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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&#95;LV˃̳35%) and on a continuous noradrenaline of <1.0 μg/kg.min were included. Echocardiography was performed at the arrhythmia onset, 1 h and 4 h post cardioversion on an infusion of propafenone or amiodarone., Results: Cardioversion was achieved in 96% of the 209 patients within a median time of 6(1.8-15.6)h, 134(64.1%) patients experienced at least one SVA recurrence after cardioversion. At 4 h the left atrial emptying fraction (LA&#95;EF, cut-off 38.4%, AUC 0.69,p˂0.001), and transmitral A wave velocity-time-integral (Avti, cut-off 6.8 cm, AUC 0.65,p = 0.001) showed as limited predictors of a single arrhythmia recurrence. The LA&#95;EF 44(36,49)%, (p = 0.005) and the Avti 8.65(7.13,9.50)cm, (p < 0.001) were associated with sustained sinus rhythm and decreased proportionally to increasing numbers of arrhythmia recurrences (p < 0.001 and p = 0.007, respectively). The enlarged left atrial end-systolic diameter at the arrhythmia onset (p = 0.04) and elevated systolic pulmonary artery pressure at 4 h (p = 0.007) were weak predictors of multiple(˃3) recurrences., Conclusion: The LA&#95;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., Competing Interests: Declaration of competing interest None., (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: A recently published trial has shown no differences in outcomes between patients with new-onset supraventricular arrhythmia (SVA) in septic shock treated with either propafenone or amiodarone. However, these outcome data have not been evaluated in relation to the presence or absence of a dilated left atrium (LA)., Methods and Results: Patients with SVA and a left ventricular ejection fraction ≥ 35% were randomized to receive intravenous propafenone (70 mg bolus followed by 400-840 mg/24 h) or amiodarone (300 mg bolus followed by 600-1800 mg/24 h). They were divided into groups based on whether their end-systolic left atrial volume (LAVI) was ≥40 mL/m². The subgroup outcomes assessed were survival at ICU discharge, 1 month, 3 months, 6 months, and 12 months. Propafenone cardioverted earlier (P = 0.009) and with fewer recurrences (P = 0.001) in the patients without LA enlargement (n = 133). Patients with LAVI < 40 mL/m2 demonstrated a mortality benefit of propafenone over the follow-up of 1 year [Cox regression, hazard ratio (HR) 0.6 (95% CI 0.4; 0.9), P = 0.014]. Patients with dilated LA (n = 37) achieved rhythm control earlier in amiodarone (P = 0.05) with similar rates of recurrences (P = 0.5) compared to propafenone. The outcomes for patients with LAVI ≥ 40 mL/m2 were less favourable with propafenone compared to amiodarone at 1 month [HR 3.6 (95% CI 1.03; 12.5), P = 0.045]; however, it did not reach statistical significance at 1 year [HR 1.9 (95% CI 0.8; 4.4), P = 0.138]., Conclusion: Patients with non-dilated LA who achieved rhythm control with propafenone in the setting of septic shock had better short-term and long-term outcomes than those treated with amiodarone, which seemed to be more effective in patients with LAVI ≥ 40 mL/m²., Trial Registration: ClinicalTrials.gov identifier: NCT03029169, registered on 24 January 2017., Competing Interests: Conflict of interest: None declared., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For commercial re-use, please contact reprints@oup.com for reprints and translation rights for reprints. All other permissions can be obtained through our RightsLink service via the Permissions link on the article page on our site—for further information please contact journals.permissions@oup.com.)

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., Competing Interests: There are no interests of conflict associated with this article among all authors., (Copyright © 2020 RongDa Huang et al.)

A novel sensor based on a modification of glassy carbon electrode (GCE) with NH 2 -functionalized multi-walled carbon nano-tubes (NH 2 fMWCNTs) 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 modified 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 μM, limit of quantification (LOQ) being 0.03 μM and limit of detection (LOD) 0.01 μM, 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., (Copyright © 2019 Elsevier B.V. All rights reserved.)

