Association between amiodarone use and risk of cataract: a population-based active-comparator study.

BACKGROUND: Despite previous concerns about ocular side effects related to amiodarone, the relationship between amiodarone and cataract remains uncertain. Therefore, this study aimed to assess the potential association between amiodarone use and the subsequent risk of cataract, taking into account potential confounders. METHODS: This population-based, active comparator-controlled cohort study utilized the data from the Taiwan National Health Insurance program and involved adults over 40 years old between 2001 and 2013. We analyzed 12 055 new amiodarone users and contrasted them with a propafenone user cohort. The primary outcome was the incidence of cataract. Inverse-probability treatment-weighting (IPTW) was further used to eliminate the potential confounding effects, and Cox proportional-hazard regression analyses were performed to calculate the risk of cataract. Serial subgroup analyses were also performed. RESULTS: In the main analysis, amiodarone users did not exhibit a significant causal relationship in both full cohort [adjusted hazard ratio (aHR): 0.994, 95% confidence interval (CI): 0.913-1.082] and IPTW cohort (IPTW-aHR 0.977, 95% CI: 0.900-1.060). Furthermore, it is important to highlight a significantly reduced risk of cataract among patients with heart failure (IPTW-aHR 0.708, 95% CI: 0.554-0.905) and during the 2-year follow-up period (IPTW-aHR 0.889, 95% CI: 0.794-0.996), implying potential advantages linked to the use of amiodarone. CONCLUSIONS: The study found no increased risk of cataract with amiodarone, one of the most frequently used antiarrhythmic medications, compared to the use of propafenone. Future research is recommended to explore potential mechanisms and their implications for clinical practice.

Medical cardioversion of atrial fibrillation and flutter with class IC antiarrhythmic drugs in young patients with and without congenital heart disease.

INTRODUCTION: The use of flecainide and propafenone for medical cardioversion of atrial fibrillation (AF) and atrial flutter/intra-atrial reentrant tachycardia (IART) is well-described in adults without congenital heart disease (CHD). Data are sparse regarding their use for the same purpose in adults with CHD and in adolescent patients with anatomically normal hearts and we sought to describe the use of class IC drugs in this population and identify factors associated with decreased likelihood of success. METHODS: Single center retrospective cohort study of patients who received oral flecainide or propafenone for medical cardioversion of AF or IART from 2000 to 2022. The unit of analysis was each episode of AF/IART. We performed a time-to-sinus rhythm analysis using a Cox proportional hazards model clustering on the patient to identify factors associated with increased likelihood of success. RESULTS: We identified 45 episodes involving 41 patients. As only episodes of AF were successfully cardioverted with medical therapy, episodes of IART were excluded from our analyses. Use of flecainide was the only factor associated with increased likelihood of success. There was a statistically insignificant trend toward decreased likelihood of success in patients with CHD. CONCLUSIONS: Flecainide was more effective than propafenone. We did not detect a difference in rate of conversion to sinus rhythm between patients with and without CHD and were likely underpowered to do so, however, there was a trend toward decreased likelihood of success in patients with CHD. That said, medical therapy was effective in >50% of patients with CHD with AF.

Electrophysiological effects and clinical utility of propafenone in children.

AIM: This retrospective case series study sought to describe the safety and clinical effectiveness of propafenone for the control of arrhythmias in children with and without CHD or cardiomyopathy. METHODS: We reviewed baseline characteristics and subsequent outcomes in a group of 63 children treated with propafenone at 2 sites over a 15-year period Therapy was considered effective if no clinically apparent breakthrough episodes of arrhythmias were noted on the medication. RESULTS: Sixty-three patients (29 males) were initiated on propafenone at a median age of 2.3 years. CHD or cardiomyopathy was noted in 21/63 (33%). There were no significant differences between demographics, clinical backgrounds, antiarrhythmic details, side effect profiles, and outcomes between children with normal hearts and children with CHD or cardiomyopathy. Cardiac depression at the initiation of propafenone was more common amongst children with CHD or cardiomyopathy compared to children with normal hearts. Systemic ventricular function was diminished in 15/63 patients (24%) prior to starting propafenone and improved in 8/15 (53%) of patients once better rhythm control was achieved. Other than one child in whom medication was stopped due to gastroesophageal reflux, no other child experienced significant systemic or cardiac side effects during treatment with propafenone. Propafenone achieved nearly equal success in controlling arrhythmias in both children with normal hearts and children with congenital heart disease or cardiomyopathy (90% versus 86%, p = 0.88). CONCLUSION: Propafenone is a safe and effective antiarrhythmic medication in children.

