Focus on the Role of Inflammation as a Bridge between Ferroptosis and Atrial Fibrillation: A Narrative Review and Novel Perspective.

In this comprehensive review, we examine the intricate interplay between inflammation, ferroptosis, and atrial fibrillation (AF), highlighting their significant roles in AF pathophysiology and pathogenesis. Augmented inflammatory responses are pivotal to AF, potentially leading to atrial remodeling and reentry phenomena by impacting calcium channels and atrial tissue fibrosis. A strong correlation exists between inflammatory cytokines and AF, underscoring the importance of inflammatory signaling pathways, such as NOD-like receptor thermal protien domain associated protein 3 (NLRP3) inflammasome, Nuclear Factor kappa B (NF- κ B) signaling, and Tumor necrosis factor- α (TNF- α ) signaling in AF development. Ferroptosis, a non-apoptotic regulated mode of cell death, has been widely studied in relation to cardiovascular diseases including heart failure, myocardial infarction, cardiomyopathy, and reperfusion injury. The interaction between ferroptosis and inflammation is complex and mutually influential. While significant progress has been made in understanding the inflammation-AF relationship, the role of inflammation as a conduit linking ferroptosis and AF remains underexplored. The specific pathogenesis and key molecules of atrial fibrosis caused by ferroptosis are still not fully understood. Here we review the role of inflammatory signaling in ferroptosis and AF. We elucidated the association between ferroptosis and AF, aiming to unveil mechanisms for targeted inhibition of atrial cell fibrosis and to propose novel therapeutic strategies for AF. This exploration is vital for advancing our knowledge and developing more effective interventions for AF, a condition deeply intertwined with inflammatory processes and ferroptotic pathways.

A case of atrial tachycardia originating from the left atrial roof successfully ablated via the pulmonary artery approach.

A 60-year-old male patient suffered from frequent episodes of atrial tachycardia (AT), after the index procedure of catheter ablation for paroxysmal atrial fibrillation. During the repeat procedure, the activation map showed that the earliest activation site was located at the roof of left atrium. Multiple ablations at the earliest activation site on the roof failed to terminate the AT; however, ablation within the pulmonary artery at an adjacent anatomical site successfully eliminated the AT, even without recording distinct near-field potential.

Long Non-coding RNA Involved in the Pathophysiology of Atrial Fibrillation.

BACKGROUND: Atrial fibrillation (AF) is a prevalent and chronic cardiovascular disorder associated with various pathophysiological alterations, including atrial electrical and structural remodeling, disrupted calcium handling, autonomic nervous system dysfunction, aberrant energy metabolism, and immune dysregulation. Emerging evidence suggests that long non-coding RNAs (lncRNAs) play a significant role in the pathogenesis of AF. OBJECTIVE: This discussion aims to elucidate the involvement of AF-related lncRNAs, with a specific focus on their role as miRNA sponges that modulate crucial signaling pathways, contributing to the progression of AF. We also address current limitations in AF-related lncRNA research and explore potential future directions in this field. Additionally, we summarize feasible strategies and promising delivery systems for targeting lncRNAs in AF therapy. CONCLUSION: In conclusion, targeting AF-related lncRNAs holds substantial promise for future investigations and represents a potential therapeutic avenue for managing AF.

Puerarin Protects against Myocardial Ischemia/Reperfusion Injury by Inhibiting Ferroptosis.

This study investigated whether pretreatment with puerarin could alleviate myocardial ischemia/reperfusion (I/R) injury in a cardiomyocyte oxygen-glucose deprivation and reoxygenation (OGD/R) model and in a mouse I/R injury model. For in vitro experiments, H9C2 cells were divided into control, erastin, OGD/R, OGD/R + puerarin, and OGD/R + ferrostatin (Fer)-1 groups. Parameters related to ferroptosis included levels of malondialdehyde (MDA), 4-hydroxynonenal (4-HNE), ATP, reactive oxygen species (ROS), glutathione (GSH), prostaglandin endoperoxide synthase (Ptgs) 2 mRNA, glutathione peroxidase (GPX) 4 protein and iron. In H9C2 cells, puerarin or Fer-1 pretreatment reduced ferroptosis, as indicated by decreased ROS and increased GSH, ATP levels. In vivo, wild-type mice were randomly divided into sham, I/R + vehicle, I/R + puerarin, and IR + Fer-1 groups. The I/R model was established by 30 min of left anterior descending artery occlusion followed by 24 h of reperfusion. Pretreatment with puerarin or Fer-1 significantly reduced infarct size in I/R mice, and decreased the activities of Myeloperoxidase (MPO) and cardiac enzymes such as creatine kinase MB isoenzyme (CK-MB), aspartate aminotransferase (AST), and lactate dehydrogenase (LDH) compared to those in the vehicle-treated group. Puerarin also reduced the production of MDA and 4-HNE, reduced the mRNA expression of Ptgs2 mRNA, and increased GPX4 protein expression. These results showed that puerarin exerted protective effects against myocardial I/R injury by inhibiting ferroptosis and inflammation, and therefore may have therapeutic potential for treatment of acute myocardial infarction.

