Anatomical Substrate Research Articles

Mahaim Revisited.

The name Ivan Mahaim is well-known to electrophysiologists. However, alternative anatomical substrates can produce the abnormal rhythms initially interpreted on the basis of the pathways he first described. These facts have prompted suggestions that Mahaim should be deprived of his eponym. It is agreed that specificity is required when describing the pathways that produce the disordered cardiac conduction, and that the identified pathways should now be described in an attitudinally appropriate fashion. The authors remain to be convinced that understanding will be enhanced simply by discarding the term ‘Mahaim physiology’ from the lexicon. It is fascinating to look back at the history of accessory atrioventricular junctional conduction pathways outside the normal accessory atrioventricular conduction system, and their possible role in rhythm disturbances. It took both the anatomist and the clinical arrhythmologist quite some time to understand the complex anatomical architecture and the ensuing electrophysiological properties. Over the years, the name Mahaim was often mentioned in those discussions, although these pathways were not the ones that produced the eponym. The reason for this review, therefore, is to present relevant information about the person and what followed thereafter.

Feasibility of electroanatomic mapping and radiofrequency catheter ablation in Boxer dogs with symptomatic ventricular tachycardia.

BackgroundTreatment for Boxers with ventricular tachycardia (VT) is limited. Electroanatomic mapping (EAM) facilitates identification of arrhythmogenic substrate for radiofrequency catheter ablation (RFCA).ObjectiveDescribe the use of EAM to guide RFCA in Boxers with VT.AnimalsFive client‐owned Boxers with symptomatic VT or persistent VT despite antiarrhythmic medications.MethodsCase series evaluating clinical, EAM, and before and after RFCA Holter data.ResultsSustained VT was inducible in 3 dogs, but required aggressive stimulation protocols. Low‐voltage areas consistent with electroanatomic scar were found in 2 dogs, located at the right ventricular (RV) outflow tract and cranial RV. Two dogs had a focal activation pattern of VT and 1 dog had a reentrant mechanism. After RFCA, all dogs no longer collapsed and had fewer runs of VT, 3 of which had 0 runs of VT. Number of ventricular premature beats increased in 3 dogs and decreased in 2 dogs, 1 of which had nearly complete resolution of all arrhythmias. Procedural complications included ventricular fibrillation (n = 2) with successful defibrillation, bruising or hemorrhage at the vascular access site (n = 4), retroperitoneal hemorrhage (n = 1), aortic and mitral regurgitation (n = 1), onset of frequent supraventricular tachycardia (n = 1), and persistent right pelvic limb lameness (n = 1).Conclusions and Clinical ImportanceElectroanatomic mapping and RFCA are feasible in Boxers with VT. Based on this small cohort, RFCA may help decrease runs of VT and improve clinical signs. The anatomic substrate and electrophysiologic mechanisms are variable and require further study.

Delusions and hallucinations correlates in Parkinson's disease psychosis

<h3>Introduction</h3> Patients with Parkinson disease (PD) can experience hallucinations (spontaneous aberrant perceptions) and illusions (misinterpretations of real perceptual stimuli). Of such phenomena, visual hallucinations and illusions are the most frequently encountered, although auditory, olfactory and tactile hallucinations can also occur. Hallucinations can have substantial psychosocial effects and, historically, were the main reason for placing patients in nursing homes. Concomitant or overlapping mechanisms are probably active during visual hallucinations, and these include the following: central dopaminergic over-activity and an imbalance with cholinergic neurotransmission; dysfunction of the visual pathways, alterations of brainstem sleep-wake and dream regulation; and impaired attention focus.The aim of this is to present epidemiological, genetic and pathophysiological aspects of psychosis in PD. <h3>Methods</h3> Pacific Northwest Udall Center (PANUC) was analyzed. MOCA was used to assess cognition and the NPI to examine neuropsychological symptoms including psychosis. Patients with PD without hallucinations or delusions served as controls Comparing characteristics of the PD cohort according to having either no psychosis or delusions with or without hallucinations (using the 10-item Neuropsychiatric Inventory (NPI).Chi-square test was applied to compare categorical variables; Fisher's exact test was applied to compare categorical variables when cell frequency is less than 5. Categorical factors were presented as frequencies (percentages). Unavailable logistic regression models were employed to assess association between predictors and outcome.All tests was two-tailed and performed at a significance level of 0.05. R version 3.5.1 (The R Foundation for Statistical Computing, Vienna, Austria) was used for all analyses. <h3>Results</h3> 129 persons (11% of analyzed sample) were included to the study. Of the entire patient's who reported psychotic symptoms: (84%) experienced hallucinations without delusions, (36%) had symptoms dominated by delusions. Severity and/or number of hallucination subtypes were significantly correlated with lower scores in language, memory, attention, executive functioning, and visuospatial ability. Correlations with delusions were non-significant. Tests of differences in the size of the correlations between groups revealed a significant relationship between language and visuospatial performance with hallucinations. Results suggested a significant association between APOE4 status and hallucinations. Compared to APOE4 non-carrier, APOE carrier patients have 4.509 times of odds to develop hallucinations. <h3>Conclusions</h3> Genetic and cognitive correlates of hallucinations and delusions appear to be different in PD, suggesting distinct pathogenic mechanisms and possibly anatomical substrates. Hence, delusions may not share the same associations with dementia as hallucinations

