Torsten Linde

In vitro comparison of dabigatran, unfractionated heparin, and low-molecular-weight heparin in preventing thrombus formation on mechanical heart valves

INTRODUCTION Lifelong oral anticoagulation (OAC) therapy is required for the prevention of thromboembolic events after implantation of an artificial heart valve. Thromboembolism and anticoagulant-related bleedings account for approximately 75% of all complications experienced by heart valve recipients (2-9% of patients per year). The present study investigated the efficacy of dabigatran, a new direct thrombin inhibitor for oral use, as compared to unfractionated heparin (UFH) and low-molecular-weight heparin (LMWH) in preventing thrombus formation on mechanical heart valves in vitro. MATERIAL AND METHODS Blood (230 ml) from healthy young male volunteers was anticoagulated either by dabigatran (1 micromol/l), UFH (150 IU), or LMWH (100 IU). Mechanical heart valve prostheses were placed in an in vitro thrombosis tester and exposed to the anticoagulated blood samples under continuous circulation at a rate of 75 beats per minute. RESULTS In whole blood with no anticoagulant, the apparatus completely clotted in 15-20 minutes. When blood was treated with dabigatran, the mean thrombus weight was 164+/-55 mg, in the UFH group 159+/-69 mg, and in the LMWH group 182+/-82 mg (p-value: 0.704). Electron microscopy showed no significant difference in thrombus formation in any group. CONCLUSIONS Dabigatran was as effective as UFH and LMWH in preventing thrombus formation on mechanical heart valves in our in vitro investigation. Thus, we hypothesize that dabigatran etexilate might potentially be a useful and competitive orally administered alternative to UFH and LMWH for recipients of alloplastic heart valve prostheses.

The Impact of Aortic/Subclavian Outflow Cannulation for Cardiopulmonary Bypass and Cardiac Support: A Computational Fluid Dynamics Study

Approximately 100 000 cases of oxygen deficiency in the brain occur during cardiopulmonary bypass (CPB) procedures each year. In particular, perfusion of the carotid and vertebral arteries is affected. The position of the outflow cannula influences the blood flow to the cardiovascular system and thus end organ perfusion. Traditionally, the cannula returns blood into the ascending aorta. But some surgeons prefer cannulation to the right subclavian artery. A computational fluid dynamics study was initially undertaken for both approaches. The vessel model was created from real computed tomography/magnetic resonance imaging data of young healthy patients. The simulations were run with usual CPB conditions. The flow distribution for different cannula positions in the aorta was studied, as well as the impact of the cannula tip distance to vertebral artery for the subclavian position. The study presents a fast method of analyzing the flow distribution in the cardiovascular system, and can be adapted for other applications such as ventricular assist device support. It revealed that two effects cause the loss of perfusion seen clinically: a vortex under the brachiocephalic trunk and low pressure regions near the cannula jet. The results suggest that cannulation to the subclavian artery is preferred if the cannula tip is sufficiently far away from the branch of the vertebral artery. For the aortic positions, however, the cannula should be injected from the left body side.

Argatroban and bivalirudin compared to unfractionated heparin in preventing thrombus formation on mechanical heart valves: Results of an in-vitro study

