Postoperative atrial fibrillation (POAF) complicates 20-40% of cardiac surgical procedures and 10-20% of non-cardiac thoracic operations. Typical features include onset at 2-4 days postoperatively, ...episodes that are often fleeting and a self-limited time course. Associated adverse consequences of POAF include haemodynamic instability, increased risk of stroke, lengthened hospital and intensive care unit stays and greater costs. Underlying mechanisms are incompletely defined but include intraoperative and postoperative phenomena, such as inflammation, sympathetic activation and cardiac ischaemia, that combine to trigger atrial fibrillation, often in the presence of pre-existing factors, making the atria vulnerable to atrial fibrillation induction and maintenance. A better understanding of the underlying mechanisms might enable the identification of new therapeutic targets. POAF can be prevented by targeting autonomic alterations and inflammation. β-Blocker prophylaxis is the best-established preventive therapy and should be started or continued before cardiac surgery, unless contraindicated. When POAF occurs, rate control usually suffices, and routine rhythm control is unnecessary; rhythm control should be reserved for patients who develop haemodynamic instability or show other indications that rate control alone will be insufficient. In this Review, we summarize the epidemiological and clinical features of POAF, the available pathophysiological evidence from clinical and experimental investigations, the results of prophylactic and therapeutic approaches and the consensus recommendations of various national and international societies.
Atrial fibrillation (AF) is the most common clinically relevant arrhythmia and is associated with increased morbidity and mortality. The incidence of AF is expected to continue to rise with the aging ...of the population. AF is generally considered to be a progressive condition, occurring first in a paroxysmal form, then in persistent, and then long-standing persistent (chronic or permanent) forms. However, not all patients go through every phase, and the time spent in each can vary widely. Research over the past decades has identified a multitude of pathophysiological processes contributing to the initiation, maintenance, and progression of AF. However, many aspects of AF pathophysiology remain incompletely understood. In this review, we discuss the cellular and molecular electrophysiology of AF initiation, maintenance, and progression, predominantly based on recent data obtained in human tissue and animal models. The central role of Ca(2+)-handling abnormalities in both focal ectopic activity and AF substrate progression is discussed, along with the underlying molecular basis. We also deal with the ionic determinants that govern AF initiation and maintenance, as well as the structural remodeling that stabilizes AF-maintaining re-entrant mechanisms and finally makes the arrhythmia refractory to therapy. In addition, we highlight important gaps in our current understanding, particularly with respect to the translation of these concepts to the clinical setting. Ultimately, a comprehensive understanding of AF pathophysiology is expected to foster the development of improved pharmacological and nonpharmacological therapeutic approaches and to greatly improve clinical management.
Atrial fibrillation (AF) is an extremely prevalent arrhythmia that presents a wide range of therapeutic challenges. AF usually begins in a self-terminating paroxysmal form (pAF). With time, the AF ...pattern often evolves to become persistent (nonterminating within 7 days). Important differences exist between pAF and persistent AF in terms of clinical features, in particular the responsiveness to antiarrhythmic drugs and ablation therapy. AF mechanisms have been extensively reviewed, but few or no Reviews focus specifically on the pathophysiology of pAF. Accordingly, in this Review, we examine the available data on the electrophysiological basis for pAF occurrence and maintenance, as well as the molecular mechanisms forming the underlying substrate. We first consider the mechanistic insights that have been obtained from clinical studies in the electrophysiology laboratory, noninvasive observations, and genetic studies. We then discuss the information about underlying molecular mechanisms that has been obtained from experimental studies on animal models and patient samples. Finally, we discuss the data available from animal models with spontaneous AF presentation, their relationship to clinical findings, and their relevance to understanding the mechanisms underlying pAF. Our analysis then turns to potential factors governing cases of progression from pAF to persistent AF and the clinical implications of the basic mechanisms we review. We conclude by identifying and discussing questions that we consider particularly important to address through future research in this area.
