Loss of Continuity in the Thin Epicardial Layer Because of Endomysial Fibrosis Increases the Complexity of Atrial Fibrillatory Conduction

Introduction: Transition of paroxysmal to longstanding persistent atrial fibrillation (LsPAF) is associated with progressive longitudinal dissociation in conduction and a higher incidence of focal fibrillation waves. The aim of this study was to provide direct evidence that the substrate of LsPAF consists of an electrical double-layer of dissociated waves, and that focal fibrillation waves are caused by endo-epicardial breakthrough. Hypothesis: LsPAF in humans is caused by electrical dissociation of the endo- and epicardial layer. Methods: Intra-operative mapping of the endo- and epicardial right atrial wall was performed in 9 patients with induced (N=4), paroxysmal (N=1), persistent (N=2) or longstanding-persistent AF (N=2). A clamp of two rectangular electrode-arrays (128 electrodes; inter-electrode distance 2mm) was introduced through an incision in the right atrial appendage. Series of 10 seconds of AF were analyzed and the incidence of endo-epicardial dissociation (≥15ms) was determined for all 128 endo-epicardial recording sites. Results: In patients with LsPAF the averaged degree of endo-epicardial dissociation was highest (24.9% vs. 5.9%). Using strict criteria for breakthrough (presence of an opposite wave within 4mm and <15ms before the origin of the focal wave), the far majority (77%) of all focal fibrillation waves could be attributed to endo-epicardial excitation. Conclusions: During LsPAF considerable differences in activation of the right endo- and epicardial wall exist. Endo-epicardial fibrillation waves that are out of phase, may conduct transmurally and create breakthrough waves in the opposite layer. This may explain the high persistence of AF and the low succes rate of ablative therapies in patients with LsPAF.

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Embryonic development of the heart

Development ◽

10.1242/dev.22.3.333 ◽

1969 ◽

Vol 22 (3) ◽

pp. 333-348

Author(s):

Francis J. Manasek

Keyword(s):

Cell Layer ◽

Embryonic Heart ◽

Outer Cell ◽

Chick Embryos ◽

Myocardial Wall ◽

Undifferentiated Cells ◽

Epicardial Layer ◽

Outer Cell Layer ◽

Heart Wall

The mature heart may be thought of as consisting of three layers, endocardium, myocardium, and an outer investing tissue called the epicardium. During early formation of the tubular heart of chick embryos, at about the 8-somite stage, two tissue layers become clearly discernible with the light microscope: the endocardium and the developing myocardial wall. The outer epicardial layer does not appear until later in development. It is generally accepted that embryonic heart wall or ‘epimyocardium’ is composed of muscle and undifferentiated cells. As its name implies, the epimyocardium is thought to give rise to myocardium and epicardium. Kurkiewicz (1909) suggested that the epicardium was not an epimyocardial derivative but rather is formed from cells originating in the sinus venosus region, which migrate over the surface of the heart. Nevertheless, it has become generally accepted that the outer cell layer of the embryonic heart wall differentiates in situ to give rise to the definitive visceral epicardium (Patten, 1953).

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Abstract 18492: Phase Analysis Detects Human Atrial Fibrillation Sources While Classical Activation Mapping May Not: Reconciling Classical and Computational Mapping

Circulation ◽

10.1161/circ.132.suppl_3.18492 ◽

2015 ◽

Vol 132 (suppl_3) ◽

Author(s):

Junaid A Zaman ◽

Gautam G Lalani ◽

Tina Baykaner ◽

Shirley Park ◽

David E Krummen ◽

...

Keyword(s):

