FIX-HF-5 (Fix Heart Failure 5) is a clinical study designed to investigate the safety and effectiveness of a new system called the Optimizer for treating heart failure patients. The study is planning to enroll over 400 patients with New York Heart Association (NYHA) Class III or Class IV heart failure patients at sites across the United States. The trial began in mid 2004 and is expected to be completed by late 2006. The following is an update on the study’s progress at the Texas Cardiac Arrhythmia (TCA) Institute, which is one of the sites participating in the trial.

The Technology and Device
       The Optimizer technology is based on a new concept of treating heart failure known as Cardiac Contractility Modulation (CCM). Cardiac Contractility Modulation is a method for treating failing hearts in which non-excitatory electrical impulses are delivered to the heart during the absolute refractory period (ARP). Unlike signals generated by other cardiac devices (i.e., pacemakers), CCM signals do not initiate a heartbeat or action potential. Traditional pacing signals are delivered during the ‘excitatory’ period of the cardiac cycle and are able to initiate a new heartbeat.

Staff at the Texas Cardiac Arrhythmia Institute:

Rodney P. Horton, MD, Larry D. Price, DO, Javier E. Sanchez, MD, Jason D. Zagrodzky, MD, Robert C. Canby, MD, and G. Joseph Gallinghouse, MD.

       In contrast, CCM signals are intended to modify heart cell function in a manner that affects the contractility of the heart muscle and strengthens the muscular contraction. The system itself consists of a programmable implantable pulse generator (IPG), a programmer which communicates with the IPG, and three standard pacing leads (1 atrial lead and 2 right ventricular leads). The IPG produces CCM signals and delivers the pulses through the ventricular leads. The programmer allows medical personnel to customize the CCM signal parameters according to each patient’s needs and to obtain diagnostic information about the performance of the device. The system also includes the ability for the patient to recharge the battery of the IPG at home. The implant procedure is minimally invasive; it requires only local anesthesia, and is quite similar to the implant of a pacemaker. A pressure measurement catheter is also placed in the left ventricle of the heart to evaluate the acute effects of CCM therapy on cardiac contractility.
       The effects of the CCM signal are monitored during the implant procedure, and the Optimizer System is only implanted after these measurements are completed. If proven safe and effective, the Optimizer System may provide physicians with another tool for treatment of heart failure patients.

FIX-HF-5 Study Objective and Design
       The purpose of the FIX-HF-5 study is to determine whether treatment with the Optimizer System is safe and effective in patients with moderate to severe heart failure. This study is a randomized, multi-center trial. Subjects are randomly assigned to the treatment or control groups. Those patients randomized to the treatment group will receive the Optimizer System. In addition, all subjects will continue to receive optimal medical therapy for the treatment of their heart failure.

The Optimizer III.

FIX-HF-5 at Texas Cardiac Arrhythmia
       Our institution was among the first 10 sites to participate in the FIX-HF-5 trial in 2004. The initial study, now referred to as the Feasibility Phase of the study, utilized the Optimizer II, a non-rechargeable pulse generator that required replacement after six to nine months when the battery was depleted. We enrolled seven patients in the Feasibility Phase. We entered the Pivotal Phase of the study when the Optimizer III, a rechargeable version of the device, was introduced. Our institution has enrolled 10 patients so far into this portion of the trial. The initial experiences with both the Optimizer II and Optimizer III devices have been positive; however, the trial is ongoing and data is still being collected.

Study Endpoints
       Effectiveness measures include improvements in exercise capacity measured during cardiopulmonary treadmill testing, quality of life, NYHA Class, left ventricular end diastolic dimension, and left ventricular ejection fraction. Safety measures include changes in the rate of all-cause mortality, rate of all-cause hospitalization, rate of cardiac-related hospitalization, and the overall severity and incidence of adverse events.

Optimizer Charger & Wand.

Initial Observations at TCA
       The concept of CCM has been circulating in the medical community for a while; we first heard about it in the late 1990s. The idea of strengthening the contraction was becoming well known. At TCA, we are always looking for innovative medical advancement for our patients. We first heard about CCM at the Heart Rhythm Society meeting several years ago — that is how we became involved in the trial. We have a sound infrastructure for recruiting patients at TCA, and believe this trial could potentially benefit the larger population. In regards to the ongoing results at this time, I would really like to preface it by reiterating that we are still at the early stages of gathering all the data in its entirety. Anecdotally, we did have a patient with a lead fracture. It took us a while to figure out the exact problem. When we finally realized that the patient needed a lead replacement, the patient felt enormously better. Overall, it appears that the patients are getting the same benefit as they are getting from CRT therapy. We did note a strong placebo effect in the beginning. All the patients have been satisfied with the therapy, I think in large part because of the great medical attention they receive here at TCA. We have an open-door policy for all research patients. The class of patients for this type of therapy do not have a lot of options. I think as the device becomes smaller or perhaps as it is incorporated into existing platforms, the market will expand enormously.
       Although some of the first published abstracts showed that there was general improvement in heart outcomes, there needs to be a stronger powered program with a larger population base, and that’s what we are trying to achieve at TCA.
       We did the first initial study to try out the therapy, and the trial we are doing now is to see if there any benefits of the therapy. It is too early to be overly enthusiastic, but we have enough data to be optimistic. We continue to seek additional study candidates to further assess the safety and efficacy of the device.

About the Author
       Texas Cardiac Arrhythmia, a division of Texas Cardiovascular Consultants, was founded in 1996 by Dr. Rodney Horton. It has grown to include six clinical electrophysiologists and two nurse practitioners.
Texas Cardiac Arrhythmia Research, directed by Deb Cardinal, RN, is a division of Texas Cardiovascular Consultants. Texas Cardiac Arrhythmia Research is committed to providing opportunity for patients in central Texas to participate in studies utilizing the latest technology in the area of cardiac electrophysiology.