Anatomical Substrate Research Articles

Individual Variability in the Structural Connectivity Architecture of the Human Brain.

The human brain exhibits high degree of individual variability in both its structure and function, which underlies inter-subject differences in cognition and behavior. It was previously shown that functional connectivity is more variable in the hetero-modal association cortex but less variable in the unimodal cortices. Structural connectivity is the anatomical substrate of functional connectivity, but the spatial and temporal patterns of individual variability in structural connectivity (IVSC) remain largely unknown. In the present study, we discovered a detailed and robust chart of IVSC obtained by applying diffusion MRI and tractography techniques to 1724 adults (770 males and 954 females) from multiple imaging datasets. Our results showed that the structural connectivity exhibited the highest and lowest variability in the limbic regions and the unimodal sensorimotor regions, respectively. With increased age, higher IVSC was observed across most brain regions. Moreover, the specific spatial distribution of IVSC is related to the cortical laminar differentiation and myelination content. Finally, we proposed a modified ridge regression model to predict individual cognition and generated idiographic brain mapping, which was significantly correlated with the spatial pattern of IVSC. Overall, our findings further contribute to the understanding of the mechanisms of individual variability in brain structural connectivity and link to the prediction of individual cognitive function in adult subjects.Significance Statement White matter connectivity between grey matter regions plays an important role in integrating information from distributed regions when individuals performing complex cognitive functions. Unique white matter connectivity is the neuroanatomical identity of each individual. The authors systematically explored the spatio-temporal pattern of individual variability in structural connectivity, and the results show higher variability in structural connectivity relates to higher neuroplasticity. In addition, this study reveals that structural connectivity involved in executive function and attention task is different among individuals and highlights the importance of individualized statistical methods for mapping neural pathway of complex cognition.

Electrophysiological Phenotype-Genotype Study of Sustained Monomorphic Ventricular Tachycardia in Inherited, High Arrhythmic Risk, Left Ventricular Cardiomyopathy.

Among inherited cardiomyopathies involving the left ventricle, whether dilated or not, certain genotypes carry a well-established arrhythmic risk, notably manifested as sustained monomorphic ventricular tachycardia (SMVT). Nonetheless, the precise localization and electrophysiological profile of this substrate remain undisclosed across different genotypes. Patients diagnosed with cardiomyopathy and left ventricle involvement due to high-risk genetic variants and SMVT treated by electrophysiological study were recruited from 18 European/US centers. Electrophysiological study, imaging, and outcomes data after ablation were assessed in relation to genotype. Seventy-one patients were included (49.6 Q1-Q3 [40-60] years, 76% men). They were divided into 4 groups according to the affected protein: desmosomal (DSP, PKP2, DSG2, and DSC2), nuclear membrane (LMNA and TMEM43), cytoskeleton (FLNC and DES), and sarcoplasmic reticulum (PLN). Desmosomal genes, TMEM43, and PLN were associated with biventricular disease, while variants in LMNA and cytoskeleton genes had predominant left ventricle involvement (P=0.001). The location of the clinical-SMVT substrate was significantly different based on genotype (P=0.005). DSP and cytoskeleton genes presented SMVTs with right bundle branch block morphology, which origin was identified in the inferolateral segments of the left ventricle. The other desmosomal genes (PKP2 and DSG2), along with TMEM43, showed SMVTs with left bundle branch block morphology and predominantly right ventricular substrate. In contrast, LMNA substrate was mainly observed in the interventricular septum. During a median of 26 Q1-Q3 (10.6-65) months, 27% of patients experienced recurrences of clinical SMVT with differences between genotypes (log-rank 0.016). Nuclear membrane genes demonstrated the highest recurrence rate compared with desmosomal genes (hazard ratio, 4.56 [95% CI, 1.5-13.8]). The anatomic substrate of SMVTs shows a strong correlation with the underlying genotype, electrocardiographic morphology, and recurrence rate. Particularly, patients with nuclear membrane gene variants have a significantly higher recurrence rate compared with those with desmosomal gene variants.

Dispersion of Activation in Single-Beat Global Maps During Programmed Ventricular Stimulation Identifies Infarct-Related Ventricular Tachycardia Isthmus Sites.

