Native Heart Valves Research Articles

Visual grading of valvular regurgitation is inferior to measurement – results from the VIAVA-study (VIsual Assessment of VAlvular Regurgitation)

While the visual estimation of systolic left ventricular function by experienced examiners closely aligns with quantitative methodologies, the accuracy of visual estimation in determining the severity of valvular regurgitation using colour flow Doppler assessment of native heart valves remains largely unexplored. This study analysed the ability of 262 physicians to visually estimate the severity of 12 native valve regurgitations by grading colour Doppler transthoracic echocardiography loops in an online questionnaire. The assessments of the participants were compared to standardized quantitative evaluations conducted by certified echocardiography experts. Of the three valves to assess, evaluations by the participants showed the best correlation (Rs = 0.75, p < 0.0001) and agreement (percent agreement: 66.4%) with those of the experts in mitral valve regurgitation (MR). High agreement was observed for mild regurgitation across all valves (MR 94.5%, AR 80.3% and TR 88.7%), while consensus diminished in moderate (MR 55.9%, AR 49.5% and TR 55.0%) and severe regurgitation (MR 57.6%, AR 67.4%, TR 14.6%). The study underscores the potential utility of visual estimation of valvular regurgitation in clinical settings for identifying clinically relevant regurgitations. However, our findings also highlight the importance of integrating visual estimation with quantitative methods, particularly in moderate and severe cases of regurgitation.

Cure and Prevention of Cardiovascular Diseases: Herbs for Heart

Context: Cardiovascular diseases (CVDs) account for 30% of deaths worldwide, making them the leading cause of mortality. Prosthetic valve endocarditis (PVE) is a microbial infection that occurs on the surface of a prosthetic valve or on a surgically reconstructed native heart valve. As age increases, the mortality rate from CVDs also rises. Additionally, gender differences were observed, with the mortality rate from cardiovascular disease being higher in women (51%) compared to men (42%). Methods: In this review study, English keywords such as "medicinal plants," "heart," "cardiomyopathy," and "cinnamaldehyde," as well as Persian keywords related to "medicinal plants" and "cardiovascular," were used in the title and abstract of articles. Databases including PubMed, Science Direct, Web of Science, Google Scholar, Scopus, and the academic database of Jihad Daneshgahi were searched without a time limit until March 2021. Results: The results show that several medicinal plants are known to effectively treat CVDs. Conclusions: The findings of this review indicate that medicinal plants have a positive impact on the treatment of cardiovascular diseases and can be considered as potential therapeutic options for managing these conditions.

Ten questions about infective endocarditis

Infective endocarditis (IE) is an infective process involving the endocardium and, more frequently, the native heart valves, valvular prostheses and cardiac implantable electronic devices. IE can manifest with various non-specific symptoms making the diagnosis challenging. This condition is associated with high in-hospital and long-term mortality. Therefore, it is particularly important to prevent it by implementing an adequate antibiotic prophylaxis especially in patients at high risk undergoing invasive procedures. Moreover, it is pivotal to promptly diagnose IE, detect the presence of local and systemic complications, establish appropriate antibiotic therapy and identify the indication and timing for surgical treatment. In this focused review, we will provide answers to the most common questions regarding the epidemiology, causes, prophylaxis, diagnosis and antibiotic and surgical treatment of IE.

Folic acid modified silver nanoparticles promote endothelialization and inhibit calcification of decellularized heart valves by immunomodulation with anti-bacteria property

