MicroRNA-1976 regulates degeneration of the sinoatrial node by targeting Cav1.2 and Cav1.3 ion channels.

Sick sinus syndrome (SSS) is primarily a disease of the elderly, and age-dependent decrease in Cav1.2 and Cav1.3 Ca2+ channels within the sinus node has been shown to play an important role in sinoatrial node (SAN) degeneration; however, posttranscriptional mechanisms regulating decrease in Cav1.2 and Cav1.3 Ca2+ channels remain unclear. Some studies have reported that microRNAs (miRNAs) are involved in age-related cardiovascular diseases. Nevertheless, little is known about the roles of miRNAs in age-related SSS. This study investigated whether miR-1976 was involved in the regulation of SAN degeneration by targeting Cav1.2 and Cav1.3 Ca2+ channels. First, using microarray-based miRNA expression profiling and qRT-PCR, we confirmed that miR-1976 was upregulated in the plasma of patients with age-related SSS relative to healthy controls. By employing target gene prediction software, luciferase assay and western blotting, we further confirmed Cav1.2 and Cav1.3 as direct targets of miR-1976. Furthermore, miR-1976 levels in rabbit SAN tissues were negatively correlated with Cav1.2 and Cav1.3 expression and intrinsic heart rates but positively correlated with corrected sinus node recovery time (CSNRT). Additionally, miR-1976 transgenic mice displayed attenuated Cav1.2 and Cav1.3 protein expression, which led to sinus node dysfunction. These results suggest that miR-1976 plays an important role in the SAN aging process by targeting Cav1.2 and Cav1.3. Thus, miR-1976 could have great potential as a noninvasive diagnostic tool and therapeutic target for SSS. These findings may reveal important insights into the pathogenesis of SSS.

Ventricular activation pattern of left ventricular septal pacing in a canine model.

BACKGROUND: Left bundle branch pacing (LBBP) is a feasible and effective physiological pacing technique. The QRS morphology of left ventricular septal pacing (LVSP) is similar to that of LBBP. The ventricular activation pattern of LBBP is well-known, whereas the pattern of LVSP still needs further investigation. The present study aimed to determine ventricular activation pattern difference between LVSP and LBBP in a canine model. METHOD: All six canines underwent successful LBBP and LVSP through trans-ventricular septum using intracardiac echocardiography and intracardiac electrogram. Their hearts were isolated and stained with Lugol's iodine to determine the position of the pacing lead. The activation sequences of the left ventricular myocardium and His-Purkinje system were recorded by placing multiple electrode catheters. RESULTS: First, the left His-Purkinje system in LVSP was activated simultaneously from apical and basal regions to the left ventricular middle septal region, whereas the left ventricular septal myocardium was activated from the apical to basal region. The left His-Purkinje system activation in LBBP occurred in the direction of the apex from the pacing lead, but the left ventricular septal myocardium was activated in the apical to basal direction. Furthermore, the left intraventricular electrical synchrony was similar between LVSP and LBBP as determined by mapping the left ventricular septal to free wall activation time (46.7 ± 1.8 ms vs. 45.0 ± 1.4 ms, p = 0.11). CONCLUSION: The ventricular activation sequence of LVSP was similar to LBBP. LVSP can capture LBB due to the wide distribution of LBB. These findings suggest a rationale for clinical application of LVSP.

Composite dietary antioxidant index and the risk of heart failure: A cross-sectional study from NHANES.

BACKGROUND: Previous studies show that oxidative stress is important in heart failure (HF) pathogenesis. The composite dietary antioxidant index (CDAI), which reflects the antioxidant profile of nutrient supplements, is associated with cardiovascular mortality risk. However, the association between CDAI and the risk of HF remains unknown. HYPOTHESIS: In this study, we investigated the relationship between CDAI and HF risk using National Health and Nutritional Examination Survey (NHANES) data. METHODS: The data of participants aged >40 years old from the NHNANES between 2001 and 2018 were obtained and used to assess the relationship between CDAI and the risk of HF. Logistic regression was used to calculate the odds ratio (OR) of CDAI for the risk of HF. RESULTS: A total of 29 101 participants were divided into the HF (n = 1419; 4.88%) and non-HF groups (n = 27 682; 95.12%), HF group participants had lower CDAI than the non-HF group (-0.32 ± 0.14 vs. 0.67 ± 0.05, p < .0001). Compared with the lowest CDAI quartile (Q1), the OR for HF risk was 0.88 (0.68-1.13) for Q2 (p = .30), 0.77 (0.61-0.99) for Q3 (p = .04), and 0.68 (0.52-0.89) for Q4 (p = .01). CONCLUSIONS: CDAI was negatively associated with the risk of HF. Our findings show that the intake of an antioxidant-rich dietary is a potential method to reduce the risk of HF.

Intracardiac Echocardiography-Guided Implantation for Proximal Left Bundle Branch Pacing.

