The therapeutic use of ventricular assist devices (VADs) for end-stage heart failure (HF) patients who are ineligible for transplant has increased steadily in the last decade. In parallel, improvements in VAD design have reduced device size, cost, and device-related complications. These complications include infection and thrombosis which share underpinning contribution from the inflammatory response and remain common risks from VAD implantation. An added and underappreciated difficulty in designing a VAD that supports heart function and aids the repair of damaged myocardium is that different types of HF are accompanied by different inflammatory profiles that can affect the response to the implanted device. Circulating inflammatory markers and changes in leukocyte phenotypes receive much attention as biomarkers for mortality and disease progression. However, they are seldom used to monitor progress during and outcomes from VAD therapy or during the design phase for new devices. Even the partial reversal of heart damage associated with heart failure is a desirable outcome from VAD use. Therefore, improved understanding of the interplay between VADs and the recipient's inflammatory response would potentially increase their uptake, improve patient lives, and fuel research related to other blood-contacting medical devices. Here we provide a review of what is currently known about inflammation in heart failure and how this inflammatory profile is altered in heart failure patients receiving VAD therapy.

Ventricular assist devices (VADs) are a life-saving form of mechanical circulatory support in heart failure patients. However, VADs have not yet reached their full potential due to the associated side effects (thrombosis, bleeding, infection) related to the activation and damage of blood cells and proteins caused by mechanical stress and foreign materials. Studies of the effects of VADs on leukocytes are limited, yet leukocyte activation and damage including microparticle generation can influence both thrombosis and infection rates. Therefore, the aim was to develop a multicolor flow cytometry assessment of leukocyte microparticles (LMPs) using ovine blood and the CentriMag VAD as a model for shear stress. Ovine blood was pumped for 6 h in the CentriMag and regular samples analyzed for hemolysis, complete blood counts and LMP by flow cytometry during three different pump operating conditions (low flow, standard, high speed). The high speed condition caused significant increases in plasma-free hemoglobin; decreases in total leukocytes, granulocytes, monocytes, and platelets; increases in CD45 LMPs as well as two novel LMP populations: CD11b /HLA-DR and CD11b /HLA-DR , both of which were CD14 /CD21 . CD11b /HLA-DR LMPs appeared to respond to an increase in shear magnitude whereas the CD11b /HLA-DR LMPs significantly increased in all pumping conditions. We propose that these two populations are released from granulocytes and T cells, respectively, but further research is needed to better characterize these two populations.

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Background: Left ventricular assist devices (LVADs) offer live-saving therapy to transplant-ineligible heart failure patients. A major limitation of the technology includes pump thrombosis, bleeding, and recurrent infection that prove difficult to predict from in vivo animal testing. Shear stress introduced by the LVAD affects more than just haemolysis since platelets, leukocytes, and plasma proteins all contribute to the propensity for complications. It is important to assess overall damage by a new device against a base line as early as possible in the development process so that design iterations can be made if required. Methods: Explanted VADs currently in clinical use (HeartMate 2 and HVAD) were carefully cleaned, inspected, and run at 5 L/min and pressure at 100 mmHg in a standard 500 mL mock circulatory loop using bovine blood. The CentriMag was used as a control pump due to its low blood damage profile. Samples were collected at regular intervals and the following analysed: complete cell counts; haemolysis; platelet activation; leukocyte-derived microparticles (LMPs); and von Willebrand factor (vWF) degradation. Results: The HeartMate 2 had the highest levels of haemolysis and platelet activation after 6 hours compared to the HVAD and CentriMag. A decreased granulocyte count, high numbers of LMPs and CD11b Bright HLADR-LMPs, and decreased vWF collagen binding activity was most evident in the HVAD. Conclusions: The results indicate that it is possible to observe differences between different pump designs during in vitro testing that might translate to clinical performance. This study demonstrates the importance of developing standard in vitro total blood damage methods against which device developers could use to modify design to reduce complication risk long before implantation.