Xenogeneic decellularized heart valves (DHVs) have become one of the most commonly used scaffolds for tissue engineered heart valves (TEHVs) due to extensive resources and possessing the distinct three-layer structure similar to native heart valves. However, DHVs as scaffolds face the shortages such as poor mechanical properties, proneness to thrombosis and calcification, difficulty in endothelialization and chronic inflammatory responses etc., which limit their applications in clinic. In this work, we constructed a novel TEHV with immunomodulatory functions by loading folic acid modified silver nanoparticles (FS NPs) on DHVs to overcome these issues. The FS NPs preferentially targeted M1 macrophages and reduced their intracellular H2O2 level, resulting in polarizing them into M2 phenotype. The increased M2 macrophages facilitated to eliminate inflammation, recruit endothelial cells, and promote their proliferation and endothelialization by secreting relative factors. We founded that FS NPs with the size of 80 nm modified DHVs (FSD-80) performed optimally on cytocompatibility and regulating macrophage phenotype ability in vitro. In addition, the FSD-80 had excellent mechanical properties, hemocompatibility and anti-bacteria property. The results of the subcutaneous implantation in rats revealed that the FSD-80 also had good performance in regulating macrophage phenotype, promoting endothelialization, remolding the extracellular matrix and anti-calcification in vivo. Therefore, FS NPs-loaded DHVs possess immunomodulatory functions, which is a feasible and promising strategy for constructing TEHVs with excellent comprehensive performance.

Role of 3D transoesophageal echocardiography in the study of infective endocarditis. Demonstration in a case collection.

Infective endocarditis (IE) is a condition that predominantly affects native or prosthetic heart valves, which is currently on the rise due to the increase in invasive cardiology procedures, such as the utilization of cardiac implantable electronic devices and transcatheter interventions. The recommended imaging tests for diagnosis are 2D transthoracic echocardiography (2D TTE) and 2D transoesophageal echocardiography (2D TOE). However, these modalities present limitations in detecting vegetations and estimating their dimensions. These disadvantages can be overcome by 3D transoesophageal echocardiography (3D TOE), particularly with the multiplanar reconstruction tool, which allows for the visualization of infinite valve planes, thus optimizing the detection of lesions and precise measurements. Furthermore, the volume rendering provides insight into the anatomical relationships between lesions, which is particularly useful for surgical planning. In this review, we aim to discuss the role of this recent imaging modality in the diagnosis, prognosis, and therapeutic of IE. Finally, we present a collection of images that illustrate the use of 3D TOE tools.

Native Infective Endocarditis: A State-of-the-Art-Review.

Native valve infective endocarditis (NVE) is a global phenomenon, defined by infection of a native heart valve and involving the endocardial surface. The causes and epidemiology of the disease have evolved in recent decades, with a doubling of the average patient age. A higher incidence was observed in patients with implanted cardiac devices that can result in right-sided infection of the tricuspid valve. The microbiology of the disease has also changed. Previously, staphylococci, which are most often associated with health-care contact and invasive procedures, were the most common cause of the disease. This has now been superseded by streptococci. While innovative diagnostic and therapeutic strategies have emerged, mortality rates have not improved and remain at 30%, which is higher than that for many cancer diagnoses. The lack of randomized trials and logistical constraints impede clinical management, and long-standing controversies such as the use of antibiotic prophylaxis persist. This state of the art review addresses clinical practice, controversies, and strategies to combat this potentially devastating disease. A multidisciplinary team will be established to provide care for patients with presumptive NVE. The composition of the team will include specialists in cardiology, cardiovascular surgery, and infectious disease. The prompt administration of combination antimicrobial therapy is essential for effective NVE treatment. Additionally, a meticulous evaluation of each patient is necessary in order to identify any indications for immediate valve surgery. With the intention of promoting a more comprehensive understanding of the procedural management of native infective endocarditis and to furnish clinicians with a reference, the current evidence for the utilization of distinct strategies for the diagnosis and treatment of NVE are presented.