Electrophysiological characterization of ventricular tachycardia (VT) isthmus sites is complex and time-consuming. We aimed at developing and validating a global mapping strategy during programmed ventricular stimulation (PVS) to reveal the underlying electrophysiological properties of the infarct-related substrate and to enable identification of highly heterogeneous activation sites associated with protected VT isthmus sites. Experimental study that included 22 pigs with established myocardial infarction undergoing invivo characterization of the anatomical and functional myocardial substrate associated with potential arrhythmogenicity. High-density sequential activation maps during ventricular pacing and VT were compared with single-beat maps using a 64-pole basket catheter positioned in the left ventricle. Further analyses were performed using a novel local activation time-dispersion score to identify regional activation time heterogeneities on both baseline drive pacing and each of the extrastimuli of the PVS protocol. Basket catheter splines covered a median of 81.2% of the endocardial surface of the left ventricle. Basket-catheter-derived single-beat activation maps (N=16) during pacing showed a linear relationship with high-density sequential activation maps. Induction of ventricular arrhythmias was associated with higher local activation time-dispersion score values on single-beat global maps during PVS (N=6, 46 arrhythmia induction attempts). Single-beat-derived local activation time-dispersion score maps during successive coupled extrastimuli of the PVS showed a progressive increase in the predictive performance to identify monomorphic VT isthmus sites within the scar region (area under the curve = 0.779 in S2, area under the curve = 0.859 in S4; N=7). Sixty-four-pole-derived single-beat local activation time-dispersion score global maps during PVS identify infarct-related endocardial regions with highly heterogeneous activation times that are associated with protected VT isthmus sites.

Anatomic and non-anatomic substrates in infants with two ventricles undergoing aortic arch repair.

We sought to examine the relative importance of surgical lesion complexity versus the presence of genetic/syndromic/extracardiac anomalies (GSAs) in determining survival, morbidity or need for reinterventions following repair for aortic arch hypoplasia. A single-centre, retrospective cohort study of infants undergoing biventricular aortic arch repair via sternotomy from 2010 to 2021 was conducted. Survival analysis was performed using Kaplan-Meier methods, with additional Bayesian survival modelling for subgroups. Composite morbidity comprised respiratory, renal, neurologic, or sepsis-related complications. Of 83 included infants, n = 13/83 (15.7%) had complex repairs; 27/83 (32.5%) were GSA+. Operative mortality was significantly higher in GSA+ versus GSA- patients (18.5% vs. 1.8%; p = 0.01), though not for complex versus non-complex repairs. Overall 10-year Kaplan-Meier survival was 86.7%. Bayesian modelling suggested equivalent post-discharge attrition in non-complex/GSA+ and complex/GSA- patients, with the poorest outcomes in complex/GSA+ patients; non-complex/GSA- patients had 100% survival. GSA+ patients exhibited higher composite morbidity (44.4% vs. 7.1% in GSA- p < 0.001), with their mode of death seemingly related to a high incidence of respiratory and neurological morbidity, notably in Dandy-Walker syndrome. The 10-year freedom from arch reinterventions was 87.7%; neither complexity, GSA status, nor post-repair peak arch velocity predicted the need for arch reinterventions. Whilst anatomic complexity may have been somewhat neutralised as a risk factor for operative mortality, in contrast to GSA+ status, there is further post-discharge attrition attributable to complexity or GSA+ status, with additive risk effects. Morbidity directly related to certain syndromes underlies some of this risk. Non-anatomic substrates represent a persistent limitation to outcomes of surgical aortic arch repair in infants.

Novel systematic processing of cardiac magnetic resonance imaging identifies target regions associated with infarct-related ventricular tachycardia.

There is lack of agreement on late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) imaging processing for guiding ventricular tachycardia (VT) ablation. We aim at developing and validating a systematic processing approach on LGE-CMR images to identify VT corridors that contain critical VT isthmus sites. This is a translational study including 18 pigs with established myocardial infarction and inducible VT undergoing in vivo characterization of the anatomical and functional myocardial substrate associated with VT maintenance. Clinical validation was conducted in a multicentre series of 33 patients with ischaemic cardiomyopathy undergoing VT ablation. Three-dimensional LGE-CMR images were processed using systematic scanning of 15 signal intensity (SI) cut-off ranges to obtain surface visualization of all potential VT corridors. Analysis and comparisons of imaging and electrophysiological data were performed in individuals with full electrophysiological characterization of the isthmus sites of at least one VT morphology. In both the experimental pig model and patients undergoing VT ablation, all the electrophysiologically defined isthmus sites (n = 11 and n = 19, respectively) showed overlapping regions with CMR-based potential VT corridors. Such imaging-based VT corridors were less specific than electrophysiologically guided ablation lesions at critical isthmus sites. However, an optimized strategy using the 7 most relevant SI cut-off ranges among patients showed an increase in specificity compared to using 15 SI cut-off ranges (70 vs. 62%, respectively), without diminishing the capability to detect VT isthmus sites (sensitivity 100%). Systematic imaging processing of LGE-CMR sequences using several SI cut-off ranges may improve and standardize procedure planning to identify VT isthmus sites.

