Bioprosthetic Total Artificial Heart in Autoregulated Mode Is Biologically Hemocompatible: Insights for Multimers of von Willebrand Factor.

BACKGROUND: Carmat bioprosthetic total artificial heart (Aeson; A-TAH) is a pulsatile and autoregulated device. The aim of this study is to evaluate level of hemolysis potential acquired von Willebrand syndrome after A-TAH implantation. METHODS: We examined the presence of hemolysis and acquired von Willebrand syndrome in adult patients receiving A-TAH support (n=10) during their whole clinical follow-up in comparison with control subjects and adult patients receiving Heartmate II or Heartmate III support. We also performed a fluid structure interaction model coupled with computational fluid dynamics simulation to evaluate the A-TAH resulting shear stress and its distribution in the blood volume. RESULTS: The cumulative duration of A-TAH support was 2087 days. A-TAH implantation did not affect plasma free hemoglobin over time, and there was no association between plasma free hemoglobin and cardiac output or beat rate. For VWF (von Willebrand factor) evaluation, A-TAH implantation did not modify multimers profile of VWF in contrast to Heartmate II and Heartmate III. Furthermore, fluid structure interaction coupled with computational fluid dynamics showed a gradually increase of blood damage according to increase of cardiac output (P<0.01), however, the blood volume fraction that endured significant shear stresses was always inferior to 0.03% of the volume for both ventricles in all regimens tested. An inverse association between cardiac output, beat rate, and high-molecular weight multimers ratio was found. CONCLUSIONS: We demonstrated that A-TAH does not cause hemolysis or AWVS. However, relationship between HMWM and cardiac output depending flow confirms relevance of VWF as a biological sensor of blood flow, even in normal range.

Enhanced water and oxygen barrier performance of flexible polyurethane membranes for biomedical application.

In order to improve water and oxygen barrier properties, the surface of two commercial medical grade polyurethane (PU) membranes (Chronoflex® AR-LT and Bionate® II) was modified by a spray deposited film of poly(ethylene-co-vinyl alcohol) (EVOH). The influence of the temperature, the deposited layer thickness and the EVOH ethylene group percentage (27%, 32%, and 44% for EVOH27, EVOH32, and EVOH44, respectively) on the barrier properties of the PU/EVOH multilayered membranes was investigated. The increase of the EVOH layer thickness leads to higher oxygen barrier properties (the highest barrier improvement factor of 412 was obtained). However, in case of the deposited layer thickness higher than 18 µm, microcracks appeared on the treated surface promote a significant loss of the barrier effect. Due to its higher crystallinity degree, EVOH27 provides a higher oxygen barrier effect compared to EVOH32 and EVOH44. On the contrary, an increase of the water barrier properties was observed with the increase of the percentage of ethylene groups. Moreover, the delamination of the EVOH layer was noted after water permeation, especially in case of EVOH44, which is the most hydrophobic layer. Nevertheless, significant decrease of the water and oxygen permeability of the modified PU membranes was achieved, thus showing the benefit of using the EVOH spray deposition for the biomedical application, which requires high performance material with flexible and barrier properties.

Hemocompatibility and safety of the Carmat Total Artifical Heart hybrid membrane.

The Carmat bioprosthetic total artificial heart (C-TAH) is a biventricular pump developed to minimize drawbacks of current mechanical assist devices and improve quality of life during support. This study aims to evaluate the safety of the hybrid membrane, which plays a pivotal role in this artificial heart. We investigated in particular its blood-contacting surface layer of bovine pericardial tissue, in terms of mechanical aging, risks of calcification, and impact of the hemodynamics shear stress inside the ventricles on blood components. Hybrid membranes were aged in a custom-designed endurance bench. Mechanical, physical and chemical properties were not significantly modified from 9 months up to 4 years of aging using a simulating process. Exploration of erosion areas did not show no risk of oil diffusion through the membrane. Blood contacting materials in the ventricular cavities were subcutaneously implanted in Wistar rats for 30 days as a model for calcification and demonstrated that the in-house anti-calcification pretreatment with Formaldehyde-Ethanol-Tween 80 was able to significantly reduce the calcium concentration from 132 µg/mg to 4.42 µg/mg (p < 0.001). Hemodynamic simulations with a computational model were used to reproduce shear stress in left and right ventricles and no significant stress was able to trigger hemolysis, platelet activation nor degradation of the von Willebrand factor multimers. Moreover, explanted hybrid membranes from patients included in the feasibility clinical study were analyzed confirming preclinical results with the absence of significant membrane calcification. At last, blood plasma bank analysis from the four patients implanted with C-TAH during the feasibility study showed no residual glutaraldehyde increase in plasma and confirmed hemodynamic simulation-based results with the absence of hemolysis and platelet activation associated with normal levels of plasma free hemoglobin and platelet microparticles after C-TAH implantation. These results on mechanical aging, calcification model and hemodynamic simulations predicted the safety of the hybrid membrane used in the C-TAH, and were confirmed in the feasibility study.

