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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.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.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%.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.

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.

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.

AimsElectrical 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 resultsThis 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%).ConclusionLGE-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.

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.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.

Resumen Introduccion y objetivos Se han desarrollado puntuaciones multiparametricas para una mejor estratificacion del riesgo en el sindrome de Brugada (SBr). Nuestro objetivo es validar 3 abordajes multiparametricos (las escalas Delise, Sieira y Shanghai BrS) en una cohorte de pacientes con sindrome de Brugada y estudio electrofisiologico (EEF). Metodos Pacientes diagnosticados de SBr y con un EEF previo entre 1998-2019 en 23 hospitales. Se utilizaron analisis mediante estadistico C y modelos de regresion de riesgos proporcionales de Cox. Resultados Se incluyo en total a 831 pacientes con una media de edad de 42,8 ± 13,1 anos; 623 (75%) eran varones; 386 (46,5%) tenian patron electrocardiografico (ECG) tipo 1; 677 (81,5%) estaban asintomaticos y 319 (38,4%) tenian un desfibrilador automatico implantable. Durante un seguimiento de 10,2 ± 4,7 anos, 47 (5,7%) sufrieron un evento cardiovascular. En la cohorte total, un ECG tipo 1 y sincope fueron predictivos de eventos arritmicos. Todas las puntuaciones de riesgo se asociaron significativamente con los eventos. Las capacidades discriminatorias de las 3 escalas fueron discretas (particularmente al aplicarlas a pacientes asintomaticos). La evaluacion de las puntuaciones de Delise y Sieira con diferente numero de extraestimulos (1 o 2 frente a 3) no mejoro sustancialmente el indice c de prediccion de eventos. Conclusiones En el SBr, los factores de riesgo clasicos como el ECG y el sincope previo predicen eventos arritmicos. El numero de extraestimulos necesarios para inducir arritmias ventriculares influye en las capacidades predictivas del EEF. Las escalas que combinan factores de riesgo clinico con EEF ayudan a identificar las poblaciones con mas riesgo, aunque sus capacidades predictivas siguen siendo discretas tanto en poblacion general con SBr como en pacientes asintomaticos.

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]; p0.001). 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.

Introducción: un evento de muerte súbita supone un gran impacto para la sociedad, siendo importante su estudio para aportar conocimiento y fortalecer estrategias de promoción y prevención. Objetivo: determinar la prevalencia de los diagnósticos anatomopatológicos cardiacos definitivos y los hallazgos histopatológicos asociados con la muerte súbita de origen cardíaco en los pacientes sometidos a autopsias clínicas realizadas en el Hospital de San José de Bogotá DC, Colombia, durante el período 2015 a 2018. Métodos: estudio descriptivo de corte transversal retrospectivo en pacientes a quienes se les realizó autopsia con diagnóstico de muerte súbita de origen cardiovascular en el servicio de patología del Hospital de San José, Bogotá DC, Colombia. Resultados: se incluyeron 178 autopsias con diagnóstico de muerte súbita cardíaca. El promedio global de edad fue 56.1 años (DE: 15.06) con una relación hombre-mujer de 3:1. El hallazgo macroscópico más frecuente fue cardiomegalia (promedio 428.1 g (DE 112.8), acompañado de la presencia de coronariopatía esclerótica (p=0.000) con obstrucción de la luz de las arterias coronarias mayores de 80% (p=0.037). Conclusiones: los diagnósticos anatomopatológicos definitivos prevalentes en la muerte súbita cardiaca fueron cardiopatía isquémica crónica complicada (65%) e infarto agudo de miocardio (16%), datos similares a los reportados a nivel mundial. La cardiomegalia es un hallazgo frecuente que debe valorarse en forma cuidadosa.

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.

Aims: Neither the long-term development of ablation lesions nor the capability of late gadolinium enhancement (LGE)-MRI to detect ablation-induced fibrosis at late stages of scar formation have been defined. We sought to assess the development of atrial ablation lesions over time using LGE-MRI and invasive electroanatomical mapping (EAM). Methods and results: Ablation lesions and total atrial fibrosis were assessed in serial LGE-MRI scans 3 months and >12 months post pulmonary vein (PV) isolation. High-density EAM performed in subsequent repeat ablation procedures served as a reference. Serial LGE-MRI of 22 patients were analyzed retrospectively. The PV encircling ablation lines displayed an average LGE, indicative of ablation-induced fibrosis, of 91.7% ± 7.0% of the circumference at 3 months, but only 62.8% ± 25.0% at a median of 28 months post ablation (p < 0.0001). EAM performed in 18 patients undergoing a subsequent repeat procedure revealed that the consistent decrease in LGE over time was owed to a reduced detectability of ablation-induced fibrosis by LGE-MRI at time-points > 12 months post ablation. Accordingly, the agreement with EAM regarding detection of ablation-induced fibrosis and functional gaps was good for the LGE-MRI at 3 months (κ .74; p < .0001), but only weak for the LGE-MRI at 28 months post-ablation (κ .29; p < .0001). Conclusion: While non-invasive lesion assessment with LGE-MRI 3 months post ablation provides accurate guidance for future redo-procedures, detectability of atrial ablation lesions appears to decrease over time. Thus, it should be considered to perform LGE-MRI 3 months post-ablation rather than at later time-points > 12 months post ablation, like for example, prior to a planned redo-ablation procedure.

