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Heart valve replacement surgeries are performed on patients suffering from abnormal heart valve function. In these operations, the problematic tissue is replaced with mechanical valves or with bioprosthetics that are being developed. The thrombotic effect of mechanical valves, reflecting the need for lifelong use of anticoagulation drugs, and the short‐lived nature of biological valves make these two types of valves problematic. In addition, they cannot adapt to the somatic growth of young patients. Although decellularized scaffolds have shown some promise, a successful translation has so far evaded. Although decellularized porcine xenografts have been extensively studied in the literature, they have several disadvantages, such as a propensity for calcification in the implant model, a risk of porcine endogenous retrovirus (PERV) infection, and a high xenoantigen density. As seen in clinical data, it is clear that there are biocompatibility problems in almost all studies. However, since decellularized sheep heart valves have not been tried in the clinic, a large data pool could not be established. This review compares and contrasts decellularized porcine and sheep xenografts for heart valve tissue engineering. It reveals that decellularized sheep heart valves can be an alternative to pigs in terms of biocompatibility. In addition, it highlights the potential advantages of bioinks derived from the decellularized extracellular matrix in 3D bioprinting technology, emphasizing that they can be a new alternative for the application. We also outline the future prospects of using sheep xenografts for heart valve tissue engineering. [ABSTRACT FROM AUTHOR]

During the Ross procedure, an aortic heart valve is replaced by a patient's own pulmonary valve. The pulmonary autograft subsequently undergoes substantial growth and remodeling (G&R) due to its exposure to increased hemodynamic loads. In this study, we developed a homogenized constrained mixture model to understand the observed adaptation of the autograft leaflets in response to the changed hemodynamic environment. This model was based on the hypothesis that tissue G&R aims to preserve mechanical homeostasis for each tissue constituent. To model the Ross procedure, we simulated the exposure of a pulmonary valve to aortic pressure conditions and the subsequent G&R of the valve. Specifically, we investigated the effects of assuming either stress- or stretch-based mechanical homeostasis, the use of blood pressure control, and the effect of root dilation. With this model, we could explain different observations from published clinical studies, such as the increase in thickness, change in collagen organization, and change in tissue composition. In addition, we found that G&R based on stress-based homeostasis could better capture the observed changes in tissue composition than G&R based on stretch-based homeostasis, and that root dilation or blood pressure control can result in more leaflet elongation. Finally, our model demonstrated that successful adaptation can only occur when the mechanically induced tissue deposition is sufficiently larger than tissue degradation, such that leaflet thickening overrules leaflet dilation. In conclusion, our findings demonstrated that G&R based on mechanical homeostasis can capture the observed heart valve adaptation after the Ross procedure. Finally, this study presents a novel homogenized mixture model that can be used to investigate other cases of heart valve G&R as well. [ABSTRACT FROM AUTHOR]

Background: Partial heart transplantation delivers growing heart valve implants by transplanting the part of the heart containing the necessary heart valve only. In contrast to heart transplantation, partial heart transplantation spares the native ventricles. This has important implications for partial heart transplant biology, including the allowable ischemia time, optimal graft preservation, primary graft dysfunction, immune rejection, and optimal immunosuppression. Aims: Exploration of partial heart transplant biology will depend on suitable animal models. Here we review our experience with partial heart transplantation in rodents, piglets, and non‐human primates. Materials & Methods: This review is based on our experience with partial heart transplantation using over 100 rodents, over 50 piglets and one baboon. Results: Suitable animal models for partial heart transplantation include rodent heterotopic partial heart transplantation, piglet orthotopic partial heart transplantation, and non‐human primate partial heart xenotransplantation. Discussion: Rodent models are relatively cheap and offer extensive availability of research tools. However, rodent open‐heart surgery is technically not feasible. This limits rodents to heterotopic partial heart transplant models. Piglets are comparable in size to children. This allows for open‐heart surgery using clinical grade equipment for orthoptic partial heart transplantation. Piglets also grow rapidly, which is useful for studying partial heart transplant growth. Finally, nonhuman primates are immunologically most closely related to humans. Therefore, nonhuman primates are most suitable for studying partial heart transplant immunobiology and xenotransplantation. Conclusions: Animal research is a privilege that is contingent on utilitarian ethics and the 3R principles of replacement, reduction and refinement. This privilege allows the research community to seek fundamental knowledge about partial heart transplantation, and to apply this knowledge to enhance the health of children who require partial heart transplants. [ABSTRACT FROM AUTHOR]

Background: Enhanced recovery after surgery (ERAS) protocols aim to reduce postoperative complications and promote earlier recovery. Although it is well established in noncardiac surgery fields, the ERAS approach has only recently been adopted in cardiac surgery. The aim of this review is to evaluate the status and implementation of ERAS protocols in patients undergoing heart valve surgery and to summarise associated clinical results. Methods: A literature search for the period January 2015 and January 2024 was performed through online databases. Clinical studies (randomised controlled trials and cohort studies) on patients undergoing heart valve surgical procedures and comparing ERAS and conventional approaches were included. The data extracted covered studies and populations characteristics, early outcomes and the features of each ERAS protocol. Results: There were 14 studies that fulfilled the final search criteria and were ultimately included in the review. Overall, 5142 patients were identified in the 14 studies, with 2501 in ERAS groups and 2641 patients who were representative of control groups. Seven experiences exclusively included patients who underwent heart valve surgery. Twelve out of fourteen protocols involved multiple interventions from the preoperative to postoperative phase, while two studies reported actions limited to intraoperative and postoperative care. We found high heterogeneity among the included protocols regarding key actions targeted for improvement and measured outcomes. All the studies showed that ERAS pathways can be safely adopted in cardiac surgery and in most of the experiences were associated with shorter mechanical ventilation time, reduced postoperative opioid use and reduced ICU and hospital stays. Conclusions: As demonstrated in noncardiac surgery, the adoption of structured ERAS protocols has the potential to improve results in patients undergoing heart valve surgery. Further evidence based on larger populations is needed, including more homogenous pathways and reporting further outcomes in terms of patient satisfaction, recovery and quality of life after surgery. [ABSTRACT FROM AUTHOR]

Objectives APS-associated heart valve disease (HVD) is well described. Nonetheless, limited data exist on clinical parameters associated with the course of primary APS (pAPS) patients with HVD. The goal of this study was to assess clinical features and related outcomes in patients with APS-associated HVD. Methods In this multicentre retrospective study, we identified 33 pAPS patients with HVD (pAPS-HVD group) and compared their clinical course with 128 pAPS patients with normal heart valves on echocardiography (pAPS-control group). Results pAPS-HVD patients had more cerebrovascular events (56.3% vs 25%, P  = 0.005) and livedo reticularis (24.2% vs 7.8%, P  = 0.013) than pAPS-controls. Furthermore, catastrophic-APS (CAPS) (12.1% vs 2.4%, P  = 0.034), recurrent thrombosis (33.3% vs 4.7%, P  < 0.001) and need for advanced therapy (i.e. IVIG, plasmapheresis or rituximab) were more frequent in pAPS-HVD patients. Anti-β2-glycoprotein 1 IgG (84.8% vs 63.2%, P  = 0.034), anti-cardiolipin IgG (90.9% vs 64.8%, P  = 0.005) and triple positive aPL (75.8% vs 56.5%, P  = 0.047) were commoner in pAPS-HVD patients vs pAPS-controls. Ten of the 33 patients with pAPS-HVD underwent valve surgery, which was associated with male gender, smoking, arterial limb ischaemia and livedo reticularis. Conclusion pAPS-HVD patients had a more severe APS clinical course including CAPS and thrombotic events as well as a specific serology, namely IgG isotype aPL antibodies and triple positivity. Our data suggest that pAPS-HVD represents a high-risk subgroup of APS patients. [ABSTRACT FROM AUTHOR]

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. [ABSTRACT FROM AUTHOR]

Bioprosthetic 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. [ABSTRACT FROM AUTHOR]

