Blockade of SK4 channels suppresses atrial fibrillation by attenuating atrial fibrosis in canines with prolonged atrial pacing.

Background: We previously found that intermediate conductance Ca2+-activated K+ channel (SK4) might be an important target in atrial fibrillation (AF). Objective: To investigate the role of SK4 in AF maintenance. Methods: Twenty beagles were randomly assigned to the sham group (n=6), pacing group (n=7), and pacing+TRAM-34 group (n=7). Rapid atrial pacing continued for 7 days in the pacing and TRAM-34 groups. During the pacing, the TRAM-34 group received TRAM-34 intravenous injection (10 mg/Kg) 3 times per day. Atrial fibroblasts isolated from canines were treated with angiotensin II or adenovirus carrying the SK4 gene (Ad-SK4) to overexpress SK4 channels. Results: TRAM-34 treatment significantly suppressed the increased intra-atrial conducting time (CT) and AF duration in canines after rapid atrial pacing (P<0.05). Compared with the sham group, the expression of SK4 in atria was higher in the pacing group, which was associated with an increased number of myofibroblasts and levels of extracellular matrix in atrium (all P<0.05), and this effect was reversed by TRAM-34 treatment (all P<0.05). In atrial fibroblasts, the increased expression of SK4 induced by angiotensin II stimulation or Ad-SK4 transfection contributed to higher levels of P38, ERK1/2 and their downstream factors c-Jun and c-Fos, leading to the increased expression of α-SMA (all P<0.05), and all these increases were markedly reduced by TRAM-34 treatment. Conclusion: SK4 blockade suppressed AF by attenuating cardiac fibroblast activity and atrial fibrosis, which was realized through not only a decrease in fibrogenic factors but also inhibition of fibrotic signaling pathways.

Supraventricular tachycardia in patients with coronary sinus stenosis/atresia: Prevalence, anatomical features, and ablation outcomes.

BACKGROUND: Supraventricular tachycardia (SVT) with coronary sinus (CS) ostial atresia (CSA) or coronary sinus stenosis (CSS) causes difficulty in electrophysiological procedures, but its characteristics are poorly understood. OBJECTIVE: Study the anatomical and clinical features of SVT patients with CSA/CSS. METHODS: Of 6128 patients with SVT undergoing electrophysiological procedures, consecutive patients with CSA/CSS were enrolled, and the baseline characteristics, imaging materials, intraoperative data, and follow-up outcomes were analyzed. RESULTS: Thirteen patients, seven with CSA and six with CSS, underwent the electrophysiological procedure. Decapolar catheters were placed into the proximal CS in three cases, while the rest were placed at the free wall of the right atrium. Fourteen arrhythmias were confirmed: four atrioventricular nodal reentrant tachycardias, five left-sided accessory pathways, three paroxysmal atrial fibrillations, and two atrial flutters (AFLs). In addition to three patients who underwent only an electrophysiological study, the acute ablation success rate was 100% in 10 cases, with no procedure-related complications. After a median follow-up period of 59.6 months, only one case of atypical AFL recurred. For those cases (seven CSA and two CSS) with a total of 10 anomalous types of CS drainage, three types were classified: from the CS to the persistent left superior vena cava (n = 3), from an unroofed CS (n = 3), and from the CS to the small cardiac vein (n = 3) or Thebesian vein (n = 1). CONCLUSION: Patients with CSA/CSS may develop different kinds of SVT. Electrophysiological procedures for such patients are feasible and effective. An individualized mapping strategy based on the three types of CS drainage will be helpful.

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.

Blocking Intermediate-Conductance Calcium-Activated Potassium Channels in the Macrophages Around Ganglionated Plexi Suppresses Atrial Fibrillation Vulnerability in Canines With Rapid Atrial Pacing.

Previous studies have indicated that ganglionated plexi (GP) function influences atrial fibrillation (AF) vulnerability, and intermediate-conductance calcium-activated potassium channels (SK4) have a close relationship with cardiomyocyte automaticity and the induction of AF. However, the effects of the SK4 inhibitor on GP function and AF vulnerability are unknown. Eighteen beagles were randomly divided into a control group (n = 6), rapid atrial pacing (RAP) group (n = 6), and triarylmethane-34 (TRAM-34, an SK4 inhibitor) group (n = 6). TRAM-34 (0.3 ml, 15 mmol/L) and saline were locally injected into GPs in the TRAM-34 group dogs and dogs from the other groups, respectively. After that, dogs in the RAP and TRAM-34 groups were subjected to RAP, and the neural activity of anterior right GP (ARGP) and atrial electrophysiology were measured. The levels of inflammatory cytokines and function of macrophages in the ARGP were measured in the three groups. At 10 min after TRAM-34 injection, ARGP activity and atrial electrophysiology did not significantly change. The atrial pacing shortened effective refractory period (ERP) values at all sites and increased the AF vulnerability and ARGP neural activity, while TRAM-34 reversed these changes. The levels of CD68 + cells, induced nitric oxide synthase (iNOS), interleukin (IL)-1ß, IL-6, and tumor necrosis factor (TNF)-α in the ARGP tissues were higher in the RAP group and TRAM-34 group than they were in the control group. Furthermore, the levels of the CD68 + cells, iNOS, and inflammatory cytokines in the ARGP tissues were higher in the pacing group than those in the TRAM-34 group. Based on these results, administration of TRAM-34 into the atrial GP can suppress GP activity and AF vulnerability during atrial pacing. The effects of TRAM-34 might be related to macrophage polarization and the inflammatory response of GP.

Radiofrequency Catheter Ablation of Supraventricular Tachycardia in Patients With Pulmonary Hypertension: Feasibility and Long-Term Outcome.

BACKGROUND: Supraventricular tachycardia (SVT) occurs commonly and is strongly correlated with clinical deterioration in patients with pulmonary hypertension (PH). This study aimed to investigate the feasibility and long-term outcome of radiofrequency catheter ablation (RFCA) in PH patients with SVT. MATERIALS AND METHODS: Consecutive PH patients with SVT who were scheduled to undergo electrophysiological study and RFCA between September 2010 and July 2019 were included. The acute results and long-term success of RFCA were assessed after the procedure. RESULTS: In total, 71 PH patients with 76 episodes of SVT were analyzed. Cavotricuspid isthmus-dependent atrial flutter (n = 33, 43.5%) was the most common SVT type, followed by atrioventricular nodal reentrant tachycardia (n = 16, 21.1%). Of the 71 patients, 60 (84.5%) underwent successful electrophysiological study and were subsequently treated by RFCA. Among them, acute sinus rhythm was restored in 54 (90.0%) patients, and procedure-related complications were observed in 4 (6.7%) patients. Univariate logistic regression analysis showed that cavotricuspid isthmus-independent atrial flutter [odds ratio (OR) 25.00, 95% confidence interval (CI) 3.45-180.98, p = 0.001] and wider pulmonary artery diameter (OR 1.19, 95% CI 1.03-1.38; p = 0.016) were associated with RFCA failure. During a median follow-up of 36 (range, 3-108) months, 7 patients with atrial flutter experienced recurrence, yielding a 78.3% 3-year success rate for RFCA treatment. CONCLUSION: The findings suggest that RFCA of SVT in PH patients is feasible and has a good long-term success rate. Cavotricuspid isthmus-independent atrial flutter and a wider PAD could increase the risk for ablation failure.