Heart Rhythm 2012: Meeting Highlights

Did you miss the recent Heart Rhythm sessions in Boston? The Heart Rhythm Society’s 33rd Annual Scientific Sessions were held in Boston from May 9-12, 2012. Enclosed below is a compilation of clinical news highlights from the meeting.

Biosense Webster Collaborates to Bring Innovative Solutions to Electrophysiologists Around the World

Biosense Webster, Inc. announced the execution of strategic collaboration agreements with two leading global imaging companies, GE Healthcare and Siemens Healthcare.

The announcement was made during the Heart Rhythm Society’s 33rd Annual Scientific Sessions.

Biosense Webster, Inc. has developed an image integration solution for electrophysiology (EP) labs around the world. This solution integrates real-time x-ray images, from Siemens Healthcare and GE Healthcare X-Ray systems, into the company’s Carto^® 3, 3D Electroanatomical Mapping & Ablation System. Under the terms of the two agreements, Biosense Webster, Inc. plans to offer an integrated solution, compatible with both manufacturers’ fluoroscopy systems, in 2012.

“Minimizing x-ray exposure for patients and clinicians has long been a focus of healthcare technology manufacturers,” said Shlomi Nachman, Worldwide President, Cardiovascular Care franchise. “These two important strategic agreements will allow Biosense Webster to address the growing need to combine multiple images from different systems in the EP lab into a single display on our Carto^® 3 System.”

These latest agreements mark a significant step toward Biosense Webster, Inc.’s vision of providing a comprehensive integrated lab solution to electrophysiologists and hospitals around the world. GE Healthcare and Siemens Healthcare collectively, represent over 50% of the installed base of x-ray systems across the globe.

“These strategic collaborations and the resulting technology advancements, continue our commitment to bringing innovation to the cardiac electrophysiology community so they may better serve their patients and protect themselves,” said Nachman.

Study of First-in-Class WATCHMAN^® Device Shows 75 Percent Reduction in Stroke Risk in Patients with Atrial Fibrillation Not Eligible for Oral Anticoagulation Therapy

Boston Scientific Corporation announced results from the ASA Plavix (ASAP) Study, which studied the WATCHMAN^® Left Atrial Appendage Closure (LAAC) device. The data showed a reduction in the risk of ischemic stroke by 75 percent in patients with atrial fibrillation who have a contraindication to oral anticoagulants such as warfarin. Vivek Reddy, MD, Director of Cardiac Arrhythmia Service at Mount Sinai Medical Center in New York and Coordinating Investigator of the study presented results during a late-breaking session at the Heart Rhythm Society’s 33rd Annual Scientific Sessions.

The prospective multi-center ASAP Study evaluated 150 patients with contraindications to warfarin, who were implanted with the WATCHMAN Device and treated with dual antiplatelet therapy for six months post-procedure. Subjects were followed for a mean average of 14.4 months. The study employed the widely recognized CHADS2 risk stratification score, which provides a clinical prediction tool for estimating the risk of stroke in patients with atrial fibrillation. The CHADS2 score has been validated by numerous studies and is regularly used to determine whether treatment is required with anticoagulation or antiplatelet therapy.

“WATCHMAN is the most studied LAA closure device with more than 2,000 patients enrolled in prospective studies and nearly 4,000 patient-years of follow up,” said Keith D. Dawkins, MD, global chief medical officer for Boston Scientific. “This novel device has been well received in more than 30 countries where it offers a safe and effective alternative to long-term treatment with oral anticoagulants.”

Atrial fibrillation affects approximately 15 million patients worldwide and is a disorder that disrupts the ability of the heart to beat regularly and pump blood efficiently. Patients in atrial fibrillation are at greater risk for stroke due to the migration of clots formed in the left atrial appendage (LAA). Anticoagulants such as warfarin have traditionally been the only therapy for reducing stroke risk in these patients. The Boston Scientific percutaneously delivered WATCHMAN Device is an alternative to long-term anticoagulation in patients eligible for anticoagulant therapy. It is designed to close the LAA, thereby preventing clots forming within the appendage and being dislodged into the bloodstream where they can potentially cause a stroke.

