Echocardiography predictors of sustained sinus rhythm after cardioversion of supraventricular arrhythmia in patients with septic shock.

PURPOSE: The echocardiography parameters may predict the maintenance of sinus rhythm after cardioversion of a supraventricular arrhythmia (SVA). MATERIALS AND METHODS: Patients in septic shock with onset of an SVA, normal to moderately reduced LV systolic function (EF_LV˃̳35%) and on a continuous noradrenaline of <1.0 µg/kg.min were included. Echocardiography was performed at the arrhythmia onset, 1 h and 4 h post cardioversion on an infusion of propafenone or amiodarone. RESULTS: Cardioversion was achieved in 96% of the 209 patients within a median time of 6(1.8-15.6)h, 134(64.1%) patients experienced at least one SVA recurrence after cardioversion. At 4 h the left atrial emptying fraction (LA_EF, cut-off 38.4%, AUC 0.69,p˂0.001), and transmitral A wave velocity-time-integral (Avti, cut-off 6.8 cm, AUC 0.65,p = 0.001) showed as limited predictors of a single arrhythmia recurrence. The LA_EF 44(36,49)%, (p = 0.005) and the Avti 8.65(7.13,9.50)cm, (p < 0.001) were associated with sustained sinus rhythm and decreased proportionally to increasing numbers of arrhythmia recurrences (p < 0.001 and p = 0.007, respectively). The enlarged left atrial end-systolic diameter at the arrhythmia onset (p = 0.04) and elevated systolic pulmonary artery pressure at 4 h (p = 0.007) were weak predictors of multiple(˃3) recurrences. CONCLUSION: The LA_EF and Avti are related to arrhythmia recurrences post-cardioversion suggesting potential guidance to the choice between rhythm and rate control strategies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03029169, registered on 24th of January 2017.

Class 1C Antiarrhythmics for Premature Ventricular Complex Suppression in Nonischemic Cardiomyopathy With Implantable Cardioverter-Defibrillators.

BACKGROUND: Premature ventricular complexes (PVCs) are common and associated with worse outcomes in patients with heart failure. Class 1C antiarrhythmic drugs (AADs) effectively suppress PVCs, but guidelines currently restrict their use in structural heart disease. OBJECTIVES: This study aimed to assess the safety and efficacy of class 1C AADs in patients with nonischemic cardiomyopathy (NICM) and implantable cardioverter-defibrillators (ICDs). METHODS: All patients with NICM and an ICD treated with flecainide or propafenone at the Hospital of the University of Pennsylvania between 2014 and 2022 were identified. PVC burden, left ventricular ejection fraction (LVEF), and biventricular pacing percentage were compared before and during class 1C AAD treatment. Safety outcomes included sustained atrial and ventricular arrhythmias, heart failure admissions, and death. RESULTS: We identified 34 patients, 23 receiving flecainide and 11 propafenone. Most patients (62%) had failed other AADs or catheter ablation (68%) prior to class 1C AAD initiation. PVC burden decreased from 20% ± 13% to 6% ± 7% (P < 0.001), LVEF increased from 33% ± 9% to 37% ± 10% (P = 0.01), and biventricular pacing percentage increased from 85% ± 9% to 93% ± 7% (P = 0.01). Sustained ventricular tachycardia (2 vs 9 patients) and admissions for decompensated heart failure (2 vs 3 patients) decreased compared with the 12 months prior to class 1C AAD initiation. CONCLUSIONS: Class 1C AADs effectively suppressed PVCs in patients with NICM and ICDs, leading to increases in LVEF and biventricular pacing percentage. In this limited sample, their use was safe. Larger studies are needed to confirm the safety of this approach.

The outcomes of patients with septic shock treated with propafenone compared to amiodarone for supraventricular arrhythmias are related to end-systolic left atrial volume.

