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Lee G.,Royal Melbourne Hospital | Roberts-Thomson K.,University of Adelaide | Madry A.,Royal Melbourne Hospital | Spence S.,Royal Melbourne Hospital | And 8 more authors.
Heart Rhythm | Year: 2011

Background: Complex fractionated atrial electrograms (CFAEs) and regions of high dominant frequency (DF) both may identify sites critical to the maintenance of atrial fibrillation (AF). CFAEs may be defined by either (1) complex multicomponent electrograms (EGMs) and/or continuous electrical activity (multicomponent/continuous EGM) or (2) discrete high-frequency EGMs. Objective: The purpose of this study was to test if the 2 definitions of CFAE identify the same arrhythmia substrate and determine the relationship of CFAE to areas of high DF. Methods: High-density epicardial mapping of the posterior left atrium was performed in 10 patients with long-lasting persistent AF. Point-by-point analysis was performed to determine the spatial distribution and correlation of CFAE defined as either (1) multicomponent/continuous-EGMs or (2) AF cycle length <120 ms. Additionally, spatial analysis was performed to determine the relationship of high DF sites to CFAE sites defined by each of the 2 definitions. Results: The percentage of sites deemed CFAE varied markedly between patients and was different depending on the definition of CFAE adopted. There was a poor correlation between CFAE defined by multicomponent/continuous EGMs and AF cycle length <120 ms (r = 0.18). High DF sites were arranged in clusters evenly distributed throughout the posterior left atrium, with 4.2 ± 1.0 high DF clusters per patient. Although there was poor point-by-point correlation between multicomponent/continuous EGMs and high DF sites (r = 0.107), spatial analysis revealed that 96% of multicomponent/ continuous EGMs were found adjacent to and partially surrounding (≤5 mm) high DF sites. Conclusion: There is poor anatomic overlap between CFAE defined by multicomponent/continuous EGMs and CFAE defined by AF cycle length <120 ms. Multicomponent/continuous EGMs are found adjacent to and surrounding sites of high DF. Further studies are needed to determine the mechanisms responsible for these different signals. © 2011 Heart Rhythm Society. All rights reserved. Source

Cropley J.E.,Victor Chang Cardiac Research Institute | Cropley J.E.,University of New South Wales | Eaton S.A.,Victor Chang Cardiac Research Institute | Eaton S.A.,University of New South Wales | And 16 more authors.
Molecular Metabolism | Year: 2016

Objective: Parental obesity can induce metabolic phenotypes in offspring independent of the inherited DNA sequence. Here we asked whether such non-genetic acquired metabolic traits can be passed on to a second generation that has never been exposed to obesity, even as germ cells. Methods: We examined the F1, F2, and F3 a/a offspring derived from F0 matings of obese prediabetic A vy/a sires and lean a/a dams. After F0, only lean a/a mice were used for breeding. Results: We found that F1 sons of obese founder males exhibited defects in glucose and lipid metabolism, but only upon a post-weaning dietary challenge. F1 males transmitted these defects to their own male progeny (F2) in the absence of the dietary challenge, but the phenotype was largely attenuated by F3. The sperm of F1 males exhibited changes in the abundance of several small RNA species, including the recently reported diet-responsive tRNA-derived fragments. Conclusions: These data indicate that induced metabolic phenotypes may be propagated for a generation beyond any direct exposure to an inducing factor. This non-genetic inheritance likely occurs via the actions of sperm noncoding RNA. © 2016 The Author(s). Source

Lee G.,Royal Melbourne Hospital | Lee G.,University of Melbourne | Kumar S.,Royal Melbourne Hospital | Kumar S.,University of Melbourne | And 19 more authors.
European Heart Journal | Year: 2014

Objectives To characterize the nature of atrial fibrillation (AF) activation in human persistent AF (PerAF) using modern tools including activation, directionality analyses, complex-fractionated electrogram, and spectral information.BackgroundThe mechanism of PerAF in humans is uncertain.Methods and resultsHigh-density epicardial mapping (128 electrodes/6.75 cm2) of the posterior LA wall (PLAW), LA and RA appendage (LAA, RAA), and RSPV-LA junction was performed in 18 patients with PerAF undergoing open heart surgery. Continuous 10 s recordings were analysed offline. Activation patterns were characterized into four subtypes (i) wavefronts (broad or multiple), (ii) rotational circuits (≥2 rotations of 360), (iii) focal sources with centrifugal activation of the entire mapping area, or (iv) disorganized activity [isolated chaotic activation(s) that propagate ≤3 bipoles or activation(s) that occur as isolated beats dissociated from the activation of adjacent bipole sites].Activation at a total of 36 regions were analysed (14 PLAW, 3 RSPV-LA, 12 LAA, and 7 RAA) creating a database of 2904 activation patterns. In the majority of maps, activation patterns were highly heterogeneous with multiple unstable activation patterns transitioning from one to another during each recording. A mean of 3.8 ± 1.6 activation subtypes was seen per map. The most common patterns seen were multiple wavefronts (56.2 ± 32%) and disorganized activity (24.2 ± 30.3%). Only 2 of 36 maps (5.5%) showed a single stable activation pattern throughout the 10-s period. These were stable planar wavefronts. Three transient rotational circuits were observed. Two of the transient circuits were located in the posterior left atrium, while the third was located on the anterior surface of the LAA. Focal activations accounted for 11.3 ± 14.2% of activations and were all short-lived (≤2 beats), with no site demonstrating sustained focal activity.ConclusionHuman long-lasting PerAF is characterized by heterogeneous and unstable patterns of activation including wavefronts, transient rotational circuits, and disorganized activity. © 2013 The Author. Source

