Search

Aims To evaluate the effectiveness and safety of dronedarone compared with other commonly used antiarrhythmic drugs (AADs) for preventing atrial fibrillation (AF) recurrences. Methods and results An international observational cohort study in Germany, Spain, Italy, and the USA enrolling patients with AF receiving AAD therapy. Patients with New York Heart Association (NYHA) Class IV heart failure were excluded. Participants were followed for up to 18 months, regardless of discontinuation or subsequent AAD switches. Atrial fibrillation recurrence was captured by hospitalization, emergency room visit, or electrocardiogram-based documentation of AF. Confounding bias was controlled for in the analysis of AF recurrence using multivariate models of 19 variables for adjustment. A total of 1009 participants [mean age 67.2 (10.8) years, male to female ratio 1.3] were recruited from 170 centres, 693 (69%) of which were from across Europe and the remaining 316 (31%) from the USA. At the time of enrolment, participants were taking dronedarone (51%) or other AADs (49%) [flecainide or propafenone (42%), sotalol (11%), and amiodarone (47%)]. No significant differences in the risk of first confirmed AF recurrence with dronedarone vs. other AADs [crude hazard ratio (HR) 1.10 (95% confidence interval 0.85–1.42); adjusted HR 1.16 (0.87–1.55)] were found, irrespective of whether univariate or multivariate models were used. Reported safety events were in accordance with the known safety profile of dronedarone. Conclusion In this population of patients from either Europe or the USA receiving dronedarone or another AAD, the effectiveness of dronedarone was comparable to that observed for other AADs in preventing first AF recurrence.

Congenital junctional ectopic tachycardia (CJET) is a rare tachyarrhythmia that remains difficult to manage, with suboptimal control in most cases. Here, we report literature research on the use of ivabradine in the treatment of pediatric junctional ectopic tachycardia (JET), both congenital and postoperative, and describe the successful use of ivabradine–flecainide association for CJET therapy resistant to other antiarrhythmic agents. This new drug combination was effective in completely suppressing JET. Ivabradine–flecainide combination may be considered a new therapeutic strategy of CJET with a satisfactory efficacy/tolerability ratio in patients resistant to conventional drug combinations.

Dual atrioventricular nodal nonreentrant tachycardia (DAVNNT) is a rare form of supraventricular tachycardia. In some patients, the presence of a dual pathway physiology results in two paths in the atrioventricular (AV) node with different conduction velocities. An atrial impulse arriving at the AV node may unfold and travel along these two pathways simultaneously, causing two ventricular activations. Thus, the ventricular rate will be twice the atrial rate. DAVNNT is less common than AVNRT, but its frequency may be underestimated. The ECG is crucial to suspect the diagnosis. At first glance it looks like an irregular tachycardia, but a more careful look shows a rhythmic pattern. A sinus P wave followed by two QRS complexes (narrow or wide) should raise suspicion of this arrhythmia. It is often unnoticed by the patient, and ventricular dysfunction due to tachycardiomyopathy is not uncommon. The response of DAVNNT to medication, including beta-blockers, flecainide, and amiodarone is very poor or absent, so the treatment of choice is slow pathway ablation. We report a Case of cardiomyopathy caused by this entity.

A 39-year-old man presented to the Emergency Department (ED) with a 10-hour history of palpitations but denied any chest pain, breathlessness or syncope. His medical history and family history were unremarkable. On admission, he was tachycardic with an irregularly irregular pulse at 180 beats/min. ECG showed atrial fibrillation with fast ventricular response (figure 1A). Bed-side transthoracic echocardiogram demonstrated a structurally normal heart. Chemical cardioversion was therefore attempted with intravenous flecainide. A postcardioversion 12-lead ECG was obtained (figure 1B). Figure 1 (A) 12-lead ECG showing a narrow complex tachycardia with no discernible P-waves and irregular R–R intervals in keeping with atrial fibrillation. …

Background:Prognosis of fetuses with hydrops and tachyarrhythmia has been portrayed as poor in most published reports. This might lead to biased counselling, unnecessary caesarean section, preterm delivery, and even termination of pregnancy.Aims:To evaluate contemporary fetal and postnatal outcomes of hydropic fetuses with fetal tachyarrhythmia when it is treated effectively and monitored systematically.Methods:This is a retrospective review of a single centre experience at the University Hospital of Wales over a 20-year period. All fetuses received high doses of flecainide and digoxin combination treatment. Tachycardia response rate, time to arrhythmia and hydrops resolution, fetal and postnatal morbidity, and mortality rates were analysed.Results:Twenty fetuses were diagnosed with hydrops fetalis and received treatment. The mechanism of fetal tachyarrhythmia was supraventricular tachycardia in thirteen and atrial flutter in eight cases. Among the 20 fetuses treated, the overall tachycardia response rate was 90% (18/20) with the restoration of sinus rhythm in 85% (17/20) of the cases. The median time to restore sinus rhythm or to rate control of the arrhythmia was 1.5 days (range 12 hours to 13 days). Hydrops resolved in 17 of the 20 fetuses, with a median time of 12 days (range 3–21 days). Four fetuses went into spontaneous preterm birth and one fetus was delivered early due to worsening hydrops. No significant neurological morbidity was observed in surviving neonates and infants on clinical examination. There was one postnatal death due to respiratory complications of prematurity in the non-responsive supraventricular tachycardia case.Conclusions:High-dose flecainide and digoxin combination offers effective treatment strategy in fetuses with hydrops and tachyarrhythmia with favourable outcomes. This study may guide more realistic counselling for pregnancies complicated by tachyarrhythmia and hydrops.

Background: Flecainide is a useful antiarrhythmic for atrial fibrillation (AF). However, because of ventricular proarrhythmia risk, a history of myocardial infarction (MI) or coronary artery disease (CAD) is a flecainide exclusion, and stress testing is used to exclude ischemia. We assessed whether absent/mild coronary artery calcium (CAC) can supplement or avoid the need for stress testing. Methods: We assessed ischemic burden using regadenoson Rb-82 PET/CT in 1372 AF patients ≥50 years old without symptoms or signs of clinical CAD. CAC was determined qualitatively by low dose attenuation computed tomography (CT) (n = 816) or by quantitative CT (n = 556). Ischemic burden and clinical outcomes were compared by CAC burden. Results: Patients with CAC absent or mild (n = 766, 57.2%) were younger, more frequently female, and had higher BMI but lower rates of diabetes, hypertension, and dyslipidemia. Average ischemic burden was lower in CAC-absent/mild patients, and CAC-absent/mild patients showed greater coronary flow reserve, had fewer referrals for coronary angiography, and less often had obstructive CAD. Revascularization at 90 days was lower, and the rate of longer-term major adverse cardiovascular events was favorable. Conclusions: An easily administered, inexpensive, low radiation CAC scan can identify a subset of flecainide candidates with a low ischemic burden on PET stress testing that rarely needs coronary angiography/intervention and has favorable outcomes. Absent or mild CAC-burden combined with other clinical information may avoid or complement routine stress testing. However, additional, ideally randomized and multicenter trials are indicated to confirm these findings before replacing stress testing with CAC screening in selecting patients for flecainide therapy in clinical practice.

