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Background: Brugada syndrome (BrS) is associated with mutations in the cardiac sodium channel gene, SCN5A. However, genetic studies of patients with BrS with arrhythmic events have been limited. We sought to compare various clinical, ECG, and electrophysiological parameters according to SCN5A genotype in a large cohort of BrS probands with first arrhythmic event., Methods: Survey on Arrhythmic Events in Brugada Syndrome is a survey of 10 Western and 4 Asian countries, gathering 678 patients with BrS with first arrhythmic event. Only probands were included, and SCN5A genotype adjudicated. Patients without appropriate genetic data were excluded. Associations of genotype with clinical features were analyzed., Results: The study group comprised 392 probands: 92 (23.5%) SCN5A+ (44 pathogenic/likely pathogenic [P/LP] and 48 variants of unknown significance) and 300 (76.5%) SCN5A-. SCN5A missense variants and the patients hosting them were similar regardless of adjudication. A higher proportion of patients with P/LP were pediatric (<16 years) compared with SCN5A- (11.4% versus 3%, P =0.023). The proportion of females was higher among patients with P/LP compared with SCN5A - (18.2% versus 6.3%, P =0.013). P/LP probands were more likely to have a family history of sudden cardiac death compared with SCN5A - (41.9% versus 16.8%, P <0.001). A higher proportion of patients with P/LP were White compared with SCN5A- (87.5% versus 47%, P <0.001). Ethnicity (odds ratio, 5.41 [2.8-11.19], P <0.001) and family history of sudden cardiac death (odds ratio, 2.73 [1.28-5.82], P =0.009) were independent variables associated with P/LP genotype following logistic regression., Conclusions: The genetic basis of BrS has a complex relationship with gender, ethnicity, and age. Probands hosting a P/LP variant tended to experience their first arrhythmic event at a younger age and to have events triggered by fever compared with patients with SCN5A- . In addition, they were more likely to be White and to have family history of sudden cardiac death. Among females, a P/LP variant suggests an increased risk of being symptomatic. This association should be further studied on an ethnically specific basis in large prospectively collected international cohorts.

Background: A male predominance in Brugada syndrome (BrS) has been widely reported, but scarce information on female patients with BrS is available., Objective: The purpose of this study was to investigate the clinical characteristics and long-term prognosis of women with BrS., Methods: A multicenter retrospective study of patients diagnosed with BrS and previous electrophysiological study (EPS) was performed., Results: Among 770 patients, 177 (23%) were female. At presentation, 150 (84.7%) were asymptomatic. Females presented less frequently with a type 1 electrocardiographic pattern (30.5% vs 55.0%; P <.001), had a higher rate of family history of sudden cardiac death (49.7% vs 29.8%; P <.001), and had less sustained ventricular arrhythmias (VAs) on EPS (8.5% vs 15.1%; P = .009). Genetic testing was performed in 79 females (45% of the sample) and was positive in 34 (19%). An implantable cardioverter-defibrillator was inserted in 48 females (27.1%). During mean (± SD) follow-up of 122.17 ± 57.28 months, 5 females (2.8%) experienced a cardiovascular event compared to 42 males (7.1%; P = .04). On multivariable analysis, a positive genetic test (18.71; 95% confidence interval [CI] 1.82-192.53; P = .01) and atrial fibrillation (odds ratio 21.12; 95% CI 1.27-350.85; P = .03) were predictive of arrhythmic events, whereas VAs on EPS (neither with 1 or 2 extrastimuli nor 3 extrastimuli) were not., Conclusion: Women with BrS represent a minor fraction among patients with BrS, and although their rate of events is low, they do not constitute a risk-free group. Neither clinical risk factors nor EPS predicts future arrhythmic events. Only atrial fibrillation and positive genetic test were identified as risk factors for future arrhythmic events., (Copyright © 2021 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: Electrocardiographic QT interval prolongation is the most widely used risk marker for ventricular arrhythmia potential and thus an important component of drug cardiotoxicity assessments. Several antimalarial medicines are associated with QT interval prolongation. However, interpretation of electrocardiographic changes is confounded by the coincidence of peak antimalarial drug concentrations with recovery from malaria. We therefore reviewed all available data to characterise the effects of malaria disease and demographic factors on the QT interval in order to improve assessment of electrocardiographic changes in the treatment and prevention of malaria., Methods and Findings: We conducted a systematic review and meta-analysis of individual patient data. We searched clinical bibliographic databases (last on August 21, 2017) for studies of the quinoline and structurally related antimalarials for malaria-related indications in human participants in which electrocardiograms were systematically recorded. Unpublished studies were identified by the World Health Organization (WHO) Evidence Review Group (ERG) on the Cardiotoxicity of Antimalarials. Risk of bias was assessed using the Pharmacoepidemiological Research on Outcomes of Therapeutics by a European Consortium (PROTECT) checklist for adverse drug events. Bayesian hierarchical multivariable regression with generalised additive models was used to investigate the effects of malaria and demographic factors on the pretreatment QT interval. The meta-analysis included 10,452 individuals (9,778 malaria patients, including 343 with severe disease, and 674 healthy participants) from 43 studies. 7,170 (68.6%) had fever (body temperature ≥ 37.5°C), and none developed ventricular arrhythmia after antimalarial treatment. Compared to healthy participants, patients with uncomplicated falciparum malaria had shorter QT intervals (-61.77 milliseconds; 95% credible interval [CI]: -80.71 to -42.83) and increased sensitivity of the QT interval to heart rate changes. These effects were greater in severe malaria (-110.89 milliseconds; 95% CI: -140.38 to -81.25). Body temperature was associated independently with clinically significant QT shortening of 2.80 milliseconds (95% CI: -3.17 to -2.42) per 1°C increase. Study limitations include that it was not possible to assess the effect of other factors that may affect the QT interval but are not consistently collected in malaria clinical trials., Conclusions: Adjustment for malaria and fever-recovery-related QT lengthening is necessary to avoid misattributing malaria-disease-related QT changes to antimalarial drug effects. This would improve risk assessments of antimalarial-related cardiotoxicity in clinical research and practice. Similar adjustments may be indicated for other febrile illnesses for which QT-interval-prolonging medications are important therapeutic options., Competing Interests: I have read the journal's policy and the authors of this manuscript have the following competing interests: GV was an employee of Sigma Tau S.p.A from 1986 to 2017; EAA and NJW are members of the Editorial Board of PLOS Medicine.

Introduction and Objectives: The resting 12-lead electrocardiogram (ECG) has been used in the evaluation of young asymptomatic individuals to detect pre-existing heart disease, but systematic ECG use is controversial and there are no data on this population in our environment. We aimed to determine the prevalence and spectrum of electrocardiographic findings in a population of secondary school students., Methods: We conducted an observational, cross-sectional study of resting ECG findings in all 13 to 14-year-old secondary school students in a region of the province of Gerona between 2009 and 2017. ECG findings were classified into 3 groups according to the modified criteria of Corrado et al.: normal ECG findings, ECG findings suggestive of adaptive changes, and pathologic findings. Students with pathologic ECG findings were referred to a tertiary hospital, and complementary tests were performed according to a pre-established protocol., Results: A total of 1911 ECGs were obtained, with a participation rate of 79% of all high school students. In all, 1321 students (69%) had a normal ECG, 554 (29%) showed ECG findings suggestive of adaptive changes, and 36 (2%) had pathologic ECG findings. Among the group with pathologic findings, 5 (14%) had cardiovascular disease. The prevalence of heart disease in this group of asymptomatic secondary school students was 0.3%., Conclusions: One third of the students had ECG findings that were mostly suggestive of physiological adaptation. One seventh of the students with pathologic ECG findings had pre-existing heart disease, although the overall prevalence of pre-existing heart disease was low., (Copyright © 2018 Sociedad Española de Cardiología. Published by Elsevier España, S.L.U. All rights reserved.)