Decision cost hypersensitivity underlies Huntington's disease apathy.

The neuropsychiatric syndrome of apathy is now recognized to be a common and disabling condition in Huntington's disease (HD). However, the mechanisms underlying it are poorly understood. One way to investigate apathy is to utilise a theoretical framework of normal motivated behaviour, to determine where breakdown has occurred in people with this behavioural disruption. A fundamental computation underlying motivated, goal-directed behaviour across species is weighing up the costs and rewards associated with actions. Here, we asked whether people with apathy are more sensitive to costs of actions (physical effort and time delay), less sensitive to rewarding outcomes, or both. Based on the unique anatomical substrates associated with HD pathology, we hypothesised that a general hypersensitivity to costs would underpin HD apathy. Genetically confirmed carriers of the expanded Huntingtin gene (premanifest to mild motor manifest disease (n=53) were compared to healthy controls (n = 38). Participants performed a physical effort-based decision-making task (Apple Gathering Task) and a delay discounting task (Money Choice Questionnaire). Choice data was analysed using linear regression and drift diffusion models that also accounted for the time taken to make decisions. Apathetic people with HD accepted fewer offers overall on the Apple Gathering Task, specifically driven by increased sensitivity to physical effort costs, and not explained by motor severity, mood, cognition, or medication. Drift diffusion modelling provided further evidence of effort hypersensitivity, with apathy associated with a faster drift rate towards rejecting offers as a function of varying effort. Increased delay sensitivity was also associated with apathy, both when analysing raw choice and also drift rate, where there was moderate evidence of HD apathy drifting faster towards the immediately available (low cost) option. Furthermore, the effort and delay sensitivity parameters from these tasks were positively correlated. The results demonstrate a clear mechanism for apathy in HD, cost hypersensitivity, which manifests in both the effort and time costs associated with actions towards rewarding goals. This suggests that HD pathology may cause a domain-general disruption of cost processing, which is distinct to apathy occurrence in other brain disorders, and may require different therapeutic approaches.

Mechanisms of Mitral Isthmus Reconnection After Ablation With and Without Vein of Marshall Ethanol Infusion

BackgroundReconnection of the mitral isthmus (MI) is common after radiofrequency ablation (RFA). Vein of Marshall ethanol infusion (VOMEI) expedites MI ablation, but long-term results are unclear. ObjectivesThis study sought to determine anatomic substrates of failed MI ablation, with and without VOMEI. MethodsConsecutive VOMEI procedures were included (n = 231; of which 140 were de novo ablations and 91 were prior RFA failures (rescue VOMEI). MI conduction mechanisms were studied with vein of Marshall (VOM) electrograms obtained with a 2-F octapolar catheter, mapping, and differential pacing. ResultsIn rescue VOMEI, intact VOM electrograms showed epicardial connections, epi-endocardial dissociation, and VOM conduction in pseudo-MI block. After VOMEI, after a follow-up of 725 ± 455 days, 78 patients (33.7%) experienced recurrence. Of those, 36 (46%) had evidence of MI reconnection and 42 had other mechanisms. Of the 36 patients with MI reconnection, endocardial radiofrequency (RF) at the annular MI restored block in 16 (45%), and coronary sinus (CS) RF was required in 20 (55%). Post-VOMEI recurrence mechanisms included CS connection–dependent arrhythmias: CS-mediated perimitral flutter, CS–to–left atrium (LA) and CS ostial re-entry, and CS focal activity. Intraprocedural factors associated with MI reconnection included volume of ethanol delivered ≥4 mL (OR: 0.74; P = NS), CS ablation at VOMEI (OR: 4.05; P = 0.003), and age (OR: 1.06; P = 0.011). ConclusionsMI reconnections after RFA are due to epicardial connections from VOM. Recurrences after VOMEI are due to incomplete annular MI RFA and CS arrhythmogenesis including CS-mediated perimitral flutter, CS-to-LA re-entry and CS focal activity. Adding complete CS disconnection to VOMEI may prevent recurrences.