Single-dose oral anti-arrhythmic drugs for cardioversion of recent-onset atrial fibrillation: a systematic review and network meta-analysis of randomized controlled trials.

AIMS: Single oral dose anti-arrhythmic drugs (AADs) are used to cardiovert recent-onset atrial fibrillation (AF); however, the optimal agent is uncertain. METHODS: We performed a systematic review and network meta-analysis of randomized trials testing single oral dose AADs vs. any comparator to cardiovert AF <7 days duration. We searched MEDLINE, Embase, and CENTRAL to April 2020. The primary outcome was successful cardioversion at timepoint nearest 8 h after administration. RESULTS: From 12 712 citations, 22 trials (2320 patients) were included. Thirteen trials included patients with some degree of heart failure; 19 included patients with some degree of ischaemic heart disease vs. placebo or rate-control (32% success) at 8 h, flecainide [73%, network odds ratio (OR) 7.6, 95% credible interval (CrI) 4.4-14.0], propafenone (70%, OR 4.6, CrI 2.9-7.3), and pilsicainide (59%, OR 10.0, CrI 1.8-69.0), but not amiodarone (28%, OR 1.0, CrI 0.4-2.8) were superior. Flecainide (OR 7.5, CrI 2.6-24.0) and propafenone (OR 4.5, CrI 1.6-13.0) were superior to amiodarone; propafenone vs. flecainide did not statistically differ (OR 0.6, CrI 0.3-1.1). At longest follow-up, amiodarone was superior to placebo (OR 11.0, CrI 3.2-41.0), flecainide vs. amiodarone (OR 0.79, CrI 0.19-3.1), and propafenone vs. amiodarone (OR 0.36, CrI 0.092-1.4) were not statistically different, and flecainide was superior to propafenone (OR 2.2, CrI 1.1-4.8). Atrial and ventricular tachyarrhythmias, bradyarrhythmias, and hypotension were rare with PO AADs. CONCLUSION: Single oral dose Class 1C AADs are effective and safe for cardioversion of recent-onset AF. Flecainide may be superior to propafenone. Amiodarone is a slower acting alternative.

Radiofrequency ablation as initial therapy in paroxysmal atrial fibrillation.

BACKGROUND: There are limited data comparing radiofrequency catheter ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation. METHODS: We randomly assigned 294 patients with paroxysmal atrial fibrillation and no history of antiarrhythmic drug use to an initial treatment strategy of either radiofrequency catheter ablation (146 patients) or therapy with class IC or class III antiarrhythmic agents (148 patients). Follow-up included 7-day Holter-monitor recording at 3, 6, 12, 18, and 24 months. Primary end points were the cumulative and per-visit burden of atrial fibrillation (i.e., percentage of time in atrial fibrillation on Holter-monitor recordings). Analyses were performed on an intention-to-treat basis. RESULTS: There was no significant difference between the ablation and drug-therapy groups in the cumulative burden of atrial fibrillation (90th percentile of arrhythmia burden, 13% and 19%, respectively; P=0.10) or the burden at 3, 6, 12, or 18 months. At 24 months, the burden of atrial fibrillation was significantly lower in the ablation group than in the drug-therapy group (90th percentile, 9% vs. 18%; P=0.007), and more patients in the ablation group were free from any atrial fibrillation (85% vs. 71%, P=0.004) and from symptomatic atrial fibrillation (93% vs. 84%, P=0.01). One death in the ablation group was due to a procedure-related stroke; there were three cases of cardiac tamponade in the ablation group. In the drug-therapy group, 54 patients (36%) underwent supplementary ablation. CONCLUSIONS: In comparing radiofrequency ablation with antiarrhythmic drug therapy as first-line treatment in patients with paroxysmal atrial fibrillation, we found no significant difference between the treatment groups in the cumulative burden of atrial fibrillation over a period of 2 years. (Funded by the Danish Heart Foundation and others; MANTRA-PAF ClinicalTrials.gov number, NCT00133211.).

Electric cardioversion of atrial fibrillation resulting in pulmonary oedema in patient with apical hypertrophic cardiomyopathy.

