Characteristics of Right-Sided Accessory Pathways Associated With Right Cardiac Veins.

BACKGROUND: The anatomy of myocardial fibers around the right cardiac veins (RCVs) and their roles in accessory pathways (APs) are rarely reported. METHODS: Six RCV-APs were identified from 566 patients with right-sided APs. Mapping of retrograde atrial activation was performed using CARTO 3 system under orthodromic tachycardia or right ventricular pacing. Venography of RCVs was acquired at the earliest retrograde atrial activation. RESULTS: Patients enrolled had a median age of 30 (11-51) years, 5 of them were male. Venography of RCVs could be classified into 3 distinct patterns based on the identified ventricular branches, right marginal vein only (type I; n=3), both right marginal vein and anterior cardiac veins (type II; n=2), and anterior cardiac vein only (type III; n=1). Patients with type I venography had rS QRS pattern in lead V1, negative delta wave in lead III and negative or isoelectric delta wave in lead aVF. However, patients with type II and III venography had QS QRS patterns in lead V1 and variable patterns of delta wave in inferior leads. Earliest retrograde atrial activation was found at a median of 16.75 (14.60-20.00) mm away from the tricuspid annulus, all with A larger than V. At the earliest retrograde atrial activation, far-field ventricular electrogram was found 30 ms later than QRS onset in 1 patient under sinus rhythm. AP conduction was eliminated by mechanical pressure in 2 and by radiofrequency ablation in 4 at the ostium of the veins colocalizing with the earliest retrograde activation of the right atrium. No recurrence was observed during 36 (10-60) months follow-up. CONCLUSIONS: The RCV-AP is a rare form of right-sided APs characterized by atrial insertions distant from the annulus. ECG-speculated ventricular insertion sites conformed to the location of identified RCVs.

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.

Safety and efficacy of His-bundle pacing/left bundle branch area pacing versus right ventricular pacing: a systematic review and meta-analysis.

BACKGROUND: Recent studies have demonstrated that right ventricular pacing (RVP) has deleterious effects on non-synchronized ventricular contraction, while His-bundle pacing (HBP) or left bundle branch area pacing (LBBaP) contribute to improvements in patients' mid- and long-term outcomes. This meta-analysis aimed to compare the safety and efficacy of physiologic pacing (HBP/LBBaP) versus those of RVP. METHODS: A systematic search of PubMed, Cochrane Library, and Embase was conducted for studies that compared the effects of physiologic pacing and RVP. All eligible studies were published before January 1, 2021 and were conducted in humans. STATA software version 15.0 was used for all the data analyses. RESULTS: Twenty articles (n = 2787 patients) were included in this meta-analysis. Compared to RVP, physiologic pacing was associated with a significantly shorter QRS duration and better cardiac function. Physiologic pacing was also correlated with lower rates of mitral regurgitation, pacing-induced cardiomyopathy, death, heart failure hospitalization, and atrial fibrillation, although the above results were not statistically significant. In addition, RVP led to the achievement of higher success rates than physiologic pacing, a shorter fluoroscopic time and mean procedure duration, a lower pacing threshold: the results were statistically significant. Compared with HBP, LBBaP appeared to have some advantages in R wave amplitudes, pacing threshold, fluoroscopic time, procedure time, and success rate, with statistically significant differences. Whereas HBP was associated with fewer surgical complications and shorter QRS duration, the results were not statistically significant. CONCLUSION: Physiologic pacing (HBP/LBBaP) might be a better strategy than RVP and improve long-term clinical outcomes like cardiac function. Although LBBaP appears to have some advantages over HBP, the long-term benefits are still controversial. More large-scale randomized clinical trials are needed for further verification.

Effects of SGLT2 inhibitors on cardiovascular, renal, and major safety outcomes in heart failure: A meta-analysis of randomized controlled trials.

