Deborah L. Wolbrette

Old and new antiarrhythmic drugs for converting and maintaining sinus rhythm in atrial fibrillation: comparative efficacy and results of trials

In managing atrial fibrillation (AF), the main therapeutic strategies include rate control, termination of the arrhythmia, and the prevention of recurrences and thromboembolic events. Safety and efficacy considerations are important in optimizing the choice of an antiarrhythmic drug for the treatment of AF. Recently approved antiarrhythmics, such as dofetilide, and promising investigational drugs, such as azimilide and dronedarone, may change the treatment landscape for AF. For medical conversion of recent-onset AF, class IC antiarrhythmic drugs, administered as an oral bolus, have been demonstrated to be the most efficacious pharmacologic conversion agents. Intravenous ibutilide and oral dofetilide both have efficacies superior to placebo in controlled trials for converting persistent AF. Comparative trials in paroxysmal AF have demonstrated that flecainide, propafenone, quinidine, and sotalol are equally effective in preventing recurrences of AF. Amiodarone has been demonstrated to be more efficacious than propafenone or sotalol in the Canadian Trial of Atrial Fibrillation. In persistent AF, twice-daily dofetilide has been shown to be as or more effective than low-dose sotalol given twice daily for the maintenance of sinus rhythm in patients with AF. Trials have demonstrated that subjective adverse effects are less frequent with class IC drugs, sotalol, and dofetilide compared with such drugs as quinidine. In patients without structural heart disease, flecainide, propafenone, and D,L-sotalol are the initial drugs of choice, given their reasonable efficacy, low incidence of subjective side effects, and lack of significant end-organ toxicity. Treating AF in patients with left ventricular dysfunction can be difficult because of associated electrophysiologic derangements, potential proarrhythmic concerns, and negative inotropic effects of antiarrhythmics. Some data exist suggesting that angiotensin-converting enzyme inhibitors and angiotensin receptor blockers can prevent AF either by preventing atrial dilation and stretch-induced arrhythmias or by blocking the renin-angiotensin system. In post-myocardial infarction patients, D,L-sotalol, dofetilide, and amiodarone-and in congestive heart failure patients, amiodarone and dofetilide-have demonstrated neutral effects on survival in controlled trials. In the Congestive Heart Failure Survival Trial of Antiarrhythmic Therapy (CHF-STAT), amiodarone lowered the frequency of AF development and improved left ventricular ejection fraction over time. In CHF-STAT, there was lower mortality in patients who converted from AF to sinus rhythm. Dofetilide decreased rehospitalization for congestive heart failure in the Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) trials. Neutral effects on survival and favorable hemodynamics have positioned amiodarone and dofetilide as the antiarrhythmics of choice in patients with left ventricular dysfunction. In post-myocardial infarction patients, sotalol is an additional agent to consider for treatment of AF in this setting.

Risk of proarrhythmia with class III antiarrhythmic agents: sex-based differences and other issues

Although men have a higher risk of atrial fibrillation compared with women, the absolute number of women with atrial fibrillation is greater. Congestive heart failure increases the risk of developing atrial fibrillation in women more than in men, and the prognosis for women with atrial fibrillation is worse than for men. The longer baseline corrected QT interval in women is well known. The mechanism is likely the result of increased circulating androgens, causing the QT interval to shorten in men after puberty. Female sex is associated with an increased risk of torsades de pointes in the setting of potassium antagonists. Class III antiarrhythmic drugs are frequently used for the treatment of atrial fibrillation in heart failure patients because of their neutral effect on mortality and their tolerance by patients with low ejection fractions. Although amiodarone and azimilide carry a low potential for producing torsades de pointes compared with sotalol and dofetilide, the prevalence of torsades de pointes in women is at least twice that in men for all these drugs. Careful monitoring of the QT interval and potassium level, as well as control of congestive heart failure, can help reduce the risk of proarrhythmia. Avoidance of polypharmacy with other potassium antagonists and unmonitored drug formulation changes are important in the management of all patients taking class III agents, but they are particularly crucial in women with additional risk factors for torsades de pointes.

Metabolic syndrome, its preeminent clusters, incident coronary heart disease and all-cause mortality--results of prospective analysis for the Atherosclerosis Risk in Communities study.

Objective.  To investigate the prospective association between Metabolic Syndrome (MetS) and coronary heart disease (CHD) and all‐cause mortality.

Acute treatment of atrial fibrillation : Spontaneous conversion rates and cost of care

Acute treatment of atrial fibrillation is costly although spontaneous conversion rates are high. We reviewed 114 patients admitted to our inpatient service via the emergency department with a principal diagnosis of atrial fibrillation and found the spontaneous conversion rate was 50% in 48 hours, the average length of stay was 3.9 +/- 5.2 days, and the average cost was

Arrhythmias and women.

6,692 +/-

A Decade of Clinical Trial Developments in Postmyocardial Infarction, Congestive Heart Failure, and Sustained Ventricular Tachyarrhythmia Patients: From CAST to AVID and Beyond

4,928.

