Implantable loop recorders in patients with Brugada syndrome: the BruLoop study.

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

Impact of SMART Pass filter in patients with ajmaline-induced Brugada syndrome and subcutaneous implantable cardioverter-defibrillator eligibility failure: results from a prospective multicentre study.

AIMS: Ajmaline challenge can unmask subcutaneous implantable cardioverter-defibrillator (S-ICD) screening failure in patients with Brugada syndrome (BrS) and non-diagnostic baseline electrocardiogram (ECG). The efficacy of the SMART Pass (SP) filter, a high-pass filter designed to reduce cardiac oversensing (while maintaining an appropriate sensing margin), has not yet been assessed in patients with BrS. The aim of this prospective multicentre study was to investigate the effect of the SP filter on dynamic Brugada ECG changes evoked by ajmaline and to assess its value in reducing S-ICD screening failure in patients with drug-induced Brugada ECGs. METHODS AND RESULTS: The S-ICD screening with conventional automated screening tool (AST) was performed during ajmaline challenge in subjects with suspected BrS. The S-ICD recordings were obtained before, during and after ajmaline administration and evaluated by the means of a simulation model that emulates the AST behaviour with and without SP filter. A patient was considered suitable for S-ICD if at least one sensing vector was acceptable in all tested postures. A sensing vector was considered acceptable in the presence of QRS amplitude >0.5 mV, QRS/T-wave ratio >3.5, and sense vector score >100. Of the 126 subjects (mean age: 42 ± 14 years, males: 61%, sensing vectors: 6786), 46 (36%) presented with an ajmaline-induced Brugada type 1 ECG. Up to 30% of subjects and 40% of vectors failed the screening during the appearance of Brugada type 1 ECG evoked by ajmaline. The S-ICD screening failure rate was not significantly reduced in patients with Brugada ECGs when SP filter was enabled (30% vs. 24%). Similarly, there was only a trend in reduction of vector-failure rate attributable to the SP filter (from 40% to 36%). The most frequent reason for screening failure was low QRS amplitude or low QRS/T-wave ratio. None of these patients was implanted with an S-ICD. CONCLUSION: Patients who pass the sensing screening during ajmaline can be considered good candidates for S-ICD implantation, while those who fail might be susceptible to sensing issues. Although there was a trend towards reduction of vector sensing failure rate when SP filter was enabled, the reduction in S-ICD screening failure in patients with Brugada ECGs did not reach statistical significance. CLINICAL TRIAL REGISTRATION: https://clinicaltrials.gov Unique Identifier NCT04504591.

Brugada phenocopy in a patient with unstable angina and three-vessel coronary artery disease.

A 52-year-old male was admitted with unstable angina and three-vessel coronary artery disease. Electrocardiography (ECG) changes consistent with type-1 Brugada ECG pattern were noted during admission. The patient was asymptomatic for syncope and had no family history of sudden cardiac death, ICD implantation, and Brugada syndrome. After coronary by-pass graft the Brugada ECG pattern resolved, and ajmaline test did not elicit type-1 ECG pattern, confirming the suspicion of Brugada phenocopy.

Predictors of inappropriate shock in Brugada syndrome patients with a subcutaneous implantable cardiac defibrillator.

BACKGROUND: Subcutaneous implantable cardioverter defibrillators (S-ICDs) avoid complications secondary to transvenous leads, but inappropriate shocks (ISs) are frequent. Furthermore, IS data from patients with Brugada syndrome (BrS) with an S-ICD are scarce. OBJECTIVE: We aimed to establish the frequency and predictors of IS in this population. METHODS: We analyzed the clinical and electrocardiographic characteristics, automated screening test data, device programming, and IS occurrence in adult patients with BrS with an S-ICD. RESULTS: Thirty-nine patients were enrolled (69% male, mean age at diagnosis 46 ± 13 years, mean age at implantation 48 ± 13 years). During a mean follow-up of 26 ± 21 months, 18% patients experienced IS. Patients with IS were younger at the time of diagnosis (36 ± 8 vs. 48 ± 13 years, p = .018) and S-ICD implantation (38 ± 9 vs. 50 ± 23 years, p = .019) and presented with spontaneous type 1 Brugada electrocardiogram pattern more frequently at diagnosis or during follow-up (71% vs. 25%, p = .018). During automated screening tests, patients with IS showed lower QRS voltage in the primary vector in the supine position (0.58 ± 0.26 vs. 1.10 ± 0.35 mV, p = .011) and lower defibrillator automated screening score in the primary vector in the supine (123 ± 165 vs. 554 ± 390 mV, p = .005) and standing (162 ± 179 vs. 486 ± 388 mV, p = .038) positions. Age at diagnosis was the only independent predictor of IS (hazard ratio = 0.873, 95% confidence interval: 0.767-0.992, p = .037). CONCLUSION: IS was a frequent complication in patients with BrS with an S-ICD. Younger age was independently associated with IS. A more thorough screening process might help prevent IS in this population.