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.

Rationale: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a rare but potentially lethal inherited arrhythmia syndrome induced by adrenergic stress. Due to the atypical clinical manifestations in early age, limited recognition and experience of pediatric cardiologists, and low awareness of the significance of genetic diagnosis in some underdeveloped areas in China, a delayed or missed diagnosis of CPVT in children is common and concerning., Patient Concerns: A 9-year and 3-month male child with recurrent exercise-induced syncope accompanied by convulsion was initially misdiagnosed as epilepsy since the first manifestation at the age of 3 years. Due to the identification of polymorphic ventricular premature beats, nonsustained ventricular tachycardia (VT), and supraventricular tachycardia, a cardiogenic etiology was established. The patient received a successive treatment by propafenone, amiodarone, a combination of amiodarone with metoprolol, and metoprolol alone for up to 6 years., Diagnoses: Given the poor response to conventional antiarrhythmics, excise-induced syncope, QRS morphology and a structurally normal heart, the diagnosis of CPVT was suspected, and ultimately confirmed by detection of polymorphic and bidirectional VT with degeneration into ventricular fibrillation during exercise testing. In addition, a heterozygous mutant of RYR2 at c.7580T > G was identified by genetic testing., Interventions: Due to the unavailability of flecainide in China and the refusal of implantable cardioverter defibrillator implantation by his parents, this patient continued to be treated with oral metoprolol., Outcomes: Unfortunately, the effect was unfavorable during 4 months outpatient follow-up., Lessons: CPVT should be suspected in young patients with a normal baseline electrocardiogram (EKG), a structurally normal heart and polymorphic and/or bidirectional ventricular tachycardia induced by exercise or emotional stress. Exercise and genetic testing is essential and significant for a timely and accurate diagnosis of CPVT. The current study firstly reported a case with CPVT associated with a mutant of RYR2 at c.7580T > G in children.

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 (I K,ACh ) represents an atrial selective target for future AF management. We investigated the effects of the I K,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 I K ,ACh may represent a novel, atrial-specific target for the management of AF in chronic AF.

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 C 8 (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., (Copyright © 2017 John Wiley & Sons, Ltd.)

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., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Background: Ventricular arrhythmia (VA) can occur during propafenone therapy in atrial fibrillation (AF) patients with structurally normal heart., Objective: The purpose of this study was to evaluate the incidence and characteristics of propafenone-associated VAs in AF patients with structurally normal heart., Methods: We studied and compared the risk of new-onset VAs between AF patients with structurally normal heart taking and those not taking propafenone in a nationwide longitudinal cohort in Taiwan (n = 127,197 since 2000). We then investigated the association between propafenone and VA in AF patients with structurally normal heart in a single-center database (n = 396)., Results: In the nationwide cohort, 102 patients (0.008% per patient-year) developed ventricular tachycardia (VT)/ventricular fibrillation (VF) during a follow-up period of 9.8 ± 3.5 years. After multivariate Cox regression analysis, propafenone treatment was a significant risk factor for new-onset VT/VF with a hazard ratio (HR) of 3.59 (95% confidence interval [CI] 1.30-9.89, P = .0136). Propafenone treatment offered protection against ischemic stroke with HR 0.649 (95% CI 0.55-0.77, P<.001). In the single-center study using ECG and medical records, the presence of inferior J wave, wider QRS, and old age were independent risk factors for VA after adjustment for clinical, biochemical, and echocardiographic variables., Conclusion: Albeit with low incidence, propafenone therapy for AF was associated with new-onset VA in the nationwide longitudinal cohort study in Taiwan. Old age, presence of inferior lead J wave, and wider QRS on ECG were significant risk factors in our single-center study., (Copyright © 2015 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Vernakalant is a new, safe and effective drug used intravenously, which has proved to be more rapid in converting recent onset atrial fibrillation (AF) to sinus rhythm compared to placebo, amiodarone, propafenone, and flecainide in clinical studies. Until now no study has been conducted comparing the perception of state of health in patients who received vernakalant versus propafenone or flecainide for conversion of recent-onset AF. The aim of our study is to compare the change of perception of state of health from screening to hour 2 in patients treated with vernakalant and propafenone or flecainide for conversion of recent-onset AF., Methods: Eighty hemodynamically stable patients with recent onset AF without structural heart disease were prospectively included. A single oral dose of propafenone 600 mg was administered to 30 patients, 30 patients received intravenous vernakalant and the remaining 20 patients received a single oral dose of flecainide 300 mg. Clinical, laboratory variables and perception of state of health from screening to hour 2 treated with these drugs measured by the EQ-5 D quality-of-life assessments visual analog scale were recorded., Results: Baseline characteristics were similar in the three groups. Treatment with vernakalant resulted in a significantly greater improvement in patient perception of state of health at hour 2 compared with propafenone and flecainide. In the vernakalant group, a mean increase (from baseline) of 12.1 points was seen compared with a mean increase of 5.4 points in the propafenone group or 5.2 points in flecainide group (p < 0.01)., Conclusions: The change of perception of state of health from screening to hour 2 treated with vernakalant had a significantly statistical improvement compared with propafenone or flecainide for conversion recent-onset AF.