“Findings from the ASAP Study are promising in that closure of the LAA with the WATCHMAN Device produced a significant reduction in the expected ischemic stroke rate for this patient population,” said Dr. Reddy. “These results are very impressive and show potential for an effective device-based solution for higher-risk patients with limited pharmacologic options to reduce their risk of stroke.”

For patients in the ASAP Study, the average baseline CHADS2 score of 2.8 equated to a predicted ischemic stroke rate of approximately 7.1 percent per year. The observed rate of ischemic stroke for patients implanted with the WATCHMAN Device was 1.7 percent per year, a 75 percent reduction in stroke risk from the predicted stroke rate based on the CHADS2 score (p<0.01). The corresponding upper confidence bound yielded a stroke rate of 4.4 percent per year, lower than the predicted stroke rate of 7.1 percent.

Stroke rates in the ASAP study were similar to those observed in the PROTECT AF study, which assessed similar subjects not contraindicated to warfarin. In the multi-center, randomized PROTECT AF trial, the WATCHMAN Device proved to be non-inferior to warfarin and demonstrated a 38 percent relative risk reduction for stroke, cardiovascular death and systemic embolism compared to long-term warfarin therapy in 707 patients.

The WATCHMAN Device was approved for marketing in Europe and other CE Mark countries in 2009. Boston Scientific is currently enrolling U.S. patients in the PREVAIL study, a confirmatory study designed to gain U.S. Food and Drug Administration approval. Enrollment is expected to be completed in the second quarter of 2012. The WATCHMAN Device is contraindicated in patients who are not eligible for anticoagulation therapy. In the U.S., the WATCHMAN Device is an investigational device, limited by applicable law to investigational use and not available for sale. The device was developed by Atritech, which Boston Scientific acquired in March 2011.

Sorin Group Announces FDA Approval and Commercial Launch of PARADYM^™ RF ICDs and CRT-D Implantable Heart Devices

Sorin Group announced at Heart Rhythm 2012 the FDA approval and commercial launch of the PARADYM^™ RF family of implantable cardioverter defibrillators (ICDs) and cardiac resynchronization therapy (CRT-D) devices. These new heart devices, including the single-chamber PARADYM^™ RF VR, the dual-chamber PARADYM^™ RF DR and the PARADYM^™ RF CRT-D, are designed to be monitored remotely.

The PARADYM^™ RF family offers Sorin’s powerful proprietary SafeR^™ and Parad^™+ algorithms that automatically adjust to each individual patient to minimize right ventricular (RV) pacing and inappropriate shocks. PARADYM^™ devices are the only clinically proven ICDs that both reduce RV pacing below one percent^1,2 and offer the lowest recorded inappropriate shock rate3 of any devices available to date.

The new devices are designed to provide patients with the optimal combination of thinness, high power and longevity. Utilizing state-of-the-art battery and capacitor technology, the PARADYM^™ RF CRT-D and ICD devices deliver 37J of energy with longevity over 6 years⁴ and 9 years,⁵ respectively, in an 11mm thin device.

The PARADYM^™ RF CRT-D also features a new programming option to electronically reprogram the device to avoid phrenic nerve stimulation, a common side effect of cardiac resynchronization therapy. In addition, PARADYM^™ RF CRT-Ds include Sorin’s exclusive Brady-Tachy Overlap (BTO^™) algorithm that provides pacing therapy during exercise while maintaining the ability to detect and treat slow ventricular arrhythmias.

“The combination of features offered within the PARADYM^™ RF devices will be appreciated by many U.S. physicians who treat patients at risk of sudden cardiac arrest, including some whose heart failure can be managed by cardiac resynchronization therapy,” said Dr. Freddy Abi-Samra, MD, Ochsner Medical Center, Louisiana.