Aims: Monitoring of patients after ablation had wide variations in the ESC-EHRA atrial fibrillation ablation long-term (AFA-LT) registry. We aimed to compare four different monitoring strategies after catheter AF ablation., Methods and Results: The ESC-EHRA AFA-LT registry included 3593 patients who underwent ablation. Arrhythmia monitoring during follow-up was performed by 12-lead electrocardiogram (ECG), Holter ECG, trans-telephonic ECG monitoring (TTMON), or an implanted cardiac monitoring (ICM) system. Patients were selected to a given monitoring group according to the most extensive ECG tool used in each of them. Comparison of the probability of freedom from recurrences was performed by censored log-rank test and presented by Kaplan-Meier curves. The rhythm monitoring methods were used among 2658 patients: ECG (N = 578), Holter ECG (N = 1874), TTMON (N = 101), and ICM (N = 105). A total of 767 of 2658 patients (28.9%) had AF recurrences during follow-up. Censored log-rank test discovered a lower probability of freedom from relapses, which was detected with ICM compared to TTMON, ECG, and Holter ECG (P < 0.001). The rate of freedom from AF recurrences was 50.5% among patients using the ICM while it was 65.4%, 70.6%, and 72.8% using the TTMON, ECG, and Holter ECG, respectively., Conclusion: Comparing all main electrocardiographic monitoring methods in a large patient sample, our results suggest that post-ablation recurrences of AF are significantly underreported by TTMON, ECG, and Holter ECG. The ICM estimates AF ablation recurrences most reliably and should be a preferred mode of monitoring for trials evaluating novel AF ablation techniques., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author(s) 2019. For permissions, please email: journals.permissions@oup.com.)

Aims: To define the clinical characteristics and long-term clinical outcomes of a large cohort of patients with idiopathic ventricular fibrillation (IVF) and normal 12-lead electrocardiograms (ECGs)., Methods and Results: Patients with ventricular fibrillation as the presenting rhythm, normal baseline, and follow-up ECGs with no signs of cardiac channelopathy including early repolarization or atrioventricular conduction abnormalities, and without structural heart disease were included in a registry. A total of 245 patients (median age: 38 years; males 59%) were recruited from 25 centres. An implantable cardioverter-defibrillator (ICD) was implanted in 226 patients (92%), while 18 patients (8%) were treated with drug therapy only. Over a median follow-up of 63 months (interquartile range: 25-110 months), 12 patients died (5%); in four of them (1.6%) the lethal event was of cardiac origin. Patients treated with antiarrhythmic drugs only had a higher rate of cardiovascular death compared to patients who received an ICD (16% vs. 0.4%, P = 0.001). Fifty-two patients (21%) experienced an arrhythmic recurrence. Age ≤16 years at the time of the first ventricular arrhythmia was the only predictor of arrhythmic recurrence on multivariable analysis [hazard ratio (HR) 0.41, 95% confidence interval (CI) 0.18-0.92; P = 0.03]., Conclusion: Patients with IVF and persistently normal ECGs frequently have arrhythmic recurrences, but a good prognosis when treated with an ICD. Children are a category of IVF patients at higher risk of arrhythmic recurrences., (© The Author(s) 2019. Published by Oxford University Press on behalf of the European Society of Cardiology.)

Background: There is limited information on ethnic differences between patients with Brugada syndrome (BrS) and arrhythmic events (AEs)., Objective: The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between white and Asian patients with BrS and AEs., Methods: The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter survey from Western and Asian countries, gathering 678 patients with BrS and first documented AE. After excluding patients with other (n = 14 [2.1%]) or unknown (n = 30 [4.4%]) ethnicity, 364 (53.7%) whites and 270 (39.8%) Asians comprised the study group., Results: There was no difference in AE age onset (41.3 ± 16.1 years in whites vs 43.3 ± 12.3 years in Asians; P = .285). Higher proportions of whites were observed in pediatric and elderly populations. Asians were predominantly men (98.1% vs 85.7% in whites; P < .001) and frequently presented with aborted cardiac arrest (71.1% vs 56%; P < .001). Asians tended to display more spontaneous type 1 BrS-ECG pattern (71.5% vs 64.3%; P = .068). A family history of sudden cardiac death was noted more in whites (29.1% vs 11.5%; P < .001), with a higher rate of SCN5A mutation carriers (40.1% vs 13.2% in Asians; P < .001), as well as more fever-related AEs (8.5% vs 2.9%; P = .011). No difference was observed between the 2 groups regarding history of syncope and ventricular arrhythmia inducibility., Conclusion: There are important differences between Asian and white patients with BrS. Asian patients present almost exclusively as male adults, more often with aborted cardiac arrest and spontaneous type 1 BrS-ECG. However, they have less family history of sudden cardiac death and markedly lower SCN5A mutation rates. The striking difference in SCN5A mutation rates should be tested in future studies., (Copyright © 2019 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Electrocardiogram (ECG) analysis trying to understand the mechanisms of QRS widening is often problematic. During WCTs, identification of P waves and atrioventricular relationship is often difficult and increasingly so if the number of recording leads available for examination is limited. For this reason, it is necessary to use every information available in an ECG tracing. The goal of this article is to focus on the reasons for QRS variations occurring during tachycardia. Correct interpretation of these data can offer the key to understand the arrhythmia mechanism., (Copyright © 2019 Elsevier Inc. All rights reserved.)

Background: Sudden death of a newborn is a rare entity, which may be caused by genetic cardiac arrhythmias. Among these diseases, Long QT syndrome is the most prevalent arrhythmia in neonates, but other diseases such as Brugada syndrome, Short QT syndrome and Catecholaminergic Polymorphic Ventricular Tachycardia also cause sudden death in infants. All these entities are characterized by well-known alterations in the electrocardiogram and the first symptom of the disease may be an unexpected death. Despite the low prevalence of these diseases, the performance of an electrocardiogram in the first hours or days after birth could help identify these electrical disruptions and adopt preventive measures. In recent years, there has been an important impulse by some experts in the scientific community towards the initiation of a newborn electrocardiogram-screening program, for the detection of these electrocardiographic abnormalities. In addition, the use of genetic analysis in neonates could identify the cause of these heart alterations. Identification of relatives carrying the genetic alteration associated with the disease allows adoption of measures to prevent lethal episodes., Conclusion: Recent technological advances enable a comprehensive genetic screening of a large number of genes in a cost-effective way. However, the interpretation of genetic data and its translation into clinical practice are the main challenges for cardiologists and geneticists. However, there is important controversy as to the clinical value, and cost-effectiveness of the use of electrocardiogram as well as of genetic testing to detect these cases. Our review focuses on these current matters of argue., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.)

Background: There is limited information on gender differences in patients with Brugada syndrome (BrS) who experienced arrhythmic events (AEs)., Objective: The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between males and females in patients with BrS with their first AE., Methods: The multicenter Survey on Arrhythmic Events in BRUgada Syndrome collected data on the first AE in 678 patients with BrS including 619 males (91.3%) and 59 females (8.7%) aged 0.27-84 years (mean age 42.5 ± 14.1 years) at the time of AE occurrence., Results: After excluding pediatric patients, it was found that females were older than males (49.5 ± 14.4 years vs 43 ± 12.7 years, respectively; P = .001). Higher proportions of females were observed in the pediatric and elderly populations. In Asians, the male to female ratio for AEs was ≈9-fold higher than that in White. Spontaneous type 1 BrS ECG was associated with an earlier onset of AEs in pediatric females. A similar prevalence (≈65%) of spontaneous type 1 BrS ECG was present in males and females above the age of 60 years. Females less frequently showed spontaneous type 1 BrS ECG (41% vs 69%; P < .001) or arrhythmia inducibility at electrophysiology study (36% vs 66%; P < .001). An SCN5A mutation was more frequently found in females (48% vs 28% in males; P = .007)., Conclusion: This study confirms that female patients with BrS are much rarer, display less type 1 Brugada ECG, and exhibit lower inducibility rates than do males. It shows for the first time that female patients with BrS with AE have higher SCN5A mutation rates as well as the relationship between gender vs age at the onset of AEs and ethnicity., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: The literature on fever-related arrhythmic events (AEs) in Brugada syndrome (BrS) is currently limited to few case reports and small series., Objective: The present study aimed to describe the characteristics of fever-related AE in a large cohort of patients with BrS., Methods: The Survey on Arrhythmic Events in Brugada Syndrome is a multicenter study on 678 patients with BrS with first AE documented at the time of aborted cardiac arrest (n = 426) or after prophylactic implantable cardioverter-defibrillator implantation (n = 252)., Results: In 35 of 588 patients (6%) with available information, the AE occurred during a febrile illness. Most of the 35 patients were male (80%), Caucasian (83%), and proband (70%). The mean age at the time of AE was 29 ± 24 years (range 0.3-76 years). Most patients (80%) presented with aborted cardiac arrest and 6 (17%) with arrhythmic storm. Family history of sudden death, history of syncope, and spontaneous type 1 Brugada electrocardiogram were noted in 17%, 40%, and 71% of patients, respectively. Ventricular fibrillation was induced at electrophysiology study in 9 of 19 patients (47%). An SCN5A mutation was found in 14 of 28 patients (50%). The highest proportion of fever-related AE was observed in the pediatric population (age <16 years), with a disproportionally higher event rate in the very young (age 0-5 years) (65%). Males were involved in all age groups and females only in the pediatric and elderly groups. Fever-related AE affected 17 Caucasians aged <24 years, but no Asians aged <24 years., Conclusion: The risk of fever-related AE in BrS markedly varies according to age group, sex, and ethnicity. Taking these factors into account could help the clinical management of patients with BrS with fever., (Copyright © 2018 Heart Rhythm Society. All rights reserved.)

