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Longitudinal dissociation of the aggregated specialized cardiomyocytes within the non-branching portion of atrioventricular conduction axis has proved a controversial topic for both morphologists and electrophysiologists. We have now used morphological methods, including three-dimensional assessment, to revisit, in human, canine, and bovine hearts, the presence or absence of interconnections between the aggregated cardiomyocytes making up the non-branching bundle. We analyzed three datasets from human and canine hearts, and two from bovine hearts, using longitudinal and orthogonal serial histological sections. In addition, we assessed three hearts using translucent India ink injected specimens, permitting assessment of the three-dimensional arrangement of the cardiomyocytes. Using the longitudinal sections, we found numerous oblique interconnections between the groups of specialized cardiomyocytes. When assessing orthogonal sections, we noted marked variation in the grouping of the cardiomyocytes. We interpreted this finding as evidence of bifurcation and convergence of the groups seen in the longitudinal sections. The three-dimensional assessment of the bovine material confirmed the presence of the numerous interconnections. The presence of multiple connections between the cardiomyocytes in the non-branching bundle rules out the potential for longitudinal dissociation., (© 2023 American Association of Clinical Anatomists and British Association of Clinical Anatomists.)

The function of a cell is defined by its intrinsic characteristics and its niche: the tissue microenvironment in which it dwells. Here we combine single-cell and spatial transcriptomics data to discover cellular niches within eight regions of the human heart. We map cells to microanatomical locations and integrate knowledge-based and unsupervised structural annotations. We also profile the cells of the human cardiac conduction system 1 . The results revealed their distinctive repertoire of ion channels, G-protein-coupled receptors (GPCRs) and regulatory networks, and implicated FOXP2 in the pacemaker phenotype. We show that the sinoatrial node is compartmentalized, with a core of pacemaker cells, fibroblasts and glial cells supporting glutamatergic signalling. Using a custom CellPhoneDB.org module, we identify trans-synaptic pacemaker cell interactions with glia. We introduce a druggable target prediction tool, drug2cell, which leverages single-cell profiles and drug-target interactions to provide mechanistic insights into the chronotropic effects of drugs, including GLP-1 analogues. In the epicardium, we show enrichment of both IgG + and IgA + plasma cells forming immune niches that may contribute to infection defence. Overall, we provide new clarity to cardiac electro-anatomy and immunology, and our suite of computational approaches can be applied to other tissues and organs., (© 2023. The Author(s).)

The cardiac conduction system (CCS) is crucial for regulating heartbeats; therefore, clinicians and comedicals involved in cardiovascular medicine treatment must have a thorough understanding of the CCS structure and function. However, anatomical education of the CCS based on actual dissection and observation is uncommon, although such educational methodology promotes three-dimensional structural understanding of the observed object. Based on previous studies, we examined the CCS structure in the heart of a swine (pig, Sus scrofa domestica) which has been used in the biological, medical and anatomical curricula as science teaching materials, by using macroscopic dissection procedures. Most CCS structures in a young pig heart were successfully identified and illustrated on a macroscopic scale. The atrioventricular bundle (His bundle) was located on the lower edge of the membranous interventricular septum and was clearly distinguished from the general myocardial fibres by its colour and fibre arrangement direction. Following the atrioventricular bundle towards the atrium or ventricle with properly removing the endocardium and myocardium, the atrioventricular node or the right and left bundles appeared respectively. In contrast, the sinoatrial node was not identified. The anatomy of the CCS in young pig hearts was essentially similar to that previously reported in humans and several domestic animals. Our findings of the CCS in young pig hearts are expected to be useful for medical and anatomical education for medical and comedical students, young clinicians and comedical workers., (© 2022 Wiley-VCH GmbH.)

Aims: The arrangement of the conduction axis is markedly different in various mammalian species. Knowledge of such variation may serve to question the validity of using animals as prospective models for design of systems for clinical use., Methods and Results: We compared the arrangement of the atrioventricular conduction axis in human, murine, canine, porcine, and bovine hearts, examining serially sectioned datasets from 20 human, 16 murine, 3 porcine, 5 canine, and 1 bovine hearts. We also analysed computed tomographic datasets obtained from bovines and one human heart. Unlike the situation in the human heart, there is no formation of an atrioventricular fibrous membranous septum in the murine, canine, porcine, nor bovine hearts. Canine, porcine, and bovine hearts also lack an infero-septal recess, when defined as a fibrous plate supporting the buttress of the atrial septum. In these species, half of the non-coronary leaflet is directly opposed to the ventricular septal surface., Conclusion: There is a long right-sided non-branching component of the axis, which skirts the attachment of the non-coronary sinus of the aortic root. In the bovine heart, moreover, the left bundle branch usually extends intramyocardially as a solitary tape before surfacing and ramifying on the left ventricular septal surface. The difference in the atrioventricular conduction axis between species may influence the anatomical substrates for atrioventricular re-entry tachycardia, as well as providing inferences for assessing the risks of transcatheter implantation of the aortic valve. Further studies are now needed to assess these possibilities., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2022. For permissions, please email: journals.permissions@oup.com.)

Background: Subtle differences exist between dog and human, despite use of the dog as a model for cardiac surgical and electrophysiological research., Objective: The purpose of this study was to investigate the differences in the atrioventricular conduction axis and adjacent structures between dogs and humans., Methods: We prepared 33 human and 5 canine hearts for serial histologic sections of the atrioventricular conduction axis, making correlations with gross anatomic findings. We additionally examined and photographed 15 intact normal human hearts obtained from infants undergoing autopsy. Furthermore, we interrogated a computed tomographic dataset from a human adolescent and from 2 autopsied canine hearts, both with normal cardiac anatomy., Results: All canine hearts lacked an inferoseptal recess, with the noncoronary leaflet of the aortic valve and the right fibrous trigone having direct attachments to the septal surface of the left ventricular outflow tract. This correlated with an extensive nonbranching component of the ventricular conduction axis, which skirted half of the noncoronary aortic sinus. This anatomic arrangement was observed in 2 of 15 of autopsied infant hearts. In the human hearts with an inferoseptal recess, the relatively shorter nonbranching bundle is embedded within the fibrous tissue forming its right wall., Conclusion: We found a major difference between canine and the majority of human hearts, namely, the presence or absence of an inferoseptal recess. When this recess is absent, as in the canine heart and in some human hearts, a greater proportion of the atrioventricular conduction axis is found within the circumference of the subaortic outflow tract., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

The principal function of the ventricular conduction system is rapid electrical activation of the ventricles. The aim of this study is to conduct a morphometric study to pinpoint the morphological parameters that define cardiac conduction cells, allowing us to distinguish them from other cells. Five male horse hearts and five male dog hearts were used in the study. The hearts were fixed in a 5% formaldehyde solution. Histological sections of 5 μm thickness were acquired and stained with hematoxylin-eosin and Masson's trichrome and cardiac conduction cells and their junctions were identified by desmin, connexin 40 and a PAS method. We found statistically significant differences in cardiac conduction fibers density and thickness, which was much higher in horses than in dogs (p = 0.000 for both values). By comparing the measured parameters of the cells in both species, we determined that cardiac conduction cells area and diameters were greater in horses than in dogs (p = 0.000 for all values). In dogs there are more junctions (30.8%) than in horses (26.1%), a statistically significant difference (p = 0.041). Our findings regarding the cardiac conduction fibers distribution in the animal species studied becomes new knowledge that contributes to the morphological study of this component of the cardiac conduction system and also makes it possible to locate exactly the site with the highest density of cardiac conduction fibers as a contribution to the cardiological study of these structures that lead to the prevention of ventricular arrhythmias and the identification of their treatment site., (Copyright © 2021 Elsevier Ltd. All rights reserved.)

