Bioprosthetic Total Artificial Heart, Hemolysis, and Acquired von Willebrand Syndrome

A study was conducted to determine the rate of hemolysis potential acquired van Willebrand syndrome in patients who have received a total artificial heart implantation.

The Carmat bioprosthetic total artificial heart (Aeson; A-TAH) does not cause hemolysis or acquired von Willebrand syndrome and the relationship between cardiac output depending flow and high molecular-weight multimers (HMWM) confirms the relevance of the von Willebrand factor as a biological sensor of blood flow in all ranges. These findings were published in Arteriosclerosis, Thrombosis, and Vascular Biology.

Hemolysis and acquired von Willebrand syndrome (AVWS) are the primary trigger of thrombotic and bleeding complications in patients with end-stage heart failure who seek alternative therapy to heart transplantation, including left ventricular devices (LVAD) and total artificial hearts. The A-TAH is an autoregulated pulsatile device that mimics cardiac physiology. It was designed for patients with biventricular end-stage heart failure and its bioprosthetic surfaces exhibit a high degree of hemocompatibility.

Researchers sought to evaluate the level of hemolysis potential AVWS after A-TAH implantation. To accomplish this, they conducted a study trial (ClinicalTrials.gov identifier: NCT02962973) that included the first 10 patients implanted with A-TAH (100% men, aged 59.6±10.2 years). Twenty-seven adult patients who were implanted with the Heartmate II or Heartmate III LVADs between January 2014 and December 2020 in the Georges Pompidou European Hospital, Paris, France, were enrolled as controls.

Patients in the test cohort were examined for the presence of hemolysis and AVWS throughout the clinical follow-up, and compared with patients in the control cohort. A fluid structure interaction model and computational fluid dynamics simulation were performed to evaluate the resulting shear stress and distribution in the blood volume.

The follow-up (cumulative duration of support) was 2087 days. Over that time, the A-TAH did not affect plasma free hemoglobin, and no association existed between plasma free hemoglobin and cardiac output or beat rate. The A-TAH did not modify multimers profile of the von Willebrand factor in contrast to the control patients’ implants. Computational fluid dynamics coupled with fluid structure interaction showed a gradual increase of blood damage according to increase of cardiac output (P <.01). The blood volume fraction that endured significant shear stresses remained inferior to 0.03% of the volume for both ventricles. An inverse association was discovered between cardiac output, beat rate, and HMWM.

Limitations to the study that were noted were the low number of patients in the study cohort, the patients implanted with HeartMate II and HeartMate III were in significantly worse clinical condition than patients in the study cohort, and the choice of multimers restricted detection of results.

The researchers believe they demonstrated that the A-TAH does not cause hemolysis or AWVS, thus reducing risk for clinically relevant hemocompatibility-related adverse events. “Moreover, we confirm that [von Willebrand factor] is a good biological sensor of blood flow and pulsatility in cardiac assistance,” the study authors wrote. “Influence of shear stress and pulsatile flow on vascular function but also [von Willebrand factor] involvement in hemocompatibility-related side effect need further exploration to make in the future the most relevant mechanical circulatory support to improve outcomes of patients.”

Disclosure: Some study authors declared affiliations with biotech, pharmaceutical, and/or device companies. Please see the original reference for a full list of authors’ disclosures.

Reference

Poitier B, Chocron R, Peronino C, et al. Bioprosthetic total artificial heart in autoregulated mode is biologically hemocompatible: Insights for multimers of von Willebrand factor. Arterioscler Thromb Vasc Biol. Published online February 10, 2022. doi:10.1161/ATVBAHA.121.316833