Disparate Evolution of Right and Left Atrial Rate During Ablation of Long-Lasting Persistent Atrial Fibrillation

Hocini, Mélèze; Nault, Isabelle; Wright, Matthew; Veenhuyzen, George D.; Narayan, Sanjiv M.; Jaı̈s, Pierre; Lim, Kang‐Teng; Knecht, Sébastien; Matsuo, Seiichiro; Forclaz, Andrei; Miyazaki, Shinsuke; Jadidi, Amir; O’Neill, Mark; Sacher, Frédéric; Clémenty, Jacques; Haı̈ssaguerre, Michel

doi:10.1016/j.jacc.2009.09.060

Cited by 111 publications

(98 citation statements)

References 37 publications

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“…The presence of a dominant frequency gradient also makes the multiple wavelet hypothesis less plausible because a hierarchy in frequencies defies randomness as postulated in this theory. 28 As demonstrated in our models, constitutive activation of I K,ACh may be one of the determinants of the seemingly increasing role of reentry in the maintenance of AF over time. We show that the constitutively active I K,ACh causes APD alternans, making the atrial tissue prone to wave break and reentry initiation.…”

Section: Mechanisms Of Af Maintenancementioning

confidence: 65%

Atrium-Specific Kir3.x Determines Inducibility, Dynamics, and Termination of Fibrillation by Regulating Restitution-Driven Alternans

et al. 2013

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Background— Atrial fibrillation is the most common cardiac arrhythmia. Ventricular proarrhythmia hinders pharmacological atrial fibrillation treatment. Modulation of atrium-specific Kir3.x channels, which generate a constitutively active current ( I K,ACh-c ) after atrial remodeling, might circumvent this problem. However, it is unknown whether and how I K,ACh-c contributes to atrial fibrillation induction, dynamics, and termination. Therefore, we investigated the effects of I K,ACh-c blockade and Kir3.x downregulation on atrial fibrillation. Methods and Results— Neonatal rat atrial cardiomyocyte cultures and intact atria were burst paced to induce reentry. To study the effects of Kir3.x on action potential characteristics and propagation patterns, cultures were treated with tertiapin or transduced with lentiviral vectors encoding Kcnj3 - or Kcnj5 -specific shRNAs. Kir3.1 and Kir3.4 were expressed in atrial but not in ventricular cardiomyocyte cultures. Tertiapin prolonged action potential duration (APD; 54.7±24.0 to 128.8±16.9 milliseconds; P <0.0001) in atrial cultures during reentry, indicating the presence of I K,ACh-c . Furthermore, tertiapin decreased rotor frequency (14.4±7.4 to 6.6±2.0 Hz; P <0.05) and complexity (6.6±7.7 to 0.6±0.8 phase singularities; P <0.0001). Knockdown of Kcnj3 or Kcnj5 gave similar results. Blockade of I K,ACh-c prevented/terminated reentry by prolonging APD and changing APD and conduction velocity restitution slopes, thereby altering the probability of APD alternans and rotor destabilization. Whole-heart mapping experiments confirmed key findings (eg, >50% reduction in atrial fibrillation inducibility after I K,ACh-c blockade). Conclusions— Atrium-specific Kir3.x controls the induction, dynamics, and termination of fibrillation by modulating APD and APD/conduction velocity restitution slopes in atrial tissue with I K,ACh-c . This study provides new molecular and mechanistic insights into atrial tachyarrhythmias and identifies Kir3.x as a promising atrium-specific target for antiarrhythmic strategies.

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Section: Mechanisms Of Af Maintenancementioning

confidence: 65%

Atrium-Specific Kir3.x Determines Inducibility, Dynamics, and Termination of Fibrillation by Regulating Restitution-Driven Alternans

et al. 2013

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“…14,28 An interesting finding was the proximity of foci and reentrant events suggesting that they possibly share common underlying tissue-level pathology or a functional link whereby foci promote formation of reentry in the vicinity. Recent data indicate that reentrant drivers have an affinity for the patchy zones bordering dense fibrosis shown by atrial MRI.…”

