Medtronic Announces Results from TTOP-AF Trial Demonstrating Clinical Benefits of Its Phased RF Ablation System in Treating Persistent Atrial Fibrillation
Medtronic, Inc. announced results from its Tailored Treatment of Permanent Atrial Fibrillation (TTOP-AF) clinical trial, the first randomized study comparing ablation therapy with the Medtronic Phased RF Ablation System ablation system to traditional medical management (antiarrhythmic drugs and direct current cardioversion) in 210 patients with persistent or longstanding persistent atrial fibrillation (AF). The findings, presented at Venice Arrhythmias 2011, the 12th International Workshop on Cardiac Arrhythmias, demonstrated that 55.8 percent of ablation management patients had an AF and atrial flutter burden reduction of greater than 90 percent and were free of antiarrhythmic drug therapy at six months compared to 26.4 percent in the traditional medical management arm (p<0.0001), thus meeting the chronic effectiveness endpoint. When including patients still on antiarrhythmic drug therapy following the procedure with the ablation system, 67.4 percent had a greater than 90 percent reduction of AF burden at six months.
While the ablation patients in the trial demonstrated a reduction in AF burden, the acute safety event rate in the trial was 12.3 percent with an upper 95 percent confidence interval of 19 percent, which did not meet the pre-defined performance goal of 16 percent. At the time the trial was designed, no benchmark for the persistent AF patient population existed, so the performance goal of 16 percent was established based on a literature review evaluating ablation procedures for right-sided and paroxysmal AF ablation procedures. In the TTOP-AF trial, 12.3 percent (17) of patients experienced one or more protocol-defined procedural and/or device-related adverse events within seven days of the procedure. A total of four strokes (1.7 percent acute procedural stroke rate) occurred within the acute period after an ablation procedure. The stroke incidence was higher for the first few subjects undergoing an ablation procedure rather than for subjects enrolled later at each site, with three of the four strokes occurring during the first five procedures for each clinical trial center. Two of the four patients had complete resolution of symptoms within the six-month follow-up period; the other two patients had minor residual effects from the stroke.
“Due to the advanced state of the disease and the attendant increase in the complexity of the procedure, persistent AF patients undergoing ablation have a higher risk than paroxysmal AF patients for adverse events; therefore, the acute safety findings from the TTOP-AF trial are not unexpected,” said John Hummel, MD, director of clinical electrophysiology research at The Ohio State Medical Center. “I believe these data are promising given the reduction in AF burden, and therefore this ablation technology may ultimately represent an important option for drug refractory, symptomatic, persistent AF patients who are more difficult to treat.”
There is a significant unmet need for US patients with symptomatic, drug refractory persistent AF. The only FDA-approved AF ablation therapies are indicated for the treatment of paroxysmal AF. As the disease progresses into persistent AF (recurrent AF episodes that last more than seven days), it becomes more complex to treat. Persistent AF patients often have increased hospitalizations and healthcare costs, and the condition is more debilitating for the patients in terms of quality of life. Additionally, persistent AF often causes structural, functional and electrical changes to the heart.
“We believe these data demonstrate the Medtronic Phased RF Ablation System can fill an unmet need for persistent AF patients who have few treatment options with significant limitations,” said Reggie Groves, vice president and general manager of Medtronic’s AF Solutions business.
About the TTOP-AF Clinical Trial
The prospective multi-center, controlled clinical trial — the largest to date to study the phased radiofrequency ablation technology — included a total of 210 patients with persistent and longstanding persistent AF who were randomized in a 2:1 fashion to either receive ablation treatment (138) or traditional medical management (72). Medical management treatment failures were permitted to crossover and receive an ablation, no sooner than four months after enrollment with a target of six months. Twenty-three sites participated in the United States and one in the Netherlands. Patients in the ablation arm were allowed up to two ablations with Medtronic’s Phased RF Ablation System to achieve treatment success, and were followed at one, three and six months post-treatment. Patients in the medical management arm received antiarrhythmic drug changes and direct current cardioversions to achieve and maintain sinus rhythm, and were followed at one, three and six months.
