Innovation in surgical treatment of hypertrophic obstructive cardiomyopathy in children.

Hypertrophic cardiomyopathy is the second most common cardiomyopathy affecting children and adolescents and is the main cause of sudden death of young athletes. The natural prognosis of children with severe hypertrophic obstructive cardiomyopathy is not optimistic, and it is not uncommon for children with hypertrophic obstructive cardiomyopathy who do not respond to medication. Surgical treatment is often the only solution. Conventional surgical methods in the past include classic or modified extended Morrow operation, classic or modified Konno operation, and Ross-Konno operation. In recent years, with the development of minimally invasive surgery, various minimally invasive surgical methods have emerged endlessly. Because the incision of minimally invasive cardiac surgery is significantly smaller than that of traditional surgery, it causes less trauma, recovers quickly after surgery, and has the advantage of no difference in surgical effect compared with traditional median sternotomy. Tally endoscopic transmitral myectomy, RTM, minimally right thoracotomy, and other surgical methods have achieved encouraging results in adults and some older children with hypertrophic obstructive cardiomyopathy. The appearance of transapical beating-heart septectomy has brought the treatment of hypertrophic obstructive cardiomyopathy from the era of cardiopulmonary bypass and cardiac arrest to a new era of minimally invasive beating-heart surgery. In the past, there were few articles about the treatment of children with hypertrophic obstructive cardiomyopathy. This article reviewed the new progress and prognosis of surgical treatment of children with hypertrophic obstructive cardiomyopathy at home and abroad.

Predictive Value of Myocardial Markers for Early Postoperative Mortality in Children with Congenital Heart Disease.

To investigate the influencing factors of postoperative creatine kinase-MB (CK-MB) elevation in children with congenital heart disease and its peak value in predicting early postoperative mortality. The clinical data of 521 children with congenital heart disease under the age of 14 who underwent elective surgery in Beijing Children's Hospital from December 2018 to December 2020 were retrospectively analyzed. Stepwise multiple linear regression was used to analyze independent risk factors for postoperative CK-MB elevation, receiver operating characteristic (ROC) curve was used to determine the predictive value of postoperative CK-MB peak, CK peak, and LDH peak on mortality, and linear correlation and regression analysis were used to analyze the interdependence among postoperative CK-MB peak, CK peak, and LDH peak, and multivariate Logistic regression was used to identify independent risk factors for early postoperative mortality. Preterm birth (P = 0.004), ventriculotomy (P = 0.009), the re-establish of bypass (P = 0.007), cardiopulmonary bypass time (P = 0.024), deep hypothermic circulatory arrest time (P = 0.000), assisted ventilation time (P = 0.049), CK peak (P = 0.000), and LDH peak (P = 0.000) were independently associated with increased postoperative CK-MB elevation. The ROC curve showed that CK-MB peak had the strongest predictive value for death (AUC = 0.924), followed by LDH peak (AUC = 0.864) and CK peak (AUC = 0.758). The cut-off value of the postoperative CK-MB peak was 144.5 IU/L, with a sensitivity of 87% and a specificity of 97%. CK-MB peak was moderately correlated with CK peak (Pearson Correlation coefficient r = 0.514, P = 0.000) and strongly correlated with LDH peak (Pearson Correlation coefficient r = 0.601, P = 0.000). Multivariate analysis showed that delayed chest closure (OR = 4.865, P = 0.004) and postoperative CK-MB peak (OR = 1.031, P = 0.000) were independent risk factors for postoperative mortality. The postoperative CK-MB peak has a certain predictive value for the early postoperative mortality of children with congenital heart disease. It is affected by many factors, and the risk of mortality is significantly increased in children with severely elevated postoperative CK-MB.

Clinical phenotype and genetic function analysis of a rare family with hereditary leiomyomatosis and renal cell carcinoma complicated with Birt-Hogg-Dubé syndrome.

