Pharmacogenetic testing in the management of patients with prosthetic heart valves

Abstract Background This study examined clinical, demographic, anthropometric, and inheritance factors that influence individual sensitivity to warfarin therapy after heart valve surgery. The clinical significance of the pharmacogenetic approach was assessed using the individual time frame and time spent in the INR therapeutic range. Purpose To study the influence of the preemptive panel-based pharmacogenetic testing on the effectiveness and safety of anticoagulant therapy in patients with prosthetic heart valves. Materials and methods The study included 928 patients (519 men and 409 female) (mean age 56±10 years) living in Western Siberia, Russia. Mainly there were patients with rheumatic heart disease, heart failure III NYHA and atrial fibrillation in 35% of cases. Mechanical heart valve prostheses were used in 70% of cardiac surgery cases. Real-time polymerase chain reaction was used for molecular genetic testing for polymorphisms VKORC, CYP2C9*2, CYP2C9*3, and CYP4F2. Results The frequencies of alleles and genotypes of CYP2C9 and VKORC1 in the study population of patients with heart valves prosthetic correspond to the distribution in Caucasian populations. Correlation between the calculated and actual therapeutic doses of warfarin was found according to the B.F Gage algorithm. In analyzing the dependence of the actual therapeutic dose of warfarin on polymorphic variants of the CYP2C9 and VKORC1 genes, it was shown that all the studied variants were associated with a therapeutic dose of warfarin, which was significantly different in carriers of different genotypes. Genotypes A/A CYP2C9*3 and G/G VKORC1 were associated with the largest deviations of the actual therapeutic dose from the calculated one. The clinical effectiveness of the pharmacogenetic approach was assessed according to the prevalence of the studied polymorphic variants of the CYP2C9 and VKORC1 genes in patients with prosthetic heart valves in the Kemerovo region. As a result, two groups of patients were formed using the “copy pair” method, without statistically significant differences in genetic, clinical, demographic, and anthropometric data. Usage of the pharmacogenetic testing at the beginning of warfarin therapy twice reduced time required to select a therapeutic dose of the anticoagulant, while the time within therapeutic INR range was increased by 20.2%. Conclusion The use of the panel-based pharmacogenetic approach at the beginning of warfarin therapy in patients with prosthetic heart valves increases the effectiveness and safety of anticoagulant therapy in the early postoperative period. Funding Acknowledgement Type of funding source: None

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Efficiency of pharmacogenetic approach to anticoagulant therapy in patients with prosthetic heart valves

Kardiologiia ◽

10.18087/cardio.n681 ◽

2019 ◽

Vol 59 (9S) ◽

pp. 25-30

Author(s):

E. V. Gorbunova ◽

V. V. Rozhnev ◽

A. V. Ponasenko ◽

Olga Leonidovna Barbarash

Keyword(s):

Anticoagulant Therapy ◽

Therapeutic Range ◽

Heart Valves ◽

Warfarin Therapy ◽

Molecular Genetic ◽

Time Frame ◽

Prosthetic Heart Valves ◽

Main Diagnosis ◽

Mechanical Prostheses ◽

Time Required

Background. This study examined clinical, demographic, anthropometric, and inheritance factors that influence individual sensitivity to warfarin therapy after heart valve surgery. The clinical significance of the pharmacogenetic approach was assessed using the individual time frame and time spent in the INR therapeutic range. Aims. We determined the clinical outcome of the pharmacogenetic approach at the start of warfarin therapy in patients with prosthetic heart valves. Materials and methods. The study included 915 patients, of which 512 women and 403 men (mean age 56±10 years), living in Western Siberia. Rheumatic heart disease was the main diagnosis that caused the acquired defect. Mechanical prostheses were used in 70% of cases of cardiac surgery. Real-time polymerase chain reaction used for molecular genetic testing. Results. The frequencies of the alleles and genotypes of CYP2C9 and VKORC1 in the study population of patients with heart valves prosthetic correspond to the distribution in Caucasoid populations. The use of pharmacogenetic testing results at the beginning of warfarin therapy reduced the time required for selecting a therapeutic dose of anticoagulant by 2 times and increased the duration of stay in the INR therapeutic range by 20.2%. Conclusion. The use of the pharmacogenetic approach at the begin‑ ning of warfarin therapy contributes to the effectiveness and safety of anticoagulant therapy in this category of patients.