Summary Inadequacies in current therapies for atrial fibrillation have made new drug development crucial. Conventional antiarrhythmic drugs increase the risk of ventricular proarrhythmia. In drug ...development, the focus has been on favourable multichannel-blocking profiles, atrial-specific ion-channels, and novel non-channel targets (upstream therapy). Molecular modification of the highly effective multichannel blocker, amiodarone, to improve safety and tolerability has produced promising analogues such as dronedarone, although this drug seems less effective than does amiodarone. Vernakalant, an atrial-selective drug with reduced proarrhythmic risk, might be useful for cardioversion in atrial fibrillation. Ranolazine, another atrial-selective agent initially developed as an antianginal, has efficacy for atrial fibrillation and is being tested in prospective clinical trials. So-called upstream therapy with angiotensin-converting enzyme and angiotensin-receptor inhibitors, statins, or omega-3 fatty acids and fish oil that target atrial remodelling could be effective, but need further clinical validation. We focus on the basic and clinical pharmacology of newly emerging antiarrhythmic drugs and non-traditional approaches such as upstream therapy for atrial fibrillation.
Calcium Signaling and Cardiac Arrhythmias Landstrom, Andrew P; Dobrev, Dobromir; Wehrens, Xander H T
Circulation research,
2017-Jun-09, Letnik:
120, Številka:
12
Journal Article
Recenzirano
Odprti dostop
There has been a significant progress in our understanding of the molecular mechanisms by which calcium (Ca
) ions mediate various types of cardiac arrhythmias. A growing list of inherited gene ...defects can cause potentially lethal cardiac arrhythmia syndromes, including catecholaminergic polymorphic ventricular tachycardia, congenital long QT syndrome, and hypertrophic cardiomyopathy. In addition, acquired deficits of multiple Ca
-handling proteins can contribute to the pathogenesis of arrhythmias in patients with various types of heart disease. In this review article, we will first review the key role of Ca
in normal cardiac function-in particular, excitation-contraction coupling and normal electric rhythms. The functional involvement of Ca
in distinct arrhythmia mechanisms will be discussed, followed by various inherited arrhythmia syndromes caused by mutations in Ca
-handling proteins. Finally, we will discuss how changes in the expression of regulation of Ca
channels and transporters can cause acquired arrhythmias, and how these mechanisms might be targeted for therapeutic purposes.
Atrial fibrillation (AF), the most prevalent arrhythmia, is often associated with enhanced inflammatory response. Emerging evidence points to a causal role of inflammatory signaling pathways in the ...evolution of atrial electrical, calcium handling and structural remodeling, which create the substrate of AF development. In this review, we discuss the clinical evidence supporting the association between inflammatory indices and AF development, the molecular and cellular mechanisms of AF, which appear to involve multiple canonical inflammatory pathways, and the potential of anti-inflammatory therapeutic approaches in AF prevention/treatment.
•Atrial fibrillation (AF), the most prevalent arrhythmia, is often associated with enhanced inflammatory response.•In this review, we discuss the involvement of inflammatory signaling pathways in the pathogenesis of AF.•We also discuss the potential of anti-inflammatory therapeutic approaches in AF prevention/treatment.
Atrial fibrillation (AF) is the most frequent arrhythmia in adults. The prevalence and incidence of AF is going to increase substantially over the next few decades. Because AF increases the risk of ...stroke, heart failure, dementia, and others, it severely impacts the quality of life, morbidity, and mortality. Although the pathogenesis of AF is multifaceted and complex, focal ectopic activity and reentry are considered as the fundamental proarrhythmic mechanisms underlying AF development. Over the past 2 decades, large amount of evidence points to the key role of intracellular Ca
2+
dysregulation in both initiation and maintenance of AF. More recently, emerging evidence reveal that NLRP3 (NACHT, LRR, PYD domain-containing 3) inflammasome pathway contributes to the substrate of both triggered activity and reentry, ultimately promoting AF. In this article, we review the current state of knowledge on Ca
2+
signaling and NLRP3 inflammasome activity in AF. We also discuss the potential crosstalk between these two quintessential contributors to AF promotion.
Atrial fibrillation (AF) is an extremely common cardiac rhythm disorder that causes substantial morbidity and contributes to mortality. The mechanisms underlying AF are complex, involving both ...increased spontaneous ectopic firing of atrial cells and impulse reentry through atrial tissue. Over the past ten years, there has been enormous progress in understanding the underlying molecular pathobiology. This article reviews the basic mechanisms and molecular processes causing AF. We discuss the ways in which cardiac disease states, extracardiac factors, and abnormal genetic control lead to the arrhythmia. We conclude with a discussion of the potential therapeutic implications that might arise from an improved mechanistic understanding.
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