Efficacy and Safety of Left Atrial Appendage Occlusion in Mild Mitral Stenosis Patients with High Bleeding Risk.

Atrial fibrillation (AF) is highly prevalent in patients with mitral stenosis (MS), but the efficacy of left atrial appendage occlusion (LAAO) in these patients remains unclear.The aim of this study was to evaluate the efficacy and safety of LAAO in patients with MS complicated by AF at high risk of bleeding.We recruited patients from September 2015 to September 2018. We compared the 3-year outcomes of LAAO in 21 patients with AF complicated by MS and 42 sex- and age-matched patients with AF without MS.The MS group had more cases of peripheral arterial embolism (28.6% versus 2.4%, P = 0.004), more spontaneous echo contrast (47.6% versus 9.5%, P = 0.001), a larger LAA orifice diameter (P < 0.01), and a slower LAA flow (P < 0.05) than the Non-MS group. The mean size of the selected occluder device was bigger for patients with MS than for patients with Non-MS (29.2 ± 3.7 versus 26.9 ± 3.1 mm, P = 0.014). In the first 45 follow-up days, 2 (9.5%) patients with MS had device-related thrombi (DRT); one of them had transient ischemic attack 24 hours postoperatively. From 45 days to 6 months, one patient in each group had DRT. After 6 months, two patients in the Non-MS group still had residual leaks; one of them had a stroke, with a small DRT. The proportion of dual antiplatelet therapy was higher in the Non-MS group than in the MS group (33.3% versus 4.8%, P = 0.012), but this population had an increased bleeding risk.LAAO is relatively effective and safe for preventing embolic events in patients with MS complicated by AF, at high risk of bleeding.

LincRNA-Cox2 promotes pulmonary arterial hypertension by regulating the let-7a-mediated STAT3 signaling pathway.

It is well supported by the literature that the proliferation and migration of pulmonary arterial smooth muscle cells (PASMCs) are critical for the development of pulmonary arterial hypertension (PAH). Long intergenic noncoding RNA COX2 (lincRNA-COX2) is a regulator of inflammation and might be conducive to the progression of atherosclerosis, while its role in PAH is still unclear. This study was performed to explore the role and mechanism of lincRNA-COX2 in PASMCs proliferation and migration in an anaerobic environment. PASMCs were treated by hypoxia to construct PAH cell models. RT-PCR and western blot were recruited to evaluate the expression levels of lincRNA-COX2, miR-let-7a and STAT3. Their roles in proliferation and cell and migration of PASMCs were determined by the CCK-8 assay, wound-healing assay, and flow cytometry. In peripheral blood samples from PAH patients and hypoxic PASMCs, lincRNA-COX2 expression was enhanced. Silencing lincRNA-COX2 inhibited hypoxia-induced PASMCs proliferation by influencing the G2/M phase of the cell cycle. Meanwhile, lincRNA-COX2 regulated STAT3 through miR-let-7a and its effects on hypoxic PASMCs worked through miR-let-7a/STAT3 axis. To conclude, silencing lincRNA-COX2 attenuated the development of hypoxic PASMCs. LincRNA-COX2/miR-let-7a/STAT3 axis might be considered as a novel target to treat PAH.

Feasibility of Device Closure for Multiple Atrial Septal Defects With an Inferior Sinus Venosus Defect: Procedural Planning Using Three-Dimensional Printed Models.

