RESUMEN
PURPOSE: The clinical usefulness of therapeutic drug monitoring (TDM) of propafenone, a sodium channel blocker, has been unclear due to the lack of information regarding optimal blood sampling time and therapeutic concentration range. Antiarrhythmic effects of sodium channel blockers are affected by the activity of the cardiac sodium channel (SCN5A). We investigated the optimal sampling time and the clinical implication of the SCN5A promoter haplotype in propafenone TDM. METHODS: We evaluated serum concentrations of propafenone, the SCN5A promoter haplotype, and antiarrhythmic efficacy in 55 patients with supraventricular tachy-arrhythmias. Blood samples obtained 1.5-6 and 10-24 h after the last dose were categorized as peak and trough samples, respectively. RESULTS: The peak propafenone concentration was significantly higher in effectively treated patients than that in patients showing insufficient response (337 ± 213 vs. 177 ± 93 ng/mL, P = 0.005), but the trough propafenone concentration was not significantly different between the two groups (68 ± 48 vs. 42 ± 36 ng/mL). Clinically relevant propafenone efficacy was achieved significantly more often in SCN5A haplotype B carriers than in wild-type haplotype A homozygotes (90 vs. 60%, P < 0.05). Among the haplotype A homozygotes, peak propafenone concentration was higher in effectively treated patients than that in patients showing insufficient response (299 ± 177 vs. 177 ± 93 ng/mL, P = 0.061). CONCLUSION: The present study found that antiarrhythmic efficacy of propafenone was associated with peak propafenone concentration rather than trough concentration and was affected by the SCN5A promoter haplotype.
Asunto(s)
Monitoreo de Drogas/métodos , Canal de Sodio Activado por Voltaje NAV1.5/genética , Propafenona , Taquicardia Supraventricular/tratamiento farmacológico , Adulto , Antiarrítmicos , Electrocardiografía/métodos , Femenino , Haplotipos , Homocigoto , Humanos , Masculino , Persona de Mediana Edad , Variantes Farmacogenómicas , Regiones Promotoras Genéticas , Propafenona/administración & dosificación , Propafenona/sangre , Propafenona/farmacocinética , Bloqueadores de los Canales de Sodio/administración & dosificación , Bloqueadores de los Canales de Sodio/sangre , Bloqueadores de los Canales de Sodio/farmacocinética , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/genética , Factores de Tiempo , Resultado del TratamientoRESUMEN
Atrial fibrillation (AF) is the most common sustained cardiac arrhythmia and a major cause of morbidity and mortality. Traditional antiarrhythmic agents used for restoration of sinus rhythm have limited efficacy in long-term AF and they may possess ventricular proarrhythmic adverse effects, especially in patients with structural heart disease. The acetylcholine receptor-activated potassium channel (IK,ACh) represents an atrial selective target for future AF management. We investigated the effects of the IK,ACh blocker tertiapin-Q (TQ), a derivative of the honeybee toxin tertiapin, on chronic atrial tachypacing-induced AF in conscious dogs, without the influence of anesthetics that modulate a number of cardiac ion channels. Action potentials (APs) were recorded from right atrial trabeculae isolated from dogs with AF. TQ significantly and dose-dependently reduced AF incidence and AF episode duration, prolonged atrial effective refractory period, and prolonged AP duration. The reference drugs propafenone and dofetilide, both used in the clinical management of AF, exerted similar effects against AF in vivo. Dofetilide prolonged atrial AP duration, whereas propafenone increased atrial conduction time. TQ and propafenone did not affect the QT interval, whereas dofetilide prolonged the QT interval. Our results show that inhibition of IK,ACh may represent a novel, atrial-specific target for the management of AF in chronic AF.