BACKGROUND: Multiple screw-in attempts under fluoroscopy are often needed to place the pacing lead tip near or at the left bundle branch (LBB). This study was conducted to evaluate the feasibility of implanting an LBB pacing lead in the proximal LBB (PLBB) guided by intracardiac echocardiography (ICE). METHODS: The distribution of the LBB was initially determined by ICE anatomic imaging and 3-dimensional electrical mapping of His and LBB potentials in 20 patients in the first parts of the study. In the second part, 101 consecutive pacemaker-indicated patients were randomized into the ICE-guided and non-ICE groups for LBB pacing implantation. The procedural details and electrophysiological characteristics of the 2 groups were compared. RESULTS: In the first part of the study, PLBB was identified at 10 to 20 mm from the tricuspid annulus toward the apex with an area of 4.5±1.1 cm2. In the second part, the number of lead screw-in attempts in the septum was fewer in the ICE group than in the non-ICE group (1.43±0.62 versus 1.98±0.75, P=0.0002). The duration of the procedure (26±8 versus 43±9 minutes, P<0.001) and fluoroscopy for LBB pacing implantation (7.4±1.8 versus 10.7±2.4 minutes, P<0.001) in the ICE group was significantly shorter than those in the non-ICE group. LBB pacing in the ICE group generated a lesser QRS duration with more cases of LBB trunk pacing (46.8% versus 25%, P=0.031) and PLBB (91.5% versus 72.7%, P=0.0267) pacing compared with that in the non-ICE group. CONCLUSIONS: The basal left ventricular septum can be better visualized using ICE. ICE-guided PLBB pacing is feasible and safe, with a shorter duration required for the procedure and fluoroscopy, and generates greater LBB trunk pacing and PLBB pacing.

Integrated Analysis of circRNA-miRNA-mRNA-Mediated Network and Its Potential Function in Atrial Fibrillation.

Background: Atrial fibrillation (AF) is one of the most prevalent arrhythmias, characterized by a high risk of heart failure and embolic stroke. Competing endogenous RNA network has been reported to play an important role in cardiovascular diseases. The main objective of the present study was to construct a circRNA-miRNA-mRNA-mediated network and explore the potential function in AF. Methods: The microarray data of circRNA, miRNA, and mRNA in AF were downloaded from the Gene Expression Omnibus database. The RobustRankAggreg method was used to screen the different expression circRNAs(DECs). Then the circRNA-miRNA-mRNA-mediated network was constructed by using the CircInteractome database and the miRWalk online tool. A quantitative real-time polymerase chain reaction was used to detect the circRNA expression level in plasma. The left atrial fibrosis was evaluated with the left atrial low voltage area (LVA) by using left atrial voltage matrix mapping. Results: Three DECs (hsa_circRNA_102461, hsa_circRNA_103693, and hsa_circRNA_059880) and 4 miRNAs were screened. Then a circRNA-miRNA-mRNA-mediated network was constructed, which included 2 circRNAs, 4 miRNAs, and 83 genes. Furthermore, the plasma's hsa_circ_0070391 expression level was confirmed to be upregulated and positively correlated with left atrial fibrosis in AF (r = 0.88, P < 0.001), whereas hsa_circ_0003935 was downregulated. Moreover, the ROC curve analysis revealed hsa_circ_0070391 and hsa_circ_0003935 could differentiate AF from the healthy controls with an AUC of 0.95 (95% sensitivity and 90% specificity) and 0.86 (70% sensitivity and 75% specificity), respectively. Finally, the free of atrial tachyarrhythmia rate was dramatically lower in the hsa_circ_0070391 high expression group than in the low expression group post catheter ablation (70.0 vs. 90.0%, p = 0.04). Conclusion: This study provides a novel insight to further understand the AF pathogenesis from the perspective of the circRNA-miRNA-mRNA network, suggesting that plasma circRNAs could serve as a novel atrial fibrosis and prognosis biomarker for AF.

RESCUE-AF in Patients Undergoing Atrial Fibrillation Ablation: The RESCUE-AF Trial

BACKGROUND: Although contact force (CF)­sensing catheters improve procedural effectiveness and safety of atrial fibrillation ablation, recent reports documented a higher incidence of atrioesophageal fistula formation relative to ablation with non­CF-sensing catheters.The present study was to assess whether restricting CF to <20 g reduced risk for esophageal injury (EI) in patients with atrial fibrillation undergoing circumferential pulmonary vein isolation. METHODS: This prospective, single-center, randomized study enrolled 89 consecutive patients (mean age, 57.2±11.3 years; 57.3% men) with atrial fibrillation (68.5% paroxysmal and 31.5% persistent). Computed tomography angiography, transesophageal echocardiography, and esophageal endoscopy were conducted before the procedure, and a repeat esophageal endoscopy was performed after the procedure. Patients were randomized to restricted-CF group (n=44) or non-CF group (n=45), with circumferential pulmonary vein isolation using a CF-sensing (CF restricted to <20 g) or non­CF-sensing catheter, respectively. The primary end point was rate of EI post ablation. RESULTS: Baseline characteristics were evenly distributed between groups, without a case of preprocedural EI. With the same power setting, similar ablation time and average measured catheter tip temperature during posterior wall ablation just opposite to the esophagus in all patients in the restricted-CF group versus non-CF groups, there were no cases versus 9 (20%) cases of EI post ablation, respectively, with similar rate of freedom from atrial tachyarrhythmias at mean 31.3±6.5 months follow-up (68.2% versus 64.4%; P=0.3798). CONCLUSIONS: Risk for EI was minimized when CF was restricted to <20 g at the posterior left atrial wall, where the circumferential pulmonary vein isolation lesion set and the course of the esophagus overlapped in all subjects.