Digital twinning of the human ventricular activation sequence to Clinical 12-lead ECGs and magnetic resonance imaging using realistic Purkinje networks for in silico clinical trials.

Cardiac in silico clinical trials can virtually assess the safety and efficacy of therapies using human-based modelling and simulation. These technologies can provide mechanistic explanations for clinically observed pathological behaviour. Designing virtual cohorts for in silico trials requires exploiting clinical data to capture the physiological variability in the human population. The clinical characterisation of ventricular activation and the Purkinje network is challenging, especially non-invasively. Our study aims to present a novel digital twinning pipeline that can efficiently generate and integrate Purkinje networks into human multiscale biventricular models based on subject-specific clinical 12-lead electrocardiogram and magnetic resonance recordings. Essential novel features of the pipeline are the human-based Purkinje network generation method, personalisation considering ECG R wave progression as well as QRS morphology, and translation from reduced-order Eikonal models to equivalent biophysically-detailed monodomain ones. We demonstrate ECG simulations in line with clinical data with clinical image-based multiscale models with Purkinje in four control subjects and two hypertrophic cardiomyopathy patients (simulated and clinical QRS complexes with Pearson's correlation coefficients > 0.7). Our methods also considered possible differences in the density of Purkinje myocardial junctions in the Eikonal-based inference as regional conduction velocities. These differences translated into regional coupling effects between Purkinje and myocardial models in the monodomain formulation. In summary, we demonstrate a digital twin pipeline enabling simulations yielding clinically consistent ECGs with clinical CMR image-based biventricular multiscale models, including personalised Purkinje in healthy and cardiac disease conditions.

Anatomical and molecular mapping of the left and right ventricular His-Purkinje conduction networks.

Functioning of the cardiac conduction system depends critically on its structure and its complement of ion channels. Therefore, the aim of this study was to document both the structure and ion channel expression of the left and right ventricular His-Purkinje networks, as we have previously done for the sinoatrial and atrioventricular nodes. A three-dimensional (3D) anatomical computer model of the His-Purkinje network of the rabbit heart was constructed after staining the network by immunoenzyme labelling of a marker protein, middle neurofilament. The bundle of His is a ribbon-like structure and the architecture of the His-Purkinje network differs between the left and right ventricles. The 3D model is able to explain the breakthrough points of the action potential on the ventricular epicardium during sinus rhythm. Using quantitative PCR, the expression levels of the major ion channels were measured in the free running left and right Purkinje fibres of the rabbit heart. Expression of ion channels differs from that of the working myocardium and can explain the specialised electrical activity of the Purkinje fibres as suggested by computer simulations; the expression profile of the left Purkinje fibres is more specialised than that of the right Purkinje fibres. The structure and ion channel expression of the Purkinje fibres are highly specialised and tailored to the functioning of the system. The His-Purkinje network in the left ventricle is more developed than that in the right ventricle and this may explain its greater clinical importance.

Histological study on the heart ventricle of Egyptian bovines (Bos aegyptiacus).

Background: The heart ventricles have thicker walls than atrium as they pump blood through blood vessels into all body organs. Aim: This study aimed to describe the histological changes of the heart ventricles in Egyptian bovine (Bos aegyptiacus) with special reference to Purkinje fibers. Methods: A total of 10 male Egyptian bovines of 1-10 years old were divided into three groups according to age; immature, mature, and adult animals. Results: The histological sections from all examined animals' groups revealed three different layers of the wall of both right and left ventricles; endocardium, myocardium, and epicardium. The endocardium was lined with endothelium and filled with fibrous connective tissue. The endocardium of adult bovine was the thickest. Purkinje fibers appeared of pale cytoplasm with few myofibrils. They were present in the deep layer of the endocardium and in the myocardium. The size of Purkinje fibers and the amount of their myofibrils appeared to be increased with advanced age. Bundles of cardiac muscles were the main constituent of the myocardium. The myocardial bundles were separated by fine connective tissue in immature animals that showed an increased amount in the adult animals. The hypereosinophilic cardiac muscle cells were observed in the ventricles of both mature and adult animals suggesting hypercontraction during rigor mortis. An external layer of the ventricles was the epicardium which consisted of connective tissue and covered with mesothelium. Conclusion: Overall, this study revealed histological changes in the wall of the ventricle and Purkinje fibers of Egyptian bovines (B. aegyptiacus) in relation to age. Additionally, the hypereosinophilia of the cardiac muscle cells was recorded in the ventricles of mature and adult bovines.

