Use Of Propafenone Research Articles

Evaluation of Amiodarone Administration in Patients with New-Onset Atrial Fibrillation in Septic Shock.

Background and Objective: New-onset atrial fibrillation (NOAF) is a common cardiac condition often observed in intensive care units. When amiodarone is used to treat this condition, either to maintain sinus rhythm after electrical cardioversion or to control heart rate, complications can arise when a systemic pathology is present. Systemic pathology can result in a decrease in cardiac output and blood pressure, making the management of NOAF and septic shock challenging. Limited international research exists on the coexistence of NOAF and septic shock, making it difficult to determine the optimal course of treatment. While amiodarone is not the primary choice of antiarrhythmic drug for patients in septic shock, it may be considered for those with underlying cardiac issues. This paper aims to investigate the safety of administering amiodarone to patients with septic shock and explore whether another antiarrhythmic drug may be more effective, especially considering the cardiac conditions that patients may have. Materials and Methods: To write this article, we searched electronic databases for studies where authors used amiodarone and other medications for heart rate control or sinus rhythm restoration. Results: The studies reviewed in this work have shown that for the patients with septic shock and NOAF along with a pre-existing cardiac condition like a dilated left atrium, the use of amiodarone may provide greater benefits compared to other antiarrhythmic drugs. For patients with NOAF and septic shock without underlying heart disease, the initial use of propafenone has been found to be advantageous. However, a challenge arises when deciding between rhythm or heart rate control using various drug classes. Unfortunately, there is limited literature available on this specific scenario. Conclusions: NOAF is a frequent and potentially life-threatening complication occurring in one out of seven patients with sepsis, and its incidence is rising among patients with septic shock.

Association between amiodarone use and risk of cataract: a population-based active-comparator study.

Despite previous concerns about ocular side effects related to amiodarone, the relationship between amiodarone and cataract remains uncertain. Therefore, this study aimed to assess the potential association between amiodarone use and the subsequent risk of cataract, taking into account potential confounders. This population-based, active comparator-controlled cohort study utilized the data from the Taiwan National Health Insurance program and involved adults over 40years old between 2001 and 2013. We analyzed 12 055 new amiodarone users and contrasted them with a propafenone user cohort. The primary outcome was the incidence of cataract. Inverse-probability treatment-weighting (IPTW) was further used to eliminate the potential confounding effects, and Cox proportional-hazard regression analyses were performed to calculate the risk of cataract. Serial subgroup analyses were also performed. In the main analysis, amiodarone users did not exhibit a significant causal relationship in both full cohort [adjusted hazard ratio (aHR): 0.994, 95% confidence interval (CI): 0.913-1.082] and IPTW cohort (IPTW-aHR 0.977, 95% CI: 0.900-1.060). Furthermore, it is important to highlight a significantly reduced risk of cataract among patients with heart failure (IPTW-aHR 0.708, 95% CI: 0.554-0.905) and during the 2-year follow-up period (IPTW-aHR 0.889, 95% CI: 0.794-0.996), implying potential advantages linked to the use of amiodarone. The study found no increased risk of cataract with amiodarone, one of the most frequently used antiarrhythmic medications, compared to the use of propafenone. Future research is recommended to explore potential mechanisms and their implications for clinical practice.

Efficacy and Safety of Wenxin Granules and Propafenone in Treatment of Atrial Premature Beats: A Systematic Review and Meta-Analysis.

Objective A meta-analysis was conducted on the clinical efficacy and safety of Wenxin granules and propafenone for the therapy of atrial premature beats (APBs). Methods A randomized controlled trial (RCT) of Wenxin granules and propafenone in the therapy of APB was systematically searched until June 1, 2019. Meta-analysis was conducted with review manager (RevMan) 5.3. For the evaluation of methodological quality for randomized controlled trials, the Cochrane tool was used to assess the risk of bias. For the evaluation of the evidence quality, the online GRADEpro GDT was used. Results Eleven RCTs with 1149 participants were included in this study. It has been identified that Wenxin granules combined with propafenone have better clinical efficacy than the use of propafenone alone in the treatment of APB (OR = 3.89, 95% CI (2.03, 7.44), P < 0.0001, low-dose propafenone; OR = 4.24, 95% CI (1.32, 13.60), P = 0.02, high-dose propafenone). There is no difference in clinical efficacy between the Wenxin granules alone and high-dose propafenone in the treatment of APB (OR = 1.17, 95% CI (0.65, 2.11), P = 0.60), and Wenxin granules alone are superior to the low-dose propafenone in the treatment of APB (OR = 2.56, 95% CI (1.34, 4.89), P = 0.004). Wenxin granules combined with propafenone can reduce the incidence of sinus bradycardia caused by propafenone (OR = 0.15, 95% CI (0.03, 0.70), P = 0.02). There was no significant difference between Wenxin granules combined with propafenone and propafenone alone in causing the atrioventricular block, dizziness, xerostomia, gastrointestinal symptoms, and tongue paresthesia. There was no significant difference between Wenxin granules alone and propafenone alone in causing dizziness, xerostomia, gastrointestinal symptoms, tongue paresthesia, frequent premature ventricular contractions, and prolongation of R-R interval. Conclusion Very low-quality evidence showed that Wenxin granules may be superior to low-dose propafenone in the treatment of APB. Wenxin granules may reduce the incidence of sinus bradycardia caused by propafenone. Limited by the quality of included RCTs, the conclusions of this study still need further verification.