Stefano Di Lullo, Sorin Group, President of the CRM Business Unit, commented: “We are pleased to extend our family of PARADYM^™ devices for U.S. physicians and patients with the FDA approval of PARADYM RF and PARADYM RF CRT-D. The introduction of these new devices adds to Sorin’s growing portfolio of innovative implantable heart therapies designed to save lives and improve patient symptoms.”

1. “AAIsafeR preserves ventricular activity in case of Paroxysmal AV Block while maintaining ventricular pacing below 0.1% in 28/35 (80%) of non-selected DDD patients” p. S246, Anselme, F., et al. First clinical results of AAIsafeR2, a new mode to prevent ventricular pacing. Heart Rhythm 2005; 2, supp 5; p4-99 (abs).
2. With SafeR mode.
3. Anselme F, et al. Prevention of inappropriate shocks in ICD recipients: A review of 10,000 tachycardia episodes. PACE, 2007;30 (Suppl 1):S128-33. Study made using dual-chamber ICDs with standard dual-chamber arrhythmia classification algorithms.
4. Biventricular pacing in DDD mode, 1% in atrium, 100% in both ventricles, 500 Ohm, 3.5 V, 0.35 ms, 60 min-1, one 42 J shock per quarter, sensors OFF, remote monitoring: daily check, 4 remote follow-ups and 5 alerts with full reports per year.
5. Pacing in VVI mode 1%, 500 Ohm, 3.5 V, 0.35 ms, 60 min-1, one 42 J shock per quarter, sensors OFF, remote monitoring: daily check, 4 remote follow-ups and 5 full alert reports per year.

Cameron Health’s S-ICD^® System Meets Primary Safety and Efficacy Endpoints in IDE Clinical Study

Cameron Health, Inc. announced that the S-ICD^® System met the primary safety and efficacy endpoints defined in their 330-patient IDE clinical study. The data were presented at Heart Rhythm 2012 by Martin C. Burke, DO, as part of the Late-Breaking Scientific Sessions.

The S-ICD System is the world’s first completely subcutaneous implantable defibrillator (ICD) for the treatment of patients at risk for sudden cardiac arrest (SCA). The S-ICD System offers the same defibrillation therapy option as most conventional ICDs, but without transvenous leads — thereby eliminating many of the serious complications commonly associated with transvenous leads.

“Conventional ICDs are a proven therapy with a long clinical track record; however, complications related to transvenous leads, or wires placed in the heart, can be quite serious for patients,” said Dr. Martin C. Burke, Professor of Medicine and Director of the Heart Rhythm Center at the University of Chicago. “We did not observe the typical lead-related complications with the S-ICD System, so having an alternative treatment for patients that can virtually eliminate transvenous lead complications is an important step forward for ICD therapy.”

The S-ICD System IDE trial is a prospective, non-randomized, multicenter clinical study that enrolled 330 patients meeting current AHA/ACC/HRS Class I and II ICD indications and who did not require long-term bradycardia pacing. The primary endpoints for the study were designed to demonstrate safety and efficacy of the S-ICD System for the treatment of life-threatening ventricular arrhythmias.

“The compelling results of this landmark clinical study add to the growing body of evidence that demonstrate the benefits of this important alternative for patients at risk from sudden cardiac arrest. Furthermore, we are equally committed to evaluating the real-world performance of the S-ICD System via our long-term EFFORTLESS S-ICD Registry,” said Kevin Hykes, President and CEO of Cameron Health. The preliminary results from the registry were also reported at the HRS.

On March 8, 2012, Boston Scientific Corporation announced that it would exercise its option to acquire Cameron Health, Inc. Closing of the transaction is subject to customary conditions, including relevant antitrust clearance, and is expected to occur in the second or third quarter of 2012.