The direct-current electric shock is considered to be safe treatment of arrhythmias and rarely leads to serious hemodynamic complications. A 62-year-old patient was admitted to the hospital due to a first symptomatic episode of atrial fibrillation. Patient was diagnosed with apical hypertrophic cardiomyopathy 20 years ago. Transoesophageal echocardiography was performed to exclude an atrial thrombus followed by electrical cardioversion with restoration of sinus rhythm. After 6 hours symptoms of pulmonary oedema developed. The patient's condition improved after furosemide administration. As the possible cause of the oedema, inotropic effect of administered propafenone and atrial stunning were considered. The atria seem to be responsible for important part of forward cardiac output even during AF, especially in cardiomyopathies. Contractility deterioration of the left atrium (stunning) along with earlier resumption of the right atrium contractile function could be associated with hemodynamic instability causing pulmonary oedema in subjects with hypertrophied myocardium. It is necessary to take into consideration the atrial function while administrating antiarrhythmic drugs, especially those with negative inotropic effect.

Propafenone associated severe central nervous system and cardiovascular toxicity due to mirtazapine: a case of severe drug interaction.

We describe a rare case of severe drug-drug interaction between propafenone and mirtazapine leading to propafenone toxicity. A 69-year-old Caucasian male taking propafenone for atrial fibrillation was prescribed mirtazapine for insomnia. Subsequent to the first dose of mirtazapine the patient experienced seizures, bradycardia and prolonged QRS as well as QTc intervals on EKG. The patient was admitted to the ICU and recovered after supportive management. Propafenone is an established class IC antiarrhythmic drug commonly used in the treatment of atrial fibrillation. It is metabolized through the CYP4502D6 pathway. Five to 10 percent of Caucasians are poor metabolizers. Mirtazapine is a commonly prescribed antidepressant drug, which is also metabolized through and may modulate the CYP4502D6 pathway leading to altered metabolism of propafenone and possible adverse effects. In this case, toxicity was reversed once the offending drugs were discontinued. An extensive review of the literature revealed this to be the first described case of drug interaction between propafenone and mirtazapine.

Medical therapy with flecainide and propafenone in atrial fibrillation: Long-term clinical experience in the tertiary care setting.

BACKGROUND: Flecainide and propafenone are Class Ic antiarrhythmic drugs that block the cardiac fast inwards Na+ current and are used for rhythm control in patients with atrial fibrillation (AF). However, data on long-term clinical efficacy and safety of these drugs in a real-world setting are scarce. METHODS: Patients with AF who received chronic flecainide or propafenone therapy were retrospectively studied from the database of a tertiary care center. The primary outcome of the study was clinical efficacy of Class Ic antiarrhythmics, which was assessed based on the improvement of arrhythmia-related symptoms at the time of last follow-up. RESULTS: Among the 361 patients (261 males, 72.3%) with a mean age of 56 ± 12 years, 287 (79.5%) were using long-term flecainide, and 74 (20.5%) patients propafenone. The majority of the patients had paroxysmal AF (n = 331, 91.7%) and had an atrioventricular-nodal blocking co-medication (n = 287, 79.5%). A total of 117 (32%) patients discontinued therapy after a median of 210 days (interquartile range 62-855 days). Clinical efficacy was observed in 188 (52%) patients. The most common reason for therapy discontinuation was adverse drug effects, particularly proarrhythmic effects (48% for flecainide and 33% for propafenone). Patients who did not clinically benefit from Class Ic antiarrhythmics more often underwent pulmonary vein isolation (p = 0.02). CONCLUSIONS: Long-term therapy with Class Ic antiarrhythmics showed clinical efficacy in approximately half of the patients with paroxysmal or persistent AF. However, these drugs were also associated with a relatively high rate of adverse events, and in particular proarrhythmic effects, which often resulted in therapy discontinuation rendering appropriate patient selection and therapy surveillance essential.

Flecainide in clinical practice.

Flecainide, similar to encainide and propafenone, is IC class antiarrhythmic, inhibiting Nav1.5 sodium channels in heart muscle cells and modulates cardiac conduction. Despite its over 40-year presence in clinical practice, strong evidence and well-known safety profile, flecainide distribution in Europe has not always been equal. In Poland, the drug has been available in pharmacies only since October this year, and previously it had to be imported on request. Flecainide can be used successfully in both the acute and chronic treatment of cardiac arrhythmias. The main indication for flecainide is the treatment of paroxysmal supraventricular tachycardias, including atrial fibrillation, atrioventricular nodal re-entrant tachycardia, atrioventricular re-entrant tachycardia and ventricular arrhythmias in patients without structural heart disease. Beyond that, it may be used in some supraventricular tachycardia in children and for sustained fetal tachycardia. Many studies indicate its efficacy comparable to or better than previously used drugs such as propafenone and amiodarone, depending on the indication. This review aims to highlight the most important clinical uses of flecainide in the light of the latest scientific evidence and to provide an overview of the practical aspects of treatment, including indications, off-label use, contraindications, areas of use, monitoring of treatment and most common complications, taking into account special populations: children and pregnant women.