Integration of Dysphagia Therapy Techniques into Voice Rehabilitation: Design and Content Validation of a Cross-Therapy Protocol

BackgroundThe intricate relationship between swallowing and phonation, sharing anatomical and physiological substrates, underscores a clinical demand for integrated therapeutic approaches. Existing interventions often address these functions in isolation, overlooking their interconnected dynamics. ObjectiveTo design and validate a cross-therapy protocol incorporating dysphagia therapy techniques (maneuvers/exercises) invoice rehabilitation. This protocol aims to exploit the shared biomechanical components of swallowing and phonation to improve both functions simultaneously in patients with underlying hypofunctional laryngeal pathology. MethodsA descriptive research design was employed, consisting of three phases: a comprehensive literature review and expert discussions in a German seminar format to conceptualize the protocol; detailed analysis and categorization of swallowing maneuvers/exercises; and content validation by a panel of seven experts through a structured evaluation instrument. The process integrated motor learning and exercise physiology principles to ensure the protocol's clinical applicability and theoretical coherence. ResultsThe developed cross-therapy protocol incorporates four core swallowing therapy techniques to voice therapy procedures. Selected swallowing therapy techniques target laryngeal excursion and vocal fold closure because they are critical components of swallowing and phonation. Expert validation yielded a Content Validity Coefficient (CVC) exceeding 0.90 for most items, indicating high consensus on the protocol’s relevance, clarity, and applicability. Adjustments were made based on feedback, enhancing the protocol's precision and user-friendliness. ConclusionWe present a novel, evidence-based therapy protocol for voice and swallowing difficulties resulting from hypofunctional laryngeal pathology. Its development marks a significant step toward bridging the gap between swallowing and voice therapy. Future empirical studies are needed to assess its effectiveness in clinical settings.

Architecture and anatomy of executive processes: evidence from verbal fluency and Trail Making Test in 2009 stroke patients.

The few voxel-wise lesion-symptom mapping (VLSM) studies aimed at identifying the anatomy of executive function are limited by the absence of a model and by small populations. Using Trail Making Test (TMT) and verbal fluency and a model of their architectures, our objective was to identify the key structures underlying two major executive processes, set-shifting and strategic word search. We applied a validated VLSM analysis to harmonized cognitive and imaging data from 2009 ischemic stroke patients as a part of the Meta VCI Map consortium. All contrast analyses used an adjusted threshold with 2000 Freedman-Lane permutations (p ≤ 0.05). The TMT parts A and B were associated with structures involved in visual-spatial processing, the motor system, the frontal lobes, and their subcortical connections. Set-shifting depended on the left dorsomedial frontal region. Both semantic and phonemic fluency tests depended on verbal output abilities and processing speed with similar slopes in different languages. The strategic search process depended on Broca's area, F2 and related tracts, temporal and deep regions. Lastly, the lesion map of set-shifting did not overlap with those of strategic word search processes. Our results identify the anatomical substrates of two main executive processes, revealing that they represent only a specific subpart of previously reported structures. Finally, our results indicate that executive functions depend on several specific, anatomically separable executive processes mainly operating in various parts of the frontal lobes.

Suppurative Cervicomediastinitis From the Perspective of the Head and Neck Surgeon in a Tertiary Treatment Unit.