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Hemodynamic Performance of Dysfunctional Prosthetic Heart Valve with the Concomitant Presence of Subaortic Stenosis: In Silico Study

Bioengineering ◽

10.3390/bioengineering7030090 ◽

2020 ◽

Vol 7 (3) ◽

pp. 90

Author(s):

Othman Smadi ◽

Anas Abdelkarim ◽

Samer Awad ◽

Thakir D. Almomani

Keyword(s):

Early Detection ◽

Heart Valve ◽

Heart Valves ◽

Cfd Simulation ◽

Treatment Plan ◽

Mechanical Heart Valve ◽

Prosthetic Heart Valve ◽

Subaortic Stenosis ◽

Prosthetic Heart Valves ◽

The Impact

The prosthetic heart valve is vulnerable to dysfunction after surgery, thus a frequent assessment is required. Doppler electrocardiography and its quantitative parameters are commonly used to assess the performance of the prosthetic heart valves and provide detailed information on the interaction between the heart chambers and related prosthetic valves, allowing early detection of complications. However, in the case of the presence of subaortic stenosis, the accuracy of Doppler has not been fully investigated in previous studies and guidelines. Therefore, it is important to evaluate the accuracy of the parameters in such cases to get early detection, and a proper treatment plan for the patient, at the right time. In the current study, a CFD simulation was performed for the blood flow through a Bileaflet Mechanical Heart Valve (BMHV) with concomitant obstruction in the Left Ventricle Outflow Tract (LVOT). The current study explores the impact of the presence of the subaortic on flow patterns. It also investigates the accuracy of (BMHV) evaluation using Doppler parameters, as proposed in the American Society of Echocardiography (ASE) guidelines.

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Modeling of Tissue Fatigue Damage in Bio-Prosthetic Heart Valve

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53888 ◽

2011 ◽

Cited By ~ 1

Author(s):

Caitlin Martin ◽

Wei Sun

Keyword(s):

Fatigue Damage ◽

Heart Valve ◽

Anticoagulant Therapy ◽

Heart Valves ◽

Prosthetic Heart Valve ◽

Bovine Pericardium ◽

Prosthetic Heart Valves ◽

Mechanical Valves ◽

In Vivo Degradation

Bio-prosthetic heart valves (BHVs) with leaflets made of glutaraldehyde-treated bovine pericardium (GLBP), have been used extensively to replace diseased heart valves. BHVs display superior hemodynamics to mechanical valves and eliminate the need for anticoagulant therapy; however, they exhibit poor durability resulting from in vivo degradation and fatigue damage of the leaflets.

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TRIZ Based Tool Management Applied in Mechanical Heart Valve Engineering Systems

Advanced Materials Research ◽

10.4028/www.scientific.net/amr.569.521 ◽

2012 ◽

Vol 569 ◽

pp. 521-524

Author(s):

Feng Zhou ◽

Yuan Yuan Cui ◽

Liang Liang Wu ◽

Yin Chen ◽

Jie Yang ◽

...

Keyword(s):

Heart Valve ◽

Heart Valves ◽

Production Systems ◽

Mechanical Heart Valve ◽

Complex Case ◽

Evolutionary Development ◽

Prosthetic Heart Valves ◽

Engineering Systems ◽

Device Structure

Artificial mechanical heart valve (MHV) replacement is the common cardiovascular surgical procedure, yet its effect is far from satisfaction. Most important reasons lie in the model design and choice of the materials in the fabrication of the prosthetic heart valves. Based on systematic design methodology of TRIZ theory (Russian acronym for Theory of Solving Inventive Problem), the device structure is analyzed by comparing the past successful designs generated during the evolution of MHV. This paper represents a modeling technique integrating the well-established TRIZ with the conflict and contradiction modeling, substance-field and product functional analysis tools and provides some important trends in evolutionary development of production systems in MHV design. By analyzing the structural behavior and material performance, a complex case study from the research of different structural patterns and characteristics of current tri-leaflet modeling shows the validity of TRIZ theory to guide MHV design.

