Repetitive 4-Week Periods of Atrial Electrical Remodeling Promote Stability of Atrial Fibrillation

Todd, Derick; Fynn, Simon P.; Walden, Andrew; Hobbs, W J; Arya, Sunil; Garratt, Clifford J.

doi:10.1161/01.cir.0000124006.84596.d9

Cited by 51 publications

(24 citation statements)

References 41 publications

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“…This allowed us to assess rotigaptide effects at the time of maximal ERP shortening, as well as at a later time when "second factors" came into play. 23 Electrophysiological variables during open-chest electrophysiological study in 3W-ATP dogs are illustrated in Figure 1. ERP was shortened significantly by ATP compared with A-sham dogs, and ERP rate-adaptation was eliminated in both RA ( Figure 1A) and LA ( Figure 1B).…”

Section: Changes In Electrophysiological Variables At Open-chest Elecmentioning

confidence: 99%

Model-Dependent Effects of the Gap Junction Conduction–Enhancing Antiarrhythmic Peptide Rotigaptide (ZP123) on Experimental Atrial Fibrillation in Dogs

et al. 2007

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Background-Abnormal intercellular communication caused by connexin dysfunction may be involved in atrial fibrillation (AF). The present study assessed the effect of the gap junctional conduction-enhancing peptide rotigaptide on AF maintenance in substrates that result from congestive heart failure induced by 2-week ventricular tachypacing (240 bpm), atrial tachypacing (ATP; 400 bpm for 3 to 6 weeks), and isolated atrial myocardial ischemia. Methods and Results-Electrophysiological study and epicardial mapping were performed before and after rotigaptide administration in dogs with ATP and congestive heart failure, as well as in similarly instrumented sham dogs that were not tachypaced. For atrial myocardial ischemia, dogs administered rotigaptide before myocardial ischemia were compared with no-drug myocardial ischemia controls. ATP significantly shortened the atrial effective refractory period (Pϭ0.003) and increased AF duration (Pϭ0.008), with AF lasting Ͼ3 hours in all 6-week ATP animals. Rotigaptide increased conduction velocity in ATP dogs slightly but significantly (Pϭ0.04) and did not affect the effective refractory period, AF duration, or atrial vulnerability. In dogs with congestive heart failure, rotigaptide also slightly increased conduction velocity (Pϭ0.046) but failed to prevent AF promotion. Rotigaptide had no statistically significant effects in sham dogs. Myocardial ischemia alone increased AF duration and impaired conduction (based on conduction velocity across the ischemic border and indices of conduction heterogeneity). Rotigaptide prevented myocardial ischemiainduced conduction slowing and AF duration increases. Conclusions-Rotigaptide improves conduction in various AF models but suppresses AF only for the acute ischemia substrate. These results define the atrial antiarrhythmic profile of a mechanistically novel antiarrhythmic drug and suggest that gap junction dysfunction may be more important in ischemic AF than in ATP remodeling or congestive heart failure substrates. (Circulation. 2007;115:310-318.)

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Section: Changes In Electrophysiological Variables At Open-chest Elecmentioning

confidence: 99%

Model-Dependent Effects of the Gap Junction Conduction–Enhancing Antiarrhythmic Peptide Rotigaptide (ZP123) on Experimental Atrial Fibrillation in Dogs

et al. 2007

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“…This results in a shortening of the atrial effective refractory period in order to compensate for calcium overload at the expense of a decrease in wavelength, thus promoting multiple wave reentry (electrical remodelling). 11 If AF persists, ultrastructural changes, such as increased cellular volume, sarcomere misalignment, proteolysis and loss of contractile elements, and accumulation of glycogen, may occur, leading to atrial myopathy. 12 Further changes involve remodelling of gap-junctions with reduction in the expression of connexin Cx40 and Cx43.…”

Section: Mechanisms and Remodellingmentioning

confidence: 99%

Atrial fibrillation – all change!

Savelieva

Camm

2007

Clinical Medicine

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Atrial fibrillation (AF) is said to be an epidemic, affecting 1-1.5% of the population in the developed world. 1 Lifetime risks for development of AF are 1 in 4 for men and women 40 years of age and older. 2 Atrial fibrillation is 12 to 20 times more common in people aged 80-85 years compared with individuals 50-60 years of age. 2,3 The high lifetime risk of AF and increased longevity underscore the important public health burden posed by the condition. The arrhythmia presently costs approximately 1% of the healthcare budget in the UK. 4 The clinical significance of AF lies in a fivefold increased risk of strokes, which are more severe and are associated with greater disability, and a threefold increased risk of congestive heart failure. 5,6 Atrial fibrillation leads to more hospital admissions than any other arrhythmia and according to recent surveys, the number of AF-related hospitalisations across the world almost tripled in 2000 compared with two decades ago. 7,8 Although AF is classically caused by hypertension, heart failure, myocardial infarction, mitral stenosis, thyrotoxicosis and alcohol, previously unrecognised risk factors, such as obesity, sleep apnoea, and tall stature, have now emerged. Furthermore, genetic predisposition to AF or specific genetically predetermined forms of the arrhythmia (eg in association with short QT syndrome) have been described.Recently, the challenge of asymptomatic, or silent, AF has been recognised. 9 Paroxysmal and recurrent forms are more likely to be symptomatic, while permanent AF is more often associated with few or no symptoms. The prevalence of sustained silent AF is believed to be 25-30%. Mechanisms and remodellingSeveral theories emerged regarding the mechanism of AF, which can be combined into two groups: the single focus hypothesis (automatic focus, mother wave, fixed rotor, moving rotor) and the multiple sources hypothesis (multiple foci, multiple wavelets, unstable reentry circuits, the combination of a single focus and multiple wavelets). 10 Those who advocate the single focus hypothesis believe that AF is due to a single rapid macroreentry circuit, with wavefronts emanating from the primary driver circuit (rotor) breaking against regions of varying refractoriness, giving rise to irregular global activity characterising the arrhythmia. A single focus fires at a regular, but very rapid rate, which cannot be followed by the rest of the atrial tissue in a 1:1 fashion, thus producing fibrillatory conduction. According to the multiple sources hypothesis, electrical activation in AF proceeds as multiple reentrant wavelets separated by lines of functional conduction block, generating irregular reentrant activity which occurs in a dyssynchronous fashion in various atrial regions (multiple circuit reentry).It has become obvious over the last few years that atrial electrical properties are altered by sustained AF, such that the atria become more susceptible to the initiation and maintenance of the arrhythmia. 10 Sustained AF in turn induces further electrophysiologica...

