Search

Background: Little is known about the distribution and clinical course of patients with inherited arrhythmia syndrome (IAS) and concomitant atrial arrhythmias (AAs)., Aim: 1) to characterize the distribution of AAs in patients with IAS and 2) evaluate the long-term clinical course of these patients., Methods: An international multicenter study was performed and involved 28 centers in 16 countries. Inclusion criteria were: 1) IAS and 2) ECG documentation of AAs. The primary endpoint was a composite of sudden cardiac death, sustained VAs or appropriate ICD interventions. Strokes, inappropriate ICD shocks due to AAs, and the occurrence of sinus node dysfunction were assessed., Results: A total of 522 patients with IAS and AAs were included. Most patients were diagnosed with Brugada syndrome (n=355, 68%) and long-QT syndrome (n=93, 18%). The remaining patients (n=71, 14%) presented with short-QT syndrome, early repolarization syndrome (ERS), catecholaminergic polymorphic ventricular tachycardia (CPVT), progressive cardiac conduction diseases, or idiopathic ventricular fibrillation. Atrial fibrillation (AF) was the most prevalent AA (82%), followed by atrial flutter (9%) and atrial tachycardia (9%). AA was the first clinical manifestation of IAS in 52% of patients. More than one type of AAs was documented in 23% of patients. Nine patients (3%) experienced VA before the diagnosis of IAS, due the use of anti-arrhythmic medications taken for the AA. The incidence of the primary endpoint was 1.4% per year, with a twofold increase observed in patients who experienced their first AA before the age of 20 (OR 2.2, p=0.043). This was consistent across the different forms of IAS. Inappropriate ICD shock due to AAs were reported in 2.8% of patients, strokes in 4.4% and sinus node dysfunction in 9.6%., Conclusions: Among patients with IAS and AAs, AA is the first clinical manifestation in about half of the cases, with more than one form of AAs present in one-fourth of the patients. The occurrence of AA earlier in life may be associated with a higher risk of ventricular arrhythmias. The occurrence of stroke and sinus node dysfunction is not-infrequently in this cohort., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Genetic testing is recommended in the diagnosis of short QT syndrome. This rare inherited lethal entity is characterized by structural normal hearts with short QT intervals in the electrocardiogram. Few families diagnosed with this arrhythmogenic disease have been reported worldwide so far, impeding a comprehensive understanding of this syndrome. Unraveling the origin of the disease helps to the early identification of genetic carriers at risk. However, only rare variants with a definite deleterious role should be actionable in clinical practice. Our aim was to perform a comprehensive update and reinterpretation, according to the American College of Medical Genetics and Genomics recommendations of all rare variants currently associated with short QT syndrome. We identified 34 rare variants. Reanalysis showed that only nine variants played a deleterious role associated with a definite short QT syndrome phenotype. These variants were located in the four main genes: KCNQ1, KCNH2, KCNJ2 or SLC4A3. Additional rare variants located in other genes were associated with other conditions with phenotypic shortened QT intervals, but not definite diagnosis of short QT syndrome. Periodically updating of rare variants, especially those previously classified as unknown, helps to clarify the role of rare variants and translate genetic data into clinical practice., (© 2024. The Author(s).)

Background: Risk stratification in drug-induced type-1 Brugada syndrome (BrS) patients is challenging. The role of electrophysiological study (EPS) is debated as the majority of drug-induced type-1 BrS patients would not be studied according to the latest recommendations., Methods: A complete systematic literature search was performed to gauge the EPS role in this population. Three subgroups were defined: positive-EPS group, negative-EPS group, no-EPS group., Results: Among 1318 drug-induced type-1 BrS patients, no significant difference in the incidence rate of arrhythmic events was observed between groups (I2 = 45%, P for subgroup difference = 0.10) during a mean follow-up of 5.1 years, also considering symptomatic status., Conclusion: In long-term follow-up of drug-induced type-1 BrS patients, EPS does not seem to aid prognostic stratification., (Copyright © 2024 Italian Federation of Cardiology - I.F.C. All rights reserved.)

Background: Voltage mapping could identify the conducting channels potentially responsible for ventricular tachycardia (VT). Standard thresholds (0.5-1.5 mV) were established using bipolar catheters. No thresholds have been analyzed with high-density mapping catheters. In addition, channels identified by cardiac magnetic resonance (CMR) has been proven to be related with VT., Objective: The purpose of this study was to analyze the diagnostic yield of a personalized voltage map using CMR to guide the adjustment of voltage thresholds., Methods: All consecutive patients with scar-related VT undergoing ablation after CMR (from October 2018 to December 2020) were included. First, personalized CMR-guided voltage thresholds were defined systematically according to the distribution of the scar and channels. Second, to validate these new thresholds, a comparison with standard thresholds (0.5-1.5 mV) was performed. Tissue characteristics of areas identified as deceleration zones (DZs) were recorded for each pair of thresholds. In addition, the relation of VT circuits with voltage channels was analyzed for both maps., Results: Thirty-two patients were included [mean age 66.6 ± 11.2 years; 25 (78.1%) ischemic cardiomyopathy]. Overall, 52 DZs were observed: 44.2% were identified as border zone tissue with standard cutoffs vs 75.0% using personalized voltage thresholds (P = .003). Of the 31 VT isthmuses detected, only 35.5% correlated with a voltage channel with standard thresholds vs 74.2% using adjusted thresholds (P = .005). Adjusted cutoff bipolar voltages that better matched CMR images were 0.51 ± 0.32 and 1.79 ± 0.71 mV with high interindividual variability (from 0.14-1.68 to 0.7-3.21 mV)., Conclusion: Personalized voltage CMR-guided personalized voltage maps enable a better identification of the substrate with a higher correlation with both DZs and VT isthmuses than do conventional voltage maps using fixed thresholds., Competing Interests: Disclosures Drs Mont and Brugada report activities as a consultant, lecturer, and advisory board member for Abbott Medical, Boston Scientific, Biosense Webster, Medtronic, and Biotronik. They are also shareholders of ADAS 3D Medical. Drs Roca-Luque, Tolosana, and Porta-Sánchez report activities as a consultant and lecturer for Biosense Webster, Medtronic, Boston Scientific, and Abbott Medical. All other authors report that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: Longitudinal dyssynchrony correction and 'strain' improvement by comparable cardiac resynchronization therapy (CRT) techniques is unreported. Our purpose was to compare echocardiographic dyssynchrony correction and 'strain' improvement by conduction system pacing (CSP) vs. biventricular pacing (BiVP) as a marker of contractility improvement during 1-year follow-up., Methods and Results: A treatment-received analysis was performed in patients included in the LEVEL-AT trial (NCT04054895), randomized to CSP or BiVP, and evaluated at baseline (ON and OFF programming) and at 6 and 12 months (n = 69, 32% women). Analysis included intraventricular (septal flash), interventricular (difference between left and right ventricular outflow times), and atrioventricular (diastolic filling time) dyssynchrony and 'strain' parameters [septal rebound, global longitudinal 'strain' (GLS), LBBB pattern, and mechanical dispersion). Baseline left ventricular ejection fraction (LVEF) was 27.5 ± 7%, and LV end-systolic volume (LVESV) was 138 ± 77 mL, without differences between groups. Longitudinal analysis showed LVEF and LVESV improvement (P < 0.001), without between-group differences. At 12-month follow-up, adjusted mean LVEF was 46% with CSP (95% CI 42.2 and 49.3%) vs. 43% with BiVP (95% CI 39.6 and 45.8%), (P = 0.31), and LVESV was 80 mL (95% CI 55.3 and 104.5 mL) vs. 100 mL (95% CI 78.7 and 121.6 mL), respectively (P = 0.66). Longitudinal analysis showed a significant improvement of all dyssynchrony parameters and GLS over time (P < 0.001), without differences between groups. Baseline GLS significantly correlated with LVEF and LVESV at 12-month follow-up., Conclusion: CSP and BiVP provided similar dyssynchrony and 'strain' correction over time. Baseline global longitudinal 'strain' predicted ventricular remodelling at 12-month follow-up., Competing Interests: Conflict of interest: M.P.-L. has received speaker honoraria from Medtronic. J.M.T. has received honoraria as a lecturer and consultant from Abbott, Boston Scientific, and Medtronic. L.M. has received unrestricted research grants, fellowship programme support, and honoraria as a lecturer and consultant from Abbott, Biotronik, Boston Scientific, Livanova, and Medtronic; he holds stock in Galgo Medical and Corify. I.R.-L. has received honoraria as a lecturer and consultant from Abbott and Biosense Webster. M.S. has received consultant fees and speaker honoraria from Abbott, Medtronic, General Electric, and Edwards Lifesciences. M.A.C. has received speaker honoraria from Boston Scientific, Abbott, and Microport. E.A. has received speaker honoraria from Biosense Webster and Bayer. A.P.-S. has received honoraria as a lecturer and consultant from Biosense Webster, Abbott, and Boston Scientific. All remaining authors have declared no conflicts of interest., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Atrial arrhythmogenic substrate is a key determinant of atrial fibrillation (AF) recurrence after pulmonary vein isolation (PVI), and reduced conduction velocities have been linked to adverse outcome. However, a noninvasive method to assess such electrophysiologic substrate is not available to date., Objective: This study aimed to noninvasively assess regional conduction velocities and their association with arrhythmia-free survival after PVI., Methods: A consecutive 52 patients scheduled for AF ablation (PVI only) and 19 healthy controls were prospectively included and received electrocardiographic imaging (ECGi) to noninvasively determine regional atrial conduction velocities in sinus rhythm. A novel ECGi technology obviating the need of additional computed tomography or cardiac magnetic resonance imaging was applied and validated by invasive mapping., Results: Mean ECGi-determined atrial conduction velocities were significantly lower in AF patients than in healthy controls (1.45 ± 0.15 m/s vs 1.64 ± 0.15 m/s; P < .0001). Differences were particularly pronounced in a regional analysis considering only the segment with the lowest average conduction velocity in each patient (0.8 ± 0.22 m/s vs 1.08 ± 0.26 m/s; P < .0001). This average conduction velocity of the "slowest" segment was independently associated with arrhythmia recurrence and better discriminated between PVI responders and nonresponders than previously proposed predictors, including left atrial size and late gadolinium enhancement (magnetic resonance imaging). Patients without slow-conduction areas (mean conduction velocity <0.78 m/s) showed significantly higher 12-month arrhythmia-free survival than those with 1 or more slow-conduction areas (88.9% vs 48.0%; P = .002)., Conclusion: This is the first study to investigate regional atrial conduction velocities noninvasively. The absence of ECGi-determined slow-conduction areas well discriminates PVI responders from nonresponders. Such noninvasive assessment of electrical arrhythmogenic substrate may guide treatment strategies and be a step toward personalized AF therapy., Competing Interests: Disclosures Dr Till Althoff has received research grants for investigator-initiated trials from Biosense Webster and honoraria as consultant from Corify Care. Prof Lluís Mont has received honoraria as a lecturer and consultant and has received research grants from Abbott Medical, Biosense Webster, Boston Scientific, and Medtronic; he is a shareholder of Galgo Medical SL and Corify Care. Drs Andreu Climent and María S. Guillem are co-founders of Corify Care and receive honoraria from the company. Dr Ismael Hernández is co-founder of Corify Care. Jana Reventos is employed by Corify Care. Drs Ivo Roca-Luque, Jose M. Tolosana, and Andreu Porta-Sanchez received honoraria as consultants for Biosense Webster, Boston Scientific, and Medtronic. Dr Jean-Baptiste Guichard reports honoraria as a consultant from Microport CRM and as lecturer from Microport CRM and Abbott and an unrestricted grant support for a fellowship from Abbott Laboratories., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Chronic diseases have a negative impact on quality of life (QOL) and psychological health. There are limited related data regarding this topic in Brugada syndrome (BrS). We evaluated the effects of the diagnosis of BrS on health-related QOL and psychological status among patients and their relatives., Methods: Patients with BrS and their relatives underwent psychological evaluation at diagnosis (T0), 1 and 2 years after diagnosis (T1 and T2) using questionnaires on mental QOL, anxiety, depression, stress, post-traumatic stress, and resilience resources., Results: Sixty-one patients and 39 relatives were enrolled. Compared with controls, patients showed increased physical QOL (54.1 ± 6.5 vs. 50.1 ± 8.0, p  = 0.014), reduced mental QOL (43.2 ± 11.8 vs. 49.6 ± 9.1, p  = 0.018) and increased anxiety (9.9 ± 6.6 vs. 6.9 ± 7.7, p  = 0.024) at T0; reduced resilience scores (3.69 ± 0.40 vs. 3.96 ± 0.55, p  = 0.008) at T1; and reduced resilience (3.69 ± 0.35 vs. 3.96 ± 0.55, p  = 0.019) and increased anxiety scores (16.4 ± 12.8 vs. 6.9 ± 7.7, p  = 0.006) at T2. Relatives presented higher stress (17.63 ± 3.77 vs. 12.90 ± 6.0, p  = 0.02) at T0 and higher anxiety scores at T0 (13.5 ± 7.6 vs. 6.9 ± 7.7, p  < 0.001), T1 (12.0 ± 8.7 vs. 6.9 ± 7.7, p  = 0.005), and T2 (16.4 ± 12.8 vs. 6.9 ± 7.7, p  = 0.006) than controls. Female sex was significantly independently associated with worse mental QOL scores in patients at T0 (odds ratio = 0.10; 95% confidence interval = 0.05-0.94; p  = 0.04)., Conclusions: The diagnosis of BrS impairs the QOL and psychological status of patients and their relatives. Female sex is independently associated with worse mental QOL in patients at diagnosis., 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. The author(s) declared that they were an editorial board member of Frontiers, at the time of submission. This had no impact on the peer review process and the final decision., (© 2024 Berne, Usai, Silva, Melis, Fancello, Onida, Merella, Figus, Brugada and Casu.)

