BB&T Contributing Writer
SAN FRANCISCO — As has been the case in recent years, the 32nd annual scientific sessions of the Heart Rhythm Society (HRS; Washington) sponsored an AF Summit, focusing attention on atrial fibrillation (AF) with a full day of presentations.
The atrial fibrillation device market is a significant one. At its February investor conference, St. Jude Medical (Saint Paul, Minnesota) pegged the 2011 global AF device market at about $2.2 billion. Moreover, it is one of the fastest growing device markets, with St. Jude forecasting that the market will grow at 11% to 13% this year. The company believes that catheters used to ablate cardiac arrhythmias account for the largest individual category at about $640 million, or 29% of the total AF device market. St. Jude expects that in 2011 the global catheter ablation market will grow roughly 10% over 2010 levels.
According to Hugh Calkins, MD, an electrophysiologist (EP) and professor of medicine at Johns Hopkins Heart & Vascular Institute (Baltimore) who was one of the key featured speakers at this symposia, “the pace of progress in catheter ablation is very impressive.“ He said the understanding of AF, an extraordinarily complex disease and the most common arrhythmia in the U.S., has clearly been increasing at a rapid clip.
He cited the steady improvements in the success rate of catheter ablation, pointing to the results of six randomized clinical trials that yielded a 77% success rate for catheter ablation versus a paltry 29% for medical management. The 77% rate is for multiple ablation procedures (the single procedure rate is estimated at 57%) and includes drugs to supplement catheter ablation but nevertheless these results are encouraging and are far better than for drugs.
Yet, Calkins cautioned that “there is much we still do not know.“ For example, the long term safety, efficacy and survival rates for patients treated with catheter ablation. He said that the EP community is eagerly awaiting the results from the multicenter international Catheter Ablation Versus Anti-arrhythmic Drug Therapy for Atrial Fibrillation Trial (CABANA) trial. Funded by the National Heart, Lung, and Blood Institute (Bethesda. Maryland), this landmark 3,000 patient trial was designed to test the hypothesis that the treatment strategy of left atrial catheter ablation will be superior to medical management.
CABANA has an estimated duration of five years, with the primary end point of total mortality and secondary end points including a host of cardiovascular end points such as hospitalizations, bleeding, and stroke. According to the ClinicalTrials.gov website, the final data from this trial is not due for at least another four years.
One of the most intriguing AF topics at HRS was discussed at the Late Breaking Abstract Session, when the results of the Conventional Ablation for Atrial Fibrillation With Or Without Focal Impulse and Rotor Modulation (CONFIRM) trial were reported by Sanjiv Narayan, MD, from the University of California San Diego (UCSD). According to Dr. Narayan, who has spent about a decade working on this diagnostic technology with grants from the National Institutes of Health (Bethesda), this approach looks at the “basic ways that the heart responds to arrhythmias, with patient tailored physiological mapping.“
The CONFIRM trial tested the hypotheses that: (1) AF is caused by localized electrical rotors or focal beats. These rotors – or, as Narayan described them, “localized areas of electrical activity“ that can be found all over the atria – can be visualized for the first time using a physiological mapping system that utilizes a conventional basket, mapping catheter as part of the approach; (2) Localized ablation, called focal impulse and rotor modulation or FIRM, will acutely terminate or slow AF and improve efficacy when added to conventional AF ablation techniques.
Narayan's scientific collaborator, Ruchir Sehra, MD, provided Medical Device Daily with an analogy of the concept of localized electrical rotors. Ruchir Sehra, MD, during a post-HRS interview with BB&T. Ruchir, who has been intimately involved in this project, likened AF to a fire, which requires both a spark or match plus kindling to cause the fire to start. Conventional ablation or isolation of the pulmonary veins, now described in the EP world as “the cornerstone of AF catheter ablation, eliminates the matches or sparks. The role of FIRM is to identify where the kindling is and then to remove it.
The CONFIRM trial, which began enrolling in October 2005, ultimately enrolled a total of 103 patients, with about two-thirds of the patients persistent or long standing AF.
