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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Safety and efficacy of two-port thoracoscopic aortic valve replacement.

BACKGROUND: Pure aortic valve disease is common and has been treated with sternotomy aortic valve replacement for decades. Minimally invasive cardiac surgery has been widely used in atrioventricular valve lesions, but totally thoracoscopic aortic valve replacement has rarely been reported. METHOD: The profiles of 9 patients who were diagnosed with severe aortic valve diseases and treated with two-port thoracoscopic aortic valve replacement between February 2021 and February 2022 were retrospectively reviewed. The clinical data, including baseline characteristics, operative data, postoperative complications, and short-term outcomes, were reported. RESULTS: All nine patients successfully underwent two-port thoracoscopic aortic valve replacement, with a cardiopulmonary bypass time of 137.56 ± 27.99 min and an aortic cross-clamp time of 95.33 ± 17.96 min. Seven (77.78%) patients underwent mechanical valve replacement, and two (22.22%) patients underwent bioprosthetic valve replacement. Two (22.22%) patients underwent a concomitant aortic root enlargement procedure. There were no intraoperative or postoperative deaths. The incidence of procedural complications was 0%, while the results of ventilation time, intensive care unit stay length, blood transfusion, chest tube drainage, and kidney function were satisfactory. CONCLUSION: Two-port thoracoscopic aortic valve replacement is a safe and effective surgical treatment option for carefully selected patients with pure aortic valve diseases.

Tissue-specific metabolomic profiling after cardiopulmonary bypass in fetal sheep.

Objective: Fetal cardiopulmonary bypass (CPB) is essential to fetal heart surgery, while its development is limited by vital organ dysfunction after CPB. Studying organ metabolism may help to solve this problem. The objective of this study was to describe the tissue-specific metabolic fingerprints of fetal sheep under CPB and to associate them with organ functions. Methods: Ten pregnant ewes at 90-120 days of gestation were randomly divided into two groups. The bypass group underwent a 1-h fetal CPB, whereas the control group underwent only a fetal sternotomy. During bypass, echocardiography, blood gases, and blood biochemistry were measured. After bypass, lambs were sacrificed, and tissues of the heart, liver, brain, kidney, and placenta were harvested. The metabolites extracted from these tissues were analyzed using non-targeted metabolomics based on liquid chromatography-mass spectrometry techniques. Results: All tissues except the placenta displayed significant metabolic changes, and the fetal heart displayed obvious functional changes. Fetal sheep that underwent CPB had common and tissue-specific metabolic signatures. These changes can be attributed to dysregulated lipid metabolism, altered amino acid metabolism, and the accumulation of plasticizer metabolism. Conclusion: Fetal CPB causes tissue-specific metabolic changes in fetal sheep. Studying these metabolic changes, especially cardiac metabolism, is of great significance for the study of fetal CPB.

Anomalous left coronary artery from the pulmonary artery: Outcomes and management of mitral valve.

Objective: Use of concomitant mitral valve repair remains controversial in the anomalous left coronary artery from the pulmonary artery (ALCAPA) with mitral regurgitation (MR). This study aimed to evaluate postoperative mitral valve function and explore the indication for concomitant mitral valve repair. Materials and methods: The medical records of 111 patients with ALCAPA and MR who underwent ALCAPA surgery between April 2006 and November 2020 were reviewed. The patients were categorized into three groups for comparison, namely, group I consisted of 38 patients with trivial or mild MR who underwent ALCAPA repair only; group II consisted of 37 patients with moderate or severe MR who similarly had only surgery of the ALCAPA performed; and group III consisted of 36 patients who had concomitant mitral valve repair for moderate or severe MR. Result: Overall mortality was 7.2% (8 of 111). The mortality of group II (16.2%, 6 of 37) was higher than those of groups I (5.3%, 2 of 38) and III (0%, 0 of 36) (p = 0.027). All three patients who underwent mitral valve reintervention were in group II. At the last follow-up, none of the patients had more than moderate MR in group I. The percentage of patients with improved MR grade was 79.4% (27 of 34) in group III and 51.4% (19 of 37) in group II (p = 0.001). The multivariate logistic regression revealed that concomitant mitral valve repair (adjusted odds ratio = 4.492, 95% CI: 1.909-12.794; p < 0.001) was the major factor influencing MR grade improvement. Conclusion: The long-term outcomes after ALCAPA repair were favorable. For mild MR, ALCAPA repair only can be performed. For moderate and severe MR, we suggest concomitant mitral valve repair.

