Current Status of and Opinions on Heart Transplantation in China

The purpose of this review is to provide a comprehensive update on recent advances in heart transplantation in China.Despite advances in pharmacologic and device treatment of chronic heart failure,long-term morbidity and mortality remain high,and many patients progress to end-stage heart failure.Heart transplantation has become standard treatment for selected patients with end-stage heart failure,though challenges still exist.However,multiple advances over the past few years will improve the survival and quality-of-life of heart transplant recipients.This article elaborates on the specific characteristics of heart transplantation in China,the current issues,development trends,and related experiences with heart transplantation in Wuhan Union Hospital.

Role of TGF-βl Signaling in Heart Valve Calcification Induced by Abnormal Mechanical Stimulation in a Tissue Engineering Model

A tissue engineering model of heart valve calcification induced in a bio-reactor was established to evaluate the calcification induced by abnormal mechanical stimulation and explore the underlying molecular mechanisms.Polyethylene glycol (PEG)-modified decellularized porcine aortic leaflets seeded with human valve interstitial cells (huVICs)were mounted on a Ti-Ni alloy frame to fabricate two-leaflet and three-leaflet tissue engineered valves.The two-leaflet model valves were exposed to abnormal pulsatile flow stimulation with null (group A),low (1000mL/min,group B),medium (2000mL/min,group C),and high velocity (3000mL/min,group D)for 14 days. Morphology and calcification were assessed by yon Kossa staining,alkaline phosphatase (ALP)content,and Runx2 immunostaining.Leaflet calcification and mRNA and protein expression of transforming growth factor (TGF)-β1,bone morphogenetic protein 2 (BMP2),Smadl,and MSX2 were measured at different time points.ALP content was examined in two-leaflet valves seeded with BMP2 shRNA plasmid-infected huVICs and exposed to the same stimulation conditions.The results showed that during 14 days of flow stimulation,huVICs on the leaflet surface proliferated to generate normal monolayer coverage in groups A,B,and C.Under mechanical stimulation,huVICs showed a parallel growth pattern in the direction of the fluid flow,but huVICs exhibited disordered growth in the high-velocity flow environment,yon Kossa staining,ALP measurement,and immunohistochemical staining for Runx2 confirmed the lack of obvious calcification in group A and significant calcification in group D.Expression levels of TGF-β1,BMP2, and MSX2 mRNA and protein were increased under fluid stimulation.ALP production by BMP2 shRNA plasmid-infected huVICs on model leaflets was significantly reduced.In conclusion,abnormal mechanical stimulation in a bioreactor induced calcification in the tissue engineering valve model.The extent of calcification correlated positively with the flow velocity,as did the mRNA and protein levels of TGF-β1,BMP2,and MSX2.These findings indicate that TGF-β1/BMP2 signaling is involved in valve calcification induced bv abnormal mechanical stimulation.

Application of Endoscopic Vein Harvesting in Obese Patients Undergoing Coronary Artery Bypass Grafting

This study aims to evaluate the clinical outcomes of endoscopic vein harvesting （EVH） for coronary artery bypass grafting （CABG） in obese patients. Totally, 153 obese patients who underwent EVH （n=81） or standard bridging technique （SBT, n=72） in CABG surgery from May 2012 to October 2014 in our hospital were enrolled in this retrospective non-randomized controlled study. The general situation of operation, postoperative complications and short medium-term outcomes were analyzed. The baseline characteristics were similar between these two groups （P〉0.05）. There were no statistical differences in total operation time （226±28 min vs. 224±30 min, P〉0.05）, number of damaged vessels （0.12±0.05 vs. 0.16±0.06, P〉0.05） and short medium-term outcomes including revascularization rate （1.25% vs. 2.78%, P〉0.05）, vessel dysfunction rate （11.25% vs. 11.11%, P〉0.05） and mortality （0.00% vs. 0.00%, P〉0.05）. Use of EVH was associated with significant reduction of total harvesting time （41±6 min vs. 63±11 min, P〈0.05）, incision length （4.4±1.1 cm vs. 18.2±4.5 cm, P〈0.05） and postoperative lower extremity complications （P〈0.05）. EVH can reduce the risk of wound complications, whereas does not influence short- and medium-term outcomes in obese patients. It can be considered a reliable procedure of harvesting vessel conduits for obese patients undergoing CABG.

