Recurrent mitral regurgitation after repair of Barlow's disease in a single-center retrospective cohort study.

Background: Barlow's disease (BD) is a common etiology of degenerative mitral valve (MV) disease, often causing significant mitral regurgitation (MR). The pathology of BD is challenging for surgeons performing MV repair (MVR). However, most MVR effectiveness studies have been based on survival and risk of reoperation. The aim of this study was to analyze the safety, efficacy, and durability of MVR in patients with BD and to identify factors that influence recurrent MR. Methods: We retrospectively analyzed the clinical outcomes of 274 patients undergoing MVR for BD at a tertiary hospital (Guangdong People's Hospital, Guangzhou, China) between January 2010 and June 2022. To analyze the results of MVR and identify the risk factors for MR recurrence, we defined two groups: a total of 240 patients with MR grade <2+ (group A) and a total of 34 patients who had recurrent MR after MVR (group B; the patients with MR ≥2+). All patients were operated on using standard repair techniques. Recurrent MR was the primary outcome. Secondary outcomes were death and reoperation after MVR. Patients were followed up until March 2023. Patients were followed up by clinic visits, telephone calls, and postal or electronic questionnaires. Results: The median [range] patient age was 46.00 [16-75] years and 186 (67.9%) patients were male. Concomitant procedures were performed in 123 patients: tricuspid valve repair 71 (25.9%), maze or pulmonary vein isolation (PVI) 12 (4.4%), atrial septal defect (ASD) repair 3 (1.1%), and left atrial appendage (LAA) closure 28 (10.2%). Hospital mortality was 0.4%. Long-term complications included radiofrequency ablation in 7 patients (2.6%), pacemaker implantation in 1 patient (0.4%), and stroke in 3 patients (1.1%). The median follow-up was 3.28 (range, 0-12.39) years. Considering the competing risk of mortality, the cumulative incidence of MR progression 2+ or more grades was 2.6%, 5.9%, 14.5%, and 27.7% at 1 month, 1, 5, and 10 years, respectively. Overall survival at 1, 5, and 10 years was 99.3%, 98.6%, and 98.6%, respectively. The immediate postoperative MR area [hazard ratio (HR) =1.723; 95% confidence interval (CI): 1.051-2.824; P=0.031], postoperative left ventricular end-diastolic dimension (LVEDD) (HR =1.149; 95% CI: 1.016-1.300; P=0.027), and postoperative MR grade {HR = Exp[4.500 - 0.544 × ln(t + 20)]; P=0.008} were associated with an increased risk of MR recurrence, whereas a higher left ventricular ejection fraction (LVEF) (HR =0.931; 95% CI: 0.868-0.999; P=0.049) was associated with a decreased risk. Conclusions: MVR in patients with BD can be performed with low mortality and complications and is associated with superior long-term outcomes. However, MVR was associated with a certain risk of MR recurrence, especially in those with high postoperative LVEDD, residual MR >1+, and decreased postoperative LVEF. We recommend MVR for patients with BD, especially for those with early-stage disease. However, future randomized controlled trials are needed to confirm this.

Application of Bovine Pericardium and Expanded Polytetrafluoroethylene Patches in Tricuspid Valvuloplasty after Cardiac Surgery.