Background: Left bundle branch pacing (LBBP) is considered an alternative to cardiac resynchronization therapy (CRT). However, LBBP is not suitable for all patients with heart failure., Objective: The aim of our study was to identify predictors of unsuccessful LBBP implantation in CRT candidates., Methods: A cohort of consecutive patients with indications for CRT were included. Clinical, echocardiographic, and electrocardiographic variables were prospectively recorded., Results: A total of 187 patients were included in the analysis. LBBP implantation was successful in 152 of 187 patients (81.2%) and failed in 35 of 187 patients (18.7%). The causes of unsuccessful implantation were unsatisfactory paced QRS morphology (28 of 35 [80%]), inability to screw the helix (4 of 35 [11.4%]), lead instability (2 of 35 [5.7%]), and high pacing thresholds (1 of 35 [2.8%]). The left ventricular end-diastolic diameter (LVEDD), non-LBBB (left bundle branch block) QRS morphology, and QRS width were predictors of failed implantation according to the univariate analysis. According to the multivariate regression analysis, LVEDD (odds ratio 1.31 per 5-mm increase; 95% confidence interval 1.05-1.63 per 5-mm increase; P = .02) and non-LBBB (odds ratio 3.07; 95% confidence interval 1.08-8.72; P = .03) were found to be independent predictors of unsuccessful LBBP implantation. An LVEDD of 60 mm has 60% sensitivity and 71% specificity for predicting LBBP implant failure., Conclusion: When LBBP was used as CRT, LVEDD and non-LBBB QRS morphology predicted unsuccessful implantation. Non-LBBB triples the likelihood of failed implantation independent of LVEDD. Caution should be taken when considering these parameters to plan the best pacing strategy for patients., Competing Interests: Disclosures Dr Pujol-López has received speaker honoraria from Medtronic. Dr Tolosana has received honoraria as a lecturer and consultant from Abbott, Boston Scientific, and Medtronic. Dr Mont has received unrestricted research grants, fellowship program support, and honoraria as a lecturer and consultant from Abbott, Biotronik, Boston Scientific, LivaNova, and Medtronic; he holds stock in Galgo Medical and Corify. Dr Roca-Luque has received honoraria as a lecturer and consultant from Abbott and Biosense Webster. Dr Sitges has received consultant fees and speaker honoraria from Abbott, Medtronic, General Electric, and Edwards Lifesciences. Dr Castel has received speaker honoraria from Boston Scientific, Abbott, and MicroPort. Dr Arbelo has received speaker honoraria from Biosense Webster and Bayer. Dr Porta-Sánchez has received honoraria as a lecturer and consultant from Biosense Webster, Abbott, and Boston Scientific. Dr Guichard has received honoraria as a consultant from MicroPort CRM, honoraria as a lecturer from MicroPort CRM and Abbott, and unrestricted grant support for a fellowship from Abbott. The remaining authors declare that they have no conflicts of interest., (Copyright © 2024 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background and Aims: Available data on continuous rhythm monitoring by implantable loop recorders (ILRs) in patients with Brugada syndrome (BrS) are scarce. The aim of this multi-centre study was to evaluate the diagnostic yield and clinical implication of a continuous rhythm monitoring strategy by ILRs in a large cohort of BrS patients and to assess the precise arrhythmic cause of syncopal episodes., Methods: A total of 370 patients with BrS and ILRs (mean age 43.5 ± 15.9, 33.8% female, 74.1% symptomatic) from 18 international centers were included. Patients were followed with continuous rhythm monitoring for a median follow-up of 3 years., Results: During follow-up, an arrhythmic event was recorded in 30.7% of symptomatic patients [18.6% atrial arrhythmias (AAs), 10.2% bradyarrhythmias (BAs), and 7.3% ventricular arrhythmias (VAs)]. In patients with recurrent syncope, the aetiology was arrhythmic in 22.4% (59.3% BAs, 25.0% VAs, and 15.6% AAs). The ILR led to drug therapy initiation in 11.4%, ablation procedure in 10.9%, implantation of a pacemaker in 2.5%, and a cardioverter-defibrillator in 8%. At multivariate analysis, the presence of symptoms [hazard ratio (HR) 2.5, P = .001] and age >50 years (HR 1.7, P = .016) were independent predictors of arrhythmic events, while inducibility of ventricular fibrillation at the electrophysiological study (HR 9.0, P < .001) was a predictor of VAs., Conclusions: ILR detects arrhythmic events in nearly 30% of symptomatic BrS patients, leading to appropriate therapy in 70% of them. The most commonly detected arrhythmias are AAs and BAs, while VAs are detected only in 7% of cases. Symptom status can be used to guide ILR implantation., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Same-day discharge (SDD) after atrial fibrillation (AF) ablation is an effective means to spare healthcare resources. However, safety remains a concern, and besides structural adaptations, SDD requires more efficient logistics and coordination. Therefore, in this study, we implement a streamlined, nurse-coordinated SDD programme following a standardized protocol., Methods and Results: As a dedicated SDD coordinator, a nurse specialized in ambulatory cardiac interventions was in charge of the full SDD protocol, including eligibility, patient flow, in-hospital logistics, patient education, and discharge as well as early post-discharge follow-up by smartphone-based virtual visits. Patients planned for AF ablation were considered eligible if they had a left ventricular ejection fraction (LVEF) ≥35%, with basic support at home and accessibility of the hospital within 60 min also forming a part of the eligibility criteria. A total of 420 consecutive patients were screened by the SDD coordinator, of whom 331 were eligible for SDD. The reasons for exclusion were living remotely (29, 6.9%), lack of support at home (19, 4.5%), or LVEF <35% (17, 4.0%). Of the eligible patients, 300 (91%) were successfully discharged the same day. There were no major post-SDD complications. Rates of unplanned medical attention (19, 6.3%) and 30-day readmission (5, 1.6%) were extremely low and driven by femoral access-site complications. These were significantly reduced upon the introduction of compulsory ultrasound-guided punctures after the initial 150 SDD patients (P = 0.0145). Standardized SDD coordination resulted in efficient workflows and reduced the total workload of the medical staff., Conclusion: Same-day discharge after AF ablation following a nurse-coordinated standardized protocol is safe and efficient. The concept of ambulatory cardiac intervention nurses functioning as dedicated coordinators may be key in the future transition of hospitals to SDD. Ultrasound-guided femoral puncture virtually eliminated relevant femoral access-site complications in our cohort and should therefore be a prerequisite for SDD., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Dilated cardiomyopathy is a heterogeneous entity that leads to heart failure and malignant arrhythmias. Nearly 50% of cases are inherited; therefore, genetic analysis is crucial to unravel the cause and for the early identification of carriers at risk. A large number of variants remain classified as ambiguous, impeding an actionable clinical translation. Our goal was to perform a comprehensive update of variants previously classified with an ambiguous role, applying a new algorithm of already available tools. In a cohort of 65 cases diagnosed with dilated cardiomyopathy, a total of 125 genetic variants were classified as ambiguous. Our reanalysis resulted in the reclassification of 12% of variants from an unknown to likely benign or likely pathogenic role, due to improved population frequencies. For all the remaining ambiguous variants, we used our algorithm; 60.9% showed a potential but not confirmed deleterious role, and 24.5% showed a potential benign role. Periodically updating the population frequencies is a cheap and fast action, making it possible to clarify the role of ambiguous variants. Here, we perform a comprehensive reanalysis to help to clarify the role of most of ambiguous variants. Our specific algorithms facilitate genetic interpretation in dilated cardiomyopathy.

