Univariate Risk Factors for Prolonged Mechanical Ventilation in Patients Undergoing Prosthetic Heart Valves Replacement Surgery

Data from 736 patients undergoing prosthetic heart valve replacement surgery and concomitant surgery （combined surgery） from January 1998 to January 2004 at Union Hospital were retrospectively reviewed. Univariate logistic regression analyses were conducted to identity risk factors for prolonged mechanical ventilation. The results showed that prolonged cardiopulmonary bypass duration, prolonged aortic cross clamp time and low ejection fraction less than 50 percent （50 %） were found to be independent predictors for prolonged mechanical ventilation. Meanwhile age, weight, and preoperative hospital stay （days） were not found to be associated with prolonged mechanical ventilation. It was concluded that. for age and weight, this might be due to the lower number of old age patients （70 years and above） included in our study and genetic body structure of majority Chinese population that favor them to be in normal weight, respectively.

Imaging of pannus formation in patients with mechanical heart valves

Patient-prosthesis mismatch(PPM) should be recognized in patients with elevated transprosthetic gradients but without leaflet immobility, since the treatment strategy may differ in either etiology. However, thrombus and/or pannus formation should be excluded before a diagnosis of PPM is made. Particularly, pannus formation may not be diagnosed with 2-dimensional transesophageal echocardiography. Electrocardiographically gated 64-section multidetector computed tomography(MDCT) may be a promising tool in diagnosing or excluding pannus formation. Our report underlines the utility of MDCT in this regard and also emphasizes the importance of recognition of PPM as a differential diagnosis in such patients.

Low-intensity anticoagulation therapy in the pregnant women with mechanical heart valves:a report with 56 cases

Objective To evaluate the method of low-intensity anticoagulation therapy in the pregnant women who had received mechanical heart valve replacemant,and the effects of warfarin on the pregnant women and their fetus. Methods This retrospective study involved 56 pregnant women (61 pregnancies) who had received mechanical heart valve replacement. Their pregnant status,delivery, and anticoagulation therapy were observed

In vitro calcification studies on bioprosthetic and decellularized heart valves under quasi-physiological flow conditions

The lifespan of biological heart valve prostheses available in the market is limited due to structural alterations caused by calcium phosphate deposits formed from blood plasma in contact with the tissues.The objective of this work is to present a comparative methodology for the investigation of the formation of calcium phosphate deposits on bioprosthetic and tissue-engineered scaffolds in vitro and the influence of mechanical forces on tissue mineralization.Based on earlier investigations on biological mineralization at constant supersaturation,a circulatory loop simulating dynamic blood flow and physiological pressure conditions was developed.The system was appropriately adapted to evaluate the calcification potential of decellularized(DCV)and glutaraldehyde-fixed(GAV)porcine aortic valves.Results indicated that DCV calcified at higher,statistically nonsignificant,rates in comparison with GAV.This difference was attributed to the tissue surface modifications and cell debris leftovers from the decellularization process.Morphological analysis of the solids deposited after 20 h by scanning electron microscopy in combination with chemical microanalysis electron-dispersive spectroscopy identified the solid formed as octacalcium phosphate(Ca8(PO4)6H2·5H2O,OCP).OCP crystallites were preferentially deposited in high mechanical stress areas of the test tissues.Moreover,GAV tissues developed a significant transvalvular pressure gradient increase past 36 h with a calcium deposition distribution similar to the one found in explanted prostheses.In conclusion,the presented in vitro circulatory model serves as a valuable prescreening methodology for the investigation of the calcification process of bioprosthetic and tissue-engineered valves under physiological mechanical load.

Pathogenic Mineralization of Calcium Phosphate on Human Heart Valves

When calcium phosphate forms in soft tissues such as blood vessels and heart valves, it causes disease. The abnormal formation of calcium phosphate is called pathogenic mineralization or pathogenic calcification. Cases of rheumatic heart disease （RHD） always occur with fibrotic and calcified tissue of heart valve. In this article, samples taken from calcified human heart wdves were studied. The characterization was performend by scanning electronic microscope, X-ray Diffraction and transmission electron microscopy with selective diffraction patterns. It is found for the first time that calcium phosphate grains existing in the calcified human heart valves contain octacalcium phosphate （ OCP ）.

