Early management of atrial fibrillation to prevent cardiovascular complications.

Atrial fibrillation (AF) is generally considered a progressive disease, typically evolving from paroxysmal through persistent to 'permanent' forms, a process attributed to electrical and structural remodelling related to both the underlying disease and AF itself. Medical treatment has yet to demonstrate clinical efficacy in preventing progression. Large clinical trials performed to date have failed to show benefit of rhythm control compared with rate control, but these trials primarily included patients at late stages in the disease process. One possible explanation is that intervention at only an early stage of progression may improve prognosis. Evolving observations about the progressive nature of AF, along with the occurrences of major complications such as strokes upon AF presentation, led to the notion that earlier and more active approaches to AF detection, rhythm-reversion, and maintenance of sinus rhythm may be a useful strategy in AF management. Approaches to early and sustained rhythm control include measures that prevent development of the AF substrate, earlier catheter ablation, and novel antiarrhythmic drugs. Improved classifications of AF mechanism, pathogenesis, and remodelling may be helpful to enable patient-specific pathophysiological diagnosis and therapy. Potential novel therapeutic options under development include microRNA-modulation, heatshock protein inducers, agents that influence Ca(2+) handling, vagal stimulators, and more aggressive mechanism-based ablation strategies. In this review, of research into the basis and management of AF in acute and early settings, it is proposed that progression from paroxysmal to persistent AF can be interrupted, with potentially favourable prognostic impact.

Coexistent HCN4 and GATA5 Rare Variants and Atrial Fibrillation in a Large Spanish Family.

BACKGROUND: Familial association of atrial fibrillation (AF) can involve single gene variants related to known arrhythmogenic mechanisms; however, genome-wide association studies often disclose complex genetic variants in familial and nonfamilial AF, making it difficult to relate to known pathogenetic mechanisms. METHODS: The finding of 4 siblings with AF led to studying 47 members of a family. Long-term Holter monitoring (average 298 hours) ruled out silent AF. Whole-exome sequencing was performed, and variants shared by the index cases were filtered and prioritised according to current recommendations. HCN4 currents (IHCN4) were recorded in Chinese hamster ovary cells expressing human p.P1163H or native HCN4 channels with the use of the patch-clamp technique, and topologically associating domain analyses of GATA5 variant were performed. RESULTS: The clinical study diagnosed 2 more AF cases. Five family members carried the heterozygous p.P1163H HCN4 variant, 14 carried the intronic 20,61040536,G,A GATA5 rare variant, and 9 carried both variants (HCN4+GATA5). Five of the 6 AF cases (onset age ranging from 33 to 70 years) carried both variants and 1 carried the GATA5 variant alone. Multivariate analysis showed that the presence of HCN4+GATA5 variants significantly increased AF risk (odds ratio 32.7, 95% confidence interval 1.8-591.4) independently from age, hypertension, and overweight. Functional testing showed that IHCN4 generated by heterozygous p.P1163H were normal. Topologically associating domain analysis suggested that GATA5 could affect the expression of many genes, including those encoding microRNA-1. CONCLUSION: The coincidence of 2 rare gene variants was independently associated with AF, but functional studies do not allow the postulation of the arrhythmogenic mechanisms involved.

Interatrial blocks. A separate entity from left atrial enlargement: a consensus report.

Impaired interatrial conduction or interatrial block is well documented but is not described as an individual electrocardiographic (ECG) pattern in most of ECG books, although the term atrial abnormalities to encompass both concepts, left atrial enlargement (LAE) and interatrial block, has been coined. In fact, LAE and interatrial block are often associated, similarly to what happens with ventricular enlargement and ventricular block. The interatrial blocks, that is, the presence of delay of conduction between the right and left atria, are the most frequent atrial blocks. These may be of first degree (P-wave duration >120 milliseconds), third degree (longer P wave with biphasic [±] morphology in inferior leads), and second degree when these patterns appear transiently in the same ECG recording (atrial aberrancy). There are evidences that these electrocardiographic P-wave patterns are due to a block because they may (a) appear transiently, (b) be without associated atrial enlargement, and (c) may be reproduced experimentally. The presence of interatrial blocks may be seen in the absence of atrial enlargement but often are present in case of LAE. The most important clinical implications of interatrial block are the following: (a) the first degree interatrial blocks are very common, and their relation with atrial fibrillation and an increased risk for global and cardiovascular mortality has been demonstrated; (b) the third degree interatrial blocks are less frequent but are strong markers of LAE and paroxysmal supraventricular tachyarrhythmias. Their presence has been considered a true arrhythmological syndrome.

