Body surface localization of left and right atrial high-frequency rotors in atrial fibrillation patients: A clinical-computational study

Abstract Aims Gp91-containing NADPH oxidases (NOX2) are a significant source of myocardial superoxide production. An increase in NOX2 activity accompanies atrial fibrillation (AF) induction and electrical remodelling in animal models and predicts incident AF in humans; however, a direct causal role for NOX2 in AF has not been demonstrated. Accordingly, we investigated whether myocardial NOX2 overexpression in mice (NOX2-Tg) is sufficient to generate a favourable substrate for AF and further assessed the effects of atorvastatin, an inhibitor of NOX2, on atrial superoxide production and AF susceptibility. Methods and results NOX2-Tg mice showed a 2- to 2.5-fold higher atrial protein content of NOX2 compared with wild-type (WT) controls, which was associated with a significant (twofold) increase in NADPH-stimulated superoxide production (2-hydroxyethidium by HPLC) in left and right atrial tissue homogenates (P = 0.004 and P = 0.019, respectively). AF susceptibility assessed in vivo by transoesophageal atrial burst stimulation was modestly increased in NOX2-Tg compared with WT (probability of AF induction: 88% vs. 69%, respectively; P = 0.037), in the absence of significant alterations in AF duration, surface ECG parameters, and LV mass or function. Mechanistic studies did not support a role for NOX2 in promoting electrical or structural remodelling, as high-resolution optical mapping of atrial tissues showed no differences in action potential duration and conduction velocity between genotypes. In addition, we did not observe any genotype difference in markers of fibrosis and inflammation, including atrial collagen content and Col1a1, Il-1β, Il-6, and Mcp-1 mRNA. Similarly, NOX2 overexpression did not have consistent effects on RyR2 Ca2+ leak nor did it affect PKA or CaMKII-mediated RyR2 phosphorylation. Finally, treatment with atorvastatin significantly inhibited atrial superoxide production in NOX2-Tg but had no effect on AF induction in either genotype. Conclusion Together, these data indicate that while atrial NOX2 overexpression may contribute to atrial arrhythmogenesis, NOX2-derived superoxide production does not affect the electrical and structural properties of the atrial myocardium.

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Left and right atrial size and the occurrence predictors in patients with paroxysmal atrial fibrillation

International Journal of Cardiology ◽

10.1016/j.ijcard.2007.07.006 ◽

2008 ◽

Vol 130 (1) ◽

pp. 69-71 ◽

Cited By ~ 10

Author(s):

Qiqiong Cui ◽

Wei Zhang ◽

Hu Wang ◽

Xin Sun ◽

Huanyi Yang ◽

...

Keyword(s):

Atrial Fibrillation ◽

Paroxysmal Atrial Fibrillation ◽

Right Atrial ◽

Atrial Size ◽

Left And Right

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GW24-e1882 Quantitative proteomics analysis of changes in myocardial energy metabolism related proteins between left and right atrial appendages from patients with permanent atrial fibrillation

Heart ◽

10.1136/heartjnl-2013-304613.91 ◽

2013 ◽

Vol 99 (Suppl 3) ◽

pp. A35.1-A35

Author(s):

Tu Tao ◽

Zhou Sheng-hua ◽

Li Xu-ping ◽

Liu Zhen-jiang ◽

Liu Qi-ming

Keyword(s):

Atrial Fibrillation ◽

Energy Metabolism ◽

Quantitative Proteomics ◽

Right Atrial ◽

Proteomics Analysis ◽

Myocardial Energy Metabolism ◽

Permanent Atrial Fibrillation ◽

Left And Right ◽

Related Proteins

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Heterogeneous and anisotropic integrative model of pulmonary veins: computational study of arrhythmogenic substrate for atrial fibrillation

Interface Focus ◽

10.1098/rsfs.2012.0069 ◽

2013 ◽

Vol 3 (2) ◽

pp. 20120069 ◽

Cited By ~ 28

Author(s):

Oleg V. Aslanidi ◽

Michael A. Colman ◽

Marta Varela ◽

Jichao Zhao ◽

Bruce H. Smaill ◽

...

