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Abstract Background Alcohol use disorder (AUD) belongs to the most burdensome clinical disorders worldwide. Current treatment approaches yield unsatisfactory long-term effects with relapse rates up to 85%. Craving for alcohol is a major predictor for relapse and can be intentionally induced via cue exposure in real life as well as in Virtual Reality (VR). The induction and habituation of craving via conditioned cues as well as extinction learning is used in Cue Exposure Therapy (CET), a long-known but rarely used strategy in Cognitive Behavioral Therapy (CBT) of AUD. VR scenarios with alcohol related cues offer several advantages over real life scenarios and are within the focus of current efforts to develop new treatment options. As a first step, we aim to analyze if the VR scenarios elicit a transient change in craving levels and if this is measurable via subjective and psychophysiological parameters. Methods A single-arm clinical study will be conducted including n = 60 patients with AUD. Data on severity of AUD and craving, comorbidities, demographics, side effects and the feeling of presence in VR will be assessed. Patients will use a head-mounted display (HMD) to immerse themselves into three different scenarios (neutral vs. two target situations: a living room and a bar) while heart rate, heart rate variability, pupillometry and electrodermal activity will be measured continuously. Subjective craving levels will be assessed before, during and after the VR session. Discussion Results of this study will yield insight into the induction of alcohol craving in VR cue exposure paradigms and its measurement via subjective and psychophysiological parameters. This might be an important step in the development of innovative therapeutic approaches in the treatment of patients with AUD. Trial registration This study was approved by the Charité—Universitätsmedizin Berlin Institutional Review Board (EA1/190/22, 23.05.2023). It was registered on ClinicalTrials.gov (NCT05861843).

In rodents, cells in the medial entorhinal cortex and subiculum are known to encode the allocentric direction to nearby walls and boundaries. Here, using fMRI the authors show that this is also true in humans, with allocentric boundary direction being encoded in posterior entorhinal cortex and subiculum.

Recent advances in MRI and increasing knowledge on the characterization and anatomical variability of medial temporal lobe (MTL) anatomy have paved the way for more specific subdivisions of the MTL in humans. In addition, recent studies suggest that early changes in many neurodegenerative and neuropsychiatric diseases are better detected in smaller subregions of the MTL rather than with whole structure analyses. Here, we developed a new protocol using 7 Tesla (T) MRI incorporating novel anatomical findings for the manual segmentation of entorhinal cortex (ErC), perirhinal cortex (PrC; divided into area 35 and 36), parahippocampal cortex (PhC), and hippocampus; which includes the subfields subiculum (Sub), CA1, CA2, as well as CA3 and dentate gyrus (DG) which are separated by the endfolial pathway covering most of the long axis of the hippocampus. We provide detailed instructions alongside slice-by-slice segmentations to ease learning for the untrained but also more experienced raters. Twenty-two subjects were scanned (19–32 yrs, mean age = 26 years, 12 females) with a turbo spin echo (TSE) T2-weighted MRI sequence with high-resolution oblique coronal slices oriented orthogonal to the long axis of the hippocampus (in-plane resolution 0.44×0.44 mm2) and 1.0 mm slice thickness. The scans were manually delineated by two experienced raters, to assess intra- and inter-rater reliability. The Dice Similarity Index (DSI) was above 0.78 for all regions and the Intraclass Correlation Coefficients (ICC) were between 0.76 to 0.99 both for intra- and inter-rater reliability. In conclusion, this study presents a fine-grained and comprehensive segmentation protocol for MTL structures at 7 T MRI that closely follows recent knowledge from anatomical studies. More specific subdivisions (e.g. area 35 and 36 in PrC, and the separation of DG and CA3) may pave the way for more precise delineations thereby enabling the detection of early volumetric changes in dementia and neuropsychiatric diseases.

Competing Interests: Disclosures Dr Saguner received educational grants through his institution from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, Bristol-Myers Squibb/Pfizer, and Medtronic and speaker/advisory board/consulting fees from Bayer Healthcare, Biotronik, Medtronic, Novartis, Pfizer, StrideBio, and Zoll. The rest of the authors report no conflicts of interest.