Background Bioprosthetic stentless aortic valves may degenerate over time and will require replacement. This study aimed to evaluate early- and mid-term outcomes after isolated surgical redo aortic valve replacement (redo-SAVR) and transcatheter valve-in-valve implantation (TAVI-VIV) for degenerated stentless Freestyle bioprostheses. Methods We reviewed records of 56 patients at a single center. Overall, 37 patients (66.1%) received TAVI-VIV and 19 (33.9%) received redo-SAVR. Results Thirty-day survival was similar in both groups (100%). One-year survival was comparable between groups (97.3% in TAVI-VIV and 100% in redo-SAVR, p = 1.0). The difference in mid-term survival after adjusting for age and EuroScore II was not significant (p = 0.41). The incidence of pacemaker implantation after TAVI-VIV was higher than after redo-SAVR (19.4% vs. 0%, p = 0.08). Conclusion The 30-day and 1-year survival rates after both procedures were outstanding, irrespective of baseline characteristics. Isolated redo-SAVR should be favored in young patients, as the pacemaker implantation rate is lower. TAVI-VIV for degenerated Freestyle prosthesis can be a method of choice in elderly patients and those with high operative risk. [ABSTRACT FROM AUTHOR]

Background We aimed to compare hemodynamic performance of the Avalus (Medtronic) and the Perimount Magna Ease (PME, Edwards Lifesciences) bioprosthesis up to 5 years by serial echocardiographic examinations. Methods In patients undergoing aortic valve replacement, 58 received PME prostheses between October 2007 and October 2008, and another 60 received Avalus prostheses between October 2014 and November 2015. To ensure similar baseline characteristics, we performed a propensity score matching based on left ventricular ejection fraction, age, body surface area, and aortic annulus diameter measured by intraoperative transesophageal echocardiography. Thereafter, 48 patients remained in each group. Mean age at operation was 67 ± 6 years and mean EuroSCORE-II was 1.7 ± 1.1. Both values did not differ significantly between the two groups. Results At 1 year the mean pressure gradient (MPG) was 15.4 ± 4.3 mm Hg in the PME group and 14.7 ± 5.1 mm Hg in the Avalus group (p = 0.32). The effective orifice area (EOA) was 1.65 ± 0.45 cm2 in the PME group and 1.62 ± 0.45 cm2 in the Avalus group (p = 0.79). At 5 years the MPG was 16.6 ± 5.1 mm Hg in the PME group and 14.7 ± 7.1 mm Hg in the Avalus group (p = 0.20). The EOA was 1.60 ± 0.49 cm2 in the PME group and 1.51 ± 0.40 cm2 in the Avalus group (p = 0.38). Five-year survival was 88% in the PME group and 91% in the Avalus group (p = 0.5). In the PME group, there were no reoperations on the aortic valve, whereas in the Avalus group three patients required a reoperation due to endocarditis. Conclusion Both bioprostheses exhibit similar hemodynamic performance during a 5-year follow-up. [ABSTRACT FROM AUTHOR]

Aortic stenosis, hypertension, and left ventricular hypertrophy often coexist in the elderly, causing a detrimental mismatch in coupling between the heart and vasculature known as ventricular−vascular (VA) coupling. Impaired left VA coupling, a critical aspect of cardiovascular dysfunction in aging and disease, poses significant challenges for optimal cardiovascular performance. This systematic review aims to assess the impact of simulating and studying this coupling through computational models. By conducting a comprehensive analysis of 34 relevant articles obtained from esteemed databases such as Web of Science, Scopus, and PubMed until July 14, 2022, we explore various modeling techniques and simulation approaches employed to unravel the complex mechanisms underlying this impairment. Our review highlights the essential role of computational models in providing detailed insights beyond clinical observations, enabling a deeper understanding of the cardiovascular system. By elucidating the existing models of the heart (3D, 2D, and 0D), cardiac valves, and blood vessels (3D, 1D, and 0D), as well as discussing mechanical boundary conditions, model parameterization and validation, coupling approaches, computer resources and diverse applications, we establish a comprehensive overview of the field. The descriptions as well as the pros and cons on the choices of different dimensionality in heart, valve, and circulation are provided. Crucially, we emphasize the significance of evaluating heart−vessel interaction in pathological conditions and propose future research directions, such as the development of fully coupled personalized multidimensional models, integration of deep learning techniques, and comprehensive assessment of confounding effects on biomarkers. [ABSTRACT FROM AUTHOR]

Appropriate load‐bearing function of soft connective tissues is provided by their nonlinear and often anisotropic mechanics. Recapitulating such complex mechanical behavior in tissue‐engineered structures is particularly crucial, as deviation from native tissue mechanics can trigger pathological biomechanical pathways, causing adverse tissue remodeling and dysfunction. Here, a novel method combining computational modeling, melt electrowriting (MEW), and design of experiments (DOE) is reported to generate scaffolds composed of sinusoidal fibers with prescribed biaxial mechanical properties, recapitulating the distinct nonlinear, anisotropic stress–strain behavior of three model tissues: adult aortic valve, pediatric pulmonary valve, and pediatric pericardium. Finite element analysis is used to efficiently optimize scaffold architecture over a broad parameter space, representing up to 65 conditions, to define MEW print parameters to achieve polycaprolactone scaffolds with target mechanical properties. Architectural parameters are further optimized experimentally using DOE and regression to account for uncertainties involved in the simulation, yielding functional scaffolds with accurate, prescribed mechanics. The prescribed architecture also primarily governs the mechanics of hybrid structures generated by casting cell‐laden fibrin hydrogel within the scaffolds. This high‐fidelity approach recapitulates biaxial mechanical properties over a broad range of mechanical nonlinearity and anisotropy and is generalizable for programmed biofabrication in a variety of tissue engineering applications. [ABSTRACT FROM AUTHOR]

Introduction: The prevalence of valvular heart diseases remain considerably high in Africa, largely but not solely due to rheumatic heart disease. Valvular heart surgeries have emerged as the cornerstone in their management. While several studies have reported data on outcomes following heart valve surgery in many developed countries, there is a staggering paucity of data and evidence reporting the outcomes in the Africa population. The aim of this study is to report the perioperative outcomes following valvular heart surgery in Africa. Methods: The Preferred Reporting Items for Systematic Reviews and Meta‐analysis guideline was utilized. Electronic searches were performed using PubMed, African journal online, and Research gate from inception to June 2023. The primary endpoints were overall mortality and 30‐day mortality, and secondary endpoints included postoperative complications, length of hospital, and intensive care stays. The outcome data were pooled together and analyzed with the random effect model for proportions and mean for meta‐analysis using the R software. Results: This systematic review identified 31 studies that fulfilled the study eligibility criteria and all were observational studies. The countries in which these studies were carried out include South Africa, Ethiopia, Egypt, Mali, Rwanda, Nigeria, Cameroon, Ghana, Senegal, Tanzania, and Kenya. Statistical analysis reported a pooled overall mortality of 10.48% and a pooled 30‐day mortality of 4.59%. Conclusion: Several obstacles, such as lack of financial resources and inadequate infrastructure, continue to impede valvular heart surgery practice in many parts of Africa. Future studies need to focus on identifying factors associated with this poor early mortality. [ABSTRACT FROM AUTHOR]

The heart valve is crucial for the human body, which directly affects the efficiency of blood transport and the normal functioning of all organs. Generally, decellularization is one method of tissue-engineered heart valve (TEHV), which can deteriorate the mechanical properties and eliminate allograft immunogenicity. In this study, removable polyvinyl alcohol (PVA) is used to encapsulate decellularized porcine heart valves (DHVs) as a dynamic template to improve the processability of DHVs, such as suturing. Mechanical tests show that the strength and elastic modulus of DHVs treated with different concentrations of PVA significantly improve. Without the PVA layer, the valve would shift during suture puncture and not achieve the desired suture result. The in vitro results indicate that decellularized valves treated with PVA can sustain the adhesion and growth of human umbilical vein endothelial cells (HUVECs). All results above show that the DHVs treated with water-soluble PVA have good mechanical properties and cytocompatibility to ensure post-treatment. On this basis, the improved processability of DHV treated with PVA enables a new paradigm for the manufacturing of scaffolds, making it easy to apply. [ABSTRACT FROM AUTHOR]