Unlabelled: The scientific documentation supporting the potential clinical and economic benefits of a growing use of off-patent generic drugs in clinical practice seems to be limited in Italy as yet., Methods: We compared differences in outcomes between off-patent generic drugs and off-patent brand drugs in real clinical practice. The outcomes were: persistence and compliance with therapy, mortality, and other health resources consumption (hospitalizations, specialist examinations, other drugs) and total costs. Retrospective analysis was carried out by using the administrative databases of five Local Healthcare Units (ASLs - Aziende Sanitarie Locali) in the Lombardy Region of Italy. Data from the five ASLs were aggregated through a meta-analysis, which produced an estimate indicator of the mean or percentage difference between the two groups (branded vs. generic) and their respective significance tests. The therapeutic areas and studied drugs were: diabetes: metformin - A10BA02; hypertension: amlodipine - C08CA01; dyslipidemia: simvastatin - C10AA01; psychiatry: sertraline - N06AB06; cardiology: propafenone - C01BC03; osteoporosis: alendronate - M05BA04., Results: The 5 Local Healthcare Units (ASL) represent a population of 3,847,004 inhabitants. The selected sample included 347,073 patients, or 9.02% of the total ASL population; 67% of the patients were treated with off-patent brand drugs. The average age was 68 years, with no difference between the two groups. After 34 months of observation, compliance and persistence were in favor to generic drugs in all therapeutic areas and statistically significant in the metformin, amlodipine, simvastatin, and sertraline groups. The clinical outcomes (hospitalizations, mortality, and other health costs) show no statistically significant differences between off-patent generic vs. off-patent brand medicines., Conclusions: Off-patent generic drugs appear to be a therapy option of choice in Italy as well, based on clinical outcomes and economic consequences, both for the National Health Service and patients, considering that the price difference between brand and generic drugs is completely charged on patients.

