Very early versus early referral for ablation in young patients with newly diagnosed paroxysmal atrial fibrillation.

Background: Catheter ablation (CA) has emerged as an effective therapy for the treatment of paroxysmal atrial fibrillation (AF); however it is unclear whether proceeding expeditiously to CA improves clinical outcomes in a real-world population. This study compares outcomes of CA for new AF within 6 months of diagnosis (very early) 6 to 12 months after diagnosis (early) and 12 to 24 months after diagnosis (later).

Methods: A large nationally-representative sample of patients ages 18 to 64 who underwent CA from January 2011 to June 2019 was studied using the IBM MarketScan Database.

Site-specific cancer risk following cobalt exposure via orthopedic implants or in occupational settings: A systematic review and meta-analysis.

In 2020, the European Commission up-classified metal cobalt as Class 1B Carcinogen (presumed to have carcinogenic potential) based primarily on data from rodent inhalation carcinogenicity studies. This up-classification requires an assessment under the Medical Device Regulations of cobalt cancer risk from medical devices. We performed a systematic review and meta-analysis to evaluate site-specific cancer risks with cobalt exposure from either total joint replacement (TJR) or occupational exposure (OC).

An integrated benefit-risk assessment of cobalt-containing alloys used in medical devices: Implications for regulatory requirements in the European Union.

In 2017, the European Union (EU) Committee for Risk Assessment (RAC) recommended the classification of metallic cobalt (Co) as Category 1B with respect to its carcinogenic and reproductive hazard potential and Category 2 for mutagenicity but did not evaluate the relevance of these classifications for patients exposed to Co-containing alloys (CoCA) used in medical devices. CoCA are inherently different materials from Co metal from a toxicological perspective and thus require a separate assessment. CoCA are biocompatible materials with a unique combination of properties including strength, durability, and a long history of safe use that make them uniquely suited for use in a wide-range of medical devices.

Carcinogenic assessment of cobalt-containing alloys in medical devices or cobalt in occupational settings: A systematic review and meta-analysis of overall cancer risk from published epidemiologic studies.

In 2020, the European Commission up-classified pure cobalt metal to a Category 1B hazard, based primarily on data from rodent inhalation carcinogenicity studies of metallic cobalt. The European Commission review did not evaluate cobalt-containing alloys in medical devices, which have very different properties vs. pure cobalt metal and did not include a systematic epidemiologic review.

A hazard evaluation of the reproductive/developmental toxicity of cobalt in medical devices.

Cobalt (Co) is an essential element with human exposure occurring from the diet, supplement ingestion, occupational sources, and medical devices. The European Chemical Agency (ECHA) recently voted to classify Co metal as a Reproductive Hazard Category 1B; presumed human reproductive toxicant due to adverse testicular effects in male rodents. A weight of evidence evaluation of the preclinical reproductive and developmental toxicity studies and available clinical data was performed to critically evaluate the relevance of this proposed classification for Co in medical devices.

Carcinogenic hazard assessment of cobalt-containing alloys in medical devices: Review of in vivo studies.

Cobalt (Co) alloys have been used for over seven decades in a wide range of medical devices, including, but not limited to, hip and knee implants, surgical tools, and vascular stents, due to their favorable biocompatibility, durability, and mechanical properties. A recent regulatory hazard classification review by the European Chemicals Agency (ECHA) resulted in the classification of metallic Co as a Class 1B Carcinogen (presumed to have carcinogenic potential for humans), primarily based on inhalation rodent carcinogenicity studies with pure metallic Co. The ECHA review did not specifically consider the carcinogenicity hazard potential of forms or routes of Co that are relevant for medical devices.

Predictors of Cardiac Perforation With Catheter Ablation of Atrial Fibrillation.

Objectives: This study identified factors associated with risk for cardiac perforation in the setting of atrial fibrillation (AF) ablation in contemporary clinical practice.

Background: Cardiac perforation is an uncommon but potentially fatal complication of AF ablation. An improved understanding of factors associated with cardiac perforation could facilitate improvements in procedural safety.

Cumulative experience of azimilide-associated torsades de pointes ventricular tachycardia in the 19 clinical studies comprising the azimilide database.

Objectives: The purpose of this study was to assess the incidence, temporal characteristics, and risk factors associated with azimilide-associated torsades de pointes (TdP) ventricular tachycardia.

