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PubMed2003

Pharmacotherapy of atrial fibrillation.

Atrial fibrillation is the most common sustained arrhythmia of clinical significance. Its prevalence rises with age. It is a significant cause of thromboembolic phenomena. We describe briefly the etiology and classification of atrial fibrillation, the risk factors for thromboembolism and stroke associated with it, the indications for hospitalization, and the therapeutic goal. We discuss in depth the management strategies for such patients and compare the impact of rate versus rhythm control in reducing morbidity and mortality attributed to arrhythmia, in light of past and present trials. A brief overview of the drugs used in the management of atrial fibrillation, their pharmacology and dosage, their effects and use in rhythm versus rate control with important side effects are also included. Finally, the prevention and treatment of thromboembolism in patients with atrial fibrillation, an important aspect of therapy, is revisited in light of recent advances.

Anti-Arrhythmia Agents↗

PubMed2003

[Atrial fibrillation].

Atrial fibrilation is the most frequent arrhythmia, the occurrence increasing with age and associated diseases. The incidence at the age below 60 years is markedly lower than one per cent, whereas in persons above 80 years of age it exceeds six per cent. The occurrence in patients with heart failure is from 10% (NYHA II) up to 50% (NYHA IV). Atrial fibrillation is classified into that observed for the first time and permanent, respectively, while transient forms include paroxyzmal and persistent atrial fibrillation. The diagnosis is based on ECG recording, while echocardiography is most significant. The therapy includes two basic questions--anticoagulant or anti-aggregation treatment and the control of rhythm or frequency. The anticoagulant therapy should be introduced in all patients, where contraindications are not present, being necessary before every cardioversion, provided atrial fibrillation lasts more than two days. In patients without any heart disease and with a physiological echocardiogram it is possible to administer only anti-aggregation treatment. Cardioversion (the control of rhythm) is recommended to all symptomatic patients, in other cases and especially in older persons the control of frequency is safer and of more advantage. Electrical cardioversion is more effective that a pharmacological treatment, the sinus rhythm is preferably controlled by dofetilid, ibutilid, propafenon and amiodaron. For the control of heart rate beta-blockers, diltiazem, verapamil and digitalis are recommended.

Atrial Fibrillation↗

PubMed1996

The management of atrial fibrillation.

Atrial fibrillation affects approximately one million persons in the United States, making it the most common cardiac arrhythmia seen in clinical practice. Its prevalence increases with age, and occurs in up to 10% of the population in the eighth decade of life. Unlike coronary heart disease, atrial fibrillation affects men and women approximately equally and, in an increasingly elderly population, will become an increasing burden to the health care system. The management of atrial fibrillation has undergone significant change in recent years. Large randomized controlled trials have shown that anticoagulation markedly reduces the risk of stroke, and a number of new antiarrhythmic agents are available for the restoration and maintenance of sinus rhythm. Furthermore, physicians have become more aware of the potential proarrhythmic side effects of all antiarrhythmic drugs. Finally, new procedures such as radiofrequency ablation of the atrioventricular junction and permanent pacing are playing increasing roles in the management of this arrhythmia. In this review, the identification of underlying causes and/or precipitating factors of atrial fibrillation, methods to control the ventricular response with atrioventricular nodal blocking drugs, the questions of whether restoration of sinus rhythm is a possible or desirable goal and how best to maintain sinus rhythm, should sinus rhythm be restored, and the importance of long-term anticoagulation with warfarin or antiplatelet therapy with aspirin are discussed.

Anti-Arrhythmia Agents↗

PubMed2006

Optimising stroke prevention in non-valvular atrial fibrillation.

Atrial fibrillation is associated with substantial morbidity and mortality. Pooled data from trials comparing antithrombotic treatment with placebo have shown that warfarin reduces the risk of stroke by 62%, and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin is superior to aspirin in preventing strokes, with a relative risk reduction of 36%. Ximelagatran, an oral direct thrombin inhibitor, was found to be as efficient as vitamin K antagonist drugs in the prevention of embolic events, but has been recently withdrawn because of abnormal liver function tests. The ACTIVE-W (Atrial Fibrillation Clopidogrel Trial with Irbesartan for Prevention of Vascular Events) study has demonstrated that warfarin is superior to platelet therapy (clopidogrel plus aspirin) in the prevention af embolic events. Idraparinux, a Factor Xa inhibitor, is being evaluated in patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs hold promise in atrial fibrillation through cardiac remodelling. Preliminary studies suggest that statins could interfere with the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for the exclusion of left atrial appendage are under investigation in high-risk patients.

Adult↗

PubMed1995

[The treatment of chronic atrial fibrillation].