Atrioventricular node is responsible for delaying the passage of the electrical impulse to ventricles in order to protect them from fast depolarizations coming from the atria. The importance of this study is to identify the morphological variations of the components of atrioventricular zone that affect the conduction system and its clinical relationship in different species of mammals. We analyzed ten human hearts, nine from horses, eight from pigs, and five from dogs without a clinical history of cardiac pathologies. Histological section thickness of 5 μm were obtained with a microtome and stained with hematoxylin-eosin and Masson's trichrome. We observed both an increase in collagen fibers and a decrease in the size of P cells (nodal pacemaker cells) within the atrioventricular node in dogs, horses and pigs in cases that presented cartilage in fibrous body. The percentage of fundamental substance in atrioventricular node was significantly higher in dogs and the percentage of collagen fibers was higher in pigs, both than in humans. The presence of cartilaginous metaplasia in cardiac fibrous skeleton from different species decreases the size of atrioventricular node and its cells and increases the percentage of collagen fibers within the node, which can reduce the transmission of the electrical impulse to ventricles and therefore predispose to the presentation of ventricular arrhythmias. Morphometric analysis has allowed us to objectively quantify each of the components of AV node and compare them in the different species.

The specialized cardiomyocytes that constitute the conduction system in the human heart, initiate the electric impulse and result in rhythmic and synchronized contraction of the atria and ventricles. Although the atrioventricular (AV) conduction axis was described more than a century ago by Sunao Tawara, the anatomic pathway for propagation of impulse from atria to the ventricles has been a topic of debate for years. Over the past 2 decades, there has been a resurgence of conduction system pacing (CSP) by implanting pacing leads in the His bundle region in lieu of chronic right ventricular pacing that is associated with worse clinical outcomes. The inherent limitations of implanting the leads in the His bundle region has led to the emergence of left bundle branch area pacing in the past 3 years as an alternative strategy for CSP. The clinical experience from performing CSP has helped electrophysiologists gain deeper insight into the anatomy and physiology of cardiac conduction system. This review details the anatomy of the cardiac conduction system, and highlights some of the recently published articles that aid in better understanding of the AV conduction axis and its variations, the knowledge of which is critical for CSP. The remarkable evolution in technology has led to visualization of the cardiac conduction system using noninvasive, nondestructive high-resolution contrast-enhanced micro-computed tomography imaging that may aid in future CSP. We also discuss from anatomical perspective, the differences seen clinically with His bundle pacing and left bundle branch area pacing., (© 2020 Wiley Periodicals LLC.)

Accessory pathways that bypass all or part of the normal atrioventricular conduction system traverse the atrioventricular junction. The atrioventricular junction comprises of a limited septal component and much more extensive right and left parietal components. Its composition forms a plane of insulation between atrial and ventricular myocardium, preventing direct continuity between them. Typical accessory atrioventricular pathways located anywhere along the atrioventricular junction are muscle bundles or may involve muscle around the walls of coronary sinus aneurysms or coronary veins. Increasingly, variants or unusual accessory pathways, some involving an accessory node, are reported in clinical studies., Competing Interests: Disclosure The author has nothing to disclose., (Copyright © 2020 Elsevier Inc. All rights reserved.)

It was Sunao Tawara who, in 1906, established the foundations for knowledge of the arrangement of the atrioventricular conduction axis in man and other mammals. Study of the hearts of ungulates was a central part in his investigation, which assessed other species, including man. He described several subtle differences between the mammals. We have now ourselves studied the cardiac conduction tissue of the ox heart, comparing our findings with our knowledge of the arrangement in man, and providing new insights into the differences illustrated by Tawara. It is, perhaps, surprising that these differences, although subtle, have not attracted more attention. We show that the major difference is the fact that the noncoronary aortic sinus in the ox heart is mainly supported by the myocardium of the ventricular septum, whereas in the human heart the sinus, and its leaflet, are in fibrous contiguity with the aortic leaflet of the mitral valve. It is this feature that determines the difference in the arrangement of the conduction axis between the species. We also show that the emergence of the left bundle branch on the left ventricular aspect of the muscular septum is more variable than previously described. Clin. Anat. 33:383-393, 2020. © 2019 Wiley Periodicals, Inc., (© 2019 Wiley Periodicals, Inc.)

Introduction: Left bundle branch pacing (LBBP), a form of conduction system pacing in addition to His bundle pacing (HBP), can potentially maintain left ventricular electrical synchrony with better sensing and a low and stable capture threshold., Methods: We performed both HBP and LBBP using a canine model (n = 3; male; weight 30-40 kg). The electrocardiogram (ECG), intracardiac electrogram characteristics, and pacing parameters were compared between HBP and LBBP. The hearts were isolated and stained by Lugol's iodine (5%) to assess the relative locations of the leads in relation to the conduction system., Results: The average potential to ventricle interval was longer with HBP compared to LBBP (26.67 ± 3.06 ms vs 12.67 ± 1.15 ms; P = .002). There were also notable differences in the pacing parameters between HBP and LBBP: R-wave amplitude (2.67 ± 0.42 mV vs 11.33 ± 3.06 mV; P = .008), pacing impedance (423.3 ± 40.4 vs 660.0 ± 45.8; P = .003), and threshold (2.30 ± 0.66 V/0.4ms vs 0.67 ± 0.15 V/0.4 ms; P = .014). The paced morphology of ECG was similar to the intrinsic with HBP while a right bundle branch block pattern was noted with LBBP. The anatomical evaluation revealed the location of the leads and the average lead depth was significantly more with LBBP as compared to HBP (12.33 ± 1.53 mm vs1.83 ± 0.29 mm; P < .0001). Furthermore, with LBBP, the tip of the lead helix was noted to be around the LBB., Conclusion: This in vivo canine model study confirms the significant differences between HBP and LBBP. Furthermore, this model provides a precise anatomic evaluation of the location and the depth of the leads in relation to the conduction system., (© 2019 Wiley Periodicals, Inc.)

Variant accessory pathways include atriofascicular, nodofascicular, nodoventricular, atrio-Hisian, and fasciculoventricular pathways. Atriofascicular pathways are the most common with others occurring rarely. The anatomical descriptions, electrocardiographic findings, electrophysiologic findings, and clincial manifestations are discussed., (© 2019 Wiley Periodicals, Inc.)

