RESUMEN
We report the case of a female neonate admitted to the neonatal ICU with a rapid, narrow-complex tachyarrhythmia determined to be supraventricular tachycardia. Multimodality imaging and genetic testing confirmed a diagnosis of tuberous sclerosis complex with multiple cardiac rhabdomyomas. At 13 days of age, the patient was readmitted, exhibiting recurrent supraventricular tachycardia non-responsive to first-line treatment. Management required triple-drug therapy, whereafter the patient remained stable without recurrences. This is a rare report of supraventricular tachycardia in a functionally normal heart with the occurrence of supraventricular tachycardia due to structural abnormalities, with the possibility of multiple concealed accessory pathways.
RESUMEN
INTRODUCTION: The use of flecainide and propafenone for medical cardioversion of atrial fibrillation (AF) and atrial flutter/intra-atrial reentrant tachycardia (IART) is well-described in adults without congenital heart disease (CHD). Data are sparse regarding their use for the same purpose in adults with CHD and in adolescent patients with anatomically normal hearts and we sought to describe the use of class IC drugs in this population and identify factors associated with decreased likelihood of success. METHODS: Single center retrospective cohort study of patients who received oral flecainide or propafenone for medical cardioversion of AF or IART from 2000 to 2022. The unit of analysis was each episode of AF/IART. We performed a time-to-sinus rhythm analysis using a Cox proportional hazards model clustering on the patient to identify factors associated with increased likelihood of success. RESULTS: We identified 45 episodes involving 41 patients. As only episodes of AF were successfully cardioverted with medical therapy, episodes of IART were excluded from our analyses. Use of flecainide was the only factor associated with increased likelihood of success. There was a statistically insignificant trend toward decreased likelihood of success in patients with CHD. CONCLUSIONS: Flecainide was more effective than propafenone. We did not detect a difference in rate of conversion to sinus rhythm between patients with and without CHD and were likely underpowered to do so, however, there was a trend toward decreased likelihood of success in patients with CHD. That said, medical therapy was effective in >50% of patients with CHD with AF.
Asunto(s)
Fibrilación Atrial , Aleteo Atrial , Cardiopatías Congénitas , Taquicardia Supraventricular , Adulto , Adolescente , Humanos , Antiarrítmicos/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/inducido químicamente , Flecainida/efectos adversos , Propafenona/efectos adversos , Cardioversión Eléctrica/efectos adversos , Estudios Retrospectivos , Taquicardia Supraventricular/inducido químicamente , Aleteo Atrial/diagnóstico , Aleteo Atrial/tratamiento farmacológico , Taquicardia , Cardiopatías Congénitas/complicaciones , Cardiopatías Congénitas/diagnóstico , Cardiopatías Congénitas/terapiaRESUMEN
RATIONALE: The class Ic antiarrhythmic drug flecainide prevents ventricular tachyarrhythmia in patients with catecholaminergic polymorphic ventricular tachycardia (CPVT), a disease caused by hyperactive RyR2 (cardiac ryanodine receptor) mediated calcium (Ca) release. Although flecainide inhibits single RyR2 channels in vitro, reports have claimed that RyR2 inhibition by flecainide is not relevant for its mechanism of antiarrhythmic action and concluded that sodium channel block alone is responsible for flecainide's efficacy in CPVT. OBJECTIVE: To determine whether RyR2 block independently contributes to flecainide's efficacy for suppressing spontaneous sarcoplasmic reticulum Ca release and for preventing ventricular tachycardia in vivo. METHODS AND RESULTS: We synthesized N-methylated flecainide analogues (QX-flecainide and N-methyl flecainide) and showed that N-methylation