Aims: Patients with the Brugada type 1 ECG (Br type 1) without previous aborted sudden death (aSD) who do not have a prophylactic ICD constitute a very large population whose outcome is little known. The objective of this study was to evaluate the risk of SD or aborted SD (aSD) in these patients., Methods and Results: We conducted a meta-analysis and cumulative analysis of seven large prospective studies involving 1568 patients who had not received a prophylactic ICD in primary prevention. Patients proved to be heterogeneous. Many were theoretically at low risk, in that they had a drug-induced Br type 1 (48%) and/or were asymptomatic (87%), Others, in contrast, had one or more risk factors. During a mean/median follow-up ranging from 30 to 48 months, 23 patients suffered SD and 1 had aSD. The annual incidence of SD/aSD was 0.5% in the total population, 0.9% in patients with spontaneous Br type 1 and 0.08% in those with drug-induced Br type 1 (P = 0.0001). The paper by Brugada et al. reported an incidence of SD more than six times higher than the other studies, probably as a result of selection bias. On excluding this paper, the annual incidence of SD/aSD in the remaining 1198 patients fell to 0.22% in the total population and to 0.38 and 0.06% in spontaneous and drug-induced Br type 1, respectively. Of the 24 patients with SD/aSD, 96% were males, the mean age was 39 ± 15 years, 92% had spontaneous Br type 1, 61% had familial SD (f-SD), and only 18.2% had a previous syncope; 43% had a positive electrophysiological study. Multiple meta-analysis of individual trials showed that spontaneous Br type 1, f-SD, and previous syncope increased the risk of SD/aSD (RR 2.83, 2.49, and 3.03, respectively). However, each of these three risk factors had a very low positive predictive value (PPV) (1.9-3.3%), while negative predictive values (NPV) were high (98.5-99.7%). The incidence of SD/aSD was only slightly higher in patients with syncope than in asymptomatic patients (2% vs. 1.5%, P = 0.6124). Patients with SD/aSD when compared with the others had a mean of 1.74 vs. 0.95 risk factors (P = 0.026)., Conclusion: (i) In patients with Br type 1 ECG without an ICD in primary prevention, the risk of SD/aSD is low, particularly in those with drug-induced Br type 1; (ii) spontaneous Br type 1, f-SD, and syncope increase the risk. However, each of these risk factors individually has limited clinical usefulness, owing to their very low PPV; (iii) patients at highest risk are those with more than one risk factor.

Background: Detailed information on the profile of patients with Brugada syndrome (BrS) presenting their first arrhythmic event (AE) after prophylactic implantation of an implantable cardioverter-defibrillator (ICD) is limited., Objectives: The objectives of this study were (1) to compare clinical, electrocardiographic, electrophysiologic, and genetic profiles of patients who exhibited their first documented AE as aborted cardiac arrest (group A) with profiles of those in whom the AE was documented after prophylactic ICD implantation (group B) and (2) to characterize group B patients' profile using the class II indications for ICD implantation established by HRS/EHRA/APHRS expert consensus statement in 2013., Methods: A survey of 23 centers from 10 Western and 4 Asian countries enabled data collection of 678 patients with BrS who exhibited their AE (group A, n = 426; group B, n = 252)., Results: The first AE occurred in group B patients 6.7 years later than in group A (mean age 46.1 ± 13.3 years vs 39.4 ± 15.1 years; P < .001). Group B patients had a higher incidence of family history of sudden cardiac death and SCN5A mutations. Of the 252 group B patients, 189 (75%) complied with the HRS/EHRA/APHRS indications whereas the remaining 63 (25%) did not., Conclusion: Patients with BrS with the first AE documented after prophylactic ICD implantation exhibited their AE at a later age with a higher incidence of positive family history of sudden cardiac death and SCN5A mutations as compared with those presenting with aborted cardiac arrest. Only 75% of patients who exhibited an AE after receiving a prophylactic ICD complied with the 2013 class II indications, suggesting that efforts are still required for improving risk stratification., (Copyright © 2018 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Objectives: This study investigates the electrocardiographic-electrophysiological effects of administration of anesthetic drugs for general anesthesia (GA) in patients with BrS at high risk of sudden cardiac death (SCD)., Background: The safety of anesthetic agents in Brugada syndrome (BrS) is under debate., Methods: All consecutive patients with spontaneous type 1 BrS electrocardiographic (ECG) patterns undergoing epicardial ablation of the arrhythmogenic substrate (AS) under GA were enrolled. Anesthesia was induced with single bolus of propofol and maintained with sevofluorane. ECG measurements were collected before, immediately after, and 20 min after induction of GA. Three-dimensional maps during GA and after ajmaline indicated the epicardial AS before ablation., Results: Thirty-six patients with BrS (32 male, 88.9%; mean age 38.8 ± 12.0 years) with a spontaneous type 1 ECG pattern underwent GA. Induction was performed using propofol at mean dose of 1.6 to 2.6 mg/kg (2.1 ± 0.3 mg/kg). Twenty-eight (28 of 36, 77.8%) patients showed a reversion to a nondiagnostic pattern. ST-segment elevation (0.32 ± 0.01 mV vs. 0.19 ± 0.02 mV; p < 0.001) and J-wave amplitude (0.47 ± 0.02 mV vs. 0.31 ± 0.03 mV; p < 0.001) decreased after propofol. The AS area during GA, in the absence of BrS pattern, significantly enlarged after administration of ajmaline (3.6 ± 0.5 cm 2 vs. 20.3 ± 0.8 cm 2 ). No patient developed malignant arrhythmias during GA induction and maintenance., Conclusions: This study shows that GA using single-bolus propofol and volatile anesthetics is safe in high-risk patients with BrS, and it may exert a modulating effect by reducing the manifestation of type 1 BrS pattern and AS in the form of epicardial abnormal ECGs. (Epicardial Ablation in Brugada Syndrome: An Extension Study of 200 BrS Patients; NCT03106701)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Objectives: The aim of this study was to compare patient response to cardiac resynchronization therapy (CRT) using fusion-optimized atrioventricular (AV) and interventricular (VV) intervals versus nominal settings., Background: The additional benefit obtained by AV- and VV-interval optimization in patients undergoing CRT remains controversial. Previous studies show short-term benefit in hemodynamic parameters; however, midterm randomized comparison between electrocardiogram optimization and nominal parameters is lacking., Methods: A group of 180 consecutive patients with left bundle branch block treated with CRT were randomized to fusion-optimized intervals (FOI) or nominal settings. In the FOI group, AV and VV intervals were optimized according to the narrowest QRS, using fusion with intrinsic conduction. Clinical response was defined as an increase >10% in the 6-min walk test or an increment of 1 step in New York Heart Association functional class. The left ventricular (LV) remodeling was defined as >15% decrease in left ventricular end-systolic volume (LVESV) at 12-month follow-up. Additionally, patients with LVESV reduction >30% relative to baseline were considered super-responders; by contrast, negative responders had increased LVESV relative to baseline., Results: Participant characteristics included a mean age of 65 ± 10 years, 68% male, 37% with ischemic cardiomyopathy, LV ejection fraction 26 ± 7%, and QRS 180 ± 22 ms. Baseline QRS was shortened significantly more by FOI, compared with nominal settings (-56.55 ± 17.65 ms vs. -37.81 ± 22.07 ms, respectively; p = 0.025). At 12 months, LV reverse remodeling was achieved in a larger proportion of the FOI group (74% vs. 53% [odds ratio: 2.02 (95% confidence interval: 1.08 to 3.76)], respectively; p = 0.026). No significant differences were observed in clinical response (61% vs. 53% [odds ratio: 1.43 (95% confidence interval: 0.79 to 2.59)], respectively; p = 0.24)., Conclusions: Device optimization based on FOI achieves greater LV remodeling, compared with nominal settings. (ECG Optimization of CRT: Evaluation of Mid-Term Response [BEST]; NCT01439529)., (Copyright © 2018 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Background: Implantable cardioverter-defibrillator (ICD) indications for primary prevention in Brugada syndrome (BrS) are still debated., Objectives: The authors investigated the long-term outcome after ICD implantation in a large cohort of BrS patients., Methods: Of a total of 370 patients with BrS in follow-up (age 43 ± 14 years; 74% male), 104 patients (28.1%) were treated with ICDs. The authors analyzed the long-term incidence of shocks and complications., Results: An ICD was implanted for secondary prevention in 10 patients (9.6%) and for primary prevention in 94 patients (90.4%). After a follow-up of 9.3 ± 5.1 years, 21 patients (20.2%) experienced a total of 81 appropriate shocks (incidence rate 2.2 per 100 person-years). The rate of appropriate shocks was higher in secondary prevention patients (p < 0.01). However, 4 of the 45 asymptomatic patients (8.9%) experienced appropriate ICD therapy, all with a spontaneous type 1 electrocardiogram and inducible ventricular arrhythmias. In the multivariable analysis, type 1 electrocardiogram with syncope (hazard ratio: 4.96; 95% confidence interval: 1.87 to 13.14; p < 0.01) and secondary prevention indication (hazard ratio: 6.85; 95% confidence interval: 2.29 to 20.50; p < 0.01) were significant predictors of appropriate therapy. Nine patients (8.7%) experienced 37 inappropriate shocks (incidence rate 0.9 per 100 person-years). Twenty-one patients (20.2%) had other ICD-related complications (incidence rate 1.4 per 100 person-years). Three patients (2.9%) died (1 electrical storm and 2 noncardiovascular deaths)., Conclusions: ICD therapy is an effective therapy in high-risk patients with BrS. However, it is also associated with a significant risk of device-related complications. Special care during ICD implantation, adequate device programming, and regular follow-up may allow reducing the number of adverse events., (Copyright © 2017 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Introduction Pre-participation screening in athletes attempts to reduce the incidence of sudden death during sports by identifying susceptible individuals. The objective of this study was to evaluate the diagnostic capacity of the different pre-participation screening points in adolescent athletes and the cost effectiveness of the programme. Methods Athletes were studied between 12-18 years old. Pre-participation screening included the American Heart Association questionnaire, electrocardiogram, echocardiogram, and stress test. The cost of test was established by the Catalan public health system. Results Of 1650 athletes included, 57% were men and mean age was 15.09 ± 1.82 years. Positive findings were identified as follows: in American Heart Association questionnaire 5.09% of subjects, in electrocardiogram 3.78%, in echocardiogram 4.96%, and in exercise test 1.75%. Six athletes (0.36%) were disqualified from participation and 10 (0.60%) were referred for interventional treatment. Diagnostic capacity was assessed by the area under the curve for detection of diseases that motivated disqualification for sport practice (American Heart Association questionnaire, 0.55; electrocardiogram, 0.72; echocardiogram, 0.88; stress test, 0.57). The cost for each athlete disqualified from the sport for a disease causing sudden death was €45,578. Conclusion The electrocardiogram and echocardiogram were the most useful studies to detect athletes susceptible to sudden death, and the stress test best diagnosed arrhythmias with specific treatment. In our country, pre-participatory screening was cost effective to detect athletes who might experience sudden death in sports.