Transcatheter aortic valve implantation (TAVI) is currently becoming the treatment of choice for patients with calcific aortic stenosis. Despite several technical improvements, the incidence of conduction disturbances has not diminished and remains TAVI's major complication. These disturbances include the occurrence of left bundle branch block and/or high-grade atrioventricular block often requiring pacemaker implantation. The proximity of the aortic valve to the conduction system (conduction pathways) accounts for the occurrence of these complications. Several factors have been identified as carrying a high risk of conduction disturbances like the presence of pre-existing right bundle branch block, the type of valve implanted, the volume of aortic and mitral calcifications, the size of the annulus and the depth of valve implantation. Left bundle branch block is the most frequent post TAVI conduction disturbance. Whereas the therapeutic strategy for persistent complete atrioventricular block is simple, it becomes complex in the presence of fluctuating changes in PR interval and left bundle branch block duration. The QRS width threshold value (150-160 ms) indicative of the need for pacemaker implantation is still being debated. Although there are currently no recommendations regarding the management of these conduction disturbances, the extension of TAVI indications to patient at low surgical risk calls for a standardization of our practice. However, a decision algorithm was recently proposed by a group of experts composed of interventional cardiologists, electrophysiologists and cardiac surgeons. There are still uncertainties about the appropriate timing of pacemaker implantation and the management of new onset left bundle branch block., (Copyright © 2019 Elsevier Masson SAS. All rights reserved.)

Cavo-tricuspid isthmus (CTI) anatomies are highly variable, and specific anatomies lead to a difficult CTI ablation. This study aimed to compare the clinical utility of angiography and intracardiac echocardiography (ICE) in evaluating CTI anatomies, and to investigate the impact of the CTI anatomy on the procedure when the ablation tactic was adjusted to the anatomy. This study included 92 consecutive patients who underwent a CTI ablation. The CTI morphology was assessed with both right atrial angiography and ICE before the ablation, and the ablation tactic was adjusted to the anatomy. The mean CTI length was 34 ± 9 mm. On ICE imaging, 21 (23%) patients had a flat CTI, while 41 (45%) had a concave CTI with a mean depth of 5.6 ± 2.7 mm. The remaining 30 (32%) had a distinct pouch with a mean depth of 6.4 ± 2.3 mm, located at the posterior, middle, and anterior isthmus in 15, 14, and 1 patients, respectively. The Eustachian ridge (ER) was visualized in 46 (50%) patients. On angiography, a pouch and ER were detected in 22 and 15 patients, but not in the remaining 8 and 31, respectively. A complete CTI block line was created in all patients without any complications. The CTI anatomy did not significantly impact any procedural parameters. ICE was superior to angiography in evaluating the detailed CTI anatomy, especially pouches and the ER. An adjustment of the ablation tactic to the anatomy could overcome the procedural difficulties of the CTI ablation in cases with specific anatomies.

Background: Mathematical models of electrical propagation in the atria necessitate the specification of fiber orientation, often visualized over the epicardial and endocardial surfaces. Clear graphical representation of an orientation field over a surface remain challenging, which hinders the comparison between published models., Method: A method for the placement of evenly-spaced streamlines over a triangulated surface is proposed. Streamlines tangent to an orientation field are integrated, starting from a set of seed points. Distribution of seed points can be either uniformly random or located in the vicinity of existing streamlines. Stopping conditions are designed to prevent streamlines from getting closer than a threshold referred to as the separation distance. At each iteration, the longest among candidate streamlines is kept. Streamlines are finally rendered on the surface as tubes. The outcome is assessed subjectively by visual inspection and objectively by measuring average streamline length and average lateral distance between streamlines., Results: Fiber orientation fields are conveniently created by angle-based interpolation from fiber tracts manually drawn based on literature review. The zebra-like representation of evenly-spaced streamlines enables clear identification of local fiber orientation. The results show that streamline density can be controlled since the lateral distance between streamlines is guaranteed to vary between 1 and 2 times the separation distance. Average streamline length can be increased by using more seed points, which offers a trade-off between quality and speed., Conclusion: Evenly-spaced streamline visualization of fiber orientation facilitates the description and the comparison of fiber structure in computer models of the atria., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Successful mapping and ablation of ventricular tachycardias remains a challenging clinical task. Whereas conventional entrainment and activation mapping was for many years the gold standard to identify reentrant circuits in ischaemic ventricular tachycardia ablation procedures, substrate mapping has become the cornerstone of ventricular tachycardia ablation. In the last decade, technology has dramatically improved. In parallel to high-density automated mapping, cardiac imaging and image integration tools are increasingly used to assess the structural ventricular tachycardia substrate. The aim of this review is to describe the technologies underlying these new mapping systems and to discuss their possible role in providing new insights into identification and visualization of reentrant tachycardia mechanisms., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Human natural killer (HNK)-1 antibody is an established marker of developing cardiac conduction system (CCS) in birds and mammals. In our search for the evolutionary origin of the CCS, we tested this antibody in a variety of sauropsid species (Crocodylus niloticus, Varanus indicus, Pogona vitticeps, Pantherophis guttatus, Eublepharis macularius, Gallus gallus, and Coturnix japonica). Hearts of different species were collected at various stages of embryonic development and studied to map immunoreactivity in cardiac tissues. We performed detection on alternating serial paraffin sections using immunohistochemistry for smooth muscle actin or sarcomeric actin as myocardial markers, and HNK-1 to visualize overall staining pattern and then positivity in specific myocyte populations. We observed HNK-1 expression of various intensity distributed in the extracellular matrix and mesenchymal cell surface of cardiac cushions in most of the examined hearts. Strong staining was found in the cardiac nerve fibers and ganglia in all species. The myocardium of the sinus venosus and the atrioventricular canal exhibited transitory patterns of expression. In the Pogona and Crocodylus hearts, as well as in the Gallus and Coturnix ones, additional expression was detected in a subset of myocytes of the (inter)ventricular septum. These results support the use of HNK-1 as a conserved marker of the CCS and suggest that there is a rudimentary CCS present in developing reptilian hearts. Anat Rec, 302:69-82, 2019. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

Background: Reports of conduction abnormalities necessitating permanent pacemaker implantation due to atrioventricular node artery injury and increasing evidence of stenosis of the atrioventricular node artery in cases of sudden death are of unsolved clinical importance. Unfortunately, technical issues associated with physical and virtual dissections of the atrioventricular conduction axis make it difficult to accurately assess its arterial supply., Methods: We used a specialized dissection technique to gather anatomical information on the atrioventricular node artery and described them using attitudinally appropriate terminology., Results: The mean number of atrioventricular node artery branches was 1.6 in 103 submacroscopic examinations and 2.3 in 17 histological reconstructions. The artery had 5 origins in the modified AHA anatomy guidelines: distal RCA (#3), 10.4%; right posterior interventricular artery (#4PI), 7.3%; proximal RCA posterolateral branch (proximal #4PL), 76.8%; distal RCA posterolateral branch detouring the coronary sinus (distal #4PL), 1.8%; distal LCX (#13), 3.7%. Histological examination revealed that most atrioventricular node arteries immediately left the distal compact node (71.8%), suggesting that they supply mainly the proximal part of the AV conduction axis. The artery to the atrioventricular node tended to originate from the medial and atrial aspect of RCA posterolateral branch, and supplied adjacent structures within the inferior pyramidal space before entering the compact atrioventricular node., Conclusions: Based on the visualisation of the atrioventricular conduction axis and its arterial supply, we herein provide the 'gold standard' for understanding the origin, course and distribution of the artery to the atrioventricular node., (Copyright © 2018 Elsevier B.V. All rights reserved.)