reduces flecainide's inhibitory potency on RyR2 channels incorporated into artificial lipid bilayers. N-methylation did not alter flecainide's inhibitory activity on human cardiac sodium channels expressed in HEK293T cells. Antiarrhythmic efficacy was tested utilizing a Casq2 (cardiac calsequestrin) knockout (Casq2-/-) CPVT mouse model. In membrane-permeabilized Casq2-/- cardiomyocytes-lacking intact sarcolemma and devoid of sodium channel contribution-flecainide, but not its analogues, suppressed RyR2-mediated Ca release at clinically relevant concentrations. In voltage-clamped, intact Casq2-/- cardiomyocytes pretreated with tetrodotoxin to inhibit sodium channels and isolate the effect of flecainide on RyR2, flecainide significantly reduced the frequency of spontaneous sarcoplasmic reticulum Ca release, while QX-flecainide and N-methyl flecainide did not. In vivo, flecainide effectively suppressed catecholamine-induced ventricular tachyarrhythmias in Casq2-/- mice, whereas N-methyl flecainide had no significant effect on arrhythmia burden, despite comparable sodium channel block. CONCLUSIONS: Flecainide remains an effective inhibitor of RyR2-mediated arrhythmogenic Ca release even when cardiac sodium channels are blocked. In mice with CPVT, sodium channel block alone did not prevent ventricular tachycardia. Hence, RyR2 channel inhibition likely constitutes the principal mechanism of antiarrhythmic action of flecainide in CPVT.
Asunto(s)
Antiarrítmicos/farmacología , Bloqueadores de los Canales de Calcio/farmacología , Flecainida/farmacología , Frecuencia Cardíaca/efectos de los fármacos , Miocitos Cardíacos/efectos de los fármacos , Canal Liberador de Calcio Receptor de Rianodina/efectos de los fármacos , Retículo Sarcoplasmático/efectos de los fármacos , Taquicardia Ventricular/prevención & control , Potenciales de Acción , Animales , Señalización del Calcio , Calsecuestrina/genética , Calsecuestrina/metabolismo , Modelos Animales de Enfermedad , Femenino , Células HEK293 , Humanos , Masculino , Ratones Noqueados , Miocitos Cardíacos/metabolismo , Fosforilación , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo , Oveja Doméstica , Taquicardia Ventricular/genética , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/fisiopatología , Bloqueadores del Canal de Sodio Activado por Voltaje/farmacologíaRESUMEN
BACKGROUND: In patients with a type 2 or 3 Brugada pattern, the pharmacological (IC drugs) induction of a type 1 pattern confirms the diagnosis of Brugada syndrome. OBJECTIVE: To evaluate the value of various ECG markers in predicting IC drug test results. METHODS: We retrospectively analysed 443 consecutive patients referred to our Center (from January 2010 to December 2019) to undergo Ajmaline/Flecainide testing; all had a type 2 or 3 Brugada pattern or were relatives with Brugada syndrome. Clinical parameters and ECG markers (r1V1 and SV6 duration and amplitude, QRSV1/QRSV6 duration, V1 and V2 ST amplitude) were independently evaluated for their association to pharmacological test positivity, and a logistic regression model was applied. RESULTS: The drug test was positive in 151 (34%) patients. On multivariate logistic regression analysis, age > 45 years, female gender, HR >60 bpm, QRSV1/QRSV6 duration >1 and non-isoelectric pattern in V2 were associated with a positive test. The percentage of patients who tested positive increased according to the presence of the above ECG markers (from 11.3% in the absence to 57.6% in the presence of both factors). During long-term follow-up, the clinical event rate was higher in patients with predictive ECG markers and very low in those without. CONCLUSIONS: In our population we confirmed the ability of QRSV1/QRSV6 duration >1 and of a non-isoelectric pattern in V2 to predict a pharmacologically induced type 1 Brugada pattern. Patients with neither of these ECG markers had a rather low event rate during follow-up.