Keyword(s):

Atrial Fibrillation ◽

High Frequency ◽

Computational Study ◽

Pulmonary Veins ◽

Three Dimensional ◽

Primary Source ◽

Integrative Model ◽

Micro Computed Tomography ◽

Three Dimensional Model ◽

Arrhythmogenic Substrate

Mechanisms underlying the genesis of re-entrant substrate for the most common cardiac arrhythmia, atrial fibrillation (AF), are not well understood. In this study, we develop a multi-scale three-dimensional computational model that integrates cellular electrophysiology of the left atrium (LA) and pulmonary veins (PVs) with the respective tissue geometry and fibre orientation. The latter is reconstructed in unique detail from high-resolution (approx. 70 μm) contrast micro-computed tomography data. The model is used to explore the mechanisms of re-entry initiation and sustenance in the PV region, regarded as the primary source of high-frequency electrical activity in AF. Simulations of the three-dimensional model demonstrate that an initial break-down of normal electrical excitation wave-fronts can be caused by the electrical heterogeneity between the PVs and LA. High tissue anisotropy is then responsible for the slow conduction and generation of a re-entrant circuit near the PVs. Evidence of such circuits has been seen clinically in AF patients. Our computational study suggests that primarily the combination of electrical heterogeneity and conduction anisotropy between the PVs and LA tissues leads to the generation of a high-frequency (approx. 10 Hz) re-entrant source near the PV sleeves, thus providing new insights into the arrhythmogenic mechanisms of excitation waves underlying AF.

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Changes in left and right atrial size after cardioversion of atrial fibrillation: Role of mitral valve disease

Journal of the American College of Cardiology ◽

10.1016/0735-1097(93)90593-p ◽

1993 ◽

Vol 22 (6) ◽

pp. 1666-1672 ◽

Cited By ~ 66

Author(s):

A.T.Marcel Gosselink ◽

Harry J.G.M. Crijns ◽

Hans P.M. Hamer ◽

Hans Hillege ◽

Kong I. Lie

Keyword(s):

Atrial Fibrillation ◽

Mitral Valve ◽

Mitral Valve Disease ◽

Valve Disease ◽

Right Atrial ◽

Atrial Size ◽

Left And Right

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High-frequency atrial electrical activity

Journal of Applied Physiology ◽

10.1152/jappl.1961.16.2.300 ◽

1961 ◽

Vol 16 (2) ◽

pp. 300-304 ◽

Cited By ~ 9

Author(s):

Cesar A. Caceres ◽

George A. Kelser ◽

Juan Calatayud

Keyword(s):

High Frequency ◽

Electrical Potential ◽

P Wave ◽

Right Atrial ◽

High Frequencies ◽

Pr Interval ◽

Frequency Components ◽

Left And Right ◽

Electronic Filters ◽

High Frequency Content

Left and right atrial intracavitary and conventional surface leads were used to study electrocardiographic activity during the PR interval. Electronic filters were employed for analysis of wave frequency and harmonic content from 1.7 to 1700 cps. Amplifiers permitting standardization sensitivity to 500 mm/mv were used to obtain oscilloscopic tracings recorded at a paper speed of 75 mm/sec. Frequency analysis of the electrical potential recorded during P wave inscription demonstrated the presence of high-frequency content that is excluded by conventional electrocardiographic amplifiers. The high-frequency components are associated with the time of inscription of the electrocardiographic intrinsic deflection and have a relationship to the characteristics of the pressure-pulse curve. These relationships suggest that intracavitary high frequencies and the electrocardiographic intrinsic deflection originate from electrical discharges associated with initiation of contractile events. Submitted on June 6, 1960

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Effects of Atrial Fibrillation Cardioversion after Percutaneous Mitral Balloon Valvuloplasty on Echocardiographic Left and Right Atrial Functions

Ain Shams Medical Journal ◽

10.12816/0013847 ◽

2014 ◽

Vol 65 (1-3) ◽

pp. 69-75

Author(s):

Aly Ramzy ◽

Amal Ayoub ◽

Said Khaled ◽

Sameh Samir ◽

Ayman Mortada ◽

...

Keyword(s):

Atrial Fibrillation ◽

Balloon Valvuloplasty ◽

Right Atrial ◽

Left And Right ◽

Atrial Functions

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Effects of atrial fibrillation on left and right atrial dimensions, pressures, and compliances

AJP Heart and Circulatory Physiology ◽

10.1152/ajpheart.1993.264.4.h1093 ◽

1993 ◽

Vol 264 (4) ◽

pp. H1093-H1097 ◽

Cited By ~ 5

Author(s):

E. Leistad ◽

G. Christensen ◽

A. Ilebekk

Keyword(s):

