Background: The potential effectiveness of integrated management in further improving the prognosis of patients with atrial fibrillation has been demonstrated; however, the best strategy for implementation remains to be discovered. Objective: The aim of this study was to ascertain the feasibility of implementing integrated atrial fibrillation care via the Hospital-Community-Family–Based Telemedicine (HCFT-AF) program. Methods: In this single-arm, pre-post design pilot study, a multidisciplinary teamwork, supported by efficient infrastructures, provided patients with integrated atrial fibrillation care following the Atrial fibrillation Better Care (ABC) pathway. Eligible patients were continuously recruited and followed up for at least 4 months. The patients’ drug adherence, and atrial fibrillation–relevant lifestyles and behaviors were assessed at baseline and at 4 months. The acceptability, feasibility, and usability of the HCFT-AF technology devices and engagement with the HCFT-AF program were assessed at 4 months. Results: A total of 73 patients (mean age, 68.42 years; 52% male) were enrolled in November 2019 with a median follow up of 132 days (IQR 125–138 days). The patients’ drug adherence significantly improved after the 4-month intervention (P<.001). The vast majority (94%, 64/68) of indicated patients received anticoagulant therapy at 4 months, and none of them received antiplatelet therapy unless there was an additional indication. The atrial fibrillation–relevant lifestyles and behaviors ameliorated to varying degrees at the end of the study. In general, the majority of patients provided good feedback on the HCFT-AF intervention. More than three-quarters (76%, 54/71) of patients used the software or website more than once a week and accomplished clinic visits as scheduled. Conclusions: The atrial fibrillation–integrated care model described in this study is associated with improved drug adherence, standardized therapy rate, and lifestyles of patients, which highlights the possibility to better deliver integrated atrial fibrillation management. Trial Registration: Clinicaltrials.gov NCT04127799; https://clinicaltrials.gov/ct2/show/NCT04127799

The use of stem cells in generating cell-based pacemaker therapies for bradyarrhythmia is currently being considered. Due to the propensity of stem cells to form tumors, as well as ethical issues surrounding their use, the seed cells used in cardiac biological pacemakers have limitations. Very small embryonic-like stem cells (VSELs) are a unique and rare adult stem cell population, which have the same structural, genetic, biochemical, and functional characteristics as embryonic stem cells without the ethical controversy. In this study, we investigated the ability of rat bone marrow- (BM-) derived VSELs to differentiate in vitro into cardiomyocytes by 5-Azacytidine (5-AzaC) treatment. The morphology of VSELs treated with 10 μM 5-AzaC increased in volume and gradually changed to cardiomyocyte-like morphology without massive cell death. Additionally, mRNA expression of the cardiomyocyte markers cardiac troponin-T (cTnT) and α-sarcomeric actin (α-actin) was significantly upregulated after 5-AzaC treatment. Conversely, stem cell markers such as Nanog, Oct-4, and Sox2 were continuously downregulated posttreatment. On day 14 post-5-AzaC treatment, the positive expression rates of cTnT and α-actin were 18.41±1.51% and 19.43±0.51%, respectively. Taken together, our results showed that rat BM-VSELs have the ability to differentiate into cardiomyocytes in vitro. These findings suggest that VSELs would be useful as seed cells in exploring the mechanism of biological pacemaker activity.

Although lncRNAs have been identified as playing critical roles in the development of germ cells, their potential involvement in the development of PGCs in chickens remains poorly understood. Differentially expressed lncRNAs (DELs) from previous RNA-seq of embryonic stem cells (ESCs), PGCs, and spermatogonial stem cells (SSCs) were analyzed by K-means clustering, from which a key candidate, lncRNA (lncRNA PGC regulator, LncPGCR) was obtained. We confirmed that LncPGCR plays a positive role in the development of PGCs by increasing the expression of the PGC marker gene (Cvh and C-kit), while downregulating the pluripotency-associated gene (Nanog) in vitro and in vivo. The activation and expression of LncPGCR are regulated by histone acetylation, and transcription factor TCF7L2. Mechanistically, a rescue assay was performed to further confirm that LncPGCR contributed to the development of PGCs by regulating the gga-miR-6577-5p/Btrc signaling pathway. Adsorption of gga-miR-6577-5p activated the WNT signaling cascade by relieving the gga-miR-6577-5p-dependent inhibition of Btrc expression. Taken together, our study discovered the growth-expedited role of LncPGCR in PGCs development, showing the potential LncPGCR/miR-6577-5p/Btrc pathway. The results and findings provide a novel insight into the development of PGCs.

