Factor Xa Inhibitors for Patients after Mechanical Heart Valve Replacement?

2021 ◽  
Author(s):  
Stephen Gerfer ◽  
Maria Grandoch ◽  
Thorsten C.W. Wahlers ◽  
Elmar W. Kuhn
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Oral Anticoagulants ◽  
Mechanical Heart Valve ◽  
Factor Xa ◽  
Mechanical Heart Valves ◽  
Factor Xa Inhibitors ◽  
Current Evidence ◽  
Small Scale ◽  
Number Of Patients

AbstractPatients with a mechanical heart valve need a lifelong anticoagulation due to the increased risk of valve thrombosis and thrombo-embolism. Currently, vitamin K antagonists (VKA) are the only approved class of oral anticoagulants, but relevant interactions and side effects lead to a large number of patients not achieving the optimal therapeutic target international normalized ration (INR). Therefore, steady measurements of the INR are imperative to ensure potent anticoagulation within a distinctive range. Direct oral anticoagulants (DOACs) with newer agents could serve as a possible alternative to VKAs in this patient cohort. DOACs are approved for several indications, e.g., atrial fibrillation (AF). They only have a minor interaction potential, which is why monitoring is not needed. Thereby, DOACs improve the livability of patients in need of chronical anticoagulation compared with VKAs. In contrast to dual platelet inhibition using aspirin in combination with an ADP receptor antagonist and the direct thrombin inhibitor dabigatran, the oral factor Xa inhibitors apixaban and rivaroxaban show promising results according to current evidence. In small-scale studies, factor Xa inhibitors were able to prevent thrombosis and thrombo-embolic events in patients with mechanical heart valves. Finally, DOACs seem to represent a feasible treatment option in patients with mechanical heart valves, but further studies are needed to evaluate clinical safety. In addition to the ongoing PROACT Xa trial with apixaban in patients after aortic On-X valve implantation, studies in an all-comer collective with rivaroxaban could be promising.

scholarly journals Potentially inappropriate prescribing of DOACs to patients with mechanical heart valves: a federated analysis of 57.9 million patients' primary care records in situ using OpenSAFELY

2021 ◽  
Author(s):  
◽  
Louis Fisher ◽  
Victoria Speed ◽  
Helen J Curtis ◽  
Christopher T Rentsch ◽  
...  
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Inappropriate Prescribing ◽  
Mechanical Heart Valve ◽  
Mechanical Heart Valves ◽  
Audit And Feedback ◽  
National Guidance

National guidance was issued during the COVID-19 pandemic to switch patients on warfarin to direct oral anticoagulants (DOACs) where appropriate as these require less frequent blood testing. DOACs are not recommended for patients with mechanical heart valves. We conducted a retrospective cohort study of DOAC prescribing in people with a record of a mechanical heart valve between September 2019 and May 2021, and describe the characteristics of this population. We identified 15,457 individuals with a mechanical heart valve recorded in their records, of whom 1058 (6.8%) had been prescribed a DOAC during the study period. 767 individuals with a record of a mechanical heart valve were currently prescribed a DOAC as of May 31st 2020. This is suggestive of inappropriate prescribing of DOACs in individuals with mechanical heart valves. Direct alerts have been issued to clinicians through their EHR software informing the issue. We show that the OpenSAFELY platform can be used for rapid audit and feedback to mitigate the indirect health impacts of COVID-19 on the NHS. We will monitor changes in prescribing for this risk group over the following months.

scholarly journals Heparin is more effective than apixaban in inhibiting in vitro contact activated coagulation

2020 ◽  
Vol 41 (Supplement_2) ◽  
Author(s):  
M.M Engelen ◽  
C Van Laer ◽  
M Jacquemin ◽  
C Vandenbriele ◽  
K Peerlinck ◽  
...  
Keyword(s):  
Thrombin Generation ◽  
Heart Valves ◽  
Thrombus Formation ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Coagulation Factor ◽  
Mechanical Heart Valves ◽  
Contact Activation