Atrial fibrillation is a common arrhythmia. It is associated with increased morbidity and mortality, in part secondary to an increased rate of thromboembolism. Considering the arrhythmia's duration, a chronic and paroxysmal type can be recognized. Only the former will be discussed here. Treatment of atrial fibrillation should be aimed at restoring sinus rhythm. This may improve exercise tolerance and alleviate symptoms. In addition, it may obviate the need for antithrombotic therapy. Electrical cardioversion is the method of choice to restore sinus rhythm in patients with chronic atrial fibrillation. To prevent arrhythmia relapses, anti-arrhythmic drugs are often prescribed. These drugs, however, may have serious side effects, e.g. proarrhythmia. The pros and cons of antiarrhythmics should therefore be considered seriously before prescribing these drugs. An alternative strategy is to optimize ventricular rate response (usually pharmacologically) while the patient maintains in atrial fibrillation. To prevent thromboembolism, however, the use of antithrombotic is strongly recommended in most of these patients.

Anti-Arrhythmia Agents↗

PubMed2005

[Preventing cerebrovascular accidents during atrial fibrillation].

Atrial fibrillation, the most commonly encountered arrhythmia in clinical practice, is associated with substantial morbidity and mortality. Its incidence and prevalence are increasing, and it represents a growing clinical and economic burden. Recent research has highlighted new approaches to both pharmacological and non-pharmacological management. Pooled data from trials comparing antithrombotic treatment with placebo show that warfarin reduces the risk of stroke by 62% and that aspirin alone reduces the risk by 22%. Overall, in high-risk patients, warfarin was better than aspirin in preventing strokes, with a relative risk reduction of 36%, but the risk of major hemorrhage with warfarin was twice that with aspirin. Anticoagulation treatment needs to be tailored individually for patients on the basis of age, comorbidities, and contraindications. However, warfarin remains under-prescribed in clinical practice, for reasons related to patients (comorbidities) and physicians. The limitations of warfarin treatment have prompted the development of new anticoagulants with predictable pharmacokinetics that do not require as frequent monitoring. Ximelagatran, an oral direct thrombin inhibitor, was compared with warfarin in the SPORTIF program, which found both agents to be broadly effective in the prevention of embolic events, but observed abnormal liver function tests in 6% of patients on ximelagatran. Liver function monitoring during treatment is thus needed. Idraparinux, a factor Xa inhibitor administered by once weekly subcutaneous injections, is being evaluated in patients with atrial fibrillation. The ACTIVE trial is currently assessing the role of aspirin plus clopidogrel, compared with adjusted dose warfarin, in the prevention of vascular events in high-risk patients with atrial fibrillation. Angiotensin-converting enzyme inhibitors and angiotensin II receptor-blocking drugs interfere with atrial remodeling and show promise in atrial fibrillation, as suggested in the LIFE trial. Preliminary studies suggest that statins may reduce the risk of recurrence after electrical cardioversion. Finally, percutaneous methods for occlusion of the left atrial appendage are currently under investigation in patients at high risk of thromboembolism but with contraindications for chronic warfarin.

Administration, Oral↗

PubMed1998

Atrioventricular nodal modification and atrioventricular junctional ablation for control of ventricular rate in atrial fibrillation.

Atrial fibrillation results in several structural and functional changes in the heart that lead to worsening ventricular function. Although restoration of sinus rhythm is the ideal goal, it is not always feasible. Pharmacologic therapy is associated with adverse effects and is not always effective. We have reviewed the current status of nonpharmacologic therapy in the management of rapid ventricular response due to atrial fibrillation. Electrophysiologic studies have confirmed that the posterior inputs to the AV node have a shorter refractory period and are mainly responsible for maintaining rapid ventricular response in atrial fibrillation. AV nodal modification involves ablation of these posterior inputs in a sequential fashion until a significant reduction of ventricular response is achieved. This procedure has been reported to be successful in maintaining the controlled ventricular response in about 70% of the patients over long-term follow-up. Ablation of the AV node with implantation of a permanent pacemaker is a more definitive procedure and simpler to perform. Reduction in ventricular response achieved with this procedure results in improvement of the patient's clinical symptoms as well as the underlying left ventricular function. Nonpharmacologic therapy for control of ventricular rate should be considered for patients with atrial fibrillation, in whom pharmacologic therapy for rate control is ineffective or poorly tolerated.

Atrial Fibrillation↗

PubMed1996

Anticoagulation in nonvalvular atrial fibrillation.