Introduction: Implantable cardioverter-defibrillators (ICDs) can prevent sudden cardiac death due to ventricular arrhythmias in patients with arrhythmogenic right ventricular cardiomyopathy (ARVC). The aim of our study was to assess the cumulative burden, evolution and potential triggers of appropriate ICD shocks during long-term follow-up, which may help to reduce and further refine individual arrhythmic risk in this challenging disease., Methods: This retrospective cohort study included 53 patients with definite ARVC according to the 2010 Task Force Criteria from the multicentre Swiss ARVC Registry with an implanted ICD for primary or secondary prevention. Follow-up was conducted by assessing all available patient records from patient visits, hospitalisations, blood samples, genetic analysis, as well as device interrogation and tracings., Results: Fifty-three patients (male 71.7%, mean age 43±2.2 years, genotype positive 58.5%) were analysed during a median follow-up of 7.9 (IQR 10) years. In 29 (54.7%) patients, 177 appropriate ICD shocks associated with 71 shock episodes occurred. Median time to first appropriate ICD shock was 2.8 (IQR 3.6) years. Long-term risk of shocks remained high throughout long-term follow-up. Shock episodes occurred mainly during daytime (91.5%, n=65) and without seasonal preference. We identified potentially reversible triggers in 56 of 71 (78.9%) appropriate shock episodes, the main triggers representing physical activity, inflammation and hypokalaemia., Conclusion: The long-term risk of appropriate ICD shocks in patients with ARVC remains high during long-term follow-up. Ventricular arrhythmias occur more often during daytime, without seasonal preference. Reversible triggers are frequent with the most common triggers for appropriate ICD shocks being physical activity, inflammation and hypokalaemia in this patient population., Competing Interests: Competing interests: AMS received educational grants through his institution from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, BMS/Pfizer, Medtronic and Novartis, and speaker/consultant fees from Bayer Healthcare, Biotronik, BMS/Pfizer, Daiichi-Sankyo, Medtronic, Novartis and Stride Bio. DH reports educational grants, consultant or speaker fees and fellowship support from Abbott, Bayer, Biotronik, Biosense Webster, Boston Scientific, Medtronic, Novartis, Pfizer and Spectranetics/Philips. AB has received consultant and/or speaker fees from Abbott, Bayer Healthcare, Biosense Webster, Biotronik, Boston Scientific, Bristol-Myers Squibb, Cook Medical, Daiichi Sankyo, Medtronic, Pfizer, Spectranetics/Philipps and ZOLL. AM-D is the founder of SwissDNAlysis. FR has not received personal payments by pharmaceutical companies or device manufacturers in the last 3 years (remuneration for the time spent in activities, such as participation as steering committee member of clinical trials and member of the Pfizer Research Award selection committee in Switzerland were made directly to the University of Zurich). The Department of Cardiology (University Hospital of Zurich/University of Zurich) reports research, educational and/or travel grants from Abbott, Amgen, Astra Zeneca, Berlin Heart, B. Braun, Biosense Webster, Biosensors Europe AG, Biotronik, BMS, Boehringer Ingelheim, Boston Scientific, Bracco, Cardinal Health Switzerland, Corteria, Daiichi, Diatools AG, Edwards Lifesciences, Guidant Europe NV (BS), Hamilton Health Sciences, Kaneka Corporation, Kantar, Labormedizinisches Zentrum, Medtronic, MSD, Mundipharma Medical Company, Novartis, Novo Nordisk, Orion, Pfizer, Quintiles Switzerland Sarl, Roche Diagnostics, Sahajanand IN, Sanofi, Sarstedt AG, Servier, SIS Medical, SSS International Clinical Research, Terumo Deutschland, Trama Solutions, V-Wave, Vascular Medical, Vifor, Wissens Plus and ZOLL. The research and educational grants do not impact on FR's personal remuneration. The other authors have nothing to disclose related to the content of this article., (© Author(s) (or their employer(s)) 2023. No commercial re-use. See rights and permissions. Published by BMJ.)

