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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]

Enhancing the mechanical properties and cytocompatibility of decellularized heart valves is the key to promote the application of biological heart valves. In order to further improve the mechanical properties, the electrospinning and non-woven processing methods are combined to prepare the polylactic acid (PLA)/decellularized heart valve nanofiber-reinforced sandwich structure electrospun scaffold. The effect of electrospinning time on the performance of decellularized heart valve is investigated from the aspects of morphology, mechanical properties, softness, and biocompatibility of decellularized heart valve. Results of the mechanical tests show that compared with the pure decellularized heart valve, the mechanical properties of the composite heart valve were significantly improved with the tensile strength increasing by 108% and tensile strain increased by 571% when the electrospinning time exceeded 2 h. In addition, with this electrospinning time, the composite heart valve has a certain promoting effect on the human umbilical vein endothelial cells proliferation behavior. This work provides a promising foundation for tissue heart valve reendothelialization to lay the groundwork for organoid. [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]

Abstract 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.

Melt electrowriting (MEW) is an electric-field-assisted additive biofabrication technique that has brought significant advancements to bioinspired scaffold design for soft tissue engineering and beyond. Owing to its targeted microfiber placement, MEW has become a powerful platform technology for the fabrication of in vitro disease models up to functional biohybrid constructs that are investigated in vivo to reach clinical translation soon. This work provides a concise overview of this rapidly evolving field by highlighting the key contributions of MEW to cardiovascular tissue engineering. Specifically, we i) pinpoint the methods to introduce microvascular networks in thick 3D constructs benefitting from (sacrificial) MEW microfibers, ii) report MEW-based concepts for small-diameter vascular grafts and stents, iii) showcase how contracting cardiac tissues can profit from the tunable structure–property relationship of MEW scaffolds, and iv) address how complete regenerative heart valves can be built on complex fiber scaffold architectures that recapitulate J-shaped tensile properties and tissue heterogeneity. Lastly, we touch on novel biomaterial advancements and discuss the technological challenges of MEW to unlock the full potential of this transformative technology.

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]

Polymeric heart valves offer the potential to overcome the limited durability of tissue based bioprosthetic valves and the need for anticoagulant therapy of mechanical valve replacement options. However, developing a single‐phase material with requisite biological properties and target mechanical properties remains a challenge. In this study, a composite heart valve material was developed where an electrospun mesh provides tunable mechanical properties and a hydrogel coating confers an antifouling surface for thromboresistance. Key biological responses were evaluated in comparison to glutaraldehyde‐fixed pericardium. Platelet and bacterial attachment were reduced by 38% and 98%, respectively, as compared to pericardium that demonstrated the antifouling nature of the hydrogel coating. There was also a notable reduction (59%) in the calcification of the composite material as compared to pericardium. A custom 3D‐printed hydrogel coating setup was developed to make valve composites for device‐level hemodynamic testing. Regurgitation fraction (9.6 ± 1.8%) and effective orifice area (1.52 ± 0.34 cm2) met ISO 5840‐2:2021 requirements. Additionally, the mean pressure gradient was comparable to current clinical bioprosthetic heart valves demonstrating preliminary efficacy. Although the hemodynamic properties are promising, it is anticipated that the random microarchitecture will result in suboptimal strain fields and peak stresses that may accelerate leaflet fatigue and degeneration. Previous computational work has demonstrated that bioinspired fiber microarchitectures can improve strain homogeneity of valve materials toward improving durability. To this end, we developed advanced electrospinning methodologies to achieve polyurethane fiber microarchitectures that mimic or exceed the physiological ranges of alignment, tortuosity, and curvilinearity present in the native valve. Control of fiber alignment from a random fiber orientation at a normalized orientation index (NOI) 14.2 ± 6.9% to highly aligned fibers at a NOI of 85.1 ± 1.4%. was achieved through increasing mandrel rotational velocity. Fiber tortuosity and curvilinearity in the range of native valve features were introduced through a post‐spinning annealing process and fiber collection on a conical mandrel geometry, respectively. Overall, these studies demonstrate the potential of hydrogel‐polyurethane fiber composite as a heart valve material. Future studies will utilize the developed advanced electrospinning methodologies in combination with model‐directed fabrication toward optimizing durability as a function of fiber microarchitecture. [ABSTRACT FROM AUTHOR]

