Mitral valve disease is the most prevalent heart valve dysfunction in the U.S., affecting approximately 0.7% of the total population and 3.5% of the population over age 75. With the aging population, the occurrence of severe mitral regurgitation (MR) in the U.S. and Europe is projected to exceed 5M by 2020 and will present an increasing economic burden. The Problem: MR causes a volume overload on the left ventricle which in turn progresses to ventricular dilation, decreased ejection performance, pulmonary hypertension, symptomatic congestive heart failure, atrial fibrillation, right ventricular dysfunction and death. While conventional mitral valve surgery is safe and effective, it remains very invasive and morbid and is significantly underutilized. The Solution: Harpoon Medical has developed technology for minimally invasive, image-guided, beating-heart mitral valve repair, performed via a keyhole incision between the ribs. The innovative device allows an operator to eliminate MR by securing artificial chordae tendineae (neochords) to a prolapsed mitral valve leaflet with a bulky knot anchor and resuspending the leaflet in its normal position. The Harpoon device eliminates the need crack the chest, put the patient on a heart-lung machine and stop the heart. This will transform conventional mitral valve surgery from a complex 3-6 hour operation to a sixty minute procedure and allow patients to return to normal daily activities within a week. Preliminary Data: An ongoing early feasibility study has confirmed that the Harpoon device successfully reduced severe MR to trace in two patients suffering from degenerative mitral valve disease. Specific Aims: This project entails the development work and preclinical testing necessary to create an automated delivery system for human trials in the U.S and accelerate the commercialization of Harpoon's minimally invasive, beating heart mitral valve repair device. In Specific Aim 1 we will develop an automated delivery system with a single button actuator and validate it at the bench and in acute pig studies. In Specific Aim 2 we will develop a method for titrating the length of multiple neochords under echocardiographic guidance and securing them to the epicardial surface of the heart. The automated delivery system developed in Aim 1 and the method for titrating the length of the neochords developed in Aim 2 will be evaluated as part of a clinical study in dogs with degenerative mitral valve disease in Specific Aim 3 to validate the safety, performance and efficacy of the device in a naturally occurring disease model. Expected Outcomes: At the end of this Direct to Phase II SBIR Grant, Harpoon will have a minimally invasive, beating heart mitral valve repair device that has been validated in acute and chronic animal studies and is ready for clinical testing in the U.S. to support FDA approval.
Public Health Relevance Statement: Public Health Relevance: In this Direct to Phase II SBIR, Harpoon Medical plans to develop a medical device for minimally invasive, beating heart mitral valve repair performed via a keyhole incision between the ribs. The device will transform conventional open-heart surgery from a complex 3-6 hour operation that requires a month or more for recovery to a simple 60 minute procedure where the patient can return to normal daily activities within a week.
Project Terms: Acute; Affect; Age; aging population; Animal Model; Animals; aortic valve; Atrial Fibrillation; Caliber; Canis familiaris; Cardiac Surgery procedures; Cardiopulmonary Bypass; Cessation of life; Chest; Chronic; Clinical; Clinical Research; Clinical Trials; commercialization; Complex; Congestive Heart Failure; Conventional Surgery; Data; Dependence; design; Development; Devices; Disease; Disease model; Economic Burden; Economics; Europe; experience; Family suidae; Feasibility Studies; follow-up; Functional disorder; Goals; Grant; Heart; Heart Arrest; Heart Atrium; Heart Valves; Heart-Lung Machine; Hour; Human; image guided; Implant; innovation; Left ventricular structure; Length; Marketing; Measures; Medical; Medical Device; Methods; minimally invasive; Mitral Valve; Mitral Valve Insufficiency; Mitral Valve Prolapse; Needles; operation; Operative Surgical Procedures; Outcome; Patients; Performance; Phase; Population; Positioning Attribute; pre-clinical; Preclinical Testing; Procedures; Process; product development; public health relevance; Pulmonary Hypertension; Recovery; repaired; research clinical testing; Resources; rib bone structure; Right Ventricular Dysfunction; Risk; Safety; sample fixation; Secure; Side; skills; Small Business Innovation Research Grant; Sternotomy; Structure of chordae tendineae cordis; Surface; Surgical incisions; Surgical sutures; System; Technology; Time; tool; United States; Ventricular; Visit; Work
