The H19 lncRNA, a highly abundant and conserved imprinted gene, has been implicated in many essential biological processes and diseases. However, the function of H19 in the heart remains unknown. In this study, we investigated the function and underlying mechanism of H19 in regulating cardiomyocyte hypertrophy. We first detected the expression of H19 and its encoded miR-675 in both normal and diseased hearts and verified their up-regulations in pathological cardiac hypertrophy and heart failure. Adenovirus-mediated expression and a siRNA-mediated silence of H19 showed that H19 overexpression reduced cell size both at baseline and in response to phenylephrine, whereas knock-down of H19 induced cardiomyocyte hypertrophy. Overexpression or knock-down of miR-675 in cardiomyocytes demonstrated that miR-675 also inhibited cardiomyocyte hypertrophy. Moreover, inhibition of miR-675 reversed the reduction of cardiomyocyte size in H19-overexpressing cardiomyocytes, while infection with an adenovirus carrying H19 fragment without pre-miR-675 (H19-Tru) or with mutant sequences of pre-miR-675 (H19-Mut) failed to reduce cardiomyocyte size, indicating that miR-675 mediated the inhibitory effect of H19 on cardiomyocyte hypertrophy. We also identified that CaMKIIδ was a direct target of miR-675 and partially mediated the effect of H19 on cardiomyocyte hypertrophy. Furthermore, in vivo silencing of miR-675 using a specific antagomir in a pressure overload-induced mouse model of heart failure increased cardiac CaMKIIδ expression and exacerbated cardiac hypertrophy. These findings reveal a novel function of H19-miR-675 axis targeting CaMKIIδ as a negative regulator of cardiac hypertrophy, suggesting its potential therapeutic role in cardiac diseases.

// <![CDATA[ $('.header-date').hide();$('#titleAuthors').hide();$('#abstractHeader').hide(); // ]]> Fengyan Jin1, Hai Lin1, Sujun Gao1, Zheng Hu2, Song Zuo2, Liguang Sun2, Chunhui Jin1, Wei Li1, Yanping Yang1 1Department of Hematology, The First Bethune Hospital of Jilin University, Changchun, China 2Institute of Translational Medicine, The First Bethune Hospital of Jilin University, Changchun, China Correspondence to: Yanping Yang, email: yangyanping_1978@163.com Keywords: natural killer cells, interleukin, interferon-γ, NKG2D, leukemia Received: December 13, 2015 Accepted: October 26, 2016 Published: November 01, 2016

BACKGROUND: Observational studies have suggested that SGLT2 (sodium-glucose cotransporter 2) inhibitors are associated with a lower risk of atrial fibrillation (AF) recurrence after catheter ablation in patients with AF with concomitant diabetes, heart failure, or chronic kidney disease. However, no randomized trial to date has tested whether SGLT2 inhibitors reduce AF recurrence after ablation in patients without established indications. We therefore investigated the effect of dapagliflozin on prevention of early recurrence of AF after catheter ablation in patients without current indications for SGLT2 inhibitors. METHODS: The DARE-AF trial (Dapagliflozin on Recurrence After Catheter Ablation for Atrial Fibrillation) was a prospective, open-label, parallel-assignment randomized controlled trial that enrolled 200 patients with persistent AF between July 2024 and March 2025, scheduled to undergo a first catheter ablation procedure and without established indications for dapagliflozin (diabetes, heart failure, or chronic kidney disease). Patients were randomly assigned at a 1:1 ratio to dapagliflozin (10 mg once daily for 3 months after the ablation) or control. The primary end point was AF burden at 3 months after ablation, assessed by 7-day single-lead ECG patches. Secondary outcomes included time to events, quality of life, and improvement of atrial remodeling. RESULTS: A total of 200 patients (mean age 58.5 years, 19.5% women, 29.0% with persistent AF ≥1 year) were randomized, and 198 patients (98 in the dapagliflozin group, 100 in the control group) were included in the primary analysis. Three months after ablation, the difference in AF burden was insignificant between the dapagliflozin group and the control group (7.5±23.6% versus 8.1±25.5%; P =0.48). Atrial arrhythmia recurrence occurred in 29 patients (29.6%) in the dapagliflozin group and 28 patients (28.0%) in the control group (hazard ratio, 1.11 [95% CI, 0.66–1.86]; P =0.70). No significant between-group differences were observed in changes in quality of life or left atrial diameter. CONCLUSIONS: Three-month treatment with dapagliflozin did not reduce the early recurrence of arrhythmia after catheter ablation in patients with persistent AF. REGISTRATION: URL: https://www.clinicaltrials.gov ; Unique identifier: NCT06433479.

