Native Heart Valves Research Articles

Paravalvular Abscess as a Complication of Streptococcus Salivarius Infective Endocarditis of a Bioprosthetic Aortic Valve.

Rates of implantation of prosthetic valves and cardiac devices have increased significantly in the last thirty years, accounting, at least in-part, for the growing incidence of infective endocarditis cases. Prosthetic valve endocarditis (PVE) is an endovascular, microbial infection occurring on parts of a valve prosthesis or on reconstructed native heart valves. We present a case of a 63-year-old man with multiple comorbidities including extensive cardiovascular disease, who recently underwent bioprosthetic aortic valve replacement. Patient presented to the emergency department with exertional chest pain, dyspnea, fever, melena and lethargy. Blood cultures grew Streptococcus salivarius and transesophageal echocardiography confirmed PVE with an aortic paravalvular abscess. The patient was treated with appropriate antimicrobial therapy based on culture sensitivity and subsequently referred to cardiothoracic surgery for urgent evaluation. This case highlights several important points which include but are not limited to: investigation into the pathogen Streptococcus salivarius and its relationship to other known pathogens, understanding of the complications associated with PVE, and the importance of early identification of PVE and initiation of medical and surgical therapy with respect to prognosis.

Trilayered tissue construct mimicking the orientations of three layers of a native heart valve leaflet.

A tissue-engineered heart valve can be an alternative to a prosthetic valve in heart valve replacement; however, it is not fully efficient in terms of long-lasting functionality, as leaflets in engineered valves do not possess the trilayered native leaflet structure. Previously, we developed a flat, trilayered, oriented nanofibrous (TN) scaffold mimicking the trilayered structure and orientation of native heart valve leaflets. In vivo tissue engineering-a practical regenerative medicine technology-can be used to develop an autologous heart valve. Thus, in this study, we used our flat, trilayered, oriented nanofibrous scaffolds to develop trilayered tissue structures with native leaflet orientations through in vivo tissue engineering in a rat model. After 2months of in vivo tissue engineering, infiltrated cells and their deposited collagen fibrils were found aligned in the circumferential and radial layers, and randomly oriented in the random layer of the scaffolds, i.e., trilayered tissue constructs (TTCs) were developed. Tensile properties of the TTCs were higher than that of the control tissue constructs (without any scaffolds) due to influence of fibers of the scaffolds in tissue engineering. Different extracellular matrix proteins-collagen, glycosaminoglycans, and elastin-that exist in native leaflets were observed in the TTCs. Gene expression of the TTCs indicated that the tissue constructs were in growing stage. There was no sign of calcification in the tissue constructs. The TTCs developed with the flat TN scaffolds indicate that an autologous leaflet-shaped, trilayered tissue construct that can function as a native leaflet can be developed.

Infective endocarditis in South Africa

Infective endocarditis (IE) is defined by infection of either a native or prosthetic heart valve, endocardial surface or any cardiac prosthetic device. It is a disease of both the developed and developing world, although IE has evolved in the developed world to a disease markedly different to the disease encountered in the developing world. IE in developed nations is mainly a disease of older patients with degenerative heart valve disease or cardiac prosthetic material, with virulent Staphylococci the most common causative organism. Data regarding the epidemiology of IE in South Africa, a developing country, is limited. The available data suggest it is still a disease of younger patients with rheumatic heart disease (RHD), associated with penicillin-sensitive Streptococcal infection. Although novel diagnostic techniques and improved therapeutic options has emerged, the 1-year mortality rate has remained high in both the developed and developing world at around 30%.

What is the Remodeling Potential of the Native Heart Valve?

Objective: Regenerative therapies directed at the restoration of heart valve function rely on an understanding on how native heart valve structures remodel and possibly regenerate. However, we know...

Improving the Stability of Blood Flow through Mechanical Artificial Tricuspid Valves of the Heart

Hemodynamic characteristics of two models of mechanical artificial tricuspid valves of the heart were compared: Tricardix (RF Patent No. 2325874) and MAHV (RF Patent No. 181544). 3D models of the artificial heart valves under study were created. The operational environment conditions were simulated using SolidWorks. SolidWorks Flow Simulation was used for hemodynamic calculations. The efficiency criteria were determined on the basis of the hemodynamic parameters of a native aortic heart valve.

