Publications by authors named "Olivier Bernus"

84 Publications

3D MRI of explanted sheep hearts with submillimeter isotropic spatial resolution: comparison between diffusion tensor and structure tensor imaging.

MAGMA 2021 Feb 27. Epub 2021 Feb 27.

IHU Liryc, Electrophysiology and Heart Modeling Institute, Hopital Xavier Arnozan, 33600, Pessac, France.

Objective: The aim of the study is to compare structure tensor imaging (STI) with diffusion tensor imaging (DTI) of the sheep heart (approximately the same size as the human heart).

Materials And Methods: MRI acquisition on three sheep ex vivo hearts was performed at 9.4 T/30 cm with a seven-element RF coil. 3D FLASH with an isotropic resolution of 150 µm and 3D spin-echo DTI at 600 µm were performed. Tensor analysis, angles extraction and segments divisions were performed on both volumes.

Results: A 3D FLASH allows for visualization of the detailed structure of the left and right ventricles. The helix angle determined using DTI and STI exhibited a smooth transmural change from the endocardium to the epicardium. Both the helix and transverse angles were similar between techniques. Sheetlet organization exhibited the same pattern in both acquisitions, but local angle differences were seen and identified in 17 segments representation.

Discussion: This study demonstrated the feasibility of high-resolution MRI for studying the myocyte and myolaminar architecture of sheep hearts. We presented the results of STI on three whole sheep ex vivo hearts and demonstrated a good correspondence between DTI and STI.
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http://dx.doi.org/10.1007/s10334-021-00913-4DOI Listing
February 2021

3D magnetization transfer (MT) for the visualization of cardiac free-running Purkinje fibers: an ex vivo proof of concept.

MAGMA 2021 Jan 23. Epub 2021 Jan 23.

IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Hopital Xavier Arnozan, Avenue du Haut Lévêque, 33604, Pessac cedex, France.

Objectives: We investigate the possibility to exploit high-field MRI to acquire 3D images of Purkinje network which plays a crucial role in cardiac function. Since Purkinje fibers (PF) have a distinct cellular structure and are surrounded by connective tissue, we investigated conventional contrast mechanisms along with the magnetization transfer (MT) imaging technique to improve image contrast between ventricular structures of differing macromolecular content.

Methods: Three fixed porcine ventricular samples were used with free-running PFs on the endocardium. T1, T2*, T2, and M0 were evaluated on 2D slices for each sample at 9.4 T. MT parameters were optimized using hard pulses with different amplitudes, offset frequencies and durations. The cardiac structure was assessed through 2D and 3D T1w images with isotropic resolutions of 150 µm. Histology, immunofluorescence, and qPCR were performed to analyze collagen contents of cardiac tissue and PF.

Results: An MT preparation module of 350 ms duration inserted into the sequence with a B1 = 10 µT and frequency offset = 3000 Hz showed the best contrast, approximately 0.4 between PFs and myocardium. Magnetization transfer ratio (MTR) appeared higher in the cardiac tissue (MTR = 44.7 ± 3.5%) than in the PFs (MTR = 25.2 ± 6.3%).

Discussion: MT significantly improves contrast between PFs and ventricular myocardium and appears promising for imaging the 3D architecture of the Purkinje network.
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http://dx.doi.org/10.1007/s10334-020-00905-wDOI Listing
January 2021

Insights Into the Spatiotemporal Patterns of Complexity of Ventricular Fibrillation by Multilead Analysis of Body Surface Potential Maps.

Front Physiol 2020 23;11:554838. Epub 2020 Sep 23.

Institute of Electrophysiology and Heart Modeling (IHU Liryc), Foundation Bordeaux University, Bordeaux, France.

Background: Ventricular fibrillation (VF) is the main cause of sudden cardiac death, but its mechanisms are still unclear. We propose a noninvasive approach to describe the progression of VF complexity from body surface potential maps (BSPMs).

Methods: We mapped 252 VF episodes (16 ± 10 s) with a 252-electrode vest in 110 patients (89 male, 47 ± 18 years): 50 terminated spontaneously, otherwise by electrical cardioversion (DCC). Changes in complexity were assessed between the onset ("VF start") and the end ("VF end") of VF by the nondipolar component index ( ), measuring the fraction of energy nonpreserved by an equivalent 3D dipole from BSPMs. Higher NDI reflected lower VF organization. We also examined other standard body surface markers of VF dynamics, including fibrillatory wave amplitude ( ), surface cycle length ( ) and Shannon entropy ( ). Differences between patients with and without structural heart diseases (SHD, 32 vs. NSHD, 78) were also tested at those stages. Electrocardiographic features were validated with simultaneous endocardium cycle length (CL) in a subset of 30 patients.

Results: All BSPM markers measure an increase in electrical complexity during VF ( < 0.0001), and more significantly in NSHD patients. Complexity is significantly higher at the end of sustained VF episodes requiring DCC. Intraepisode intracardiac CL shortening (VF start 197 ± 24 vs. VF end 169 ± 20 ms; < 0.0001) correlates with an increase in NDI, and decline in surface CL, f-wave amplitude, and entropy ( < 0.0001). In SHD patients VF is initially more complex than in NSHD patients ( , = 0.0007; , < 0.0001), with moderately slower ( , = 0.06), low-amplitude f-waves ( , < 0.0001). In this population, lower NDI ( = 0.004) and slower surface CL ( = 0.008) at early stage of VF predict self-termination. In the NSHD group, a more abrupt increase in VF complexity is quantified by all BSPM parameters during sustained VF ( < 0.0001), whereas arrhythmia evolution is stable during self-terminating episodes, hinting at additional mechanisms driving VF dynamics.

Conclusion: Multilead BSPM analysis underlines distinct degrees of VF complexity based on substrate characteristics.
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http://dx.doi.org/10.3389/fphys.2020.554838DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7538856PMC
September 2020

Long-Lasting Ventricular Fibrillation in Humans ECG Characteristics and Effect of Radiofrequency Ablation.

Circ Arrhythm Electrophysiol 2020 10 10;13(10):e008639. Epub 2020 Sep 10.

LIRYC Institute/INSERM 1045, Bordeaux University, France (J.D., M. Hocini, F.S., P.J., O.B., M. Haïssaguerre, R.D.).

Background: Studies of ventricular fibrillation (VF) in humans are limited because of the short available duration. We sought to study surface ECG waveforms and effect of ablation in long-lasting VF in patients with left assist devices.

Methods: Continuous 12-lead ECG of 5 episodes of long-lasting VF occurring in 3 patients with left ventricular assist device were analyzed. Spectral analysis (dominant frequency) and quantification of waveform amplitude, regularity (Unbiased Regularity Index), and complexity (Nondipolar Index) were performed over a median of 24 minutes of VF. Radiofrequency ablation was performed during VF in 2 patients.

Results: There was a significant increase in dominant frequency between VF onset and termination but none of the other parameters significantly changed. Some VF parameters varied from patient to patient and from lead to lead. Dominant frequency decreased after radiofrequency ablation in both cases and VF terminated spontaneously shortly after ablation in one case. The previously incessant VFs in these 2 patients did not recur afterward.

