Effect Of Antiarrhythmic Drug Therapy Research Articles

Antiarrhythmic drugs-safety and efficacy during pregnancy.

When deciding on antiarrhythmic drug (AAD) treatment, athorough knowledge of the physiological adaptation processes that occur during pregnancy and their effect on metabolism and the efficacy of AAD is mandatory. Beyond the desired effects of AAD therapy, side effects can occur in pregnant women. Furthermore, potential harm to fetal development-depending on gestational age-needs to be considered. Athorough evaluation of potential risks opposed to expected benefits for mother and fetus should be carried out before initiation of AAD treatment. Regular maternal echocardiography and fetal sonographic examination during pregnancy under AAD treatment are advisable. If possible, serum concentrations of AAD should be measured on aregular basis. Due to electrolyte and volume imbalances after delivery, maternal monitoring is recommended for approximately 48 h under AAD therapy. Current guidelines are based on almost historic analyses, where AAD were often prescribed for other indications than rhythm disorders. In clinical practice, AAD predominantly used during pregnancy are intravenous adenosine for acute treatment of atrioventricular nodal dependent tachycardias, whereas betablockers, sotalol, and flecainide can be orally administered for long-term therapy.

16-05: Galectin 3 as a risk factor recurrence of atrial fibrillation in patients with metabolic syndrome

Purpose: Galectin 3 (Gal 3) – biomarker of fibrosis is increased in serum patients with atrial fibrillation (AF) and metabolic syndrome (MetS). We propose that Gal 3 can impact on progression of the arrhythmia. Objective of the study is to evaluate the role of Gal 3 in predicting the effect of antiarrhythmic drug therapy in patients with AF and MetS. Method: 180 patients with MetS (IDF, 2005) and paroxysmal (n = 100) or persistent (n = 80) AF were examined. Groups did not differ significantly by gender, age, eGFR (p > 0,05), volumes left and right atrium. The examination includes: medical history, anthropometry, echocardiography, serum Gal 3 (ELISA). Patients were taking antiarrhythmic drugs: amiodarone (32%), beta-blockers (42%), sotalol (12%), propafenone (14%) during 16,7 ± 6,9 months. After that we analyzed the clinical data and the effectiveness of antiarrhythmic drug therapy, which is considered effective if there were no reported paroxysms of AF during follow-up. Results: Serum Gal 3 in patients with persistent AF was higher compared to patients with paroxysmal AF (1,02 [0,52;3,14] and 0,54 [0,41;1,31] ng/ml, р = 0,03). In patients with 1-2 paroxysms in month serum Gal 3 was higher than in patients with 1-2 paroxysms in year (1,31 [0,92;4,21] and 0,53 [0,41;0,72] ng/ml, р < 0,001). Serum Gal 3 in patients with recurrent paroxysms of AF and without the effect of antiarrhythmic therapy was higher than in patients without recurrent paroxysms of AF irrespective of antiarrhythmic drug (1,31 [0,75,2,49] and 0,50 [0,41;0,72] ng / ml, p < 0.001). The multivariate regression analysis demonstrated that Gal 3 is an independent predictor of non-effective antiarrhythmic drug therapy of AF (OR = 2,38, 95% CI 1,12-5,04, p = 0.024). In patients with AF and MetS who had serum Gal 3 above 0,77 ng/ml (cut-off point on ROC-curve) the risk of non-effective antiarrhythmic therapy was in 3,6 fold higher during follow-up the study (RR = 3,6, 95% CI 1,6-7,9, p = 0,002). Conclusions: The level of serum galectin 3 in patients with persistent atrial fibrillation is higher than in patients with paroxysmal. Patients with higher level of galectin 3 have a higher risk of non-effective antiarrhythmic drug therapy, that may be an additional indication for surgical treatment.

Atrial Fibrillation and Acute Decompensated Heart Failure

Atrial fibrillation (AF) is a common rhythm in patients with acute decompensated heart failure (ADHF). Registry and trial data1,2 indicate that 20% to 35% of patients with ADHF who are admitted to the hospital will be in AF at presentation. In about one third of these patients, the AF will be of recent onset. Despite the high frequency with which the combination of AF and ADHF is encountered, there are few published data that specifically address this problem. AF and worsening heart failure interact in a dangerous pattern. The adverse effects of AF in patients with heart failure may include loss of atrial transport, rapid and irregular ventricular rates, and toxic effects of antiarrhythmic drug therapy. Worsened heart failure, in turn, leads to increased atrial stretch and heightened sympathetic tone. These latter changes make the AF more resistant to treatment using either a rate-control or a rhythm-control strategy (Figure 1). Figure. Adverse interactions between AF and heart failure. AAD indicates antiarrhythmic drug. The immediate general goals of therapy in ADHF are to improve symptoms, restore oxygenation, improve organ perfusion, and limit cardiac and renal injury.3 In patients with sinus rhythm and ADHF, the appropriate use of vasodilators, oxygen, diuretics, positive inotropic agents, and mechanical devices to support ventilation or cardiac output forms the cornerstone of therapy. In patients who present with AF, however, additional treatment decisions are required. ### Initial Assessment The clinical history provides critical information that should be used to guide treatment. Five key questions that should be asked before starting therapy …