The trigeminal pathways.

The role of the trigeminal system in facial and dural sensitivity has been recognized for a long time. More recently, the trigeminal system has also been considered a prominent actor in brain nociceptive innervation. It is the anatomical substrate of several frequent conditions, such as primary or secondary headaches, trigeminal neuralgia, and other orofacial pains. Appreciation of the delicate anatomical arrangement of the trigeminal pathway is one of the keys to understanding these conditions' pathophysiology and to proposing innovative treatments. This review provides a structured presentation of existing knowledge about the trigeminal system, from classical anatomical data to the most recent literature. First, we present the organization of the trigeminal pathway from the trigeminal divisions, nerve, and nuclei to the thalamus and somatosensory cortex. We describe the neurons and fibers' repartition at each level, depending on the location (somatotopic organization) and the type of receptors (modal organization). Such a dual somatotopic-modal arrangement of the trigeminal fibers is especially clear for the juxtapontine segment of the trigeminal nerve and the trigeminal nuclei of the brainstem. It has significant clinical consequences both for diagnosis and treatment. Second, we explore how the trigeminal system is modulated and involved in reflexes, for instance the trigemino-cardiac and the trigemino-autonomic reflexes, which could play an essential role in the autonomic symptoms observed in cluster headache. Finally, we present how to interact with this complex system to relieve pain mediated by the trigeminal system. This section covers both neuromodulatory and lesional approaches.

Mechanical support for the failing single ventricle after Fontan

Mechanical support for the failing single ventricle after Fontan

Tricuspid regurgitation: recent advances in understanding pathophysiology, severity grading and outcome.

Heightened interest in tricuspid regurgitation (TR) stems from the consistent association of mortality with greater severity of TR, and a low use of surgical solutions in the setting of high in-hospital mortality attributed to the late presentation of the disease. The delay in intervention is likely related to a limited understanding of the valvular/ventricular anatomy and disease pathophysiology, along with an underestimation of TR severity by standard imaging modalities. With the rapid development of transcatheter solutions which have shown early safety and efficacy, there is a growing need to understand and accurately diagnose the valvular disease process in order to determine appropriate management solutions. The current review will describe both normal and pathologic tricuspid valvular anatomy, the classification of these anatomic substrates of TR, the strengths and limitations of the current guidelines-recommended multi-parametric echocardiographic approach and the role of multi-modality imaging, as well as the role of transcatheter device therapy in the management of the disease.

