Understanding Of Atrial Fibrillation Research Articles

The Role of MicroRNAs in Antiarrhythmic Therapy for Atrial Fibrillation.

Atrial fibrillation (AF) is the most common arrhythmia worldwide and has an enormous impact on our healthcare system as it is a major contributor of morbidity and mortality. Although there are several therapeutic options available, treatment of AF still remains challenging. AF pathophysiology is complex and still incompletely understood. In general, our understanding of AF is based on two mechanistic paradigms as functional hallmarks of AF: ectopic activity and reentry. Both ectopic activity and reentry are the result of remodelling processes. Functional and/or expressional changes in ion channels, connexins or calcium-handling proteins are important factors in electrical remodelling, whereas signalling processes leading to atrial dilatation and atrial fibrosis are key factors of structural remodelling. In recent years, new intriguing key players in AF pathophysiology have been identified: microRNAs (miRNAs). MiRNAs are short, non-coding RNA fragments that can regulate gene expression and have been demonstrated as important modifiers in signalling cascades leading to electrical and structural remodelling. In this article we review the miRNA-mediated molecular mechanisms underlying AF with special emphasis on the perspective of miRNAs as potential therapeutic targets for AF treatment.

Lone atrial fibrillation: electrophysiology, risk factors, catheter ablation and other non-pharmacologic treatments.

Atrial fibrillation occurring in the absence of cardiovascular disease in individuals younger than 60 years is known as lone atrial fibrillation. Nearly 1-12% of atrial fibrillation is considered to be lone atrial fibrillation. As our understanding of atrial fibrillation grows, we wonder as to whether there is such as thing as "lone" atrial fibrillation? We know that male sex, obesity, obstructive sleep apnea, alcohol consumption and endurance sports increase the risk of developing lone atrial fibrillation. Family history of atrial fibrillation increases the risk strongly and there are several recognized mutations that are causative of lone atrial fibrillation. Common triggers for origin of atrial fibrillation are the pulmonary veins. The atrial substrate provides the reentry circuits for perpetuating the arrhythmia. The autonomic nervous system is a key modulator and allows the continuation of the atrial fibrillation. Catheter ablation has been very effective in the treatment of this condition. The ablation procedure involves isolation of the pulmonary veins, antrum, complex fractionated electrograms and other sites. Alternatively surgical techniques can be used to isolate the pulmonary veins and surgical techniques have evolved to minimally invasive procedures and these are as effective as catheter ablation. Early intervention improves the left atrial remodeling and may lead to fewer recurrences.

Abstract 161: Atrial Fibrillation in India: Insights from the PINNACLE India Outpatient Registry

Background: Atrial fibrillation (AF) is the most common arrhythmia worldwide. Most studies of AF focus on white populations in North America or Europe. Less is known about prevalence, etiology and treatment patterns of AF in India. To better understand the disease burden, we examined data from the PINNACLE India registry. Methods: PINNACLE India is the first cardiovascular data collection and reporting program in India. Data are collected by transmission from paper scanners and an electronic data collection tool. Patients are followed longitudinally if they return to a data collecting site. Results: AF is recorded in 0.39% (246) unique patients and 0.59% (865) of all encounters. The gender breakdown among AF patients is consistent with literature, but prevalence is low compared to other countries. Although we suspect that the diagnosis or documentation of AF is low, it appears that those diagnosed get treatment, since 35.77% are on Warfarin, 4.07% are on Dabigatran, and a substantial proportion is on other antithrombotic therapies. Conclusion: AF is tough to diagnose since it is often asymptomatic and clinicians need many tests to confirm diagnosis. Lack of documentation or detection of AF and its associated conditions is a concern. AF can lead to life threatening problems such as stroke and heart failure. The surveillance of AF in India is important in order to identify opportunities for intervention. Continued data collection through the use of a cardiovascular registry can improve the understanding of AF in India.

Rotors as drivers of atrial fibrillation and targets for ablation.

Atrial fibrillation (AF) is the most common arrhythmia targeted by catheter ablation. Despite significant advances in our understanding of AF, ablation outcomes remain suboptimal, and this is due in large part to an incomplete understanding of the underlying sustaining mechanisms of AF. Recent developments of patient-tailored and physiology-based computational mapping systems have identified localized electrical spiral waves, or rotors, and focal sources as mechanisms that may represent novel targets for therapy. This report provides an overview of Focal Impulse and Rotor Modulation (FIRM) mapping, which reveals that human AF is often not actually driven by disorganized activity but instead that disorganization is secondary to organized rotors or focal sources. Targeted ablation of such sources alone can eliminate AF and, when added to pulmonary vein isolation, improves long-term outcome compared with conventional ablation alone. Translating mechanistic insights from such patient-tailored mapping is likely to be crucial in achieving the next major advances in personalized medicine for AF.