Lee G.,Royal Melbourne Hospital | Lee G.,University of Melbourne | Spence S.,Royal Melbourne Hospital | Teh A.,Royal Melbourne Hospital | And 13 more authors.
Heart Rhythm | Year: 2012

Background: The pulmonary veins (PVs) and the PVLA (left atrium) junction are established sources of triggers initiating atrial fibrillation. In addition, they have been implicated in the maintenance of arrhythmia. Objective: To undertake high-density electrophysiological characterization of the right superior PVLA junction in humans. Methods: Mapping was performed in 18 patients without a history of atrial fibrillation undergoing cardiac surgery. A high-density epicardial plaque was positioned at the anterior right superior pulmonary vein covering 3 regions: LA, PVLA junction, and the PV. Isochronal maps were created during (1) sinus rhythm (SR); (2) LA pacing (LA-Pace); (3) PV pacing (PV-Pace); (4) LA programmed electrical stimulation (LA-PES); and (5) PV programmed electrical stimulation (PV-PES). Regional differences in conduction slowing/conduction block (CS/CB) and the prevalence of fractionated signals (FS) and double potentials (DPs) were assessed. Results: A region of isochronal crowding representing CS/CB developed at the PVLA junction in 84% of the maps. Three distinct activation patterns were seen. Pattern 1: Uniform SR activation without CS/CB. LA-Pace and PES caused 1 to 2 lines of isochronal crowding (CS/CB) at the PVLA junction. Pattern 2: CS/CB occurred at the PVLA junction in SR. LA/PV-Pace and LA/PV-PES caused an increase in CS/CB at the PVLA junction with widely split DPs and FS. Pattern 3: A single incomplete line of CS at the PVLA junction in SR. With LA/PV pacing and LA/PV-PES, multiple lines (<3) of CS/CB developed at the PVLA junction with evidence of circuitous activation and a marked increase in DPs and FS. Conclusion: High-density epicardial mapping of the right superior pulmonary vein demonstrates marked functional conduction delay and circuitous activation patterns at the PVLA junction, creating the substrate for reentry. © 2012 Heart Rhythm Society. Source

Lee G.,Royal Melbourne Hospital | Kalman J.M.,Royal Melbourne Hospital | Kalman J.M.,University of Melbourne | Vohra J.K.,Royal Melbourne Hospital | And 6 more authors.
Heart | Year: 2011

Background: Pulmonary vein (PV) reconnection is the Achilles heel of pulmonary vein isolation (PVI) for atrial fibrillation (AF). Dissociated pulmonary vein potentials (dPVP) may reflect abnormal PV automaticity, indicate more extensive PV muscular sleeve or may simply be an epiphenomenon. Objective: This study sought to determine the incidence, characteristics and prognostic significance of dPVP following PVI for AF. Methods: 89 consecutive patients (mean age 58.2±8.4 years, 75% male, 74% paroxysmal, 26% persistent AF) underwent antral PVI using threedimensional mapping systems with image integration with the endpoint of bidirectional PV block. Following PV electrical isolation the presence and characteristics of dPVP were recorded. Holter monitoring was performed at 3, 6 and 12 months. Acute PV reconnection was assessed over a 30-min waiting period. Results: Electrical isolation was achieved in all 372 PV targeted for ablation. 69 of 372 isolated PV (19%) demonstrated dPVP after acute electrical isolation. Sites of dPVP origin were the left superior in 36%, left inferior in 20%, right superior in 31% and right inferior in 12%. All 69 dPVP demonstrated slow activity (cycle length >1500 ms) with only four persisting more than 30 min after acute isolation. There was no difference in the clinical characteristics between dPVP-positive vs dPVP-negative patients. At a mean follow-up of 21±8 months the single procedure success was 25/33 (76%) in dPVPpositive versus 39/60 (64%) in dPVP-negative patients (p=-0.3). In the eight dPVP-positive patients who underwent a second procedure, 11 of the 14 (79%) veins with initial dPVP demonstrated PV - left atrial reconnection. Conclusion: dPVP are present in 19% of PV following acute antral electrical isolation. The presence of dPVP did not predict recurrent AF following PVI. Source

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