The data is very promising, with the 32 FIRM guided patients achieving an 84% success rate, compared to only 51% for the 63 conventionally treated patients. The results are even more impressive for several reasons: (1) 84% of the FIRM patients were monitored by implantable loop monitors, which is a very precise means to accurately detect episodes of AF; (2) this data described two year outcomes, which speaks to the durability of the approach; (3) this data was accomplished with a single procedure and is considerably better than the conventional method. (4) the success in treating patients in the trial with persistent AF is remarkable; typically this patient subset achieves the poorest outcomes with catheter ablation and often require a second or third catheter ablation to overcome their AF and return to normal sinus rhythm; (5) FIRM rapidly terminated AF predominantly to normal sinus rhythm in less than 10 minutes prior to conventional ablation.
“Our current AF ablation procedures are very time consuming and shortening them would be a huge benefit,“ said Doug Packer, MD, and EP from the Mayo Clinic (Rochester, Minnesota), commenting on the CONFIRM trial at an HRS sponsored press conference. “This technology could usher in a paradigm shift in AF ablation, where we would move from anatomic ablation to a physiological-based approach.“
This technology was licensed three years to privately-owned, angel funded Topera Medical (Lexington, Massachusetts). The company filed a 510(k) application in March and plans a limited U.S. commercial launch of the diagnostic system under the tradename RhythmView in the first half of 2012. The company said it hopes to launch in Europe at the end of 2012.
CardioFocus demonstrates notable progress for AF
There has been considerable progress in treating AF with catheter-based technologies in recent years. However, the rate of success, estimated at 57% for a single procedure, is far from satisfactory. Thus, the quest for better methods to perform AF catheter ablation continues at a strong pace. One company, which is demonstrating impressive progress, is privately-owned, venture capital-backed CardioFocus (Marlborough, Massachusetts). Two important abstracts that were presented here at the HRS meeting demonstrated that the company's technology could be a force to be reckoned with in the coming years.
CardioFocus has developed an approach, a visually guided laser balloon (VGLB), primarily addresses paroxysmal (intermittent) AF. It features a 12 Fr deflectable sheath, a compliant and adjustable balloon that can be maneuvered easily into the pulmonary veins, ablative laser energy and direct endoscopic visualization. According to several industry experts that have been spoken to BB&T in the past, the company's two key attributes are the direct visualization and its compliant balloon. The compliant balloon allows the physician to achieve optimal contact with the oft irregularly-sized pulmonary veins.
Direct visualization is very important because other ablation technologies (mainly radiofrequency) have used indirect X-ray guidance, which can be technically challenging and often results in incomplete isolation (ablation) of the PVs, leading to mediocre success in eliminating the AF.
Vivek Reddy, MD, from Mount Sinai School of Medicine (New York) presented the results of the first 200 patients treated in a multicenter clinical setting. A second important study, presented by one of Reddy's colleagues at Mount Sinai, Srinivas Dukkipati, MD, addressed the durability of pulmonary vein isolation.
Reddy presented the results of 200 patients treated at nine clinical sites with 33 operators, showing 78.4% of the PVs isolated on the first attempt, with 98.8% of the PVs isolated with a second ablation. Reddy also reported that the results improved substantially with more operator experience. For example, total procedure time dipped 16% after 15 cases, while fluoroscopy time decreased nearly by half.
Most importantly, after a six-month follow-up for over half the 200 patients enrolled in the study, the single procedure, drug-free rate of freedom from AF was 65%. This compares favorably to the single procedure success rate of 57% from a meta analysis of numerous randomized clinical trials and the less than 50% success rate reported in the PMA trials by both the Biosense Webster's (Diamond Bar, California) Thermocool catheter and the Medtronic (Minneapolis) Arctic Front cryoablation catheter.
Reddy concluded his presentation commenting that “this favorable experience sets the stage for truly comparative long-term efficacy and safety studies (versus radiofrequency ablation).“ Indeed, CardioFocus hopes to initiate a randomized, multicenter trial comparing radiofrequency (RF) to VGLB in the U.S. in the second half of 2011.
Dukkipati also reported very positive results. This trial, conducted at both domestic and international sites with 56 patients, revealed that 86% of the patients' pulmonary veins were persistently isolated at three months, compared with previous rates of 38% to 57% with the “gold standard,“ traditional RF ablation.