This case report presents a 33-year-old woman with premature ventricular contractions (PVCs). Her genetic testing was positive for KCNJ2 missense mutation at chr17:68171832;NM_000891.2. This mutation was compatible with Andersen-Tawil syndrome. We made an electrophysiological study to determine origin of PVCs however at endocardial mapping there was not any focus of PVC and at epicardial mapping we ablated low voltage areas in the inferior segments of both ventricles. She was discharged with flecainide and metoprolol therapy. After 3 months, her PVC burden was significantly decreased at Holter monitoring. (c) 2021 Elsevier Inc. All rights reserved.

Aims Maintaining sinus rhythm in patients with persistent atrial fibrillation (AF) is challenging. We explored the efficacy of class I and III antiarrhythmic drugs (AADs) in patients with persistent AF and mild to moderate heart failure (HF). Methods and results In the RACE 3 trial, patients with early persistent symptomatic AF and short history of mild to moderate HF with preserved or reduced left ventricular ejection fraction (LVEF) were randomized to targeted or conventional therapy. Both groups received AF and HF guideline-driven treatment. Additionally, the targeted-group received mineralocorticoid receptor antagonists, statins, angiotensin-converting enzyme inhibitors and/or receptor blockers, and cardiac rehabilitation. Class I and III AADs could be instituted in case of symptomatic recurrent AF. Eventually, pulmonary vein isolation could be performed. Primary endpoint was sinus rhythm on 7-day Holter after 1-year. Included were 245 patients, age 65 ± 9 years, 193 (79%) men, AF history was 3 (2–6) months, HF history 2 (1–4) months, 72 (29.4%) had HF with reduced LVEF. After baseline electrical cardioversion (ECV), 190 (77.6%) had AF recurrences; 108 (56.8%) received class I/III AADs; 19 (17.6%) flecainide, 36 (33.3%) sotalol, 3 (2.8%) dronedarone, 50 (46.3%) amiodarone. At 1-year 73 of 108 (68.0%) patients were in sinus rhythm, 44 (40.7%) without new AF recurrences. Maintenance of sinus rhythm was significantly better with amiodarone [n = 29/50 (58%)] compared with flecainide [n = 6/19 (32%)] and sotalol/dronedarone [n = 9/39 (23%)], P = 0.0064. Adverse events occurred in 27 (25.0%) patients, were all minor and reversible. Conclusion In stable HF patients with early persistent AF, AAD treatment was effective in nearly half of patients, with no serious adverse effects reported.

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.

Flecainide is a class IC antiarrhythmic drug that is contraindicated in patients who have a history of myocardial infarction, but its effect on mortality and risk of proarrhythmia in patients with stable obstructive and nonobstructive epicardial coronary artery disease (CAD) has not been assessed. We sought to compare the safety of flecainide administration in patients who had angiographic evidence of either no or minimal CAD versus nonobstructive CAD, and those who underwent nuclear stress testing with perfusion defects versus those without perfusion defects. We conducted a retrospective chart review of 348 patients who were treated with flecainide for at least 1 year duration and underwent evaluation for CAD with coronary angiography or myocardial perfusion imaging (MPI) stress testing within 3 months of initiating flecainide. We compared overall mortality and proarrhythmia between varying levels of CAD and perfusion defects. There was a similar 10-year survival between those with no or minimal CAD, nonobstructive CAD, and obstructive CAD (p = 0.6). Additionally, there was no difference in arrhythmia burden, including sustained ventricular tachycardias or frequent premature ventricular contractions (> 5% daily burden; p = 0.25). There was also no increase in mortality among those who had reversible perfusion defects >0% compared with those without, among subjects who underwent MPI (p = 0.14). On subgroup analysis, there was no increased risk in all-cause mortality with any specific coronary artery involvement, or with obstructive multivessel CAD (p = 0.89). Flecainide use is not associated with an increase in either all-cause mortality or ventricular arrhythmias in low-risk patients with stable nonobstructive CAD.

Purpose To compare risks of interstitial lung disease (ILD) between patients treated with dronedarone versus other antiarrhythmics. Methods Parallel retrospective cohort studies were conducted in the United States Department of Defense Military Health System database (DoD) and the HealthCore Integrated Research Database (HIRD). Study patients were treated for atrial fibrillation (AF) with dronedarone, amiodarone, sotalol, or flecainide. Propensity score matching was employed to create analysis cohorts balanced on baseline variables considered potential confounders of treatment decisions. The study period of July 20, 2008 through September 30, 2014 included a 1‐year baseline and minimum 6 months of follow‐up, for patients with drugs dispensed between July 20, 2009 and March 31, 2014. Suspect ILD outcomes were reviewed by independent adjudicators. Cox proportional hazards regression compared risk of confirmed ILD between dronedarone and each comparator cohort. A sensitivity analysis examined the effect of broadening the outcome definition. Results A total 72 ILD cases (52 DoD; 20 HIRD) were confirmed among 27 892 patients. ILD risk was significantly higher among amiodarone than dronedarone initiators in DoD (HR = 2.5; 95% CI = 1.1–5.3, p = 0.02). No difference was detected in HIRD (HR = 1.0; 95% CI = 0.4–2.4). Corresponding risks in sotalol and flecainide exposure groups did not differ significantly from dronedarone in either database. Conclusions ILD risk among AF patients initiated on dronedarone therapy was comparable to or lower than that of amiodarone initiators, and similar to that of new sotalol or flecainide users. This finding suggests that elevated ILD risk associated with amiodarone does not necessarily extend to dronedarone or other antiarrhythmic drugs.

Atrial fibrillation (AF) constitutes an increasing health problem in the aging population. Animal models reflecting human phenotypes are needed to understand the mechanisms of AF, as well as to test new pharmacological interventions. In recent years, a number of large animal models, primarily pigs, goats, dog and horses have been used in AF research. These animals can to a certain extent recapitulate the human pathophysiological characteristics and serve as valuable tools in investigating new pharmacological interventions for treating AF. This review focuses on anti-arrhythmic investigations in large animals. Initially, spontaneous AF in small and large mammals is discussed. This is followed by a short presentation of frequently used methods for inducing short- and long-term AF. The major focus of the review is on anti-arrhythmic compounds either frequently used in the human clinic (ranolazine, flecainide, vernakalant and amiodarone) or being promising new AF medicine candidates (IK,Ach , ISK,Ca and IK2P blockers).