BACKGROUND: Multiple atrial septal defects (ASD) with an inferior sinus venosus defect (SVD) have always been considered to be contraindications for interventional therapy. On the basis of early experience using a patent ductus arteriosus (PDA) occluder for interventional treatment for inferior ASD, this study investigated the feasibility of transcatheter closure of multiple ASDs with an inferior SVD under the guidance of three-dimensional (3D) printed heart models. METHODS: Between August 2016 and February 2017, five patients who were diagnosed with multiple ASDs with an inferior SVD at the First Affiliated Hospital of Xi'an Jiaotong University underwent cardiac computed tomography (CT) scans and three-dimensional (3D) echocardiography to generate heart disease models by a 3D printing technique. The best occlusion program was determined through a simulated closure on the model. Percutaneous device closure of multiple ASDs with an inferior SVD was performed following the predetermined program, guided only by fluoroscopy. Follow-up included electrocardiography, transthoracic echocardiography, and transoesophageal echocardiography. RESULTS: Three-dimensional (3D) printed models for all five patients were produced successfully. Four (4) patients had a secundum ASD with an inferior sinus venosus ASD, and one patient had a patent foramen ovale (PFO) with an inferior sinus venosus ASD. All patients were successfully treated with interventional therapy. Inferior sinus venosus ASD was percutaneously closed using the PDA occluder, and the additional secundum ASD or PFO in each patient was percutaneously closed using an ASD or PFO occluder at the same time. There was no device embolisation, procedure-related death or pericardial tamponade. During the 1-year follow-up, a minor residual shunt was detected in one patient. CONCLUSION: The use of 3D printed ASD models provides a useful reference for transcatheter device closure of multiple ASD with an inferior SVD. This approach can provide a new treatment strategy for inferior sinus venosus ASD, which has been considered a contraindication for interventional therapy. However, long-term follow-up in a large number of patients is still warranted.

Multidisciplinary assessment of PFO with substantial right-to-left shunting and medium-term follow-up after PFO device closure: A single-center experience.

OBJECTIVES: To describe the multidisciplinary assessment of patent foramen ovale (PFO) with substantial right-to-left shunting (RLS) and medium-term follow-up after PFO closure for stroke or transient ischemic attack (TIA). BACKGROUND: PFO closure is a therapeutic option to prevent recurrent ischemic event in patients with cryptogenic stroke and TIA. The apparent lack of benefit seen in previous studies was in part due to the inclusion of patients with alternate mechanisms of stroke/TIA. However, the long-term follow-up results of RESPECT trial confirmed that PFO closure could reduce the recurrence rate of stroke compared to medical therapy. The obvious difference between RESPECT and the other studies is that RESPECT recruited more relevant patients with substantial RLS. METHODS: From May 2013 to October 2015, all subjects diagnosed as cryptogenic stroke or TIA with substantial RLS who underwent PFO closure at our institution were included. All patients underwent multidisciplinary assessment to exclude stroke/TIA with definite etiology. Baseline characteristics, clinical manifestations, procedural, and follow-up data were reviewed. RESULTS: A total of 219 consecutive patients with substantial RLS undergoing PFO closure were identified. There were no procedure-related deaths, strokes, or TIA. Mean follow-up was 2.0 ± 0.7 years. Early residual shunting was visible in 9 patients (4.1%); however, during follow-up, only 3 patients (1.4%) had residual RLS detected by contrast transthoracic echocardiography (cTTE). The annual risk of recurrent ischemic stroke or TIA was 0.457%. CONCLUSIONS: PFO closure can be performed safely and effectively in patients with cryptogenic stroke or TIA. In selected patients with substantial RLS, following appropriate multidisciplinary assessment, excellent results with low incidence of recurrent events may be achieved.

A Case Report on Pulmonary Arteriovenous Fistula with Recurrent Cerebral Infarction.

Patent foramen ovale (PFO) and pulmonary arteriovenous fistula (PAVF) have been both proposed as a mechanism for cerebral infarction. However, there are only a few reports on how to distinguish the role of the two factors in cerebral infarction.

CTRP9 Ameliorates Pulmonary Arterial Hypertension Through Attenuating Inflammation and Improving Endothelial Cell Survival and Function.