To date, over 200 families with hereditary leiomyomatosis and renal cell carcinoma (HLRCC) and over 600 families with Birt-Hogg-Dubé (BHD) syndrome have been reported, with low incidence. Here, we describe a patient with suspected rare HLRCC complicated by BHD syndrome. The proband (II1) had characteristic cutaneous leiomyoma-like protrusions on the neck and back, a left renal mass and multiple right renal, liver and bilateral lung cysts. Three family members (I1, II2, II3) had a history of renal cancer and several of the aforementioned clinical features. Two family members (II1, II3) diagnosed with fumarate hydratase (FH)-deficient papillary RCC via pathological biopsy carried two heterozygous variants: FH (NM_000143.3) missense mutation c.1189G>A (p.Gly397Arg) and FLCN (NM_144997.5) frameshift mutation c.1579_1580insA (p.Arg527Glnfs*75). No family member carrying a single variant had renal tumours. In HEK293T cells transfected with mutant vectors, mRNA and protein expression after FLCN p.Arg527Glnfs*75 and FH p.Gly397Arg mutations were significantly lower than those in wild-type (WT) cells. Cell immunofluorescence showed altered protein localisation and reduced protein expression after FLCN p.Arg527Glnfs*75 mutation. The FH WT was uniformly distributed in the cytoplasm, whereas FH protein expression was reduced after the p.Gly397Arg mutation and scattered sporadically with altered cell localisation. Patients with two variants may have a significantly increased penetrance of RCC.

Han family with essential tremor caused by the P421L variant of the TENM4 gene in China.

BACKGROUND: Essential tremor (ET) is an autosomal dominant inheritance disorder. Mutations in fusion sarcoma (FUS), mitochondrial serine peptidase 2 (HTRA2), teneurin transmembrane protein 4 (TENM4), sortilin1 (SORT1), SCN11A, and notch2N-terminal-like (NOTCH2NLC) genes are associated with familial ET. METHODS: A proband with ET was tested using whole-exome sequencing and repeat-primed polymerase chain reaction. Subsequently, the family members were screened for the suspected mutation, and the results were verified using Sanger sequencing. The relationship between pedigree and phenotype was also analyzed, and structural and functional changes in the variants were predicted using bioinformatics analysis. RESULTS: In a family with ET, the proband (III4) and the proband's father (II1), grandfather (I1), uncle (II2), and cousin (III5) all presented with involuntary tremors of both upper limbs. The responsible mutation was identified as TENM4 c.1262C > T (p.P421L), which showed genetic co-segregation in the family survey. AlphaFold predicted a change in the spatial position of TENM4 after the P421L mutation, which may have affected its stability. AlphaFold also predicted P421L to be a deleterious variation, which would lead to lower degrees of freedom of the TENM4 protein, thereby affecting the protein's structure and stability. According to the bioinformatics analysis, TENM4 (p.P421L) may reduce the signal reaching the nucleus by affecting the expression of TENM4 messenger RNA (mRNA), thereby impairing the normal oligodendrocyte differentiation process and leading to impaired myelination. CONCLUSION: This study revealed that the TENM4 (p.P421L) pathogenic missense variation was responsible for ET in the proband.

Surgical Outcomes for Children with Anomalous Origin of the Left Coronary Artery from the Pulmonary Artery.

Objective of this study is to summarize surgical outcomes of patients with anomalous origin of the left coronary artery from the pulmonary artery (ALCAPA) in a single center. The clinical data of 89 children undergoing surgical treatment in Beijing Children's Hospital from January 2007 to January 2022 were retrospectively analyzed. seven patients underwent ECMO support for acute left heart failure after operation, and 2 patients were discharged after weaning successfully. Eight patients died in the early postoperative period, all of them were infants, of which 5 patients underwent ECMO support, 2 patients died of cerebral hemorrhage, 2 patients died of multiple organ dysfunction, and 4 patients died of left heart failure. Three patients died late, 3 patients were lost to follow-up, and 78 patients (96.3%) completed long-term follow-up. A logistic regression model multivariate analysis showed that postoperative moderate or severe mitral regurgitation (MR) (OR 26.948 P = 0.024) and prolonged aortic cross-clamp time (OR 1.038 P = 0.050) were independent risk factors of early mortality. Compared with the Non-MVP group (20/36), the MVP group (patients with moderate or severe MR who underwent MVP at the same time) (16/36) had more significant improvement in early postoperative LEVEF [(50.68 ± 13.85)% vs (40.50 ± 13.58)% P = 0.033] and had a lower proportion of moderate or severe MR after operation (2/16 vs 11/20 P = 0.014). Children with ALCAPA can obtain a good prognosis by reconstructing the blood supply of both coronary arteries. Mitral valvuloplasty (MVP) is more helpful in improving the prognosis of children with moderate or severe MR and mitral valve structural disease. Reasonable placement of ECMO can help reduce the mortality of critically ill children after operation, but be alert to complications in the central system.