More than 1000 donated aortic and pulmonary valves from predominantly European tissue banks were centrally decellularized and delivered to hospitals in Europe and Japan. Here, we report on the processing and quality controls before, during and after the decellularization of these allografts. Our experiences show that all tissue establishments, which provide native cardiovascular allografts for decellularization, meet comparably high-quality standards, regardless of their national origin. A total of 84% of all received allografts could be released as cell-free allografts. By far the most frequent reasons for rejection were non-release of the donor by the tissue establishment or severe contaminations of the native tissue donation. Only in 2% of all cases the specification for freedom from cells was not fulfilled, indicating that decellularization of human heart valves is a safe process with a very low discard ratio. In clinical use, cell-free cardiovascular allografts have been shown to be advantageous over conventional heart valve replacements, at least in young adults. These results open the discussion on the future gold standard and funding of this innovative therapeutic option for heart valve replacement. [ABSTRACT FROM AUTHOR]

Abstract 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.

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]

In pursuit of a suitable scaffold material for cardiac valve tissue engineering applications, an acellular, electrospun, biodegradable polyester carbonate urethane urea (PECUU) scaffold was evaluated as a pulmonary valve leaflet replacement in vivo. In sheep (n = 8), a single pulmonary valve leaflet was replaced with a PECUU leaflet and followed for 1, 6, and 12 weeks. Implanted leaflet function was assessed in vivo by echocardiography. Explanted samples were studied for gross pathology, microscopic changes in the extracellular matrix, host cellular re‐population, and immune responses, and for biomechanical properties. PECUU leaflets showed normal leaflet motion at implant, but decreased leaflet motion and dimensions at 6 weeks. The leaflets accumulated α‐SMA and CD45 positive cells, with surfaces covered with endothelial cells (CD31+). New collagen formation occurred (Picrosirius Red). Accumulated tissue thickness correlated with the decrease in leaflet motion. The PECUU scaffolds had histologic evidence of scaffold degradation and an accumulation of pro‐inflammatory/M1 and anti‐inflammatory/M2 macrophages over time in vivo. The extent of inflammatory cell accumulation correlated with tissue formation and polymer degradation but was also associated with leaflet thickening and decreased leaflet motion. Future studies should explore pre‐implant seeding of polymer scaffolds, more advanced polymer fabrication methods able to more closely approximate native tissue structure and function, and other techniques to control and balance the degradation of biomaterials and new tissue formation by modulation of the host immune response. [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]

Heart valve disease is an important cause of morbidity and mortality among cardiac patients worldwide. However, the pathogenesis of heart valve disease is not clear, and a growing body of evidence hints at the importance of the genetic basis and developmental origins of heart valve disease. Therefore, understanding the developmental mechanisms that underlie the formation of heart valves has important implications for the diagnosis, prevention, and treatment of congenital heart disease. Endothelial to mesenchymal transition is a key step in initiating cardiac valve development. The dynamic changes in the relative localization and proportion of different cell sources in the heart valve mesenchymal population are still not fully understood. Here, we used the Cdh5-CreER;R26R-tdTomato mouse line to trace endocardial cushion-derived endothelial cells to explore the dynamic contribution of these cells to each layer of the valve during valve development. This is beneficial for elaborating on the role of endocardial cells in the process of valve remodeling from a precise angle. [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]

Abstract 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.