Rate-Dependent and Relaxation Properties of Porcine Aortic Heart Valve Biomaterials.

Objective: This work evaluates the rate-dependent and relaxation properties of native porcine heart valves, glutaraldehyde fixed porcine pericardium, and decellularized sterilized porcine pericardium. Methods: Biaxial tension testing was performed at strain-rates of 0.001 s−1, 0.01 s−1, 0.1 s−1, and 1 s−1. Finally, relaxation testing for 300 s was performed on all heart valve biomaterials. Results: No notable rate-dependent response was observed for any of the three biomaterials with few significant differences between any strain-rates. For relaxation testing, native tissues showed the most pronounced drop in stress and glutaraldehyde the lowest drop in stress although no tissues showed anisotropy in the relaxation. Conclusions: Increasing the strain-rate of the three biomaterials considered does not increase the stress within the tissue. This indicates that there will not be increased fatigue from accelerated wear testing compared to loading at physiological strain-rates as the increase strain-rates would likely not significantly alter the tissue stress.

The expression level of cytokine genes in the cases of native heart valves in infectious endocarditis

The expression level of IL1B, IL6, IL8, IL10, IL12A, IL12B, IL18, IL23, IL33, CCL2, and IL1RL1 has been investigated using biopsies of native mitral, aortic, and tricuspid valves obtained during surgical correction of acquired defect from 25 patients with infectious endocarditis. Biopsies of native mitral and aortic valve cusps from 12 patients who underwent surgical correction of acquired heart disease of non-infectious etiology were used as control. We used quantitative PCR with fluorescent dye SYBR Green for determination of the cytokine gene expression level. This study revealed that genes could be subdivided into three groups: (i) genes with increased expression (IL1B, IL6, and IL8); (ii) genes with reduced expression (IL33 and IL1RL1); (iii) genes with unchanged expression (IL12A, IL18, IL23, and CCL2). The IL8 gene expression was characterized by the most pronounced increase (9.83 times versus control), while the IL1RL1 gene demonstrated the most pronounced decrease in its expression (4.17 times). Expression of IL10 and IL12B genes was negligible in all samples.

In vivo tissue engineering of a trilayered leaflet-shaped tissue construct.

Aim: We aimed to develop a leaflet-shaped trilayered tissue construct mimicking the morphology of native heart valve leaflets. Materials & methods: Electrospinning and in vivo tissue engineering methods were employed. Results:We developed leaflet-shaped microfibrous scaffolds, each with circumferentially, randomly and radially oriented three layers mimicking the trilayered, oriented structure of native leaflets. After 3 months in vivo tissue engineering with the scaffolds, the generated leaflet-shaped tissue constructs had a trilayered structure mimicking the orientations of native heart valve leaflets. Presence of collagen, glycosaminoglycans and elastin seen in native leaflets was observed in the engineered tissue constructs. Conclusion: Trilayered, oriented fibrous scaffolds brought the orientations of the infiltrated cells and their produced extracellular matrix proteins into the constructs.

P641 Severe pulmonary steno-insufficiency due to metastatic carcinoid tumor in a 57 years old patient treated with MTPV implantation: first experience

