SBIR-STTR Award

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.

Public Health Relevance Statement:
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.

Project Terms:
Animals; Ascites; abdominal dropsy; hydroperitonia; hydrops abdominis; peritoneal dropsy; peritoneal exudate; Atmospheric Pressure; Blood capillaries; capillary; Cause of Death; Clinical Research; Clinical Study; Cessation of life; Death; Economics; economic; Edema; Dropsy; Hydrops; Engineering; Goals; Heart failure; cardiac failure; Congestive Heart Failure; Cardiac Failure Congestive; Heart Decompensation; chronic heart failure; hemodynamics; Hospitalization; Hospital Admission; Hospitals; Hydrostatic Pressure; Infection; Inpatients; Acute Kidney Failure; Acute Kidney Insufficiency; Acute Renal Failure; Acute Renal Insufficiency; Lead; Pb element; heavy metal Pb; heavy metal lead; Lower Extremity; Lower Limb; Membrum inferius; Literature; Lung; Lung Respiratory System; pulmonary; Methods; Morbidity - disease rate; Morbidity; mortality; Noise; Outpatients; Out-patients; Patients; Physical Examination; Medical Inspection; physical examinations; Physicians; Physiology; Play; pressure; Pulmonary Edema; lung edema; Quality of life; QOL; Kidney Failure; Kidney Insufficiency; Renal Failure; Renal Insufficiency; Research; Role; social role; Signal Transduction; Cell Communication and Signaling; Cell Signaling; Intracellular Communication and Signaling; Signal Transduction Systems; Signaling; biological signal transduction; Signs and Symptoms; Diagnostic Findings; Sodium Chloride; salt; Family suidae; Pigs; Suidae; Swine; porcine; suid; Technology; Temperature; Testing; Time; Tissues; Body Tissues; vasoconstriction; vascular constriction; Work; Generations; Measures; Ischemic Heart; Ischemic Heart Disease; Ischemic myocardium; cardiac ischemia; coronary ischemia; heart ischemia; myocardial ischemia/hypoxia; myocardium ischemia; Myocardial Ischemia; Interstitial Fluids; Intercellular Fluid; bases; base; sensor; improved; Hepatic; Left; Peripheral; Acute; Chronic; Clinical; Residual; Residual state; Phase; Variation; Variant; Physiologic; Physiological; Medical; Death Rate; insight; Individual; Policies; Measurement; Early Intervention; Dysfunction; Physiopathology; pathophysiology; Functional disorder; fluid; liquid; Liquid substance; Sturnus vulgaris; Starlings; Sturnidae; Central venous pressure; Diastolic blood pressure; Diastolic Pressure; Hour; Event; Stream; subcutaneous; subdermal; System; Fluid overload; hypervolemia; interstitial; monitoring device; Performance; success; animal data; Animal Model; Animal Models and Related Studies; model of animal; hospital readmission; hospital re-admission; re-admission; re-hospitalization; readmission; rehospitalization; Devices; Therapeutic Intervention; intervention therapy; Admission activity; Admission; Sampling; response; Membrum superius; Upper Limb; Upper Extremity; Leg; Address; Symptoms; Data; Detection; Small Business Innovation Research Grant; SBIR; Small Business Innovation Research; Monitor; transmission process; Transmission; Ventricular; Development; developmental; pre-clinical; preclinical; digital; designing; design; Outcome; Consumption; innovate; innovative; innovation; prototype; standard of care; data transfer; data transmission; data exchange; Phase I Study; phase 1 study; accelerometry; activity monitor; activity tracker; Accelerometer; experiment; experimental research; experiments; experimental study; wearable electronics; wearable system; wearable technology; wearable tool; wearables; wearable device; hospital re-admission rates; hospital readmission rate; re-admission rates; re-hospitalization rate; rehospitalization rate; readmission rates; hospitalization rates; remote care; remote healthcare; remote health care; pressure sensor; pig model; piglet model; swine model; porcine model; pulmonary arterial pressure; lung artery blood pressure; pressure in pulmonary arteries; pulmonary arterial blood pressure; pulmonary artery pressure; pulmonary artery systolic pressure; design verification; design validation; Compensation; Continuous Glucose Monitor; battery life