Aims: The widespread use of three-dimensional (3D) mapping systems and echocardiography in the field of cardiac electrophysiology has made it possible to perform transseptal punctures (TSP) with low or no fluoroscopy. However, such attempts in adults with congenital heart disease (ACHD) who have previously undergone surgical or interventional treatment are limited. Therefore, we sought to explore the feasibility and safety of an approach to perform zero- or low-fluoroscopy TSP in ACHD patients undergoing left atrial cardiac ablation procedures., Methods and Results: This study included 45 ACHD patients who underwent TSP for ablation of left-sided tachycardias (left atrium or pulmonary venous atrium). Computed tomography (CT) of the heart was performed in all patients prior to ablation. 3D mapping of the right-sided heart chambers before TSP was used to superimpose the registered anatomy, which was subsequently used for the mapping-guided TSP technique. TSP was performed with zero-fluoroscopy in 27 patients, and the remaining 18 patients had a mean fluoroscopy exposure of 315.88 ± 598.43 μGy.m 2 and a mean fluoroscopy duration of 1.9 ± 5.4 min. No patient in this cohort experienced TSP-related complications., Conclusion: Our study describes a fluoroscopy-free or low-dose fluoroscopy approach for TSP in ACHD patients undergoing catheter ablation of left-sided tachyarrhythmias who had been previously treated surgically or interventionally due to congenital heart defects. By superimposing 3D electroanatomic mapping with cardiac CT anatomy, this protocol proved to be highly effective, feasible and safe.

Background Data on the incidence of arrhythmias, associated cardiac interventions, and outcome in patients with dextro-transposition of the great arteries and atrial switch are scarce. Methods and Results In this multicenter analysis, we included adult patients with dextro-transposition of the great arteries and atrial switch regularly followed up at 3 Swiss tertiary care hospitals. The primary outcome was a composite of left ventricular assist device, heart transplantation, and death. The secondary outcome was occurrence of ventricular tachycardia, ventricular fibrillation, or sudden cardiac death. We identified 207 patients (34% women; median age at last follow-up, 35 years) with dextro-transposition of the great arteries and atrial switch. Arrhythmias occurred in 97 patients (47%) at a median age of 22 years. A pacemaker or an implantable cardioverter-defibrillator was implanted in 39 (19%) and 13 (6%) patients, respectively, and 33 (16%) patients underwent a total of 51 ablation procedures to target 60 intra-atrial re-entry tachycardias, 4 atrioventricular nodal re-entry tachycardias, and 1 atrial fibrillation. The primary outcome occurred in 21 patients (10%), and the secondary outcome occurred in 18 patients (9%); both were more common in patients with concomitant ventricular septum defect than in those without (hazard ratio [HR], 3.06 [95% CI, 1.29-7.27], P =0.011; and HR, 3.62 [95% CI, 1.43-9.18], P =0.007, respectively). Conclusions In patients with dextro-transposition of the great arteries and atrial switch reaching adulthood, arrhythmias occur in almost half of patients, and associated rhythm interventions are frequent. One-tenth of those patients do not survive until the age of 35 years free from left ventricular assist device or heart transplantation, and the outcome is worse in patients with concomitant ventricular septum defect.

Aim: To investigate the clinical significance of right atrial mapping prior to cavotricuspid isthmus (CTI) ablation in patients with typical atrial flutter (AFL)., Methods: Clinical and ablation parameters were retrospectively assessed and compared in patients undergoing CTI ablation with or without a first-step right atrial mapping (FRAM) by using the CARTO 3D mapping system., Results: CTI block by radiofrequency ablation (RFA) was achieved in all 143 patients. In the FRAM group there was a shorter ablation duration and fluoroscopy exposure compared with the non-FRAM group. CHA 2 DS 2 -VASc score was associated with higher ablation durations, more ablation applications and increased fluoroscopy exposure. Body mass index (BMI) was associated with longer ablation duration and more ablation applications. Furthermore, patients with reduced left ventricular ejection fraction (LVEF) had longer ablation durations and more fluoroscopy exposure. One patient in the non-FRAM group developed cardiac effusion after ablation. None of the patients had recurrence after 6 months of follow-up., Conclusions: Patients with high BMI, high CHA 2 DS 2 -VASc score and reduced LVEF may benefit from the FRAM approach by reducing ablation duration, number of ablation applications and fluoroscopy exposure., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2023 Guan, Saguner, Breitenstein, Wang, Molitor, Brunckhorst, Wolber and Duru.)