When do patients with Tetralogy of Fallot need a transannular patch.

OBJECTIVES: The objective of this study was to evaluate the predictive value of main pulmonary artery (MPA) Z score, pulmonary valve annulus (PVA) prop, great aortic valve annulus (GA) ratio, PVA index (PAI), and PVA area index (PAAI) indicators in patients with Tetralogy of Fallot (TOF) and whether or not to undergo transannular patch (TAP). METHODS: A retrospective analysis was performed on the clinical data of 263 patients with TOF who underwent radical operations from 2010 to 2021 at Beijing Children's Hospital. Sixteen cases were excluded, and 247 cases (male/female = 155/92) were included in this study. Based on whether TAP was selected intraoperatively, the patients were divided into the TAP group (82/247) and the non-TAP group (165/247). The diameter of the PVA, the aortic valve annulus, and the MPA were measured by echocardiography, and the PVA Z score, MPA Z score, PVA prop, GA ratio, PAI, and PAAI indexes were calculated, and statistical analysis was carried out. RESULTS: The PVA Z score, MPA Z score, PVA prop, GA ratio, PAI, and PAAI of the TAP group were lower than those of the non-TAP group (p < .0001, p < .0001, p < .0001, p < .0001, p < .0001, and p < .0001). Receiver-operating curve analysis showed that the cut-off value of PVA Z score was -1.96 (area under the curve [AUC]: 0.822; 95% confidence interval [CI]: 0.769-0.874); the cut-off value of MPA Z score was -1.04 (AUC: 0.778; 95% CI: 0.711-0.845); the cut-off value of PVA prop was 0.37 (AUC: 0.812; 95% CI: 0.751-0.874); the cut-off value of GA ratio was 0.64 (AUC: 0.812; 95% CI: 0.750-0.874); the cut-off value of PAI is 0.78 (AUC: 0.812; 95% CI: 0.750-0.874); and the cut-off value of PAAI is 0.4 (AUC: 0.812; 95% CI: 0.750-0.874). Pulmonary valve bicuspid malformation is one reason why predictive models fail to predict the possible avoidance of TAP. Pearson's correlation and linear regression analysis showed that PAI had the strongest correlation with PVA Z score, followed by that between PVA prop and PVA Z score, and the weakest correlation between PAAI and PVA Z score. CONCLUSIONS: PVA prop, GA ratio, PAI, and PAAI can well predict TAP selection, and the measurement is simple and convenient. Compared with PVA Z score, they are not hindered by other confounding factors, and can well replace the application value of PVA Z score in TAP prediction. The predictive efficacy of PAI and PVA prop is numerically better than the GA ratio, and PAAI, PAI, and PVA prop combined with MPA Z score can improve the predictive value of PAI and PVA prop, respectively. Although various echocardiographic parameters can be used as indicators to predict surgical approach in patients with TOF, PV morphology and tissue characteristics should also be considered.

Comprehensive analysis of immune ferroptosis gene in renal clear cell carcinoma: prognosis and influence of tumor microenvironment.

OBJECTIVE: We conducted an in-depth study of the immune system and ferroptosis to identify prognostic biomarkers and therapeutic targets for renal clear cell carcinoma. METHODS: Immune ferroptosis-related differentially expressed genes (IFR-DEGs) were selected from The Cancer Genome Atlas (TCGA). A lasso-Cox risk scoring model was established; its prognostic value was determined using prognostic analysis and single multivariate Cox analysis. Model genes were subjected to subcellular fluorescence localization, mRNA and protein expression analyses, and single-cell RNA sequencing localization analysis. Risk score was analyzed using the immune score, immune infiltrating cell correlation, immune checkpoint, TIDE, and drug sensitivity. RESULTS: A total of 103 IFR-DEGs were identified; a risk model comprising ACADSB, CHAC1, LURAP1L, and PLA2G6 was established. The survival curve, single multivariate Cox regression, and receiver operating characteristic (ROC) curve analysis showed that the model had good predictive ability (p < 0.05). It was also validated using the validation set and total cohort. Subcellular fluorescence localization revealed that ACADSB, CHAC1, and PLA2G6 were distributed in the cytoplasm and LURAP1L in the nucleus. The mRNA and protein expression trends were consistent. Single-cell RNA sequencing mapping revealed that ACADSB was enriched in distal tubule cell clusters. In the Kidney renal clear cell carcinoma (KIRC) mutation correlation analysis, 1.56% of the patients were found to have genetic alterations; The Spearman correlation analysis of model gene mutations showed that ACADSB was positively correlated with LURAP1L, which may have a synergistic effect; it was negatively correlated with CHAC1 and PLA2G6, and CHAC1 was negatively correlated with LURAP1L, which may have an antagonistic effect. Model and immune correlation analyses found that high-risk patients had significantly higher levels of CD8+ T cells, regulatory T cells (Tregs), immune checkpoints, immune scores, and immune escape than those in low-risk patients. High-risk patients had a higher susceptibility to small-molecule drugs. CONCLUSION: A novel prognostic model of immune ferroptosis-related genes (ACADSB, CHAC1, LURAP1L, and PLA2G6), which plays an important role in immune infiltration, microenvironment, and immune escape, was constructed. It effectively predicts the survival of patients with KIRC.