Transcatheter pulmonary valve replacement is a minimally-invasive alternative treatment for right ventricular outflow tract dysfunction and has been rapidly evolving over the past years. Heart valve prostheses currently available still have major limitations. Therefore, one of the significant challenges for the future is the roll out of transcatheter tissue engineered pulmonary valve replacement to more patients. In the present study, biodegradable poly-ε-caprolactone (PCL) nanofiber scaffolds in the form of a 3D leaflet matrix were successfully seeded with human endothelial colony-forming cells (ECFCs), human induced pluripotent stem cell-derived MSCs (hMSCs), and porcine MSCs (pMSCs) for three weeks for the generation of 3D tissue-engineered tri-leaflet valved stent grafts. The cell adhesion, proliferation, and distribution of these 3D heart leaflets was analyzed using fluorescence microscopy and scanning electron microscopy (SEM). All cell lineages were able to increase the overgrown leaflet area within the three-week timeframe. While hMSCs showed a consistent growth rate over the course of three weeks, ECFSs showed almost no increase between days 7 and 14 until a growth spurt appeared between days 14 and 21. More than 90% of heart valve leaflets were covered with cells after the full three-week culturing cycle in nearly all leaflet areas, regardless of which cell type was used. This study shows that seeded biodegradable PCL nanofiber scaffolds incorporated in nitinol or biodegradable stents will offer a new therapeutic option in the future. [ABSTRACT FROM AUTHOR]

Background Transcatheter aortic valve replacement (TAVR) for a degenerated surgical bioprosthesis (valve-in-valve [ViV]) has become an established procedure. Elevated gradients and patient-prosthesis mismatch (PPM) have previously been reported in mixed TAVR cohorts. We analyzed our single-center experience using the third-generation self-expanding Medtronic Evolut R prosthesis, with an emphasis on the incidence and outcomes of PPM. Methods This is a retrospective analysis of prospectively collected data from our TAVR database. Intraprocedural and intrahospital outcomes are reported. Results Eighty-six patients underwent ViV-TAVR with the Evolut R prosthesis. Mean age was 75.5 ± 9.5 years, 64% were males. The mean log EuroScore was 21.6 ± 15.7%. The mean time between initial surgical valve implantation and ViV-TAVR was 8.8 ± 3.2 years. The mean true internal diameter of the implanted surgical valves was 20.9 ± 2.2 mm. Post-AVR, 60% had no PPM, 34% had moderate PPM, and 6% had severe PPM. After ViV-TAVR, 33% had no PPM, 29% had moderate, and 39% had severe PPM. After implantation, the mean transvalvular gradient was reduced significantly from 36.4 ± 15.2 to 15.5 ± 9.1 mm Hg (p < 0.001). No patient had more than mild aortic regurgitation after ViV-TAVR. No conversion to surgery was necessary. Estimated Kaplan–Meier survival at 1 year for all patients was 87.4%. One-year survival showed no significant difference according to post-ViV PPM groups (p = 0.356). Conclusion ViV-TAVR using a supra-annular valve resulted in low procedural and in-hospital complication rates. However, moderate or severe PPM was common, with no influence on short-term survival. PPM may not be a suitable factor to predict survival after ViV-TAVR. [ABSTRACT FROM AUTHOR]

Background Coronary artery disease (CAD) is frequently diagnosed in patients with aortic valve stenosis. Treatment options include surgical and interventional approaches. We therefore analyzed short-term outcomes of patients undergoing either coronary artery bypass grafting with simultaneous aortic valve replacement (CABG + AVR) or staged percutaneous coronary intervention and transcatheter aortic valve implantation (PCI + TAVI). Methods From all patients treated since 2017, we retrospectively identified 237 patients undergoing TAVI within 6 months after PCI and 241 patients undergoing combined CABG + AVR surgery. Propensity score matching was performed, resulting in 101 matched pairs. Results Patients in the CABG + AVR group were younger compared with patients in the PCI + TAVI group (71.9 ± 4.9 vs 81.4 ± 3.6 years; p < 0.001). The overall mortality at 30 days before matching was higher after CABG + AVR than after PCI + TAVI (7.8 vs 2.1%; p = 0.012). The paired cohort was balanced for both groups regarding demographic variables and the risk profile (age: 77.2 ± 3.7 vs78.5 ± 2.7 years; p = 0.141) and EuroSCORE II (6.2 vs 7.6%; p = 0.297). At 30 days, mortality was 4.9% in the CABG + AVR group and 1.0% in the PCI + TAVI group (p = 0.099). Rethoracotomy was necessary in 7.9% in the CABG + AVR, while conversion to open heart surgery was necessary in 2% in the PCI + TAVI group. The need for new pacemaker was lower after CABG + AVR than after PCI + TAVI (4.1 vs 6.9%; p = 0.010). No paravalvular leak (PVL) was noted in the CABG + AVR group, while the incidence of moderate-to-severe PVL after PCI + TAVI was 4.9% (p = 0.027). Conclusion A staged interventional approach comprises a short-term survival advantage compared with combined surgery for management of CAD and aortic stenosis. However, PCI + TAVI show a significantly higher risk of atrioventricular block and PVL. Further long-term trials are warranted. [ABSTRACT FROM AUTHOR]

Cardiovascular calcification can occur in vascular and valvular structures and is commonly associated with calcium deposition and tissue mineralization leading to stiffness and dysfunction. Patients with chronic kidney disease and associated hyperphosphatemia have an elevated risk for coronary artery calcification (CAC) and calcific aortic valve disease (CAVD). However, there is mounting evidence to suggest that the susceptibility and pathobiology of calcification in these two cardiovascular structures may be different, yet clinically they are similarly treated. To better understand diversity in molecular and cellular processes that underlie hyperphosphatemia-induced calcification in vascular and valvular structures, we exposed aortic vascular smooth muscle cells (AVSMCs) and aortic valve interstitial cells (AVICs) to high (2.5 mM) phosphate (Ph) conditions in vitro, and examined cell-specific responses. To further identify hyperphosphatemic-specific responses, parallel studies were performed using osteogenic media (OM) as an alternative calcific stimulus. Consistent with clinical observations made by others, we show that AVSMCs are more susceptible to calcification than AVICs. In addition, bulk RNA-sequencing reveals that AVSMCs and AVICs activate robust ossification-programs in response to high phosphate or OM treatments, however, the signaling pathways, cellular processes and osteogenic-associated markers involved are cell- and treatment-specific. For example, compared to VSMCs, VIC-mediated calcification involves biological processes related to osteo-chondro differentiation and down regulation of 'actin cytoskeleton'-related genes, that are not observed in VSMCs. Furthermore, hyperphosphatemic-induced calcification in AVICs and AVSMCs is independent of P13K signaling, which plays a role in OM-treated cells. Together, this study provides a wealth of information suggesting that the pathogenesis of cardiovascular calcifications is significantly more diverse than previously appreciated. [Display omitted] • Aortic vascular smooth muscle cells (AVSMCs) are more susceptible to calcific stimuli than aortic valve interstitial cells (AVICs) • Transcriptomic analysis demonstrates molecular diversity between AVSMCs and AVICs, and calcific stimuli • In response to calcific stimuli, AVICs, unlike AVSMCs, downregulate actin stress fiber makers • PI3K/AKT signaling plays a role in osteogenic media, but not high phosphate mediated calcification [ABSTRACT FROM AUTHOR]

In order to overcome the disadvantages of existing treatments in heart valve tissue engineering, decellularization studies are carried out. The main purpose of decellularization is to eliminate the immunogenicity of biologically derived grafts and to obtain a scaffold that allows recellularization while preserving the natural tissue architecture. SD and SDS are detergent derivatives frequently used in decellularization studies. The aim of our study is to decellularize the pulmonary heart valves of young Merino sheep by using low-density SDS and SD detergents together, and then to perform their detailed characterization to determine whether they are suitable for clinical studies. Pulmonary heart valves of 4–6-month-old sheep were decellularized in detergent solution for 24 h. The amount of residual DNA was measured to determine the efficiency of decellularization. Then, the effect of decellularization on the ECM by histological staining was examined. In addition, the samples were visualized by SEM to determine the surface morphologies of the scaffolds. A uniaxial tensile test was performed to examine the effect of decellularization on biomechanical properties. In vitro stability of scaffolds decellularized by collagenase treatment was determined. In addition, the cytotoxic effect of scaffolds on 3T3 cells was examined by MTT assay. The results showed DNA removal of 94% and 98% from the decellularized leaflet and pulmonary wall portions after decellularization relative to the control group. No cell nuclei were found in histological staining and it was observed that the three-layer leaflet structure was preserved. As a result of the tensile test, it was determined that there was no statistically significant difference between the control and decellularized groups in the UTS and elasticity modulus, and the biomechanical properties did not change. It was also observed that decellularized sheep pulmonary heart valves had no cytotoxic effect. In conclusion, we suggest that the pulmonary valves of decellularized young Merino sheep can be used as an initial matrix in heart valve tissue engineering studies. [ABSTRACT FROM AUTHOR]

