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.

miR-425-5p is negatively associated with atrial fibrosis and promotes atrial remodeling by targeting CREB1 in atrial fibrillation.

BACKGROUND: Progression of atrial fibrosis is vital for atrial remodeling in atrial fibrillation (AF). The main objective of the present study was to explore the association between miR-425-5p and atrial fibrosis as well as the resultant impact on atrial remodeling in AF. METHODS: Firstly, miRNAs sequencing and quantitative real-time polymerase chain reaction was used to screen and verify the miRNAs expression level in plasma and atrial tissue in AF patients. The left atrial fibrosis was evaluated with the left atrial low voltage area by using left atrial voltage matrix mapping. Cell counting kit-8 was used to detect fibroblasts proliferation. The AF mouse model was established using acetylcholine-CaCl2 injection for 7 days. Target gene prediction software, luciferase assay, and western blotting were employed to confirm the direct targets of miR-425-5p. RESULTS: Firstly, we demonstrated that miR-425-5p was downregulated in plasma and atrial tissue among the patients who suffered from AF. We then confirmed that the plasma's miR-425-5p level was negatively correlated with left atrial fibrosis in persistent AF, and catheter ablation could restore the decreased plasma miR-425-5p. Besides, receiver operating characteristic curve analysis revealed the miR-425-5p not only could differentiate AF from healthy control wit area under the curve (AUC) 0.921, but also discriminated persistent AF from paroxysmal AF with AUC 0.888. Furthermore, downregulation of miR-425-5p could promote atrial remodeling, and overexpression of miR-425-p could improve atrial remodeling and decrease susceptibility to atrial fibrillation. Finally, CREB1 was verified to be a direct target for miR-425-5p. CONCLUSIONS: Our findings suggested that miR-425-5p could serve as novel atrial fibrosis biomarker and contributed to atrial remodeling in AF.

Upregulation of miR­423 improves autologous vein graft restenosis via targeting ADAMTS­7.

Coronary artery bypass graft (CABG) is one of the primary methods of treating coronary heart disease (CHD); however, vein graft restenosis is a major limiting factor of the effectiveness of CABG. Emerging evidence has indicated that miR­423 is associated with vascular diseases. Additionally, upregulation of a disintegrin and metalloproteinase with thrombospondin motifs­7 (ADAMTS­7) contributes to neointima formation by promoting the proliferation and migration of vascular smooth muscle cells and inhibiting the proliferation and migration of endothelial cells. The aim of the present study was to examine the effects of miR­423 target, ADAMTS­7, on regulating vein graft disease and identify novel biomarkers for use in therapy of vein graft failure (VGF). Aberrant expression of miR­423 in plasma of patients with CHD prior to and following CABG confirms that miR­423 may be a suitable target for preventing VGF. Furthermore, a dual­luciferase reporter gene assay indicated that miR­423 directly interacted with ADAMTS­7 and suppressed its expression. Ectopic expression of miR­423 suppressed ADAMTS­7, resulting in decreased proliferation and migration rates of human umbilical vein smooth muscle cells by targeting ADAMTS­7, but resulted in increased proliferation and migration of human umbilical vein endothelial cells in vitro. Overexpression of miR­423 also enhanced re­endothelialization and decreased neointimal formation in a rat vein graft model. In conclusion, the results of the present study demonstrated that the miR­423/ADAMTS­7 axis may possess potential clinical value for the prevention and treatment of restenosis in patients with CHD following CABG.

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.

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.

Qualitative research of alternatively splice variants of fibronectin in different development stage of mice heart.

BACKGROUND: Fibronectin (FN) plays vital roles in cell adhesion, differentiation, proliferation and migration. It is involved in the process of embryonic development and is highly conserved during evolution. The EIIIA and EIIIB of FN show a very high degree of homology among vertebrates. Embryos deleting both EIIIA and EIIIB displayed multiple embryonic cardiovascular defects, implying their crucial role during embryogenesis. The correlation of spliced EIIIB, EIIIA, and IIICS of FN to heart development was studied by observing their chronological expression in mice heart. METHODS: C57 mice embryos at E11.5, E12.5, E13.5, E14.5, E15.5, E16.5, E17.5, E18.5, E19.5 days, postnatal day 1 (P1d), and adult male mice (3 months) were used. For each alternatively spliced FN1 domain (EIIIB, EIIIA and IIICS), primer pairs were designed for specific amplification. Total RNA was extracted from the heart tissue, reverse transcripted to cDNA, followed by RT-PCR with specific primers. The PCR amplification was verified by agarose gel electrophoresis, showing specific fragments of the expected sizes. RESULTS: In adult mice heart, only alternatively splice variants of EIIIA-, EIIIB-, IIICS+ were expressed. While in embryonic mice, spliced variant of EIIIA+/-, EIIIB+/-, IIICS+ were observed. The expression of EIIIA and EIIIB changed during heart development. CONCLUSIONS: FN is crucial for the normal development of the embryonic heart by modulating cardiac neural crest (CNC) proliferation and survival, and maintenance of CNC cells. FN1 gene seems to play a significant role by expression of highly conserved EIIIA and EIIIB in embryonic heart development.