Individual-level PM 2.5 exposure and the time course of impaired heart rate variability: the APACR Study

The incidence and risk factors for a variety of arrhythmias differ among men and women. Although symptomatic atrial reentrant tachycardias have a female predominance, the reverse is true for atrial fibrillation. Women have a lower incidence of sudden death. On the other hand, drug-induced torsades de pointes and symptomatic long QT syndrome have a female predominance. The incidence of arrhythmias seem to be increased during pregnancy. The mechanisms of these gender differences are unclear but may be related to hormonal effects and the shorter QT interval in men. Pharmacologic and nonpharmacologic therapy are equally efficacious in men and women.

Amiodarone: clinical trials.

A Decade of Clinical Trials. Multiple trials using antiarrhythmic drugs, pharmacologic therapy, and implantable cardioverter defibrillators have been performed in an attempt to improve survival in patients: (1) postmyocardial infarction; (2) with congestive heart failure, with and without nonsustained ventricular tachycardia; and (3) with sustained ventricular tachycardia and those who have survived an out‐of‐hospital cardiac arrest. This article reviews some of the key findings and limitations of completed and ongoing trials. We also make recommendations for the current treatment of such patients based on the results of these trials.

Atrial Fibrillation in Heart Failure: Prognostic Significance and Management

In 106 community-dwelling middle-aged non-smokers we examined the time-course and the acute effects of fine particles (PM2.5) on heart rate variability (HRV), which measures cardiac autonomic modulation (CAM). Twenty-four hours beat-to-beat ECG data were visually examined. Artifacts and arrhythmic beats were removed. Normal beat-to-beat RR data were used to calculate HRV indices. Personal PM2.5 nephelometry was used to estimate 24-h individual-level real-time PM2.5 exposures. We use linear mixed-effects models to assess autocorrelation- and other major confounder-adjusted regression coefficients between 1–6 h moving averages of PM2.5 and HRV indices. The increases in preceding 1–6 h moving averages of PM2.5 was significantly associated with lower HF, LF, and SDNN, with the largest effect size at 4–6 h moving averages and smallest effects size at 1 h moving average. For example, a 10 μg/m3 increase in 1 and 6-h moving averages was associated with 0.027 and 0.068 ms2 decrease in log-HF, respectively, and with 0.024 and 0.071 ms2 decrease in log-LF, respectively, and with 0.81 and 1.75 ms decrease in SDNN, respectively (all P-values <0.05). PM2.5 exposures are associated with immediate impairment of CAM. With a time-course of within 6 h after elevated PM2.5 exposure, with the largest effects around 4–6 h.

Acute adverse effects of fine particulate air pollution on ventricular repolarization

Amiodarone is an antiarrhythmic agent commonly used in the treatment of supraventricular and ventricular tachyarrhythmias. This article reviews the results and clinical implications of primary and secondary prevention trials in which amiodarone was used in one of the treatment arms. Key post-myocardial infarction primary prevention trials include the European Myocardial Infarct Amiodarone Trial (EMIAT) and the Canadian Amiodarone Myocardial Infarction Trial (CAMIAT), both of which demonstrated that amiodarone reduced arrhythmic but not overall mortality. In congestive heart failure patients, amiodarone was studied as a primary prevention strategy in two pivotal trials: Grupo de Estudio de la Sobrevida en la Insuficiencia Cardiac en Argentina (GESICA) and Amiodarone in Patients With Congestive Heart Failure and Asymptomatic Ventricular Arrhythmia (CHF-STAT). Amiodarone was associated with a neutral overall survival and a trend toward improved survival in nonischemic cardiomyopathy patients in CHF/STAT and improved survival in GESICA. In post-myocardial infarction patients with nonsustained ventricular tachycardia and a depressed ejection fraction, the Multicenter Automatic Defibrillator Implantation Trial (MADIT) demonstrated that implantable cardioverter-defibrillators (ICD) statistically improved survival compared to the antiarrhythmic drug arm, most of whose patients were taking amiodarone. In patients with histories of sustained ventricular tachycardia or ventricular fibrillation, the Cardiac Arrest Study in Seattle: Conventional Versus Amiodarone Drug Evaluation (CASCADE) trial demonstrated that empiric amiodarone lowered arrhythmic recurrence rates compared to other drugs guided by serial Holter or electrophysiologic studies. However, arrhythmic death rates were high in both treatment arms of the study. Several secondary prevention trials, including the Antiarrhythmics Versus Implantable Defibrillators Study (AVID), the Canadian Implantable Defibrillator Study (CIDS), and the Cardiac Arrest Study Hamburg (CASH), have demonstrated the superiority of ICD therapy compared to empiric amiodarone in improving overall survival. Based on the above findings, amiodarone is safe to use in post-myocardial infarction and congestive heart failure patients that need antiarrhythmic therapy. Although amiodarone is effective in treating malignant arrhythmias, high-risk patients should be considered for an ICD as frontline therapy.