Transcatheter Device for Congestive Heart Failure Treatment Through Left Atrial Decompression

ABSTRACT Congestive heart failure (CHF) is a chronic and progressive condition that currently affects over 6 million patients in the US. It accounts for over $35B in annual healthcare expenditure and is responsible for over one million hospitalizations each year. CHF is a chronic and progressive condition in which the heart is unable to pump enough blood to maintain adequate circulation - the heart is failing to meet the body’s needs. The prognosis for these patients is poor: despite best available pharmacological therapy, patients have 5-year and 10-year mortality rates of 50% and 90%, respectively. Morbidity is high and patients commonly exhibit symptoms of breathlessness, exercise intolerance, and fatigue upon minimal exertion. Although existing pharmacological therapies have demonstrated symptomatic improvement and mortality benefit in patients with heart failure with reduced ejection fraction there are currently limited FDA-approved treatment options (pharmacological or device- based) for the heart failure with preserved ejection fraction patient population. Recently the concept of interatrial shunting has gained attention as a potential therapeutic option for patients with CHF. By creating a connection between the high-pressure left atrium to the low-pressure right atrium elevated left atrial pressure (LAP) may be effectively lowered thereby relieving CHF symptoms. Recently, several implantable interatrial shunt devices have been shown to enable left atrial to right atrial blood flow, resulting in left atrial decompression, a reduction in CHF symptoms, and improved quality of life in a number of promising human clinical studies. Nonetheless intracardiac implants carry proven clinical risks including clot formation device fracture, migration, and implantation failure. There is currently no device available that can provide therapeutic left atrial decompression without the long- term clinical risks and concerns of leaving behind a foreign body in the heart. We believe a no implant option is achievable and should be provided for the vast number of patients. Alleviant Medical has developed a novel transcatheter approach to relieve left atrial pressure by creating an interatrial shunt without the need for a cardiac implant. Phase I was utilized to iteratively design, develop, and establish feasibility of a novel catheter system for the creation of a reproducible and stable interatrial shunt as demonstrated in benchtop, acute, and chronic animal studies. In Phase II, we will optimize remaining design elements, complete exhaustive performance verification and validation testing, and conduct a GLP chronic animal studies to demonstrate device reliability, safety, shunt durability, and biocompatibility consistent with clinical, regulatory, and product development objectives. The first aim is to complete final design optimization prior to testing. The second aim is to conduct design verification testing for an FDA Pivotal IDE submission. The third aim is to complete a GLP Chronic Animal study for an FDA Pivotal IDE submission. Successful execution of the work outlined in this program will yield a system design and dataset for an FDA pivotal IDE submission and progress towards clinical and commercial efforts.