Background: Leaflet augmentation is often required to correct an inadequate leaflet size due to leaflet thickening, contracture and junctional fusion in patients with tricuspid valve regurgitation (TR) after left-side valve surgery (LSVS). However, the ideal material for leaflet augmentation remains controversial. This article aims to compare the medium- and long-term results of tricuspid valve repair with bovine pericardium (BP) and expanded Polytetrafluoroethylene (ePTFE) patches for the augmentation of tricuspid leaflets and to compare the durability of the two materials. Methods: From January 2015 to April 2023, a total of 69 patients with severe isolated TR underwent tricuspid valvuloplasty (TVP) by leaflets augmentation with patches in our institute. According to the different types of patches, they were divided into the BP group (n = 44) and the ePTFE group (n = 25). Results: There were 3 perioperative deaths (4.3%), one case was due to low cardiac output syndrome in the BP group, and 2 cases were due to acute respiratory dysfunction syndrome and low cardiac output syndrome in the ePTFE group, respectively. Before discharge, the area of the TR jet on echocardiography decreased from 23.5 ± 9.1 to 4.2 ± 3.4 cm 2 . One case in each group was found to have increased blood flow velocity at the tricuspid orifice. After discharge, one patient in each group underwent repeat TVP, in the BP group because of shortened chordae and in the ePTFE group because of calcification of the patch. During the entire follow-up period, there were 7 cases of severe TR (10.1%), 5 in the BP group and 2 in the ePTFE group, a total of 5 cases of tricuspid stenosis (7.2%), 4 in the BP group and 1 in the ePTFE group, and a total of 6 deaths (8.7%), 5 in the BP group and 1 in the ePTFE group. Transthoracic ultrasound in a patient with tricuspid stenosis suggests stiff leaflet movement and poor motion. Conclusions: Leaflet patch enlargement can be safely used in tricuspid valve repair, but BP patches carry a risk of reduced flexibility and stiffness of movement, and ePTFE patches carries a risk of calcification.

Transcatheter mitral valve-in-valve for pregnancy with anti-phospholipid syndrome: a case report.

BACKGROUND: Perioperative management and cardiac surgery in pregnant women with anti-phospholipid syndrome combined with heart valve disease have been rarely reported. CASE PRESENTATION: We describe a case of transcatheter mitral valve-in-valve replacement in a pregnant woman with bioprosthetic valve failure and anti-phospholipid syndrome at 18 weeks' gestation. The patient underwent a cesarean section delivery at 34 weeks of gestation, resulting in the birth of a healthy baby. CONCLUSIONS: Transapical mitral valve-in-valve surgery resulted in safe maternal and infant outcomes in a pregnant woman with anti-phospholipid syndrome combined with mitral bioprosthetic valve failure. The success of this procedure underscored the importance of multidisciplinary teamwork.

Management of left atrial myxoma in pregnant women: a case series.

BACKGROUND: Left atrial myxoma during pregnancy is rare. We present three cases in order to aid in the management. CASE PRESENTATION: Three cases of left atrial myxoma during pregnancy were presented in this article. Three patients all received multidisciplinary team work and acquired good outcomes. The case 1 had no symptoms and delivered before traditional cardiac surgery. The case 2 and case 3 undergone totally endoscopic minimally invasive cardiac surgery during pregnancy. The case 3 maintained pregnancy to term and gave birth to a healthy baby via vaginal delivery. No relapse of the tumor was observed. CONCLUSIONS: The management of left atrial myxoma during pregnancy ought to be individualized and combined with the gestational age. If the diagnosis was made in the first two trimesters of pregnancy, totally endoscopic minimally invasive cardiac surgery during pregnancy would be an optimal choice. The patients can benefit from the multidisciplinary team work.

Thymidine Phosphorylase Promotes the Formation of Abdominal Aortic Aneurysm in Mice Fed a Western Diet.