Identification of Two Mutations in PCDHGA4 and SLFN14 Genes in an Atrial Septal Defect Family

Atrial septal defect (ASD)is a common acyanotic congenital cardiac disorder associated with genetic mutations.The objective of this study was to identify the genetic factors in a Chinese family with ASD patients by a whole exome sequencing approach.Causative ASD gene mutations were examined in 16 members from a three-generation family,among which 6 individuals were diagnosed as having ASD.One hundred and eighty-three unrelated healthy Chinese were recruited as a normal control group.Peripheral venous blood was collected from every subject for genetic analysis.Exome sequencing was performed in the ASD patients.Potential causal mutations were detected in non-ASD family members and normal controls by polymerase chain reaction and sequencing analysis.The results showed that all affected family members carried two novel compound mutations,c.1187delT of PCDHGA4 and c.2557insC of SLFN14,and these two mutations were considered to have synergetic function on ASD.In conclusion,the mutations of c.1187delT of PCDHGA4 and c.2557insC of SLFN14 may be pathogenic factors contributing to the development of ASD.

Aβ40 Promotes the Osteoblastic Differentiation of Aortic Valve Interstitial Cells through the RAGE Pathway

Amyloid beta(AB)peptide 40 enhances the activation of receptor for advanced glycation end products(RAGE)in immune-inflammatory diseases.RAGE exhibits several ffects in the setting of numerous cardiovascular events.We bypothesized that the Aβ40/RAGE pathway is involved in the osteoblastic differentiation of the valvular interstitial cell(VIC)phenotype,and RAGE knockout intervention could reduce the calcification of aortic valve interstitial cells(AVICs)by inhibiting the extracellular-regulated kinase1/2(ERK 1/2)/nuclear factor kappa-B(NF-kB)signaling pathway.To test this hypothesis,the activation of AB40/RAGE pathway in human calcific AVs was evaluated with immunohistochemical staining.Cultured calcific VIC models were used in vitro.The VICs were stimulated using Aβ40,with or without RAGE small interfering ribonucleic acid(siRNA),and ERK1/2 and NF-κB inhibitors for analysis.Our data revealed that AB40 induced the ERK 1/2/NF-κB signaling pathway and osteoblastic differentiation of AVICs via the RAGE pathway in vitro.

Role of Interleukin 17A in Aortic Valve Inflammation in Apolipoprotein E-deficient Mice

Summary:Interleukin 17A(IL 17A)is reported to be involved in many inflammatory processes,but its role in aortic valve diseases remains unknown.We examined the role of IL17A based on an ApoE^-/-mouse model with strategies as fed with high-fat diet or treated with ILI7A monoclonal antibody(mAb).12 weeks of high-fat diet feeding can elevate cytokines secretion,inflammatory cells infiltration and myofibroblastic transition of valvular interstitial cells(VICs)in aortic valve.Moreover,diet-induction accelerated interleukin 17 receptor A(IL17RA)activation in VICs.In an IL17A inhibition model,the treatment group was intra-peritoneally injected with anti-IL17A mAb while controls received irrelevant antibody.Functional blockade of IL17A markedly reduced cellular infiltration and transition in aortic valve.To investigate potential mechanisms,NF-kB was co-stained in IL17RA^+VICs and IL17RA macrophages,and further confirmed by Western blotting in VICs.High-fat diet could activate NF-kB nuclear translocation in IL17RA^+VICs and IL17RA^+macrophages and this process was depressed after IL17A mAb-treatment.In conclusion,high-fat diet can lead to IL17A upregulation,VICs myofibroblastic transition and inflammatory cells infiltration in the aortic value of ApoE^-/-mice.Blocking IL17A with IL17A mAb can alleviate aortic valve inflammatory states.

Role of Neuroimmune Interactions in COVID-19-related Cardiovascular Damage

Coronavirus disease 2019(COVID-19)has caused a global pandemic impacting over 200 countries/regions and more than 200 million patients worldwide.Among the infected patients,there is a high prevalence of COVID-19-related cardiovascular injuries.However,the specific mechanisms linking cardiovascular damage and COVID-19 remain unclear.The COVID-19 pandemic also has exacerbated the mental health burden of humans.Considering the close association between neuroimmune interactions and cardiovascular disease,this review assessed the complex pathophysiological mechanisms connecting neuroimmune interactions and cardiovascular disease.It was revealed that the mental health burden might be a pivotal accomplice causing COVID-19-associated cardiovascular damage.Specifically,the proinflammatory status of patients with a terrible mood state is closely related to overdrive of the hypothalamus-pituitary-adrenal(HPA)axis,sympathovagal imbalance,and endothelial dysfunction,which lead to an increased risk of developing cardiovascular injury during COVID-19.Therefore,during the prevention and treatment of cardiovascular complications in COVID-19 patients,particular attention should be given to relieve the mental health burden of these patients.