Application of sutureless technique in total anomalous pulmonary venous connection repair.

The sutureless technique was initially used for the treatment of postoperative pulmonary vein obstruction (PVO) in patients with total anomalous pulmonary venous connection (TAPVC). However, as the effectiveness of the sutureless technique has been confirmed and widely developed, the sutureless technique has been used for the primary treatment of high-risk children with TAPVC who are at high risk of PVO. Compared with traditional surgery, the sutureless technique significantly reduces the incidence of postoperative PVO, re-intervention rate due to PVO, and postoperative mortality, but there are potential complications such as pericardial and confluent venous anastomosis, phrenic nerve damage, air embolism. In addition, the sutureless technique is not effective in dealing with the progressive stenosis of the pulmonary veins after sutureless surgery and diffuse stenosis of extrapulmonary proximal veins and intrapulmonary veins. These make the efficacy and safety of this procedure controversial. This paper reviews the research status of the sutureless technique in TAPVC repair at home and abroad over the years.

Incidence and risk factors for late complications after the arterial switch operation.

OBJECTIVE: The purpose of this study was to evaluate our institution's 16-year arterial switch operation (ASO) experience and to determine early and late mortality and late morbidity, as well as the need for reoperation and catheter intervention, and finally, to explore risk factors for late complications and reintervention. METHODS: The clinical data of 185 transposition of the great arteries (TGA) patients who received ASO treatment in our center from January 2006 to January 2022 were continuously included for retrospective study. RESULTS: There were 13 early deaths (7.03%), 5 late deaths (3.01%), and 6 lost to follow-up. The median follow-up time for the 166 hospitalized survivors was 88.5 (2190) months. Moderate or above new aortic valve regurgitation (NAR; in this article, NAR represents moderate or greater reflux unless otherwise specified) occurred in 19 cases (11.45%), and aortic root dilation (ARD) occurred in 28 cases (16.87%). Late right ventricular outflow tract obstruction (RVOTO) occurred in 33 cases (19.88%). There were 18 patients (10.84%) who underwent late re-intervention, and the most common indication for intervention was RVOTO, followed by recurrent aortic coarctation in patients undergoing concurrent arch repair and NAR or ARD. Receiver operating characteristics analysis found that NAR had the strongest predictive power for ARD, followed by RVOTO, followed by bicuspid native pulmonary valve (BPV), and aorto-pulmonary diameter mismatch (APDMM) was the weakest. Multivariate analysis showed that APDMM, previous pulmonary artery banding (PAB), and mild NAR at discharge were independent risk factors for late NAR and ARD. Low surgical weight was an independent risk factor specific to NAR, and BPV was an independent risk factor specific to ARD. Older surgical age and ARD were independent risk factors for late RVOTO. Older surgical age, operation before 2014, late RVOTO, and late ARD were independent risk factors for late intervention. No reintervention events for coronary dysfunction were found in the late stage, but one patient occurred myocardial infarction due to coronary embolism after reoperation. CONCLUSION: Early and late survival rates after ASO in TGA patients have been remarkably improved in recent decades. Increased rates of NAR, ARD, recurrent coarctation of the aorta, and RVOTO as children age are major future outcomes of concern and may imply more late reinterventions. Careful follow-up of neo-aortic valve and root function is imperative, especially in patients with APDMM, previous PAB, mild NAR at discharge, low surgical weight, and BPV structures.

Prognosis and related risk factors analysis of total anomalous pulmonary venous connection correction.