Aims: The precise molecular drivers of abdominal aortic aneurysm (AAA) remain unclear. Thymidine phosphorylase (TYMP) contributes to increased platelet activation, thrombosis, and inflammation, all of which are key factors in AAA development. Additionally, TYMP suppresses the proliferation of vascular smooth muscle cells (VSMCs), which are central to the development and progression of AAA. We hypothesize that TYMP plays a key role in AAA development. Methods and Results: We conducted a histological study using human AAA samples and normal abdominal aortas, revealing heightened levels of TYMP in human AAA vessel walls. To validate this observation, we utilized an Ang II perfusion-induced AAA model in wild-type C57BL/6J (WT) and Tymp-/- mice, feeding them a Western diet (TD.88137) starting from 4 weeks of age. We found that Tymp-/- mice were protected from Ang II perfusion-induced AAA formation. Furthermore, by using TYMP-expressing VSMCs as well as primarily cultured VSMCs from WT and Tymp-/- mice, we elucidated the essential role of TYMP in regulating MMP2 expression and activation. TYMP deficiency or inhibition by tipiracil, a selective TYMP inhibitor, led to reduced MMP2 production, release, and activation in VSMCs. Additionally, TYMP was found to promote pro-inflammatory cytokine expression systemically, and its absence attenuates TNF-α-stimulated activation of MMP2 and AKT. By co-culturing VSMCs and platelets, we observed that TYMP-deficient platelets had a reduced inhibitory effect on VSMC proliferation compared to WT platelets. Moreover, TYMP appeared to enhance the expression of activated TGFß1 in cultured VSMCs in vitro and in human AAA vessel walls in vivo. TYMP also boosted the activation of thrombospondin-1 type 1 repeat domain-enhanced TGFß1 signaling, resulting in increased connective tissue growth factor production. Conclusion: Our findings collectively demonstrated that TYMP serves as a novel regulatory force in vascular biology, exerting influence over VSMC functionality and inflammatory responses that promote the development of AAA.

Case Report: Totally endoscopic minimally invasive mitral valve surgery during pregnancy: a case series.

A totally endoscopic minimally invasive approach is widely used for cardiac valve surgery in normal adults. However, minimally invasive cardiac surgery during pregnancy is rarely reported. In addition to traditional median thoracotomy, totally endoscopic minimally invasive approaches can now be used for pregnant patients. We describe our experience with totally endoscopic cardiac valve surgery (TECVS) during pregnancy, which is safe for both mothers and fetuses.

IP3R2-mediated Ca2+ release promotes LPS-induced cardiomyocyte pyroptosis via the activation of NLRP3/Caspase-1/GSDMD pathway.

Pyroptosis plays a crucial role in sepsis, and the abnormal handling of myocyte calcium (Ca2+) has been associated with cardiomyocyte pyroptosis. Specifically, the inositol 1,4,5-trisphosphate receptor type 2 (IP3R2) is a Ca2+ release channel in the endoplasmic reticulum (ER). However, the specific role of IP3R2 in sepsis-induced cardiomyopathy (SIC) has not yet been determined. Thus, this study aimed to investigate the underlying mechanism by which IP3R2 channel-mediated Ca2+ signaling contributes to lipopolysaccharide (LPS)-induced cardiac pyroptosis. The SIC model was established in rats by intraperitoneal injection of LPS (10 mg/kg). Cardiac dysfunction was assessed using echocardiography, and the protein expression of relevant signaling pathways was analyzed using ELISA, RT-qPCR, and western blot. Small interfering RNAs (siRNA) and an inhibitor were used to explore the role of IP3R2 in neonatal rat cardiomyocytes (NRCMs) stimulated by LPS in vitro. LPS-induced NLRP3 overexpression and GSDMD-mediated pyroptosis in the rats' heart. Treatment with the NLRP3 inhibitor MCC950 alleviated LPS-induced cardiomyocyte pyroptosis. Furthermore, LPS increased ATP-induced intracellular Ca2+ release and IP3R2 expression in NRCMs. Inhibiting IP3R activity with xestospongin C (XeC) or knocking down IP3R2 reversed LPS-induced intracellular Ca2+ release. Additionally, inhibiting IP3R2 reversed LPS-induced pyroptosis by suppressing the NLRP3/Caspase-1/GSDMD pathway. We also found that ER stress and IP3R2-mediated Ca2+ release mutually regulated each other, contributing to cardiomyocyte pyroptosis. IP3R2 promotes NLRP3-mediated pyroptosis by regulating ER Ca2+ release, and the mutual regulation of IP3R2 and ER stress further promotes LPS-induced pyroptosis in cardiomyocytes.