Solid-liquid equilibrium (SLE) for binary mixture of Propafenone Hydrocloride (PP) with Metoprolol Tartrate (MT) was investigated using differential scanning calorimetry (DSC) and corresponding activity coefficients were calculated. Simple eutectic behavior for this system was observed. The excess thermodynamic functions: G(E) and S(E) for the pre-, post-, and eutectic composition have been obtained using the computed activity coefficients data of the eutectic phase with their excess chemical potentials μi(E) (i=1, 2). The experimental solid-liquid phase temperatures were compared with predictions obtained from available eutectic equilibrium models. The results indicate non-ideality in this mixture. Also, the compatibility of each component and their eutectic mixture with usual excipients was investigated, and the DSC experiments indicate possible weak interactions with α-lactose monohydrate and compatibility with corn starch. The results obtained were confirmed by FT-IR measurements., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Atrial fibrillation (AF) is the most frequent cardiac arrhythmia seen in clinical practice. Several therapeutical approaches have been developed to terminate the AF and the effects are evaluated by the reduction of the wavelet number after the treatments. Most of the previous studies focus on modeling and analysis the mechanism, and the characteristic of AF. But no one discusses about the prediction of the result after the drug treatment. This paper is the first study to predict whether the drug treatment for AF is active or not. In this paper, the linear autoregressive model with exogenous inputs (ARX) that models the system output-input relationship by solving linear regression equations with least squares method was developed and applied to estimate the effects of pharmacological therapy on AF. Recordings (224-site bipolar recordings) of plaque electrode arrays placed on the right and left atria of pigs with sustained AF induced by rapid atrial-pacing were used to train and test the ARX models. The cardiac mapping data from twelve pigs treated with intravenous administration of antiarrhythmia drug, propafenone (PPF) or dl-sotalol (STL), was evaluated. The recordings of cardiac activity before the drug treatment were input to the model and the model output reported the estimated wavelet number of atria after the drug treatment. The results show that the predicting accuracy rate corresponding to the PPF and STL treatment was 100% and 92%, respectively. It is expected that the developed ARX model can be further extended to assist the clinical staffs to choose the effective treatments for the AF patients in the future.

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.

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.

Propafenone and its 5-hydroxy metabolite exhibit different electrophysiological properties. Objectives of the CAQ-PAF study were (1) to develop a strategy favoring propafenone instead of 5-hydroxypropafenone in plasma following oral administration of propafenone and (2) to evaluate the potential of low-dose quinidine to chronically inhibit CYP2D6. Patients (n = 102) with atrial fibrillation received propafenone 150 mg 3 times daily with either quinidine 100 mg twice daily or placebo. Throughout the study (follow-up, 199 ± 155 days), quinidine successfully inhibited CYP2D6: propafenone concentrations were 3 times higher in patients receiving quinidine (1033 ± 611 ng/mL vs 328 ± 229 ng/mL; P < .001). Moreover, 80% (n = 10) of patients with propafenone levels greater than 1500 ng/mL were in sinus rhythm at 1 year. In contrast, recurrence of atrial fibrillation occurred in 22 of 23 patients with propafenone levels less than 1000 ng/mL (P < .0001). Thus, chronic inhibition of CYP2D6 is achievable with low-dose quinidine in humans. Increased plasma levels of propafenone may be highly beneficial to prevent recurrence of atrial fibrillation., (2012 American College of Clinical Pharmacology.)

Objective: In this study, we randomly compared single oral doses of flecainide, amiodarone and propafenone versus placebo for the conversion of recent atrial fibrillation (AF) (within 48 hours)., Methods: This is a randomized prospective, placebo-controlled single-blind study that included 160 consecutive patients with recent AF who were randomly assigned to single oral doses of flecainide (3 mg/kg of weight, n=40), amiodarone (30 mg/kg weight, n=40), propafenone (8.5 mg/kg of weight, n=40) or placebo (n=40). The primary end-point was conversion rate at 24 hours after the drug intake. The association between antiarrhythmic use and conversion rate was tested with multiple logistic regressions., Results: The primary end-point was achieved in 87.5% of patients with flecainide, 85% of patients with amiodarone, 85% of patients with propafenone and 17.5% of patients with placebo (p<0.001 compared with placebo for all 3 drugs). Conversion rate within 3 hours after drug intake was greater with propafenone (57.5%) or flecainide (45%) compared with amiodarone (0%) or placebo (10%). Between 6 and 24 hours, significantly more patients were converted to sinus rhythm with amiodarone than with flecainide or propafenone. The use of antiarrhythmic drugs was a significant predictor of conversion to sinus rhythm compared to placebo (adjusted OR=19.53, 95% CI 3.14-121.55, p<0.001). No serious side effect occurred., Conclusion: In patients with recent-onset AF, oral flecainide, amiodarone or propafenone are superior to placebo in restoring sinus rhythm within the 24-hour period following the drug intake.