Atrial fibrillation is a common cardiac arrhythmia. Management of atrial fibrillation should focus on prevention of thromboembolic complications and the treatment of arrhythmia related symptoms. This article will discuss anticoagulant therapy in nonvalvular atrial fibrillation and review results from several controlled trials.

Aged↗

PubMed2002

The immediate future for the medical treatment of atrial fibrillation.

Atrial fibrillation is the most commonly sustained cardiac arrhythmia and a common reason for mortality and morbidity. Atrial fibrillation causes disease for three reasons: i) the ventricular rate is often high, which leads to symptoms ranging from discomfort to life threatening heart failure; ii) the rhythm causes loss of atrioventricular synchrony, which reduces diastolic filling and may lead to heart failure; and iii) atrial contraction is lost leading to stagnant blood that again may lead to atrial thrombi and peripheral embolism. Thus, the treatment of atrial fibrillation is focused on the maintenance of sinus rhythm, rate control and prevention of embolism. For the maintenance of sinus rhythm, all drugs under current development are potassium channel blockers; the so-called class III anti-arrhythmic drugs. Those which have been further investigated appear to be valuable for maintenance of sinus rhythm but all carry a significant risk of pro-arrhythmia, in particular Torsade de Pointe ventricular tachycardia. Rate control has been a focus of treatment for many years and several very old drugs, including digoxin, are used for this. There is, to the author's knowledge, no current effort for evaluating new drugs for this indication. Prevention of embolism has for many years been obtained with vitamin K antagonists for which the clinical evidence is overwhelming. Previous attempts to replace vitamin K antagonists with aspirin have not been fruitful. A large number of newer anticoagulation regimes are in development, but to the author's knowledge only a single thrombin inhibitor is actively being developed for atrial fibrillation.

Journal Article↗

PubMed2000

Atrial Fibrillation.

Atrial fibrillation will present the most significant arrhythmia management challenge for clinicians in the new millennium, particularly as the percentage of elderly patients and longevity increase worldwide. The clinical manifestations of the arrhythmia are wide ranging: paroxysmal to permanent modes of occurrence and asymptomatic to severely symptomatic presentations. Perhaps most important, the major risks of atrial fibrillation are stroke and death. Current therapies remain heavily focused on pharmacologic efforts to reduce the severity of primary symptoms and to prevent stroke and other thromboembolic complications by means of anticoagulation. It has not yet been proven that prevention of atrial fibrillation will prolong survival, however. Nonpharmacologic therapies remain under intense basic and clinical investigation as promising means to improve outcome further for patients suffering from atrial fibrillation.

Journal Article↗

PubMed2001

Evaluation and management of atrial fibrillation.

Atrial fibrillation is a common cardiac arrhythmia with significant sequela. The goals of treating atrial fibrillation are rate control, prevention of thromboembolism, and maintenance of sinus rhythm. The epidemiology and pathophysiology of atrial fibrillation is reviewed, as well as strategies and recommendations for achieving therapeutic goals. The authors also review investigational therapeutic options using nonpharmacologic modalities.

Animals↗

PubMed1998

Mechanisms of pacing interventions in atrial fibrillation.

Atrial flutter is due to large single reentrant loops, typically oriented around the caval veins and a line of functional conduction block in between. These reentrant circuits can easily be terminated by properly timed extra beats colliding in the antidromic direction with the reentrant orthodromic wavefront and being blocked in the orthodromic direction within the area of slow conduction. Due to the complex situation in atrial fibrillation with multiple, ever-changing wavelets and a marked functional inhomogeneity of the atrial tissue, these simple concepts do not apply. However, regional control of atrial tissue by rapid pacing is feasible during atrial fibrillation, and through a multisite approach, this pacing modality might lead to a situation where the remaining nonentrained atrial tissue is just no longer reaching the critical mass. Single-site, dual-site, and biatrial pacing seems to reduce the incidence of atrial fibrillation recurrences. Specific advantages and disadvantages of each approach still need to be elucidated. Apart from preventing bradycardia, preventive pacing modes reduce intra-atrial conduction times and might reduce intra-atrial dispersion of refractoriness. Still, the specific mechanisms relevant for their effectiveness need further clarification.

Atrial Fibrillation↗

PubMed2000

[Antithrombotic therapy of atrial fibrillation].

Atrial fibrillation is a major source of stroke. During the past decade, large trials demonstrated the efficacy of anticoagulation and, to a lesser extent, aspirin in primary and secondary prevention of stroke in high risk patients with atrial fibrillation. In this article we reviewed the results of these studies and we present the current guidelines for the antithrombotic treatment of atrial fibrillation.

Atrial Fibrillation↗

PubMed2006

Controversies in atrial fibrillation.