Revealing the Selectivity of Neuroanatomical Alteration in Autism Spectrum Disorder via Reverse Inference

BackgroundAlthough neuroimaging research has identified atypical neuroanatomical substrates in individuals with autism spectrum disorder (ASD), it is at present unclear whether and to what extent disorder-selective gray matter alterations occur in this spectrum of conditions. In fact, a growing body of evidence shows a substantial overlap between the pathomorphological changes across different brain diseases, which may complicate identification of reliable neural markers and differentiation of the anatomical substrates of distinct psychopathologies. MethodsUsing a novel data-driven and Bayesian methodology with published voxel-based morphometry data (849 peer-reviewed experiments and 22,304 clinical subjects), this study performs the first reverse inference investigation to explore the selective structural brain alteration profile of ASD. ResultsWe found that specific brain areas exhibit a >90% probability of gray matter alteration selectivity for ASD: the bilateral precuneus (Brodmann area 7), right inferior occipital gyrus (Brodmann area 18), left cerebellar lobule IX and Crus II, right cerebellar lobule VIIIA, and right Crus I. Of note, many brain voxels that are selective for ASD include areas that are posterior components of the default mode network. ConclusionsThe identification of these spatial gray matter alteration patterns offers new insights into understanding the complex neurobiological underpinnings of ASD and opens attractive prospects for future neuroimaging-based interventions.

Sex-specific echocardiographic phenotypes in left ventricular outflow tract obstruction

Abstract Funding Acknowledgements Type of funding sources: None. Background Previous studies have reported major sex differences in prevalence, demographics, and timing of intervention in left ventricular outflow tract (LVOT) obstruction. Whether the observed differences are related to LVOT anatomy is less explored. Purpose The aim of this study was to assess the anatomic substrate for LVOT obstruction by echocardiography to identify sex-specific phenotypes. Methods We included 76 patients (37% women) with symptomatic LVOT obstruction referred to a tertiary care centre between 2005-2020 to be considered for septal ablation or myectomy. A standardized echocardiography was extended with systematic measurements of parasternal LVOT dimensions at 5, 10 and 15 mm below the aortic valve, proximal septal thickness at 10, 20 and 30 mm, subaortic septal bulge radius and aortoseptal angle in all patients prior to intervention (Image). Measurements were also adjusted for body surface area (BSA). A total of 3 patients had to be excluded from analysis due to poor image quality. Results Women were older (p &amp;lt; 0.001, Table), while there were no differences in body mass index (27.6 v.s. 27.5, p = ns), systolic and diastolic blood pressure (133 v.s 133 mmHg, p = ns and 75 v.s 80 mmHg, p = ns, respectively), or prevalence of hypertension (24% v.s. 29%, p = n.s). Left ventricular end-diastolic diameter, LVOT diameters and septum thickness measured 30 mm from the aortic valve were lower in women (Table). However, in all these measurements the differences disappeared after adjusting for BSA. There were no sex differences in posterior wall thickness. Furthermore, the aortoseptal angle was steeper among women, and the septum bulge radius smaller, remaining so even after adjustment for BSA(Table). Conclusion In women with LVOT obstruction, the septum bulge radius adjusted for BSA was smaller, and the aortoseptal angle steeper. Our findings suggest that there may be important sex differences in the echocardiographic phenotype in LVOT obstruction. Abstract Table Abstract Figure. Image

Twelve-month clinical outcomes of "nano-crush technique" for the treatment of bifurcation lesions using ultra-thin (60 µm) sirolimus-eluting coronary stents.

Provisional stenting is preferred for bifurcation lesion; however, certain anatomical substrate does require two stents as a part of dedicated stent technique. Here, the present study evaluated outcomes of ultra-thin (60 µm) Supra family sirolimus-eluting stent (SES) (Sahajanand Medical Technologies Limited, Surat, India) for dedicated bifurcation lesions using nano-crush technique at 12 months angiographic follow-up. This was prospective, single-center observational study which enrolled patients with de novo bifurcation lesion and underwent angioplasty with Supra family SES using nano-crush technique at a tertiary care center in India, between March-2017 and February-2019. Primary endpoint at 12 months was target lesion failure (TLF), a composite of cardiac death, target vessel myocardial infarction (TV-MI), and clinically driven target lesion revascularization (CD-TLR). Secondary endpoints included patient-oriented composite endpoint (POCE), all-cause death, any revascularization, clinically driven target vessel revascularization, stent thrombosis, periprocedural and spontaneous MI, and device failure. The study enrolled total 63 patients with a mean age of 62.5±4.9 years and had male dominance (89%). Left main (LM) bifurcation and non-LM bifurcation were observed in 21 (33%) and 42 (67%) patients, respectively. Total 50 (80%) patients had Medina class- 1,1,1. At 12 months, TLF occurred in 4 (6%) patients which included one cardiac death (1.5%), two (3.0%) TV-MI, and one CD-TLR (1.5%). POCE was observed in 6 (9.6%) patients. Stent failure was seen in 2 (3.1%) patient and one patient (1.5%) developed late stent thrombosis. Twelve months angiographic follow-up indicated intact stent patency in all other patients. On multivariate analysis, LM bifurcation, renal dysfunction, LM bifurcation with renal dysfunction, ejection fraction (<35%) and calcified lesion were found as predictors of TLF. Dedicated stenting with ultra-thin Supra family SES for complex bifurcation lesion using nano-crush technique reported acceptable clinical outcomes among real-world patients and can be performed safely with ease without any procedural complications.