Aims: Non-invasive myocardial scar characterization with cardiac magnetic resonance (CMR) has been shown to accurately identify conduction channels and can be an important aid for ventricular tachycardia (VT) ablation. A new mapping method based on targeting deceleration zones (DZs) has become one of the most commonly used strategies for VT ablation procedures. The aim of the study was to analyse the capability of CMR to identify DZs and to find predictors of arrhythmogenicity in CMR channels., Methods and Results: Forty-four consecutive patients with structural heart disease and VT undergoing ablation after CMR at a single centre (October 2018 to July 2021) were included (mean age, 64.8 ± 11.6 years; 95.5% male; 70.5% with ischaemic heart disease; a mean ejection fraction of 32.3 ± 7.8%). The characteristics of CMR channels were analysed, and correlations with DZs detected during isochronal late activation mapping in both baseline maps and remaps were determined. Overall, 109 automatically detected CMR channels were analysed (2.48 ± 1.15 per patient; length, 57.91 ± 63.07 mm; conducting channel mass, 2.06 ± 2.67 g; protectedness, 21.44 ± 25.39 mm). Overall, 76.1% of CMR channels were associated with a DZ. A univariate analysis showed that channels associated with DZs were longer [67.81 ± 68.45 vs. 26.31 ± 21.25 mm, odds ratio (OR) 1.03, P = 0.010], with a higher border zone (BZ) mass (2.41 ± 2.91 vs. 0.87 ± 0.86 g, OR 2.46, P = 0.011) and greater protectedness (24.97 ± 27.72 vs. 10.19 ± 9.52 mm, OR 1.08, P = 0.021)., Conclusion: Non-invasive detection of targets for VT ablation is possible with CMR. Deceleration zones found during electroanatomical mapping accurately correlate with CMR channels, especially those with increased length, BZ mass, and protectedness., Competing Interests: Conflict of interest: L.M. and J.B. report activities as consultants, lecturers, and advisory board members for Abbott Medical, Boston Scientific, Biosense Webster, Medtronic, and Biotronik. They are also shareholders of Galgo Medical, S.L. I.R.-L., J.M.T., and A.P.-S. report activities as consultants and lecturers for Biosense Webster, Medtronic, Boston Scientific, and Abbott Medical. J.M.C. is currently an Abbott employee. R.M.F.V. is currently an ADAS 3D employee. All other authors report that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2024. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Conducting channels (CCs) detected by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related to ventricular tachycardia (VT). The aim of this work was to study the ability of post-ablation LGE-CMR to evaluate ablation lesions., Methods and Results: This is a prospective study of consecutive patients referred for a scar-related VT ablation. LGE-CMR was performed 6-12 months prior to ablation and 3-6 months after ablation. Scar characteristics of pre- and post-ablation LGE-CMR were compared. During the study period (March 2019-April 2021), 61 consecutive patients underwent scar-related VT ablation after LGE-CMR. Overall, 12 patients were excluded (4 had poor-quality LGE-CMR, 2 died before post-ablation LGE-CMR, and 6 underwent post-ablation LGE-CMR 12 months after ablation). Finally, 49 patients (age: 65.5 ± 9.8 years, 97.9% male, left ventricular ejection fraction: 34.8 ± 10.4%, 87.7% ischaemic cardiomyopathy) were included. Post-ablation LGE-CMR showed a decrease in the number (3.34 ± 1.03 vs. 1.6 ± 0.2; P < 0.0001) and mass (8.45 ± 1.3 vs. 3.5 ± 0.6 g; P < 0.001) of CCs. Arrhythmogenic CCs disappeared in 74.4% of patients. Dark core was detected in 75.5% of patients, and its presence was not related to CC reduction (52.2 ± 7.4% vs. 40.8 ± 10.6%, P = 0.57). VT recurrence after one year follow-up was 16.3%. The presence of two or more channels in the post-ablation LGE-CMR was a predictor of VT recurrence (31.82% vs. 0%, P = 0.0038) with a sensibility of 100% and specificity of 61% (area under the curve 0.82). In the same line, a reduction of CCs < 55% had sensibility of 100% and specificity of 61% (area under the curve 0.83) to predict VT recurrence., Conclusion: Post-ablation LGE-CMR is feasible, and a reduction in the number of CCs is related with lower risk of VT recurrence. The dark core was not present in all patients. A decrease in VT substrate was also observed in patients without a dark core area in the post-ablation LGE-CMR., Competing Interests: Conflict of interest: L.M. and J.B. report activities as a consultant, lecturer, and advisory board member for Abbott Medical, Boston Scientific, Biosense Webster, Medtronic, and Biotronik. They are also shareholders of Adas3D Medical S.L. I.R.-L. and A.P.-S. have served as a consultant for Biosense Webster, Medtronic, Boston Scientific, and Abbott Medical. M.S. reports activities as a consultant, lecturer, advisory board member, and grant recipient for Abbott Medical, Edwards Lifesciences, Sanofi, General Electric, and Medtronic. All other authors report that they have no relationships relevant to the contents of this paper to disclose., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background and Objectives : Left atrial (LA) remodelling and dilatation predicts atrial fibrillation (AF) recurrences after catheter ablation. However, whether right atrial (RA) remodelling and dilatation predicts AF recurrences after ablation has not been fully evaluated. Materials and Methods : This is an observational study of 85 consecutive patients (aged 57 ± 9 years; 70 [82%] men) who underwent cardiac magnetic resonance before first catheter ablation for AF (40 [47.1%] persistent AF). Four-chamber cine-sequence was selected to measure LA and RA area, and ventricular end-systolic image phase to obtain atrial 3D volumes. The effect of different variables on event-free survival was investigated using the Cox proportional hazards model. Results : In patients with persistent AF, combined LA and RA area indexed to body surface area (AILA + RA) predicted AF recurrences (HR = 1.08, 95% CI 1.00-1.17, p = 0.048). An AILA + RA cut-off value of 26.7 cm 2 /m 2 had 72% sensitivity and 73% specificity for predicting recurrences in patients with persistent AF. In this group, 65% of patients with AILA + RA > 26.7 cm 2 /m 2 experienced AF recurrence within 2 years of follow-up (median follow-up 11 months), compared to 25% of patients with AILA + RA ≤ 26.7 cm 2 /m 2 (HR 4.28, 95% CI 1.50-12.22; p = 0.007). Indices of LA and RA dilatation did not predict AF recurrences in patients with paroxysmal AF. Atrial 3D volumes did not predict AF recurrences after ablation. Conclusions : In this pilot study, the simple measurement of AILA + RA may predict recurrences after ablation of persistent AF, and may outperform measurements of atrial volumes. In paroxysmal AF, atrial dilatation did not predict recurrences. Further studies on the role of RA and LA remodelling are needed.

