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Single-Nucleus RNA Sequencing Reveals Cardiac Macrophage Landscape in hypoplastic left heart syndrome

Congenital heart Disease 2024年第2期19卷 233-246页

作者： Xiaozhuo Xu Yilin Huang Xu Han First Clinical Medical College Affiliated Hospital of Nanjing University of Chinese MedicineNanjing210008China Department of Geriatrics Affiliated Hospital of Nanjing University of Chinese MedicineNanjing210029China

Background:hypoplastic left heart syndrome(HLHS)is one of the most challenging congenital heart diseases in clinical *** cardiac tissues,resident macrophages fulfill critical functions in maintaining a stable cardiac state and have strong regenerative capacity and organ ***,the molecular mechanisms of macro-phages in HLHS remained ***:Single-nucleus RNA sequencing(snRNA-seq)data of HLHS and healthy control(donors)samples obtained from the Gene Expression Omnibus(GEO)database were normalized and clustered using the Seurat ***“FindMarkers”function was used to screen differentially expressed genes(DEGs)between the HLHS and donor groups and to analyze the functional enrichment of the set of genes of ***,cell-cell communication,pseudotime,and single-cell regulatory network inference and cluster-ing(SCENIC)analyses were used to study the mechanisms of macrophages in ***:Based on the snRNA-seq data of HLHS and donors,we identified a total of 9 cell clusters,among which the proportion of macrophages was significantly less in the HLHS group than in the control *** of macrophage subpopulations(Macrophages 1,2,and 3)showed that Macrophages 1 was mainly involved in nervous system development,angiogenesis,and apoptotic *** addition,analysis of communication between Macro-phages 1 and cardiomyocytes revealed that ligand-acceptor pairs such as GAS6/AXL,IL6,IGF1,THY1,and L1CAM were present only in the donor ***,pesudotime and SCENIC analyses demonstrated that FOXO3 and ELF2 played a critical role for Macrophages 1 to maintain cardiac function in patients with ***:Our study improved the current understanding of the molecular mechanisms of macrophage devel-opment in HLHS,showing that manipulating the regulatory role of macrophages in the heart can be a novel treat-ment for HLHS.

关键词： hypoplastic left heart syndrome single-nucleus RNA sequencing macrophage cellular subpopulation transcription factor

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A 20-Year Follow-up after the Fontan Operation in a Population with hypoplastic left heart syndrome

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Congenital heart Disease 2022年第5期17卷 579-590页

作者： Eleni P.Asimacopoulos Steven J.Staffa Peter C.Laussen Kirsten C.Odegard Department of Boston Children’s Hospital Department of Anesthesiology Critical Care and Pain Medicine Division of Cardiac AnesthesiaBoston02115USA

Background:Thromboembolic events are a cause of significant morbidity and mortality in the Fontan *** previously reported on coagulation profile changes in a cohort of patients with hypoplastic left heart syndrome(HLHS)from Stage I through Fontan *** this report,we examine their clinical status,anticoagulation and incidence of thromboembolic events up to 20 years post ***:A retrospective chart review was conducted for twenty(20)surviving patients,from 1998 through December *** who underwent orthotopic heart transplantation(OTx)were followed until their *** who were found in the original study to have a factor VIII activity level>160%,were examined ***:Most patients had follow-up within the last two years(2018–2020).Two patients underwent OTx and two patients *** strategy was *** patients were on aspirin *** was a total of twelve thrombotic events(63.2%).These included six cerebrovascular accidents(two of which were fatal).Three out of the seven patients with elevated factor VIII activity from the original study had thromboembolic events(42.9%).Fontan complications were *** degree of Fontan Associated Liver Disease was ***:This retrospective review of a group of single-ventricle patients post Fontan,illustrates the variability in anticoagulation therapy that exists in this population.A large proportion of patients suffered a significant thromboembolic event,including the patients with elevated factor *** investigation into the patients with elevated factor VIII may help determine whether a different antithrombotic strategy post Fontan would be beneficial.