Comparisons of electrophysiological characteristics, pacing parameters and mid- to long-term effects in right ventricular septal pacing, right ventricular apical pacing and left bundle branch area pacing.

BACKGROUND: As a near-physiological pacing innovation, left bundle branch area pacing (LBBAP) has drawn much attention recently. This study was aimed to investigate the electrophysiological characteristics, unipolar/bipolar pacing parameters and mid- to long-term effects and safety of three different pacing methods and identify possible predictors of adverse left ventricular remodeling. METHODS: Ninety-two patients were divided into the LBBAP group, right ventricular septal pacing (RVSP) group and right ventricular apical pacing (RVAP) group. Baseline information, electrophysiological, pacing and echocardiographic parameters were collected. RESULTS: The three pacing methods were performed with a similar high success rate. The paced QRSd was significantly different among the LBBAP, RVSP and RVAP groups (105.93 ± 15.85 ms vs. 143.63 ± 14.71 ms vs. 155.39 ± 14.17 ms, p < 0.01). The stimulus to left ventricular activation time (Sti-LVAT) was the shortest in the LBBAP group, followed by the RVSP and RVAP groups (72.80 ± 12.07 ms vs. 86.29 ± 8.71 ms vs. 94.14 ± 10.14 ms, p < 0.001). LBBAP had a significantly lower tip impedance during the procedure and 3-month follow up as compared to RVSP and RVAP (p < 0.001). Higher bipolar captured thresholds were observed in LBBAP during the procedure (p < 0.001). Compared to the baseline values, there was a greater reduction in left ventricular end-diastolic dimension (LVEDD) in the LBBAP group (p = 0.046) and a significant enlargement in LVEDD in the RVAP group (p = 0.008). Multiple regression analysis revealed that the Sti-LVAT was a significant predictor of LVEDD at 12 months post-procedure. At the 24-h post-procedure, significant elevations were observed in the cTnI levels in LBBAP (p < 0.001) and RVSP (p < 0.05). More transient RBB injury was observed in LBBAP. But no significant difference was found in cardiac composite endpoints among three groups (p > 0.05). CONCLUSIONS: LBBAP demonstrated a stable captured threshold, a low tip impedance and a high R-wave amplitude during the 12-month follow-up. Left ventricular remodeling was improved at 12 months post-procedure through LBBAP. The Sti-LVAT was a significant predictor of left ventricular remodeling. LBBAP demonstrated its feasibility, effectiveness, safety and some beneficial electrophysiological characteristics during this mid- to long-term follow-up, which should be confirmed by further studies.

Emergency catheter ablation: A feasible option for acute treatments of patients with unstable pre-excited atrial fibrillation.

