Intravenous Antiarrhythmic Agents Research Articles

Incidence, Predictors, and Outcome Associated With Ventricular Tachycardia or Fibrillation in Patients Undergoing Primary Percutaneous Coronary Intervention for Acute Myocardial Infarction.

The characteristics and clinical outcomes associated with sustained ventricular tachycardia and fibrillation (VT/VF) in Japanese acute myocardial infarction (AMI) patients remain unknown. Consecutive AMI patients (n=1,941) transferred to the Hirosaki University Hospital and treated with primary percutaneous coronary intervention (PCI) within 12 h of onset were retrospectively studied. The incidence of VT/VF during hospitalization was 8.3%, and 75% of cases occurred by the end of PCI. Independent predictors associated with VT/VF occurrence by the end of PCI and after PCI, respectively, were identified. Additionally, the differences between patients with VT and VF were examined, which revealed that the characteristics of patients and predictors for VT and VF were clearly different. Additionally, the QRS duration during VT was measured, which demonstrated the possible involvement of Purkinje fibers for VT in the acute phase of AMI. Of the patients with VT/VF, 12% required ECMO support due to refractory VT/VF despite intravenous antiarrhythmic agents such as β-blockers, amiodarone, and nifekalant. Among the patients discharged alive, 1,690 were followed up for a mean of 3.7 years. VT/VF occurrence during hospitalization did not affect the mid-term clinical outcomes even in patients with VT. The results clearly indicated that VT/VF is still a serious complications of AMI. We need to identify patients at high risk of developing VT/VF for careful observation and appropriate intervention.

Prediction of Successful Pharmacological Cardioversion in Acute Symptomatic Atrial Fibrillation: The Successful Intravenous Cardioversion for Atrial Fibrillation (SIC-AF) Score.

Background: Modern personalised medicine requires patient-tailored decisions. This is particularly important when considering pharmacological cardioversion for the acute treatment of haemodynamically stable atrial fibrillation and atrial flutter in a shared decision-making process. We aimed to develop and validate a predictive model to estimate the individual probability of successful pharmacological cardioversion using different intravenous antiarrhythmic agents. Methods: We analysed data from a prospective atrial fibrillation registry comprising 3053 cases of first-detected or recurrent haemodynamically stable, non-permanent, symptomatic atrial fibrillation presenting to an Austrian academic emergency department between January 2012 and December 2017. Using multivariable analysis, a prediction score was developed and externally validated. The clinical utility of the score was assessed using decision curve analysis. Results: A total of 1528 cases were included in the development cohort (median age 69 years, IQR 58–76; 43.9% female), and 1525 cases were included in the validation cohort (median age 68 years, IQR (58–75); 39.5% female). Finally, 421 cases were available for score development and 330 cases for score validation The weighted score included atrial flutter (8 points), duration of symptoms associated with AF (<24 h; 8 points), absence of previous electrical cardioversion (10 points), and the specific intravenous antiarrhythmic drug (amiodarone 10 points, vernakalant 11 points, ibutilide 13 points). The final score, the “Successful Intravenous Cardioversion for Atrial Fibrillation (SIC-AF) score,” showed good calibration (R2 = 0.955 and R2 = 0.954) and discrimination in both sets (c-indices: 0.68 and 0.66) and net clinical benefit. Conclusions: A predictive model was developed to estimate the success of intravenous pharmacological cardioversion using different antiarrhythmic agents in a cohort of patients with haemodynamically stable, non-permanent, symptomatic atrial fibrillation. External temporal validation confirmed good calibration, discrimination, and clinical usefulness. The SIC-AF score may help patients and physicians jointly decide on the appropriate treatment strategy for acute symptomatic atrial fibrillation. Registration: NCT03272620.