Conclusions: VF rate increases over time in patients with left ventricular assist devices and is lowered by ablation. Long-lasting VF may be modified or even terminated by ablation.
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http://dx.doi.org/10.1161/CIRCEP.120.008639DOI Listing
October 2020

Body Surface Mapping of Ventricular Repolarization Heterogeneity: An Multiparameter Study.

Front Physiol 2020 13;11:933. Epub 2020 Aug 13.

Institute of Electrophysiology and Heart Modeling (IHU Liryc), Foundation Bordeaux University, Pessac-Bordeaux, France.

Background: Increased heterogeneity of ventricular repolarization is associated with life-threatening arrhythmia and sudden cardiac death (SCD). T-wave analysis through body surface potential mapping (BSPM) is a promising tool for risk stratification, but the clinical effectiveness of current electrocardiographic indices is still unclear, with limited experimental validation. This study aims to investigate performance of non-invasive state-of-the-art and novel T-wave markers for repolarization dispersion in an model.

Methods: Langendorff-perfused pig hearts ( = 7) were suspended in a human-shaped 256-electrode torso tank. Tank potentials were recorded during sinus rhythm before and after introducing repolarization inhomogeneities through local perfusion with dofetilide and/or pinacidil. Drug-induced repolarization gradients were investigated from BSPMs at different experiment phases. Dispersion of electrical recovery was quantified by duration parameters, i.e., the time interval between the peak and the offset of T-wave (T-T) and QT interval, and variability over time and electrodes was also assessed. The degree of T-wave symmetry to the peak was quantified by the ratio between the terminal and initial portions of T-wave area (). Morphological variability between left and right BSPM electrodes was measured by dynamic time warping (DTW). Finally, T-wave organization was assessed by the complexity of repolarization index (CR), i.e., the amount of energy non-preserved by the dominant eigenvector computed by principal component analysis (PCA), and the error between each multilead T-wave and its 3D PCA approximation (NMSE). Body surface indices were compared with global measures of epicardial dispersion of repolarization, and with local gradients between adjacent ventricular sites.

Results: After drug intervention, both regional and global repolarization heterogeneity were significantly enhanced. On the body surface, T-T was significantly prolonged and less stable in time in all experiments, while QT interval showed higher variability across the interventions in terms of duration and spatial dispersion. The rising slope of the repolarization profile was steeper, and T-waves were more asymmetric than at baseline. Interventricular shape dissimilarity was enhanced by repolarization gradients according to DTW. Organized T-wave patterns were associated with abnormal repolarization, and they were properly described by the first principal components.

Conclusion: Repolarization heterogeneity significantly affects T-wave properties, and can be non-invasively captured by BSPM-based metrics.
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http://dx.doi.org/10.3389/fphys.2020.00933DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7438571PMC
August 2020

A total closed chest sheep model of cardiogenic shock by percutaneous intracoronary ethanol injection.

Sci Rep 2020 07 24;10(1):12417. Epub 2020 Jul 24.

Univ. Bordeaux, INSERM, UMR 1034, Biology of Cardiovascular Diseases, 33600, Pessac, France.

To develop a reproducible and stable closed chest model of ischemic cardiogenic shock in sheep, with high survival rate and potential insight into human pathology. We established a protocol for multi-step myocardial alcoholisation of the left anterior descending coronary artery by percutaneous ethanol injection. A thorough hemodynamic assessment was obtained by invasive and non-invasive monitoring devices. Repeated blood samples were obtained to determine haemoglobin and alcohol concentration, electrolytes, blood gas parameters and cardiac troponin I. After sacrifice, tissue was excised for quantification of infarction and histology. Cardiogenic shock was characterized by a significant decrease in mean arterial pressure (- 33%), cardiac output (- 29%), dP/dt (- 28%), carotid blood flow (- 22%), left ventricular fractional shortening (- 28%), and left ventricle end-systolic pressure-volume relationship (- 51%). Lactate and cardiac troponin I levels increased from 1.4 ± 0.2 to 4.9 ± 0.7 mmol/L (p = 0.001) and from 0.05 ± 0.02 to 14.74 ± 2.59 µg/L (p = 0.001), respectively. All haemodynamic changes were stable over a three-hour period with a 71% survival rate. The necrotic volume (n = 5) represented 24.0 ± 1.9% of total ventricular mass. No sham exhibited any variation under general anaesthesia. We described and characterized, for the first time, a stable, reproducible sheep model of cardiogenic shock obtained by percutaneous intracoronary ethanol administration.
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http://dx.doi.org/10.1038/s41598-020-68571-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7381645PMC
July 2020

Comparison of Two Percutaneous Atrial Septal Defect Occluders for Device Healing and Nickel Release in a Chronic Porcine Model.

J Interv Cardiol 2020 20;2020:8413831. Epub 2020 Jun 20.

Department of Paediatric and Adult Congenital Cardiology, Bordeaux University Hospital (CHU), Pessac F-33600, Bordeaux, France.

Aims: To investigate the healing process and nickel release of the Hyperion occluder (Comed BV, Netherlands), as compared to the Amplatzer septal occluder (ASO) (St. Jude Medical Inc., St. Paul, MN, USA) in a chronic swine model.

Background: Some long-term complications occurring after percutaneous atrial septal defect (ASD) closure may be partially associated with an inappropriate healing of the device and increased nickel release. There is no direct comparative study of different occluders for healing and nickel release.

Methods: After percutaneous ASD creation, 12 pigs were implanted with 15 mm Hyperion ( = 6) and 15 mm ASO ( = 6) devices. After 1 month ( = 3 for each device) and 3 months ( = 3 for each device) of follow-up, device explantation was performed and healing was assessed using histopathological workup. Systemic and tissular nickel release was performed.

Results: Implantation was successful in 100% without complications. Device coverage was observed as early as 1 month after implantation and was almost complete after 3 months. A granulation tissue with a predominantly mononuclear inflammatory reaction was observed in contact with nitinol wires while an inflammatory reaction was seen in contact with textile fibers. We found no statistically significant difference between the 2 devices whether for histological grading scores or systemic nickel release, regardless to follow-up duration.

Conclusions: In this preclinical study, we demonstrated that Amplatzer septal occluder and Hyperion occluder were not significantly different for device healing and nickel release processes.
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http://dx.doi.org/10.1155/2020/8413831DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7327569PMC
November 2020

Idiopathic Ventricular Fibrillation: Role of Purkinje System and Microstructural Myocardial Abnormalities.

JACC Clin Electrophysiol 2020 06;6(6):591-608

Institut Hospitalo-Universitaire Electrophysiology and Heart Modeling Institute, Centre Hospitalier Universitaire de Bordeaux, France; Cardiothoracic Research Center Bordeaux, Université de Bordeaux, Bordeaux, France.

