Transaction Description:
MINIMALLY INVASIVE HIGH INTENSITY THERAPEUTIC ULTRASOUND FOR THE TREATMENT OF OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY - PROJECT SUMMARY OBSTRUCTIVE HYPERTROPHIC CARDIOMYOPATHY (OHCM) IS A COMMON INHERITED HEART DISEASE THAT CAN CAUSE MAJOR LIMITATIONS TO DAILY ACTS OF LIVING, POOR PROGNOSIS, AND MORTALITY. THERE ARE AS MANY AS 1.5 M PEOPLE WITH HCM IN THE US ALONE, 2/3 OF WHOM HAVE THE OBSTRUCTIVE FORM OF THE DISEASE WITH OVER 50K REMAINING REFRACTORY TO MEDICAL MANAGEMENT AND ARE CANDIDATES FOR SEPTAL REDUCTION THERAPY (SRT). DESPITE THIS, ONLY ~1,200 PATIENTS PER YEAR OF THE 50K CURRENTLY INDICATED RECEIVE SRT, LEAVING THE VAST MAJORITY OF THE MOST SEVERE PATIENTS UNTREATED. THE REASON FOR IS THE HIGHLY INVASIVE NATURE OF EXISTING SRTS THAT CAUSE FREQUENCY CARDIAC RHYTHM ABNORMALITIES REQUIRING IMPLANTATION OF A PACEMAKER OR CARDIOVERTER DEFIBRILLATOR (ICD) AND HAVE UNACCEPTABLY HIGH RATES OF PERI- AND POST- PROCEDURAL MORTALITY (UP TO 10%). ADDITIONALLY, MANY PATIENTS ARE UNSUITABLE FOR EXISTING SRT PROCEDURES DUE TO EXISTING CO-MORBIDITIES AND/OR ANATOMICAL LIMITATIONS. THIS PHASE II SBIR PROPOSES DEVELOPMENT OF A NOVEL TREATMENT FOR OHCM BY PRECISELY TARGETING THE SOURCE OF THE OBSTRUCTION ON THE INTERVENTRICULAR SEPTUM (IVS) USING A NOVEL HIGH-INTENSITY THERAPEUTIC ULTRASOUND (HITU) CATHETER. OUR APPROACH TAKES A RELATIVELY SAFE, FEMORAL VENOUS APPROACH TO THE RIGHT VENTRICLE (RV) USING EXISTING DELIVERY TOOLS AND KNOWHOW WITHIN CARDIAC ELECTROPHYSIOLOGY. TREATMENT FOCUSES ON DELIVERY OF HITU TO SELECTIVELY ABLATE THE ENTIRE MID-MYOCARDIUM OF THE IVS WHILE SPARING THE CARDIAC CONDUCTION SYSTEM ON THE SUB-ENDOCARDIUM (HIS-PURKINJE), THEREBY REDUCING RISK OF HEART BLOCK REQUIRING PACEMAKER OR ICD INSERTION. THIS PROPOSAL BUILDS UPON THE PHASE I-EQUIVALENT WORK IN ACOUSTIC PHYSICS, AND PRE-CLINICAL PROOF OF CONCEPT WITH A PROTOTYPE CATHETER DEMONSTRATING THAT, BY GENERATING DEEP LESIONS IN THE MID-SEPTUM WITH A HITU, THE IVS THICKNESS CAN BE REDUCED BY APPROXIMATELY 30%. BASED ON CATHETER IRRIGATION FEATURES AND HITU’S NATURAL FOCUSING CHARACTERISTICS SPARING THE SUB- ENDOCARDIUM, HEART BLOCK CAN BE AVOIDED EVEN IN THE SETTING OF EXTENSIVE ABLATION IN THIS REGION. THE AIMS OF THIS PROPOSAL WILL FOCUS ON MATURATION OF CATHETER DESIGN ELEMENTS AND MANUFACTURING METHODS TO MAKE THE PROTOTYPE DEVICE SUITABLE FOR CLINICAL EVALUATION, VERIFY THE FUNCTIONALITY AND SAFETY OF THE SYSTEM TO RELEVANT INTERNATIONAL SAFETY STANDARDS (PARTICULARLY IEC 60601-2-62 STANDARDS), AND VALIDATE THE SAFETY, EFFICACY, AND DURABILITY OF THIS THERAPY IN ACUTE AND CHRONIC (3-MONTH) PRECLINICAL MODELS VIA CLINICALLY ACCEPTED MODALITIES (CARDIAC MRI, TTE, CLINICAL PATHOLOGY, GROSS PATHOLOGY AND HISTOPATHOLOGY). THE INFORMATION OBTAINED IN THIS GRANT WILL BE USED IN DIRECT SUPPORT OF EARLY FEASIBILITY IDE SUBMISSION WITH THE FDA AS PART OF A FUTURE PHASE OF THE GRANT. COMMERCIALIZATION OF OUR SYSTEM WILL BRING LIFESAVING THERAPY TO THOUSANDS OF CRITICALLY ILL PATIENTS EVERY YEAR AND EVENTUALLY EXPAND TO TREATMENT OF HCM PATIENTS IN EARLIER STAGES OF THE DISEASE BEFORE LONG- STANDING OBSTRUCTIVE HYPERTROPHY RESULTED IN IRREVERSIBLE HEALTH CONSEQUENCES.