Asunto(s)
Síndrome de Brugada , Humanos , Femenino , Persona de Mediana Edad , Síndrome de Brugada/complicaciones , Estudios Retrospectivos , Electrocardiografía/métodos , Ajmalina/efectos adversos , FlecainidaRESUMEN
Therapeutic drug monitoring of flecainide in children using plasma concentration measurements is undertaken by some clinicians. There is very little published evidence surrounding factors which influence plasma flecainide concentration, particularly in paediatric populations. We undertook a retrospective study of 45 children receiving flecainide to identify factors that influence its plasma concentration. Patients receiving a dose of 6 mg/kg/day had a higher mean plasma flecainide concentration than those receiving lower doses. Younger age and lighter weight were also associated with higher plasma flecainide concentrations. Children aged younger than 1 year receiving flecainide three times a day had a higher mean plasma flecainide concentration than older children who received flecainide twice a day. All supratherapeutic levels occurred in children aged less than 1 year who were receiving flecainide three times a day. Supratherapeutic levels were more common in those receiving 6 mg/kg/day while subtherapeutic levels were more common in those receiving 2 mg/kg/day. A supratherapeutic level did not correlate with adverse effects or clinical toxicity. Our results would suggest the need for a change of practice from prescribing flecainide at a frequency of three times a day in children aged younger than 1 year to twice a day in line with other ages.
Asunto(s)
Efectos Colaterales y Reacciones Adversas Relacionados con Medicamentos , Flecainida , Humanos , Niño , Adolescente , Flecainida/uso terapéutico , Estudios Retrospectivos , Antiarrítmicos/uso terapéutico , ElectrocardiografíaRESUMEN
Atrial fibrillation (AF) affects over 1% of the population and is a leading cause of stroke and heart failure in the elderly. A feared side effect of sodium channel blocker therapy, ventricular pro-arrhythmia, appears to be relatively rare in patients with AF. The biophysical reasons for this relative safety of sodium blockers are not known. Our data demonstrates intrinsic differences between atrial and ventricular cardiac voltage-gated sodium currents (INa), leading to reduced maximum upstroke velocity of action potential and slower conduction, in left atria compared to ventricle. Reduced atrial INa is only detected at physiological membrane potentials and is driven by alterations in sodium channel biophysical properties and not by NaV1.5 protein expression. Flecainide displayed greater inhibition of atrial INa, greater reduction of maximum upstroke velocity of action potential, and slowed conduction in atrial cells and tissue. Our work highlights differences in biophysical properties of sodium channels in left atria and ventricles and their response to flecainide. These differences can explain the relative safety of sodium channel blocker therapy in patients with atrial fibrillation.
Asunto(s)
Fibrilación Atrial , Flecainida , Potenciales de Acción , Anciano , Antiarrítmicos/farmacología , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/metabolismo , Flecainida/metabolismo , Flecainida/farmacología , Flecainida/uso terapéutico , Atrios Cardíacos/metabolismo , Humanos , Sodio/metabolismo , Bloqueadores de los Canales de Sodio/farmacología , Canales de Sodio/metabolismoRESUMEN
BACKGROUND: Cardiac mesenchymal stromal cells (C-MSC) were recently shown to differentiate into adipocytes and myofibroblasts to promote the aberrant remodeling of cardiac tissue that characterizes arrhythmogenic cardiomyopathy (ACM). A calcium (Ca2+) signaling dysfunction, mainly demonstrated in mouse models, is recognized as a mechanism impacting arrhythmic risk in ACM cardiomyocytes. Whether similar mechanisms influence ACM C-MSC fate is still unknown. Thus, we aim to ascertain whether intracellular Ca2+ oscillations and the Ca2+ toolkit are altered in human C-MSC obtained from ACM patients, and to assess their link with C-MSC-specific ACM phenotypes. METHODS AND RESULTS: ACM C-MSC show enhanced spontaneous Ca2+ oscillations and concomitant increased Ca2+/Calmodulin dependent kinase II (CaMKII) activation compared to control cells. This is manly linked to a constitutive activation of Store-Operated Ca2+ Entry (SOCE), which leads to enhanced Ca2+ release from the endoplasmic reticulum through inositol-1,4,5-trisphosphate receptors. By targeting the Ca2+ handling machinery or CaMKII activity, we demonstrated a causative link between Ca2+ oscillations and fibro-adipogenic differentiation of ACM C-MSC. Genetic silencing of the desmosomal gene PKP2 mimics the remodelling of the Ca2+ signalling machinery occurring in ACM C-MSC. The anti-arrhythmic drug flecainide inhibits intracellular Ca2+ oscillations and fibro-adipogenic differentiation by selectively targeting SOCE. CONCLUSIONS: Altogether, our results extend the knowledge of Ca2+ dysregulation in ACM to the stromal compartment, as an etiologic mechanism of C-MSC-related ACM phenotypes. A new mode of action of flecainide on a novel mechanistic target is unveiled against the fibro-adipose accumulation in ACM.