Idiopathic ventricular fibrillation is diagnosed in patients who survived a ventricular fibrillation episode without any identifiable structural or electrical cause after extensive investigations. It is a common cause of sudden death in young adults. The study reviews the diagnostic value of systematic investigations and the new insights provided by detailed electrophysiological mapping. Recent studies have shown the high incidence of microstructural cardiomyopathic areas, which act as the substrate of ventricular fibrillation re-entries. These subclinical alterations require high-density endo- and epicardial mapping to be identified using electrogram criteria. Small areas are involved and located individually in various sites (mostly epicardial). Their characteristics suggest a variety of genetic or acquired pathological processes affecting cellular connectivity or tissue structure, such as cardiomyopathies, myocarditis, or fatty infiltration. Purkinje abnormalities manifesting as triggering ectopy or providing a substrate for re-entry represent a second important cause. The documentation of ephemeral Purkinje ectopy requires continuous electrocardiography monitoring for diagnosis. A variety of diseases affecting Purkinje cell function or conduction are potentially at play in their pathogenesis. Comprehensive investigations can therefore allow the great majority of idiopathic ventricular fibrillation to ultimately receive diagnoses of a cardiac disease, likely underlain by a mosaic of pathologies. Precise phenotypic characterization has significant implications for interpretation of genetic variants, the risk assessment, and individual therapy. Future improvements in imaging or electrophysiological methods may hopefully allow the identification of the subjects at risk and the development of primary prevention strategies.
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http://dx.doi.org/10.1016/j.jacep.2020.03.010DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7308805PMC
June 2020

Selective inhibition of electrical conduction within the pulmonary veins by α1-adrenergic receptors activation in the Rat.

Sci Rep 2020 03 25;10(1):5390. Epub 2020 Mar 25.

EA7349, Laboratoire STIM, Groupe Physiologie des Cellules Cardiaques et Vasculaires, Université de Tours, Tours, France.

Pulmonary veins (PV) are involved in the pathophysiology of paroxysmal atrial fibrillation. In the rat, left atrium (LA) and PV cardiomyocytes have different reactions to α1-adrenergic receptor activation. In freely beating atria-PV preparations, we found that electrical field potential (EFP) originated from the sino-atrial node propagated through the LA and the PV. The α1-adrenergic receptor agonist cirazoline induced a progressive loss of EFP conduction in the PV whereas it was maintained in the LA. This could be reproduced in preparations electrically paced at 5 Hz in LA. During pacing at 10 Hz in the PV where high firing rate ectopic foci can occur, cirazoline stopped EFP conduction from the PV to the LA, which allowed the sino-atrial node to resume its pace-making function. Loss of conduction in the PV was associated with depolarization of the diastolic membrane potential of PV cardiomyocytes. Adenosine, which reversed the cirazoline-induced depolarization of the diastolic membrane potential of PV cardiomyocytes, restored full over-shooting action potentials and EFP conduction in the PV. In conclusion, selective activation of α1-adrenergic receptors results in the abolition of electrical conduction within the PV. These results highlight a potentially novel pharmacological approach to treat paroxysmal atrial fibrillation by targeting directly the PV myocardium.
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http://dx.doi.org/10.1038/s41598-020-62349-5DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7096464PMC
March 2020

Assessment of the healing process after percutaneous implantation of a cardiovascular device: a systematic review.

Int J Cardiovasc Imaging 2020 Mar 19;36(3):385-394. Epub 2019 Nov 19.

IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, 33600, Pessac- Bordeaux, France.

The healing process, occurring after intra-cardiac and intra-vascular device implantation, starts with fibrin condensation and attraction of inflammatory cells, followed by the formation of fibrous tissue that slowly covers the device. The duration of this process is variable and may be incomplete, which can lead to thrombus formation, dislodgement of the device or stenosis. To better understand this process and the neotissue formation, animal models were developed: small (rats and rabbits) and large (sheep, pigs, dogs and baboons) animal models for intra-vascular device implantation; sheep and pigs for intra-cardiac device implantation. After intra-vascular and intra-cardiac device implantation in these animal models, in vitro techniques, i.e. histology, which is the gold standard and scanning electron microscopy, were used to assess the device coverage, characterize the cell constitution and detect complications such as thrombosis. In humans, optical coherence tomography and intra-vascular ultrasounds are both invasive modalities used after stent implantation to assess the structure of the vessels, atheroma plaque and complications. Non-invasive techniques (computed tomography and magnetic resonance imaging) are in development in humans and animal models for tissue characterization (fibrosis), device remodeling evaluation and device implantation complications (thrombosis and stenosis). This review aims to (1) present the experimental models used to study this process on cardiac devices; (2) focus on the in vitro techniques and invasive modalities used currently in humans for intra-vascular and intra-cardiac devices and (3) assess the future developments of non-invasive techniques in animal models and humans for intra-cardiac devices.
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http://dx.doi.org/10.1007/s10554-019-01734-2DOI Listing
March 2020

Animal Models of Repaired Tetralogy of Fallot: Current Applications and Future Perspectives.

Can J Cardiol 2019 Dec 26;35(12):1762-1771. Epub 2019 Jul 26.

Department of Pediatric and Adult Congenital Cardiology, Bordeaux University Hospital (CHU), Bordeaux, France; IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France; INSERM, Centre de recherche Cardio-Thoracique de Bordeaux, Bordeaux, France.

Tetralogy of Fallot is the most common cyanotic congenital heart disease. Despite ongoing improvements in the initial surgical repair, there are lingering concerns regarding the long-term outcomes that may be complicated by right ventricular dysfunction, right ventricular dyssynchrony, and sudden cardiac death. The mechanisms leading to these late complications remain incompletely understood. Experimental animal models have been developed as preclinical steps to gain better insight into the pathophysiology of diseases and to develop new therapeutic strategies. This article summarizes the various types of experimental animal models of repaired tetralogy of Fallot published to date in the literature, with the aim of achieving a greater understanding of the deleterious mechanisms that may lead to these known late and sometimes lethal complications. In addition to analysing the type of animals that can be used according to a given study's objectives, needs, and constraints, the present review also evaluates the type of dysfunction that can be reproduced in our model according to the research objectives, as well as the different types of studies in which these models can be used. In view of all that, we propose a decision algorithm to create an animal model of repaired tetralogy of Fallot. This synthesis should furthermore help in the development of future studies and in the design of new experimental models, thus allowing greater insight into this disease, while not forgetting the ultimate goal of broadening future therapeutic measures to reduce the morbidity and mortality of this prevalent congenital heart disease.
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http://dx.doi.org/10.1016/j.cjca.2019.07.622DOI Listing
December 2019

The Spectrum of Idiopathic Ventricular Fibrillation and J-Wave Syndromes: Novel Mapping Insights.

Card Electrophysiol Clin 2019 12;11(4):699-709

IHU LIRYC, Electrophysiology and Heart Modeling Institute, Avenue du Haut Leveque, Bordeaux 33604, Passes Cedex, France; Univ Bordeaux, CRCTB, U1045, Bordeaux, France.