AIMS: Sodium-glucose co-transporter 2 inhibitor (SGLT2i), initially introduced for the treatment of diabetes mellitus (DM), demonstrates cardiovascular and renal benefits in patients with heart failure (HF). We aimed to conduct a meta-analysis of its effects on cardiovascular, renal, and major safety outcomes in HF. METHODS AND RESULTS: PubMed, Embase, Cochrane Library, and Web of Science were searched using the terms of "SGLT2i and HF" or "SGLT2i *". Seven randomized, placebo-controlled trials comprising 14,113 HF patients (mean age, 66.0 years; female, 27.6%; DM, 58.9%) were included. SGLT2i treatment was associated with lower incidences (compared with placebo) of the composite outcomes of cardiovascular death or hospitalization for HF (HHF) (ratio risk [RR] 0.773; 95% confidence interval [CI], 0.719-0.831; p < 0.001; I2 = 8.1%), cardiovascular death (RR 0.872; 95% CI, 0.788-0.964; p = 0.008; I2 = 0.0%), HHF (RR 0.722; 95% CI, 0.657-0.793; p < 0.001; I2 = 15.4%) and serious decrease in renal function (RR 0.673; 95% CI, 0.549-0.825; p < 0.001; I2 = 17.7%). SGLT2i treatment was associated with a lower incidence of serious adverse events (SAEs) (RR 0.867; 95% CI, 0.808-0.930; p < 0.001; I2 = 60.1%), but a higher incidence of volume depletion (RR 1.177; 95% CI, 1.040-1.333; p = 0.010; I2 = 0.0%). Analysis on patients without DM showed consistent results, except for cardiovascular death. CONCLUSION: SGLT2i treatment contributed to better cardiovascular and renal outcomes in patients with HF, regardless of the presence or absence of DM. SGLT2i also resulted in a lower incidence of SAEs, although a higher incidence of volume depletion was observed.

Effects of Hot Balloon vs. Cryoballoon Ablation for Atrial Fibrillation: A Systematic Review, Meta-Analysis, and Meta-Regression.

Background: Balloon-based catheter ablations, including hot balloon ablation (HBA) and cryoballoon ablation (CBA), have rapidly emerged as alternative modalities to conventional catheter atrial fibrillation (AF) ablation owing to their impressive procedural advantages and better clinical outcomes and safety. However, the differences in characteristics, effectiveness, safety, and efficacy between HBA and CBA remain undetermined. This study compares the characteristic and prognosis differences between HBA and CBA. Methods: Electronic search was conducted in six databases (PubMed, Embase, Cochrane Library, Web of Science, ClinicalTrial.gov, and medRxiv) with specific search strategies. Eligible studies were selected based on specific criteria; all records were identified up to June 1, 2021. The mean difference, odds ratios (ORs), and 95% confidence intervals (CIs) were calculated to evaluate the clinical outcomes. Heterogeneity and risk of bias were assessed using predefined criteria. Results: Seven studies were included in the final meta-analysis. Compared with CBA, more patients in the HBA group had residual conduction and required a higher incidence of touch-up ablation (TUA) [OR (95% CI) = 2.76 (2.02-3.77), P = 0.000]. The most frequent sites of TUA were the left superior pulmonary veins (PVs) in the HBA group vs. the right inferior PVs in the CBA group. During HBA surgery, the left and right superior PVs were more likely to have a higher fluid injection volume. Furthermore, the procedure time was longer in the HBA group than in the CBA group [weighted mean difference (95% CI) = 14.24 (4.39-24.09), P = 0.005]. Patients in the CBA group could have an increased risk of AF occurrence, and accepted more antiarrhythmic drug therapy; however, the result was insignificant. Conclusions: HBA and CBA are practical ablation approaches for AF treatment. Patients who received HBA had a higher incidence of TUA and longer procedure time. Clinical outcomes during the mid-term follow-up between HBA and CBA were comparable. Systematic Review Registration: https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=259487, identifier: CRD42021259487.

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.

A novel ablation strategy of premature ventricular contractions originating from summit guided by CartoUNIVU module.

BACKGROUND: Premature ventricular contractions (PVCs) from left ventricular (LV) summit remain challenging for the risk of coronary artery injury. Computed tomographic or intracardiac echocardiography may be helpful, but both still have many limitations. CartoUNIVU module has rarely been used in PVC ablation. METHODS: A total of 22 patients (14 men: mean age 56.4 ± 13.3 years) with an electrocardiogram indication of summit PVCs were included in the two centers study. A novel strategy ablation with the Image Integration Module CartoUNIVUTM module was performed for all the patients with PVCs originating from LV summit area, especially to prevent the coronary artery injury. RESULTS: The procedure time was 78.6 ± 22.7 minutes, and the fluoroscopy time was 12.5 ± 3.1 minutes. The distance between the target and nearest coronary artery was 8.0 ± 3.1 mm. Three patients with the distance to the nearest coronary artery <5 mm. During a mean follow-up of 11.0 ± 1.7 months, 21/22 (95.5%) patients were free from clinical PVC. No coronary artery injury was detected in the all the ablation procedures. CONCLUSION: The novel strategy ablation with the Image Integration Module CartoUNIVU module is safe and effective for PVCs originating from LV summit area, especially to prevent the coronary artery injury.

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.

Lambda-like ST-segment elevation in acute myocardial infarction triggered by coronary spasm may be a new risk predictor for lethal ventricular arrhythmia: A case report.