Systematic review of the safety and efficacy of antazoline in the treatment of atrial fibrillation

Context: In the emergency department, patients with recent-onset atrial fibrillation are typically managed with intravenous antiarrhythmic agents. However, the currently used agents have a low efficacy and safety profile. Antazoline is an antihistaminic agent that has been shown to have a strong antiarrhythmic effect when administered intravenously, facilitating rapid conversion to normal sinus rhythm. Aims: To systematically review the literature on the safety and efficacy of antazoline in the treatment of recent-onset short-duration atrial fibrillation and to compare the clinical efficacy of antazoline to that of other antiarrhythmic agents listed in clinical guidelines. Methods: The study was written in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) protocol. A comprehensive search of databases (PubMed, Scopus, ScienceDirect, Web of Sciences, Google Scholar, Clinical trial.gov) for relevant studies in English from inception to 2021 using keywords involving “antazoline” AND other terms such as “antiarrhythmic”, “atrial fibrillation”, and “arrhythmia”. Results: Of the 478 studies identified, 446 were screened, and 7 were included, one of which was a randomized control trial, and the others were observational studies. The majority of studies indicated that antazoline resulted in rapid cardioversion to sinus rhythm. When compared to other pharmacological cardioversion options, antazoline achieved higher cardioversion rates than amiodarone or propafenone and was generally a safer option. Conclusions: Antazoline appears to be an effective pharmacological agent for the rapid cardioversion of short-term atrial fibrillation. More randomized clinical trials, however, should be conducted to strengthen the evidence.

Cardioversion of recent-onset atrial fibrillation using intravenous antiarrhythmics: A European perspective.

Pharmacological cardioversion using intravenous antiarrhythmic agents is commonly indicated in symptomatic patients with recent-onset atrial fibrillation (AF). Except in hemodynamically unstable patients who require emergency direct current electrical cardioversion, for the majority of hemodynamically stable patients, pharmacological cardioversion represents a valid option and requires the clinician to be familiar with the properties and use of antiarrhythmic agents. The main characteristics of selected intravenous antiarrhythmic agents for conversion of recent-onset AF, the reported success rates, and possible adverse events are discussed. Among intravenous antiarrhythmics, flecainide, propafenone, amiodarone, sotalol, dofetilide, ibutilide, and vernakalant are commonly used. Antazoline, an old antihistaminic agent with antiarrhythmic properties was also reported to give encouraging results in Poland. Intravenous flecainide and propafenone are the only Class I agents still recommended by recent guidelines. Intravenous new Class III agents as dofetilide and ibutilide have high and rapid efficacy in converting AF to sinus rhythm but require strict surveillance with electrocardiogram (ECG) monitoring during and after intravenous administration because of the potential risk of QT prolongation and Torsades de Pointes, which can be prevented and properly managed. Vernakalant, a partial atrial selective was shown to have a high success rate and to be safe in real-life use.

216-23: A prospective multicenter, open-label study of landiolol for tachyarrhythmias in children: Control of the HEART rate in inFant and child arrhythmias Using Landiolol (HEARTFUL) study

Introduction: Persistent tachycardia in pediatric patients with heart failure sometimes deteriorates their hemodynamic condition, which requires immediate intervention to control their heart rate. Particularly, tachyarrhythmias after congenital heart surgery may sometimes become fatal. In Japan, there are only a few intravenous anti-arrhythmic agents that have been approved to control pediatric arrhythmias. Although, treatment of tachyarrhythmias in young patients with cardiac dysfunction are mandatory, there are no approved medications to treat them in these patients. Consequently, novel and effective medications for these patients are required. Landiolol, an ultra-short-acting beta-blocker was approved in 2013 for tachyarrhythmias in adult patients with cardiac dysfunction. However, its efficacy and safety in pediatrics remain unknown. Methods: This study is a phase IIb/phase III study to investigate the efficacy and safety of landiolol in pediatric patients with tachyarrhythmias (atrial fibrillation, atrial flutter, and supraventricular tachycardia) and heart failure. This study was designed as a prospective multicenter open-label study. Successful heart rate control was defined as a ≥20% reduction in the heart rate or conversion to normal sinus rhythm within 2hr after starting the intravenous administration of landiolol. This study was started in April 2015 and will end within a few years. Conclusion: The data from the HEARTFUL study may establish the efficacy and safety of landiolol for various tachyarrhythmias in pediatric patients, even if the patients have cardiac dysfunction.

Continuous intravenous antiarrhythmic agents in the intensive care unit: strategies for safe and effective use of amiodarone, lidocaine, and procainamide.