BACKGROUND: Pre-excited atrial fibrillation (AF) is associated with increased risk of life-threatening events. However, at times, patients with pre-excited AF still repetitively suffer from hemodynamic disturbance, with resistance to acute treatments of antiarrhythmic therapy and cardioversion. METHODS: To evaluate the feasibility in correcting hemodynamic disturbance, patients with pre-excited AF who underwent catheter ablation of accessory pathway as an emergency procedure, were retrospectively collected from two centers of China. The medical records of patients were analyzed and summarized in this case series. RESULTS: Five patients with pre-excited AF who received emergency catheter ablation of accessory pathway, were collected from two contributor centers and reported in this case series. All collected patients still repetitively suffered from hemodynamic disturbance induced by rapid anterograde conduction of AF via pathway, even guideline recommended acute interventions of intravenous antiarrhythmic therapy and cardioversion had been performed. Finally, as an emergency procedure, catheter ablation of accessory pathway was performed in collected patients. Correspondingly, the hemodynamic unstable status was greatly relieved. Meanwhile, all collected patients with high risk of pre-excited AF were combined with left-sided accessory pathway, with shortest RR interval of widened pre-excited QRS complex less than 250 ms. Thus, combination with left-sided pathway is proposed as an indicator for the increased risk of life-threatening events in patients with high risk of pre-excited AF. CONCLUSIONS: Emergency catheter ablation of accessory pathway is an effective option for the acute managements of patients with high risk of pre-excited AF in unstable hemodynamics, which is resistant to antiarrhythmic therapy and cardioversion.

Long-term outcomes of a time to isolation - based strategy for cryoballoon ablation compared to radiofrequency ablation in patients with symptomatic paroxysmal atrial fibrillation.

BACKGROUND: Cryoballoon ablation (CBA) is one of the most commonly used technologies designed for pulmonary vein isolation (PVI) for paroxysmal atrial fibrillation (PAF), although the dosing of CBA remains controversial. We evaluated the long-term efficacy and safety of a novel individualized strategy of CBA compared to radiofrequency ablation (RFA) for patients with PAF. METHODS: In this observational study, symptomatic patients with drug-refractory paroxysmal AF were prospectively consented and enrolled in four centers, being assigned either to the CBA or RFA arm for ablation. In the CBA group, we used a time to isolation (TTI) - based dosing protocol. The primary endpoint was the recurrence of atrial arrhythmia >30 s following a 90-day blanking period. The secondary endpoint was procedure-related complications and procedure parameters. RESULTS: A total of 500 patients were recruited in either the CBA group (n = 247) or the RFA group (n = 253) between January 2017 and July 2018. After a median follow-up of 778 days, the atrial tachyarrhythmia-free survival was 71.7% in the CBA group and 67.0% in the RFA group. CBA and RFA displayed similar major or minor complication occurrence, while the former had a significantly shorter procedure duration (82.5 min vs. 141.1 min, p < .001) and left atrial dwell time (60.1 min vs. 109.9 min, p < .001) but longer fluoroscopy exposure (13.8 min vs. 8.1 min, p < .001). CONCLUSION: Compared to RFA, our TTI-based CBA dosing protocol showed comparable efficacy and safety, with a significantly reduced procedure duration in patients with PAF.

Efficacy of ablation index-guided pulmonary vein isolation in patients with paroxysmal atrial fibrillation.

BACKGROUND: Ablation index (AI) is a novel technology of ablation lesion quality to help improve homogeneity of lesion size and continuity. In this study, we aim to evaluate whether AI-guided PVI improves clinical outcomes compared to CF-guided PVI in patients with paroxysmal AF (PAF). METHODS: Patients undergoing first-time radiofrequency ablation for PAF were randomized in a 2:1 ratio to two groups: AI-guided PVI and CF-guided PVI. In the AI group, AI ≥500 was recommended at the anterior/superior/inferior walls, 350-400 at the posterior wall, and inter-lesion distance ≤4 mm. The primary endpoint is the freedom from atrial arrhythmia recurrence during 12 months follow-up, without antiarrhythmic drug therapy (ADT). The key secondary endpoints include intra-procedural efficiency and peri-procedural complications. RESULTS: Two hundred twenty five patients were randomized (AI group [n = 149] and CF group [n = 76]). First-pass isolation rate in AI group was significantly higher than that in CF group (58.3% vs. 43.4%, p = .035). After a median follow-up of 12.2 months, 154/225 (68.4%) of patients were free from atrial arrhythmia recurrence without ADT, which was higher in AI group compared with CF group, but without significant difference (71.1% vs. 63.2%, p = .253). The incidence of peri-procedural complications is low and without difference between two groups. CONCLUSIONS: AI-guided ablation provided higher acute efficacy than CF-guided ablation in PV isolation for patients with paroxysmal AF. The long-term success rate in AI group was higher than CF group, but did not reach statistical significance.

C-reactive protein and atrial fibrillation: Insights from epidemiological and Mendelian randomization studies.