Abstract Funding Acknowledgements none Background Right side heart valve involvement is a well known phenomenon in metastatic carcinoid disease. In recent times bioprosthetic valves have been widely used for replacement of stenotic and regurgitant native heart valves. Melody Transcatheter Pulmonary Valve (MTPV, Medtronic, Minneapolis, MN, USA) has been approved for treatment of native pulmonary valves as well as failing biological prostheses and conduits. We present the first case to our knowledge of severe native pulmonary valve steno-insufficiency due to metastatic carcinoid syndrome treated with MTPV implantation. Case report A 57-year-old woman is known since 2007 for metastatic carcinoid syndrome treated with surgical resection followed by chemotherapy (tamoxifene, everolimus) and radiotherapy. For 2 years she has been known for tricuspid and pulmonary involvement, which aggravated progressively, leading to symptomatic right heart failure. She was therefore submitted for multimodality imaging evaluation (see picture) and right heart catheterization. Transthoracic echocardiogram, cardiac MRI and right heart catheterization confirmed severe pulmonary valve steno-insufficiency. Cardiopulmonary exercise testing revealed a severe limitation of aerobic exercise capacity (VO2 max 14.4 ml/min/kg). After heart team discussion it was decided to treat the patient in a 2 step approach, initially with implantation of a Melody valve in pulmonary position and subsequently with surgical repair of the tricuspid valve. Pulmonary valve was treated by placement of a 39 x 25 mm ANDRA stent and subsequent implantation of a 22 mm Melody valve. Before stenting, coronary angiography with simultaneous balloon inflation in RVOT was performed to exclude coronary artery compression. During the procedure the patient developed hypotension, which was treated effectively with Octeotride. Post-operative echocardiogram showed a significant reduction in pulmonary valve gradient and no significant residual regurgitation. Conclusions We treated effectively severe pulmonary steno-insufficiency due to metastatic carcinoid tumor with MTPV implantation. No complications occurred. Multimodality imaging is fundamental for patients selection and preoperative planning of prosthetic valve dimensions. Abstract P641 Figure. Multimodality imaging of PV

Structure and Rheological Properties of Bovine Aortic Heart Valve and Pericardium Tissue: Implications in Bioprosthetic and Tissue-Engineered Heart Valves.

Heart valve (HV) diseases are among the leading causes of cardiac failure and deaths. Of the various HV diseases, damaged HV leaflets are among the primary culprits. In many cases, impaired HV restoration is not always possible, and the replacement of valves becomes necessary. Bioprosthetic HVs have been used for the replacement of the diseased valves, which is obtained from the sources of bovine and porcine origin, while tissue-engineered heart valves (TEHV) have emerged as a promising future solution. The bioprosthetic valves are prone to become calcified, and thus they last for only ten to fifteen years. The adequate understanding of the correlations between the biomechanics and rheological properties of native HV tissues can enable us to improve the durability of the bioprosthetic HV as well as help in the development of tissue-engineered heart valves (TEHV). In this study, the structural and rheological properties of native bovine aortic HV and pericardium tissues were investigated. The microstructures of the tissues were investigated using scanning electron microscopy, while the rheological properties were studied using oscillatory shear measurement and creep test. The reported results provide significant insights into the correlations between the microstructure and viscoelastic properties of the bovine aortic HV and pericardium tissues.

Bio-inspired anisotropic polymeric heart valves exhibiting valve-like mechanical and hemodynamic behavior

Native heart valve leaflets with layered fibrous structures show anisotropic characteristics, allowing them to withstand complex mechanical loading for long-term cardiac cycles. Herein, two types of silk fibroin (SF) fiber membranes with anisotropic (ASF) and isotropic (ISF) properties were prepared by electrospinning, and were further combined with poly(ethylene glycol) diacrylate (PEGDA) hydrogels to serve as polymeric heart valve (PHV) substitutes (PEGDA-ASF and PEGDA-ISF). The uniaxial tensile tests showed obvious anisotropy of PEGDA-ASF with elastic moduli of 10.95±1.09 and 3.55± 0.32 MPa, respectively, along the directions parallel and perpendicular to the fiber alignment, while PEGDA-ISF possessed isotropic property with elastic moduli of 4.54± 0.43 MPa. The PHVs from both PEGDA-ASF and PEGDA-ISF presented appropriate hydrodynamic properties from pulse duplicator tests according to the ISO 5840-3 standard. However, finite element analysis (FEA) revealed the anisotropic PEGDA-ASF valve showed a lower maximum principle stress value (2.20 MPa) in commissures during diastole compared with that from the isotropic PEGDA-ISF valve (2.37 MPa). In the fully open state, the bending area of the PEGDA-ASF valve appeared in the belly portion and near the attachment line like native valves, however, which was close to free edges for the PEGDA-ISF valve. The Gauss curvature analysis also indicated that the anisotropic PEGDA-ASF valve can produce appropriate surface morphology by dynamically adjusting the movement of bending area during the opening process. Hence, anisotropy of PHVs with bio-inspired layered fibrous structures played important roles in mechanical and hydrodynamic behavior mimicking native heart valves.

