Corrigendum: Anomalous papillary muscle insertion into the mitral valve leaflet in hypertrophic obstructive cardiomyopathy: a lip nevus sign in echocardiography.

[This corrects the article DOI: 10.3389/fcvm.2023.1292142.].

Reprogramming of DNA methylation patterns mediates perfluorooctane sulfonate-induced fetal cardiac dysplasia.

Prenatal exposure to perfluorooctane sulfonate (PFOS) is associated with adverse health effects, including congenital heart disease, yet the underlying mechanisms remain elusive. Herein, we aimed to evaluate the embryotoxicity of PFOS using C57BL/6 J mice to characterize fetal heart defects after PFOS exposure, with the induction of human embryonic stem cells (hESC) into cardiomyocytes (CMs) as a model of early-stage heart development. We also performed DNA methylation analysis to clarify potential underlying mechanisms and identify targets of PFOS. Our results revealed that PFOS caused septal defects and excessive ventricular trabeculation cardiomyopathy at 5 mg/kg/day in embryonic mice and inhibited the proliferation and pluripotency of ESCs at concentrations >20 µM. Moreover, it decreased the beating rate and the population of CMs during cardiac differentiation. Decreases were observed in the abundances of NPPA+ trabecular and HEY2+ compact CMs. Additionally, DNA methyl transferases and ten-eleven translocation (TET) dioxygenases were regulated dynamically by PFOS, with TETs inhibitor treatment inducing significant decreases similar as PFOS. 850 K DNA methylation analysis combined with expression analysis revealed several potential targets of PFOS, including SORBS2, FHOD1, SLIT2, SLIT3, ADCY9, and HDAC9. In conclusion, PFOS may reprogram DNA methylation, especially demethylation, to induce cardiac toxicity, causing ventricular defects in vivo and abnormal cardiac differentiation in vitro.

Single-cell RNA sequencing reveals the role of mitochondrial dysfunction in the cardiogenic toxicity of perfluorooctane sulfonate in human embryonic stem cells.

Perfluorooctane sulfonate (PFOS), an endocrine-disrupting chemical pollutant, affects embryonic heart development; however, the mechanisms underlying its toxicity have not been fully elucidated. Here, Single-cell RNA sequencing (scRNA-seq) was used to investigate the overall effects of PFOS on myocardial differentiation from human embryonic stem cells (hESCs). Additionally, apoptosis, mitochondrial membrane potential, and ATP assays were performed. Downregulated cardiogenesis-related genes and inhibited cardiac differentiation were observed after PFOS exposure in vitro. The percentages of cardiomyocyte and cardiac progenitor cell clusters decreased significantly following exposure to PFOS, while the proportion of primitive endoderm cell was increased in PFOS group. Moreover, PFOS inhibited myocardial differentiation and blocked cellular development at the early- and middle-stage. A Gene Ontology analysis and pseudo-time trajectory illustrated that PFOS disturbed multiple processes related to cardiogenesis and oxidative phosphorylation in the mitochondria. Furthermore, PFOS decreased mitochondrial membrane potential and induced apoptosis. These results offer meaningful insights into the cardiogenic toxicity of PFOS exposure during heart formation as well as the adverse effects of PFOS on mitochondria.

Maternal serum neonicotinoids during early-mid pregnancy and congenital heart diseases in offspring: An exploratory study.

