Implantable Cardiac Patch Continuously Monitors Inflammation and Atrial Fibrillation Biomarkers in Human Epicardial Adipose Tissue Ex Vivo.

Introduction: Atrial fibrillation (AF) is a type of arrhythmia commonly encountered by clinicians and plays a vital contribution to cardiovascular morbidity and mortality. In addition to the underlying pathophysiological hallmarks of the disease, inflammation has been outlined by various studies as a strong indicator of disease progression. Here, we perform reagentless electrochemical detection of responsible biomarkers namely, BNP, Troponin I, IL-1, and MCP1in human epicardial adipose tissue (hEAT) obtained from donor patients continuously for as long as five hours. The present work reports a) the successful integration of backend microelectronics and sensors on a miniaturized cardiac patch (area= 25cm^2) and b) its application to continuously monitor aforementioned biomarkers in hEAT for five hours. The timeframe depends on our ability to sustain the donor heart with extracorporeal oxygenation.
So far, no study or technology has been able to measure and report the same.

Materials and

Methods: A power harvesting circuit, potentiostat, and microneedle-based sensors were fabricated, miniaturized, and integrated into a cardiac patch. Its functional characterization and feedback signal obtained from the patch were respectively confirmed by SEM and our IOS application script written in Python. The patch was subsequently implanted in the hEAT to monitor and record the dynamic activity of relevant analytes via chronoamperometry for five hours; the longest a human heart can survive outside the body by extracorporeal oxygenation. The electrochemical detection of proteins was investigated further by ELISA, flow cytometry, immunohistochemistry, and Real-Time PCR. Antifouling coating was developed by electrospinning PLGA-based nanofibers. Pores in individual fibers were introduced to increase the flexibility of the patch. PEG (mw=5000) was functionalized on the fibers to increase its antifouling properties. These fibers were cross-linked to the substrate of the patch, i.e polyimide. SEM and AFM were used to investigate the pore size of individual fibers, functionalization of PEG and the flexibility of the substrate.

Results, Conclusions, and Discussions: No negative changes were observed as a result of implanting the cardiac patch in hEAT on heart tissue in terms of localized strain, fibrosis or trauma. Our results established our implantable cardiac patch’s stability, sensitivity, and high signal-to-noise ratio (SNR) irrespective of miniaturization. We report its novelty in continuously monitoring relevant biomarkers in hEAT for five hours suggesting that our technology can be used to track AF progression via measuring inflammation in the hEAT. Our results indicate the feasibility of integrated miniaturized technologies for early detection of disease hallmarks and their clinical translation in vivo. Further miniaturization of the system is required to perform in vivo experiments in small animal models. The cardiac patch reported here enables the in vivo monitoring of physiologically relevant proteins responsible for AF and inflammation. Although some similar technologies have been outlined in literature, especially with the boom in the field of wearable technologies, their overall interface and operation are distinct in many ways. Owing to the mechanism of the electrochemical sensing utilized in the cardiac patch, proteins relevant to AF can be monitored directly in the adipose tissue encapsulating the heart. Current biosensors for AF focus primarily on possible anomalies in the ECG, proteins found in blood, or ISF to monitor the progression of AF. Here, we report a novel implantation site and an integrated miniaturized cardiac patch that can monitor the relevant proteins directly in hEAT which is the hub of inflammation and relevant proteins indicative of a diseased microenvironment.

Acknowledgements (Optional): Dr. Kelley, NIH and CZI biohub.