Influence of age and sex on the diagnostic yield of inherited cardiac conditions in sudden arrhythmic death syndrome decedents.

Aims: Sudden arrhythmic death syndrome (SADS) refers to a sudden death, which remains unexplained despite comprehensive post-mortem examination and a toxicological screen. We aimed to investigate the impact of age and sex on the overall diagnostic yield and underlying aetiology in decedents with SADS using a combined approach of familial evaluation (FE) and molecular autopsy (MA).

Methods And Results: Consecutive referrals to a single centre for FE only, MA only or both, following a SADS death were included.

Mutation Type and a Genetic Risk Score Associate Variably With Brugada Syndrome Phenotype in Families.

Background: Brugada syndrome (BrS) is characterized by the type 1 Brugada ECG pattern. Pathogenic rare variants in (mutations) are identified in 20% of BrS families in whom incomplete penetrance and genotype-negative phenotype-positive individuals are observed. E1784K- is the most common mutation identified.

Transethnic Genome-Wide Association Study Provides Insights in the Genetic Architecture and Heritability of Long QT Syndrome.

Background: Long QT syndrome (LQTS) is a rare genetic disorder and a major preventable cause of sudden cardiac death in the young. A causal rare genetic variant with large effect size is identified in up to 80% of probands (genotype positive) and cascade family screening shows incomplete penetrance of genetic variants. Furthermore, a proportion of cases meeting diagnostic criteria for LQTS remain genetically elusive despite genetic testing of established genes (genotype negative).

An International Multicenter Evaluation of Type 5 Long QT Syndrome: A Low Penetrant Primary Arrhythmic Condition.

Background: Insight into type 5 long QT syndrome (LQT5) has been limited to case reports and small family series. Improved understanding of the clinical phenotype and genetic features associated with rare variants implicated in LQT5 was sought through an international multicenter collaboration.

Methods: Patients with either presumed autosomal dominant LQT5 (N = 229) or the recessive Type 2 Jervell and Lange-Nielsen syndrome (N = 19) were enrolled from 22 genetic arrhythmia clinics and 4 registries from 9 countries.

The yield of postmortem genetic testing in sudden death cases with structural findings at autopsy.

Sudden cardiac death (SCD) is often associated with structural abnormalities of the heart during autopsy. This study sought to compare the diagnostic yield of postmortem genetic testing in (1) cases with structural findings of uncertain significance at autopsy to (2) cases with autopsy findings diagnostic of cardiomyopathy. We evaluated 57 SCD cases with structural findings at cardiac autopsy.

Ethnic differences in patients with Brugada syndrome and arrhythmic events: New insights from Survey on Arrhythmic Events in Brugada Syndrome.

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.

Characterization and Management of Arrhythmic Events in Young Patients With Brugada Syndrome.

Background: Information on young patients with Brugada syndrome (BrS) and arrhythmic events (AEs) is limited.

Objectives: The purpose of this study was to describe their characteristics and management as well as risk factors for AE recurrence.

Methods: A total of 57 patients (age ≤20 years), all with BrS and AEs, were divided into pediatric (age ≤12 years; n = 26) and adolescents (age 13 to 20 years; n = 31).

Time-to-first appropriate shock in patients implanted prophylactically with an implantable cardioverter-defibrillator: data from the Survey on Arrhythmic Events in BRUgada Syndrome (SABRUS).

Aims: Data on predictors of time-to-first appropriate implantable cardioverter-defibrillator (ICD) therapy in patients with Brugada Syndrome (BrS) and prophylactically implanted ICD's are scarce.

Methods And Results: SABRUS (Survey on Arrhythmic Events in BRUgada Syndrome) is an international survey on 678 BrS patients who experienced arrhythmic event (AE) including 252 patients in whom AE occurred after prophylactic ICD implantation. Analysis was performed on time-to-first appropriate ICD discharge regarding patients' characteristics.

SCN5A mutations in 442 neonates and children: genotype-phenotype correlation and identification of higher-risk subgroups.

Aims: To clarify the clinical characteristics and outcomes of children with SCN5A-mediated disease and to improve their risk stratification.

