Establishment of a lipid metabolism disorder model in ApoEb mutant zebrafish.

BACKGROUND AND AIMS: ApoEb is a zebrafish homologous to mammalian ApoE, whose deficiency would lead to lipid metabolism disorders (LMDs) like atherosclerosis. We attempted to knock out the zebrafish ApoEb, then establish a zebrafish model with LMD. METHODS: ApoEb was knocked out using the CRISPR/Cas9 system, and the accumulation of lipids was confirmed by Oil Red O staining, confocal imaging, and lipid measurements. The lipid-lowering effects of simvastatin (SIM), ezetimibe (EZE) and Xuezhikang (XZK), an extract derived from red yeast rice, were evaluated through in vivo imaging in zebrafish larvae. RESULTS: In the ApoEb mutant, significant vascular lipid deposition occurred, and lipid measurement performed in the whole-body homogenate of larvae and adult plasma showed significantly increased lipid levels. SIM, EZE and XZK apparently relieved hyperlipidemia in ApoEb mutants, and XZK had a significant inhibitory effect on the recruitment of neutrophils and macrophages. CONCLUSIONS: In this study, an LMD model has been established in ApoEb mutant zebrafish. We suggest that this versatile model could be applied in studying hypercholesterolemia and related vascular pathology in the context of early atherosclerosis, as well as the physiological function of ApoE.

An updated meta-analysis of device related thrombus following left atrial appendage closure in patients with atrial fibrillation.

Aims: Device related thrombus (DRT) is a known complication of left atrial appendage closure (LAAC). However, the relation between DRT and elevated risk of ischemic events remains controversial. This study is sought to reassessed the incidence of DRT following LAAC and the relation between DRT and elevated risk of ischemic stroke and systemic embolism (SE) with latest clinical trials included. Methods: The PubMed, Embase, and Cochrane Library databases were systematically searched from their inception until April 2022 for studies that reported the incidence of DRT and compared the incidence of both stroke and SE between DRT patients and non-DRT patients. Results: In 59 eligible studies, the incidence of DRT was 366/12,845 (2.8%, ranging from 0 to 11%, I 2 = 64%). The incidence of DRT was not statistically different between single-seal device (SS) and dual-seal device (DS) in subgroup analysis [171/6,190 (2.8%) vs. 78/3,023 (3.6%); p = 0.93]. The pooled incidence of stroke (26 studies, 7,827 patients) in patients with and without DRT was 11.5% in DRT patients and 2.9% among non-DRT patients (OR: 5.08; 95% CI = 3.47-7.44). In the sensitivity analysis, DRT was associated with higher rate of stroke (12.1 vs. 3.2%; OR: 4.14; 95% CI = 2.69-6.38) and SE (16.0 vs. 3.8%; OR: 4.48; 95% CI = 3.04-6.62). Conclusion: The incidence of DRT was low and similar between SS and DS devices. DRT was associated with increased rates of ischemic events. The occurrence rate of ischemic events associated DRT was comparable between two occlusion mechanism devices. Systematic review registration: [https://www.crd.york.ac.uk/], identifier [CRD42022326179].

The Application and Teaching Value of a Ventricular Septal Defect Canine Model Established by Transcatheter Puncture.

This study aimed to improve and further explore a ventricular septal defect (VSD) canine model on the basis of the transcatheter puncture method and to evaluate its application and teaching value.In order to lessen the complications of VSD closure, it is necessary to improve the currently available treatment devices using appropriate animal models.In this study, we used 16 healthy adult canines as our models. After anesthesia, the VSD puncture was performed, followed by balloon dilatation of the perforation. VSD was confirmed by angiography. The venous-artery orbit was established, and the VSD was then closed once the catheter and occluder were across the defect.Of the experimental canines, 14 of the 16 canines were successfully modeled, giving a success rate of 87.5%. The canines underwent an immediate creation of a venous-artery orbit for teaching practice and were implanted with an occluder during the procedure. After 4 weeks, 13 canines survived. As per our findings, most VSD types established by the puncture were perimembranous (10 of 13, 77%).The current model has a high success rate. The model can not only avoid the risk of infection and hemodynamic disorders associated with an open thoracotomy, but can also be effectively used in evaluating the impact of occluders. It can also directly measure the parameters of the devices during the procedure, thus having a very high experimental and teaching value.