AIMS: A recently published trial has shown no differences in outcomes between patients with new-onset supraventricular arrhythmia (SVA) in septic shock treated with either propafenone or amiodarone. However, these outcome data have not been evaluated in relation to the presence or absence of a dilated left atrium (LA). METHODS AND RESULTS: Patients with SVA and a left ventricular ejection fraction ≥ 35% were randomized to receive intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). They were divided into groups based on whether their end-systolic left atrial volume (LAVI) was ≥40 mL/m². The subgroup outcomes assessed were survival at ICU discharge, 1 month, 3 months, 6 months, and 12 months. Propafenone cardioverted earlier (P = 0.009) and with fewer recurrences (P = 0.001) in the patients without LA enlargement (n = 133). Patients with LAVI < 40 mL/m2 demonstrated a mortality benefit of propafenone over the follow-up of 1 year [Cox regression, hazard ratio (HR) 0.6 (95% CI 0.4; 0.9), P = 0.014]. Patients with dilated LA (n = 37) achieved rhythm control earlier in amiodarone (P = 0.05) with similar rates of recurrences (P = 0.5) compared to propafenone. The outcomes for patients with LAVI ≥ 40 mL/m2 were less favourable with propafenone compared to amiodarone at 1 month [HR 3.6 (95% CI 1.03; 12.5), P = 0.045]; however, it did not reach statistical significance at 1 year [HR 1.9 (95% CI 0.8; 4.4), P = 0.138]. CONCLUSION: Patients with non-dilated LA who achieved rhythm control with propafenone in the setting of septic shock had better short-term and long-term outcomes than those treated with amiodarone, which seemed to be more effective in patients with LAVI ≥ 40 mL/m². TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03029169, registered on 24 January 2017.

Efficacy and safety of antazoline vs propafenone for conversion of paroxysmal atrial fibrillation to sinus rhythm: a randomized, double-blind study (AnProAF).

INTRODUCTION: Antazoline is a frequently used antiarrhythmic drug (AAD); however, to date, no randomized controlled trial has evaluated its efficacy and safety for cardioversion of recent­onset atrial fibrillation (AF) in comparison with other approved AADs. OBJECTIVES: This study aimed to compare clinical efficacy and safety of antazoline and propafenone for a rapid conversion of nonvalvular paroxysmal AF to sinus rhythm in patients without heart failure. PATIENTS AND METHODS: This was a single­center, randomized, double­blind study. It included patients with AF (lasting <48 hours) who were in a stable cardiopulmonary condition and eligible for cardioversion. The individuals who fulfilled the inclusion criteria were randomly assigned to receive either antazoline (up to 300 mg) or propafenone (up to 140 mg) intravenously. The primary end point was conversion of AF to sinus rhythm confirmed on electrocardiography. RESULTS: Overall, 94 participants (46 [48.9%] in the antazoline group and 48 [51.1%] in the propafenone group) were included. The mean (SD) age was 67.5 (14) years, and 40 participants (42.5%) were men. Successful AF conversion was observed in 29 patients (63%) from the antazoline group and 25 individuals (52.1%) from the propafenone group (P = 0.39). The median time to conversion was 10 minutes in the antazoline group and 30 minutes in the propafenone group (P = 0.03). Severe adverse events were observed in 5 patients (10.8%) treated with antazoline and 5 individuals (10.4%) who received propafenone. CONCLUSIONS: Intravenous antazoline demonstrated efficacy and safety comparable to those of intravenous propafenone for acute conversion of nonvalvular paroxysmal AF to sinus rhythm in patients without heart failure.

Propafenone versus amiodarone for supraventricular arrhythmias in septic shock: a randomised controlled trial.