Neonatal lymphatic flow disorders: central lymphatic flow disorder and isolated chylothorax, diagnosis and treatment using novel lymphatic imaging and interventions technique.

Neonatal lymphatic disorders (NLDs) are conditions that are relatively rare and difficult to treat. The recent development of lymphatic imaging, such as Dynamic Contrast-Enhanced MR Lymphangiography and Intranodal Lymphangiography has led to a new, better understanding of the anatomical substrate and pathophysiological mechanisms of the diseases. Consequently, this has allowed the development of new targeted therapeutic interventions as well as prognostication for this population with lymphatic flow disorders. The underlying causes of all NLD is an obstruction or altered flow of the central lymphatic flow. Two types of NLD have been described: isolated neonatal chylothorax and central lymphatic flow disorder (CLFD). Isolated neonatal chylothorax can be treated successfully with oil-based contrast (lipiodol) embolization. CLFD secondary to obstruction of the thoraco-venous junction can be successfully treated with surgical thoracic duct-venous anastomosis. CLFD caused by elevated central pressure and/or thoracic duct dysplasia can be treated medically, including with new systemic therapies such as mammalian target of rapamycin inhibitors. New diagnostic and interventional tools have recently allowed for classification, prognostication, and targeted interventions for neonatal patients with lymphatic flow disorders. Further research will build on these discoveries.

Importance of Acute Anterior Angulation in Double Aortic Arch Needing Attention at Primary Surgery.

BackgroundVascular rings are rare congenital abnormalities of the aortic arch. There are many embryological variants including a double aortic arch. In symptomatic children, division of ring and release of airway structures may be sufficient. Persistence of symptoms can be related to an anterior angle formed between the two arches. The aim of this study is to evaluate the clinical efficacy in improving symptoms and on changing this angle at the primary surgery.MethodsAll children who had surgery for double aortic arch between 2005 and 2020, were studied. Relevant factors were analyzed for persistent symptoms including anatomical substrates and surgical details.ResultsA total of 87 out of 224 children had surgery for a double aortic arch. At presentation, airway symptoms (n = 74/87) were more common than esophageal symptoms (n = 27/87). Early onset symptoms within 1 year were seen in 49 children. In addition to division of one arch, surgical steps also included realigning the anterior left arch, thereby eliminating the acute angle in 36 children (after 2014). After surgery, symptom relief within 12 months following surgery was seen in 64% of children (56 out of 87) but in 27 out of 36 children (75%) with additional surgical modification, as against 29 out of 51 (57%) in those with division of the arch. Symptoms persisted beyond 1 year needing reintervention in eight children.ConclusionAnterior arch angulation plays an important role in double aortic arch by causing a “nutcracker” phenomenon. Repair in double aortic arch should consider this aspect and include modification of surgical steps by realigning the corresponding aortic arch branches and an anterior pexy in selected cases.

Sigma-1 receptors and progesterone metabolizing enzymes in nociceptive sensory neurons of the female rat trigeminal ganglia: A neural substrate for the antinociceptive actions of progesterone.