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Prophylaxis of thrombotic complications in a pregnant patients with prosthetic heart valves

Journal of obstetrics and women s diseases ◽

10.17816/jowd61510-24 ◽

2012 ◽

Vol 61 (5) ◽

pp. 10-24

Author(s):

Aleksandr Davidovich Makatsariya ◽

Viktoriya Omarovna Bitsadze ◽

Dzhamilya Khizriyevna Khizroyeva ◽

Vyacheslav Borisovich Nemirovskiy ◽

Svetlana Vladimirovna Akinshina

Keyword(s):

Heart Valve ◽

Heart Valves ◽

Anticoagulation Therapy ◽

Mechanical Heart Valve ◽

Prosthetic Heart Valves ◽

Dose Selection ◽

Heart Valve Prostheses ◽

Adequate Dose ◽

Thrombotic Complications ◽

Valve Prostheses

In patients with prosthetic heart valves pregnancy and labor are associated with high risk. There are no established anticoagulation guidelines in pregnant women with mechanical heart valve prostheses. More often physiological hypercoagulable state during pregnancy can reveal acquired and/or inherited hemostasis abnormalities which were asymptotic before pregnancy. The presence in the history of patients the foetal loss syndrome, severe obstetric complications (severe preeclampsia, abruptio placenta, antenatal fetal death, feto-placental insufficiency), thrombosis events is an indication for the screening for genetic thrombophilia and antiphospholipid syndrome. The diagnosis of thrombophilia in patients with mechanical heart valve prostheses can explain the inefficiency of anticoagulation therapy, warfarin resistance, «floating» hemostasis markers and difficulties in adequate dose selection

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Simulations of the Hinge Flow Fields of a Bileaflet Mechanical Heart Valve Under Physiologic Pulsatile Aortic Conditions

ASME 2008 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2008-192939 ◽

2008 ◽

Author(s):

Hélène A. Simon ◽

Liang Ge ◽

Iman Borazjani ◽

Fotis Sotiropoulos ◽

Ajit P. Yoganathan

Keyword(s):

Heart Valve ◽

Heart Valves ◽

Mechanical Heart Valve ◽

Prosthetic Heart Valve ◽

Prosthetic Heart Valves ◽

Valve Design ◽

Bileaflet Mechanical Heart Valve ◽

Hinge Flow ◽

Blood Elements

Native heart valves with limited functionality are commonly replaced by prosthetic heart valves. Since the first heart valve replacement in 1960, more than three million valves have been implanted worldwide. The most widely implanted prosthetic heart valve design is currently the bileaflet mechanical heart valve (BMHV), with more than 130,000 implants every year worldwide. However, studies have shown that this valve design can still cause major complications, including hemolysis, platelet activation, and thromboembolic events. Clinical reports and recent in vitro experiments suggest that these thrombogenic complications are associated with the hemodynamic stresses imposed on blood elements by the complex non-physiologic flow induced by the valve, in particular in the hinge region.

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Identification of mechanical prosthetic heart valves based on distinctive cinefluoroscopic and echocardiographic markers

The International Journal of Artificial Organs ◽

10.1177/0391398819860845 ◽

2019 ◽

Vol 42 (11) ◽

pp. 603-610 ◽

Cited By ~ 2

Author(s):

Macit Kalçık ◽

Ahmet Güner ◽

Mahmut Yesin ◽

Emrah Bayam ◽

Semih Kalkan ◽

...

