Pharmacological Treatment Of Atrial Fibrillation Research Articles

What determines the optimal pharmacological treatment of atrial fibrillation? Insights from in silico trials in 800 virtual atria.

The best pharmacological treatment for each atrial fibrillation (AF) patient is unclear. We aim to exploit AF simulations in 800 virtual atria to identify key patient characteristics that guide the optimal selection of anti-arrhythmic drugs. The virtual cohort considered variability in electrophysiology and low voltage areas (LVA) and was developed and validated against experimental and clinical data from ionic currents to ECG. AF sustained in 494 (62%) atria, with large inward rectifier K+ current (IK1 ) and Na+ /K+ pump (INaK ) densities (IK1 0.11±0.03 vs. 0.07±0.03 SmF-1 ; INaK 0.68±0.15 vs. 0.38±26 SmF-1 ; sustained vs. un-sustained AF). In severely remodelled left atrium, with LVA extensions of more than 40% in the posterior wall, higher IK1 (median density 0.12±0.02 SmF-1 ) was required for AF maintenance, and rotors localized in healthy right atrium. For lower LVA extensions, rotors could also anchor to LVA, in atria presenting short refractoriness (median L-type Ca2+ current, ICaL , density 0.08±0.03 SmF-1 ). This atrial refractoriness, modulated by ICaL and fast Na+ current (INa ), determined pharmacological treatment success for both small and large LVA. Vernakalant was effective in atria presenting long refractoriness (median ICaL density 0.13±0.05 SmF-1 ). For short refractoriness, atria with high INa (median density 8.92±2.59 SmF-1 ) responded more favourably to amiodarone than flecainide, and the opposite was found in atria with low INa (median density 5.33±1.41 SmF-1 ). In silico drug trials in 800human atria identify inward currents as critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics. KEY POINTS: Atrial fibrillation (AF) maintenance is facilitated by small L-type Ca2+ current (ICaL ) and large inward rectifier K+ current (IK1 ) and Na+ /K+ pump. In severely remodelled left atrium, with low voltage areas (LVA) covering more than 40% of the posterior wall, sustained AF requires higher IK1 and rotors localize in healthy right atrium. For lower LVA extensions, rotors can also anchor to LVA, if the atria present short refractoriness (low ICaL ) Vernakalant is effective in atria presenting long refractoriness (high ICaL ). For short refractoriness, atria with fast Na+ current (INa ) up-regulation respond more favourably to amiodarone than flecainide, and the opposite is found in atria with low INa . The inward currents (ICaL and INa ) are critical for optimal stratification of AF patient to pharmacological treatment and, together with the left atrial LVA extension, for accurately phenotyping AF dynamics.

Inhibitory Effect of a Late Sodium Current Blocker, NCC-3902, on the Automaticity of the Guinea Pig Pulmonary Vein Myocardium.

The effect of blocking the persistent component of the sodium channel current (late INa) on the automatic activity of the isolated guinea pig pulmonary vein myocardium was examined. NCC-3902 blocked late INa, but did not affect other major ion channel currents stably expressed in cell lines. In isolated pulmonary vein cardiomyocytes, NCC-3902 blocked the late INa induced by a ramp depolarizing voltage clamp pulse similar to that of the pacemaker depolarization observed in the pulmonary vein myocardium. In isolated pulmonary vein tissue, NCC-3902 decreased the frequency of automatic firing of the myocardium through a reduction of the pacemaker depolarization slope. In isolated pulmonary vein cardiomyocytes, NCC-3902 significantly reduced the firing frequency of Ca2+ transients, but had no effect on Ca2+ sparks. NCC-3902 affected neither the spontaneous beating rate of the right atrium nor the contractile force of the ventricular myocardium. Selective blockers of late INa like NCC-3902, which inhibit the automatic activity of the pulmonary vein myocardium, appear to be promising as drugs for the pharmacological treatment of atrial fibrillation.

