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.

Totally endoscopic aortic valve replacement: Techniques and early results.

Objective: To demonstrate the technical details of total endoscopic aortic valve replacement using a standard prosthesis, compare the clinical effect and safety of endoscopic aortic valve replacement and traditional aortic valve replacement. Methods: From 2020 to 2021, 60 consecutive patients underwent elective isolated aortic valve replacement (AVR). They were divided into two groups: the total endoscopic AVR group (TE-AVR group, 29 patients, nine women, aged 51.65 ± 11.79 years), and the traditional full-sternotomy group (AVR group, 31 patients, 13 women, aged 54.23 ± 12.06 years). Three working ports were adopted in the TE-AVR procedure. Results: No patient died in either group. The cardiopulmonary bypass (CPB) time and aortic cross-clamp (ACC) time in the TE-AVR group were longer than those in the AVR group (CPB time: 177.6 ± 43.2 vs. 112.1 ± 18.1 min, p < 0.001; ACC time: 118.3 ± 29.7 vs. 67.0 ± 13.2 min, p < 0.001). However, the mechanical ventilation duration (14.2 ± 9.3 vs. 24.0 ± 18.9 h, p = 0.015) and postoperative hospital stay (6.0 ± 1.7 vs. 8.0 ± 4.5 days, p = 0.025) were shorter in patients of TE-AVR group than those of AVR group. Although the ICU stay (55.1 ± 26.9 vs. 61.5 ± 44.8 h, p = 0.509) and post-operative chest drainage of the first 24 h (229.8 ± 125.0 vs. 273.2 ± 103.2 ml, p = 0.146) revealed no statistical difference, there was a decreasing trend in the TE-AVR group. Among the patients of the TE-AVR group, two patients were converted to thoracotomy because of mild to moderate paravalvular leakage identified by intraoperative transesophageal echocardiography. Conclusion: Total endoscopic aortic valve replacement is safe and feasible, with less trauma and quicker recovery.

Endoscopic repeat isolated tricuspid valve surgery after left-sided valve replacement: valvuloplasty or replacement.

BACKGROUND: The strategy of isolated tricuspid valve surgery has undergone innovations in recent years. This study aimed to summarize our experience using an endoscopic approach to repeat isolated tricuspid valve surgery (RITS) after left-sided valve replacement (LSVR). METHODS: From June 2013 to May 2019, 79 patients underwent endoscopic RITS after LSVR at our institution. Patients were divided into the tricuspid valvuloplasty (TVP) group (N.=49) and the tricuspid valve replacement (TVR) group (N.=30); perioperative outcomes and follow-up results were compared. RESULTS: There were seven postoperative deaths (8.9%). In-hospital mortality was higher in the TVR group than in the TVP group, although this difference was not statistically significant (13.3% vs. 6.1%, P=0.417). More patients experienced residual moderate-to-severe tricuspid regurgitation (TR) at discharge in the TVP group than in the TVR group (26.7% vs. 0%, P=0.003). Five patients died from heart, and multiorgan failure during follow-up; the overall 3- and 5-year survival rates were 93.8% [95% confidence interval (CI): (87.1-99.9%)] and 85.3% (95% CI: 73.3-99.2%), respectively, and no significant differences were found between the two groups (P=0.103). The overall rates of the 3- and 5-year freedom from severe recurrent TR were 93.2% (95% CI: 85.9-99.9%) and 89.0% (78.7-99.9%), respectively, and no significant difference was found between groups (P=0.176). CONCLUSIONS: Repeat isolated tricuspid valve surgery after left-sided valve replacement is associated with adverse perioperative outcomes. Endoscopic access offers an alternative approach for RITS after LSVR with acceptable results. TVP results in lower surgical mortality than TVR while carrying a higher risk of residual moderate-to-severe TR.

Outcomes of redo-isolated tricuspid valve surgery after left-sided valve surgery.