Atrial Fibrillation ◽

Phase Analysis ◽

Atrial Tachycardia ◽

Source Detection ◽

Perfect Agreement ◽

Classical Activation ◽

Electrode Noise ◽

Fibrillatory Conduction ◽

Activation Mapping ◽

Human Atrial Fibrillation

Introduction: The mechanisms maintaining human persistent AF are elusive. It is striking how most optical mapping studies in animal and recently human AF show rotors and focal sources, while most classical activation mapping studies of electrograms do not. We tested the hypothesis that sites in human persistent AF showing rotors by phase analysis may, due to precession (‘wobble’) and fibrillatory collision, rarely reveal sources in activation maps. Methods: We studied 25 patients with persistent AF (LA 47 mm, CHADS2=1.9), in whom phase-mapping of electrograms from 64 pole baskets revealed rotors/focal sources where ablation terminated AF. Electrograms (fig A) were annotated (Matlab) using minimum dV/dt (unipoles, fig B) and peak amplitude criteria (bipoles) to create contours (isochrones), that were classified into a) complete, b) partial or c) unresolvable sources. Results: In each case, ablation at phase-identified rotors/sources (4.0±5.7 mins) terminated persistent AF to sinus rhythm (fig C, 64%) or atrial tachycardia. Notably, isochrones detected sources in only 5/25 (20%) of cases (fig D), more easily in unipolar than bipolar signals. Isochrones revealed partial sources in 11 (44%) and were unresolvable in 9 (36%). Source detection in classical maps was obscured by low signal: noise, varying sequence (rotor precession), or electrode noise that phase analysis resolved by analyzing neighboring sites (fig E). The figure summarizes these steps for a case with perfect agreement between activation and phase maps. Conclusions: Rotors and focal sources for human persistent AF detected by phase analysis were mostly undetected in activation maps, due to rotor precession and fibrillatory conduction. These data may inform approaches to revise classical criteria to better map AF.

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The outcome of ablation for non-paroxysmal atrial fibrillation targeting spatiotemporal electrogram dispersion compared with ganglionated plexi ablation

European Heart Journal ◽

10.1093/ehjci/ehaa946.0617 ◽

2020 ◽

Vol 41 (Supplement_2) ◽

Author(s):

K Sakata ◽

T Tanaka ◽

S Yamashita ◽

K Yamashiro

Keyword(s):

Atrial Fibrillation ◽

Study Groups ◽

Atrial Arrhythmia ◽

Single Procedure ◽

Ganglionated Plexi ◽

Kaplan Meier ◽

Significant Difference ◽

Left And Right ◽

Fibrillatory Conduction ◽

And Control

Abstract Background Although catheter ablation targeting ganglionated plexi (GP) playing an important role in formation of triggers and substrates of atrial fibrillation (AF) has been reported as one of the effective ablation strategies in non-paroxysmal AF (non-PAF) patients, its effectiveness varies among the study groups. More recently, ablation targeting spatiotemporal electrogram dispersion (STED) areas, assumed to contain AF drivers in forms of rotational activation is proposed. However, the optimal ablation strategy for non-PAF is still controversial since the exact mechanisms of non-PAF are not well understood. Purpose To investigate the effectiveness of GP ablation for autonomic modification and STED ablation for modulation of AF drivers. Methods Consecutive 149 non-PAF patients who underwent STED ablation in our center were enrolled. We detected STED areas within the whole left and right atrium during AF using PentaRay®, and ablated them. If AF was terminated during STED ablation, we finished the procedure without burning the remaining STED areas. If not, electrical cardioversion was applied. The outcome was compared with that in consecutive 156 non-PAF patients undergoing GP ablation previously in our center. Results (1) The clinical characteristics were comparable between two groups (see Table). (2) A Kaplan-Meier curve showed that there was no significant difference between the freedom rates from non-PAF/non-paroxysmal atrial tachycardia (non-PAT) after single procedure in STED group and GP group (Figure, left). (3) However, the freedom rates from non-PAT in STED group was significantly lower than that GP group (Figure, right). Conclusions The recurrence type of atrial arrhythmia after ablation was remarkably different between ablation of STED and GP. STED ablation might eliminate fibrillatory conduction and control AF driver in patients with non-PAF. Freedom from atrial arrhythmia Funding Acknowledgement Type of funding source: None

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Epicardial prestrained confinement and residual stresses: a newly observed heart ventricle confinement interface

Journal of The Royal Society Interface ◽

10.1098/rsif.2019.0028 ◽

2019 ◽

Vol 16 (152) ◽

pp. 20190028 ◽

Cited By ~ 2

Author(s):

Xiaodan Shi ◽

Yue Liu ◽

Katherine M. Copeland ◽

Sara R. McMahan ◽

Song Zhang ◽

...