Background: Cortical deafness is an unusual occurrence caused by injury to the central auditory pathway but not to the hearing organ. This paper reports the first case of cortical deafness as a sequel of recurrent stroke in a patient with prosthetic heart valves and atrial fibrillation in Asia. Case presentation: A 40-year-old man with a history of atrial fibrillation and valvular heart disease comes with weakness on the right side of the body and slurred speech. Examination showed hemiplegia with increased d-dimer and activated partial thromboplastin time. (APTT). Brain MRI showed multiple subacute infarctions in the temporal lobe. Diffusion Tensor Imaging (DTI) tractography showed no visible auditory tract. Pure tone audiogram and brainstem auditory evoked potential test was normal, but speech reception threshold test was very poor. The patient has been diagnosed with recurrent ischemic stroke with sequel cortical deafness and received anticoagulant therapy and speech therapy. The patient reported minimal subjective impairment 1 month later with no further neurological deterioration. Conclusions: A multidisciplinary clinical approach is needed in patients with cortical deafness, especially distinguishing it from other central hearing losses. [ABSTRACT FROM AUTHOR]

Valvular heart disease is a globally prevalent cause of morbidity and mortality, with both congenital and acquired clinical presentations. Tissue engineered heart valves (TEHVs) have the potential to radically shift the treatment landscape for valvular disease by functioning as life-long valve replacements that overcome the current limitations of bioprosthetic and mechanical valves. TEHVs are envisioned to meet these goals by functioning as bioinstructive scaffolds that guide the in situ generation of autologous valves capable of growth, repair, and remodeling within the patient. Despite their promise, clinical translation of in situ TEHVs has proven challenging largely because of the unpredictable and patient-specific nature of the TEHV and host interaction following implantation. In light of this challenge, we propose a framework for the development and clinical translation of biocompatible TEHVs, wherein the native valvular environment actively informs the valve's design parameters and sets the benchmarks by which it is functionally evaluated. [Display omitted] • Biocompatible TEHVs represent potential alternatives to prostheses for replacement of diseased valves. • Valve design and prototyping should be informed by the native valve environment. • A predictable host interface will facilitate clinical application of engineered valves. [ABSTRACT FROM AUTHOR]

Bioprosthetic heart valves (BHVs) are important for transcatheter valve replacement. Current commercial BHVs on the market are basically porcine or bovine pericardium (BP) crosslinked with glutaraldehyde (GA). Simply applying GA to BHVs can enhance mechanical stability, but cannot alleviate in vivo calcification. In this work, we developed a two-step decellularization (TSD) strategy to modify this biomacromolecular network, in which BP was post-treated, as the second step of decellularization, with a mild biosurfactant n-dodecyl-β-D-maltoside in a mixture of isopropanol and phosphate-buffered saline after the first step of traditional decellularization and GA cross-linking. The TSD-treated BP exhibited not only low cytotoxicity and excellent mechanical properties in vitro, but also low immune responses and significant anticalcification in vivo. After 60 days of subcutaneous implantation in the back of Wistar rats, the calcium content was, as quantified with an inductively coupled plasma optical emission spectrometer, only 1.1 µg/mg compared to 138.6 µg/mg in the control group without the post-treatment. In addition, collagen fibrils were observed with field emitting scanning electron microscopy (SEM), and the morphology and composition of the calcified sites resulting from in vivo biomineralization were studied with SEM with energy dispersive spectroscopy and also X-ray diffraction. This study proposes a facile yet effective anticalcification strategy for the modification of the bovine pericardial bioprosthetic heart valve, a natural biomacromolecular network. [ABSTRACT FROM AUTHOR]

Background Endocarditis is continuously increasing. Evidence exist that the prognosis is adversely affected by the extent of the disease. We looked at risk factors influencing in-hospital mortality (HM). Patients and Methods Between 2010 and 2019, 484 patients, 338 males (69.8%) with mean age of 66.1 years were operated on because of proven endocarditis. In a retrospective study, a risk factor analysis was performed. Results Overall HM was 30.17%. Significant influencing factors (odds ratios [ORs] or p -value) for HM were: age (p = 0.004), logistic EuroSCORE (p < 0.001), gender (OR = 1.64), dialysis (OR = 2.64), hepatic insufficiency (OR = 2.17), reoperation (OR = 1.77), previously implanted valve (OR = 1.97), periannular abscess (OR = 9.26), sepsis on admission (OR = 12.88), and number of involved valves (OR = 1.96). Development of a sepsis and HM was significantly lower if Streptococcus mitis was the main pathogen in contrast to other bacteria (p < 0.001). Staphylococcus aureus was significantly more often found in patients with a previously implanted prosthesis (p = 0.03) and in recurrent endocarditis (p = 0.02), while it significantly more often showed peripheral septic emboli than the other pathogens (p < 0.001). Conclusion Endocarditis remains life-threatening. Severe comorbidities adversely affected early outcome, particularly, in presence of periannular abscesses. Patients with suspected endocarditis should be admitted to a specialized heart center as early as possible. Streptococcus mitis appears to be less virulent than S. aureus. Further studies are required to verify these findings. [ABSTRACT FROM AUTHOR]

Current surgical aortic valve (AV) replacement options include bioprosthetic and mechanical heart valves (MHVs), each with inherent limitations. Bioprosthetic valves offer superior hemodynamics but suffer from durability issues, typically initiating deterioration within 7–8 years. MHVs, while durable, necessitate lifelong anticoagulation therapy, presenting risks such as severe bleeding and thromboembolic events. The need for anticoagulants is caused by non-physiological flow through the hinge area during the closed phase and large spikes of regional backflow velocity (RBV) during the closing phase that produces high shear events. This study introduces the iValve, a novel MHV designed to combine the hemodynamic benefits of bioprosthetic valves with the durability of MHVs without requiring anticoagulation. The iValve features eye-like leaflets, a saddle-shaped housing, and an optimized hinge design to enhance blood flow and minimize thrombotic risk. Fabricated using 6061-T6 aluminum and polyether ether ketone (PEEK), twelve iValve iterations were evaluated for their opening and closing dynamics. The reported top-performing prototypes demonstrated competitive performance against industry standards. The proposed iValve prototype exhibited a mean RBV of −4.34 m/s with no spikes in RBV, performing similarly to bioprosthetic valves and significantly outperforming existing MHVs. The iValve's optimized design showed a 7–10% reduction in closing time and a substantial decrease in RBV spikes, potentially reducing the need for anticoagulation therapy. This study highlights the iValve's potential to revolutionize prosthetic heart valve technology by offering a durable, hemodynamically superior solution that mitigates the drawbacks of current MHVs. [ABSTRACT FROM AUTHOR]

The aim of this study was to minimize the risk of life-threatening thromboembolism in the ventricle through the use of a new biomimetic heart valve based on metal–polymer composites. Finite volume element simulations of blood adhesion to the material were carried out, encompassing radial flow and the cone and plane test together with determination of the effect of boundary conditions. Both tilt-disc and bicuspid valves do not have optimized blood flow due to their design based on rigid valve materials (leaflet made of pyrolytic carbon). The main objective was the development of materials with specific properties dedicated to contact with blood. Materials were evaluated by dynamic tests using blood, concentrates, and whole human blood. Hemostability tests under hydrodynamic conditions were related to the mechanical properties of thin-film materials obtained from tribological tests. The quality of the coatings was high enough to avoid damage to the coating even as they were exposed up to maximum loading. Analysis towards blood concentrates of the hydrogenated carbon sample and the nitrogen-doped hydrogenated carbon sample revealed that the interaction of the coating with erythrocytes was the strongest. Hemocompatibility evaluation under hydrodynamic conditions confirmed very good properties of the developed coatings. [ABSTRACT FROM AUTHOR]