The anatomy of the cardiac conduction system.

All the myocytes within the heart have the capacity to conduct the cardiac impulse. A population of myocytes is specialized so as to generate the cardiac impulse and then to conduct it from the atrial to the ventricular chambers. This population has become known as the conduction system. Anatomists who seek to demonstrate the location of the components of this system must contend with the fact that the components of the system cannot be distinguished from the working myocardial elements by gross dissection. In important presentations to the German Pathological Society in 1910, rules were suggested for the histological distinction of these conducting cells. These rules proposed that the myocytes, to be considered as part of the conduction system, should be histologically discrete, traceable from section to section in serially prepared material, and if to be considered as tracts, should be insulated by fibrous tissue from the adjacent myocytes. Immunohistochemical techniques have now been developed that better demonstrate the distinction between the cells specialized to conduct from working myocytes. These new techniques, for the most part, confirm the accuracy of the initial descriptions. They also reveal additional areas with the characteristics of conduction tissues. These additional areas are located in a paranodal area adjacent to the sinus node, in the vestibules of both atrioventricular valvar orifices, and in a partial ring around the aortic root. In this review, we describe all these features, emphasizing the relationship of the newly recognized components to the established parts of the cardiac conduction system, and how the new findings need to be assessed in the light of the old criteria.

Cardiac Corpuscles: A "New" Morphofunctional Entity? / Corpúsculos Cardíacos: ¿Una "Nueva" Entidad Morfofuncional?

SUMMARY: The existence of "transitional muscular structures" between subendocardial branches (Purkinje fibers) and ventricular working muscle fibers (WF) was first described by the German anatomist, Kurt Goerttler, in 1964. He designated them as "subendocardial nucleus organs." He supposed such fibers functioned as mechanoreceptors, controlling of the intensity of contraction of the ventricular musculature. Brazilian anatomist Ferraz de Carvalho described similar structures in 1993. A thorough literature search failed to identify any other research articles confirming or denying their existence. The objective of this work was to find such structures in subendocardial ventricular walls in human hearts. We collected fifteen formalin-preserved hearts from the Anatomy Department of São Paulo University and sectioned the apical portions on the right and left ventricles according to method used by Goerttler. We utilized conventional histology (light microscopy- LM), scanning electron microscopy (SEM), and a new preservation method called micro- plastination (MP). At the anterior wall of the right ventricle in the subendocardial region between the interventricular septum and moderator band, we found several bundles of fusiform and helicoidal fibers of similar histology to the WF. The bundles measured between 400 and 1150 µm in length and were separated from adjacent muscular fibers by thin collagen fiber, thus acting as a "pseudo capsule." Some structures seemed to be linked to PF and were appeared to be lymphatic and blood vessels and nerves. We called those structures "cardiac corpuscles" (CC). The observation of the previously "unknown" CC in this initial study confirmed the previous descriptions and its discovery may contribute to new perspectives in the study of cardiac muscle structure and function.