Asunto(s)
Potenciales de Acción , Fibrilación Atrial/tratamiento farmacológico , Remodelación Atrial , Estado de Conciencia , Atrios Cardíacos/fisiopatología , Bloqueadores de los Canales de Potasio/uso terapéutico , Canales de Potasio/metabolismo , Receptores Colinérgicos/metabolismo , Potenciales de Acción/efectos de los fármacos , Animales , Fibrilación Atrial/fisiopatología , Remodelación Atrial/efectos de los fármacos , Venenos de Abeja/administración & dosificación , Venenos de Abeja/farmacología , Venenos de Abeja/uso terapéutico , Estado de Conciencia/efectos de los fármacos , Perros , Electrocardiografía , Atrios Cardíacos/efectos de los fármacos , Masculino , Fenetilaminas/administración & dosificación , Fenetilaminas/farmacología , Fenetilaminas/uso terapéutico , Bloqueadores de los Canales de Potasio/administración & dosificación , Bloqueadores de los Canales de Potasio/farmacología , Propafenona/administración & dosificación , Propafenona/farmacología , Propafenona/uso terapéutico , Periodo Refractario Electrofisiológico/efectos de los fármacos , Sulfonamidas/administración & dosificación , Sulfonamidas/farmacología , Sulfonamidas/uso terapéuticoRESUMEN
Propafenone is a potent antiarrhythmic agent; clinically propafenone has been used for a number of cardiac arrhythmias because it possesses multiple modes of action, via beta adrenergic receptor blockade and calcium antagonistic activity. Propafenone (PPF) exhibits extensive saturable presystemic biotransformation (first-pass effect) resulting in two active metabolites: 5-hydroxypropafenone (5-OH PPF) formed by CYP2D6 and N-depropylpropafenone (NDP) formed by both CYP3A4 and CYP1A2 enzymes. A specific and sensitive LC-MS/MS method was developed and validated for quantitation of PPF, 5-OH PPF and NDP using turboion spray in a positive ion mode. A solid-phase extraction was employed for the extraction from human plasma. Chromatographic separation of analytes was achieved using an ACE-5 C8 (50 × 4.6 mm) column with a gradient mobile phase comprising ammonium acetate containing 0.01% TFA in purified water and acetonitrile. The retention times achieved were 1.36, 1.23, 1.24 min and 1.34 min for PPF, 5-OH PPF, NDP and IS (carbamazepine), respectively. Quantitation was performed by monitoring multiple reaction monitoring transition pairs of m/z 342.30 to m/z 116.20, m/z 358.30 to m/z 116.20, m/z 300.30 to m/z 74.20 and m/z 237.20 to m/z 194.10, respectively. The developed method was validated for various parameters. The calibration curves of PPF and 5-OH PPF showed linearity from 1 to 500 ng/mL, with a lower limit of quantitation of 1.0 ng/mL and for NDP linearity from 0.1 to 25 ng/mL with a lower limit of quantitation of 0.1 ng/mL. The bias and precision for intra- and-inter batch assays were <10 and 5%, respectively. The developed assay was used to evaluate pharmacokinetic properties of propafenone and its major metabolites in healthy human subjects.
Asunto(s)
Cromatografía Liquida/métodos , Propafenona/análogos & derivados , Propafenona/sangre , Espectrometría de Masas en Tándem/métodos , Administración Oral , Estabilidad de Medicamentos , Ácido Edético , Humanos , Límite de Detección , Modelos Lineales , Propafenona/administración & dosificación , Propafenona/química , Propafenona/farmacocinética , Reproducibilidad de los ResultadosRESUMEN
AIMS: Propafenone is a well-known Class Ic antiarrhythmic agent. It has the typical chemical structure of a beta-blocker, but human studies on its beta-blocking effects revealed conflicting results. METHODS AND RESULTS: Twelve healthy males received single oral doses of 600 mg propafenone and placebo according to a randomized, double-blind, placebo-controlled, cross-over protocol. Four hours following drug intake, heart rate and blood pressure were measured, and plasma concentrations of propafenone were determined at rest, during exercise and after recovery. At exercise, propafenone significantly decreased heart rate (-6%, P < 0.05), systolic blood pressure (-6%, P < 0.05), and the rate-pressure product (-11%, P < 0.05). Plasma concentrations of propafenone increased during exercise (+23%, P < 0.05) and decreased during recovery (-33%, P < 0.05). CONCLUSION: Both effects on heart rate and blood pressure as well as the changes of plasma concentrations of propafenone during exercise represent two particular features of beta-blockers. Therefore, we conclude that propafenone is both a Class Ic and a Class II antiarrhythmic agent, and 600 mg propafenone, i.e. the dose recommended in current guidelines for cardioversion of paroxysmal atrial fibrillation, cause clinically significant beta-blockade. Thus, single oral doses of 600 mg propafenone appear also suitable for cardioversion of paroxysmal atrial fibrillation in patients with structural heart disease since beta-blockers are explicitly indicated in the treatment of both coronary artery disease and heart failure.