Asunto(s)
Cardiomiopatías , Células Madre Mesenquimatosas , Ratones , Animales , Humanos , Flecainida , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Miocitos Cardíacos , Calcio , Cardiomiopatías/genéticaRESUMEN
BACKGROUND: Excessive 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. OBJECTIVE: The aim of this study is to evaluate the safety and efficacy of THN102 in PD patients with EDS. METHODS: The 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. RESULTS: Both 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. CONCLUSIONS: THN102 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.
Asunto(s)
Trastornos de Somnolencia Excesiva , Flecainida , Modafinilo , Enfermedad de Parkinson , Trastornos de Somnolencia Excesiva/etiología , Método Doble Ciego , Combinación de Medicamentos , Flecainida/efectos adversos , Humanos , Modafinilo/efectos adversos , Enfermedad de Parkinson/tratamiento farmacológicoRESUMEN
AIMS: Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited cardiomyopathy associated with a high risk of ventricular arrhythmia (VA). Current guidelines recommend beta-blockers as first-line medical therapy and if ineffective, sotalol or amiodarone. We describe our experience, as a tertiary centre for ARVC, with the effectiveness and tolerance of flecainide in addition to beta-blockers to prevent VA in ARVC. METHODS AND RESULTS: We retrospectively included 100 consecutive ARVC patients who received flecainide with beta-blockers between May 1999 and November 2017. Treatment persistence and related side effects were assessed, as was VA-free survival on treatment, 24-h Holter monitoring and programmed ventricular stimulation (PVS) off- and on-treatment. Tolerance was good, with 10% flecainide discontinuations (lack of efficacy in six, atrial fibrillation in one, and side effects in three). No Brugada-induced electrocardiography pattern on flecainide or haemodynamic impairment was reported. Premature ventricular contraction burden at 24-h Holter monitoring was significantly decreased under treatment [median 415 (interquartile range, IQR 97-730) vs. 2370 (1572-3400) at baseline, P < 0.0001, n = 46]. Among the 33 patients with PVS under treatment, PVS was positive in 40% on-treatment vs. 94% off-treatment (P < 0.001). During a median follow-up of 47 months (IQR 23-73), 22 patients presented sustained VA on treatment, corresponding to an event rate of 5% [95% confidence interval (CI) (0.6-9)] at 1 year and 25% [95% CI (14-35)] at 5 years under treatment. No patient died. CONCLUSION: This study suggests that flecainide and beta-blockers association is complementary to implantable cardioverter-defibrillator and catheter ablation and is safe for treating persistent symptomatic VA in patients with ARVC.