Recent progress in functional modification and crosslinking of bioprosthetic heart valves

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

Bioinspired polymeric heart valves derived from polyurethane and natural cellulose fibers

In this work,bioinspired anisotropic polymeric heart valves were fabricated using composite materials from polyurethane(PU)and natural cellulose fiber bundles.Cellulose fibers with good alignment were obtained from balsa wood by a top-down process,which were then distributed in polyurethane to pre-pare cellulose fiber bundles reinforced polyurethane(CPU)by hot pressing.The storage modulus of the CPU along the direction parallel to the fiber alignment was 16.70±0.80 MPa,whereas that along the direction perpendicular to the fiber alignment was 8.41±0.94 MPa by dynamic mechanical analysis(DMA)tests at 1 Hz,comparable to aortic valve leaflets.Moreover,2-methacryloyloxyethyl phosphoryl-choline(MPC)was grafted onto the CPU surface(CPU-MPC)to improve hemocompatibility.With MPC modification,the water contact angle decreased significantly from 54.58°±2.98°to 26.42°±3.50°,and the platelet adhesion was reduced by 92%,compared to the original CPU.In vitro cell culture proved that both CPU and CPU-MPC samples did not show any cytotoxicity.Furthermore,the CPU composites were used to fabricate polymeric heart valves,which showed excellent hydrodynamic performance with a large orifice area(1.70 cm 2)and low regurgitation fraction(0.7%),meeting the requirements of ISO 5840-2 standard.

Immunological and functional features of decellularized xenogeneic heart valves after transplantation into GGTA1-KO pigs

Decellularization of xenogeneic heart valves might lead to excellent regenerative implants,from which many patients could benefit.However,this material carries various xenogeneic epitopes and thus bears a considerable inherent immunological risk.Here,we investigated the regenerative and immunogenic potential of xenogeneic decellularized heart valve implants using pigs deficient for the galactosyltransferase gene(GGTA1-KO)as novel large animal model.Decellularized aortic and pulmonary heart valves obtained from sheep,wild-type pigs or GGTA1-KO pigs were implanted into GGTA1-KO pigs for 3,or 6 months,respectively.Explants were analyzed histologically,immunhistologically(CD3,CD21 and CD172a)and anti-aGal antibody serum titers were determined by ELISA.Xenogeneic sheep derived implants exhibited a strong immune reaction upon implantation into GGTA1-KO pigs,characterized by massive inflammatory cells infiltrates,presence of foreign body giant cells,a dramatic increase of anti-aGal antibody titers and ultimately destruction of the graft,whereas wild-type porcine grafts induced only a mild reaction in GGTA1-KO pigs.Allogeneic implants,wild-type/wild-type and GGTA1-KO/GGTA1-KO valves did not induce a measurable immune reaction.Thus,GGTA1-KO pigs developed a‘human-like’immune response toward decellularized xenogeneic implants showing that immunogenicity of xenogeneic implants is not sufficiently reduced by decellularization,which detracts from their regenerative potential.

Mechanical versus biological prosthetic heart valves in pregnant women with valvular heart disease