Zfp36l1b protects angiogenesis through Notch1b/Dll4 and Vegfa regulation in zebrafish.

BACKGROUND AND AIMS: Angiogenesis is a key process for establishing functional vasculature during embryogenesis and involves different signaling mechanisms. The RNA binding protein Zfp36l1 was reported to be involved in various diseases in different species, including cardiovascular diseases. However, whether Zfp36l1b, one of the 2 paralogs of Zfp36l1 in zebrafish, works like mammalian Zfp36l1, and if the molecular mechanisms are different remains unclear. Here, we show that Zfp36l1b plays a crucial protective role in angiogenesis of zebrafish embryos. METHODS: We used transparent transgenic and wild-type zebrafish larvae to dynamically investigate the early stage of angiogenesis with confocal in vivo, after the knockdown of Zfp36l1b by morpholinos (MOs). In situ hybridization and fluorescence-activated cell sorting were performed to detect Zfp36l1b expression. mRNA rescue and CRISPR/Cas9 knockdown, and luciferase reporter experiments were performed to further explore the role of Zfp36l1b in angiogenesis. RESULTS: We found that knockdown of Zfp36l1b led to defected angiogenesis in intersomitic vessels and sub-intestinal veins (SIVs), which could be rescued by the addition of Zfp36l1b mRNA. Moreover, knockdown of Zfp36l1b suppressed Notch1b expression, while knockdown of Notch1b resulted in a partial relief of angiogenesis defects induced by Zfp36l1b down-regulation. Besides, Zfp36l1b knockdown alleviated the excessive branch of SIVs caused by Vegfa over-expression. CONCLUSIONS: Our results show that Zfp36l1b is responsible for establishing normal vessel circuits by affecting the extension of endothelial tip cells filopodia and the proliferation of endothelial cells partly through Notch1b/Fll4 suppression and synergistic function with Vegfa.

Percutaneous occlusion of transseptal puncture-related free wall perforation at the coronary sinus with a ventricular septal occluder during left atrial appendage closure: A case report.

Coronary sinus perforation is a life-threatening complication of transseptal puncture and needs to be repaired immediately. In this study, we report a case of a 74-year-old female patient with nonvalvular atrial fibrillation, who is a poor long-term anticoagulation candidate. During the manipulation of transseptal puncture, a perforation of the free right atrial wall at the coronary sinus ostium occurred, which was caused by the Brockenbrough needle and followed by the immediate advancement of an 8.5-French transseptal sheath. In consideration of the danger of cardiac tamponade after sheath removal, we decided to leave the 8.5-French sheath in the pericardial cavity. Then, we advanced a 6 mm ventricular septal occluder through the sheath. Finally, we achieved successful deployment of the device and closure of the perforation under the guidance of fluoroscopy and transthoracic echocardiography. Subsequently, the left atrial appendage orifice was occluded with a 21 mm Watchman device. This case illustrates that percutaneous device closure is feasible for inadvertent perforation of the free right atrial wall at the coronary sinus during transseptal puncture and should be considered as an alternative to surgery.

Neoblast-enriched zinc finger protein FIR1 triggers local proliferation during planarian regeneration.

Regeneration, relying mainly on resident adult stem cells, is widespread. However, the mechanism by which stem cells initiate proliferation during this process in vivo is unclear. Using planarian as a model, we screened 46 transcripts showing potential function in the regulation of local stem cell proliferation following 48 h regeneration. By analyzing the regeneration defects and the mitotic activity of animals under administration of RNA interference (RNAi), we identified factor for initiating regeneration 1 (Fir1) required for local proliferation. Our findings reveal that Fir1, enriched in neoblasts, promotes planarian regeneration in any tissue-missing context. Further, we demonstrate that DIS3 like 3'-5' exoribonuclease 2 (Dis3l2) is required for Fir1 phenotype. Besides, RNAi knockdown of Fir1 causes a decrease of neoblast wound response genes following amputation. These findings suggest that Fir1 recognizes regenerative signals and promotes DIS3L2 proteins to trigger neoblast proliferation following amputation and provide a mechanism critical for stem cell response to injury.

Plasma miR-451 with echocardiography serves as a diagnostic reference for pulmonary hypertension.