Experimental evidence has indicated a correlation between in-utero exposure to neonicotinoid pesticides (NEOs) and adverse birth outcomes in mammals. However, the distribution of NEO exposure during human pregnancy, as well as its association with congenital heart diseases (CHDs), the most common birth defects, are unclear. Our purpose was to explore the distribution of and contributing factors to NEO exposure in pregnant women during early-mid pregnancy and to assess the associations between NEOs and CHDs. This nested case-control study was conducted within an ongoing prospective birth cohort study and enrolled 141 CHD singletons and their 282 individually matched controls. Six "parent" NEOs and three NEO metabolites were measured in maternal serum collected at an average gestational age of 16 weeks, using liquid chromatography-tandem mass spectrometry. Logistic regression was used to quantify the NEOs-CHDs associations and explore potential contributing factors to serum NEO levels in controls. N-desmethyl acetamiprid (N-dm-ACE) and imidacloprid (IMI) were the most frequently detected NEOs, found in 100% and 20% of maternal sera, respectively. We did not find a statistically significant association between total NEOs and overall CHDs. However, there was a trend towards a higher risk of septal defects with greater serum NEOs (ORs ranged from 1.80 to 2.36), especially nitro-containing NEOs represented by IMI. Pregnant women with lower education had elevated serum total NEOs compared to women with higher education (OR = 48.39, 95% CI: 23.48-99.72). Pregnant women were primarily exposed to N-dm-ACE and IMI during early-mid pregnancy. Gestational exposure to NEOs may be associated with an increased risk of septal defects, but the evidence is limited at present. Education is a potential contributing factor to NEO exposure in pregnant women. Larger and more precise studies with longitudinal biospecimen collection, are recommended to validate our exploratory findings.

Native mitral valve fungal endocarditis caused by Aspergillus fumigatus: A case report.

INTRODUCTION: Aspergillus endocarditis is a rare fungal infection associated with a poor prognosis. Most cases of Aspergillus endocarditis involve prosthetic valves, with native valve involvement being rarely reported. CASE PRESENTATION: A 53-year-old asian female patient presented with fever, chills, dyspnea, generalized fatigue, and significant weight loss one month after undergoing left lower lobectomy for a pulmonary abscess. Echocardiogram showed a large mobile vegetation with a broad base on the anterior leaflet of the mitral valve, resembling atrial myxoma. Despite negative blood cultures, circulating DNA of Aspergillus fumigatus was detected by metagenome Next Generation Sequencing, prompting the initiation of empiric antifungal therapy with voriconazole. Emergency surgery, involving thorough debridement and mitral valve replacement, was successfully performed. Indefinite fungal suppression therapy with oral voriconazole is continued to mitigate the risk of recurrence. The patient survived with no signs of Aspergillus disease recurrence for four years. CLINICAL DISCUSSION: Diagnosis of Aspergillus endocarditis requires a high index of suspicion and is often delayed due to consistently negative results from blood cultures. Non-culture-based methods, particularly metagenome Next-Generation Sequencing, play a crucial role in early diagnosis and therapeutic decision-making. Surgical debridement and valve replacement are imperative for survival in cases of Aspergillus endocarditis. Voriconazole should be considered the primary fungicidal agent for its treatment. Moreover, lifelong fungal suppression therapy is strongly recommended for all survivors to ensure long-term survival and minimize the risk of recurrence. CONCLUSION: Despite grim prognosis associated with Aspergillus endocarditis, patients can attain long-term survival through meticulous surgical debridement and lifelong antifungal therapy.

Detection of pathogens from venous or arterial blood of patients with left-sided infective endocarditis by metagenomic next-generation sequencing: A prospective study.

BACKGROUND: Infective endocarditis is a life-threatening uncommon infectious disease, and we aimed to explore the clinical utility of venous or arterial blood-based metagenomic next-generation sequencing (mNGS) approaches to diagnose left-sided infective endocarditis (LSIE). METHODS: We prospectively studied 79 LSIE patients who received valvular surgery in our hospital. Results of blood culture, valve culture, venous blood-based mNGS, arterial blood-based mNGS, venous blood-based mNGS plus blood culture, and arterial blood-based mNGS plus blood culture were evaluated and compared. RESULTS: Both venous blood- and arterial blood-based mNGS methods displayed significantly higher positive detection rates than blood culture and valve culture (43.0 %, 49.4 % vs. 32.9 %, 19.0 %; P < 0.001). Strikingly, when combining blood-based mNGS and blood culture, the positive rate could be further improved to more than 60 %. Moreover, we found mNGS LSIE detection was closely associated with preoperative leukocyte (P = 0.027), neutrophil value (P = 0.018), vegetation ≥ 14 mm (P = 0.043), and vegetations in aortic valve (P = 0.048). In addition, we discovered that blood-based mNGS had a superir capacity over blood culture to detect gram-negative bacteria, fungi, Bartonella Quintana, and mixed infections than blood culture. CONCLUSION: This study indicates that venous blood- and arterial blood-based mNGS displayed high positive rate in the rapid detection of pathogens in high-risk LSIE patients.

