Comparison of the in vitro electrophysiologic and proarrhythmic effects of amiodarone and sotalol in a rabbit model of acute atrioventricular block.

The mechanisms for the different proarrhythmic potential of antiarrhythmic drugs in the presence of comparable QT prolongation are not completely understood. The reasons for the lower proarrhythmic potential of amiodarone as compared with other class-III antiarrhythmic drugs such as sotalol, a fact that has been well established for years, is insufficiently known. Therefore, the aim of our study was to assess the different electrophysiologic effects of amiodarone and sotalol in a previously developed experimental model of proarrhythmia.

Gene dose-dependent atrial arrhythmias, heart block, and brady-cardiomyopathy in mice overexpressing A(3) adenosine receptors.

Objective: An increased expression of adenosine receptors is a promising target for gene therapy aimed at protecting the myocardium against ischemic damage, but may alter cardiac electrophysiology. We therefore studied the effects of heart-directed overexpression of A(3) adenosine receptors (A(3)ARs) at different gene doses on sinus and atrio-ventricular (AV) nodal function in mice.

Methods And Results: Mice with heart-specific overexpression of A(3)AR at high (A(3)(high)) or low (A(3)(low)) levels and their wild-type littermates were studied.

Amiodarone-induced postrepolarization refractoriness suppresses induction of ventricular fibrillation.

It is still incompletely understood why amiodarone is such a potent antiarrhythmic drug. We hypothesized that chronic amiodarone treatment produces postrepolarization refractoriness (PRR) without conduction slowing and that PRR modifies the induction of ventricular arrhythmias. In this study, the hearts of 15 amiodarone-pretreated (50 mg/kg p.

Anterior-posterior versus anterior-lateral electrode positions for external cardioversion of atrial fibrillation: a randomised trial.

Background: External cardioversion is a readily available treatment for persistent atrial fibrillation. Although anatomical and electrophysiological considerations suggest that an anterior-posterior electrode position should create a more homogeneous shock-field gradient throughout the atria than an anterior-lateral position, both electrode positions are equally recommended for external cardioversion in current guidelines. We undertook a randomised trial comparing the two positions with the endpoint of successful cardioversion.

Divergent proarrhythmic potential of macrolide antibiotics despite similar QT prolongation: fast phase 3 repolarization prevents early afterdepolarizations and torsade de pointes.

Macrolide antibiotics are known to have a different proarrhythmic potential in the presence of comparable QT prolongation in the surface ECG. Because the extent of QT prolongation has been used as a surrogate marker for cardiotoxicity, we aimed to study the different electrophysiological effects of the macrolide antibiotics erythromycin, clarithromycin, and azithromycin in a previously developed experimental model of proarrhythmia. In 37 Langendorff-perfused rabbit hearts, erythromycin (150-300 microM, n = 13) clarithromycin (150-300 microM, n = 13), and azithromycin (150-300 microM, n = 11) led to similar increases in QT interval and monophasic action potential (MAP) duration.

Body surface area of ST elevation and the presence of late potentials correlate to the inducibility of ventricular tachyarrhythmias in Brugada syndrome.

Introduction: The value of noninvasive markers reflecting repolarization and/or conduction abnormalities in identifying patients with abnormal ECG showing a pattern of atypical right bundle branch block and ST elevation syndrome (Brugada syndrome) at risk for life-threatening arrhythmias is controversial. Because right precordial ST elevation reflects inhomogeneous repolarization, we hypothesized that a correlation between the area of ST elevation, that is, the area of inhomogeneous repolarization, and the inducibility of ventricular tachyarrhythmias (VT) exists. Therefore, the body surface area of ST elevation and the presence of late potentials were compared to the inducibility of VT in patients with the characteristic ECG of Brugada syndrome.

Electrophysiologic investigation in Brugada syndrome; yield of programmed ventricular stimulation at two ventricular sites with up to three premature beats.

Introduction: Numerous reports on the inducibility of ventricular tachyarrhythmias (VT) in patients with atypical right bundle branch block and right precordial ST-elevation (Brugada syndrome) are based on multicentre studies that have used different stimulation protocols. Therefore, we prospectively investigated the inducibility of VT in these patients using a uniform protocol.