Verapamil-sensitive left fascicular monomorphic ventricular tachycardia (LF-VT) was first described ~4 decades ago. Our knowledge regarding this arrhythmia is evolving continuously. The current review aims to highlight up to date aspects of this arrhythmia focusing on its ECG recognition, new considerations of the reentrant circuit, ablation targets in inducible and non-inducible patients and the approach to LF-VT with multiform morphology., (Copyright © 2018 Elsevier Inc. All rights reserved.)

Knowledge of the anatomy of the membranous septum, as a surrogate to the location of the atrioventricular conduction axis, is a prerequisite for those undertaking transcatheter implantation of the aortic valve (TAVI). Equally important is its relationship of the virtual basal ring. This feature, however, has yet to be adequately described in the living heart. We analyzed computed tomographic angiographic datasets from 107 candidates (84.1 ± 5.2 years, 68% women) for TAVI. Using multiplanar reconstructions, we measured the height and width of the membranous septum, and the distances of its superior and inferior margins from the virtual basal ring plane. We also assessed the extent of wedging of the aortic root between the mitral valve and the ventricular septum. Mean heights and widths of the membranous septum were 6.6 ± 2.0, and 10.2 ± 3.1 mm, respectively, with its size significantly associated with that of the aortic root (P < 0.05). Its superior and inferior margins were 4.5 ± 2.3 and 2.1 ± 2.1 mm, respectively, from the plane of the basal ring. The inferior distance, the surrogate for the adjacency of the atrioventricular conduction axis, was ≤ 5mm in 91% of the patients. Deeper wedging of the aortic root was independently correlated with a shorter inferior distance (β = 0.0569, P = 0.0258). The membranous septum is appreciably closer to the virtual basal ring than previously appreciated. These findings impact on estimations of the risk of damage to the atrioventricular conduction axis during TAVI. Clin. Anat. 31:525-534, 2018. © 2018 Wiley Periodicals, Inc., (© 2018 Wiley Periodicals, Inc.)

The left septal fascicular block (LSFB) or blockage of the middle fibers of the left bundle branch is probably caused mainly by - in the developed world - the proximal obstruction of the left anterior descending artery (LAD) before its first anterior septal perforator branch (S 1 ). The association of transient LSFB and left anterior fascicular block (LAFB) - left bifascicular block - and the electrocardiographic type 1 Brugada pattern (BrP) has not been described in the literature yet., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Aim: The human right atrium and sinoatrial node (SAN) anatomy is complex. Optical mapping experiments suggest that the SAN is functionally insulated from atrial tissue except at discrete SAN-atrial electrical junctions called SAN exit pathways, SEPs. Additionally, histological imaging suggests the presence of a secondary pacemaker close to the SAN. We hypothesise that a) an insulating border-SEP anatomical configuration is related to SAN arrhythmia; and b) a secondary pacemaker, the paranodal area, is an alternate pacemaker but accentuates tachycardia. A 3D electro-anatomical computational model was used to test these hypotheses., Methods: A detailed 3D human SAN electro-anatomical mathematical model was developed based on our previous anatomical reconstruction. Electrical activity was simulated using tissue specific variants of the Fenton-Karma action potential equations. Simulation experiments were designed to deploy this complex electro-anatomical system to assess the roles of border-SEPs and paranodal area by mimicking experimentally observed SAN arrhythmia. Robust and accurate numerical algorithms were implemented for solving the mono domain reaction-diffusion equation implicitly, calculating 3D filament traces, and computing dominant frequency among other quantitative measurements., Results: A centre to periphery gradient of increasing diffusion was sufficient to permit initiation of pacemaking at the centre of the 3D SAN. Re-entry within the SAN, micro re-entry, was possible by imposing significant SAN fibrosis in the presence of the insulating border. SEPs promoted the micro re-entry to generate more complex SAN-atrial tachycardia. Simulation of macro re-entry, i.e. re-entry around the SAN, was possible by inclusion of atrial fibrosis in the presence of the insulating border. The border shielded the SAN from atrial tachycardia. However, SAN micro-structure intercellular gap junctional coupling and the paranodal area contributed to prolonged atrial fibrillation. Finally, the micro-structure was found to be sufficient to explain shifts of leading pacemaker site location., Conclusions: The simulations establish a relationship between anatomy and SAN electrical function. Microstructure, in the form of intercellular gap junction coupling, was found to regulate SAN function and arrhythmia.

Cardiac arrhythmias and conduction disturbances are accompanied by structural remodelling of the specialised cardiomyocytes known collectively as the cardiac conduction system. Here, using contrast enhanced micro-computed tomography, we present, in attitudinally appropriate fashion, the first 3-dimensional representations of the cardiac conduction system within the intact human heart. We show that cardiomyocyte orientation can be extracted from these datasets at spatial resolutions approaching the single cell. These data show that commonly accepted anatomical representations are oversimplified. We have incorporated the high-resolution anatomical data into mathematical simulations of cardiac electrical depolarisation. The data presented should have multidisciplinary impact. Since the rate of depolarisation is dictated by cardiac microstructure, and the precise orientation of the cardiomyocytes, our data should improve the fidelity of mathematical models. By showing the precise 3-dimensional relationships between the cardiac conduction system and surrounding structures, we provide new insights relevant to valvar replacement surgery and ablation therapies. We also offer a practical method for investigation of remodelling in disease, and thus, virtual pathology and archiving. Such data presented as 3D images or 3D printed models, will inform discussions between medical teams and their patients, and aid the education of medical and surgical trainees.

We studied the morphology of the atrioventricular conduction system (AVCS) and Purkinje fibers of the yak. Light and transmission electron microscopy were used to study the histological features of AVCS. The distributional characteristics of the His-bundle, the left bundle branch (LBB), right bundle branch (RBB), and Purkinje fiber network of yak hearts were examined using gross dissection, ink injection, and ABS casting. The results showed that the atrioventricular node (AVN) of yak located in the right side of interatrial septum and had a flattened ovoid shape. The AVN of yak is composed of the slender, interweaving cells formed almost entirely of the transitional cells (T-cells). The His-bundle extended from the AVN, and split into left LBB and RBB at the crest of the interventricular septum. The LBB descended along the left side of interventricular septum. At approximately the upper 1/3 of the interventricular septum, the LBB typically divided into three branches. The RBB ran under the endocardium of the right side of interventricular septum, and extended to the base of septal papillary muscle, passed into the moderator band, crossed the right ventricular cavity to reach the base of anterior papillary muscle, and divided into four fascicles under the subendocardial layer. The Purkinje fibers in the ventricle formed a complex spatial network. The distributional and cellular component characteristics of the AVCS and Purkinje fibers ensured normal cardiac function., (© 2017 Wiley Periodicals, Inc.)