Endothelial dysfunction and inflammation are believed to be 2 primary instigators of pulmonary arterial hypertension (PH). C1q/TNF-related protein 9 (CTRP9) plays important roles in anti-inflammation and improvement of epithelial function. However, the role of CTRP9 in the progression of PH remains still unclear. In this study, the role and mechanism of CTRP9 in the PH progression were explored. First, serum CTRP9 contents and CTRP9 mRNA expression in the pulmonary artery epithelial cells from patients with PH were detected. Our data on enzyme-linked immunosorbent assay and real-time quantitative Polymerase Chain Reaction showed that CTRP9 mRNA and protein content were markedly downregulated in the patients with PH. Then the pcDNA-CTRP9 expression vector or CTRP9 siRNA was transfected into the primary pulmonary artery epithelial cells from the patients with PH in vitro. CTRP9 overexpression significantly improved endothelial NOS protein expression and reduced the secretion of endothelin-1 (ET-1) and matrix metalloproteinase-2 (MMP-2), whereas knockdown of CTRP9 sharply reduced eNOS protein expression and promoted the secretion of ET-1 and MMP-2 in the cultured human epithelial cells. Moreover, the levels of phosphatidylinositol 3-kinase (PI3K) and pAkt were reduced in the epithelial cells and CTRP9 overexpression activated the PI3K/Akt pathway. CTRP9 could inhibit cell apoptosis and eNOS expression reduction in the cells pretreated with the PI3K/Akt inhibitor LY294002 and resist LY294002-induced ET-1 and MMP-2 secretion. Finally, to verify the role of CTRP9 in the progression of PH in vivo, the pcDNA-CTRP9 expression vector or CTRP9 siRNA was intravenously injected into rats with PH. Pulmonary arterial pressures of the rats were notably reduced by the pcDNA-CTRP9 injection and elevated by the CTRP9 siRNA injection. In conclusion, CTRP9 ameliorated PH by attenuating inflammation and improving endothelial cell survival and function.

miR-223 Inhibits Lipid Deposition and Inflammation by Suppressing Toll-Like Receptor 4 Signaling in Macrophages.

Atherosclerosis and its complications rank as the leading cause of death with the hallmarks of lipid deposition and inflammatory response. MicroRNAs (miRNAs) have recently garnered increasing interests in cardiovascular disease. In this study, we investigated the function of miR-223 and the underlying mechanism in atherosclerosis. In the atherosclerotic ApoE-/- mice models, an obvious increase of miR-223 was observed in aortic atherosclerotic lesions. In lipopolysaccharide (LPS) activated macrophages, its expression was decreased. The miR-223 overexpression significantly attenuated macrophage foam cell formation, lipid accumulation and pro-inflammatory cytokine production, which were reversed by anti-miR-223 inhibitor transfection. Mechanism assay corroborated that miR-223 negatively regulated the activation of the toll-like receptor 4 (TLR4)-nuclear factor-κB (NF-κB) pathway. Pretreatment with a specific inhibitor of NF-κB (pyrrolidinedithiocarbamate, PDTC) strikingly abrogated miR-223 silence-induced lipid deposition and inflammatory cytokine production. Furthermore, PI3K/AKT was activated by miR-223 up-regulation. Pretreatment with PI3K/AKT inhibitor LY294002 strikingly ameliorated the inhibitory effects of miR-223 on the activation of TLR4 and p65, concomitant with the increase in lipid deposition and inflammatory cytokine production. Together, these data indicate that miR-223 up-regulation might abrogate the development of atherosclerosis by blocking TLR4 signaling through activation of the PI3K/AKT pathway, and provides a promising therapeutic avenue for the treatment of atherosclerosis.

[The effect of oversized occluder on endothelialization after percutaneous closure of experimental atrial septal defect in dogs].

OBJECTIVE: To observe the effect of oversized occluder on endothelialization post percutaneous closure of experimental atrial septal defect (ASD) in dogs. METHODS: ASD was established with the help of transthoracic echocardiography in 18 dogs. ASD size was (6.0 ± 0.2) mm. Dogs were randomly divided into normal size group (implanted with 8 mm occlude, n = 9) and oversized group (implanted with 12 mm occluder, n = 9). Dogs were randomly killed at 3, 6 and 14 months after percutaneous closure. The endothelialization process on device surface was observed by scanning electron microscope. RESULTS: Four animals died around 1 month post procedure. Microscopic sections from normal group showed nearly complete endothelialization at 3 months after device implantation and complete endothelialization at 6 and 14 months after device implantation. While microscopic sections showed lack of endothelialization at 3 months post implantation, nearly endothelialization at 6 months, and complete endothelialization at 14 months after device implantation in oversized group. CONCLUSION: Incomplete endothelialization of occluder surface is observed at 6 months after implantation of an oversized ASD occluder device in this model.

A Prospective, Single-Center, Phase I Clinical Trial to Evaluate the Value of Transesophageal Echocardiography in the Closure of Patent Foramen Ovale With a Novel Biodegradable Occluder.