La existencia de "estructuras musculares de transición" entre los ramos subendocárdicos (fibras de Purkinje) y las fibras musculares ventriculares activas(FMV) fue descrita por primera vez por el anatomista alemán Kurt Goerttler en 1964, quien las denominó "órganos del núcleo subendocárdico". Supuso que tales fibras funcionaban como mecanoreceptores, controlando la intensidad de la contracción de la musculatura ventricular. El anatomista brasileño Ferraz de Carvalho describió estructuras similares en 1993. Una búsqueda bibliográfica exhaustiva no logró identificar ningún otro artículo de investigación que confirmara o negara su existencia. El objetivo de este trabajo fue encontrar dichas estructuras en las paredes ventriculares subendocárdicas de corazones humanos. Recolectamos 15 corazones conservados en formalina del Departamento de Anatomía de la Universidad de São Paulo y seccionamos las porciones apicales de los ventrículos derecho e izquierdo según el método utilizado por Goerttler. Utilizamos histología convencional (microscopía de luz-LM), microscopía electrónica de barrido (SEM) y un nuevo método de conservación llamado microplastinación (MP). En la pared anterior del ventrículo derecho en la región subendocárdica entre el tabique interventricular y la banda moderadora, encontramos varios haces de fibras fusiformes y helicoidales de histología similar a la FMV. Los haces medían entre 400 y 1150 µm de longitud y estaban separados de las fibras musculares adyacentes por una fina fibra de colágeno, actuando así como una "pseudocápsula". Algunas estructuras parecían estar vinculadas a la fibras de purkinje y parecían ser vasos linfáticos, sanguíneos y nerviosos. Llamamos a esas estructuras "corpúsculos cardíacos" (CC). La observación del CC previamente "desconocido" en este estudio inicial confirmó las descripciones anteriores y su descubrimiento puede contribuir a nuevas perspectivas en el estudio de la estructura y función del músculo cardíaco.

Purkinje physiology and pathophysiology.

There has always been an appreciation of the role of Purkinje fibers in the fast conduction of the normal cardiac impulse. Here, we briefly update our knowledge of this important set of cardiac cells. We discuss the anatomy of a Purkinje fiber strand, the importance of longitudinal conduction within a strand, circus movement within a strand, conduction, and excitability properties of Purkinjes. At the cell level, we discuss the important components of the ion channel makeup in the nonremodeled Purkinjes of healthy hearts. Finally, we discuss the role of the Purkinjes in forming the heritable arrhythmogenic substrates such as long QT, heritable conduction slowing, CPVT, sQT, and Brugada syndromes.

Activation pattern of the avian left ventricle during ventricular pacing.

OBJECTIVE: This study was planned to investigate ventricular myocardial excitation in birds in which Purkinje fibres penetrate into the ventricular wall and reach the epicardium to advance our knowledge about the evolution of the ventricular activation process in vertebrates. METHODS: A depolarization pattern of the left ventricular free wall in seven open-chest laying hens was mapped by 14 seven-electrode plunge needles under ventricular pacing from different sites. RESULTS: Duration of activation of the left ventricular free wall is significantly increased during ventricular ectopic excitation as compared with sinus rhythm. Its lowest increase occurs during subendocardial pacing of the middle part of the left ventricle, but its greatest increase is observed during subepicardial pacing of the left ventricular base. Multifocality and mosaicity of depolarization of the left ventricular myocardium are expressed in a considerably less degree during ventricular pacing in comparison with sinus rhythm. CONCLUSION: Ectopic excitation of avian heart ventricles occurs mostly due to successive spreading of the activation wave from a pacing site during both ipsi- and contraventricular pacing. During ipsiventricular pacing at least, ectopic excitation of the heart ventricles with the "rich" Purkinje network behaves like one of the mammalian ventricles with the subendocardial Purkinje network.

[Functional and developmental view on Purkinje fibers system]. / Funkcní a vývojový pohled na systém Purkynových vláken.

The cardiac conducting system is vital for generating and synchronizing the heartbeat. Beginning with Tawara, Einthoven and other pioneering workers, a wealth of information has been collected over the last 100 years on the histologic, morphologic and physiologic characteristics of specialized cardiac tissues. However, in the last ten years considerable effort has been put into understanding the cellular and molecular mechanisms governing its development. During this latter period, controversies have also arisen as to the nature of the signaling mechanisms involved in induction and patterning of the conducting system, particularly with respect to the pathways functioning in mammals. In this review, we will try to summarize the current state of knowledge in this field and point out some of the remaining questions.

Crista Supraventricularis Purkinje Network and Its Relation to Intraseptal Purkinje Network.