Background: His bundle (HB) potentials vary in amplitude and duration in patients with and without slow pathways. The aim of this study was to determine the characteristics of HB potentials and to elucidate whether they can provide clues for identification of slow pathway (SP)., Methods: The present research prospectively studied the electrophysiological findings of 162 patients with symptomatic atrioventricular nodal reentrant tachycardia (AVNRT) due to slow-fast or fast-slow type and atrioventricular reentrant tachycardia (AVRT). Maximal HB potential (HBmax, HB with the highest amplitude) among HB cloud was recorded in both groups. For AVNRT patients, the following were measured: (1) AH interval at the "jump" during programmed atrial stimulation (A2H2, taken as a reflection of SP conduction time); (2) Distance from HBmax to the successful SP ablation site (HBmax-ABL) and from HBmax to the ostium of coronary sinus (HBmax-CSO)., Results: HBmax was 0.29 ± 0.10 mV in AVNRT patients, whereas it was 0.17 ± 0.05 mV in AVRT group (p < 0.0001). Likewise, the HBmax duration was 22 ± 5 ms in AVNRT group and 16 ± 3 ms in AVRT group (p < 0.0001). The area under the receiver operating characteristic curve of HBmax amplitude in AVNRT patients was 0.86 and the optimal HBmax cut-off to predict AVNRT was ≥ 0.22 mV with a sensitivity of 0.78 and specificity of 0.84. HBmax-CSO was positively correlated with HBmax-ABL, and HBmax-ABL was positively correlated with A2H2., Conclusions: HBmax amplitudes were higher and durations longer in patients with AVNRT, as compared to those with AVRT. Moreover, the distance between HBmax and successful ablation site was positively correlated with the SP conduction time and with the distance from HBmax to the CSO.

Background: Left atrial (LA) fibrosis in patients with atrial fibrillation (AF) is associated with an increased risk of AF recurrence after catheter ablation. Therefore, we searched for clinical risk factors that confer an increased risk of LA fibrosis, which can influence the treatment strategy., Methods: We included 94 patients undergoing 3-dimensional electroanatomical voltage mapping-guided catheter ablation of AF. LA low-voltage areas during sinus rhythm as a surrogate parameter of fibrosis were measured with the CARTO3 mapping system and adjusted for LA volumes obtained by computed tomography. Blood tests including N-terminal prohormone of B-type natriuretic peptide (NT-proBNP) and echocardiographic parameters of left ventricular function were also analyzed., Results: Patients were 62.5 ± 11.4 years old, and 29% were female. LA fibrosis was present in 65%, with 50% having a fibrotic area > 5% (≥ Utah-Stage 1). Mean left ventricular ejection fraction (LVEF) was 53.9 ± 10.5%. Patients with LA fibrosis had higher NT-proBNP levels (869 ± 1056 vs. 552 ± 859 ng/L, p = 0.001) and larger LA volumes (body surface area-corrected 63.3 ± 19.3 vs. 80 ± 27.1 mL/m2, p = 0.003). In univariable analyses, LA fibrosis was significantly associated with female gender, older age, increased LA volumes, hypertension, statin therapy, higher NT-proBNP values, and echocardiographic E/e'. In bivariable analyses, higher NT-proBNP, echocardiographic parameters of diastolic dysfunction, female gender, older age, and higher DR-FLASH scores remained as independent predictors of LA fibrosis., Conclusions: In this single-center longitudinal study, surrogate parameters of elevated left-sided cardiac filling pressures such as higher NT-proBNP levels and higher echocardiographic E/e' values as well as female gender independently predicted the prevalence of LA fibrosis in patients referred for catheter ablation of AF.

