UNASSIGNED: There is inadequate awareness of the effect of food on the bioavailability of dronedarone. We report results from two phase 1 studies assessing the effect of food on dronedarone\'s bioavailability.
UNASSIGNED: Study 1; single-center, open-label, randomized study in healthy adults (males and females). Study 2; single-center, open-label, randomized study in healthy males.
UNASSIGNED: Study 1; a single 400-mg oral dose of dronedarone (marketed formulation) in fed (high-fat [47.4 g] meal) and fasted states. Study 2; a single 800-mg oral dose of dronedarone (two 400-mg tablets) after fat-rich (37.3 g) and low-fat (5.3 g) meals, and after fasting.
UNASSIGNED: Pharmacokinetic parameters including maximum plasma concentration (Cmax) and area under the curve from time 0 to last measurable time (AUClast) were assessed for dronedarone and its active N-debutyl metabolite.
UNASSIGNED: Twenty-six participants were included in Study 1 and nine in Study 2. In Study 1, administration of 400 mg dronedarone with a high-fat meal vs. fasted state resulted in 2.8-fold and 2.0-fold increases in Cmax and AUClast, respectively. In Study 2, administration of 800 mg dronedarone with a fat-rich or low-fat meal vs. fasted state resulted in 4.6-fold and 3.2-fold increases in Cmax, respectively, and 3.1-fold and 2.3-fold increases, respectively, in AUClast. Results for the N-debutyl metabolite were similar to dronedarone. No adverse events were considered related to dronedarone.
UNASSIGNED: With food, the bioavailability of dronedarone is markedly increased. In clinical practice, dronedarone should be administered with a complete meal to maximize drug absorption.

The global prevalence of atrial fibrillation (AF) is rising, paralleling increased life expectancy. Early rhythm control benefits AF management. However, in low-risk, often asymptomatic, AF patients, anticoagulant monotherapy is the selected treatment, aligning with current guidelines. However, early AF progression in these low-risk individuals is not well-understood. Thus, this study aims to: 1) determine the proportion of low-risk AF patients who worsen within a year of initial AF diagnosis and 2) identify risk factors such treatment transitions. We analyzed data from 18623 AF patients, spanning January 2005 to June 2017. Low-risk patients were those on anticoagulant monotherapy ± rate control, following the JCS/JHRS 2020 Guideline on Pharmacotherapy of Cardiac Arrhythmias. We defined 2 patterns of treatment transition for 1) initiating ablation or antiarrhythmic drug therapy and 2) solely using antiarrhythmic drugs. This retrospective cohort study was employed a 12-month study, following a 6-month screening period. We included 1874 patients for all rhythm control (analysis 1) and 1503 for only medication-based control (analysis 2). The primary endpoint, treatment transition of AF under monotherapy, occurred in 28.4% of patients in analysis 1 and 10.8% in analysis 2. Risk factors common to both scenarios were male gender, baseline rate control drug use, and rivaroxaban selection, as identified by multiple logistic regression. These findings suggest a higher AF treatment transition trend in patients starting rivaroxaban, calling for further research. The study highlights the importance of informed early rhythm control initiation decisions in clinical settings.

To characterize utility of atrioventricular block (AVB) dogs as atrial fibrillation (AF) model, we studied remodeling processes occurring in their atria in acute (<2 weeks) and chronic (>4 weeks) phases. Fifty beagle dogs were used. Holter electrocardiogram demonstrated that paroxysmal AF occurred immediately after the production of AVB, of which duration tended to be prolonged in chronic phase. Electrophysiological analysis showed that inter-atrial conduction time and duration of burst pacing-induced AF increased in the chronic phase compared with those in the acute phase, but that atrial effective refractory period was hardly altered. Echocardiographic study revealed that diameters of left atrium, right pulmonary vein and inferior vena cava increased similarly in the acute and chronic phases. Histological evaluation indicated that hypertrophy and fibrosis in atrial tissue increased in the chronic phase. Electropharmacological characterization showed that i.v. pilsicainide effectively suppressed burst pacing-induced AF with increasing atrial conduction time and refractoriness of AVB dogs in chronic phase, but that i.v. amiodarone did not exert such electrophysiological effects. Taken together, AVB dogs in chronic phase appear to possess such pathophysiology as developed in the atria of early-stage AF patients, and therefore they can be used to evaluate drug candidates against early-stage AF.

Supraventricular tachyarrhythmias pose a significant challenge in neonates and infants, particularly within the first year of life, where prompt and effective management is crucial. By synthesizing available evidence and clinical experience, this review aims to provide a comprehensive overview of antiarrhythmic therapy in this vulnerable population, with a focus on narrow QRS supraventricular tachyarrhythmias. This review examines the current understanding of supraventricular tachyarrhythmia management and discusses the challenges associated with antiarrhythmic therapy in newborns and infants during the critical first year of life, evaluating the efficacy and safety of various antiarrhythmic agents commonly utilized in this population, including dosing considerations, adverse effects, and strategies for acute management and prophylactic long-term antiarrhythmic treatment.