About the Medtronic Phased RF Ablation System
The Medtronic Phased RF Ablation System is investigational in the United States and currently approved for use in regions of Europe, Asia, and Africa, as well as in Canada. The system is a percutaneous cardiac catheter and generator system that delivers customized radiofrequency energy designed to eliminate or isolate abnormal electrical impulses in the left atrium that initiate or sustain atrial fibrillation. The anatomically designed, multi-electrode catheters are intended to allow physicians to identify and selectively ablate a broader area of heart tissue without the use of current single point catheters and complex mapping and navigation equipment.
The Medtronic Phased RF Ablation System includes:
- Pulmonary Vein Ablation Catheter (PVAC)™ - designed for mapping, ablating and verifying isolation of the pulmonary veins;
- Multi-Array Septal Catheter (MASC)™ - designed for mapping and ablating the left atrial septal wall;
- Multi-Array Ablation Catheter (MAAC)™ - designed for mapping and ablating the left atrial body; and
- GENius Multi-Channel Radiofrequency Generator – the unique RF energy delivery system allows physicians to tailor the location, depth and fill of each ablation lesion.
More than 13,000 patients in 24 countries have been treated with the Medtronic Phased RF Ablation System since January 2009.
BIOTRONIK Selectra Lead Introducer System Gets Strong Reviews in First Cases
The BIOTRONIK Selectra CS Lead Introducer System has received overwhelmingly positive reviews in the first device implantation cases across the US and Europe. Physicians are unanimous that Selectra delivers a significant advancement in lead placement systems for cardiac resynchronization therapy (CRT) devices.
Ishu Rao, MD, clinical cardiac electrophysiologist with Cardiology Associates Medical Group in Ventura, California, comments, “Selectra demonstrates that BIOTRONIK is responsive to the needs of electrophysiologists — they understood the problems we face in these delicate and demanding procedures and developed a tool set that makes a difference.”
Selectra’s streamlined hub with a fully integrated hemostatic valve minimizes handling complexity and maximizes the working length of the sheath during implant. The hydrophilic inner coating and low-friction valve are designed to reduce resistance and facilitate maneuverability of the lead.
“The Selectra system provides the right amount of flexibility, torqueability and visibility to easily access the coronary sinus,” describes Craig McCotter, MD, director of the Upstate Atrial Fibrillation and Arrhythmia Center in Greenville, South Carolina. “The design of the hub with an integrated slittable valve is made for ease of use, and lowers concerns for lead dislodgement as the sheath is removed.”
Physicians who provided feedback to the company did so after using Selectra in multiple patient procedures, of which many were described as “difficult anatomy.” EPs consistently gave Selectra very high marks for performance, most often citing “secure lead placement” and “ease of use.”
The Selectra lead introducer system complements BIOTRONIK’s broad CRT portfolio, which includes Corox BP leads and premium Lumax CRT-D devices. This new entry follows the January 2011 launch of the Corox OTW-L BP left ventricular lead, a third unique design with excellent stability and handling characteristics.
Sorin Group Launches SonR® Sensor Based Cardiac Resynchronization Therapy Optimization System1
SonR is the Only Weekly Self-Adjusting CRT Optimization System Providing Optimized Timing at Rest and Exercise for Improved CRT Response2
Sorin Group announced at the Venice Arrhythmias 2011 Congress the CE Mark approval and the European commercial launch of its SonR CRT optimization system. The SonR system includes the SonR hemodynamic sensor embedded in the SonRtip™ atrial pacing lead and the Paradym™ RF SonR CRT-D device. SonR is the first and only system to provide weekly automatic optimization during patients’ real-life activities as an alternative to in-clinic manual echocardiography-based device optimization for improved CRT response.3
Studies have shown that around one-third of patients with advanced heart failure do not effectively respond to cardiac resynchronization therapy (CRT).4,5 In order to improve therapy success rate, it is important to offer each patient a tailor-made programming of the timing between electrical impulses sent to different parts of the heart (CRT settings) on a regular basis. Current optimization methods include echocardiography and other device-based timing features. Echocardiography is difficult and time-consuming, while other device-based CRT optimization features have shown limited benefits.2 All of these current methods require manual steps. They are typically performed only once and only while the patient is resting. SonR is the only CRT optimization system that automatically optimizes patients every week and importantly, while the patient is active, providing real-life optimization. Promising early clinical results suggest that SonR increases responder rates and reduces heart failure hospitalizations compared with standard medical practice over a one-year follow-up.6
The result of a 10-year clinical science program, the SonR sensor uniquely measures patients’ cardiac muscle vibrations. These real-time measurements are transmitted to the CRT-D device, which uses them to determine the best settings for the patient. Every week, the system automatically optimizes to adapt to the patient’s changing condition. SonR measurements correspond to LVdP/dtmax, the gold standard for assessing left ventricular (LV) contractility, a key indicator of cardiac performance.