Abstract Introduction Contact of blood with artificial surfaces such as mechanical support devices, catheters, and mechanical heart valves activates the contact activation (CA) pathway of coagulation. Furthermore, recent animal data and clinical studies suggest a more important contribution of CA in pathological thrombus formation in other cardiovascular diseases. Direct oral anticoagulants (DOACs) are recommended as first-line treatment in most patients who require long-term anticoagulation. However, because DOACs directly inhibit a single downstream coagulation factor (thrombin (fXIIa) or factor Xa (fXa)), it has been suggested that their efficacy could be reduced in the presence of strong activation of the CA pathway as compared to anticoagulants that target multiple, more upstream located coagulation factors. Purpose To compare the efficacy of a DOAC (apixaban) and heparin to suppress thrombin generation in the presence of strong CA pathway activation. Methods Pooled platelet-poor plasma was spiked with either apixaban (dissolved in DMSO and PBS) or unfractionated heparin to achieve therapeutic plasma levels. SynthASil, a commercially available mixture of phospholipids and silica, was used to stimulate the CA pathway in two different dilutions (1–80 and 5–80). Downstream coagulation was accessed by Thrombin Generation Test using Thrombinoscope by Stago and associated Thrombin Calibrator (activity 640 nM). The endogenous thrombin potential (area under the thrombin generation curve; ETP), peak thrombin generation (PTG), time to peak (ttPeak) and time to start (ttStart) were accessed. Results With decreasing concentrations of apixaban, stimulation with the lower dose SynthASil reveals an increasing ETP and PTG. As expected, ttPeak and ttStart decreased. Even supratherapeutic levels of apixaban (i.e. 1120 ng/mL) could not inhibit thrombin from being generated, in striking contrast with UFH where no thrombin was formed. Using a five times higher dose of SynthASil showed comparable ETP for all concentrations of apixaban, allocated around the control value. PTG, however, slightly increased with decreasing concentrations of apixaban. ttPeak and ttStart slightly decreased. Except for the subtherapeutic UFH concentration of 0,114 IU/mL, no thrombin was generated with UFH. Conclusion UFH is more effective in inhibiting downstream thrombin generation compared to apixaban as a response to activation of the CA pathway in vitro. These findings could help explain why direct inhibitors were not able to show non-inferiority in patients with mechanical heart valves and support the development of specific CA pathway inhibitors for patients with conditions that activate the CA pathway. Thrombin generation curves Funding Acknowledgement Type of funding source: None

scholarly journals Statistical Characteristics of Flow Field through Open and Semi-Closed Bileaflet Mechanical Heart Valve

2020 ◽  
Vol 2 (4) ◽  
pp. 184-196
Author(s):  
Oleksandr Voskoboinyk ◽  
Lidiia Tereshchenko ◽  
Vladimir Voskoboinick ◽  
Gabriela Fernandez ◽  
Andrey Voskoboinick ◽  
...  
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Mechanical Heart Valve ◽  
Pressure Sensors ◽  
Jet Flow ◽  
Operating Conditions ◽  
Mechanical Heart Valves ◽  
Statistical Characteristics ◽  
Diagnostic Tools ◽  
Bileaflet Mechanical Heart Valve

The formation of thrombi on the streamlined surface of the bileaflet mechanical heart valves is one of the main disadvantages of such valves. Thrombi block the valve leaflets and disrupt the cardiovascular system. Diagnosis of thrombosis of the bileaflet mechanical heart valves is relevant and requires the creation of effective diagnostic tools. Hydroacoustic registration of the heart noise is one of the methods for diagnosing the operation of a mechanical heart valve. The purpose of the research is to determine the statistical characteristics of the vortex and jet flow through the open and semi-closed bileaflet mechanical heart valve, to identify hydroacoustic differences and diagnostic signs to determine the operating conditions of the valve. Experimental studies were conducted in laboratory conditions on a model of the left atrium and left ventricle of the heart between which there was the bileaflet mechanical heart valve. Hydrodynamic noise was recorded by miniature pressure sensors, which were located downstream of the valve. The vortex and jet flow behind the prosthetic heart valve were non-linear, random processes and were analyzed using the methods of mathematical statistics and probability theory. The integral and spectral characteristics of the pressure field were obtained and the differences in the noise levels and their spectral components near the central and side jets for the open and semi-closed mitral valve were established. It was shown that hydroacoustic measurements could be an effective basis for developing diagnostic equipment for monitoring the bileaflet mechanical heart valve operation. Doi: 10.28991/SciMedJ-2020-0204-1 Full Text: PDF

Effect of Blood Pressure on Closing Dynamics of Bileaflet Mechanical Heart Valves

