Factor Xa Inhibitors for Patients after Mechanical Heart Valve Replacement?

Patients 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.

Biofilm Matrix Formation in Human: Clinical Significance, Diagnostic Techniques, and Therapeutic Drugs

Context: Some recent reports have indicated that almost 80% of clinical infections in humans have biofilm origin and impose additional healthcare costs. This study was an updated review of extracellular polymeric substance matrix (Biofilm) formation in humans and elaborated on its clinical significance, diagnosis, and therapeutic approaches. Evidence Acquisition: This narrative study reviewed the most recent information on the significance of microbial biofilm formation in clinical settings, common biofilm-producing bacterial species, its diagnosis, antibiotic drug resistance, and new approaches to the treatment of infections associated with biofilm formation. Results: Evidence indicated a permanent increase in the frequency of microbial biofilm in the central venous catheter, mechanical heart valve, and urinary catheter, as well as persistent infections. However, antimicrobial resistance induced by biofilms formation and the antimicrobial treatment of biofilms were problematic. Moreover, several assays and lab devices were described to evaluate biofilm formation. Furthermore, new attitudes towards anti-biofilm treatments were introduced in this paper. Conclusions: The number of different mechanisms were in accordance with the recent knowledge on how biofilms play a critical role in the disease pathogenesis. Biofilm strikes the treatment and surveillance of patients bearing infectious diseases under different conditions. The use of new methods in anti-biofilm treatments is effective for the recovery of infected patients.

DESIGN AND DEVELOPMENT OF IMPURITIES FREE PYROLYTIC COATED MECHANICAL BI-LEAFLET HEART VALVE PROTOTYPE

Heart valve problems affect more than 100 million people worldwide. According to statistics, around 55% of valvular diseases are treated by a mechanical prosthesis. The first heart valve replaced model was the caged-ball valve, more than 50 models of heart valves designed by different companies. Each design has different aspects such as valve geometry, leaflets design, materials used for model manufacturing, coating techniques, and coating materials. Depending on the patient's need and condition, the native heart valve either replaced by a biological or mechanical heart valve. Biological valves are made of living tissues whereas mechanical valves manufactured by the biomaterials, which are biocompatible and do not causes any reaction inside the body. The prototype discussed in this paper provides good hemocompatibility, because of the biomaterial used in this prototype manufacturing. It will reduce tissue ingrowth, due to the enhanced leaflet ear of the orifice ring. Moreover, it will cause less thrombotic effects into the host due to greater contact angel of graphite and smooth surface of graphite after pyrolytic coating. The significant evolution of mechanical valve designs consists of valve geometry, coating technique, and materials. In this research, the 3D-CAD model of Bileaflet Mechanical Mitral Heart Valve was designed using SOLID WORKS 2016 and fabricated by 5-axis Computer Numeric Control (CNC) machine. Graphite was used for the fabrication of prototype and Pyrolytic Carbon (PyC) coating was performed with Chemical Vapor deposition (CVD) technique. Scanning electron microscopy (SEM), Fourier Transform Infrared Spectroscopy (FTIR), and X-ray Diffraction (XRD) were used to determine the effects of CVD on surface topography and chemical structure of graphite model before and after coating. Furthermore, hemocompatibility of graphite and PyC analyzed through in-vitro hemolytic activity. The Characterization results showed that the Bileaflet Mechanical Mitral Heart valve prototype after PyC coating provides a smooth surface with improved hemocompatibility and less adhesion. Besides, the Mechanical Heart valves showed no hemolysis during the hemolytic activity. By virtue of its smooth and nonporous surface, it is antithrombotic and provides good hemodynamics. The advance long leaflet ear design reduces the tissue ingrowth around the orifice which will further limit the leaflets movement.

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

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.