Background: Azimilide dihydrochloride is a class III antiarrhythmic drug possessing Ikr and Iks channel-blocking properties.

Methods: Oral azimilide (75 to 125 mg/day) was taken by 5,375 patients in 19 clinical trials conducted at 775 international centers.

The efficacy of azimilide in the treatment of atrial fibrillation in the presence of left ventricular systolic dysfunction: results from the Azimilide Postinfarct Survival Evaluation (ALIVE) trial.

Objectives: The purpose of this study was to assess the effect of oral azimilide dihydrochloride (AZ) 100 mg versus placebo on the onset, termination, and prevalence of atrial fibrillation (AF) in a subpopulation of patients in the Azimilide Postinfarct Survival Evaluation (ALIVE) trial.

Background: Previous clinical trials have demonstrated the antiarrhythmic effects of AZ in patients with AF. Azimilide was investigated for its effects on mortality in patients with depressed left ventricular (LV) function after recent myocardial infarction (MI) and in a subpopulation of patients with AF.

Azimilide for atrial fibrillation: clinical trial results and implications.

Azimilide dihydrochloride (or azimilide) is a class III antiarrhythmic drug currently under investigation that has been tested in atrial fibrillation in four randomized, placebo-controlled clinical trials to assess efficacy and dose range. These investigational trials showed that doses of azimilide 100 and 125 mg once daily prolonged the time to symptomatic arrhythmia recurrence in patients with a history of symptomatic atrial fibrillation, atrial flutter or both. Doses of 75 mg or less were not useful in this indication.

Symptoms at the time of arrhythmia recurrence in patients receiving azimilide for control of atrial fibrillation or flutter: results from randomized trials.

Background: Azimilide is a new antiarrhythmic agent being developed for the management for atrial fibrillation and flutter (AF). Four randomized, placebo-controlled, double-blind trials have been performed that investigated the effect of azimilide on time to first recurrence of symptomatic AF. This paper examines the data collected during those studies regarding the symptoms reported by patients at the time of AF recurrence

Methods: At the time that patients reported their first documented symptomatic recurrence of arrhythmia, they were systematically asked whether or not they were experiencing any of the following 6 symptoms: palpitation, fatigue, chest pain, shortness of breath, dizziness, or sweating.

Asymptomatic or "silent" atrial fibrillation: frequency in untreated patients and patients receiving azimilide.

Background: Asymptomatic, or "silent" atrial fibrillation could increase the risk of stroke. Little is known about the frequency of asymptomatic atrial fibrillation in patients who also have symptomatic atrial fibrillation; similarly, little is known about the effect of antiarrhythmic drug therapy on asymptomatic atrial fibrillation.

Methods And Results: Patients in sinus rhythm with a history of symptomatic atrial fibrillation or atrial flutter received placebo or azimilide (35 to 125 mg) once daily for 6 or 9 months in 4 similar double-blind trials.

Effects of azimilide on heart rate and ECG conduction intervals during sinus rhythm in patients with a history of atrial fibrillation.

The purpose of this study was to assess the effect of azimilide, a Class III antiarrhythmic drug, on ECG conduction intervals recorded during sinus rhythm in patients with a history of symptomatic atrial fibrillation or atrial flutter. In Phase I clinical pharmacology studies, azimilide was associated with prolongation of the QT and QTc intervals on electrocardiograms recorded during sinus rhythm in normal subjects, but the effect of azimilide on the target population of patients with atrial fibrillation has not been reported in detail previously. Patients with a history of atrial fibrillation, atrial flutter, or both were randomly assigned to receive placebo or azimilide twice daily for 3 days and then qd thereafter.

Antiarrhythmic effects of azimilide in paroxysmal supraventricular tachycardia: efficacy and dose-response.

Background: Azimilide is a novel classification III antiarrhythmic agent that blocks both I(Kr)and I(Ks)and shows evidence of efficacy in patients with atrial fibrillation or flutter. Its effect on paroxysmal supraventricular tachycardia (PSVT) has not been reported.

Methods And Results: One hundred ninety-three patients with symptomatic PSVT were enrolled in 4 double-blind, randomized, placebo-controlled clinical trials with almost identical trial design (supraventricular arrhythmia-1 [SVA-1], SVA-2, SVA-3, and SVA-4), performed as a separate stratum of studies that also included a stratum of patients with atrial fibrillation or flutter.