Idiopathic ventricular fibrillation and J-wave syndromes are causes of sudden cardiac death (SCD) without any identified structural cardiac disease after extensive investigations. Recent data show that high-density electrophysiological mapping may ultimately offer diagnoses of subclinical diseases in most patients including those termed "unexplained" SCD. Three major conditions can underlie the occurrence of SCD: (1) localized depolarization abnormalities (due to microstructural myocardial alteration), (2) Purkinje abnormalities manifesting as triggering ectopy and inducible reentry; or (3) repolarization heterogeneities. Each condition may result from a spectrum of pathophysiologic processes with implications for individual therapy.
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http://dx.doi.org/10.1016/j.ccep.2019.08.011DOI Listing
December 2019

Wide-area low-energy surface stimulation of large mammalian ventricular tissue.

Sci Rep 2019 11 1;9(1):15863. Epub 2019 Nov 1.

IHU-LIRYC, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université. Pessac, Bordeaux, France.

The epicardial and endocardial surfaces of the heart are attractive targets to administer antiarrhythmic electrotherapies. Electrically stimulating wide areas of the surfaces of small mammalian ventricles is straightforward given the relatively small scale of their myocardial dimensions compared to the tissue space constant and electrical field. However, it has yet to be proven for larger mammalian hearts with tissue properties and ventricular dimensions closer to humans. Our goal was to address the feasibility and impact of wide-area electrical stimulation on the ventricular surfaces of large mammalian hearts at different stimulus strengths. This was accomplished by placing long line electrodes on the ventricular surfaces of pig hearts that span wide areas, and activating them individually. Stimulus efficacy was assessed and compared between surfaces, and tissue viability was evaluated. Activation time was dependent on stimulation strength and location, achieving uniform linear stimulation at 9x threshold strength. Endocardial stimulation activated more tissue transmurally than epicardial stimulation, which could be considered a potential target for future cardiac electrotherapies. Overall, our results indicate that electrically stimulating wide areas of the ventricular surfaces of large mammals is achievable with line electrodes, minimal tissue damage, and energies under the human pain threshold (100 mJ).
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http://dx.doi.org/10.1038/s41598-019-51364-wDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6825186PMC
November 2019

Advantages and pitfalls of noninvasive electrocardiographic imaging.

J Electrocardiol 2019 Nov - Dec;57S:S15-S20. Epub 2019 Aug 9.

IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, F-33600 Pessac, Bordeaux, France; Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France; INSERM, Centre de Recherche Cardio-Thoracique de Bordeaux, U1045, F-33000 Bordeaux, France.

Background: With increasing clinical use of Electrocardiographic Imaging (ECGI), it is imperative to understand the limits of this technique. The objective of this study is to evaluate a potential-based ECGI approach for activation and repolarization mapping in sinus rhythm.

Method: Langendorff-perfused pig hearts were suspended in a human-shaped torso tank. Electrograms were recorded with a 108-electrode sock and ECGs with 256 electrodes embedded in the tank surface. Left bundle branch block (LBBB) was developed in 4 hearts through ablation, and repolarization abnormalities in another 4 hearts through regional perfusion of dofetilide and pinacidil. Electrograms were noninvasively reconstructed and reconstructed activation and repolarization features were compared to those recorded.

Results: Visual consistency between ECGI and recorded activation and repolarization maps was high. While reconstructed repolarization times showed significantly more error than activation times quantitatively, patterns were reconstructed with a similar level of accuracy. The number of epicardial breakthrough sites was underestimated by ECGI and these were misplaced (>20 mm) in location. Likewise, ECGI reconstructed activation maps demonstrated artificial lines of block resulting from a W-shaped QRS waveform that were not present in recorded maps. Nevertheless, ECGI allowed identification of regions of abnormal repolarization reasonably accurately in terms of size, location and timing.

Conclusions: This study validates a potential-based ECGI approach to noninvasively image activation and recovery in sinus rhythm. Despite inaccuracies in epicardial breakthroughs and lines of conduction block, other important clinical features such as regions of abnormal repolarization can be accurately derived making ECGI a valuable clinical tool.
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http://dx.doi.org/10.1016/j.jelectrocard.2019.08.007DOI Listing
August 2019

Idiopathic ventricular fibrillation with repetitive activity inducible within the distal Purkinje system.

Heart Rhythm 2019 08 10;16(8):1268-1272. Epub 2019 Apr 10.

IHU Liryc, Electrophysiology and Heart Modeling Institute, Foundation Bordeaux Université, Bordeaux, France; Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux, INSERM U1045, Bordeaux, France.

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http://dx.doi.org/10.1016/j.hrthm.2019.04.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6659587PMC
August 2019

Optical Imaging of Ventricular Action Potentials in a Torso Tank: A New Platform for Non-Invasive Electrocardiographic Imaging Validation.

Front Physiol 2019 26;10:146. Epub 2019 Feb 26.

IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, Bordeaux, France.

Non-invasive electrocardiographic imaging (ECGI) is a promising tool to provide high-resolution panoramic imaging of cardiac electrical activity noninvasively from body surface potential measurements. Current experimental methods for ECGI validation are limited to comparison with unipolar electrograms and the relatively low spatial resolution of cardiac mapping arrays. We aim to develop a novel experimental set up combining a human shaped torso tank with high-resolution optical mapping allowing the validation of ECGI reconstructions. Langendorff-perfused pig hearts ( = 3) were suspended in a human torso-shaped tank, with the left anterior descending artery (LAD) cannulated on a separate perfusion. Electrical signals were recorded from an 108-electrode epicardial sock and 128 electrodes embedded in the tank surface. Simultaneously, optical mapping of the heart was performed through the anterior surface of the tank. Recordings were made in sinus rhythm and ventricular pacing ( = 55), with activation and repolarization heterogeneities induced by perfusion of hot and cold solutions as well as Sotalol through the LAD. Fluoroscopy provided 3D cardiac and electrode geometries in the tank that were transformed to the 2D optical mapping window using an optimization algorithm. Epicardial unipolar electrograms were reconstructed from torso potentials using ECGI and validated using optical activation and repolarization maps. The transformation and alignment of the 3D geometries onto the 2D optical mapping window was good with an average correlation of 0.87 ± 0.10 and error of 7.7 ± 3.1 ms with activation derived from the sock. The difference in repolarization times were more substantial (error = 17.4 ± 3.7 ms) although the sock and optical repolarization patterns themselves were very similar (correlation = 0.83 ± 0.13). Validation of ECGI reconstructions revealed ECGI accurately captures the pattern of activation (correlation = 0.79 ± 0.11) and identified regions of late and/or early repolarization during different perfusions through LAD. ECGI also correctly demonstrated gradients in both activation and repolarization, although in some cases these were under or over-estimated or shifted slightly in space. A novel experimental setup has been developed, combining a human-shaped torso tank with optical mapping, which can be effectively used in the validation of ECGI techniques; including the reconstruction of activation and repolarization patterns and gradients.
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http://dx.doi.org/10.3389/fphys.2019.00146DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6399141PMC
February 2019

Depolarization versus repolarization abnormality underlying inferolateral J-wave syndromes: New concepts in sudden cardiac death with apparently normal hearts.

Heart Rhythm 2019 05 2;16(5):781-790. Epub 2018 Nov 2.