PURPOSE: Acute onset supraventricular arrhythmias can contribute to haemodynamic compromise in septic shock. Both amiodarone and propafenone are available interventions, but their clinical effects have not yet been directly compared. METHODS: In this two-centre, prospective controlled parallel group double blind trial we recruited 209 septic shock patients with new-onset arrhythmia and a left ventricular ejection fraction above 35%. The patients were randomised in a 1:1 ratio to receive either intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). The primary outcomes were the proportion of patients who had sinus rhythm 24 h after the start of the infusion, time to restoration of the first sinus rhythm and the proportion of patients with arrhythmia recurrence. RESULTS: Out of 209 randomized patients, 200 (96%) received the study drug. After 24 h, 77 (72.8%) and 71 (67.3%) were in sinus rhythm (p = 0.4), restored after a median of 3.7 h (95% CI 2.3-6.8) and 7.3 h (95% CI 5-11), p = 0.02, with propafenone and amiodarone, respectively. The arrhythmia recurred in 54 (52%) patients treated with propafenone and in 80 (76%) with amiodarone, p < 0.001. Patients with a dilated left atrium had better rhythm control with amiodarone (6.4 h (95% CI 3.5; 14.1) until cardioversion vs 18 h (95% CI 2.8; 24.7) in propafenone, p = 0.05). CONCLUSION: Propafenone does not provide better rhythm control at 24 h yet offers faster cardioversion with fewer arrhythmia recurrences than with amiodarone, especially in patients with a non-dilated left atrium. No differences between propafenone and amiodarone on the prespecified short- and long-term outcomes were observed.

Early initiation of anti-relapse antiarrhythmic therapy in patients with atrial fibrillation and flutter after pharmacological cardioversion with refralon.

Aim      Evaluating the efficacy and safety of early administration of antirecurrence antiarrhythmic therapy (AAT) following restoration of sinus rhythm (SR) with refralon.Aim      Evaluating the efficacy and safety of early administration of antirecurrence antiarrhythmic therapy (AAT) following restoration of sinus rhythm (SR) with refralon.Material and methods  The study included 247 patients with atrial fibrillation/atrial flutter (AF/AFL) (142 men) who underwent pharmacological cardioversion (PCV) with refralon. A 4-step schedule of drug administration was used (successive intravenous infusions at doses of 5, 5, 10, and 10 µg/kg; maximum total dose was 30 µg/kg). Patients who recovered SR and had no contraindications were prescribed antirecurrence AAT in the early (≤24 h; n=101) or delayed (≥24 h; n=95) period. Lappaconitine hydrobromide, propafenone, and sotalol were administered orally as the antirecurrence therapy. The decision on the time of initiating ATT and the choice of the drug and its dose was taken by the attending physician individually. The safety criteria included a prolonged PQ interval >200 ms; second- or third-degree atrioventricular block; QRS complex duration >120 ms; QT prolongation >500 ms; and heartbeat pauses >3 s. The efficacy criteria included the absence of sustained recurrence of AF/AFL after initiation of AAT and the duration of hospitalization after PCV. Patients were followed up during the study until they were discharged from the hospital.Results SR was recovered in 229 (92.7 %) patients. In the group of early AAT initiation, a PQ duration >200 ms was observed in 8 (7.9 %) patients, whereas in the group of delayed AAT initiation, in 7 patients (7.4 %; p=1.000). A wide QRS complex >120 ms was recorded in 1 (1.1 %) patient of the delayed AAT initiation group and in none of the patients of the early AAT initiation group (p=0.485). Ventricular arrhythmogenic effects and QT prolongation >500 ms were not detected in any patient. Numbers of early AF recurrence did not differ in the groups of early and delayed AAT initiation: 6 (5.9 %) vs. 5 (5.3 %), respectively (p=1.000). Median duration of hospitalization after PCV was 4 days in the group of early AAT initiation and 5 days in the group of delayed AAT initiation (р=0.009).Conclusion      Early initiation of the refralon AAT does not increase the risk of drug adverse effects and reduces the duration of stay in the hospital.

Clinical and economic outcomes associated with use of anti-arrhythmic drugs versus ablation in atrial fibrillation.