Background: A proband of Brugada syndrome (BrS) is the first patient diagnosed in a family. There are no data regarding this specific, high-risk population., Objectives: This study sought to investigate the Brugada probands diagnosed from 1986 through the next 28 years., Methods: We included 447 probands belonging to families with a diagnostic type 1 electrocardiogram Brugada pattern. The database was divided into 2 periods: the first period identified patients who were part of the initial cohort that became the consensus document on BrS in 2002 (early group); the second period reflected patients first diagnosed from 2003 to January 2014 (latter group)., Results: There were 165 probands in the early group and 282 in the latter group. Aborted sudden death as the first manifestation of the disease occurred in 12.1% of the early group versus 4.6% of the latter group (p = 0.005). Inducibility during programmed electrical stimulation was achieved in 34.4% and 19.2% of patients, respectively (p < 0.001). A spontaneous type 1 electrocardiogram pattern at diagnosis was present in 50.3% early versus 26.2% latter patients (p = 0.0002). Early group patients had a higher probability of a recurrent arrhythmia during follow-up (19%) than those of the latter group (5%) (p = 0.007). The clinical suspicion and use of a sodium-channel blocker to unmask BrS has allowed earlier diagnoses in many patients., Conclusions: Since being first described, the presentation of BrS has changed. There has been a decrease in aborted sudden cardiac death as the first manifestation of the disease among patients who were more recently diagnosed. These variations in initial presentation have important clinical consequences. In this setting, the value of inducibility to stratify individuals with BrS has changed., (Copyright © 2016 American College of Cardiology Foundation. Published by Elsevier Inc. All rights reserved.)

Aims: Brugada phenocopies (BrPs) are electrocardiogram (ECG) patterns that are identical to true Brugada syndrome (BrS) but are induced by various clinical conditions. The concept that both ECG patterns are visually identical has not been formally demonstrated. The aim of our study was to determine if experts on BrS were able to accurately distinguish between the BrS and BrP ECG patterns., Methods and Results: Six ECGs from confirmed cases of BrS and six ECGs from previously published cases of BrP were included in the study. Surface 12-lead ECGs were scanned, saved in JPEG format, and sent to 10 international experts on BrS for evaluation (no clinical history provided). Evaluators were asked to label each case as a Brugada ECG pattern or non-Brugada ECG pattern by visual interpretation alone. The overall accuracy was 53 ± 33% for all cases. Within the BrS cases, the mean accuracy was 63 ± 34% and within the BrP cases, the mean accuracy was 43 ± 33%. Intra-observer repeatability was moderate (κ = 0.56) and inter-observer agreement was fair (κ = 0.36) while evaluator accuracy vs. the true diagnosis was only marginally better than chance (κ = 0.05). Similarly, diagnostic operating characteristics were poor (sensitivity 62%, specificity 43%, +LR 1.1, -LR 0.9)., Conclusion: Our results provide strong evidence that BrP and BrS ECG patterns are visually identical and indistinguishable. These findings support the use of systematic diagnostic criteria for differentiating BrP vs. BrS as an erroneous diagnosis may have a negative impact on patient morbidity and mortality., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2015. For permissions please email: journals.permissions@oup.com.)