Pharmacologic Prophylaxis of Postoperative Atrial Fibrillation in Patients Undergoing Cardiac Surgery: Beyond β‐Blockers

Postoperative atrial fibrillation (POAF) is a frequent complication of cardiac surgery that increases patient morbidity, length of stay, and hospital costs. A substantial body of evidence exists evaluating various pharmacologic and nonpharmacologic methods to decrease the occurrence of POAF in an effort to decrease its burden on the health care system. Evidence-based guidelines support the use of beta-blockers as standard prophylaxis of POAF in patients undergoing cardiac surgery. Traditional prophylactic therapy for POAF targets the sympathetic nervous system, refractory period, and atrial conduction. However, associations between the development of POAF and the inflammatory process, oxidative stress, and atrial remodeling have prompted the investigation of novel therapies targeting these processes. To evaluate the role of pharmacologic strategies beyond beta-blockers in the prevention of POAF, we conducted a search of the PubMed database to identify studies published from 1950-February 2009. Emphasis was placed on how these therapies could be used in patients intolerant to beta-blockers or as additive therapy in high-risk patients. We found that sufficient evidence exists to recommend the use of amiodarone, sotalol, and possibly magnesium as monotherapy in patients unable to take beta-blockers or as add-on therapy for the prevention of POAF. Currently, available evidence does not support the use of propafenone, procainamide, digoxin, thiazolidinediones, triiodothyronine, or calcium channel blockers in the prevention of POAF. Preliminary evidence suggests that dofetilide, angiotensin-converting enzyme inhibitors, angiotensin II receptor blockers, 3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors (statins), nonsteroidal antiinflammatory drugs, corticosteroids, omega-3 fatty acids, ascorbic acid, N-acetylcysteine, and sodium nitroprusside may be effective in preventing POAF. Additional large-scale, adequately powered clinical studies are needed to determine the benefit of these agents before they can be considered for routine use.

Use of propafenone for conversion of chronic atrial fibrillation in horses

To investigate effects of IV administration of propafenone for naturally occurring and experimentally induced chronic atrial fibrillation in horses. 2 horses with naturally occurring atrial fibrillation and 4 horses with pacing-induced atrial fibrillation. 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. 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. 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.

Effects of propafenone associated with propofol on myocardial contractility, heart rate, coronary flow, and the incidence of arrhythmia in isolated hearts of rats.

To study the influence of propafenone associated with propofol on myocardial contractility (dP/dt and heart rate), coronary flow, and the incidence of arrhythmia in isolated rat hearts. Forty albino rats were anesthetized with sulfuric ether, a modified Langendorff method was performed, and the rats were fed with Krebs-Henseleit (K-H) solution, (95% O2, 5% CO2, pH 7.4+/-0.1, perfusion pressure between 90 and 100cm of water, and temperature 37+/- 0.5 masculine C). Control records were obtained after a stabilization period and rats were distributed into the following 4 groups: I (control), II (100mcg propafenone), III (25mcg propofol), and IV (propafenone-propofol). A decrease (P<0.05) in the heart rate in groups II and IV was observed, with a greater decrease in group II. A decrease was noted in the dP/dt ratio (P< 0.05) in groups II and IV, during all periods. Group III experienced depression from the 1st to the 3rd minute. Coronary flow had a decrease (P<0.05) in all groups, compared with the control group, especially in group IV with a decrease from 14mL/min to 11mL/min. Arrhythmogenic effects of propafenone (pro-arrhythmia) were verified in 50% of group II. In the association with propofol (group IV), no significant difference occurred, and arrhythmias (pro-arrhythmic effect) were observed in 40% of the hearts. The association propafenone-propofol was not harmful to the use of propafenone solely, regarding the effects observed in myocardial contractility, coronary flow, and in the incidence of arrhythmias.

Using the right drug: a treatment algorithm for regular supraventricular tachycardias.

