Design of a Pulsatile Flow Facility to Evaluate Thrombogenic Potential of Implantable Cardiac Devices

Abstract

Due to expensive nature of clinical trials, implantable cardiac devices should first be extensively characterized in vitro. Prosthetic heart valves (PHVs), an important class of these devices, have been shown to be associated with thromboembolic complications. Although various in vitro systems have been designed to quantify blood-cell damage and platelet activation caused by nonphysiological hemodynamic shear stresses in these PHVs, very few systems attempt to characterize both blood damage and fluid dynamics aspects of PHVs in the same test system. Various numerical modeling methodologies are also evolving to simulate the structural mechanics, fluid mechanics, and blood damage aspects of these devices. This article presents a completely hemocompatible small-volume test-platform that can be used for thrombogenicity studies and experimental fluid mechanics characterization. Using a programmable piston pump to drive freshly drawn human blood inside a cylindrical column, the presented system can simulate various physiological and pathophysiological conditions in testing PHVs. The system includes a modular device-mounting chamber, and in this presented case, a 23 mm St. Jude Medical (SJM) Regents® mechanical heart valve (MHV) in aortic position was used as the test device. The system was validated for its capability to quantify blood damage by measuring blood damage induced by the tester itself (using freshly drawn whole human blood). Blood damage levels were ascertained through clinically relevant assays on human blood while fluid dynamics were characterized using time-resolved particle image velocimetry (PIV) using a blood-mimicking fluid. Blood damage induced by the tester itself, assessed through Thrombin-anti-Thrombin (TAT), Prothrombin factor 1.2 (PF1.2), and hemolysis (Drabkins assay), was within clinically accepted levels. The hydrodynamic performance of the tester showed consistent, repeatable physiological pressure and flow conditions. In addition, the system contains proximity sensors to accurately capture leaflet motion during the entire cardiac cycle. The PIV results showed skewing of the leakage jet, caused by the asymmetric closing of the two leaflets. All these results are critical to characterizing the blood damage and fluid dynamics characteristics of the SJM Regents® MHV, proving the utility of this tester as a precise system for assessing the hemodynamics and thrombogenicity for various PHVs.

Three-dimensional extent of flow stagnation in transcatheter heart valves

“…Hence, significant effort has been directed towards understanding, minimizing and avoiding thrombosis in the cardiovascular system and on implantable devices. Studies have progressed from extensive in vivo [16,18] and in vitro [19,20] studies to modern multi-scale numerical simulations [21,22]. Additionally, substantial focus is on identifying and defining metrics that characterize flow-mediated thrombogenic potential in the cardiovascular system.…”

Integrated strategy for in vitro characterization of a bileaflet mechanical aortic valve

“…As for valve dynamics, attention has been most devoted to study the behavior in time of the valve area for both biological and mechanical prosthesis [ 17 – 20 ], while the leaflets motion of bileaflet mechanical heart valve (BMHV) has been somehow less investigated despite the importance of the issue [ 10 , 21 – 23 ]. Several numerical studies focused on the occluders dynamics using fluid–structure interactions approach [ 22 , 24 – 27 ]. Flow patterns and shear stress distribution in correspondence of the valve have been extensively investigated both numerically [ 6 , 24 , 28 , 29 ] and in vitro [ 20 , 30 – 34 ].…”

Hydrodynamic Noise of Pulsating Jets through Bileaflet Mechanical Mitral Valve

“…Therefore, the fine structure of blood flow through the mechanical heart valves is investigated in the laboratory with the help of miniature sensors and complexes for detecting the movement of labelled particles with an increased spatial and temporal resolution [18,19]. Several complex experimental setups that were used for hemodynamic and hydrodynamic studies have been described in the literature [20][21][22].…”