Introduction Cervical suppurations represent an emergency pathology, with a dramatic evolution in the absence of adequate treatment. It frequently affects young people, hence the medico-legal implications of these cases. The anatomical substrate for the development of these deep cervical suppurations is represented by the cervical fascia and spaces. A distinct and extremely serious sub-chapter within diffuse cervical suppurations is necrotic cervical fasciitis, a polymicrobial infection with the most common oropharyngeal or odontogenic starting point, with rapidly progressive, destructive evolution in the deep fascial planes of the neck. Materials and method We will present a retrospective clinical study carried out on 26 cases diagnosed and treated between September 2013 and September 2018 in the ENT Clinic Department of the Bucharest University Emergency Hospital. Results Our retrospective analysis of a cohort of 26 patients in a tertiary referral center showed that deep cervical suppurations are slightly more common in men than in women. The most affected age groups were 50-59 years, followed by 20-29 years, representing a percentage of 53.84% of all cases. Also, 53.84% of the studied patients with deep cervical suppurations had a precarious and modest status. The most common clinical signs at presentation were malaise, cervical swelling, neck pain, dysphagia, fever, dysphonia, dyspnea, and cervical erythema. More than 60% of suppurations were odontogenic and 23% were caused by a traumatic element. Diabetes mellitus represents a comorbidity in 30.8% of patients, while 42.3% of patients had no personal pathological history, and thus this pathology has a lethal potential also in a patient in full health. In the study group, 46 (15%) had cervicomediastinitis, and 61.53% developed necrotizing fasciitis. One-third (34.61%) of our patients had undergone previous drainage surgery. Bacteriological examinations of the wound were with group C, D, G betahemolytic streptococcus, while 61.53% of the cultures were negative. Most patients required at least two cervicotomies. The average duration of hospitalization was 28.26 days, and the mortality rate was 23.07%; therefore, practically, one out of four cases resulted in death. In the studied group, no direct relationship can be established between the length of hospitalization and the favorable and unfavorable evolution of the patient. We propose a 10-step management protocol for the management of a cervical suppuration. Conclusion The multidisciplinary approach to these suppurations by the head and neck surgeon, the thoracic surgeon, the oromaxillofacial surgeon, anesthetist, imagist, specialist in infectious diseases, pathologist, psychologist, and so on, is the key to success in a patient who presents not only a suppuration in the throat but also a disease with systemic resonance and significant lethal potential.

Can Lesions in the Right Basal Ganglia Cause Aphasia? Crossed Aphasia in a Right-Handed Patient.

Aphasia is a common neurocognitive disorder caused by impaired speech and language, with stroke being the most frequent cause. The neuroanatomical mechanism underlying this condition is not yet fully understood. This case describes a 74-year-old Caucasian woman admitted with a clinical picture of right total anterior circulation infarct (TACI) and aphasia, scoring 17 on the National Institutes of Health Stroke Scale. Neuroimaging showed a large cortico-subcortical frontotemporoparietal and insular infarct involving the basal ganglia of the right hemisphere and bilateral focal atherosclerotic stenosis on the M1 segment of the middle cerebral artery. There was no left hemispheric lesion or abnormal electric activity on the electroencephalogram. A formal evaluation was compatible with transcortical motor aphasia. The aetiological study revealed atrial fibrillation, and the case was admitted as an ischaemic stroke of undetermined aetiology with two possible causes - intracranial atherosclerotic stenosis or atrial fibrillation. Our patient fulfilled all the formal criteria for crossed aphasia in dextral (CAD): aphasia, a lesion in the right hemisphere coupled with the structural integrity of the left hemisphere, an established preference for right-hand use without a familial history of left-handedness individuals, and an absence of brain damage in childhood. Our patient's case adds to the evidence that deep structures - alone or in combination with cortical structures - are primarily affected in CAD. The diagnostic criteria for crossed aphasia in dextral (CAD) are derived from clinical case studies and include aphasia, a lesion in the right hemisphere, a strong preference for using the right hand, the structural integrity of the left hemisphere and no history of brain damage during childhood.The right lentiform nucleus was found to be the most frequent anatomical substrate involved in CAD patients, consistent with our case description.Our patient experienced transcortical motor aphasia due to a stroke in the right hemisphere, adding to the evidence that in CAD patients, deep structures are primarily affected. In contrast, in left hemispheric lesions, cortical structures seem to be the main culprits.

A case of biatrial tachycardia involving the intercaval bundle with assumed dual loop reentry.

Epicardial connections provided the anatomical substrate for the biatrial reentry circuit. The connections between the right atrium and right pulmonary vein were called "intercaval bundle," and there are few reports of atrial flutter related to this bundle. We present a case of a biatrial tachycardia, involving the intercaval bundle.

Status epilepticus and psychosis: Lessons from SEEG

Psychotic manifestations are a classic feature of non-convulsive status epilepticus (NCSE) of temporal origin. For several decades now, the various psychiatric manifestations of NCSE have been described, and in particular, the diagnostic challenges they pose. However, studies using stereotactic-EEG (SEEG) recordings are very rare. Only a few cases have been reported, but they demonstrated the anatomical substrate of certain manifestations, including hallucinations, delusions, and emotional changes. The post-ictal origin of some of the manifestations should be emphasized. More generally, SEEG has shown that seizures affecting the temporal and frontal limbic systems can lead to intense emotional experiences and behavioural disturbances.