RATIONALE: The lambda-like ST-elevation electrocardiography (ECG) pattern is extremely rare in patients with type 2 myocardial infarction (T2MI) triggered by coronary spasm. When this ECG pattern appears, sudden cardiac death (SCD) caused by lethal ventricular arrhythmia may occur because clinicians do not pay sufficient attention to this phenomenon. PATIENT CONCERNS: We describe a 41-year-old man who presented with steep down-sloping ST-segment elevation, paroxysmal ventricular tachycardia, severe sinus bradycardia, and intermittent complete atrioventricular block on ECG during the sudden recurrence of clinical symptoms. DIAGNOSIS: T2MI complicated with lethal arrhythmia and caused by coronary spasm. INTERVENTIONS: The patient received an implantable cardioverter defibrillator (ICD) for SCD caused by lethal ventricular arrhythmia and received long-term calcium-blocker and nitroglycerin therapy. OUTCOMES: At a 3-month follow-up, no recurrence was noted. LESSONS: The lambda-like ST-elevation pattern is identified with other ST-elevation patterns by geometry and may be a new risk predictor for lethal ventricular arrhythmia on ECG. When this pattern is identified, clinicians should adopt aggressive therapeutic strategies, including ICD implantation and etiological treatment.

Combination of catheter ablation for non-valvular atrial fibrillation and left atrial appendage occlusion in a single procedure.

Patients with atrial fibrillation (AF) have an increased risk of stroke and systemic embolism. Catheter ablation (CA) is increasingly applied for the treatment for drug-refractory AF; however, its long-term success rate is <50%. It has been proved that percutaneous left atrial appendage occlusion (LAAO) exerts the same efficacy as novel oral anti-coagulants [(N)OACs] in reducing thromboembolic events. The present study investigated whether a combined procedure of AF ablation and LAAO may be feasible and efficacious. CA was performed for patients with AF and a high risk of stroke according to their CHADS2 or CHA2DS2-VASc score, and LAAO was performed using the Watchman device. A total of 25 patients (40% females; mean age, 64.2±3.5 years) who were treated between July 2016 and June 2017 were included in the present study. The median CHA2DS2-VASc score was 4.5 (range, 2-6) and the median HAS-BLED score was 3.17 (range, 1-7). Successful CA and LAAO were performed in 100% of cases. All patients met the criteria for successful LAAO. At the 6-month follow-up, complete sealing of the LAA was achieved in 23 patients (92%), while a minimal residual flow (<5 mm) was detected in 2 patients (8%). In 24 patients (96%), the administration of (N)OACs was terminated and aspirin administration was initiated at the 6-month follow-up. (N)OAC treatment was maintained in 1 patient (4%) on the basis of transient ischemic attack. During the 6-month follow-up period, 3 patients who had a recurrence of AF received a repeated ablation. In conclusion, the combination of CA and LAAO in a single procedure is feasible, safe and efficacious for patients with non-valvular AF at a high risk of stroke, and a contraindication regarding the use of (N)OACs.

Novel hydroxybutyl chitosan nanoparticles for siRNA delivery targeting tissue factor inhibits proliferation and induces apoptosis in human vascular smooth muscle cells.

Chitosan, a polysaccharide isolated from shrimp and other crustacean shells, has been widely investigated for DNA and siRNA delivery. Despite substantial effort having been made to improve chitosan as a non­viral gene delivery vector, the application is severely limited by its poor solubility under physiological conditions. Hydroxybutyl chitosan (HBC), a modified chitosan, is soluble under neutral conditions. Tissue factor (TF) is involved in the pathogenesis of cardiovascular diseases by promoting thrombus formation and inducing the migration and proliferation of vascular smooth muscle cells. Targeting TF is an attractive therapeutic strategy for cardiovascular diseases. In the present study, the use of HBC for the transfer of TF­siRNAs into human umbilical vein smooth muscle cells (HUVSMCs) was investigated, and the effects of TF knockdown on cell proliferation and apoptosis were examined. HBC/siRNA nanoparticles were produced by mixing HBC and siRNA solutions with the assistance of tripolyphosphate buffer. The transfection efficiency with these nanoparticles was 74±2.5%, which was determined using a fluorescence­labeled siRNA under fluorescence microscopy. The delivery of HBC/TF­siRNA resulted in reductions in the production of cellular and soluble TF protein in HUVMSCs, which were measured using western blotting and enzyme­linked immunosorbent assay, respectively. TF knockdown led to inhibited cell proliferation, as assessed using a Cell Counting Kit­8 assay, and increased cell apoptosis, determined using Annexin V­fluorescein isothiocyanate staining. These findings suggested that HBC may be a promising vector for siRNA delivery, and that in vivo HBC/siRNA nanoparticle delivery targeting TF may be a potential option for the treatment of cardiovascular diseases, which warrants further investigation.