A clinical study was conducted to assess the ability of a microdose (100 μg) to predict the human pharmacokinetics (PK) following a therapeutic dose of clarithromycin, sumatriptan, propafenone, paracetamol (acetaminophen) and phenobarbital, both within the study and by reference to the existing literature on these compounds and to explore the source of any nonlinearity if seen. For each drug, 6 healthy male volunteers were dosed with 100 μg (14)C-labelled compound. For clarithromycin, sumatriptan, and propafenone this labelled dose was administered alone, i.e. as a microdose, orally and intravenously (iv) and as an iv tracer dose concomitantly with an oral non-labelled therapeutic dose, in a 3-way cross over design. The oral therapeutic doses were 250, 50, and 150 mg, respectively. Paracetamol was given as the labelled microdose orally and iv using a 2-way cross over design, whereas phenobarbital was given only as the microdose orally. Plasma concentrations of total (14)C and parent drug were measured using accelerator mass spectrometry (AMS) or HPLC followed by AMS. Plasma concentrations following non-(14)C-labelled oral therapeutic doses were measured using either HPLC-electrochemical detection (clarithromycin) or HPLC-UV (sumatriptan, propafenone). For all five drugs an oral microdose predicted reasonably well the PK, including the shape of the plasma profile, following an oral therapeutic dose. For clarithromycin, sumatriptan, and propafenone, one parameter, oral bioavailability, was marginally outside of the normally acceptable 2-fold prediction interval around the mean therapeutic dose value. For clarithromycin, sumatriptan and propafenone, data obtained from an oral and iv microdose were compared within the same cohort of subjects used in the study, as well as those reported in the literature. For paracetamol (oral and iv) and phenobarbital (oral), microdose data were compared with those reported in the literature only. Where 100 μg iv (14)C-doses were given alone and with an oral non-labelled therapeutic dose, excellent accord between the PK parameters was observed indicating that the disposition kinetics of the drugs tested were unaffected by the presence of therapeutic concentrations. This observation implies that any deviation from linearity following the oral therapeutic doses occurs during the absorption process., (Copyright © 2011 Elsevier B.V. All rights reserved.)

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.

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.

Ventricular ectopic beats are commonly observed in daily clinical practice, either in symptomatic or asymptomatic subjects. In many subjects these arrhythmias are casually detected during a screening visit. Their occurrence is usually associated with no clinical significance. However, in some cases the presence of ventricular ectopic beats indicates susceptibility towards life-threatening arrhythmias or ventricular dysfunction. Appropriate ECG analysis and clinical evaluation are important to detect subjects in whom effective treatment is necessary.

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., (Copyright © 2010 Elsevier Inc. All rights reserved.)

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.

A 72-year-old woman presented with a decreased level of consciousness and hypotension. The initial electrocardiogram demonstrated atrial fibrillation with a wide QRS complex. Her medical history revealed that she had just been started on propafenone. A diagnosis of propafenone toxicity was made and sodium bicarbonate was administered. A rare phenomenon in which toxicity occurred at therapeutic dosing is reported. Acute propafenone toxicity manifests in a wide range of organ systems; in particular, cardiovascular compromise in the form of hypotension, bradycardia and QRS widening can occur. Sodium bicarbonate therapy is advocated to directly counteract the toxic effects of propafenone. In the case described, this treatment resulted in rapid normalization of the QRS duration and stabilization of the hemodynamic profile.