Complications and management of functional single ventricle patients with Fontan circulation: From surgeon's point of view.

Fontan surgery by step-wise completing the isolation of originally mixed pulmonary and systemic circulation provides an operative approach for functional single-ventricle patients not amenable to biventricular repair and allows their survival into adulthood. In the absence of a subpulmonic pumping chamber, however, the unphysiological Fontan circulation consequently results in diminished cardiac output and elevated central venous pressure, in which multiple short-term or long-term complications may develop. Current understanding of the Fontan-associated complications, particularly toward etiology and pathophysiology, is extremely incomplete. What's more, ongoing efforts have been made to manage these complications to weaken the Fontan-associated adverse impact and improve the life quality, but strategies are ill-defined. Herein, this review summarizes recent studies on cardiac and non-cardiac complications associated with Fontan circulation, focusing on significance or severity, etiology, pathophysiology, prevalence, risk factors, surveillance, or diagnosis. From the perspective of surgeons, we also discuss the management of the Fontan circulation based on current evidence, including post-operative administration of antithrombotic agents, ablation, pacemaker implantation, mechanical circulatory support, and final orthotopic heart transplantation, etc., to standardize diagnosis and treatment in the future.

Transmembrane protein 121 as a novel inhibitor of cervical cancer metastasis.

Transmembrane protein 121 (TMEM121) is isolated from the chicken heart using subtraction hybridisation. A previous study by the authors indicated that TMEM121 is highly expressed in adult mouse hearts and acts as an inhibitor of pathological cardiac hypertrophy. In the present study, the association between TMEM121 and cancer was investigated using bioinformatics tools, including Tumour Immune Estimation Resource (TIMER) 2.0, cBioPortal, LinkedOmics analysis, Kaplan-Meier plotter and UALCAN analysis. The expression, genetic variation, gene interaction network and co-expression pattern of TMEM121 in tumours were analysed. The results revealed that TMEM121 was expressed in various tumours and significantly downregulated in cervical squamous cell carcinoma and endocervical adenocarcinoma (CESC) when compared with its expression in paracancerous tissues, whereas the methylation level of its promoter was increased in tumour tissues. Additionally, associations between TMEM121 and the PI3K/AKT signalling pathway, as well as the expression of cancer-related molecules, were detected. The aforementioned bioinformatics analysis suggests that TMEM121 may be involved in the development of cervical cancer. Therefore, gain-of-function and loss-of-function experiments in HeLa cells were conducted to verify the role of TMEM121 in cervical cancer. The assay using Cell Counting Kit-8 (CCK-8) revealed that the cell viability of HeLa cells with TMEM121 overexpression was significantly reduced. High TMEM121 expression inhibited HeLa cell migration, as indicated by the decrease in the cell scratch healing rate. The western blot assay revealed that TMEM121 overexpression downregulated the expression of B-cell lymphoma 2 (BCL-2), cyclin D1, cyclin E2 and phosphorylated (p)-AKT, while upregulating that of p27, E-cadherin and p-p38. When TMEM121 was knocked down, retinoblastoma protein (RB), p53, p27, E-cadherin, p-JNK and p-p38 were inhibited, but cyclin E1 was promoted. By combining bioinformatics and experimental biology in the present study, the results demonstrated for the first time, to the best of our knowledge, that TMEM121 may be a novel inhibitor of cervical cancer that is linked to multiple signalling pathways, paving the way for the development of novel diagnostic and therapeutic strategies.