Introduction Antiarrhythmic drugs (AADs) are commonly used for the treatment of newly-diagnosed symptomatic atrial fibrillation (AF), however initial AAD choice, duration of therapy, rates of discontinuation and factors associated with a durable response to therapy are poorly understood. This study assesses initial choice and duration of antiarrhythmic drug therapy in the first two years after diagnosis of atrial fibrillation in a younger, commercially-insured population. Methods A large nationally-representative sample of patients age 20 to 64 was studied using the IBM MarketScan Database. Patients who started an AAD within 90 days of AF diagnosis with continuous enrollment for 1 year pre-index diagnosis and 2 years post-index were included. A Cox proportional hazards model was used to determine factors associated with AAD discontinuation. Results Flecainide was used most frequently (26.8%), followed by amiodarone (22.5%), dronedarone (18.3%), sotalol (15.8%), and propafenone (14.0%), with other AADs used less frequently. Twenty-two percent of patients started on an AAD underwent ablation within 2 years, with 79% discontinuing the AAD after ablation. Ablation was the strongest predictor of AAD discontinuation (HR: 1.70; CI: 1.61 - 1.80), followed by male gender (HR: 1.10; CI: 1.02 - 1.19). Older patients (HR: 0.76; CI: 0.72 - 0.80; reference age 18-49) and those with comorbidities, including cardiomyopathy (HR: 075; CI: 0.61 - 0.91), diabetes (HR: 0.83; CI: 0.75 - 0.91) and hypertension (HR: 0.87; CI: 0.81 - 0.94) were less likely to discontinue AADs. Conclusion Only 31% of patients remained on the initial AAD at 2 years, with mean duration of initial therapy 7.6 months prior to discontinuation. Unstructured abstract Antiarrhythmic drugs (AADs) are commonly used for the treatment of newly-diagnosed atrial fibrillation, but practice patterns and duration of treatment is poorly understood. This study examined AAD initiation in a young, commercially-insured population. Flecainide was used most frequently (26.8%), followed by amiodarone (22.5%), with other AADs used less frequently. Only 31% of patients remained on the initial AAD at 2 years, with an average duration of therapy of 7.6 months before discontinuation. This article is protected by copyright. All rights reserved.

Lack of age-appropriate commercially available drugs hinders adequate pharmacotherapy in children. The European Union Paediatric Regulation (EC No1901/2006) and the establishment of the EU Paediatric Committee PDCO (2007) were aimed to stimulate research into the use of medicines in children and to lead to the authorisation of more medicines among all age groups. Since then, we have seen indeed an increase in the number of authorised medicines for children.1 But progress has been slow, as is expressed by the fact that 47.7% of all oral medicines on the 2019 WHO Essential Medicines List for Children do not have an age-appropriate dosage form registered by the European Medicines Agency (EMA).2 In our comprehensive paediatric care hospital, we see that more than half of oral drugs need to be manipulated somehow, for instance, by crushing, splitting or dissolving adult-dosed tablets, before they can be administered to children. The drugs that need to be manipulated represent a broad range of therapeutic subgroups like antiepileptics, corticosteroids, antihypertensives, immunosuppressants and antiarrhythmic drugs. For example, the class Ic antiarrhythmic drug flecainide has no authorised paediatric formulation in the EU. The adult oral product is a flecainide tablet with a minimum strength of 50 mg. To achieve the correct dose for the child (sometimes as low as a few milligrams in small children), flecainide tablets are split, suspensions are compounded, or bad tasting intravenous liquids are given orally using a syringe. Manipulating medication in such way inevitably leads to serious medication errors sooner or later.3 We want to stress the importance to continuously promote the development of suitable palatable paediatric dosage forms. Catalysing the integration of three-dimensional (3D) printing technology in medicines’ development can support this purpose. 3D-printing technology is a fast developing novel method to …

When deciding on antiarrhythmic drug (AAD) treatment, a thorough knowledge of the physiological adaptation processes that occur during pregnancy and their effect on metabolism and the efficacy of AAD is mandatory. Beyond the desired effects of AAD therapy, side effects can occur in pregnant women. Furthermore, potential harm to fetal development—depending on gestational age—needs to be considered. A thorough evaluation of potential risks opposed to expected benefits for mother and fetus should be carried out before initiation of AAD treatment. Regular maternal echocardiography and fetal sonographic examination during pregnancy under AAD treatment are advisable. If possible, serum concentrations of AAD should be measured on a regular basis. Due to electrolyte and volume imbalances after delivery, maternal monitoring is recommended for approximately 48 h under AAD therapy. Current guidelines are based on almost historic analyses, where AAD were often prescribed for other indications than rhythm disorders. In clinical practice, AAD predominantly used during pregnancy are intravenous adenosine for acute treatment of atrioventricular nodal dependent tachycardias, whereas betablockers, sotalol, and flecainide can be orally administered for long-term therapy.

El síndrome QT largo (SQTL) congénito representa un grupo de enfermedades cardiacas de origen genético, caracterizado por la prolongación del intervalo QT y una onda T anormal en el electrocardiograma (ECG). Pueden tener una expresión dominante o recesiva, esta última asociada con sordera neurosensorial. En ambos casos su presentación clínica está asociada con síncopes recurrentes y muerte súbita como consecuencia de una taquicardia ventricular, específicamente a torsades de pointes. Actualmente se clasifican en función del defecto genético específico, pudiendo comprometer alrededor de 16 genes y casi 2000 mutaciones. Debe ser sospechada en individuos con la clínica relacionada, hallazgos electrocardiográficos y antecedentes familiares. El manejo está basado en la disminución o eliminación de los síntomas y, concomitantemente, la prevención de la muerte súbita (MS), en aquellos niños con sordera congénita el manejo requiere la aplicación de medidas propias del otorrinolaringólogo. Desde el punto de vista cardiovascular, el manejo implica la modificación de estilos de vida, principalmente la prohibición de deportes competitivos, entre ellos la natación, evitar la exposición a sonidos intensos o factores desencadenantes. La medicación usada abarca a los betabloqueadores y, más raramente, flecainida, ranozalina y verapamilo; el manejo invasivo consiste el implante de un cardiodesfibrilador o, incluso, la denervación simpática izquierda, cada una de ellas con sus propios riesgos y beneficios. En cualquiera de los casos debemos evitar las circunstancias que incrementen el intervalo QT, así como realizar el adecuado análisis de los beneficios y riesgos de cada posible medida invasiva.

Aims The transcription factor Tbx5 controls cardiogenesis and drives Scn5a expression in mice. We have identified two variants in TBX5 encoding p. D111Y and p. F206L Tbx5, respectively, in two unrelated patients with structurally normal hearts diagnosed with long QT (LQTS) and Brugada (BrS) syndrome. Here, we characterized the consequences of each variant to unravel the underlying disease mechanisms. Methods and results We combined clinical analysis with in vivo and in vitro electrophysiological and molecular techniques in human-induced pluripotent stem-cell-derived cardiomyocytes (hiPSC-CMs), HL-1 cells, and cardiomyocytes from mice trans-expressing human wild-type (WT) or mutant proteins. Tbx5 increased transcription of SCN5A encoding cardiac Nav1.5 channels, while repressing CAMK2D and SPTBN4 genes encoding Ca/calmodulin kinase IIδ (CaMKIIδ) and βIV-spectrin, respectively. These effects significantly increased Na current (INa) in hiPSC-CMs and in cardiomyocytes from mice trans-expressing Tbx5. Consequently, action potential (AP) amplitudes increased and QRS interval narrowed in the mouse electrocardiogram. p. F206L Tbx5 bound to the SCN5A promoter failed to transactivate it, thus precluding the pro-transcriptional effect of WT Tbx5. Therefore, p. F206L markedly decreased INa in hiPSC-CM, HL-1 cells and mouse cardiomyocytes. The INa decrease in p. F206L trans-expressing mice translated into QRS widening and increased flecainide sensitivity. p. D111Y Tbx5 increased SCN5A expression but failed to repress CAMK2D and SPTBN4. The increased CaMKIIδ and βIV-spectrin significantly augmented the late component of INa (INaL) which, in turn, significantly prolonged AP duration in both hiPSC-CMs and mouse cardiomyocytes. Ranolazine, a selective INaL inhibitor, eliminated the QT and QTc intervals prolongation seen in p. D111Y trans-expressing mice. Conclusions In addition to peak INa, Tbx5 critically regulates INaL and the duration of repolarization in human cardiomyocytes. Our original results suggest that TBX5 variants associate with and modulate the intensity of the electrical phenotype in LQTS and BrS patients.