Background: Awareness of risks associated with radiation exposure to patients and medical staff has significantly increased. It has been reported before that the use of advanced three-dimensional electroanatomical mapping (EAM) system significantly reduces fluoroscopy time, however this study aimed for zero or near zero fluoroscopy ablation to assess its feasibility and safety in ablation of atrial fibrillation (AF) and other tachyarrhythmias in a "real world" experience of a single tertiary care center., Methods: This was a single-center study where ablation procedures were attempted without fluoroscopy in 34 consecutive patients with different tachyarrhythmias under the support of EAM system. When transseptal puncture (TSP) was needed, it was attempted under the guidance of intracardiac echocardiography (ICE)., Results: Among 34 patients consecutively enrolled in this study, 28 (82.4%) patients were referred for radiofrequency ablation (RFA) of AF, 3 (8.8%) patients for ablation of right ventricular outflow tract (RVOT) ventricular extrasystole (VES), 1 (2.9%) patient for ablation of atrioventricular nodal reentry tachycardia (AVNRT), 2 (5.9%) patients for typical atrial flutter ablation. In 21 (62%) patients the en- tire procedure was carried out without the use of fluoroscopy. Among 28 AF patients, 15 (54%) patients underwent ablation without the use of fluoroscopy and among these 15 patients, 10 (67%) patients required TSP under ICE guidance while 5 (33%) patients the catheters were introduced to left atrium through a patent foramen ovale. In 13 AF patients, fluoroscopy was only required for double TSP. The total procedure time of AF ablation was 130 ± 50 min. All patients referred for atrial flutter, AVNRT, and VES of the RVOT ablation did not require any fluoroscopy., Conclusions: This study demonstrates the feasibility of zero or near zero fluoroscopy procedure including TSP with the support of EAM and ICE guidance in a "real world" experience of a single tertiary care center. When fluoroscopy was required, it was limited to TSP hence keeping the radiation dose very low.

Background: Population based studies show a steady increase in adult patients with congenital heart defects. The aim of this study was to assess the evolution of such a patient cohort and its burden on clinical care at a dedicated tertiary care centre., Methods: All patients with congenital heart disease followed up by a dedicated multidisciplinary team at our institution were identified (n = 1725). Disease characteristics, the increase in patient numbers and interventions and the increase in selected complications were analysed and compared between the first (1996-2005) and second (2006-2015) decades of the study period., Results: Between the two decades of the study period, the number of patients in follow-up increased by 109%, the number of patients who died or underwent transplantation more than doubled and the number of outpatient visits increased by 195%. One fourth of all patients underwent at least one surgical procedure and 14% had at least one percutaneous intervention. The increase in surgical procedures between the two decades was 27% and the increase in percutaneous interventions 159%. Between the two decades the number of patients requiring direct current cardioversion increased from 32 to 95 (+197%), the number of patients requiring admission for infective endocarditis increased from 7 to 29 (+314%) and the number of women followed up during pregnancy increased from 18 to 115 (+539%)., Conclusion: As a result of the increasing number and complexity of adult survivors with congenital heart disease more resources will be needed to cope with the demands of this novel cohort of complex patients in adult cardiology.

A 50-year-old male patient who had undergone Senning repair for transposition of the great arteries at the age of 7 years was referred to our electrophysiology lab with recurrent supraventricular tachycardias. Fast anatomical mapping of the systemic venous atrium was performed with the CARTO electroanatomical mapping system. Propagation mapping with animated dynamic maps facilitates the understanding of the underlying mechanism and provides visualization of reentrant circuits of tachycardias in cardiac chambers with native barriers and surgical scars.

[This corrects the article DOI: 10.1155/2012/498102.].