Aims: Steam pops present a significant concern during radiofrequency (RF) ablation of atrial fibrillation (AF). It is crucial to analyse the incidence and ablation characteristics associated with steam pops. This study aims to investigate the occurrence and potential predictors of steam pops. Methods and results: This study included 3263 patients with AF who underwent RF ablation. Patients with paroxysmal AF received bilateral circumferential pulmonary vein (PV) ablation, while those with persistent AF underwent additional linear ablation. The ablation parameters at the sites of steam pops were compared to those at adjacent anatomical locations. A total of 81 steam pops (2.5%) with one pericardial tamponade were recorded. Steam pops were observed at liner ablation sites: 6 (0.4%) at the mitral isthmus, 16 (0.9%) at the tricuspid isthmus (CTI), and 7 (0.5%) along the roofline. The most common sites of steam pops were the anterior edge of the left superior PV and the inferior vena cava side of the CTI. The impedance drop was significantly higher (18.2 ± 9.5 Ω vs. 13.5 ± 4.8 Ω, P < 0.001) at steam pop sites. The optimal cut-off points of impedance drop for predicting steam pops were > 9.5 Ω within the first 3 s, > 10.5 Ω within the first 5 s, > 13.5 Ω within the first 10 s, and > 18.5 Ω in the whole ablation, respectively. Conclusion: The incidence of steam pops during ablation of AF is infrequent. Impedance drop is the only ablation parameter that could predict the occurrence of steam pops.

Background: Atrial arrhythmia recurrence after atrial fibrillation (AF) catheter ablation is conventionally assessed as a binary end point. However, the prognostic value of recurrence patterns is less studied. Methods and Results: This study included patients undergoing catheter ablation from the multicenter China Atrial Fibrillation Registry study (2011–2022). Postablation AF patterns within 1 year were categorized as nonrecurrence, paroxysmal AF recurrence, or persistent AF (PersAF) recurrence. Cardiovascular outcomes included cardiovascular death, thromboembolism, and cardiovascular hospitalization. Cox proportional models with landmark analysis were used to assess the relationship between recurrence patterns and outcomes. Sensitivity analyses were conducted using Fine‐Gray models, considering death unrelated to the outcomes as the competing risk and evaluating 2‐year recurrence patterns. Among 13 811 patients (mean age, 60.5±10.8 years; 66.1% men), those with preablation PersAF, prior stroke/transient ischemic attack/systemic embolism, and increased left atrial diameter were more likely to develop PersAF postablation. Compared with nonrecurrence, PersAF recurrence was associated with higher risks of cardiovascular death (hazard ratio [HR], 2.03 [95% CI, 1.20–3.43]; P =0.009), thromboembolism (HR, 1.50 [95% CI, 1.09–2.06]; P =0.012), and cardiovascular hospitalization (HR, 1.74 [95% CI, 1.56–1.94]; P <0.001) during a median follow‐up of 3.02 years (interquartile range, 1.44–5.03 years), while paroxysmal AF recurrence was only significantly associated with an increased risk of cardiovascular hospitalization (HR, 1.98 [95% CI, 1.83–2.14], P <0.001). Sensitivity analyses yielded consistent results. Conclusions: Postablation PersAF recurrence was associated with significantly higher risks of cardiovascular death and thromboembolism, compared with paroxysmal AF recurrence and nonrecurrence, indicating the prognostic importance of recurrence patterns. Registration: URL: www.chictr.org.cn/ ; unique identifier: ChiCTR‐OCH‐13003729.