Obstructions of prosthetic heart valves: diagnosis and treatment considerations

Objectives: Since the first years of native heart valve replacement by - prosthetic valves; prosthesis thrombogenicity has kept its importance as a serious problem causing post-operative morbidities and mortality. This study aims to evaluate early postoperative morbidity and mortality of patients diagnosed with prosthetic valve thrombosis and treated surgically or non-surgically. Methods: Thirty-one patients diagnosed with and treated for prosthetic valve thrombosis were evaluated retrospectively. The patients were followed up for 58 months. Results: There were 24 females and 7 males. The mean patient age at the time of prosthetic valve thrombosis diagnosis was 40.7±11 (range, 10-57) years. The mean duration between prosthetic valve replacement and the first signs of prosthetic valve thrombosis was 67.67±66 (range, 1 to 300) months. All patients presented with a functional capacity of NYHA Class III or IV. A total of 32 interventions; 27 surgical and 5 thrombolytic treatments due to elevated aortic prosthetic valve pressure gradient which did not improve with thrombolysis. Of 27 surgical interventions for thrombosed prosthetic valves, 21 involved mitral, 2 aortic, and 4 tricuspid positions. A total of 9 patients died during follow-up. The overall mortality rate was 29.03%. The mortality rate was 29.62% after surgical interventions and 20% after thrombolytic treatment. Conclusion: Currently prosthetic valve replacement is the basic palliation method in the management of patients with diseased native heart valves. In the majority of mechanical prosthetic valve obstructions, the main pathology is fibrous tissue proliferation-related to irregular warfarin usage, which in turn causes the development of acute symptoms secondary to acute valve thrombosis. The necessary treatment method for prosthetic valve obstructions should be either the use of thrombolytic agents or the replacement of the obstructed prosthetic valve with a new one.

Melt-electrowriting-enabled anisotropic scaffolds loaded with valve interstitial cells for heart valve tissue Engineering

Tissue engineered heart valves (TEHVs) demonstrates the potential for tissue growth and remodel, offering particular benefit for pediatric patients. A significant challenge in designing functional TEHV lies in replicating the anisotropic mechanical properties of native valve leaflets. To establish a biomimetic TEHV model, we employed melt-electrowriting (MEW) technology to fabricate an anisotropic PCL scaffold. By integrating the anisotropic MEW-PCL scaffold with bioactive hydrogels (GelMA/ChsMA), we successfully crafted an elastic scaffold with tunable mechanical properties closely mirroring the structure and mechanical characteristics of natural heart valves. This scaffold not only supports the growth of valvular interstitial cells (VICs) within a 3D culture but also fosters the remodeling of extracellular matrix of VICs. The in vitro experiments demonstrated that the introduction of ChsMA improved the hemocompatibility and endothelialization of TEHV scaffold. The in vivo experiments revealed that, compared to their non-hydrogel counterparts, the PCL-GelMA/ChsMA scaffold, when implanted into SD rats, significantly suppressed immune reactions and calcification. In comparison with the PCL scaffold, the PCL-GelMA/ChsMA scaffold exhibited higher bioactivity and superior biocompatibility. The amalgamation of MEW technology and biomimetic design approaches provides a new paradigm for manufacturing scaffolds with highly controllable microstructures, biocompatibility, and anisotropic mechanical properties required for the fabrication of TEHVs.

Gross morphology and morphometry of native and decellularized heart valves of caprine: A comparative study.

The gross morphological examination of native caprine heart valves revealed distinctive structural characteristics of the caprine's cardiac anatomy. Four primary orifices were identified, each protected by thin, valve-like structures. Atrioventricular orifices featured tricuspid and bicuspid valves, while the aorta and pulmonary arteries were guarded by semilunar valves. Within the atrioventricular apparatus, distinct features were observed including the tricuspid valve's three leaflets and the bicuspid valve's anterior and posterior leaflets. Ultrasonography provided insights into valve thickness and chordae tendineae lengths. Morphometric studies compared leaflets/cusps within individual native valves, showcasing significant variations in dimensions. Comparative analysis between native and decellularized valves highlighted the effects of decellularization on leaflet thickness and chordae tendineae lengths. Decellularized valves exhibited reduced dimensions compared to native valves, indicating successful removal of cellular components. While some dimensions remained unchanged post-decellularization, significant reductions were observed in leaflet thicknesses and chordae tendineae lengths. Notably, semilunar valve cusps displayed varying responses to decellularization, with significant reductions in cusp lengths observed in the aortic valve, while the pulmonary valve exhibited more subtle changes. These findings underscore the importance of understanding structural alterations in heart valves post-decellularization, providing valuable insights for tissue engineering applications and regenerative medicine.