Orofacial pain disorders are predominately experienced by women. Progesterone, a major ovarian hormone, is neuroprotective and antinociceptive. We recently reported that progesterone attenuates estrogen-exacerbated orofacial pain behaviors, yet it remains unclear what anatomical substrate underlies progesterone’s activity in the trigeminal system. Progesterone has been reported to exert protective effects through actions at intracellular progesterone receptors (iPR), membrane-progesterone receptors (mPR), or sigma 1 receptors (Sig-1R). Of these, the iPR and Sig-1R have been reported to have a role in pain. Progesterone can also have antinociceptive effects through its metabolite, allopregnanolone. Two enzymes, 5α-reductase and 3α-hydroxysteroid dehydrogenase (3α-HSD), are required for the metabolism of progesterone to allopregnanolone. Both progesterone and allopregnanolone rapidly attenuate pain sensitivity, implicating action of either progesterone at Sig-1R and/or conversion to allopregnanolone which targets GABAA receptors. In the present study, we investigated whether Sig-1 Rs are expressed in nociceptors within the trigeminal ganglia of cycling female rats and whether the two enzymes required for progesterone metabolism to allopregnanolone, 5α-reductase and 3α-hydroxysteroid dehydrogenase, are also present. Adult female rats from each stage of the estrous cycle were rapidly decapitated and the trigeminal ganglia collected. Trigeminal ganglia were processed by either fluorescent immunochemistry or western blotting to for visualization and quantification of Sig-1R, 5α-reductase, and 3α-hydroxysteroid dehydrogenase. Here we report that Sig-1Rs and both enzymes involved in progesterone metabolism are highly expressed in a variety of nociceptive sensory neuron populations in the female rat trigeminal ganglia at similar levels across the four stages of the estrous cycle. These data indicate that trigeminal sensory neurons are an anatomical substrate for the reported antinociceptive activity of progesterone via Sig-1R and/or conversion to allopregnanolone.

Miniseries 1-Part II: the comparative anatomy of the atrioventricular conduction axis.

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. 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. 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.

Classification and Treatment of Sleep Disorders by Clinical Syndrome, Anatomic Localization and Pathophysiology

The treatment of sleep disorders is problematic because the diagnoses consist of an array of unrelated terms, there is little knowledge or link to disease processes, and progression from the patient presentation to effective therapy is not systematic. The purpose of this paper is to provide a coherent framework for understanding sleep disorders, based on anatomy and pathophysiology. A classification of sleep disorders based on classical neurological diagnosis is presented. First, the diagnostic process in classical, clinical neurology is reviewed. In this traditional approach, diagnoses are not inferred directly from symptoms. Rather, symptoms are used to identify putative anatomic localizations, and pathophysiological mechanisms. Diagnoses are inferred as a second step from the localizations and mechanisms of disease. Subsequently, testing may be applied as necessary, using a probabilistic interpretation to guide treatment. Treatment for diseases classified in this manner is more likely to be successful. In addition, be generating alternative hypotheses during this process, if initial treatments are not successful, alternative approaches may be considered. The anatomy and physiology of sleep disorders is briefly reviewed. The process of diagnosis is then presented, starting with specific symptoms, including insomnia, hypersomnia, limb movement disorders, fatigue and pain syndromes. Groups of symptoms, as syndromes, are considered. By relating the symptoms to the localizations and pathophysiology, a more ordered approach to management is presented. The distinction of etiology from diagnosis is discussed. Etiologies that have resolved are typically not treatable. Prior research on fibromyalgia is summarized, including possible anatomic and pathophysiological substrates, and underlying sleep disorders. Other forms of fatigue are contrasted, with implications for different treatments.

Identification of novel pulmonary vein nodes as generators of ectopic arrhythmic foci for atrial fibrillation: an immunohistochemical proof.

The atrial muscle sleeve (AMS) of the pulmonary vein is the most common source of the arrhythmogenic triggers in atrial fibrillation (AF). Anatomical substrate generating these ectopic currents is still elusive. The present study was designed to study the AMS of pulmonary veins with an emphasis on the structural basis which might govern AF initiation and perpetuation. The study was conducted on a longitudinal tissue section of pulmonary vein, taken from 15 human cadaveric nondiseased hearts. Tissue was studied histologically using H&E and Gömöri trichrome stain. The pacemaker channels were identified by immunohistochemistry using monoclonal HCN4 and HCN1 antibodies. The AMS was identified in each pulmonary vein, located between the tunica adventitia and tunica media. A node-like arrangement of myocytes was seen within the AMS in 30% of veins. It had a compact zone limited by a fibrous capsule and contained much smaller, paler and interconnected myocytes. Outside the capsule, there was a zone of dispersed, singly placed myocytes separating the compact zone from the working myocytes of the AMS. HCN4 and HCN1 antibodies were expressed on the cell membrane of nodal myocytes, while the working myocytes demonstrated none to minimal staining. Pulmonary veins nodes are similar to the specialized cardiac conductive tissue in the histological arrangement of compact and transitional zones, cellular characteristics and the presence of pacemaker channels. They might be the anatomical basis of ectopic arrhythmogenic foci. To our knowledge, these nodes are being described for the first time in human.