Aim: To evaluate the clinical and economic impact of antiarrhythmic drugs (AADs) compared with ablation both as individual treatments and as combination therapy without/with considering the order of treatment among patients with atrial fibrillation (AFib). Materials & methods: A budget impact model over a one-year time horizon was developed to assess the economic impact of AADs (amiodarone, dofetilide, dronedarone, flecainide, propafenone, sotalol, and as a group) versus ablation across three scenarios: direct comparisons of individual treatments, non-temporal combinations, and temporal combinations. The economic analysis was conducted in accordance with CHEERS guidance as per current model objectives. Results are reported as costs per patient per year (PPPY). The impact of individual parameters was evaluated using one-way sensitivity analysis (OWSA). Results: In direct comparisons, ablation had the highest annual medication/procedure cost ($29,432), followed by dofetilide ($7661), dronedarone ($6451), sotalol ($4552), propafenone ($3044), flecainide ($2563), and amiodarone ($2538). Flecainide had the highest costs for long-term clinical outcomes ($22,964), followed by dofetilide ($17,462), sotalol ($15,030), amiodarone ($12,450), dronedarone ($10,424), propafenone ($7678) and ablation ($9948). In the non-temporal scenario, total costs incurred for AADs (group) + ablation ($17,278) were lower compared with ablation alone ($39,380). In the temporal scenario, AADs (group) before ablation resulted in PPPY cost savings of ($22,858) compared with AADs (group) after ablation ($19,958). Key factors in OWSA were ablation costs, the proportion of patients having reablation, and withdrawal due to adverse events. Conclusion: Utilization of AADs as individual treatment or in combination with ablation demonstrated comparable clinical benefits along with costs savings in patients with AFib.

Cardiovascular outcomes in patients with atrial fibrillation concomitantly treated with antiarrhythmic drugs and non-vitamin k antagonist oral anticoagulants.

AIMS: Limited data compared antiarrhythmic drugs (AADs) with concomitant non-vitamin K antagonist oral anticoagulants in atrial fibrillation patients, hence the aim of the study. METHODS AND RESULTS: National health insurance database were retrieved during 2012-17 for study. We excluded patients not taking AADs, bradycardia, heart block, heart failure admission, mitral stenosis, prosthetic valve, incomplete demographic data, and follow-up <3 months. Outcomes were compared in Protocol 1, dronedarone vs. non-dronedarone; Protocol 2, dronedarone vs. amiodarone; and Protocol 3, dronedarone vs. propafenone. Outcomes were acute myocardial infarction (AMI), ischaemic stroke/systemic embolism, intracranial haemorrhage (ICH), major bleeding, cardiovascular death, all-cause mortality, and major adverse cardiovascular event (MACE) (including AMI, ischaemic stroke, and cardiovascular death). In Protocol 1, 2298 dronedarone users and 6984 non-dronedarone users (amiodarone = 4844; propafenone = 1914; flecainide = 75; sotalol = 61) were analysed. Dronedarone was associated with lower ICH (HR = 0.61, 95% CI = 0.38-0.99, P = 0.0436), cardiovascular death (HR = 0.24, 95% CI = 0.16-0.37, P < 0.0001), all-cause mortality (HR = 0.33, 95% CI = 0.27-0.42, P < 0.0001), and MACE (HR = 0.56, 95% CI = 0.45-0.70, P < 0.0001). In Protocol 2, 2231 dronedarone users and 6693 amiodarone users were analysed. Dronedarone was associated with significantly lower ICH (HR = 0.53, 95%=CI 0.33-0.84, P = 0.0078), cardiovascular death (HR = 0.20, 95% CI = 0.13-0.31, P < 0.0001), all-cause mortality (HR 0.27, 95% CI 0.22-0.34, P < 0.0001), and MACE (HR = 0.53, 95% CI = 0.43-0.66, P < 0.0001), compared with amiodarone. In Protocol 3, 812 dronedarone users and 2436 propafenone users were analysed. There were no differences between two drugs for primary and secondary outcomes. CONCLUSION: The use of dronedarone with NOACs was associated with cardiovascular benefits in an Asian population, compared with non-dronedarone AADs and amiodarone.

An open-label randomized noninferior study of generic name and brand name of propafenone for rhythm control in patients with paroxysmal atrial fibrillation.

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).

Effect of Rythmol (propafenone HCl) administration during pregnancy in Wistar rats.