Pain in Parkinson's disease: a neuroanatomy-based approach.

Parkinson's disease is a progressive neurodegenerative disorder characterized by the deposition of misfolded alpha-synuclein in different regions of the central and peripheral nervous system. Motor impairment represents the signature clinical expression of Parkinson's disease. Nevertheless, non-motor symptoms are invariably present at different stages of the disease and constitute an important therapeutic challenge with a high impact for the patients' quality of life. Among non-motor symptoms, pain is frequently experienced by patients, being present in a range of 24-85% of Parkinson's disease population. Moreover, in more than 5% of patients, pain represents the first clinical manifestation, preceding by decades the exordium of motor symptoms. Pain implies a complex biopsychosocial experience with a downstream complex anatomical network involved in pain perception, modulation, and processing. Interestingly, all the anatomical areas involved in pain network can be affected by a-synuclein pathology, suggesting that pathophysiology of pain in Parkinson's disease encompasses a 'pain spectrum', involving different anatomical and neurochemical substrates. Here the various anatomical sites recruited in pain perception, modulation and processing are discussed, highlighting the consequences of their possible degeneration in course of Parkinson's disease. Starting from peripheral small fibres neuropathy and pathological alterations at the level of the posterior laminae of the spinal cord, we then describe the multifaceted role of noradrenaline and dopamine loss in driving dysregulated pain perception. Finally, we focus on the possible role of the intertwined circuits between amygdala, nucleus accumbens and habenula in determining the psycho-emotional, autonomic and cognitive experience of pain in Parkinson's disease. This narrative review provides the first anatomically driven comprehension of pain in Parkinson's disease, aiming at fostering new insights for personalized clinical diagnosis and therapeutic interventions.

Clinical and neuroimaging aspects of formal thought disorder in schizophrenia: a brief narrative review

Aim. To analyze current sources regarding the clinical and neuroimaging aspects of formal thought disorder (FTD) in patients with schizophrenia to create an up-to-date pathogenetic model of its main forms. Materials and methods. English-language publications in the Medline database (PubMed) were analyzed for this review. We analyzed only structural magnetic resonance imaging (MRI) studies in which a clear clinical assessment of FTD in schizophrenia is provided and the neuroimaging protocol meets generally accepted standards (as in the ENIGMA Schizophrenia Working Group). For the clinical division of FTD, positive and negative FTD were distinguished according to the positive and negative syndrome scale (PANSS). Results. From a clinical point of view, FTD includes at least 30 phenomena. For clinical and neuroimaging studies, division into positive and negative FTD is used according to the PANSS. Positive FTD is manifested by the disorganization of thinking processes and exhibits mainly in violations of its purposeful sequence. Negative FTD is manifested by violations of the abstract-symbolic way of thinking, lack of spontaneity, and stereotyping. According to morphometric MRI data, atrophic changes in brain regions related to neuronal networks of cognition and impulse control (prefrontal and anterior cingulate cortex), emotional processing (amygdala), abstract thinking, and imagination (lateral occipital cortex) are important for the development of both forms of FTD. Negative FTD is mainly associated with damage to the prefronto-cingulate circles, which are the anatomical and functional substrates of executive functions. A unique feature of positive FTD is atrophy of the structures of the left temporal lobe, which leads to language disorders at the semantic level. Using the method of virtual histology, it was established that both forms of FTD are associated with bilateral changes in astrocytes and dendritic spines in the involved anatomical regions. A positive FTD is also associated with pathological changes in microglia in two hemispheres, while with a negative FTD, microglial damages are present only in the right hemisphere. Conclusions. Positive FTD in schizophrenia is mainly associated with atrophic (astroglial-microglial) processes of cognitive control networks, negative – with the atrophy of networks of semantic processing of verbal information. In both forms, networks of emotional processing, abstract thinking, and imagination are involved. Treatment strategies for FTD should include effects on astroglial and microglial dysfunction.