ENDOCARDITIS TEAM? DESIGNING AN ORIGINAL AND TAILORED CLINICAL PATHWAY

Abstract Infective endocarditis (IE) remains a poorly understood disease that primarily affects either native or prosthetic heart valves. Its incidence has increased over the past two decades, now affecting 3 to 10 individuals per 100.000/year in the general population. Despite advances in early diagnosis and surgical intervention, IE continues to pose a significant challenge, often leading to severe complications and carrying a substantial burden of morbidity and mortality. Data from the EURO–Endo registry show a drastic change in IE and provide an accurate picture of IE disease today. In European countries, it tends to affect older patients with a remarkable 12% of cases occurring in those aged ≥ 80 years. The traditional care pathway is often fragmented into multiple and potentially dangerous steps, resulting in delayed diagnosis and treatment. Such a “patchy” approach may cause suboptimal patient management, especially in the subset of frail patients with important concomitant diseases and high surgical risk. Clinical pathways (CPs) are an evidence–based multidisciplinary care plans involving diagnosis, treatment and rehabilitation phases, through which to follow patients from hospital admission to discharge, in order to manage a specific health condition, aiming to optimize patient and hospital/team outcomes, while contributing to a better organized care processes. In 2018, a working group composed by healthcare managers, infectious disease specialists, cardiac surgeons, cardiologists, anesthesiologists, geriatricians and other professionals involved in the care of IE patients have engineered a dedicated CP for IE at our institution. The CP introduced significant changes in the management of patients with IE. As a result, the quality of care and services offered increased, a faster and more appropriate diagnosis and treatment were achieved, patient outcomes and safety improved and a better coordination and continuity of care between different settings was guaranteed. The growing burden of IE in western countries demands an evidence–based multidisciplinary care plan. The creation of a territorial network ensures continuity and appropriateness of care in conjunction with the referring physicians/hospital and rationalization of resources. Although some controversies still exist, we believe that CP will have a positive impact on quality in health care.

Optimization of Enzymatic and Chemical Decellularization of Native Porcine Heart Valves for the Generation of Decellularized Xenografts.

One of the most important medical interventions for individuals with heart valvular disease is heart valve replacement, which is not without substantial challenges, particularly for pediatric patients. Due to their biological properties and biocompatibility, natural tissue-originated scaffolds derived from human or animal sources are one type of scaffold that is widely used in tissue engineering. However, they are known for their high potential for immunogenicity. Being free of cells and genetic material, decellularized xenografts, consequently, have low immunogenicity and, thus, are expected to be tolerated by the recipient's immune system. The scaffold ultrastructure and ECM composition can be affected by cell removal agents. Therefore, applying an appropriate method that preserves intact the structure of the ECM plays a critical role in the final result. So far, there has not been an effective decellularization technique that preserves the integrity of the heart valve's ultrastructure while securing the least amount of genetic material left. This study demonstrates a new protocol with untraceable cells and residual DNA, thereby maximally reducing any chance of immunogenicity. The mechanical and biochemical properties of the ECM resemble those of native heart valves. Results from this study strongly indicate that different critical factors, such as ionic detergent omission, the substitution of Triton X-100 with Tergitol, and using a lower concentration of trypsin and a higher concentration of DNase and RNase, play a significant role in maintaining intact the ultrastructure and function of the ECM.