Use of telemedicine in the diagnosis of paroxysmal atrial fibrillation and to monitor the effect of antiarrhythmic drug therapy

We present the case of a patient with highly symptomatic tachyarrhythmias for 2 years without any arrhythmia documentation despite numerous ECG and Holter registrations. By means of telemedicine, it was possible to document the arrhythmia--in this case atrial fibrillation--within 10 days and to start antiarrhythmic drug treatment with flecainide and metoprolol. This case demonstrates the diagnostic potential of telemedicine in patients with recurrent episodes of tachyarrhythmias in whom episodes are not sufficiently frequent to allow diagnosis by Holter monitoring. Telemedicine may also be advantageous for ECG monitoring during the early phase after cardioversion or initiation of specific antiarrhythmic pharmacotherapy in order to detect potential drug-induced proarrhythmic changes.

Targeted pharmacological reversal of electrical remodeling after cardioversion—Rationale and design of the Flecainide Short-Long (Flec-SL) trial

Persistent atrial fibrillation (AF) causes relevant mortality and cardiovascular and noncardiovascular morbidity. Therefore, maintenance of sinus rhythm is an important clinical goal, especially when the patient is symptomatic, despite the fact that current treatment strategies are not sufficient to completely prevent recurrent AF. In addition to underlying atrial disease that predisposes to AF, AF in itself induces structural and electrical adaptations ("electrical remodeling" and "structural remodeling"). Underlying disease processes and parts of structural remodeling are not always reversible. Electrical remodeling, in contrast, is reversed by a few weeks of maintenance of sinus rhythm under experimental conditions. This corresponds to the period when most of the recurrent episodes of AF occur after cardioversion. Antiarrhythmic drugs that prolong the atrial action potential can assist in the prevention of recurrent AF by promoting the reversal of electrical remodeling. Such drugs, which are currently used over long periods after cardioversion, may only be needed until the physiological action potential duration is restored, for example, during the first few weeks after cardioversion of persistent AF. This treatment concept that we call "targeted pharmacological reversal of electrical remodeling" would limit both cost and drug-induced side effects of antiarrhythmic drug therapy after cardioversion. The Flec-SL trial, ISECTN62728743, therefore tests the main hypothesis that targeted pharmacological reversal of electrical remodeling by short-term antiarrhythmic drug therapy for 4 weeks after cardioversion is not inferior to standard long-term antiarrhythmic drug therapy for the prevention of recurrent AF after cardioversion in a parallel group, randomized, multicenter, open, blinded end point analysis design. Based on its effectiveness and pharmacokinetic profile, flecainide is used to test the study hypothesis. The trial uses daily transtelephonic electrocardiographic monitoring for all patients and will be conducted within the German Atrial Fibrillation Competence NETwork (AFNET) to facilitate inclusion of patients from electrophysiologically oriented cardiology centers, ordinary hospitals, and office-based physicians.

Effects of antiarrhythmic drug therapy on atrioventricular nodal function during atrial fibrillation in humans*

To assess the effects of metoprolol and amiodarone on atrial and ventricular activity during atrial fibrillation (AF) in post-surgical patients, and to develop and use a mathematical model of the atrioventricular (AV) node during AF that incorporates parameters describing the properties of the AV node to evaluate the physiological basis of the drug effects. Ten post-surgical patients were evaluated where three received no medical therapy, three received metoprolol, three received amiodarone, and one received both metoprolol and amiodarone. The medications led to increases of 37-310 ms in the mean VV interval in treated patients, but much smaller changes in the mean AA intervals in the right and left atria. The mathematical model incorporating a random influence of the concealed conduction parameter was capable of reproducing the histograms of the VV intervals based on the input from the right atrium by systematically searching parameter space. Changes in the ventricular rate are mainly due to the alteration in the AV nodal properties rather than changes in the atrial rhythm. The medications can display differential effects on the physiological properties of the AV node, and therefore the mathematical model may help to identify novel pharmacological targets.