More and more biological valves have been used in aortic valve replacement in the world due to their unique advantages; however, due to the poor durability of biological valves and other reasons, valve deterioration is an inevitable problem of artificial biological valves. Once severe valve deterioration occurs, it can lead to valve stenosis or regurgitation, which may result in cardiac enlargement and cardiac insufficiency and often require valve re-replacement. Surgical valve replacement has long been the gold standard for the treatment of aortic valve deterioration, but since biological valves are mostly used in the elderly and there is a high risk of surgical valve re-replacement, many patients are rejected from surgery. In recent years, due to the accumulation of experience in transcatheter aortic valve replacement (TAVR) and related technical advances, it has been increasingly applied in the treatment of biological valve deterioration, especially the application of “valve-in-valve” TAVR.

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]

Valvular heart disease (VHD) is one of the commonest causes of cardiovascular morbidity and mortality worldwide, with acquired VHD especially prevalent in countries with aging populations. The scope and pattern of disease are not well understood, as some patients are asymptomatic and available options for invasive treatment vary by affected valve. We sought to understand the burden of VHD in Japan including the distribution of patients by valve disease type and age, using administrative claims data from acute care hospitals. This was a retrospective descriptive study of patients with VHD diagnosis and at least one record of echocardiography in 2019 documented in the Medical Data Vision database. Affected valve(s) and type of valve disease were characterized using ICD-10 codes; patients undergoing invasive treatment for VHD at the same facility and during the same year as their diagnosis were assessed using procedure codes. Of 203,398 patients with VHD diagnosis and a record of echocardiography in 2019, 49.0 % had a mitral valve disorder, 44.9 % aortic valve, 22.9 % tricuspid valve, and 2.2 % pulmonic valve (14.9 % of patients had more than one disordered valve). A total of 7201 patients (<4 % of the total diagnosed population) received invasive treatment for VHD in 2019 at the diagnosing hospital. Patients with aortic stenosis (AS) had the highest mean age, at 79 years. Although mitral regurgitation was the most common VHD among diagnosed patients, AS predominated in the cohort of treated patients. A substantial portion of patients undergoing treatment for AS were age 85 years or older (27.2 %). The cohort of treated patients in 2019 was a small fraction of the total population with a VHD diagnosis in that year. Wide availability of transcatheter treatment for AS in Japan may be allowing more elderly patients to receive intervention than in other types of VHD. [Display omitted] • Mitral regurgitation was the most common valvular heart disease diagnosed in 2019. • The cohort of treated patients at the diagnosing hospital was small. • Aortic stenosis (AS) predominated in the cohort of treated patients. • The proportion of elderly was notably higher for patients with treatment for AS. [ABSTRACT FROM AUTHOR]

Background: Percutaneous transvenous mitral commissurotomy (PTMC) is one of the non-surgical methods for patients with significant mitral stenosis. It is less invasive, less complicating with better outcomes compared to surgery. The Wilkins score ≤8 is used to select patients for PTMC, but the results of several studies suggest that PTMC can also be successful in a higher Wilkins score. The aim of this study is to compare the outcomes of PTMC between two groups. Methods: In this retrospective study, patients who underwent PTMC between April 2011 and December 2019 were included. Patients were divided into two groups based on Wilkins score: 196 patients (57.64%) with a Wilkins score ≤8 (group I) and 134 patients (39.4%) with a Wilkins score >8 (group II). Results: There was no difference in demographic characteristics between two groups except for age (p = 0.04). Pre and post-interventional echocardiographic and catheterization measurements including left atrial pressure, pulmonary artery pressure, mitral valve area, mitral valve mean, and peak gradient were measured, and there was no difference between the two groups (p > 0.05). The most common complication was mitral regurgitation (MR). Serious complications such as stroke and arrhythmias were rare in both groups (<1%). There was no difference between MR, ASD (atrial septal defect) and serious complications between the two groups. Conclusion: This study shows that the Wilkins score with a cutoff value of 8 is not suitable for patient selection and novel criteria including both mitral valve features and other variables affecting the PTMC outcomes is needed. [ABSTRACT FROM AUTHOR]