Due to the lack of typical clinical symptoms, the average delay time for diagnosis of pulmonary hypertension (PH) is longer than 2 years. It is urgent to find biomarkers for PH diagnosis. In this study we investigated whether plasma microRNAs (miRNAs) can be used as biomarkers for PH diagnosis. We used microarray to identify dynamic miRNAs between PH and non-PH patients. The candidate miRNAs were verified using qRT-PCR in a mouse model of PH, which was induced by monocrotaline (MCT) injection. We observed that miR-21, miR-126, miR-145, miR-191 and miR-150 had no differences between control mice and MCT-treated mice; but plasma miR-451 was significantly decreased in the 2wk-MCT group, with no further decrease in the 4wk-MCT group. Plasma miR-451 was also markedly decreased in PH patients, whereas miR-21, miR-126, miR-150 and miR-320 did not show differences between 53 PH patients and 54 non-PH patients. Receiver operating characteristic curves (ROCs) were constructed from the patient data to assess the clinical diagnostic values of circulating miR-451 and Doppler echocardiography (D-ECHO). The areas under the curve (AUCs) of ROCs for miR-451 and D-ECHO were 0.710 and 0.766, respectively. Combination of miR-451 and D-ECHO with AUC of 0.825 was superior to the use of either miR-451 or D-ECHO alone for PH diagnosis. In conclusion, plasma miR-451 has a moderate diagnostic value in PH comparable to that of D-ECHO, and the combination of miR-451 with D-ECHO has better diagnostic value than either method alone, which may have implications for PH diagnosis.

Rapamycin and CHIR99021 Coordinate Robust Cardiomyocyte Differentiation From Human Pluripotent Stem Cells Via Reducing p53-Dependent Apoptosis.

BACKGROUND: Cardiomyocytes differentiated from human pluripotent stem cells can serve as an unexhausted source for a cellular cardiac disease model. Although small molecule-mediated cardiomyocyte differentiation methods have been established, the differentiation efficiency is relatively unsatisfactory in multiple lines due to line-to-line variation. Additionally, hurdles including line-specific low expression of endogenous growth factors and the high apoptotic tendency of human pluripotent stem cells also need to be overcome to establish robust and efficient cardiomyocyte differentiation. METHODS AND RESULTS: We used the H9-human cardiac troponin T-eGFP reporter cell line to screen for small molecules that promote cardiac differentiation in a monolayer-based and growth factor-free differentiation model. We found that collaterally treating human pluripotent stem cells with rapamycin and CHIR99021 during the initial stage was essential for efficient and reliable cardiomyocyte differentiation. Moreover, this method maintained consistency in efficiency across different human embryonic stem cell and human induced pluripotent stem cell lines without specifically optimizing multiple parameters (the efficiency in H7, H9, and UQ1 human induced pluripotent stem cells is 98.3%, 93.3%, and 90.6%, respectively). This combination also increased the yield of cardiomyocytes (1:24) and at the same time reduced medium consumption by about 50% when compared with the previous protocols. Further analysis indicated that inhibition of the mammalian target of rapamycin allows efficient cardiomyocyte differentiation through overcoming p53-dependent apoptosis of human pluripotent stem cells during high-density monolayer culture via blunting p53 translation and mitochondrial reactive oxygen species production. CONCLUSIONS: We have demonstrated that mammalian target of rapamycin exerts a stage-specific and multifaceted regulation over cardiac differentiation and provides an optimized approach for generating large numbers of functional cardiomyocytes for disease modeling and in vitro drug screening.

MicroRNA-199a acts as a potential suppressor of cardiomyocyte autophagy through targeting Hspa5.

Autophagy is an adaptive response to cardiomyocytes survival under stress conditions. MicroRNAs (miRNAs, miR) have been described to act as potent modulators of autophagy. To investigate whether and how miR-199a modulated autophagy in vitro, primary cardiomyocytes were treated under starvation to induce autophagy. Results showed that down-regulation of miR-199a was sufficient to activate cardiomyocytes autophagy. MiR-199a suppressed cardiomyocytes autophagy through direct inhibiting heat shock protein family A member 5 (Hspa5). Forced overexpression of Hspa5 recovered the inhibitory effect of miR-199a in autophagy activation. Our results suggested miR-199a as an effective suppressor of starvation-induced cardiomyocytes autophagy and that Hspa5 was a direct target during this process. These results extend the understanding of the role and pathway of miR-199a in cardiomyocytes autophagy, and may introduce a potential therapeutic strategy for the protection of cardiomyocytes in myocardial infarction or ischemic heart disease.