Keyword(s):

Residual Stresses ◽

Resistance Mechanism ◽

Mechanical Effect ◽

Fe Model ◽

Prosthetic Devices ◽

Dominant Component ◽

Myocardial Stress ◽

Epicardial Layer ◽

Additional Resistance ◽

Biaxial Mechanical Testing

The heart epicardial layer, with elastin as the dominant component, has not been well investigated, specifically on how it contributes to ventricular biomechanics. In this study, we revealed and quantitatively assessed the overall status of prestraining and residual stresses exerted by the epicardial layer on the heart left ventricle (LV). During porcine heart wall dissection, we discovered that bi-layered LV surface strips, consisting of an epicardial layer and cardiac muscle, always curled towards the epicardial side due to epicardial residual stresses. We hence developed a curling angle characterization technique to intuitively and qualitatively reveal the location-dependency and direction-dependency of epicardial residual stresses. Moreover, by combining prestrain measurement and biaxial mechanical testing, we were able to quantify the epicardial prestrains and residual stresses on the unpressurized intact LV. To investigate the potential mechanical effect of epicardial prestraining, a finite-element (FE) model has been constructed, and we demonstrate that it is the prestraining of the epicardial layer, not the epicardial layer alone, providing an additional resistance mechanism during LV diastolic expansion and ventricular wall protection by reducing myocardial stress. In short, our study on healthy, native porcine hearts has revealed an important phenomenon—the epicardial layer, rich in elastin, acts like a prestrained ‘balloon’ that wraps around the heart and functions as an extra confinement and protection interface. The obtained knowledge fills a gap in ventricular biomechanics and will help design novel biomimicking materials or prosthetic devices to target the maintenance/recreation of this ventricle confinement interface.

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Global, segmental and layer specific analysis of myocardial involvement in Duchenne muscular dystrophy by cardiovascular magnetic resonance native T1 mapping

Journal of Cardiovascular Magnetic Resonance ◽

10.1186/s12968-021-00802-8 ◽

2021 ◽

Vol 23 (1) ◽

Author(s):

Ke Xu ◽

Hua-yan Xu ◽

Rong Xu ◽

Lin-jun Xie ◽

Zhi-gang Yang ◽

...

Keyword(s):

Cardiovascular Magnetic Resonance ◽

Duchenne Muscular Dystrophy ◽

Magnetic Resonance ◽

Muscular Dystrophy ◽

T1 Mapping ◽

Healthy Controls ◽

Native T1 ◽

Specific Analysis ◽

Epicardial Layer ◽

Myocardial Involvement

Abstract Background Progressive cardiomyopathy accounts for almost all mortality among Duchenne muscular dystrophy (DMD) patients.‍ Thus, our aim was to comprehensively characterize myocardial involvement by investigating the heterogeneity of native T1 mapping in DMD patients using global and regional (including segmental and layer-specific) analysis across a large cohort. Methods We prospectively enrolled 99 DMD patients (8.8 ± 2.5 years) and 25 matched male healthy controls (9.5 ± 2.5 years). All subjects underwent cardiovascular magnetic resonance (CMR) with cine, T1 mapping and late gadolinium enhancement (LGE) sequences. Native T1 values based on the global and regional myocardium were measured, and LGE was defined. Results LGE was present in 49 (49%) DMD patients. Global native T1 values were significantly longer in LGE-positive (LGE +) patients than in healthy controls, both in basal slices (1304 ± 55 vs. 1246 ± 27 ms, p < 0.001) and in mid-level slices (1305 ± 57 vs. 1245 ± 37 ms, p < 0.001). No significant difference in global native T1 was found between healthy controls and LGE-negative (LGE−) patients. In segmental analysis, LGE + patients had significantly increased native T1 in all analyzed segments compared to the healthy control group. Meanwhile, the comparison between LGE− patients and healthy controls showed significantly elevated values only in the basal anterolateral segment (1273 ± 62 vs. 1234 ± 40 ms, p = 0.034). Interestingly, the epicardial layer had a significantly higher native T1 in LGE− patients than in healthy controls (p < 0.05), whereas no such pattern was noticed in the global myocardium. Epicardial layer native T1 resulted in the highest diagnostic performance for distinguishing between healthy controls and DMD patients in receiver operating curve analyses (area under the curve [AUC] 0.84 for basal level and 0.85 for middle level) when compared to global native T1 and endocardial layer native T1. Conclusions Myocardial regional native T1, particularly epicardial native T1, seems to have potential as a novel robust marker of very early cardiac involvement in DMD patients. Trial registration: Chinese Clinical Trial Registry (http://www.chictr.org.cn/index.aspx) ChiCTR1800018340, 09/12/2018, Retrospectively registered.