P-026 Effect of antiarrhythmic drug therapy on the development of atrial fibrillation paroxysms after CABG

P-026 Effect of antiarrhythmic drug therapy on the development of atrial fibrillation paroxysms after CABG

P-026 effect of antiarrhythmic drug therapy on the development of atrial fibrillation paroxysms after CABG

P-026 effect of antiarrhythmic drug therapy on the development of atrial fibrillation paroxysms after CABG

Concomitant device and drug therapy: current trends, potential benefits, and adverse interactions

Antiarrhythmic drug therapy in patients with implantable cardioverter defibrillators (ICDs) has decreased over the last 10 years. This trend, primarily seen with class I agents, has occurred mainly in patients with a cardiac arrest. However, despite this overall decrease, antiarrhythmic drug therapy remains an important adjuvant to ICD therapy. In addition to primary prevention of ventricular tachycardia and supraventricular tachycardia, antiarrhythmic drug therapy may potentiate tachycardia rate slowing and make ventricular tachycardia more tolerated hemodynamically and possibly more amendable to pacing therapy. Some of the class III antiarrhythmic drugs may actually lower defibrillation threshold. Unfortunately, these drugs may have adverse interactions with ICDs. An increase in defibrillation threshold or rate-dependent increase in pacing threshold may interfere with the effectiveness of device therapy. Proarrhythmic effects of antiarrhythmic drugs may enhance the frequency of device use. The bradycardic effects of antiarrhythmic drug therapy may similarly enhance the requirements for persistent bradycardia pacing and lead to early battery depletion and other adverse consequences. An awareness of potential benefits and adverse effects of antiarrhythmic drug therapy along with careful electrophysiologic assessment are necessary for optimum combination drug and device therapy.

Late Outcome of Survivors of Idiopathic Ventricular Fibrillation

This report describes clinical, hemodynamic, and electrophysiologic characteristics of 18 consecutive survivors of sudden cardiac arrest due to idiopathic ventricular fibrillation (VF) between 1986 and 1996. Long-term data in relation to the prescribed therapy are presented. The mean age of the 18 patients was 48 ± 14 years (median 49). Electrophysiologic studies showed a low inducibility of sustained ventricular tachyarrhythmias in 4 patients (22%). Treatment consisted of class III agents, β blockers, or implantable cardioverter-defibrillators. Two patients were discharged without any therapy. Therapy control was undertaken either by serial drug testing or by the empirical approach. Serious complications of therapy occurred in 2 patients: 1 patient experienced a proarrhythmic effect of antiarrhythmic drug therapy, and the other patient received multiple inadequate defibrillator discharges due to a defect in the transvenous lead. All but 1 patient (94%) remained free of recurrences of sudden cardiac arrest during a follow-up time of 45 ± 29 months (median 41). One patient died 2 weeks after surviving cardiac arrest due to intractable VF while receiving sotalol treatment. Therapy guided by electrophysiologic studies did not have any impact on survival. Adverse effects or noncompliance led to discontinuation of drug therapy in 7 patients after a mean period of 31 ± 30 months. Without any treatment 9 patients remained without recurrences over 45 ± 33 months. Because of the absence of risk factors for arrhythmia recurrence and criteria to select therapy, randomized prospective studies are warranted to assess the optimal therapies in these young, ostensibly healthy patients.

Electrophysiologic effects of antiarrhythmic drug therapy in the prediction of successful suppression of induced ventricular tachycardia

Predictors of a successful outcome of serial electrophysiologic (EP) and drug studies have been identified from among baseline patient characteristics but not from among measures of baseline and drug-related EP effects. Identifying such predictors would be useful in explaining the mechanism of successful drug therapy and in guiding drug development and selection. We prospectively studied EP characteristics in 159 trials in 62 patients with ventricular tachycardia or ventricular fibrillation during antiarrhythmic therapy and compared EP measures between successful ( n = 30) and failed trials ( n = 129). The average age of the patients was 64 years (range 27 to 78 years); 82% were men and 18% women; and 87% had coronary artery disease. Measurements included R-R, QRS, and QT intervals during intrinsic rhythm and during pacing at cycle lengths of 600 of 400 msec; ventricular effective refractory periods (ERP) during pacing at cycle lengths of 600 and 400 msec; and changes in these measures, comparing treatment with drug-free baseline. Univariate predictors of success (in order of significance) included ERP 600 QRS 600 , sotalol versus other drugs, ERP 400 QRS 400 , ΔERP 600, ΔR-R, ERP 600, QRS 400 (negative association), ΔERP 400, QRS 600 (negative association), ERP 400 (all p < 0.1). In two separate multivariate models, one for each drive cycle length, only the ratio ERP 600 QRS 600 ( p = 0.01) in the first model and ERP 400 QRS 400 ( p = 0.01) in the second model were significantly and independently associated with achieving noninducibility with drug therapy. Therefore measures of greater refractoriness and lesser delays in conduction velocity (ie, greater “wavelength”) relate to drug success. These observations may assist in new drug development and, with other predictors, in drug selection for the treatment of patients.