“The concordance of the SonR signal with measurements of LVdP/dtmax suggests that this new, operator-independent system is a reliable means of tailored optimization of CRT devices,” commented Philippe Ritter, MD, at University Hospital, in Bordeaux, France. “Providing weekly optimization both at rest and exercise is a significant step forward in the treatment of heart failure patients.”
“The SonR system is the result of Sorin Group’s tradition of excellence in innovation,” commented Stefano Di Lullo, Sorin Group, President of the CRM Business Unit, “We are proud to bring this technological breakthrough to market. The introduction of this new CRT-D system provides new horizons in heart failure treatment options.”
1 Not for distribution in the US.
2 Sorin Group, data on file.
3 CLEAR results obtained through 1st generation SonR.
4 Abraham WT, Fisher WG, Smith AL, et al. Cardiac resynchronization in chronic heart failure. N Engl J Med 2002;346:1845-1853.
5 Abraham WT, Gras D, Yu CM, et al. Results from the FREEDOM trial – assess the safety and efficacy of frequent optimization of cardiac resynchronization therapy. SP08. Late-Breaking Clinical Trials, HRS 2010. Denver, Colorado.
6 Padeletti L. Clinical efficacy of CRT continuous optimization with SonR versus standard clinical practice. HRS 2010;7(5S):AB27_4.
Cardiac Device Infections Cost Money and Lives; TYRX, Sohail and Collaborators Present Findings of Medicare Study at IDSA 2011
Infections associated with the implantation or replacement of electronic cardiac devices result in incremental increases in mortality, both in the hospital and after discharge as well as substantially higher financial costs, compared to rates in uninfected patients. Increased costs in intensive care, routine care and pharmacy costs vary with the type of implanted device and account for the majority of the cost increase with infection, with almost half of the incremental hospital cost attributed to intensive care. These and other important findings from a large retrospective study of more than 200,000 Medicare beneficiaries undergoing cardiac device procedures, both with and without infection, were presented at the 49th Annual Meeting of the Infectious Diseases Society of America (IDSA), held October 20–23 in Boston, Massachusetts.
“Cardiac implantable electronic devices (CIEDs) like pacemakers, implanted cardioverter defibrillators (ICD), and cardiac resynchronization therapy/defibrillators (CRT-D) can reduce illness and extend life, but this benefit can be greatly reduced in terms of patient health, mortality and treatment costs if device implantation or replacement procedure is complicated by infection. Unfortunately, the rate of CIED infections today is increasing even faster than the rate of CIED implantation. The aim of this study was to better understand the mortality and costs associated with CIED infections, and the relationship of these outcomes to different CIED types,” said Daniel Lerner, MD, chief medical officer of TYRX, Inc., which supported the study.
The study, conducted by M. Rizwan Sohail, MD, Mayo Clinic College of Medicine, and collaborators including Dr. Lerner, looked at 200,219 admissions of Medicare beneficiaries undergoing CIED procedures, 5,817 of whom were associated with device infection. The researchers found that the risk-adjusted length of hospital stay and costs were significantly higher for infected patients compared to the standard length of stay for individuals undergoing CIED procedures in the absence of infection. The risk-adjusted incremental and total admission costs with infection were $14,360 to $16,498 and $28,676 to $53,349, respectively, depending on CIED type. The largest incremental cost associated with infection was intensive care, which accounted for more than 40% of the difference. Infection was also associated with significant increases in adjusted admission mortality (rate ratios, 4.8–7.7; standardized rates, 4.6–11.3%) and long-term mortality (rate rations, 1.6–2.1; standardized rates, 26.5–35.1%, depending on CIED type). Importantly, about half of the incremental long-term mortality occurred after hospital discharge.