This article reviewed the main anatomic and physiopathological aspects of the left bundle branch from its origin in the His bundle and its intraventricular distribution on the left endocardial surface. The results are based on the relevant literature and on personal observations executed on 206 hearts distributed as follows: 67 dogs, 60 humans, 45 sheep, 22 pigs, 10 cows, 2 monkeys, 1 guanaco, and 1 sea lion. The main anatomical features of the His-Purkinje conducting system may be summarized as follows: The bundle of His is composed by two segments: the penetrating and branching portions. LBB originates in the branching portion located underneath the membranous septum. There is no true bifurcation of the bundle of His in a human heart. Short after its origin the LBB gives rise to its two main fascicles, anterior and posterior, both heading the anterior and posterior papillary muscles, respectively. The anterior division is thinner and longer than the posterior one. The RBB and the most anterior fibers of the LBB arise at the end of the branching portion. In some cases a well-defined left septal fascicle can be identified, usually arising from the posterior division. Each division gives off small fibers and false tendons crossing the left ventricular cavity connecting the papillary between them or the papillary muscles with the septal surface. From each division of the LBB, their corresponding Purkinje networks emerge covering the subendocardium of the septum and the free wall of the left ventricles. There are critical relationships of the proximal segments of the His-Purkinje system with the surrounding cardiac structures whose pathologic processes may damage the conducting tissue., (Copyright © 2017 Elsevier Inc. All rights reserved.)

Introduction: Extracellular potentials measured on the heart surfaces are used to infer events that originate deep within the heart wall. We have reconstructed intramural potentials in three dimensions for the first time, and compare these with epicardial and endocardial surface potentials and cardiac microstructure., Methods and Results: Extracellular potentials from intramural point stimulation were measured from a high density 3-D electrode array in the in vivo pig LV. MR and extended volume imaging were used to register electrode locations and characterize fiber and laminar orientations throughout the recording volume. Measured potentials were compared with predictions of tissue-specific bidomain computer activation models. Positive potentials recorded in the LV wall preceded the depolarization wavefront as it spread in the fiber direction. Transverse to this, passive and active potentials spread preferentially in the laminar direction (anisotropy ratio ∼1.6:1). Epicardial surface potentials reflect initial intramural propagation at the stimulus location, but endocardial potentials do not, particularly adjacent to papillary muscles. Measured 3-D potentials were consistently better captured by computer models that incorporate three distinct conductivities aligned with local microstructural axes, but the preferential spread of potentials in the laminar direction was not fully predicted., Conclusions: This study provides evidence for preferential transmural conduction and raises questions about the extent to which intramural electrical events can be inferred from endocardial potentials., (© 2017 Wiley Periodicals, Inc.)

Objective: Cardiac mapping is an important diagnostic step in cardiac electrophysiology. One of its purposes is to generate a map of the depolarization sequence. This map is constructed in clinical routine either by directly analyzing cardiac electrograms (EGMs) recorded invasively or an estimate of these EGMs obtained by a noninvasive technique. Activation maps based on noninvasively estimated EGMs often show artefactual jumps in activation times. To overcome this problem, we present a new method to construct the activation maps from reconstructed unipolar EGMs., Methods: On top of the standard estimation of local activation time from unipolar intrinsic deflections, we propose to mutually compare the EGMs in order to estimate the delays in activation for neighboring recording locations. We then describe a workflow to construct a spatially coherent activation map from local activation times and delay estimates in order to create more accurate maps. The method is optimized using simulated data and evaluated on clinical data from 12 different activation sequences., Results: We found that the standard methodology created lines of artificially strong activation time gradient. The proposed workflow enhanced these maps significantly., Conclusion: Estimating delays between neighbors is an interesting option for activation map computation in electrocardiographic imaging.

For modeling the propagation of action potentials in the human atria, various models have been developed in the past, which take into account in detail the influence of the numerous ionic currents flowing through the cell membrane. Aiming at a simplified description, the Bueno-Orovio-Cherry-Fenton (BOCF) model for electric wave propagation in the ventricle has been adapted recently to atrial physiology. Here, we study this adapted BOCF (aBOCF) model with respect to its capability to accurately generate spatio-temporal excitation patterns found in anatomical and spiral wave reentry. To this end, we compare results of the aBOCF model with the more detailed one proposed by Courtemanche, Ramirez and Nattel (CRN model). We find that characteristic features of the reentrant excitation patterns seen in the CRN model are well captured by the aBOCF model. This opens the possibility to study origins of atrial fibrillation based on a simplified but still reliable description., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

It is difficult for anatomists to dissect the human cardiac conduction system (CCS) on specimens as well as for cardiovascular clinicians to locate the CCS during cardiac operations. Here, we demonstrate a new method for locating the CCS using a 3D model of its nutritious arteries. First, we perfused the coronary arteries with contrast material and then acquired a set of data of thin computer tomography (CT) scans. Then, we generated a 3D model of the coronary artery and distinguished the arteries that supply the CCS. We then located the CCS on the 3D model via its nutritious arteries and dissected the CCS. Finally, the structures that were dissected were removed for histological and immunofluorescent staining. The results of histological and immunofluorescence examination proved the structure to be the CCS. Thus, we successfully located the CCS using a 3D model of its nutritious arteries. We suggest that with this new method, cardiac surgeons can locate a patient's CCS during cardiac surgeries such as transcatheter aortic valve implantation (TAVI) or radiofrequency catheter ablation (RFCA).

The specialised conducting tissues present in the ventricles are responsible for the fast distribution of the electrical impulse from the atrio-ventricular node to regions in the subendocardial myocardium. Characterisation of anatomical features of the specialised conducting tissues in the ventricles is highly challenging, in particular its most distal section, which is connected to the working myocardium via Purkinje-myocardial junctions. The goal of this work is to characterise the architecture of the distal section of the Purkinje network by differentiating Purkinje cells from surrounding tissue, performing a segmentation of Purkinje fibres at cellular scale, and mathematically describing its morphology and interconnections. Purkinje cells from rabbit hearts were visualised by confocal microscopy using wheat germ agglutinin labelling. A total of 16 3D stacks including labeled Purkinje cells were collected, and semi-automatically segmented. State-of-the-art graph metrics were applied to estimate regional and global features of the Purkinje network complexity. Two types of cell types, tubular and star-like, were characterised from 3D segmentations. The analysis of 3D imaging data confirms the previously suggested presence of two types of Purkinje-myocardium connections, a 2D interconnection sheet and a funnel one, in which the narrow side of a Purkinje fibre connect progressively to muscle fibres. The complex network analysis of interconnected Purkinje cells showed no small-world connectivity or assortativity properties. These results might help building more realistic computational PK systems at high resolution levels including different cell configurations and shapes. Better knowledge on the organisation of the network might help in understanding the effects that several treatments such as radio-frequency ablation might have when the PK system is disrupted locally., Competing Interests: The authors have declared that no competing interests exist.