The development of cardiac arrhythmias in the intensive care unit is common and associated with poor prognoses and outcomes. Because of the complexity of patients admitted to the intensive care unit, the management of arrhythmias is often difficult and may require multiple therapeutic interventions. In order for clinicians to appropriately manage arrhythmias, a thorough understanding of all available therapies, including intravenous antiarrhythmic agents, is essential. Suitable antiarrhythmic agents for use in the critical care setting include amiodarone, lidocaine, and procainamide. While these agents can be effective in managing cardiac arrhythmias, they also possess significant disadvantages and require additional monitoring during use. Therapy with these agents is often complicated because of the presence of significant associated adverse effects, clinician unfamiliarity, variable dosing strategies, and the potential for drug-drug interactions. The purpose of this review is to discuss indications and strategies for safe and effective use of amiodarone, lidocaine, and procainamide.

Vernakalant – a promising therapy for conversion of recent-onset atrial fibrillation

Background: This paper reviews the pharmacology, electrophysiology, efficacy and safety of intravenous and oral vernakalant hydrochloride (RSD-1235), a novel antiarrhythmic drug that has relative atrial selectivity by blocking potassium channels that are present in the atria and not the ventricle. In addition, this drug has important rate-dependent sodium channel blocking properties. Methods: Currently, there few commercially approved intravenous antiarrhythmic agents for the conversion of atrial fibrillation. Intravenously, vernakalant has been demonstrated to be useful in terminating over 50% of recent-onset atrial fibrillation (< 7 days duration) with minimal ventricular proarrhythmic effects. Intravenous vernakalant is not effective in terminating atrial flutter. Oral vernakalant is currently undergoing study and appears to be effective in suppressing atrial fibrillation recurrences after cardioversion of persistent atrial fibrillation. Results/conclusion: Intravenous vernakalant has the potential to be an important agent in the conversion of atrial fibrillation and oral vernakalant may be a useful drug for the suppression of atrial fibrillation recurrences.

Idiopathic Ventricular Fibrillation Successfully Terminated by Radiofrequency Ablation of the Distal Purkinje Fibers

A 21-year-old woman was admitted for evaluation of recurrent episodes of syncope. She had several spontaneous and abrupt loss of consciousness episodes while at the emergency department, caused by sustained and nonsustained ventricular fibrillation episodes. Each episode was initiated by a certain premature ventricular complex, which remained the same in subsequent ventricular fibrillation episodes. She had a total of eight more episodes of ventricular fibrillation during her admission, despite administration of intravenous antiarrhythmic agents. A diagnosis of idiopathic ventricular fibrillation was made. Radiofrequency catheter ablation was performed, targeting the distal Purkinje system. Ventricular fibrillation was noninducible after the procedure, and the patient has been symptom-free for the past 1 year.

Lidocaine Hydrochloride

Lidocaine hydrochloride is used as a topical and an injectable anesthetic agent as well as an intravenous antiarrhythmic agent. It is also commonly found in over-the-counter moisturizers, sunburn relief agents, hemorrhoidal creams, and topical antibiotic formulations. There are few reports of immediate hypersensitivity to lidocaine; however, delayed-type hypersensitivity has been even less recognized. Type IV hypersensitivity, although not life threatening, may result in limiting therapeutic options in the surgical candidate.

Advanced cardiac life support controversy: where do antiarrhythmic agents fit in?

Approximately half of all cardiovascular fatalities are attributable to sudden cardiac death, and the majority of sudden cardiac deaths result from ventricular fibrillation (VF). Antiarrhythmic agents are needed to manage refractory VF and ventricular tachycardia (VT); the primary reason for their administration is to prevent recurrence of VF and to abolish VT. The American Heart Association recommends lidocaine hydrochloride as a first-line antiarrhythmic agent in the advanced cardiac life support (ACLS) setting, followed by bretylium tosylate. Although the newly approved intravenous antiarrhythmic agent, amiodarone hydrochloride, may potentially be effective in ACLS, studies are needed to document its clinical benefit in this setting. Such studies are currently under way to document this potential use.