A preliminary study on atrial epicardial mapping signals based on Graph Theory

In order to get a better understanding of atrial fibrillation, we introduced a method based on Graph Theory to interpret the relations of different parts of the atria. Atrial electrograms under sinus rhythm and atrial fibrillation were collected from eight living mongrel dogs with cholinergic AF model. These epicardial signals were acquired from 95 unipolar electrodes attached to the surface of the atria and four pulmonary veins. Then, we analyzed the electrode correlations using Graph Theory. The topology, the connectivity and the parameters of graphs during different rhythms were studied. Our results showed that the connectivity of graphs varied from sinus rhythm to atrial fibrillation and there were parameter gradients in various parts of the atria. The results provide spatial insight into the interaction between different parts of the atria and the method may have its potential for studying atrial fibrillation.

Oxidative Stress and Atrial Fibrillation

Atrial fibrillation (AF), one of the most prevalent cardiac arrhythmias, afflicts >3 million people in the United States.1 Because the risk of developing AF increases with age, the prevalence of AF is projected to be 7.6 million in 2050,1 when 1 in 5 Americans will be over the age of 65.2 AF not only causes debilitating symptoms and functional impairments owing to worsened hemodynamics and embolic stroke, it also increases the risk of mortality up to 1.5- to 1.9-fold.3 Despite the significant morbidity and mortality burden incurred with AF, there are limited therapeutic options that may improve the outcomes of AF patients, and these options are associated with significant AF recurrence rates.4 Article see p 1748 One possible explanation for the limitations of current therapies is that they do not address effectively or completely the underlying causes of AF. Evidence has been mounting that AF is associated with systemic and cardiac oxidation.4,5 Risk factors for AF are similar to those of atherosclerosis, a disease known to be perpetuated by oxidative stress. These risk factors, such as hypertension, aging, diabetes mellitus, and coronary artery bypass surgery, have each been associated with increases in the systemic markers of oxidation.4 In addition, there is also evidence of increased cardiac oxidation of myofibrillar protein5 and membrane lipids6 with AF or with risk factors linked to AF. Although it is not clear whether cardiac oxidation leads to systemic markers of oxidation or whether systemic oxidation leads to cardiac oxidation, the association of oxidative stress and AF is robust and suggests that AF is possibly a manifestation of a systemic disease. Despite the link between oxidative stress and AF, systemic antioxidant therapy for arrhythmias has not met with much success in clinical trials.7, …

The challenge of defining procedural endpoints for the surgical treatment of atrial fibrillation

The challenge of defining procedural endpoints for the surgical treatment of atrial fibrillation

An update on cardioembolic stroke

About one-fifth of all ischaemic strokes are cardioembolic. Recent years have seen considerable progress in our understanding of atrial fibrillation, the most important cause of cardioembolism, and evidence-based treatment strategies...

From MAZE to ICE: new concepts and new technologies for surgical ablation of atrial fibrillation

Curative treatment strategies for patients with atrial fibrillation were introduced in the late 1980s by Cox and co-coworkers.1 Following extensive animal experimental studies, the Maze procedure was developed and applied clinically. Subsequently, modifications of the initial surgical strategy were introduced, i.e. the Maze II and Maze III procedure.2,3 The efficacy of the Maze operation to establish permanent and stable sinus rhythm in >90% of patients treated was impressive.4 For a long time, the Maze III was cited as the ‘gold standard’ for the curative treatment of atrial fibrillation, but the extensive and time-consuming nature of this ‘cut and sew’ procedure prevented its widespread use. However, the curative potential of the Maze operation was recognized and inspired interventional electrophysiologists to attempt to reproduce the Maze procedure by means of transcatheter ablation techniques. Although never published as a full manuscript, the pioneering studies performed by John Swartz which were based on the Maze concept actually opened a new window for interventional electrophysiology, i.e. the development of catheter ablation of atrial fibrillation. Thus, the roots of curative treatment of atrial fibrillation clearly go back to cardiac surgery and it is unlikely that catheter interventional techniques would have made such significant progress without this initial ignition from the surgical theatre. In the late 1990s, the first surgical modifications of the classical Maze operation using radiofrequency energy were developed. Some of these concepts aimed at the partial or complete reproduction of the Maze III lesion line concept while others introduced new treatment strategies based on the growing pathophysiological understanding of atrial fibrillation.5–7 Subsequently, new energy sources such as microwave, cryoenergy, and highly focused ultrasound were introduced to facilitate lesion induction in the atria during cardiac surgery. Recently, Khargi and co-workers published a meta-analysis of … *Corresponding author. E-mail address : hindg{at}medizin.uni-leipzig.de

Our Unadorned Atrial Fibrillation: The Challenge of New Enigmas

In concert with many other areas of cardiovascular pathophysiology, our understanding of atrial fibrillation (AF), which not all that long ago seemed to be essentially devoid of any major unexplored domains, nonetheless continues to evolve, often in rather unpredictable directions. Novel mechanisms and operational postulates seem to be evolving continuously: new terms such as “electrical remodeling” (denominating the shortened atrial action potential) and “atrial fibrosis and atrial ionic remodeling” (simply, “structural remodeling”) are being introduced into the description of chronic AF.

