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 direct healthcare expenditure and over one million hospitalizations each year. Patients exhibit shortness of breath, decreased exercise tolerance and overall reduced quality of life. Despite best medical therapy, the prognosis of CHF remains poor: 5-year and 10-year mortality rates are 50% and 90% respectively. Patients with CHF have progressive dysfunction of their heart muscle, which limits its ability to eject blood out of the heart. As the heart fails, pressure builds up in the left atrium and this pressure backs up further into the pulmonary circulation leading to pulmonary fluid accumulation and its associated symptoms. 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. Two early-stage companies have developed interatrial stents to create such a shunt and have shown improved quality of life and increased exercise tolerance at one year. Nonetheless, intracardiac implants carry proven clinical risks including clot formation, device fracture and implantation failure. Alleviant Medical is developing a novel minimally invasive medical device ? the Left Atrial Decompression System (LADS) - that creates a precise interatrial shunt without a cardiac implant. Under fluoroscopic guidance in the catheterization lab, the LADS is intended to excise and safely remove a portion of the interatrial septum, thereby creating a therapeutic interatrial shunt with long-term patency. The current stage of the LADS is a working prototype that successfully cuts and captures tissue in an ex vivo porcine heart. The proposed SBIR grant establishes a clear plan to move from working design to a fully-functional prototype that demonstrates success in vivo and affords LAP reduction in a porcine elevated LAP (e-LAP) model.
In Specific Aim 1, two key components of the LADS (blade and tensioner) will be optimized and the full system will be used to demonstrate reproducible shunt creation on ex vivo porcine hearts and successful deployment in vivo in an acute porcine model.
In Specific Aim 2, the fully functional LADS will be used to evaluate LAP reduction in vivo in an acute (e-LAP) porcine model. Successful completion of the work outlined in this proposal will result in a fully functional LADS capable of reproducibly creating an interatrial shunt in vivo, and which demonstrates LAP reduction in an e-LAP animal model. Further work, to be detailed in a subsequent Phase II grant application, will seek to finalize LADS design in compliance with FDA design controls, complete product verification and validation, and demonstrate safety through a statistically-powered chronic animal study, as required to obtain FDA 510(k) clearance as a Class II medical device.
Public Health Relevance Congestive heart failure is a chronic and progressive condition that currently affects over 6 million patients in the US and poses a major public health burden. Symptoms of the disease are due, in large part, to elevated left atrial pressure, which results from failure of the heart to adequately eject blood from its main pumping chamber (left ventricle). The proposed project seeks to develop a novel medical device that effectively lowers left atrial pressure through a simple, low-risk, minimally invasive procedure and thereby reduce the symptoms and morbidity associated with the disease.