Atrial Fibrillation ◽

Right Atrial ◽

Ventricular Rate ◽

Maximal Diameter ◽

Filling Phase ◽

Left And Right ◽

Wave Rose ◽

V Wave ◽

The Right ◽

Complete Av Block

The effects of atrial fibrillation on left and right atrial dimensions, pressures, and compliances were examined in two groups of seven barbiturate-anesthetized open-chest pigs. Atrial diameters and pressures were recorded during atrioventricular (AV) pace and thereafter during atrial fibrillation. Both rhythms were studied with constant ventricular rate after complete AV block. Left atrial maximal diameter, which appeared at the end of the atrial filling phase, decreased from 32.4 (28.9-36.7; median and 95% confidence interval) to 31.3 (28.4-35.7) mm after induction of atrial fibrillation. The right atrial maximal diameter also decreased, although not significantly. Atrial pressure at the peak of the v wave rose from 7.0 (5.5-8.5) to 9.6 (8.3-11.2) mmHg in the left atrium and from 5.0 (4.3-5.6) to 7.3 (6.2-8.7) mmHg in the right atrium. Left and right atrial chamber stiffness constants increased from 0.25 (0.19-0.48) to 0.41 (0.28-0.66) mm-1 and from 0.21 (0.11-0.31) to 0.33 (0.30-0.39) mm-1, respectively. Instantaneous diastolic atrial compliance decreased in both atria after induction of atrial fibrillation. Thus, during atrial fibrillation with regular ventricular rate, changes in atrial diameter, pressure, and compliance take place.

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Panoramic Endocardial Optical Mapping Demonstrates Serial Rotors Acceleration and Increasing Complexity of Activity During Onset of Cholinergic Atrial Fibrillation

Journal of the American Heart Association ◽

10.1161/jaha.121.022300 ◽

2021 ◽

Author(s):

Óscar Salvador‐Montañés ◽

Rafael J. Ramirez ◽

Yoshio Takemoto ◽

Steven R. Ennis ◽

Daniel Garcia‐Iglesias ◽

...

Keyword(s):

Atrial Fibrillation ◽

Cycle Length ◽

Optical Mapping ◽

Dominant Frequency ◽

Right Atrial ◽

Mapping System ◽

Left And Right ◽

Initiation Stage ◽

Mean Cycle ◽

Onset Atrial Fibrillation

Background Activation during onset of atrial fibrillation is poorly understood. We aimed at developing a panoramic optical mapping system for the atria and test the hypothesis that sequential rotors underlie acceleration of atrial fibrillation during onset. Methods and Results Five sheep hearts were Langendorff perfused in the presence of 0.25 µmol/L carbachol. Novel optical system recorded activations simultaneously from the entire left and right atrial endocardial surfaces. Twenty sustained (>40 s) atrial fibrillation episodes were induced by a train and premature stimuli protocol. Movies obtained immediately (Initiation stage) and 30 s (Early Stabilization stage) after premature stimulus were analyzed. Serial rotor formation was observed in all sustained inductions and none in nonsustained inductions. In sustained episodes maximal dominant frequency increased from (mean±SD) 11.5±1.74 Hz during Initiation to 14.79±1.30 Hz at Early Stabilization ( P <0.0001) and stabilized thereafter. At rotor sites, mean cycle length (CL) during 10 prerotor activations increased every cycle by 0.53% ( P =0.0303) during Initiation and 0.34% ( P =0.0003) during Early Stabilization. In contrast, CLs at rotor sites showed abrupt decreases after the rotors appearances by a mean of 9.65% ( P <0.0001) during both stages. At Initiation, atria‐wide accelerations and decelerations during rotors showed a net acceleration result whereby post‐rotors atria‐wide minimal CL (CLmin) were 95.5±6.8% of the prerotor CLmin ( P =0.0042). In contrast, during Early Stabilization, there was no net acceleration in CLmin during accelerating rotors (prerotor=84.9±11.0% versus postrotor=85.8±10.8% of Initiation, P =0.4029). Levels of rotor drift distance and velocity correlated with atria‐wide acceleration. Nonrotor phase singularity points did not accelerate atria‐wide activation but multiplied during Initiation until Early Stabilization. Increasing number of singularity points, indicating increased complexity, correlated with atria‐wide CLmin reduction ( P <0.0001). Conclusions Novel panoramic optical mapping of the atria demonstrates shortening CL at rotor sites during cholinergic atrial fibrillation onset. Atrial fibrillation acceleration toward Early Stabilization correlates with the net result of atria‐wide accelerations during drifting rotors activity.

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