Prevention of SAM phenomenon after reconstructive mitral valve surgery

Systolic anterior motion (SAM) of the mitral valve (MV) can be a life-threatening condition. The SAM can result in severe left ventricular outflow tract obstruction and/or mitral regurgitation and is associated with up to 20% risk of sudden death (which is substantially lower in hypertrophic cardiomyopathy (HCM)).The mechanisms of SAM are complex and depend on the functional status of the ventricle. The SAM can occur in all cases, but is typically observed in patients with HCM or following MV repair.Echocardiography (2D, 3D and stress) has a central diagnostic role as the application of echocardiographic SAM predictors allows the incorporation of prevention techniques during surgery and post-operative SAM assessment.MRI (magnetic resonance imaging) has a special role in understanding the dynamic nature of SAM, especially in anatomically atypical hearts (including HCM).This article describes what the clinician needs to know about SAM ranging from pathophysiological mechanisms and imaging modalities to conservative (medical) and surgical approaches and their respective outcomes.A stepwise approach consisting of medical therapy, followed by aggressive volume loading and beta-adrenoreceptor blockers. Surgery is the final option. The correct choice of surgical technique requires an understanding of the anatomical substrate of SAM.

Bicuspid valve CT registry of balloon-expandable TAVR: BETTER TAVR registry.

The anatomic substrate of bicuspid valves may lead to suboptimal TAVR stent expansion and geometry. We evaluated determinants of stent geometry in bicuspid valves treated with Sapien transcatheter aortic valve replacement (TAVR) valves. A multicenter retrospective registry of patients (February 2019 to August 2022) who underwent post-TAVR computed tomography to determine stent area (vs. nominal valve area) and stent ellipticity (maximum diameter/minimum diameter). Predictors of relative stent expansion (minimum area/average of inflow + outflow area) and stent ellipticity were evaluated in a multivariable regression model, including valve calcium volume (indexed by annular area), presence of raphe calcium, sinus diameters indexed by area-derived annular diameter, and performance of pre-dilation and post-dilation. The registry enrolled 101 patients from four centers. The minimum stent area (vs. nominal area) was 88.1%, and the maximum ellipticity was 1.10, with both observed near the midframe of the valve in all cases. Relative stent expansion ≥90% was observed in 64/101 patients. The only significant predictor of relative stent expansion ≥90% was the performance of post-dilation (OR: 4.79, p = 0.018). Relative stent expansion ≥90% was seen in 86% of patients with post-dilation compared to 57% without (p < 0.001). The stent ellipticity ≥1.1 was observed in 47/101 patients. The significant predictors of stent ellipticity ≥1.1 were the indexed maximum sinus diameter (OR: 0.582, p = 0.021) and indexed intercommisural diameter at 4 mm (OR: 2.42, p = 0.001). Stent expansion has a weak negative correlation with post-TAVR mean gradient (r = -0.324, p < 0.001). Relative stent expansion ≥90% was associated with the performance of post-dilation, and stent ellipticity ≥1.1 was associated with indexed intercommisural diameter and indexed maximum sinus diameter. Further studies to determine optimal deployment strategies in bicuspid valves are needed.

The use of left bundle branch pacing as a bail-out in case of CRT pacing failure: a case series

Abstract Introduction LBBB pacing has emerged as a novel alternative to CS pacing for cardiac resynchronization therapy in patients with heart failure. Purpose We hereby present a series of four cases wherein the use of LBB pacing, although not initially planned as first choice, was able to overcome a variety of different limitations of traditional CRT pacing. Presentation Patient #1 was an 81-year old man with a history of ischemic HF and AF who was admitted with recurring episodes of sustained ventricular tachycardia (VT) below the detection zone of the CRT-D that had been implanted 11 years ago. Interrogation of the device revealed fracture in the RV lead, intact values of the RV defibrillation coil and inability to capture from an LV lead in an anterior vein. Following initial stabilization the patient underwent successful LBB lead implantation combined with a new RV pace-sense lead as backup due to acceptable but non-optimal LBB lead values attributed to ischemic septal scarring. We were able to retain the previous CRT-D device by relegating the LBB lead to the atrial port and with the use of DDDR programming with custom AV delay values in order to achieve LBB pacing with RV pacing as backup. Patient #2 was a 51-year old man with a history of ischemic HF and permanent AF with a previously implanted CRT-D who was also admitted due to episodes of VT. Device interrogation revealed high threshold of an LV lead located in an anterior vein. The patient underwent supplementary LBB lead implantation which was then connected to the atrial port of the pre-existing CRT-D device, providing primarily LBB pacing with RV pacing backup through the use of custom DDDR programming same as in the previous case. Patient #3 was a 71–year old man with newly-diagnosed ischemic cardiomyopathy and multiple episodes of hemodynamically unstable VT that persisted even after successful reperfusion, necessitating VT ablation. The patient had narrow QRS at baseline and was not eligible for CRT-D, however after medical therapy to suppress ventricular arrhythmias the patient seemed prone to developing LBBB-like QRS widening. The decision was made to proceed with standard ICD implantation and combine a standard defibrillation lead with an LBB lead through the use of a DF1 port, so as to be able to provide LBB pacing as needed in the future. Patient #4 was a 62-year old man with a history of hypertrophic cardiomyopathy and HF with extensive apical scar scheduled for CRT-D implantation. CS venography during implantation revealed a single lateral vein draining the apical LV, lead was implanted but with no capture. An LBB pacing lead was successfully implanted and used instead of the LV lead in the conventional CRT-D set up. Conclusion In this case series we demonstrate that LBB pacing is a viable option as a bail-out in various cases of CRT pacing failure, including both septal scar and hypertrophy, as well as different anatomical substrates and CRT status.LBB pacing characteristics summary

