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Increasing evidence has shown that circular RNAs (circRNAs) participate in the process of cardiac remodeling. CircRNA circ_0036176 originating from the back-splicing of exon 2 to exon4 of myosin IXA (Myo9a) gene was shown to be increased in the myocardium of patients with heart failure (HF) and riched in exosomes from human AC16 cardiomyocytes with overexpression of circ_0036176. Proliferation activity was inhibited in mCFs subjected to exosomal circ_0036176 treatment and in mCFs with overexpression of circ_0036176. Interestingly, circ_0036176 contains an IRES element and an ORF of 627 nt encoding a 208-amino acid protein (termed as Myo9a-208). Myo9a-208 was shown to mediate the inhibitory effect of circ_0036176 on CFs proliferation, and miR-218-5p could inhibit Myo9a-208 expression by binding to circ_0036176, resulting in abolishing the effect of circ_0036176 on inactivating cyclin/Rb signal and suppressing CFs proliferation. Our findings suggest that circ_0036176 inhibits mCFs proliferation by translating Myo9a-208 protein to suppress cyclin/Rb pathway. [ABSTRACT FROM AUTHOR]

Increasing evidence has shown that microRNAs (miRNAs) participate in cardiac fibrosis. We aimed to elucidate the effect of miRNA miR-25-3p on cardiac fibrosis. MiRNA microarray was used to profile miRNAs in the myocardium of angiotensin-II (Ang-II)-infused mice. Effect of miR-25-3p on expression of fibrosis-related genes, including Col1a1, Col3a1, and Acta2, was investigated both in vitro and in vivo. MiR-25-3p was shown increased in the myocardium of Ang-II-infused mice and patients with heart failure. MiR-25-3p enhanced fibrosis-related gene expression in mouse cardiac fibroblasts (mCFs) and in the myocardium of Ang-II-infused mice. Dickkopf 3 (Dkk3) was identified as a target gene of miR-25-3p, and Dkk3 could ameliorate Smad3 activation and fibrosis-related gene expression via enhancing Smad7 expression in mCFs. Additionally, NF-κB signal was proven to mediate upregulation of miR-25-3p in cardiac fibrosis. Our findings suggest that miR-25-3p enhances cardiac fibrosis by suppressing Dkk3 to activate Smad3 and fibrosis-related gene expression. [ABSTRACT FROM AUTHOR]

Aims Circular RNAs (circRNAs) are involved in gene regulation in a variety of physiological and pathological processes. The present study aimed to investigate the effect of circRNA_000203 on cardiac hypertrophy and the potential mechanisms involved. Methods and results CircRNA_000203 was found to be up-regulated in the myocardium of Ang-II-infused mice and in the cytoplasma of Ang-II-treated neonatal mouse ventricular cardiomyocytes (NMVCs). Enforced expression of circRNA_000203 enhances cell size and expression of atrial natriuretic peptide and β-myosin heavy chain in NMVCs. In vivo , heart function was impaired and cardiac hypertrophy was aggravated in Ang-II-infused myocardium-specific circRNA_000203 transgenic mice (Tg-circ203). Mechanistically, we found that circRNA_000203 could specifically sponge miR-26b-5p, -140-3p in NMVCs. Further, dual-luciferase reporter assay showed that miR-26b-5p, -140-3p could interact with 3′-UTRs of Gata4 gene, and circRNA_000203 could block the above interactions. In addition, Gata4 expression is transcriptionally inhibited by miR-26b-5p, -140-3p mimic in NMVCs but enhanced by over-expression of circRNA_000203 in vitro and in vivo. Functionally, miR-26b-5p, -140-3p, and Gata4 siRNA, could reverse the hypertrophic growth in Ang-II-induced NMVCs, as well as eliminate the pro-hypertrophic effect of circRNA_000203 in NMVCs. Furthermore, we demonstrated that NF-κB signalling mediates the up-regulation of circRNA_000203 in NMVCs exposed to Ang-II treatment. Conclusions Our data demonstrated that circRNA_000203 exacerbates cardiac hypertrophy via suppressing miR-26b-5p and miR-140-3p leading to enhanced Gata4 levels. [ABSTRACT FROM AUTHOR]

Objective To determine the risk factors for thromboembolism in lower risk patients with non-valvular atrial fibrillation (AF) and low CHA2DS2-VASc scores, which remain undefined. Methods We retrospectively analyzed the baseline clinical characteristics, routine laboratory parameters, and echocardiographic measurements of 705 patients (71.1% male; mean age: 52.10 ± 9.64 years) with low CHA2DS2- VASc score (0 or 1; 1 point for female sex) out of 1346 consecutive patients with non-valvular AF who underwent transesophageal echocardiography (TEE) at Guangdong Cardiovascular Institute between January 2013 and December 2015. Results Patients with left atrial thrombus (LAT) or spontaneous echo contrast (SEC) on TEE (24/705, 4%) showed a higher incidence rate of vascular disease (54.2% vs. 32.9%, P = 0.045) and non-paroxysmal AF (79.2% vs. 29.4%, P < 0.001), larger left atrial diameter (43.08 ± 4.59 vs. 36.02 ± 5.53 mm, P < 0.001), and lower left ventricular ejection fraction (58.23 ± 8.82% vs. 64.15 ± 7.14%, P < 0.001) than those without. Multivariate logistic regression analysis identified left atrial diameter [odds ratio (OR) = 1.171, 95% confidence interval (CI): 1.084-1.265, P < 0.001] and non-paroxysmal AF (OR = 3.766, 95% CI: 1.282-11.061, P = 0.016) as independent risk factors for LAT/SEC. In ROC curve analysis, a left atrial dimeter cutoff of 37.5 mm yielded 95.0% sensitivity and 62.7% specificity (AUC: 0.847, P < 0.0001, 95% CI: 0.793-0.914). Conclusion In patients with non-valvular AF with low CHA2DS2-VASc score, the presence of LAT or SEC was associated with left atrial enlargement, which had moderate predictive value, and non-paroxysmal AF. [ABSTRACT FROM AUTHOR]