IHU LIRYC, Electrophysiology and Heart Modeling Institute, Bordeaux, France; University of Bordeaux, U1045, Bordeaux, France.

Early repolarization indicates a distinct electrocardiographic phenotype affecting the junction between the QRS complex and the ST segment in inferolateral leads (inferolateral J-wave syndromes). It has been considered a benign electrocardiographic variant for decades, but recent clinical studies have demonstrated its arrhythmogenicity in a small subset, supported by experimental studies showing transmural dispersion of repolarization. Here we review the current knowledge and the issues of risk stratification that limit clinical management. In addition, we report on new mapping data of patients refractory to pharmacologic treatment using high-density electrogram mapping at the time of inscription of J wave. These data demonstrate that distinct substrates, delayed depolarization, and abnormal early repolarization underlie inferolateral J-wave syndromes, with significant implications. Finally, based on these data, we propose a new simplified mechanistic classification of sudden cardiac deaths without apparent structural heart disease.
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http://dx.doi.org/10.1016/j.hrthm.2018.10.040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6486498PMC
May 2019

Performance and limitations of noninvasive cardiac activation mapping.

Heart Rhythm 2019 03 26;16(3):435-442. Epub 2018 Oct 26.

IHU LIRYC, Bordeaux University, Bordeaux, France.

Background: Activation mapping using noninvasive electrocardiographic imaging (ECGi) has recently been used to describe the physiology of different cardiac abnormalities. These descriptions differ from prior invasive studies, and both methods have not been thoroughly confronted in a clinical setting.

Objective: The goal of the present study was to provide validation of noninvasive activation mapping in a clinical setting through direct confrontation with invasive epicardial contact measures.

Methods: Fifty-nine maps were obtained in 55 patients and aligned on a common geometry. Nearest-neighbor interpolation was used to avoid map smoothing. Quantitative comparison was performed by computing between-map correlation coefficients and absolute activation time errors.

Results: The mean activation time error was 20.4 ± 8.6 ms, and the between-map correlation was poor (0.03 ± 0.43). The results suggested high interpatient variability (correlation -0.68 to 0.82), wide QRS patterns, and paced rhythms demonstrating significantly better mean correlation (0.68 ± 0.17). Errors were greater in scarred regions (21.9 ± 10.8 ms vs 17.5 ± 6.7 ms; P < .01). Fewer epicardial breakthroughs were imaged using noninvasive mapping (1.3 ± 0.5 vs 2.3 ± 0.7; P < .01). Primary breakthrough locations were imaged 75.7 ± 38.1 mm apart. Lines of conduction block (jumps of ≥50 ms between contiguous points) due to structural anomalies were recorded in 27 of 59 contact maps and were not visualized at these same sites noninvasively. Instead, artificial lines appeared in 33 of 59 noninvasive maps in regions of reduced bipolar voltage amplitudes (P = .03). An in silico model confirms these artificial constructs.

Conclusion: Overall, agreement of ECGi activation mapping and contact mapping is poor and heterogeneous. The between-map correlation is good for wide QRS patterns. Lines of block and epicardial breakthrough sites imaged using ECGi are inaccurate. Further work is required to improve the accuracy of the technique.
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http://dx.doi.org/10.1016/j.hrthm.2018.10.010DOI Listing
March 2019

Arrhythmogenic Remodeling of the Left Ventricle in a Porcine Model of Repaired Tetralogy of Fallot.

Circ Arrhythm Electrophysiol 2018 10;11(10):e006059

IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Pessac, France (V.D., D.B., F.R., S.H.G., M.C., S.C., D.E., B.Q., H.C., M.H., C.R., P.B., J.-B.T., O.B.).

Background: Ventricular arrhythmias are frequent in patients with repaired tetralogy of Fallot (rTOF), but their origin and underlying mechanisms remain unclear. In this study, the involvement of left ventricular (LV) electrical and structural remodeling was assessed in an animal model mimicking rTOF sequelae.

Methods: Piglets underwent a tetralogy of Fallot repair-like surgery (n=6) or were sham operated (Sham, n=5). Twenty-three weeks post-surgery, cardiac function was assessed in vivo by magnetic resonance imaging. Electrophysiological properties were characterized by optical mapping. LV fibrosis and connexin-43 localization were assessed on histological sections and protein expression assessed by Western Blot.

Results: Right ventricular dysfunction was evident, whereas LV function remained unaltered in rTOF pigs. Optical mapping showed longer action potential duration on the rTOF LV epicardium and endocardium. Epicardial conduction velocity was significantly reduced in the longitudinal direction in rTOF LVs but not in the transverse direction compared with Sham. An elevated collagen content was found in LV basal and apical sections from rTOF pigs. Moreover, a trend for connexin-43 lateralization with no change in protein expression was found in the LV of rTOFs. Finally, rTOF LVs had a lower threshold for arrhythmia induction using incremental pacing protocols.

Conclusions: We found an arrhythmogenic substrate with prolonged heterogeneous action potential duration and reduced conduction velocity in the LV of rTOF pigs. This remodeling precedes LV dysfunction and is likely to contribute to ventricular arrhythmias and sudden cardiac death in patients with rTOF.
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http://dx.doi.org/10.1161/CIRCEP.117.006059DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6553519PMC
October 2018

Compartmentalized Structure of the Moderator Band Provides a Unique Substrate for Macroreentrant Ventricular Tachycardia.

Circ Arrhythm Electrophysiol 2018 08;11(8):e005913

Université de Bordeaux, Centre de recherche Cardio-Thoracique de Bordeaux, U1045, France (R.D.W., A.P., M.E.M, M.C., J.D., L.B., C.C., C.P-A., Y.G., D.B., V.D., N.R.F., S.C., S.D., D.D., L.P., P.P., F.B., J.R., L.L., M.H., M.H., O.B.).

Background Papillary muscles are an important source of ventricular tachycardia (VT). Yet little is known about the role of the right ventricular (RV) endocavity structure, the moderator band (MB). The aim of this study was to determine the characteristics of the MB that may predispose to arrhythmia substrates. Methods Ventricular wedge preparations with intact MBs were studied from humans (n=2) and sheep (n=15; 40-50 kg). RV endocardium was optically mapped, and electrical recordings were measured along the MB and septum. S1S2 pacing of the RV free wall, MB, or combined S1-RV S2-MB sites were assessed. Human (n=2) and sheep (n=4) MB tissue constituents were assessed histologically. Results The MB structure was remarkably organized as 2 excitable, yet uncoupled compartments of myocardium and Purkinje. In humans, action potential duration heterogeneity between MB and RV myocardium was found (324.6±12.0 versus 364.0±8.4 ms; P<0.0001). S1S2-MB pacing induced unidirectional propagation via MB myocardium, permitting sustained macroreentrant VT. In sheep, the incidence of VT for RV, MB, and S1-RV S2-MB pacing was 1.3%, 5.1%, and 10.3%. Severing the MB led to VT termination, confirming a primary arrhythmic role. Inducible preparations had shorter action potential duration in the MB than RV (259.3±45.2 versus 300.7±38.5 ms; P<0.05), whereas noninducible preparations showed no difference (312.0±30.3 versus 310.0±24.6 ms, respectively). Conclusions The MB presents anatomic and electrical compartmentalization between myocardium and Purkinje fibers, providing a substrate for macroreentry. The vulnerability to sustain VT via this mechanism is dependent on MB structure and action potential duration gradients between the RV free wall and MB.
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http://dx.doi.org/10.1161/CIRCEP.117.005913DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661046PMC
August 2018

Role of animal models for percutaneous atrial septal defect closure.