Propafenone is a well-known Class 1C antiarrhythmic agent that has sodium channel blocking properties as well as the ability to block 13 other channels and a modest calcium antagonistic effect. Propafenone has a profound electrophysiologic effect on auxiliary atrioventricular circuits and in patients with atrioventricular nodal reentry tachycardia can obstruct conduction in the fast conducting pathway. Furthermore, propafenone is less likely than other Class 1C drugs to cause proarrhythmia. However, although this medicine can pass through the placenta, the effects during pregnancy remain unknown. Here, we investigated the potential teratogenic and genotoxic effects of Rythmol during rat development. Pregnant Wistar rats received 46.25 mg/kg body weight of propafenone daily by gavage from Gestation Day (GD) 5 to GD 19. At GD 20, the dams were dissected, and their fetuses were assessed via morphologic, skeletal, and histologic investigation. In addition, a comet assay was used to measure DNA impairment of fetal skull osteocytes and hepatic cells. The study showed that propafenone treatment of pregnant rats led to a marked decrease in gravid uterine weight, number of implants/litter, number of viable fetuses, and bodyweight of fetuses but a clear increase in placental weight and placental index in the treated group. Frequent morphologic abnormalities and severe ossification deficiency in the cranium bones were observed in the treatment group. Various histopathological changes were observed in the liver, kidney, and brain tissues of maternally treated fetuses. Similarly, propafenone induced DNA damage to examined samples. Thus, our study indicates that propafenone may be embryotoxic in humans.

Efficacy and speed of conversion of recent onset atrial fibrillation using oral propafenone versus parenteral amiodarone: A randomized controlled comparative study.

BACKGROUND: Atrial fibrillation is the most commonly encountered arrhythmia. Several antiarrhythmic agents are effective in restoring and maintaining sinus rhythm. AIM OF THE WORK: To compare the efficacy and rapidity of conversion of recent onset atrial fibrillation using oral propafenone versus intravenous infusion of amiodarone. METHODS: The study included 200 patients with recent onset atrial fibrillation. Patients were equally divided into 2 groups; group A where intravenous infusion amiodarone was given and group B where oral propafenone was administrated. The effectiveness and the time needed for conversion of atrial fibrillation to sinus rhythm were compared in both groups. RESULTS: The success of conversion of atrial fibrillation to sinus rhythm was 83% in group A and 85% in group B, p-value = 0.699. The time elapsed from drug administration till conversion of atrial fibrillation was 9.07 ± 5.04 hours in group A versus 3.9 ± 1.54 hours in group B, p-value = 0.001. In both groups, patients who showed failed conversion had a significantly larger left atrial diameter and a significantly higher high sensitivity C-reactive protein (hsCRP) level. CONCLUSION: Oral propafenone was faster than parenteral amiodarone in the conversion of recent onset atrial fibrillation to sinus rhythm. Patients with failed conversion had a bigger left atrial diameter and a higher hsCRP when compared to patients with successful conversion.

Propafenone use in coronary artery disease patients undergoing atrial fibrillation ablation.

BACKGROUND: Antiarrhythmic drugs (AADs) are frequently used after atrial fibrillation (AF) ablation. Class IC AAD use after AF ablation in patients with coronary artery disease (CAD) is uncertain. The aim was to evaluate propafenone use in CAD patients undergoing AF ablation and to compare propafenone with amiodarone regarding ventricular arrhythmia and mortality. METHODS: In this retrospective, longitudinal cohort study, consecutive patients with mild to moderate CAD, undergoing AF ablation and receiving either propafenone (study group, n = 263) or amiodarone (control group, n = 499) in the blanking period, were included. After propensity score matching, 212 patients in each group were compared for the primary outcome defined as a composite of ventricular arrhythmic events, which included sudden cardiac death, sustained ventricular tachycardia or fibrillation, or non-sustained ventricular tachycardia (NSVT). Cardiovascular and non-cardiovascular mortality were evaluated as secondary outcomes. RESULTS: Baseline variables of the study and control groups were well matched after propensity score matching. At 12-month follow up, 20 patients (4.7%) (11 in propafenone group and 9 in amiodarone group) experienced the primary outcome measure of NSVT (Gray test p = 0.645). No sustained ventricular tachycardia, ventricular fibrillation, sudden cardiac death, or cardiovascular mortality were observed. On multivariable competing analysis, age and diabetes but not propafenone use (hazard ratio 1.017; p = 0.804) were found to be independent and significant predictors of the primary outcome measure. CONCLUSION: Propafenone use after AF ablation in patients with mild to moderate CAD had a safety profile similar to amiodarone and was not associated with major arrhythmic events.