Prevention of valve thrombosis in patients after prosthetic mechanical heart valve replacement and heparin-induced thrombocytopenia (HIT) is still an open issue. The aim of the present in-vitro study was to investigate the efficacy of argatroban and bivalirudin in comparison to unfractionated heparin (UFH) in preventing thrombus formation on mechanical heart valves. Blood (230 ml) from healthy young male volunteers was anticoagulated either by UFH, argatroban bolus, argatroban bolus plus continuous infusion, bivalirudin bolus, or bivalirudin bolus plus continuous infusion. Valve prostheses were placed in a newly developed in-vitro thrombosis tester and exposed to the anticoagulated blood samples. To quantify the thrombi, electron microscopy was performed, and each valve was weighed before and after the experiment. Mean thrombus weight in group 1 (UFH) was 117 + 93 mg, in group 2 (argatroban bolus) 722 + 428 mg, in group 3 (bivalirudin bolus) 758 + 323 mg, in group 4 (argatroban bolus plus continuous infusion) 162 + 98 mg, and in group 5 (bivalirudin bolus plus continuous infusion) 166 + 141 mg (p-value <0.001). Electron microscopy showed increased rates of thrombus formation in groups 2 and 3. Argatroban and bivalirudin were as effective as UFH in preventing thrombus formation on valve prostheses in our in-vitro investigation when they were administered continuously. We hypothesise that continuous infusion of argatroban or bivalirudin are optimal treatment options for patients with HIT after mechanical heart valve replacement for adapting oral to parenteral anticoagulation or vice versa.

Numerical washout study of a pulsatile total artificial heart

Purpose For blood pumps with long term indication, blood stagnation can result in excessive thromboembolic risks for patients. This study numerically investigates the washout performance of the left pump chamber of a pulsatile total artificial heart (TAH) as well as the sensitivity of the rotational orientation of the inlet bileaflet mechanical heart valve (MHV) on blood stagnation. Methods To quantitatively evaluate the washout efficiency, a fluid-structure interaction (FSI) simulation of the artificial heart pumping process was combined with a blood washout model. Four geometries with different orientations (0°, 45°, 90° and 135°) of the inlet valve were compared with respect to washout performance. Results The calculated flow field showed a high level of agreement with particle image velocimetry (PIV) measurements. Almost complete washout was achievable after three ejection phases. Remains of old blood in relation to the chamber volume was below 0.6% for all configurations and were mainly detected opposite to the inlet and outlet port at the square edge where the membrane and the pump chamber are connected. Only a small variation in the washout efficiency and the general flow field was observed. An orientation of 0° showed minor advantages with respect to blood stagnation and recirculation. Conclusions Bileaflet MHVs were demonstrated to be only slightly sensitive to rotation regarding the washout performance of the TAH. The proposed numerical washout model proved to be an adequate tool to quantitatively compare different configurations and designs of the artificial organ regarding the potential for blood stagnation where experimental measurements are limited.

Transient, three-dimensional flow field simulation through a mechanical, trileaflet heart valve prosthesis.

Thromboembolic complications are one of the major challenges faced by designers and researchers in development of artificial organs with blood-contacting devices such as heart valve prostheses, especially mechanical valves. Besides increasing the thrombogenic potential, these valves change the hydrodynamic performance of the heart. In this study, the flow through a trileaflet, mechanical heart valve prosthesis was modeled with transient computational fluid dynamics to analyze flow patterns causing thrombus formations on valves. The valve was simulated under conditions of a test rig (THIA II), which was specially designed to analyze different valves with respect to thrombosis. The main goal of this study was to mimic the exact conditions of the test rig to be able to compare numerical and experimental results. The boundary conditions were obtained from experimental data as leaflet kinematics and pressure profiles. One complete cycle of the valve was simulated. Numerical flow and pressure results were analyzed and compared with experimental results. Shear stress and shear rates were determined with respect to thrombogenic potential, especially in the pivot regions, which seem to be the main influence for activation and deposition of thrombocytes. Approximately 0.7% of the blood volume moving through the fluid domain of the valve was exposed to shear rates high enough to cause platelet activation. However, shear rates of up to 20,000 s−1 occurred in pivot regions. The pressure differences between the simulation and experimental data were approximately 2.5% during systole and increased up to 25% during diastole. The presented method, however, can be used to gain more information about the flow through different heart valve prostheses and, thus, improve the development process.