Background The pregnant women with a prosthetic heart valve(PHV)are considered to have a higher risk of cardiovascular,obstetric and fetal/neonatal complications when they underwent anticoagulation therapy in all 3 trimesters.This report evaluated the comparative results of pregnant women wearing mechanical and biological PHV.Methods The outcomes of different types of PHV were assessed retrospectively in pregnant women in Guangdong Provincial People’s Hospital from January 2008 to May 2021.A total of 243 women(319 pregnancies)were enrolled and divided into mechanical PHV group and biological PHV group according to the types of PHV implanted.The baseline data of all pregnancies were studied.Cardiovascular,obstetric and fetal/neonatal complications in 201 completed pregnancies of 165 women with different PHV were analyzed.Results 319 pregnancies occurred,of which 201 pregnancies(165 women)≥20 weeks duration,including 159 pregnancies with mechanical PHV and 42 pregnancies with biological PHV.Miscarriages were more common in women with mechanical PHV[40 pregnancies(14.65%),≤20 weeks],while only one case was noted in women with biological PHV(P<0.05).The induced abortion rate of women with mechanical PHV(27.11%vs.6.52%,P<0.05)was significantly higher compared with that in women with biological PHV.The incidence of cardiovascular,obstetric and fetal/neonatal complications was equally frequent in both groups after 20 weeks of gestation.Conclusions Pregnant women with mechanical PHV were more likely to have a complication of miscarriages than those with biological PHV,mainly due to the anticoagulation therapy.On the other hand,more women with mechanical PHV may choose not to become pregnant than women with biological PHV after counseling the risks of pregnancy.There was no significant difference in other aspects of maternal and fetal complications after 20 weeks of gestation.Women who cannot maintain therapeutic anticoagulation and frequent monitoring of mechanical PHV may consider biological PHV.

Functional non-glutaraldehyde treated porcine pericardium for anti-coagulation,anti-calcification,and endothelial proliferation bioprosthetic heart valves

In the last decade,the number of transcatheter heart valve replacement for severe heart valve disease has increased exponentially.Although the bioprosthetic artificial heart valve(BHV)has similar fluid dynamics performance to the original heart valve compared with mechanical heart valve so that there is no need to take long-term anticoagulant drugs to prevent thromboembolism,transcatheter BHV replacement are still at risk for thrombosis during the first few months according to the clinical data.However,the use of antithrombotic drugs can also increase the risk of bleeding.Therefore,it is particularly important to improve the anticoagulant properties for the BHV itself.In this work,a kind of non-glutaraldehyde cross-linked BHV material with excellent antithrombotic ability has been prepared from carboxylated oxazolidine treated porcine pericardium(consisting of collagen,elastin and glycoprotein)with the further graft of the anticoagulant heparin sodium via hydrophilic modified chitosan.Along with the similar mechanical properties and collagen stability comparable to the glutaraldehyde cross-linked porcine pericardium(PP),these functional non-glutaraldehyde cross-linked PPs exhibit better biocompatibility,promoted endothelial proliferation and superior anti-calcification ability.More importantly,excellent anticoagulant activity can be observed in the hematological experiments in vivo and in vitro.In summary,these excellent performances make these functional non-glutaraldehyde cross-linked PPs great potentialities in the BHV applications.

Heart Valves Grown from Womb Fluid Cells

科学家们首次从人体子宫的流体细胞中培育出了人类的心瓣膜,这一发现为有先天心脏缺陷的患者带来了福音。这种由自身组织培植的心瓣膜被移植入人体后,其性能将比人工心脏或者通过器官捐献而来的心脏更持久有效;并且,此项研究的前期动物试验已经成功。

Construction of tissue-engineered heart valves by using decellularized scaffolds and endothelial progenitor cells