Transcatheter Closure of Perimembranous Ventricular Septal Defects Using Dual Wire-Maintaining Technique.

OBJECTIVE: The present study was designed to evaluate the safety and feasibility of transcatheter closure of perimembranous ventricular septal defects (PmVSDs) with dual wire-maintaining technique (DWMT). PATIENTS/METHODS: From January 2010 to December 2013, a total of 241 patients (men: 109, women: 132; mean age: 22.2±15.4 years) with congenital PmVSDs were randomised to either the conventional technique (CT) group (n=118) or the DWMT group (n=123). RESULTS: In the CT group, the track wire was withdrawn before occluder insertion. In the DWMT group, the track wire was maintained in the delivery sheath during the procedure. Both the procedure time and fluoroscope time were reduced significantly in the DWMT group patients who required device replacement compared with CT group patients (median time: 46.0±14.8min vs. 56.0±15.2min, p<0.05; 15.0±11.6min vs. 22.0±10.1min, p<0.05). There was no difference in the incidence of complications between the two groups. CONCLUSION: The DWMT is safe and feasible for transcatheter treatment of PmVSDs, especially in patients requiring device replacement, for it avoids reconstruction of the "arteriovenous wire loop", left ventriculography from the contralateral femoral route, or the use of a larger femoral artery short sheath.

MicroRNA-126a Directs Lymphangiogenesis Through Interacting With Chemokine and Flt4 Signaling in Zebrafish.

OBJECTIVE: MicroRNA-126 (miR-126) is an endothelium-enriched miRNA and functions in vascular integrity and angiogenesis. The application of miRNA as potential biomarker and therapy target has been widely investigated in various pathological processes. However, its role in lymphatic diseases had not been widely explored. We aimed to reveal the role of miR-126 in lymphangiogenesis and the regulatory signaling pathways for potential targets of therapy. APPROACH AND RESULTS: Loss-of-function studies using morpholino oligonucleotides and CRISPR/Cas9 (clustered regularly interspaced short palindromic repeats/CRISPR-associated protein 9) system showed that silencing of miR-126a severely affected the formation of parachordal lymphangioblasts and thoracic duct in zebrafish embryos, although their development in miR-126b knockdown embryos was normal. Expression analyses by in situ hybridization and immunofluorescence indicated that miR-126a was expressed in lymphatic vessels, as well as in blood vessels. Time-lapse confocal imaging assay further revealed that knockdown of miR-126a blocked both lymphangiogenic sprouts budding from the posterior cardinal vein and lymphangioblasts extension along horizontal myoseptum. Bioinformatics analysis and in vivo report assay identified that miR-126a upregulated Cxcl12a by targeting its 5' untranslated region. Moreover, loss- and gain-of-function studies revealed that Cxcl12a signaling acted downstream of miR-126a during parachordal lymphangioblast extension, whereby Flt4 signaling acts as a cooperator of miR-126a, allowing it to modulate lymphangiogenic sprout formation. CONCLUSIONS: These findings demonstrate that miR-126a directs lymphatic endothelial cell sprouting and extension by interacting with Cxcl12a-mediated chemokine signaling and Vegfc-Flt4 signal axis. Our results suggest that these key regulators of lymphangiogenesis may be involved in lymphatic pathogenesis of cardiovascular diseases.

Forkhead containing transcription factor Albino controls tetrapyrrole-based body pigmentation in planarian.

Pigmentation processes occur from invertebrates to mammals. Owing to the complexity of the pigmentary system, in vivo animal models for pigmentation study are limited. Planarians are capable of regenerating any missing part including the dark-brown pigments, providing a promising model for pigmentation study. However, the molecular mechanism of planarian body pigmentation is poorly understood. We found in an RNA interference screen that a forkhead containing transcription factor, Albino, was required for pigmentation without affecting survival or other regeneration processes. In addition, the body color recovered after termination of Albino double stranded RNA feeding owing to the robust stem cell system. Further expression analysis revealed a spatial and temporal correlation between Albino and pigmentation process. Gene expression arrays revealed that the expression of three tetrapyrrole biosynthesis enzymes, ALAD, ALAS and PBGD, was impaired upon Albino RNA interference. RNA interference of PBGD led to a similar albinism phenotype caused by Albino RNA interference. Moreover, PBGD was specifically expressed in pigment cells and can serve as a pigment cell molecular marker. Our results revealed that Albino controls planarian body color pigmentation dominantly via regulating tetrapyrrole biogenesis. These results identified Albino as the key regulator of the tetrapyrrole-based planarian body pigmentation, suggesting a role of Albino during stem cell-pigment cell fate decision and provided new insights into porphyria pathogenesis.

