The objective of this proposal is to develop a less invasive long-term copulsation device to treat patients in late Class III and early Class IV stages of heart failure (HF). Chronic congestive heart failure is the largest unsolved problem in cardiac care today. There are over 5.5 million people in the United States with this diagnosis and the number of patients is expected to double over the course of this decade. ABIOMED's key innovation will be an apically placed implantable partial left ventricular assist device (LVAD) system designed for copulsation, called the Apical Copulsation Device (ACD). Synchronizing assist with the heart will reduce the work required by the heart during systole and unload the left ventricle during diastole. Phase I proved the feasibility of the ACD both in bench testing using a specially designed mock loop and in three in vivo animal studies. The system control is based on the left ventricular pressure and it successfully and consistently ejected 30 ml of blood during systole after the native ventricle opened the aortic valve and completed this ejection before the valve closed. No dilatation was observed and the ACD reduced the mechanical external work required by the ventricle up to 45% with no significant increase in end-systolic pressure compared to baseline. This device can be implanted through a thoracotomy and without cardiopulmonary support, reducing the risks associated with more invasive techniques. Phase II of the program will focus on developing a durable, integrated system for extended use and characterizing its effects on the heart. There is currently no published chronic in vivo data for copulsation therapy and studies will be conducted to assess the system's hemocompatibility and how the body reacts to this type of support over time.
Chronic heart failure (CHF) affects over 5 million Americans, with 550,000 new cases diagnosed annually. The associated mortality rates are high with CHF patients under age 65, 80% of men and 70% of women die within 8 yrs. The 1-yr mortality rate is 20%, and that figure jumps to 60% for patients with end-stage (decompensated or New York Heart Association Class IV) heart failure. There are few treatment options for end-stage CHF and medical management is the first line of treatment with limited results. Heart transplantation can provide significant individual benefit, but its impact is limited by the number of donor organs available;worldwide, less than 2900 heart transplants occurred in 2005. Over the past 15 years, mechanical circulatory support has become an established means of treating end- stage CHF. A ventricular assist device (VAD) is a blood pump that is designed to assist or replace the function of either the left or right ventricle. The device is most commonly deployed on the left side (i.e. as an LVAD), where blood is withdrawn from either the left atrium or the apex of the left ventricle. The blood then passes through the pump and is returned to the ascending aorta. The Apical Copulsation Device (ACD) proposed here affords a very effective ventricular decompression and unloading without requiring cardiopulmonary bypass or a sternotomy. The role of VADs has evolved since their clinical introduction. For end-stage CHF patients, the Thoratec HeartMate LVAD that originally received approval for bridge-to-transplant (BTT) use is now approved for alternative-to-transplant (destination therapy or DT). The results from the REMATCH study showed that for patients who are not candidates for cardiac transplantation, mechanical support increased not only the survival rate, but also scores on physical and emotional tests at one year compared to patients treated with medication. While extending the life of these patients is important, the quality of this life is paramount. Earlier treatment of HF using the ACD approach provides the opportunity to treat many more patients and may also be more effective in preserving end organ function and restoring quality of life. With over 100,000 patients in the United States receiving biventricular pacemakers each year, it is anticipated that up to 50,000 patients may be candidates for chronic copulsation therapy. The market for copulsation technologies is a sizable portion of the moderate to severe HF patient population (represented by approximately 250,000 to 300,000 annual cases in the U.S. alone) and, hypothetically, may have a very significant total market potential (estimated at $0.8 to $1.0 billion).
