Evaluation of the Safety and Effectiveness of the OPTIMIZER System in Subjects With Heart Failure: FIX-HF-5

Evaluation of the Safety and Efficacy of the OPTIMIZER System With Active Fixation Leads in Subjects With Heart Failure Resulting From Systolic Dysfunction: FIX-HF-5

The purpose of this study is to determine whether treatment with the OPTIMIZER System is safe and effective in patients with moderate to severe heart failure symptoms.

IMPULSE Dynamics' FIX HF 5 US Study is a prospective, multi-center, study to evaluate the safety and efficacy of cardiac contractility modulation (CCM) signals delivered by the implantable OPTIMIZER™ System in patients with NYHA class III/IV heart failure. The study will involve the recruitment of approximately 420 subjects at a total of up to 50 sites nationwide.

Those subjects who fulfill all inclusion and exclusion criteria based upon baseline test results will be randomized to receive the OPTIMIZER™ System or to a control group. All subjects randomized will be followed for 1 year and shall receive the same study related assessments throughout the course of the study. In addition, all subjects will continue to receive optimal medical therapy for the treatment of their heart failure.

The primary efficacy assessment consists of a change in exercise tolerance measured by cardiopulmonary exercise testing at baseline and 6 months. Safety variables, such as the rate and cause of hospitalizations or death, shall be collected in both groups and shall be compared at 12 months.

Inclusion Criteria:

• Subjects who are 18 years of age or older
• Subjects who are either male or female
• Subjects who have a baseline ejection fraction of 35% or less by echocardiography.
• Subjects who have been treated for heart failure for at least 90 days (including treatment with a β-blocker for at least 90 days unless the patient is intolerant) and are in New York Heart Association functional Class III or IV at the time of enrollment.
• Subjects receiving appropriate, stable medical therapy during the 30 days prior to enrollment for treatment of heart failure, consisting of the appropriate doses of diuretics, ACE-inhibitor or angiotensin II receptor blocker and β-blocker. Stable is defined as no more than a 100% increase or 50% decrease in dose.
• Subjects who, in the opinion of the Principle Investigator (based on the current guidelines for clinical practice), have a clinical indication for an implanted cardiac defibrillator (ICD) and/or pacemaker, must have an existing device or agree to undergo implantation of such a device unless the patient refuses to undergo the implantation of such device for personal reasons.
• Subjects who are willing and able to return for all follow-up visits.

Exclusion Criteria:

• Subjects whose baseline VO2,max is <9 ml 02/min/kg.
• Subjects who have a potentially correctible cause of heart failure, such as valvular heart disease or congenital heart disease.
• Subjects who have clinically significant angina pectoris, consisting of angina during daily life (i.e., Canadian Cardiovascular Society Angina score of II or more), an episode of unstable angina within 30 days of enrollment, or angina and/or electrocardiography (ECG) changes during exercise testing performed during baseline evaluation.
• Subjects who have been hospitalized for heart failure which required the use of inotropic support within 30 days of enrollment.
• Subjects who have a clinically significant amount of ambient ectopy, defined as more than 8,900 premature ventricular complexes (PVCs) per 24 hours on baseline Holter monitoring.
• Subjects who have chronic atrial fibrillation or chronic atrial flutter or those cardioverted within 30 days of enrollment.
• Subjects whose exercise tolerance is limited by a condition other than heart failure (e.g., angina, chronic obstructive pulmonary disease [COPD], peripheral vascular disease, orthopedic or rheumatologic conditions) or who are unable to participate in a 6-minute walk or a cardiopulmonary stress test.
• Subjects who are scheduled for a coronary artery bypass graft (CABG) or a percutaneous transluminal coronary angioplasty (PTCA) procedure, or who have undergone a CABG procedure within 90 days or a PTCA procedure within 30 days of enrollment.
• Subjects who have a biventricular pacing system or who have an accepted indication for such a device.
• Subjects who have had a myocardial infarction within 90 days of enrollment.
• Subjects who have mechanical tricuspid or aortic valves.
• Subjects who have a prior heart transplant.
• Subjects who are participating in another experimental protocol.
• Subjects who are unable to provide informed consent.