Electrophysiology and Pharmacology of Ibutilide

Ibutilide fumarate is a new class III intravenous antiarrhythmic agent indicated for the acute termination of atrial fibrillation and flutter. Ibutilide prolongs repolarization in the atria and ventricle by enhancing the inward depolarizing, slow sodium current, a unique mechanism of action for a class III agent. Atrial refractoriness is prolonged with no evidence of reverse use dependence. Ibutilide may also block the delayed rectifier current, but this does not appear to be clinically relevant. In vitro and at high doses, ibutilide may shorten action potential duration, although this effect has not been noted clinically. Ibutilide can cause torsades de pointes in a rabbit model of proarrhythmia dependent on the formation of early afterdepolarizations. However, it causes less proarrhythmia than sotalol, dofetilide, or sematilide in this model. The pharmacokinetics of ibutilide are linear, its extravascular distribution is rapid and extensive, while its systemic clearance is high (elimination half-life 3–6 hours). Eight metabolites are formed by the liver, only one of which is slightly active. QT prolongation is dose dependent, is maximal at the end of the infusion, and returns to baseline within 2–4 hours following infusion. The pharmacokinetics and electrophysiologic characteristics of ibutilide are complementary in that any risk of proarrhythmia is made manageable by a short half-life. Almost all reported cases of drug-induced torsades de pointes ventricular tachycardia associated with ibutilide have occurred within 40 minutes of starting the infusion. Nevertheless, clinicians using ibutilide can further reduce the chance of torsades de pointes by being very familiar with the criteria for patient selection, and by being prepared to treat it should it occur. When used with full knowledge of its potential risks, ibutilide is a very effective intravenous agent for the acute termination of atrial fibrillation and flutter and is likely to become a significant treatment option for these arrhythmias. (Am J Cardiol 1996;78 (suppl 8A):12–16)

Parenteral Antiarrhythmic Drug Therapy in Ventricular Tachycardia/Ventricular Fibrillation: Evolving Role of Class III Agents—Focus on Amiodarone

More effective intravenous antiarrhythmic agents are required for treatment of patients with refractory malignant ventricular arrhythmias. More recently, a great deal of interest has been focused on use of intravenous amiodarone for these patients. Uncontrolled early studies showed that intravenous amiodarone was effective in 42% to 81% of treated patients. Recent large cooperative trials have documented the efficacy of intravenous amiodarone in these patients and have shown an efficacy comparable to bretylium in patients with refractory sustained ventricular tachycardia or fibrillation.

Comparison of intravenous lorcainide with lidocaine for acute therapy of complex ventricular arrhythmias: Results of a randomized study with crossover option

There is a need for effective, well tolerated, intravenous antiarrhythmic agents. The effects of lorcainide, a new class I antiarrhythmic agent, were compared with those of lidocaine in a randomized parallel study with cross-over option in 30 hospitalized patients with frequent (greater than 1/min) complex ventricular arrhythmias. Lorcainide loading dose was 2 mg/kg (at 2 mg/min) supplemented, if needed, with 100 mg in 1 hour; maintenance dose was 8 mg/h. Lidocaine loading dose was 1 mg/kg (at 25 mg/min) supplemented, if needed, with 50 mg in 2 minutes; maintenance dose was 2 or 3 mg/min (as needed). Arrhythmias were compared for 2 hours before and after drug loading. Initially responding patients (minimum of 70% arrhythmia suppression) were continued on maintenance therapy for 24 hours. Patients initially failing or with later arrhythmia escape crossed over to alternating therapy (seven to lidocaine, nine to lorcainide). The median frequency of premature ventricular complexes decreased by 76% after lidocaine (p less than 0.05) and by 93% after lorcainide (p less than 0.001); this difference approached significance (p = 0.06). More than 95% arrhythmia suppression was achieved by lorcainide in 47% of patients and by lidocaine in only 13% (p less than 0.05). Couplets decreased by a median of 100% after lorcainide and by 89% after lidocaine. Couplets were eliminated in 62% of the patients after lorcainide and in 27% after lidocaine (p = 0.06). There was 100% suppression of runs of premature beats in 11 patients after lorcainide and 99% suppression in 10 patients after lidocaine.(ABSTRACT TRUNCATED AT 250 WORDS)