Thromb Haemost 2020; 120(09): 1313-1322
DOI: 10.1055/s-0040-1713751
Endothelium and Angiogenesis

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

David M. Smadja
1   Inserm UMR-S 1140, Innovative Therapies in Haemostasis, Service d'Hématologie et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), Université de Paris, Georges Pompidou European Hospital, Paris, France
,
Richard Chocron
2   Inserm UMR-S 970 PARCC, Service d’urgences, Université de Paris, Georges Pompidou European Hospital, Paris, France
,
3   Innovative Therapies in Haemostasis, Université de Paris, Paris, France
,
Bastien Poitier
4   Innovative Therapies in Haemostasis, Service de Chirurgie Cardiaque et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), Université de Paris, Georges Pompidou European Hospital, Paris, France
,
Yuri Pya
5   National Research Cardiac Surgery Center, Astana, Kazakhstan
,
Mahabbat Bekbossynova
5   National Research Cardiac Surgery Center, Astana, Kazakhstan
,
Christophe Peronino
1   Inserm UMR-S 1140, Innovative Therapies in Haemostasis, Service d'Hématologie et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), Université de Paris, Georges Pompidou European Hospital, Paris, France
,
Jeanne Rancic
1   Inserm UMR-S 1140, Innovative Therapies in Haemostasis, Service d'Hématologie et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), Université de Paris, Georges Pompidou European Hospital, Paris, France
,
Jean Christian Roussel
6   Service de Chirurgie Thoracique et Cardiovasculaire, Unité de transplantation thoracique, CHU de Nantes, Hôpital Nord Laënnec, Saint-Herblain, Nantes Cedex 1, France
,
Michel Kindo
7   Service de Chirurgie Cardiovasculaire, NHC - Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 1, Place de L'Hôpital, Strasbourg, Cedex, France
,
Nicolas Gendron
1   Inserm UMR-S 1140, Innovative Therapies in Haemostasis, Service d'Hématologie et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), Université de Paris, Georges Pompidou European Hospital, Paris, France
,
Ludovica Migliozzi
4   Innovative Therapies in Haemostasis, Service de Chirurgie Cardiaque et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), Université de Paris, Georges Pompidou European Hospital, Paris, France
,
Antoine Capel
8   Carmat SAS, Velisy-Villacoublay, France
,
Jean Christophe Perles
8   Carmat SAS, Velisy-Villacoublay, France
,
Pascale Gaussem
9   Innovative Therapies in Haemostasis, Service d'Hématologie, Université de Paris, Georges Pompidou European Hospital, Paris, France
,
Peter Ivak
10   Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
,
Piet Jansen
8   Carmat SAS, Velisy-Villacoublay, France
,
Claude Girard
11   Unité d'Anesthesie Réanimation Cardio-Vasculaire, CHU François Mitterrand, Dijon Cedex, France
,
Alain Carpentier
3   Innovative Therapies in Haemostasis, Université de Paris, Paris, France
,
Christian Latremouille
4   Innovative Therapies in Haemostasis, Service de Chirurgie Cardiaque et Laboratoire de Recherches Biochirugicales (Fondation Carpentier), Université de Paris, Georges Pompidou European Hospital, Paris, France
,
Coralie Guerin
12   Innovative Therapies in Haemostasis, Plateforme de Cytométrie, Institut Curie, Université de Paris, Paris, France
,
Ivan Netuka
10   Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic
› Author Affiliations
Funding This work was supported by CARMAT.

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.

Authors' Contributions

D.M.S. supervised the work, analyzed the data, and wrote the paper. R.C. analyzed the data and performed statistical analysis. E.R. and L.M. performed and analyzed ECFC in vitro assays. B.P., C.P., N.G., and J.R. performed analysis and analyzed data. C.G. performed analysis, analyzed data, and wrote the paper. Y.P., M.B., J.C.R., M.K., P.I., C.L., and I.N. included patients and reviewed the paper. C.L. and I.N. are principal investigator, respectively, of feasibility and pivotal study. C.G. and P.G. analyzed the data and reviewed the paper. A.C., J.C.P., and P.J. organized clinical trials. A.C. is inventor of C-TAH and reviewed the paper.


Supplementary Material



Publication History

Received: 02 January 2020

Accepted: 18 May 2020

Article published online:
20 July 2020

© 2020. Thieme. All rights reserved.

Georg Thieme Verlag KG
Stuttgart · New York

 
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