The alterations of cardiac function during venovenous artificial placenta support in fetal goats.

INTRODUCTION: Venovenous artificial placenta (VVAP) may mimic the intrauterine environment for maintaining fetal circulation. However, changes in ventricular function in fetal goats undergoing VVAP support remain unclear. METHODS: Pump-assisted VVAPs were established in five fetal goats for 9 h. The myocardial performance index (Tei index), cardiac output (CO), and blood biochemical parameters were measured during VVAP support. RESULTS: An increasing trend of the right ventricular (RV) Tei index was seen during VVAP support (p for trend < 0.01). The right ventricular cardiac output (RVCO) increased after the initiation of VVAP, while a significant trend of reduction was observed after 3 h (p for trend = 0.03). During VVAP support, we observed remarkable elevations of plasma cTnI and arterial lactic acid, which were positively correlated with the RV Tei index, but not the left ventricular (LV) Tei index, LVCO, and RVCO. CONCLUSIONS: The RVCO increases initially while a tendency of decrease could be observed during VVAP support. Special attention should be paid to right ventricular dysfunction during VVAP support.

Anomalous papillary muscle insertion into the mitral valve leaflet in hypertrophic obstructive cardiomyopathy: a lip nevus sign in echocardiography.

Background: Anomalous papillary muscle (APM) insertion into the mitral valve leaflet is rare but clinically important in hypertrophic obstructive cardiomyopathy (HOCM). In this study, we report the detection rate of APM insertion into the mitral valve using preoperative imaging modalities and the surgical outcomes of the patients. Methods: By retrospectively reviewing the clinical records of patients with HOCM who underwent surgical treatment by a single operation group at our center from January 2020 to June 2023, patients with APM insertion into the mitral valve leaflet were identified. Baseline data, image characteristics, and surgical outcomes were analyzed. Results: The incidence of APM insertion into the mitral valve leaflet was 5.1% (8/157). The insertion site was located at A3 in six cases, which was more common than at A2 (n = 2). Preoperative echocardiography was used to identify two patients (25%) with APM insertion. We observed a particular echocardiographic feature for APM in HOCM patients, which was noted as a "lip nevus sign", with a higher detection rate (62.5%). All patients successfully underwent septal myectomy with concomitant APM excision or mitral valve replacement via the transaortic (n = 5) or transmitral (n = 3) approach. The mean age was 49.0 ± 17.4 years and seven patients (87.5%) were female. Interventricular septum thickness (17.0 mm vs. 13.3 mm, P = 0.012) and left ventricular outflow gradient (117.5 mmHg vs. 7.5 mmHg, P = 0.012) were significantly decreased after surgery. Residual outflow obstruction, systolic anterior motion, and ≥3+ mitral regurgitation were negative. During the follow-up of 26.2 ± 12.2 months, there were no reported operations, adverse events, mitral regurgitation aggravations, recurrences of outflow obstruction, or instances of SAM. Conclusions: Papillary muscles inserted into the mitral valve leaflet are a subtype of subvalvular malformation in HOCM that requires surgical correction. The lip nevus sign on echocardiography is a characteristic of APM insertion in HOCM and may improve the preoperative detection rate. Adequate myectomy with anomalous papillary muscle excision has achieved good results in reducing the outflow gradient and eliminating mitral regurgitation, with good outcomes at short-to-intermediate follow-up.

Protocol for the PORT study: short-term perioperative rehabilitation to improve outcomes in cardiac valvular surgery - a randomised control trial.