Section: Characteristics Of Af Driversmentioning

confidence: 99%

Driver Domains in Persistent Atrial Fibrillation

et al. 2014

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Background-Specific noninvasive signal processing was applied to identify drivers in distinct categories of persistent atrial fibrillation (AF). Methods and Results-In 103 consecutive patients with persistent AF, accurate biatrial geometry relative to an array of 252 body surface electrodes was obtained from a noncontrast computed tomography scan. The reconstructed unipolar AF electrograms acquired at bedside from multiple windows (duration, 9±1 s) were signal processed to identify the drivers (focal or reentrant activity) and their cumulative density map. The driver domains were catheter ablated by using AF termination as the procedural end point in comparison with the stepwise-ablation control group. The maps showed incessantly changing beat-to-beat wave fronts and varying spatiotemporal behavior of driver activities. Reentries were not sustained (median, 2.6 rotations lasting 449±89 ms), meandered substantially but recurred repetitively in the same region.In total, 4720 drivers were identified in 103 patients: 3802 (80.5%) reentries and 918 (19.5%) focal breakthroughs; most of them colocalized. Of these, 69% reentries and 71% foci were in the left atrium. Driver ablation alone terminated 75% and 15% of persistent and long-lasting AF, respectively. The number of targeted driver regions increased with the duration of continuous AF: 2 in patients presenting in sinus rhythm, 3 in AF lasting 1 to 3 months, 4 in AF lasting 4 to 6 months, and 6 in AF lasting longer. The termination rate sharply declined after 6 months. The mean radiofrequency delivery to AF termination was 28±17 minutes versus 65±33 minutes in the control group (P<0.0001). At 12 months, 85% patients with AF termination were free from AF, similar to the control population (87%,); P=not significant. Conclusions-Persistent Methods Study PopulationThis is a hospital-based study of patients with persistent AF. All consecutive patients referred for ablation of persistent AF were enrolled between May 2012 and June 2013. Persistent AF was defined as continuous AF from 7 days to 12 months and long-lasting AF beyond 12 months. There were no exclusion criteria based on the left atrial size, ventricular ejection fraction, or structural heart disease. All patients gave written informed consent to participate in the study, which involved the use of an investigational system for mapping. The study protocol was approved by the institutional Clinical Research and Ethics Committee. Noninvasive MappingIf patients presented in ongoing AF, mapping was performed bedside, within 24 hours preceding the invasive procedure. For those presenting in sinus rhythm, AF was induced in the electrophysiological laboratory by rapid atrial pacing decrementing up to 200-ms cycle length at the beginning of the invasive procedure and before transseptal puncture. Induced AF was analyzed after >30 minutes of sustenance (during this time, intracardiac catheter placement and invasive mapping were undertaken). Isoproterenol was not used to facilitate induction.The noninvasive mapping techniq...

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“…In terms of risk prediction additionally right atrial AF drivers [28][29][30] might be assessed by evaluation of temporal and spatial synchronicity of cyclic bi-atrial strain.…”

Section: Discussionmentioning

confidence: 99%

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2013

J Cardiobiol

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Purpose: Pulmonary vein isolation (PVI) is established as interventional treatment in atrial fibrillation (AF). Recent studies suggest that atrial reservoir function (preload) is involved in initiation of paroxysmal AF (AFparox) and conduit function (after-load) may be crucial in persistent AF (AFpers). Methods:We enrolled 336 consecutive patients scheduled for PVI (age 60±10 years). Point-to-point radiofrequency ablation was used in the majority of cases. Success was defined as a minimum of 3 months (median 12 months) follow-up as absence of recurrence of AF in any Holter ECG since PVI. in particular pulmonary vein isolation (PVI), can be considered as an early option in the management of patients with AF [5]. Success rates of the initial ablation procedure depend on the definition of success; they vary between 60 and 85% for AFparox and are lower for persistent AF (AFpers) [3,[6][7][8][9].The initiation of AF requires both a trigger and a susceptible substrate. In recurrent AFparox ectopic focal activity is thought to be local and limited to one or a few sites. On the contrary in AFpers there tend to be multiple ectopic sites throughout the atria and advanced damage of atrial myocardium (more susceptible substrate) [10][11][12][13]. Large left atrial (LA) size was found to be a predictor of recurrence of AF after electrical or pharmacological cardio-version as well as after ablative treatment [14][15][16][17]. The prognostic value of volume seems to be absent in AFparox, however [18].LA function comprises three phases: reservoir, conduit and active contraction phase [19]. LA-active function increases with slight volume load as long as LA structural dilatation is limited [19,20]. Thus, in early LA dysfunction as expected in AFparox systolic LA dimensions are ambiguous, because an increased systolic volume may reflect increased loading and/or size (history of dilatation).Recent studies suggest that preserved atrial reservoir function related to preload is a predictor of success [21]. Impairment of atrial reservoir function and poor long-term success of PVI in small left atria was related to enhanced fibrosis [22]. Whereas conduit function related to after-load may become increasingly important for PVI success in large atria with poor emptying.Thus, we tested the hypothesis that in AFparox atrial reservoir function and in AFpers residual conduit function is crucial for success of PVI by an analysis in the function-size plane in a retrospective study in our PVI data-base. As second end points we wanted to identify echocardiographic parameters potentially predicting recurrence of AF after PVI and elucidate the impact of body mass index (BMI) in this context.

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Disparate Evolution of Right and Left Atrial Rate During Ablation of Long-Lasting Persistent Atrial Fibrillation

Cited by 111 publications

References 37 publications

Atrium-Specific Kir3.x Determines Inducibility, Dynamics, and Termination of Fibrillation by Regulating Restitution-Driven Alternans

Atrium-Specific Kir3.x Determines Inducibility, Dynamics, and Termination of Fibrillation by Regulating Restitution-Driven Alternans

Driver Domains in Persistent Atrial Fibrillation

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