Transcatheter Device Closure of a Perimembranous Ventricular Septal Defect in Congenitally Corrected Transposition of the Great Arteries

The majority of patients with congenitally corrected transposition of the great arteries, also known as transposition of the great arteries {S,L,L} have ventricular septal defects (VSD), most commonly perimembranous VSD (pmVSD). Transcatheter device closure of pmVSD in these patients has not been widely described. We present a case of device closure of pmVSD in L-TGA with an Amplatzer Duct Occluder II (ADOII) device using a deployment starting in the subpulmonary left ventricle. The case demonstrates some of the technical advantages of the ADOII device for VSD closure, specifically its low profile, symmetric shape, and soft material. These characteristics are advantageous in closing conventional pmVSD but are especially useful in patients with challenging anatomic substrates.

Revealing Continuous Brain Dynamical Organization with Multimodal Graph Transformer.

Brain large-scale dynamics is constrained by the heterogeneity of intrinsic anatomical substrate. Little is known how the spatio-temporal dynamics adapt for the heterogeneous structural connectivity (SC). Modern neuroimaging modalities make it possible to study the intrinsic brain activity at the scale of seconds to minutes. Diffusion magnetic resonance imaging (dMRI) and functional MRI reveals the large-scale SC across different brain regions. Electrophysiological methods (i.e. MEG/EEG) provide direct measures of neural activity and exhibits complex neurobiological temporal dynamics which could not be solved by fMRI. However, most of existing multimodal analytical methods collapse the brain measurements either in space or time domain and fail to capture the spatio-temporal circuit dynamics. In this paper, we propose a novel spatio-temporal graph Transformer model to integrate the structural and functional connectivity in both spatial and temporal domain. The proposed method learns the heterogeneous node and graph representation via contrastive learning and multi-head attention based graph Transformer using multimodal brain data (i.e. fMRI, MRI, MEG and behavior performance). The proposed contrastive graph Transformer representation model incorporates the heterogeneity map constrained by T1-to-T2-weighted (T1w/T2w) to improve the model fit to structure-function interactions. The experimental results with multimodal resting state brain measurements demonstrate the proposed method could highlight the local properties of large-scale brain spatio-temporal dynamics and capture the dependence strength between functional connectivity and behaviors. In summary, the proposed method enables the complex brain dynamics explanation for different modal variants.

Cognitive and affective theory of mind double dissociation after parietal and temporal lobe tumours

Abstract Extensive neuroimaging literature suggests that understanding others’ thoughts and emotions engages a wide network encompassing parietal, temporal and medial frontal brain areas. However, the causal role played by these regions in social inferential abilities is still unclear. Moreover very little is known about theory of mind deficits in brain tumours and whether potential anatomical substrates are comparable to those identified in functional MRI literature. This study evaluated the performance of 105 tumour patients, before and immediately after brain surgery, on a cartoon-based non-verbal task evaluating cognitive (intention attribution) and affective (emotion attribution) theory of mind, as well as a non-social control condition (causal inference). Across multiple analyses, we found converging evidence of a double dissociation between patients with right superior parietal damage, selectively impaired in intention attribution, and those with right anteromedial temporal lesion, exhibiting deficits only in emotion attribution. Instead, patients with damage to the frontal cortex were impaired in all kinds of inferential processes, including those from the non-social control conditions. Overall, our data provide novel reliable causal evidence of segregation between different aspects of the theory of mind network from both the cognitive and also the anatomical point of view.