INTRODUCTION: Perioperative rehabilitation (PORT) has shown a positive effect on patients undergoing cardiac surgery. However, there are minimal data on the impact of short-term PORT in cardiac surgery, which is associated with higher postoperative morbidity and mortality. The trial will assess the efficacy of short-term PORT in reducing in-hospital mortality, postoperative pulmonary complications and length of stay, compared with the usual care in cardiac surgical patients. METHODS AND ANALYSIS: This is a single-centre prospective, randomised, open, controlled trial with a 1:1 ratio. Consecutive 800 adult patients undergoing elective valve surgery will be randomised to either usual care or in-hospital short-term PORT that consists of education, inspiratory muscle training, active cycle of breathing techniques and early mobilisation. The primary outcome of this study will be a composite of in-hospital all-cause mortality, incidence of postoperative pulmonary complications and the ratio of postoperative hospitalisation >7 days. ETHICS AND DISSEMINATION: The PORT study was granted by the Medical Research Ethics Committee of Guangdong Provincial People's Hospital in August 2018. Findings will be disseminated to patients, clinicians and commissioning groups through peer-reviewed publication. TRIAL REGISTRATION NUMBER: NCT03709511.

Management of the mitral valve in thoracoscopic trans-mitral myectomy for hypertrophic obstructive cardiomyopathy.

Objective: This study aimed to compare clinical outcomes of different mitral valve (MV) management methods in thoracoscopic transmitral myectomy (TTM) and guide surgeons' decision making for hypertrophic obstructive cardiomyopathy (HOCM). Methods: Seventy-three consecutive patients (41 females; mean age, 53.7 ± 13.6 years) with HOCM who underwent TTM between January 2019 and October 2022 were enrolled and divided into 3 groups according to MV surgical strategy. Clinical outcomes were analyzed and compared among the groups. Results: None of the patients experienced postoperative residual left ventricular outflow tract obstruction. Percentages of patients with mitral regurgitation (MR) grade ≥3+ (57.5% vs 1.4%) and systolic anterior motion (95.9% vs 2.7%) were significantly decreased postoperatively (P < .001 for both). The preoperative anterior mitral leaflet length was longer in patients in the anterior mitral leaflet direct reattachment group (median, 2.9 cm [interquartile range (IQR), 2.7-3.3 cm] vs 2.7 [IQR, 2.4-2.9 cm]; P = .018), but the postoperative coaptation length was shorter (mean, 8.3 ± 2.1 mm vs 11.1 ± 3.8 mm; P = .038). After a median echocardiography follow-up of 11.8 months, the left ventricular outflow tract gradient (LVOTG) and mitral regurgitation grades remained significantly improved in all 3 groups (P < .05 for all). Conclusions: Total TTM in selected patients is safe and effective, and all 3 MV management strategies can significantly reduce the LVOTG while improving MR. Mitral valvuloplasty is the preferred initial management strategy over valve replacement except in the scenario of irreparable intrinsic MV disease and valvuloplasty failure.

Bronchus compression is a predictor for reobstruction in coarctation with hypoplastic arch repair.

OBJECTIVES: The surgical treatment of coarctation of aorta with hypoplastic aortic arch (CoA/HAA) was challenging to achieve long-lasting arch patency. We reviewed early and late outcomes in our centre and identified predictors for arch reobstruction. METHODS: A retrospective analysis of medical records was performed to identify CoA/HAA patients who underwent primary arch reconstruction via median sternotomy between 2011 and 2020. Preoperative aortic arch geometry was analysed with cardiac computed tomographic angiography. Bedside flexible fibre-optic bronchoscopy was routinely performed after surgery in intensive care unit. RESULTS: There were 104 consecutive patients (median age 39.5 days) who underwent extended end-to-end anastomosis, extended end-to-side anastomosis and autograft patch augmentation. Early mortality was 3.8% and overall survival was 94.1% [95% confidence interval (CI) 89.6-98.8%] at 1, 3 and 5 years. Reobstruction-free survival was 85.1% (95% CI 78.4-92.3%) at 1 year, 80.6% (95% CI 73.1-88.9%) at 3 years and 77.4% (95% CI 69.2-86.6%) at 5 years. Preoperative aortic arch geometric parameters were not important factors for reobstruction. Nineteen patients (18.3%) were detected with left main bronchus compression (LMBC) on flexible fibre-optic bronchoscopy. Cardiopulmonary bypass time [P < 0.001, hazard ratio (95% CI): 1.02 (1.01-1.03)] and postoperative LMBC [P = 0.034, hazard ratio (95% CI): 2.99 (1.09-8.23)] were independent predictive factors on multivariable Cox regression analysis of reobstruction-free survival. CONCLUSIONS: Aortic arch can be satisfactorily repaired by extended end-to-end anastomosis, extended end-to-side anastomosis and autograft patch augmentation via median sternotomy in CoA/HAA. Cardiopulmonary bypass time and postoperative LMBC detected by flexible fibre-optic bronchoscopy are significant predictors for long-term arch reobstruction.

