circCELF1 Inhibits Myocardial Fibrosis by Regulating the Expression of DKK2 Through FTO/m6A and miR-636.

The aim of this study is to explore the role of circCELF1/miR-636/DKK2 pathway in myocardial fibrosis (MF). RT-qPCR and western blot were used to detect the expression of circCELF1, miR-636, and DKK2 in activated cardiac fibroblasts (CFs) and the hearts of acute myocardial infarction (AMI) mice. The m6A level of DKK2 was detected by RIP and RT-qPCR. The regulation of circCELF1/miR-636/DKK2 pathway on CF viability, activation, apoptosis, and migration was verified by CCK-8, western blot, flow cytometry, and Transwell. Ang II induced downregulation of circCELF1 expression, while circCELF1 enhanced the expression of DKK2 by adsorbing miR-636. circCELF1 also reduced DKK2 m6A level by upregulating FTO expression, thereby inhibiting the binding of miR-636 to DKK2 and promoting DKK2 expression. Ang II promoted CF viability, activation, and migration through the circCELF1/miR-636/DKK2 pathway. Both miR-636 inhibitors and DKK2 effectively reduced MF and improved cardiac function in AMI mice.

Pulmonary vein isolation guided by moderate ablation index targets combined with strict procedural endpoints for patients with paroxysmal atrial fibrillation.

INTRODUCTION: Ablation index (AI)-guided radiofrequency ablation has been increasingly used for the treatment of drug-resistant paroxysmal atrial fibrillation (AF)，but the optimal AI targets remain to be determined. We aimed to examine the efficacy and safety of catheter ablation guided by moderate AI values but more strict procedural endpoints in patients with paroxysmal AF. METHODS: We conducted a retrospective review of a consecutive series of patients who received their first AI-guided ablation for paroxysmal AF from 2017 to 2018. The standard procedural protocol recommends AI targets as follows: anterior: 400-450; posterior: 280-330; and roof/inferior wall: 380-430. After circumferential pulmonary vein isolation (PVI), we performed bipolar pacing along the ablation line, adenosine triphosphate (ATP)-provocation, and waited for 30 min to verify PVI. The primary clinical outcome was the rate of freedom from AF recurrence at 12 months. RESULTS: A total of 140 consecutive patients were included. The mean procedure and ablation times were 132.2 ± 30.2 min and 24.2 ± 7.9 min, respectively. The first-pass isolation and final isolation rates were documented in 49.3% and in 100% of the patients, respectively. At 12 months, single-procedure freedom from atrial tachyarrhythmias was observed in 92.1% of patients. No major procedure-related complications were encountered. CONCLUSIONS: Moderate AI-guided catheter ablation is highly effective for the treatment of drug-refractory paroxysmal AF in real-world settings. Over 90% of patients achieved single-procedure arrhythmia-free survival at 1 year. The outcome was obtained without major complications and the procedure involved relatively short procedure and ablation times.

One-stop hybrid procedure combining catheter ablation and left atrial appendage closure increases long-term risk for adverse events in patients with atrial fibrillation.

INTRODUCTION: Combined catheter ablation (CA) and left atrial appendage closure (LAAC) have proven to be a feasible and safe strategy in treating patients with nonvalvular atrial fibrillation (AF). However, the interactions between CA and LAAC have not been systematically explored. We analyzed the impact of CA on long-term outcomes of LAAC in patients with AF treated with the hybrid procedure. METHODS: A total of 107 consecutive patients with AF who underwent LAAC were divided into two groups: group A (n = 61) included patients who underwent CA followed by LAAC during the same procedure and group B (n = 46) included patients who underwent LAAC only. All patients underwent systematic transesophageal echocardiography (TEE) follow-up. RESULTS: In group A, CA resulted in severe edema of the left atrial ridge (LAR), which manifested as an increase in LAR thickness from 4.6 ± 0.4 mm before CA to 6.8 ± 0.6 mm (P < .01) after CA. TEE at 45 days showed that the incidence of peri-device leakage was significantly higher in group A than in group B (45.9% vs 4.3%, P < .001). At the 12-month follow-up, the peri-device leakage rate remained higher in group A than in group B (14.8% vs 2.2%, P < .01). Three (4.9%) patients in group A experienced transient ischemia attacks; no events were reported in group B during the 1-year follow-up. CONCLUSION: Edema of LAR with the single-stage procedure that consists of CA followed by LAAC could result in increased peri-device leakage and decreased compression rate over time, which may be also associated with elevated risk profiles when compared with an LAAC-only procedure.