UNASSIGNED: Patients with atrial fibrillation (AF) who undergo radiofrequency catheter ablation (RFCA) necessitate the administration of antiarrhythmic drugs to prevent early recurrence. The clinical outcomes among these patients may be influenced by varying antiarrhythmic regimens.
UNASSIGNED: To identify the risk factors associated with early recurrence and compare the clinical outcomes among different antiarrhythmic regimens in elderly patients with AF following radiofrequency catheter ablation (RFCA) during a 3-month period.
UNASSIGNED: A retrospective observational study encompassed 420 elderly patients with AF following RFCA. Baseline data were collected during the initial postoperative visit and clinical outcomes were carefully monitored over a 3-month follow-up period. Logistic regression and Cox-proportional hazard regression analyses were performed to investigate the relationship between various antiarrhythmic regimens and the clinical outcomes.
UNASSIGNED: Multivariate logistic regression analysis revealed that age (p = 0.001), left atrial diameter (p < 0.001), left ventricular diameter (p = 0.015), reactive hyperemia index (RHI) (p < 0.001), antiarrhythmic drug (p < 0.001) and hs-cTnI (p = 0.017) were independent risk factors of early recurrence. Furthermore, in cox survival regression analysis model, survival rate of early recurrence in the amiodarone group was higher than in the propafenone group (HR 2.30, 95%CI 1.17-4.53, p = 0.016) and in the sotalol group (HR 3.60, 95%CI 2.17-5.95, p < 0.001). Compared to the amiodarone group, the incidence of liver dysfunction was lower in the dronedarone group (p = 0.046) and the propafenone group (p = 0.021). The incidence of bradyarrhythmia (p = 0.003), QT interval prolongation (p = 0.035) and atrioventricular transmission block (p = 0.021) were higher in the sotalol group than in the amiodarone group.
UNASSIGNED: RHI was identified as an independent risk factor for early recurrence among elderly AF patients after RFCA. Compared to amiodarone, propafenone and sotalol exhibited an elevated risk of early recurrence. Although there was no significant difference in early recurrence between amiodarone and dronedarone, dronedarone emerged as the preferred option due to its lower frequency of adverse drug reactions than amiodarone.

Premature ventricular complexes (PVCs) are commonly encountered problems in clinical settings. The range of symptoms can be from asymptomatic to palpitations, fatigue, or heart failure symptoms. A higher burden of PVCs is a risk factor for development of PVC-induced cardiomyopathy (PIC). Rhythm evaluation by 12-lead ECG and an ambulatory monitoring device are essential. Currently, several imaging modalities, such as echocardiography and cardiac magnetic resonance imaging, are utilized to evaluate the underlying structure that may be related to PIC. Beta blockers and antiarrhythmic drugs are typically part of the initial management strategy. If these fail, catheter ablation of PVCs is typically the next step. The purpose of this article is to summarize the current evidence/knowledge about PIC.

Background: Initiation of dofetilide requires hospital admission because of its proarrhythmic risk. To reduce the risk of adverse events associated with dofetilide, our institution has a standard operating protocol for dofetilide initiation. Regardless, patients are sometimes admitted for dofetilide initiation with unaddressed pharmacotherapy concerns that may delay therapy initiation and/or increase the risk for adverse events. Objective: To characterize interventions associated with pharmacist evaluation of scheduled dofetilide admissions prior to hospitalization. Methods: Patients scheduled for dofetilide initiation were evaluated by a pharmacist prior to admission. Identified interventions were categorized into the following recommendations: (1) against the use of dofetilide; (2) dofetilide starting dose adjustment; (3) appropriate washout of previous antiarrhythmic drug; (4) transesophageal echocardiogram prior to dofetilide initiation; (5) discontinuation or dose adjustment of interacting drug; (6) electrolyte supplementation upon discharge; (7) other intervention. The primary outcome measure was the frequency and types of identified and accepted interventions. Results: Twenty-two patients were evaluated during the 9-month study period. Fourteen interventions were identified, 13 of which were accepted by an electrophysiology provider. The most common intervention was for recommendation of a transesophageal echocardiogram prior to initiating dofetilide because of inadequate oral anticoagulation (n = 6). Other accepted interventions were for discontinuation or dose adjustment of interacting drug (n = 3), dofetilide starting dose adjustment (n = 2), electrolyte supplementation upon discharge (n = 2), and remeasurement of interventricular septal wall thickness (n = 1). Conclusion: Pharmacist evaluation of scheduled dofetilide admissions prior to hospitalization can serve to identify and resolve pharmacotherapy concerns related to dofetilide use.