About the S-ICD System

The S-ICD System was designed to provide the same proven defibrillation protection as conventional ICDs, but without the serious complications associated with leads that reside in the heart and blood vessels. In contrast to conventional ICDs, Cameron Health’s electrode is implanted just under the skin. Implantation is straightforward, since the heart and blood vessels are untouched. The S-ICD System detects highly accelerated and disorganized heart rhythms caused by ventricular arrhythmias that can lead to sudden cardiac arrest. When abnormal arrhythmias are detected, the S-ICD System delivers an 80 Joule shock to restore the heart’s normal rhythm. Left unaddressed, these disorganized heart rhythms are often fatal.

New Data from Landmark Study Shows Cost-Effectiveness of Medtronic Life-Saving CRT-D Therapy in Mildly Symptomatic Heart Failure Patients

Medtronic, Inc. announced findings from an economic analysis of the landmark RAFT (Resynchronization / Defibrillation in Ambulatory Heart Failure Trial) trial demonstrating that cardiac resynchronization therapy with defibrillation (CRT-D) is a cost-effective treatment for mildly symptomatic heart failure patients. The findings showed a $33,025 (USD) cost per Quality Adjusted Life Year (QALY) gained using Medtronic CRT-Ds in a mild, New York Heart Association (NYHA)-designated Class II-III heart failure patient population, substantially lower than the benchmark for therapy cost effectiveness of other serious chronic conditions that cost at least $50,000 per QALY gained.¹ QALY is a measure of the quantity and quality of life.

Presented at Heart Rhythm 2012, the RAFT economic analysis is the only study to demonstrate cost-effectiveness in conjunction with the significant mortality benefit of CRT-D in mildly symptomatic heart failure patients. It complements the expansive body of clinical evidence for CRT-D illustrating the benefits of the Medtronic CRT-D portfolio of devices, as shown previously in the Medtronic-sponsored REVERSE (Resynchronization Reverses Remodeling in Systolic Left Ventricular Dysfunction) trial.

In the RAFT economic analysis, patients who received CRT-D were estimated to gain more than one quality-adjusted life year (1.07) at an additional cost of $35,308 (USD) over a lifetime horizon, the typical time period commonly cited by health economists.

“The large-scale RAFT trial has provided us with a wealth of clinical insight into the overall benefits of CRT-D in treating mild heart failure, proving that this advanced therapy significantly decreases mortality and reduces heart failure hospitalization rates with an economic value to the healthcare system as a whole,” said George Wells, PhD, University of Ottawa Heart Institute, Ottawa, Canada.

Approximately 6 million people in the United States suffer from heart failure, and the estimated cost for treating the life-threatening condition is almost $40 billion per year.² In line with numerous clinical trials showing that CRT-D is a cost-effective treatment approach in treating moderate-to-severe disease, this new data confirms it is also associated with a cost-effectiveness benefit per QALY gained in mild heart failure patients.

Last month, the U.S. Food & Drug Administration (FDA) approval expanded the indication for Medtronic’s CRT-D devices to treat NYHA Class II heart failure patients with a left ventricular ejection fraction (LVEF) of less than or equal to 30 percent, left bundle branch block (LBBB), and a QRS duration greater than or equal to 130 milliseconds. The expanded indication fulfills a serious unmet need by enabling treatment with CRT-D in indicated patients in the earlier stages of heart failure, before their symptoms start impacting their quality of life.

“The recent FDA approval expanding the indication of our CRT-D devices — coupled with this strong economic data — showcases our commitment to treating heart failure and enhancing patient outcomes at every stage of care with our innovative portfolio of CRT-D therapies,” said David Steinhaus, MD, Vice President and General Manager, Heart Failure, and Medical Director for the Cardiac Rhythm Disease Management business, Medtronic. “With the rising cost of healthcare significantly impacting our global economy, it is critically important to provide high-value, safe, effective therapies like CRT-D, that provide significant improvements at cost thresholds deemed acceptable to health care decision makers, as this analysis demonstrated.”