Background: Patients with congenital left ventricular aneurysms and diverticula may present with arrhythmia. The incidence of ventricular arrhythmias and the clinical outcome of these patients have not been reported to date., Methods: Among 250 consecutive patients with congenital left ventricular aneurysms and diverticula detected by echocardiography, the clinical outcome of patients who presented with ventricular arrhythmias or associated symptoms was investigated., Results: Of 250 patients with congenital left ventricular aneurysms and diverticula, 30 had ventricular arrhythmias or syncope at initial presentation. During a follow-up of 85 months, spontaneous ventricular tachycardia occurred in 17 of these patients (57%). Ventricular tachycardia was sustained in 13, with a monomorphic pattern in 9 patients. In 82% (11 patients), ventricular tachycardia was inducible during electrophysiologic testing. In 7 patients a sustained monomorphic ventricular tachycardia with a right bundle branch block pattern similar to the clinical tachycardia was induced. Twenty patients were treated with antiarrhythmic agents. Eleven patients received an implantable cardioverter defibrillator. Appropriate device discharges were observed in 73% during a follow-up of 61 months. One patient underwent surgical resection of a congenital left ventricular aneurysm. Three patients underwent successful catheter ablation for incessant ventricular tachycardia. Of these, 2 were free of any clinically relevant arrhythmia during follow-up. Three patients died (10, 41, and 89 months after initial presentation). In 2 of them, the cause of death was attributed to ventricular arrhythmia., Conclusion: The clinical outcome of patients with congenital left ventricular aneurysms and diverticula and arrhythmia is variable. Clinical ventricular tachycardia in these patients is often monomorphic and usually inducible during electrophysiologic study, indicating a role for this test in risk stratification. Appropriate discharges are frequent in implantable cardioverter defibrillator recipients with congenital left ventricular aneurysms and diverticula., (Copyright © 2015 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: Pulmonary vein isolation (PVI) is an established treatment for atrial fibrillation (AF). During PVI an electrical conduction block between pulmonary vein (PV) and left atrium (LA) is created. This conduction block prevents AF, which is triggered by irregular electric activity originating from the PV. However, transmural atrial lesions are required which can be challenging. Re-conduction and AF recurrence occur in 20 - 40% of the cases. Robotic catheter systems aim to improve catheter steerability. Here, a procedure with a new remote catheter system (RCS), is presented. Objective of this article is to show feasibility of robotic AF ablation with a novel system., Materials and Methods: After interatrial trans-septal puncture is performed using a long sheath and needle under fluoroscopic guidance. The needle is removed and a guide wire is placed in the left superior PV. Then an ablation catheter is positioned in the LA, using the sheath and wire as guide to the LA. LA angiography is performed over the sheath. A circular mapping catheter is positioned via the long sheath into the LA and a three-dimensional (3-D) anatomical reconstruction of the LA is performed. The handle of the ablation catheter is positioned in the robotic arm of the Amigo system and the ablation procedure begins. During the ablation procedure, the operator manipulates the ablation catheter via the robotic arm with the use of a remote control. The ablation is performed by creating point-by-point lesions around the left and right PV ostia. Contact force is measured at the catheter tip to provide feedback of catheter-tissue contact. Conduction block is confirmed by recording the PV potentials on the circular mapping catheter and by pacing maneuvers. The operator stays out of the radiationfield during ablation., Conclusion: The novel catheter system allows ablation with high stability on low operator fluoroscopy exposure.

Background: Arrhythmogenic right ventricular cardiomyopathy/dysplasia (ARVC/D) is considered a progressive cardiomyopathy. However, data on the clinical features of disease progression are limited. The aim of this study was to assess 12-lead surface electrocardiographic (ECG) changes during long-term follow-up, and to compare these findings with echocardiographic data in our large cohort of patients with ARVC/D., Methods: Baseline and follow-up ECGs of 111 patients from three tertiary care centers in Switzerland were systematically analyzed with digital calipers by two blinded observers, and correlated with findings from transthoracic echocardiography., Results: The median follow-up was 4 years (IQR 1.9-9.2 years). ECG progression was significant for epsilon waves (baseline 14% vs. follow-up 31%, p = 0.01) and QRS duration (111 ms vs. 114 ms, p = 0.04). Six patients with repolarization abnormalities according to the 2010 Task Force Criteria at baseline did not display these criteria at follow-up, whereas in all patients with epsilon waves at baseline these depolarization abnormalities also remained at follow-up. T wave inversions in inferior leads were common (36% of patients at baseline), and were significantly associated with major repolarization abnormalities (p = 0.02), extensive echocardiographic right ventricular involvement (p = 0.04), T wave inversions in lateral precordial leads (p = 0.05), and definite ARVC/D (p = 0.05)., Conclusions: Our data supports the concept that ARVC/D is generally progressive, which can be detected by 12-lead surface ECG. Repolarization abnormalities may disappear during the course of the disease. Furthermore, the presence of T wave inversions in inferior leads is common in ARVC/D.