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Electrophysiological remodeling of the right ventricle in experimental heart failure of different etiologies

Bulletin of Siberian Medicine ◽

10.20538/1682-0363-2019-2-165-174 ◽

2019 ◽

Vol 18 (2) ◽

pp. 165-174

Author(s):

A. S. Tsvetkova ◽

V. V. Krandycheva ◽

S. N. Kharin

Keyword(s):

Heart Failure ◽

Right Ventricle ◽

Right Ventricular ◽

Ventricular Repolarization ◽

Channel System ◽

Electrophysiological Properties ◽

Experimental Heart Failure ◽

Epicardial Layer ◽

Measured Activation ◽

The Right

The aim of the study was to evaluate electrophysiological remodeling of the right ventricle in rats in experimental heart failure of different etiologies. Materials and methods. Isadrin-, doxorubicin- and monocrotaline-induced heart failure models were developed. Unipolar epicardial electrograms of the ventricles (256 recording sites) were recorded using a 144-channel system. The cardiac output and pressure in both ventricles of the heart were measured. Activation-recovery intervals were used as an index of duration of local repolarization, and the general and local dispersions of activation-recovery intervals were used as an index of heterogeneity of ventricular repolarization. Results. In all models of heart failure, the following were identified: 1) non-uniform prolongation of repolarization with the greatest elongation at the apex of the right ventricle; 2) an increase in apicobasal differences of repolarization with the greatest change in the right ventricle; 3) an increase in the heterogeneity of the repolarization of the epicardial layer of the ventricles with heterogeneous changes in the local heterogeneity of repolarization and a decrease in the interregional differences in the heterogeneity of the electrophysiological properties of the myocardium; 4) more pronounced changes in the repolarization of the right ventricle than in the repolarization of the left ventricle. Conclusion. Thus, irrespective of the cause of the heart failure, the following changes occur: 1) prolongation of the right ventricular repolarization occurs non-uniformly (mostly due to the apical area), which results in an increase in the right ventricular repolarization heterogeneity; 2) an increase in the heterogeneity of right ventricular repolarization is observed, which causes an increase in the overall heterogeneity of the ventricular epicardial surface.

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Fibrillatory Conduction and Exit Block in the Pulmonary Veins. Two Mechanisms Seldom Seen During Catheter Ablation of Paroxysmal Atrial Fibrillation

Revista Argentina de Cardiología ◽

10.7775/rac.v82.i3.2224 ◽

2014 ◽

Vol 82 (3) ◽

pp. 240-241

Author(s):

Gaston Albina ◽

Fernando Scazzuso ◽

Diego Belardi ◽

Luis Gómez ◽

Andrés Klein ◽

...

Keyword(s):

Atrial Fibrillation ◽

Catheter Ablation ◽

Paroxysmal Atrial Fibrillation ◽

Pulmonary Veins ◽

Fibrillatory Conduction ◽

Exit Block

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Understanding inter-tissue crosstalk during zebrafish cardiovascular development

10.21248/gups.63405 ◽

2021 ◽

Author(s):

◽

Giulia L. M. Boezio

Keyword(s):

Heart Development ◽

Cardiovascular Development ◽

Paracrine Signalling ◽

Myocardial Wall ◽

Endothelial Proliferation ◽

Cell Organization ◽

Epicardial Layer ◽

Multicellular Interactions ◽

Intercellular Communications ◽

Pharmacological Manipulations

My PhD work employed genetic and pharmacological manipulations, coupled with highresolution live imaging, to understand intercellular communications during zebrafish cardiovascular development. The heart is the first organ to form, and it is composed of several tissues, among which interactions are crucial. I identified two important interactions between muscular and non-muscular tissues in poorly characterized contexts, and the molecules required for the signalling. First, I discovered an important cellular and molecular crosstalk orchestrating the development of the cardiac outflow tract (i.e., the aortic root in mammals). Endothelial-derived TGF-beta signalling controls the generation of the local extracellular matrix (ECM). The ECM in turn affects endothelial proliferation as well as smooth muscle cell organization (Boezio et al, 2020; Bensimon-Brito*, Boezio* et al, 2020). In my second project, I investigated the crosstalk between the epicardial layer and the myocardial wall. By generating epicardial-impairment models, I identified a novel role for the epicardium in regulating cardiomyocyte volume during heart development (Boezio et al, 2021). Ultimately, this research contributed to our understanding of how paracrine signalling controls the multicellular interactions integral to organogenesis.

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