Materials and manufacturing perspectives in engineering heart valves: a review.

Valvular heart diseases (VHD) are a major health burden, affecting millions of people worldwide. The treatments for such diseases rely on medicine, valve repair, and artificial heart valves including mechanical and bioprosthetic valves. Yet, there are countless reports on possible alternatives noting long-term stability and biocompatibility issues and highlighting the need for fabrication of more durable and effective replacements. This review discusses the current and potential materials that can be used for developing such valves along with existing and developing fabrication methods. With this perspective, we quantitatively compare mechanical properties of various materials that are currently used or proposed for heart valves along with their fabrication processes to identify challenges we face in creating new materials and manufacturing techniques to better mimick ​the performance of native heart valves.

Systematic review and meta-analysis of surgical outcomes comparing mechanical valve replacement and bioprosthetic valve replacement in infective endocarditis.

Infective endocarditis (IE) is an infection involving either native or prosthetic heart valves, the endocardial surface of the heart or any implanted intracardiac devices. IE is a rare condition affecting 3-15 patients per 100,000 population. In-hospital mortality rates in patients with IE remain high at around 20% despite treatment advances. There is no consensus recommendation favoring either bioprosthetic valve or mechanical valve implantation in the setting of IE; patient age, co-morbidities and preferences should be considered selecting the replacement prosthesis. A systematic review and meta-analysis of studies reporting the outcomes of patients undergoing bioprosthetic or mechanical valve replacement for infective endocarditis with data extracted for overall survival, valve reinfection rates and valve reoperation. Eleven relevant studies were identified, with 2,336 patients receiving a mechanical valve replacement and 2,057 patients receiving a bioprosthetic valve replacement. There was no significant difference for overall survival between patients treated with mechanical valves and those treated with bioprosthetic valves [hazard ratio (HR) 0.94, 95% confidence interval (CI): 0.73-1.21, P=0.62]. There was no significant difference in reoperation rates between patients treated with a bioprosthetic valve and those treated with a mechanical valve (HR 0.82, 95% CI: 0.34-1.98, P=0.66) and there was no significant difference in the rate of valve reinfection rates (HR 0.95, 95% CI: 0.48-1.89, P=0.89). The presence of infective endocarditis alone should not influence the decision of which type of valve prosthesis that should be implanted. This decision should be based on patient age, co-morbidities and preferences.

1357. Mycobacterium abscessus Native Tricuspid Valve Endocarditis. Is a 6-Week Course of Combination Antibiotic Therapy Enough?

BackgroundInfective endocarditis of the native heart valves due to M. abscessus has been reported in individuals who inject drugs. Only one case thus far has been reported with survival beyond 4 months after completion of antibiotic therapy. 24-year-old Caucasian woman with a history of intravenous drug use presented with intermittent fevers for 3–4 months. She was having chills, night sweats, and productive cough. She acknowledged using intravenous cocaine and heroin every few days after being discharged from our hospital 6 months previously when she was treated for tricuspid valve endocarditis. Chest radiograph demonstrated right lower lobe airspace disease suggestive of pneumonia. Three days later her blood cultures grew acid-fast bacilli, later identified as M. abscessus.MethodsShe was empirically treated with azithromycin, amikacin, and imipenem. Transthoracic and transesophageal echocardiograms were suggestive of tricuspid valve endocarditis. CT angiogram of the chest showed filling defects within several large right lower lobe pulmonary arteries and dense right lower lobe consolidation with pleural effusion. The patient underwent bronchoscopy with bronchoalveolar lavage (BAL) and therapeutic thoracoscopy with drainage and thoracostomy tube placement. BAL cultures also grew AFB. Multiple sets of blood cultures drawn after commencement of antibiotic therapy during the hospital course were negative. Drug susceptibilities were available 3 weeks later. The isolate was susceptible to amikacin. Linezolid, imipenem, and cefoxitin exhibited intermediate activity, and TMP/SMX, ciprofloxacin, moxifloxacin, doxycycline, minocycline, and clarithromycin were reported resistant. Inducible erm gene was present. Azithromycin and linezolid were discontinued and tigecycline was added.ResultsPatient completed 6 weeks of antibiotics from the day of the first negative blood culture. Repeat TTE 1 month after completion of therapy revealed a decrease in tricuspid valve vegetation. Blood culture done 3 months later was sterile. AFB blood cultures done a year later did not report any growth.ConclusionThis case opens a debate, if in a selected group of patients, a short course of combination antibiotic therapy is enough to obtain cure. This will require further analysis. Disclosures All authors: No reported disclosures.

