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Aims Macrophage migration inhibitory factor (MIF), a pleiotropic inflammatory cytokine, is highly expressed in patients with atrial fibrillation (AF). Inflammation increases the risk of AF and is primarily triggered by pulmonary vein (PV) arrhythmogenesis. This study investigated whether MIF can modulate the electrical activity of the PV and examined the underlying mechanisms of MIF. Methods and results A conventional microelectrode, a whole-cell patch clamp, western blotting, and immunofluorescent confocal microscopy were used to investigate electrical activity, calcium (Ca2+) regulation, protein expression, ionic currents, and cytosolic reactive oxygen species (ROS) in rabbit PV tissue and isolated single cardiomyocytes with and without MIF incubation (100 ng/mL, treated for 6 h). The MIF (100 ng/mL)-treated PV tissue (n = 8) demonstrated a faster beating rate (1.8 ± 0.2 vs. 2.6 ± 0.1 Hz, P < 0.05), higher incidence of triggered activity (12.5 vs. 100%, P < 0.05), and premature atrial beat (0 vs. 100%, P < 0.05) than the control PV tissue (n = 8). Compared with the control PV cardiomyocytes, MIF-treated single PV cardiomyocytes had larger Ca2+ transients (0.6 ± 0.1 vs. 1.0 ± 0.1, Δ F / F 0, P < 0.05), sarcoplasmic reticulum Ca2+ content (0.9 ± 0.20 vs. 1.7 ± 0.3 mM of cytosol, P < 0.05), and cytosolic ROS (146.8 ± 5.3 vs. 163.7 ± 3.8, Δ F / F 0, P < 0.05). Moreover, MIF-treated PV cardiomyocytes exhibited larger late sodium currents (INa-Late), L-type Ca2+ currents, and Na+/Ca2+ exchanger currents than the control PV cardiomyocytes. KN93 [a selective calcium/calmodulin-dependent protein kinase II (CaMKII) blocker, 1 μM], ranolazine (an INa-Late inhibitor, 10 μM), and N -(mercaptopropionyl) glycine (ROS inhibitor, 10 mM) reduced the beating rates and the incidence of triggered activity and premature captures in the MIF-treated PV tissue. Conclusion Macrophage migration inhibitory factor increased PV arrhythmogenesis through Na+ and Ca2+ dysregulation through the ROS activation of CaMKII signalling, which may contribute to the genesis of AF during inflammation. Anti-CaMKII treatment may reverse PV arrhythmogenesis. Our results clearly reveal a key link between MIF and AF and offer a viable therapeutic target for AF treatment. [ABSTRACT FROM AUTHOR]

Background: The management of refractory electrical storm (ES) requiring mechanical circulation support (MCS) remains a clinical challenge in structural heart disease (SHD). Objective: The study sought to explore the 30‐day and 1‐year outcome of rescue ablation for refractory ES requiring MCS in SHD. Methods: A total of 81 patients (mean age: 55.3 ± 18.9, 73 men [90.1%]) undergoing ablation were investigated, including 26 patients with ES requiring MCS (group 1) and 55 patients without (group 2). The 30‐day and 1‐year outcome, including mortality and recurrent ventricular tachyarrhythmias (VAs) receiving appropriate implantable cardioverter defibrillators therapies, were assessed. Results: The patients in group 1 were characterized by older age, more ischemic cardiomyopathies, worse left ventricular ejection fraction, and more comorbidities. Thirty days after ablation, overall events were seen in 15 patients (mortality in 10 and recurrent VA in 7), including pumping failure‐related mortality in 6 (60%). During a 30‐day follow‐up, higher mortality was noted in group 1. After a 1‐year follow‐up, in spite of the higher mortality in group 1 (P <.001), the overall events and VA recurrences were similar between these two groups (P =.154 and P =.466, respectively). There was a significant reduction of VA burden in both groups and two patients had recurrent ES. Conclusion: Higher 30‐day mortality was observed in patients undergoing rescue ablation for refractory ES requiring MCS, and pumping failure was the major cause of periprocedural death. Rescue ablation successfully prevented VA recurrences and resulted in a comparable 1‐year prognosis between ES with and without MCS. [ABSTRACT FROM AUTHOR]

Background: Propafenone is a class IC antiarrhythmic agent that is commonly used as the first-line therapy for patients with paroxysmal atrial fibrillation (AF) in Taiwan. This study compared the efficacy and safety of generic (Rhynorm) and brand name (Rytmonorm) propafenone for rhythm control of paroxysmal AF in Taiwan., Methods: This was an open-label randomized multicenter noninferior study conducted in Taiwan. We enrolled 76 patients with AF. To investigate the efficacy of propafenone, we used a wearable electrocardiogram (ECG) event recorder to evaluate the daily burden of AF episodes in patients for 24 weeks. The primary efficacy endpoint was the frequency of AF with clinical significance, which was indicated by AF duration ≥30 seconds. The safety endpoints included proarrhythmic or hemodynamic adverse events., Result: To analyze the efficacy and safety of these agents, 71 patients (five patients with screen failure) were randomized to two groups, specifically a Rhynorm group (n = 37) and a Rytmonorm group (n = 34), for 24 weeks of the treatment period. The baseline patient characteristics were comparable between the groups. However, the Rhynorm group was older (65.4 ± 8.40 vs 59.8 ± 10.8 years; p = 0.02). The primary efficacy endpoint at week 24 decreased by 4.76% ± 18.5% (from 24.3% ± 33.9% to 19.0% ± 28.7%; p = 0.13) in the Rhynorm group and by 3.27% ± 15.2% (from 16.9% ± 26.4% to 13.6% ± 19.2%; p = 0.22) in the Rytmonorm group, with an intergroup difference of 1.5% ± 17.0%; p = 0.71. This finding indicates that Rhynorm is not inferior to Rytmonorm ( p = 0.023 for noninferiority). The safety profile of the agents was comparable between the two groups., Conclusion: Our results verified that Rhynorm was noninferior to Rytmonorm in terms of efficacy and safety for treating paroxysmal AF in Taiwan ( ClinicalTrials.gov Identifier: NCT03674658)., Competing Interests: Conflicts of interest: The authors declare that they have no conflicts of interest related to the subject matter or materials discussed in this article., (Copyright © 2023, the Chinese Medical Association.)