BIOLOGICAL PROSTHESES FOR CARDIOVASCULAR SURGERY – A HALF-CENTURY HISTORY AND DEVELOPMENT PROSPECTS

HighlightsSurgical correction of cardiovascular deformities is inextricably linked with the use of prostheses. The development and clinical testing of biological prostheses has been conducted under the guidance of the Member of Russian Academy of Sciences Leonid Barbarash at the Kuzbass Cardiology Center for more than 50 years. The uniqueness of the developed products lies in the use of a new biological tissue preservative – ethylene glycol diglycidyl ether, and an integrated approach involving the development and manufacture of products, study of long-term replacement outcome, causes of prosthetic dysfunction and genetic aspects of the use of bioprostheses in patients. AbstractThis article highlights the main achievements in the development of biological prostheses for cardiovascular surgery under the leadership of the Member of Russian Academy of Sciences L.S. Barbarash since the 1980s. Throughout this period, Leonid Barbarash and his team have developed and mass-produced various designs of bioprosthetic heart valves and tissue preservation methods, arterial grafts, and patches. The article presents the results of developing next-generation vascular biodegradable grafts capable of complete remodeling and stimulating endothelialization after the implantation into the vascular bed. Moreover, we conducted a series of genetic studies evaluating the significance of gene polymorphisms of various pathogenetic pathways involved in the pathological calcification of native heart valves and their prostheses.

Smoothed particle hydrodynamics based FSI simulation of the native and mechanical heart valves in a patient-specific aortic model

The failure of the aortic heart valve is common, resulting in deterioration of the pumping function of the heart. For the end stage valve failure, bi-leaflet mechanical valve (most popular artificial valve) is implanted. However, due to its non-physiological behaviour, a significant alteration is observed in the normal haemodynamics of the aorta. While in-vivo experimentation of a human heart valve (native and artificial) is a formidable task, in-silico study using computational fluid dynamics (CFD) with fluid structure interaction (FSI) is an effective and economic tool for investigating the haemodynamics of natural and artificial heart valves. In the present work, a haemodynamic model of a natural and mechanical heart valve has been developed using meshless particle-based smoothed particle hydrodynamics (SPH). In order to further enhance its clinical relevance, this study employs a patient-specific vascular geometry and presents a successful validation against traditional finite volume method and 4D magnetic resonance imaging (MRI) data. The results have demonstrated that SPH is ideally suited to simulate the heart valve function due to its Lagrangian description of motion, which is a favourable feature for FSI. In addition, a novel methodology for the estimation of the wall shear stress (WSS) and other related haemodynamic parameters have been proposed from the SPH perspective. Finally, a detailed comparison of the haemodynamic parameters has been carried out for both native and mechanical aortic valve, with a particular emphasis on the clinical risks associated with the mechanical valve.

Clinicopathological differences between Bartonella and other bacterial endocarditis-related glomerulonephritis - our experience and a pooled analysis.

Although Staphylococcus aureus is the leading cause of acute infective endocarditis (IE) in adults, Bartonella spp. has concomitantly emerged as the leading cause of "blood culture-negative IE" (BCNE). Pre-disposing factors, clinical presentation and kidney biopsy findings in Bartonella IE-associated glomerulonephritis (GN) show subtle differences and some unique features relative to other bacterial infection-related GNs. We highlight these features along with key diagnostic clues and management approach in Bartonella IE-associated GN. We conducted a pooled analysis of 89 cases of Bartonella IE-associated GN (54 published case reports and case series; 18 published conference abstracts identified using an English literature search of several commonly used literature search modalities); and four unpublished cases from our institution. Bartonella henselae and Bartonella quintana are the most commonly implicated species causing IE in humans. Subacute presentation, affecting damaged native and/or prosthetic heart valves, high titer anti-neutrophil cytoplasmic antibodies (ANCA), mainly proteinase-3 (PR-3) specificity, fastidious nature and lack of positive blood cultures of these Gram-negative bacilli, a higher frequency of focal glomerular crescents compared to other bacterial infection-related GNs are some of the salient features of Bartonella IE-associated GN. C3-dominant, but frequent C1q and IgM immunofluorescence staining is seen on biopsy. A "full-house" immunofluorescence staining pattern is also described but can be seen in IE -associated GN due to other bacteria as well. Non-specific generalized symptoms, cytopenia, heart failure and other organ damage due to embolic phenomena are the highlights on clinical presentation needing a multi-disciplinary approach for management. Awareness of the updated modified Duke criteria for IE, a high index of suspicion for underlying infection despite negative microbiologic cultures, history of exposure to animals, particularly infected cats, and use of send-out serologic tests for Bartonella spp. early in the course of management can help in early diagnosis and initiation of appropriate treatment. Diagnosis of IE-associated GN can be challenging particularly with BCNE. The number of Bartonella IE-associated GN cases in a single institution tends to be less than IE due to gram positive cocci, however Bartonella is currently the leading cause of BCNE. We provide a much-needed discussion on this topic.