Differential diagnosis of hypertrophic cardiomyopathy (HCM) vs athlete's heart is challenging in individuals with mild-moderate left-ventricular hypertrophy. This study aimed to assess ECG and echocardiographic parameters proposed for the differential diagnosis of HCM. The study included 75 men in three groups: control (n=30), "gray zone" athletes with interventricular septum (IVS) measuring 13-15mm (n=25) and HCM patients with IVS of 13-18mm (n=20). The most significant differences were found in relative septal thickness (RST), calculated as the ratio of 2 x IVS to left ventricle end-diastolic diameter (LV-EDD) (0.37, 0.51, 0.71, respectively; p<0.01) and in spatial QRS-T angle as visually estimated (9.8, 33.6, 66.2, respectively; p<0.01). The capacity for differential HCM diagnosis of each of the 5 criteria was assessed using the area under the curve (AUC), as follows: LV-EDD<54 (0.60), family history (0.61), T-wave inversion (TWI) (0.67), spatial QRS-T angle>45 (0.75) and RST>0.54 (0.92). Pearson correlation between spatial QRS-T angle>45 and TWI was 0.76 (p 0.01). The combination of spatial QRS-T angle>45 and RST>0.54 for diagnosis of HCM had an AUC of 0.79. The best diagnostic criteria for HCM was RST>0.54. The spatial QRS-T angle>45 did not add sensitivity if TWI was present. No additional improvement in differential diagnosis was obtained by combining parameters., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Introduction: The diagnosis of Brugada syndrome based on the ECG is hampered by the dynamic nature of its ECG manifestations. Brugada syndrome patients are only 25% likely to present a type 1 ECG. The objective of this study is to provide an ECG diagnostic criterion for Brugada syndrome patients that can be applied consistently even in the absence of a type 1 ECG., Methods and Results: We recorded 67-lead body surface potential maps from 94 Brugada syndrome patients and 82 controls (including right bundle branch block patients and healthy individuals). The spatial propagation direction during the last r' wave and the slope at the end of the QRS complex were measured and compared between patients groups. Receiver-operating characteristic curves were constructed for half of the database to identify optimal cutoff values; sensitivity and specificity for these cutoff values were measured in the other half of the database. A spontaneous type 1 ECG was present in only 30% of BrS patients. An orientation in the sagittal plane < 101º during the last r' wave and a descending slope < 9.65 mV/s enables the diagnosis of the syndrome with a sensitivity of 69% and a specificity of 97% in non-type 1 Brugada syndrome patients., Conclusion: Spatiotemporal characteristics of surface ECG recordings can enable a robust identification of BrS even without the presence of a type 1 ECG., (© 2016 Wiley Periodicals, Inc.)

Background: Isolated cases of monomorphic ventricular tachycardia (MVT) in patients with Brugada syndrome (BrS) have been reported., Objective: We aimed to describe the incidence and characteristics of MVT in a cohort of patients with BrS who had received an implantable cardioverter-defibrillator (ICD)., Methods: Data from 834 patients with BrS implanted with an ICD in 15 tertiary hospitals between 1993 and 2014 were included., Results: The mean age of enrolled patients was 45.3 ± 13.9 years; 200 patients (24%) were women. During a mean follow-up of 69.4 ± 54.3 months, 114 patients (13.7%) experienced at least 1 appropriate ICD intervention, with MVT recorded in 35 patients (4.2%) (sensitive to antitachycardia pacing in 15 [42.8%]). Only QRS width was an independent predictor of MVT in the overall population. Specifically, 6 (17.1%) patients presented with right ventricular outflow tract tachycardia (successfully ablated from the endocardium in 4 and epicardial and endocardial ablation in 1), 2 patients with MVT arising from the left ventricle (1 successfully ablated in the supra lateral mitral annulus), and 2 (5.7%) patients with bundle branch reentry ventricular tachycardia. Significant structural heart disease was ruled out by echocardiography and/or cardiac magnetic resonance imaging., Conclusion: In this retrospective study, 4.2% of patients with BrS implanted with an ICD presented with MVT confirmed as arising from the right ventricular outflow tract tachycardia in 6, patients with MVT arising from the left ventricle in 2, and patients with bundle branch reentry ventricular tachycardia in 2. Endocardial and/or epicardial ablation was successful in 80% of these cases. These data imply that the occurrence of MVT should not rule out the possibility of BrS. This finding may also be relevant for ICD model selection and programming., (Copyright © 2016 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Background: It is thought that dedicated bipolar are more susceptible to T-wave oversensing when compared with integrated bipolar leads. This could be of extreme importance in patients with Brugada syndrome (BrS) because T-wave oversensing in this population is more frequent when compared with other implantable cardioverter defibrillator (ICD) recipients without BrS. We aimed to compare the incidence of T-wave oversensing in patients with BrS according to the type of lead (integrated bipolar versus true/dedicated bipolar)., Methods and Results: All patients diagnosed with BrS with an ICD implant in 10 tertiary hospitals between 1993 and 2013 were included in the study. A total of 480 patients were included (mean age, 45.6±14 years). During a mean follow-up of 74.9±51.7 months (median, 69; range, 2-236), 28 patients had T-wave oversensing (5.8%), leading to inappropriate shock in 18 (3.8%). All these events occurred in patients with true bipolar ICD leads (P=0.01) and in 2 patients it was solved instantaneously by changing the configuration from a dedicated to an integrated bipolar sensing configuration. In the stepwise multivariate models, only integrated bipolar ICD leads (hazard ratio, 0.34; 95% confidence interval, 0.171-0.675; P=0.002) was independent predictor of non-T-wave oversensing., Conclusions: T-wave oversensing is a potential reason of inappropriate shocks in patients with BrS receiving ICDs. In the vast majority it can be solved by reprogramming. However, in some patients it still requires invasive intervention. Importantly, incidence is significantly lower using an integrated bipolar lead system when compared with a dedicated bipolar lead system and hence the latter should be routinely used in BrS cases., (© 2015 American Heart Association, Inc.)

Background: Biventricular pacing (CRT) shows clear benefits in heart failure with wide QRS, but results in narrow QRS have appeared conflicting. We tested the hypothesis that study design might have influenced findings., Method and Results: We identified all reports of CRT-P/D therapy in subjects with narrow QRS reporting effects on continuous physiological variables. Twelve studies (2074 patients) met these criteria. Studies were stratified by presence of bias-resistance steps: the presence of a randomized control arm over a single arm, and blinded outcome measurement. Change in each endpoint was quantified using a standardized effect size (Cohen's d). We conducted separate meta-analyses for each variable in turn, stratified by trial quality. In non-randomized, non-blinded studies, the majority of variables (10 of 12, 83%) showed significant improvement, ranging from a standardized mean effect size of +1.57 (95%CI +0.43 to +2.7) for ejection fraction to +2.87 (+1.78 to +3.95) for NYHA class. In the randomized, non-blinded study, only 3 out of 6 variables (50%) showed improvement. For the randomized blinded studies, 0 out of 9 variables (0%) showed benefit, ranging from -0.04 (-0.31 to +0.22) for ejection fraction to -0.1 (-0.73 to +0.53) for 6-minute walk test., Conclusions: Differences in degrees of resistance to bias, rather than choice of endpoint, explain the variation between studies of CRT in narrow-QRS heart failure addressing physiological variables. When bias-resistance features are implemented, it becomes clear that these patients do not improve in any tested physiological variable. Guidance from studies without careful planning to resist bias may be far less useful than commonly perceived., (© 2015 The Authors. Published on behalf of the American Heart Association, Inc., by Wiley Blackwell.)

Aims: Diagnosis of Type-2 Brugada pattern remains challenging and it could be confused with other electrocardiogram (ECG) patterns presenting an r'-wave in leads V1-V2 like in healthy athletes. This could impact their ability to perform competitive sports. The aim of the study was to evaluate, as a proof of concept, the new ECG criteria to differentiate the Type-2 Brugada pattern from the ECG pattern of healthy athletes depicting an r'-wave in leads V1-V2., Methods and Results: Surface ECGs from 50 patients with Brugada syndrome and type-2 Brugada pattern and 58 healthy athletes with an r'-wave in leads V1-V2 were analysed. Different criteria based on the characteristics of the triangle formed by the ascendant and descendant arms of the r'-wave in leads V1-V2 were compared. The duration of the base of the triangle at 0.5 mV (5 mm) from high take-off ≥160 ms (4 mm) has a specificity (SP) of 95.6%, sensitivity (SE) 85%, positive predictive value (PPV) 94.4%, and negative predictive value (NPV) 87.9%. The duration of the base of the triangle at the isoelectric line ≥60 ms (1.5 mm) in leads V1-V2 has an SP of 78%, SE 94.8%, PPV 79.3%, and NPV 93.5%. The ratio of the base at isoelectric line/height from the baseline to peak of r'-wave in leads V1-V2 has an SP of 92.1%, SE 82%, PPV 90.1%, and NPV 83.3%., Conclusions: The three new ECG criteria were accurate to distinguish the Type-2 Brugada pattern from the ECG pattern with an r'-wave in healthy athletes. The duration of the base of the triangle at 0.5 mV from the high take-off is the easiest to measure and may be used in clinical practice., (Published on behalf of the European Society of Cardiology. All rights reserved. © The Author 2014. For permissions please email: journals.permissions@oup.com.)