Objective: Traditional metal alloy occluders for the closure of patent foramen ovale (PFO) may be associated with some potential complications, and may restrict the trans-septal access to the left atrium for future treatment of left-sided heart disease. Increasing attention has been paid to novel biodegradable occluders (NBOs) to achieve PFO closure. We aimed to evaluate the role of transesophageal echocardiography (TEE) in the diagnostic and anatomical evaluation of PFO, as well as in the Post-procedural assessment after transcatheter closure with a NBO. Methods: We conducted a prospective, single-center clinical study of 44 patients who were diagnosed with PFO by contrast transthoracic echocardiography (c-TTE) and TEE from June 2019 to June 2020. All patients underwent PFO occlusion with NBO under TTE guidance. Follow-up was performed at 2 days and 3 months after the procedure with TTE, and at 6 months and 1 year after the procedure with c-TTE, TTE, and TEE. Results: Interventional treatment was successfully performed in all patients. The left and right sides of the occluder device disc were significantly reduced at 3, 6, and 12 months compared to 2 days after the procedure (all P < 0.01), and decreased gradually. The thickness was significantly reduced at 12 months compared to the first three time points (all P < 0.01). Thrombus was found on the surface of the occluder device in three patients (6.4%) at 3 and 6 months after occlusion. At 6 months after procedure, there were 3 (6.8%) cases of extensive residual right-to-left shunt (RLS), 2 (4.5%) cases of moderate shunt, and 7 (15.9%) cases of small shunts. One year after procedure, 2 (4.5%) cases had a extensive residual shunt, 6 (13.6%) cases of small shunts were confirmed to originate from pulmonary veins by TEE, and the PFO-RLS occlusion rate reached 95.5%. Conclusion: This study demonstrates the feasibility, safety, and effectiveness of NBO for the closure of PFO in humans, with a high rate of complete shunt closure. Accurate TEE assessment of the PFO anatomy before closure with NBO is important to ensure that the procedure remains safe and effective. Furthermore, TEE plays a crucial role in the Post-procedure follow-up.

Application of Transesophageal Echocardiography in Amplatzer Atrial Septal Defect Occluder for Percutaneous Closure of Large Patent Foramen Ovale.

Objective: The Amplatzer patent foramen ovale (PFO) occluder is the most commonly used device for percutaneous closure of a large PFO. However, its use may predispose the patient to postoperative residual shunting. To reduce the incidence of residual shunting, we investigated the safety and effectiveness of the Amplatzer atrial septal defect (ASD) occluder for percutaneous closure of a large PFO measured by transesophageal echocardiography (TEE) and evaluated the value of TEE in this procedure. Methods: Overall, 118 patients who were diagnosed with a large PFO (all with a ≥ 2 mm left atrial side height after the Valsalva maneuver (VM) excluding those with a small ASD) using contrast transthoracic echocardiography (c-TTE) and TEE underwent closure under TEE guidance at The First Affiliated Hospital of Xi'an Jiaotong University. An ASD device was used in 48 patients (group I) and a PFO device in 70 (group II). After the procedure, we verified the safety and efficacy of different devices using c-TTE, TTE, and TEE. Results: In both groups, the preoperative TEE results showed a significantly increased left height of the PFO after VM compared with that at rest (all P < 0.01). Compared with the left height of the PFO measured using TEE after VM, the PFO-stretch diameter (SD) measured by TEE after the delivery sheath passed the PFO was higher (all P < 0.01). We selected the ASD occluder size according to this PFO-SD. In group II, most patients underwent the implantation of the larger PFO devices. Interventional treatment was successfully performed on all patients. The effective occlusion rate in group I at 12 months after the procedure was significantly higher than that in group II (93.7% vs. 78.6%, P < 0.05). The TEE results showed that 18 patients with a medium and large residual shunt at 12 months after the procedure exhibited an intradisc tunnel-like shunt. Conclusion: The Amplatzer ASD device and Amplatzer PFO device are safe for large PFO closure, but the Amplatzer ASD device has a higher effective occlusion rate. TEE plays a crucial role in the use of the Amplatzer ASD occluder for percutaneous closure of a large PFO.

Adults with current asthma but not former asthma have higher all-cause and cardiovascular mortality: a population-based prospective cohort study.

