Endothelial Dysfunction During Continuous Flow Left Ventricular Assist Device Support: Effects on the Number and Function of Endothelial Progenitor Cells

Background: Contemporary continuous flow left ventricular assist devices (Cf-LVADs) support non-pulsatile physiology. This was associated with impaired endothelial function and the common occurrence of vascular complications. The mechanism of endothelial dysfunction in patients on LVAD support has not been determined.

Methods: In this prospective observational study patients in stage D heart failure (HF) were evaluated before and at 1 and 3 months after Cf-LVAD implantation. We measured reactive hyperemia index (RHI) for endothelial function using peripheral arterial tonometry (Itamar Medical Ltd., Caesarea, Israel). Circulating endothelial progenitor cells (EPC) were identified using flow cytometry and represented as the proportion of mononuclear cells expressing VEGFR-2/CD133, or VEGFR-2/CD34. Functional aspects of EPCs were evaluated after 7 days of culture by identification of colony forming units and the MTT assay for viability of cells.

Results: Twenty-one patients supported on the device for more than 3 months were included. Patients were 62±7 years old, 18(86%) males and 14(67%) had ischemic etiology. Twelve (57%) were implanted with HeartMate II (Thoratec) and 9 (43%) received an HVAD (Heartware) LVAD. RHI and EPC results are shown in the table. At 3 months early EPCs (VEGFR-2/CD133) and MTT significantly increased. RHI at 3 months strongly correlated with EPCs at 1 month (spearman’s -0.8, p≤0.001for both). Pre and post LVAD EPCs did not form colonies in culture.

Conclusion: While pre-operative endothelial dysfunction persists after surgery, EPCs increase in number but remain dysfunctional, suggesting possible damage caused by the Cf-LVAD circulation. Newer LVADs with maintained pulsatility may be more protective of endothelial physiology.