Additionally, Dukkipati reported in a post-presentation interview that limited 12-month follow-up data on 35 patients showed that 71% were free of atrial fibrillation and are not taking anti-arrhythmic drugs.
Addressing the issue of a short learning curve, in the three centers in the study, seven operators performed fewer than 10 procedures, while two performed more than 10. “Even for the less experienced operators, more than three out of four pulmonary veins were isolated at the time of remapping,“ he said.
Regarding the safety profile, no patients experienced atrial esophageal fistula, stroke, transient ischemic attack or death, while one patient experienced cardiac tamponade and one had phrenic nerve palsy. There also were no cases of significant pulmonary vein stenosis.
Dukkipati concluded that the “visually-guided laser balloon can achieve high rates of acute and durable pulmonary vein isolation safely, even with limited operator experience.“
Another company showing substantial progress in the field of AF ablation is Endosense (Geneva, Switzerland). The company's flagship product is the TactiCath, the first force-sensing ablation catheter designed to give physicians a real-time, objective measure of contact force during the catheter ablation procedure.
Numerous pre-clinical and human studies in the past couple of years have shown that insufficient force may lead to subpar results (low efficacy, longer procedure times) while excessive force can cause various adverse events (tamponade, esophageal injury).
Endosense recently reported that its TactiCath contact-force sensing ablation catheter has been used to perform more than 1,000 AF patient cases in Europe. Its distributor, Biotronik (Berlin) has built and is continuing to grow the market for the TactiCath as its exclusive distributor in Europe as well as Latin America, Canada, Africa and the Middle East.
In addition, Endosense recently said that it has engaged with Rhythmia Medical (Burlington, Massachusetts) and in a joint development project to integrate the contact-force data into Rhythmia's advanced three-dimensional cardiac mapping, visualization and navigation system.
Finally, Endosense and Siemens Healthcare reported the completion of prototype software integrating the contact-force data with Siemens' electrophysiology solutions. The new application, which was created under a joint development agreement originally announced in January, was designed to allow electrophysiologists to view catheter tip-to-tissue contact force within a fluoroscopically enabled, three-dimensional anatomic heart model during catheter ablation procedures.
A host of new clinical results were presented at HRS, with favorable early data from the company's EFFICAS I post-market clinical trial that shed new insights into the relationship between catheter tip-to-tissue contact force and early pulmonary vein isolation line reconduction.
EFFICAS I is a 45-patient, single-arm, prospective, multi-center European clinical trial that was designed to demonstrate the correlation between contact forces applied during pulmonary vein isolation and atrial fibrillation treatment efficacy at three months. While investigators performed the procedure with the TactiCath, they were blinded to contact force measurements; however, the contact forces applied were recorded. Patients were re-assessed with a mapping catheter at three months to identify potential gaps in the PVI lines. Contact force parameters from initial procedures were then analyzed to determine the relationship with lesion formation.
Karl-Heinz Kuck, MD, Asklepios Klinik St. Georg (Hamburg, Germany), a veteran in the field of electrophsiology, said that “EFFICAS I shows for the first time a direct correlation between low contact force and post-operative PV isolation line reconduction at three month follow-up.“ The EFFICAS I data showed this to be particularly true when low contact forces were applied at the first ablation site.
Full results from EFFICAS I will be applied to EFFICAS II, in which investigators will take full advantage of the real-time, objective TactiCath contact-force control features to improve their ablation technique during lesion creation. Now enrolling patients, the EFFICAS II study will measure reduction in PVI gaps as well as procedural improvements as compared to EFFICAS I.
Reddy is also very enthused about this technology, saying that “contact force is the last missing piece of informatio n needed to improve the treatment of AF.“
AF imposes significant cost burden
Atrial fibrillation is the most common cardiac arrhythmia and it is widely appreciated that it imposes a significant burden to its patients. A new study now shows that the annual cost per year higher for a patient with atrial fibrillation is $8,700 a year than one without AF, for a national annual cost of about $26 billion.
Less than one-fourth of the extra cost in patients with AF was directly attributable to AF, about $6 billion on a national basis, while almost 40% – more than $10 billion nationally – was for non-cardiovascular reasons, report the authors, led by Michael Kim, MD, Northwestern University (Chicago).