Idiopathic premature ventricular complexes treatment: Comparison of flecainide, propafenone, and sotalol.

BACKGROUND: Beta-blockers (BB) or dihydropyridine calcium channel blockers (CCBs) are still the first choices in the treatment of idiopathic premature ventricular complexes (PVCs), with low-modest efficacy. Antiarrhythmic drugs (AADs) of Ic class are moderate to highly efficient but the evidence on their benefits is still limited. AIM: To compare effectiveness and safety of flecainide, propafenone, and sotalol in the treatment of symptomatic idiopathic PVCs. METHODS: Our single-center retrospective study analyzed 104 consecutive patients with 130 medication episodes of frequent idiopathic PVCs treated with AADs flecainide, propafenone (Ic class) or sotalol (III class). The primary outcome was complete/near complete reduction of PVCs after medication episode (PVCs burden reduction >99%), and the secondary outcome was significant PVC burden reduction (≥80%). RESULTS: The complete/near complete PVCs burden reduction occurred in 31% and was significant in 43% of treated patients. A reduction of PVC burden for >99% was achieved in 56% of patients on flecainide, in 11% of patients on propafenone (p = .002), and in 21% of patients receiving sotalol (p = .031). There was no difference between propafenone and sotalol (p = .174). A reduction of PVC burden for ≥80% was achieved in 64% of patients on flecainide, in 30% of patients on propafenone (p = .009), and 33% of patients on sotalol (p = .020). There was no difference between propafenone and sotalol (p = .661). CONCLUSIONS: The efficacy of AADs class Ic and III in the treatment of idiopathic PVCs was modest. Flecainide was the most effective AAD in the achievement of complete/near complete or significant PVC burden reduction, compared to propafenone and sotalol.

Antiarrhythmic drugs for pharmacological cardioversion of atrial fibrillation and sex differences: Insights from the CANT II Study.

BACKGROUND: Data on sex differences in terms of action of antiarrhythmic agents (AADs) are limited. This study aimed to evaluate the clinical profile of patients with atrial fibrillation (AF), and efficacy and safety of AADs used for pharmacological cardioversion (PCV) of AF. METHODS: This research was a sub-analysis of the retrospective multicenter Cardioversion with ANTazoline II (CANT) registry, which comprised 1365 patients with short-duration AF referred for urgent PCV with the use of AAD. Patients were categorized according to and compared in terms of clinical parameters and PCV outcomes. The primary endpoint was return of sinus rhythm within 12 hours after drug infusion, and the composite safety endpoint involved bradycardia <45 bpm, hypotension, syncope, or death. RESULTS: The sex distribution of patients qualified for PCV was even (men, n = 725; 53.1%). Females were older and more symptomatic and had higher CHA2DS2-VASc scores, higher prevalence of tachyarrhythmia, and higher use of chronic anticoagulation. The overall efficacy (71.4% vs. 70.1%; P = 0.59) and safety (5.2% vs. 4.6%; P = 0.60) of PCV was comparable in men and women. Amiodarone (68.3% vs. 65.9%; P = 0.66) and antazoline (77.1% vs. 80.0%; P = 0.19) had similar efficacy in men and women, but propafenone had a lower rate of rhythm conversion in men (64.7% vs. 79.3%; P = 0.046). None of the assessed AADs differed in terms of safety profile in both sexes. CONCLUSION: Female patients with AF have different clinical profiles but similar efficacy and safety of AADs as compared to male participants. Propafenone has significantly lower efficacy in men, which requires further investigation.

Electrophysiological predictors of propafenone efficacy in prevention of atrioventricular nodal re-entrant and atrioventricular re-entrant tachycardia.