Cavutilide (niferidil, refralon) is a new class III antiarrhythmic drug which effectively terminates persistent atrial fibrillation (AF; 84.6% of patients, mean AF duration 3 months) and demonstrates low risk of torsade de pointes (1.7%). ERG channels of rapid delayed rectifier current(IKr) are the primary target of cavutilide, but the particular reasons of higher effectiveness and lower proarrhythmic risk in comparison with other class III IKr blockers are unclear. The inhibition of hERG channels expressed in CHO-K1 cells by cavutilide was studied using whole-cell patch-clamp. The present study demonstrates high sensitivity of IhERG expressed in CHO-K1 cells to cavutilide (IC50 = 12.8 nM). Similarly to methanesulfonanilide class III agents, but unlike amiodarone and related drugs, cavutilide does not bind to hERG channels in their resting state. However, in contrast to dofetilide, cavutilide binds not only to opened, but also to inactivated channels. Moreover, at positive constantly set membrane potential (+ 60 mV) inhibition of IhERG by 100 nM cavutilide develops faster than at 0 mV and, especially, - 30 mV (τ of inhibition was 78.8, 103, and 153 ms, respectively). Thereby, cavutilide produces IhERG inhibition only when the cell is depolarized. During the same period of time, cavutilide produces greater block of IhERG when the cell is depolarized with 2 Hz frequency, if compared to 0.2 Hz. We suggest that, during the limited time after injection, cavutilide produces stronger inhibition of IKr in fibrillating atrium than in non-fibrillating ventricle. This leads to beneficial combination of antiarrhythmic effectiveness and low proarrhythmicity of cavutilide.

OBJECTIVE: Nifekalant is a class III antiarrhythmic drug that exerts antiarrhythmic effects by inhibiting rapid rectifying potassium channels and extending the effective refractory period of cardiomyocytes. It has a high success rate in converting atrial fibrillation (AF) to sinus rhythm. Whether the failure of intravenous nifekalant cardioversion is an independent predictor for persistent AF recurrence after catheter ablation has not been reported.
METHODS: A total of 92 patients with drug-refractory persistent AF were retrospectively enrolled. After all ablations, intravenous nifekalant was administrated. Patients were assigned to the success group (group 1) and failure group (group 2) based on nifekalant cardioversion results and followed for 12 months to note any episode of atrial arrhythmia recurrence.
RESULTS: Each group included 46 patients. After 12 months of follow-up, nine (19.6%) patients from group 1 and 23 (50.0%) patients from group 2 had a recurrence of atrial tachyarrhythmia (P = 0.002). AF duration and type 2 diabetes were strongly associated with failure of intravenous nifekalant cardioversion. Univariable Cox proportional hazard regression showed that failure of intravenous nifekalant cardioversion, AF duration, and type 2 diabetes were potential risk factors. Multivariable Cox proportional hazard regression showed that failure of nifekalant cardioversion was statistically associated with AF recurrence (adjusted RR = 2.257, 95% CI: 1.006-5.066, P = 0.048). Failure of intravenous nifekalant cardioversion could bring a positive effect on the prognostic differentiation when added into the multivariable model (0.767 ± 0.042 vs. 0.774 ± 0.045, P = 0.025).
CONCLUSIONS: Failure of nifekalant cardioversion is an independent predictor for persistent AF recurrence after catheter ablation.

UNASSIGNED: Atrial fibrillation (AF) increases heart failure (HF) risk. Whereas the risk of HF-related hospitalization and mortality are known in the setting of AF, the impact of AF treatment on HF development is understudied.
UNASSIGNED: The purpose of this study was to compare HF incidence among AF patients treated with antiarrhythmic drugs (AADs) vs catheter ablation (CA).
UNASSIGNED: AF patients with 1 prior AAD usage were identified in 2014-2022 Optum Clinformatics database. Patients were classified into 2 cohorts: those receiving CA vs those receiving a different AAD prescription. The 2 cohorts were matched on sociodemographic and clinical covariates using propensity score matching technique. Cox regression model was used to compare incident HF risk in the 2 cohorts. Subgroup analyses were performed by race/ethnicity, sex, AF subtype, and CHA2DS2-VASc score.
UNASSIGNED: After matching, 9246 patients were identified in each cohort (AAD and CA). Patients receiving CA had a 57% lower risk of incident HF than those treated with AADs (hazard ratio [HR] 0.43; 95% confidence interval [CI] 0.40-0.46). Subgroup analysis by race/ethnicity depicted similar results, with non-Hispanic White (HR 0.43; 95% CI 0.40-0.46), non-Hispanic Black (HR 0.46; 95% CI 0.35-0.60), Hispanic (HR 0.53; 95% CI 0.40-0.70), and Asian (HR 0.46; 95% CI 0.24-0.92) patients treated with CA (vs AAD) having significantly lower risk of HF, respectively. The effect size of CA remained significant in subgroups defined by sex, AF subtypes, and CHA2DS2-VASc score.
UNASSIGNED: AF patients receiving CA had ∼57% lower risk of developing HF than those receiving AAD. The lower risk of HF associated with CA vs AAD persisted across different race/ethnicity, sex, AF subtypes, and CHA2DS2-VASc score.