DESCRIPTION (provided by applicant): Congenital Heart Disease (CHD) ranges from benign lesions to life-threatening structural abnormalities. While benign lesions may resolve without intervention, severe structural lesions require complex pediatric cardiac surgery. Severe congenital heart defects include transposition of the great vessels, hypoplastic left heart/single ventricle, and severe aortic stenosis. The specific operations required to treat these lesions differ, but have at least two important similarities: 1) they require surgical augmentation of the great vessels (aorta and pulmonary artery), and 2) the severity of the lesions require an operation in the neonatal period. The reconstruction of the aortic arch in children with severe congenital heart disease often requires transection of the great vessels, significant augmentation (often with a biological patch material), then suture repair using very small caliber sutures placed extremely close together to ensure repair integrity. However, due to the complex nature of the repair, the anatomy of the neonatal arch, and the anti-coagulation regimen that is required during the cardio-pulmonary bypass, perioperative bleeding is a significant, important and frequent complication. There is a critical, unmet clinical need for an effective method to effect perioperative hemostasis in such patients. This proposal addresses this need. High Intensity Focused Ultrasound (HIFU) provides a novel approach for treating perioperative bleeding. The primary clinical application of ultrasound is for diagnostic imaging; however, the field of therapeutic ultrasound is growing rapidly. Therapeutic modalities of ultrasound such as HIFU differ from diagnostic ultrasound in that the ultrasound transducer is designed such that the ultrasound energy focuses to a small region. Focusing the ultrasound can result in heating the target tissue to greater than 100o C within seconds. This rapid heating has induced hemostasis in numerous solid organ and vascular bleeding models. Our overarching research objective is to mitigate the effects of perioperative bleeding in surgically reconstructed great vessels, thus reducing the perinatal morbidity and mortality associated with surgical procedures. The objective of this Phase II proposal is to establish the feasibility and required parameters in an animal model such that HIFU can be used safely and effectively to mitigate perioperative bleeding. To accomplish this objective we will: (i) Evaluate the effect of HIFU on the integrity and strength of surgically reconstructed vasculature in situ (acute animal studies) (SPECIFIC AIM 1); (ii) refine the clinical hand-held HIFU system for treating neonatal perioperative bleeding (SPECIFIC AIM 2); (iii) design and development of a user interface and instruction manual for the automated control module for treatment setup, parameter logging, and device self-testing (SPECIFIC AIM 3); and (iv) perform a series of experiments to test the safety and efficacy of our clinical device in survival animal studies (SPECIFIC AIM 4).

PUBLIC HEALTH RELEVANCE: Moderate to severe Congenital Heart Disease (CHD) occurs in about 6/1,000 live births. Severe structural lesions that require complex pediatric surgeries, such as transposition of the great vessels, hypoplastic left heart, single ventricle, and severe aortic stenosis, have been reported as about 1/1,000 of live births. The Pediatric Heart Network recently completed the Single Ventricle Reconstruction Trial, which enrolled 555 children which indicated that peri-procedural morbidity and mortality are significant.