Asunto(s)
Antagonistas Adrenérgicos beta/administración & dosificación , Antiarrítmicos/administración & dosificación , Frecuencia Cardíaca/efectos de los fármacos , Propafenona/administración & dosificación , Administración Oral , Antagonistas Adrenérgicos beta/sangre , Antagonistas Adrenérgicos beta/clasificación , Antagonistas Adrenérgicos beta/farmacocinética , Adulto , Antiarrítmicos/sangre , Antiarrítmicos/clasificación , Antiarrítmicos/farmacocinética , Austria , Presión Sanguínea/efectos de los fármacos , Estudios Cruzados , Método Doble Ciego , Monitoreo de Drogas , Ejercicio Físico , Prueba de Esfuerzo , Voluntarios Sanos , Humanos , Masculino , Estructura Molecular , Propafenona/sangre , Propafenona/clasificación , Propafenona/farmacocinética , Recuperación de la Función , Relación Estructura-Actividad , Adulto JovenAsunto(s)
Fibrilación Atrial , Síndrome de Brugada , Sustitución de Medicamentos/métodos , Ecocardiografía/métodos , Cardioversión Eléctrica/métodos , Propafenona , Quinidina/administración & dosificación , Antiarrítmicos/administración & dosificación , Antiarrítmicos/efectos adversos , Fibrilación Atrial/diagnóstico , Fibrilación Atrial/tratamiento farmacológico , Fibrilación Atrial/terapia , Síndrome de Brugada/inducido químicamente , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/fisiopatología , Síndrome de Brugada/terapia , Toma de Decisiones Clínicas , Femenino , Humanos , Persona de Mediana Edad , Propafenona/administración & dosificación , Propafenona/efectos adversos , Resultado del TratamientoRESUMEN
PURPOSE: The echocardiography parameters may predict the maintenance of sinus rhythm after cardioversion of a supraventricular arrhythmia (SVA). MATERIALS AND METHODS: Patients in septic shock with onset of an SVA, normal to moderately reduced LV systolic function (EF_LVË̳35%) and on a continuous noradrenaline of <1.0 µg/kg.min were included. Echocardiography was performed at the arrhythmia onset, 1 h and 4 h post cardioversion on an infusion of propafenone or amiodarone. RESULTS: Cardioversion was achieved in 96% of the 209 patients within a median time of 6(1.8-15.6)h, 134(64.1%) patients experienced at least one SVA recurrence after cardioversion. At 4 h the left atrial emptying fraction (LA_EF, cut-off 38.4%, AUC 0.69,pË0.001), and transmitral A wave velocity-time-integral (Avti, cut-off 6.8 cm, AUC 0.65,p = 0.001) showed as limited predictors of a single arrhythmia recurrence. The LA_EF 44(36,49)%, (p = 0.005) and the Avti 8.65(7.13,9.50)cm, (p < 0.001) were associated with sustained sinus rhythm and decreased proportionally to increasing numbers of arrhythmia recurrences (p < 0.001 and p = 0.007, respectively). The enlarged left atrial end-systolic diameter at the arrhythmia onset (p = 0.04) and elevated systolic pulmonary artery pressure at 4 h (p = 0.007) were weak predictors of multiple(Ë3) recurrences. CONCLUSION: The LA_EF and Avti are related to arrhythmia recurrences post-cardioversion suggesting potential guidance to the choice between rhythm and rate control strategies. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT03029169, registered on 24th of January 2017.
Asunto(s)
Ecocardiografía , Cardioversión Eléctrica , Choque Séptico , Humanos , Masculino , Femenino , Choque Séptico/terapia , Choque Séptico/fisiopatología , Choque Séptico/complicaciones , Anciano , Persona de Mediana Edad , Antiarrítmicos/uso terapéutico , Recurrencia , Amiodarona/uso terapéutico , Amiodarona/administración & dosificación , Propafenona/uso terapéutico , Propafenona/administración & dosificación , Taquicardia Supraventricular/terapia , Taquicardia Supraventricular/fisiopatología , Taquicardia Supraventricular/diagnóstico por imagen , Estudios ProspectivosRESUMEN
AIMS: A recently published trial has shown no differences in outcomes between patients with new-onset supraventricular arrhythmia (SVA) in septic shock treated with either propafenone or amiodarone. However, these outcome data have not been evaluated in relation to the presence or absence of a dilated left atrium (LA). METHODS AND RESULTS: Patients with SVA and a left ventricular ejection fraction ≥ 35% were randomized to receive intravenous propafenone (70â mg bolus followed by 400-840â mg/24â h) or amiodarone (300â mg bolus followed by 600-1800â mg/24â h). They were divided into groups based on whether their end-systolic left atrial volume (LAVI) was ≥40â mL/m². The subgroup outcomes assessed were survival at ICU discharge, 1 month, 3 months, 6 months, and 12 months. Propafenone cardioverted earlier (P = 0.009) and with fewer recurrences (P = 0.001) in the patients without LA enlargement (n = 133). Patients with LAVI < 40â mL/m2 demonstrated a mortality benefit of propafenone over the follow-up of 1 year [Cox regression, hazard ratio (HR) 0.6 (95% CI 0.4; 0.9), P = 0.014]. Patients with dilated LA (n = 37) achieved rhythm control earlier in amiodarone (P = 0.05) with similar rates of recurrences (P = 0.5) compared to propafenone. The outcomes for patients with LAVI ≥ 40â mL/m2 were less favourable with propafenone compared to amiodarone at 1 month [HR 3.6 (95% CI 1.03; 12.5), P = 0.045]; however, it did not reach statistical significance at 1 year [HR 1.9 (95% CI 0.8; 4.4), P = 0.138]. CONCLUSION: Patients with non-dilated LA who achieved rhythm control with propafenone in the setting of septic shock had better short-term and long-term outcomes than those treated with amiodarone, which seemed to be more effective in patients with LAVI ≥ 40â mL/m². TRIAL REGISTRATION: ClinicalTrials.gov identifier: NCT03029169, registered on 24 January 2017.