Valve leaflet‐inspired elastomeric scaffolds with tunable and anisotropic mechanical properties

Fibrous scaffolds, which can mimic the elastic and anisotropic mechanical properties of native tissues, hold great promise in recapitulating the native tissue microenvironment. We previously fabricated electrospun fibrous scaffolds made of hybrid synthetic elastomers (poly(1,3‐diamino‐2‐hydroxypropane‐co‐glycerol sebacate)‐co‐poly (ethylene glycol) (APS‐co‐PEG) and polycaprolactone (PCL)) to obtain uniaxial mechanical properties similar to those of human aortic valve leaflets. However, conventional electrospinning process often yields scaffolds with random alignment, which fails to recreate the anisotropic nature of most of the soft tissues such as native heart valves. Inspired by the structure of native valve leaflet, we designed a novel valve leaflet‐inspired ring‐shaped collector to modulate the electrospun fiber alignment and studied the effect of polymer formulation (PEG amount [mole %] in APS‐co‐PEG; ratio between APS‐co‐PEG and PCL; and total polymer concentration) in tuning the biaxial mechanical properties of the fibrous scaffolds. The fibrous scaffolds collected on the ring‐shaped collector displayed anisotropic biaxial mechanical properties, suggesting that their biaxial mechanical properties are closely associated with the fiber alignment in the scaffold. Additionally, the scaffold stiffness was easily tuned by changing the composition and concentration of the polymer blend. Human valvular interstitial cells (hVICs) cultured on these anisotropic scaffolds displayed aligned morphology as instructed by the fiber alignment. Overall, we generated a library of biologically relevant fibrous scaffolds with tunable mechanical properties, which will guide the cellular alignment.

Trilayer scaffold with cardiosphere‐derived cells for heart valve tissue engineering

Natural polymers collagen, glycosaminoglycans, and elastin are promising candidate materials for heart valve tissue engineering scaffolds. This work produced trilayer scaffolds that resembled the layered structures of the extracellular matrices of native heart valves. The scaffolds showed anisotropic bending moduli (in both dry and hydrated statuses) depending on the loading directions (lower in the With Curvature direction than in the Against Curvature direction), which mimicked the characteristic behavior of the native heart valves. The interactions between cardiosphere-derived cells and the scaffolds were characterized by multiphoton microscopy, and relatively similar cell distributions were observed on different layers (a cell density of 3,000-4,000 mm-3 and a migration depth of 0.3-0.4 mm). The trilayer scaffold has represented a forwarding step from the previous studies, in attempting to better replicate a native heart valve structurally, mechanically, and biologically.

Biologically Inspired Scaffolds for Heart Valve Tissue Engineering via Melt Electrowriting.