Although cardiac resynchronization therapy (CRT) is effective in most patients with heart failure (HF) and ventricular dyssynchrony, a significant minority of patients (approximately 30%) are non-responders. Optimal atrioventricular and interventricular delays often change over time and reprogramming these intervals might increase CRT effectiveness. The SonR algorithm automatically optimizes atrioventricular and interventricular intervals each week using an accelerometer to measure change in the SonR signal, which was shown previously to correlate with hemodynamic improvement (left ventricular [LV] dP/dtmax). The RESPOND CRT trial will evaluate the effectiveness and safety of the SonR optimization system in patients with HF New York Heart Association class III or ambulatory IV eligible for a CRT-D device. Enrolled patients will be randomized in a 2:1 ratio to either SonR CRT optimization or to a control arm employing echocardiographic optimization. All patients will be followed for at least 24 months in a double-blinded fashion. The primary effectiveness end point will be evaluated for non-inferiority, with a nested test of superiority, based on the proportion of responders (defined as alive, free from HF-related events, with improvements in New York Heart Association class or improvement in Kansas City Cardiomyopathy Questionnaire quality of life score) at 12 months. The required sample size is 876 patients. The two primary safety end points are acute and chronic SonR lead-related complication rates, respectively. Secondary end points include proportion of patients free from death or HF hospitalization, proportion of patients worsened, and lead electrical performance, assessed at 12 months. The RESPOND CRT trial will also examine associated reverse remodeling at 1 year., (Copyright © 2014 The Authors. Published by Mosby, Inc. All rights reserved.)

Preparticipation screening programmes for underlying cardiac pathologies are now commonplace for many international sporting organisations. However, providing medical clearance for an asymptomatic athlete without a family history of sudden cardiac death (SCD) is especially challenging when the athlete demonstrates particularly abnormal repolarisation patterns, highly suggestive of an inherited cardiomyopathy or channelopathy. Deep T-wave inversions of ≥ 2 contiguous anterior or lateral leads (but not aVR, and III) are of major concern for sports cardiologists who advise referring team physicians, as these ECG alterations are a recognised manifestation of hypertrophic cardiomyopathy (HCM) and arrhythmogenic right ventricular cardiomyopathy (ARVC). Subsequently, inverted T-waves may represent the first and only sign of an inherited heart muscle disease, in the absence of any other features and before structural changes in the heart can be detected. However, to date, there remains little evidence that deep T-wave inversions are always pathognomonic of either a cardiomyopathy or an ion channel disorder in an asymptomatic athlete following long-term follow-up. This paper aims to provide a systematic review of the prevalence of T-wave inversion in athletes and examine T-wave inversion and its relationship to structural heart disease, notably HCM and ARVC with a view to identify young athletes at risk of SCD during sport. Finally, the review proposes clinical management pathways (including genetic testing) for asymptomatic athletes demonstrating significant T-wave inversion with structurally normal hearts.

Brugada syndrome is an inherited heart disease without structural abnormalities that is thought to arise as a result of accelerated inactivation of Na channels and predominance of transient outward K current (I(to)) to generate a voltage gradient in the right ventricular layers. This gradient triggers ventricular tachycardia/ventricular fibrillation possibly through a phase 2 reentrant mechanism. The Brugada electrocardiographic (ECG) pattern, which can be dynamic and is sometimes concealed, being only recorded in upper precordial leads, is the hallmark of Brugada syndrome. Because of limitations of previous consensus documents describing the Brugada ECG pattern, especially in relation to the differences between types 2 and 3, a new consensus report to establish a set of new ECG criteria with higher accuracy has been considered necessary. In the new ECG criteria, only 2 ECG patterns are considered: pattern 1 identical to classic type 1 of other consensus (coved pattern) and pattern 2 that joins patterns 2 and 3 of previous consensus (saddle-back pattern). This consensus document describes the most important characteristics of 2 patterns and also the key points of differential diagnosis with different conditions that lead to Brugada-like pattern in the right precordial leads, especially right bundle-branch block, athletes, pectus excavatum, and arrhythmogenic right ventricular dysplasia/cardiomyopathy. Also discussed is the concept of Brugada phenocopies that are ECG patterns characteristic of Brugada pattern that may appear and disappear in relation with multiple causes but are not related with Brugada syndrome., (Copyright © 2012 Elsevier Inc. All rights reserved.)

Background: The proximity of the outflow tracts (OTs) frequently results in an overlap in surface electrocardiographic features of ventricular arrhythmias originating from this anatomic region, particularly when the transition occurs in lead V3. In addition, no reliable criteria to discriminate between a right ventricular OT (RVOT) and a left ventricular OT (LVOT) site of origin (SOO) are derived from intracardiac mapping., Methods and Results: A series of 15 patients underwent ablation because of OT ventricular arrhythmias having a V3 transition, and a septal earliest activation on the RVOT was included in the study. Electrocardiographic and mapping data were collected to analyze accuracy in predicting the RVOT versus the LVOT SOO of the ventricular arrhythmia. A 10-ms isochronal map area in the RVOT was smaller in the RVOT SOO group (1.2 [0.4-2.1] versus 3.4 [2.4-3.9] cm2, respectively; P=0.004) and had a shorter perpendicular diameter (13 [7-17] versus 28 [20-29] mm; P=0.001) and a higher longitudinal/perpendicular axis ratio (1.04 [0.95-1.11] versus 0.49 [0.44-0.57]; P=0.001). A 10-ms isochronal map area>2.3 cm2 predicted an LVOT origin with 85.7% sensitivity and 87.5% specificity, whereas a longitudinal/perpendicular axis ratio<0.8 predicted an LVOT origin with 100% sensitivity and 100% specificity. Electrocardiography-derived parameters showed lower values of sensitivity and specificity. The distal coronary sinus activation mapping did not permit distinction between RVOT and LVOT SOO., Conclusions: The 10-ms isochronal map area and the longitudinal/perpendicular axis ratio accurately predict the RVOT versus the LVOT SOO in patients with OT ventricular arrhythmias, a V3 transition, and a septal earliest activation.

Introduction: Echocardiographic optimization of the VV interval may improve CRT response, but it is time-consuming and not routinely performed. The aim of this study was to compare the response to cardiac resynchronization therapy (CRT) when the interventricular pacing (VV) interval was optimized by tissue Doppler imaging (TDI) to CRT response when it was optimized following QRS width criteria., Methods and Results: The study included 156 consecutive CRT patients with severe heart failure and left bundle-branch block configuration. Atrioventricular interval was selected according to a pulsed Doppler assessment, and VV optimization was randomly assigned to echocardiography (ECHO group, n = 78) or electrocardiography (ECG group, n = 78). Optimal VV was defined for the ECHO group as producing the best LV intraventricular synchrony according to TDI displacement curves and for the ECG group as resulting in the narrowest QRS measured from the earliest deflection. At 6-month follow-up, percentage of echocardiographic responders (defined as neither death nor heart transplantation and a LV end-systolic volume reduction >10%) was higher in the ECG optimized group (50.0% vs 67.9%; P = 0.023), whereas clinical response (defined as neither death nor heart transplantation and >10% improvement in the 6-minute walking test) was similar in both groups (71.8% vs 73.1%; P = 0.858)., Conclusions: VV optimization based on QRS width obtained a higher percentage of responders in terms of LV reverse remodeling compared to the TDI method., (© 2011 Wiley Periodicals, Inc.)

Brugada Syndrome and Ketamine Overdose.  A 31-year-old man was referred for ketamine overdose. He presented initially with transient major Brugada ECG pattern. Complete investigation led to the diagnosis of slowly resolvent toxic myocarditis. Brugada-like ECG was suspected to be caused by the ketamine intoxication in this case., (© 2010 Wiley Periodicals, Inc.)