Introduction: Catecholaminergic polymorphic ventricular tachycardia (CPVT) is a cardiac inherited arrhythmogenic disease potentially leading to sudden cardiac death that is determined by electrical instability exacerbated by acute adrenergic tone., Methods and Results: Despite its life-threatening nature, CPVT remains potentially unnoticed since diagnosis may be difficult especially in apparently healthy athletes. This review summarizes current knowledge and shortcomings of CPVT, focusing on genetics, arrhythmic mechanisms, sport preparticipation screening, and current recommendations., Conclusions: The paper captures the importance of CPVT athletes regarding the necessity of risk stratification, as well as the importance of maintaining a healthy lifestyle., (© 2023 Wiley Periodicals LLC.)

Brugada syndrome is a rare hereditary arrhythmia disorder characterized by a distinctive electrocardiogram pattern and an elevated risk of ventricular arrhythmias and sudden cardiac death in young adults. Despite recent advances, it remains a complex condition, encompassing mechanisms, genetics, diagnosis, arrhythmia risk stratification, and management. The underlying electrophysiological mechanism of Brugada syndrome requires further investigation, with current theories focusing on abnormalities in repolarization, depolarization, and current-load match. The genetic basis of the syndrome is strong, with mutations found in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as genes involved in channel trafficking and regulation. While the initial discovery of mutations in the SCN5A gene provided valuable insights, Brugada syndrome is now recognized as a multifactorial disease influenced by several loci and environmental factors, challenging the traditional autosomal dominant inheritance model. This comprehensive review aims to provide a current understanding of Brugada syndrome, focusing on its pathophysiology, genetic mechanisms, and novel models of risk stratification. Advancements in these areas hold the potential to facilitate earlier diagnosis, improve risk assessments, and enable more targeted therapeutic interventions.

Background: A new functional mapping strategy based on targeting deceleration zones (DZs) has become one of the most commonly used strategies within the armamentarium of substrate-based ablation methods for ventricular tachycardia (VT) in patients with structural heart disease. The classic conduction channels detected by voltage mapping can be accurately determined by cardiac magnetic resonance (CMR)., Objectives: The purpose of this study was to analyze the evolution of DZs during ablation and their correlation with CMR., Methods: Forty-two consecutive patients with scar-related VT undergoing ablation after CMR in Hospital Clinic (October 2018-December 2020) were included (median age 65.3 ± 11.8 years; 94.7% male; 73.7% ischemic heart disease). Baseline DZs and their evolution in isochronal late activation remaps were analyzed. A comparison between DZs and CMR conducting channels (CMR-CCs) was realized. Patients were prospectively followed for VT recurrence for 1 year., Results: Overall, 95 DZs were analyzed, 93.68% of which were correlated with CMR-CCs: 44.8% located in the middle segment and 55.2% located in the entrance/exit of the channel. Remapping was performed in 91.7% of patients (1 remap: 33.3%, 2 remaps: 55.6%, and 3 remaps: 2.8%). Regarding the evolution of DZs, 72.2% disappeared after the first ablation set, with 14.13% not ablated at the end of the procedure. A total of 32.5% of DZs in remaps correlated with a CMR-CCs already detected, and 17.5% were associated with an unmasked CMR-CCs. One-year VT recurrence was 22.9%., Conclusions: DZs are highly correlated with CMR-CCs. In addition, remapping can lead to the identification of hidden substrate initially not identified by electroanatomic mapping but detected by CMR., Competing Interests: Funding Support and Author Disclosures This study was supported by Emile Letang Grand of Hospital Clinic de Barcelona/Instituto de Salud Carlos III (ISCIII) PI20/00693/CB16/11/00354, co-funded by the European Union. Drs Mont and Brugada are consultants, lecturers, and advisory board members for Abbott Medical, Boston Scientific, Biosense Webster, Medtronic, and Biotronik; and shareholders of ADAS3D Medical, S.L. Drs Roca-Luque, Tolosana, and Porta-Sanchez are consultants and lecturers for Biosense Webster, Medtronic, Boston Scientific, and Abbott Medical. Judit Mas Casanovas is currently an Abbott employee. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2023 The Authors. Published by Elsevier Inc. All rights reserved.)

Aims: Heterogeneous tissue channels (HTCs) detected by late gadolinium enhancement cardiac magnetic resonance (LGE-CMR) are related to ventricular arrhythmias, but there are few published data about their arrhythmogenic characteristics., Methods and Results: We enrolled 34 consecutive patients with ischaemic and non-ischaemic cardiomyopathy who were referred for ventricular tachycardia (VT) ablation. LGE-CMR was performed prior to ablation, and the HTCs were analyzed. Arrhythmogenic HTCs linked to induced VT were identified during the VT ablation procedure. The characteristics of arrhythmogenic HTCs were compared with those of non-arrhythmogenic HTCs. Three patients were excluded due to low-quality LGE-CMR images. A total of 87 HTCs were identified on LGE-CMR in 31 patients (age:63.8 ± 12.3 years; 96.8% male; left ventricular ejection fraction: 36.1 ± 10.7%). Of the 87 HTCs, only 31 were considered arrhythmogenic because of their relation to a VT isthmus. The HTCs related to a VT isthmus were longer [64.6 ± 49.4 vs. 32.9 ± 26.6 mm; OR: 1.02; 95% CI: (1.01-1.04); P < 0.001] and had greater mass [2.5 ± 2.2 vs. 1.2 ± 1.2 grams; OR: 1.62; 95% CI: (1.18-2.21); P < 0.001], a higher degree of protectedness [26.19 ± 19.2 vs. 10.74 ± 8.4; OR 1.09; 95% CI: (1.04-1.14); P < 0.001], higher transmurality [number of wall layers with CCs: 3.8 ± 2.4 vs. 2.4 ± 2.0; OR: 1.31; 95% CI: (1.07-1.60); P = 0.008] and more ramifications [3.8 ± 2.0 vs. 2.7 ± 1.1; OR: 1.59; 95% CI: (1.15-2.19); P = 0.002] than non-arrhythmogenic HTCs. Multivariate logistic regression analysis revealed that protectedness was the strongest predictor of arrhythmogenicity., Conclusion: The protectedness of an HTC identified by LGE-CMR is strongly related to its arrhythmogenicity during VT ablation., Competing Interests: Conflict of interest: I.R.L. and J.M.T. have served as consultants for Boston Scientific and Abbott Medical.L.M. and J.B. report activities as consultants, lecturers, and advisory board members for Abbott Medical, Boston Scientific, Biosense Webster, Medtronic, and Biotronik. They are also shareholders of Galgo Medical, S.L. M.S and R.FV work for ADAS3D Medical S.L. All other authors declare no conflict of interest., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Little is known about patients with right bundle branch block (RBBB)-ventricular tachycardia (VT) and arrhythmogenic cardiomyopathy (ACM). Our aims were: (i) to describe electrocardiogram (ECG) characteristics of sinus rhythm (SR) and VT; (ii) to correlate SR with RBBB-VT ECGs; and (iii) to compare VT ECGs with electro-anatomic mapping (EAM) data., Methods and Results: From the European Survey on ACM, 70 patients with spontaneous RBBB-VT were included. Putative left ventricular (LV) sites of origin (SOOs) were estimated with a VT-axis-derived methodology and confirmed by EAM data when available. Overall, 49 (70%) patients met definite Task Force Criteria. Low QRS voltage predominated in lateral leads (n = 37, 55%), but QRS fragmentation was more frequent in inferior leads (n = 15, 23%). T-wave inversion (TWI) was equally frequent in inferior (n = 28, 42%) and lateral (n = 27, 40%) leads. TWI in inferior leads was associated with reduced LV ejection fraction (LVEF; 46 ± 10 vs. 53 ± 8, P = 0.02). Regarding SOOs, the inferior wall harboured 31 (46%) SOOs, followed by the lateral wall (n = 17, 25%), the anterior wall (n = 15, 22%), and the septum (n = 4, 6%). EAM data were available for 16 patients and showed good concordance with the putative SOOs. In all patients with superior-axis RBBB-VT who underwent endo-epicardial VT activation mapping, VT originated from the LV., Conclusions: In patients with ACM and RBBB-VT, RBBB-VTs originated mainly from the inferior and lateral LV walls. SR depolarization and repolarization abnormalities were frequent and associated with underlying variants., (© The Author(s) 2023. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Laminopathies are caused by rare alterations in LMNA , leading to a wide clinical spectrum. Though muscular dystrophy begins at early ages, disease progression is different in each patient. We investigated variability in laminopathy phenotypes by performing a targeted genetic analysis of patients diagnosed with LMNA -related muscular dystrophy to identify rare variants in alternative genes, thereby explaining phenotypic differences. Methods: We analyzed 105 genes associated with muscular diseases by targeted sequencing in 26 pediatric patients of different countries, diagnosed with any LMNA -related muscular dystrophy. Family members were also clinically assessed and genetically analyzed. Results: All patients carried a pathogenic rare variant in LMNA . Clinical diagnoses included Emery-Dreifuss muscular dystrophy (EDMD, 13 patients), LMNA -related congenital muscular dystrophy (L-CMD, 11 patients), and limb-girdle muscular dystrophy 1B (LGMD1B, 2 patients). In 9 patients, 10 additional rare genetic variants were identified in 8 genes other than LMNA . Genotype-phenotype correlation showed additional deleterious rare variants in five of the nine patients (3 L-CMD and 2 EDMD) with severe phenotypes. Conclusion: Analysis f known genes related to muscular diseases in close correlation with personalized clinical assessments may help identify additional rare variants of LMNA potentially associated with early onset or most severe disease progression., 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., (Copyright © 2023 Cesar, Coll, Fiol, Fernandez-Falgueras, Cruzalegui, Iglesias, Moll, Perez-Serra, Martínez-Barrios, Ferrer-Costa, Olmo, Puigmulè, Alcalde, Lopez, Pico, Berrueco, Brugada, Zschaeck, Natera-de Benito, Carrera-García, Exposito-Escudero, Ortez, Nascimento, Brugada, Sarquella-Brugada and Campuzano.)

