Download Endothelial dysfunction during continuous flow left ventricular assist

Endothelial dysfunction during continuous flow left ventricular assist device support:
effects on the number and function of endothelial progenitor cells
Tal Hasin, Eli Lev, Dorit Leshem-Lev, Daniel Murninkas, Benjamin Ben-Avraham,
Miriam Abuhazira, Dmitry Golubov, Victor Rubchevsky, Dan Aravot, Ran
Kornowski, Tuvia Ben-Gal
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
Inthisprospectiveobservationalstudypatients in stage D heart failure (HF) were
evaluated before and at 1 and 3 months after Cf-LVAD implantation.Wemeasured
reactivehyperemiaindex(RHI)forendothelialfunctionusingperipheralarterial
tonometry(ItamarMedicalLtd.,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%) wereimplantedwithHeartMateII(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 CfLVAD circulation. Newer LVADs with maintained pulsatility may be more protective
of endothelial physiology.
Variable
Pre-LVAD
1mo after LVAD 3mo after LVAD
RHI
1.46±0.41
1.38±0.25(n=13) 1.41±0.31(n=18)
VEGFR-2/CD133%
3(1;7)
2(1;9) (n=17)
7(2;17) (n=18)*
VEGFR-2/CD34%
3(1;4)
4(2;9) (n=17)
4(2;11) (n=18)
MTT 570nm
0.4±0.3 (n=20)
0.4±0.3 (n=17)
0.6±0.4 (n=17)§
mean±SD or median (IQR). *p=0.04;§p=0.01 versus pre-LVAD using Wilcoxon
signed rank test.