Bigeminy Pacing: A New Protocol to Unmask Atrial Vulnerability

One of the most exciting developments in our understanding of atrial fibrillation (AF) mechanisms has been the recognition that "AF begets AF" in a process termed atrial remodeling. Little information is available about the events that mediate short-term remodeling. In a bigeminy atrial pacing protocol that produces a continuous extrasystole-postextrasystole cycle length, we sought to evaluate the electrophysiologic consequences of irregular atrial pacing. This study included 22 consecutive patients with documented paroxysmal AF and 10 control subjects. After evaluating the effective refractory period (ERP) and functional refractory period (FRP), bigeminy atrial pacing was performed for 5 minutes. The S1-S2 coupling interval during bigeminy pacing was programmed to a mean value of 275 +/- 45 msec, i.e., 45 msec longer than the basic ERP measured at 100 beats/min. During bigeminy pacing, AF that lasted longer than 1 minute occurred in 12 AF patients and in none of the control subjects (group I). Short salvos of AF occurred in 5 patients and 3 controls (group II). No arrhythmia occurred in 5 patients and 7 controls (group III). Sensitivity, specificity, and negative and positive predictive values of sustained AF induced by bigeminy pacing were 54%, 100%, 50%, and 100%, respectively. No differences were observed between different pacing rates during bigeminy, the premature coupling interval S1-S2, or the conduction parameters S2-A2 and A2. Group I had the shortest basic ERP (222 +/- 38 msec) and group III the longest ERP (242 +/- 21 msec, P < 0.05); group II was intermediate. Atrial ERPs and FRPs measured immediately after termination of 5 minutes of bigeminy pacing were shorter than during baseline. The degree of shortening was similar in AF patients and in controls. The locoregional conduction delay A2 did not change after the bigeminy protocol. This study demonstrates that atrial bigeminy pacing highly increases atrial vulnerability. This protocol appears interesting because its sensitivity and specificity are higher than those of the conventional extrastimulation test. This makes it attractive for routine diagnosis of undocumented paroxysmal AF. Because it may induce atrial arrhythmias independently of the classic mechanisms of wavelength shortening, this study emphasizes the need for new modalities in the prevention of atrial arrhythmias.

Atrial Fibrillation in Practice

With rapid advances in our understanding of atrial fibrillation, the focus in clinical practice is switching from prevention and palliation to complete cure. For information on the subject, clinicians can turn to numerous websites, and the topic is covered in many textbooks. However, Professor Lip and his publisher have identified the need for a pocket-size book on this most common of arrhythmias. In 68 pages and nine chapters he concisely covers all major aspects of atrial fibrillation from epidemiology to management strategies. The book is intended especially for internists, general practitioners, junior physicians and medical students, yet Professor Lip's simplification of the pathophysiology and electrophysiological mechanisms and pharmacological management will not rob it of interest to cardiologists or even cardiac electrophysiologists; indeed, it will prove a good reference source on the subject. Although a ‘British’ theme is evident throughout the book, especially in the chapters on epidemiology and management strategies, the coverage of all issues is based on worldwide research. On the inside of the cover is a simple flow diagram for management of atrial fibrillation that will help clinicians choose a pharmacological treatment and decide when to refer to a specialist centre for non-pharmacological therapy. In the USA, we are seeing increasing use of non-pharmacological methods—especially radiofrequency ablations—as adjunctive and at times curative modalities. The remarkable economy of space is achieved by liberal use of tables, boxes and bullet points; each chapter ends with a useful list of references as ‘further reading’. The quality of illustrations is good, and tables on pharmacological agents (referring to classification, route of administration, dosages and potential adverse effects) offer a quick and reliable source of information. Professor Lip has succeeded brilliantly with this brief guide.

Atrial electrophysiological remodeling caused by rapid atrial activation: underlying mechanisms and clinical relevance to atrial fibrillation.

One of the most exciting developments in our understanding of atrial fibrillation (AF) over the last several years has been the recognition that AF itself modifies atrial electrical properties in a way that promotes the occurrence and maintenance of the arrhythmia, a process termed 'atrial remodeling'. The principle stimulus for AF-induced atrial remodeling is the rapid atrial rate that results: rapid regular atrial pacing produces changes similar to those caused by AF in animal models. The mechanisms of atrial tachycardia-induced remodeling have been extensively explored, and involve changes in atrial electrophysiology associated with altered ion channel function. The most important ionic change is a reduction in L-type Ca2+ current, which reduces action potential duration (APD) and APD adaptation to rate. AF-induced changes in ion channel function appear to be due both to rapid voltage- and time-dependent alterations in channel availability caused by tachycardia and to slower downregulation of messenger RNA concentrations encoding alpha-subunits of specific ion channels. Atrial remodeling likely contributes importantly to a wide variety of clinical phenomena of previously unrecognized mechanism, including atrial dysfunction after cardioversion of AF, the increasing resistance to therapy of longer-standing AF, the association of AF with other forms of supraventricular tachyarrhythmia and the tendency of paroxysmal AF to become chronic. The present paper reviews the state of knowledge regarding the mechanisms and clinical consequences for AF of atrial remodeling caused by rapid atrial activation.