Anatomical location of the conduction system may influence the characteristics of the depolarization and thus characteristics of the QRS complex. It is known that in the heart, there are electro-anatomical relationships, such as relationships among the molecular, genetic and anatomic components of the conduction system and papillary muscles. This review aims to discuss how knowledge of the electro-anatomical developmental relationships helps in understanding the known variability to be observed in the human electrocardiograms., (Copyright © 2016 Elsevier Inc. All rights reserved.)

In this article, the authors outline the key components behind the automated generation of the cardiac impulses and the effect these impulses have on cardiac myocytes. Also, a description of the key components of the normal cardiac conduction system is provided, including the sinoatrial node, the atrioventricular node, the His bundle, the bundle branches, and the Purkinje network. Finally, an outline of how each stage of the cardiac conduction system is represented on the electrocardiogram is described, allowing the reader of the electrocardiogram to translate background information about the normal cardiac conduction system to everyday clinical practice., (Crown Copyright © 2016. Published by Elsevier Inc. All rights reserved.)

We have reviewed the evidence relative to the initial description of the penetrating atrioventricular bundle, seeking to determine whether Wilhelm His Junior is deserving of his eponym., (Copyright © 2016 Elsevier Inc. All rights reserved.)

The cardiac conduction system (CCS) is responsible for the initiation and propagation of action potentials through the heart ensuring efficient pumping of blood. Understanding the anatomy of the CCS and its relationship with other major cardiac components is important to help understand arrhythmias and how certain procedures may increase the incidence of arrhythmias developing. We sectioned a whole human heart and performed Masson's trichrome histology in order to identify the components of the CCS. The histology images were used to construct a 3D anatomical model. We have shown that it is possible to create a 3D anatomical model of the human heart incorporating the CCS based on histological images, and that this model can be used to perform computer simulations of cardiac excitation. From the reconstruction we have been able to show the relative positions of the CCS components to each other. We have also shown how the close proximity of the CCS to the aortic valve can explain some of the conduction complications, such as left bundle branch block, that arise after aortic valve replacement procedures.

How the cardiomyocytes are aggregated within the heart walls remains contentious. We still do not fully understand how the end-to-end longitudinal myocytic chains are arranged, nor the true extent and shape of the lamellar units they aggregate to form. In this article, we show that an understanding of the complex arrangement of cardiac musculature requires knowledge of three-dimensional myocyte orientation (helical and intrusion angle), and appreciation of myocyte packing within the connective tissue matrix. We show how visualization and segmentation of high-resolution three-dimensional image data can accurately identify the morphology and orientation of the myocytic chains, and the lamellar units. Some maintain that the ventricles can be unwrapped in the form of a "helical ventricular myocardial band," that is, as a compartmentalized band with selective regional innervation and deformation, and a defined origin and insertion like most skeletal muscles. In contrast to the simpler interpretation of the helical ventricular myocardial band, we provide insight as to how the complex myocytic chains, the heterogeneous lamellar units, and connective tissue matrix form an interconnected meshwork, which facilitates the complex internal deformations of the ventricular wall. We highlight the dangers of disregarding the intruding cardiomyocytes. Preparation of the band destroys intruding myocytic chains, and thus disregards the functional implications of the antagonistic auxotonic forces they produce. We conclude that the ventricular myocardium is not analogous to skeletal muscle, but is a complex three-dimensional meshwork, with a heterogeneous branching lamellar architecture., (© 2015 Wiley Periodicals, Inc.)

The rabbit is widely used in experimental cardiac physiology, but the neuroanatomy of the rabbit heart remains insufficiently examined. This study aimed to ascertain the architecture of the intrinsic nerve plexus in the walls and septum of rabbit cardiac ventricles. In 51 rabbit hearts, a combined approach involving: (i) histochemical acetylcholinesterase staining of intrinsic neural structures in total cardiac ventricles; (ii) immunofluorescent labelling of intrinsic nerves, nerve fibres (NFs) and neuronal somata (NS); and (iii) transmission electron microscopy of intrinsic ventricular nerves and NFs was used. Mediastinal nerves access the ventral and lateral surfaces of both ventricles at a restricted site between the root of the ascending aorta and the pulmonary trunk. The dorsal surface of both ventricles is supplied by several epicardial nerves extending from the left dorsal ganglionated nerve subplexus on the dorsal left atrium. Ventral accessing nerves are thicker and more numerous than dorsal nerves. Intrinsic ventricular NS are rare on the conus arteriosus and the root of the pulmonary trunk. The number of ventricular NS ranged from 11 to 220 per heart. Four chemical phenotypes of NS within ventricular ganglia were identified, i.e. ganglionic cells positive for choline acetyltransferase (ChAT), neuronal nitric oxide synthase (nNOS), and biphenotypic, i.e. positive for both ChAT/nNOS and for ChAT/tyrosine hydroxylase. Clusters of small intensely fluorescent cells are distributed within or close to ganglia on the root of the pulmonary trunk, but not on the conus arteriosus. The largest and most numerous intrinsic nerves proceed within the epicardium. Scarce nerves were found near myocardial blood vessels, but the myocardium contained only a scarce meshwork of NFs. In the endocardium, large numbers of thin nerves and NFs proceed along the bundle of His and both its branches up to the apex of the ventricles. The endocardial meshwork of fine NFs was approximately eight times denser than the myocardial meshwork. Adrenergic NFs predominate considerably in all layers of the ventricular walls and septum, whereas NFs of other neurochemical phenotypes were in the minority and their amount differed between the epicardium, myocardium and endocardium. The densities of NFs positive for nNOS and ChAT were similar in the epicardium and endocardium, but NFs positive for nNOS in the myocardium were eight times more abundant than NFs positive for ChAT. Potentially sensory NFs positive for both calcitonin gene-related peptide and substance P were sparse in the myocardial layer, but numerous in epicardial nerves and particularly abundant within the endocardium. Electron microscopic observations demonstrate that intrinsic ventricular nerves have a distinctive morphology, which may be attributed to remodelling of the peripheral nerves after their access into the ventricular wall. In conclusion, the rabbit ventricles display complex structural organization of intrinsic ventricular nerves, NFs and ganglionic cells. The results provide a basic anatomical background for further functional analysis of the intrinsic nervous system in the cardiac ventricles., (© 2015 Anatomical Society.)