The data, which was published online in the May 3 issue of Circulation: Cardiovascular Quality and Outcome, results from a study of payment data from both Medicare and commercial third-party payers.
Total annual direct medical costs were 73% higher for the study's patients with AF compared with an equal number of patients without the arrhythmia, Consistent with their higher cost, those with AF were hospitalized at several times the rate of patients without AF.
“I think it's going to be surprising to people how expensive atrial fibrillation really is,“ Kim said. “They get hospitalized twice as much in general. They have three times the rate of multiple hospitalizations and four times the number of cardiovascular hospitalizations relative to what is apparently the same group of patients but without atrial fibrillation.“
Kim went on to say that atrial fibrillation is not generally seen as a condition that is nearly as costly as heart failure or end-stage renal disease, “but it's still a very expensive problem for our society, and the most expensive reason is cardiovascular hospitalization.“
Study data shows benefit of CRT vs. RV pacing
Data presented at Heart Rhythm 2011 showed the clinical benefit of cardiac resynchronization therapy (CRT) vs. conventional right-ventricle (RV) pacing in improving heart failure (HF) in patients undergoing atrioventricular (AV) junction ablation for permanent AF. In the clinical trial, patients receiving CRT had a 26% reduction in the primary composite endpoint of death from HF, hospitalization from HF, or worsening HF when compared to patients undergoing RV pacing (11%). The APAF (Assessment of Cardiac Resynchronization Therapy in Patients with Permanent Atrial Fibrillation) clinical trial was supported by Medtronic. The use of Medtronic CRT devices in permanent AF patients with depressed LV function undergoing AV nodal ablation is investigational and not an approved use in the U.S.
Often referred to as “ablate and pace“ therapy, AV junction ablation, which produces complete AV block to assure heart rate control and rhythm regulation, followed by implantation of a cardiac pacing device, is a routine, clinically validated treatment for patients with symptomatic, drug-refractory permanent AF. Additionally, CRT is a well-established treatment for heart failure that uses a specialized cardiac pacing device to improve the pumping efficiency of the heart. While heart failure and AF are increasingly common, life-threatening diseases that often predispose one another, CRT has not been extensively studied in the treatment of AF. Based on current U.S. and European treatment guidelines, CRT is not currently recommended as a treatment for all patients with permanent AF and refractory heart failure.
Approximately 25% of patients in the APAF trial met the current CRT indication criteria set forth in the treatment guidelines, while 75% did not. The findings showed that the relative clinical benefit of CRT over RV pacing was significant and independent of whether the patients were indicated for CRT in the guidelines.
Royal Philips Electronics (Amsterdam, the Netherlands) and HRS have teamed up to showcase current solutions and future developments that shape the diagnosis and minimally invasive treatment of heart rhythm disorders.
Heart rhythm disorders are caused by disturbed electrical signals that regulate the heart and can lead to serious health risks, including heart failure or stroke. Many rhythm disorders can be treated using minimally invasive electrophysiology (EP) procedures, carried out in an EP lab. These procedures require image guidance and interventional tools that enable physicians to achieve the optimum clinical outcome, while minimizing adverse events.
The industry collaboration between Philips and the Heart Rhythm Society is displayed in the Networked EP Lab. The Lab is an educational pavilion where advanced clinical technologies, new processes and integrated data-sharing solutions are demonstrated to help EP teams optimize patient safety, outcomes and improve procedural management.
In the Networked EP Lab, integration of real-time information from all relevant technologies and patient health records is illustrated. Harnessing vital procedural and imaging information from various sources, such as electrograms, 3-D mapping and imaging systems, a connected lab provides EP team members with the information they need to take confident decisions. For efficient workflow, all information is presented on one display that can be controlled from the same keyboard and mouse.
“Philips is honored to provide this learning opportunity together with the Heart Rhythm Society,“ said Steve Rusckowski, CEO for Philips Healthcare. “This initiative further reinforces Philips' commitment to provide healthcare professionals with meaningful innovations that simplify complex procedures. Together with the Heart Rhythm Society and our industry partners, we aim to supply clinicians with the tools they need to treat patients more efficiently and effectively. The Networked EP Lab is a perfect example of this approach.“