Higher mortality in asthmatics has been shown previously. However, evidence on different asthma phenotypes on long-term mortality risk is limited. The aim was to evaluate the impact of asthma phenotypes on mortality in general population. Data from the National Health and Nutrition Examination Survey from 2001-2002 to 2013-2014 linked mortality files through December 31, 2015, were used (N = 37,015). Cox proportional hazards regression was used to estimate the risk of all-cause and cause-specific mortality adjusting for sociodemographic characteristics, smoking, body mass index, and chronic conditions. During the mean follow-up time of 7.5 years, 4326 participants died from a variety of causes. Current asthma, but not former asthma was associated with increased all-cause mortality (current asthma: HR = 1.37; 95% CI 1.20-1.58; Former asthma: HR = 0.93; 95% CI 0.73-1.18); as well as mortality from cardiovascular disease (HRCurrent = 1.41; 95% CI 1.08-1.85) and chronic lower respiratory diseases (HRCurrent = 3.17; 95% CI 1.96-5.14). In addition, we found that the HR for cardiovascular disease (CVD) mortality was slightly greater in people with childhood-onset asthma than those with adult-onset asthma. The HR for chronic lower respiratory diseases (CLRD) mortality was greater in people with adult-onset asthma than those with childhood-onset asthma. However, the differences were not statistically significant. Our study suggested that current asthma but not former asthma was associated with increased all-cause, CLRD and CVD mortality. Future well-designed studies with larger sample are required to demonstrate the association and clarify the potential mechanisms involved.

Efficacy of patent foramen ovale closure for treating migraine: a prospective follow-up study.

This study aims to evaluate the potential of percutaneous patent foramen ovale (PFO) closure to improve the headache in patients with migraine and PFO, and discuss the difference between the randomized controlled trials (RCTs) and the single-center studies. Patients of migraine with a large shunt of PFO, who experienced ≥2 headache attacks per month and failed ≥2 categories of standardized medication, underwent PFO closure in First Affiliated Hospital of Xi'an Jiao Tong University. The clinical outcomes, including frequency and duration of headache attacks, Headache Impact Test (HIT-6) score, and Visual Analogue Scale (VAS) score, were evaluated at 3, 6, and 12 months of follow-up after the PFO closure. The different efficacies of the clinical outcomes between patients with and without aura as well as different grades of PFO were also evaluated, respectively. 134 patients with migraine (39 male and 95 female) with PFO were enrolled, whose average age was 39.21±11.37 years. After PFO closure, there was a significant reduction in frequency and duration of headache attacks, HIT-6 score, and VAS score at 3, 6, and 12 months' follow-up (p<0.001). Migraine was completely relieved in 54 (40.30%) patients during 12 months' follow-up. The frequency of migraine was reduced by >50% in 44 (32.84%) patients at 3 months' follow-up and increased to 48 (35.82%) at 12 months' follow-up. 31.03% patients remained residual shunt after 6 months of closure with varying improvements of headache. This study confirmed that PFO closure can effectively reduce frequency and duration of migraine and improve quality of life, but the definitive indications and long-term effect still need further research.

Importance of Persistent Right-to-Left Shunt After Patent Foramen Ovale Closure in Cryptogenic Stroke Patients.

Percutaneous closure of patent foramen ovale (PFO) is widely performed to prevent recurrent stroke or transient ischemic attack in patients with cryptogenic stroke. However, the influence of different degrees of right-to-left shunting (RLS) has rarely been reported. We retrospectively evaluated the cases of 268 patients with cryptogenic stroke who underwent PFO closure at our hospital from April 2012 through April 2015. In accordance with RLS severity, we divided the patients into 2 groups: persistent RLS during normal breathing and the Valsalva maneuver (n=112) and RLS only during the Valsalva maneuver (n=156). Baseline characteristics, morphologic features, and procedural and follow-up data were reviewed. The primary endpoint was stroke or transient ischemic attack. More patients in the persistent group had multiple or bilateral ischemic lesions, as well as a larger median PFO diameter (2.5 mm [range, 1.8-3.9 mm]) than did patients in the Valsalva maneuver group (1.3 mm [range, 0.9-1.9 mm]) (P <0.001). Atrial septal aneurysm was more frequent in the persistent group: 25 patients (22.3%) compared with 18 (11.5%) (P=0.018). Three patients in the persistent group had residual shunting. The annual risk of recurrent ischemic stroke was similar between groups: 0.298% (persistent) and 0.214% (Valsalva maneuver). Our findings suggest that patients with persistent RLS have more numerous severe ischemic lesions, larger PFOs, and a higher incidence of atrial septal aneurysm than do those without. Although our persistent group had a greater risk of residual shunting after PFO closure, recurrence of ischemic events did not differ significantly from that in the Valsalva maneuver group.