AB0330 ANTIPHOSPHOLIPID ANTIBODIES AND ANTICOAGULANT TREATMENT: CAPILLAROSCOPIC FINDINGS

Background:Antiphospholipid syndrome (APS) is an autoimmune condition characterized by arterial and/or venous thrombosis and/or obstetric morbidity, associated with the presence in the serum of antiphospholipid antibodies (aPL) [1]. Subjects with confirmed positivity of aPL in absence of thrombotic/obstetric manifestations are identified as aPL carriers [2] The microangiopathy detected by nailfold videocapillaroscopy (NVC) in APS and in aPL-carrier patients is poorly investigated, as well as the possible interference of anticoagulant drugs [3].Objectives:To compare microvascular damage in APS, aPL carriers and a group of patients (CTR) without aPL positivity and on regular warfarin therapy for cardiovascular indicationsMethods:NVC investigations were performed as part of standard procedures in APS patients (18, mean age 50.0±12.8 years), aPL carriers (24, mean age 46.4±16.4 years) and CTR without aPL (18, mean age 74±12.5 years) in therapy with oral anticoagulant (warfarin) for non-immunological vascular complications (atrial fibrillation, mechanical heart valve, deep venous thrombosis). Only patients affected by primary APS form were selected from data files (2006 Sapporo classification criteria). The following NVC parameters were availble: dilated capillaries, giant capillaries, microhemorrhages (with particular attention to linear and thin hemosiderin deposits, arranged perpendicularly and parallel to the nailfold bed, “comb-like”), abnormal shape (i.e. brunched “bushy” capillaries) and capillary number reduction. Those parameters were scored according to a semi-quantitative scale [4,5]. Statistical analysis was performed by non-parametric tests. Any p values equal or lower than 0.05 was considered statistically significant.Results:APS patients showed a higher score for dilated capillaries (p=0.001), more frequent microhemorrhages (p=0.03), in particular “comb-like” microhemorrhages (p=0.007) than simply aPL carriers. Of note, there wasn’t a statistically significant difference in the number of microhemorrhages between APS and CTR group (p=0.23), but again the number of “comb-like” hemorrhages, was almost absent in the CTR group (p=0.03). No significant correlation was found between the different aPL subtypes and the NVC parameters.Conclusion:APS patients showed significantly higher number of non-specific NVC abnormalities than aPL carriers. Anticoagulant treatment could represent a further risk factor for the appearance of microhemorrhages in all the patients, being the NVC “comb-like“ pattern mainly associated with the APS. Further investigations with larger cohorts of patients are needed for the definition of a possible APS specific NVC-pattern.References:[1]Ruiz-Irastorza G et al. Lancet. 2010;376(9751):1498-509. 2. Pengo V et al. Semin Thromb Hemost. 2012;38:322-7. 3. Sulli A et al. J Rheumatol. 2000;27:1574-6. 4. Smith V et al. 2020. Autoimmun Rev. 19:102458. 5. Sulli A et al. Ann Rheum Dis. 2008;67:885-7.Disclosure of Interests:None declared

A Computational Study of a Passive Flow Device in a Mechanical Heart Valve for the Anatomic Aorta and the Axisymmetric Aorta

Artificial heart valves for replacing diseased indigenous heart valves were widely used. The treatment of certain types of heart disease requires mechanical valves to be implanted operatively. Healthy cardiac valves are essential to proper cardiac function. The current study presents an investigation of the pulsatile blood flow through a bileaflet mechanical heart valve (BMHV) with a vortex generator (VG) in fully open position. A St. Jude Medical Regent valve with a diameter of 23 mm was used to mount triangular VGs as a means of improving pressure gradients and reducing turbulence. The anatomic aorta and axisymmetric aorta was computed by large eddy simulation (LES) approached. The implications for both models with VGs were observed in terms of velocity magnitude, vortices and wall shear stress. The results suggested that the anatomic aorta is prone to develop more blood clotting at the leading edge of the leaflets with 2.03 m/s. Furthermore, the anatomic aorta produces higher wall shear stress with 69Pa, which possibly contributes to a high risk of thrombosis.

New internet-based warfarin anticoagulation management approach after mechanical heart valve replacement: a prospective, multicenter, randomized controlled trial (Preprint)

BACKGROUND Mechanical heart valve replacement (MHVR) is an effective method for the treatment of severe heart valve disease, while the patient who was administered with warfarin therapy after MHVR facing a high risk of bleeding and thrombosis. Therefore, as internet-based warfarin management emerged, whether it reduces the complications and improves patient’s life quality remain unknown. OBJECTIVE This study aimed to compare effects of internet-based warfarin management and conventional approach in patients who received MHVR. In order to provide evidence regarding alternative strategies for a long-term anticoagulation. METHODS This is a prospective, multicenter, randomized, open-label, controlled clinical trial with a follow-up for 1 year. Patients who need long-term warfarin anticoagulation after MHVR were enrolled, then randomly divided into traditional and internet-based management group. The percentage of time in the therapeutic range (TTR) was used as the primary outcome, and the bleeding, thrombosis and other event as secondary outcome. RESULTS A total of 721 patients were enrolled and the baseline is not reach statistical different between the two groups, suggesting the random assignment is successful. As a result, the internet-based group showed a significantly higher TTR (0.53±0.24 vs. 0.46±0.21, P<0.01) and fraction of time in therapeutic range (FTTR, 0.48±0.22 vs. 0.42±0.19, P<0.01), than those in the traditional group. Furthermore, as expected, the anticoagulation complications, including the bleeding and embolic events (6.94% vs. 12.74%, P<0.01) have lower frequency in the internet-based group than in the traditional group. Logistic regression shows that internet-based management increased the TTR by 7% (OR=1.07, 95%CL 1.05-1.09, P<0.01), and reduced the bleeding and embolic risk by 6% (OR=0.94, 95%CL 0.92-0.96, P<0.05). Moreover, low TTR is the risk factor of bleeding and embolic events (OR=0.87, 95%CL 0.83-0.91, P<0.05) CONCLUSIONS The internet-based warfarin management is superior than the traditional way by reducing the anticoagulation complications in patients who received long-term warfarin anticoagulation after MHVR. CLINICALTRIAL ChiCTR1800016204; http://www.chictr.org.cn/showproj.aspx?proj=27518 INTERNATIONAL REGISTERED REPORT RR2-10.1136/bmjopen-2019-032949