Asunto(s)
Amiodarona , Antiarrítmicos , Atrios Cardíacos , Propafenona , Choque Séptico , Taquicardia Supraventricular , Humanos , Propafenona/uso terapéutico , Propafenona/administración & dosificación , Amiodarona/uso terapéutico , Amiodarona/administración & dosificación , Choque Séptico/tratamiento farmacológico , Choque Séptico/fisiopatología , Masculino , Femenino , Antiarrítmicos/uso terapéutico , Antiarrítmicos/administración & dosificación , Anciano , Atrios Cardíacos/fisiopatología , Atrios Cardíacos/diagnóstico por imagen , Atrios Cardíacos/efectos de los fármacos , Taquicardia Supraventricular/tratamiento farmacológico , Taquicardia Supraventricular/fisiopatología , Resultado del Tratamiento , Persona de Mediana Edad , Volumen Sistólico/fisiología , Volumen Sistólico/efectos de los fármacosRESUMEN
PURPOSE: The aim was to prepare and evaluate unitary doses of propafenone (UDP) used in children with supraventricular tachycardia. METHODS: UDP were prepared from four brands of tablets at doses of propafenone, 11, 25 and 90 mg, used in the Cardiology Service of this Institute. The stability of doses was determined at 20±5°C and 40°C for up to day 30. Besides, a weight variation test was performed. Plasma levels of propafenone were determined at steady state in 3 children diagnosed with supraventricular tachycardia under treatment with UDP. Concentrations of drug in blood were measured using a high pressure liquid chromatography method, previously validated. RESULTS: The stability of UDP, showed no significant statistical differences (p > 0.05) between doses or brands up to day 30, at both temperatures. The coefficient of variation from the weight variation was less than 6%. The plasma levels of propafenone at steady state were: patient 1, 31.57 ng/ml; patient 2, 226.46 ng/ml; and patient 3, 221.29 ng/ml. CONCLUSIONS: The actual administered dose for the patients could vary up to 6%, and doses prepared from different brands of tablets remain stables for up to day 30 at both temperatures. UDP is a temporal, safe and alternative option when pediatrics formulation of this drug is lacking.
Asunto(s)
Antiarrítmicos/uso terapéutico , Propafenona/administración & dosificación , Taquicardia Supraventricular/tratamiento farmacológico , Niño , Humanos , Proyectos Piloto , Propafenona/sangreRESUMEN
BACKGROUND: Strategies to restore sinus rhythm in patients with atrial fibrillation (AF) lasting less than 48 h with haemodynamic stability remain controversial. The aim of this study was to test the hypothesis that electrical cardioversion (EC) would be more effective and safer in converting acute AF to sinus rhythm, compared with intravenous propafenone treatment. METHODS: In the emergency department (ED) of Valduce Hospital, a single-centre randomised trial was conducted to compare EC with pharmacological cardioversion (PC) to restore the sinus rhythm in selected patients with acute AF. A total of 247 patients was enrolled (121 in the EC group and 126 in the PC group). RESULTS: EC was more successful than PC in restoring sinus rhythm. Successful cardioversion was achieved in 108 out of 121 patients in the EC group (89.3%) and 93 out of 126 patients in the PC group (73.8%) (HR in the EC group, 0.34; 95% CI 0.17 to 0.68; p=0.02). The time patients spent in the ED undergoing treatment was significantly lower in the EC group compared with the PC group (median (range), 180 (120-900) vs 420 (120-1400) min; p<0.001). CONCLUSIONS: EC was more effective in patients with acute AF and resulted in a shorter length of stay in the ED than PC. Adverse events were small in number and transient in both groups of patients. Clinical trials registration number NCT00933634.
Asunto(s)
Fibrilación Atrial/terapia , Cardioversión Eléctrica , Servicio de Urgencia en Hospital , Enfermedad Aguda , Anciano , Anciano de 80 o más Años , Antiarrítmicos/administración & dosificación , Servicio de Urgencia en Hospital/estadística & datos numéricos , Femenino , Humanos , Inyecciones Intravenosas , Tiempo de Internación , Masculino , Persona de Mediana Edad , Propafenona/administración & dosificación , Estudios ProspectivosRESUMEN
It has been reported that Brugada syndrome is responsible for about half of the sudden cardiac death events with no evidence of structural heart disease. We report a case of hidden ECG Brugada pattern, revealed after oral propafenone administration in the setting of pharmaceutical atrial fibrillation cardioversion.