Electrophysiological effects of ranolazine in a goat model of lone atrial fibrillation

There is still an unmet need for pharmacologic treatment of atrial fibrillation (AF) with few effects on ventricular electrophysiology. Ranolazine is an antiarrhythmic drug reported to have strong atrial selectivity. The purpose of this study was to investigate the electrophysiological effects of ranolazine in atria with AF-induced electrical remodeling in a model of lone AF in awake goats. Electrode patches were implanted on the atrial epicardium of 8 Dutch milk goats. Experiments were performed at baseline and after 2 and 14 days of electrically maintained AF. Several electrophysiological parameters and AF episode duration were measured during infusion of vehicle and different doses of ranolazine (target plasma levels 4, 8, and 16 μM, respectively). The highest dose of ranolazine significantly prolonged atrial effective refractory period and decreased atrial conduction velocity at baseline and after 2 days of AF. After 2 weeks of AF, ranolazine prolonged the p5 and p50 of AF cycle length distribution in a dose-dependent manner but was not effective in restoring sinus rhythm. No adverse ventricular arrhythmic events (eg, premature ventricular beats or signs of hemodynamic instability) were observed during infusion of ranolazine at any point in the study. The lowest investigated dose of ranolazine, which is expected to block both late INa and atrial peak INa, had no effect on the investigated electrophysiological parameters. The highest dose affected both atrial and ventricular electrophysiological parameters at different stages of AF-induced remodeling but was not efficacious in cardioverting AF to sinus rhythm in a goat model of lone AF.

Prevalence, Risk Factors and Pharmacological Treatment of Atrial Fibrillation in Older Hospitalized Patients in Vietnam

<p>Background. The evidence about prevalence of atrial fibrillation (AF) in Vietnam is very limited. This study aims to investigate the prevalence of AF, its associated factors and pharmacological treatment in older patients in Vietnam.The secondary aim is to investigate the impact of frailty on the pharmacological treatment of AF.</p><p>Methods. We used data from a study of the prevalence of frailty in older hospitalised patients at the National Geriatric Hospital in Hanoi, Vietnam. Consecutive patients aged ≥60 years were recruited from 4/2015 to 10/2015.</p><p>Results. A total of 461 patients was recruited (56.8% female, mean age 76.2±8.9). The prevalence of AF was 3.9% (18 patients). Amongst patients with AF, the most common medical conditions were hypertension (72.2%), followed by stroke (55.6%), heart failure (50.0%), type2 diabetes (44.4%). Living alone (OR=10.2, 95%CI 1.5–70.1), having a habit of using vitamins at home (OR=3.8, 95%CI 1.1–13.4), having heart failure (OR=31.3, 95%CI 9.6–101.8), and having type 2 diabetes (OR=3.5, 95%CI 1.2–10.7) were associated with the presence of AF on admission. All patients with AF had a high risk of stroke (CHA2DS2-VASc score≥2) and 72.2% of them had a high risk of bleeding with anticoagulant medications (HAS-BLED score≥3). Only 22.2% were anticoagulated on admission and 22.2% upon discharge, with no difference between frail and non-frail patients.</p>Conclusions. The prevalence of AF among older hospitalised patients in Vietnam is similar to that reported in other countries. Anticoagulation for stroke prevention was underused, without any significant difference between frail and non-frail patients.

Antiarrhythmic effect of the Ca2+-activated K+ (SK) channel inhibitor ICA combined with either amiodarone or dofetilide in an isolated heart model of atrial fibrillation.

Dose is an important parameter in terms of both efficacy and adverse effects in pharmacological treatment of atrial fibrillation (AF). Both of the class III antiarrhythmics dofetilide and amiodarone have documented anti-AF effects. While dofetilide has dose-related ventricular side effects, amiodarone primarily has adverse non-cardiac effects. Pharmacological inhibition of small conductance Ca2+-activated K+ (SK) channels has recently been reported to be antiarrhythmic in a number of animal AF models. In a Langendorff model of acutely induced AF on guinea pig hearts, it was investigated whether a combination of the SK channel blocker N-(pyridin-2-yl)-4-(pyridin-2-yl)thiazol-2-amine (ICA) together with either dofetilide or amiodarone provided a synergistic effect. The duration of AF was reduced with otherwise subefficacious concentrations of either dofetilide or amiodarone when combined with ICA, also at a subefficacious concentration. At a concentration level effective as monotherapy, dofetilide produced a marked increase in the QT interval. This QT prolonging effect was absent when combined with ICA at non-efficacious monotherapy concentrations. The results thereby reveal that combination of subefficacious concentrations of an SK channel blocker and either dofetilide or amiodarone can maintain anti-AF properties, while the risk of ventricular arrhythmias is reduced.

Catheter ablation in atrial fibrillation: a valid therapeutic option also for older patients?