Background This study aims to evaluate early postoperative arrhythmias in children undergoing congenital cardiac surgery. Methods A total of 670 pediatric patients (355 males, 315 females; median age: 4 months; range, 1 day to 18 years) who underwent cardiac surgery due to congenital heart defects between December 2018 and November 2019 were included. The rate of postoperative arrhythmias, diagnosis, potential risk factors, and management strategies were evaluated. Multivariate regression analysis was used to identify significant factors of development of postoperative arrhythmias. Results Tachyarrhythmia was detected in 54 patients (8.1%), and the most common tachyarrhythmia was junctional ectopic tachycardia. Medical treatment was required in 25/38 (66%) of junctional ectopic tachycardia patients. Amiodarone was initiated in 18, dexmedetomidine in five, and flecainide + amiodarone in two of the patients. Different degrees of atrioventricular block were observed in 30 patients (4.5%). In 12 patients, permanent pacemakers were implanted during hospitalization. Age at the time of surgery under one-year-old, high inotropic scores, prolonged operation time, and high Aristotele"s scores were independent risk factors associated with early postoperative arrhythmia (p

Introduction A drug provocation test (DPT) is important for the diagnosis of Brugada syndrome (BrS). The link, however, between dynamic changes of ECG features after DPT and unstable ventricular arrhythmia (VA) in BrS remains unknown. Methods Between 2014 and 2019, we assessed 27 patients with BrS (median age: 37.0 [interquartile range, IQR: 22.0-51.0] years; 25 men], including 9 (33.3%) with a history of unstable VA and 18 (66.7%) without. All patients in the study presented with Brugada-like ECG features before DPT. The ECG parameters and dynamic changes (∆) in 12-lead ECGs recorded from the 2nd , 3rd , and 4th intercostal spaces (ICS) before and at 1, 6, 12, 18, 24 hours after DPT (oral flecainide 400 mg) were analyzed. Results The total amplitude of V1 at the 3rd ICS 18 and 24 hours after DPT was significantly lower in patients with history of unstable VA than in those without. Patients with BrS and unstable VAs had a significantly larger ∆ amplitude of V1 at the 2nd ICS 12 hours after DPT than in those without unstable VAs (0.28[0.18-0.41] mV vs. 0.08[0.01-0.15] mV, p=0.01). A multivariate analysis revealed that the amplitude of V1 at the 3rd ICS 18 and 24 hours after DPT and the ∆ amplitude of V1 at the 2nd ICS 12 hours after DPT were associated with history of unstable VA. Conclusion Nonuniform changes and spatiotemporal differences in precordial ECG features after DPT were observed in patients with BrS and these may be surrogate markers for risk stratification. This article is protected by copyright. All rights reserved.

We sought to indirectly compare and rank antiarrhythmic agents focusing exclusively on adults with paroxysmal atrial fibrillation in order to identify the most effective for pharmacologic cardioversion over different time settings (4 h as primary, and 12, 24 h as secondary outcomes). We searched several databases from inception to March 2020 without language restrictions, ClinicalTrials.gov, references of reviews, and meeting abstract material. We included randomized controlled trials of patients with AF lasting ≤7 days comparing either two or more intravenous (i.v.) or oral (p.o.) pharmacologic cardioversion agents or an agent against placebo. For each outcome, we performed network meta-analysis based on the frequentist approach. Forty-one trials (6013 patients) were included in our systematic review. Moderate confidence evidence suggests that i.v. vernakalant and flecainide have the highest conversion rate within 4 h, possibly allowing discharge from the emergency department and reducing hospital admissions. Intravenous and p.o. formulations of class IC antiarrhythmics (flecainide more so than propafenone) are superior regarding conversion rates within 12 h, while amiodarone efficacy is exhibited in a delayed fashion (within 24 h), especially if ranolazine is added. Our network meta-analysis identified with sufficient power and consistency the most effective antiarrhythmics for pharmacologic cardioversion over different time settings, with vernakalant and flecainide exhibiting a safer and more efficacious profile toward faster cardioversion.

An 86-year-old man with paroxysmal atrial fibrillation on flecainide, a class IC antiarrhythmic, presented with cardiac arrest. The patient had extremely wide QRS complexes with inconsistent pacemaker capture on electrocardiography. Due to cardiac failure and renal failure, the patient developed progressive flecainide toxicity, which led to pacemaker failure, and ultimately, death. (Level of Difficulty: Beginner.), Central Illustration

Newborn male with symptomatic bradycardia initially diagnosed with complete atrioventricular block. Isoproterenol drip was initiated, and the patient was scheduled for pacemaker implantation. During the hospital course, repeat electrocardiogram and Holter monitor revealed evidence of near continuous blocked atrial bigeminy with occasional aberrantly conducted premature atrial contractions. Flecainide was started, resulting in normal sinus rhythm, and the pacemaker implantation was cancelled.

Differential diagnosis of wide complex tachycardia in patients taking anti-arrhythmic can be challenging. Conventional ECG diagnostic criteria are poorly specific and should be applied with caution. Patients who develop life-threatening arrhythmias after flecainide infusion should be screened for Brugada Syndrome, especially if concomitant sinus node dysfunction is present. (Level of Difficulty: Intermediate.), Central Illustration

A young man with baseline early repolarization was initiated on flecainide and diltiazem for symptomatic atrial arrhythmias. A treadmill stress test induced a type 1 Brugada electrocardiogram pattern at higher heart rates. Flecainide was discontinued. Genetic testing revealed no SCN5A mutations, and a 3-generation pedigree revealed no events of concern. In this case report, we review the use-dependent properties of flecainide. We also discuss how this property can be exploited during exercise stress testing to provoke the diagnostic type 1 Brugada pattern at higher heart rates. Résumé: Chez un jeune homme présentant au départ une repolarisation précoce, un traitement à base de flécaïnide et de diltiazem a été instauré pour lutter contre les arythmies auriculaires symptomatiques. Une épreuve d'effort sur tapis roulant a permis d'obtenir un électrocardiogramme caractéristique d'un syndrome de Brugada de type 1 à des fréquences cardiaques plus élevées. Le traitement par le flécaïnide a été arrêté. Des analyses génétiques ont mis en évidence un résultat négatif pour les mutations du gène SCN5A, et un examen de l'arbre généalogique sur 3 générations n'a révélé aucun événement préoccupant. Dans cette étude de cas, nous analysons la propriété du flécaïnide d'avoir une efficacité proportionnelle à son utilisation. Nous évoquons également la possibilité d'exploiter cette propriété lors des épreuves d'effort afin de provoquer l'apparition du profil d'ECG du syndrome de Brugada de type 1 à des fréquences cardiaques plus élevées.