“The high cost of health care is a growing national concern, as is the increased rates of hospital-acquired infections that add significantly to those costs,” commented Dr. Lerner. “This study found that increases in routine care, pharmacy cost, and especially intensive care costs accounted for the majority of the incremental cost associated with infection — areas that can be targeted to reduce costs associated with infection management. However, it is quite clear that the strategy that would have the greatest impact on costs associated with CIED infections, as well as patient mortality, is to prevent CIED infections in the first place.”
About TYRX, Inc.
TYRX, Inc. commercializes innovative, implantable combination drug+device products focused on infection control, including the AIGISRx® Antibacterial Envelope & Flat Sheet technologies, designed to reduce surgical-site infections associated with CIEDs. AIGISRx products contain antimicrobial agents, rifampin and minocycline, which have been shown to help reduce infection by organisms representing a majority of the infections reported in implantable pacemaker and defibrillator related endocarditis, including “superbugs” or MRSA*. Following commercial release, the AIGISRx Envelope has been implanted in over 20,000 patients nationwide. The company estimates that over 2% of all US implantable pacemaker and defibrillator patients in 2011 will receive an AIGISRx product during their procedure. TYRX is preparing to commercialize its second AIGISRx technology, the AIGISRx ST, designed to reinforce soft tissue where weakness exists and for the surgical repair of damaged or ruptured soft tissue. Current research & development projects are focusing on a fully-resorbable version of AIGISRx.
* Based upon preclinical in vitro and in vivo data. Data on file at TYRX and published in PACE 2009;32(7):898-907.
ECG Screenings in Over 32,000 Young Adults Efficiently Identifies Potential Risk of Sudden Cardiac Death
A new study proves the importance of electrocardiographic (ECG) screenings to identify heart abnormalities in young adults, including both athletes and non-athletes. The study, published in the October edition of HeartRhythm, the official journal of the Heart Rhythm Society, demonstrates the success of a high-volume ECG screening program designed to identify potential life-threatening heart arrhythmias in high school students. Of the more than 32,000 students screened, ECG abnormalities that may be associated with the risk of sudden cardiac death (SCD) were identified in over 800 students.
More than 250,000 deaths occur each year as a result of sudden cardiac arrest (SCA) and, more specifically, SCD occurs in an estimated 2,000 young adults annually in the United States.1 While SCA among young adults is a serious concern, the primary challenge with ECG screenings on a large scale is the lack of efficiency and the likelihood for a large number of false positive results. The study, led by Joseph Marek, MD, of the Midwest Heart Foundation, used a standardized and community-based screening program following strict quality controls and performed an average of 880 ECG screenings each day.
The screenings were performed during regular school hours in 24 Chicago suburban high schools between September 2006 and May 2009. In order to complete the study on a large scale, community volunteers participated in a successful and controlled training program. With the aid of the trained community volunteers, 32,561 students between the ages of 14 to 19, including athletes and non-athletes, were successfully screened.
Results showed that 817 (2.5 percent) of the 32,561 screened had ECG abnormities that could be associated with SCD. Specifically, left ventricular hypertrophy (LVH) was found in 141 participants, which may be associated with hypertrophic cardiomyopathy (HCM), the most common cause of SCD. In addition, 100 participants were found with prolonged QTc, which may indicate long QT syndrome and also be associated with SCD.
“The screening process is an important step in trying to save lives because it helps us identify the individuals who are at the greatest risk of SCA and, ultimately, it has the potential to prevent incidents of sudden death from occurring,” said Marek. “As proof, some European countries have implemented successful screening programs in high volume that show great success in reducing SCA in young adults.”
In a study conducted in Italy over a 26-year period,2 ECG screenings in young athletes demonstrated an 89 percent reduction in SCD. It was proven that the incidence of sudden cardiac death in young competitive athletes substantially declined in the region of Italy where a nationwide systematic screening was introduced. Studies like this show that it is important to understand the preventative and implementable measures that can be taken to decrease the death rate of young adults from SCA.
“We believe our findings demonstrate the feasibility of performing high-quality, low-cost ECG screenings in large US populations, which creates the potential to reduce the overall rate of SCD in our country,” said Marek.
1 Atkins D, et al. Epidemiology and Outcomes From Out-of-Hospital Cardiac Arrest in Children. Circulation 2009;119:1484-1491.