Novel systematic processing of cardiac magnetic resonance imaging identifies target regions associated with infarct-related ventricular tachycardia

Abstract Introduction In the clinic, complete characterization of reentrant ventricular tachycardia (VT) circuits using classical electrophysiological criteria and state-of-the-art high density mapping during VT is complex, and often cannot be completed because of hemodynamic instability. This common limitation has motivated the implementation of mapping strategies during sinus rhythm or ventricular pacing aiming to identify scar regions associated with VT isthmuses or potential arrhythmogenicity. Complementary imaging-based strategies including advanced analyses of scar tissue characteristics have been also proposed for procedure planning and identification of potential arrhythmogenic regions. However, the most recent expert consensus report on catheter ablation of ventricular arrhythmia highlights the lack of agreement on the preferable signal intensity (SI) cut-off values for assessment of tissue heterogeneity and scar areas on late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) images. The latter makes LGE-CMR imaging processing highly operator-dependent and potentially sensitive to selection bias. Purpose We aimed at developing and validating a systematic processing approach on LGE-CMR images to identify potential VT corridors that may include protected isthmuses associated with VT maintenance. Methods Translational study including 18 pigs with established myocardial infarction and inducible VT undergoing in vivo characterization of the anatomical and functional myocardial substrate associated with VT maintenance. Clinical validation was conducted in a multicenter series of 33 patients with ischemic cardiomyopathy undergoing VT ablation. Three-dimensional CMR-LGE images were processed using systematic scanning of 15 signal intensity cut-off ranges to obtain surface visualization of all potential VT corridors. Analysis and comparisons of imaging and electrophysiological data were performed in individuals with full electrophysiological characterization of the isthmus sites of at least one VT morphology. Results In both the experimental pig model and patients undergoing VT ablation, all the electrophysiologically-defined isthmus sites (n=11 and n=19, respectively) showed overlapping regions with CMR-based potential VT corridors. Such imaging-based VT corridors were less specific than electrophysiologically-guided ablation lesions at functionally relevant isthmus sites (Figure). However, in patients, decreasing from 15 to 7 the number of signal intensity cut-off ranges for systematic imaging processing significantly reduced the area of imaging-based potential VT corridors, without diminishing the capability to detect functionally relevant VT isthmus sites. Conclusions Systematic processing of 3D LGE-CMR images provides unbiased identification of imaging based potential VT corridors that contain functionally relevant protected isthmus sites.

The Connection Between Anatomical Substrate and Clinical Severity in Fetal Ebstein Anomaly.

Ebstein anomaly (EA) is a rare congenital heart defect characterized by abnormal development of the tricuspid valve (TV) and right ventricular myocardium. This study documents 2 dramatic cases of fetal EA characterized by hydrops and cardiomegaly, leading to intrauterine or early neonatal death. These clinical outcomes were associated with morphological abnormalities including severe tricuspid regurgitation, unguarded TV orifice, pulmonary atresia, and flattened right ventricular myocardium. This study highlights that these adverse anatomical features may result in unfavorable clinical outcomes in fetal EA. While timely identification of such features by prenatal ultrasound is crucial for providing accurate prognostic stratification and guiding treatment decisions, fetopsy may be necessary to discern EA among the spectrum of right-heart anomalies.