[Clinical observation of heparin-induced thrombocytopenia].

OBJECTIVE: To explore the treatment of heparin-induced thrombocytopenia (HIT) in venous thromboembolism. METHODS: A total of 202 patients with venous thromboembolism without anticoagulation contraindications were enrolled. All of them were treated with low molecular weight heparin (LMWH) and/or unfractionated heparin (UFH). The peripheral blood cells were examined regularly. RESULTS: HIT occurred in 6 patients. And argatroban was used to treat HIT. The overall incidence rate of HIT in this study was 2.97%. The time of occurrence of HIT was about Days 3 - 9 after using heparin. The platelet recovered to the basic level at Days 3 - 7 after withdrawing heparin and initiating argatroban. CONCLUSION: The count of platelet should be measured in the patients receiving regular LMWH and/or UFH therapy. And the above regimen should be discontinued timely when the platelet count declined progressively by over 50%. Argatroban was effective.

Safety of an improved patent ductus arteriosus occluder for transcatheter closure of perimembranous ventricular septal defects with abnormally attached tricuspid chordae tendineae.

BACKGROUND: The off-label use of various devices has been reported for the transcatheter closure of perimembranous ventricular septal defects (PmVSD) because of serious complications, such as heart block and tricuspid regurgitation (TR), associated with conventional ventricular septal defect devices. However, whether certain defects such as PmVSD with abnormally attached tricuspid are fit for interventional treatment is still disputable. AIM: To explore the feasibility and safety of transcatheter closure of PmVSD with abnormally attached tricuspid chordae tendineae using an improved patent ductus arteriosus (PDA) occluder. METHODS: We retrospectively analyzed 20 patients diagnosed with PmVSD with abnormally attached tricuspid chordae tendineae who underwent interventional treatment using an improved PDA occluder at our center from January 2012 to January 2016. Baseline characteristics and procedural and follow-up data were analyzed. RESULTS: All 20 patients achieved procedure success. No heart block occurred during the operation. One patient had a transient complete right bundle branch block within 48 h post-procedure and reverted to normal rhythm after intravenous injections of dexamethasone for 3 d. For all 20 patients, no residual shunt was observed by transthoracic echocardiography post-procedure. During the average follow-up period of 2.4 years, no severe TR was observed. CONCLUSION: Using of the improved PDA occluder for the transcatheter closure of PmVSD with abnormally attached tricuspid chordae tendineae is a safe and promising treatment option. However, long-term follow-up in a large group of patients is still warranted.

Clinical relevance of atrial septal aneurysm and patent foramen ovale with migraine.

AIM: To test the potential association between atrial septal aneurysm (ASA) and migraine in patent foramen ovale (PFO) closure patients through an observational, single-center, case-controlled study. METHODS: We studied a total of 450 migraineurs who had right-to-left shunts and underwent PFO closure in a retrospective single-center non-randomized registry from February 2012 to October 2016 on the condition that they were aged 18-45 years old. Migraine was diagnosed according to the International Classification of Headache Disorders, 3rd edition and evaluated using the Headache Impact Test-6 (HIT-6). All patients underwent preoperative transesophageal echocardiography, contrast transthoracic echocardiography, and computed tomography or magnetic resonance imaging examinations, with subsequent fluoroscopy-guided PFO closure. Based on whether they have ASA or not, the patients were divided into two groups: A (PFO with ASA, n = 80) and B (PFO without ASA, n = 370). Baseline characteristics and procedural and follow-up data were reviewed. RESULTS: Compared to group B, group A had an increased frequency of ischemic lesions (11.3% vs 6.2%, P = 0.038) and migraine with aura (32.5% vs 21.1%, P = 0.040). The PFO size was significantly larger in group A (P = 0.007). There was no significant difference in HIT-6 scores between the two groups before and at the one-year follow-up after the PFO closure [61 (9) vs 63 (9), P = 0.227; 36 (13) vs 36 (10), P = 0.706]. CONCLUSION: Despite its small sample size, our study suggests that the prevalence of ASA in PFO with migraine patients is associated with ischemic stroke, larger PFO size, and migraine with aura.