Long-term outcomes of pulmonary atresia with ventricular septal defect by different initial rehabilitative surgical age.

Background: There is a lack of evidence guiding the surgical timing selection in pulmonary atresia with ventricular septal defect. This study aims to compare the long-term outcomes of different initial rehabilitative surgical ages in patients with pulmonary atresia with ventricular septal defect (PAVSD). Methods: From January 2011 to December 2020, a total of 101 PAVSD patients undergoing the initial rehabilitative surgery at our center were retrospectively reviewed. Receiver-operator characteristics curve analysis was used to identify the cutoff age of 6.4 months and therefore to classify the patients into two groups. Competing risk models were used to identify risk factors associated with complete repair. The probability of survival and complete repair were compared between the two groups using the Kaplan-Meier curve and cumulative incidence curve, respectively. Results: The median duration of follow-up was 72.76 months. There were similar ΔMcGoon ratio and ΔNakata index between the two groups. Multivariate analysis showed that age ≤6.4 months (hazard ratio (HR) = 2.728; 95% confidence interval (CI):1.122-6.637; p = 0.027) and right ventricle-to-pulmonary artery connection (HR = 4.196; 95% CI = 1.782-9.883; p = 0.001) were associated with increased probability of complete repair. The cumulative incidence curve showed that the estimated complete repair rates were 64% ± 8% after 3 years and 69% ± 8%% after 5 years in the younger group, significantly higher than 28% ± 6% after 3 years and 33% ± 6% after 5 years in the elder group (p < 0.001). There was no significant difference regarding the estimated survival rate between the two groups. Conclusion: Compared with those undergoing the initial rehabilitative surgery at the age >6.4 months, PAVSD patients at the age ≤6.4 months had an equal pulmonary vasculature development, a similar probability of survival but an improved probability of complete repair.

Right ventricular dilatation score: a new assessment to right ventricular dilatation in adult patients with repaired tetralogy of Fallot.

BACKGROUND: Patients with repaired tetralogy of Fallot (rTOF) experience long-term chronic pulmonary valve regurgitation resulting in right ventricular (RV) dilatation. According to current guidelines, the evaluation of patients with rTOF for RV dilatation should be based on cardiac magnetic resonance (CMR). However, for many asymptomatic patients, routine CMR is not practical. Our study aims to identify screening methods for CMR based on echocardiographic data, with the goal of establishing a more practical and cheap method of screening for severity of RV dilatation in patients with asymptomatic rTOF. METHODS: Thirty two rTOF patients (mean age, 21(10.5) y, 21 males) with moderate to severe pulmonary regurgitation (PR) were prospectively recruited. Each patient received CMR and echocardiogram examination within 1 month prior to operation and collected clinical data, and then received echocardiogram examination at discharge and 3-6 months post-surgery. RESULTS: RV moderate-severe dilatation was defined as right ventricular end-diastolic volume index (RVEDVI) ≥ 160 ml/m2 or right ventricular end-systolic volume index (RVESVI) ≥ 80 ml/m2 in 15 of 32 patients (RVEDVI, 202.15[171.51, 252.56] ml/m2, RVESVI, 111.99 [96.28, 171.74] ml/m2). The other 17 (RVESDI, 130.19 [117.91, 139.35] ml/m2, RVESVI = 67.91 [63.35, 73.11] ml/m2) were defined as right ventricle mild dilatation, i.e., RVEDVI < 160 ml/m2 and RVESVI < 80 ml/m2, and the two parameters were higher than normal values. Compared with the RV mild dilatation group, patients of RV moderate-severe dilatation have worse cardiac function before surgery (right ventricular ejection fraction, 38.92(9.19) % versus 48.31(5.53) %, p < 0.001; Left ventricular ejection fraction, 59.80(10.26) versus 66.41(4.15), p = 0.021). Patients with RV moderate-severe dilatation faced longer operation time and more blood transfusion during operation (operation time, 271.53(08.33) min versus 170.53(72.36) min, p < 0.01; Intraoperative blood transfusion, 200(175) ml versus 100(50) ml, p = 0.001). Postoperative RV moderate-severe dilatation patients have poor short-term prognosis, which was reflected in a longer postoperative hospital stay (6.59 [2.12] days versus 9.80 [5.10] days, p = 0.024) and a higher incidence of hypohepatia (0[0] % versus 4[26.7] %, p = 0.023). Patients with RV dilatation score > 2.35 were diagnosed with RV moderate-severe dilatation (AUC = 0,882; Sensitivity = 94.1%; Specificity = 77.3%). CONCLUSIONS: RV moderate-severe dilatation is associated with worse preoperative cardiac function and short-term prognosis after PVR in rTOF patients with moderate to severe PR. The RV dilatation score is an effective screening method. When RV dilatation score > 2.35, the patient is indicated for further CMR examination and treatment.

