In vitro study on the hemocompatibility of plasma electrolytic oxidation coatings on titanium substrates.

Passively levitated ventricular assist devices (VADs) are vulnerable to impeller-housing contact and could benefit from surface coatings that improve wear resistance. Such coatings can be manufactured by plasma electrolytic oxidation (PEO), but their suitability for blood-contact applications needs further investigation. We therefore compared blood-surface interactions of polished titanium grade 5 (Ti Gr 5), as a general VAD reference material, uncoated ground titanium grade 4 (Ti Gr 4) and two commercially available PEO coatings on Ti Gr 4. In n = 4 static platelet adhesion tests, material samples were incubated with platelet-rich plasma (PRP) and consecutively analyzed for adhesive platelets by immunofluorescence microscopy. Additionally, PRP supernatant of incubated material samples was analyzed for changes in antithrombin III and fibrinogen concentrations by turbodimetry and enzyme-linked immunosorbent assay, respectively. We could not find any significant differences between the materials in the analyzed hemocompatibility markers (P > .05). Thus, we conclude that PEO coatings might offer a similar hemocompatibility to that of polished Ti Gr 5 and uncoated Ti Gr 4. Nevertheless, future studies should investigate blood-surface interactions of PEO coatings under realistic VAD-related flow conditions to better evaluate their potential for VAD applications.

Assessing the Thrombogenic Potential of Heart Valve Prostheses: An Approach for a Standardized In-Vitro Method.

PURPOSE: Thrombogenic complications are still a main issue in the general performance of cardiovascular implants, especially heart valves. To date, the thrombogenic potential of those prostheses is pre-clinically assessed in time consuming animal studies with questionable evidence. METHODS: In this study, we present a new in-vitro method to assess and compare deficiencies of heart valve substitutes concerning their thrombogenic performance and locate initial clot formation under physiological conditions using porcine blood. Therefore, an athrombogenic pulse duplicator (THIA3) was developed that simulates the anatomic and hemodynamic conditions in the vicinity of the aortic valve. Validation of this tester was carried out with regard to hemodynamics, reproducibility and using positive and negative control valves and by comparison of clot locations with literature data from chronic animal trials with sheep using a St. Jude bileaflet valve. RESULTS: Validation of the tester showed quasi-physiological hemodynamics and reproducible clot formation. Identical clot formations were found comparing findings in vitro with chronic animal trials. CONCLUSION: The THIA 3 has proven its suitability for valid, reproducible evaluation of thrombogenic potential of heart valves in a short period of time.

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.

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.

A low-volume tester for the thrombogenic potential of mechanical heart valve prostheses.

BACKGROUND AND AIM OF THE STUDY: During the development of a mechanical heart valve prosthesis, many studies are conducted to guarantee its correct function. Currently, investigations into the thrombogenic potential of a valve after its replacement are conducted with expensive and time-consuming chronic animal trials. Hence, the study aim was to develop and test an alternative system to resolve such thrombogenic issues. METHODS: The Thrombosis Tester of the Helmholtz Institute Aachen (THIA II) has a reasonably small priming volume (220-270 ml) that allows analysis of the thrombogenic potential of two valves, using one human blood bottle. RESULTS: Hydrodynamic evaluation demonstrated an absolutely stable physiological pressure and flow progression at the aortic and pulmonary positions. A sinus geometry of the human aortic root is implemented downstream of the valve in order to guarantee physiological leaflet motion. The tester remained absolutely thrombus-free during several tests carried out with minimally anticoagulated porcine blood, while the valves showed reproducible thrombus formation in reasonable locations. Tests with fully heparinized porcine blood showed that a soft silicon fixture for the valve could reduce hemolysis in the THIA II. CONCLUSION: This in-vitro test protocol can enable the optimization of a valve design during the early stages of its research and development. The system can provide a unique and suitable supplement to animal trials for testing thrombogenic performance, under constant and reproducible boundary conditions, including considerable physiological and pathological circumstances such as the influence of valve position (aortic, pulmonic), and a comparison of different valve types.

Comparison of unfractionated heparin, low-molecular-weight heparin, low-dose and high-dose rivaroxaban in preventing thrombus formation on mechanical heart valves: results of an in vitro study.

Thromboembolism and bleeding after mechanical heart valve replacement are still unsolved problems, particularly for patients requiring anticoagulative bridging therapy. The aim of this study was to investigate whether rivaroxaban, a new oral selective and direct coagulation factor Xa inhibitor, is as effective as enoxaparin and unfractionated heparin (UFH) in preventing thrombus formation on mechanical heart valves using an in vitro system. Blood from healthy male donors was anticoagulated with either UFH, enoxaparin, rivaroxaban at 300 ng/ml, (n = 10 each), or rivaroxaban at 30 ng/ml (n = 3). Mechanical aortic valve prostheses were placed into the in vitro testing system THIA II and exposed to the anticoagulant blood mixtures at a pulsatile flow for 60 min. Overall thrombus weight, coagulation parameters, and electron microscopic features of thrombus formation on the valve surface were quantified as endpoints. The mean thrombus weights were 163 ± 64 mg for group 1 (UFH), 341 ± 63 mg for the group 2 (enoxaparin), 238 ± 83 mg for group 3 (rivaroxaban 300 ng/ml) and 1.739 ± 16 mg for group 4 (rivaroxaban 30 ng/ml). Whereas high-dosed rivaroxaban showed no significant differences compared to UFH or enoxaparin, low-dosed rivaroxaban generated a massive thrombus generation, thus differing significantly from all other treatment groups regarding the thrombus weight. We hypothesize that high-dose rivaroxaban is a competitive oral available alternative to UFH and LMWH's, that might be a worthwhile alternative for patients in need of anticoagulative bridging therapy. Prospective studies have to evaluate if rivaroxaban might even overcome the limitations of OAC in patients after implantation of artificial heart valves.

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 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.

Stent-based, off-pump creation of an apico-aortic conduit.

An apico-aortic conduit (AAC) is an alternative therapy in patients with aortic valve stenosis and severe concomitant disease. We investigated whether it is feasible to create an apico-aortic conduit off-pump with a newly developed, stent-based coring- and cannulation-device in the animal model. A new self-expandable, stent equipped and hooked prosthesis and a sheath enabling both airtight removal of tissue and introduction of the prosthesis were designed and experimentally investigated in six pigs. Hemodynamic- and echocardiographic investigations were performed without and with aortic stenosis. In three animals MRI was performed. There was no significant blood loss, no relevant contamination with air and no hemodynamic depression during the whole procedure. It was possible to yield the entire cardiac output through the conduit after creating a high grade aortic stenosis. Autopsy revealed an excellent anchorage of the prosthesis. Neither relevant intracavitary injury nor thrombotic formation was seen. This study proves the feasibility of a stent-based, off-pump creation of an AAC. The principle of this approach might be used for other purposes.

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.