J Thorac Dis 2018 Sep;10(Suppl 24):S2966-S2974

Department of Paediatric and Adult Congenital Cardiology, Bordeaux University Hospital (CHU), F-33600 Pessac, France.

As for any preclinical development of new implantable device, bench testing has been followed by experimental studies on large animal models for the development of atrial septal defect closure devices. Various models have been used according to studied species (porcine, ovine or canine model) and whether the septal defect was percutaneously or surgically created. Animal models of percutaneous atrial septal defect closure aim to assess the healing process and device endothelialisation, as well as the development of magnetic resonance imaging guided procedures, the short-term effects of volume overload on right ventricular contractility through haemodynamic studies and the understanding of other complications such as nickel hypersensitivity. Each technique has its own advantages and drawbacks, and leads to different punch-related, acute septal injuries that could have an effect on the healing process after device implantation. It has been suggested that some long-term, major device-related complications such as thrombosis or infective endocarditis may be associated with an inappropriate healing process or insufficient endothelialisation of the device, leading industrial companies to pay a great deal of attention to the healing process. Tissue reactions in animal models were shown to adequately reproduce the healing response after device implantation in humans, with an endothelial device coverage observed as early as 30 days after implantation and complete after 3 to 6 months. Research perspectives may evaluate both animal models and studies in parallel with a view to clarify the endothelialisation process using human endothelial cells through experiments. Self-sensing device for detecting the presence of endothelial cells on the surface of intracardiac occluders and high-resolution imaging techniques that could non-invasively assess the complete endothelialisation of a device would also be promising tools which would need large animal models studies before their clinical application.
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http://dx.doi.org/10.21037/jtd.2018.07.119DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6174152PMC
September 2018

Unanesthetized Rodents Demonstrate Insensitivity of QT Interval and Ventricular Refractory Period to Pacing Cycle Length.

Front Physiol 2018 11;9:897. Epub 2018 Jul 11.

Cardiac Arrhythmia Research Laboratory, Department of Physiology and Cell Biology, Faculty of Health Sciences, Ben-Gurion University of the Negev, Beer-Sheva, Israel.

The cardiac electrophysiology of mice and rats has been analyzed extensively, often in the context of pathological manipulations. However, the effects of beating rate on the basic electrical properties of the rodent heart remain unclear. Due to technical challenges, reported electrophysiological studies in rodents are mainly from preparations or under deep anesthesia, conditions that might be quite far from the normal physiological state. The aim of the current study was to characterize the ventricular rate-adaptation properties of unanesthetized rats and mice. An implanted device was chronically implanted in rodents for atrial or ventricular pacing studies. Following recovery from surgery, QT interval was evaluated in rodents exposed to atrial pacing at various frequencies. In addition, the frequency dependence of ventricular refractoriness was tested by conventional ventricular programmed stimulation protocols. Our findings indicate total absence of conventional rate-adaptation properties for both QT interval and ventricular refractoriness. Using monophasic action potential recordings in isolated mice hearts we could confirm the previously reported shortening of the action potential duration at fast pacing rates. However, we found that this mild shortening did not result in similar decrease of ventricular refractory period. Our findings indicate that unanesthetized rodents exhibit flat QT interval and ventricular refractory period rate-dependence. This data argue against empirical use of QT interval correction methods in rodent studies. Our new methodology allowing atrial and ventricular pacing of unanesthetized freely moving rodents may facilitate more appropriate utility of these important animal models in the context of cardiac electrophysiology studies.
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http://dx.doi.org/10.3389/fphys.2018.00897DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6050393PMC
July 2018

Localized Structural Alterations Underlying a Subset of Unexplained Sudden Cardiac Death.

Circ Arrhythm Electrophysiol 2018 07;11(7):e006120

IHU Liryc, Electrophysiology and Heart Modeling Institute, Fondation Bordeaux Université, France (M. Haïssaguerre, M. Hocini, G.C., J.D., F.S., S.P., H.C., M.T., A.D., R.M., N.D., P.B., P.R., S.P., T.P., N.K., G.M., X.P., C.D., L.L., R.C., P.J., D.B., E.V., M.P., R.W., O.B., R.D.).

Background: Sudden cardiac death because of ventricular fibrillation (VF) is commonly unexplained in younger victims. Detailed electrophysiological mapping in such patients has not been reported.

Methods: We evaluated 24 patients (29±13 years) who survived idiopathic VF. First, we used multielectrode body surface recordings to identify the drivers maintaining VF. Then, we analyzed electrograms in the driver regions using endocardial and epicardial catheter mapping during sinus rhythm. Established electrogram criteria were used to identify the presence of structural alterations.

Results: VF occurred spontaneously in 3 patients and was induced in 16, whereas VF was noninducible in 5. VF mapping demonstrated reentrant and focal activities (87% versus 13%, respectively) in all. The activities were dominant in one ventricle in 9 patients, whereas they had biventricular distribution in others. During sinus rhythm areas of abnormal electrograms were identified in 15/24 patients (62.5%) revealing localized structural alterations: in the right ventricle in 11, the left ventricle in 1, and both in 3. They covered a limited surface (13±6 cm) representing 5±3% of the total surface and were recorded predominantly on the epicardium. Seventy-six percent of these areas were colocated with VF drivers (<0.001). In the 9 patients without structural alteration, we observed a high incidence of Purkinje triggers (7/9 versus 4/15, =0.033). Catheter ablation resulted in arrhythmia-free outcome in 15/18 patients at 17±11 months follow-up.

Conclusions: This study shows that localized structural alterations underlie a significant subset of previously unexplained sudden cardiac death. In the other subset, Purkinje electrical pathology seems as a dominant mechanism.
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http://dx.doi.org/10.1161/CIRCEP.117.006120DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7661047PMC
July 2018

Role of the Purkinje-Muscle Junction on the Ventricular Repolarization Heterogeneity in the Healthy and Ischemic Ovine Ventricular Myocardium.

Front Physiol 2018 14;9:718. Epub 2018 Jun 14.

Centre de Recherche Cardio-Thoracique de Bordeaux, Université de Bordeaux, Bordeaux, France.