Infectious endocarditis caused by Cutibacterium avidum in a patient with endocardial pacemaker and multiple drug hypersensitivity reactions: a clinical case

Cutibacterium avidum is a well-known skin commensal, that sometimes can cause superficial or invasive infections, including infectious endocarditis. Cases of C. avidum-induced infectious endocarditis of native heart valves, prosthetic valves or other cardiac implantable devices are described, which is associated with the biological feature of the pathogen with a tendency to form biofilms. The article presents a clinical case of infectious endocarditis, caused by C. avidum, associated with implantation of pacemaker in 42-yearold patient with a history of multiple drug hypersensitivity reactions to antibacterial drugs. This individual feature interfered with effective antibacterial therapy of local infection of the intracardiac device, which led to the development of infectious endocarditis with vegetations, required surgery with tricuspid valve repair and pacemaker replacement.

Templated Assembly of Silk Fibroin for a Bio‐Feedstock‐Derived Heart Valve Leaflet

AbstractBioprosthetic valves are employed to replace defective heart valves. However, structural degeneration is prevalent in bioprosthetic valves because the heart valve leaflets are exposed to extreme and repetitive cardiovascular pressure. Herein, a silk fibroin‐based heart valve leaflet, which executes the physiological role of a heart valve, is developed. To this end, a templated assembly technology is developed. Notably, a physically optimal hierarchical structure for replacing the natural heart valve leaflet is realized by numerous firmly stacked β‐sheet crystals distributed within collective tyrosine‐reinforcing amorphous strands. Almost half (46.9%) of the silk fibroin‐based heart valve leaflet comprises strongly stacked β‐sheet crystals, leading to a 292% enhancement in stacking strength. The templated assembly results in the entanglement of amorphous strands, upregulating the non‐covalent interactions within the tyrosine. Consequently, the strength is enhanced by 1380% compared to native silk fibroin. Moreover, the templated assembly enhances the static and dynamic mechanical properties, thereby delivering a desirable performance for its use in heart valve replacement. Interestingly, the aortic valve composed of silk fibroin‐based leaflets does not fail under the cardiovascular pressure of 60–180 mmHg. Furthermore, the valve performance is satisfactory and surmounts the requirements of the industrial standard ISO 5840.

Recent progress in functional modification and crosslinking of bioprosthetic heart valves.

Valvular heart disease (VHD), clinically manifested as stenosis and regurgitation of native heart valve, is one of the most prevalent cardiovascular diseases with high mortality. Heart valve replacement surgery has been recognized as golden standard for the treatment of VHD. Owing to the clinical application of transcatheter heart valve replacement technic and the excellent hemodynamic performance of bioprosthetic heart valves (BHVs), implantation of BHVs has been increasing over recent years and gradually became the preferred choice for the treatment of VHD. However, BHVs might fail within 10-15 years due to structural valvular degeneration (SVD), which was greatly associated with drawbacks of glutaraldehyde crosslinked BHVs, including cytotoxicity, calcification, component degradation, mechanical failure, thrombosis and immune response. To prolong the service life of BHVs, much effort has been devoted to overcoming the drawbacks of BHVs and reducing the risk of SVD. In this review, we summarized and analyzed the research and progress on: (i) modification strategies based on glutaraldehyde crosslinked BHVs and (ii) nonglutaraldehyde crosslinking strategies for BHVs.

Partial heart transplantation: Growing heart valve implants for children.