Introduction: LMNA-related muscular dystrophy is a rare entity that produce "laminopathies" such as Emery-Dreifuss muscular dystrophy (EDMD), limb-girdle muscular dystrophy type 1B (LGMD1B), and LMNA-related congenital muscular dystrophy (L-CMD). Heart failure, malignant arrhythmias, and sudden death may occur. No consensus exists on cardiovascular management in pediatric laminopathies. The aim was to perform an exhaustive cardiologic follow-up in pediatric patients diagnosed with LMNA-related muscular dystrophy. Methods: Baseline cardiac work-up consisted of clinical assessment, transthoracic Doppler echocardiography, 12-lead electrocardiogram, electrophysiological study, and implantation of a long-term implantable cardiac loop recorder (ILR). Results: We enrolled twenty-eight pediatric patients diagnosed with EDMD (13 patients), L-CMD (11 patients), LGMD1B (2 patients), and LMNA-related mild weakness (2 patients). Follow-up showed dilated cardiomyopathy (DCM) in six patients and malignant arrhythmias in five (four concomitant with DCM) detected by the ILR that required implantable cardioverter defibrillator (ICD) implantation. Malignant arrhythmias were detected in 20% of our cohort and early-onset EDMD showed worse cardiac prognosis. Discussion: Patients diagnosed with early-onset EDMD are at higher risk of DCM, while potentially life-threatening arrhythmias without DCM appear earlier in L-CMD patients. Early onset neurologic symptoms could be related with worse cardiac prognosis. Specific clinical guidelines for children are needed to prevent sudden death., 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. The reviewer AF declared a shared affiliation with the authors ID, MG, SQR to the handling editor at the time of review., (Copyright © 2023 Cesar, Campuzano, Cruzalegui, Fiol, Moll, Martínez-Barrios, Zschaeck, Natera-de Benito, Ortez, Carrera, Expósito, Berrueco, Bautista-Rodriguez, Dabaj, Gómez García-de-la-Banda, Quijano-Roy, Brugada, Nascimento and Sarquella-Brugada.)

Introduction and Objectives: Late gadolinium-enhanced cardiac magnetic resonance (LGE-CMR) allows noninvasive detection of left atrial fibrosis in patients with atrial fibrillation (AF). However, whether the same methodology can be used in the right atrium (RA) remains unknown. Our aim was to define a standardized threshold to characterize RA fibrosis in LGE-CMR., Methods: A 3 Tesla LGE-CMR was performed in 53 individuals; the RA was segmented, and the image intensity ratio (IIR) calculated for the RA wall using 1 557 767 IIR pixels (40 994±10 693 per patient). The upper limit of normality of the IIR (mean IIR+2 standard deviations) was estimated in healthy volunteers (n=9), and patients who had undergone previous typical atrial flutter ablation (n=9) were used to establish the dense scar threshold. Paroxysmal and persistent AF patients (n=10 each) were used for validation. IIR values were correlated with a high-density bipolar voltage map in 15 patients undergoing AF ablation., Results: The upper normality limit (total fibrosis threshold) in healthy volunteers was set at an IIR = 1.21. In the postablation group, 60% of the maximum IIR pixel (dense fibrosis threshold) was calculated as IIR = 1.29. Endocardial bipolar voltage showed a weak but significant correlation with IIR. The overall accuracy between the electroanatomical map and LGE-CMR to characterize fibrosis was 56%., Conclusions: An IIR > 1.21 was determined to be the threshold for the detection of right atrial fibrosis, while an IIR > 1.29 differentiates interstitial fibrosis from dense scar. Despite differences between the left and right atria, fibrosis could be assessed with LGE-CMR using similar thresholds in both chambers., (Copyright © 2023 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Sudden death cases in the young population remain without a conclusive cause of decease in almost 40% of cases. In these situations, cardiac arrhythmia of genetic origin is suspected as the most plausible cause of death. Molecular autopsy may reveal a genetic defect in up to 20% of families. Most than 80% of rare variants remain classified with an ambiguous role, impeding a useful clinical translation. Our aim was to update rare variants originally classified as of unknown significance to clarify their role. Our cohort included fifty-one post-mortem samples of young cases who died suddenly and without a definite cause of death. Five years ago, molecular autopsy identified at least one rare genetic alteration classified then as ambiguous following the American College of Medical Genetics and Genomics' recommendations. We have reclassified the same rare variants including novel data. About 10% of ambiguous variants change to benign/likely benign mainly because of improved population frequencies. Excluding cases who died before one year of age, almost 21% of rare ambiguous variants change to benign/likely benign. This fact makes it important to discard these rare variants as a cause of sudden unexplained death, avoiding anxiety in relatives' carriers. Twenty-five percent of the remaining variants show a tendency to suspicious deleterious role, highlighting clinical follow-up of carriers. Periodical reclassification of rare variants originally classified as ambiguous is crucial, at least updating frequencies every 5 years. This action aids to increase accuracy to enable and conclude a cause of death as well as translation into the clinic., (© 2023. The Author(s).)

Aims: Electrical reconnection of pulmonary veins (PVs) is considered an important determinant of recurrent atrial fibrillation (AF) after pulmonary vein isolation (PVI). To date, AF recurrences almost automatically trigger invasive repeat procedures, required to assess PVI durability. With recent technical advances, it is becoming increasingly common to find all PVs isolated in those repeat procedures. Thus, as ablation of extra-PV targets has failed to show benefit in randomized trials, more and more often these highly invasive procedures are performed only to rule out PV reconnection. Here we aim to define the ability of late gadolinium enhancement (LGE)-magnetic resonance imaging (MRI) to rule out PV reconnection non-invasively., Methods and Results: This study is based on a prospective registry in which all patients receive an LGE-MRI after AF ablation. Included were all patients that-after an initial PVI and post-ablation LGE-MRI-underwent an invasive repeat procedure, which served as a reference to determine the predictive value of non-invasive lesion assessment by LGE-MRI.: 152 patients and 304 PV pairs were analysed. LGE-MRI predicted electrical PV reconnection with high sensitivity (98.9%) but rather low specificity (55.6%). Of note, LGE lesions without discontinuation ruled out reconnection of the respective PV pair with a negative predictive value of 96.9%, and patients with complete LGE lesion sets encircling all PVs were highly unlikely to show any PV reconnection (negative predictive value: 94.4%)., Conclusion: LGE-MRI has the potential to guide selection of appropriate candidates and planning of the ablation strategy for repeat procedures and may help to identify patients that will not benefit from a redo-procedure if no ablation of extra-PV targets is intended., Competing Interests: Conflict of interest: T.F.A. has received research grants for investigator-initiated trials from Biosense Webster. L.M. has received honoraria as a lecturer and consultant and has received research grants from Abbott Medical, Biosense Webster, Boston Scientific, and Medtronic. He is a shareholder of Galgo Medical SL. M.S. has received grants, consulting honoria and speakers’ fees from General Electric, Edwards Lifesciences, Abbott Medical, and Medtronic. J.-B.G. has received an unrestricted fellowship grant from Abbott Medical. All remaining authors have declared no conflicts of interest., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Aims: Atrial fibrillation (AF) recurrence during the first year after catheter ablation remains common. Patient-specific prediction of arrhythmic recurrence would improve patient selection, and, potentially, avoid futile interventions. Available prediction algorithms, however, achieve unsatisfactory performance. Aim of the present study was to derive from ESC-EHRA Atrial Fibrillation Ablation Long-Term Registry (AFA-LT) a machine-learning scoring system based on pre-procedural, easily accessible clinical variables to predict the probability of 1-year arrhythmic recurrence after catheter ablation., Methods and Results: Patients were randomly split into a training (80%) and a testing cohort (20%). Four different supervised machine-learning models (decision tree, random forest, AdaBoost, and k-nearest neighbour) were developed on the training cohort and hyperparameters were tuned using 10-fold cross validation. The model with the best discriminative performance on the testing cohort (area under the curve-AUC) was selected and underwent further optimization, including re-calibration. A total of 3128 patients were included. The random forest model showed the best performance on the testing cohort; a 19-variable version achieved good discriminative performance [AUC 0.721, 95% confidence interval (CI) 0.680-0.764], outperforming existing scores (e.g. APPLE score: AUC 0.557, 95% CI 0.506-0.607). Platt scaling was used to calibrate the model. The final calibrated model was implemented in a web calculator, freely available at http://afarec.hpc4ai.unito.it/., Conclusion: AFA-Recur, a machine-learning-based probability score predicting 1-year risk of recurrent atrial arrhythmia after AF ablation, achieved good predictive performance, significantly better than currently available tools. The calculator, freely available online, allows patient-specific predictions, favouring tailored therapeutic approaches for the individual patient., Competing Interests: Conflict of interest: M.A. is consultant for Biosense Webster and Boston Scientific, proctor for Medtronic, and received educational support from Abbott., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology. All rights reserved. For permissions, please email: journals.permissions@oup.com.)