Introduction: Despite a century of extensive study on the human sinoatrial node (SAN), the structure-to-function features of specialized SAN conduction pathways (SACP) are still unknown and debated. We report a new method for direct analysis of the SAN microstructure in optically-mapped human hearts with and without clinical history of SAN dysfunction., Methods: Two explanted donor human hearts were coronary-perfused and optically-mapped. Structural analyses of histological sections parallel to epicardium (∼13-21 μm intervals) were integrated with optical maps to create 3D computational reconstructions of the SAN complex. High-resolution fiber fields were obtained using 3D Eigen-analysis of the structure tensor, and used to analyze SACP microstructure with a fiber-tracking approach., Results: Optical mapping revealed normal SAN activation of the atria through a lateral SACP proximal to the crista terminalis in Heart #1 but persistent SAN exit block in diseased Heart #2. 3D structural analysis displayed a functionally-observed SAN border composed of fibrosis, fat, and/or discontinuous fibers between SAN and atria, which was only crossed by several branching myofiber tracts in SACP regions. Computational 3D fiber-tracking revealed that myofiber tracts of SACPs created continuous connections between SAN #1 and atria, but in SAN #2, SACP region myofiber tracts were discontinuous due to fibrosis and fat., Conclusions: We developed a new integrative functional, structural and computational approach that allowed for the resolution of the specialized 3D microstructure of human SACPs for the first time. Application of this integrated approach will shed new light on the role of the specialized SAN microanatomy in maintaining sinus rhythm., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Aims: Atrial stunning, a loss of atrial mechanical contraction, can occur following a successful cardioversion. It is hypothesized that persistent atrial fibrillation-induced electrical remodeling (AFER) on atrial electrophysiology may be responsible for such impaired atrial mechanics. This simulation study aimed to investigate the effects of AFER on atrial electro-mechanics., Methods and Results: A 3D electromechanical model of the human atria was developed to investigate the effects of AFER on atrial electro-mechanics. Simulations were carried out in 3 conditions for 4 states: (i) the control condition, representing the normal tissue (state 1) and the tissue 2-3 months after cardioversion (state 2) when the atrial tissue recovers its electrophysiological properties after completion of reverse electrophysiological remodelling; (ii) AFER-SR condition for AF-remodeled tissue with normal sinus rhythm (SR) (state 3); and (iii) AFER-AF condition for AF-remodeled tissue with re-entrant excitation waves (state 4). Our results indicate that at the cellular level, AFER (states 3 & 4) abbreviated action potentials and reduced the Ca2+ content in the sarcoplasmic reticulum, resulting in a reduced amplitude of the intracellular Ca2+ transient leading to decreased cell active force and cell shortening as compared to the control condition (states 1 & 2). Consequently at the whole organ level, atrial contraction in AFER-SR condition (state 3) was dramatically reduced. In the AFER-AF condition (state 4) atrial contraction was almost abolished., Conclusions: This study provides novel insights into understanding atrial electro-mechanics illustrating that AFER impairs atrial contraction due to reduced intracellular Ca2+ transients.

The Purkinje network is not macroscopically visible in human hearts. Sunao Tawara found himself in trouble in the early 1900s, when studying the human heart network. He gained a much better understanding of the net after starting to work with ungulates' hearts. The ungulate heart is proposed as an auxiliary didactic model for the study of the human conduction system. This work provides a detailed description of the India ink injection technique to allow a naked eye visualization of the Purkinje network. The heart muscle was made diaphanous for direct visualization of the ungulate heart intramyocardial network, and computer tomography was employed for visualization of the three dimensional structure of the whole network. The intramyocardial network in the interventricular septum was identified. The pattern of the Purkinje network is described as a connected noneulerian graph, and its possible implications on the mechanism of arrhythmias is discussed. The main differences between the ungulate and human heart conduction systems are stressed.

Although many studies have described the detailed anatomy of the inferior pyramidal space, it may not be easy for cardiologists who have few chances to study cadaveric hearts to understand the correct morphology of the structure. The inferior pyramidal space is the part of extracardiac fibro-adipose tissue wedging between the 4 cardiac chambers from the diaphragmatic surface of the heart. Many cardiologists have interests in pericardial adipose tissue, but the inferior pyramidal space seems to have been neglected. A number of important structures, including the coronary sinus, atrioventricular node, atrioventricular nodal artery, membranous septum, muscular atrioventricular sandwich (previously called the "muscular atrioventricular septum"), atrial septum, ventricular septum, aortic valvar complex, mitral valvar attachment, and tricuspid valvar attachment are associated with the inferior pyramidal space. We previously revealed its 3-dimensional live anatomy using multidetector-row computed tomography. Moreover, the 3-dimensional understanding of the anatomy in association with the cardiac contour is important from the viewpoints of clinical cardiac electrophysiology. The purpose of this article is to demonstrate extended findings regarding the clinical structural anatomy of the inferior pyramidal space, which was reconstructed in combination with the cardiac contour using multidetector-row computed tomography, and discuss the clinical implications of the findings., (© 2015 Wiley Periodicals, Inc.)

A 3-D cardiac visualization is significantly helpful toward clinical applications of magnetocardiography (MCG), but the cardiac reconstruction requires a segmentation process using additional image modalities. This paper proposes a 3-D cardiac outline reconstruction method using only MCG measurement data without further imaging techniques. The cardiac outline was reconstructed by a combination of both spatial filtering and coherence mapping method. The strength of cardiac activities was first estimated by the array-gain constraint minimum-norm spatial filter with recursively updated gram matrix (AGMN-RUG). Then, waveforms were reconstructed at whole source grids, and the maximum source points of an atrium and ventricle were selected as a reference, respectively. Next, the coherence between each maximum source point and whole source points was compared by the coherence mapping method. A reconstructed cardiac outline was validated by comparing with an overlapped volume ratio when the reconstructed volume was identically matched with the original volume. The results obtained by the AGMN-RUG were compared to the results by other spatial filters. The accuracy of numerical simulation and phantom experiment by the AGMN-RUG was superior 10% and 8%, respectively, than the accuracy by the standardized low-resolution electromagnetic tomography. This accuracy demonstrated the efficacy of the proposed 3-D cardiac reconstruction method.

To properly describe the electrical activity of the left ventricle, it is necessary to model the Purkinje fibers, responsible for the fast and coordinate ventricular activation, and their interaction with the muscular propagation. The aim of this work is to propose a methodology for the generation of a patient-specific Purkinje network driven by clinical measurements of the activation times related to pathological propagations. In this case, one needs to consider a strongly coupled problem between the network and the muscle, where the feedback from the latter to the former cannot be neglected as in a normal propagation. We apply the proposed strategy to data acquired on three subjects, one of them suffering from muscular conduction problems owing to a scar and the other two with a muscular pre-excitation syndrome (Wolff-Parkinson-White). To assess the accuracy of the proposed method, we compare the results obtained by using the patient-specific Purkinje network generated by our strategy with the ones obtained by using a non-patient-specific network. The results show that the mean absolute errors in the activation time is reduced for all the cases, highlighting the importance of including a patient-specific Purkinje network in computational models., (Copyright © 2014 John Wiley & Sons, Ltd.)

Computational models have become a fundamental tool in cardiac research. Models are evolving to cover multiple scales and physical mechanisms. They are moving towards mechanistic descriptions of personalised structure and function, including effects of natural variability. These developments are underpinned to a large extent by advances in imaging technologies. This article reviews how novel imaging technologies, or the innovative use and extension of established ones, integrate with computational models and drive novel insights into cardiac biophysics. In terms of structural characterization, we discuss how imaging is allowing a wide range of scales to be considered, from cellular levels to whole organs. We analyse how the evolution from structural to functional imaging is opening new avenues for computational models, and in this respect we review methods for measurement of electrical activity, mechanics and flow. Finally, we consider ways in which combined imaging and modelling research is likely to continue advancing cardiac research, and identify some of the main challenges that remain to be solved., (Copyright © 2014 Elsevier Ltd. All rights reserved.)