Brugada syndrome (BrS) causes sudden death in patients with structurally normal hearts. Manifestation of BrS in the ECG is dynamic and most patients do not show unequivocal signs of the syndrome during ECG screening. Electrograms (EGMs) of BrS patients show conduction delay and fractionation at the right ventricular outflow tract area (RVOT) and thus could be used for diagnosis, but their recording requires an invasive procedure. We have obtained 67-lead body surface potential mapping recordings (BSPM) of 6 BrS patients and 6 controls and computed their EGMs by solving the inverse problem of electrocardiography by using Tikhonov's regularization method. Inverse-computed EGMs presented similar activation times and durations in controls and BrS patients for apex and septum. However, RVOT EGMs showed a later activation in BrS patients than in controls (58 ± 7 vs. 39 ± 5 ms, p<0.01) and EGMs were longer (122 ± 22 vs. 85 ± 8 ms, p<0.01). Inverse-computed EGMs of BrS patients showed abnormalities consistent with those observed in electrophysiological studies and could be used for a non-invasive diagnosis and characterization of Brugada syndrome.

Background: Differential diagnosis of wide QRS complex tachycardias using the 12-lead ECG may be difficult in many clinical settings., Objective: The purpose of this study was to determine the value of ECG lead II, specifically, the duration at its beginning, defined as R-wave peak time (RWPT), in differentiating ventricular tachycardia (VT) from supraventricular tachycardia (SVT) in patients with wide QRS complex tachycardia., Methods: Two hundred eighteen ECGs showing wide QRS complex tachycardias were evaluated. Two cardiologists blinded to the diagnosis measured RWPT duration at lead II (from the isoelectric line to the point of first change in polarity), and results between VT and SVT were compared, with the findings of electrophysiologic study used as the gold standard., Results: One hundred sixty-three VTs had a significantly longer RWPT at DII (76.7 +/- 21.7 ms vs 26.8 +/- 9.5 ms in 55 SVT, P = .00001). Receiver operating characteristic curve identified RWPT > or =50 ms at lead II as having greater specificity and sensitivity in discriminating VT from SVT. Area under the curve was 0.97 (95% confidence interval 0.95-0.99), positive likelihood ratio was 34.8, and kappa coefficient (kappa) was 0.86. Bivariate analysis identified higher age in VT patients (60.7 vs 50.1 years, P < or =.01) and wider QRS complex duration at lead II in VT patients (169.4 vs 128.3 ms, P <.0001). QRS width at DII was not superior to RWPT in diagnosing VT., Conclusion: RWPT > or =50 ms at DII is a simple and highly sensitive criterion that discriminates VT from SVT in patients with wide QRS complex tachycardia., (Copyright 2010 Heart Rhythm Society. Published by Elsevier Inc. All rights reserved.)

Aims: According to the diagnostic consensus criteria, the electrocardiographic (ECG) diagnosis of Brugada syndrome requires coved-type > or =2 mm ST-segment elevation in >1 right precordial lead (RPL) V1-V3 in the presence or absence of a sodium-channel blocker. However, this consensus has not been evaluated. We aimed to assess the distribution of coved-type ST-segment elevation on RPLs in a large patient cohort to reevaluate the appropriateness of the diagnostic consensus criteria., Methods and Results: We included 186 individuals with spontaneous and/or drug-induced ECGs of coved-type > or =2 mm ST-segment elevation in at least one RPL. A total of 376 ECGs were analysed for the number, distribution and maximal J-point elevation of diagnostic RPLs. Among all ECGs, 27 (7%) showed a coved-type pattern in 3 RPLs, 205 (55%) in 2 RPLs, and 144 (38%) in only 1 RPL. Leads V1 and V2 were diagnostic in 99% of all ECGs with two diagnostic RPLs. Lead V3 alone was not diagnostic in any ECG. Maximal J-point elevation was significantly higher in lead V2 than V1. Sixty case subjects (32%) had only ECGs with one RPL displaying a coved-type ST-segment elevation. There was no significant difference in clinical presentation and outcome compared with the 126 Brugada patients with ECGs displaying >1 diagnostic RPL. Major arrhythmic events occurred with the same rate (8%) in both groups during a follow-up >5 years., Conclusion: Lead V3 does not yield diagnostic information in Brugada syndrome. Individuals with ECGs displaying only one diagnostic RPL have a similar clinical profile and arrhythmic risk as Brugada patients with ECGs displaying >1 diagnostic RPL. Revision of the consensus criteria should be considered.

The Brugada syndrome is an inherited cardiac disorder initially described in 1992 by Pedro and Josep Brugada, with variable electrocardiographic features characteristic of right bundle-branch block, persistent ST-segment elevation in the precordial leads (VI-V3) at rest and sudden cardiac death. The genetic abnormalities that cause Brugada syndrome have been linked to mutations in the ion channel gene SCN5A which encodes for the alpha-subunit of the cardiac sodium channel. A consensus conference report published in 2002 described the diagnostic criteria for the Brugada syndrome and described the three distinct types of Brugada syndrome. In 2005, a second consensus report was published which described the risk stratification and approaches to therapy. Two specific types of ST-segment elevation, coved and saddleback, are observed in the Brugada syndrome, the former of which is reported to relate to a higher incidence of ventricular tachycardial ventricular fibrillation (VTNF) and sudden cardiac death.The objective of this paper is to review the genetics and the molecular biology behind the Brugada syndrome, the diagnostic criteria, including clinical and electrocardiographic characteristics, and current management.

Optimization of the interventricular pacing delay (VV) in cardiac resynchronization therapy is time-consuming and not routinely performed. The aim of the present study was to compare the acute hemodynamic response obtained by different VV programming methods. Several methods for optimizing the VV using electrocardiographic or echocardiographic measurements were performed. The effect of programming an empirical prefixed VV of 0 ms was also evaluated. Invasive first derivative of left ventricular (LV) pressure over time (dP/dt max) was measured at several VV values, and the hemodynamic response that could be obtained by each noninvasive VV selection method was extrapolated from the curve of LV dP/dt max versus VV. The study included 25 patients (80% men, age 66 +/- 9 years, 44% ischemic). The maximum achievable LV dP/dt during biventricular pacing was obtained by a median left ventricular preactivation of 30 ms and increased the baseline unpaced LV dP/dt from 774 +/- 181 to 934 +/- 179 mm Hg/s (p <0.001). The noninvasive optimization method selected the VV leading to the narrowest QRS measured from the earliest deflection and obtained the smallest difference with regard to the maximum achievable LV dP/dt. Furthermore, of all the VV optimization methods tested, this was the only 1 that significantly improved on the hemodynamic response obtained by programming a predefined VV of 0 ms in all patients (925 +/- 178 vs 906 +/- 183 mm Hg/s; p = 0.003). In conclusion, achieving the narrowest QRS measured from the earliest deflection obtained a better acute hemodynamic response than the other VV optimization methods. It also improved the response obtained by default simultaneous biventricular pacing, although this improvement was limited in magnitude.

Aims: Implantable cardioverter defibrillators (ICDs) are increasingly being used for treatment of ventricular tachycardia (VT)/fibrillation. Inappropriate therapy delivery remains the most frequent complication in patients with ICDs, resulting in psychological distress, proarrhythmia, and battery life reduction. We aim to determine if inappropriate therapies could be reduced by using a morphology discrimination criterion., Methods and Results: We evaluated the performance of the Wavelet morphology discrimination algorithm (Medtronic, Inc.) independently from other discrimination enhancements (rate onset and interval stability). A non-randomized, prospective, multicenter, and observational study was designed to determine the sensitivity and specificity of the new morphology criterion. Sensitivity and specificity in slow tachycardia with cycle length (CL) between 340 and 500 ms were analysed as a pre-specified secondary endpoint. A total of 771 spontaneous episodes in 106 patients were analysed. Five hundred and twenty-two episodes corresponded to true supraventricular tachycardia (SVT) with ventricular CL in the VT or FVT zone, of which 473 had therapy appropriately withheld. Of the 249 episodes of true VT/FVT, 21 were classified according to the Wavelet criteria as SVT (specificity: 90.6%; sensitivity: 91.6%). All of them were spontaneously terminated with no adverse clinical consequences. No syncopal episodes occurred. For VTs in the slowest analysed range (CL: 340-500 ms), a total of 235 episodes were studied, yielding a specificity of 95.9% and sensitivity of 83.2%., Conclusion: Wavelet discrimination criteria in single-chamber ICDs as the sole discriminator can significantly reduce inappropriate therapy for SVT, not only in the range of VTs in the slowest analysed range (340-500 ms for this study) but also for faster VTs. No significant clinical consequences were found when the algorithm was used, but final data should prompt the use of the algorithm in combination with a high rate time-out feature.