Percutaneous Closure of Perimembranous Ventricular Septal Defect with Modified Double-disk Occluder: What Is the Outcome at 10-year Follow-up?

OBJECTIVE: Percutaneous closure of perimembranous ventricular septal defect is one of the greatest challenges in interventional cardiology. The long-term follow-up data are still limited. This report presents our experience in percutaneous closure of perimembranous ventricular septal defect with modified double-disk occluder. DESIGN: The study is a retrospective analysis of cases from the Changhai Hospital clinic database. SETTING: We reviewed the clinic database from December 2001 to December 2005. PATIENTS: We included 117 patients who underwent percutaneous closure of perimembranous ventricular septal defects. OUTCOME MEASURES: Procedural data and complications were assessed by an expert panel of cardiologists. RESULTS: Device implantation was successfully accomplished in 113 of a total 117 patients (96.6%). The mean age was 31.1 ± 12.5 years (range 2-56 years). The patients were followed for a period of 86-134 months. The diameter of defect was 2-15 mm (mean 4.9 ± 2.9 mm). The ventricular septal defect rim below the aortic valve was 1-5 mm. The mean diameter of device used was 6.9 ± 3.7 (range 4-24 mm). Four patients presented complete atrio-ventricular block within 1 week after the procedure and recovered within 3 weeks. No other patient encountered serious adverse events during the follow-up. CONCLUSIONS: Percutaneous closure of ventricular septal defect is safe and effective in most selected patients with modified double-disk occluder. Additional studies with larger cohorts and longer follow-up are needed to evaluate its safety.

Complete atrioventricular block after percutaneous device closure of perimembranous ventricular septal defect: A single-center experience on 1046 cases.

BACKGROUND: Complete atrioventricular block (cAVB) has been deemed a rare complication after transcatheter closure for ventricular septal defect (VSD). However, this serious event appears to be underrecognized and is worth being investigated further. OBJECTIVES: To determine the incidence and predisposing factors of cAVB associated with closure of VSD using a modified double-disk occluder (MDO). METHODS: From December 21, 2001 to December 31, 2014, 1046 patients with perimembranous ventricular septal defect underwent percutaneous closure using the MDO. Electrocardiography was evaluated before the procedure, within 1 week after the procedure, and then at 1, 3, 6, and 12 months and every year thereafter. Other baseline and procedural parameters were also evaluated and a comparison between patients requiring pacemakers and those not suffering from cAVB was done. RESULTS: cAVB occurred in 17 patients (1.63%) after the procedure. Of the 17 patients, 8 underwent permanent pacemaker (PPM) implantation. The cAVB occurred within 30 days after the procedure in 14 patients and after 1 year in 3 patients. In comparison patients aged ≤18 years, patients aged >18 years were more prone to cAVB (P = .025). Logistic regression revealed no significant parameter to predict later requirement for PPM. CONCLUSIONS: The incidence of cAVB after transcatheter closure of VSD was acceptable, as part of the cAVB population recovered after administration of corticosteroid and application of a temporary pacemaker. Late cAVB (>1 year) appears to make it more difficult to restore normal conduction block. Because of the recurrence of cAVB, life-long follow-up with periodic electrocardiography examination may be mandatory.

Transcatheter closure of medium and large congenital coronary artery fistula using wire-maintaining technique.