Veterans affairs congestive heart failure antiarrhythmic trial

This is a prospective, double-blind, placebo-controlled trial to determine the effect of antiarrhythmic drug therapy on mortality in patients with congestive heart failure and ventricular arrhythmia. Patients will be assigned to receive either amiodarone or placebo. Eligible patients include those with ischemic and nonischemic congestive heart failure and with ≥10 ventricular premature beats per hour. All patients must have shortness of breath with minimal exertion or paroxysmal nocturnal dyspnea, a left ventricular internal dimension (LVIDd) by echocardiogram of ≥55 mm or a cardiothoracic ratio of >0.5 and an ejection fraction of ≤40%. All patients will receive vasodilator therapy, unless they find it intolerable. Patients will be entered into the study for 2.5 years and followed for an additional 2 years. Drug therapy will be continued for all patients throughout the entire study unless adverse reactions occur that necessitate individualized treatment. The expectation is that 674 patients will be entered into the study from 25 participating centers. This sample size will allow for the detection of a 33% decrease in 2-year mortality (20% vs 30%) in the treated patients compared with those in the placebo group, with a power of 0.90 and a 2-sided alpha level of 0.05. Intermittent Holter monitoring, radionuclide ventriculograms, pulmonary function tests, echocardiograms, and blood tests, including arterial blood gases, will be required for each patient. The study analysis will address differences in total mortality, cardiac mortality, and sudden cardiac death between patients receiving antiarrhythmic drug therapy and those receiving placebo. Other factors to be examined include the effects of antiarrhythmic therapy on suppression of arrhythmias and ejection fraction.

Comparative study on the proarrhythmic effects of some antiarrhythmic agents.

A main side effect of antiarrhythmic drug therapy is the tendency of these drugs to promote arrhythmia within the therapeutic concentration range, i.e., the proarrhythmic activity of these drugs. However, a model for in vitro assessment, quantification, and comparison of proarrhythmic drug activities was still lacking, and only sparse data were available. To analyze the arrhythmogenic risk of common antiarrhythmic drugs in a quantitative and comparative manner, isolated perfused rabbit hearts were treated with increasing concentrations of antiarrhythmic drugs corresponding to low, medium, and high therapeutic concentrations. For analysis of the epicardial activation process, an epicardial mapping (256 unipolar leads) was performed. For each electrode, the activation time was determined. From these data, the origins of epicardial activation ("breakthrough points" [BTP]) were determined. At each electrode, an activation vector (VEC) was calculated giving direction and velocity of the local excitation wave. The beat similarity of various heartbeats (under treatment) compared with control was evaluated by determination of the percentage of identical BTPs (deviation < or = 1 mm) and of similar VECs (deviation < or = 5 degrees). BTP and VEC were reduced by all antiarrhythmic agents tested (propafenone = flecainide > quinidine > ajmaline > procainamide > disopyramide > mexiletine = lidocaine > sotalol), indicating a more or less pronounced disturbance of the epicardial activation process. Treatment with propafenone, quinidine, and disopyramide and to a lesser extent sotalol prolonged the activation-recovery interval (ARI). ARI dispersion was greatly enhanced by flecainide and was reduced by sotalol. In addition, it could be shown that propranolol is able to reduce the proarrhythmic action of flecainide. This effect seemed to be due to a reduction of the flecainide-induced increase in ARI dispersion. From the results of our study, we propose the following rank order of the arrhythmogenic risk: flecainide > propafenone > quinidine > ajmaline > disopyramide > procainamide > mexiletine, lidocaine > sotalol. Moreover, we conclude that propranolol given additionally may be helpful in reducing the proarrhythmic risk of flecainide.