Surface properties of octavinyl polyhedral oligomeric silsesquioxane (OVS), grafted polyurethane (PU) and heparinized carbon nanotubes (HCNTs) nanocomposite thin-films were evaluated, and the effect of OVS presence on platelet adhesion on the surface of nanocomposite films for artificial heart valve application was investigated using in-vitro tests. OVS was synthesized, then PU and CNT (PU/CNT) nanocomposite films were dipped in the solution of OVS in toluene for grafting. Synthesized OVS was investigated by XRD, FTIR, and NMR tests. SEM-EDX micrographs showed that the morphology of the PU/HCNT surface was obviously changed due to OVS grafting. Surface studies proved OVS grafting on the surface. Surface roughness was increased after grafting PU/HCNT surface with OVS in comparison to the untreated PU/HCNT nanocomposite surface. The contact angle was increased from 88° for PU/HCNT sample to 165° for OVS-grafted PU/HCNT sample. After the addition of CNTs to the matrix, the modulus was increased. According to the MTT test, modified polymeric nanocomposite has no cytotoxicity, and the adhesion of L929 fibroblast cells on the grafted surface was increased. Its shown in the platelet adhesion test that blood compatibility of the OVS grafted films are increased in comparison with PU/HCNT. Surface calcification of OVS-grafted PU/HCNT was reduced according to the in-vitro calcification test. It has been concluded that the combination of physical and mechanical properties of PU/HCNT and the calcification resistance of OVS is a suitable achievement for heart valve application. [ABSTRACT FROM AUTHOR]

Heart valve cryopreservation was employed as a model for the development of complex tissue preservation methods based upon vitrification and nanowarming. Porcine heart valves were loaded with cryoprotectant formulations step wise and vitrified in 1–30 mL cryoprotectant formulations ± Fe nanoparticles ± 0.6 M disaccharides, cooled to −100 °C, and stored at −135 °C. Nanowarming was performed in a single ~100 s step by inductive heating within a magnetic field. Controls consisted of fresh and convection-warmed vitrified heart valves without nanoparticles. After washing, cell viability was assessed by metabolic assay. The nanowarmed leaflets were well preserved, with a viability similar to untreated fresh leaflets over several days post warming. The convection-warmed leaflet viability was not significantly different than that of the nanowarmed leaflets immediately after rewarming; however, a significantly higher nanowarmed leaflet viability (p < 0.05) was observed over time in vitro. In contrast, the associated artery and fibrous cardiac muscle were at best 75% viable, and viability decreased over time in vitro. Supplementation of lower concentration cryoprotectant formulations with disaccharides promoted viability. Thicker tissues benefited from longer-duration cryoprotectant loading steps. The best outcomes included a post-warming incubation step with α-tocopherol and an apoptosis inhibitor, Q-VD-OPH. This work demonstrates progress in the control of ice formation and cytotoxicity hurdles for the preservation of complex tissues. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases remain number 1 killer world-wide. New technologies, particularly the novel approaches at genetics, transcriptomics, proteomics and metabolomics levels have provided new insights into the disease aetiology, pathophysiology and diagnosis, as well as therapeutics from molecular level. These omics by integrating the nuclear, cellular components, proteins, enzymes generate large data sets gather the information with support of organised and systematic computational methods. The integrated analyses may give deeper view on the development, treatment and prevention of the disease. In recent years, multi-omics technologies have been used in research on cardiovascular diseases including coronary artery disease, heart valve disease and congenital heart disease. These studies help in understanding the aetiology and pathophysiology of the disease and facilitate the precision diagnosis, therapy and prognosis. [ABSTRACT FROM AUTHOR]

Cardiovascular diseases persist as a leading cause of mortality and morbidity, despite significant advances in diagnostic and surgical approaches. Computational Fluid Dynamics (CFD) represents a branch of fluid mechanics widely used in industrial engineering but is increasingly applied to the cardiovascular system. This review delves into the transformative potential for simulating cardiac surgery procedures and perfusion systems, providing an in-depth examination of the state-of-the-art in cardiovascular CFD modeling. The study first describes the rationale for CFD modeling and later focuses on the latest advances in heart valve surgery, transcatheter heart valve replacement, aortic aneurysms, and extracorporeal membrane oxygenation. The review underscores the role of CFD in better understanding physiopathology and its clinical relevance, as well as the profound impact of hemodynamic stimuli on patient outcomes. By integrating computational methods with advanced imaging techniques, CFD establishes a quantitative framework for understanding the intricacies of the cardiac field, providing valuable insights into disease progression and treatment strategies. As technology advances, the evolving synergy between computational simulations and clinical interventions is poised to revolutionize cardiovascular care. This collaboration sets the stage for more personalized and effective therapeutic strategies. With its potential to enhance our understanding of cardiac pathologies, CFD stands as a promising tool for improving patient outcomes in the dynamic landscape of cardiovascular medicine. [ABSTRACT FROM AUTHOR]

We tested the hypotheses (i) that elevated lipoprotein(a) is causally associated with both mitral and aortic valve calcification and disease, and (ii) that aortic valve calcification mediates the effect of elevated lipoprotein(a) on aortic valve stenosis. From the Copenhagen General Population study, we included 12,006 individuals who underwent cardiac computed tomography to measure mitral and aortic valve calcification and 85,884 to examine risk of heart valve disease. Participants had information on plasma lipoprotein(a) and genetic instruments associated with plasma lipoprotein(a) to investigate potential causality. At age 70–79 years, 29% and 54% had mitral and aortic valve calcification, respectively. For 10-fold higher lipoprotein(a) levels, multifactorially adjusted odds ratios for mitral and aortic valve calcification were 1.26 (95% confidence interval: 1.13–1.41) and 1.62 (1.48–1.77). For mitral and aortic valve stenosis, corresponding hazard ratios were 0.93 (95%CI:0.40–2.15, 19 events) and 1.54 (1.38–1.71, 1158 events), respectively. For ≤23 versus ≥36 kringle IV type 2 number of repeats, the age and sex adjusted odds ratios for mitral and aortic valve calcification were 1.53 (1.18–1.99) and 2.23 (1.81–2.76). For carriers versus non-carriers of LPA rs10455872, odds ratios for mitral and aortic valve calcification were 1.33 (1.13–1.57) and 1.86 (1.64–2.13). For aortic valve stenosis, 31% (95%CI:16%–76%) of the effect of lipoprotein(a) was mediated through calcification. Elevated lipoprotein(a) was genetically and observationally associated with mitral and aortic valve calcification and aortic valve stenosis. Aortic valve calcification mediated 31% of the effect of elevated lipoprotein(a) on aortic valve stenosis. [Display omitted] • More than 12,000 individuals were CT scanned for heart valve calcification. • More than 85,000 individuals were followed in nationwide registries. • Lipoprotein(a) is causally associated with mitral valve calcification. • Lipoprotein(a) causes aortic valve stenosis but not mitral valve regurgitation. • Aortic valve calcification mediates 31% lipoprotein(a) effect on aortic stenosis. [ABSTRACT FROM AUTHOR]

Background: Pulmonary regurgitation is imminent after transannular patch (TAP). We analyze the long-term performance of untreated autologous pericardium (UAP) as valve substitute at pulmonary position in patients requiring TAP.Material and Methods: This cross-sectional study include patients operated between 2007 and 2012 (n = 92). A sample of 19 patients was selected for this study which had a follow-up of more than 3 years. This includes patients with no TAP (n = 4) and with TAP and valve substitute, a monocusp (n = 11) or a tricuspid valve (n = 4) at neopulmonary annulus. Patients underwent echocardiography for assessment of right ventricle function and 18 fluoro-deoxyglucose PET CT scan for measurements of valve substitute at neopulmonary annulus. The target to blood ratio (TBR) of uptake of glucose by monocusp was measured at the cooptation edge of the neopulmonary valve.Results: The median age of the patients is 14 (9 - 37). RV function is preserved (TAPSE 18.9 (10.6 - 22.8)) at a mean follow-up of 4 years (3-9). The measurements of monocusp shows a shrinkage in height of the cusp by 35.5% (70% - 1.0%) and length by 7% (-44% - +104%). There was less shrinkage observed in patients below 15 years of age. The TBR of monocusp was 0.945 (0.17 - 3.35) with a strong correlation between the TBR values of aortic valve leaflet and monocusp leaflet of same patient.Conclusion: The UAP is functional and successful as a valve substitute at neo pulmonary annulus at long-term follow-up. It has resisted calcification and has shown uptake of glucose in physiological limits. [ABSTRACT FROM AUTHOR]