BACKGROUND: For medium and large coronary artery fistula (CAF), the initially selected device sometimes has to be exchanged by reconstruction of track wire loop due to the complexity of CAF. OBJECTIVES: We sought to evaluate the feasibility and safety of transcatheter closure of medium and large CAF by using the wire-maintaining technique (WMT). METHODS: A total of 18 patients aged 15-56 years with congenital CAF underwent percutaneous transcatheter closure by WMT between April 2006 and October 2012. The immediate and long-term outcomes were evaluated. RESULTS: Of the 18 patients (11 females), 16 (88%) underwent successful transcatheter closure of fistula using WMT. The CAFs originated from the right coronary artery (67%), the left circumflex coronary artery (28%), and the left anterior descending coronary artery (5%). The drainage sites were the right ventricle (56%), right atrium (22%), left ventricle (11%), and coronary sinus (11%). The mean diameter of fistulas was 9.5±1.71mm and mean size of the devices was 13.6±3.03mm. An angiogram following device deployment showed complete occlusion in 11 patients, mild residual shunt in 2 patients, and trivial residual shunt in 3 patients. One patient had transient ST-T wave changes, and one patient had hemolysis after the procedure. Follow-up ranged from 1 month to 54 months (median 39 months). Echocardiogram showed trivial residual shunt in 3 patients at 6-month follow-up and in 1 patient at 12-month follow-up. Coronary artery thrombosis was observed in 1 patient by multislice computed tomography at 12-month follow-up. CONCLUSION: For those patients with medium and large complex fistula, transcatheter closure of CAF can be performed by using the wire-maintaining technique.

Transcatheter aortic valve implantation assisted with microcatheter: a new method to avoid coronary artery obstruction.

BACKGROUND: Lack of fluoroscopic landmarks can make valve deployment more difficult in patients with absent aortic valve (AV) calcification. The goal of this article was to evaluate the feasibility and effectiveness of transcatheter implantation of a valved stent into the AV position of a goat, assisted with a microcatheter which provides accurate positioning of coronary artery ostia to help valved stent deployment. METHODS: The subjects were 10 healthy goats in this study. A microcatheter was introduced into the distal site of right coronary artery (RCA) through femoral artery sheath. A minimal thoracic surgery approach was used to access the apex of the heart. The apex of the left ventricle was punctured; a delivery catheter equipped with the valved stent was introduced over a stiff guidewire into the aorta arch. We could accurately locate the RCA ostia through the microcatheter placed in the RCA under fluoroscopy. After correct valve position was confirmed, the valved stent was implanted after rapid inflation of the balloon. The immediate outcome of the function of the valved stents was evaluated after implantation. RESULTS: All ten devices were successfully implanted into the AV position of the goats. Immediate observation after the procedure showed that the valved stents were in the desired position after implantation by angiography, echocardiogram. No obstruction of coronary artery ostia occurred, and no moderate to severe aortic regurgitation was observed. CONCLUSIONS: When the procedure of transcatheter implantation of a balloon-expandable valved stent into the AV position of goats is assisted with microcatheter positioning coronary artery ostia, the success rate of operation can be increased in those with noncalcified AV.

Transcatheter closure of atrial septal defects improves cardiac remodeling and function of adult patients with permanent atrial fibrillation.

BACKGROUND: Permanent atrial fibrillation (AF) is the most common form of dysrhythmia associated with atrial septal defects (ASDs) in patients older than 40 years. However, little is known about cardiac remodeling after transcatheter closure in patients with permanent AF. This study was designed to compare cardiac events and remodeling effects after transcatheter closure in such patients. METHODS: Clinical data of 289 adult patients older than 40 years who underwent ASD closure at our center were analyzed retrospectively. Of them, 63 patients with permanent AF were assigned to the case group, and the other 226 patients without permanent AF were assigned to the control group. Cardiac events and changes in left and right cardiac cavity dimensions before the procedure and 6 months after the procedure were compared between the two groups. RESULTS: Patients in the case group were significantly older than those in the control group. The right ventricular (RV) volume and right atrial (RA) volume were decreased significantly in both the groups during a median follow-up period of 6 months after closure (P < 0.001). The left atrial dimensions, left ventricular end-systolic dimensions, left ventricular end-diastolic dimensions and left ventricular ejection fraction showed no significant change before and after the procedure in both the groups. Changes of the RV volume and RA volume in the case group were significantly smaller than those in the control group (P = 0.005 and P < 0.001). The New York Heart Association cardiac function was improved in both the groups during the 6 months follow-up period. CONCLUSIONS: The transcatheter closure of ASD can improve the cardiac remodeling and cardiac function in patients with or without AF.

Immediate- and medium-term effects of simultaneous percutaneous corrections of secundum type atrial septal defect combined with pulmonary valve stenosis in local anesthesia and without transesophageal echocardiography guidance.