Atrial fibrillation (AF) represents the arrhythmic epidemics of the 21st century. It is not only the most common cardiac arrhythmia encountered in daily clinical practice, but it is associated as well with high cardiac morbidity and mortality. Its incidence increases exponentially with aging, with about 10% of the population over 80 years old being affected. Pharmacological treatment of AF in the elderly deals with several issues related to differences in the mechanisms underlying this arrhythmia and pharmacokinetics, and to the anatomical and electrical remodeling associated with aging. Catheter ablation of AF might represent a good therapeutic option in this patient population, since it is conceived to cure patients from this arrhythmia and it is not associated with the common side effects of antiarrhythmic drugs. The aim of this brief review is to summarize the available evidence on the safety and efficacy of catheter ablation of AF in geriatric age, trying to balance the natural enthusiasm of cardiac electrophysiologists with some expected skepticism of geriatricians.

Future perspectives in the pharmacological treatment of atrial fibrillation and ventricular arrhythmias in heart failure.

Heart failure (HF) is a clinical syndrome characterized by significant impairment of cardiac ventricular function. Atrial fibrillation (AF) is the most commonly observed sustained arrhythmia in clinical practice. Both HF and AF are associated with increased morbidity and mortality and their prevalence increases with age. Approximately 50% of patients with moderate HF die due to ventricular fibrillation that leads to sudden cardiac death. Patients with AF exhibit increased mortality due to HF and stroke. HF and AF often co-exist, and the development of the other condition further deteriorates prognosis. Both chronic HF and AF lead to structural and electrophysiological changes in the heart called remodeling, modifying therapeutic targets including those for antiarrhythmic intervention. Current pharmacological treatment of arrhythmias has major limitations due to low efficacy and serious adverse effects. In this review, the main aspects of electrical remodeling in HF and AF are discussed along with possible novel targets identified for future pharmacological antiarrhythmic therapy.

Pharmacological Treatment of Atrial Fibrillation in Patients with Heart Failure

Atrial fibrillation (AF) frequently occurs in patients with heart failure. It is recognized that AF leads to clinical deterioration and results in worsening heart failure. AF also increases the risk of mortality and morbidity in patients with heart failure. ESC guideline 2010 introduces treatment recommendations for the management of AF in patients with heart failure. 1) Background heart failure treatment should be optimized, 2) Oral anticoagulant is generally indicated when AF is present, 3) Ventricular rate control is required. Beta-blockers are preferred over digitalis and have favorable effects on mortality and morbidity in patients with systolic heart failure. 4) The rhythm control strategy has not been shown to be superior to rate control in heart failure patients with AF (AF-CHF trial). However, restoration of sinus rhythm may improve symptoms and hemodynamics in heart failure patients with AF. Amiodarone can be safely used in patients with heart failure. In patients with AF and severe and unstable heart failure, intravenous amiodarone should be used to maintain sinus rhythm. The goal of pharmacological management is to improve in survival and quality of life in heart failure patients with AF. Atrial fibrillation (AF) frequently occurs in patients with heart failure. It is recognized that AF leads to clinical deterioration and results in worsening heart failure. AF also increases the risk of mortality and morbidity in patients with heart failure. ESC guideline 2010 introduces treatment recommendations for the management of AF in patients with heart failure. 1) Background heart failure treatment should be optimized, 2) Oral anticoagulant is generally indicated when AF is present, 3) Ventricular rate control is required. Beta-blockers are preferred over digitalis and have favorable effects on mortality and morbidity in patients with systolic heart failure. 4) The rhythm control strategy has not been shown to be superior to rate control in heart failure patients with AF (AF-CHF trial). However, restoration of sinus rhythm may improve symptoms and hemodynamics in heart failure patients with AF. Amiodarone can be safely used in patients with heart failure. In patients with AF and severe and unstable heart failure, intravenous amiodarone should be used to maintain sinus rhythm. The goal of pharmacological management is to improve in survival and quality of life in heart failure patients with AF.

Cardiac Potassium Channel Subtypes: New Roles in Repolarization and Arrhythmia

About 10 distinct potassium channels in the heart are involved in shaping the action potential. Some of the K+ channels are primarily responsible for early repolarization, whereas others drive late repolarization and still others are open throughout the cardiac cycle. Three main K+ channels drive the late repolarization of the ventricle with some redundancy, and in atria this repolarization reserve is supplemented by the fairly atrial-specific KV1.5, Kir3, KCa, and K2P channels. The role of the latter two subtypes in atria is currently being clarified, and several findings indicate that they could constitute targets for new pharmacological treatment of atrial fibrillation. The interplay between the different K+ channel subtypes in both atria and ventricle is dynamic, and a significant up- and downregulation occurs in disease states such as atrial fibrillation or heart failure. The underlying posttranscriptional and posttranslational remodeling of the individual K+ channels changes their activity and significance relative to each other, and they must be viewed together to understand their role in keeping a stable heart rhythm, also under menacing conditions like attacks of reentry arrhythmia.