Aims: Macrophage migration inhibitory factor (MIF), a pleiotropic inflammatory cytokine, is highly expressed in patients with atrial fibrillation (AF). Inflammation increases the risk of AF and is primarily triggered by pulmonary vein (PV) arrhythmogenesis. This study investigated whether MIF can modulate the electrical activity of the PV and examined the underlying mechanisms of MIF., Methods and Results: A conventional microelectrode, a whole-cell patch clamp, western blotting, and immunofluorescent confocal microscopy were used to investigate electrical activity, calcium (Ca2+) regulation, protein expression, ionic currents, and cytosolic reactive oxygen species (ROS) in rabbit PV tissue and isolated single cardiomyocytes with and without MIF incubation (100 ng/mL, treated for 6 h). The MIF (100 ng/mL)-treated PV tissue (n = 8) demonstrated a faster beating rate (1.8 ± 0.2 vs. 2.6 ± 0.1 Hz, P < 0.05), higher incidence of triggered activity (12.5 vs. 100%, P < 0.05), and premature atrial beat (0 vs. 100%, P < 0.05) than the control PV tissue (n = 8). Compared with the control PV cardiomyocytes, MIF-treated single PV cardiomyocytes had larger Ca2+ transients (0.6 ± 0.1 vs. 1.0 ± 0.1, ΔF/F0, P < 0.05), sarcoplasmic reticulum Ca2+ content (0.9 ± 0.20 vs. 1.7 ± 0.3 mM of cytosol, P < 0.05), and cytosolic ROS (146.8 ± 5.3 vs. 163.7 ± 3.8, ΔF/F0, P < 0.05). Moreover, MIF-treated PV cardiomyocytes exhibited larger late sodium currents (INa-Late), L-type Ca2+ currents, and Na+/Ca2+ exchanger currents than the control PV cardiomyocytes. KN93 [a selective calcium/calmodulin-dependent protein kinase II (CaMKII) blocker, 1 μM], ranolazine (an INa-Late inhibitor, 10 μM), and N-(mercaptopropionyl) glycine (ROS inhibitor, 10 mM) reduced the beating rates and the incidence of triggered activity and premature captures in the MIF-treated PV tissue., Conclusion: Macrophage migration inhibitory factor increased PV arrhythmogenesis through Na+ and Ca2+ dysregulation through the ROS activation of CaMKII signalling, which may contribute to the genesis of AF during inflammation. Anti-CaMKII treatment may reverse PV arrhythmogenesis. Our results clearly reveal a key link between MIF and AF and offer a viable therapeutic target for AF treatment., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Precordial T-wave inversion (TWI) is an important diagnostic criterion for arrhythmogenic right ventricular cardiomyopathy (ARVC)., Objective: This study aimed to characterize the initial repolarization features of definite ARVC in patients who first presented with right ventricular outflow tract ventricular arrhythmia (RVOT-VA) and TWI., Methods: Patients who presented with RVOT-VA and TWI ≥ V 2 were retrospectively assessed. The initial characteristics of repolarization between patients with and without a final diagnosis of definite ARVC during follow-up were compared., Results: TWI ≥ V 2 was observed in 61 of 553 patients (mean age: 44.1 ± 14.7 years; 14 men) with RVOT-VAs. After an average follow-up time of 54.9 ± 33.7 months, 31 (50.8%) patients were classified into the definite ARVC group and 30 (49.2%) into the non-definite ARVC group. The disappearance of precordial TWI ≥ V 2 was observed in eight (13.1%) patients after the elimination of RVOT-VAs. In a multivariate analysis of the initial electrocardiogram features, only fragmented QRS [odds ratio (OR): 15.45, 95% confidence interval (CI): 1.61-148.26, p = 0.02] and precordial V 2 TpTe interval (OR: 1.03, 95% CI: 1.01-1.06, p = 0.02) could independently predict definite ARVC during longitudinal follow-up. An initial V 2 TpTe cutoff value > 88.5 ms could predict the final diagnosis of definite ARVC, with a sensitivity and specificity of 74.2% and 78.6%, respectively., Conclusions: Despite the high risk of ARVC in RVOT-VAs and TWI ≥ V 2 , "normalization" of TWI was observed after ventricular arrhythmia elimination in 13.1% of the patients. Fragmented QRS and longer V 2 TpTe interval were associated with definite ARVC during longitudinal follow-up.