BACKGROUND: The feasibility and efficacy of simultaneous percutaneous treatment of secundum type atrial septal defect (ASD) combined with pulmonary valve stenosis (PS) have not been proved. OBJECTIVE: To evaluate the safety and efficacy on the clinical benefit of simultaneous percutaneous correction of these two pathologies under local anesthesia and without transesophageal echocardiography guidance. METHODS: Transpulmonary gradient, functional status, pulmonary regurgitation (PR), and tricuspid regurgitation (TR) were studied in 35 patients undergoing percutaneous balloon pulmonary valvuloplasty and ASD closure from March 2004 to July 2012. All patients were followed up until January 2013, an average of 39 months. RESULTS: According to color Doppler transthoracic echocardiography (TTE) before the intervention, the ASD defect size and transpulmonary gradient were 17±8.4 mm and 88±37.8 mmHg, respectively. Post-interventionally, the peak-to-peak transpulmonary gradient decreased from 77±37.6 mmHg to 20±16.2 mmHg (p<0.001) and the ASD occluder size was 23±10.5 mm. In all those patients, there was no residual shunt detected, and moderate and severe TR decreased from 45.7% (16/35) and 20% (7/35) to 8.6% (3/35) and 5.7% (2/35) before and after intervention detected by TTE, respectively. Eight patients had mild PR after procedure and two of them recovered at 6 months and no patient encountered severe adverse events at the latest follow-up. CONCLUSION: Simultaneous percutaneous corrections of ASD combined with PS are feasible, safe, and effective with satisfactory results.

Decreased tricuspid regurgitation following percutaneous closure of congenital perimembranous ventricular septal defect: immediate and 6-month echocardiographic assessment.

As a common concomitant performance and the most frequent complications of transcatheter perimembranous ventricular septal defect (VSD) closure, tricuspid regurgitation (TR) has rarely been concerned. From January 2008 to December 2012, a total of 70 patients (men: 33, women: 37; mean age: 30.0 ± 17.1 years) with at least mild TR before VSD closure were examined in 508 consecutive congenital perimembranous VSD patients to investigate the outcomes of TR. After VSD closure, the jet area decreased from 3.4 ± 2.5 to 1.2 ± 2.5 cm(2) (p < 0.001); however, no significant decrease was found in 3 patients (mean age 59.7 ± 2.5 years) with severe TR (12.0 ± 1.2 versus 11.2 ± 3.2 cm(2), p = 0.668). Compared to the early outcome after VSD closure, the jet area detected by TTE at 6-month follow-up had further decreased (1.2 ± 2.5 versus 0.9 ± 2.2 cm(2), p < 0.001). In 6 patients, a slight residual shunt was detected immediately after VSD closure and diminished in 3 patients at 6-month follow-up. The hemolysis occurred in one of these six patients and recovered after 3 days. In conclusion, functional TR was ameliorated after percutaneous VSD closure, although persistent abundant TR was common in patients with severe TR before procedure.

Balloon-expanding stent and delivery system for transcatheter aortic valve implantation: An animal study.

OBJECTIVE: To evaluate the feasibility and satefy of transcatheter aortic valve implantation in animals by using a new balloon-expanding valved stent. METHODS: The balloon-expandable stent is made from cobalt-based alloy material and designed with a tubular, slotted structure. Fresh bovine pericardium was treated, sutured and fixed on the balloon-expandable stent. Ten healthy sheep (five males and five females), weighing an average of (25.16 ± 1.83) kg, were selected to undergo transcatheter implantation of the valve stents. The function of the valve stent was evaluated by angiography, echocardiography, and histology six months after the procedure. RESULTS: Of the ten experimental sheep, two sheep died during the operation because the higher position of the artificial valve affected the opening of the coronary artery. We successfully implanted the aortic valve stent in other eight sheep; however, one sheep died of heart failure two weeks after the operation due to the lower position of the valve stent. The valve stents were implanted in the desired position in seven sheep. Ascending aortic angiographic and autoptic findings immediately after the operation confirmed the satisfactory location and function of the valved stent. Echocardiography, angiography, and histology at six postoperative months confirmed the satisfactory location and function of the valve stent. CONCLUSION: We successfully implanted our new valve stent as a replacement of native aortic valve via the transcatheter route with satisfactory outcome.