Methods And Results: A multicentre, international, retrospective cohort study was conducted in 25 tertiary hospitals in 13 countries between 1990 and 2015. All patients ≤16 years of age diagnosed with a genetically confirmed SCN5A mutation were included in the analysis.

Gender differences in patients with Brugada syndrome and arrhythmic events: Data from a survey on arrhythmic events in 678 patients.

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.

Fever-related arrhythmic events in the multicenter Survey on Arrhythmic Events in Brugada Syndrome.

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).

Profile of patients with Brugada syndrome presenting with their first documented arrhythmic event: Data from the Survey on Arrhythmic Events in BRUgada Syndrome (SABRUS).

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).

Age of First Arrhythmic Event in Brugada Syndrome: Data From the SABRUS (Survey on Arrhythmic Events in Brugada Syndrome) in 678 Patients.

Background: Data on the age at first arrhythmic event (AE) in Brugada syndrome are from limited patient cohorts. The aim of this study is 2-fold: (1) to define the age at first AE in a large cohort of patients with Brugada syndrome, and (2) to assess the influence of the mode of AE documentation, sex, and ethnicity on the age at first AE.

Methods And Results: A survey of 23 centers from 10 Western and 4 Asian countries gathered data from 678 patients with Brugada syndrome (91.

Loss-of-Function Variants: True Monogenic Culprits of Long-QT Syndrome or Proarrhythmic Variants Requiring Secondary Provocation?

Background: Insight into type 6 long-QT syndrome (LQT6), stemming from mutations in the -encoded voltage-gated channel β-subunit, is limited. We sought to further characterize its clinical phenotype.

Methods And Results: Individuals with reported pathogenic mutations identified during arrhythmia evaluation were collected from inherited arrhythmia clinics and the Rochester long-QT syndrome (LQTS) registry.

Utility of Post-Mortem Genetic Testing in Cases of Sudden Arrhythmic Death Syndrome.

Background: Sudden arrhythmic death syndrome (SADS) describes a sudden death with negative autopsy and toxicological analysis. Cardiac genetic disease is a likely etiology.

Objectives: This study investigated the clinical utility and combined yield of post-mortem genetic testing (molecular autopsy) in cases of SADS and comprehensive clinical evaluation of surviving relatives.

Late gadolinium enhancement in Brugada syndrome: A marker for subtle underlying cardiomyopathy?

Background: There is increasing evidence that the Brugada ECG pattern is a marker of subtle structural heart disease.

Objective: The purpose of this study was to characterize patients with Brugada syndrome (BrS) using cardiovascular magnetic resonance (CMR) with late gadolinium enhancement (LGE).

Methods: BrS was diagnosed according to international guidelines.

Sudden death and cardiac arrest without phenotype: the utility of genetic testing.

Approximately 4% of sudden cardiac deaths are unexplained [the sudden arrhythmic death syndrome (SADS)], and up to 6-10% of survivors of cardiac arrest do not have an identifiable cardiac abnormality after comprehensive clinical evaluation [idiopathic ventricular fibrillation (IVF)]. Genetic testing may be able to play a role in diagnostics and can be targeted to an underlying phenotype present in family members following clinical evaluation. Alternatively, post-mortem genetic testing (the "molecular autopsy") may diagnose the underlying cause if a clearly pathogenic rare variant is found.

A platelet P-selectin test predicts adverse cardiovascular events in patients with acute coronary syndromes treated with aspirin and clopidogrel.

There is wide variation in response to antiplatelet therapy and high on-treatment platelet reactivity is associated with adverse cardiovascular events. The objective here was to determine whether the results of a novel strategy for assessing platelet reactivity (based on P-selectin measurement) are associated with clinical outcomes in patients with acute coronary syndromes (ACS). This was a prospective cohort study of 100 ACS patients taking aspirin and clopidogrel.

Ticagrelor: a P2Y12 antagonist for use in acute coronary syndromes.

Agents that inhibit platelet function are used routinely in the treatment and prevention of acute coronary syndromes. The main antiplatelet treatments used combine aspirin with one of the thienopyridine P2Y(12) antagonists, either clopidogrel or prasugrel. By blocking the synthesis of thromboxane A(2) in platelets and by blocking the effects of ADP, respectively, these agents reduce platelet activity, platelet aggregation and thrombus formation.