Red blood cell mechanical fragility as potential metric for assessing blood damage caused by implantable durable ventricular assist devices: Comparison of two types of centrifugal flow left ventricular assist devices

Implantable Ventricular Assist Devices (VADs) have become a treatment of choice for patients with end-stage heart failure or cardiogenic shock, significantly increasing both survival rates and the quality of life of patients. Moreover, VAD use is growing as destination therapy for patients who require permanent mechanical cardiac circulatory support. This heightens the need to ensure VAD reliability and safety, even amidst challenges in optimization of pump design for minimal blood damage. Advanced design LVADs like the HVAD (Medtronic, Inc., Minneapolis, MN) and the Heartmate 3 (HM3; Abbott Labs, Chicago, IL) are centrifugal systems that had been favorably compared to the continuous flow axial pumps, such as the HeartMate II (HMII; Abbott Labs, Chicago, IL). While the HVAD and HMII are increasingly utilized in older pediatric populations in addition to the Berlin Heart Excor (Berlin Heart GmbH, Berlin Germany), implementation of VAD support for pediatric patients still lags behind adults. Recently, the HM3 has demonstrated superior performance to the HMII with respect to pump thrombosis in clinical trials and may also find utility in pediatric applications, particularly for adolescents. In this present work, performance of HVAD and HM3 were compared using basic laboratory tests and Red Blood Cell (RBC) Mechanical Fragility (MF), an assay that provides assessment of sub-hemolytic RBC damage which can be caused by VAD operation. RBC MF was assessed using electromagnetically driven bead milling with cylindrical beads in multiple different regimes for different sample stressing configurations. Induced hemolysis in the sample was measured non-invasively at different (increasing) cumulative stress duration intervals, to obtain a MF profile for each stressing regime. In a cohort of 13 HVAD and 7 HM3 patients, blood samples were obtained before surgery and at 1 h, 24 h, 1 week and 4 weeks after surgery. No significant differences were observed between the two VAD devices in conventional hemolysis markers including free hemoglobin, bilirubin, total LDH and haptoglobin, as well as in changes patient hemoglobin. HM3 demonstrated elevated, compared to HVAD, levels of LDH-1 at 24 h (p < 0.05) and 1 week (0.05 < p < 0.1) after surgery, with LDH-1 reverting to about pre-surgery levels at 4 weeks. These differences between pumps may have been attributed to confounders such as duration of cardiopulmonary bypass at time of LVAD implant. By one metric, RBC MF was similarly elevated for HM3 at both 24 h and 1 week after surgery, and also reverted to about pre-surgery levels at 4 weeks. Such changes in RBC MF results were observed for only one of the employed stressing regimes, highlighting the potential importance of matching the applied in vitro stress parameters to the particular nature of in vivo blood damage involved. Forthcoming work is planned for further analysis and reporting on additional aspects of this study.