Pre-Clinical Development of a Fetal Micropacemaker

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DESCRIPTION (provided by applicant): We have developed a novel micropacemaker to address the critical problem of complete heart block in the fetus. This condition is a life-threatening emergency in a fetus, and is nearly always fatal if hydrops fetalis develops at a young gestational age. There are currently no effective treatment options in these cases, and attempts to implant an extra-uterine pacemaker with electrodes on the fetal heart have invariably failed due to lead dislodgement from fetal movement. The novel design is a self-contained single-chamber micropacemaker that can be percutaneously implanted into the fetus without exteriorized leads, allowing for subsequent fetal movement without risk of electrode dislodgement. Such a design and application is possible because of advances in fetal intervention that allow percutaneous placement of the pacing system through the maternal abdomen and fetal chest wall under ultrasound and fetoscopic guidance. With successful fetal pacing, a complete recovery from hydrops fetalis is expected with survival to term and a nearly normal life. A functional prototype of the device has been built, and animal testing using adult rabbits has provided compelling data regarding key aspects of the electronic and mechanical design strategies. In addition, the device was recently awarded a Humanitarian Use Device designation from the Federal Drug Administration. The next translational step of the project requires the successful implantation of a functional device into a fetal sheep to demonstrate proof of concept in a relevant pre-clinical animal model. A novel packaging system intended to protect the circuitry from bodily fluids will be developed and tested in vitro. The device will the be implanted in a series of fetal sheep, and ventricular stimulation of the fetal myocardium will be confirmed at regular intervals during gestation. The micropacemaker is powered by a tiny, commercially available, rechargeable lithium ion cell which can provide power for 2-3 weeks of pacing. Therefore, we will also design and build an inductive recharging system that allows the cell to be recharged weekly from outside the mother. This research project is only possible through a multidisciplinary collaboration among a team of investigators with diverse experience and skills. These range from device design and fabrication to knowledge of specific electrical and pacing properties of the developing heart to proficiency in fetal surgical interventions. Dr. Ramen Chmait is a fetal surgeon who has successfully and safely performed numerous surgical procedures and interventions on fetuses. Dr. Yaniv Bar-Cohen specializes in pediatric heart rhythm disorders and has expert knowledge of cardiac pacing devices. Dr. Gerald Loeb has extensive experience with miniature device technology and has previously developed an FDA-approved, injectable device to stimulate skeletal muscle. Dr. Michael Silka is a world-renowned pediatric electrophysiologist with expertise in pediatric heart rhythm disorders in fetuses. Dr. Ja Pruetz has unique expertise in fetal cardiac imaging and fetal cardiovascular physiology, which will be vital for the implantation and follow-up of the device. PUBLIC HEALTH RELEVANCE: Complete heart block in the fetus is a life-threatening emergency, and is nearly always fatal if hydrops fetalis develops at a young gestational age. There are currently no effective treatment options in these cases, and attempts to implant an extra-uterine pacemaker with electrodes on the fetal heart have invariably failed due to lead dislodgement from fetal movement. The goal of this research is to design, build and test a self-contained, battery-powered micropacemaker that can be percutaneously implanted into the fetus from outside the mother and recharged by radio waves as needed until delivery.