BACKGROUND AND AIMS: This study aimed to investigate the role of C-reactive protein (CRP) in atrial fibrillation (AF) from epidemiological and genetic perspectives. METHODS AND RESULTS: Individual-level data from the Kailuan cohort recruited between 2006 and 2017 were included. Serum CRP levels were measured at baseline and at biennial follow-up visits, and incident AF was ascertained from biennial 12-lead ECG assessment and medical records. Cox proportional hazards models were used to assess the association between baseline CRP levels or cumulative exposure to CRP and incident AF. A meta-analysis including nine prospective cohort studies and our current study was also conducted. Mendelian randomization (MR) analysis was performed to evaluate the aetiological role of CRP in AF. In our observational study (n = 86,424), high baseline CRP levels (>3 mg/L), compared with low CRP (<1 mg/L), were not significantly associated with AF risk (HR: 1.18; 95% CI: 0.99-1.40). High cumulative exposure to CRP (HR: 1.49; 95%CI: 1.01-2.21) was significantly associated with an increased risk of AF. Our meta-analysis suggested a positive association between elevated CRP levels and incident AF (relative risk: 1.27; 95% CI: 1.14-1.42). However, no significant association between genetically determined CRP and AF risk was observed in the MR analysis. CONCLUSION: Evidence from observational studies suggested that elevated serum CRP levels were positively associated with incident AF, while the causal effects of CRP on AF were not supported by the MR analysis. CLINICAL TRIAL REGISTRATION: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR-TNRC-11001489.

Sub-pocket small-hole drainage for pocket hematoma after cardiac device implantation.

AIMS: Pocket hematoma is a common complication associated with cardiac device implantation, but there are limited strategies to deal with this problem. We aimed to evaluate the effectiveness of sub-pocket small-hole drainage (SSD) as a new way to manage severe pocket hematoma. METHODS: A total of 11 patients with severe pocket hematoma were selected for this case series study. The SSD procedure was performed and wound healing was monitored. RESULTS: The SSD procedure was successfully performed on all 11 patients. The time window for SSD was 10-14 days (mean 12.0 ± 1.3 days) after cardiac device implantation. On average, 18.3 ± 2.3 ml of hematoma was drained , with a mean procedural time of 21.3 ± 2.6 min. The patients were followed up for 4-12 months and all pockets healed well, without any complications such as pocket infection, bleeding, device exposure, and electrode fracture. CONCLUSION: Sub-pocket small-hole drainage is an alternative approach for dealing with severe pocket hematoma after cardiac device implantation.

Anatomical insights into posterior wall isolation in patients with atrial fibrillation: A hypothesis to protect the esophagus.

INTRODUCTION: Left atrial posterior wall (LAPW) isolation may be performed as an additional atrial fibrillation (AF) ablation strategy based on pulmonary vein isolation. A modified posterior-inferior line (MPL) was proposed for reducing esophageal injury. The aim of this study was to evaluate the anatomical characteristics of the MPL, compared with the conventional posterior line (CPL). METHODS AND RESULTS: Multidetector computed tomography was performed in 102 consecutive AF patients (male/female = 60/42) preoperative, and the parameters were evaluated as follows: the distance from MPL and CPL to the esophagus, fat pad presence and thickness in the course of MPL and CPL, and the esophageal route below CPL. The average distance from the MPL to the esophagus was longer than from CPL to the esophagus (3.7 ± 1.5 vs. 1.7 ± 0.4 mm, p < .001). Proportion of fat pad was higher in the course of MPL than CPL. The myocardium tissue and fat pad under MPL was thicker than under CPL (2.9 ± 1.1 vs. 1.6 ± 0.3 mm, p < .001; 1.4 ± 0.6 vs. 0.9 ± 0.2 mm, p < .001), respectively. In patients whose esophagus was unconfined in a triangular space at the left inferior pulmonary vein level, the average distance from MPL to esophagus was longer than the confined patients (4.0 ± 1.7 vs. 3.2 ± 1.0 mm, p = .001). CONCLUSION: The MPL was far away from the esophagus with thicker myocardium tissue and more fat pad than the CPL; thus, MPL could serve as a favorable alternative in linear ablation for LAPW isolation.

Coexistence of sinus bradycardia and junctional tachycardia in a patient with fibrotic atrial cardiomyopathy.