Using transparent specimens with a dual color injection, microscopy, and computer tomography, this report shows that the right and left ventricular subendocardial Purkinje networks are connected by an extensive septal network in the bovine heart. The septal network is present along the entire septum except at a free zone below ventricular valves. Being the only communication of the basal right septum with the right free wall, the supraventricular crest is an enigmatic but not, by any means, hidden muscular structure. It is one of the last structures to be activated in human heart. It is shown here that the supraventricular crest Purkinje network connects the anterosuperior right ventricular basal free wall Purkinje network to anterior right ventricular basal septal Purkinje network. It is suggested that the stimulus initiated at middle left ventricular endocardium will activate the supraventricular crest. The intraseptal connection found between the basal left ventricular subendocardial septal Purkinje network and the right ventricular basal septal Purkinje network is, probably, the pathway for the stimulus. An anatomic basis is provided to explain why the inflow tract contracts earlier than the outflow tract in the right ventricle systole. Anat Rec, 2017. © 2017 Wiley Periodicals, Inc. Anat Rec, 300:1793-1801, 2017. © 2017 Wiley Periodicals, Inc.

Cellular Physiology and Clinical Manifestations of Fascicular Arrhythmias in Normal Hearts.

Fascicular ventricular arrhythmias represent a spectrum of ventricular tachycardias dependent on the specialized conduction system. Although they are more common in structurally abnormal hearts, there is an increasing body of literature describing their role in normal hearts. In this review, the authors present data from both basic and clinical research that explore the current understanding of idiopathic fascicular ventricular arrhythmias. Evaluation of the cellular electrophysiology of the Purkinje cells shows clear evidence of enhanced automaticity and triggered activity as potential mechanisms of arrhythmias. Perhaps more importantly, heterogeneity in conduction system velocity and refractoriness of the left ventricular conduction system in animal models are in line with clinical descriptions of re-entrant fascicular arrhythmias in humans. Further advances in our understanding of the conduction system will help bridge the current gap between basic science and clinical fascicular arrhythmias.

Morphological study of the atrioventricular conduction system and Purkinje fibers in yak.

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.

[Purkynje fibers of the heart conduction system--history and the present time]. / Purkynova vlákna prevodního systému srdce--historie a soucasnost Purkynových objevu.

It has been 160 years now since Purkynje published the finding of conduction fibers in the heart in Archiv f. Anatomie u. Physiologie and it has been 166 years since his publication in polish version. Already during Purkynje's life, some anatomists had solved the morphology of these fibers but nobody at that time knew of what great physiological and medical importance this discovery would be for medicine. It was seen as late as in the 20th century and in contemporary times. Purkynje's work indicated the cascade of these discoveries, which were leading in the beginning of the previous century to the formulation of the basic scheme of the conduction system. Purkynje fibers or Purkynje cardiomyocytes are part of the whole complex of the cardiac conduction system which today is classified as specific heart muscle tissue, being responsible for the generation of the heart impulses. From the point of view of ultrastructural composition, the cells of different parts of the cardiac conduction system are partly similar. In contrast to the heart contractile cardiomyocytes, the cells of the cardiac conduction system including Purkynje fibers have a small amount of myofibrils,small mitochondrias, light cytoplasm and a higher glycogen content, but no T-tubular system. They can be detected with some morphological methods. Nevertheless the cells of the conduction system are not completely uniform. They differ in size, number of nexuses-gaps and intercalar discs in individual parts of the conduction system. Nevertheless, these specialized cells work as a whole-unit. Nowadays, the morphology research of all the parts of cardiac conduction system, including Purkynje fibers, is focused on ultrastructural, histochemical and genetical problems. The question is, wheather with future gene/cell therapy disturbances of the conduction system such as arrythmias, can be prevented and cured by replacing the electrical pacemakers with biological ones. If Jan Evangelista Purkynje lived today, he would be surprised but surely delighted with the high degree of research concerning his discovery and its clinical application.

Incidence, Distribution and Morphology of Left Ventricular False Tendons in Cat Hearts.

The incidence, distribution, and macro- and microscopic structures of left ventricular false tendons (LVFTs) in the cat heart were studied using 25 normal and 57 diseased hearts. The fibrous bands were observed in the left ventricle of all 82 cat hearts examined and most commonly extended between the papillary muscles and the ventricular septum. Histologically, the LVFTs were composed of central Purkinje fibres and surrounding dense collagenous fibres covered by endothelium. There was no appreciable difference in the incidence, distribution or morphology of LVFTs between the normal and the diseased hearts, indicating that LVFTs are a common anatomic variant in the cat heart.

Protective Role of False Tendon in Subjects with Left Bundle Branch Block: A Virtual Population Study.