Heart valves serve a vital hemodynamic function to ensure unidirectional blood flow. Additionally, native heart valves serve biological functions such as growth and self-repair. Heart valve implants mimic the hemodynamic function of native heart valves, but are unable to fulfill their biological functions. We developed partial heart transplantation to deliver heart valve implants that fulfill all functions of native heart valves. This is particularly advantageous for children, who require growing heart valve implants. This invited review outlines the past, present and future of partial heart transplantation.

Clinical and morphological features of infective endocarditis of native and prosthetic heart valves

Aim. To evaluate clinical and morphological data of infective endocarditis (IE) of native and prosthetic heart valves.Material and methods. This retrospective cohort study included 354 patients that had signs of IE according to pathological study of surgical material from native valves and prosthetic heart valves. The patients were divided into two groups: the first group included patients with native valve IE (n=328), while the second group — with prosthetic valve IE (n=26).Results. Among patients with native valve IE, aortic (AV) and mitral valve (MV) IE was recorded in 67,6% and 20,7%, respectively. In the group of patients with prosthetic IE, AV IE also predominated — 57,7% vs 26,9% in MV IE. In the majority of patients in the first group, secondary IE was detected (68,9%). The development of IE in the presence of bicuspid AV (BAV), degenerative AV disease, and rheumatic valve disease was revealed in 40,7%, 31,4% and 6,7%, respectively. In the group of patients with native valve IE, subactive IE was most often detected — in 38,4%, while in 7,1% — signs of process remission were detected. In the group of patients with prosthetic valve IE, IE with moderate activity was detected more often than in the group of patients with native valve IE (42,3% vs 26,8%, p=0,042). In the group of patients with prosthetic valve IE, the presence of colonies of microorganisms and neutrophilic infiltration in the histological material was somewhat more common, while in patients with native valve IE there was a tendency towards a higher percentage of necrosis in the studied material (42,4% vs 38,5%, p&gt;0,05).Conclusion. This work confirms changes in the epidemiological characteristics of patients with IE. A high frequency of subactive forms of IE was noted according in patients with native valve IE, which requires individual approach to antibacterial therapy depending on the pathomorphological IE activity.

Cytokine expression profile of native heart valves obtained from patients with infective endocarditis

Infectious endocarditis is characterized by dysfunction of heart valves and contribute significantly to the cardiovascular morbidity and mortality worldwide, especially in low- and middle-income countries. Immune response is playing the important role in the pathophysiology of this disease. This work was aimed to study the local cytokine profile in native heart valves obtained from the patients with infectious endocarditis. Cytokine profiling were performed in biopsies of native heart valves explanted from 4 patients with infective endocarditis (experimental group) and 10 patients with rheumatic heart disease (comparison group) by dot blotting using the Proteome Profiler™ Human Cytokine Array Kit (ARY005B). The results of dot blotting were validated by the gene expression profiling using quantitative polymerase chain reaction. MIF, PAI-1, ICAM-1 and CXCL12 were found in the native heart valves explanted from both infective endocarditis and rheumatic heart disease patients. Upon a semi-quantitative assessment, the heart valves explanted from the infective endocarditis patients were characterized by 4-fold increased secretion of PAI-1 and twofold decreased secretion of ICAM-1 and CXCL12 compared to the heart valves ffected by rheumatic heart disease. MIF was expressed on similar levels in the both studied groups. IL-1ra, IL-6, IL-8, IL-16, CCL4, CCL5 and CXCL1 were detected only in heart valves affected by infectious endocarditis. At the gene expression level, MIF, IL6, IL8 genes were upregulated and PAI1, IL1RA, CXCL1 genes were downregulated in heart valves explanted from infectious endocarditis patients compared to the subjects affected by rheumatic heart disease. Native heart valves in cases of infectious endocarditis are characterized by nonspecific local inflammatory response associated with pathogenic bacteremia, along with active neovascularization. The data obtained can help to better understand fundamental pathogenetic mechanisms of infectious endocarditis.