Numerical Approach to Study the Behavior of an Artificial Ventricle: Fluid-Structure Interaction Followed By Fluid Dynamics With Moving Boundaries.

Heart failure is a progressive and often fatal pathology among the main causes of death in the world. An implantable total artificial heart (TAH) is an alternative to heart transplantation. Blood damage quantification is imperative to assess the behavior of an artificial ventricle and is strictly related to the hemodynamics, which can be investigated through numerical simulations. The aim of this study is to develop a computational model that can accurately reproduce the hemodynamics inside the left pumping chamber of an existing TAH (Carmat-TAH) together with the displacement of the leaflets of the biological aortic and mitral valves and the displacement of the pericardium-made membrane. The proposed modeling workflow combines fluid-structure interaction (FSI) simulations based on a fixed grid method with computational fluid dynamics (CFD). In particular, the kinematics of the valves is accounted for by means of a dynamic mesh technique in the CFD. The comparison between FSI- and CFD-calculated velocity fields confirmed that the presence of the valves in the CFD model is essential for realistically mimicking blood dynamics, with a percentage difference of 2% during systole phase and 13% during the diastole. The percentage of blood volume in the CFD simulation with a shear stress above the threshold of 50 Pa is less than 0.001%. In conclusion, the application of this workflow to the Carmat-TAH provided consistent results with previous clinical studies demonstrating its utility in calculating local hemodynamic quantities in the presence of complex moving boundaries.

First clinical use of a bioprosthetic total artificial heart: report of two cases.

BACKGROUND: The development of artificial hearts in patients with end-stage heart disease have been confronted with the major issues of thromboembolism or haemorrhage. Since valvular bioprostheses are associated with a low incidence of these complications, we decided to use bioprosthetic materials in the construction of a novel artificial heart (C-TAH). We report here the device characteristics and its first clinical applications in two patients with end-stage dilated cardiomyopathy. The aim of the study was to evaluate safety and feasibility of the CARMAT TAH for patients at imminent risk of death from biventricular heart failure and not eligible for transplant. METHODS: The C-TAH is an implantable electro-hydraulically actuated pulsatile biventricular pump. All components, batteries excepted, are embodied in a single device positioned in the pericardial sac after excision of the native ventricles. We selected patients admitted to hospital who were at imminent risk of death, having irreversible biventricular failure, and not eligible for heart transplantation, from three cardiac surgery centres in France. FINDINGS: The C-TAH was implanted in two male patients. Patient 1, aged 76 years, had the C-TAH implantation on Dec 18, 2013; patient 2, aged 68 years, had the implantation on Aug 5, 2014. The cardiopulmonary bypass times for C-TAH implantation were 170 min for patient 1 and 157 min for patient 2. Both patients were extubated within the first 12 postoperative hours and had a rapid recovery of their respiratory and circulatory functions as well as a normal mental status. Patient 1 presented with a tamponade on day 23 requiring re-intervention. Postoperative bleeding disorders prompted anticoagulant discontinuation. The C-TAH functioned well with a cardiac output of 4·8-5·8 L/min. On day 74, the patient died due to a device failure. Autopsy did not detect any relevant thrombus formation within the bioprosthesis nor the different organs, despite a 50-day anticoagulant-free period. Patient 2 experienced a transient period of renal failure and a pericardial effusion requiring drainage, but otherwise uneventful postoperative course. He was discharged from the hospital on day 150 after surgery with a wearable system without technical assistance. After 4 months at home, the patient suffered low cardiac output. A change of C-TAH was attempted but the patient died of multiorgan failure. INTERPRETATION: This preliminary experience could represent an important contribution to the development of total artificial hearts using bioprosthetic materials. FUNDING: CARMAT SA.