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.

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.

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.

Accurate assessment of the response to the antiarrhythmic drug (AAD) in atrial fibrillation (AF) is crucial to achieve adequate rhythm control. We evaluated the effectiveness of extended cardiac monitoring using an adhesive ECG patch in the detection of drug-refractory paroxysmal AF. Patients diagnosed with paroxysmal AF and receiving AAD therapy were enrolled. The subjects simultaneously underwent 11-day adhesive ECG patch monitoring and a 24-h Holter test. The primary study outcome was a detection rate of drug-refractory AF or atrial tachycardia (AT) lasting ≥30 s. A total of 59 patients were enrolled and completed the study examinations. AF or AT was detected in 28 (47.5%) patients by an 11-day ECG patch monitor and in 8 (13.6%) patients by a 24-h Holter test (p < 0.001). The 11-day ECG patch monitor identified an additional 20 patients (33.8%) with drug-refractory AF not detected by the 24-h Holter, and as a result, the treatment plan was changed in 11 patients (10 catheter ablations, one medication change). In conclusion, extended cardiac rhythm monitoring using an adhesive ECG patch in patients with paroxysmal AF under AAD therapy led to over a threefold higher detection of drug-refractory AF episodes, compared to the 24-h Holter test.

UNASSIGNED: Three recent randomized controlled trials have demonstrated that, as an initial rhythm control strategy, first-line cryoballoon ablation (cryoablation) reduces atrial arrhythmia recurrence compared with antiarrhythmic drugs (AADs) in patients with symptomatic paroxysmal atrial fibrillation (PAF).
UNASSIGNED: The study sought to evaluate the cost-effectiveness of first-line cryoablation compared with first-line AADs for treating symptomatic PAF from a U.S. Medicare payer perspective.
UNASSIGNED: Individual patient-level data from 703 participants with PAF enrolled into the Cryo-FIRST (NCT01803438), STOP AF First (NCT03118518), and EARLY-AF (NCT02825979) trials were used to derive parameters for the cost-effectiveness model. The cost-effectiveness model used a hybrid decision tree and Markov structure. The decision tree had a 1-year time horizon and was used to inform the initial health state allocation in the first cycle of the Markov model. The Markov model used a 40-year time horizon (3-month cycle length). Health benefits were expressed in quality-adjusted life years (QALYs). Costs and benefits were discounted at 3% per year.
UNASSIGNED: Cryoablation was estimated to yield higher QALYs (+0.17) and higher costs (+$4274) per patient over a 40-year time horizon than AADs. Ultimately, this produced an average incremental cost-effectiveness ratio of $24,637 per QALY gained. Independent of initial treatment, individuals were expected to receive ∼1.2 ablations over a lifetime. There was a 45% relative reduction in time spent in atrial fibrillation health states for those initially treated with cryoablation compared with AADs.
UNASSIGNED: Initial rhythm control with first-line cryoballoon ablation is highly cost-effective compared with first-line AADs from a U.S. Medicare payer perspective.

Drug-induced taste disorders reduce quality of life, but little is known about the molecular mechanisms by which drugs induce taste disturbances. In this study, we investigated the short-term and long-term effects of the antiarrhythmic drug flecainide, which is known to cause taste dysfunction. Analyses of behavioral responses (licking tests) revealed that mice given a single intraperitoneal injection of flecainide exhibited a significant reduction in preference for a sour tastant (HCl) but not for other taste solutions (NaCl, quinine, sucrose, KCl and monopotassium glutamate) when compared with controls. Mice administered a single dose of flecainide also had significantly higher taste nerve responses to HCl but not to other taste solutions. Compared with controls, mice administered flecainide once-daily for 30 d showed a reduced preference for HCl without any changes in the behavioral responses to other taste solutions. The electrophysiological experiments using HEK293T cells transiently expressing otopetrin-1 (Otop1; the mouse sour taste receptor) showed that flecainide did not alter the responses to HCl. Taken together, our results suggest that flecainide specifically enhances the response to HCl in mice during short-term and long-term administration. Although further studies will be needed to elucidate the molecular mechanisms, these findings provide new insights into the pathophysiology of drug-induced taste disorders.

Background: Atrial flutter is an infrequent yet potentially fatal arrhythmia. Digoxin is the preferred first-line treatment for fetal atrial flutter due to its efficacy and favorable safety profile. The optimal digoxin serum target level for neonatal atrial flutter management remains uncertain, with the standard target level ranging from 1.0 to 2.0 ng/mL due to potential toxicity concerns above this threshold. Case Presentation: We present a case of atrial flutter in a fetus within a monochorionic diamniotic (MCDA) twin pregnancy that was successfully managed using a higher-than-standard target level of digoxin. A 34-year-old nulliparous woman was referred to our institution at 31 + 3 weeks of gestation due to fetal distress in an MCDA twin pregnancy. Fetal echocardiography revealed a ventricular rate of 214 bpm in twin A, while twin B exhibited no abnormal findings. Conclusions: Our case highlights a distinct correlation between the serum digoxin level and its impact on atrial flutter. A higher target serum level of digoxin may be necessary to achieve sinus conversion due to the unique maternal and fetal circulatory characteristics in MCDA pregnancies.

UNASSIGNED: Favorable clinical outcomes are difficult to achieve in long-standing persistent atrial fibrillation (LSPAF) with catheter ablation (CA). The CONVERGE (Convergence of Epicardial and Endocardial Ablation for the Treatment of Symptomatic Persistent Atrial FIbrillation) trial evaluated the effectiveness of hybrid convergent (HC) ablation vs endocardial CA.
UNASSIGNED: The study sought to evaluate the safety and effectiveness of HC vs CA in the LSPAF subgroup from the CONVERGE trial.
UNASSIGNED: The CONVERGE trial was a prospective, multicenter, randomized trial that enrolled 153 patients at 27 sites. A post hoc analysis was performed on LSPAF patients. The primary effectiveness was freedom from atrial arrhythmias off new or increased dose of previously failed or intolerant antiarrhythmic drugs (AADs) through 12 months. The primary safety endpoint was major adverse event incidence through 30 days with HC. Key secondary effectiveness measures included (1) percent of patients achieving ≥90% AF burden reduction vs baseline and (2) AF freedom.
UNASSIGNED: Sixty-five patients (42.5% of total enrollment) had LSPAF; 38 in HC and 27 in CA. Primary effectiveness was 65.8% (95% confidence interval [CI] 50.7%-80.9%) with HC vs 37.0% (95% CI 5.1%-52.4%) with CA (P = .022). Through 18 months, these rates were 60.5% (95% CI 50.0%-76.1%) with HC vs 25.9% (95% CI 9.4%-42.5%) with CA (P = .006). Secondary effectiveness rates were higher than CA with HC at 12 and 18 months. Freedom from atrial arrhythmias off AADs was 52.6% (95% CI 36.8%-68.5%) and 47.4% (95% CI 31.5%-63.2%) with HC at 12 and 18 months vs 25.9% (95% CI 9.4%-42.5%) and 22.2% (95% CI 6.5%-37.9%) with CA, respectively (12 months: P = .031; 18 months: P = .038). Three (7.9%) major adverse events occurred within 30 days of HC.
UNASSIGNED: Post hoc analysis demonstrated effectiveness and acceptable safety of HC compared with CA in LSPAF.