We present a 16-year-old female with multisystemic disorder characterized by cutaneous hyperpigmentation, hypertrichosis, hepatosplenomegaly, hearing loss, heart anomalies, hypogonadism, low height (short stature), hyperglycemia and hallux valgus and pathogenic variant in SLC29A3 gene (encoding the human equilibrate nucleoside transporter (hENT3), was referred for evaluation due to recurrent non-sustained pleomorphic ventricular tachycardia refractory to amiodarone and catheter ablation. Two-dimensional echocardiography and cardiac magnetic resonance with late-gadolinium enhancement showed reduced biventricular ejection fraction without signs of inflammation or fibrosis. The administration of propranolol and flecainide controlled her ventricular arrhythmias and improved ventricular function. To our knowledge, this the first time that this arrhythmic phenotype has been demonstrated in this unusual syndrome presenting probably as a cardiomyopathy secondary to recurrent non-sustained pleomorphic ventricular tachycardia that was reversed with administration of flecainide and propranolol.

Background/Objectives: Amiodarone (AmoD) is an effective antiarrhythmic drug whose use is limited by life-threatening pulmonary fibrosis. Although Wnt/β-catenin signaling contributes to several lung diseases, its involvement in AmoD-induced pulmonary fibrosis remains unknown. This study investigated whether Wnt/β-catenin signaling is altered during AmoD-induced pulmonary fibrosis and whether its pharmacological modulation with pyrvinium (Pyrv) attenuates this toxicity. Methods: Rats were allocated into four groups and treated for five weeks as follows: normal control, AmoD (30 mg/kg/day), Pyrv (60 µg/kg/day), and AmoD + Pyrv. Pulmonary injury and fibrosis were evaluated using histopathological examination, Masson's trichrome staining, immunohistochemical assessment of collagen I, α-smooth muscle actin (α-SMA), and transforming growth factor-β1 (TGF-β1), and measurement of inflammatory cytokines, tumor necrosis factor-α (TNF-α) and interleukin-6 (IL-6), and Th1/Th2-related cytokines. Wnt/β-catenin-associated proteins, including Wnt3a, active β-catenin, and glycogen synthase kinase-3β (GSK-3β), were evaluated by Western blotting. Results: AmoD induced marked pulmonary architectural disruption, inflammatory cell infiltration, increased lung weight/body weight ratio, collagen deposition, and increased expression of TGF-β1, α-SMA, and collagen I, as well as increased levels of TNF-α, IL-6, and disruption of Th1/Th2 immune balance. At the molecular level, AmoD increased Wnt3a, active β-catenin, and the p-GSK-3β/total GSK-3β ratio. Co-administration of Pyrv significantly attenuated the histopathological, inflammatory, immune, and fibrotic alterations and reduced the AmoD-associated changes in Wnt/β-catenin-related proteins. Conclusions: The findings indicate that AmoD-induced pulmonary injury and fibrosis are associated with modulation of Wnt/β-catenin related proteins and that Pyrv treatment attenuates these pathological changes. Targeting this pathway could be a promising protective strategy to prevent fibrogenesis during AmoD treatment.

Background and Objectives: Electrical cardioversion (ECV) restores sinus rhythm in patients with atrial fibrillation (AF) and requires uninterrupted anticoagulation to prevent thromboembolic events. Despite the predictable pharmacokinetic profile of direct oral anticoagulants (DOACs), variability in plasma concentrations and possible drug-drug interactions may have clinical implications. Therefore, this study aimed to describe DOAC plasma concentrations before elective ECV under routine clinical, using expected concentration ranges reported in the guidelines as descriptive reference points. Materials and Methods: A cross-sectional study included adult patients with AF receiving rivaroxaban, dabigatran, or edoxaban before elective ECV. Blood samples were collected before the procedure irrespective of the timing of DOAC administration, and plasma concentrations were measured using drug-specific chromogenic assays and compared with the expected peak and trough concentration ranges. Comparisons with expected peak and trough concentration distributions were descriptive only. Results: Thirty-seven patients were analysed, with polypharmacy observed in 83.8% of participants. Ten measurements (27.0%) exceeded the upper bounds of expected peak concentration distributions, while two measurements (5.4%) fell below the lower bounds of trough distributions. Two patients were receiving standard DOAC doses despite meeting renal criteria for dose reduction. Conclusions: Considerable variability in randomly timed DOAC concentrations was observed before ECV. Observed dosing discrepancies highlight the importance of periodically reassessing prescribed doses against current patient characteristics. Larger prospective studies with standardized sampling and clinical follow-up are needed to clarify the clinical significance of these findings.

To overcome the side effects of conduction block and QT prolongation associated with antiatrial fibrillation (AF) drug dronedarone, a novel class of dual IKr and late sodium current (late INa) inhibitors was developed through computational modeling, chemical modification, and electrophysiological screening. Lead compound 8b retained potent IKr inhibition (IC50 = 1.5 μM) comparable to dronedarone. Crucially, 8b avoided dronedarone's peak INa inhibition while enhancing late INa suppression (IC50 = 2.5 μM) to counteract excessive QT prolongation and avoid conduction block. Compound 8b exhibited favorable pharmacokinetic properties (T1/2 = 5.02 h, F = 110% in mice, p.o.) and high ion channel selectivity. In an ex vivo rabbit heart model of AF, 8b demonstrated antiarrhythmic efficacy. Furthermore, 8b was effective in treating doxorubicin-induced heart failure in mice, a condition where dronedarone shows no therapeutic benefit. Collectively, 8b could serve as a potential new class III antiarrhythmic candidate.