Emerging Evidence Linking the Liver to the Cardiovascular System: Liver-derived Secretory Factors.

Cardiovascular diseases (CVDs) remain the leading cause of morbidity and mortality worldwide. Recently, accumulating evidence has revealed hepatic mediators, termed as liver-derived secretory factors (LDSFs), play an important role in regulating CVDs such as atherosclerosis, coronary artery disease, thrombosis, myocardial infarction, heart failure, metabolic cardiomyopathy, arterial hypertension, and pulmonary hypertension. LDSFs presented here consisted of microbial metabolite, extracellular vesicles, proteins, and microRNA, they are primarily or exclusively synthesized and released by the liver, and have been shown to exert pleiotropic actions on cardiovascular system. LDSFs mainly target vascular endothelial cell, vascular smooth muscle cells, cardiomyocytes, fibroblasts, macrophages and platelets, and further modulate endothelial nitric oxide synthase/nitric oxide, endothelial function, energy metabolism, inflammation, oxidative stress, and dystrophic calcification. Although some LDSFs are known to be detrimental/beneficial, controversial findings were also reported for many. Therefore, more studies are required to further explore the causal relationships between LDSFs and CVDs and uncover the exact mechanisms, which is expected to extend our understanding of the crosstalk between the liver and cardiovascular system and identify potential therapeutic targets. Furthermore, in the case of patients with liver disease, awareness should be given to the implications of these abnormalities in the cardiovascular system. These studies also underline the importance of early recognition and intervention of liver abnormalities in the practice of cardiovascular care, and a multidisciplinary approach combining hepatologists and cardiologists would be more preferable for such patients.

Improving long-term care and outcomes of congenital heart disease: fulfilling the promise of a healthy life.

Advances in the prevention, diagnosis, and treatment for congenital heart disease (CHD), the most common birth defect in China, have drastically improved survival for individuals with the disease. However, China's current health system is not well prepared to manage the growing population of people with CHD and their complex medical needs, which range from early detection of the condition and intervention for physical, neurodevelopmental, and psychosocial impairment, to long-term management of major complications and chronic health problems. Health disparities caused by long-standing regional differences in access to care pose challenges when major complications such as pulmonary hypertension arise, and when individuals with complex CHD become pregnant and give birth. Currently, no data sources track neonates, children, adolescents, and adults with CHD in China and delineate their clinical characteristics and use of health resources. This scarcity of data should warrant attention from the Chinese Government and relevant specialists in the field. In the third paper of the Series on CHD in China, we summarise key literature and current data to identify knowledge gaps and call for concerted efforts by the government, hospitals, clinicians, industries, and charitable organisations to develop an actionable, lifelong framework of congenital cardiac care that is accessible and affordable for all individuals with CHD. TRANSLATION: For the Chinese translation of the abstract see Supplementary Materials section.

Novel biphasic mechanism of the canonical Wnt signalling component PYGO2 promotes cardiomyocyte differentiation from hUC-MSCs.