Despite the recent advent of and the successful results from catheter ablation, pharmacological therapy is still used by most clinicians as the first line therapy in patients with regular supraventricular tachycardias. Before prescribing an antiarrhythmic agent, documentation of the arrhythmia using a 12-lead electrocardiogram (ECG) is necessary to identify the type of tachycardia. The ECG diagnosis is based on the presence and polarity of the P wave, the P to QRS relationship, the presence of QRS alternation and the effect of bundle branch block on tachycardia rate. Most regular supraventricular tachycardias use the atrioventricular node either passively, as in atrial tachycardias or flutter, or actively, as paroxysmal junctional tachycardias. The Sicilian Gambit approach attempted to introduce some rationale in the choice of an antiarrhythmic agent, taking into account tachycardia mechanism, by defining the critical components of the tachycardia and the vulnerable parameter, i.e. the component that may readily be affected by an appropriate antiarrhythmic agent. For this approach, an electrophysiological study is particularly useful. The most common regular paroxysmal supraventricular tachycardias include atrioventricular nodal re-entrant tachycardias and atrioventricular re-entrant tachycardias which use an overt or concealed accessory atrioventricular connection (Kent bundle) or atriofascicular connection (Mahaim). For acute termination of paroxysmal junctional tachycardia, intravenous adenosine is the drug of choice. For the prevention of the tachycardia attacks in atrioventricular nodal re-entrant tachycardia, the agents with a depressive effect on the antegrade slow pathway, such as calcium channel blockers or beta-blockers, are likely to be effective. If they fail, sodium channel blockers (propafenone or flecainide) may be indicated. In tachycardias involving accessory connections, agents that affect fast channel dependent tissue (propafenone, flecainide, cibenzoline, disopyramide or hydroquinidine) are effective. Potassium current blockers, such as sotalol or amiodarone, represent an alternative therapy. In atrial tachycardias, the use of propafenone, flecainide or sotalol constitute a logical choice. In drug-resistant cases, amiodarone is the most potent agent. Radiofrequency ablation of the slow atrioventricular nodal pathway, of an accessory connection or of an atrial focus, is indicated in drug-resistant or drug-intolerant patients and is increasingly offered as an alternative therapy.

Effects of oral propafenone on defibrillation and pacing thresholds in patients receiving implantable cardioverter-defibrillators

The effects of propafenone, a predominantly class IC antiarrhythmic drug, on defibrillation and pacing thresholds were evaluated in patients undergoing cardioverter-defibrillator implantation. Previous studies have shown that the class IC agents encainide and flecainide may increase the energy requirements for pacing and defibrillation. Animal studies with propafenone have shown inconsistent results regarding its effect on defibrillation energy requirements. This report investigated the effects of propafenone on defibrillation and pacing thresholds in humans. After cardioverter-defibrillator implantation, 47 patients were enrolled in a double-blind, three-way parallel, randomized trial of 450 mg/day (Group 1) or 675 mg/day (Group 2) of oral propafenone or placebo (Group 3) for 3 to 7 days. Predischarge defibrillation and pacing thresholds after treatment were compared with baseline thresholds obtained at implantation. There was no statistically significant difference between implantation and predischarge defibrillation thresholds in the three groups (Group 1: [mean +/- SE] 11.0 +/- 1.3 vs. 12.1 +/- 1.5 J; Group 2: 11.5 +/- 1.1 vs. 13.6 +/- 1.3 J; Group 3: 12.5 +/- 1.2 vs. 13.3 +/- 1.6 J), and no significant difference between treatment groups was found with a 0.86 power to detect a 5-J difference between groups. Paired pulse width pacing thresholds at 2.8 V were compared in 14 patients. A small increase of 0.02 ms was noted at predischarge testing in patients treated with propafenone and placebo. Short-term oral propafenone (450 and 675 mg/day) does not significantly affect defibrillation or pacing thresholds. Concomitant use of propafenone in patients with implantable cardioverter-defibrillators with recurrent ventricular or atrial tachyarrhythmias should not interfere with proper device function.

Propafenone-Induced Peripheral Neuropathy

Propafenone hydrochloride, a class IC antiarrhythmic drug, is used in the treatment of ventricular and supraventricular arrhythmias. Herein we describe a patient with episodic jabbing and crushing pain in his hands and feet, aching in his forearms, and hyperesthesias of his extremities. He had been taking propafenone for 1 year because of ventricular arrhythmias. Results of a nerve conduction velocity test were abnormal. Electron microscopic findings on a sural nerve biopsy specimen represented distal small fiber neuropathy. Findings on a thermoregulatory sweat test and on autonomic tests were abnormal, compatible with a distal small fiber neuropathy. To our knowledge, peripheral neuropathy has not previously been reported to occur with use of propafenone. In this patient, propafenone seemed to be responsible for the development of peripheral neuropathy, which resolved after use of the drug had been discontinued.