关键词： Fontan procedure hypoplastic left heart syndrome antiplatelet drugs anticoagulation strategy thrombosis

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Creation of high position fetal balloon atrial septoplasty for hypoplastic left heart syndrome and highly restrictive atrial septum: A case report and literature review

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Journal of Interventional Medicine 2020年第1期3卷 55-57页

作者： Ai Zhang Gang Luo Yue Sun Taotao Chen Silin Pan Qingdao Women and Children’s Hospital Qingdao UniversityQingdao266034PR China

Background:Fetal balloon atrial septoplasty(BAS)is performed through the restrictive foramen ovale in fetal cases with established hypoplastic left heart syndrome(HLHS)and an intact or highly restrictive atrial septum(RAS).Methods:In the current report,we present a case of high position BAS in a fetus with HLHS/***:Echocardiography confirmed an adequate atrial opening above the foramen ovale and fetal pleural effusion resolved spontaneously 1 day after the ***:To the best of our knowledge,the creation of a high position hole in the thinner part of the atrial septum,instead of the restrictive tiny hole,has not been reported in fetal cases with HLHS/RAS.

关键词： Congenital heart disease Fetal balloon atrial septoplasty hypoplastic left heart syndrome Intact or highly restrictive atrial septum

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A novel splice-site NOTCH1 mutation in a neonatewith hypoplastic left heart syndrome

A novel splice-site NOTCH1 mutation in a neonatewith hypopla...

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第十三届江浙沪儿科学术会议暨2016年浙江省医学会儿科学学术年会

作者： Chen Dong Wenhao Zhou Children’s Hospital of Fudan University

Background:hypoplastic left heart syndrome(HLHS) is a rare congential heart defect(CHD),which is the leading cause of death in infants with CHD before the age of one *** imbalance and mutations of single genes can both result in this ***,for most individuals with HLHS,the genetic basis of their disorder is *** presentation:We performed exome sequencing in a neonate who presented with hypoplastic left heart syndrome,including aortic valve atresia,hypoplastic aortic arch,mitral atresia and interrupted aortic arch after *** were not consanguineous and there were no family history of the *** analysis found a novel heterozygous splicing variant in NOTCH1(c.4587-lG>A).NOTCH1 has been reported to be a disease-causing gene of aortic valve *** mutation that we identify here may lead to cause exon 26 skipping of N0 TCH1 and a inframe deletion,which may cause a defect in its ***:The novel splice-site mutation of N0 TCH1(c.4587-lG>A) may cause the phenotype of the patient,and may indicate a new etiology of HLHS.

关键词： hypoplastic left heart syndrome NOTCH1 gene splicing variant

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A Ring-Reinforced Right Ventricle to Pulmonary Artery Conduit Is Associated with Better Regional Mechanics after Stage I Norwood Operation

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Congenital heart Disease 2022年第5期17卷 591-603页

作者： Benjamin Zielonka David M.Harrild Sunil J.Ghelani Eleni G.Elia Christopher W.Baird Andrew J.Powell Rahul H.Rathod Department of Cardiology Boston Children’s HospitalBostonUSA Department of Pediatrics Harvard Medical SchoolBostonUSA Department of Cardiothoracic Surgery Boston Children’s HospitalBostonUSA Department of Surgery Harvard Medical SchoolBostonUSA

Background:The right ventricle to pulmonary artery conduit(RVPAC)may impair right ventricular(RV)function in patients with functional single right *** of the RVPAC using a ring-reinforced end with dunked insertion into the RV through a limited ventriculotomy may reduce the impact on RV *** compared RV segmental strain between patients with a traditional RVPAC and ring-reinforced RVPAC using feature tracking cardiovascular magnetic resonance(CMR)***:Patients with CMR examinations after Stage I operation with RVPAC between 2000 and 2018 were *** mass,volumes,late gadolinium enhancement(LGE),and peak radial and circumferential strain of the 4 segments near the RVPAC insertion site were ***:The study included 71 CMR examinations in 61 patients(30 traditional RVPAC,31 ring-reinforced RVPAC).Prior to Stage II,the ring-reinforced RVPAC group had better peak radial strain and circumferential strain in 1 of 4 segments proximal to the RVPAC insertion site compared to the traditional RVPAC *** to Stage III operation,the ring-reinforced group had better peak radial and circumferential strain in 2 of 4 *** at the RVPAC insertion site was observed in 97%of patients before Stage II and 95%of patients before Stage *** type and regional strain were not associated with transplant-free survival during a median follow-up of 6.3 ***:Compared to a traditional RVPAC,the ring-reinforced RVPAC is associated with improved regional mechanics at the conduit insertion *** investigation of long-term outcomes after ring-reinforced RVPAC is warranted.