Asunto(s)
Antiarrítmicos/administración & dosificación , Fibrilación Atrial/etiología , Fibrilación Atrial/terapia , Síndrome de Brugada/complicaciones , Síndrome de Brugada/diagnóstico , Cardioversión Eléctrica , Propafenona/administración & dosificación , Electrocardiografía , Humanos , Masculino , Persona de Mediana EdadRESUMEN
A 31-year-old male patient was admitted to the emergency department with acute atrial fibrillation. After diltiazem infusion, a single oral dose of 600 mg propafenone was given to the patient for medical cardioversion. Approximately four hours later, sinus rhythym was restored. Re-evaluation of the admission ECG revealed right bundle branch block and saddleback-type ST-segment elevation of about 2 mm in V1-2 leads. Following propafenone, this type 2 Brugada ECG pattern turned to the coved type 1 Brugada pattern with ST elevation of more than 2 mm. After disappearance of propafenone effect, the ECG pattern turned to the type 2 Brugada pattern. Considering that the patient also had a family history of sudden cardiac death, electrophysiological study was conducted. During ventricular tachycardia stimulation, no ventricular arrhythmia was observed, thus the patient was scheduled to a close follow-up program.
Asunto(s)
Fibrilación Atrial/terapia , Síndrome de Brugada/diagnóstico , Adulto , Antiarrítmicos/administración & dosificación , Fibrilación Atrial/complicaciones , Síndrome de Brugada/fisiopatología , Electrofisiología Cardíaca , Fármacos Cardiovasculares/administración & dosificación , Diltiazem/administración & dosificación , Cardioversión Eléctrica , Electrocardiografía , Humanos , Masculino , Propafenona/administración & dosificaciónRESUMEN
BACKGROUND: Patients with acute atrial fibrillation with a history of mild structural heart disease could be considered for rhythm conversion. METHODS: Patients received intravenous flecainide, propafenone, or amiodarone on presentation and a second dose after 6 hours if atrial fibrillation persisted. No randomization was used, and drugs were given at the discretion of the treating physician. Primary end point was rhythm conversion within the first 6 hours from presentation. Secondary end points included rhythm conversion, time to rhythm conversion, and adverse drug effects within 24 hours. RESULTS: Among the 378 patients enrolled, 37 (10%) recovered sinus rhythm before therapy was given. Of the remaining 341 patients, 43 (13%) received flecainide, 187 (55%) received propafenone, and 111 (32%) received amiodarone. Baseline clinical characteristics were homogeneous among groups. Rhythm conversion was obtained in 87% of treated patients overall. Within 6 hours, the primary end point was achieved in a higher proportion in the flecainide and propafenone groups (72% and 55%, respectively) as compared with the amiodarone group (30%; P < .001). The mean time to the end point overall was shorter in the flecainide and propafenone groups (178 ± 227 and 292 ± 285 minutes, respectively) as compared with the amiodarone group (472 ± 269 minutes; P < .001). Length of in-hospital stay in the amiodarone group was significantly higher (26.1 ± 22.4 hours) compared with the flecainide and propafenone groups (8.9 ± 10.3 and 11.0 ± 13.8 hours; respectively; P = .001). No significant differences were found in adverse drug effects. CONCLUSIONS: Flecainide and propafenone achieve rhythm control in a higher proportion of patients as compared with amiodarone within a 6-hour management.
Asunto(s)
Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Fibrilación Atrial/tratamiento farmacológico , Flecainida/uso terapéutico , Propafenona/uso terapéutico , Enfermedad Aguda , Anciano , Amiodarona/administración & dosificación , Amiodarona/efectos adversos , Antiarrítmicos/administración & dosificación , Antiarrítmicos/efectos adversos , Cardioversión Eléctrica , Servicio de Urgencia en Hospital , Femenino , Flecainida/administración & dosificación , Flecainida/efectos adversos , Humanos , Inyecciones Intravenosas , Tiempo de Internación , Masculino , Propafenona/administración & dosificación , Propafenona/efectos adversos , Factores de Tiempo , Resultado del TratamientoRESUMEN
A prospective randomized study was conducted to compare the antiarrhythmic activity of amiodarone and propafenone used to prevent atrial fibrillation (AF) after aortocoronary bypass surgery (ACBS). The study included 100 patients who had undergone myocardial revascularization. The patients were divided into 2 groups that did not significantly differ in their baseline condition, history data, the type of a surgical intervention, and the incidence of postoperative complications. Antiarrhythmic therapy was initiated within the first 24 hours after surgery. Group 1 (n=50) was given intravenous amiodarone in a dose of 6 mg/kg/day. Rhythm disturbances occurred in 13 (26%) patients. Group 2 (n=50) received oral propaferone in a dose of 6.6 mg/kg/day. AF occurred in 5 (10%) patients. The difference between Groups 1 and 2 was statistically significant (p = 0.047). The preventive use of propafenone recovered sinus rhythm in earlier periods (4602 +/- 71 min) than that of amiodarone (760 +/- 82 min); p = 0.049. Thus, propafenone was found to be a more effective drug used to prevent AF after ACBS, which is attributable to different pharmacodynamic behavior of the agents.