Congestive heart failure: Survival trial of antiarrhythmic therapy (CHF STAT)

This study is a prospective, double-masked, randomized, clinical trial to determine the effect of anti-arrhythmic drug therapy on mortality in patients with congestive heart failure and ventricular arrhythmia. Patients will be assigned to receive either amiodarone or placebo. Eligible patients include those with ischemic and nonischemic congestive heart failure (New York heart Association class III or VI) and with 10 or more ventricular premature beats per hour. All patients must have shortness of breath with minimal exertion or paroxysmal nocturnal dyspnea, a left ventricular internal dimension (LVIDd) by echocardiogram of 55 mm or greater (⩾ 55 mm) or a CT ratio of greater than 0.5, and an ejection fraction of 40% of less. Patients will be entered into the study for 2.5 years and followed for an additional 2 years. Drug therapy will be continued for all patients throughout the entire study unless adverse reactions occur that necessitate individualized treatment. The expectation is that 674 patients are to be entered into the study from 25 participating centers. This sample size will allow for the detection of a 33% decrease in 2-year mortality (20% vs. 30%) in the treated patients as compared to those in the placebo group with a power of 0.90 and a two-sided α level of 0.05. Intermittent Holter monitoring, radionuclide ventriculograms, pulmonary function tests, echocardiograms, and blood tests, including arterial blood gases, will be required for each patient. The study analysis will address differences in total mortality, cardiac mortality, and sudden cardiac death between patients receiving anti-arrhythmic drug therapy and those receiving placebo. Other factors to be examined include the effects of antiarrhythmic therapy on suppression of arrhythmais, on ejection fraction, and relation of ischemic events to mortality.

Effect of Antiarrhythmic Drug Therapy on the Incidence of Shocks in Patients who Receive an Implantable Cardioverter Defibrillator after a Single Episode of Sustained Ventricular Tachycardia/Fibrillation

Seventy-four patients (16 women, 58 men, age 58 +/- 11 years, mean +/- standard deviation) who received an implantable cardioverter defibrillator (ICD) after experiencing a single episode of ventricular tachycardia or ventricular fibrillation were followed to determine if antiarrhythmic drug therapy affects the incidence of ICD discharges. Thirty-three patients (group A) were treated with an antiarrhythmic drug that was either untested or previously demonstrated during electropharmacological testing to be ineffective in suppressing the induction of ventricular tachycardia. Forty-one patients (group B) were not treated with an antiarrhythmic drug. There were no significant differences between the two groups in regards to age, sex, incidence of coronary artery disease, left ventricular function or the type of ICD pulse generator used. During a mean follow-up of 14 months for the entire cohort, 15 patients (46%) in group A and 18 patients (44%) in group B experienced at least one ICD shock. The time to the first appropriate shock (5 +/- 5 months in both groups) and the frequency of ICD shocks (0.3 +/- 0.2/month in group A vs 0.4 +/- 0.5/month in group B) were similar in both groups. The incidence of syncope at the time of ICD discharge was higher in group A than group B patients (31% vs 5%, P less than 0.05). In conclusion, antiarrhythmic drugs that are untested or have failed electropharmacological testing do not appear to reduce the probability of ICD discharge over a short-term (mean 14 months) follow-up in patients who have had only one clinical episode of VT/VF and may increase the risk of syncope during ICD discharge.(ABSTRACT TRUNCATED AT 250 WORDS)

Contribution of ambulatory electrocardiographic monitoring to antiarrhythmic management

To date, ambulatory electrocardiographic monitoring has contributed to our understanding of the occurrence and significance of arrhythmias. Our appreciation of the spontaneous variability of ventricular arrhythmias, the relations between symptoms and the occurrence of arrhythmias, and the use of ambulatory monitoring in documenting drug effect for new antiarrhythmic drugs and for defining relations among drug dose, plasma concentration and antiarrhythmic effect have contributed to our ability to make more rational recommendations for prescribing and monitoring drug therapy. Further work is necessary to define the occurrence of arrhythmias in normal persons and to determine the prognostic importance of arrhythmias in normal subjects and patients with heart disease other than coronary artery disease. Studies assessing the role of spontaneous variation have indicated the problems that can occur in attempting to evaluate antiarrhythmic drug therapy in individual patients. These variations are so great that it may not be practical to monitor antiarrhythmic drug therapy in certain patients. For patients with coronary artery disease, ambulatory electrocardiographic monitoring can identify those with frequent complex arrhythmias who are at high risk of subsequent sudden cardiac death. Such monitoring can document the effectiveness of antiarrhythmic drug therapy for ventricular irritability and define the dosing regimens or plasma concentrations that are effective for most patients. Ultimately, multicenter intervention trials must document whether or not such antiarrhythmic drug therapy can influence the outcome in the high risk patients identified with ambulatory electrocardiographic recordings. It will be important to determine whether any observed reduction in sudden death in these trials can be related to suppression of asymptomatic ventricular ectopy as determined with ambulatory electrocardiographic recordings.