A 65-year-old woman was referred for catheter ablation in the treatment of persistent tachycardia after surgery for atrial fibrillation and mitral regurgitation. Bipolar voltage mapping of both atria revealed that severe and extensive atrial fibrosis isolated the sinoatrial node from the atrioventricular junction and led to the coexistence of sinus bradycardia and persistent junctional tachycardia.

Tailored ablation index for pulmonary vein isolation according to wall thickness within the ablation circle.

BACKGROUND: Ablation index (AI), a novel lesion quality marker, includes contact force, time, and power of radiofrequency (RF) application, but not regional variation in wall thickness within the wide antral catheter ablation (WACA) circle. This study explored the relationships among AI target value, atrial wall thickness, and gap formation within the WACA circle in patients with paroxysmal atrial fibrillation (PAF). METHODS: We evaluated 102 consecutive patients (mean age, 65 ± 9 years) with PAF who underwent AI-guided WACA for ipsilateral pulmonary vein isolation (PVI). Each WACA circle was subdivided into eight segments, and overall 7143 RF applications were delivered, including 125 gaps in PVI ablation lines. For each RF tag within the ablation circle, we collected data on ablation lesion depth surrogates (time of application, delivery power, impedance drop, average contact force, force-time integral [FTI], and AI) and left atrial wall thickness measured by multidetector computer tomography scanning. RESULTS: The anterior and roof walls were the thickest segments of the ablation circle, in which 85.8% of gaps concentrated, while the posterior and inferior walls were the thinnest. Gap formation was significantly associated with FTI, AI, wall thickness, FTI/wall thickness, and AI/wall thickness. AI/wall thickness had the highest predictive value for gap formation, with a cutoff of 195.6 au/mm for effective ablation. CONCLUSIONS: In AI-guided PVI of PAF, AI/wall thickness by normalizing myocardial thickness variation along the WACA circle was a strong predictor of gap formation, with a target of 195.6 au/mm appearing suitable for effective ablation.

Alternating and gradually changing narrow QRS complex tachycardia in a patient with heart failure: What is the mechanism?

A 23-year-old woman with palpitations for 9 years was referred for catheter ablation. ECG showed an irregular narrow complex tachycardia with alternating and gradually changing QRS morphologies after alternating and changing RR intervals, with a clear pattern of 2 alternating QRS complexes. An electrophysiology study was performed and confirmed that the mechanism of tachycardia was an automatic left-side His-Purkinje system (HPS) ventricular tachycardia. The gradually changing type-2 QRS complexes was the conduction delayed in the left anterior fascicle due to the short RR interval or the short left-side HH interval. Nine months after the index electrophysiology study, the patient encounter a progressive of heart failure with increased heart rate to 130-150 bpm during rest. Radiofrequency ablation was performed at the upper-septum for eliminating the tachycardia and resulted in complete atrioventricular block. A permanent pacemaker with left bundle branch pacing was implanted. Twelve months after the ablation, the enlarged heart shrink to normal with normal left ventricular ejection fraction. In conclusion, careful interpretation of the ECG can identify the sinus P waves followed by irregular narrow complexes, thus avoiding misdiagnosis and unnecessary treatment. Unifocal HPS tachycardia could present with alternating and gradually changing narrow QRS complexes tachycardia and lead to tachycardia cardiomyopathy. Electrophysiology study and catheter ablation were useful for the diagnosis and treatment of HPS tachycardia but with high risk of atrioventricular block. However, successfully elimination the tachycardia would resolve and reverse the enlarged heart and deteriorative heart function.

QRS complex axis deviation changing in catheter ablation of left fascicular ventricular tachycardia.