Pulmonary vein isolation in patients with Brugada syndrome and atrial fibrillation: a 2-year follow-up

Pharmacological treatment of atrial fibrillation (AF) in the setting of Brugada syndrome (BS) might be challenging as many antiarrhythmic drugs (AADs) with sodium channel blocking properties might expose the patients to the development of ventricular arrhythmias. Moreover, patients with BS and implantable cardioverter-defibrillator (ICD) might experience inappropriate shocks because of AF with rapid ventricular response. The role of pulmonary vein isolation (PVI) in patients with BS and recurrent episodes of AF has not been established yet. In this study, we analysed the outcome of PVI using radiofrequency energy or cryoballoon (CB) ablation at 2 years follow-up. Consecutive patients with BS having undergone PVI for drug-resistant paroxysmal AF were eligible for this study. Nine patients (three males; mean age: 52 ± 26 years) were included. Six patients (67%) had an ICD implanted of whom three had inappropriate shocks because of rapid AF. At a mean 22.1 ± 6.4 months follow-up, six patients (67%) were free of AF without AADs. None of the three patients who had experienced inappropriate ICD interventions for AF had further ICD shocks after ablation. In our study PVI can be an effective and safe procedure to treat patients with BS and recurrent episodes of paroxysmal AF.

Atrial fibrillation in heart failure: drug therapies for rate and rhythm control

Pharmacological treatment of atrial fibrillation in the context of heart failure poses numerous challenges. Management decisions are limited by contraindications to several drugs and the paucity of robust clinical trials that provide evidence-based guidance. This review proposes a structured action plan for managing atrial fibrillation coexisting with heart failure that considers published clinical guidelines and integrates recent data derived from substudies of randomized trials, including the atrial fibrillation and congestive heart failure (AF-CHF) trial. Areas of uncertainty, such as target heart rates in atrial fibrillation and upstream therapies, are also discussed.

Genetic suppression of Gαs protein provides rate control in atrial fibrillation

Gene therapy-based modulation of atrioventricular (AV) conduction by overexpression of a constitutively active inhibitory Gα(i) protein effectively reduced heart rates in atrial fibrillation (AF). However, catecholamine stimulation caused an excessive increase in ventricular rate. We hypothesized that modest genetic suppression of a stimulatory G protein in the AV node would allow persistent rate control in acute AF and would prevent undesired heart rate acceleration during β-adrenergic activation. Atrial fibrillation was induced in 12 pigs by atrial burst pacing via an implanted cardiac pacemaker. Study animals were then assigned to receive either Ad-siRNA-Gα(s) gene therapy to inactivate Gα(s) protein or Ad-β-gal as control. Gα(s) protein inactivation resulted in a 20 % heart rate reduction (P < 0.01). AH and HV intervals were prolonged by 37 ms (P < 0.001) and 28 ms (P < 0.001), respectively, demonstrating atrioventricular conduction delay. Impairment of left ventricular ejection fraction (LVEF) during AF was attenuated by Gα(s) suppression (LVEF 49 %) compared with controls (LVEF 34 %; P = 0.03). Isoproterenol application accelerated ventricular heart rate from 233 to 281 bpm (P < 0.001) in control animals but did not significantly affect pigs treated with Ad-siRNA-Gα(s) (192 vs. 216 bpm; P = 0.19). In conclusion, genetic inhibition of Gα(s) protein in the AV node reduced heart rate and prevented AF-associated reduction of cardiac function in a porcine model. Rate control by gene therapy may provide an alternative to current pharmacological treatment of AF.

The Na+/K+ pump is an important modulator of refractoriness and rotor dynamics in human atrial tissue.