547 Supernormal conduction of an accessory pathway: the case of a young sportsman

Abstract Aims Ventricular pre-excitation is defined by the presence of all of the following electrocardiographic criteria: PQ interval duration ≤120 ms, QRS duration ≥120 ms, and presence of δ wave (defined as initial ‘slurring’ of the QRS complex). Ventricular pre-excitation together with the presence of symptoms (orthodromic and/or antidromic atrioventricular reentry tachycardia, atrial fibrillation) defines Wolff–Parkinson–White (WPW) syndrome. The anatomical substrate of ventricular pre-excitation consists of an extranodal accessory atrio-ventricular connection: the so-called Kent bundle. Such pathways can have antegrade, retrograde, or mixed conductive properties. Accessory pathways endowed with anterograde conductive capability may be responsible for manifest, intermittent, or non-manifest ventricular pre-excitation depending on whether it is respectively always visible on the ECG, not always visible on the ECG and not visible on the ECG even though the pathway has the ability to antegrade conduction. The rare phenomenon of supernormal conduction of anomalous pathways is part of the manifest pre-excitation, which represents the topic of the case reported below. Methods and results We report the clinical case of a young not agonist sportsman undergoing an electrophysiological study (SEF) because of he is suffering from ventricular pre-excitation. The SEF did not showed the inducibility of arrhythmias and, at the same time, apparently it showed low risk characteristics of the pathway even during adrenergic stimulus. However, a careful study, performed with atrial stimulation with couplings up to refractoriness of the atrioventricular node revealed supernormal conduction properties of the Kent bundle which proved to have high risk characteristics according to current guidelines and, therefore, was effectively treated with catheter ablation. Conclusions This case invites us to careful studying of accessory pathways properties, especially since, although rare, they may possess supernormal conduction characteristics capable of determining high ventricular rates in the case of sustained atrial tachyarrhythmias, especially in conditions of adrenergic hyperactivity.

Abstract 9970: Prevalence of ECG Abnormalities and Association with Arrhythmic Risk and Myocardial Fibrosis in a Large Cohort of Patients with Mitral Valve Prolapse

Background: Inverted or biphasic T-waves (IBTWs) in the inferior leads on a 12-lead electrocardiogram (ECG) have been previously described in small, retrospective samples of MVP with sudden cardiac arrest (SCA) or sudden cardiac death (SCD). However, prior studies are limited by selection of bileaflet involvement, referral bias or targeted autopsies. Moreover, the association of IBTWs with focal fibrosis remains poorly defined. Objective: To assess the rates of IBTWs and their association with arrhythmic risk and late gadolinium enhancement (LGE) by cardiac magnetic resonance (CMR) in an unselected, longitudinal MVP cohort. Methods: We reviewed available 12-lead ECGs from a cohort of 570 MVP patients with clinical and ambulatory ECG or telemetry monitoring evaluated at the University of California San Francisco between 2012 and 2020. IBTWs were considered clinically relevant if present in at least 2 of 3 inferior ECG leads. Complex ventricular ectopy (ComVE) was defined as &gt;5% burden of premature ventricular contractions, bigeminy, or non-sustained ventricular tachycardia. SCD cases were identified through the National Death Index. In a subset of 86 (15%) patients with available contrast CMR, we assessed the presence and location of LGE. Results: Among 570 MVP patients (52% male, mean age 64±17), 86 (15%) had IBTWs, 160 (28%) had ComVE, and 26 (5%) had severe arrhythmic events (2 sustained VT, 13 SCA, and 11 SCD). Of these 26, 15 (58%) were bileaflet. Rates of IBTWs were similar between MVPs with severe arrhythmic events (9/26, 35%), ComVE (28/160, 18%), and no ventricular arrhythmia (58/410, 14%) ( p= 0.33). Among MVPs with contrast CMR, there were higher rates of IBTWs in those with LGE (papillary muscles or basal inferolateral wall in all) versus without LGE (7/22 vs 6/64, respectively, p = 0.01). Conclusions: In a large, unselected MVP sample inclusive of all arrhythmic presentations and leaflet subtypes, the prevalence of IBTWs is overall low and similar in those with and without ventricular arrhythmia, including SCA/SCD. In those with IBTWs, LGE in the papillary muscles or basal inferolateral wall is common, suggesting focal myocardial traction/fibrosis as the underlying anatomical substrate for repolarization abnormalities in the MVP population.