Aortic valve stenosis (AVS) patients experience pathogenic valve leaflet stiffening due to excessive extracellular matrix (ECM) remodeling. Numerous microenvironmental cues influence pathogenic expression of ECM remodeling genes in tissue-resident valvular myofibroblasts, and the regulation of complex myofibroblast signaling networks depends on patient-specific extracellular factors. Here, we combined a manually curated myofibroblast signaling network with a data-driven transcription factor network to predict patient-specific myofibroblast gene expression signatures and drug responses. Using transcriptomic data from myofibroblasts cultured with AVS patient sera, we produced a large-scale, logic-gated differential equation model in which 11 biochemical and biomechanical signals were transduced via a network of 334 signaling and transcription reactions to accurately predict the expression of 27 fibrosis-related genes. Correlations were found between personalized model-predicted gene expression and AVS patient echocardiography data, suggesting links between fibrosisrelated signaling and patient-specific AVS severity. Further, global network perturbation analyses revealed signaling molecules with the most influence over network-wide activity, including endothelin 1 (ET1), interleukin 6 (IL6), and transforming growth factor β (TGFβ), along with downstream mediators c-Jun N-terminal kinase (JNK), signal transducer and activator of transcription (STAT), and reactive oxygen species (ROS). Lastly, we performed virtual drug screening to identify patient-specific drug responses, which were experimentally validated via fibrotic gene expression measurements in valvular interstitial cells cultured with AVS patient sera and treated with or without bosentan—a clinically approved ET1 receptor inhibitor. In sum, our work advances the ability of computational approaches to provide a mechanistic basis for clinical decisions including patient stratification and personalized drug screening [ABSTRACT FROM AUTHOR]

Background: High plasma lipoprotein(a) and high body mass index are both causal risk factors for calcific aortic valve disease.Objectives: This study sought to test the hypothesis that risk of calcific aortic valve disease is the highest when both plasma lipoprotein(a) and body mass index are extremely high.Methods: From the Copenhagen General Population Study, we used information on 69,988 randomly selected individuals recruited from 2003 to 2015 (median follow-up 7.4 years) to evaluate the association between high lipoprotein(a) and high body mass index with risk of calcific aortic valve disease.Results: Compared with individuals in the 1st to 49th percentiles for both lipoprotein(a) and body mass index, the multivariable adjusted HRs for calcific aortic valve disease were 1.6 (95% CI: 1.3-1.9) for the 50th to 89th percentiles of both (16% of all individuals) and 3.5 (95% CI: 2.5-5.1) for the 90th to 100th percentiles of both (1.1%) (P for interaction = 0.92). The 10-year absolute risk of calcific aortic valve disease increased with higher lipoprotein(a), body mass index, and age, and was higher in men than in women. For women and men 70-79 years of age with body mass index ≥30.0 kg/m2, 10-year absolute risks were 5% and 8% for lipoprotein(a) ≤42 mg/dL (88 nmol/L), 7% and 11% for 42-79 mg/dL (89-169 nmol/L), and 9% and 14% for lipoprotein(a) ≥80 mg/dL (170 nmol/L), respectively.Conclusions: Extremely high lipoprotein(a) levels and extremely high body mass index together conferred a 3.5-fold risk of calcific aortic valve disease. Ten-year absolute risk of calcific aortic valve disease by categories of lipoprotein(a) levels, body mass index, age, and sex ranged from 0.4% to 14%. [ABSTRACT FROM AUTHOR]

Acinetobacter baumannii is an opportunistic bacterial pathogen predominantly associated with hospital-acquired infections. Here we present a case of infective endocarditis of native Mitral and Aorta valves caused by A. baumannii in a 73-year-old man. He underwent surgical excision and Pathologic specimen showed A. baumannii growth after 48 hours that was extensively drug-resistant (XDR). He was treated with colistin and tigecycline. Finally, he discharged with no important complication. To our best knowledge, it is the first case of Acinetobacter endocarditis has ever been reported in Iran. Although XDR A. baumannii is a life-threatening pathogen, proper and timely treatment can be life-saving. [ABSTRACT FROM AUTHOR]

As research continues to demonstrate successes in the use of percutaneous trans-vascular techniques in structural heart intervention, both the subspecialty trained and non-subspecialty trained cardiac imager find themselves performing and reporting larger amounts of information regarding cardiovascular findings. It is therefore imperative that the imager gains understanding and appreciation for how these various measurements are obtained, as well as their implication in a patient's care. Cardiac gated computed tomography (CT) has solidified its role and ability at providing high resolution images that can be used to obtain the key measurements used in structural heart intervention planning. This manuscript aims to provide an overview of what measurements are necessary to report when interpreting CT examinations purposed for structural heart intervention. This includes a review on indications and brief discussion on complications related to these procedures. • Percutaneous structural heart interventions continue to increase owing to their less invasive approach compared to surgery • Cardiac imagers should be familiar with indications for percutaneous structural heart inventions • Understanding where and why key pre-procedural CT measurements are obtained gives cardiac imagers greater insight into our role in the care of these patients [ABSTRACT FROM AUTHOR]

In an article published in Advanced Functional Materials, researchers Sangmin Lee, Se Yong Jung, Jinkee Hong, and their colleagues present a silk fibroin-based heart valve leaflet that has a hierarchical structure suitable for replacing natural heart valve leaflets. The silk fibroin-based leaflets demonstrate excellent valve performance, indicating their potential as a cost-effective and reliable cardiovascular device. This research offers promising advancements in the development of bioprosthesis for heart valves. [Extracted from the article]

Background: Acute Kidney Injury (AKI) adversely affects outcomes after cardiac surgery. A major mediator of AKI is the activation of leukocytes through exposure to the cardiopulmonary bypass circuit. We evaluate the use of leukodepletion filters throughout bypass to protect against post-operative AKI by removing activated leukocytes during cardiac surgery.Methods: This is a single-centre, double-blind, randomized controlled trial comparing the use of leukodepletion versus a standard arterial filter throughout bypass. Elective adult patients undergoing heart valve surgery with or without concomitant procedures were investigated. The primary clinical outcome measured was the development of AKI according to the KDIGO criteria. Secondary measures included biomarkers of renal tubular damage (urinary Retinol Binding Protein and Kidney Injury Molecule-1), glomerular kidney injury (urinary Micro Albumin and serum Cystatin C) and urinary Neutrophil Gelatinase Associated Lipocalin, as well as the length of hospital stay and quality of life measures through EQ-5D-5L questionnaires.Results: The ROLO trial randomized 64 participants with a rate of recruitment higher than anticipated (57% achieved, 40% anticipated). The incidence of AKI was greater in the leukodepletion filter group (44% versus 23%, risk difference 21, 95% CI - 2 to 44%). This clinical finding was supported by biomarker levels especially by a tendency toward glomerular insult at 48 h, demonstrated by a raised serum Cystatin C (mean difference 0.11, 95% CI 0.00 to 0.23, p = 0.068) in the leukodepleted group. There was however no clear association between the incidence or severity of AKI and length of hospital stay. On average, health related quality of life returned to pre-operative levels in both groups within 3 months of surgery.Conclusions: Leukocyte depletion during cardiopulmonary bypass does not significantly reduce the incidence of AKI after valvular heart surgery. Other methods to ameliorate renal dysfunction after cardiac surgery need to be investigated.Trial Registration: The trial was registered by the International Standard Randomized Controlled Trial Number Registry ISRCTN42121335 . Registered on the 18 February 2014. The trial was run by the Bristol Clinical Trials and Evaluation Unit. This trial was financially supported by the National Institute of Health Research (Research for Patient Benefit), award ID: PB-PG-0711-25,090. [ABSTRACT FROM AUTHOR]