Visualizing the anatomy of the atrioventricular (AV) conduction axis substantiates that there is remarkable inter-individual variation at the macro- and microscopic levels, and that the atrioventricular bundle and left bundle branch are located more anteriorly, distally, and cranially and much closer to the aortic root complex than previously thought. The AV conduction system may therefore be compromised during implantation of a transcatheter aortic valve prosthesis, which may account for the relatively high incidence of new cardiac conduction abnormalities when conventional prosthetic valves are used. The design of the newer JenaValve® may afford advantages over more conventional valves by avoiding the high-risk implantation area and the potential for coronary ostia obstruction., (Copyright © 2014 Elsevier Ireland Ltd. All rights reserved.)

Cardiac imaging is routinely used to evaluate cardiac tissue properties prior to therapy. By integrating the structural information with electrophysiological data from e.g. electroanatomical mapping systems, knowledge of the properties of the cardiac tissue can be further refined. However, as in other clinical modalities, electrophysiological data are often sparse and noisy, and this results in high levels of uncertainty in the estimated quantities. In this study, we develop a methodology based on Bayesian inference, coupled with a computationally efficient model of electrical propagation to achieve two main aims: (1) to quantify values and associated uncertainty for different tissue conduction properties inferred from electroanatomical data, and (2) to design strategies to optimize the location and number of measurements required to maximize information and reduce uncertainty. The methodology is validated in an in silico study performed using simulated data obtained from a human image-based ventricular model, including realistic fibre orientation and a transmural scar. We demonstrate that the method provides a simultaneous description of clinically-relevant electrophysiological conduction properties and their associated uncertainty for various levels of noise. By using the developed methodology to investigate how the uncertainty decreases in response to added measurements, we then derive an a priori index for placing electrophysiological measurements in order to optimize the information content of the collected data. Results show that the derived index has a clear benefit in minimizing the uncertainty of inferred conduction properties compared to a random distribution of measurements, reducing the number of required measurements by over 50% in several of the investigated settings. This suggests that the methodology presented in this work provides an important step towards improving the quality of the spatiotemporal information obtained using electroanatomical mapping., (Copyright © 2013 Elsevier B.V. All rights reserved.)

Background: The cardiac conduction system consists of the sinus node, nodal extensions, atrioventricular (AV) node, penetrating bundle, bundle branches, and Purkinje fibers. Node-like AV ring tissue also exists at the AV junctions, and the right and left rings unite at the retroaortic node. The study aims were to (1) construct a 3-dimensional anatomical model of the AV rings and retroaortic node, (2) map electrical activation in the right ring and study its action potential characteristics, and (3) examine gene expression in the right ring and retroaortic node., Methods and Results: Three-dimensional reconstruction (based on magnetic resonance imaging, histology, and immunohistochemistry) showed the extent and organization of the specialized tissues (eg, how the AV rings form the right and left nodal extensions into the AV node). Multiextracellular electrode array and microelectrode mapping of isolated right ring preparations revealed robust spontaneous activity with characteristic diastolic depolarization. Using laser microdissection gene expression measured at the mRNA level (using quantitative PCR) and protein level (using immunohistochemistry and Western blotting) showed that the right ring and retroaortic node, like the sinus node and AV node but, unlike ventricular muscle, had statistically significant higher expression of key transcription factors (including Tbx3, Msx2, and Id2) and ion channels (including HCN4, Cav3.1, Cav3.2, Kv1.5, SK1, Kir3.1, and Kir3.4) and lower expression of other key ion channels (Nav1.5 and Kir2.1)., Conclusions: The AV rings and retroaortic node possess gene expression profiles similar to that of the AV node. Ion channel expression and electrophysiological recordings show the AV rings could act as ectopic pacemakers and a source of atrial tachycardia.

The chronological succession of discoveries on the location and structure of the atrio-ventricular conducting system are described. The starting point of this system is located in the sinus atrial node, identified by the English scientists A. Keith and M. W. Flack in 1907. The atrioventricular conducting system was pointed out by the Swiss physician Wilhelm His Jr. in 1893. The atrioventricular node (AV) was first identified by the Japanese pathologist Sumao Tawara and his German professor Ludwig Aschoff in 1906. Likewise the structure and routes of the three internodal bundles are described. These bundles include: Bachmann's bundle (1916) connecting the right with the left atrium and the AV node; the middle Wenckebach's bundle (1910) and the posterior or Thörel's bundle (1910), extending from the region of the sinus atrial node towards the posterior margin of the AV node. Lastly, the ventricular left and right conduction systems are detailed. These include the main trunk and their peripheral subdivisions with respective networks. Regarding the controversial existence of the left middle subdivision, it can exist in animal and human hearts. Nevertheless, an intermediate left septal network of specialized fibers seems to act as a functional equivalent of this subdivision., (Copyright © 2012 Instituto Nacional de Cardiología Ignacio Chávez. Published by Masson Doyma México S.A. All rights reserved.)

Introduction: Direct catheter ablation for atrial fibrillation does not yield reproducible permanent control as for other atrial arrhythmias. Therefore, there is a need for an alternative intervention, i.e., left atrial exclusion, based on elective ablation of the interatrial connecting bundles., Methods and Results: We describe the "operative anatomy" of the three major interatrial connections: the Bachmann bundle, the coronary sinus bundle, and the left atrial-atrioventricular node connection, based on macroscopic dissections of human and porcine hearts and our previous experience. We identified the three right atrial attachments, with the coronary sinus (CS) and left atrial (LA)-atrioventricular (AV) nodal connection being most problematic for safe ablation., Conclusions: To obtain a complete isolation of the left from the right atrium, all three connections must be ablated. The CS connection must be ablated distal to the ostium. If present, the LA-AV nodal connection can be safely ablated from the left atrium.

It is now over 100years since the discovery of the cardiac conduction system, consisting of three main parts, the sinus node, the atrioventricular node and the His-Purkinje system. The system is vital for the initiation and coordination of the heartbeat. Over the last decade, immense strides have been made in our understanding of the cardiac conduction system and these recent developments are reviewed here. It has been shown that the system has a unique embryological origin, distinct from that of the working myocardium, and is more extensive than originally thought with additional structures: atrioventricular rings, a third node (so called retroaortic node) and pulmonary and aortic sleeves. It has been shown that the expression of ion channels, intracellular Ca(2+)-handling proteins and gap junction channels in the system is specialised (different from that in the ordinary working myocardium), but appropriate to explain the functioning of the system, although there is continued debate concerning the ionic basis of pacemaking. We are beginning to understand the mechanisms (fibrosis and remodelling of ion channels and related proteins) responsible for dysfunction of the system (bradycardia, heart block and bundle branch block) associated with atrial fibrillation and heart failure and even athletic training. Equally, we are beginning to appreciate how naturally occurring mutations in ion channels cause congenital cardiac conduction system dysfunction. Finally, current therapies, the status of a new therapeutic strategy (use of a specific heart rate lowering drug) and a potential new therapeutic strategy (biopacemaking) are reviewed., (Copyright © 2013 Elsevier Inc. All rights reserved.)