OBJECTIVES: To compare early and long-term outcomes of redo-isolated tricuspid surgery (RITS) after left-sided valve surgery. METHODS: We retrospectively reviewed 173 patients who underwent RITS for severe tricuspid regurgitation after previous left-sided valve surgery from January 1999 to December 2019. Patients were divided into two groups: RITS by median sternotomy (m-RITS; n = 78) and totally endoscopic approach (e-RITS; n = 95). Perioperative outcomes and follow-up results were analyzed. RESULTS: There were 19 (11%) in-hospital deaths (14.1% in m-RITS and 8.4% in e-RITS, p = .234) that decreased from 16.7% (1999-2014) to 6.9% (2015-2019) (p = .044). Tricuspid valve replacement (odds ratio [OR] = 4.989, 95% confidence interval [CI]: 1.133-29.790, p = .041) and NYHA function class IV (OR = 9.611, 95% CI: 2.102-43.954, p = .004) were independent risk factors for in-hospital mortality. The overall 1-, 5-, 10-, and 15-year survival rates were 97.2% (95% CI: 94.5%-99.9%), 80.3% (95% CI: 71.7%-88.9%), 59.2% (95% CI: 43.5%-75.5%), and 49.3% (95% CI: 27.2%-71.4%), respectively. CONCLUSION: Patients undergoing RITS carry a high risk of early mortality. There was no significant difference in early mortality or long-term survival between the endoscopy and median sternotomy, whereas the endoscopy approach was associated with shorter intensive care unit stays and fewer reoperations. Repair resulted in lower surgical mortality than replacement with acceptable residual tricuspid regurgitation.

Total thoracoscopic repair of ventricular septal defect: A single-center experience.

OBJECTIVES: To explore the safety and efficacy of total thoracoscopic repair of ventricular septal defects (VSD). We compared clinical outcomes of VSD via a total thoracoscopic approach with those of mini-sternotomy. METHODS: We retrospectively reviewed clinical data from patients with VSD from 2012 to January 2019. According to the surgical pattern, they were divided into two groups: the total thoracoscopic surgery group (36 patients, 27 females, aged 29 ± 9.52 years), and a mini-sternotomy group (31 patients, 12 females, aged 28 ± 8.67 years). RESULTS: There were no deaths in either group. In the thoracoscopic group, cardiopulmonary bypass (CPB) time and aortic cross-clamping (ACC) time were significantly longer than those of the mini-sternotomy group (CPB time: 112 ± 23.16 min vs. 78 ± 37.90 min, respectively, p < .001; ACC time: 65 ± 19.94 min vs. 50 ± 24.90 min, respectively, p < .001). postoperative hospital stay time (5.11 ± 2.48 days vs. 5.90 ± 6.27 days, p = .488) and chest drainage (139.86 ± 111.71 ml vs. 196.13 ± 147.34 ml, p = .081) tended to be lower in the thoracoscopy group, although there was no significant difference. No residual shunt or tricuspid regurgitation was found at follow-up. CONCLUSIONS: Total thoracoscopic repair is safe and effective in patients with VSD, with or without tricuspid regurgitation.

Modified unicaval drainage in reoperative isolated tricuspid valve repair via totally thoracoscopic approach.

AIM: The aim of this study was to investigate the feasibility, safety, and clinical effect of modified unicaval drainage for thoracoscopic reoperative isolated tricuspid valve repair, compared with conventional bicaval drainage. METHODS: A total of 45 consecutive cases of patients who underwent thoracoscopic reoperative isolated tricuspid valve repair on beating-heart were enrolled and divided into two groups according to the different venous drainage (Group A: modified unicaval drainage, Group B: conventional bicaval drainage). A retrospective analysis of perioperative data and clinical outcomes were performed and all the surviving cases were followed up. Re-evaluation of echocardiography and electrocardiogram was performed prior to discharge, and at first month, sixth month, and every year follow-up. RESULTS: The overall postoperative 30-day mortality was 4.5% in Group A and 8.7% in Group B. The postoperative tricuspid valve regurgitation grade of both groups decreased significantly from preoperative regurgitation grade, p < 0.001, without intergroup significant difference, p = 0.815. Follow-up duration ranged from 6 to 38 months, there was one death at 24 months in Group A, and another at 9 months in Group B, respectively. Nobody from both groups experienced reintervention for residual tricuspid regurgitation. No significant difference could be identified about the incidence of postoperative morbidities and follow-up adverse events. CONCLUSION: Both strategies of caval venous drainage can provide satisfactory exposure for thoracoscopic reoperative isolated tricuspid valve repair and equivalent favorable postoperative outcome. And the modified unicaval drainage group may even preserve the anesthetic time and decrease the risk of iatrogenic jugular injury, achieving a more simplified procedure with better cosmetic outcome.

Adverse effects of nicotine on cardiogenic differentiation from human embryonic stem cells detected by single-cell RNA sequencing.