Permanent junctional reciprocating tachycardia (PJRT) is a rare form of atrioventricular reentrant tachycardia that is commonly resistant to most antiarrhythmic medication therapy and over an extended duration can result in tachycardia-induced cardiomyopathy. The prenatal presentation of PJRT is typically similar to that of other types of fetal supraventricular tachycardia (SVT), making it difficult to distinguish from other forms of SVT in utero by fetal echocardiography. Surface electrocardiography after delivery is typically required to make a definitive diagnosis of PJRT. We report a case of fetal SVT at 19 weeks’ gestation refractory to maternal transplacental treatment with digoxin, amiodarone, flecainide, sotalol, metoprolol, intraumbilical amiodarone, and fetal intramuscular digoxin over the course of 12 weeks. Repeat cesarean delivery was performed at 30 2/7 weeks’ gestation for tachycardia-induced cardiomyopathy with hydrops fetalis. Postnatal electrocardiogram and continuous rhythm monitoring confirmed the diagnosis of PJRT. Combined neonatal treatment with amiodarone, digoxin, and propranolol was successful in reestablishment of sinus rhythm, with radiofrequency ablation planned if medical therapy eventually fails or once early childhood is reached. To our knowledge, this is the first described case of fetal PJRT refractory to multiple standard in utero antiarrhythmic modalities and highlights the importance of inclusion in the differential diagnosis.

Supraventricular tachyarrhythmia (SVT) is the most common type of arrhythmia in childhood. Management can be challenging with an associated risk of mortality. A female neonate was diagnosed with episodes of SVT, controlled antenatally with digoxin. Flecainide was commenced prophylactically at birth. Despite treatment, the infant developed a narrow complex tachycardia at 5 days of age. The electrocardiogram features were suggestive of either re-entry tachycardia or of automatic atrial tachycardia (AAT). Following several unsuccessful treatments, a wide complex tachycardia developed. A transesophageal electrophysiological study led to a diagnosis of AAT. Stable sinus rhythm was finally achieved through increasing daily administrations of flecainide up to six times a day, in association with nadolol. The shortening of intervals to this extent has never been reported before and supports the evidence of a personal, age-specific variability in pharmacokinetics of flecainide. Larger studies are needed to better define the appropriate dose and timing of administration.

Fetal supraventricular tachycardia management is challenging, with consequences for both the fetus and the mother. If left untreated, fetal hydrops may ensue, at which point delivery and treatment of the arrhythmia is preferred. However, if the fetus is not at term nor near-term, significant doses of antiarrhythmics may be needed to achieve adequate transplacental bioavailability. Although digoxin has classically been the mainstay of treatment, the use of flecainide or sotalol as monotherapy or in combination with digoxin is being studied. Interdisciplinary team management and shared decision-making between the physician and patient are key to achieving successful outcomes. Adult cardiologists, particularly inpatient consultation services or through burgeoning cardio-obstetrics programs, may, in some practice settings, be asked to evaluate or co-manage pregnant women with fetal arrhythmia.

SCN5A gene mutations are described in 2% of patients with dilated cardiomyopathy (DCM) and different rhythm disturbances, including multifocal ectopic Purkinje‐related premature contractions. Recent data indicate that sodium channel blockers are particularly effective monotherapy in carriers of the R222Q SCN5A variant. Our purpose is to describe the effectiveness of antiarrhythmic treatment in a family with genetically determined arrhythmogenic DCM associated with the R814W variant in the SCN5A gene. We examined a family with arrhythmogenic DCM (multifocal ectopic Purkinje‐related premature contractions phenotype, atrial tachyarrhythmias, automatism, and conduction disorders) and described antiarrhythmic treatment efficacy in heart failure symptoms reduction and myocardial function improvement. We found a heterozygotic mutation R814W in SCN5A by whole exome sequencing in the proband and confirmed its presence in all affected subjects. There were two sudden cardiac deaths and one heart transplantation among first‐degree relatives. The 58‐year‐old father and his 37‐year‐old daughter had full spectrum of symptoms associated with R814W SCN5A mutation. Both had implanted cardioverter defibrillator. In the father, adding mexiletine to quinidine therapy reduced ventricular arrhythmia (50–60% → 6–8% of whole rhythm) and reverted long‐standing atrial fibrillation to sinus rhythm. In the daughter, mexiletine and overdrive pacing were effective in ventricular arrhythmia reduction (25% → 0.01%). Because of a growing number of atrial fibrillation recurrences, a reduced dose of quinidine (subsequently flecainide) was added, resulting in arrhythmia significant reduction. In both cases, antiarrhythmic effectiveness correlated with clinical improvement. In SCN5A R814W‐associated DCM, a combination of Class I antiarrhythmics and overdrive pacing is an effective treatment of severe ventricular and atrial arrhythmias.

Flecainide overdose is associated with an approximately 10% mortality rate. The drug’s slow rate of elimination and high oral bioavailability make successful management extremely challenging. I present the management of a life-threatening flecainide overdose of an infant who had a protracted course due to the exposure to the drug in both the fetal and neonatal periods.

Bidirectional ventricular tachycardia is a rare form of tachycardia. We hereby report a case of bidirectional ventricular tachycardia in an 8-year-old boy wherein careful clinical exami-nation led to the diagnosis of Andersen Tawil syndrome. The case also demonstrates the efficacy of flecainide in managing bidirectional ventricular tachycardia in the setting of Andersen Tawil syndrome.

The effects of class I antiarrhythmic drugs on the automaticity of isolated guinea pig pulmonary vein myocardia were investigated using microelectrode and voltage clamp methods. All of the drugs examined reduced the maximum rate of rise of automatic action potentials. The firing frequency and rate of diastolic depolarization were decreased by aprindine, flecainide and propafenone, but not by cibenzoline, disopyramide and pilsicainide, which correlated with blockade of the sodium current component induced by ramp depolarization mimicking the diastolic depolarization. In conclusion, class I antiarrhythmic drugs which block the diastolic sodium current component inhibit the automaticity of the pulmonary vein myocardium.