Background: Repolarization abnormalities in the inferior-lateral leads in Brugada syndrome (BS) have not been systematically investigated., Methods and Results: 280 patients (age, 41+/-18 years; 168 males) with BS were screened for inferior-lateral repolarization abnormalities. The repolarization abnormalities were classified either as early repolarization pattern or coved > or = 2-mm Brugada pattern and as spontaneous or class I antiarrhythmic drug (AAD) induced. Thirty-two patients (11%) had inferior-lateral spontaneous early repolarization pattern. These patients were less likely to be asymptomatic at first presentation (13 of 32 versus 156 of 248 patients, P=0.02), and spontaneous type I ECG was more frequent among them (38% versus 21%, P=0.05). The spontaneous early repolarization pattern occurred more frequently among patients with BS than in 283 family members not having BS (11% versus 6%, P=0.03). Class I AAD administration provoked inferior-lateral coved Brugada pattern in 13 patients with BS. These patients had longer baseline PR intervals (206+/-48 versus 172+/-31 ms, P<0.001) and class I AAD-induced QRS interval prolongation (108 to 178 versus 102 ms to 131 ms, P<0.001). In 3 patients, the class I AAD-provoked coved Brugada pattern was only present in the inferior leads., Conclusions: Inferior-lateral early repolarization pattern occurs spontaneously relatively frequently in BS. These patients have a more severe phenotype. Class I AAD administration provokes inferior-lateral coved Brugada pattern in 4.6% of patients. We report for the first time 3 patients in whom the class I AAD-provoked coved Brugada pattern was only observed in the inferior leads.

Introduction: The spontaneous presence of a coved-type ECG is considered as an important risk factor in Brugada syndrome. However, diagnosis making and risk stratification may be hampered by the dynamic nature of the ECG abnormalities. The objective of this study was to determine the variability and predictive value of the electrocardiogram in Brugada patients implanted with a cardioverter-defibrillator (ICD)., Methods and Results: We analyzed consecutive 12-lead ECGs from 89 ICD patients (44 +/- 14 years, 69 males) with Brugada syndrome. A total of 1,161 ECGs were included for analysis (13 +/- 8 ECGs/patient). Twenty-four percent of the ECGs/patient were coved-type I, 25% saddleback-type II or III, and 51% normal. Fifty-seven patients had a diagnostic coved-type ECG spontaneously (group A), 32 patients only after drug challenge (group B). In group A, 38% of the ECGs/patient were diagnostic, 25% saddleback-type, and 37% normal. Fifty-five group A patients (96%) had transient normalization and/or conversion to saddleback-type ECGs. During a mean follow-up of 48 +/- 35 months, 16 patients (18%) experienced appropriate shocks. All patients with appropriate shocks had spontaneous diagnostic ECGs. They tended to have more coved-type ECGs (36 vs 22%, respectively, P = 0.05) than patients without appropriate shocks., Conclusions: Analysis of serial ECG recordings in an ICD patient population shows that the Brugada-ECG pattern is highly variable over time. In patients with spontaneous coved-type ECG, only every third ECG is diagnostic and every third ECG normal. Patients with spontaneous coved-type ST-segment elevation have a high incidence of appropriate shocks. Spontaneous saddleback-type electrocardiograms are not helpful for risk stratification.

Objectives: We sought to assess differences in phenotype and prognosis between men and women in a large population of patients with Brugada syndrome., Background: A male predominance has been reported in the Brugada syndrome. No specific data are available, however, concerning gender differences in the clinical manifestations and their role in prognosis., Methods: Patients with Brugada syndrome were prospectively included in the study. Data on baseline characteristics, electrocardiogram parameters before and after pharmacological test, and events in follow-up were recorded for all patients., Results: Among 384 patients, 272 (70.8%) were men and 112 (29.2%) women. At inclusion, men had experienced syncope more frequently (18%) or aborted sudden cardiac death (6%) than women (14% and 1%, respectively, p = 0.04). Men also had greater rates of spontaneous type-1 electrocardiogram, greater ST-segment elevation, and greater inducibility of ventricular fibrillation (p < 0.001 for all). Conversely, conduction parameters and corrected QT intervals significantly increased more in women in response to sodium blockers (p = 0.03 and p = 0.001, respectively). During a mean follow-up of 58 +/- 48 months, sudden cardiac death or documented ventricular fibrillation occurred in 31 men (11.6%) and 3 women (2.8%; p = 0.003). The presence of previous symptoms was the most important predictor for cardiac events in men, whereas a longer PR interval was identified among those women with a greater risk in this series., Conclusions: Men with Brugada syndrome present with a greater risk clinical profile than women and have a worse prognosis. Although classical risk factors identify male patients with worse outcome, conduction disturbances could be a marker of risk in the female population.

Introduction: Brugada syndrome (BrS) is an inherited disorder that predisposes some subjects to sudden cardiac death (SCD). It is not well established which BrS patients are at risk of severe arrhythmias. Our aim was to study whether standard 12-lead electrocardiogram (ECG) would give useful information for this purpose., Methods: This study included 200 BrS probands (142 male, 62%; mean age 42 +/- 16 years). Symptoms related to BrS were defined as syncope, documented ventricular tachyarrhythmia, or SCD. We determined PR, QRS, QTc, T(peak), and T(end) interval from leads II and V(2) and QRS from lead V(5), R'/S ratio from lead aVR (aVR sign), QRS axis, and J-point elevation amplitude from right precordial leads from the baseline ECGs., Results: Sixty-six subjects (33%) had experienced symptoms related to BrS. The only significant difference between the symptomatic and asymptomatic BrS subjects was the QRS duration measured from lead II or lead V(2), for example, the mean QRS in V(2) was 115 +/- 26 ms in symptomatic versus 104 +/- 19 ms in asymptomatic patients (P < 0.001). The optimized cut-off point of V(2) QRS > or =120 ms gave an odds ratio (OR) of 2.5 (95% CI: 1.4-4.6, P = 0.003) for being symptomatic. In a multivariate analysis adjusted with gender, age, and SCN5A mutation, the OR was 2.6 (95% CI: 1.4-4.8, P = 0.004)., Conclusion: Prolonged QRS duration, measured from standard 12-lead ECG, is associated with symptoms and could serve as a simple noninvasive risk marker of vulnerability to life-threatening ventricular arrhythmias in BrS.

Aims: Though right atrial appendage tachycardia (RAAT) has been described, no studies to date have focused on its clinical characterization. The aim of the present study was to analyze its clinical, electrocardiographic (ECG), and electrophysiologic (EP) characteristics and the results of radiofrequency ablation (RFA) in RAAT., Methods and Results: Out of 186 consecutive patients undergoing RFA for AT, 15 (8%) had focal RAAT. Mapping was performed using conventional catheters or a 3D electroanatomic mapping system. Patients with RAAT were more likely to be male (66 vs. 38%; P= 0.013) and younger (32 +/- 12.6 vs. 55 +/- 13.2 years; P < 0.001) than patients with AT originating elsewhere. They were also more likely to have dyspnea (27 vs. 7.6%; P = 0.03), incessant tachycardia (53 vs. 16%; P < 0.001), and left ventricular systolic dysfunction (27 vs. 5%; P = 0.018). RFA was effective in all patients (100 vs. 75%; P = 0.022) and no recurrences (0 vs. 8%; P = 0.31) were observed during a mean follow-up of 37 +/- 36 months. A specific ECG pattern was identified, consisting of negative P-waves in leads V1-V2 and a transition to positivity in the rest of the precordial leads. This ECG pattern correctly identified RAAT with a sensitivity of 100%, a specificity of 98%, a positive predictive value of 88%, and a negative predictive value of 100%., Conclusion: Right atrial appendage tachycardia is more prevalent in young male patients and is commonly associated with tachycardiomyopathy. RFA is effective over long-term follow-up. A characteristic ECG pattern identifies RAAT with a very high sensitivity and specificity.