Prediction Model for Postoperative Pressure Injury in Patients with Acute Type A Aortic Dissection.

OBJECTIVE: To establish a risk assessment model to predict postoperative National Pressure Injury Advisory Panel stage 2 or higher pressure injury (PI) risk in patients undergoing acute type A aortic dissection surgery. METHODS: This retrospective assessment included consecutive patients undergoing acute type A aortic dissection surgery in the authors' hospital from September 2017 to June 2021. The authors used LASSO (logistic least absolute shrinkage and selection operator) regression analysis to identify the most relevant variables associated with PI by running cyclic coordinate descent with 10-times cross-validation. The variables selected by LASSO regression analysis were subjected to multivariate logistic analysis. A calibration plot, receiver operating characteristic curve, and decision curve analysis were used to validate the model. RESULTS: There were 469 patients in the study, including 94 (27.5%) with postoperative PI. Ten variables were selected from LASSO regression: body mass index, diabetes, Marfan syndrome, stroke, preoperative skin moisture, hemoglobin, albumin, serum creatinine, platelet, and d-dimer. Four risk factors emerged after multivariate logistic regression: Marfan syndrome, preoperative skin moisture, albumin, and serum creatinine. The area under the receiver operating characteristic curve of the model was 0.765. The calibration plot and the decision curve analysis both suggested that the model was suitable for predicting postoperative PI. CONCLUSIONS: This study built an efficient predictive model that could help identify high-risk patients.

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.

2022 CMICS Expert Consensus on the Management of Isolated Tricuspid Regurgitation after Left-Sided Valve Surgery.

Tricuspid regurgitation (TR) may occur late after left-sided valve surgery (LSVS). Isolated tricuspid regurgitation after left-sided valve surgery (iTR-LSVS) refers to isolated TR without significant lesions in the mitral and/or aortic position late after mitral and/or aortic replacement or repair. Severe TR has a negative impact on long-term prognosis and requires surgical or transcatheter treatment. However, there is no clear recommendation on when and how intervention should be performed for patients with iTR-LSVS in the current guidelines for the management of valvular heart disease. The historically high operative mortality may be reduced by current minimally invasive techniques and transcatheter therapy. To further understand iTR-LSVS, standardize the treatment, improve the prognosis, and promote the collaboration, the Chinese Minimally Invasive Cardiovascular Surgery Committee (CMICS) wrote this expert consensus on the management of iTR-LSVS from the aspects of etiology, preoperative evaluation, indications for intervention, surgical treatment, transcatheter therapy, and postoperative management.

Mettl3-mediated m6A modification of Fgf16 restricts cardiomyocyte proliferation during heart regeneration.

Cardiovascular disease is the leading cause of death worldwide due to the inability of adult heart to regenerate after injury. N6-methyladenosine (m6A) methylation catalyzed by the enzyme methyltransferase-like 3 (Mettl3) plays an important role in various physiological and pathological bioprocesses. However, the role of m6A in heart regeneration remains largely unclear. To study m6A function in heart regeneration, we modulated Mettl3 expression in vitro and in vivo. Knockdown of Mettl3 significantly increased the proliferation of cardiomyocytes and accelerated heart regeneration following heart injury in neonatal and adult mice. However, Mettl3 overexpression decreased cardiomyocyte proliferation and suppressed heart regeneration in postnatal mice. Conjoint analysis of methylated RNA immunoprecipitation sequencing (MeRIP-seq) and RNA-seq identified Fgf16 as a downstream target of Mettl3-mediated m6A modification during postnatal heart regeneration. RIP-qPCR and luciferase reporter assays revealed that Mettl3 negatively regulates Fgf16 mRNA expression in an m6A-Ythdf2-dependent manner. The silencing of Fgf16 suppressed the proliferation of cardiomyocytes. However, the overexpression of ΔFgf16, in which the m6A consensus sequence was mutated, significantly increased cardiomyocyte proliferation and accelerated heart regeneration in postnatal mice compared with wild-type Fgf16. Our data demonstrate that Mettl3 post-transcriptionally reduces Fgf16 mRNA levels through an m6A-Ythdf2-dependen pathway, thereby controlling cardiomyocyte proliferation and heart regeneration.

