EP Lab Digest - December 2007 - (Page 34)

NEWS DECEMBER NEWS Continued from page 39 addition, the EPC adjudication tended to increase effect size, although the CRF method of identifying heart failure hospitalizations yielded similar qualitative results. The results presented by Dr. Carson demonstrated both the beta-1 389 Arg/Arg adrenergic receptor polymorphism and the alpha-2c wild type gene variant are positively correlated with certain major clinical responses to bucindolol (all-cause mortality, cardiovascular mortality and days each patient was hospitalized for cardiovascular of heart failure causes). Moreover, Dr. Carson presented data that the pairing of these two favorable genotypes produces an even greater clinical response than either monotype alone. With this pairing, all-cause mortality was reduced by 41% (p = 0.032), cardiovascular mortality by 48% (p = 0.017), adjudicated time to first cardiovascular or heart failure hospitalizations by respectively 33% (p = 0.008) and 45% (p = 0.002), and days hospitalized/patient by 32% (cardiovascular, p = 0.012) or 36% (heart failure, p = 0.003). Such patients, termed the “very favorable diplotype” and comprising over 40% of the general population, will be the highest priority for treatment with bucindolol. Data from the Phase 3 BEST clinical trial (Presentation #2867) demonstrated a positive effect of bucindolol on clinically important arrhythmic conditions — atrial fibrillation and life-threatening ventricular arrhythmias (VT/VF). In the presentation by Christopher Lowery, MD of the University of Colorado, subjects with chronic heart failure (CHF) and Arg/Arg 389 beta-1 or wild type alpha-2c adrenergic receptors treated with bucindolol had a lower rate of new onset AF than those randomized to placebo. This treatment effect was not observed in the population of beta-1 Gly389 or the alpha-2c deletion carriers, indicating a pharmacogenetic interaction. Moreover, the “very favorable” diplotype pairing of these two favorable gene variants produced even greater positive treatment effects (reduction by 52%, p ≤ 0.048), similar to the pharmacogenetic findings observed with heart failure endpoints. As demonstrated in a presentation (Presentation #2021/C32) by William Sauer, MD of the University of Colorado, subjects with CHF and Arg/Arg 389 beta-1 or wildtype alpha2c adrenergic receptors treated with bucindolol had a lower rate of VT/VF than those randomized to placebo. This treatment effect was not observed in the population of beta-1 Gly389 or the alpha-2c deletion carriers, indicating a pharmacogenetic interaction. As for AF prevention and CHF endpoints, patients with the favorable diplotype had treatment effects that were enhanced (reduction by 64% [p = 0.001] in VT/VF occurrence by bucindolol as compared to placebo) over those for each individual favorable monotype. Bucindolol is a next-generation beta-blocker and vasodilator for heart failure and other indications. A large substudy from a Phase 3 trial published in the July 25, 2006 edition of the Proceedings of the National Academy of Sciences shows that a common genetic variation in the beta-1 adrenergic receptor may help doctors identify heart failure patients who may benefit most from bucindolol. Data presented at the 2005 American Heart Association meeting from the same DNA substudy demonstrates further enhancement of bucindolol’s efficacy by targeting both the beta-1 variant and a variant of the alpha-2cadrenergic receptor. A patient’s response to bucindolol appears to be affected by genetic variations in two cardiovascular receptors. ARCA Discovery, a privately held biopharmaceutical company, is planning to submit a New Drug Application to the FDA for bucindolol in order to gain approval of the drug with a genetic test to assist physicians in determining whether bucindolol is an appropriate therapy for their heart failure patients. The company has exclusive, worldwide rights to bucindolol. Live Case Using New Technology Demonstrates Shorter Procedure Time A blation Frontiers, Inc., a privately-held medical device company, announced its successful first public broadcast of a procedure using the company’s novel catheter ablation system. Performed by Dr. Lucas Boersma of the St. Antonius Hospital in Nieuwegein, The Netherlands, the system was used to isolate heart tissue causing a potentially dangerous irregular heart rhythm. The process was transmitted to an audience of heart specialists in Birmingham, United Kingdom, as part