Biological pacemakers, made of pacemaker-like cells, are promising in the treatment of bradyarrhythmia; however, the inefficiency of stem cell differentiation into pacemaker-like cells has limited their clinical application. Previous studies have reported that histone H3 at lysine 9 (H3K9) methylation is widely involved in the proliferation and differentiation of cardiomyocytes, but the specific role of H3K9 dimethylation (H3K9me2) in the formation of pacemaker cells remains unclear. The present study evaluated the functional role of H3K9me2 in the differentiation of bone marrow mesenchymal stem cells (BMSCs) into pacemaker-like cells. Rat BMSCs pretreated with the euchromatic histone lysine methyltransferase 2 (G9a) inhibitor BIX01294 were transfected with a T-box 18 overexpression plasmid to induce BMSCs to form pacemaker-like cells. The induced pacemaker-like cells were analyzed using reverse transcription-quantitative PCR (RT-qPCR) and immunofluorescence to assess the efficiency of differentiation. The enrichment of H3K9me2 in the hyperpolarized-activated cyclic nucleotide-gated cation channel (HCN)4 promoter region was assessed by chromatin immunoprecipitation (ChIP). In addition, BIX01294 was injected into rats, and the protein and mRNA expression levels of HCN4 were assessed using western blotting and RT-qPCR. After interference with G9a using BIX01294, ChIP results demonstrated that H3K9me2 levels in the promoter region of HCN4 were markedly decreased. Immunofluorescence and RT-qPCR demonstrated that the protein expression levels of certain cardio-specific proteins in the treated group were significantly higher compared with those in the untreated group. In vivo experiments demonstrated that interference with G9a could cause pathological hypertrophy. Furthermore, in vitro and in vivo inhibition of G9a could increase the differentiation and proliferation of pacemaker-like cells by decreasing the levels of H3K9me2 in the promoter region of HCN4 gene.

Background: The ablation of the coronary sinus (CS) is becoming more and more important in accessory pathway-related supraventricular tachycardia ablation. In comparison with temperature-controlled catheters (TCC), irrigated-tip catheter (ITC) are more expensive and cause more damage in accessory pathway-related supraventricular tachycardia ablation. We intended to develop a new method for the reasonable selection of electrode for coronary sinus(CS) ablation via assessing the relationship between the accessory pathway (AP) potential and time of successful ablation. Methods：Among the patients who had detected the bypass potential during radiofrequency ablation between 1/1/2015 and 12/31/2019. TCC was performed in 330 patients receiving endocardial ablation. 30 patients underwent radiofrequency catheter ablation (RFCA) in CS. The relationship between AP potential and time of successful ablation was analyzed. Results：330 cases of TCC ablation within the endocardium revealed that the amplitude of AP potential was significantly and negatively correlated with the time of successful ablation (r = -0.79, p < 0.001). In CS ablation, the median baseline amplitude of the AP potentials in patients with successful TCC ablation was higher than that in patients with ITC following TCC ablation failure (p = 0.02). The optimal cutoff value of the amplitude of the AP potential to guide the selection of a catheter for ablation was 1.07 mV, and the sensitivity and specificity were 80% and 90%, respectively. Conclusion：The AP potential is helpful for the electrode selection in CS ablation.

Background In accessory pathway-related supraventricular tachycardia ablation, coronary sinus (CS) ablation has received more and more attention, but there are no accurate criteria for catheter selection. Objectives We intended to develop a new method for the reasonable selection of electrode for coronary sinus ablation via assessing the relationship between the accessory pathway (AP) potential and time of successful ablation. Methods Among the patients who had detected the bypass potential during radiofre-quency ablation between 1/1/2015 and 12/31/2019, 30 patients underwent radiofrequency catheter ablation (RFCA) in CS. The relationship between AP potential and time of successful ablation was analyzed. Results In CS ablation, the median baseline amplitude of the AP potentials in patients with successful Temperature control catheter (TCC) ablation was higher than that in patients with Irrigated-tip catheter (ITC) following TCC ablation failure (p = 0.02). The optimal cutoff value of the amplitude of the AP potential to guide the selection of a catheter for ablation was 1.07 mV, and the sensitivity and specificity were 80% and 90%, respectively. Conclusions The AP potential is helpful for the electrode selection in CS ablation.