Pharmacological treatment of atrial fibrillation (AF) exhibits limited efficacy. Further developments require a comprehensive characterization of ionic modulators of electrophysiology in human atria. Our aim is to systematically investigate the relative importance of ionic properties in modulating excitability, refractoriness, and rotor dynamics in human atria before and after AF-related electrical remodeling (AFER). Computer simulations of single cell and tissue atrial electrophysiology were conducted using two human atrial action potential (AP) models. Changes in AP, refractory period (RP), conduction velocity (CV), and rotor dynamics caused by alterations in key properties of all atrial ionic currents were characterized before and after AFER. Results show that the investigated human atrial electrophysiological properties are primarily modulated by maximal value of Na(+)/K(+) pump current (G(NaK)) as well as conductances of inward rectifier potassium current (G(K1)) and fast inward sodium current (G(Na)). G(NaK) plays a fundamental role through both electrogenic and homeostatic modulation of AP duration (APD), APD restitution, RP, and reentrant dominant frequency (DF). G(K1) controls DF through modulation of AP, APD restitution, RP, and CV. G(Na) is key in determining DF through alteration of CV and RP, particularly in AFER. Changes in ionic currents have qualitatively similar effects in control and AFER, but effects are smaller in AFER. The systematic analysis conducted in this study unravels the important role of the Na(+)/K(+) pump current in determining human atrial electrophysiology.

Pharmacological treatment of atrial fibrillation: What does it take?

Among the different types of arrhythmias, atrial fibrillation (AF) is by far the most common. In fact, approximately one-third of hospitalizations related to heart rhythm disturbances can be associated with AF.1 AF is not per se a devastating condition. However, the lack of coordinated atrial contraction will result in reduced ventricular filling and, importantly, blood stasis in the atria. This latter condition increases the risk for thromboembolic stroke and heart failure.2,3 As a result, the risk for stroke in association with AF is nearly 5-fold compared with that in people in sinus rhythm.

Pharmacological Treatment of Atrial Fibrillation: An Overview

Since atrial fibrillation (AF) is the most common arrhythmia that increases with age, AF is becoming a major health issue with an increasing population of elderly people. Non-pharmacological treatment of AF with catheter-based pulmonary vein ablation or isolation has considerably progressed and it may be successfully used in younger and symptomatic patients with refractory paroxysmal AF. In addition, introduction of novel anticoagulants may have a great impact on the treatment of AF. Many large-scale clinical trials comparing rate control with rhythm control have not yet indicated that rhythm control is any better than rate control in decreasing morbidity and mortality rate of AF patients. A possible explanation for the inferiority of rhythm control may be that proarrhythmic risk and toxic effects associated with currently available antiarrhythmic drugs adversely affect outcomes. One of ideal candidates may be an antiarrhythmic drug with selective affinity for the ion channels that are specifically involved in atrial repolarization. Another candidate may be an antiarrhythmic drug with multichannel blocking action, producing successful rhythm control like amiodarone. I will review several novel antiarrhythmic drugs being developed for the treatment of AF. At the present time the rate control strategy will become the first choice for the treatment of AF, especially persistent AF. However, if an effective atrial-selective antiarrhythmic drug without serious side effects is developed, the rhythm control strategy may become another choice for AF therapy.

Modeling the Effect of Kv1.5 Block on the Canine Action Potential

A wide range of ion channels have been considered as potential targets for pharmacological treatment of atrial fibrillation. The Kv1.5 channel, carrying the I Kur current, has received special attention because it contributes to repolarization in the atria but is absent or weakly expressed in ventricular tissue. The dog serves as an important animal model for electrophysiological studies of the heart and mathematical models of the canine atrial action potential (CAAP) have been developed to study the interplay between ionic currents. To enable more-realistic studies on the effects of Kv1.5 blockers on the CAAP in silico, two continuous-time Markov models of the guarded receptor type were formulated for Kv1.5 and subsequently inserted into the Ramirez-Nattel-Courtemanche model of the CAAP. The main findings were: 1), time- and state-dependent Markov models of open-channel Kv1.5 block gave significantly different results compared to a time- and state-independent model with a downscaled conductance; 2), the outcome of Kv1.5 block on the macroscopic system variable APD 90 was dependent on the precise mechanism of block; and 3), open-channel block produced a reverse use-dependent prolongation of APD 90. This study suggests that more-complex ion-channel models are a prerequisite for quantitative modeling of drug effects.

Prevention of Torsade de Pointes during the Pharmacologic Treatment of Atrial Fibrillation

Prevention of Torsade de Pointes during the Pharmacologic Treatment of Atrial Fibrillation