Cardiovascular diseases are one of the world's biggest killers. Even for patients who survive a heart attack, recovery can be difficult. This is because ­ unlike some amphibians and fish ­ humans lack the ability to produce enough new heart muscle cells to replace damaged tissue after a heart injury. In other words, the human heart cannot repair itself. Molecules known as messenger RNA (mRNA) carry the 'instructions' from the DNA inside the cell nucleus to its protein-making machinery in the cytoplasm of the cell. These messenger molecules can also be altered by different enzymes that attach or remove chemical groups. These modifications can change the stability of the mRNA, or even 'silence' it altogether by stopping it from interacting with the protein-making machinery, thus halting production of the protein it encodes. For example, a protein called Mettl3 can attach a methyl group to a specific part of the mRNA, causing a reversible mRNA modification known as m⁶A. This type of alteration has been shown to play a role in many conditions, including heart disease, but it has been unclear whether m⁶A could also be important for the regeneration of heart tissue. To find out more, Jiang, Liu, Chen et al. studied heart injury in mice of various ages. Newborn mice can regenerate their heart muscle for a short time, but adult mice lack this ability, which makes them a useful model to study heart disease. Analyses of the proteins and mRNAs in mouse heart cells confirmed that both Mettl3 and m⁶A-modified mRNAs were present. The amount of each also increased with age. Next, experiments in genetically manipulated mice revealed that removing Mettl3 greatly improved tissue repair after heart injury in both newborn and adult mice. In contrast, mouse hearts that produced abnormally high quantities of Mettl3 were unable to regenerate ­ even if the mice were young. Moreover, a detailed analysis of gene activity revealed that Mettl3 was suppressing heart regeneration by decreasing the production of a growth-promoting protein called FGF16. These results reveal a key biological mechanism controlling the heart's ability to repair itself after injury. In the future, Jiang et al. hope that Mettl3 can be harnessed for new, effective therapies to promote heart regeneration in patients suffering from heart disease.

Histatin-1 loaded multifunctional, adhesive and conductive biomolecular hydrogel to treat diabetic wound.

Micro-/macroangiopathy, neuropathy and prolonged inflammation are common in diabetic wound, however, traditional wound dressing cannot treat these problems in the same time. Herein, we developed a multifunctional hydrogel with promoted angiogenesis, cell proliferation and anti-inflammation ability to treat diabetic wound. The hydrogel was composed of natural polymers, including gelatin and chitosan, which have excellent biocompatibility. Histatin-1 (His-1) was added into the hydrogel to improve the cell adhesion, proliferation and angiogenesis. Besides, polypyrrole based conductive nanoparticles (G-Ppy) were introduced in the hydrogel to enhance the electrical signal conduction between skin and promote the mechanical strength of the hydrogel. The polypyrrole nanoparticles were growth in the chain of methacryloyl grafted gelatin (Gel-MA), leading to a better biocompatibility and water dispersibility. In vivo wound healing experiment proved that the hydrogel accelerated the wound healing rate, down regulation the expression of pro-inflammation factor TNF-α and upregulation the expression of CD31 and α-SMA, indicating the prospects in the application of diabetic wound healing.

Injectable conductive gelatin methacrylate / oxidized dextran hydrogel encapsulating umbilical cord mesenchymal stem cells for myocardial infarction treatment.