AIMS: The mechanisms of the QRS complex axis deviation changing of idiopathic left fascicular ventricular tachycardia (FVT) during or after radiofrequency catheter ablation were investigated in this study, which were still not well defined. METHODS AND RESULTS: In the index procedure, FVTs characterized by right bundle branch block configuration and left-axis deviation (LAD-FVT) were ablated at the VT exit site guided by the earliest ventricular activation with fused presystolic Purkinje potential (PP) in 234 consecutive patients. A new type of FVT characterized by right-axis deviation (RAD-FVT) was identified after successful elimination of the LAD-FVT in 12 patients, including 9 patients during the index procedure and 3 patients during follow-up. The QRS duration of RAD-FVT was shorter than that of LAD-FVT (115.3 ± 15.2 vs. 125.3 ± 16.4 ms, P = 0.006). The RAD-FVTs showed an earliest ventricle activation site localized at anterior fascicle area in 11 patients and anterior-median fascicle area in 1. However, the earliest PP during the RAD-FVT was still identified within the posterior fascicular network. Elimination of the RAD-FVTs was successfully achieved by applying radiofrequency current at a more proximal site within the left posterior fascicular network guided by the earliest PP. After a mean of 1.6 ± 0.8 ablation procedures and median follow-up of 132 (range 19-216) months since the last procedure, no recurrence was observed in any patients. CONCLUSION: The axis deviation changing of QRS complex in FVT may be attributed to the different exit sites of the reentry.

Acute conduction recurrence of mitral isthmus: Incidence, clinical characteristics, and implications.

BACKGROUND: Data on the incidence, clinical characteristics, and implications of acute conduction recurrence during mitral isthmus (MI) ablation are scarce. METHODS: MI ablation was performed in patients with atrial fibrillation. After confirming bidirectional conduction block, the acute conduction recurrence of MI was systematically evaluated. Clinical and electrophysiological characteristics were analyzed. RESULTS: A total of 66 consecutive patients in whom bidirectional conduction block of MI was achieved were prospectively enrolled in a single center. Acute conduction recurrence of MI developed in 12 (18.2%) patients within 14.2 ± 11.5 minutes after the confirmation of bidirectional conduction block. There were two recurrent conduction breakthrough sites of MI along the course of the great cardiac vein (4.5 ± 3.5 min) in two patients and 11 along the course of the ligament of Marshall (LOM) (16.0 ± 11.6 min, P = .035) in 11 patients. LOM accounted for most (84.6%, 11/13) acute MI conduction recurrence. MI length, total ablation time, and procedure time for MI were greater in patients with acute conduction recurrence than in those without acute conduction recurrence. During follow-up, arrhythmia recurrences were less observed in patients with acute conduction when compared to patients without acute conduction recurrence (0% vs 26.4%, P = .055). CONCLUSION: Acute conduction recurrence, predominantly due to recurrent LOM conduction, was a common phenomenon during MI ablation, and its evaluation should therefore be the focus to improve MI ablation efficacy and durability.

Clinical efficacy and safety of radiofrequency catheter ablation for atrial fibrillation in patients aged ≥80 years.

AIM: To evaluate the clinical safety and efficacy of radiofrequency catheter ablation for atrial fibrillation (AF) in patients aged ≥80 years. METHODS: A total of 333 AF patients aged ≥60 years were enrolled, who underwent contact force-guided radiofrequency catheter ablation with uninterrupted anticoagulation. All patients were followed-up for at least 12 months. Success was defined by the absence of episodes of AF/atrial tachycardia lasting more than 30 seconds after a 3-month blanking period, without antiarrhythmic drugs. RESULTS: Compared to patients aged 60-79 years (Group 2, n = 244), patients aged ≥80 years (Group 1, n = 89) were presented with higher rate of diabetes (36.0% vs 22.1%, P = .011), lower body mass index (23.4 ± 3.1 vs 24.9 ± 3.4 kg/m2 , P = .001), lower creatinine clearance (56.9 ± 16.5 vs 83.3 ± 24.5 mL/min, P < .001), higher CHA2 DS2 -VASc score (4.3 ± 1.3 vs 3.3 ± 1.4, P < .001), and HAS-BLED score (2.2 ± 0.8 vs 1.8 ± 0.8, P < .001). Wide antral pulmonary vein isolation was achieved in all patients, and there was no significant difference in procedure time, ablation time, fluoroscopy time, and complications rate between two age groups (P > .05). After a mean follow-up of 24.4 ± 9.6 months, the overall success rate was 78.2% in Group 1 and 78.9% in Group 2 (P = .622). CONCLUSIONS: Radiofrequency ablation with contact force sensing catheters for AF is safe and effective in selected patients aged ≥80 years.

Atrioesophageal fistula post atrial fibrillation ablation: A multicenter study from China.