Background Flecainide is a class Ic antidysrhythmic agent used to prevent and treat both ventricular and supraventricular tachycardias, including atrial fibrillation, atrioventricular nodal re-entrant tachycardia, and Wolff-Parkinson-White syndrome. Flecainide can cause serious side effects, including cardiac arrest, dysrhythmias, and heart failure. Despite its growing use, the presenting signs and symptoms of flecainide toxicity are not familiar to most clinicians. In particular, our patient's particular presentation of acute kidney injury (AKI) resulting in flecainide accumulation is high risk for missed diagnosis in the emergency department. Case Report A 58-year-old woman presented with altered mental status and hypoxia that was later found to be secondary to sepsis. Medical history was notable for atrial fibrillation, for which she was on flecainide. Laboratory results were notable for hypokalemia and an AKI. Her wide complex tachycardia on admission was ultimately attributed to flecainide toxicity in the setting of AKI. Six days after presentation, it was found that her flecainide level was in the toxic range at 2.02 μg/mL (normal range 0.20–1.00 μg/mL, toxic >1.50 μg/mL). Why Should an Emergency Physician Be Aware of This? Flecainide intoxication is rare but serious due to the potential for cardiogenic shock. Its diagnosis can be difficult, as the flecainide serum level may take days to result. This case demonstrates the necessity of keeping flecainide toxicity on the physician's differential for patients who are taking the drug, as well as what electrocardiogram findings suggest it as the etiology. Treatment can be lifesaving if initiated promptly.

Background: Achievement of sinus rhythm (SR) is an important goal in rheumatic atrial fibrillation (AF). Studies in rheumatic AF have often used amiodarone for rhythm control. Flecainide has not been studied in these patients due to concerns of underlying structural heart disease. Methods: Pharmacological cardioversion by oral single loading dose (SLD) of Flecainide (4 mg/kg, ≤300 mg) was tested in 50 patients with rheumatic AF (MVA 1.51 ± 0.19 mm2, age 46.2 ± 10.28 yrs, AF duration 3.10 ± 1.7 yrs, LA size: 44.42 ± 7.48 mm). Non-converters underwent DC cardioversion (DCC) at 24 h. All patients received oral flecainide and ββ/diltiazem at discharge. Results: At 24 h, 38/50 (76%) achieved SR (2 with SLD; 36 after DCC). At 30 days (mean Flecainide dose 116.5 ± 10.5 mg) successful maintenance of SR was noted in 31/38 (89%). At 1 year, 30/38 (79%) of the initial converters and 60% of the overall population maintained SR. Those in SR had significantly better NYHA Class (1.1 ± 0.12 vs 1.3 ± 0.10, p = 0.03) and mean PCS8 score (50.11 ± 5.337 vs 46.84 ± 5.379, p = 0.02). AF duration (OR 0.594 CI 0.375–0.940, p = 0.02) and LA size (OR 0.840, CI 0.757–0.933, p = 0.001) were found to be the only significant predictors of successful outcomes. Patients with AF duration

Recently, cases of pharmacological resynchronization for Wolff–Parkinson–White syndrome (WPWS) in children with left ventricular dyssynchrony (LVD) were reported, but an appropriate pharmacological therapy has not yet been established. A 3-month-old, previously healthy female patient was referred to our hospital due to supraventricular tachycardia (SVT). After resolution of the SVT, 12-lead electrocardiography (ECG) showed ventricular pre-excitation. Transthoracic echocardiography showed LVD with no findings of congenital heart disease or cardiomyopathy. To prevent SVT recurrence, oral propranolol administration was started, but the SVT recurred one month later. To prevent further recurrences, oral flecainide administration was started, as the patient’s body weight was insufficient for catheter ablation to be performed safely. When the flecainide dosage was increased to 50 mg/m(2)/day, the pre-excitation resolved, and the LVD improved. Holter ECG showed that the resolution of pre-excitation depended on the serum concentration of flecainide. There are only few reports on pharmacological resynchronization in WPWS patients with LVD (LVD-WPWS). The present report is the first to examine the efficacy of flecainide in patients with recurrent SVT. Flecainide may be a safe and effective alternative resynchronization therapy for LVD-WPWS patients, especially for children in whom catheter ablation cannot be performed safely due to insufficient body weight.

Conventional treatment strategies for catecholaminergic polymorphic ventricular tachycardia (CPVT) include avoidance of strenuous exercise and competitive sports, drugs such as s-blockers and flecainide and, cervical sympathectomy. An implantable cardioverter-defibrillator (ICD) has been utilized if the response to these strategies is inadequate; however, ICD use in CPVT patients, in addition to usual complications, is associated with an increased risk of life-threatening electrical storm. Ivabradine is a selective inhibitor of hyperpolarization-activated cyclic nucleotide-gated potassium channel 4 generated funny current (If ), which has been shown to be efficacious in suppression of inappropriate sinus tachycardia, junctional tachycardia, atrial tachycardia, and ventricular ectopy in humans. We report an 18-year-old male with a severe CPVT phenotype refractory to flecainide, nadolol, and sympathectomy who exhibited suppression of ventricular arrhythmias after initiation of ivabradine. These findings are of importance as ivabradine could be an important add-on therapy in CPVT patients who are drug refractory or are unable to continue conventional therapies at the recommended doses.

Higher drug concentrations in complex clinical scenarios in which multiple factors such as drug–drug interactions (DDIs) and comorbidities are simultaneously present are not necessarily rationalized in prospective clinical studies. Physiologically based pharmacokinetic (PBPK) modeling and simulation of the anti-arrhythmic drug flecainide, as an example, were utilized to quantitatively rationalize the higher flecainide concentration in a complex clinical case involving end-stage renal disease (ESRD), cirrhosis, and the co-administration of mexiletine, a CYP1A2 inhibitor. The developed flecainide PBPK model was used to evaluate the DDI effect (as measured by AUC ratio before and after inhibition) of mexiletine and the combined disease effects of ESRD and cirrhosis on flecainide exposure. The predicted DDI effect of mexiletine was negligible or weak in anuric hemodialysis with cirrhosis population (mean [5th/95th percentiles], 1.23 [0.97–1.67]), although it was negligible in healthy volunteers (1.03 [1.02–1.05]). The predicted flecainide concentrations after multiple flecainide doses (50 mg BID) in the anuric hemodialysis with cirrhosis population were comparable with the observed value (3602 ng/mL), which fell between the predicted concentrations in the absence and presence of mexiletine (3043 [718–8499] and 5914 [880–20,624] ng/mL, respectively). The PBPK simulation proposed a likely explanation that the observed higher flecainide concentration could be attributed to the combined effects of ESRD, cirrhosis, and a potential DDI with mexiletine. This approach provides quantitative insight into theoretically conceivable extremes in drug exposure occurring in complex clinical situations even if uncommon.

Pharmacologic management of atrial fibrillation (AF) is a pressing problem. This arrhythmia afflicts >5 million individuals in the United States and prevalence is estimated to rise to 12 million by 2050. Although the pill-in-the-pocket regimen for self-administered AF cardioversion introduced over a decade ago has proven useful, significant drawbacks exist. Among these are the relatively long latency of effects in the range of hours along with potential for hypotension and other adverse effects. This experience prompted development of a new strategy for increasing plasma concentrations of antiarrhythmic drugs rapidly and for a limited time, namely, pulmonary delivery. In preclinical studies in Yorkshire pigs, intratracheal administration of flecainide was shown to cause a rapid, reproducible increase in plasma drug levels. Moreover, pulmonary delivery of flecainide converted AF to normal sinus rhythm by prolonging atrial depolarization, which slows intra-atrial conduction and seems to be directly correlated with efficacy in converting AF. The rapid rise in plasma flecainide levels optimizes its anti-AF effects while minimizing adverse influences on ventricular depolarization and contractility. A more concentrated and soluble formulation of flecainide using a novel cyclodextrin complex excipient reduced net drug delivery for AF conversion when compared to the acetate formulation. Inhalation of the beta-adrenergic blocking agent metoprolol slows ventricular rate and can also terminate AF. In human subjects, oral inhalation of flecainide acetate with a hand-held, breath-actuated nebulizer results in signature prolongation of the QRS complex without serious adverse events. Thus, pulmonary delivery is a promising advance in pharmacologic approach to management of AF.