AIM: To assess the efficacy of propafenone in prevention of atrioventricular nodal reentrant tachycardia (AVNRT) and orthodromic atrioventricular tachycardia (AVRT) based on the clinical results of arrhythmia recurrence and find the electrophysiological predictor of propafenone effectiveness. METHODS: This retrospective study included 44 participants in a 12-month period, who were divided in two groups: group A - in which propafenone caused complete ventriculo-atrial block and group B - in which propafenone did not cause complete ventriculo-atrial block. RESULTS: Group A had significantly lower incidence of tachycardia than group B (95% vs 70.8%, P=0.038), and complete ventriculo-atrial block predicted the efficacy of propafenone oral therapy in the prevention of tachycardia (sensitivity 87.5%, specificity 52.8%, positive predictive value 95%, negative predictive value 29.2%). Patients with AVNRT in group B who did not experience the recurrences of tachycardia had significantly shorter echo zone before intravenous administration of propafenone than the patients who experienced episodes of sustained tachycardia (median 40 ms [range 15-60 ms] vs 79 ms [range 50-180 ms], P=0.008). CONCLUSION: In patients with non-inducible tachycardia, complete ventriculo-atrial block can be used as an electrophysiological predictor of the efficacy of propafenone oral therapy in the prevention of tachycardia. In patients with non-inducible AVNRT, but without complete ventriculo-atrial block, propafenone was more effective in patients with shorter echo zone of tachycardia.

Safety of Pill-in-the-Pocket Class 1C Antiarrhythmic Drugs for Atrial Fibrillation.

BACKGROUND: Guidelines recommend that initial trial of a "pill-in-the-pocket" (PIP) Class 1C antiarrhythmic drug (AAD) for cardioversion of atrial fibrillation (AF) be performed in a monitored setting because of the potential for adverse reactions. OBJECTIVES: This study sought to characterize real-world, contemporary use of the PIP approach, including the setting of initiation and incidence of adverse events. METHODS: This retrospective cohort study included all patients at the Hospital of the University of Pennsylvania treated with a PIP approach for AF between 2007 and 2020. RESULTS: A total of 273 patients (age 56 ± 13 years; 182 [67%] male; CHA2DS2VASc score 1.1 ± 1.2) took a first dose of PIP AAD. Flecainide was used in 151 (55%) and propafenone in 122 (45%). The first dose of PIP AAD was taken in a monitored setting in 167 (62%). Significant adverse events occurred in 7 patients (3%), 2 of whom had taken the dose in a monitored setting. Significant adverse events included unexplained syncope (1 of 7), symptomatic bradycardia/hypotension (4 of 7), and 1:1 atrial flutter (2 of 7). All occurred in patients taking 300 mg of flecainide (n = 4) or 600 mg of propafenone (n = 3). Electrical cardioversion was performed in 29 (11%) patients because of failure of the AAD to terminate AF. One patient required intravenous fluids and vasopressors for 2 hours because of persistent hypotension and bradycardia. Two patients required permanent pacemakers for bradycardia. The remaining patients required no intervention. CONCLUSIONS: Our data support the current recommendation to initiate PIP AAD in a monitored setting because of rare significant adverse reactions that can require urgent intervention.

Influence of CYP2D6 genetic variation on adverse events with propafenone in the pediatric and young adult population.

Propafenone is an antiarrhythmic drug metabolized primarily by cytochrome P450 2D6 (CYP2D6). In adults, propafenone adverse events (AEs) are associated with CYP2D6 poor metabolizer status; however, pediatric data are lacking. Subjects were tested for 10 CYP2D6 allelic variants and copy number status, and activity scores assigned to each genotype. Seventy-six individuals (median 0.3 [range 0-26] years old) were included. Propafenone AEs occurred in 29 (38%); 14 (18%) required drug discontinuation due to AE. The most common AEs were QRS (n = 10) and QTc (n = 6) prolongation. Those with AEs were older at the time of propafenone initiation (1.58 [0.13-9.92] vs. 0.20 [0.08-2.01] years old; p = 0.042). CYP2D6 activity scores were not associated with presence of an AE (odds ratio [OR] 0.48 [0.22-1.03]; p = 0.055) but with the total number of AE (ß1  = -0.31 [-0.60, -0.03]; p = 0.029), systemic AEs (OR 0.33 [0.13-0.88]; p = 0.022), and drug discontinuation for systemic AEs (OR 0.28 [0.09-0.83]; p = 0.017). Awareness of CYP2D6 activity score and patient age may aid in determining an individual's risk for an AE with propafenone administration.