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“…In animal models, the remodeling process has been demonstrated to be reversible after restoration of the sinus rhythm, and is characterized by progressive increase in both atrial conduction velocity and refractoriness (reversal remodeling) 1,2,10,11,13,22 . Recovery has also been demonstrated in human atria 3,[23][24][25][26] .…”

Section: Introductionmentioning

confidence: 99%

Remodelagem atrial elétrica reversa após cardioversão de fibrilação atrial isolada de longa duração

Barbosa¹,

Benchimol-Barbosa²,

Bomfim³

et al. 2009

Arq. Bras. Cardiol.

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Background: Atrial fibrillation (AF) itself promotes electrophysiological changes, termed "electrical remodeling", facilitating its recurrence and maintenance. There is evidence that the remodeling process is reversible after restoration of the sinus rhythm (SR). However, the timing for the recovery of electrophysiological properties is still undefined.Objctive: The aim of this study was to assess the atrial electrical activation using P-wave signal-averaged electrocardiogram (P-SAECG) post-cardioversion of long-standing AF, focusing on the reversal remodeling process to identify the timing of the process stabilization.Methods: Subjects with lone persistent AF, eligible for cardioversion and successfully converted to SR, were enrolled at the study. SAECG was performed immediately after reversion to SR and repeated on days seven and thirty.Results: Of 31 subjects, nine presented early recurrence of atrial fibrillation, all of them in the first seven days postcardioversion; 22 remained in SR for at last one month and SAECG was obtained on days seven and thirty after cardioversion. In the latter, P-wave duration progressively abated from the first to the third SAECG (P-wave duration: 185.5±41.9 ms vs 171.7±40.5 ms vs 156.7±34.9 ms, respectively, first, second and third SAECG; p<0.001 for all matches). In the frequency domain analysis, spectral turbulence was not apparent in SAECG immediately postcardioversion, but sharply increased on day seven and remained unchanged on day thirty. Conclusion IntroductionAtrial fibrillation (AF) has been described as a selfperpetuating arrhythmia, which promotes electrophysiological changes in atrial tissue, facilitating its recurrence and maintenance [1][2][3][4][5] . Persistent AF usually progresses to a permanent form and the successful restoration and maintenance of sinus rhythm largely depend on arrhythmia duration, with longstanding AF being more resistant to cardioversion and more prone to recurrence [6][7][8][9] . Both resistance to cardioversion and tendency of recurrence are strongly related to the development of electrophysiological substrates characterized by shortened atrial effective refractory period 2,4,5,[10][11][12][13] , slow conduction in the atrial myocardium 10,11,[14][15][16] and dispersion of refractoriness 4,13,17,18 . These changes can be induced by both rapid atrial pacing and AF itself, and have been termed "electrical remodeling" 2 . The resultant electrophysiological abnormality is the presence of multiple wavelets around the atria, some of which circle back on them creating multiples reentry circuits, as proposed by Moe et al 19,20 in 1962 and 1964, and later confirmed by Allessie et al 21 in 1985.In animal models, the remodeling process has been demonstrated to be reversible after restoration of the sinus rhythm, and is characterized by progressive increase in both atrial conduction velocity and refractoriness (reversal remodeling) 1,2,10,11,13,22 . Recovery has also been demonstrated in human atria 3,[23][24][25][26] . On the other hand, a remarkab...

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Repetitive 4-Week Periods of Atrial Electrical Remodeling Promote Stability of Atrial Fibrillation

Cited by 51 publications

References 41 publications

Model-Dependent Effects of the Gap Junction Conduction–Enhancing Antiarrhythmic Peptide Rotigaptide (ZP123) on Experimental Atrial Fibrillation in Dogs

Model-Dependent Effects of the Gap Junction Conduction–Enhancing Antiarrhythmic Peptide Rotigaptide (ZP123) on Experimental Atrial Fibrillation in Dogs

Atrial fibrillation – all change!

Remodelagem atrial elétrica reversa após cardioversão de fibrilação atrial isolada de longa duração

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