Alteration of action potential duration (APD) heterogeneity contributes to arrhythmogenesis. Purkinje-muscle junctions (PMJs) present differential electrophysiological properties including longer APD. The goal of this study was to determine if Purkinje-related or myocardial focal activation modulates ventricular repolarization differentially in healthy and ischemic myocardium. Simultaneous epicardial (EPI) and endocardial (ENDO) optical mapping was performed on sheep left ventricular (LV) wedges with intact free-running Purkinje network ( = 7). Preparations were paced on either ENDO or EPI surfaces, or the free-running Purkinje fibers (PFs), mimicking normal activation. EPI and ENDO APDs were assessed for each pacing configuration, before and after (7 min) of the onset of no-flow ischemia. Experiments were supported by simulations. In control conditions, maximal APD was found at endocardial PMJ sites. We observed a significant transmural APD gradient for PF pacing with PMJ APD = 347 ± 41 ms and EPI APD = 273 ± 36 ms ( < 0.001). A similar transmural gradient was observed when pacing ENDO (49 ± 31 ms; = 0.005). However, the gradient was reduced when pacing EPI (37 ± 20 ms; = 0.005). Global dispersion of repolarization was the most pronounced for EPI pacing. In ischemia, both ENDO and EPI APD were reduced ( = 0.005) and the transmural APD gradient (109 ± 55 ms) was increased when pacing ENDO compared to control condition or when pacing EPI ( < 0.05). APD maxima remained localized at functional PMJs during ischemia. Local repolarization dispersion was significantly higher at the PMJ than at other sites. The results were consistent with simulations. We found that the activation sequence modulates repolarization heterogeneity in the ischemic sheep LV. PMJs remain active following ischemia and exert significant influence on local repolarization patterns.
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http://dx.doi.org/10.3389/fphys.2018.00718DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6010581PMC
June 2018

Dynamic Action Potential Restitution Contributes to Mechanical Restitution in Right Ventricular Myocytes From Pulmonary Hypertensive Rats.

Front Physiol 2018 12;9:205. Epub 2018 Mar 12.

Multidisciplinary Cardiovascular Research Centre, University of Leeds, Leeds, United Kingdom.

We investigated the steepened dynamic action potential duration (APD) restitution of rats with pulmonary artery hypertension (PAH) and right ventricular (RV) failure and tested whether the observed APD restitution properties were responsible for negative mechanical restitution in these myocytes. PAH and RV failure were provoked in male Wistar rats by a single injection of monocrotaline (MCT) and compared with saline-injected animals (CON). Action potentials were recorded from isolated RV myocytes at stimulation frequencies between 1 and 9 Hz. Action potential waveforms recorded at 1 Hz were used as voltage clamp profiles (action potential clamp) at stimulation frequencies between 1 and 7 Hz to evoke rate-dependent currents. Voltage clamp profiles mimicking typical CON and MCT APD restitution were applied and cell shortening simultaneously monitored. Compared with CON myocytes, MCT myocytes were hypertrophied; had less polarized diastolic membrane potentials; had action potentials that were triggered by decreased positive current density and shortened by decreased negative current density; APD was longer and APD restitution steeper. APD90 restitution was unchanged by exposure to the late Na-channel blocker (5 μM) ranolazine or the intracellular Ca buffer BAPTA. Under AP clamp, stimulation frequency-dependent inward currents were smaller in MCT myocytes and were abolished by BAPTA. In MCT myocytes, increasing stimulation frequency decreased contraction amplitude when depolarization duration was shortened, to mimic APD restitution, but not when depolarization duration was maintained. We present new evidence that the membrane potential of PAH myocytes is less stable than normal myocytes, being more easily perturbed by external currents. These observations can explain increased susceptibility to arrhythmias. We also present novel evidence that negative APD restitution is at least in part responsible for the negative mechanical restitution in PAH myocytes. Thus, our study links electrical restitution remodeling to a defining mechanical characteristic of heart failure, the reduced ability to respond to an increase in demand.
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http://dx.doi.org/10.3389/fphys.2018.00205DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5859380PMC
March 2018

Relationship Between Fibrosis Detected on Late Gadolinium-Enhanced Cardiac Magnetic Resonance and Re-Entrant Activity Assessed With Electrocardiographic Imaging in Human Persistent Atrial Fibrillation.

JACC Clin Electrophysiol 2018 01 6;4(1):17-29. Epub 2017 Nov 6.

Haut-Lévêque Cardiology Hospital, Bordeaux University Hospital Center, University of Bordeaux, France.

Objectives: This study sought to assess the relationship between fibrosis and re-entrant activity in persistent atrial fibrillation (AF).

Background: The mechanisms involved in sustaining re-entrant activity during AF are poorly understood.

Methods: Forty-one patients with persistent AF (age 56 ± 12 years; 6 women) were evaluated. High-resolution electrocardiographic imaging (ECGI) was performed during AF by using a 252-chest electrode array, and phase mapping was applied to locate re-entrant activity. Sites of high re-entrant activity were defined as re-entrant regions. Late gadolinium-enhanced (LGE) cardiac magnetic resonance (CMR) was performed at 1.25 × 1.25 × 2.5 mm resolution to characterize atrial fibrosis and measure atrial volumes. The relationship between LGE burden and the number of re-entrant regions was analyzed. Local LGE density was computed and characterized at re-entrant sites. All patients underwent catheter ablation targeting re-entrant regions, the procedural endpoint being AF termination. Clinical, CMR, and ECGI predictors of acute procedural success were then analyzed.

Results: Left atrial (LA) LGE burden was 22.1 ± 5.9% of the wall, and LA volume was 74 ± 21 ml/m. The number of re-entrant regions was 4.3 ± 1.7 per patient. LA LGE imaging was significantly associated with the number of re-entrant regions (R = 0.52, p = 0.001), LA volume (R = 0.62, p < 0.0001), and AF duration (R = 0.54, p = 0.0007). Regional analysis demonstrated a clustering of re-entrant activity at LGE borders. Areas with high re-entrant activity showed higher local LGE density as compared with the remaining atrial areas (p < 0.0001). Failure to achieve AF termination during ablation was associated with higher LA LGE burden (p < 0.001), higher number of re-entrant regions (p < 0.001), and longer AF duration (p = 0.008).

Conclusions: The number of re-entrant regions during AF relates to the extent of LGE on CMR, with the location of these regions clustering to LGE areas. These characteristics affect procedural outcomes of ablation.
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http://dx.doi.org/10.1016/j.jacep.2017.07.019DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5824731PMC
January 2018

Cardiac electrical dyssynchrony is accurately detected by noninvasive electrocardiographic imaging.

Heart Rhythm 2018 07 1;15(7):1058-1069. Epub 2018 Mar 1.

Electrophysiology and Heart Modelling Institute (IHU-LIRYC), Fondation Bordeaux Université, Pessac, France; Université de Bordeaux, Centre de Recherche Cardio-Thoracique de Bordeaux U1045, France; Inserm, U1045, Centre de Recherche Cardio-Thoracique de Bordeaux, France.

Background: Poor identification of electrical dyssynchrony is postulated to be a major factor contributing to the low success rate for cardiac resynchronization therapy.

Objective: The purpose of this study was to evaluate the sensitivity of body surface mapping and electrocardiographic imaging (ECGi) to detect electrical dyssynchrony noninvasively.