2012 ◽  
Author(s):  
Marcio H. Forleo ◽  
Brennan M. Johnson ◽  
Lakshmi P. Dasi
Keyword(s):  
Blood Pressure ◽  
Heart Valve ◽  
Heart Valves ◽  
Mechanical Heart Valve ◽  
Mechanical Heart Valves ◽  
Thromboembolic Complications ◽  
Stress Gradients ◽  
Bileaflet Mechanical Heart Valve ◽  
Sharp Stress ◽  
Rigid Design

Implantation of a bileaflet mechanical heart valve (BMHV) continues to be associated with a risk of thromboembolic complications despite anti-coagulation therapy1. This has been attributed to the structurally rigid design of the leaflets and valve mechanics combined with an intricate hinge mechanism for the rigid leaflets. The lack of a built in compliance within the valve mechanics presumably leads to sharp stress gradients within the flow as well as a violent closure of the valve often associated with the audible impact of the leaflets to the housing, and a potential for momentary cavitation of blood in the wake of leaflet impact.

scholarly journals Mechanical heart valves and pregnancy: Issues surrounding anticoagulation. Experience from two obstetric cardiac centres

2020 ◽  
pp. 1753495X2092493
Author(s):  
Francois Dos Santos ◽  
Lucia Baris ◽  
Alice Varley ◽  
Jerome Cornette ◽  
Joanna Allam ◽  
...  
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Mode Of Delivery ◽  
Mechanical Heart Valve ◽  
Significant Risk ◽  
Mechanical Heart Valves ◽  
Cardiac Complications ◽  
Anticoagulation Management ◽  
Valve Thrombosis ◽  
Heart Valve Thrombosis

Background Pregnant women with mechanical heart valves are at significant risk of obstetric/cardiac complications. This study compares the anticoagulation management in two obstetric cardiac centres. Methods Retrospective case-note review from Chelsea and Westminster/Royal Brompton Hospitals (CR) and Erasmus Medical Centre (EMC). Main outcome measure was mechanical heart valve thrombosis. Results Nineteen pregnancies from CR and 25 pregnancies from EMC were included. Most women were on low-molecular-weight heparin (LMWH) throughout pregnancy at CR, whereas at EMC most had LMWH in the first trimester and vitamin K antagonists in subsequent trimesters. Peak anti-factor Xa were performed monthly at CR, levels 0.39–1.51 IU/mL (mean 0.82 IU/mL). Anticoagulation management peri-partum was inconsistent. Delivery was mainly by Caesarean section at CR (74%) and vaginal delivery at EMC (64%). No maternal deaths and only one mechanical heart valve thrombosis at CR. Two mechanical heart valve thromboses and one maternal death at EMC. Conclusion Peri-partum anticoagulation strategies, anticoagulation monitoring and mode of delivery inconsistencies reported.

Alternative mechanical heart valves for the developing world

2019 ◽  
Vol 28 (7) ◽  
pp. 431-443
Author(s):  
Elsmari Wium ◽  
Christiaan Johannes Jordaan ◽  
Lezelle Botes ◽  
Francis Edwin Smit
Keyword(s):  
Heart Valve ◽  
Computer Aided Design ◽  
Heart Valves ◽  
Developing World ◽  
Mechanical Heart Valve ◽  
Mechanical Heart Valves ◽  
Design Approach ◽  
Element Analysis ◽  
Mechanical Valves

Due to the prevalence of rheumatic heart disease in the developing world, mechanical heart valves in the younger patient population remain the prostheses of choice if repair is not feasible. Despite their durability, mechanical valves are burdened by coagulation and thromboembolism. Modern design tools can be utilized during the design process of mechanical valves, which allow a more systematic design approach and more detailed analysis of the blood flow through and around valves. These tools include computer-aided design, manufacturing, and engineering, such as computational fluid dynamics and finite element analysis, modern manufacturing techniques such as additive manufacturing, and sophisticated in-vitro and in-vivo tests. Following this systematic approach, a poppet valve was redesigned and the results demonstrate the benefits of the method. More organized flow patterns and fewer complex fluid structures were observed. The alternative trileaflet valve design has also been identified as a potential solution and, if a similar design approach is adopted, it could lead to the development of an improved mechanical heart valve in the future. It is imperative that researchers in developing countries continue their search for a mechanical heart valve with a reduced thromboembolic risk, requiring less or no anticoagulation.