Background: Pill-in-the-pocket treatment should be prescribed only if the administration of a loading oral dose of flecainide or propafenone has been proved safe in hospital, since major adverse effects have been reported in 5% of patients during in-hospital treatment. However, in emergency rooms, the oral administration of these drugs for the conversion of atrial fibrillation (AF) is very rarely used because it is time consuming. Objective To investigate whether tolerance to intravenous administration of flecainide or propafenone might predict the safety of pill-in-the-pocket treatment-the out-of-hospital self-administration of these drugs after the onset of palpitations-in patients with AF of recent onset., Methods: One hundred and twenty-two patients with AF of recent onset who were successfully treated (conversion of AF within 2 h without major adverse effects) in hospital with intravenous flecainide or propafenone were discharged on pill-in-the-pocket treatment., Results: During a mean follow-up of 11+/-4 months, 79 patients self-treated 213 arrhythmic episodes; treatment was successful in 201 episodes (94%). Major adverse events occurred in five patients (6%) and in four (5%) of these during the first oral treatment (one syncope, two presyncope, one sinus arrest). No patient reported symptoms attributable to bradyarrhythmia or hypotension during the self-treatment of arrhythmic recurrences when the first oral treatment was not accompanied by any major adverse effects. The study was prematurely terminated because of the high incidence of major adverse effects during the first out-of-hospital treatment., Conclusion: The patient's tolerance of intravenous administration of flecainide or propafenone does not seem to predict adverse effects during out-of-hospital self-administration of these drugs.

The aim of this prospective, non-randomized interventional study was to assess electrophysiological effects, efficacy and safety of intravenous propafenone in termination of atrioventricular nodal reentrant tachycardia (AVNRT) and orthodromic atrioventricular reentrant tachycardia (AVRT). This single-center study was carried out at Department of Cardiology, Sestre milosrdnice University Hospital in Zagreb, Croatia, between January 1, 2005 and December 31, 2006. Eligibility requirements were fulfilled by a total of 70 patients with AVNRT (n=37) and AVRT (n=33). The intervention consisted of the electrophysiological study aimed at inducing tachycardia, followed by intravenous administration of 2 mg/kg propafenone in both groups. The main outcome measures were safety and efficacy of 2 mg/kg intravenous propafenone in tachycardia termination and re-induction. Out of 37 patients with AVNRT, propafenone managed to terminate it in 28 (75.7%) patients, while tachycardia was not inducible in 25 (67.56%) patients. Out of 33 patients with AVRT, propafenone managed to terminate AVRT in 29 (87.9%) patients, while tachycardia was not inducible in 22 (66.66%) patients. The overall propafenone efficacy in tachycardia termination was 81.42%. No propafenone-related adverse effects were recorded during the study period. Propafenone was found to be a safe and effective anti-arrhythmic drug and can be justifiably administered for AVNRT and AVRT termination. It could be considered as an alternative to adenosine and verapamil.

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.

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.

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.

Background: A prospective, randomized study was conducted to evaluate the efficacy and tolerability of oral propafenone and quinidine for the conversion of paroxysmal atrial fibrillation (AF)., Methods: Eighty one consecutive patients (female/male 46/35; mean age 64.0 +/- 11.6), admitted to hospital with AF lasting no longer than 48 hours, were randomized in terms of their pharmacological therapy. Forty three patients (55%) were randomly assigned to Group I and received propafenone 600 mg orally as the initial therapy, with an additional dose of 300 mg after eight hours, if the sinus rhythm had not been restored by then. Thirty eight patients (45%) (Group II) received 1 mg digoxin IV followed by an oral loading of quinidine (400 mg followed by 200 mg every two hours)., Results: The conversion rate assessed after 24 hours was the same in both groups (Gr. I vs. Gr. II: 90.7 vs. 91.4%), with the same number of mild side effects (Gr. I vs. Gr. II: 37.2% vs. 45.7%). No life-threatening adverse events were reported. Propafenone achieved a higher efficacy rate during the first eight hours (83.3 vs. 54.3%; p = 0.01), with a significantly shorter time required to sinus rhythm recovery throughout the study period, with a median time of 165 min (95% confidence interval 120-278) vs. 360 min (95% confidence interval 298-650; p < 0.05). There was some indication of greater effectiveness of propafenone than quinidine in early sinus rhythm restoration in patients with: no structural heart disease, in those with an AF duration shorter than 12 hours, and in patients with an ejection fraction > 55%., Conclusions: Although both drugs revealed the same effectiveness, the conversion to sinus rhythm in the group treated with propafenone was observed more quickly despite the longer paroxysmal AF episode duration.

