Validation of Erythrocyte Mechanical Fragility as a biometric for performance assessment of Circulatory Support Devices

Functional Fluidics is dedicated to commercialization of novel assays for improved blood cell health and function assessment. Cardiovascular Disease (CVD) is the leading cause of death in the United States with Heart Disease (HD) accounting for over 75% of all 840,678 deaths attributed to CVD in 2016. Mechanical Circulatory Support (MCS) devices provide cardiac and systemic support and reduce morbidity and mortality among high-risk patients. Multiple MCS device types are currently available, different in hemodynamic effects and clinical applicability, with improved efficacy and safety. MCS- induced blood damage, however, still remains a serious problem. FDA requires premarket bench testing of MCS devices to evaluate the potential for causing blood damage. Due to a lack of standardized testing “blood damage” is often assessed as either direct hemolysis or coagulopathy, ignoring rheological and biochemical impact of sublethal blood trauma. Medical device manufacturers invest up to 15% of sales into Randamp;D to address ever increasing demands on MCS performance. MCS-induced blood damage is the root cause of a wide range of adverse events that are often associated with blood thrombosis and hemolysis. Hemolysis rates of 5-8% are common, larger for ECMO, procedures like Cardiopulmonary Bypass (CPB) and for pediatric population. Development of an assay to assess sub-lethal blood damage could reduce uncertainties in development and evaluation of MCS devices and contribute to monitoring of their performance. Mechanical trauma in MCS devices in general and in ECMO in particular, arises from a combination of factors including shear stress from direct mechanical impact, turbulence, high flow rates, interaction with non-physiological surfaces, etc., with trauma different between different devices. Standardized Mechanical Fragility (MF) assay can assess induced blood trauma, including sub- hemolytic, however, the type of applied shear stress needs to be optimized to correlate to pre-existing sub-lethal RBC damage. We previously demonstrated that post LVAD implantation, RBC MF assessed using some stress application regimes, but not others, was a predictor of longer-term (4 weeks) hemolysis. Device type (HeartMate 3 and HeartWare) was also a significant predictor of RBC MF determined by some, but not all, stress regimes, with MF in turn correlated with the duration of CPB procedure. Functional Fluidics is providing the first rapid RBC MF assay, via a bench-top device using single-use cartridges. The technological innovation includes a patented MF system and means to assess RBC MF through the construction and use of MF profiles, as well as approaches for inducing functionally different types of shear stress. The final product would be a MF Testing System for better evaluation of MCS-induced damage in system development and approval process, and in the future potentially serve to monitor MCS clinical performance by assessing MCS device performance.Mechanical circulatory support (MCS) devices provide cardiac and systemic support and reduce morbidity and mortality among high-risk patients, however their use is subject to a range of complications. However, a lack of standardized testing and quantification of “blood damage” causes uncertainties in evaluation of such devices, as there are no accepted tests to assess sub-lethal blood trauma. Development of a Mechanical Fragility Testing System (MFTS) that would enable better evaluation of MCS-induced damage in device development and approval process, and in the future potentially serve to monitor MCS clinical performance by assessing device performance, patient-specific hemolysis, and hemodynamic risks.