A large right ventricular outflow tract aneurysm in a fetus was incidentally detected during a routine third-trimester ultrasound of a 30-year-old pregnant woman. The pregnancy itself was otherwise uneventful, and the infant was delivered at term. Postnatal echocardiography confirmed the presence of the right ventricular outflow tract aneurysm. Initially, the neonate was stable; however, he developed frequent ventricular premature complexes, with electrocardiographic features indicating a right ventricular outflow tract origin. Early initiation of amiodarone therapy led to a prompt resolution of the arrhythmia. The infant remained stable and was discharged with plans for close follow-up. This case adds to the limited literature on congenital right ventricular outflow tract aneurysms detected antenatally and provides valuable insight into their potential to cause arrhythmias in early life.

This case report describes a 54-year-old woman with end-stage renal disease and heart failure who presented with BRASH syndrome: a synergistic cycle of bradycardia, renal failure, atrioventricular nodal blockade, shock, and hyperkalemia. The patient, who was adherent to metoprolol and amiodarone, presented with a profound ventricular escape rhythm of 16 bpm and hemodynamic instability after missing 4 days of hemodialysis. An interesting complication was the failure of her implantable cardioverter-defibrillator (ICD) to achieve pacing capture, a phenomenon likely driven by a potassium level of 7.8 mEq/L causing myocardial inexcitability. Additionally, the recent uptitration of a carotid sinus nerve stimulator for baroreflex activation therapy may have contributed to the bradycardic cycle. Immediate medical management of hyperkalemia with calcium, insulin, and dextrose successfully restored ICD capture, followed by emergent dialysis, which normalized her rhythm. This case emphasizes that BRASH syndrome should be considered in undifferentiated bradycardia, particularly when refractory to atropine, and highlights that correcting the underlying metabolic derangement is essential to restoring cardiac excitability and device function.

T-type calcium channels (TTCCs), including the Cav3.1 and Cav3.2 subtypes, play a critical role in regulating cardiac electrical activity. Their abnormal expression is closely associated with arrhythmias and cardiac dysfunction caused by myocardial infarction (MI). Dronedarone, a multi-target antiarrhythmic drug, is widely used to treat atrial fibrillation and atrial flutter but has shown adverse effects under pathological conditions such as MI. This study aims to investigate the direct effects and underlying mechanisms of dronedarone on TTCCs. Using neonatal rat cardiomyocytes, HEK293T cells transfected with Cav3.1 and Cav3.2, and MI rat model, we systematically analyzed the effects of dronedarone on TTCC activity. Dronedarone significantly inhibited Cav3.2 channel activity with an IC50 of 9.20 µM, while its effect on Cav3.1 was weaker (IC50 = 46.41 µM). Chronic treatment with dronedarone also slowed the activation and inactivation kinetics of TTCCs. In vivo experiments demonstrated that dronedarone exacerbated myocardial damage and fibrosis in the MI model. These findings suggest that dronedarone inhibits TTCC activity, particularly the Cav3.2 subtype, and alters its kinetic properties. This study reported the electrophysiological effects of dronedarone on T-type calcium channels, providing new insights into its electrophysiological properties and potential role in adverse cardiac events.

Background/Objectives: Vernakalant is an atrial-selective antiarrhythmic used for rapid pharmacological cardioversion of recent-onset atrial fibrillation. This systematic review and meta-analysis evaluated the efficacy and safety of vernakalant compared with placebo, active antiarrhythmic therapy, and electrical cardioversion. Methods: PubMed, Embase, Google Scholar, and the Cochrane Central Register of Controlled Trials (CENTRAL) were searched from inception to August 2026. Randomized clinical trials, clinical trials, and comparative observational studies evaluating vernakalant in adults with atrial fibrillation or atrial flutter were included. Dichotomous outcomes were pooled as risk ratios (RRs) with 95% confidence intervals (CIs) using the Mantel-Haenszel random-effects model in RevMan 5.4. Results: Twenty controlled studies involving 4523 patients were included, of whom 2349 received vernakalant and 2174 received control therapy. Vernakalant significantly increased successful conversion to sinus rhythm compared with all controls (1234/2244 (55%) vs. 991/2147 (46.2%); RR = 1.63; 95% CI [1.34, 1.99]; p < 0.00001). The effect was strongest versus placebo (RR = 5.33; 95% CI [1.95, 14.60]; p = 0.001) and remained significant versus procainamide (111/178 (62.3%) vs. 83/172 (48.2%); RR = 1.29; 95% CI [1.07, 1.57]; p = 0.009) and flecainide (209/280 vs. 209/330 (63.3%); RR = 1.18; 95% CI [1.05, 1.33]; p = 0.007), but non-significant against amiodarone, propafenone, ibutilide, or electrical cardioversion. Safety outcomes did not differ significantly between groups, including all-cause mortality (RR = 1.23), drug discontinuation (RR = 0.98), serious adverse events (RR = 0.87), ventricular tachycardia (RR = 0.68), bradycardia (RR = 1.31), and hypotension (RR = 0.80). Conclusions: Vernakalant was associated with higher rates of conversion to sinus rhythm, while no statistically significant differences were observed in major safety outcomes. These findings support its use as a pharmacological option for rapid rhythm restoration in appropriately selected patients.