BACKGROUND AND OBJECTIVE: Atrioesophageal fistula (AEF) is a rare but devastating complication with high mortality post atrial fibrillation (AF) ablation. The purpose of current study was to determine the epidemiology, clinical features, pathogenesis, and management of AEF after AF ablation. METHODS AND RESULTS: Patients with diagnosed AEF were included and retrospectively analyzed according to the registry of 11 centers in China from January 2010 to December 2019. A total of 16 AEF cases were identified from 44 794 patients who received a left atrial ablation procedure (0.035% per procedure). The interval from procedure to clinical onset of AEF averaged 18.3 days (3-39 days). The fever ranked the most common symptom, occurred in 14 of the 16 cases, followed by neurological deficits (n = 11), chest pain (n = 5), and hematemesis (n = 4). Patients undergoing surgical repair had a better prognosis compared to those receiving nonsurgical management ([4 of 8] 50.0% vs [8 of 8] 100%, P < .05) with an overall mortality rate of 75.0%. CONCLUSION: AEF is highly characterized by varied manifestations. Early diagnosis and urgent surgical repair are vital to those patients and associated with improved survival rates.

Circular RNA Ttc3 regulates cardiac function after myocardial infarction by sponging miR-15b.

The apoptotic death of cardiomyocytes critically contributes to cardiac remodeling after myocardial infarction (MI). Circular RNAs (circRNAs) are important regulators for a variety of biological functions. Circ-Ttc3 represents one of the top highest expressed circRNAs in the heart; however, its role in MI remains unknown. Herein, we found that circ-Ttc3 was markedly upregulated in the ischemic myocardium and the cardiomyocytes subjected to hypoxic insult. Forced expression of circ-Ttc3 in cardiomyocytes counteracted hypoxia-induced ATP depletion and apoptotic death, in sharp contrast to circ-Ttc3 knockdown. Accordingly, experiments with AAV9-cTnt-mediated knockdown of cardiac circ-Ttc3 in a rat model of MI recapitulated the in vitro findings, and showed the deterioration of cardiac dysfunction after MI. Furthermore, we identified that circ-Ttc3 sponged an endogenous miR-15b-5p to sequester and inhibit its activity, leading to the increased Arl2 expression. Conversely, knockdown of Arl2 partially abolished the beneficial effects of circ-Ttc3 overexpression on ATP production and apoptosis of cardiomyocytes. Thus, our findings revealed the cardioprotective role of circ-Ttc3 in MI. The miR-15b-Arl2 regulatory cascade underlies the protection against MI-induced cardiomyocyte apoptosis by circ-Ttc3.

The importance of identifying conduction breakthrough sites across the mitral isthmus by elaborate mapping for mitral isthmus linear ablation.

AIMS: Mitral isthmus (MI) ablation is challenging. We hoped to close those conduction breakthrough sites (CBS) across the MI by elaborate mapping. METHODS AND RESULTS: After the initial linear ablation, elaborately mapping large areas above and below the MI line and inside the coronary sinus (CS) was sequentially performed to identify the CBS. The shortest distance from the CBS to the MI line was measured. The distant CBS (D-CBS) was identified as those CBS >5.0 mm away from the MI line. We prospectively enrolled 177 consecutive patients. Bidirectional conduction blockage across MI was obtained in 50 (28.2%) patients after the initial linear ablation and was achieved in additional 115 (65.0%) patients following elaborate mapping and reinforcement ablation. After initial linear ablation, 272 CBS (2.14 ± 0.99 CBS/person) were identified, and 226 (83.1%) of them were characterized as D-CBS, including 98 sites (36.0%) >10.0 mm and 39 sites (14.3%) >15.0 mm away. Endocardial and epicardial (CS) reinforcement ablation eliminated 119/272 (43.8%) and 58/272 (21.3%) CBS, respectively. Among the 177 eliminated CBS, 138 D-CBS (78.0%, 11.2 ± 5.6 mm) were confirmed in 95 (74.8%) patients. Moreover, CBS along the course of ligament of Marshall was closed by endocardial ablation more frequently than that along the course of great cardiac vein (52.6%% vs. 35.1%, P = 0.004). Eventually, CS ablation was required only in 64 (38.8%) patients. CONCLUSION: Distant CBS, accounted for the majorities of the residual conduction across the MI after initial ablation, could be effectively identified and accurately eliminated by elaborate mapping and ablation around the MI ablation line.