OBJECTIVE: This study was performed to analyze the surgical outcomes of our center biventricular correction with total anomalous pulmonary venous connection (TAPVC) and to explore the risk factors associated with postoperative mortality and postoperative pulmonary venous obstruction (PVO). METHODS: In total, 104 patients diagnosed with TAPVC and underwent biventricular correction from January 1, 2009 to December 31, 2021, in Beijing Children's Hospital Affiliated with Capital Medical University were included. The primary endpoints were early and late postoperative mortality and postoperative pulmonary vein obstruction. RESULTS: Multivariable analysis indicated that prolonged cardiopulmonary bypass (CPB) time was the only independent risk factor for early postoperative mortality. Emergency surgery, preoperative moderate, and severe pulmonary hypertension (PH), and prolonged CPB time were independent risk factors for postoperative PVO. According to ROC curve analysis, the cut-off value of CPB time for predicting early mortality was 148 min (AUC = 0.916, 95% CI 0.811-1.000). CONCLUSION: In the past 12 years, with surgical technique and perioperative management advancement, the prognosis of children treated with TAPVC biventricular correction in our center has generally improved. However, surgical repair remains challenging, and early mortality remains high in children with prolonged CPB time during surgery. Postoperative PVO often occurs in children who underwent emergency surgery, combined with moderate and severe PH and prolonged CPB time.

Effect of superselective prostatic artery embolization on benign prostatic hyperplasia.

PURPOSE: To investigate the safety and effectiveness of superselective prostatic artery embolization (PAE) in patients with benign prostatic hyperplasia (BPH). METHODS: Sixty-five patients diagnosed with BPH in Fujian Provincial Hospital between December 2014 and July 2019 were included. Patients with ineffective drug treatment after 6 months, who refused surgery, or who were unsuitable for surgery were included. We observed postoperative complications, followed up at 1, 3, and 6 months, compared clinical symptoms, and monitored changes in prostate-specific antigen (PSA) and prostatic volume (PV) before and after treatment. RESULTS: Of the 65 patients, 58 (89.23%) successfully received PAE; 44 and 14 bilateral and unilateral embolization, respectively. Clinical efficacy was 94.83% (55/58) after the 6-month follow-up. Postoperative PV, International Prostate Symptom Score, quality of life, maximum flow rate, and post-void residual significantly improved after 6 months (P < 0.05). One month after PAE, the serum total PSA increased by 1.47 (10.84/7.37) times and dropped 3 months later to a level lower than that before surgery (P < 0.05). Six months after PAE, the degree of relief from obstructive symptoms was more apparent than that of irritative symptoms. No serious complications were observed after PAE. CONCLUSION: PAE was safe and effective for the treatment of BPH. The efficacy of bilateral PAE was better than that of unilateral PAE.

Optimization of Echo Views for Percutaneous Device Closure of Pediatric Atrial Septal Defect through the Femoral Vein Guided by Transthoracic Echocardiography without Radiation.

OBJECTIVES: This study aimed to explore the selection of views for transthoracic echocardiography-guided transfemoral puncture for the device closure of pediatric atrial septal defect (ASD) without radiation. METHODS: Sixty children (29 males and 31 females) were diagnosed with a central ASD, normal heart function, and no other intracardiac deformity. All procedures were performed in a surgical operating room (without radiological equipment) under basic anesthesia; the femoral vein pathway and guidance by only transthoracic echocardiography were used to complete the device closure of the ASD. The subcostal acoustic window and parasternal aorta short-axis views were used to guide the extra stiff wire and catheter into the left atrium. All procedures were performed under the subcostal biatrial section. The sheath entered the left atrium, and the apical four-chamber view was used to monitor the delivery and release of the occluder. RESULTS: Successful closure of the ASD was achieved in all cases. The operating time from the end of the puncture to the release of the occluder was 10.36 ± 3.57 minutes. No other incisions were needed in 60 cases. No occluders were removed, and no residual shunt or pericardial effusions were detected after the procedures, during the non-ICU stay time. The average hospital stay was 2.19 ± 0.58 days. CONCLUSION: The accurate selection of transthoracic echocardiographic views can better ensure the safety and effectiveness of ASD closure through the femoral vein without radiation in children.

Percutaneous device closure of pediatirc patent ductus arteriosus through femoral artery guidance by transthoracic echocardiography without radiation and contrast agents.