Efficacy and safety of antazoline for cardioversion of atrial fibrillation: propensity score matching analysis of a multicenter registry (CANT II Study).

INTRODUCTION: Due to safety concerns about available antiarrhythmic drugs (AADs), reliable agents for termination of atrial fibrillation (AF) are requisite. OBJECTIVES: The aim of the study was to evaluate the efficacy and safety of antazoline, a first­generation antihistamine, for cardioversion of recent­onset AF in the setting of an emergency department. PATIENTS AND METHODS: This multicenter, retrospective registry covered 1365 patients (median [interquartile range] age, 69.0 [61.0-76.0] years, 53.1% men) with new­onset AF submitted to urgent pharmacological cardioversion. AAD allocation was performed by the attending physician: antazoline alone was utilized in 600 patients (44%), amiodarone in 287 (21%), propafenone in 150 (11%), and ≥2 AADs in 328 patients (24%). Antazoline in monotherapy or combination was administered to 897 patients (65.7%). Matched antazoline and nonantazoline groups were identified using propensity score matching (PSM, n = 330). The primary end point was return to sinus rhythm within 12 hours after initiation of the treatment. RESULTS: Before PSM, antazoline alone was superior to amiodarone (78.3% vs 66.9%; relative risk [RR], 1.17; 95% CI, 1.07-1.28; P <0.001) and comparable to propafenone (78.3% vs 72.7%; RR, 1.08; 95% CI, 0.97-1.20; P = 0.14) in terms of rhythm conversion rate. In the post­PSM population, the rhythm conversion rate was higher among patients receiving antazoline alone than in the nonantazoline group (84.2% vs 66.7%; RR, 1.26; 95% CI, 1.11-1.43; P <0.001), and the risk of adverse events was comparable (P = 0.2). CONCLUSIONS: Antazoline appears to be an efficacious agent for termination of AF in real­world setting. Randomized controlled trials are required to evaluate its safety in specific patient populations.

Antiarrhythmic Medication in Neonates and Infants with Supraventricular Tachycardia.

Supraventricular tachycardia (SVT) is the most common arrhythmia in neonates and infants, and pharmacological therapy is recommended to prevent recurrent episodes. This retrospective study aims to describe and analyze the practice patterns, effectiveness, and outcome of drug therapy for SVT in patients within the first year of life. Among the 67 patients analyzed, 48 presented with atrioventricular re-entrant tachycardia, 18 with focal atrial, and one with atrioventricular nodal re-entrant. Fetal tachycardia was reported in 27%. Antiarrhythmic treatment consisted of beta-receptor blocking agents in 42 patients, propafenone in 20, amiodarone in 20, and digoxin in 5. Arrhythmia control was achieved with single drug therapy in 70% of the patients, 21% needed dual therapy, and 6% triple. Propafenone was discontinued in 7 infants due to widening of the QRS complex. After 12 months (6-60), 75% of surviving patients were tachycardia-free and discontinued prophylactic treatment. Patients with fetal tachycardia had a significantly higher risk of persistent tachycardia (p: 0.007). Prophylactic antiarrhythmic medication for SVT in infancy is safe and well tolerated. Arrhythmia control is often achieved with single medication, and after cessation, most patients are free of arrhythmias. Infants with SVT and a history of fetal tachycardia are more prone to suffer from persistent SVT and relapses after cessation of prophylactic antiarrhythmic medication than infants with the first episode of SVT after birth.