Asunto(s)
Displasia Ventricular Derecha Arritmogénica , Fibrilación Atrial , Desfibriladores Implantables , Taquicardia Ventricular , Displasia Ventricular Derecha Arritmogénica/complicaciones , Displasia Ventricular Derecha Arritmogénica/diagnóstico , Displasia Ventricular Derecha Arritmogénica/tratamiento farmacológico , Fibrilación Atrial/tratamiento farmacológico , Flecainida/efectos adversos , Humanos , Estudios Retrospectivos , Sotalol , Taquicardia Ventricular/complicaciones , Taquicardia Ventricular/diagnóstico , Taquicardia Ventricular/tratamiento farmacológico , Resultado del TratamientoRESUMEN
BACKGROUND: Flecainide is a commonly used IC antiarrhythmic. Clinical presentations of Flecainide toxicity are not commonly described. CASE REPORT: A 62 year old man on dialysis presented for evaluation of outpatient bradycardia and hypotension. In the ED, patient had wide-complex rhythm with heart rates ranging from 76 to 127. The previous day, Flecainide and Metoprolol were discontinued and patient was dialyzed and discharged. The patient was treated empirically for possible hyperkalemia. No significant change in ECG was noted with administration of calcium. Sodium bicarbonate produced questionable benefit. Potassium level was 4.6 mmol/L. Cardiac rhythm fluctuated between sinus rhythm and wide complex tachycardia in the ED & ICU. Flecainide level was 2.1 µg/ml (normal <1 µg/ml). Toxicity developed despite previous discontinuation and dialysis prior to presentation because of Flecainide's large volume of distribution and lipopholicity. WHY SHOULD AN EMERGENCY PHYSICIAN BE AWARE OF THIS?: Although Flecainide toxicity is uncommon, it has a high mortality rate, requiring early identification and treatment. Flecainide toxicity can develop in patients with hepatic or renal insufficiency, and can manifest with ventricular tachycardia or bradycardia. If suspicion of Flecainide toxicity arises, lidocaine and procainamide should be avoided to prevent further sodium channel blockade. Absence of response to calcium for a very wide complex QRS should raise clinicians' suspicion that WCT is not due to hyperkalemia, emphasizing the importance of reviewing patients' home medications. Sodium bicarbonate should be administered early to treat widened QRS. Amiodarone, intralipid emulsion therapy and ECMO may be considered in severe cases.
Asunto(s)
Antiarrítmicos/efectos adversos , Flecainida/efectos adversos , Taquicardia/inducido químicamente , Antiarrítmicos/administración & dosificación , Electrocardiografía , Flecainida/administración & dosificación , Humanos , Hiperpotasemia/diagnóstico , Masculino , Persona de Mediana EdadRESUMEN
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.
Asunto(s)
Enfermedades Fetales , Insuficiencia Cardíaca , Nacimiento Prematuro , Taquicardia Supraventricular , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/complicaciones , Cesárea , Digoxina/uso terapéutico , Femenino , Enfermedades Fetales/diagnóstico , Enfermedades Fetales/tratamiento farmacológico , Flecainida/uso terapéutico , Insuficiencia Cardíaca/complicaciones , Humanos , Hidropesía Fetal , Recién Nacido , Embarazo , Estudios Retrospectivos , Taquicardia/complicaciones , Taquicardia/tratamiento farmacológico , Taquicardia Supraventricular/complicaciones , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/tratamiento farmacológicoRESUMEN
Cardiac diseases are the leading causes of death, with a growing number of cases worldwide, posing a challenge for both healthcare and research. Therefore, the most relevant aim of cardiac research is to unravel the molecular pathomechanisms and identify new therapeutic targets. Cardiac ryanodine receptor (RyR2), the Ca2+ release channel of the sarcoplasmic reticulum, is believed to be a good therapeutic target in a group of certain heart diseases, collectively called cardiac ryanopathies. Ryanopathies are associated with the impaired function of the RyR, leading to heart diseases such as congestive heart failure (CHF), catecholaminergic polymorphic ventricular tachycardia (CPVT), arrhythmogenic right ventricular dysplasia type 2 (ARVD2), and calcium release deficiency syndrome (CRDS). The aim of the current review is to provide a short insight into the pathological mechanisms of ryanopathies and discuss the pharmacological approaches targeting RyR2.