AimsWith 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 resultsThis 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 12%: 55% and 44%; P = 0.007 and P = 0.029, respectively).ConclusionThis 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.

Short QT syndrome (SQTS) is an extremely rare inherited arrhythmogenic entity. Nowadays, less than 200 families affected worldwide have been reported. This syndrome is characterized by the presence of a short QT interval leading to malignant ventricular tachyarrhythmias, syncope and sudden cardiac death. It is one of the most lethal heart diseases in children and young adults. Both incomplete penetrance and variable expressivity are hallmarks of this entity, making it difficult to diagnose and manage. Currently, rare variants in nine genes have been associated with SQTS (CACNA1C, CACNA2D1, CACNB2, KCNH2, KCNJ2, KCNQ1, SLC22A5, SLC4A3 and SCN5A). However, only pathogenic variants in four genes (KCNH2, KCNQ1, KCNJ2 and SLC4A3) have been found to definitively cause SQTS. The remaining genes lack a clear association with the disease, making clinical interpretation of the variants challenging. The diagnostic yield of genetic tests is currently less than 30%, leaving most families clinically diagnosed with SQTS without a conclusive genetic diagnosis. We reviewed and updated the main genetic features of SQTS, as well as recent evidence on increasingly targeted treatment.

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.

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.

The titin gene (

Aims In arrhythmogenic cardiomyopathy (ACM), sustained ventricular tachycardia (VT) typically displays a left bundle branch block (LBBB) morphology while a right bundle branch block (RBBB) morphology is rare. The present study assesses the VT morphology in ACM patients with sustained VT and their clinical and genetic characteristics. Methods and results Twenty-six centres from 11 European countries provided information on 954 ACM patients who had ≥1 episode of sustained VT spontaneously documented during patients’ clinical course. Arrhythmogenic cardiomyopathy was defined according to the 2010 Task Force Criteria, and VT morphology according to the QRS pattern in V1. Overall, 882 (92.5%) patients displayed LBBB-VT alone and 72 (7.5%) RBBB-VT [alone in 42 (4.4%) or in combination with LBBB-VT in 30 (3.1%)]. Male sex prevalence was 79.3%, 88.1%, and 56.7% in the LBBB-VT, RBBB-VT, and LBBB + RBBB-VT groups, respectively (P = 0.007). First RBBB-VT occurred 5 years after the first LBBB-VT (46.5 ± 14.4 vs 41.1 ± 15.8 years, P = 0.011). An implanted cardioverter-defibrillator was more frequently implanted in the RBBB-VT (92.9%) and the LBBB + RBBB-VT groups (90%) than in the LBBB-VT group (68.1%) (P Conclusion RBBB-VT accounts for a significant proportion of sustained VTs in ACM. Sex and type of pathogenic mutations were associated with VT type, female sex with LBBB + RBBB-VT, and DSP mutation with RBBB-VT.

The titin gene (TTN) is associated with several diseases, including inherited arrhythmias. Most of these diagnoses are attributed to rare TTN variants encoding truncated forms, but missense variants represent a diagnostic challenge for clinical genetics. The proper interpretation of genetic data is critical for translation into the clinical setting. Notably, many TTN variants were classified before 2015, when the American College of Medical Genetics and Genomics (ACMG) published recommendations to accurately classify genetic variants. Our aim was to perform an exhaustive reanalysis of rare missense TTN variants that were classified before 2015, and that have ambiguous roles in inherited arrhythmogenic syndromes. Rare missense TTN variants classified before 2015 were updated following the ACMG recommendations and according to all the currently available data. Our cohort included 193 individuals definitively diagnosed with an inherited arrhythmogenic syndrome before 2015. Our analysis resulted in the reclassification of 36.8% of the missense variants from unknown to benign/likely benign. Of all the remaining variants, currently classified as of unknown significance, 38.3% showed a potential, but not confirmed, deleterious role. Most of these rare missense TTN variants with a suspected deleterious role were identified in patients diagnosed with hypertrophic cardiomyopathy. More than 35% of the rare missense TTN variants previously classified as ambiguous were reclassified as not deleterious, mainly because of improved population frequencies. Despite being inconclusive, almost 40% of the variants showed a potentially deleterious role in inherited arrhythmogenic syndromes. Our results highlight the importance of the periodical reclassification of rare missense TTN variants to improve genetic diagnoses and help increase the accuracy of personalized medicine This work was supported by Obra Social “La Caixa Foundation” (LCF/PR/GN16/50290001 and LCF/PR/GN19/50320002)

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.