Evaluation of the Safety and Effectiveness of the OPTIMIZER System in Subjects with Heart Failure: The FIX-HF-5 Study Update

I d like to talk about the recent announcement in just a moment, but first, let s provide a refresher for those who may be unfamiliar with the trial. Could you briefly describe the purpose and goals of the trial? How many sites and patients are involved? The FIX-HF-5 clinical study is a prospective, multi-center study for patients with symptomatic heart failure, who are classified as having New York Heart Association Class III or IV heart failure despite optimal medical therapy, an ejection fraction less than 35%, and who are not candidates for cardiac resynchronization therapy (CRT). The study involves 428 patients at 50 sites nationwide. Please also describe how the OPTIMIZER system and cardiac contractility modulation (CCM) therapy work. The idea behind CCM is that relatively large electrical impulses are delivered during the absolute refractory period. These impulses are approximately 100 times the power compared to a normal pacemaker spike, so it is a relatively large amount of energy that is being delivered. Since it is delivered through the absolute refractory period, it does not initiate a new contraction and it does not modify the activation sequence, but rather it is tended to modify the strength of the contraction. The mechanisms by which that occurs is not fully understood, but it does appear that these signals do have an impact on gene expression, of key genes involved with expectation contraction couplings, as well as the function of proteins the correlation of proteins involved with calcium cycling and contraction. Patient enrollment is now complete for the FIX-HF-5 congestive heart failure study. What does this mean, and what is important about this milestone? There are over 5 million people with heart failure in this country, and from among this population, there are approximately 1.5 million people who have Class III or Class IV symptoms despite optimal medical therapy. Right now the only option available for those patients is CRT. However, the issue with CRT is that of the approximately 1.5 to 2 million patients with symptoms of that severity, probably only around 30-34 percent have a wide QRS for dyssynchrony. In addition, of the people who get CRT, as many as a third do not respond to therapy. We re talking about a vast majority of patients with persistent symptoms of heart failure who have no treatment options. Therefore, our real hope is that if the study results are positive, it will provide a treatment option for a very large population of patients. Will there be a Phase III or IV? What about FDA approval? No, in this area of devices, we just need to do one pivotal study that proves safety and efficacy. If we get positive study results, that will allow us to obtain FDA approval. After approval, there will be many more opportunities to do additional studies such as larger-scale studies as well as small mechanism studies in patients. We are certainly looking forward to be able to continue to study CCM. When will we see results? When will the trial be completed? The last patient enrollment occurred in early June 2007, and the minimum follow-up time is 1 year. Therefore, we will be following up with these patients for the next year, monitoring data, and putting together our analysis. The results should be available a little over a year from now. Is there anything else you d like to add? The CCM device is already available in Europe, and we are in the process of exploring additional studies there. One of those studies is using the OPTIMIZER system in patients who have a CRT device already and are failing that form of therapy. We have implanted the CCM device in several patients who previously had a CRT device, and we are currently following up with those patients. We are hoping within the next several months to be able to look at that a little more systematically in the context of the study right now that is being done because the device is available commercially. However, we are interested to pursue more in the near future. About the author: After earning a Bachelor of Science degree from Cornell University in Applied and Engineering Physics, Dr. Burkhoff obtained Doctor of Philosophy and medical degrees from The Johns Hopkins School of Medicine. House staff training in Internal Medicine was completed at the Bayview Campus of The Johns Hopkins Hospital as well as fellowship training in Cardiology at The Johns Hopkins Hospital. Dr. Burkhoff then moved to Columbia University in New York, where he established the Cardiovascular Research Laboratory in the Division of Circulatory Physiology/Heart Failure and Transplant. He served as an Associate Professor of Medicine in the Division of Cardiology at the College of Physicians and Surgeons, and as an Associate Attending Physician at the New York Presbyterian Hospital until 2003. Dr. Burkhoff is currently Medical Director of Impulse Dynamics and an Adjunct Professor of Medicine at Columbia University Medical School.