Umbilical cord mesenchymal stem cells (UCMSCs) transplantation has been proposed as a promising treatment modality for myocardial infarction (MI), but the low retention rate remains a considerable challenge. Injectable natural polymer hydrogels with conductivity ability are highly desirable as cell delivery vehicles to repair infarct myocardium and restore the cardiac function. In this work, we developed a hydrogel system based on gelatin methacrylate (GelMA) and oxidized dextran (ODEX) as cell delivery vehicles for MI. And dopamine could be used as a reductant of graphene oxide (GO) to form reductive GO (rGO). By adjusting the amount of rGO, the conductivity of hydrogels with 0.5 mg/mL rGO concentration (≈10-4 S/cm) was similar to that of natural heart tissue. In vitro cell experiments showed that the prepared hydrogels had excellent biocompatibility and cell delivery ability of UCMSCs. More importantly, GelMA-O5/rGO hydrogel could promote UCMSCs growth and proliferation, improve the myocardial differentiation ability of UCMSCs, and up-regulate the expression of cTnI and Cx43. Further in vivo experiments demonstrated that GelMA-O5/rGO/UCMSCs Hydrogel could significantly improve the ejection fraction (EF) of rats and significantly reduce myocardial infarct area compared to PBS group, promote the survival of UCMSCs, enhance the expression level of cTnI and Cx43, and decrease the expression level of caspase-3. The findings of this study suggested that the injectable conductive GelMA-O5/rGO hydrogel encapsulating UCMSCs could improve damaged myocardial tissue and reconstruct myocardial function, which will be a promising therapeutic strategy for cardiac repair.

An MMP-degradable and conductive hydrogel to stabilize HIF-1α for recovering cardiac functions.

Rationale: Although a few injectable hydrogels have shown a reliable biosafety and a moderate promise in treating myocardial infarction (MI), the updated hydrogel systems with an on-demand biodegradation and multi-biofunctions to deliver therapeutic drug would achieve more prominent efficacy in the future applications. In this report, a conductive and injectable hydrogel crosslinked by matrix metalloproteinase-sensitive peptides (MMP-SP) was rationally constructed to stabilize hypoxia-inducible factor-1α (HIF-1α) to recover heart functions after MI. Methods: Firstly, tetraaniline (TA) was incorporated into partially oxidized alginate (ALG-CHO) to endow the hydrogels with conductivity. The 1,4-dihydrophenonthrolin-4-one-3-carboxylic acid (DPCA) nanodrug was manufactured with high drug loading capacity and decorated with polymerized dopamine (PDA) to achieve a stable release of the drug. Both ALG-CHO and DPCA@PDA can be cross-linked by thiolated hyaluronic acid (HA-SH) and thiolated MMP-SP to construct a MMP-degradable and conductive hydrogel. After administration in the infarcted heart of rats, echocardiographic assessments, histological evaluation, and RT-PCR were used to evaluate therapeutic effects of hydrogels. Results: The cell viability and the results of subcutaneous implantation verify a good cytocompatibility and biocompatibility of the resulting hydrogels. The hydrogel shows remarkable strength in decreasing the expression of inflammatory factors, maintaining a high level of HIF-1α to promote the vascularization, and promoting the expression of junctional protein connexin 43. Meanwhile, the multifunctional hydrogels greatly reduce the infarcted area (by 33.8%) and improve cardiac functions dramatically with ejection fraction (EF) and fractional shortening (FS) being increased by 31.3% and 19.0%, respectively. Conclusion: The as-prepared hydrogels in this report achieve a favorable therapeutic effect, offering a promising therapeutic strategy for treating heart injury.

CREB1 transcription-activated lncRNA PVT1 promotes cardiac fibrosis via miR-145/HCN1 axis.