BACKGROUND: For many years, percutaneous interventional occlusion of congenital patent ductus arteriosus (PDA) has been completed using radiation and contrast agents. In this study, transthoracic echocardiography without radiation and contrast agents was used to complete percutaneous occlusion of pediatric PDA. METHODS: Thirty-two children (8 males and 24 females) with normal heart function and no other intracardiac deformities were diagnosed with PDA (20 funnel type; 12 tube type), One patient had peripheral facial paralysis, 1 patient had epilepsy, and 1 case had multiple cervical deformities. All procedures were performed in the surgical operating room (without Digital Subtraction Angiography (DSA) equipment) under basic anesthesia through the femoral artery pathway. The procedures were guided by transthoracic echocardiography (TTE) by establishing an orbit with a catheter through the femoral artery to thepatent ductus arteriosus,pulmonary artery and right ventricle. A suitable ventricular septal defect occluder was placed using the femoral artery approach,and the treatment effect was evaluated by echocardiography after occlusion. The Outpatient follow-up was performed at 1, 3 months after the operation. RESULTS: All cases had successful closure of PDA, which took only 35.6 ± 6.4 min. The diameter of the device was 4.8 ± 2.3 mm, and the heart murmur disappeared. There was no shunt between the left pulmonary artery and the descending aortic artery, and the length of hospitalization was 3.4 ± 0.5 days. No other incisions were needed in 32 cases. No occluder was removed, and no residual shunt was found after operation; moreover, no ICU stay was needed, and the mean hospital stay was 3.4 ± 0.5 days. No residual shunt was found at the 1-, 3-month follow-up visit. CONCLUSIONS: PDA closure guided by transthoracic echocardiography via femoral artery puncture is a minimally invasive procedure that avoids injuries due to radiation and contrast agents. This method has wider application prospects in pediatrics.

Analysis of mutations in six Chinese families with autosomal dominant polycystic kidney disease.

Autosomal dominant polycystic kidney disease (ADPKD) is the common hereditary kidney disease, resulting from mutations in polycystic kidney disease 1 (PKD1) and polycystic kidney disease 2 (PKD2). Clinical data and genetic features of six Chinese families including ADPKD patients were analyzed via Next generation sequencing (NGS), Sanger sequencing, and multiplex ligation-dependent probe amplification. In family A, the proband (II5) with polycystic kidney (PK), hypertension, left ventricular hypertrophy, and valvular heart disease exhibited a heterozygous nonsense mutation, c.5086C>T (p.Gln1696Ter), in PKD1 (NM_001009944). In family B, the proband (II3) with PK, polycystic liver (PL), hypertension, hypertrophy of the left ventricle and septum, valvular heart disease, chronic kidney disease (CKD) stage 5, bilateral renal calculi, and right inguinal hernia exhibited a heterozygous missense mutation, c.6695T>C (p.Phe2232Ser), in PKD1. In family C, the proband (III1) with PK, PL, seminal vesicle cyst, hypertension, CKD stage 3, hypertrophy of the left ventricle and septum, and valvular heart disease harbored a heterozygous nonsense mutation, c.662T>G (p.Leu221Ter), in PKD2 (NM_000297). In family D, the proband (III3) with PK, hypertension, and CKD stage 5 harbored a heterozygous missense mutation, c.8311G>A (p.Glu2771Lys), in PKD1. In family E, the proband (II1) with PK, PL, hypertension, and CKD stage 5 exhibited a heterozygous deletion mutation, exon15-22, in PKD1. In family F, the proband (II2) with PK, PL, CKD stage 3, hypertension, thickened interventricular septum, and valvular heart disease carried a heterozygous missense mutation, c.1649A>G (p.His550Arg), in PKD2. Thus, three novel mutation sites which are responsible for ADPKD were discovered in this study.

Palliative Operations for Cyanotic Congenital Heart Disease with Severely Asymmetrical Pulmonary Arteries.