Background: Ventricular tachycardia (VT) is caused by the presence of a slow conduction channel (CC) of border zone (BZ) tissue inside the scar-core tissue. Electroanatomic mapping can depict this tissue by voltage mapping. Areas of slow conduction can be detected as late potentials (LPs) and their abolition is the most accepted ablation endpoint. In the current guidelines, bipolar voltage thresholds for BZ and core scar are 1.5 and 0.5 mV respectively. The performance of these values is controversial. The aim of the study is to analyze the diagnostic yield of current amplitude thresholds in voltage map to define VT substrate in terms of CCs of LPs. Predictors of usefulness of current thresholds will be analyzed., Methods: All patients with structural heart disease who underwent VT ablation in Hospital Clinic in 2016-2017 were included. Maps with delineation of CCs based on LPs were created with contact force sensor catheter. Thresholds were adjusted for every patient based on CCs. Diagnostic yield and predictors of performance of conventional thresholds were analyzed., Results: During study period, 57 consecutive patients were included (age: 60.4 ± 8.5; 50.2% ischemic cardiomyopathy, LVEF 39.8 ± 13.5%). Cutoff voltages that better identified the scar and BZ according to the LP channels were 0.32 (0.02-2 mV) and 1.84 (0.3-6 mV) respectively. Current voltage thresholds identified correctly core and BZ in 87.7% and 42.1% of the patients respectively. Accuracy was worse in non-ischemic cardiomyopathy (NICM) especially for BZ (28.6% vs 55.2%, p = 0.042)., Conclusions: Accuracy of standard voltage thresholds for scar and BZ is poor in terms of LPs detection. Diagnostic yield is worse in NICM patients specially for border zone., (© 2022. The Author(s).)

Aims: With recurrence rates up to 50% after pulmonary vein isolation (PVI) in persistent atrial fibrillation (AF), predictive tools to improve patient selection are needed. Patient selection based on left atrial late gadolinium enhancement (LGE) cardiovascular magnetic resonance (CMR) has been proposed previously (UTAH-classification). However, this approach has not been widely established, in part owed to the lack of standardization of the LGE quantification method. We have recently established a standardized LGE-CMR method enabling reproducible LGE-quantification. Here, the ability of this method to predict outcome after PVI was evaluated., Methods and Results: This dual-centre study ( n = 219) consists of a prospective derivation cohort ( n = 37, all persistent AF) and an external validation cohort ( n = 182; 66 persistent, 116 paroxysmal AF). All patients received an LGE-CMR prior to first-time PVI-only ablation. LGE was quantified based on the signal-intensity-ratio relative to the blood pool, applying a uniform LGE-defining threshold of >1.2.   In patients with persistent AF in the derivation cohort, left atrial LGE-extent above a cut-off value of 12% was found to best predict relevant low-voltage substrate (≥2 cm two with <0.5 mV during sinus rhythm) and arrhythmia-free survival 12 months post-PVI. When applied to the external validation cohort, this cut-off value was also predictive of arrhythmia-free survival for both, the total cohort and the subgroup with persistent AF (LGE < 12%: 80% and 76%; LGE > 12%: 55% and 44%; P = 0.007 and P = 0.029, respectively)., Conclusion: This dual-centre study established and validated a standardized, reproducible LGE-CMR method discriminating PVI responders from non-responders, which may improve choice of therapeutic approach or ablation strategy for patients with persistent AF., Competing Interests: Conflict of interest Dr Till Althoff has received research grants for investigator-initiated trials not related to this study from Biosense Webster. Rosa M. Figueras i Ventura is employee of Adas 3D Medical Inc. Dr Franz-Josef Neumann has received honoraria as lecturer and consultant from Boston Scientific, Biotronik, Medtronic, Edwards life science, Abbott Vascular, Pfizer, Boehringer-Ingelheim. Dr Dirk Westermann has received honoraria as lecturer and consultant from Abiomed, AstraZeneca, Bayer, Berlin-Chemie, Boehringer, Edwards, Novartis and Medtronic. Dr Lluís Mont has received honoraria as a lecturer and consultant and has received research grants from Abbott Medical, Biosense Webster, Boston Scientific and Medtronic. He is a shareholder of Galgo Medical SL., (© The Author(s) 2022. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: Conduction system pacing (CSP) has emerged as an alternative to biventricular pacing (BiVP). Randomized studies comparing both therapies are scarce and do not include left bundle branch pacing., Objectives: This study aims to compare ventricular resynchronization achieved by CSP vs BiVP in patients with cardiac resynchronization therapy indication., Methods: LEVEL-AT (Left Ventricular Activation Time Shortening with Conduction System Pacing vs Biventricular Resynchronization Therapy) was a randomized, parallel, controlled, noninferiority trial. Seventy patients with cardiac resynchronization therapy indication were randomized 1:1 to BiVP or CSP, and followed up for 6 months. Crossover was allowed when primary allocation procedure failed. Primary endpoint was the change in left ventricular activation time, measured using electrocardiographic imaging. Secondary endpoints were left ventricular reverse remodeling and the combined endpoint of heart failure hospitalization or death at 6-month follow-up., Results: Thirty-five patients were allocated to each group. Eight (23%) patients crossed over from CSP to BiVP; 2 patients (6%) crossed over from BiVP to CSP. Electrocardiographic imaging could not be performed in 2 patients in each group. A similar decrease in left ventricular activation time was achieved by CSP and BiVP (-28 ± 26 ms vs -21 ± 20 ms, respectively; mean difference -6.8 ms; 95% CI: -18.3 ms to 4.6 ms; P < 0.001 for noninferiority). Both groups showed a similar change in left ventricular end-systolic volume (-37 ± 59 mL CSP vs -30 ± 41 mL BiVP; mean difference: -8 mL; 95% CI: -33 mL to 17 mL; P = 0.04 for noninferiority) and similar rates of mortality or heart failure hospitalizations (2.9% vs 11.4%, respectively) (P = 0.002 for noninferiority)., Conclusions: Similar degrees of cardiac resynchronization, ventricular reverse remodeling, and clinical outcomes were attained by CSP as compared to BiVP. CSP could be a feasible alternative to BiVP. (LEVEL-AT [Left Ventricular Activation Time Shortening With Conduction System Pacing vs Biventricular Resynchronization Therapy]; NCT04054895)., Competing Interests: Funding Support and Author Disclosures Drs Pujol-Lopez, Tolosana, Castel, and Jiménez-Arjona have received funding for a Project in Conduction System Pacing: FIS PI21/00615 Instituto de Salud Carlos III (Madrid, Spain). Dr Pujol-Lopez has received the Catalan Society of Cardiology research grant in 2019 and 2020 (Catalonia, Spain), the Josep Font ResearchGrant in 2019 from Hospital Clínic Barcelona (Catalonia, Spain), and the Research Grant 2020 from Asociación del Ritmo Cardiaco (Spanish Society of Cardiology); and has received speaker honoraria from Medtronic. Dr Roca-Luque has received honoraria as a lecturer and consultant from Abbott and Biosense Webster. Dr Sitges has received consultant fees and speaker honoraria from Abbott, Medtronic, General Electric, and Edwards Lifesciences. Dr Tolosana has received honoraria as a lecturer and consultant from Abbott, Boston Scientific, and Medtronic. Dr Mont has received unrestricted research grants, fellowship program support, and honoraria as a lecturer and consultant from Abbott, Biotronik, Boston Scientific, Livanova, and Medtronic; and holds stock in Galgo Medical and Corify. Dr Castel has received speaker honoraria from Boston Scientific, Abbott, and Microport. Dr Arbelo has received speaker honoraria from Biosense Webster and Bayer. All other authors have reported that they have no relationships relevant to the contents of this paper to disclose., (Copyright © 2022 The Authors. Published by Elsevier Inc. All rights reserved.)