scholarly journals Pyrolytic Carbons and the Design of Mechanical Heart Valve Prostheses

2000 ◽  
Author(s):  
R. B. More
Keyword(s):  
Mechanical Properties ◽  
Wear Resistance ◽  
Heart Valve ◽  
Heart Valves ◽  
Blood Compatibility ◽  
Mechanical Heart Valve ◽  
Mechanical Valve ◽  
Pyrolytic Carbon ◽  
Mechanical Heart Valves ◽  
Pure Carbon

Abstract Pyrolytic carbons have a long successful history in mechanical heart valve prosthesis applications. Originally pyrolytic carbons had been developed for use in nuclear reactors. But in a chance interaction between a scientist studying nuclear energy and another searching for blood compatible materials, the blood compatibility of pyrolytic carbon was discovered. This discovery of blood compatibility prompted an effort that resulted in the development of a form of pyrolytic carbon specifically tailored for use in mechanical heart valves. This form developed by General Atomic Co. was an alloy of approximately 5 to 12 weight percent silicon codeposited with pyrolytic carbon. Fine silicon carbide particles dispersed in the carbon matrix increased the hardness and wear resistance of the pyrolytic carbon, which compensated for difficulties in manufacturing using the process control capabilities available at the time. Use of pyrolytic carbon instead of polymers in the early valve designs allowed the durability, stability and compatibility needed for true long-term implants. Since the first pyrolytic carbon heart valve component implant in 1968, more than 4 million pyrolytic carbon components in more than 25 different valve designs have been implanted to accumulate a clinical experience on the order of 18 million patient years. The physiochemical and mechanical properties of silicon-alloyed pyrolytic carbon, while enabling the practical utilization of mechanical heart valves, placed some severe restrictions upon design. Silicon-alloyed pyrolytic carbon is an extremely hard and nearly ideal linear elastic material with a strain to failure of approximately 1.2 percent. Traditional machining and joining techniques are not feasible, rather the carbon is prepared as a coating upon a pre-form and the coated components are then finished to size using diamond impregnated tools, grinding forms and abrasive polishing techniques. While the silicon-alloyed material was very successful, design features of known hydrodynamic advantage, such as a flared inlet, were not possible and in some valve designs annular area was sacrificed by the addition of metallic rings used to increase stiffness. As a result, mechanical valve designs in the small aortic sizes tended to be stenotic. In the early 1990’s, pyrolytic carbon coating technology was re-examined and methods of process control were redesigned in order to produce pure carbon. The resulting pure pyrolytic carbon had sufficient hardness and wear resistance, but, in addition, had higher strength and toughness with higher deformability than the silicon-alloyed material. The new material eliminated the need for the silicon and improved the carbon mechanical properties. With the improved mechanical properties, it is now possible to manufacture valve designs with greater hydrodynamic efficiency, and eliminate the need for stiffening rings, thus improving the flow behavior in the small aortic valve sizes. A mechanical valve design utilizing the pure carbon with improved hydrodynamic design features has achieved hemodynamic properties comparable to those of homografts and stentless bioprostheses.

A Detailed Fluid Mechanics Study of Tilting Disk Mechanical Heart Valve Closure and the Implications to Blood Damage

2008 ◽  
Vol 130 (4) ◽  
Author(s):  
Keefe B. Manning ◽  
Luke H. Herbertson ◽  
Arnold A. Fontaine ◽  
Steven Deutsch
Keyword(s):  
Heart Valve ◽  
Heart Valves ◽  
Mechanical Heart Valve ◽  
In Vitro Study ◽  
Mechanical Heart Valves ◽  
Single Shot ◽  
Flow Measurements ◽  
Blood Damage ◽  
Disk Valve