Available data have demonstrated important sex-related differences in patients with valvular heart disease, regarding clinical presentation, treatment, and outcomes. Although the calcific aortic stenosis (AS) is more frequent in men compared to women, the majority of AS patients over 80 years old are women, in whom fibrotic remodeling of aortic valve is typically found. Mitral valve disease is more common in women. However females are under-referred or delayed referrals to treatment, probably due to the absence of sex-based LV dimension values guiding surgical timing. The development of transcatheter devices have revolutionized the treatment of valvular heart disease and increased the interest in this topic. In this context, the consideration of gender differences in presentation, diagnosis, treatment success, and prognosis is of great importance. [ABSTRACT FROM AUTHOR]

The data presented in this article provide load-dependent collagen fiber architecture (CFA) of one representative bovine tendon tissue sample and two representative porcine mitral valve anterior leaflet tissues, and they are stored in a MATLAB MAT-file format. Each dataset contains: (i) the number of pixel points, (ii) the array of pixels x- and y-coordinates, (iii) the three acquired pixel intensity arrays, and (iv) the Delaunay triangulation for visualization purpose. This dataset is associated with a companion journal article, which can be consulted for further information about the methodology, results, and discussion of the opto-mechanical characterization of the tissues CFAs (Jett et al. [1]).

Collagen fiber networks provide the structural strength of tissues, such as tendons, skin and arteries. Quantifying the fiber architecture in response to mechanical loads is essential towards a better understanding of the tissue-level mechanical behaviors, especially in assessing disease-driven functional changes. To enable novel investigations into these load-dependent fiber structures, a polarized spatial frequency domain imaging (pSFDI) device was developed and, for the first time, integrated with a biaxial mechanical testing system. The integrated instrument is capable of a wide-field quantification of the fiber orientation and the degree of optical anisotropy (DOA), representing the local degree of fiber alignment. The opto-mechanical instruments performance was assessed through uniaxial loading on tendon tissues with known collagen fiber microstructures. Our results revealed that the bulk fiber orientation angle of the tendon tissue changed minimally with loading (median ± 0.5*IQR of 52.7° ± 3.3° and 51.9° ± 3.3° under 0 and 3% longitudinal strains, respectively), whereas on a micro-scale, the fibers became better aligned with the direction of loading: the DOA (mean ± SD) increased from 0.149 ± 0.032 to 0.198 ± 0.056 under 0 and 3% longitudinal strains, respectively, p

Abnormal developments of the cardiovascular system are common congenital malformations. Computational fluid dynamics and mathematical modeling can be used to perform quantitative predictive assessments of hemodynamic properties in varied conditions. This article addresses the development of a coupled 0D–3D model of blood flow in newborns to predict risks of complications after surgery. The 0D-model of systemic circulations is created by using the analogy between the blood flow in vessels and the flow of current through an electric circuit. A shunted section of the aorta and pulmonary artery is replaced with a 3D-model with two-way fluid-solid interaction (FSI).A section in a vessel with the aortic valve is examined in a separate 3D-model. Three-dimensional geometry is based on real CT-scans of a patient. The algorithm for coupling models of different levels relies on meeting the condition that pressures and volumetric blood flows are equal at the interaction boundary. We have developed an algorithm for identifying personal parameters from the results obtained by solving an optimization problem. Computational experiments with different individual geometry of the aorta and aortic valve made it possible to analyze blood flow velocities, near-wall stresses, flows, and valve deformations. Observable near-wall stresses can be considered risk factors that could cause calcification on valve leaflets and other valve diseases. Computational solutions in the “aorta – shunt – pulmonary artery” 3D-system allowed obtaining spatial distributions of velocities, pressures, near-wall stresses and other parameters that are significant in respect to probable pathology development. The developed approaches are primarily relevant for decision-making in surgical practice to predict risks of postoperative complications. In future, our plans are to develop the model so that it covers also saturation and oxygen exchange. This is necessary for assessing whether oxygen supply to the lungs is adequate.