Methods: Langendorff-perfused pig hearts (n = 11) were suspended in a human torso-shaped tank, with left bundle branch block (LBBB) induced through ablation. Recordings were taken simultaneously from a 108-electrode epicardial sock and 128 electrodes embedded in the tank surface during sinus rhythm and ventricular pacing. Computed tomography provided electrode and heart positions in the tank. Epicardial unipolar electrograms were reconstructed from torso potentials using ECGi. Dyssynchrony markers from torso potentials (eg, QRS duration) or ECGi (total activation time, interventricular delay [D-LR], and intraventricular markers) were correlated with those recorded from the sock.

Results: LBBB was induced (n = 8), and sock-derived activation maps demonstrated interventricular dyssynchrony (D-LR and total activation time) in all cases (P < .05) and intraventricular dyssynchrony for complete LBBB (P < .05) compared to normal sinus rhythm. Only D-LR returned to normal with biventricular pacing (P = .1). Torso markers increased with large degrees of dyssynchrony, and no reduction was seen during biventricular pacing (P > .05). Although ECGi-derived markers were significantly lower than recorded (P < .05), there was a significant strong linear relationship between ECGi and recorded values. ECGi correctly diagnosed electrical dyssynchrony and interventricular resynchronization in all cases. The latest site of activation was identified to 9.1 ± 0.6 mm by ECGi.

Conclusion: ECGi reliably and accurately detects electrical dyssynchrony, resynchronization by biventricular pacing, and the site of latest activation, providing more information than do body surface potentials.
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http://dx.doi.org/10.1016/j.hrthm.2018.02.024DOI Listing
July 2018

Platelet function and microparticle levels in atrial fibrillation: Changes during the acute episode.

Int J Cardiol 2017 Sep;243:216-222

IHU Liryc, Electrophysiology and Heart Modeling Institute, fondation Bordeaux Université, 33600, Pessac, France. Electronic address:

Background: Thrombotic risk constitutes a major complication of atrial fibrillation (AF). Platelets and microparticles (MPs) are important for hemostasis and thrombosis, however their participation during AF is not well known. The aim of this study was to characterize platelet function and MPs procoagulant and fibrinolytic activity in AF patients and to determine the effects of an acute-AF episode.

Methods: Blood was collected from paroxysmal (21) and persistent (16) AF patients referred for AF catheter ablation. Ten patients in sinus rhythm for 10days were induced in AF allowing comparisons of left atrium samples before and after induction. Platelet aggregation with ADP, TRAP, collagen, and ristocetin was studied. Platelet surface expression of PAR-1, αIIbβ3, GPIb and P-selectin were evaluated by flow cytometry, and MPs-associated procoagulant and fibrinolytic activity levels were determined by functional assays.

Results: A specific reduction in platelet aggregation to TRAP, activating the thrombin receptor PAR-1, was found in all AF patients. No differences in platelet receptor expression were found. Yet, after acute-induced AF, the platelet response was improved. Furthermore, a significant decrease of left atrium tissue factor-dependent procoagulant activity of MPs was observed.

Conclusion: Acute episodes of AF results in a decrease in MPs-associated tissue factor activity, possibly corresponding to consumption, which in turn favors coagulation and the local production of thrombin. A decreased platelet basal aggregation to TRAP may result from PAR1 desensitization, whereas the improved response after an induced episode of AF suggests activation of coagulation and PAR1 re-sensitization.
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http://dx.doi.org/10.1016/j.ijcard.2017.03.068DOI Listing
September 2017

Proarrhythmic remodelling of the right ventricle in a porcine model of repaired tetralogy of Fallot.

Heart 2017 03 8;103(5):347-354. Epub 2016 Oct 8.

IHU LIRYC, L'Institut de Rythmologie et Modélisation Cardiaque, Fondation Bordeaux Université, Bordeaux, France.

Objective: The growing adult population with surgically corrected tetralogy of Fallot (TOF) is at risk of arrhythmias and sudden cardiac death. We sought to investigate the contribution of right ventricular (RV) structural and electrophysiological remodelling to arrhythmia generation in a preclinical animal model of repaired TOF (rTOF).

Methods And Results: Pigs mimicking rTOF underwent cardiac MRI functional characterisation and presented with pulmonary regurgitation, RV hypertrophy, dilatation and dysfunction compared with Sham-operated animals (Sham). Optical mapping of rTOF RV-perfused wedges revealed a significant prolongation of RV activation time with slower conduction velocities and regions of conduction slowing well beyond the surgical scar. A reduced protein expression and lateralisation of Connexin-43 were identified in rTOF RVs. A remodelling of extracellular matrix-related gene expression and an increase in collagen content that correlated with prolonged RV activation time were also found in these animals. RV action potential duration (APD) was prolonged in the epicardial anterior region at early and late repolarisation level, thus contributing to a greater APD heterogeneity and to altered transmural and anteroposterior APD gradients in rTOF RVs. APD remodelling involved changes in Kv4.3 and MiRP1 expression. Spontaneous arrhythmias were more frequent in rTOF wedges and more complex in the anterior than in the posterior RV.

Conclusion: Significant remodelling of RV conduction and repolarisation properties was found in pigs with rTOF. This remodelling generates a proarrhythmic substrate likely to facilitate re-entries and to contribute to sudden cardiac death in patients with rTOF.
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http://dx.doi.org/10.1136/heartjnl-2016-309730DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5529985PMC
March 2017

Unexpected Internalization of a Pulmonary Artery Band in a Porcine Model of Tetralogy of Fallot.

World J Pediatr Congenit Heart Surg 2017 01;8(1):48-54

1 Department of Paediatric and Adult Congenital Heart defects, University Hospital of Bordeaux, Bordeaux, France.

Background: We report our experience of an unexpected complication of internalization of a pulmonary artery (PA) band in the vascular lumen, which occurred in a chronic porcine model of repaired tetralogy of Fallot (TOF).

Methods: Twelve piglets were divided into 3 groups: (1) TOF model animals (PA band plus pulmonary valvotomy, n = 4), (2) pulmonary insufficiency (PI) animals (pulmonary valvotomy, n = 4), and (3) control animals (n = 4). A nonabsorbable, coated braided polyester tape was used to perform the main pulmonary artery banding. Echocardiography was performed 4 months postoperatively. After each animal was euthanized, PA histological analysis was performed in animals with band internalization.

Results: Significant postsurgical pulmonary regurgitation and right ventricular enlargement were present in the TOF and PI, compared with control animals, whereas no significant pulmonary stenosis was observed in TOF animals when compared with PI group. Postmortem examination of all TOF animals revealed the constricting band to be intact but partially internalized into the PA lumen, allowing blood flow around the stenosis. Histological sections of the banded PA in the area of internalization showed a significant disorganization of the medial layer, with significant scarring and fibrotic reaction surrounding the outside of the band and the presence of inflammatory cells suggesting a significant inflammatory response during band internalization.

Conclusions: Band internalization may occur after PA banding using a nonabsorbable, coated braided polyester tape in a chronic porcine model of repaired TOF. This unusual complication was likely due to the type of material used for banding.
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http://dx.doi.org/10.1177/2150135116668828DOI Listing
January 2017