Project Summary / Abstract Heart failure (HF) remains a leading cause of death and results in huge economic and patient burden. Despite policies targeted at reducing readmission rates and improved treatment options, hospitalization rates for HF have remained largely the same. Disproportionally greater interstitial fluid accumulation versus intravascular accumulation plays a pivotal role in the symptomatic manifestation and detrimental outcomes of HF, including pulmonary and peripheral edema. Adequate management of fluid overload requires early intervention in the HF “congestion cascade” prior to the onset of symptomatic congestion. Current methods used to monitor quantitative changes in volume status are mostly limited to the intravascular space, and experimental devices targeting the measurement of subcutaneous interstitial pressure (SCIP) have unable to provide continuous, reliable data. There is a need for a non-invasive, easily placed technology that provides a clear quantitative metric that gives physicians insight into when to medically intervene earlier in the HF congestion cascade. To address this critical unmet need, NXT developed a IFPx SCIP sensor prototype (IFPx) that measures fluid status in the interstitial fluid compartment. Our long-term goal is to develop a wearable, non-invasive device to continuously monitor SCIP, with a form-factor like continuous glucose monitoring devices. The objective for this Phase 1 application is to test our NXT IFPx SCIP prototype sensor in benchtop experiments and in a large animal model of fluid- overloaded heart failure to demonstrate sensor reliability and to demonstrate SCIP signal tracking with standard, invasive metrics of congestion. Preliminary proof-of-principle studies demonstrated that the SCIP, as measured by historic methods, tracks with gold standard metrics of congestion, including left ventricular end diastolic pressure (LVEDP) and central venous pressure (CVP) in a porcine model of fluid-overloaded HF. Studies in Aim 1 are designed to improve the reliability and repeatability of the NXT IFPx SCIP prototype. We will design, test, and iterate different pressure sensing transduction devices to improve reliability and repeatability of the IFPx prototype, as assessed by benchtop testing. Studies in Aim 2 will mainly confirm that the NXT IFPx SCIP sensor can transmit and store data reliably. The most promising candidate from bench tests will then be validated in acute HF animal studies in Aim 3 with success defined as changes in SCIP correlates (Phase-adjusted correlation coefficient r2 > 0.7) or associates (Bland-Altman average±2SD) with LVEDP or CVP Successful completion of these studies will initiate a Phase II application to develop wearable technology further in chronic animal studies and to perform pilot clinical studies in patients with HF.

Project Narrative Congestive heart failure is a significant cause of hospitalization, decreased quality of life and death. Due to current limitations in detection, tissue congestion in the lungs and legs are not diagnosed until symptoms develop. NXT Biomedical has developed a prototype IFPx sensor to measure tissue congestion. The goal of this Phase 1 application is to test our NXT IFPx prototype SCIP sensor in bench-top experiments and in a large animal model of fluid-overloaded heart failure to improve sensor reliability and demonstrate signal tracking with standard, invasive measures of congestion.