Asunto(s)
Canal Liberador de Calcio Receptor de Rianodina , Taquicardia Ventricular , Displasia Ventricular Derecha Arritmogénica , Calcio/metabolismo , Señalización del Calcio , Humanos , Mutación , Canal Liberador de Calcio Receptor de Rianodina/genética , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Retículo Sarcoplasmático/metabolismo , Taquicardia Ventricular/etiología , Taquicardia Ventricular/metabolismo , Taquicardia Ventricular/terapiaRESUMEN
It is imperative to develop better approaches to predict how antiarrhythmic drugs with multiple interactions and targets may alter the overall electrical and/or mechanical function of the heart. Safety Pharmacology studies have provided new insights into the multi-target effects of many different classes of drugs and have been aided by the addition of robust new in vitro and in silico technology. The primary focus of Safety Pharmacology studies has been to determine the risk profile of drugs and drug candidates by assessing their effects on repolarization of the cardiac action potential. However, for decades experimental and clinical studies have described substantial and potentially detrimental effects of Na+ channel blockers in addition to their well-known conduction slowing effects. One such side effect, associated with administration of some Na+ channel blocking drugs is negative inotropy. This reduces the pumping function of the heart, thereby resulting in hypotension. Flecainide is a well-known example of a Na+ channel blocking drug, that exhibits strong rate-dependent block of INa and may cause negative cardiac inotropy. While the phenomenon of Na+ channel suppression and resulting negative inotropy is well described, the mechanism(s) underlying this effect are not. Here, we set out to use a modeling and simulation approach to reveal plausible mechanisms that could explain the negative inotropic effect of flecainide. We utilized the Grandi-Bers model [1] of the cardiac ventricular myocyte because of its robust descriptions of ion homeostasis in order to characterize and resolve the relative effects of QRS widening, flecainide off-target effects and changes in intracellular Ca2+ and Na+ homeostasis. The results of our investigations and predictions reconcile multiple data sets and illustrate how multiple mechanisms may play a contributing role in the flecainide induced negative cardiac inotropic effect.
Asunto(s)
Antiarrítmicos/efectos adversos , Simulación por Computador , Flecainida/efectos adversos , Contracción Miocárdica/efectos de los fármacos , Bloqueadores del Canal de Sodio Activado por Voltaje/efectos adversos , Potenciales de Acción/efectos de los fármacos , Antiarrítmicos/metabolismo , Canales de Calcio/metabolismo , Flecainida/metabolismo , Frecuencia Cardíaca/efectos de los fármacos , Ventrículos Cardíacos/citología , Ventrículos Cardíacos/efectos de los fármacos , Homeostasis/efectos de los fármacos , Humanos , Modelos Cardiovasculares , Miocitos Cardíacos/efectos de los fármacos , Miocitos Cardíacos/metabolismo , Canal Liberador de Calcio Receptor de Rianodina/metabolismo , Transducción de Señal/efectos de los fármacos , Canales de Sodio/metabolismo , Bloqueadores del Canal de Sodio Activado por Voltaje/metabolismoRESUMEN
INTRODUCTION: Sotalol and flecainide are used as second line agents in children for the treatment of supraventricular arrhythmias (SA) refractory to anti-beta adrenergic antiarrhythmics or digoxin. Efficacy and adverse events in this cohort have not been well described. Here, we report our institutional experience of second line treatment initiation for SA in children. METHODS AND RESULTS: Utilizing an institutional database, 247 patients initiated on sotalol and 81 patients initiated on flecainide were identified. Congenital heart disease (CHD) was present in 40% of patients. Arrhythmia-free discharge on single or dual agent therapy (in combination with other antiarrhythmics) was 87% for sotalol and 91% for flecainide. Neither age, sex, dosing, presence of CHD nor arrhythmia subtype were associated with alterations in in-hospital efficacy. Compared to baseline, QTc intervals in sotalol patients (436 [416-452 ms] vs. 415 [400-431 ms], p < .01) and QRS intervals in flecainide patients (75 [68-88 ms] vs. 62 [56-71 ms], p < .01) were prolonged. Dose reduction or discontinuation due to QRS prolongation occurred in 9% of patients on flecainide. QTc prolongation resulting in dose reduction/discontinuation of sotalol was encountered in 9 patients (4%) and death with documented torsade de pointes in 2 patients (1%), with 9 of 11 patients having underlying CHD. CONCLUSION: In children requiring second line agents for treatment of SA, both sotalol and flecainide appear to be highly efficacious. Although predominantly safe in otherwise healthy patients, electrocardiogram changes can occur and children with underlying cardiac disease may have an increased risk of adverse events and rhythm-related side effects during initiation.