Advances in the Pharmacological Treatment of Atrial Fibrillation

Atrial fibrillation (AF) is a growing clinical problem that is associated with increased morbidity and mortality rates. There are two principal options for the management of AF: rate and rhythm control. The rhythm control strategy aims to maintain sinus rhythm, or to restore rhythm when required, using antiarrhythmic drugs (AADs), catheter ablation, electrical cardioversion, or surgical techniques. AADs are also used to maintain sinus rhythm following catheter ablation or cardioversion. Rate control, in which fibrillation remains in the atrium, is focused on preventing the detrimental effects of rapid activation of the atria on the ventricles. Such effects include the development of cardiomyopathy and heart failure (HF). Depending on their CHADS (congestive HF, hypertension, age, diabetes mellitus, and prior stroke or transient ischemic attack) score, patients undergoing rate or rhythm control may require anticoagulation therapy to reduce the risk of stroke. Data from multicenter, randomized, prospective clinical trials suggest that rhythm control strategies with currently available AADs are not superior to rate control strategies in terms of survival rates (for a review see [1]). A common interpretation of these data is that the adverse effects of using AADs, secondary to extra-cardiac toxicity and ventricular proarrhythmia, exceed the benefit derived from their limited capability to maintain sinus rhythm [1]. However, AF patients with maintained sinus rhythm (with or without AADs) have a better survival rate and quality of life than those in whom AF persists [2,3]. Although the use and efficacy of catheter ablation-based approaches in AF treatment have increased significantly over the past decade, pharmacological agents remain the first-line therapy for rhythm management of AF [4]. It has been speculated that rhythm control using AADs would be preferable for the treatment of most AF patients if safer and more effective AADs were available [1,5]. Most AADs in current clinical use, and those that are under development, exert their anti-AF actions exclusively or primarily via modulation of cardiac ion-channel activity. However, AF is commonly associated with both atrial electrical and structural abnormalities as well as with a number of, often overlapping, intracardiac and extra-cardiac diseases (including HF, hypertension, coronary artery disease, and myocardial infarction). These abnormalities and diseases may significantly modulate the safety and anti-AF efficacy of AAD therapy. Therefore, development of anti-AF agents is focused on alteration of ion-channel activity and targeting upstream intracardiac and extracardiac, non-electrical factors that promote AF (Figure 1). Investigational approaches for pharmacological AF treatments that alter gap junctions or intracellular calcium activity have yielded some positive data but these agents remain far from clinical testing [6]. Figure 1 Current prominent investigational strategies for rhythm control of AF.

Pharmacological Treatment of Atrial Fibrillation: Mechanisms of Action and Efficacy of Class III Drugs

Atrial fibrillation represents a major clinical, social and economical matter, and its importance is expected to increase even more in the near future. The progressive ageing of population is associated with an inevitable rising in incidence and prevalence of this rhythm disorder, which limits functional capability, favours occurrence of cerebrovascular events and increases people's request for emergency room visits and hospital recovery. In spite of the increasing successes of the interventional non-pharmacological therapies, drug treatment of patients with atrial fibrillation in relation to conversion to sinus rhythm and prevention of recurrences, maintains a critical role. Several antiarrhythmic drugs are nowadays available, but their efficacy is limited by the high rate of arrhythmias recurrences and by side effects during acute and chronic treatment. Drugs interfering with potassium channels (Class III drugs) have been proposed and used in patients with atrial fibrillation. Aim of this review is to discuss the most recent data on the efficacy and feasibility of class III drugs in atrial fibrillation. Experimental and clinical data on dronedarone, ibutilide, dofetilide, azimilide, ersentilide and ambasilide will be hereby discussed.

The safety of digoxin as a pharmacological treatment of atrial fibrillation

Digoxin has traditionally been the drug of choice for ventricular rate control in patients with chronic atrial fibrillation (AF), with or without heart failure (HF) with systolic dysfunction. In patients with permanent AF, digoxin monotherapy is ineffective to control ventricular rate during exercise, but the combination of digoxin with a β-blocker or a non-dihydropyridine calcium channel antagonist can control heart rate both at rest and during exercise. Only a few randomised, controlled studies have evaluated the adverse effects of digoxin in patients with AF in a systematic way and side effects requiring drug withdrawal have rarely been reported. When reported, the most frequent adverse effects were cardiac arrhythmias (ventricular arrhythmias, AV block of varying degrees and sinus pauses). This evidence suggested that, in contrast to other antiarrhythmic drugs, digoxin is a safe drug in patients with AF. However, this safety profile can be erroneous due to the short follow-up of the studies and patient selection. Because patients with HF have been excluded in most studies, the safety profile of digoxin in this population has not been directly addressed. Early recognition that an arrhythmia is related to digoxin intoxication as well as recognition of concomitant medications or medical conditions that may directly alter the pharmacokinetic profile of digoxin, or indirectly alter its cardiac effects by pharmacodynamic interactions remain essential for safe and effective use of digoxin in patients with AF.