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]

Introduction: The heart and liver are two organs that are closely related. The Albumin-Bilirubin (ALBI) score is a developed scoring system for assessing liver function. The aims of this study were to examine the correlation between preoperative ALBI score and pulmonary artery pressure and to investigate its ability to predict heart valve surgery mortality outcomes. Methods: The data of 872 patients who underwent isolated and combined heart valve surgery from 2014 to 2021 were retrospectively screened. In the preoperative period, 152 patients with laboratory tests including albumin and total bilirubin were found and analyzed retrospectively. Thirteen of these patients were excluded from the study. The remaining 139 patients were included in the analysis. Baseline demographic data, echocardiography data, performance status, laboratory data, operative data, and postoperative status were collected. The optimal cutoff value of preoperative ALBI score was calculated. Results: The cutoff for ALBI scores was calculated as -2.44 to predict in-hospital mortality (sensitivity = 75.0%, specificity = 70%). Based on the cutoff value, 90 patients had a low ALBI score (≤ -2.44, 64.7%) and 49 patients had a high ALBI score (> -2.44, 35.3%). High ALBI score was associated with an increased incidence of acute kidney injury and in-hospital mortality, and a positive correlation was found between ALBI score and pulmonary artery pressure. Conclusion: In patients with valvular surgery, high ALBI score was an independent prognostic factor of in-hospital mortality and acute kidney injury. It is easily measurable and a cost-effective way to predict mortality. [ABSTRACT FROM AUTHOR]

The transforming growth factor beta (TGFβ) and Hippo signaling pathways are evolutionarily conserved pathways that play a critical role in cardiac fibroblasts during embryonic development, tissue repair, and fibrosis. TGFβ signaling and Hippo signaling are also important for cardiac cushion remodeling and septation during embryonic development. Loss of TGFβ2 in mice causes cardiac cushion remodeling defects resulting in congenital heart disease. In this study, we used in vitro molecular and pharmacologic approaches in the cushion mesenchymal cell line (tsA58-AVM) and investigated if the Hippo pathway acts as a mediator of TGFβ2 signaling. Immunofluorescence staining showed that TGFβ2 induced nuclear translocation of activated SMAD3 in the cushion mesenchymal cells. In addition, the results indicate increased nuclear localization of Yes-associated protein 1 (YAP1) following a similar treatment of TGFβ2. In collagen lattice formation assays, the TGFβ2 treatment of cushion cells resulted in an enhanced collagen contraction compared to the untreated cushion cells. Interestingly, verteporfin, a YAP1 inhibitor, significantly blocked the ability of cushion cells to contract collagen gel in the absence or presence of exogenously added TGFβ2. To confirm the molecular mechanisms of the verteporfin-induced inhibition of TGFβ2-dependent extracellular matrix (ECM) reorganization, we performed a gene expression analysis of key mesenchymal genes involved in ECM remodeling in heart development and disease. Our results confirm that verteporfin significantly decreased the expression of α-smooth muscle actin (Acta2), collagen 1a1 (Col1a1), Ccn1 (i.e., Cyr61), and Ccn2 (i.e., Ctgf). Western blot analysis indicated that verteporfin treatment significantly blocked the TGFβ2-induced activation of SMAD2/3 in cushion mesenchymal cells. Collectively, these results indicate that TGFβ2 regulation of cushion mesenchymal cell behavior and ECM remodeling is mediated by YAP1. Thus, the TGFβ2 and Hippo pathway integration represents an important step in understanding the etiology of congenital heart disease.

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.