of the 2007 Heart Rhythm Congress. Professor John Morgan of the Southampton General Hospital — a member of the Heart Rhythm Congress organizing committee — accompanied Dr. Boersma in performing the procedure. The 60-year-old male patient was diagnosed with paroxysmal atrial fibrillation (AF) approximately two years ago. However, in March 2007 his diagnosis worsened to persistent atrial fibrillation. He suffered from episodic heart palpitations and dyspnea. Dr. Boersma began the minimally invasive procedure by inserting the Pulmonary Vein Ablation Catheter (PVAC™) into the patient’s right leg and maneuvering up to the heart by way of a large vein.The multi-electrode circular tip catheter was used to diagnose and treat the cardiac tissue responsible for the irregular heart rhythm, which was located in the left atrium of the heart near the pulmonary veins. Simultaneously applying radiofrequency (RF) energy to all of the electrodes with the Ablation Frontiers GENius™ generator, Dr Boersma created a number of circular “lesions” that blocked the short circuit — a procedure known as pulmonary vein isolation (PVI). The patient left the catheterization laboratory with a normal heart rhythm. During the procedure, Dr. Boersma isolated all four pulmonary veins in approximately 38 minutes, or 50 minutes from the first venous access. He commented,“With this game-changing technology I can create a contiguous, circular lesion without having to drag the catheter along the surface of the heart. This greatly simplifies a once complex procedure.The novel design also allows me to perform the procedure with a single catheter for mapping and ablation. After having treated many patients with this technology, I have documented substantially reduced procedure times as well as reduced complications from what I would normally expect to see.” On the day before the procedure, Dr Boersma presented his results with the PVAC as part of a presentation entitled “New Developments and Insights into Atrial Fibrillation Ablation Therapy.” In his initial experience, Dr. Boersma reported 100% acute success — confirmed pulmonary vein isolation — with an average total procedure time of 96 minutes. Professor Morgan noted, “We have successfully used this catheter in a large number of patients at Southampton General Hospital and experienced reduced procedure times without any major complications. We are very happy with the design of both the catheter technology and the RF generator.” Ablation Frontiers has been distributing the PVAC and GENius™ RF Generator to a select number of European centers since receiving the CE Mark in December 2006.As part of the company’s “toolbox” approach for ablation of all types of arrhythmias, Ablation Frontiers also distributes the Multi-Array Ablation Catheter™ (MAAC), Multi-Array Septal Catheter™ (MASC), and the Tip-Versatile Ablation Catheter™ (T-VAC). Federal Law limits these devices to investigational use in the United States. Ablation Frontiers is a medical device company based in Carlsbad, California. Founded in 2004, the company is focused on developing and commercializing innovative products for the treatment of cardiac arrhythmias. In late 2006, Ablation Frontiers received the CE Mark and actively markets its portfolio of novel anatomicalbased catheters and a multi-channel RF generator in the European Union and other international markets.

Table of Contents Feed for the Digital Edition of EP Lab Digest - December 2007

EP Lab Digest - December 2007 Improved Anatomical Orientation During AF Catheter Ablation: Experience from Leipzig Heart Center One EP Lab’s Solution to the Administration of Deep Sedation Contents Letter from the Editor Spotlight Interview: Northeast Georgia Medical Center Emerging Technologies for the Electrophysiology Lab The Western Atrial Fibrillation Symposium About the PRECEDE-HF Trial: Interview with William T. Abraham, MD, FACP, FACC, FAHA Overview on Shire and the Discontinuation of Ethmozine®: After the Heart Rhythm Society Intervenes, the Company Changes its Decision Minimizing the Risk of Infection at Children’s Sibley Heart Center: Interview with Nicole Jarrell, RNC, MSN, and J. Renee Watson, RN, CIC Is There a Link Between Gasoline Vapors and Brugada Syndrome? Interview with Darko Kranjcec, MD and Hugues Abriel, MD, PhD New Feature! Pacemaker/ICD Puzzle Email Discussion Group Events Calendar Industry News and Products

EP Lab Digest - December 2007

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