The economic analysis assessed the healthcare-related costs and QALYs of 1,798 patients randomized to receive CRT-D or ICD therapy extrapolated across a lifetime horizon, which was facilitated by an economic model that combined RAFT patient data with long-term data on the longevity of the medical devices. Cost in regard to QALYs was discounted at 3 percent per year. Healthcare-related costs examined included the treatment device (plus any replacements), hospitalization (both cardiovascular and non-cardiovascular related), pharmaceutical treatments, physician visits and long-term care, and were calculated using U.S. expenditures.

About the RAFT Trial

The RAFT trial, sponsored by the Canadian Institutes of Health Research and Medtronic, is a double-blinded, randomized, controlled trial, and showed that CRT-D significantly reduced mortality for mildly symptomatic heart failure patients (NYHA Class II): 29 percent when compared to patients treated with guideline-recommended implantable ICDs and medical therapy (p=0.006; HR=0.71). The study also demonstrated a significant reduction (30 percent) in heart failure hospitalizations for this Class II population (p=0.003; HR=0.70), consistent with previously published studies. It involved 1,798 patients in Canada, Europe and Australia. All patients were followed for at least 18 months, and had an average follow-up of 40 months, making it the longest follow-up and largest patient months-of-experience of any randomized controlled trial of CRT therapy.

1. The Economic Argument for Disease Prevention: Distinguishing Between Value & Savings. Partnership for Prevention. February 2009. Retrieved on April 9, 2012 from https://www.prevent.org.
2. American Heart Association / American Stroke Association, Heart Disease and Stroke Statistics, 2010 Update.

Endosense Reports Strong Momentum for Contact-Force Sensing in Catheter Ablation at Heart Rhythm 2012

Endosense has reported another year of significant advancement in the move toward making contact-force sensing a standard of care in catheter ablation procedures. Participating at the Heart Rhythm 2012 meeting, the company noted a wealth of new clinical abstracts and a new HRS/EHRA/ECAS consensus statement as key validation points supporting the value of the sensory parameter in cardiac ablation.

Among the clinical data presented at Heart Rhythm 2012 were more than 20 abstracts exploring the use of contact-force sensing during catheter ablation procedures; these abstracts build on more than 50 clinical papers and presentations on the subject since 2010 alone. Fourteen of the new Heart Rhythm 2012 abstracts featured Endosense’s TactiCath, the first force-sensing catheter to give the electrophysiologist a real-time, objective measure of contact force during the catheter ablation procedure.

Key new data on the TactiCath included the results of Endosense’s EFFICAS II clinical study, presented by Dr. Josef Kautzner (Prague, Czech Republic) in “Contact Force, FTI^™ [Force Time Integral] and Lesion Continuity Are Critical to Improve Durable PV Isolation: EFFICAS II Results.” The data showed that contiguous lesions created following the Contact Force Guidelines identified in EFFICAS I (CF above 10g and FTI above 400gs) resulted in superior ablation outcomes, with durable pulmonary vein isolation of up to 98 percent found at three months via invasive follow-up. Several other studies presented showed the importance of FTI as a determinant for ablation success or for a reduction of procedure time.

Additional force sensing-related topics discussed at the Heart Rhythm meeting include the 2012 HRS/EHRA/ECAS Expert Consensus Statement on Catheter and Surgical Ablation of Atrial Fibrillation, which was released in March. For the first time, the consensus statement recognizes contact-force sensing as a parameter that has the potential to improve the efficacy and safety of catheter ablation procedures.

“The field of contact-force sensing is clearly experiencing tremendous momentum, as more and more scientific evidence and clinical use point to its value in improving outcomes and shortening procedure times of catheter ablation procedures,” said Jan Keltjens, Endosense president and chief executive officer. “Endosense is proud to have pioneered the concept of contact-force sensing in catheter ablation and to have also validated it with the groundbreaking TOCCATA and EFFICAS studies, and we are very pleased to remain at the forefront of this exciting field today.”

