Wireless implantable cardiac systems for continuous multiparametric investigation of cardiac arrhythmias in vivo

Arrhythmias are life-threatening heart rhythm disorders that significantly impact the quality of life for millions of patients in the United States. They are associated with abnormalities in myocardial electrophysiological properties and calcium handling. Specifically, heart contraction and relaxation are regulated by intracellular calcium, which rises and falls in response to membrane potential depolarization and repolarization. In turn, calcium influences membrane potential via calcium-dependent ionic currents. One major challenge in studying arrhythmia mechanisms is the lack of techniques to simultaneously map and modulate calcium transients, electrical activities, and excitation-contraction coupling over time from the beating heart in vivo. The R01 proposal aims to overcome these limitations by developing a wireless, soft, implantable platform for in vivo cardiac calcium-voltage mapping and pacing. The device will be used to gain new mechanistic insights into arrhythmia pathogenesis and treatment. It comprises a soft probe, a wireless electronics module, and graphical user interfaces. The probe integrates arrays of sensors and actuators to enable colocalized, crosstalk-free spatiotemporal mapping of electrical excitation and calcium signaling, with additional options for cardiac pacing. Its mechanically soft design allows it to conform to the highly curvilinear epicardial surfaces and withstand repetitive strains from the heartbeat. The miniaturized wireless electronics module will be optimized for energy harvesting, storage, control, and bidirectional data communication, designed for full subcutaneous implantation and long-term in vivo studies with minimal impact on small animals. The user interfaces will enable real-time control of device operation and data analysis. The proposed work will be fulfilled via three Aims: In Aim 1, we will develop the soft cardiac calcium-voltage mapping and pacing probe; In Aim 2, we will design and optimize fully implantable Bluetooth based wireless electronics and software interfaces to support chronic in vivo operations of the probe; In Aim 3, we will use the system to systematically study electrical excitation, calcium signaling, and their interactions during arrhythmia development, progression, and pacing treatment with three common clinically relevant arrhythmias: ventricular tachycardia, atrioventricular block, and atrial fibrillation. The proposed work builds on our recent development of a flexible, wireless optoelectronic interface for acute and regional calcium-voltage mapping of heart function in vivo. Successful completion of this project will produce a first-of-its-kind in vivo platform to comprehensively study calcium, voltage, and their coupling in heart function and diseases. This technology holds the potential to greatly enhance our ability to investigate and treat cardiac conditions, with implications for widespread clinical applications. To maximize the impact, the team will make all tools and methods as freely as possible, host visitors for hands-on learning, and pursue commercialization opportunities to enhance scalability, tunability, and robustness for broader adoption. Project Number: 1R01HL180676-01 | Fiscal Year: 2025 | NIH Institute/Center: National Heart Lung and Blood Institute (NHLBI) | Principal Investigator: Luyao Lu | Institution: GEORGE WASHINGTON UNIVERSITY, WASHINGTON, DC | Award Amount: $664,432 | Activity Code: R01 | Study Section: Bioengineering, Technology and Surgical Sciences Study Section[BTSS] View on NIH RePORTER: https://reporter.nih.gov/project-details/1R01HL18067601