Heart valves are characterized to be highly flexible yet tough, and exhibit complex deformation characteristics such as nonlinearity, anisotropy, and viscoelasticity, which are, at best, only partially recapitulated in scaffolds for heart valve tissue engineering (HVTE). These biomechanical features are dictated by the structural properties and microarchitecture of the major tissue constituents, in particular collagen fibers. In this study, the unique capabilities of melt electrowriting (MEW) are exploited to create functional scaffolds with highly controlled fibrous microarchitectures mimicking the wavy nature of the collagen fibers and their load-dependent recruitment. Scaffolds with precisely-defined serpentine architectures reproduce the J-shaped strain stiffening, anisotropic and viscoelastic behavior of native heart valve leaflets, as demonstrated by quasistatic and dynamic mechanical characterization. They also support the growth of human vascular smooth muscle cells seeded both directly or encapsulated in fibrin, and promote the deposition of valvular extracellular matrix components. Finally, proof-of-principle MEW trileaflet valves display excellent acute hydrodynamic performance under aortic physiological conditions in a custom-made flow loop. The convergence of MEW and a biomimetic design approach enables a new paradigm for the manufacturing of scaffolds with highly controlled microarchitectures, biocompatibility, and stringent nonlinear and anisotropic mechanical properties required for HVTE.

Ectopic mineralization in heart valves: new insights from in vivo and in vitro procalcific models and promising perspectives on noncalcifiable bioengineered valves.

Ectopic calcification of native and bioprosthetic heart valves represents a major public health problem causing severe morbidity and mortality worldwide. Valve procalcific degeneration is known to be caused mainly by calcium salt precipitation onto membranes of suffering non-scavenged cells and dead-cell-derived products acting as major hydroxyapatite nucleators. Although etiopathogenesis of calcification in native valves is still far from being exhaustively elucidated, it is well known that bioprosthesis mineralization may be primed by glutaraldehyde-mediated toxicity for xenografts, cryopreservation-related damage for allografts and graft immune rejection for both. Instead, mechanical valves, which are free from calcification, are extremely thrombogenic, requiring chronic anticoagulation therapies for transplanted patients. Since surgical substitution of failed valves is still the leading therapeutic option, progressive improvements in tissue engineering techniques are crucial to attain readily available valve implants with good biocompatibility, proper functionality and long-term durability in order to meet the considerable clinical demand for valve substitutes. Bioengineered valves obtained from acellular non-valvular scaffolds or decellularized native valves are proving to be a compelling alternative to mechanical and bioprosthetic valve implants, as they appear to permit repopulation by the host's own cells with associated tissue remodelling, growth and repair, besides showing less propensity to calcification and adequate hemodynamic performances. In this review, insights into valve calcification onset as revealed by in vivo and in vitro procalcific models are updated as well as advances in the field of valve bioengineering.

Bioprosthetic Heart Valves: Upgrading a 50-Year Old Technology.

Prosthetic heart valves have been commonly used to address the increasing prevalence of valvular heart disease. The ideal prosthetic heart valve substitute should closely mimic the characteristics of a normal native heart valve. Despite the development of various interventions, an exemplary valve replacement does not exist. This review provides an overview of the novel engineering valve designs and explores emergent immunologic insights into age-dependent structural valve degeneration (SVD).

Hybrid Pericardium with VEGF-Loaded Hyaluronic Acid Hydrogel Coating to Improve the Biological Properties of Bioprosthetic Heart Valves.

Bioprosthetic heart valves (BHVs) used in the clinic are mostly fixed by glutaraldehyde and the lack of endothelialization is a major problem for glutaraldehyde-fixed pericardia. Hyaluronic acid is a major glycosaminoglycan that exists in native heart valves. Coupled with its inherent biocompatibility, it may enhance endothelial adhesion and proliferation when associated with vascular endothelial growth factor (VEGF). In this study, an optimized system is developed to improve the endothelialization of glutaraldehyde-fixed pericardium. A hybrid pericardium with VEGF-loaded hyaluronic acid hydrogel coating is developed by the crosslinking of 1,4-butanediol diglycidyl ether. The adhesion and growth potential of human umbilical vein endothelial cells (HUVECs) on pericardia, platelet adhesion, and calcification by an in vivo rat subdermal implantation model are investigated. The results show improved HUVEC adhesion and proliferation, less platelet adhesion, and less calcification for hybrid pericardium by introducing the coating of VEGF-loaded hyaluronic acid hydrogel. Thus, the coating of VEGF-loaded hyaluronic acid hydrogel on pericardium is a promising approach to obtain bioprosthetic valves for clinical applications with increased endothelialization and antithrombotic and anticalcification properties.