Human umbilical cord-derived mesenchymal stem cells (hUC-MSCs) are used to regenerate the myocardium during cardiac repair after myocardial infarction. However, the regulatory mechanism underlying their ability to form mesodermal cells and differentiate into cardiomyocytes remains unclear. Here, we established a human-derived MSCs line isolated from healthy umbilical cords and established a cell model of the natural state to examine the differentiation of hUC-MSCs into cardiomyocytes. Quantitative RT-PCR, western blotting, immunofluorescence, flow cytometry, RNA Seq, and inhibitors of canonical Wnt signalling were used to detect the germ-layer markers T and MIXL1; the markers of cardiac progenitor cells MESP1, GATA4, and NKX2.5 and the cardiomyocyte-marker cTnT to identify the molecular mechanism associated with PYGO2, a key component of the canonical Wnt signalling pathway that regulates the formation of cardiomyocyte-like cells. We demonstrated that PYGO2 promotes the formation of mesodermal-like cells and their differentiation into cardiomyocytes through the hUC-MSC-dependent canonical Wnt signalling by promoting the early-stage entry of ß-catenin into the nucleus. Surprisingly, PYGO2 did not alter the expression of the canonical-Wnt, NOTCH, or BMP signalling pathways during the middle-late stages. In contrast, PI3K-Akt signalling promoted hUC-MSCs formation and their differentiation into cardiomyocyte-like cells. To the best of our knowledge, this is the first study to demonstrate that PYGO2 uses a biphasic mechanism to promote cardiomyocyte formation from hUC-MSCs.

Evaluation of the contribution of gut microbiome dysbiosis to cardiac surgery-associated acute kidney injury by comparative metagenome analysis.

Introduction: Cardiac surgery-associated acute kidney injury (CSA-AKI) is a common hospital-acquired AKI that carries a grave disease burden. Recently, gut-kidney crosstalk has greatly changed our understanding of the pathogenesis of kidney diseases. However, the relationship between gut microbial dysbiosis and CSA-AKI remains unclear. The purpose of this study was to investigate the possible contributions of gut microbiota alterations in CSA-AKI patients. Methods: Patients undergoing cardiac surgery were enrolled and divided into acute kidney injury (AKI) and Non_AKI groups. Faecal samples were collected before the operation. Shotgun metagenomic sequencing was performed to identify the taxonomic composition of the intestinal microbiome. All groups were statistically compared with alpha- and beta-diversity analysis, and linear discriminant analysis effect size (LEfSe) analysis was performed. Results: A total of 70 individuals comprising 35 AKI and 35 Non_AKI were enrolled in the study. There was no significant difference between the AKI and Non_AKI groups with respect to the alpha-and beta-diversity of the Shannon index, Simpson or Chao1 index values except with respect to functional pathways (p < 0.05). However, the relative abundance of top 10 gut microbiota in CSA-AKI was different from the Non_AKI group. Interestingly, both LEfSe and multivariate analysis confirmed that the species Escherichia coli, Rothia mucilaginosa, and Clostridium innocuum were associated with CSA-AKI. Moreover, correlation heat map indicated that altered pathways and disrupted function could be attributed to disturbances of gut microbiota involving Escherichia coli. Conclusion: Dysbiosis of the intestinal microbiota in preoperative stool affects susceptibility to CSA-AKI, indicating the crucial role of key microbial players in the development of CSA-AKI. This work provides valuable knowledge for further study of the contribution of gut microbiota in CSA-AKI.

Supracardiac total anomalous pulmonary venous connection type Ib: Morphology and outcomes.