False tendons (FTs) are fibrous or fibromuscular bands that can be found in both the normal and abnormal human heart in various anatomical forms depending on their attachment points, tissue types, and geometrical properties. While FTs are widely considered to affect the function of the heart, their specific roles remain largely unclear and unexplored. In this paper, we present an in silico study of the ventricular activation time of the human heart in the presence of FTs. This study presents the first computational model of the human heart that includes a FT, Purkinje network, and papillary muscles. Based on this model, we perform simulations to investigate the effect of different types of FTs on hearts with the electrical conduction abnormality of a left bundle branch block (LBBB). We employ a virtual population of 70 human hearts derived from a statistical atlas, and run a total of 560 simulations to assess ventricular activation time with different FT configurations. The obtained results indicate that, in the presence of a LBBB, the FT reduces the total activation time that is abnormally augmented due to a branch block, to such an extent that surgical implant of cardiac resynchronisation devices might not be recommended by international guidelines. Specifically, the simulation results show that FTs reduce the QRS duration at least 10 ms in 80% of hearts, and up to 45 ms for FTs connecting to the ventricular free wall, suggesting a significant reduction of cardiovascular mortality risk. In further simulation studies we show the reduction in the QRS duration is more sensitive to the shape of the heart then the size of the heart or the exact location of the FT. Finally, the model suggests that FTs may contribute to reducing the activation time difference between the left and right ventricles from 12 ms to 4 ms. We conclude that FTs may provide an alternative conduction pathway that compensates for the propagation delay caused by the LBBB. Further investigation is needed to quantify the clinical impact of FTs on cardiovascular mortality risk.

Prevalence of the coexistence of left ventricular false tendons and premature ventricular complexes in apparently healthy subjects: a prospective study in the general population.

The prevalence of left ventricular false tendons, premature ventricular complexes and their coexistence was evaluated prospectively in 187 healthy company workers aged 21 to 50 (mean 36) years. False tendons were demonstrated echocardiographically in 133 (71%). Eight subjects were withdrawn from the study because of silent mitral valve prolapse. In these 179 healthy subjects, false tendons were detected in 127 (71%) and premature ventricular complexes in 48 (27%). Their coexistence was observed in 40, which showed a significant correlation (p less than 0.05) of false tendons and premature ventricular complexes. In seven of the eight subjects without false tendons, premature ventricular complexes were uniform and infrequent (mean 3 beats/24 h). In the 40 subjects with false tendons, premature ventricular complexes were uniform in 29, multiform in 6 and repetitive in 5, and the mean frequency was 96 beats/24 h. Correlation of premature ventricular complexes with the type of false tendons showed that premature ventricular complexes were significantly associated with thick (greater than or equal to 2 mm) and longitudinal tendons (p less than 0.005). Although it is not certain that left ventricular false tendons are arrhythmogenic, the prevalence of the coexistence of left ventricular false tendons and premature ventricular complexes in the general population, and the special relation between the frequency and the form of premature ventricular complexes and the type of false tendons, suggests that false tendons may play an etiologic role in the genesis of premature ventricular complexes in apparently healthy subjects.

Architectural and functional asymmetry of the His-Purkinje system of the murine heart.

OBJECTIVE: The aim of this work was to target a vital reporter gene in the mouse cardiac conduction system (CS) to distinguish this tissue from the surrounding myocardium in the adult heart. METHODS: A transgenic mouse line has been created in which EGFP is expressed under the control of the Cx40 gene. Correlative investigations associating EGFP imaging and electrophysiological techniques were carried out on the adult heart and isolated cardiomyocytes. RESULTS: In the heart of the Cx40(EGFP/+) mice, EGFP signal was seen in the coronary arteries, the atria, the atrioventricular (AV) node and the His-Purkinje system. The latter was found to be structurally and functionally asymmetrical. The anatomical asymmetry was apparent in both the number of strands or fasciculi making up the His bundle branches (BBs) (1 strand on the right, 20 or so on the left), and the density (low on the right, high on the left) of the network of Purkinje fibers (PFs) that extends over the ventricular wall surfaces. The profiles of the electrical activation patterns recorded on the right and left flanks of the septum were also asymmetrical, mirroring the architecture of the branches. EGFP made it easy to identify the Purkinje cells in populations of dissociated cardiomyocytes and they were investigated using the patch-clamp technique. The hyperpolarization-activated current (If) was recorded in all spontaneously active Purkinje cells. CONCLUSIONS: This investigation provides positive evidence of the asymmetry of the His-Purkinje system of the adult mouse, and the first patch-clamp recording data on murine cardiac Purkinje cells. This mouse model opens up new perspectives for investigating the contribution of specific genes to the morphology and function of the His-Purkinje system.