Outcomes of Three Different Minimal Invasive Approaches for Secundum Atrial Septal Defect Closure: A Single Institute Experience

Objective:The aims of this retrospective study were to investigate and evaluate the safety and efficacy of three approaches for closure of secundum atrial septal defect(ASD).Methods:In this study,we reviewed clinical data for transcatheter occlusion(TCO,n=63),transthoracic occlusion(TTO,n=55),and right anterolateral minithoracotomy(RALT,n=60)techniques used for ASD closure.We compared the safety and efficacy of the three approaches.Results:ASD size in the TTO group was similar to that in the RALT group(P=0.645)and significantly larger than that in the TCO group(P<O.OO1).The RALT group had more non-central types of ASD than the TTO and TCO groups(P=O.019 and P<O.OO1).The operative time in the TTO group was shorter than that in the TCO and RALT groups(P<O.OO1 and P<0.001).The ventilation time and intensive care unit duration were shorter in the TTO group than in the RALT group(P<O.OO1 and P<O.OO1).Hospital duration in the TCO group was shorter than that in the TTO and RALT groups(P<O.OO1 and P<O.OO1).There were no residual shunt and mortality in any group in hospital or during follow-up.There was no significant difference in the incidence of total complications among the three groups(P=0.738).Conclusion:TCO,TTO,and RALT can be performed with favorable cosmetic and clinical results for closing ASD.Appropriate patient selection is an important factor for successful closure.These techniques are promising alternatives to standard median sternotomy and merit additional study.

New Nano-Film Single-Rivet Patent Ductus Arteriosus Occluders:A Prospective,Randomized and Double-blind Study

Nitinol alloy occluders are widely used in the transcatheter intervention treatment of congenital heart diseases like patent ductus arteriosus（PDA）.However,nitinol alloy contains high levels of nickel,which can lead to toxic effects in the immune and hematopoietic systems if released in sufficient quantities.A new type of single-rivet occluder coated with nano-film has been developed to limit the release of nickel.In total,23 patients were recruited and randomly assigned to the experimental group（n=12） with the new nano-film single-rivet occluders or the control group（n=11） with the traditional occluders.One case in the control group was lost to follow-up.The remaining 22 cases were followed up at 24 h,7 days,1 month,3 months,and 6 months after the procedure.There were no statistically significant differences in routine blood test,alanine aminotransferase,creatinine,and troponin between the experimental and control groups.Serum nickel concentration in both two groups increased at 24 h after the procedure,peaked at 1 month,and returned to preoperative levels at 6 months.Serum nickel levels in the experimental group were significantly lower than in the control group at 24 h,7 days,1 month,and 3 months after the procedure.These data suggested that the nano-film coating effectively prevented nickel release from the new occluders,and therefore has a preferable safety profile.

Chinese expert consensus on organ protection of transplantation(2022 edition)

Introduction Organ transplantation increases survival and improves qual-ity of life to many patients with end-stage organ failure.Or-gan shortage is a worldwide problem that restricts organ trans-plantation[1].Organ procurement and preservation as well as ischemia-reperfusion injury(IRI)after transplantation are the im-portant factors affecting prognosis of recipients.Since the de-velopment of organ transplantation technology in the 20th cen-tury,organ protection technology has been a most promising con-cept in this field.Organ preservation solutions such as the Collins solution,University of Wisconsin(UW)solution,and histidine-tryptophan-ketoglutarate(HTK)solution were developed sequen-tially[2],which developed rapidly in static cold storage(SCS)tech-niques.SCS remains the standard preservation technique for organ transplantation[2].

Erratum to:Current Status of and Opinions on Heart Transplantation in China

The article"Current Status of and Opinions on Heart Transplantation in China",written by Yong-feng SUN,Zhi-wen WANG,Jing ZHANG Jie CAI,Feng SHI,Nian-guo DONG was originally published electronically on the publisher s internet portal on October 2021;without open access.

Status on Heart Transplantation in China

INTRODUCTION ＂End-stage heart disease＂ commonly refers to an irreversible stage of cardiac decompensation caused by a variety of pathologies that cannot be treated using conventional drugs or traditional surgical treatments. The life expectancy of patients with end-stage heart disease ranges from 〈6 months to 1 year. Therapeutic strategies for end-stage heart disease patients are primarily based on three approaches： Internal medicine therapy, surgical therapy （heart transplantation）, and multiple organ protection therapy via the core method of mechanical circulation assistance. Among these approaches, heart transplantation has become recognized as the most efl＇ective treatment.

Preventive and protective management for coronavirus disease 2019 patients undergoing emergent cardiac surgery

The coronavirus disease 2019(COVID-19)pandemic has recently put global health services under escalating pressure.For patients who are known to be COVID-19 positive or at high suspicion for COVID-19 infection,although non-operative treatment is preferred for stable cardiovascular diseases to reduce the exposure,emergent cardiac surgery is still necessary when the primary concern is life-threatening and there is no alternative option.