BACKGROUND: Supracardiac total anomalous pulmonary venous connection is the most common subtype of total anomalous pulmonary venous connection. We aimed to describe the morphological spectrum of supracardiac total anomalous pulmonary venous connection and to identify risk factors for death and postoperative pulmonary venous obstruction. METHODS: From February 2009 to June 2019, 241 patients diagnosed with supracardiac-Ia (left-sided vertical vein, n = 185) or supracardiac-Ib (right-sided connection directly to superior vena cava, n = 56) total anomalous pulmonary venous connection underwent initial surgical repair at our institute. Cases with functionally univentricular circulations or atrial isomerism were excluded. Patients' postoperative survival was described by Kaplan-Meier curves. Cox proportional hazards models and competing risk regression models were used to identify clinical risk factors for death and postoperative pulmonary venous obstruction. RESULTS: There were 8 early deaths and 4 late deaths. The overall survivals at 30 days, 1 year, and 10 years were 97.1%, 94.8%, and 94.8%, respectively, in the supracardiac-Ia group (2.7%, 5/185) (hazard ratio, 4.8; P = .003). Five patients required reoperation for pulmonary venous obstruction, including 2 patients who required reintervention for superior vena cava syndromes (all in the supracardiac-Ib group). One patient required superior vena cava balloon dilation for superior vena cava syndromes. Multivariable analysis showed that the supracardiac-Ib group (12.5%, 7/56) had a significantly higher mortality rate than the supracardiac-Ia group (adjusted hazard ratio, 8.5, P = .008). Surgical weight less than 2.5 kg (adjusted hazard ratio, 10.8, P = .023), longer duration of cardiopulmonary bypass (adjusted hazard ratio, 1.15 per 10 minutes, P = .012), and supracardiac-Ib subtype (adjusted hazard ratio, 4.7, P = .037) were independent risk factors associated with death. The supracardiac-Ib subtype (adjusted hazard ratio, 4.8, P = .003) was an incremental risk factor associated with postoperative pulmonary venous obstruction. CONCLUSIONS: Morphological features of supracardiac total anomalous pulmonary venous connection, especially the supracardiac-Ib subtype, were risk factors associated with postoperative pulmonary venous obstruction and survival. Patients with unique anatomic subtypes might require more individualized surgical planning.

Outcomes of minimally invasive isolated tricuspid valve reoperation after left-side valve surgery: A single-center experience.

Background: Late severe tricuspid regurgitation (TR) after left-side valve surgery (LSVS) is not uncommon. However, the tricuspid valve has been deemed the forgotten valve because the isolated TR is well tolerated with medication, and reoperation has a higher rate of adverse events. With the advancement of minimally invasive techniques, isolated tricuspid valve reoperation (ITVR) via totally endoscopy or transcatheter approach brings the tricuspid valve into spotlight. Our aim is to report the safety and efficacy of minimally invasive ITVR using endoscopic and transcatheter approaches. Methods: From October 2020 to October 2021, 21 patients with LSVS history and secondary massive TR underwent minimally invasive ITVR in our institution. Baseline characteristics, surgical outcomes and follow-up results were analyzed, and data between the totally endoscopy approach and the transcatheter approach were compared. Results: Of the 21 cases, totally endoscopic isolated tricuspid valve surgery (EITVS) accounts for 16 (76.2%) cases, with 14 tricuspid valvuloplasty cases, and 2 tricuspid valve replacement cases; the remaining 5 (23.8%) cases underwent transcatheter tricuspid valve replacement (TTVR). The mean age was (60.0 ± 8.4) years, with 15 (71.4%) being female. Minimally invasive ITVR procedures were 100% successfully performed in all patients without any perioperative mortality, sternotomy conversion, or reoperation. During the median follow-up of 16.8 months (IQR, 13.0-20.6 months), New York Heart Association Class improved significantly from baseline (P = 0.004). TR severity was significantly improved during postoperative and follow-up period (both P < 0.001). Compared with the EITVS group, the TTVR group had a higher clinical risk score [8.00 (8.00, 9.00) vs. 5.00 (3.25, 5.00), P = 0.001], but a higher success rate in reducing TR to less than grade 1+ (100 vs. 43.8%, P = 0.045) at follow-up. Conclusion: In our series, minimally invasive ITVR, including EITVS and TTVR, is a safe and feasible option for severe TR after LSVS, and presents excellent early outcomes in selected patients. TTVR is a reliable alternative for patients with high surgical risk. To improve the results of ITVR, it is necessary to improve patient's preoperative status or perform reoperation before the onset of significant right heart failure. Further studies with a larger sample size and a longer follow-up period are awaited.