Background: We aimed to describe the morphology of the border zone of viable myocardium surrounded by scarring in patients with Chagas heart disease and study their association with clinical events., Methods: Adult patients with Chagas heart disease (n=22; 55% females; 65.5 years, SD 10.1) were included. Patients underwent high-resolution contrast-enhanced cardiac magnetic resonance using myocardial delayed enhancement with postprocessing analysis to identify the core scar area and border zone channels number, mass, and length. The association between border zone channel parameters and the combined end-point (cardiovascular mortality or internal cardiac defibrillator implantation) was tested by multivariable Cox proportional hazard regression analyses. The significance level was set at 0.05. Data are presented as the mean (standard deviation [SD]) or median (interquartile range)., Results: A total of 44 border zone channels (1[1-3] per patient) were identified. The border zone channel mass per patient was 1.25 (0.48-4.39) g, and the extension in layers of the border zone channels per patient was 2.4 (1.0-4.25). Most border zone channels were identified in the midwall location. Six patients presented the studied end-point during a mean follow-up of 4.9 years (SD 1.6). Border zone channel extension in layers was associated with the studied end-point independent from left ventricular ejection fraction or fibrosis mass (HR=2.03; 95% CI 1.15-3.60)., Conclusions: High-resolution contrast-enhanced cardiac magnetic resonance can identify border zone channels in patients with Chagas heart disease. Moreover, border zone channel extension was independently associated with clinical events.

Background Left atrial structural remodeling contributes to the arrhythmogenic substrate of atrial fibrillation (AF), but the role of the right atrium (RA) remains unknown. Our aims were to comprehensively characterize right atrial structural remodeling in AF and identify right atrial parameters predicting recurrences after ablation. Methods and Results A 3.0 T late gadolinium enhanced-cardiac magnetic resonance was obtained in 109 individuals (9 healthy volunteers, 100 patients with AF undergoing ablation). Right and left atrial volume, surface, and sphericity were quantified. Right atrial global and regional fibrosis burden was assessed with validated thresholds. Patients with AF were systematically followed after ablation for recurrences. Progressive right atrial dilation and an increase in sphericity were observed from healthy volunteers to patients with paroxysmal and persistent AF; fibrosis was similar among the groups. The correlation between parameters recapitulating right atrial remodeling was mild. Subsequently, remodeling in both atria was compared. The RA was larger than the left atrium (LA) in all groups. Fibrosis burden was higher in the LA than in the RA of patients with AF, whereas sphericity was higher in the LA of patients with persistent AF only. Fibrosis, volume, and surface of the RA and LA, but not sphericity, were strongly correlated. Tricuspid regurgitation predicted right atrial volume and shape, whereas diabetes was associated with right atrial fibrosis burden; sex and persistent AF also predicted right atrial volume. Fibrosis in the RA was mostly located in the inferior vena cava-RA junction. Only right atrial sphericity is significantly associated with AF recurrences after ablation (hazard ratio, 1.12 [95% CI, 1.01-1.25]). Conclusions AF progression associates with right atrial remodeling in parallel with the LA. Right atrial sphericity yields prognostic significance after ablation.

Brugada syndrome (BrS) is characterized by ventricular arrhythmias in patients without structural cardiac alteration. Some patients present repeated episodes of ventricular tachycardia. Epicardial catheter ablation makes it possible to decrease arrhythmic recurrence in these patients., (Copyright © 2021 Elsevier Inc. All rights reserved.)

Purpose of Review: Among the most common causes of cardiac syncope are arrhythmias and ischemic heart disease, both of which can coexist. The purpose of this review is to discuss the main causes of cardiac and vascular syncope related to atherosclerosis, its epidemiological and clinical aspects, warning signs, and initial approach., Recent Findings: Cardiac syncope may have a frequency of up to 34% in elderly people. Atherosclerosis-related causes of cardiac and vascular syncope may be due to cardiac arrhythmia and/or structural impairment of the heart or arteries. Late ventricular tachycardia and late-onset high-grade atrioventricular block associated with myocardial ischemia may occur with syncope, which is related to higher mortality. Besides ventricular dysfunction, concentric remodeling is also a prognostic factor. In calcific degenerative aortic stenosis, syncope carries a worse prognosis than the other cardinal signs. Cardiac syncope has a high recurrence and mortality rate. There are red flag alerts that must be considered in risk stratification., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

A proper interpretation of the pathogenicity of rare variants is crucial before clinical translation. Ongoing addition of new data may modify previous variant classifications; however, how often a reanalysis is necessary remains undefined. We aimed to extensively reanalyze rare variants associated with inherited channelopathies originally classified 5 years ago and its clinical impact. In 2016, rare variants identified through genetic analysis were classified following the American College of Medical Genetics and Genomics' recommendations. Five years later, we have reclassified the same variants following the same recommendations but including new available data. Potential clinical implications were discussed. Our cohort included 49 cases of inherited channelopathies diagnosed in 2016. Update show that 18.36% of the variants changed classification mainly due to improved global frequency data. Reclassifications mostly occurred in minority genes associated with channelopathies. Similar percentage of variants remain as deleterious nowadays, located in main known genes (SCN5A, KCNH2 and KCNQ1). In 2016, 69.38% of variants were classified as unknown significance, but now, 53.06% of variants are classified as such, remaining the most common group. No management was modified after translation of genetic data into clinics. After 5 years, nearly 20% of rare variants associated with inherited channelopathies were reclassified. This supports performing periodic reanalyses of no more than 5 years since last classification. Use of newly available data is necessary, especially concerning global frequencies and family segregation. Personalized clinical translation of rare variants can be crucial to management if a significant change in classification is identified., (© 2021. The Author(s).)

Background: Vasovagal syncope (VVS) is the most common cause of syncope. Some stages of its pathophysiological mechanisms remain unclear. Vasoactive substances such as nitric oxide metabolites (NOx) and endothelin (ET) may be involved during acute orthostatic stress., Objective: To analyze plasma changes in NOx and ET and heart rate variability (HRV) in the supine positions (T1) and during the head-up tilt test (HUTT) (T2), in patients with VVS (case group) and control group., Methods: Thirty-seven patients (17 in the case group and 20 in the control group), matched for age and sex (mean aged 31.8 years) underwent HUTT with simultaneous HRV recording and venipuncture. Blood samples were collected during phases T1 and T2 and the analysis was performed without knowledge of the HUTT result., Results: In the total sample, there was an increase in NOx values ( P  = .014), however there was no increase in ET values from phase T1 to phase T2. Patients with VVS tended to increase plasma NOx values ( P  = .057) and had significantly higher plasma values compared to ET ( P  = .033) between phases T1 to T2. In the control group, there was no significant change in the values of these vasoactive substances. Regarding HRV, there were a decrease in the component HF (high frequency) and increased of the LF (low frequency)/HF ratio during HUTT., Conclusions: There was an increase in ET during HUTT occurred only in the case group. These patients are more likely to have an imbalance between antagonistic vasoactive biomarkers during orthostatic stress., Competing Interests: Declaration of Conflicting Interests: The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article., (© The Author(s) 2022.)

Background: Substrate-based ablation has become a successful technique for ventricular tachycardia (VT) ablation. High-density (HD) mapping catheters provide high-resolution electroanatomical maps and better discrimination of local abnormal electrograms. The HD Grid Mapping Catheter is an HD catheter with the ability to map orthogonal signals on top of conventional bipolar signals, which could provide better discrimination of the arrhythmic substrate. On the other hand, conventional mapping techniques, such as activation mapping, when possible, help to identify the isthmus of the tachycardia., Aim: The purpose of this study was to compare clinical outcomes after using two different VT ablation strategies: one based on extensive mapping with the HD Grid Mapping Catheter, including VT isthmus analysis, and the other based on pure substrate ablation., Methods: Forty consecutive patients undergoing VT ablation with extensive HD mapping method in the hospital clinic (November 2018-November 2019) were included. Clinical outcomes were compared with a historical cohort of 26 consecutive patients who underwent ablation using a scar dechanneling technique before 2018., Results: The density of mapping points was higher in the extensive mapping group (2370.24 ± 920.78 vs. 576.45 ± 294.46; p < 0.001). After 1 year of follow-up, VT recurred in 18.4% of patients in the extensive mapping group vs. 34.6% of patients in the historical control group ( p = 0.14), with a significantly greater reduction of VT burden: VT episodes (81.7 ± 7.79 vs. 43.4 ± 19.9%, p < 0.05), antitachycardia pacing (99.45 ± 2.29 vs. 33.9 ± 102.5%, p < 0.001), and implantable cardioverter defibrillator (ICD) shocks (99 ± 4.5 vs. 64.7 ± 59.9%, p = 0.02)., Conclusion: The use of a method based on extensive mapping with the HD Grid Mapping Catheter and VT isthmus analysis allows better discrimination of the arrhythmic substrate and could be associated with a greater decrease in VT burden., Competing Interests: LM, EA, JB, IR-L, and JT report activities as consultant, lecturer, and advisory board member for Abbott Medical, Boston Scientific, Biosense Webster, Medtronic, and Biotronik. MP-L has received honoraria from Medtronic. The remaining 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., (Copyright © 2022 Vázquez-Calvo, Garre, Sanchez-Somonte, Borras, Quinto, Caixal, Pujol-Lopez, Althoff, Guasch, Arbelo, Tolosana, Brugada, Mont and Roca-Luque.)