Heterogeneous macrophage lineages are present in the aortic and mitral valves of the heart during development and disease. These populations include resident macrophages of embryonic origins and recruited monocyte-derived macrophages prevalent in disease. Soon after birth, macrophages from haematopoietic lineages are recruited to the heart valves, and bone marrow transplantation studies in mice demonstrate that haematopoietic-derived macrophages continue to invest adult valves. During myxomatous heart valve disease, monocyte-derived macrophages are recruited to the heart valves and they contribute to valve degeneration in a mouse model of Marfan syndrome. Here, we review recent studies of macrophage lineages in heart valve development and disease with discussion of clinical significance and therapeutic applications. [ABSTRACT FROM AUTHOR]

Use of transcatheter mitral valve replacement (TMVR) using transcatheter aortic valves in clinical practice is limited to patients with failing bioprostheses and rings or mitral valve disease associated with severe mitral annulus calcification. Whereas the use of valve-in-valve TMVR appears to be a reasonable alternative to surgery in patients at high surgical risk, much less evidence supports valve-in-ring and valve-in-mitral annulus calcification interventions. Data on the results of TMVR in these settings are derived from small case series or voluntary registries. This review summarizes the current evidence on TMVR using transcatheter aortic valves in clinical practice from the characteristics of the TMVR candidates, screening process, performance of the procedure, and description of current results and future perspectives. TMVR using dedicated devices in native noncalcified mitral valve diseases is beyond the scope of the article. [ABSTRACT FROM AUTHOR]

We recently developed the open-source library tIGAr, which extends the FEniCS finite element automation framework to isogeometric analysis. The present contribution demonstrates the utility of tIGAr in complex problems by applying it to immersogeometric fluid–structure interaction (FSI) analysis. This application is implemented as the new open-source library CouDALFISh (Coupling, via Dynamic Augmented Lagrangian, of Fluids with Immersed Shells, pronounced "cuttlefish"), which uses the dynamic augmented Lagrangian (DAL) method to couple fluid and shell structure subproblems. The DAL method was introduced previously, over a series of papers largely focused on heart valve FSI, but an open-source implementation making extensive use of automation to compile numerical routines from high-level mathematical descriptions brings newfound transparency and reproducibility to these earlier developments on immersogeometric FSI analysis. The portions of CouDALFISh that do not use code generation also illustrate how a framework like FEniCS remains useful even when some functionality is outside the scope of its standard workflow. This paper summarizes the workings of CouDALFISh and documents a variety of benchmarks demonstrating its accuracy. Although the implementation emphasizes transparency and extensibility over performance, it is nonetheless demonstrated to be sufficient to simulate 3D FSI of an idealized aortic heart valve. Source code will be maintained at https://github.com/david-kamensky/CouDALFISh. [ABSTRACT FROM AUTHOR]

Over the past few decades, the tricuspid valve (TV) interventions have been relatively lower compared to other cardiac valvular disease in terms of pathophysiology and management, especially regarding surgical intervention and therapy. However, recent crucial advances in assessment and management of the TV disease have resulted in a renewed interest in the "forgotten valve." The medical treatment aims to cure the underlying disease and address the presentation of the right heart failure. Surgical interventions have proven to yield good outcomes for those for whom surgery is indicated. For those who are not suitable for surgery, transcatheter surgery may prove to be a suitable replacement. Best practice with regard to surgical techniques is still in question due to limited data. This has been slowing the introduction of transcatheter interventions into common practical guidelines. The aim of this literature review is to discuss new insights on the pathophysiology, diagnosis, and interventions of TV disease, highlighting the surgical management and emerging transcatheter therapies. In addition, this review will provide an overview of the current state of the literature surrounding TV interventions and providing suggestions for future directives. [ABSTRACT FROM AUTHOR]

Background Polymeric heart valves are constructed from flexible synthetic materials, therefore aiming to combine the advantageous hemodynamic of biological and the longevity of mechanical valve prostheses. One such valve prototype in development is the PIZZA valve constructed of flexible triangular silicone leaflets on a foldable metal base for perspective transcatheter implantation. Here we present further improvements in its performance through structural modifications. Methods Structurally modified prototypes were constructed from silicone sheets and stainless-steel wires. Their performance was then tested in a hemodynamic testing device of the type HKP 2.0. Results Shift from a planar to a cone shape as well as overlapping of the leaflets significantly improved the valves performance, reducing regurgitation as well as systolic pressure gradients. Conclusions The results of the modified prototypes expressed superior performance and represented a step forward on the road to an easily producible, polymeric transcatheter valvular prosthesis. [ABSTRACT FROM AUTHOR]

Myxomatous mitral valve degeneration is the most acquired heart disease in dogs. To reduce the clinical progression of mitral valve degeneration and achieve the hemodynamic outcomes, many medical or surgical treatments have been motivated. The objectives of this study is to investigate the suitability of puppy deciduous teeth stem cells as a cell source for tissue engineered heart valves in dog with degenerative valve disease. Puppy deciduous teeth stem cells (pDSCs) were seeded on the scaffolds which made from polylactic acid (PLA), polycaprolactone (PLC) and silicone. The mechanical properties of the tissue engineered heart valves leaflets were characterized by biaxial tensile tests. Results showed that, deciduous teeth stem cells capable of differentiating into a variety of cell types. However, the ability of puppy deciduous teeth stem cells to differentiate declined with increasing passage number which correspond to the number of protein surface marker detection have been shown to decrease substantially by the fifth passage. PLA scaffold is significantly higher tensile strength than other materials. However, silicone showed the highest flaccidity. The results from this study may provide high regenerative capability and the essential information for future directions of heart valve tissue engineering. [ABSTRACT FROM AUTHOR]

Background Surgical aortic valve replacement (SAVR) is nowadays discussed whether it remains the gold standard of treatment. In the last decade, there has been a tremendous increase in transcatheter aortic valve implantation (TAVI) due to the growing expertise and excellent results of the catheter-based approach. We, therefore, retrospectively compared the rapid deployment valve (RDV), the Edwards Intuity valve (IEV), with the Edwards Sapien 3 (S3V) with regard to post-procedural hemodynamics. Methods A total of 246 patients treated with TAVI or SAVR between February 2009 and November 2015 were included. One-hundred twenty-five patients were analyzed in the SAVR group and compared with 121 patients undergoing TAVI. Transvalvular pressure gradients (PGs) and the incidence and extent of aortic regurgitation (AR) were compared post-procedurally by echocardiography for each valve size. In vitro hemodynamics were analyzed by placing both valves into an aortic silicone phantom connected to a pulsatile flow pump and measured using phase-contrast magnetic resonance imaging (4D flow MRI). Results Post-procedurally, mean transvalvular PGs for the 23 mm valves were 9 (7;11.5) versus 13 (9;18) (p < 0.001), whereas maximum PGs were 16.5 (14;22) versus 25.5 mm Hg (17.5;34) (p < 0.001) in IEV and S3V patients, respectively. The 21 mm IEV showed significantly lower transvalvular PGs compared with the 23 mm S3V: mean PGs: 11 (8;13) versus 13 (9;18) (p < 0.05); maximum PG: 19.5 (13;24) versus 25.5 (18;34) mm Hg (p < 0.05). Analysis revealed significantly lower post-procedural transvalvular PGs for larger valves sizes. With respect to AR, the incidence of AR was significantly lower in IEV group (p < 0.05). In vitro velocities and turbulent kinetic energy values showed similar results between both valves. Conclusion Implanted RDVs presented a lower incidence of paravalvular regurgitation and were associated with significantly lower post-procedural transvalvular PGs, especially for small valve sizes. Our data might support the application of rapid deployment aortic valves in patients with small aortic annulus in the TAVI era. [ABSTRACT FROM AUTHOR]