BACKGROUND: Surgically managing patients with complex congenital heart disease and severely asymmetrical pulmonary arteries is challenging. Here, we report our experience using combined palliative procedures. METHOD: The medical records of 28 patients with complex congenital heart disease and severely asymmetrical pulmonary arteries who underwent combined palliative procedures between January 2004 and April 2013 were retrospectively reviewed until January 2018. The patients were divided into three groups according to shunt procedure timing: in group A (n = 15), cavopulmonary and systemic-pulmonary shunting were performed simultaneously; in group B (n = 11), systemic-pulmonary shunting was performed first; and in group C (n = 2), cavopulmonary shunt was performed first. Patients were followed for a mean ± standard deviation of 4.18 ± 2.22 years. RESULTS: No operative deaths occurred. There were no postoperative complications in groups B or C, but there was one case of pulmonary effusion and one of chylothorax in group A. The superior vena cava pressures were higher in patients in groups A and B than in those in group C. The ventilatory support duration and intensive care unit stays were longer in group A than in groups B and C (p < 0.01). Hypoplastic pulmonary artery development significantly improved after the use of three systemic-pulmonary shunts (p < 0.05), while the peripheral oxygen saturation increased from 67%±17% preoperatively to 85%±8% postoperatively (p < 0.001). Haemoglobin concentration decreased from 190 ± 34 g/L preoperatively to 136 ± 26 g/L postoperatively (p < 0.001). Two patients underwent double ventricle correction. Two patients underwent Fontan procedure. One patient underwent one and a half ventricle correction. One patient underwent collateral occlusion. CONCLUSIONS: Combined palliative procedures can achieve acceptable arterial oxygen saturation without extra volume loading and rescue the hypoplastic pulmonary artery.

Inhibition of lncRNA XIST Improves Myocardial I/R Injury by Targeting miR-133a through Inhibition of Autophagy and Regulation of SOCS2.

The objective of this study was to investigate the role of lncRNA XIST and its relationship with miR-133a in myocardial I/R injury. H9C2 cells treated by hypoxia/reoxygenation (H/R) were used to establish an in vitro I/R model. The small interfering RNA (siRNA) for XIST and miR-133 mimics, inhibitor, and suppressor of cytokine signaling (SOCS2) recombinant plasmids were used to transfect the cells. Cell apoptosis was determined by flow cytometry analysis, and cell viability was used for 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, Thiazolyl Blue Tetrazolium Bromide (MTT) assay. The dual-luciferase reporter assay was performed to confirm binding between XIST and miR-133a, as well as miR-133a and SOCS2. To inhibit or overexpress XIST, miR-133a, or SOCS2 in I/R mice, we used recombinant lentivirus vectors and adenovirus vectors for tail vein injection. The expression of XIST, miR-133a, and SOCS2 was determined by quantitative real-time PCR, and LC3 I/II and Beclin1 was determined by western blotting. The expression of XIST and SOCS2 was significantly upregulated, whereas the miR-133a level was remarkably downregulated in both H/R H9C2 cells and I/R mice myocardial tissues. In both H/R H9C2 cells and I/R mice, the inhibition of XIST led to decreased apoptosis and autophagy, and inhibition of miR-133a reversed these effects. Similarly, overexpression of miR-133a resulted in reduced apoptosis and autophagy, which were reversed by overexpression of SOCS2. The inhibition of XIST and overexpression of miR-133a also promote cell viability of H/R cells. The dual-luciferase reporter assay significantly showed that XIST directly targeted on miR-133a, and miR-133a directly targeted on SOCS2. The inhibition of XIST could improve myocardial I/R injury by regulation of the miR-133a/SOCS2 axis and inhibition of autophagy.

Astragaloside-IV protects H9C2(2-1) cardiomyocytes from high glucose-induced injury via miR-34a-mediated autophagy pathway.

Diabetic cardiomyopathy (DCM) is an important cardiac disorder in patients with diabetes. High glucose (HG) levels lead to inflammation of cardiomyocytes, oxidative stress, and long-term activation of autophagy, resulting in myocardial fibrosis and remodelling. Astragaloside-IV (AS-IV) has a wide range of pharmacological effects. This study aimed to investigate the effects of AS-IV on injury induced by HG in rat cardiomyocytes (H9C2(2-1)) and the involvement of the miR-34a-mediated autophagy pathway. An AS-IV concentration of 100 µM was selected based on H9C2(2-1) cell viability using the cell counting kit-8 (CCK-8). We found that 33 mM HG induced a morphologic change in cells and caused excessive oxidative stress, whereas AS-IV inhibited lipid peroxidation and increased superoxide dismutase activity. In terms of mRNA expression, HG increased miR-34a and inhibited Bcl2 and Sirt1, whereas AS-IV and miR-34a-inhibitor reversed the above effects. Further, LC3-GFP adenovirus infection and western blotting showed that HG increased autophagy, which was reversed synergistically by AS-IV and miR-34a-inhibitor. Bcl2 and pAKT/AKT protein expressions in the HG group was significantly lower than that in controls, but AS-IV and miR-34a-inhibitor antagonized the process. Thus, AS-IV inhibits HG-induced oxidative stress and autophagy and protects cardiomyocytes from injury via the miR-34a/Bcl2/(LC3II/LC3I) and pAKT/Bcl2/(LC3II/LC3I) pathways.

