Effect of omega-three polyunsaturated fatty acids on inflammation, oxidative stress, and recurrence of atrial fibrillation.

The efficacy of omega-3 polyunsaturated fatty acids (n-3 PUFAs) in preventing recurrence of atrial fibrillation (AF) is controversial and their effects on inflammation and oxidative stress in this population are not known. This study examined the effects of high-dose marine n-3 PUFAs added to conventional therapy on the recurrence of AF and on markers of inflammation and oxidative stress. Patients with paroxysmal or persistent AF were randomized to n-3 PUFAs (4 g/day; n = 126) or placebo (n = 64) in a 2:1 ratio in a prospective, double-blind, placebo-controlled, parallel group study.

A case report of atrial fibrillation potentially induced by hydroxycut: a multicomponent dietary weight loss supplement devoid of sympathomimetic amines.

Multicomponent dietary weight loss supplements comprise the single largest segment of herbal preparations available to the public. As a result of limited de novo regulatory oversight, supplement-related adverse events are underreported secondary to the lack of adequate pharmacodynamic, pharmacokinetic, and clinical data. Here we report the case of an obese 63-year-old caucasian female with a 2-day history of symptomatic paroxysmal atrial fibrillation (AF) with rapid ventricular response following a 2-week course of therapy with hydroxycut, a multicomponent dietary weight loss supplement devoid of sympathomimetic amines.

Modulation of drug block of the cardiac potassium channel KCNA5 by the drug transporters OCTN1 and MDR1.

Background And Purpose: A common site for drug binding on voltage-gated ion channels is at the interior face of the channel pore. In this study, we tested the hypothesis that the extent of drug block of the human cardiac KCNA5 (K(v) 1.5) channel underlying the atrial-specific, ultra-rapidly activating, delayed K(+) current (I(Kur) ) is modulated by the drug uptake and efflux transporters encoded by organic cation transporter 1 (OCTN1) and multiple drug-resistant gene 1 (MDR1) and expressed in human heart.

Drug-induced QT-interval prolongation: considerations for clinicians.

Drug-induced proarrhythmia is a frequently encountered clinical problem and a leading cause for withdrawal or relabeling of prescription drugs. Suppression of the rapid component of the delayed rectifier potassium current, I(Kr), represents the principal pharmacodynamic mechanism leading to heterogeneous prolongation of the ventricular action potential and prolongation of the QT interval clinically. However, the risk of proarrhythmia by QT-interval-prolonging drugs is variable and critically dependent on several factors leading to multiple reductions in the cardiac repolarization reserve.

Role of orally available antagonists of factor Xa in the treatment and prevention of thromboembolic disease: focus on rivaroxaban.

Interpatient variability in the safety and efficacy of oral anticoagulation with warfarin presents several challenges to clinicians, thus underscoring the emergent need for new orally available anticoagulants with predictable pharmacokinetic and pharmacodynamic profiles and ability to target circulating clotting factors. Seven compounds including rivaroxaban, apixaban, betrixaban, and eribaxaban are orally available direct inhibitors of activated factor X currently in development for the prevention and treatment of venous thromboembolism and for thromboprophylaxis in patients with atrial fibrillation or following an acute coronary syndrome. At doses used in phase 2 and 3 clinical trials, rivaroxaban and apixaban demonstrated a predictable onset of effect, maximal plasma concentration, and half-life that was unaffected by age, renal, or hepatic disease.

The organic cation transporter, OCTN1, expressed in the human heart, potentiates antagonism of the HERG potassium channel.

Background: Variable function and expression of drug transporters have been proposed as mechanisms contributing to variable response to drug therapy. Block of the HERG channel, encoding IKr, can lead to serious arrhythmias, and a key drug-blocking site in HERG has been identified on the intracellular face of the pore. We begin to advance the hypothesis that active drug uptake enhances IKr block.

The emerging role of antiarrhythmic compounds with atrial selectivity in the management of atrial fibrillation.

Atrial fibrillation represents a significant source of cardiovascular morbidity and mortality in the United States. Despite a relatively high clinical failure rate, pharmacologic conversion to and maintenance of normal sinus rhythm with antagonists of the HERG potassium channel responsible for carrying the delayed rectifier current I(Kr) represent a mainstay of therapy. Suppression of I(Kr) leads to restoration of normal sinus rhythm but is also associated with ventricular proarrhythmia.

The impact of carvedilol on the defibrillation threshold.

Background: Defibrillation threshold (DFT) is the minimum energy required to successfully terminate ventricular fibrillation. Epinephrine has been shown to increase the DFT in the beta-blocker naïve, but using cardioselective beta-blockers leads to a reduction in the DFT on infusion of epinephrine and norepinephrine. We sought to determine the impact of carvedilol therapy on the DFT after infusion of epinephrine and norepinephrine.

Ranolazine in the management of chronic stable angina.

Purpose: A review of the pharmacology, pharmacokinetics, clinical trials, safety, and efficacy of ranolazine is presented.

Summary: Ranolazine has recently been approved as adjunctive treatment for chronic stable angina (CSA). Data suggest that ranolazine exerts its antiischemic effect through antagonism of the late sodium current and other cardiac ion channels.

An evaluation of the impact of oral magnesium lactate on the corrected QT interval of patients receiving sotalol or dofetilide to prevent atrial or ventricular tachyarrhythmia recurrence.

Background: Intravenous magnesium reduces the QTc interval of patients receiving ibutilide. Whether oral magnesium can reduce the QTc interval associated with oral sotalol and dofetilide is not known. This study was undertaken to evaluate the impact of oral magnesium on the QTc interval and whether an inherent intracellular magnesium deficiency exists among patients with arrhythmias.