Electroanatomic study of the left atrial insertion of an epicardial accessory pathway integrating the coronary sinus.

Endocardial electro-anatomic reconstruction of the left atrium and activation mapping defined a very large atrial accessory pathway insertion with a previously failed ablation attempt. Radiofrequency application inside the coronary sinus (CS), at a site with a sharp electrogram bridging atrial and ventricular electrograms abolished pathway conduction. The myocardium in the venous branches of the CS appeared to be responsible for this extraordinary atrial insertion area.

Delayed rhythm control of atrial fibrillation may be a cause of failure to prevent recurrences: reasons for change to active antiarrhythmic treatment at the time of the first detected episode.

Atrial fibrillation (AF) is associated with impaired functional capacity and quality of life and significant morbidity and mortality. The current management approach fails to maintain stable sinus rhythm (SR) in the majority of patients. For many years, guidelines have recommended antiarrhythmic treatment of a first AF episode only if the AF is poorly tolerated, a position that has been reinforced by studies showing no mortality or morbidity advantage of rhythm control over rate control. During the last decade, research has shown mechanisms of self-perpetuation of AF based on electrophysiological and structural remodelling induced by AF itself. There is mounting evidence that 'lone' AF is because of a host of factors, some of which may be easily treatable, such as hypertension, sleep apnoea, and obesity, thus allowing secondary prevention at the time of the first episode of AF. According to these concepts, lack of early intervention could be one of the reasons for long-term failure of maintenance of SR. In this position paper, we propose testing the working hypothesis that if an SR maintenance strategy is selected, treatment of AF should commence at the first-detected episode and should be based on a double strategy of SR restoration and aggressive treatment of associated conditions that promote atrial remodelling.

Atrial Flutter, Typical and Atypical: A Review.

Clinical electrophysiology has made the traditional classification of rapid atrial rhythms into flutter and tachycardia of little clinical use. Electrophysiological studies have defined multiple mechanisms of tachycardia, both re-entrant and focal, with varying ECG morphologies and rates, authenticated by the results of catheter ablation of the focal triggers or critical isthmuses of re-entry circuits. In patients without a history of heart disease, cardiac surgery or catheter ablation, typical flutter ECG remains predictive of a right atrial re-entry circuit dependent on the inferior vena cava-tricuspid isthmus that can be very effectively treated by ablation, although late incidence of atrial fibrillation remains a problem. Secondary prevention, based on the treatment of associated atrial fibrillation risk factors, is emerging as a therapeutic option. In patients subjected to cardiac surgery or catheter ablation for the treatment of atrial fibrillation or showing atypical ECG patterns, macro-re-entrant and focal tachycardia mechanisms can be very complex and electrophysiological studies are necessary to guide ablation treatment in poorly tolerated cases.

Executive Summary: European Heart Rhythm Association Consensus Document on the Management of Supraventricular Arrhythmias: Endorsed by Heart Rhythm Society (HRS), Asia-Pacific Heart Rhythm Society (APHRS), and Sociedad Latinoamericana de Estimulación Cardiaca y Electrofisiologia (SOLAECE).

This paper is an executive summary of the full European Heart Rhythm Association (EHRA) consensus document on the management of supraventricular arrhythmias, published in Europace. It summarises developments in the field and provides recommendations for patient management, with particular emphasis on new advances since the previous European Society of Cardiology guidelines. The EHRA consensus document is available to read in full at http://europace.oxfordjournals.org.