In Vitro Evaluation of Intra-Aneurysmal, Flow-Diverter-Induced Thrombus Formation: A Feasibility Study

BACKGROUND AND PURPOSE: Intracranial aneurysm treatment by flow diverters aims at triggering intra-aneurysmal thrombosis. By combining in vitro blood experiments with particle imaging velocimetry measurements, we investigated the time-resolved thrombus formation triggered by flow diverters. MATERIALS AND METHODS: Two test setups were built, 1 for particle imaging velocimetry and 1 for blood experiments, both generating the same pulsatile flow and including a silicone aneurysm model. Tests without flow diverters and with 2 different flow-diverter sizes (diameter: 4.5 and 4.0 mm) were performed. In the blood experiments, the intra-aneurysmal flow was monitored by using Doppler sonography. The experiments were stopped at 3 different changes of the spatial extent of the signal. RESULTS: No thrombus was detected in the aneurysm model without the flow diverter. Otherwise, thrombi were observed in all aneurysm models with flow diverters. The thrombi grew from the proximal side of the aneurysm neck with fibrin threads connected to the flow diverter and extending across the aneurysm. The thrombus resulting from the 4.0-mm flow diverter grew along the aneurysm wall as a solid and organized thrombus, which correlates with the slower velocities near the wall detected by particle imaging velocimetry. The thrombus that evolved by using the 4.5-mm flow diverter showed no identifiable growing direction. The entire thrombus presumably resulted from stagnation of blood and correlates with the central vortex detected by particle imaging velocimetry. CONCLUSIONS: We showed the feasibility of in vitro investigation of time-resolved thrombus formation in the presence of flow diverters.

Aortic Root Compliance Influences Hemolysis in Mechanical Heart Valve Prostheses: An In-Vitro Study:

Mechanical heart valve prostheses are known to activate coagulation and cause hemolysis. Both are particularly dependent on the leaflet dynamics, which in turn depends on the flow field in the aortic root influenced by the aortic root geometry and its compliance. Compliance reduction of large vessels occurs in aging patients, both in those who have atherosclerotic diseases and those who do not. In this study we investigated the correlation between hemolysis and the compliance of the proximal aorta in a novel, pulsatile in vitro blood tester using porcine blood. Two mechanical heart valves, the St Jude Medical (SJM) bileaflet valve and a trileaflet valve prototype (Triflo) were tested for hemolysis under physiological conditions (120/80 mm Hg, 4.5 l/min, 70 bpm) and using two different tester setups: with a stiff aorta and with a compliant aorta. Valve dynamics were subsequently analyzed via high-speed videos. In the tests with the Triflo valve, the free plasma hemoglobin increased by 13.4 mg/dl for the flexible and by 19.3 mg/dl for the stiff setup during the 3-hour test. The FFT spectra and closing speed showed slight differences for both setups. Free plasma hemoglobin for the SJM valve was up by 22.2 mg/dl in the flexible and 42.7 mg/dl in the stiff setup. Cavitation induced by the higher closing speed might be responsible for this, which is also indicated by the sound spectrum elevation above 16 kHz.

Comparison of different cannulation approaches for Cardio Pulmonary Bypass

The cerebral perfusion can be insufficient during Cardio Pulmonary Bypass (CPB) operations. The outflow cannula position influences the flow field in the cardiovascular system, whereby end organ perfusion is affected. There are different cannulation approaches for CPB. A Computational Fluid Dynamics study was initially undertaken to compare cannulation of the ascending aorta, regarding different cannula positions, and cannulation of the right subclavian artery, with regard to the distance between the cannula tip and the vertebral artery. Usual CPB conditions were assumed for both approaches. The models were created from CT/MRI records of young to middle-aged healthy patients. The cannula jet appears to be the main reason for the loss in cerebral perfusion seen clinically during CPB. Also, the results suggest that cannulation of the subclavian artery provides the best flow distribution if the cannula tip is a few mm away from the vertebral artery branch. For cannulation of the ascending aorta, the cannula should be placed sagital from the left body side. The presented method can be adapted for other clinical applications, e.g. support conditions of Ventricular Assist Devices. Flow fields, pressure, stress and shear rates can be analysed, which may be used for evaluation and development of new products and applications.