Asunto(s)
Amiodarona/uso terapéutico , Antiarrítmicos/uso terapéutico , Arritmias Cardíacas/prevención & control , Puente de Arteria Coronaria/efectos adversos , Propafenona/uso terapéutico , Administración Oral , Adulto , Anciano , Amiodarona/administración & dosificación , Antiarrítmicos/administración & dosificación , Arritmias Cardíacas/etiología , Femenino , Humanos , Inyecciones Intravenosas , Masculino , Persona de Mediana Edad , Propafenona/administración & dosificación , Estudios Prospectivos , Resultado del TratamientoRESUMEN
BACKGROUND: Amiodarone and propafenone are commonly used to maintain sinus rhythm in patients with atrial fibrillation (AF). However, it is not known which one is better in reducing early recurrence (ER) during the blanking period (the first three months after catheter ablation). OBJECTIVE: To compare the efficacy and safety of amiodarone and propafenone in reducing ER during the blanking period after radiofrequency catheter ablation (RFCA) in AF patients. MATERIALS AND METHODS: A total of 694 patients who underwent their first RFCA between May 2014 and May 2018 were enrolled in this retrospective study. Subsequently, 202 patients were excluded according to the exclusion criteria. The remaining 492 patients were divided into two groups based on the choice of antiarrhythmic drugs (AADs) (amiodarone or propafenone) in the blanking period. The primary outcomes were incidence of ER and AAD-associated adverse effects during the blanking period after RFCA. Propensity score matching (PSM) analyses were used to compare the outcomes of the two groups while controlling for confounders. RESULTS: Among the 492 patients who took AADs in the blanking period (187 amiodarone and 305 propafenone), PSM selected 135 unique pairs of patients with similar characteristics. Amiodarone was associated with a lower ER incidence rate (23.7% versus 48.9%, p < 0.001) and a similar rate of AAD-associated adverse effects (2.1% versus 1.5%, p = 0.652). Treatment with amiodarone in the blanking period was significantly associated with a lower ER incidence rate compared to treatment with propafenone (HR = 0.416, 95% CI 0.272-0.637, p < 0.001). CONCLUSIONS: Compared with propafenone, amiodarone was associated with a lower ER incidence rate, and they had similar rates of AAD-associated adverse effects. Treatment with amiodarone in the blanking period was shown to be more effective in reducing ER than propafenone.
Asunto(s)
Amiodarona/administración & dosificación , Fibrilación Atrial/terapia , Ablación por Catéter , Propafenona/administración & dosificación , Anciano , Amiodarona/efectos adversos , Fibrilación Atrial/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Propafenona/efectos adversos , RecurrenciaRESUMEN
OBJECTIVE: To investigate effects of IV administration of propafenone for naturally occurring and experimentally induced chronic atrial fibrillation in horses. ANIMALS: 2 horses with naturally occurring atrial fibrillation and 4 horses with pacing-induced atrial fibrillation. PROCEDURES: Horses received a bolus of propafenone (2 mg/kg, IV over 15 minutes). If atrial fibrillation persisted after 20 minutes, a continuous infusion of propafenone (7 microg/kg/min) was given for 120 minutes. Before, during, and after treatment, plasma propafenone concentrations, hematologic and serum biochemical values, and electolyte concentrations analyses were determined and clinical signs were monitored. Surface ECGs were recorded. If propafenone treatment failed, quinidine sulfate was administered. RESULTS: Bolus and continuous infusion induced minimal adverse effects. During the 15-minute bolus administration, a slight increase in heart rate was observed and horses appeared more sensitive to external stimuli. Throughout treatment, no significant changes were observed in respiratory rate, QRS or corrected QT duration, or results of hematologic analyses. Although a significant increase in F-wave interval and atrial fibrillation cycle length was observed and plasma propafenone concentrations (569 to 1,268 ng/mL) reached the human therapeutic range (64 to 1,044 ng/mL), none of the horses cardioverted to sinus rhythm. Sinus rhythm could be restored in all horses via standard oral administration of quinidine. CONCLUSIONS AND CLINICAL RELEVANCE: A slow IV bolus of 2 mg of propafenone/kg followed by a continuous infusion of 7 microg/kg/min over 2 hours was not an effective treatment for chronic atrial fibrillation in horses.