Atrial fibrillation (AF) is the most common cardiac arrhythmia with a considerable impact on patients’ quality of life (QoL). This prospective, multicenter, observational study aimed to evaluate the effect of oral treatment with controlled-release (CR) flecainide on AF patients’ QoL and treatment compliance during a 12-week period. A total of 70 sites enrolled consecutive patients with paroxysmal (PAF) or persistent AF (PerAF), treated with flecainide CR in the context of a rhythm control strategy. The effect on QoL was assessed by the Canadian Cardiovascular Society Severity of Atrial Fibrillation scale (CCS-SAF). In total, 679 patients (53.2% females, 66 ± 11.7 years, 86.9% PAF) were included. Prior antiarrhythmic medication had been administered in 43.8% of patients. A daily dose of 200 mg was administered to 66.4% of patients by the end of study. Flecainide CR resulted in a significant reduction in the CCS-SAF score (mean (SD)) at the end of the study as compared with baseline (1.32 (0.57) vs 1.64 (0.73), p

AimsWe sought to identify the most effective antidysrhythmic drug for pharmacologic cardioversion of recent-onset atrial fibrillation (AF).Methods and resultsWe searched MEDLINE, Embase, and Web of Science from inception to March 2019, limited to human subjects and English language. We also searched for unpublished data. We limited studies to randomized controlled trials that enrolled adult patients with AF ≤ 48 h and compared antidysrhythmic agents, placebo, or control. We determined these outcomes prior to data extraction: (i) rate of conversion to sinus rhythm within 24 h, (ii) time to cardioversion to sinus rhythm, (iii) rate of significant adverse events, and (iv) rate of thromboembolism within 30 days. We extracted data according to PRISMA-NMA and appraised selected trials using the Cochrane review handbook. The systematic review initially identified 640 studies; 30 met inclusion criteria. Twenty-one trials that randomized 2785 patients provided efficacy data for the conversion rate outcome. Bayesian network meta-analysis using a random-effects model demonstrated that ranolazine + amiodarone intravenous (IV) [odds ratio (OR) 39.8, 95% credible interval (CrI) 8.3–203.1], vernakalant (OR 22.9, 95% CrI 3.7–146.3), flecainide (OR 16.9, 95% CrI 4.1–73.3), amiodarone oral (OR 10.2, 95% CrI 3.1–36.0), ibutilide (OR 7.9, 95% CrI 1.2–52.5), amiodarone IV (OR 5.4, 95% CrI 2.1–14.6), and propafenone (OR 4.1, 95% CrI 1.7–10.5) were associated with significantly increased likelihood of conversion within 24 h when compared to placebo/control. Overall quality was low, and the network exhibited inconsistency. Probabilistic analysis ranked vernakalant and flecainide high and propafenone and amiodarone IV low.ConclusionFor pharmacologic cardioversion of recent-onset AF within 24 h, there is insufficient evidence to determine which treatment is superior. Vernakalant and flecainide may be relatively more efficacious agents. Propafenone and IV amiodarone may be relatively less efficacious. Further high-quality study is necessary.

Objectives: To describe a single institutional experience managing fetuses with supraventricular tachycardia (SVT) and to identify associations between patient characteristics and fetal and postnatal outcomes. Background: Sustained fetal SVT is associated with significant morbidity and mortality if untreated, yet the optimal management strategy remains unclear. Methods: Retrospective cohort study including fetuses diagnosed with sustained SVT (>50% of the diagnostic echocardiogram) between 1985 and 2018. Fetuses with congenital heart disease were excluded. Results: Sustained SVT was diagnosed in 65 fetuses at a median gestational age of 30 weeks (range, 14-37). Atrioventricular re-entrant tachycardia and atrial flutter were the most common diagnoses, seen in 41 and 16 cases, respectively. Moderate/severe ventricular dysfunction was present in 20 fetuses, and hydrops fetalis was present in 13. Of the 57 fetuses initiated on transplacental drug therapy, 47 received digoxin first-line, yet 39 of 57 (68%) required advanced therapy with sotalol, flecainide, or amiodarone. Rate or rhythm control was achieved in 47 of 57 treated fetuses. There were no cases of intrauterine fetal demise. Later gestational age at fetal diagnosis (odds ratio [OR], 1.1, 95% confidence interval [CI], 1.01-1.2, P = .02) and moderate/severe fetal ventricular dysfunction (OR, 6.1, 95% CI, 1.7-21.6, P = .005) were associated with postnatal SVT. Two postnatal deaths occurred. Conclusions: Fetuses with structurally normal hearts and sustained SVT can be effectively managed with transplacental drug therapy with minimal risk of intrauterine fetal demise. Treatment requires multiple antiarrhythmic agents in over half of cases. Later gestational age at fetal diagnosis and the presence of depressed fetal ventricular function, but not hydrops, predict postnatal arrhythmia burden.

A 64-year-old man underwent implantation of a permanent His-bundle pacemaker. A marked rise in the selective His-bundle capture threshold was noted 1 month after the patient started flecainide acetate for rhythm control of recurrent, symptomatic atrial flutter and atrial fibrillation. The capture threshold subsequently normalized 4 days after discontinuing flecainide and switching to dofetilide. To our knowledge, this is the first documented case of a rise in selective His-bundle capture threshold associated with flecainide acetate. Further studies are needed to characterize this association which could result in higher capture thresholds, decreased battery longevity, and mimic His-bundle lead failure.

Antiarrhythmic drugs are widely used in the treatment of supraventricular and ventricular arrhythmias. Yet, nationwide long-term utilization trends remain unexplored. We examined 19-year trends in the use of antiarrhythmic drugs in Denmark. Using nationwide prescription data, we obtained information on hospital and primary healthcare use of Class I-V antiarrhythmic drugs from 1999 to 2017. Data was stratified according to sex and age groups. From 1999 to 2017, the total use of antiarrhythmic drugs per 1000 inhabitants/day increased 16% from 36.3 in 1999 to 41.9 in 2017 with peak consumption in 2008 (46.5). In primary healthcare, Class I usage decreased from 0.8 to 0.5 defined daily doses (DDD) per 1000 inhabitants/day, driven by a decreased prescription rate of propafenone (0.4 to 0.1) whereas prescription of flecainide (Class Ic) increased from 0.3 to 0.4 DDD per 1000 inhabitants/day (mainly in men of age 45 to 79 years). Class II usage increased from 15.4 to 33.6 DDD per 1000 inhabitants/day. Class III usage decreased from 2.6 to 1.1 DDD per 1000 inhabitants/day, reflecting reduced prescription rate of sotalol (2.1 to 0.2) whereas amiodarone increased from 0.5 to 0.9 (mainly due to increased prescription among men and women >80 years). Class IV usage declined from 8.6 to 2.8 DDD per 1000 inhabitants/day. Finally, Class V drugs decreased 8.1 to 3.3 DDD per 1000 inhabitants/day. In conclusion, during the past 2 decades considerable changes in prescription rate of antiarrhythmic drugs have occurred, most notably a reduction in sotalol and increased usage of flecainide, Class II drugs, and amiodarone.