Tobacco smoking was one of the important adverse factors for congenital heart disease. The effects of nicotine, the main component of tobacco, on human embryonic cardiogenesis and related mechanisms remain poorly understood. This work used single-cell RNA sequencing to investigate the effects of nicotine on human embryonic stem cell (hESC) line H9 and its underlying mechanisms during cardiac differentiation. H9 was cultured in feeder-free medium and differentiated in cardiac condition medium when cells reached 90% confluent. Cell viability was detected by MTT after different concentration of nicotine treatment. Different expressed genes during cardiac differentiation was analyzed by single-cell RNA sequencing (scRNA-seq). Key gene expressions were confirmed by qPCR and Western blot. Results showed that 0.1µM-10µM nicotine did not affect H9 cell proliferation. Nicotine 1 µM down-regulated cardiac progenitor cell, mesoderm cell, smooth muscle cell and neural crest cell relatively. Snail1/2 regulating endocardial cushion development were downregulated apparently at differention day 6. Nicotine didn't affect bry-1 and mesp-1 but inhibited cardiac transcript factors. Consequently, the expression of cTnI, a marker of cardiomyocytes was decreased significantly. The data suggest direct adverse effects of nicotine on heart development at the single-cell level and offer a new approach for estimate drug and environmental toxicity on the pathogenesis of the embryonic cardiovascular system development.

Early outcomes of mitral valvuloplasty by minimally invasive surgery or sternotomy.

BACKGROUND: Disagreement exists regarding methods for repair of the mitral valve. We compared early outcomes of mitral valvuloplasty by a minimally invasive technique and by a median sternotomy. METHODS: The data of 507 patients (mean age 47.9 ± 15.2 years) undergoing mitral valvuloplasty from January 2015 to June 2018 were analyzed retrospectively. In the study group (n = 225), mitral valvuloplasty via a totally thoracoscopic approach was performed by a single surgeon. In the control group (n = 282), mitral valvuloplasty via the traditional median sternotomy was carried out by other cardiac surgeons in our hospital. Clinical data, surgical results, and follow-up findings in the two groups were comparatively analyzed. RESULTS: In the study group, the blood transfusion rate (5.3% vs. 20.9%, p < 0.05) and incidences of poor wound healing (0 vs. 5.3%, p < 0.05) and respiratory tract infection (4.4% vs. 16.3%, p < 0.05) were lower, and postoperative hospitalization was shorter (5.9 ± 4.0 vs. 10.7 ± 8.4 days, p < 0.05). Within 30 days after surgery, no patient died in the study group while one died in the control group. The duration of follow-up was 12-36 months (mean 22.9 ± 8.8 months). During follow-up, there were 1 and 0 cases of redo surgery and 1 and 3 deaths in the study group and control group, respectively. CONCLUSION: Mitral valvuloplasty via a minimally invasive approach is superior to the traditional median sternotomy in terms of early outcomes, especially when performed by experienced surgeons.

Results of surgery on adults with functional single ventricle without prior cardiac surgery in childhood.

OBJECTIVES: Patients with unoperated functional single ventricle (FSV) rarely survive into adulthood with good functional status and there are few reports about surgical results of adult patients with FSV. This study retrospectively reviews our experience with surgery in adult patients with FSV. METHODS: From January 2008 to September 2017, 65 adult patients with FSV underwent surgery in our hospital. Twenty underwent Blalock-Taussig shunt or bidirectional Glenn procedures in other hospitals prior, and four were lost to follow-up. Finally, 41 patients were included in this study. RESULTS: The early postoperative mortality was 7.3% (3/41). Postoperative systemic arterial oxygen saturation (SpO2 , 83.7% ± 4.8%) was significantly higher than preoperative SpO2 (77.9% ± 10.1%, P < .01). The mean follow-up time was 3.9 ± 3.1 years (range 1-11 years). There was only one case of late mortality and massive hemoptysis was the cause of death. Right ventricular morphology and severe atrioventricular valve regurgitation (AVVR) were the risk factors of postoperative death for patients with pulmonary stenosis(PS). There was no death case in patients who received Fontan procedure. In a follow-up, we found the grade of AVVR was reduced and the grade of heart function (New York Heart Association) was improved. CONCLUSIONS: Adult patients with FSV can also undergo surgery. The mortality was acceptable and late results were satisfactory. After surgery, oxygen saturations increased, grades of AVVR decreased and the heart functions improved. Right ventricular morphology and severe AVVR were risk factors for patients with PS.

Minimally invasive, multi-disciplinary approach for surgical management of a mediastinal congenital bronchogenic cyst in a 6-month-old infant.