Propafenone (CAS 34183-22-7) is an effective antiarrhythmic drug used in children, although in some countries no specific pediatric formulation is available. The aim of this study is to compare the relative bioavailability of a magistral (MAG) preparation of propafenone versus its commercial (COM) presentation in a group of 16 Mexican healthy volunteers. Bioavailability was determined after crossover administration of the drugs, through a randomized two-phase trial. All volunteers had normal hepatic and renal functions, determined clinically at the beginning of the study, and received 150 mg of either COM (tablets) or MAG (suspension). Blood samples were drawn for a 24-h post-dose analysis by HPLC to measure plasma levels of propafenone. Subjects (mean 25.9 +/- 5.3 years and 66.1 +/- 12.4 kg) had the following pharmacokinetic parameters: Cmax 189.9 +/- 20.92 ng/mL, Tmax 1.5 h, AUC 322.4 +/- 36.28 ng x ml(-1) x h for COM. Values for MAG were Cmax 225.8 +/- 24.38 ng/mL, Tmax 1.7 h and AUC 359.3 +/- 27.90 ng x ml(-1) x h. These values yielded a relative bioavailability of 111.42% for MAG compared with COM. No electrocardiographic changes were recorded in any subject with respect to the baseline value, in both treatment schemes. Therefore, propafenone suspension prepared as a magistral formulation may be used as an alternative drug in pediatric patients.

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.

Background: Physicians have frequently encountered difficulties when prescribing drugs not available in doses suitable for pediatric age groups. Furthermore, children have difficulty swallowing tablets. This study aimed to determine the stability of an oral propafenone suspension made from commercial tablets with a syrup vehicle and to establish its reliable use with children., Methods: An extemporaneous suspension of propafenone 1.5 mg/ml was prepared with commercial tablets. Its physicochemical and microbiologic stability was established by constant monitoring during 90 days at room temperature (15 +/- 5 degrees C) and at refrigeration (3-5 degrees C). Plasma levels of propafenona were measured in two children with supraventricular tachycardia at steady state., Results: The suspension was stable, maintaining its original physicochemical and microbiologic properties. Moreover, no apparent changes in color or odor were observed. Plasma levels of propafenone in patients demonstrated therapeutic concentrations after they had taken the suspension, with no unwanted outcome., Conclusions: The conservation of both physicochemical and microbiologic stability of the suspension represents an option for the administration of propafenone to children.

Background: Short-term conversion attempt of recent-onset atrial fibrillation (AF) in the emergency room fails too often. Many patients and doctors still prefer pharmacological to electrical solutions in such cases., Hypothesis: Sequential administration of up to 3 antiarrhythmic drugs of different classes of action (amiodarone, propafenone, and quinidine) may achieve conversion in such patients., Method: One hundred and forty consecutive patients with recent-onset AF were transferred to the intensive cardiac care unit after a failed 2-h conversion attempt in the emergency room. First-line drug for conversion was continued up to a full dose, and was chosen by AF etiology, or in recurrent AF episodes, empirically. In nonresponders, the failed drug was replaced by a drug of another class, and if the second-line drug failed it was replaced by a drug of the third-line. Electrical cardioversion was the final solution for nonresponders., Results: Sixty percent of patients reached sinus rhythm by the first-line drug therapy, 34% by the second-line, and 4% by the third-line. Seventy-five percent of patients achieved conversion within 26 h, and 95% of patients achieved conversion within 40 h. Three patients were electrically cardioverted due to hemodynamical instability. Two episodes of Torsade de Pointes ventricular tachycardia were self-terminated., Conclusion: Sequential usage of up to 3 antiarrhythmic drugs of different classes of action provides almost complete success in conversion of recent-onset AF in patients refractory to short-term conversion attempt in the emergency room., (Copyright (c) 2008 Wiley Periodicals, Inc.)