Transcatheter Closure of Perimembranous Ventricular Septal Defects in Children using a Wire-Drifting Technique.

OBJECTIVE: Explore the feasibility and safety of transcatheter closure of perimembranous ventricular septal defects using a wire-drifting technique (WT) in children. METHODS: We retrospectively analyzed 121 pediatric patients diagnosed with perimembranous ventricular septal defects who underwent interventional treatment at the First Affiliated Hospital of Xi'an Jiaotong University from Dec 2011 to Dec 2014. Based on the method used for arteriovenous loop establishment during the procedure, the patients were divided into a conventional technique (CT) group and a WT group. RESULTS: In total, 51 of the 53 patients (96.2%) in the CT group and 66 of the 68 patients (97.1%) in the WT group achieved procedural success, with no significant difference between the two groups (p>0.05). The CT group showed a nonsignificantly higher one-time success rate of arteriovenous loop establishment (94.3% vs. 91.2%, p>0.05). The procedure time was 46.0 (14.0) min and 46.5 (10.0) min in the CT and WT groups, respectively. The CT procedure was discontinued in the 2 cases (3.8%) of intraprocedural atrioventricular block in the CT group. In the one case (1.9%) of postprocedural atrioventricular block in the CT group, a permanent pacemaker was implanted to resolve third-degree atrioventricular block three months after the procedure. In the WT group, no cases of intraprocedural atrioventricular block occurred, and one case (1.5%) of postprocedural atrioventricular block occurred. In this case, intravenous dexamethasone injection for three days returned the sinus rhythm to normal. Aggravated mild to moderate tricuspid regurgitation was observed in 2 patients (3.8%) in the CT group during the 2-year follow-up period; aggravated tricuspid regurgitation was not observed in the WT group. During the 2-year follow-up period, there was no evidence of residual shunting in either group. CONCLUSION: Transcatheter closure of perimembranous ventricular septal defects with the WT is safe and effective in children.

Let-7a-transfected mesenchymal stem cells ameliorate monocrotaline-induced pulmonary hypertension by suppressing pulmonary artery smooth muscle cell growth through STAT3-BMPR2 signaling.

BACKGROUND: Cell-based gene therapy has become a subject of interest for the treatment of pulmonary arterial hypertension (PAH), a devastating disease characterized by pulmonary artery smooth muscle cell (PASMC) hyperplasia. Mesenchymal stem cells (MSCs) have been recently acknowledged as a potential cell vector for gene therapy. Here, we investigated the effect of MSC-based let-7a for PAH. METHODS: After isolation and identification of MSCs from rat bone marrow, cells were infected with recombinant adenovirus vector Ad-let-7a. Lewis rats were subcutaneously injected with monocrotaline (MCT) to induce PAH, followed by the administration of MSCs, MSCs-NC (miR-control), or MSC-let-7a, respectively. Then, right ventricular systolic pressure (RVSP), right ventricular hypertrophy, and pulmonary vascular remodeling were evaluated. Rat pulmonary artery smooth muscle cells (rPASMCs) under hypoxia were co-cultured with MSCs or MSC-let-7a. Cell proliferation and apoptosis were separately determined by 3H thymidine incorporation and flow cytometry analysis. The underlying mechanism was also investigated. RESULTS: MSC transplantation enhanced let-7a levels in MCT-induced PAH rats. After injection with MSC-let-7a, RVSP, right ventricular hypertrophy, and pulmonary vascular remodeling were notably ameliorated, indicating a protective effect of MSC-let-7a against PAH. When co-cultured with MSC-let-7a, hypoxia-triggered PASMC proliferation was obviously attenuated, concomitant with the decrease in cell proliferation-associated proteins. Simultaneously, the resistance of PASMCs to apoptosis was remarkably abrogated by MSC-let-7a administration. A mechanism assay revealed that MSC-let-7a restrained the activation of signal transducers and activators of transcription 3 (STAT3) and increased its downstream bone morphogenetic protein receptor 2 (BMPR2) expression. Importantly, preconditioning with BMPR2 siRNA dramatically abated the suppressive effects of MSC-let-7a on PASMC proliferation and apoptosis resistance. CONCLUSIONS: Collectively, this study suggests that MSCs modified with let-7a may ameliorate the progression of PAH by inhibiting PASMC growth through the STAT3-BMPR2 signaling, supporting a promising therapeutic strategy for PAH patients.