Keyword(s):

Transesophageal Echocardiography ◽

Heart Valve ◽

Prosthetic Valve ◽

Heart Valves ◽

Large Body ◽

Mechanical Heart Valve ◽

Three Dimensional ◽

Prosthetic Heart Valves ◽

Mechanical Prostheses ◽

Valve Prostheses

The past 65 years have witnessed remarkable progress in the development of safe, hemodynamically favorable mechanical heart valves. Today, there are a large number and variety of prostheses in use and many prostheses have been used for a while and then discontinued. When patients lack reliable information about their heart valve prostheses, identification of valve model becomes difficult even for specialized physicians in this area. A combination of cinefluoroscopy and echocardiography makes it possible to provide accurate and detailed information regarding identification of prosthetic valve models. Fluoroscopic examination is a useful technique to evaluate patients following mechanical heart valve replacement. However, transthoracic echocardiography and transesophageal echocardiography have almost replaced cinefluoroscopy in the evaluation of prosthetic heart valves. Especially, real-time three-dimensional transesophageal echocardiography provides distinctive images of prosthetic heart valves, particularly for those in the mitral position. A large body of literature has been published to familiarize physicians with the radiological appearance of numerous mechanical prostheses. However, there is a lack of data regarding the identification of prosthetic valve models based on echocardiographic appearance. In this review, we aimed to describe distinctive echocardiographic and cinefluoroscopic markers for identifying the type and brand of several commonly used mechanical prosthetic heart valves.

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Simulations of Flow Through Bileaflet Mechanical Heart Valves With Asymmetric Leaflet Motion

ASME 2012 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2012-80182 ◽

2012 ◽

Author(s):

B. Min Yun ◽

Lakshmi P. Dasi ◽

Cyrus K. Aidun ◽

Ajit P. Yoganathan

Keyword(s):

Heart Valve ◽

Heart Valves ◽

Mechanical Heart Valve ◽

Prosthetic Heart Valve ◽

Prosthetic Heart Valves ◽

Thromboembolic Events ◽

Complex Flow ◽

Blood Damage ◽

Flow Through ◽

Leaflet Motion

Prosthetic heart valves have been used for over 50 years to replace diseased native valves but still lead to severe complications such as platelet aggregation and thromboembolic events. The most widely implanted design is the bileaflet mechanical heart valve (BMHV). Most modern BMHV designs have better flow hemodynamics and blood damage performance than earlier-generation counterparts. However, blood element trauma and thromboembolic events still remain as major complications of current BMHV designs. These problems have been linked to blood damage caused by non-physiological stresses. These stresses are caused by the complex flow fields that arise due to prosthetic heart valve design. In order to reduce the severity of these complications, the blood damage that occurs in flows through prosthetic heart valves must be well understood.

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Simulations of Flow Through Bileaflet Mechanical Heart Valves to Assess Platelet Damage

ASME 2011 Summer Bioengineering Conference, Parts A and B ◽

10.1115/sbc2011-53842 ◽

2011 ◽

Author(s):

B. Min Yun ◽

Jingshu Wu ◽

Cyrus K. Aidun ◽

Ajit P. Yoganathan

Keyword(s):

Heart Valve ◽

Heart Valves ◽

Mechanical Heart Valve ◽

Prosthetic Heart Valve ◽

Prosthetic Heart Valves ◽

Thromboembolic Events ◽

Complex Flow ◽

Valve Design ◽

Blood Damage ◽

Flow Through

Prosthetic heart valves have been used for over 50 years to replace diseased native valves but still lead to severe complications such as hemolysis, platelet aggregation, and thromboembolic events. The most widely implanted design is the bileaflet mechanical heart valve (BMHV). Most modern BMHV designs have better flow hemodynamics and blood damage performance than their earlier-generation counterparts. However, blood element trauma and thromboembolic events still remain as major complications of current BMHV designs. These problems have been linked to blood element damage caused by non-physiological stresses. These stresses are caused by the complex flow fields that arise due to prosthetic heart valve design, particularly in the leaflet hinge region. In order to reduce the severity of these complications, the blood damage that occurs in flows through prosthetic heart valves must be well understood.

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