Introduction: Supraventricular tachycardia is the most common fetal tachyarrhythmia and if persistent often associated with fetal hydrops which can cause intrauterine and neonatal death. Case Presentation: We present a case of early second trimester supraventricular tachycardia in a hydropic fetus, initially refractory to transplacental treatment. Conclusion: The supraventricular tachycardia was successfully treated when supplemented with intraperitoneal flecainide in the fetus.

Andersen-Tawil syndrome (ATS) is a rare genetic disorder characterized by periodic paralysis, ventricular arrhythmia, and dysmorphic features. However, the classical features are not always seen in the syndrome; therefore, the diagnosis can be challenging. We describe our experience with ATS in Riyadh, Saudi Arabia, by presenting a case series involving four patients in the pediatric cardiology clinic confirmed to have ATS. Despite the diversity in phenotypes and clinical course among the four cases, all patients had bidirectional ventricular tachycardia and were confirmed to have ATS by performing genetic testing. In this case series, we identified one novel and three previously described KCNJ2 mutations. We also confirmed the beneficial effect of AAI pacing in one of our patients, together with medical therapy with β-blockers and flecainide. In Saudi Arabia, there is a distinct genetic pool and a high incidence of inherited diseases. Raising awareness about these diseases is crucial, especially in a country such as Saudi Arabia, wherein consanguinity remains a significant factor leading to an increased incidence of inherited diseases. Furthermore, because of the limited information available regarding this rare syndrome, we believe that this case series would offer an opportunity to provide a better understanding of ATS in our local region and worldwide.

Background β-Catenin/T-cell factor 4 (TCF4) signaling is enhanced in ischemic heart disease in which ventricular tachycardia (VT)/ventricular fibrillation occurs frequently. How this signaling links to arrhythmogenesis remains unclear. Objective The purpose of this study was to investigate the role of β-catenin gain of function in the development of arrhythmia. Methods A mouse model with a conditional deletion of CTNNB1 exon 3 resulting in cardiac exon 3–deleted and stabilized β-catenin (β-catΔE3) was used to determine the role of β-catenin gain of function in the regulation of cardiac rhythm. Results Western blotting showed β-catΔE3 expression and significantly decreased NaV1.5 protein in CTNNB1 E3−/− and CTNNB1 E3+/− mouse hearts. Real-time qRT-PCR revealed significantly decreased NaV1.5 messenger RNA with no changes in Na+ channel β1 to β4 expression in these hearts. Immunofluorescence revealed accumulation of β-catΔE3 in the nuclei of CTNNB1 E3−/− cardiomyocytes. Immunohistochemistry demonstrated nuclear localization of β-catenin in cardiomyocytes, which was associated with significantly decreased NaV1.5 messenger RNA in human ischemic hearts. Immunoprecipitation revealed that β-catΔE3 interacted with TCF4 in CTNNB1 E3−/− cardiomyocytes. Whole-cell recordings showed that Na+ currents and depolarization and amplitude of action potentials were significantly decreased in CTNNB1 E3−/− ventricular myocytes. Electrocardiographic recordings demonstrated that in mice with cardiac CTNNB1 E3−/−, the QRS complex was prolonged and VT was induced by the Na+ channel blocker flecainide. However, cardiac function, as determined by echocardiography and heart/body weight ratios, remained unchanged. Conclusion Enhancement of β-catenin/TCF4 signaling led to the prolongation of the QRS complex and increase in susceptibility to VT by suppression of NaV1.5 expression and Na+ channel activity in mice.

Aims Chronic tachypacing is commonly used in animals to induce cardiac dysfunction and to study mechanisms of heart failure and arrhythmogenesis. Human induced pluripotent stem cells (hiPSC) may replace animal models to overcome species differences and ethical problems. Here, 3D engineered heart tissue (EHT) was used to investigate the effect of chronic tachypacing on hiPSC-cardiomyocytes (hiPSC-CMs). Methods and results To avoid cell toxicity by electrical pacing, we developed an optogenetic approach. EHTs were transduced with lentivirus expressing channelrhodopsin-2 (H134R) and stimulated by 15 s bursts of blue light pulses (0.3 mW/mm2, 30 ms, 3 Hz) separated by 15 s without pacing for 3 weeks. Chronic optical tachypacing did not affect contractile peak force, but induced faster contraction kinetics, shorter action potentials, and shorter effective refractory periods. This electrical remodelling increased vulnerability to tachycardia episodes upon electrical burst pacing. Lower calsequestrin 2 protein levels, faster diastolic depolarization (DD) and efficacy of JTV-519 (46% at 1 µmol/L) to terminate tachycardia indicate alterations of Ca2+ handling being part of the underlying mechanism. However, other antiarrhythmic compounds like flecainide (69% at 1 µmol/L) and E-4031 (100% at 1 µmol/L) were also effective, but not ivabradine (1 µmol/L) or SEA0400 (10 µmol/L). Conclusion We demonstrated a high vulnerability to tachycardia of optically tachypaced hiPSC-CMs in EHT and the effective termination by ryanodine receptor stabilization, sodium or hERG potassium channel inhibition. This new model might serve as a preclinical tool to test antiarrhythmic drugs increasing the insight in treating ventricular tachycardia.

Rhythm-control drugs are used to terminate arrhythmias, and/or prevent their recurrence. They are a heterogeneous group of medicines with a wide range of indications, mechanisms and pharmacological properties. In this second article of a three-part series, three commonly used rhythm-control drugs are evaluated: adenosine, amiodarone and flecainide. In addition to describing each drug and its uses, important practice points are identified with the aim of promoting safe prescribing and administration.

International audience; BackgroundExcessive daytime sleepiness (EDS) is a frequent and disabling symptom of Parkinson's disease (PD) without approved treatment. THN102 is a novel combination drug of modafinil and low-dose flecainide.ObjectiveThe aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS.MethodsThe method involved a randomized, double-blind, placebo-controlled, crossover trial testing two doses of THN102 (200 mg/d modafinil with 2 mg/d [200/2] or 18 mg/d flecainide [200/18]) versus placebo; 75 patients were exposed to treatment. The primary endpoint was safety. The primary efficacy outcome was the change in Epworth Sleepiness Scale (ESS) score.ResultsBoth doses of THN102 were well tolerated. ESS significantly improved with THN102 200/2 (least square means vs. placebo [95% confidence interval, CI]: −1.4 [−2.49; −0.31], P = 0.012) but did not change significantly with the 200/18 dosage.ConclusionsTHN102 was well tolerated and showed a signal of efficacy at the 200/2 dose, supporting further development for the treatment of EDS in PD. © 2021 International Parkinson and Movement Disorder Society