Asunto(s)
Fibrilación Atrial/veterinaria , Enfermedades de los Caballos/tratamiento farmacológico , Propafenona/uso terapéutico , Análisis de Varianza , Animales , Fibrilación Atrial/tratamiento farmacológico , Ecocardiografía/veterinaria , Electrocardiografía/veterinaria , Caballos , Inyecciones Intravenosas/veterinaria , Propafenona/administración & dosificación , Propafenona/sangreRESUMEN
A case of a patient treated with antiarrhythmic drugs for ventricular arrhythmia occurring after viral infection of the respiratory tract is presented. In the course of preliminary cardiologic examination no organic heart disease was diagnosed. Due to numerous ventricular extrasystolic beats (16,500 per day) and short runs of non-sustained ventricular tachycardia (maximum of 4 subsequent beats) propafenone was introduced. Persistent arrhythmia was a reason for adding sotalol to that treatment in an outpatient clinic. After three weeks of such treatment the patient presented cardiac arrest in the mechanism of ventricular tachycardia and fibrillation. Successful resuscitation and drug discontinuation led to complete resolution of the life-threatening arrhythmia. No inducible complex ventricular arrhythmia was observed during electrophysiologic examination.
Asunto(s)
Antiarrítmicos/efectos adversos , Quimioterapia Combinada/efectos adversos , Propafenona/efectos adversos , Choque Cardiogénico/inducido químicamente , Sotalol/efectos adversos , Antiarrítmicos/administración & dosificación , Electrocardiografía , Humanos , Masculino , Persona de Mediana Edad , Propafenona/administración & dosificación , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/tratamiento farmacológico , Choque Cardiogénico/diagnóstico , Choque Cardiogénico/prevención & control , Sotalol/administración & dosificación , Taquicardia Ventricular/complicaciones , Taquicardia Ventricular/tratamiento farmacológico , Virosis/complicaciones , Virosis/tratamiento farmacológicoRESUMEN
UNLABELLED: Left atrial tachycardia is the most common arrhythmia developing after pulmonary vein (PV) isolation in patients with atrial fibrillation. AIM: To compare the clinical effectiveness of class Ic propafenone and class III D,L sotalol in antiarrhythmic treatment of post-ablation left atrial tachycardias. METHODS AND RESULTS: A total of 75 consecutive patients with an age of 55.4 +/- 7.14 (mean +/- SD) years underwent real electrical isolation of the pulmonary veins. Beside electroanatomical guidance, a circular mapping catheter was used to achieve total electrical disconnection of the pulmonary veins from left atrium at the antrum level. After procedure, the antiarrhythmic drug therapy was continued with the tendency to taper down during follow up visits. These were scheduled 1 and later 3 monthly after PV isolation. After the first 3 months follow-up period, left atrial tachycardia occurred in 21 patients (31.3 %). 11 of them were on propafenone therapy, 6 were on sotalol therapy and 4 patients with left atrial tachycardia received amiodarone. In the first and third group, after developing left atrial tachycardia, the 1C class drug or amiodarone was changed to III D,L sotalol. In the second group, after developing left atrial tachycardia, the III D,L sotalol was changed to 1C class drug. 9 months later, in III D,L sotalol treated group of left atrial tachycardia patients (15), the drug was considered effective in 12 patients. CONCLUSION: In prevention of left atrial tachycardia occurred after PV isolation, sotalol is not more effective than 1C class propafenone. Otherwise, III D,L sotalol seems to be effective in anti-arrhythmic treatment of developed post-ablation in late left atrial tachycardias.
Asunto(s)
Antiarrítmicos/uso terapéutico , Fibrilación Atrial/cirugía , Ablación por Catéter/efectos adversos , Propafenona/uso terapéutico , Sotalol/uso terapéutico , Taquicardia Supraventricular/tratamiento farmacológico , Adulto , Anciano , Amiodarona/uso terapéutico , Antiarrítmicos/administración & dosificación , Estudios de Casos y Controles , Ablación por Catéter/métodos , Esquema de Medicación , Femenino , Estudios de Seguimiento , Atrios Cardíacos/fisiopatología , Humanos , Imagen por Resonancia Magnética , Masculino , Persona de Mediana Edad , Propafenona/administración & dosificación , Venas Pulmonares/fisiopatología , Proyectos de Investigación , Tamaño de la Muestra , Sotalol/administración & dosificación , Taquicardia Supraventricular/diagnóstico , Taquicardia Supraventricular/etiología , Factores de Tiempo , Tomografía Computarizada por Rayos X , Resultado del TratamientoRESUMEN
The aim of the study was to evaluate effectiveness and safety of angiotensin II receptor blockers and inhibitors of angiotensin-converting enzyme (ECE) for protective therapy following medicamentous cardioversion with propafen at a loading dose of 600 mg in patients with paroxysmal atrial fibrillation and arterial hypertension. 101 patients were divided in 2 groups. Group 1 included 75 patients who received ACE inhibitor lisinopril (10 mg BID) after recovery of sinus rhythm by propanorm. 26 patients of group 2 were treated with angiotensin II receptor blocker candesartan (8 mg daily). Combined treatment with angiotensin II receptor blocker and propafenone leads to cardioversion faster than therapy with ACR inhibitor. It is concluded that alternative approach to the maintenance of sinus rhythm using angiotensin II receptor blockers has advantages over traditional anti-arrhythmic therapy; it is well tolerated by the patients and produced no serious side effects.
