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. 2020 Sep;120(9):1313-1322.
doi: 10.1055/s-0040-1713751. Epub 2020 Jul 20.

Autoregulation of Pulsatile Bioprosthetic Total Artificial Heart is Involved in Endothelial Homeostasis Preservation

David M Smadja  1 , Richard Chocron  2 , Elisa Rossi  3 , Bastien Poitier  4 , Yuri Pya  5 , Mahabbat Bekbossynova  5 , Christophe Peronino  1 , Jeanne Rancic  1 , Jean Christian Roussel  6 , Michel Kindo  7 , Nicolas Gendron  1 , Ludovica Migliozzi  4 , Antoine Capel  8 , Jean Christophe Perles  8 , Pascale Gaussem  9 , Peter Ivak  10 , Piet Jansen  8 , Claude Girard  11 , Alain Carpentier  3 , Christian Latremouille  4 , Coralie Guerin  12 , Ivan Netuka  10
Affiliations

Autoregulation of Pulsatile Bioprosthetic Total Artificial Heart is Involved in Endothelial Homeostasis Preservation

David M Smadja et al. Thromb Haemost. 2020 Sep.

Abstract

Pulsatile Carmat bioprosthetic total artificial heart (C-TAH) is designed to be implanted in patients with biventricular end-stage heart failure. Since flow variation might contribute to endothelial dysfunction, we explored circulating endothelial biomarkers after C-TAH implantation in seven patients and compared the manual and autoregulated mode. Markers of endothelial dysfunction and regeneration were compared before and during a 6- to 9-month follow-up after implantation. The follow-up was divided into three periods (< 3, 3-6, and > 6 months) and used to estimate the temporal trends during the study period. A linear mixed model was used to analyze repeated measures and association between tested parameters according to the mode of C-TAH and the time. Relevance of soluble endoglin (sEndoglin) level increase has been tested on differentiation and migration potential of human vasculogenic progenitor cells (endothelial colony forming cells [ECFCs]). Normal sEndoglin and soluble endothelial protein C receptor (sEPCR) levels were found in patients after implantation with autoregulated C-TAH, whereas they significantly increased in the manual mode, as compared with pretransplant values (p = 0.005 and 0.001, respectively). In the autoregulated mode, a significant increase in the mobilization of cytokine stromal cell-derived factor 1 was found (p = 0.03). After adjustment on the mode of C-TAH, creatinine or C-reactive protein level, sEndoglin, and sEPCR, were found significantly associated with plasma total protein levels. Moreover, a significant decrease in pseudotubes formation and migration ability was observed in vitro in ECFCs receiving sEndoglin activation. Our combined analysis of endothelial biomarkers confirms the favorable impact of blood flow variation achieved with autoregulation in patients implanted with the bioprosthetic total artificial heart.

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Conflict of interest statement

D.M.S. received consulting fees from CARMAT and received institutional research support related to the CE Mark Study conduct. R.C. has nothing to declare. E.R. has nothing to declare. B.P. has received a research grant from CARMAT. Y.P. received consulting fees from CARMAT. M.B. has nothing to declare. C.P. has nothing to declare. J.R. has nothing to declare. J.C.R. has nothing to declare. M.K. has nothing to declare. N.G. has nothing to declare. L.M. has nothing to declare. A.C., J.C.P., and P.J. are employed by CARMAT. P.G. has nothing to declare. P.I. received consulting fees from CARMAT and received institutional research support related to the CE Mark Study conduct. C.G. received consulting fees from CARMAT. A.C. is cofounder and shareholder of CARMAT. C.L. received consulting fees from CARMAT. C.G. has nothing to declare. I.N. received institutional research support related to the CE Mark Study conduct.