Background Tissue-engineered heart valves have the potential to overcome the limitations of present heart valve replacements. This study was designed to develop a tissue engineering heart valve by using human umbilical cord blood-derived endothelial progenitor cells （EPCs） and decellularized valve scaffolds. Methods Decellularized valve scaffolds were prepared from fresh porcine heart valves. EPCs were isolated from fresh human umbilical cord blood by density gradient centrifugation, cultured for 3 weeks in EGM-2-MV medium, by which time the resultant cell population became endothelial in nature, as assessed by immunofluorescent staining. EPC-derived endothelial cells were seeded onto the decellularized scaffold at 3 × 10^6 cells/cm^2 and cultured under static conditions for 7 days. Proliferation of the seeded cells on the scaffolds was detected using the MTT assay. Tissue-engineered heart valves were analyzed by HE staining, immunofluorescent staining and scanning electron microscopy. The anti-thrombogenic function of the endothelium on the engineered heart valves was evaluated by platelet adhesion experiments and reverse transcription-polymerase chain reaction （RT-PCR） analysis for the expression of endothelial nitric oxide synthase （eNOS） and tissue-type plasminogen activator （t-PA）.Results EPC-derived endothelial cells showed a histolytic cobblestone morphology, expressed specific markers of the endothelial cell lineage including von Willebrand factor （vWF） and CD31, bound a human endothelial cell-specific lectin, Ulex Europaeus agglutinin-1 （UEA-1）, and took up Dil-labeled low density lipoprotein （Dil-Ac-LDL）. After seeding on the decellularized scaffold, the cells showed excellent metabolic activity and proliferation. The cells formed confluent endothelial monolayers atop the decellularized matrix, as assessed by HE staining and immunostaining for vWF and CD31. Scanning electron microscopy demonstrated the occurrence of tight junctions between cells forming the confluent monolayer. Platelets adhesion experiments suggested that the neo-endothelium was non-thrombogenic. The expression levels of eNOS and t-PA genes in the neo-endothelium were quite similar to those in human umbilical vein endothelial cells. Conclusions EPCs isolated from the human umbilical cord blood can differentiate into endothelial cells in vitro and form a functional endothelium atop decellularized heart valve scaffolds. Thus, EPCs may be a promising cell source for constructing tissue-engineered heart valves.

Low standard oral anticoagulation therapy for Chinese patients with St.Jude mechanical heart valves

Objective To study the efficacy of the low standard oral anticoagulation therapy following St Jude Medical (SJM) valve implantation for Chinese patients.Methods Totally 805 patients with a mean age of 42.70±11.09 years,enrolled into this study. Among them,230 underwent aortic valve replacements (AVR),381 mitral valve replacements (MVR),189 double valve replacements (DVR) and 5 tricuspid valve replacememts (TVR). All patients received postoperative oral anticoagulation therapy based on a low standard of international normalized ratio (INR,2.0-2.5). Of the 805 patients,710 were followed up for 0.25-13 years (a median,4.15 years). Results Postoperatively,17 adverse events occurred. Operative mortality was 2.11%. The most frequent cause of operative mortality was a low cardiac output. During follow-up,there were 47 anticoagulant-induced hemorrhages [1.59%/patient-year (pt-yr)],10 cases of thromboembolism (0.34%/pt-yr),and 3 mechanical valve thromboses (0.19%/pt-yr). There were 44 late deaths and the linearized late mortality rates were 0.51%pt-yr. Estimates of actuarial survival for all patients at 5 and 10 years was 97.45% (0.70%) and 77.96% (17.44%),respectively.Conclusions A low target INR range of 2.0-2.5 is preferable for Chinese patients so as to reduce the severe bleeding complications in those with conventionally higher levels of INR. The long-term results were satisfactory in terms of the numbers of those who suffered thrombosis,embolism and bleeding.

Trilayer anisotropic structure versus randomly oriented structure in heart valve leaflet tissue engineering

It has been hypothesized that leaflet substrates with a trilayer structure and anisotropicmechanical properties could be useful for the production of functional and long-lasting tissue-engineered leaflets.To investigate the influence of the anisotropic structural and mechanical characteristics of a substrate on cells,in this study,we electrospun trilayer anisotropic fibrous substrates and randomly oriented isotropic fibrous substrates(used as controls)from polycaprolactone polymers.Consequently,the random substrates had higher radial and lower circumferential tensile properties than the trilayer substrates;however,they had similar flexural properties.Porcine valvular interstitial cells cultured on both substrates produced random and trilayer cell-cultured constructs,respectively.The trilayer cell-cultured constructs had more anisotropic mechanical properties,17%higher cellular proliferation,14%more extracellular matrix(i.e.,collagen and glycosaminoglycan)production,and superior gene and protein expression,suggesting that more cells were in a growth state in the trilayer constructs than in the random constructs.Furthermore,the random and radial layers of the trilayer constructs had more vimentin,collagen,transforming growth factor-beta 1(TGF-ß1),transforming growth factor-beta 3(TGF-ß3)gene expression than in the circumferential layer of the constructs.This study verifies that the differences in structural,tensile,and anisotropic properties of the trilayer and random substrates influence the characteristics of the cells and ECM in the constructs.