Various forms of vortex formation in the cardiovascular system convey valuable information regarding the function of heart and great vessels. The vortex ring that forms during systole in the aortic sinus is the first that was recognized and the asymmetric transmitral vortex ring that forms in the left ventricle during diastole has been most commonly used for diagnosis and follow up of heart failure patients. Adverse vortex interaction in the heart can also occur due to valvular regurgitation and may have energetic consequences to the heart. Furthermore, vortices do exist in other chambers such as the right ventricle and may even arise in the great arteries and veins due to congenital heart disease. Here, we summarize diagnostic and prognostic significance of vortices and vortex imaging in the heart, their applications in clinical medicine, and discuss how these flow features can be used to assess functional status of the heart.

Bioprosthetic valve dysfunction represent a serious drawback that limits the wider clinical use of these medical devices for valvular heart disease surgery. Modern studies describe the view of pathophysiologists on this problem as a multifactorial multi-stage process that causes irreversible changes in bioprosthesis components, ultimately leading to its dysfunction. However, in addition to under- standing the causes and manifestations of prosthetic valve dys- function, an applied question arises about the treatment strategies — determining the most attenuated and accessible low-risk method/ device. The aim of this review was to analyze and systematize current literature data on methods and designs used in repeated surgical and transcatheter interventions on heart valves.

Valvular heart disease is an important source of cardiovascular morbidity and mortality. Current prosthetic valve replacement options, such as bioprosthetic and mechanical heart valves are limited by structural valve degeneration requiring reoperation or the need for lifelong anticoagulation. Several new polymer technologies have been developed in recent years in the hope of creating an ideal polymeric heart valve substitute that overcomes these limitations. These compounds and valve devices are in various stages of research and development and have unique strengths and limitations inherent to their properties. This review summarizes the current literature available for the latest polymer heart valve technologies and compares important characteristics necessary for a successful valve replacement therapy, including hydrodynamic performance, thrombogenicity, hemocompatibility, long-term durability, calcification, and transcatheter application. The latter portion of this review summarizes the currently available clinical outcomes data regarding polymeric heart valves and discusses future directions of research.

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]

Background. Infective endocarditis (IE) is defined as an infection of a native or prosthetic heart valve, endocardial surface, or permanent cardiac apparatus. Currently, the determination of microorganisms that induce a disease or are involved in the process of pathogenesis by PCR is one of the most modern and rapid tests.The aim. To determine and to compare the spectrum of infectious pathogens in homogenate samples of native heart valves and blood of patients with IE.Materials and methods. Twenty patients with confirmed IE diagnose were examined, admitted for hospitalization at the Research Institute for Complex Issues of Cardiovascular Diseases (Kemerovo, Russia) in 2019. The range of tests used in the study was aimed at detecting such microorganisms as Streptococcus pyogenes, Streptococcus agalactiae, Enterobacter spp., Klebsiella spp., Staphylococcus spp., Streptococcus spp., Bacteroides fragilis, Bacteroides vulgatus, Bacteroides thetaiotaomicron, and Bacteroides ovatus.Results. The study found that 19 samples of heart valves were characterized by the presence of microorganisms from the genus Streptococcus spp., wherein Streptococcus agalactiae was found in two patients. Staphylococcus spp. Were found in 16 samples of valve homogenate. Detection of other pathogens revealed only two cases of Enterobacter spp., Klebsiella spp. When analyzing blood samples from patients with IE, not a single infectious agent was identified. The study revealed a statistically significant difference (p < 0.001) between the incidence of Staphylococcus spp. in samples of valve homogenate and peripheral blood of patients with IE. There was also a statistically significant difference (p < 0.001) for Streptococcus spp. both in samples of valve homogenate and peripheral blood from patients with IE.Conclusion. Molecular genetic research using PCR technologies has low efficiency in detecting the pathogen in the circulating bloodstream, as well as in blood culture. However, the study of homogenized biopsy specimens of the heart valve structures removed during surgery may allow correcting antimicrobial tactics in the early postoperative period of prosthetics.

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]