The impact of catecholamines on defibrillation threshold in patients with implanted cardioverter defibrillators.

Objectives: To determine the effect of physiologic catecholamine concentrations on the defibrillation threshold (DFT) in patients with implanted cardioverter defibrillators.

Background: DFT is the minimum energy delivered by an implanted cardioverter defibrillator that successfully converts ventricular fibrillation. DFT testing is performed under conscious sedation.

A preliminary assessment of the critical differences between novel oral anticoagulants currently in development.

Chronic anticoagulation represents a clinical conundrum for the health care community that balances unquestionable morbidity and mortality benefits against interindividual variability, leading to drug interactions, adverse events, and thromoembolic events related to underdosing. Despite the growing data regarding the appropriate use and dosing of agents used for chronic anticoagulation, use in clinical practice remains low, thus leading to a theoretical reduction in the risk-to-benefit ratio in the clinical setting relative to that reported in the literature. Oral anticoagulants currently in development represent a heterogeneous group of compounds that are specific for the final common pathway in the coagulation cascade and show indications toward a reduced drug interaction profile, reduced interpatient variation in pharmacokinetic parameters, and morbidity and mortality benefits that might be similar to currently available treatment modalities.

Hemodynamic impact of an ephedra-free multicomponent weight-loss supplement.

Purpose: The effect of Metabolife Ephedra-Free on blood pressure (BP) and hemodynamics was studied.

Methods: Healthy volunteers were randomly assigned to take a single dose of Metabolife Ephedra-Free or matching placebo and then crossed over to the opposite treatment after a seven-day washout period. BP was measured at baseline and one, three, and five hours after administration.

The impact of catecholamines in patients with or without beta-blockers on the ventricular fibrillation cycle length and ventricular fibrillation cycle length variability.

Objectives: To evaluate the impact of epinephrine, norepinephrine, or placebo on the ventricular fibrillation cycle length (VFCL) and the variability of VFCL (cvVFCL) measurements in implantable cardioverter defibrillator (ICD) patients with or without beta-blockers.

Methods: Forty-three patients scheduled for their 6-week post-ICD placement noninvasive electrophysiologic study were included in the study at the Arrhythmia Procedure Laboratory at Hartford Hospital, Hartford, CT. This randomized, double-blind, placebo-controlled evaluation was approved by the Hartford Hospital Institutional Review Board.

Electrocardiographic effects of an Ephedra-Free, multicomponent weight-loss supplement in healthy volunteers.

Study Objective: Metabolife 356, an ephedra-containing weight-loss product, substantially increases the corrected QT (QTc) interval. Metabolife Ephedra Free, a similar supplement, contains caffeine and extracts of green tea, garcinia cambogia, and yerba mate. Its electrocardiographic (ECG) effects are not known.

Critical differences among beta-adrenoreceptor antagonists in myocardial failure: debating the MERIT of COMET.

In the United States, carvedilol and metoprolol (tartrate or succinate) are the most commonly employed beta-adrenoreceptor antagonists for the treatment of heart failure. However, use of these agents in patients with heart failure remains extremely low despite overwhelming evidence of their beneficial short- and long-term effects. Because the myocardial pathophysiology associated with heart failure involves not only beta-1 adrenoreceptors but also beta-2 and alpha-1 adrenoreceptors, this indicates a more complex disease process that may require pan-receptor antagonism to provide optimal clinical benefit.

Inappropriate implantable cardioverter defibrillator discharge following consumption of a dietary weight loss supplement.

This report describes the clinical course of a 40-year-old female who experienced repetitive ICD firing after consuming Metabolife 356, a multicomponent dietary weight loss supplement. Following the initiation of Metabolife 356, the patient experienced four shocks over a 3 day period with two 30 J shocks being delivered sequentially. Interrogation of the device revealed atrial tachycardia with 1:1 AV conduction at a rate of 240 beats/min.

Anemia management in heart failure: a thick review of thin data.

Heart failure is defined as the inability of the heart to pump blood at an amount sufficient to meet the metabolic needs of the body. In heart failure, the inability to meet the body's metabolic needs is based on hemodynamic derangement and suboptimal oxygen-carrying capacity of the blood itself. Current pharmacologic therapy attempts to improve survival and reduce symptomatology by optimizing hemodynamics to increase oxygen delivery, but does not address oxygen-carrying capacity.

Electrocardiographic and hemodynamic effects of a multicomponent dietary supplement containing ephedra and caffeine: a randomized controlled trial.

Context: Metabolife 356, a multicomponent dietary supplement containing ephedra and caffeine (DSEC) in addition to several other components, is the top-selling dietary weight loss supplement. Given its common use, anecdotal reports of cardiovascular and cerebrovascular adverse events, and paucity of safety data, further research with this DSEC was warranted.

Objective: To determine the impact of the DSEC on corrected QT (QTc) interval duration and systolic blood pressure (SBP).

Levosimendan: implications for clinicians.

Levosimendan is a novel calcium sensitizing agent in development for the treatment of acute and chronic heart failure. The agent increases myocardial force without increasing myocyte calcium concentrations, thus reducing the possibility for myocardial necrosis. In addition, the agent also causes vasodilation of coronary and peripheral vessels to improve coronary blood flow and reduce afterload.

Acute decompensated heart failure: a contemporary approach to pharmacotherapeutic management.

Hospital admissions for acute decompensated heart failure (ADHF) have increased precipitously during the past few decades and are projected to continue to increase in the future. To optimize patient outcomes and reduce the costs associated with this disorder, evidenced-based pharmacotherapy is essential. Continuous infusions of loop diuretic therapy rather than bolus dosing may enhance efficacy and reduce the extent of diuretic resistance.