Comparison of Different Contrast Agents in Detecting Cardiac Right-to-Left Shunt in Patients with a Patent Foramen Ovale during Contrast-Transthoracic Echocardiography.

The aim of this study is to evaluate the ability of two different contrast agents to detect cardiac right-to-left shunting in patients with a patent foramen ovale during contrast transthoracic echocardiography and transesophageal echocardiography. Eighty-four patients who had migraines or experienced cryptogenic stroke were prospectively enrolled. Contrast echocardiography of the right portion of the heart was performed using an injection of either (i) 8 ml of agitated saline, 1 ml of blood, and 1 ml of air (ASB) or (ii) 4 ml of vitamin B6 and 6 ml of sodium bicarbonate solution (VSBS). All patients underwent contrast echocardiography with different contrast agents successively before undergoing transesophageal echocardiography. The diagnostic sensitivity of VSBS and ASB for cardiac shunting diagnosis was 94.23% and 78.85%, respectively. The diagnostic sensitivity in the VSBS group was significantly higher than that in the ASB group (χ2 = 5.283, P = 0.022). The observed semiquantitative shunt grading suggests that the positive rate in the VSBS group was higher than that in the ASB group (Z = -1.998, P = 0.046). The use of vitamin B6 and sodium bicarbonate solution as a TTE contrast agent yielded a high sensitivity compared with ASB. However, further trials with large sample size are required to confirm this finding.

Safety and efficacy of Cardi-O-fix occluder for percutaneous closure of a patent foramen ovale: A single-center prospective study.

BACKGROUND: Amplatzer occluder and Cardio-O-fix occluder are currently used in percutaneous closure of patent foramen ovale. However, there is still a lack of relevant reports comparison the differences between them. The aim of this study was to evaluate the short-term and mid-term safety and efficacy of the Cardi-O-fix occluder in preventing recurrent cerebrovascular events in patients with a patent foramen ovale (PFO). METHODS: We enrolled 246 patients (105 men) with a PFO from May 30, 2013 to March 30, 2015 in this single-center prospective study. All patients were treated by PFO interventional closure, with the Cardi-O-fix PFO occluder being used in 180 patients and the Amplatzer PFO occluder being utilized in the remaining 66 patients. After the procedure, we verified the safety and efficacy of different devices using contrast transthoracic echocardiography. RESULTS: Neither recurrent stroke nor death was encountered during the follow-up of 12 months. Transient ischemic attack (TIA) was noted in 2 patients (1.1%) in the Cardi-O-fix PFO occluder group, and 1 patient suffered from TIA (1.5%) in the Amplatzer PFO occluder group. Among them, only 1 patient exhibited a small right to left shunt (RLS). There was no statistical difference in recurrent cerebral ischemic events. Three cases of paroxysmal atrial fibrillation were observed in the Cardi-O-fix PFO occluder group. One reverted spontaneously to sinus rhythm and the other 2 cases had pharmacologic conversion to sinus rhythm. One case of paroxysmal atrial fibrillation occurred in the Amplatzer group, which underwent pharmacologic conversion to sinus rhythm. There was no significant difference between the 2 groups regarding incidence of arrhythmia. No occluder translocation, erosion, pericardial effusion, and puncture site bleeding were observed in the 2 groups within 12 months of follow-up. The complete closure rates of the Cardi-O-fix and Amplatzer PFO occluder devices at the 12 months after the procedure were 73.9% and 63.6%, respectively, and the effective closure rates were 90.6% and 86.4%, respectively. There was no statistically significant difference in the complete closure rate and effective occlusion rate (P > 0.05) between the devices. CONCLUSIONS: There was no significant difference in the short- and mid-term efficacy and safety between the Cardi-O-fix PFO occluder and Amplatzer PFO occluder. The efficacy and safety of the Cardi-O-fix occluder were comparable to those of the Amplatzer PFO occluder.