Methods: In 41 consecutive patients (29 males) showing a pattern of right bundle branch block and ST-elevation, programmed ventricular stimulation was performed in the right ventricular apex with up to three premature stimuli at sinus rhythm and at four different paced cycle lengths (500, 430, 370, and 330 ms) until refractoriness was reached or reproducible induction of a sustained (>30s) VT occurred.

Electrophysiologic characterization of the antipsychotic drug sertindole in a rabbit heart model of torsade de pointes: low torsadogenic potential despite QT prolongation.

There is growing concern that antipsychotic drugs that prolong the QT interval almost always increase the risk for patients to develop life-threatening ventricular tachyarrhythmias (VTs) of the torsade de pointes type. We therefore sought to compare the electrophysiologic effects of the psychotropic agent sertindole, which prolongs cardiac repolarization by inhibiting the rapid component of the delayed rectifier potassium current (I(Kr)) but has a low torsadogenic potential to the antiarrhythmic agent dl-sotalol. In 18 Langendorff-perfused rabbit hearts, sotalol (10 microM, n = 8) and sertindole (0.

Brugada syndrome and supraventricular tachyarrhythmias: a novel association?

Introduction: The Brugada syndrome is a distinct form of idiopathic ventricular fibrillation characterized by a unique ECG pattern consisting of a right bundle branch block-like aspect and ST segment elevation in leads V1 to V3. As a high induction rate of ventricular tachyarrhythmias has been reported in Brugada syndrome, we hypothesized that this also may be true for supraventricular tachycardias in these patients.

Methods And Results: Between January 1995 and December 2000, we identified 35 consecutive patients with Brugada syndrome; 26 had a history of cardiac arrest or syncope and 9 were asymptomatic.

Implantation of a dual chamber pacing and sensing single pass defibrillation lead.

Dual-chamber ICDs are increasingly used to avoid inappropriate shocks due to supraventricular tachycardias. Additionally, many ICD patients will probably benefit from dual chamber pacing. The purpose of this pilot study was to evaluate the intraoperative performance and short-term follow-up of an innovative single pass right ventricular defibrillation lead capable of bipolar sensing and pacing in the right atrium and ventricle.

Antitachycardia pacing for rapid VT during ICD charging: a method to prevent ICD shocks.

In patients with ICDs, rapid VTs are usually treated with shocks. It is unknown, if antitachycardia pacing (ATP) delivered once for rapid VT during capacitor charging can avoid painful shocks without increasing the risk of syncope. In patients in whom rapid monomorphic VT (cycle length 300-220 ms) could be reproducibly induced during predischarge ICD testing, the success of cardioversion (defibrillation threshold plus 10 J) and a single ATP attempt (burst with 8 or 16 stimuli) was compared using a randomized crossover study design.

Modification of stretch-induced shortening of repolarization by streptomycin in the isolated rabbit heart.

The exact mechanism of mechano-electrical feedback and stretch-induced arrhythmias is unknown, but the role of stretch-activated ion channels and specific calcium channels has been proposed. The aim of the present study was to test the hypothesis that stretch-activated ion channels and not calcium channels contribute to stretch-related alterations of repolarization and that these effects can be neutralized by stretch-activated channel block. We studied the interaction of acute ventricular dilatation and the stretch-activated channel blocker streptomycin and the specific calcium channel blocker verapamil in an isolated retrogradely perfused rabbit heart model in which the left ventricular size is modified by abruptly changing the volume of a fluid-filled balloon placed in the left ventricle.

Abnormalities of cardiac sympathetic innervation in arrhythmogenic right ventricular cardiomyopathy : quantitative assessment of presynaptic norepinephrine reuptake and postsynaptic beta-adrenergic receptor density with positron emission tomography.