Hemolysis and thrombosis are among the most detrimental effects associated with mechanical heart valves. The strength and structure of the flows generated by the closure of mechanical heart valves can be correlated with the extent of blood damage. In this in vitro study, a tilting disk mechanical heart valve has been modified to measure the flow created within the valve housing during the closing phase. This is the first study to focus on the region just upstream of the mitral valve occluder during this part of the cardiac cycle, where cavitation is known to occur and blood damage is most severe. Closure of the tilting disk valve was studied in a “single shot” chamber driven by a pneumatic pump. Laser Doppler velocimetry was used to measure all three velocity components over a 30ms period encompassing the initial valve impact and rebound. An acrylic window placed in the housing enabled us to make flow measurements as close as 200μm away from the closed occluder. Velocity profiles reveal the development of an atrial vortex on the major orifice side of the valve shed off the tip of the leaflet. The vortex strength makes this region susceptible to cavitation. Mean and maximum axial velocities as high as 7m∕s and 20m∕s were recorded, respectively. At closure, peak wall shear rates of 80,000s−1 were calculated close to the valve tip. The region of the flow examined here has been identified as a likely location of hemolysis and thrombosis in tilting disk valves. The results of this first comprehensive study measuring the flow within the housing of a tilting disk valve may be helpful in minimizing the extent of blood damage through the combined efforts of experimental and computational fluid dynamics to improve mechanical heart valve designs.

A Comparison of a Moderate with Moderate-high Intensity Oral Anticoagulant Treatment in Patients with Mechanical Heart Valve Prostheses

1997 ◽  
Vol 77 (05) ◽  
pp. 0839-0844 ◽  
Author(s):  
Vittorio Pengo ◽  
Fabio Barbero ◽  
Alberto Banzato ◽  
Elisabetta Garelli ◽  
Franco Noventa ◽  
...  
Keyword(s):  
Heart Valve ◽  
High Intensity ◽  
Oral Anticoagulant ◽  
Oral Anticoagulants ◽  
Mechanical Heart Valve ◽  
Moderate Intensity ◽  
Minor Bleeding ◽  
Anticoagulant Treatment ◽  
Oral Anticoagulant Treatment ◽  
Valve Prostheses

SummaryBackground. The long-term administration of oral anticoagulants to patients with mechanical heart valve prostheses is generally accepted. However, the appropriate intensity of oral anticoagulant treatment in these patients is still controversial.Methods and Results. From March 1991 to March 1994, patients referred to the Padova Thrombosis Center who had undergone mechanical heart valve substitution at least 6 months earlier were randomly assigned to receive oral anticoagulants at moderate intensity (target INR = 3) or moderate-high intensity (target INR = 4). Principal end points were major bleeding, thromboembolism and vascular death. Minor bleeding was a secondary end-point.A total of 104 patients were assigned to the target 3 group and 101 to the target 4 group; they were followed for from 1.5 years to up 4.5 years (mean, 3 years). Principal end-points occurred in 13 patients in the target 3 group (4 per 100 patient-years) and in 20 patients in the target 4 group (6.9 per 100 patient-years). Major hemorrhagic events occurred in 15 patients, 4 in the target 3 group (1.2 per 100 patient-years) and 11 in the target 4 group (3.8 per 100 patient-years) (p = 0.019). The 12 recorded episodes of thromboembolism, 4 of which consisted of a visual deficit, were all transient ischemic attacks, 6 in the target 3 group (1.8 per 100 patient-years) and 6 in the target 4 group (2.1 per 100 patient- years). There were 3 vascular deaths in each group (0.9 and 1 per 100 patient-years for target 3 and target 4 groups, respectively). Minor bleeding episodes occurred 85 times (26 per 100 patient-years) in the target 3 group and 123 times (43 per 100 patient-years) in the target 4 group (p = 0.001).Conclusions. Mechanical heart valve patients on anticoagulant treatment who had been operated on at least 6 months earlier experienced fewer bleeding complications when maintained on a moderate intensity regimen (target INR = 3) than those on a moderate-high intensity regimen (target INR = 4). The number of thromboembolic events and vascular deaths did not differ between the two groups.

Argatroban and bivalirudin compared to unfractionated heparin in preventing thrombus formation on mechanical heart valves

2009 ◽  
Vol 101 (06) ◽  
pp. 1163-1169 ◽  
Author(s):  
Torsten Linde ◽  
Thomas Michel ◽  
Kathrin Hamilton ◽  
Ulrich Steinseifer ◽  
Ivar Friedrich ◽  
...  
Keyword(s):  
Electron Microscopy ◽  
Unfractionated Heparin ◽  
Continuous Infusion ◽  
Valve Replacement ◽  
Heart Valves ◽  
Thrombus Formation ◽  
Mechanical Heart Valve ◽  
Mechanical Heart Valves ◽  
Valve Prostheses

SummaryPrevention 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.

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