Background There is a growing use of cerebral protection devices in patients undergoing transcatheter aortic valve replacement (TAVR). We aimed to analyze if the use of these devices itself has an impact on the complexity and the risk of TAVR. Methods Between February 2016 and July 2017, 391 patients underwent transfemoral TAVR with Medtronic CoreValve Evolut R (n = 196) or Edwards Sapien 3 (n = 195). In 39 patients, the Claret Sentinel™ embolic protection device (CS-EPD) was used. Prospectively collected data were retrospectively analyzed, comparing fluoroscopy/operation time, amount of contrast used, vascular events, and postprocedural renal function in TAVR patients with (n = 39) and without (n = 352) CS-EPD. Results The CS-EPD was placed through the right radial (n = 35) or brachial (n = 4) artery. Procedural success rate defined as correct deployment and retraction of both filters was 94.9%. No device-related vascular complications occurred. TAVR patients with CS-EPD showed a significantly higher total operation time, total fluoroscopy time, and amount of used contrast (85.4 ± 39.3 vs. 64 ± 29.8 minutes, p = 0.002; 20.7 ± 9.3 vs. 13.7 ± 7 minutes, p ≤ 0.001; 133.7 ± 42.6 vs. 109.7 ± 44.5 mL, p = 0.001). Comparing the initial third of patients receiving a CS-EPD with the last third of CS-EPD cases, procedural time had decreased significantly (102.5 ± 34.9 vs. 67 ± 11.9; p = 0.002). There were no differences in postprocedural renal failure (p = 0.80). Conclusion Our data add evidence that the application of the CS-EPD is not associated with an additional risk for the patient. Although procedural time and amount of contrast are still higher when using the CS-EPD, there were no device-related complications or increased incidence of renal failure. [ABSTRACT FROM AUTHOR]

In this integrative review, an analysis of the literature was carried out to clarify challenges and new perspectives with regard to infective endocarditis. In this sense, after analyzing the articles selected by specific inclusion and exclusion criteria, the results point to the limited knowledge of patients about oral hygiene as one of the major challenges in preventing the disease, increasing the number of cases and revealing the inadequate communication of doctors to patients about such preventive measures. In addition, the importance of correctly predicting risk factors for cardiac surgery in patients with endocarditis was observed, so that it is possible to analyze the surgical risk accurately, in order to avoid hospital mortality due to the procedure. Finally, it was clear the existence of several variables with regard to the causes and risk factors of the disease. [ABSTRACT FROM AUTHOR]

Background Three-dimensional saddle-shaped annuloplasty rings have been shown to create a larger surface of leaflet coaptation in mitral valve repair (MVR) for functional mitral regurgitation (FMR) and degenerative mitral regurgitation (DMR) which may increase repair durability. For the first time, this study reports mid-term results after MVR for DMR and FMR using a rigid three-dimensional ring (Profile 3D, Medtronic). Methods Between June 2009 and June 2012, 369 patients with DMR (n = 326) or FMR (n = 43) underwent MVR (mean age 62.3 ± 12.6 years). A total of 205 patients (55.6%) underwent isolated MVR and 164 patients (44.4%) a combined procedure. Follow-up examinations were performed in 94.9% (mean 4.9 ± 0.9 years). Echocardiographic assessment was complete in 93.2% (mean 4.3 ± 1.2 years). Results The 30-day mortality was 1.5% (5/326) for DMR (1.5% for isolated and 1.6% for combined procedures) and 9.3% (4/43) for FMR (0% for isolated and 10.5% for combined procedures). Survival at 6 years was 92.1 ± 1.9% for DMR (92.9 ± 2.6% for isolated and 90.7 ± 2.7% for combined procedures) and 66.4 ± 7.9% for FMR (80.0 ± 17.9% for isolated and 63.7 ± 8.9% for combined procedures). Cumulative risk for mitral valve-related reoperation at 6 years was 0% for FMR and 7.1 ± 1.5% for DMR. At echocardiographic follow-up, one patient presented with mitral regurgitation (MR) more than moderate. The only predictor of recurrent MR after MVR for DMR was residual mild MR at discharge. Conclusion Repair of FMR with the three-dimensional Profile 3D annuloplasty ring shows excellent mid-term results with regard to recurrence of MR. In cases of DMR, the results are conforming to the current literature. [ABSTRACT FROM AUTHOR]

The use of decellularized xenogeneic heart valves might offer a solution to overcome the issue of human valve shortage. The aim of this study was to revise decellularization protocols in combination with enzymatic deglycosylation, in order to reduce the immunogenicity of porcine pulmonary heart valves, in means of cells, carbohydrates, and, primarily, Galα1‐3Gal (α‐Gal) epitope removal. In particular, the valves were decellularized with sodium dodecylsulfate/sodium deoxycholate (SDS/SD), Triton X‐100 + SDS (Tx + SDS), or Trypsin + Triton X‐100 (Tryp + Tx) followed by enzymatic digestion with PNGaseF, Endoglycosidase H, or O‐glycosidase combined with Neuraminidase. Results showed that decellularization alone reduced carbohydrate structures only to a limited extent, and it did not result in an α‐Gal free scaffold. Nevertheless, decellularization with Tryp + Tx represented the most effective decellularization protocol in means of carbohydrates reduction. Overall, carbohydrates and α‐Gal removal could strongly be improved by applying PNGaseF, in particular in combination with Tryp + Tx treatment, contrary to Endoglycosidase H and O‐glycosidase treatments. Furthermore, decellularization with PNGaseF did not affect biomechanical stability, in comparison with decellularization alone, as shown by burst pressure and uniaxial tensile tests. In conclusion, valves decellularized with Tryp + Tx and PNGaseF resulted in prostheses with potentially reduced immunogenicity and maintained mechanical stability. [ABSTRACT FROM AUTHOR]

Transcatheter aortic valve implantation (TAVI) has been approved for the treatment of severe aortic stenosis since 2008 and recent trials have shown that TAVI is at least non-inferior to surgical aortic valve replacement (SAVR) with regards to short-term efficacy and safety in patients across all surgical risk profiles. Prosthetic valve endocarditis of the transcatheter heart valve is a feared complication; data on the risk of infective endocarditis (IE) subsequent to TAVI are now gradually emerging. We set forth to conduct a review of the incidence, diagnosis, microbial aetiologies, prevention, outcome and management of TAVI-IE. From the MEDLINE database we included a total of 12 observational studies and five studies of long-term results from randomized controlled trials. The incidence of TAVI-IE was reported to be between 0.7% and 3.0% per person-year. The most common microbes were reported to be enterococci, Staphylococcus aureus , streptococci and coagulase-negative staphylococci. International guidelines on prevention strategies of IE recommend good sanitary conditions including cutaneous care, good oral hygiene and good care of dialysis catheters. Antibiotic prophylaxis is recommended by guidelines prior to dental procedures in patients with TAVI; however, evidence is sparse. The majority of the patients included in this review with TAVI-IE had an indication for surgical intervention due to IE (50.0% or more); however, only a small subset of the patients underwent surgery (16.4% or less). The in-hospital mortality was around 25%, i.e. of the same order of magnitude as in prosthetic valve IE in general, but varied substantially between studies (from 11% to 64%). The US Food and Drug Administration's approval of TAVI in patients at low surgical risk may change the characteristics of patients with TAVI, which may influence the incidence, management, and outcome of patients with TAVI-IE. [ABSTRACT FROM AUTHOR]

Determination of age represents one of the most important aspects in forensic identification. Through aging, changes can occur in morphological structures of the heart valves. The objective is to examine the relationship between the dimensions of the rigth atrioventricular (tricuspid), pulmonary, left atrioventricular (mitral), and aortic valves and age at death. Sixty fresh human hearts were obtained from Department of Anatomy and Department of Forensic Medicine, Faculty of medicine, Chiang Mai University, Thailand. The age of individuals was between 20-90 years. We investigated the morphometric parameters of the valves were taken including: valve circumference, length, the height and area of each leaflet. All parameters were measured by using specific image analysis software. The correlation test and predictive equation were established. The positive correlation between the circumference, area of posterior leaflet, height of anterior leaflet, and area of anterior leaflet of the rigth atrioventricular valve were found. The left atrioventricular valve showed correlation with age in circumference, length and area of posterior leaflet. For the pulmonary and aortic valves, there were correlated between circumference at sinotubular junction and leaflet sizes in almost leaflets. The circumference at sinotubular junction of the pulmonary valve was highest significantly correlation with age (r=0.693). The predictive equation was age = -3.659+0.652(Circumference at sinotubular junction of the pulmonary valve) with standard error of ± 14.7 years. Additional knowledge of morphometric features in human heart valves and its relationship with age could be used as age indicator in forensic field. [ABSTRACT FROM AUTHOR]