Study on the correlation of modified Blalock Taussig duct occlusion and platelet parameters in congenital heart disease.

BACKGROUND: Platelet parameters play an important role in thrombosis. This study investigates the role of platelet parameters in the occlusion of modified Blalock Taussig (BT). OBJECTIVES: To investigate the association between mean platelet volume (MPV), platelet distribution width (PDW) and BT conduit obstruction and to evaluate the role of MPV and PDW in BT conduit obstruction. METHODS: 388 patients with modified BT shunt in the Pediatric Heart Center, Anzhen Hospital From January 1, 2008 to December 30, 2014 were divided into BT obstruction group (OBS) 11 cases and BT non-obstruction group (N-OBS) 377 cases according to whether the BT tube was occluded. The platelet count, mean platelet volume and platelet distribution width in the both groups were measured. The BT pipe occlusion related risk factors were analyzed. RESULTS: There was no significant difference in PC value of OBS group [(221 ± 28.4) × 109/L] and that of N-OBS group [(198 ± 69.1) × 109/L). MPV [(15 ± 6.8) fL] and PDW (20 ± 6.4)% in OBS group were significantly higher than those in N-OBS group [(8 ± 3.2) fL, (15 ± 2.1)%] (P < 0.05). Logistic regression showed that BT occlusion was not related to the tube diameter and PC value (P > 0.05). Abnormal increases of MPV and PDW increased the risk of ductal occlusion [(OR = 2.1, 95%CI:1.47-2.49, P < 0.05), (OR = 2.4, 95%CI:1.71-3.87, P < 0.05)]. CONCLUSION: Improved BT postoperative occlusion are closely related to MPV and PDW. Increased MPV and PDW can increase the risk of postoperative BT occlusion.

Genetic mutation of familial dilated cardiomyopathy based on next­generation semiconductor sequencing.

Dilated cardiomyopathy (DCM) is a complex myocardial disease of multifactorial etiologies, including enlarged cardiac chambers and contractile dysfunction. It has been suggested that the inheritance of DCM­associated mutations predominates its onset. Therefore, the present study investigated the pathogenesis of DCM via pedigree analysis and genetic diagnosis by massive whole­exome screening, and targeted exon capture. To study the familial gene­phenotype association, the exon and splice sites of 325 hereditary disease­associated genes in the proband with familial dilated cardiomyopathy (FDC), including 61 cardiac disease­associated genes, such as the lamins A/C (LMNA), were analyzed by ultra­high multiplex polymerase chain reaction and the Ion AmpliSeq™ Inherited Disease Panel. The present study also conducted Sanger DNA Sequencing for family members with global minor allele frequencies <1% to verify potential pathogenic mutation sites. A total of three rare missense mutations were detected, including heterozygous c.244G>A in LMNA, c.546C>G in potassium voltage­gated channel subfamily KQT (KCNQ4) and c.1276G>A in EYA transcriptional coactivator and phosphatase 1 (EYA1), indicating a glutamic acid to lysine substitution at amino acid 82 (p.E82K) in LMNA, a p.F182L in KCNQ4 (a mutation associated with pathogenic deafness) and p.G426S in EYA1 (associated with Branchiootorenal syndrome 1 and Branchiootic syndrome 1 pathogenesis). In the present study, a carrier with slight hearing impairment was detected in the family analyzed; however, no patients with deafness or branchiootorenal syndrome were observed. LMNA p.E82K revealed SIFT and PolyPhen­2 scores of 0 and 1, respectively. In the second generation, 3 patients with DCM underwent permanent pacemaker implantation due to sick sinus syndrome, atrioventricular block and unstable cardiac electrophysiology. The present study suggested that LMNA p.E82K may contribute to the pathogenesis of FDC and concomitant atrioventricular block. At present, only three families with DCM resulting from similar mutations have been reported. The present study demonstrated the strong pathogenic effects of LMNA p.E82K on DCM.