Reappraising the role of class Ic antiarrhythmics in atrial fibrillation.

PURPOSE: The objective of the present systematic review was to compare the effectiveness and safety of class Ic agents for cardioversion of paroxysmal atrial fibrillation (AF), in patients with and without structural heart disease (SHD). METHODS: We focused on RCTs enrolling at least 50 adult patients with electrocardiogram-documented paroxysmal AF that compared either two pharmacological class Ic cardioversion agents (flecainide, propafenone), regardless of study design (parallel or crossover). We searched MEDLINE and the Cochrane Central Register of Controlled Trials. Initial search was performed from inception to 15 July 2021 with no language restrictions. RESULTS: Intravenous flecainide is the most effective option for pharmacologic cardioversion of AF since only 2 patients need to be treated in order to cardiovert one more within 4 h. Most importantly, class Ic agents appear to be safe in the context of pharmacologic cardioversion of AF irrespective of the presence of SHD, pointing towards a possible reappraisal of the role in this setting. CONCLUSION: We suggest that class Ic agents (with flecainide appearing to be more effective) should be used for pharmacologic cardioversion in stable AF patients presenting in emergency department with unknown medical history, after excluding severe cardiac disease through a bedside examination. REGISTRATION NUMBER (DOI): Available in https://osf.io/apwt7/ , https://doi.org/10.17605/OSF.IO/APWT7.

Atrial resting membrane potential confers sodium current sensitivity to propafenone, flecainide and dronedarone.

BACKGROUND: Although atrial fibrillation ablation is increasingly used for rhythm control therapy, antiarrhythmic drugs (AADs) are commonly used, either alone or in combination with ablation. The effectiveness of AADs is highly variable. Previous work from our group suggests that alterations in atrial resting membrane potential (RMP) induced by low Pitx2 expression could explain the variable effect of flecainide. OBJECTIVE: The purpose of this study was to assess whether alterations in atrial/cardiac RMP modify the effectiveness of multiple clinically used AADs. METHODS: The sodium channel blocking effects of propafenone (300 nM, 1 µM), flecainide (1 µM), and dronedarone (5 µM, 10 µM) were measured in human stem cell-derived cardiac myocytes, HEK293 expressing human NaV1.5, primary murine atrial cardiac myocytes, and murine hearts with reduced Pitx2c. RESULTS: A more positive atrial RMP delayed INa recovery, slowed channel inactivation, and decreased peak action potential (AP) upstroke velocity. All 3 AADs displayed enhanced sodium channel block at more positive atrial RMPs. Dronedarone was the most sensitive to changes in atrial RMP. Dronedarone caused greater reductions in AP amplitude and peak AP upstroke velocity at more positive RMPs. Dronedarone evoked greater prolongation of the atrial effective refractory period and postrepolarization refractoriness in murine Langendorff-perfused Pitx2c+/- hearts, which have a more positive RMP compared to wild type. CONCLUSION: Atrial RMP modifies the effectiveness of several clinically used AADs. Dronedarone is more sensitive to changes in atrial RMP than flecainide or propafenone. Identifying and modifying atrial RMP may offer a novel approach to enhancing the effectiveness of AADs or personalizing AAD selection.

In Silico Assessment of Class I Antiarrhythmic Drug Effects on Pitx2-Induced Atrial Fibrillation: Insights from Populations of Electrophysiological Models of Human Atrial Cells and Tissues.