Background: The frequent provocation of ventricular tachycardia by stress or catecholamines and the efficacy of antiarrhythmic drugs with antiadrenergic properties suggest an involvement of the cardiac adrenergic system in arrhythmogenesis in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). Previous studies demonstrated abnormalities of the presynaptic uptake-1 assessed by (123)I-MIBG-single-photon emission computed tomography.

Methods And Results: This study investigated neuronal reuptake of norepinephrine (uptake-1) and beta-adrenergic receptor density in 8 patients with ARVC and 29 age-matched control subjects.

Arrhythmias in heart failure: current concepts of mechanisms and therapy.

About one half of deaths in patients with heart failure are sudden, mostly due to ventricular tachycardia (VT) degenerating to ventricular fibrillation or immediate ventricular fibrillation. In severe heart failure, sudden cardiac death also may occur due to bradyarrhythmias. Other dysrhythmias complicating heart failure include atrial and ventricular extrasystoles, atrial fibrillation (AF), and sustained and nonsustained ventricular tachyarrhythmias.

Is there a need for routine testing of ICD defibrillation capacity? Results from more than 1000 studies.

Aims: Benefits and complications of postoperative implantable cardioverter-defibrillator tests are controversial matters. This study sought to assess the necessity of defibrillation function tests after implantation.

Methods And Results: We retrospectively analysed 1007 implantable cardioverter-defibrillator tests in 587 systems and 556 patients.

Prevalence of coronary artery disease in a general population without suspicion of coronary artery disease: angiographic analysis of subjects aged 40 to 70 years referred for catheter ablation therapy.

Background: The prevalence of coronary vessel wall alterations in the general population is not known. Therefore, the aim of our study was to determine the prevalence of coronary artery disease in persons in whom the underlying disease was not related to coronary artery disease and could therefore be regarded as a near normal population.

Methods: We included 331 consecutive patients (173 men, 158 women, aged between 40 and 70 years) who were referred for catheter ablation of an accessory pathway (67.

Transient local changes in right ventricular monophasic action potentials due to ajmaline in a patient with Brugada Syndrome.

A 48-year-old patient with recurrent episodes of palpitations and syncope presented with transient ST segment elevation in the right precordial ECG leads. Structural heart disease was excluded. No arrhythmias were inducible by programmed ventricular stimulation.

Efficacy and safety of the initial use of stability and onset criteria in implantable cardioverter defibrillators.

Introduction: Inappropriate therapies are the most frequent adverse event in patients with implantable cardioverter defibrillators (ICDs). Most ICDs offer a stability criterion to discriminate ventricular tachycardia (VT) from atrial fibrillation and an onset criterion to discriminate VT from sinus tachycardia. The efficacy and safety of these criteria, if used immediately after implantation, is unknown.

Divergent effect of acute ventricular dilatation on the electrophysiologic characteristics of d,l-sotalol and flecainide in the isolated rabbit heart.

Introduction: The interaction between acute ventricular dilatation (AVD) as one aspect of ventricular dysfunction and Class I and III antiarrhythmic drugs is uncertain. We therefore investigated the effects of AVD on the electrophysiologic properties of d,l-sotalol and flecainide.

Methods And Results: The isolated rabbit heart was used as a model of AVD.

Antiarrhythmic therapy--future trends and forecast for the 21st century.

This article discusses recent changes in antiarrhythmic therapy, with a focus on nonpharmacologic therapy (electrode catheter ablation, implantable cardioverter-defibrillators [ICDs]), and puts them into perspective for the coming years. The treatment of supraventricular tachycardias and tachycardia involving accessory pathways is likely to remain the domain of catheter ablation. With promising new techniques under investigation, the spectrum of arrhythmias that can be cured will probably be expanded.

Drugs versus devices in controlling ventricular tachycardia, ventricular fibrillation, and recurrent cardiac arrest.

Patients with symptomatic ventricular tachycardia, ventricular fibrillation, or aborted sudden cardiac death remain at high risk for arrhythmia recurrence. In recent years, strategies to treat these patients have changed. Concerns about the proarrhythmia risk and uncertain efficacy of class I agents have resulted in a shift in interest to non-class I antiarrhythmic drugs such as sotalol and amiodarone.