Endosense’s leadership in the field of contact-force sensing dates back to the first abstract on the TactiCath at Heart Rhythm 2006. Since that time, the company has conducted a number of clinical studies demonstrating the safety and effectiveness of contact-force sensing over traditional ablation technologies, and has also nearly completed enrollment in the pivotal TOCCASTAR investigational device exemption clinical trial.

Caution: In the United States, the TactiCath is an investigational device. Limited by Federal (or United States) law to investigational use.

St. Jude Medical Announces Results of SCD-HeFT 10-Year Follow-up Study

St. Jude Medical, Inc. announced results of the SCD-HeFT (Sudden Cardiac Death in Heart Failure Trial) 10-Year Follow-up Study at Heart Rhythm 2012. The study demonstrated implantable cardioverter defibrillator (ICD) therapy significantly reduces mortality for at least 11 years in patients with moderate heart failure (HF).

The SCD-HeFT 10-Year Follow-up Study was led by Dr. Gust H. Bardy at the Seattle Institute for Cardiac Research (SICR), who was also the principal investigator in the original SCD-HeFT trial, and was sponsored by the National Heart, Lung, and Blood Institute (NHLBI) and the National Institutes of Health (NIH) with a subsidiary grant provided by St. Jude Medical. It adds to the results of the original trial by further comparing the mortality data of the remaining SCD-HeFT patients in the three arms of the study (ICD therapy, placebo and amiodarone) and provides additional data regarding survival benefits of ICD therapy. Mortality status was available for 2,291 patients, or 91 percent, of the original 2,521 SCD-HeFT trial participants, with a median follow-up duration of 11 years for survivors. This substantial amount of patient data has resulted in significant findings for these patient groups.

“While the original findings of the SCD-HeFT trial advanced the standard of care for patients with heart failure, the follow-up data are critical to define long-term ICD mortality benefits,” said Dr. Jeanne Poole, Professor of Medicine at the University of Washington, who presented the data in a late-breaking clinical trial session at Heart Rhythm 2012. “The SCD-HeFT findings demonstrate that patients experience the lifesaving benefit of ICD therapy over a decade of clinical heart failure.”

Among the findings, the long-term mortality of patients with a conservatively programmed, shock-only ICD was significantly lower than patients who did not receive a device. The absolute 12-year mortality rate for patients originally randomized to the ICD group was 5 percent lower than the group originally randomized to the placebo group (despite a significant number of the control patients receiving devices after the end of the original trial). As seen in the original SCD-HeFT trial results, the mortality difference was much more significant in patients with New York Heart Association (NYHA) Class II than NYHA Class III HF (who did not have the benefit of cardiac resynchronization therapy at the time of the trial). The survival benefit was also greatest in patients with an ischemic etiology (HF caused by impaired coronary artery blood flow).

“St. Jude Medical is proud to have supported the SCD-HeFT follow-up study, a trial that provides physicians with important information on the long-term efficacy of ICD therapy,” said Dr. Mark Carlson, chief medical officer and senior vice president of research and clinical affairs for the St. Jude Medical Cardiac Rhythm Management Division. “We’ll continue to support trials providing physicians with clinically relevant information that can help them to improve patient outcomes.”

The original SCD-HeFT data demonstrated superiority of ICD therapy over the control group, with a median follow up of nearly five years. The control patients were treated using optimal medical therapy (OMT) alone. A second comparison was conducted comparing the use of amiodarone to the control group. The study was instrumental in changing the national reimbursement policy for ICD therapy. The original trial remains the largest, longest, prospective, randomized, multicenter trial of ICD therapy.

The original SCD-HeFT was sponsored by the NHLBI and NIH with supplementary sponsorship by Medtronic and Wyeth Ayerst, and results were provided to the Centers for Medicare and Medicaid Services who approved payment of ICD therapy in ischemic and non-ischemic systolic dysfunction patients with left ventricular ejection fractions (EF) less than or equal to 35 percent and with NYHA Class II and Class III congestive HF.