Experimental and computational models for tissue-engineered heart valves:a narrative review

Valvular heart disease is currently a common problem which causes high morbidity and mortality worldwide.Prosthetic valve replacements are widely needed to correct narrowing or backflow through the valvular orifice.Compared to mechanical valves and biological valves,tissue-engineered heart valves can be an ideal substitute because they have a low risk of thromboembolism and calcification,and the potential for remodelling,regeneration,and growth.In order to test the performance of these heart valves,various animal models and other models are needed to optimise the structure and function of tissue-engineered heart valves,which may provide a potential mechanism responsible for substantial enhancement in tissue-engineered heart valves.Choosing the appropriate model for evaluating the performance of the tissue-engineered valve is important,as different models have their own advantages and disadvantages.In this review,we summarise the current state-of-the-art animal models,bioreactors,and computational simulation models with the aim of creating more strategies for better development of tissue-engineered heart valves.This review provides an overview of major factors that influence the selection and design of a model for tissue-engineered heart valve.Continued efforts in improving and testing models for valve regeneration remain crucial in basic science and translational researches.Future research should focus on finding the right animal model and developing better in vitro testing systems for tissue-engineered heart valve.

A NUMERICAL ANALYSIS OF THE BLOOD FLOW AROUND THE BILEAFLET MECHANICAL HEART VALVES WITH DIFFERENT ROTATIONAL IMPLANTATION ANGLES

The effects of implantation angles of Bileaflet Mechanical Heart Valves （BMHVs） on the blood flow and the leaflet motion are investigated in this paper. The physiological blood flow interacting with the moving leaflets of a BMHV is simulated with a strongly coupled implicit Fluid-Structure Interaction （FSI） method based on the Arbitrary-Lagrangian-Eulerian （ALE） approach and the dynamic mesh method （remeshing） in Fluent. BMHVs are widely used to be implanted to replace the diseased heart valves, but the patients would suffer from some complications such as hemolysis, platelet activation, tissue overgrowth and device failure. These complications are closely related to both the flow characteristics near the valves and the leaflet dynamics. The current numerical model is validated against a previous experimental study. The numerical results show that as the rotation angle of BMHV is increased the degree of asymmetry of the blood flow and the leaflet motion is increased, which may lead to an unbalanced force acting on the BMHVs. This study shows the applicability of the FSI model for the interaction between the blood flow and the leaflet motion in BMHVs.

Current progress on scaffolds of tissue engineering heart valves

Tissue engineering heart valves(TEHV)may be the most promising valve substitute,but the study has been relatively stagnant in the recent five years due to the special position,function and mechanical property of heart valves.It is one of the key factors to select an ideal scaffold material in the construction of TEHV.And this article will briefly review the current research and progress on the scaffolds of TEHV,especially based on Chinese works.

Safety and effectiveness of neuromuscular electrical stimulation in cardiac surgery:A systematic review

BACKGROUND Lack of mobilization and prolonged stay in the intensive care unit(ICU)are major factors resulting in the development of ICU-acquired muscle weakness(ICUAW).ICUAW is a type of skeletal muscle dysfunction and a common complication of patients after cardiac surgery,and may be a risk factor for prolonged duration of mechanical ventilation,associated with a higher risk of readmission and higher mortality.Early mobilization in the ICU after cardiac surgery has been found to be low with a significant trend to increase over ICU stay and is also associated with a reduced duration of mechanical ventilation and ICU length of stay.Neuromuscular electrical stimulation(NMES)is an alternative modality of exercise in patients with muscle weakness.A major advantage of NMES is that it can be applied even in sedated patients in the ICU,a fact that might enhance early mobilization in these patients.AIM To evaluate safety,feasibility and effectiveness of NMES on functional capacity and muscle strength in patients before and after cardiac surgery.METHODS We performed a search on Pubmed,Physiotherapy Evidence Database(PEDro),Embase and CINAHL databases,selecting papers published between December 2012 and April 2023 and identified published randomized controlled trials(RCTs)that included implementation of NMES in patients before after cardiac surgery.RCTs were assessed for methodological rigor and risk of bias via the PEDro.The primary outcomes were safety and functional capacity and the secondary outcomes were muscle strength and function.RESULTS Ten studies were included in our systematic review,resulting in 703 participants.Almost half of them performed NMES and the other half were included in the control group,treated with usual care.Nine studies investigated patients after cardiac surgery and 1 study before cardiac surgery.Functional capacity was assessed in 8 studies via 6MWT or other indices,and improved only in 1 study before and in 1 after cardiac surgery.Nine studies explored the effects of NMES on muscle strength and function and,most of them,found increase of muscle strength and improvement in muscle function after NMES.NMES was safe in all studies without any significant complication.CONCLUSION NMES is safe,feasible and has beneficial effects on muscle strength and function in patients after cardiac surgery,but has no significant effect on functional capacity.