Asunto(s)
Bloqueadores del Receptor Tipo 1 de Angiotensina II/administración & dosificación , Inhibidores de la Enzima Convertidora de Angiotensina/administración & dosificación , Antiarrítmicos/administración & dosificación , Fibrilación Atrial/prevención & control , Hipertensión/tratamiento farmacológico , Propafenona/administración & dosificación , Fibrilación Atrial/etiología , Fibrilación Atrial/fisiopatología , Bencimidazoles/administración & dosificación , Compuestos de Bifenilo , Presión Sanguínea/efectos de los fármacos , Relación Dosis-Respuesta a Droga , Quimioterapia Combinada , Femenino , Estudios de Seguimiento , Frecuencia Cardíaca/efectos de los fármacos , Humanos , Hipertensión/complicaciones , Hipertensión/fisiopatología , Lisinopril/administración & dosificación , Masculino , Persona de Mediana Edad , Tetrazoles/administración & dosificación , Resultado del TratamientoRESUMEN
A novel sensor based on a modification of glassy carbon electrode (GCE) with NH2-functionalized multi-walled carbon nano-tubes (NH2fMWCNTs) is reported and its applicability to the electrochemical sensing of Propafenone (PPF) demonstrated. The electrochemical catalytic activity was also utilized as a sensitive detection method for the investigation of the detailed redox mechanism of PFF using cyclic and and differential pulse voltammetry. The surface morphology of the sensor was investigated by SEM armed with EDX probe. Electrochemical impedance spectroscopy was employed as well to define the electron transfer capability of modiï¬ed and bare electrodes. Key experimental and instrumental conditions related to electrochemical determination by cyclic, differential pulse, and square wave voltammetry, such as amount of modifier, pH, scan rate, accumulation time and potential were studied and optimized. The results have shown a significant enhancement of the peak current after modifying the electrode; the calibration curves of PPF offering good linearity from 0.1 to 10⯵M, limit of quantification (LOQ) being 0.03⯵M and limit of detection (LOD) 0.01⯵M, both when using DPV technique. The proposed sensor was successfully applied to the determination of PFF in dosage form without any special purification, separation or pre-treatment steps. The results of analyses obtained with the proposed sensor were satisfactory and fully statistically relevant.
Asunto(s)
Formas de Dosificación , Nanotubos de Carbono/química , Propafenona/administración & dosificación , Tecnología Farmacéutica/instrumentación , Tecnología Farmacéutica/métodos , Antiarrítmicos , Calibración , Carbono/química , Espectroscopía Dieléctrica , Electrodos , Concentración de Iones de Hidrógeno , Límite de Detección , Microscopía Electrónica de Rastreo , Nanomedicina , Oxígeno/químicaRESUMEN
BACKGROUND: Rhythm control is an important goal in the treatment of recurrent atrial tachyarrhythmias (AT). The PITAGORA study was a randomized trial in patients paced for sinus node disease (SND), designed to test the noninferiority of class IC antiarrhythmic drugs (AADs) to amiodarone in terms of a primary end point composed of death, permanent AT, cardiovascular hospitalization, atrial cardioversion, or AAD change. METHODS: Randomization was stratified to assign 2 patients to amiodarone and 2 patients to class IC AADs: propafenone or flecainide. One hundred seventy-six patients (46% men, 72 +/- 8 years) were enrolled. Device diagnostics continuously monitored AT recurrences and duration. RESULTS: In a mean follow-up of 20 +/- 9 months, the primary end point occurred in 23 (30.7%) of 75 class IC patients and in 28 (40.0%) of 70 amiodarone patients. The absolute difference in the end point incidence (-9.3%; 95% CI between 3.7% and -22.3%) confirmed the noninferiority of class IC to amiodarone (P = .007). Kaplan-Meier 1-year freedom from AT episodes >10 minutes, 1 day, and 7 days was 40%, 73%, and 91% for amiodarone and 28%, 78%, and 86% for class IC AADs (P = nonsignificant). CONCLUSIONS: In patients paced for SND and suffering from AT, class IC AADs proved not to be inferior to amiodarone in terms of the primary composite end point described or end points which were differently composed of mortality, efficacy, or AAD side effects. The AADs studied also showed similar results in terms of symptoms, quality of life, and freedom from AT recurrences.