关键词： Single ventricle hypoplastic left heart syndrome cardiovascular magnetic resonance feature tracking

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Preoperative Feeding in Single Ventricle Neonates is Predictive of Shorter Time to Goal Feed

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Congenital heart Disease 2022年第5期17卷 505-518页

作者： Alyssia Venna Kathleen Reid Sarah Davis Jiaxiang Gai Yves d’Udekem Sarah Clauss Department of Cardiovascular Surgery Children’s National Heart InstituteThe George Washington University School of MedicineWashington DCUSA Department of Cardiology Children’s National Heart InstituteThe George Washington University School of MedicineWashington DCUSA Department of Biostatistics Children’s National Heart InstituteThe George Washington University School of MedicineWashington DCUSA

Background:Patients with single ventricle anatomy are at increased risk of growth failure and *** cardiac centers,there is little standardization of feeding practices in this complex *** hypothesized that initiation of our center’s preoperative feeding protocol would result in decreased gastrostomy tube(G-tube)use,decreased length of stay and would not result in increased Necrotizing Enterocolitis(NEC)***:A single institution review of 52 patients who had undergone stage I single ventricle palliative repair was *** diagnoses were hypoplastic left heart syndrome(39%),atrioventricular canal(15%),and other(46%).Postoperative parameters such as time to goal feed and need for gastrostomy tube(G-tube)were compared among preoperatively fed and non-preoperatively fed *** to goal feed was calculated as time from first postoperative enteral feed to goal volume of 100 mL/***:Of the 26 patients who met inclusion criteria for preoperative feeding,22 patients(85%)were fed prior to *** proportional hazard ratio revealed that age at surgery(p=0.047)and being preoperatively fed(p=0.001)were associated with reaching goal feed *** analysis revealed that being preoperatively fed made a patient twice as likely to reach goal feed sooner(p=0.047).Univariable logistic regression revealed that days on total parenteral nutrition(p=0.018),length of hospitalization(p=0.008),and time to 1st postoperative feed(p=0.020)were significantly associated with higher odds of needing a G-tube *** logistic regression did not show any predictors of postoperative G-tube ***,there was a trend towards lower G-tube usage in the preoperatively fed ***:Implementing a standardized preoperative feeding protocol in single ventricle neonates can result in significantly shorter time to goal feed in preoperatively fed *** is beneficial for institutions to begin implementi

关键词： Single ventricle feeding guidelines enteral nutrition hypoplastic left heart syndrome necrotizing enterocolitis preoperative

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Longitudinal Evaluation of Right Ventricle Function after Right Ventricle-Pulmonary Artery Shunt ***-Taussig Shunt

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Congenital heart Disease 2021年第1期16卷 27-37页

作者： Nunzia Borrelli Jolanda Sabatino Martina Avesani Josefa Paredes Manjit Josen Alain Fraisse Paolo Guccione Guido Michielon Giovanni Di Salvo Paediatric Cardiology Department Royal Brompton HospitalLondonSW36NPUK Paediatric Cardiology Department Bambino GesùPaediatric HospitalRome00165Italy Cardiology Department “Magna Graecia”UniversityCatanzaro88100Italy Paediatric Cardiology Department University of PaduaPadua35128Italy

Background:Still little is known about the impact on right ventricle function of the 2 main approaches to Norwood palliation in hypoplastic left heart syndrome,the right ventricle-pulmonary artery shunt(RVPAS)and the modified Blalock-Taussig shunt(mBTS).Methods:The cohort included 27 patients with hypoplastic left heart syndrome(10 in the mBTS group,17 in the RVPAS group).Longitudinal strain,tricuspid annulus peak systolic excursion and fractional area change were evaluated before Norwood and in four different breakpoints in the steady-state after Norwood procedure(30-days,90-days,140-days and 200-days after Norwood).Results:No significant differences were found in all standard echocardiographic functional parameters between the two groups at any ***,when we compared right ventricle function before and after Norwood procedure,longitudinal strain significantly improved in mBTS group compared to pre-surgical assessment(after 90-days:mBTS+27,35%±43,47 ***-8,20%±25,25,p=0,03;after 200-days:mBTS+10.19%±36.58 ***-21.64%±30.43,p=0.04).Conclusion:The mBTS group,which did not receive any ventriculotomy,showed a significant increase in right ventricle longitudinal strain during *** data support the use of longitudinal strain in hypoplastic left heart syndrome evaluation and may suggest potential value in terms of cardiac mechanics in using mBTS,preserving the right ventricle integrity.

关键词： hypoplastic left heart syndrome speckle tracking echocardiography congenital heart disease

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