Brugada syndrome (BrS) is classified as an inherited cardiac channelopathy attributed to dysfunctional ion channels and/or associated proteins in cardiomyocytes rather than to structural heart alterations. However, hearts of some BrS patients exhibit slight histologic abnormalities, suggesting that BrS could be a phenotypic variant of arrhythmogenic cardiomyopathy. We performed a systematic review of the literature following Preferred Reporting Items for Systematic Reviews and Meta-Analyses Statement (PRISMA) criteria. Our comprehensive analysis of structural findings did not reveal enough definitive evidence for reclassification of BrS as a cardiomyopathy. The collection and comprehensive analysis of new cases with a definitive BrS diagnosis are needed to clarify whether some of these structural features may have key roles in the pathophysiological pathways associated with malignant arrhythmogenic episodes., Competing Interests: The authors declare no conflict of interest.

Moderate exercise has well-founded benefits in cardiovascular health. However, increasing, yet controversial, evidence suggests that extremely trained athletes may not be protected from cardiovascular events as much as moderately trained individuals. In our rodent model, intensive but not moderate training promoted aorta and carotid stiffening and elastic lamina ruptures, tunica media thickening of intramyocardial arteries, and an imbalance between vasoconstrictor and relaxation agents. An up-regulation of angiotensin-converter enzyme, miR-212, miR-132, and miR-146b might account for this deleterious remodeling. Most changes remained after a 4-week detraining. In conclusion, our results suggest that intensive training blunts the benefits of moderate exercise., Competing Interests: This work was partially supported by grants from the Instituto de Salud Carlos III (PI13/01580, PI16/00703, PI19/00443), co-funded by the European Union; CERCA program/Generalitat de Catalunya; CIBERCV (16/11/00354); and Spanish Ministry of Economy and Competitiveness (DPI2017-83721-P). The authors have reported that they have no relationships relevant to the contents of this paper to disclose., (© 2022 The Authors.)

Introduction and Objectives: Multiparametric scores have been designed for better risk stratification in Brugada syndrome (BrS). We aimed to validate 3 multiparametric approaches (the Delise score, Sieira score and the Shanghai BrS Score) in a cohort with Brugada syndrome and electrophysiological study (EPS)., Methods: We included patients diagnosed with BrS and previous EPS between 1998 and 2019 in 23 hospitals. C-statistic analysis and Cox proportional hazard regression models were used., Results: A total of 831 patients were included (mean age, 42.8±13.1; 623 [75%] men; 386 [46.5%] had a type 1 electrocardiogram (ECG) pattern, 677 [81.5%] were asymptomatic, and 319 [38.4%] had an implantable cardioverter-defibrillator). During a follow-up of 10.2±4.7 years, 47 (5.7%) experienced a cardiovascular event. In the global cohort, a type 1 ECG and syncope were predictive of arrhythmic events. All risk scores were significantly associated with events. The discriminatory abilities of the 3 scores were modest (particularly when these scores were evaluated in asymptomatic patients). Evaluation of the Delise and Sieira scores with different numbers of extra stimuli (1 or 2 vs 3) did not substantially improve the event prediction c-index., Conclusions: In BrS, classic risk factors such as ECG pattern and previous syncope predict arrhythmic events. The predictive capabilities of the EPS are affected by the number of extra stimuli required to induce ventricular arrhythmias. Scores combining clinical risk factors with EPS help to identify the populations at highest risk, although their predictive abilities remain modest in the general BrS population and in asymptomatic patients., (Copyright © 2021 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Ventricular tachycardia (VT) substrate-based ablation has become the gold standard treatment for patients with structural heart disease-related VT. VT is linked to re-entry in relation to myocardial scarring, with areas of conduction block (core scar) and of slow conduction (border zone). Slow conduction areas can be detected in sinus rhythm as late potentials (LPs). LP abolition has been shown to be the best end point to avoid long-term recurrences. Our study aimed to analyze the challenges of LP abolition and the predictors of failure. We analyzed 169 consecutive patients with structural heart disease (61% ischemic cardiomyopathy, left ventricular ejection fraction: 37 ± 13%) who underwent VT ablation between 2013 and 2018. A preprocedural clinical evaluation, including cardiac magnetic resonance, was done in 66% of patients. Electroanatomical mapping with the identification of LPs was performed in all patients. Noninducibility was achieved in 71% (119), and complete LP abolition was achieved in 61% (103) of patients. Incomplete LP abolition was a powerful predictor of VT recurrence (67% vs 33%, hazard ratio 3.19 [2.1 to 4.7]; p <0.001). Lack of use of a high-density mapping catheter (odds ratio 6.2, 1.2 to 38.1; p = 0.028), the septal substrate (odds ratio 9.34, 2.27 to 38.4; p = 0.002), and larger left ventricular mass (190 ± 58 g vs 156 ± 46 g, p = 0.002) were predictors of incomplete LP abolition. The main reasons that contributed to unsuccessful LP abolition were anatomic obstacles (such as the conduction system) and large extension of the LP area. In conclusion, incomplete LP abolition is related to VT recurrence. Lack of use of a high-density mapping catheter, the septal substrate, and larger left ventricular mass are related to incomplete LP abolition., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Brugada syndrome (BrS) was initially described in 1992 by Josep and Pedro Brugada as an arrhythmogenic disease characterized by ST segment elevation in the right precordial leads and increased risk of sudden cardiac death (SCD). Alterations in the SCN5A gene are responsible for approximately 30% of cases of BrS, following an autosomal dominant pattern of inheritance. However, despite its autosomal transmission, sex-related differences are widely accepted. BrS is more prevalent in males than in females (8-10 times), with males having a 5.5-fold higher risk of SCD. There are also differences in clinical presentation, with females being more frequently asymptomatic and older than males at the time of diagnosis. Some factors have been identified that could explain these differences, among which testosterone seems to play an important role. However, only 30% of the available publications on the syndrome include sex-related information. Therefore, current findings on BrS are based on studies conducted mainly in male population, despite the wide acceptance of gender differences. The inclusion of complete clinical and demographic information in future publications would allow a better understanding of the phenotypic variability of BrS in different age and sex groups helping to improve the diagnosis, management and risk management of SCD., 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., (Copyright © 2022 Martínez-Barrios, Arbelo, Cesar, Cruzalegui, Fiol, Díez-Escuté, Hernández, Brugada, Brugada, Campuzano and Sarquella-Brugada.)

Brugada syndrome (BrS) is a cardiac arrhythmia disorder associated with sudden death in young adults. With the exception of SCN5A, encoding the cardiac sodium channel Na V 1.5, susceptibility genes remain largely unknown. Here we performed a genome-wide association meta-analysis comprising 2,820 unrelated cases with BrS and 10,001 controls, and identified 21 association signals at 12 loci (10 new). Single nucleotide polymorphism (SNP)-heritability estimates indicate a strong polygenic influence. Polygenic risk score analyses based on the 21 susceptibility variants demonstrate varying cumulative contribution of common risk alleles among different patient subgroups, as well as genetic associations with cardiac electrical traits and disorders in the general population. The predominance of cardiac transcription factor loci indicates that transcriptional regulation is a key feature of BrS pathogenesis. Furthermore, functional studies conducted on MAPRE2, encoding the microtubule plus-end binding protein EB2, point to microtubule-related trafficking effects on Na V 1.5 expression as a new underlying molecular mechanism. Taken together, these findings broaden our understanding of the genetic architecture of BrS and provide new insights into its molecular underpinnings., (© 2022. The Author(s), under exclusive licence to Springer Nature America, Inc.)

High-level sports competition is popular among Swiss youth. Even though preparticipation evaluation for competitive athletes is widespread, screening strategies for diseases responsible for sudden death during sport are highly variable. Hence, we sought to develop age-specific preparticipation cardiovascular evaluation (PPCE) proposals for Swiss paediatric and adolescent athletes (under 18 years of age). We recommend that all athletes practising in a squad with a training load of at least 6 hours per week should undergo PPCE based on medical history and physical examination from the age of 12 years on. Prior to 12 years, individual judgement of athletic performance is required. We suggest the inclusion of a standard 12-lead electrocardiogram (ECG) evaluation for all post-pubertal athletes (or older than 15 years) with analysis in accordance with the International Criteria for ECG Interpretation in Athletes. Echocardiography should not be a first-line screening tool but rather serve for the investigation of abnormalities detected by the above strategies. We recommend regular follow-up examinations, even for those having normal history, physical examination and ECG findings. Athletes with an abnormal history (including family history), physical examination and/or ECG should be further investigated and pathological findings discussed with a paediatric cardiologist. Importantly, the recommendations provided in this document are not intended for use among patients with congenital heart disease who require individualised care according to current guidelines.