Application of Decellularized Scaffold Combined with Loaded Nanoparticles for Heart Valve Tissue Engineering in vitro

The purpose of this study was to fabricate decelluarized valve scaffold modified with polyethylene glycol nanoparticles loaded with transforming growth factor-β1（TGF-β1）,by which to improve the extracellular matrix microenvironment for heart valve tissue engineering in vitro.Polyethylene glycol nanoparticles were obtained by an emulsion-crosslinking method,and their morphology was observed under a scanning electron microscope.Decelluarized valve scaffolds,prepared by using trypsinase and TritonX-100,were modified with nanoparticles by carbodiimide,and then TGF-β1 was loaded into them by adsorption.The TGF-β1 delivery of the fabricated scaffold was measured by asing enzyme-linked immunosorbent assay.Whether unseeded or reseeded with myofibroblast from rats,the morphologic,biochemical and biomechanical characteristics of hybrid scaffolds were tested and compared with decelluarized scaffolds under the same conditions.The enzyme-linked immunosorbent assay revealed a typical delivery of nanoparticles.The morphologic observations and biological data analysis indicated that fabricated scaffolds possessed advantageous biocompatibility and biomechanical property beyond decelluarized scaffolds.Altogether this study proved that it was feasible to fabricate the hybrid scaffold and effective to improve extracellular matrix microenvironment,which is beneficial for an application in heart valve tissue engineering.

Effect of L-carnitine on Cardiomyocyte Apoptosis and Cardiac Function in Patients Undergoing Heart Valve Replacement Operation

Summary： The effects of L-carnitine, as an ingredient of cardioplegia solution, on cardiac function and cardiomyocyte apoptosis in patients undergoing heart valve replacement operation were investigated. Twenty-three cases undergoing heart valve replacement with cardiopulmonary bypass （CPB） were randomly allocated into two groups： L-carnitine group （n=12, 12 g/L L-carnitine was put in the ST. Thomas cardioplegia） and control group （n=11, identical to the L-carnitine group except that normal saline was administered instead of L-carnitine）. Serum cardial troponin I （cTnI） levels, the left ventricular ejection fraction （LVEF）, and cardiac index （CI） were measured perioperatively. A bit of myocardial tissue obtained from right atria was taken before CPB and by the end of intracardiac procedure to undergo electron microscopy examination and estimate apoptosis by terminal deoxynucleotidyl transferase-mediated dUTP nick end-labeling （TUNEL）. From the end of CPB to 3 days after operation, the serum levels of cTnI in the L-carnitine group was significantly lower than that in the control group （P〈0.05）. Heart color ultrasonogram showed that the CI index and LVEF at 7th day postoperatively in the L-carnitine group were significantly higher than in the control group （P〈0.05）. Compared to the control group, L-carnitine significantly alleviated the morphologic changes of cardiac muscle cells （electron microscopy examination） and decreased the amounts of apoptotic cardiac muscle cells （TUNEL）. Furthermore, the dosage of vasoactive drugs used after operation was significantly less in the L-carnitine group （P〈0.01）. It was concluded that L-carnitine cardioplegia solution could improve cardiac function in patients undergoing heart valve replacement operation and alleviate CPB-mediated apoptosis of cardiac muscle cells.