BACKGROUND: Cardiac fibrosis is a common pathological process of most cardiac diseases, which may result in cardiac function impairment. Long noncoding RNAs (lncRNAs) have been verified as crucial regulators of cardiac fibrosis. This study explored the function and molecular mechanism of PVT1 in cardiac fibrosis. METHODS: TGF-ß1-exposed human cardiac fibroblasts (HCF-a) and isoproterenol (ISO)-treated mice were used as the in vitro and in vivo cardiac fibrosis models. PVT1, miR-145, and HCN1 expression was determined by quantitative RT-PCR. Cell proliferation was evaluated by CCK-8 and EdU fluorescence staining. α-SMA and collagen I expression was assessed by immunohistochemical staining and immunofluorescence staining. Protein levels of fibrosis-related factors were assessed by Western blotting. The interaction between miR-145 and PVT1/HCN1 was evaluated by dual luciferase assay. ChIP assay was used to validate the binding of CREB1 to the promoter of PVT1. Cardiac fibrosis in mice was observed by H&E and Masson's trichrome staining. RESULTS: PVT1 and HCN1 were up-regulated, while miR-145 was down-regulated in the cardiac fibrosis models. PVT1 knockdown restrained TGF-ß1-induced proliferation and activation of HCF-a cells. CREB1 bound to the promoter of PVT1 and activated its transcription. Mechanistically, PVT1 enhanced HCN1 expression via sponging miR-145. Finally, silencing of PVT1 attenuated cardiac fibrosis via regulating miR-145/HCN1 axis in mice in vivo. CONCLUSION: PVT1 contributed to cardiac fibrosis by increasing HCN1 expression via sponging miR-145, which suggested that targeting PVT1 may be a therapeutic option for cardiac fibrosis and cardiac diseases.

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.

Integrative Analyses of Genes Associated With Right Ventricular Cardiomyopathy Induced by Tricuspid Regurgitation.

Tricuspid regurgitation (TR) induces right ventricular cardiomyopathy, a common heart disease, and eventually leads to severe heart failure and serious clinical complications. Accumulating evidence shows that long non-coding RNAs (lncRNAs) are involved in the pathological process of a variety of cardiovascular diseases. However, the regulatory mechanisms and functional roles of RNA interactions in TR-induced right ventricular cardiomyopathy are still unclear. Accordingly, we performed integrative analyses of genes associated with right ventricular cardiomyopathy induced by TR to study the roles of lncRNAs in the pathogenesis of this disease. In this study, we used high-throughput sequencing data of tissue samples from nine clinical cases of right ventricular myocardial cardiomyopathy induced by TR and nine controls with normal right ventricular myocardium from the Genotype-Tissue Expression database. We identified differentially expressed lncRNAs and constructed a protein-protein interaction and lncRNA-messenger RNA (mRNA) co-expression network. Furthermore, we determined hub lncRNA-mRNA modules related to right ventricular myocardial disease induced by TR and constructed a competitive endogenous RNA network for TR-induced right ventricular myocardial disease by integrating the interaction of lncRNA-miRNA-mRNA. In addition, we analyzed the immune infiltration using integrated data and the correlation of each immune-related gene with key genes of the integrated expression matrix. The present study identified 648 differentially expressed mRNAs, 201 differentially expressed miRNAs, and 163 differentially expressed lncRNAs. Protein-protein interaction network analysis confirmed that ADRA1A, AVPR1B, OPN4, IL-1B, IL-1A, CXCL4, ADCY2, CXCL12, GNB4, CCL20, CXCL8, and CXCL1 were hub genes. CTD-2314B22.3, hsa-miR-653-5p, and KIF17ceRNA; SRGAP3-AS2, hsa-miR-539-5p, and SHANK1; CERS6-AS1, hsa-miR-497-5p, and OPN4; INTS6-AS1, hsa-miR-4262, and NEURL1B; TTN-AS1, hsa-miR-376b-3p, and TRPM5; and DLX6-AS1, hsa-miR-346, and BIRC7 axes were obtained by constructing the ceRNA networks. Through the immune infiltration analysis, we found that the proportion of CD4 and CD8 T cells was about 20%, and the proportion of fibroblasts and endothelial cells was high. Our findings provide some insights into the mechanisms of RNA interaction in TR-induced right ventricular cardiomyopathy and suggest that lncRNAs are a potential therapeutic target for treating right ventricular myocardial disease induced by TR.