Asunto(s)
Flecainida , Sotalol , Antiarrítmicos/efectos adversos , Arritmias Cardíacas/tratamiento farmacológico , Niño , Flecainida/efectos adversos , Hospitales , Humanos , Sotalol/efectos adversosRESUMEN
BACKGROUND: Supraventricular tachycardias (SVTs) are common in the first year of life and may be life-threatening. Acute cardioversion is usually effective, with both pharmacological and non-pharmacological procedures. However, as yet no international consensus exists concerning the best drug required for a stable conversion to sinus rhythm (maintenance treatment). Our study intends to describe the experience of a single centre with maintenance drug treatment of both re-entry and automatic SVTs in the first year of life. METHODS: From March 1995 to April 2019, 55 patients under one year of age with SVT were observed in our Centre. The SVTs were divided into two groups: 45 re-entry and 10 automatic tachycardias. As regards maintenance therapy, in re-entry tachycardias, we chose to start with oral flecainide and in case of relapses switched to combined treatment with beta-blockers or digoxin. In automatic tachycardias we first administered a beta-blocker, later combined with flecainide or amiodarone when ineffective. RESULTS: The patients' median follow-up time was 35 months. In re-entry tachycardias, flecainide was effective as monotherapy in 23/45 patients (51.1%) and in 20/45 patients (44.4%) in combination with nadolol, sotalol or digoxin (overall 95.5%). In automatic tachycardias, a beta-blocker alone was effective in 3/10 patients (30.0%), however, the best results were obtained when combined with flecainide: overall 9/10 (90%). CONCLUSIONS: In this retrospective study on pharmacological treatment of SVTs under 1 year of age the combination of flecainide and beta-blockers was highly effective in long-term maintenance of sinus rhythm in both re-entry and automatic tachycardias.
Asunto(s)
Antiarrítmicos/uso terapéutico , Frecuencia Cardíaca/efectos de los fármacos , Taquicardia Supraventricular/tratamiento farmacológico , Potenciales de Acción , Antagonistas Adrenérgicos beta/uso terapéutico , Factores de Edad , Antiarrítmicos/efectos adversos , Digoxina/uso terapéutico , Quimioterapia Combinada , Femenino , Flecainida/uso terapéutico , Humanos , Lactante , Recién Nacido , Masculino , Nadolol/uso terapéutico , Recurrencia , Estudios Retrospectivos , Sotalol/uso terapéutico , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/fisiopatología , Factores de Tiempo , Resultado del Tratamiento , Bloqueadores del Canal de Sodio Activado por Voltaje/uso terapéuticoRESUMEN
Andersen-Tawil syndrome (ATS) is a rare disorder characterized by a triad of ventricular arrhythmia (VA), dysmorphic features, and periodic paralysis. Due to the rarity of this condition, less is known about physiologic effect of pregnancy to ATS and arrhythmia. There is no established guideline for peripartum or postpartum treatment and prevention of arrhythmia in ATS; thus, the clinical management is challenging. We reported two KCNJ2-associated ATS patients who got pregnant and underwent vaginal birth safely. Both individuals had VA, micrognathia without periodic paralysis. ß-blocker plus flecainide could be an effective treatment combination when monotherapy failed to control arrhythmia. VA of two pregnant patients with ATS could be controlled by either physiologic changes associated pregnancy or the combination treatment of ß-blocker and flecainide.