Atrial fibrillation is the most common sustained cardiac arrhythmia, and contributes greatly to cardiovascular morbidity and mortality. Many aspects of the management of atrial fibrillation remain controversial. We address nine specific controversies in atrial fibrillation management, briefly focusing on the relations between mechanisms and therapy, the roles of rhythm and rate control, the definition of optimum rate control, the need for early cardioversion to prevent remodelling, the comparison of electrical with pharmacological cardioversion, the selection of patients for long-term oral anticoagulation, the roles of novel long-term anticoagulation approaches and ablation therapy, and the potential usefulness of upstream therapy targeting substrate development. The background of every controversy is reviewed and our opinions expressed. Here, we hope to inform physicians about the most important controversies in this specialty and stimulate investigators to address unresolved issues.

Aged↗

PubMed1998

Implantable atrial defibrillator for atrial fibrillation.

Atrial fibrillation is a common problem. Pharmacological and nonpharmacological approaches have limited therapeutic efficacy in many patients. Low energy transvenous atrial defibrillation using catheters positioned inside the right atrium and cornonary sinus has been shown to be efficacious in converting atrial fibrillation to sinus rhythm. We report the successful use of this technology in an implantable form in a patient with symptomatic atrial fibrillation. The patient could be kept in sinus rhythm using an implanted atrial defibrillator.

Atrial Fibrillation↗

PubMed2002

[Mechanisms of atrial fibrillation].

Atrial fibrillation occurs because of a complex interaction between an arrhythmogenic substrate, triggers factors and the autonomic nervous system. Underlying fundamental mechanisms are multiple, can cohabit and include schematically: multiple wavelet, stable microreentry, macro single meandering spiral wave reentry and focal atrial fibrillation arising from the pulmonary veins. More over, new concepts have emerged like the atrial fibrillation-induced electrical and structural remodeling which favors its own perpetuation. Experimental studies have shown a complex interaction between anatomical particularities of the atria and the activation fronts dynamic. All this recent progress open new and more efficient therapeutic perspectives for patients enduring atrial fibrillation.

Atrial Fibrillation↗

PubMed1992

The Maze procedure: a new treatment for atrial fibrillation.

Atrial fibrillation is a dysrhythmia with lethal complications afflicting thousands of people each year. Unfortunately, atrial fibrillation is frequently resistant to medical therapy and other nonsurgical treatments, such as cardioversion and catheter ablation. Past surgical procedures to correct the dysrhythmia have also proved ineffective. A surgical procedure has been developed in which multiple incisions are made in the atrium, creating an electrical maze. The maze procedure restores atrioventricular synchrony while simultaneously preventing macroreentry within the atria. It thereby eliminates the clinical sequelae often associated with atrial fibrillation and improves the quality of life for those patients refractory to current methods of treatment.

Aged↗

PubMed1997

Factors predisposing to the development of atrial fibrillation.

Atrial fibrillation (AF) is in most patients (approximately 70%) associated with organic heart disease including valvular heart disease, coronary artery disease, hypertension, hypertrophic cardiomyopathy, dilated cardiomyopathy, and congenital heart disease, mostly atrial septal defect in adults. In many chronic conditions, determining whether AF is the result or is unrelated to the underlying heart disease, remains unclear. The list of possible etiologies also include cardiac amyloidosis, hemochromatosis and endomyocardial fibrosis. Other heart diseases, such as mitral valve prolapse (without mitral regurgitation), calcifications of the mitral annulus, atrial myxoma, pheochomocytoma, and idiopathic dilated right atrium may present with AF. Atrial fibrillation may occur in the absence of detectable organic heart disease, the so-called "lone AF", in about 30% of cases. The term "idiopathic AF" implies the absence of any detectable etiology including hyperthyroidism, chronic obstructive lung disease, overt sinus node dysfunction, and overt or concealed preexcitation (Wolff-Parkinson-White syndrome), only to mention a few of other uncommon causes of AF. The autonomous nervous system may contribute to the occurrence of AF in some patients. AF occurs commonly. In patients with valvular heart disease, AF is common, particularly when the mitral valve is involved. The occurrence of AF is unrelated to the severity of mitral stenosis or mitral regurgitation but is more common in patients with enlarged left atrium and congestive heart failure. In patients with coronary artery disease, AF occurs predominantly in older patients, males, and patients with left ventricular dysfunction, Important predictive factors of AF include hypertension, left ventricular hypertrophy and diabetes. The risk of the development of AF, in an individual patient, is often difficult to assess. Increasing age, presence of valvular heart disease, and congestive heart failure increase the risk of atrial fibrillation.

Animals↗