We present a case of prenatal diagnosis of a mediastinal cyst by ultrasound, confirmed during infancy through computed tomography (CT) and magnetic resonance imaging (MRI). A 6-month-old male infant was admitted to the hospital. A mid-mediastinal cyst was detected through a province-wide fetal ultrasonography screening program. During the infancy stage, the CT scan and the MRI confirmed the finding of a mediastinal cyst. Based on the findings on prenatal ultrasonography and postnatal imaging studies (CT, MRI), a benign mediastinal cyst was suspected. The cyst was below the tracheal carina, and the patient developed symptoms of respiratory distress. Owing to the enlargement trend of the cyst, the respiratory distress it has caused, and the anxiety it caused to the patient's family, a multi-disciplinary conference reached the consensus that surgical resection is the treatment of choice and a carina-approach mediastinal lesion resection via video-assisted thoracoscopic surgery (VATS) was performed. The cyst was removed successfully. Although this report is of a single case and follow-up duration is not long enough, we nevertheless make the first move to improve the pattern to a feasible, reliable, and efficient one, which could be used to treat similar patients.

Application of bidirectional Glenn procedure in adult congenital heart disease / 中国胸心血管外科临床杂志

@#Objective    To analyze the feasibility of bidirectional Glenn procedure (BDG) in treatment of adult congenital heart disease (ACHD). Methods    From December 2004 to December 2015, 42 ACHD patients received BDG in our hospital. There were 23 males and 19 females with a mean age of 24.6±8.5 years (range: 18 to 49 years). There were functional single ventricle (FSV) in 14 patients, Ebstein’s anomaly in 11, corrected transposition of great arteries in 7, transposition of great arteries in 5, double outlet of right ventricle in 3 and tricuspid atresia in 2. Twenty patients suffered moderate or severe atrioventricular valve regurgitation (AVVR). Half of the patients were operated upon with cardiopulmonary bypass (CPB) and the others with off-pump coronary artery bypass grafting (OPCABG). Thirty-four patients underwent unilateral BDG shunt and eight bilateral BDG shunts. Concomitant procedures included correction of Ebstein’s anomaly (7 patients), atrioventricular valve replacement (7), atrial septostomy (3), ligation of patent ductus arteriosus (3), ligation of major aortopulmonary collateral arteries (2), correction of total anomalous pulmonary venous connection (1) and mitral valve repair (1). Results    The early operative mortality was 9.5% (4/42). FSV and moderate or severe AVVR were risk factors for BDG in ACHD. Early postoperative oxygen saturation increased from 78.8%±11.2% to 89.3%±6.6% (P<0.05). The follow-up time was 6-132 (41.4±33.1) months. There was no death. The heart function improved (2.7±0.5 vs. 1.9±0.4, P<0.05). Conclusion    The BDG shunt can be applied to ACHD. Although the early mortality is relatively high, the middle- and long-term results are satisfactory. The oxygen saturation increases and  the heart function improves. The life quality of patients will also improve. FSV and moderate or severe AVVR are risk factors for BDG in ACHD.

The application of autologous pulmonary artery in surgical correction of complicated aortic arch anomaly.

BACKGROUND: In the patients with longer-segment aortic arch hypoplasia or interruption with ventricular septal defect, surgery with homograft vessel or autologous pericardial patch to augment descending aortic arch will not result in adverse reactions caused by end-to-end anastomosis. In this study, we retrospectively analyzed primary experience of surgical correction of complicated aortic arch anomaly with autologous main pulmonary artery. METHODS: From July 2010 to March 2016, the twenty-one cases of aortic arch complex anomalies were reconstructed with autologous main pulmonary artery. There were 5 patients with interrupted aortic arch and 16 patients with coarctation of aorta. In patients with interrupted aortic arch, anterior wall of main pulmonary artery was excised to form a conduit whose diameter varied according to the area of patient's body surface. Both ends of the conduit were anastomosed to aortic arch and descending aorta, respectively. In other patients with coarctation of aorta, aortic arch was augmented with tailored pulmonary artery patch in oval shape. The defect of main pulmonary artery was repaired with autologous pericardial patch. RESULTS: There was only one patient died of multiple organ failure postoperatively. The other twenty patients survived without any neurologic complications. Differences of blood pressure between upper and lower limbs were not significant in all cases. During follow-up period, the echocardiography for all patients in the third, sixth, twelfth, and twenty-fourth months showed that blood flow in the descending aortic arch was fluent and there was no obvious blood pressure gradient. CONCLUSIONS: Autologous main pulmonary artery can be used to repair complicated aortic arch anomalies completely without any anastomotic tension or bronchial obstruction postoperatively. This procedure is feasible and possesses predominant early and mid-term effects, and autologous main pulmonary artery can retain growth capacity during follow-up period. Of course, it is necessary to draw a definite conclusion of this technique during long-term follow-up period.