Estimation of Purkinje trees from electro-anatomical mapping of the left ventricle using minimal cost geodesics.

The electrical activation of the heart is a complex physiological process that is essential for the understanding of several cardiac dysfunctions, such as ventricular tachycardia (VT). Nowadays, patient-specific activation times on ventricular chambers can be estimated from electro-anatomical maps, providing crucial information to clinicians for guiding cardiac radio-frequency ablation treatment. However, some relevant electrical pathways such as those of the Purkinje system are very difficult to interpret from these maps due to sparsity of data and the limited spatial resolution of the system. We present here a novel method to estimate these fast electrical pathways from the local activations maps (LATs) obtained from electro-anatomical maps. The location of Purkinje-myocardial junctions (PMJs) is estimated considering them as critical points of a distance map defined by the activation maps, and then minimal cost geodesic paths are computed on the ventricular surface between the detected junctions. Experiments to validate the proposed method have been carried out in simplified and realistic simulated data, showing good performance on recovering the main characteristics of simulated Purkinje networks (e.g. PMJs). A feasibility study with real cases of fascicular VT was also performed, showing promising results.

Ungulates heart model: a study of the Purkinje network using India ink injection, transparent specimens and computer tomography.

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.

Induction and patterning of the Purkinje fibre network.

Impulse-conducting Purkinje cells differentiate from myocytes during embryogenesis. In the embryonic chicken heart, this conversion of contractile myocytes into conduction cells occurs subendocardially and periarterially. The unique sites of Purkinje fibre differentiation suggest that a shear stress-induced paracrine signal from the endocardium and arterial beds may induce adjacent myocytes to differentiate into conduction cells. Consistent with this model, Purkinje fibre marker genes can be induced in cultured embryonic myocytes by endothelin (ET), an endothelial cell-derived signalling peptide. This inductive response is, however, gradually lost from myocytes as embryos develop, and mature myocytes express only genes characteristic of hypertrophy in response to ET. In vivo, active ET is produced, through proteolytic processing, from its precursor by ET-converting enzyme 1 (ECE1) and triggers signalling by binding to its receptors, ETA and ETB. In the embryonic heart, the expression of these ET signalling components changes dynamically, defining the site and timing of Purkinje fibre differentiation within the ventricular myocardium during chick embryogenesis.

Skeletonization of the atrioventricular node for AV node reentrant tachycardia: experience with 32 patients.

We describe our experience with operative therapy for atrioventricular (AV) node tachycardia using an anatomically guided procedure. The operative rationale was to dissect the AV node from most of its atrial inputs (AV node "skeletonization") with the intent of altering the perinodal substrate and preventing reentry. The anteroseptal and posteroseptal regions were initially approached epicardially to facilitate identification of anatomical structures. Under normothermic cardiopulmonary bypass, the right atrial septum was mobilized and the intermediate AV node was exposed anterior to the tendon of Todaro. Atrioventricular node conduction was monitored electrocardiographically throughout the procedure. Ablation of concomitant accessory pathways was done prior to AV node skeletonization. Thirty-two patients aged 9 to 67 years (mean age, 30 years) underwent operation. Five patients had concomitant accessory pathways in addition to AV node reentry. At electrophysiological study before discharge, no patient had AV block although anterograde and retrograde Wenckebach cycle lengths were significantly prolonged. Six patients had retrograde AV block. Twenty-nine patients are free from arrhythmia and require no antiarrhythmic medication after a follow-up of 1 month to 45 months (mean follow-up, 17 months). Three patients had recurrence of tachycardia ten days, 2 months, and 7 months postoperatively. All patients subsequently had a successful reoperation.