2 Corrado D, et al. Trends in Sudden Cardiovascular Death in Young Competitive Athletes After Implementation of a Preparticpation Screening Program. JAMA 2006;296:1593-1601.
Persistent AF Patient Treated with HeartLight™ Endoscopic Ablation System in Live Case at Venice Arrhythmias 2011
CardioFocus, Inc., developer of the HeartLight™ Endoscopic Ablation System (EAS) for the treatment of atrial fibrillation (AF), announced that its HeartLight EAS was used to achieve successful acute PV isolation and restore sinus rhythm in a persistent AF patient during a live case at the Venice Arrhythmias 2011 conference.
Additionally, research presented during the scientific sessions further supports the ability of the compliant balloon system to accommodate varied vein anatomy with a single catheter, achieving 99% acute isolation irrespective of vein size and shape.
“The live case outcome and clinical findings presented at the conference are exciting, as they’ve revealed the HeartLight EAS may be suitable for a larger subset of patients who are otherwise unable to be treated with a single ablation catheter. We are pleased that research continues to instill confidence in the technology and support its versatile clinical use,” said Stephen Sagon, President and CEO of CardioFocus.
In the live case, physicians successfully isolated all four PVs of a patient with persistent AF and restored the patient to normal sinus rhythm. The procedure was performed by leading electrophysiologists Sakis Themistoclakis, MD, of Dell’Angelo Hospital and Andrea Natale, MD, of Texas Cardiac Arrhythmia Institute at St. David's Medical Center, Austin, Texas. The session was chaired by Petr Neuzil, MD, of Na Homolce Hospital, Prague, Czech Republic.
To perform the case, the physicians employed the new HeartLight EAS handle configuration for the first time in Italy. The enhanced handle was designed for single-handed control of both catheter manipulation and the location of energy delivery to improve procedural efficiency.
Dr. Themistoclakis commented, “The HeartLight EAS compliant balloon catheter allows for very good contact with all PVs to deliver a circumferential lesion pattern, which in our experience has translated to more efficient, durable vein isolation. In this particular case, it even enabled conversion to normal sinus rhythm during the ablation of the right superior pulmonary vein. We are optimistic that the system will continue to achieve promising outcomes in patients with both paroxysmal and persistent AF.”
The efficacy and precision of endoscopically guided catheter ablation was further supported by a study evaluating the ability of the system to ablate PVs of varying anatomy in 29 unselected paroxysmal AF patients. The research was performed by Boris Schmidt, MD and KR Julian Chun, MD, of Cardioangiologisches Centrum Bethanien, Frankfurt, Germany and presented by Melanie Gunawardene, MD, also of Cardioangiologisches Centrum Bethanien. They found that visually guided PV isolation was achieved in 72% of veins (83/116) on the very first attempt and that electrical isolation was ultimately confirmed with a diagnostic spiral catheter in 99% of the PVs attempted (115/116) using only a single HeartLight EAS catheter.
Since its introduction in 2009, the visually-guided HeartLight EAS has been used to treat approximately 400 patients with AF in the United States and in Europe. It incorporates a compliant, dynamically adjustable balloon catheter designed for improved contact with the PV ostium, and utilizes laser energy for more efficient, durable and precise ablation treatment.
About CardioFocus, Inc.
CardioFocus, Inc. is a medical device manufacturer dedicated to advancing ablation treatment for cardiac disorders such as atrial fibrillation. Its novel HeartLight™ Endoscopic Ablation System for catheter ablation incorporates an endoscope to provide physicians with the capacity to see within the heart, and for the first time, visually direct the application of laser energy to achieve durable pulmonary vein isolation.
The HeartLight Endoscopic Ablation System received CE Mark in 2009 for the treatment of atrial fibrillation, and is commercially available at leading institutions throughout Europe. The device is investigational in the US, with a pivotal study expected to commence in 2011.
The scientific information discussed in this news release is preliminary and investigative. The CardioFocus HeartLight Endoscopic Ablation System is not approved by the U.S. Food and Drug Administration (FDA), and no conclusions can or should be drawn regarding the safety or effectiveness of the system. Only FDA can determine whether the product candidates are safe and effective for the use(s) being investigated. Healthcare professionals should refer to/rely upon FDA-approved labeling for the products, and not the information discussed in this news release.