Author + information
- David M. Smadja, PharmD, PhD∗ (, )
- Bruno Saubaméa, PhD,
- Sophie Susen, MD, PhD,
- Michel Kindo, MD, PhD,
- Patrick Bruneval, MD, PhD,
- Eric Van Belle, MD, PhD,
- Piet Jansen, MD,
- Jean-Christian Roussel, MD, PhD,
- Christian Latrémouille, MD and
- Alain Carpentier, MD, PhD
- ↵∗European Hospital Georges Pompidou, Hematology Department, 20 rue Leblanc, 75015 Paris, France
The Carmat total artificial heart (C-TAH) (Vélizy-Villacoublay, France) is an implantable electro-hydraulically actuated biventricular pump that has been developed to minimize mechanical assist device-related morbidities (1). Its blood-contacting surfaces consist of expanded polytetrafluoroethylene and bovine pericardial tissue processed in glutaraldehyde as used in cardiac bioprosthetic valves.
In the 3 first implanted patients, we investigated biological parameters of hemocompatibility (hemolysis and appearance of acquired von Willebrand syndrome) and histological characteristics of explanted devices. The 3 patients were 76, 68, and 74 years of age with severe end-stage biventricular heart failure. Patient 1 made a rapid recovery after implantation but remained in intensive care because of respiratory and renal dysfunction. Patient 2 was successfully rehabilitated and could be discharged from the hospital after 5 months. Both patients experienced a device failure and died after 74 and 270 days, respectively. Patient 3 was discharged home at 5 months. Repeated rehospitalizations for asthenia, cachexia, and renal insufficiency led to the patient’s death at 254 days.
Hemolysis, measured by plasma-free hemoglobin level, was below the clinically relevant threshold of 400 mg/l in all patients during the entire follow-up (data not shown). The levels of high-molecular-weight multimers of von Willebrand factor were measured perioperatively and during follow-up in the 3 patients. No significant time-dependent loss was observed after initiating the support (Figure 1A), with the average drop in high-molecular-weight multimer ratio (relative to baseline) reaching 0.97 ± 0.34, 0.88 ± 0.15, and 0.98 ± 0.01 at 5, 30, 60, and 180 min for all patients (repeated analysis of variance, p > 0.05). Long-term follow-up of the 3 patients did not reveal any loss in HMWMs, with a ratio relative to baseline of 1.44 ± 0.17, 1.14 ± 0.17, and 1.01 ± 0.15 in the first, second, and third trimester of follow-up, respectively (repeated analysis of variance, p > 0.05). Most left ventricular assist devices have been shown to be associated with blood trauma, hemolysis, and nonsurgical bleeding events resulting from acquired von Willebrand syndrome (2). The absence of this syndrome in C-TAH-implanted patients is testament to the improved blood-handling characteristics of this device.
Explant analysis of all C-TAH and autopsy examinations revealed no evidence of thrombotic deposits anywhere. Macroscopic examination of the explanted devices showed all the blood-contacting surfaces to be free from thrombus. Electron microscopy showed a homogeneous adherent fibrin cellular network incorporating inflammatory cells and platelets on all of the membrane blood-contacting surfaces. This fibrin network was compacted in some areas. An endothelial cell deposition with pseudotube formation on this fibrin cap was observed in patients 1 and 3, and there was a genuine endothelial covering of the cap in patient 2 (Figure 1B, left panel). This endothelial covering was most evident in the right ventricle and covered more than 30% of the membrane area. All of the membranes demonstrated cells of an endothelial phenotype, confirmed by immunohistochemical positive labeling for vascular endothelial cadherin (data not shown) and the presence of tight junctional structures, observed by electron microscopy (Figure 1B, right panel). The endothelialization of textured biomaterials surfaces has previously been published for bioprosthetic valves. The source of endothelial cells in the C-TAH would seem to come from the circulating blood because there is no physical connection to patient blood vessels. Vasculogenic cell deposition on fibrin adsorbed on xeno-pericardial tissue could be linked to circulating endothelial progenitor cells or very small embryonic-like cells (3).
This initial experience suggests that the use of the C-TAH has the potential to provide a significant advance in mechanical heart replacement therapy. Thus, physiological blood dynamics mimicking human circulatory characteristics and progressive endothelialization of C-TAH results in an acquired hemocompatibility with no thrombotic events in these 3 first implanted patients.
Please note: Funding for the study was provided by CARMAT SA and foundation Alain Carpentier. Dr. Smadja's research is supported by CARMAT and Coeny-Maeva charitable foundation. The study was approved by the French competent Authorities, the Ethics committee (Paris 3), all patients have signed informed consent forms, and the study was performed in accordance with the Declaration of Helsinki. Dr. Carpentier is a cofounder and shareholder of CARMAT SA. Drs. Smadja and Latrémouille have received consulting fees from CARMAT. Dr. Jansen is employed by CARMAT SA. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose. The authors thank the nursing staff of the cardiovascular intensive care unit and surgery departments involved in patient follow-up, and Yann Burnel, Nadège Ochat, Aurélie Dumont, and Clémentine Lavenue from the Hematology Department of Georges Pompidou Hospital for their technical help. These are results from a feasibility study registered in France as no. 2001-A00972-39.
- 2017 American College of Cardiology Foundation