it, and the cost is worth it if people benefit,” Josephson said. “But in order for ICDs to be widely applied to lower-risk populations, the cost must be drastically reduced and their efficiency enhanced to improve risk stratification.”
In other findings at the HRS conference concerning ICDs:
• Patients recently diagnosed with weak hearts unrelated to coronary artery disease may benefit from ICDs as much as patients with long-term, established disease, according to a new study. While CMS guidelines issued last year allow ICDs for patients who have been diagnosed with non-ischemic cardiomyopathy (NICMP) for more than nine months, the study indicates that ICDs are equally beneficial for newly diagnosed patients.
“Our findings suggest that the CMS guidelines may not reliably discriminate patients at high risk for sudden cardiac arrest,” said Kevin Makati, MD, lead investigator and cardiologist at Tufts-New England Medical Center (Boston). “This study sheds new light on the potential benefits of ICDs for patients who have been diagnosed with weak hearts for less than nine months.”
The study evaluated 133 patients with NICMP. A total of 76 patients had their initial diagnosis for more than nine months, while 57 patients had been diagnosed for less than nine months. During a follow-up period of 27 months, no difference was found in the occurrence of treated and lethal ventricular arrhythmias. “This study shows a clear benefit of ICDs for patients with cardiomyopathy, irrespective of when they were diagnosed,” said Stephen Hammill, MD, president of the Heart Rhythm Society. “CMS may want to revisit the coverage criteria for these patients in light of these findings.”
• Chest “thumping” over the heart has long been considered a way to terminate ventricular fibrillation (VF) and a way of resuscitating people in cardiac arrest outside of a hospital setting. But a study headed by Mark Link, MD, cardiologist at Tufts-New England Medical Center, concludes against recommending “precordial thumps to cardiac arrest victims, if external defibrillation is readily available.”
The study evaluated chest thumping in an experimental model involving 31 episodes of VF in animals. No episodes of VF were stopped with pre-cordial thumps, while all of the episodes were terminated with an external defibrillator. Commenting on the study, Hammill said, “It’s important to compare anecdotal evidence against scientific research so that people can be better educated about how to respond to life-threatening emergencies like cardiac arrest.”