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

David M. Smadja; Richard Chocron; Elisa Rossi; Bastien Poitier; Yuri Pya; Mahabbat Bekbossynova; Christophe Peronino; Jeanne Rancic; Jean Christian Roussel; Michel Kindo; Nicolas Gendron; Ludovica Migliozzi; Antoine Capel; Jean Christophe Perles; Pascale Gaussem; Peter Ivak; Piet Jansen; Claude Girard; Alain Carpentier; Christian Latremouille; Coralie Guerin; Ivan Netuka

doi:10.1055/s-0040-1713751

Thrombosis and Haemostasis, Table of Contents

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

¹Inserm 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

²Inserm UMR-S 970 PARCC, Service d’urgences, Université de Paris, Georges Pompidou European Hospital, Paris, France

,

Elisa Rossi

³Innovative Therapies in Haemostasis, Université de Paris, Paris, France

,

Bastien Poitier

⁴Innovative 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

⁵National Research Cardiac Surgery Center, Astana, Kazakhstan

,

Mahabbat Bekbossynova

⁵National Research Cardiac Surgery Center, Astana, Kazakhstan

,

Christophe Peronino

¹Inserm 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

¹Inserm 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

⁶Service de Chirurgie Thoracique et Cardiovasculaire, Unité de transplantation thoracique, CHU de Nantes, Hôpital Nord Laënnec, Saint-Herblain, Nantes Cedex 1, France

,

Michel Kindo

⁷Service de Chirurgie Cardiovasculaire, NHC - Hôpital Civil, Hôpitaux Universitaires de Strasbourg, 1, Place de L'Hôpital, Strasbourg, Cedex, France

,

Nicolas Gendron

¹Inserm 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

⁴Innovative 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

⁸Carmat SAS, Velisy-Villacoublay, France

,

Jean Christophe Perles

⁸Carmat SAS, Velisy-Villacoublay, France

,

Pascale Gaussem

⁹Innovative Therapies in Haemostasis, Service d'Hématologie, Université de Paris, Georges Pompidou European Hospital, Paris, France

,

Peter Ivak

¹⁰Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

,

Piet Jansen

⁸Carmat SAS, Velisy-Villacoublay, France

,

Claude Girard

¹¹Unité d'Anesthesie Réanimation Cardio-Vasculaire, CHU François Mitterrand, Dijon Cedex, France

,

Alain Carpentier

³Innovative Therapies in Haemostasis, Université de Paris, Paris, France

,

Christian Latremouille

⁴Innovative 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

¹²Innovative Therapies in Haemostasis, Plateforme de Cytométrie, Institut Curie, Université de Paris, Paris, France

,

Ivan Netuka

¹⁰Department of Cardiovascular Surgery, Institute for Clinical and Experimental Medicine, Prague, Czech Republic

› Author Affiliations

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.

Keywords

bioprosthetic total artificial heart - biomarker - endothelial - sEPCR - sEndoglin - endothelial progenitors - ECFC

Full Text

References

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Supplementary Material

Supplementary Material