The use of propafenone in the treatment of tachyarrhythmias in children.

Propafenone was given to 60 children (mean age 4.5 years) with paroxysmal re-entrant supraventricular tachycardia (rSVT: 41 cases), postoperative automatic junctional tachycardia (JET: eight cases), automatic atrial tachycardia (AT:four cases), ventricular tachycardia (VT:four cases) and atrial flutter (AF: three cases). In acute cases (29) propafenone was administered intravenously (mean dose 1.3 +/- 0.5 mg.kg-1) chronic oral treatment (mean dose of either 11 +/- 3.3 mg.kg.day-1 or 265 +/- 78 mg.m-2 x day-1) was given to 48 children, in 2-3 divided doses. Overall efficacy was 76% for acute and 69% for chronic treatment, with best results in paroxysmal rSVT. It was effective in 89% acutely of those treated acutely and in 69% of those administered chronically. The efficacy of propafenone in the prevention of rSVT was strictly related to the incidence of attacks before treatment:propafenone was indeed inefficacious in 6/11, 6/14 and 0/12 of patients with daily, weekly and monthly attacks respectively. Side effects were observed in 25% of patients: 6% required suspension of therapy due to pro-arrhythmic effects in one patient on intravenous administration, peripheral neuropathy in one case and hypotension in two postoperative JET patients. In conclusion, its efficacy and limited side effects make propafenone a relatively safe and very useful drug in the treatment of various tachyarrhythmias. However, risk of unpredictable toxic levels requires careful use of the drug especially in the first days of treatment, when a daily monitoring of ECG is strongly recommended.

Propafenone. A reappraisal of its pharmacology, pharmacokinetics and therapeutic use in cardiac arrhythmias.

Propafenone is an orally active sodium channel blocking agent with beta-adrenoceptor antagonist and weak calcium antagonist activity. The pharmacokinetic profile of propafenone is complex, characterised as typically nonlinear, saturable, stereoselective and dependent on both dose and debrisoquin metaboliser phenotype; individualised dosage titration is required. Both placebo- and drug-controlled studies have confirmed the efficacy of propafenone in the treatment of premature ventricular complexes, ventricular couplets and nonsustained ventricular tachycardia; in a large meta-analysis, propafenone together with amiodarone, flecainide and encainide were significantly more effective in the control of ventricular ectopy than other antiarrhythmic agents. However, the use of propafenone in these indications, like that of other antiarrhythmic agents, is likely to be limited to patients with a favourable risk-to-benefit ratio. Propafenone has also demonstrated efficacy in the treatment of malignant ventricular arrhythmias (ventricular fibrillation and sustained ventricular tachycardia); preliminary mortality data obtained with propafenone have been encouraging in this patient group. In addition, propafenone has a favourable noncardiac tolerability profile and beta-adrenoceptor antagonist activity, which may offer advantages in some specific patient groups. The area of research concerning propafenone which has shown the greatest expansion over the past 5 years is in the treatment of supraventricular arrhythmias. Propafenone has marked efficacy in patients with Wolff-Parkinson-White syndrome and has been recommended as a first-line prophylactic agent in those with rapid anterograde conduction. Propafenone is also effective in the conversion of atrial fibrillation to sinus rhythm, although comparative studies are required to determine advantages over more established agents. Propafenone use has been successfully extended to children with limited data demonstrating consistent efficacy in the control of junctional ectopic tachycardia. As with all antiarrhythmic agents, propafenone has the potential to induce arrhythmias. Comparative studies are required to assess in more detail the cardiac tolerability profile of propafenone against other class Ic agents. In conclusion, propafenone offers a broad spectrum of activity in the treatment of cardiac arrhythmias, although its use in patients with potentially malignant arrhythmias will remain limited for the present. Due to its unique pharmacodynamic profile, propafenone deserves consideration as an individual agent.

Symptomatic sinus node dysfunction associated with the use of propafenone

Propafenone is an investigational antiarrhythmic agent with demonstrated effectiveness against a variety of supraventricular and ventricular arrhythmias. 1 In vitro and in vivo studies have confirmed its class I activity in suppressing the rate of rise of phase 0 of the action potential by blocking the fast inward sodium current. 2 In addition, propafenone has a mild β-blocking effect. Clinically the drug has been shown to slow sinus rate 3 and prolong the sinus node recovery time. 4 However, advanced sinus node dysfunction leading to symptomatic bradycardia associated with the use of propafenone has been rarely reported. Herein, we report 6 such cases presenting over 3 years.