Asunto(s)
Antagonistas Adrenérgicos beta/uso terapéutico , Síndrome de Andersen/tratamiento farmacológico , Antiarrítmicos/uso terapéutico , Flecainida/uso terapéutico , Complicaciones Cardiovasculares del Embarazo/tratamiento farmacológico , Taquicardia Ventricular/tratamiento farmacológico , Adulto , Femenino , Humanos , Embarazo , Resultado del TratamientoRESUMEN
A 3-months-old infant was urgently admitted for drowsiness and lack of appetite started 24 h before. The ECG showed sinus rhythm with a prolonged AV interval (200 ms) and very large QRS complexes (280 ms) due to Flecainide overdosing following incorrectly administration for poor communication between parents resulted in both giving a dose to the infant. Flecainide serum level was 1.2µg/ml, confirming the diagnosis of an accidental drug intoxication. The patient started continue hydration with a close monitoring. Three hours later a significant narrowing of the QRS complex (150 ms) was observed, then over the following 24 h, the QRS almost completely normalized.
Asunto(s)
Antiarrítmicos , Sobredosis de Droga , Antiarrítmicos/uso terapéutico , Electrocardiografía , Flecainida , Humanos , LactanteRESUMEN
The aim of the study is to compare the efficacy of flecainide, beta-blockers, sotalol, and verapamil in children with frequent PVCs, with or without asymptomatic VT. Frequent premature ventricular complexes (PVCs) and asymptomatic ventricular tachycardia (VT) in children with structurally normal hearts require anti-arrhythmic drug (AAD) therapy depending on the severity of symptoms or ventricular dysfunction; however, data on efficacy in children are scarce. Both symptomatic and asymptomatic children (≥ 1 year and < 18 years of age) with a PVC burden of 5% or more, with or without asymptomatic runs of VT, who had consecutive Holter recordings, were included in this retrospective multi-center study. The groups of patients receiving AAD therapy were compared to an untreated control group. A medication episode was defined as a timeframe in which the highest dosage at a fixed level of a single drug was used in a patient. A total of 35 children and 46 medication episodes were included, with an overall change in PVC burden on Holter of -4.4 percentage points, compared to -4.2 in the control group of 14 patients. The mean reduction in PVC burden was only significant in patients receiving flecainide (- 13.8 percentage points; N = 10; p = 0.032), compared to the control group and other groups receiving beta-blockers (- 1.7 percentage points; N = 18), sotalol (+ 1.0 percentage points; N = 7), or verapamil (- 3.9 percentage points; N = 11). The efficacy of anti-arrhythmic drug therapy on frequent PVCs or asymptomatic VTs in children is very limited. Only flecainide appears to be effective in lowering the PVC burden.
Asunto(s)
Antiarrítmicos/uso terapéutico , Taquicardia Ventricular/tratamiento farmacológico , Complejos Prematuros Ventriculares/tratamiento farmacológico , Adolescente , Antagonistas Adrenérgicos beta/uso terapéutico , Niño , Preescolar , Femenino , Flecainida/uso terapéutico , Humanos , Masculino , Estudios Retrospectivos , Sotalol/uso terapéutico , Taquicardia Ventricular/complicaciones , Resultado del Tratamiento , Complejos Prematuros Ventriculares/complicaciones , Verapamilo/uso terapéuticoRESUMEN
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.
Asunto(s)
Sobredosis de Droga , Flecainida , Antiarrítmicos , Electrocardiografía , Humanos , Lactante , Recién NacidoRESUMEN
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.