Electrical remodelling as a result of homeodomain transcription factor 2 (Pitx2)-dependent gene regulation was linked to atrial fibrillation (AF) and AF patients with single nucleotide polymorphisms at chromosome 4q25 responded favorably to class I antiarrhythmic drugs (AADs). The possible reasons behind this remain elusive. The purpose of this study was to assess the efficacy of the AADs disopyramide, quinidine, and propafenone on human atrial arrhythmias mediated by Pitx2-induced remodelling, from a single cell to the tissue level, using drug binding models with multi-channel pharmacology. Experimentally calibrated populations of human atrial action po-tential (AP) models in both sinus rhythm (SR) and Pitx2-induced AF conditions were constructed by using two distinct models to represent morphological subtypes of AP. Multi-channel pharmaco-logical effects of disopyramide, quinidine, and propafenone on ionic currents were considered. Simulated results showed that Pitx2-induced remodelling increased maximum upstroke velocity (dVdtmax), and decreased AP duration (APD), conduction velocity (CV), and wavelength (WL). At the concentrations tested in this study, these AADs decreased dVdtmax and CV and prolonged APD in the setting of Pitx2-induced AF. Our findings of alterations in WL indicated that disopyramide may be more effective against Pitx2-induced AF than propafenone and quinidine by prolonging WL.

Safety and Effectiveness of Rivaroxaban in Combination with Various Antiarrhythmic Drugs in Patients with Non-Permanent Atrial Fibrillation.

INTRODUCTION: Rivaroxaban reduces the risk of thromboembolism in atrial fibrillation (AF) patients, who often also receive antiarrhythmic drugs (AADs) to maintain sinus rhythm. Current guidelines contraindicate concomitant use of rivaroxaban with the popular AAD dronedarone, despite little data demonstrating interactions with AADs. This study investigates the outcomes of concomitant rivaroxaban and AAD drug use in a real-world cohort. METHODS: This retrospective study included 1777 non-permanent AF patients taking rivaroxaban for ≥ 1 month between 2011 and 2016 from a multicenter cohort in Taiwan, and compared concomitant AAD use against clinical outcome endpoints for safety, effectiveness, and major adverse cardiac events (MACE). Multivariate Cox proportional hazard analyses were used to evaluate the association between concomitant AAD use and outcomes. RESULTS: Patients were divided into rivaroxaban alone (n = 1205) and with concomitant amiodarone (n = 177), dronedarone (n = 231), or propafenone (n = 164) groups. The proportion of patients using rivaroxaban 10 mg was highest in the concomitant dronedarone group: rivaroxaban alone, 53.6%; with amiodarone, 57.6%; with dronedarone, 77.1%; and with propafenone, 46.3% (p < 0.001). The cumulative incidences of safety (p = 0.892), effectiveness (p = 0.336), and MACE (p = 0.674) were similar between the four groups; however, there were significantly fewer new systemic thromboembolisms in the dronedarone group: rivaroxaban alone, 2.5%; with amiodarone, 0.6%; with dronedarone, 0%; and with propafenone, 1.2% (p = 0.029). The all-cause death rate was also lowest in the dronedarone group: rivaroxaban alone, 9.0%; with amiodarone, 9.6%; with dronedarone, 3.0%; and with propafenone: 6.1% (p = 0.013). After covariate adjustment, there were no differences in the safety, effectiveness, and MACE endpoints between patients receiving or not receiving AADs. CONCLUSION: Concomitant use of rivaroxaban with AADs appears to be well tolerated, warranting further investigation into the apparent benefits of a reduced dose of rivaroxaban combined with dronedarone.

Effect of CYP2D6 genetic polymorphism on peak propafenone concentration: no significant effect of CYP2D6*10.

Aim: The study aims to investigate the clinical implication of nonfunctional poor metabolizer (PM) alleles and intermediate metabolizer (IM) alleles of CYP2D6, including the CYP2D6*10 allele which shows substrate-dependent decrease in enzymatic activity, in antiarrhythmic therapy using propafenone. Materials & methods: We examined serum propafenone concentrations and metabolic ratio, which was expressed as serum concentrations of propafenone to 5-hydroxypropafenone, in 66 Japanese patients with tachyarrhythmias. Results: The peak propafenone concentration and metabolic ratio in CYP2D6 PM allele carriers were higher than those in extensive metabolizer (EM)/EM, EM/IM and IM/IM genotype groups. Conclusion: Results suggest that CYP2D6 PM alleles affect peak propafenone concentration, but the CYP2D6 IM allele CYP2D6*10 has no clinical implication in propafenone dosing.