Background: To estimate the prevalence of elevated blood glucose level (EBG, including type 2 diabetes mellitus and impaired fasting glucose), and its association with non-valvular atrial fibrillation (NVAF) in Guangzhou, China.Methods: The population-based follow-up Guangzhou Heart Study collected baseline data from July 2015 to August 2017 among 12,013 permanent residents aged > 35 from 4 Guangzhou districts. Two streets (Dadong and Baiyun) in the Yuexiu District, and one street (Xiaoguwei) and two towns (Xinzao and Nancun) in the Panyu District were chosen as representative of urban and rural areas, respectively. Each participant completed a comprehensive questionnaire, and underwent physical examination, blood sample collection for laboratory testing, electrocardiography, and other evaluations. Multivariable logistic regression analyses were used to estimate the independent association between hyperglycemia and NVAF prevalence.Results: The prevalence of EBG in overall study population was 29.9%. Compared with residents without EBG, the odds ratio (OR) for AF among residents with EBG was significantly higher (1.94, 95% confidence interval [CI]: 1.40-2.70, P <  0.001), even after multivariate adjustment for metabolic abnormalities (OR = 1.60, 95% CI: 1.14-2.25, P = 0.007), and driven by women (OR = 1.80, 95% CI: 1.12-2.91, P = 0.016).Conclusions: In Guangzhou, China, prevalence of EBG is high among residents aged > 35 years and associated with a multivariate adjusted increase in prevalence of NVAF overall and in women. [ABSTRACT FROM AUTHOR]

To investigate the safety and midterm outcome of concomitant left atrial appendage (LAA) closure and catheter ablation (CA) as a one-stage hybrid procedure for non-valvular atrial fibrillation (AF) in a multicenter registry. A total of 50 consecutive patients with symptomatic drug-resistant non-valvular AF with CHA2DS2-VASc score ≥ 2 and contraindications for antithrombotic therapy were included in the prospectively established LAA closure registry, and underwent concomitant LAA closure (48 for WATCHMAN and 2 for ACP) and CA procedure (40 for radiofrequency and 10 for cryoballoon CA). Two cardiac tamponades, one peripheral vascular complications and one mild air embolism were observed during perioperative period. After mean follow-up of 20.2 ± 11.5 months, 18 (36%) patients presented with atrial arrhythmia relapse and 45 (91.8%) patients presented with complete sealing; furthermore, there were two transient ischemic attacks and one ischemic stroke under an off-oral anticoagulant situation, respectively. Concomitant CA and LAA closure as a one-stage hybrid procedure might be feasible and potentially decrease costs in patients with symptomatic non-valvular AF with high stroke risk and contraindication to antithrombotic treatment, and as safe as LAA closure procedure only during the perioperative period. However, it was necessary to further validate the mid-term safety. [ABSTRACT FROM AUTHOR]

Objectives: The aim of the study was to examine the association of CHADS2/CHA2DS2-VASc scores with left atrial thrombus (LAT) and spontaneous echocardiographic contrast (SEC) in non-anticoagulated nonvalvular atrial fibrillation (NVAF) spontaneous patients, and to develop a new scoring system for LAT/SEC prediction. Methods: Consecutive non-anticoagulated NVAF patients with or without LAT/SEC by transesophageal echocardiography were identified in the Guangdong General Hospital. Results: Among 2,173 patients, the prevalence of LAT/SEC was 4.9%. Both predictive values of CHADS2 and CHA2DS2-VASc scores for the presence of LAT/SEC were low-to-moderate (receiver operating characteristic [ROC] = 0.591 and 0.608, respectively, p = 0.90). By multivariate analysis, non-paroxysmal AF, decreased left ventricular ejection fraction, and left atrial enlargement were positively associated with LAT/SEC, while CHADS2/CHA2DS2VASc scores were not. A new scoring system based on these 3 factors above significantly improved the discrimination for LAT/SEC (ROC = 0.792). Conclusions: CHADS2/CHA2DS2-VASc scores had limited value in predicting LAT/SEC; a new scoring system that combines AF type and echocardiographic parameters may better predict LAT/SEC as a surrogate for cardioembolic risk in NVAF patients. [ABSTRACT FROM AUTHOR]

Background: Catheter ablation has been established as a curative treatment strategy for ventricular arrhythmias. The standard procedure of most ventricular arrhythmias originating from the right ventricle is performed via the femoral vein. However, a femoral vein access may not achieve a successful ablation in some patients.Case Presentation: We reported a case of a 29-year old patient with symptomatic premature ventricular contractions was referred for catheter ablation. Radiofrequency energy application at the earliest endocardial ventricular activation site via the right femoral vein could not eliminate the premature ventricular contractions. Epicardial mapping could not obtain an earlier ventricular activation when compared to the endocardial mapping, and at the earliest epicardial site could not provide an identical pace mapping. Finally, we redeployed the ablation catheter via the right subclavian vein by a long sheath. During mapping of the subvalvular area of the right ventricle, a site with a good pace mapping and early ventricular activation was found, and premature ventricular contractions were eliminated successfully.Conclusion: Ventricular arrhythmias originating from the subtricuspid annulus may be successfully abolished via a trans-subclavian approach and a long sheath. Although access via the right subclavian vein for mapping and ablation is an effective alternative, it is not a routine approach. [ABSTRACT FROM AUTHOR]