Injection of contrast medium through a delivery sheath reveals interventricular septal vascular injury in a case of left bundle branch pacing.

A 70-year-old woman with symptomatic bradycardia caused by persistent atrial fibrillation and atrioventricular block was referred to our institution for pacemaker implantation. After we failed to obtain adequate His bundle capture thresholds (>2.5 V at 1.0 ms) at three pacing sites, left bundle branch pacing was attempted as an alternative technique. The tip of the 3830 lead was screwed towards the left side of the interventricular septum. Contrast medium was injected through the C315 sheath, which was placed close to the right side of the interventricular septum to determine the exact depth of the 3830 lead inside the septum. Unexpectedly, the vessels in the interventricular septum were revealed by the contrast, which showed that the lead had penetrated one of the septal vessels. To the best of our knowledge, this is the first reported case of a patient in whom injection of a contrast agent through a delivery sheath showed damage to the interventricular septal vessels. Findings from this case suggest that injection of contrast medium through a C315 sheath that is placed close to the interventricular septum is a potential method for excluding damage to interventricular septal vessels.

Identification of circumferential pulmonary vein isolation responders among patients with persistent atrial fibrillation: clinical value of the sequential low-dose ibutilide test.

AIMS: Circumferential pulmonary vein isolation can be effective as sole treatment for persistent atrial fibrillation. However, identifying those patients who will respond to this therapy remains a challenge. We investigated the clinical value of the sequential low-dose ibutilide test for identifying patients with persistent atrial fibrillation in whom pulmonary vein isolation is effective as sole therapy. METHODS AND RESULTS: In a prospective cohort of 180 consecutive patients with persistent atrial fibrillation, intravenous low-dose (0.004 mg/kg) ibutilide was administered 3 days before ablation and after the completion of circumferential pulmonary vein isolation. In patients in whom ibutilide did not terminate atrial fibrillation pre-procedurally, but successfully terminated it intraprocedurally, no further atrial substrate modification was performed. Pre-procedural low-dose ibutilide failed to terminate the arrhythmia in all patients with persistent atrial fibrillation, while pulmonary vein isolation ± low-dose ibutilide terminated persistent atrial fibrillation in 55 (30.6%) of them (PsAF group 1). The remaining 125 (69.4%) patients underwent electrogram-based ablation (PsAF Group 2). The control group comprised 379 consecutive patients with paroxysmal atrial fibrillation who underwent pulmonary vein isolation over the same period. At 24 months follow-up, 39 (70.9%) patients in PsAF Group 1 and 276 (72.8%) patients in the control group were free from atrial tachyarrhythmias (P = NS); the arrhythmia-free rates in both groups were higher than that in PsAF group 2 (58.4%, P = 0.005). CONCLUSION: The sequential low-dose ibutilide test is a simple method for identifying patients with persistent atrial fibrillation in whom pulmonary vein isolation alone is an appropriate treatment strategy.

Electrocardiographic morphology during left bundle branch area pacing: Characteristics, underlying mechanisms, and clinical implications.

AIMS: In this study, we investigated the characteristics and underlying mechanisms of the electrocardiographic (ECG) morphology during left bundle branch area pacing (LBBAP), which have not been systematically described. METHODS: Patients with indications for permanent cardiac pacing underwent LBBAP attempts. The ECGs of patients with confirmed left bundle branch (LBB) capture were compared with those of individuals with right bundle branch block (RBBB) on 12-lead ECG. Intracardiac electrograms recorded during implantation were analyzed in all patients who underwent pacing. RESULTS: LBBAP was successfully achieved in 87.5% (56/64) of patients. The QRS morphologies in lead V1 during LBBAP, which typically demonstrated Qr (60.7%), qR (19.6%), rSR' (7.1%), or QS (12.5%) patterns, differed from those of native RBBB, which featured rsR' (57.5%), M shape (23.7%), or monophasic R patterns (18.7%). The terminal R' wave duration in lead V1 was significantly shorter during LBBAP than during native RBBB (51 ± 12 ms vs 85 ± 19 ms, p < 0.001). LBB potentials were recorded in 66.1% (37/56) of the LBBAP patients. No significant differences in ECG characteristics were found between LBBAP with and without recorded LBB potentials. The presence of bundle branch block during LBBAP significantly prolonged QRS duration, R wave peak time, and terminal R' wave duration in lead V1 . CONCLUSION: LBBAP-ECG patterns are characterized by a shorter terminal R' wave duration in lead V1 compared with that of native RBBB configurations. Bundle branch conduction integrity has an impact on ECG characteristics during LBBAP.