Left Atrial Appendage Occlusion in High Bleeding Risk Patients.

OBJECTIVES: The aim of this study was to investigate the outcomes of left atrial appendage occlusion (LAAO) in high bleeding risk patients suffering atrial fibrillation (AF) and to analyze the different antithrombotic therapies following the intervention. BACKGROUND METHODS: This monocentric study included 68 patients with nonvalvular AF with an absolute contraindication to OAT or at high bleeding risk. Follow-up was done with a clinical visit at 3-6-12 months. RESULTS: Successful LAAO was achieved in 67/68 patients. At discharge, 32/68 patients were on dual antiplatelet therapy (APT), 34/68 were without any antithrombotic therapy or with a single antiplatelet drug, and 2/68 were on anticoagulant therapy. At three-month follow-up visit, 73.6% of the patients did not receive dual APT, of whom 14.7% had no thrombotic therapy and 58.9% were on single antiplatelet therapy. During a follow-up of 1.4 ± 0.9 years, 3/62 patients had late adverse effects (2 device-related thrombus without clinical consequences and 1 extracranial bleeding). The device-related thrombosis was not related to the antithrombotic therapy. CONCLUSIONS: LAAO is feasible and safe and prevents stroke in patients with AF with contraindication to oral anticoagulant therapy. After LAAO, single antiplatelet therapy seems to be a safe alternative to dual antiplatelet therapy, especially in patients at high bleeding risk. No benefit has been observed with dual APT.

Out-of-hospital cardiac arrest due to idiopathic ventricular fibrillation in patients with normal electrocardiograms: results from a multicentre long-term registry.

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.

Spatiotemporal Characteristics of QRS Complexes Enable the Diagnosis of Brugada Syndrome Regardless of the Appearance of a Type 1 ECG.

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.

A novel mutation in lamin a/c causing familial dilated cardiomyopathy associated with sudden cardiac death.

BACKGROUND: Dilated cardiomyopathy (DCM), a cardiac heterogeneous pathology characterized by left ventricular or biventricular dilatation, is a leading cause of heart failure and heart transplantation. The genetic origin of DCM remains unknown in most cases, but >50 genes have been associated with DCM. We sought to identify the genetic implication and perform a genetic analysis in a Spanish family affected by DCM and sudden cardiac death. METHODS AND RESULTS: Clinical assessment and genetic screening were performed in the index case as well as family members. Of all relatives clinically assessed, nine patients showed clinical symptoms related to the pathology. Genetic screening identified 20 family members who carried a novel mutation in LMNA (c.871 G>A, p.E291K). Family segregation analysis indicated that all clinically affected patients carried this novel mutation. Clinical assessment of genetic carriers showed that electrical dysfunction was present previous to mechanical and structural abnormalities. CONCLUSIONS: Our results report a novel pathogenic mutation associated with DCM, supporting the benefits of comprehensive genetic studies of families affected by this pathology.

Genetics of arrhythmogenic right ventricular cardiomyopathy.

Arrhythmogenic right ventricular cardiomyopathy is a rare clinical entity characterised by fibro-fatty replacement of myocardium, mainly involving right ventricular free wall, leading to malignant electrical instability and sudden cardiac death. The disease is inherited in up to 50% of cases, with incomplete penetrance and variable phenotypic expression. To date, more than 300 pathogenic mutations have been identified in 12 genes, mainly with autosomal dominant inheritance. Here, we focus on recent advances in the genetics of arrhythmogenic right ventricular cardiomyopathy. Despite continuous improvements, current genotype-phenotype studies have not contributed yet to establish a genetic risk stratification of the disease.

Diagnosis of Brugada syndrome affects quality of life and psychological status.

Background: Chronic diseases have a negative impact on quality of life (QOL) and psychological health. There are limited related data regarding this topic in Brugada syndrome (BrS). We evaluated the effects of the diagnosis of BrS on health-related QOL and psychological status among patients and their relatives. Methods: Patients with BrS and their relatives underwent psychological evaluation at diagnosis (T0), 1 and 2 years after diagnosis (T1 and T2) using questionnaires on mental QOL, anxiety, depression, stress, post-traumatic stress, and resilience resources. Results: Sixty-one patients and 39 relatives were enrolled. Compared with controls, patients showed increased physical QOL (54.1 ± 6.5 vs. 50.1 ± 8.0, p = 0.014), reduced mental QOL (43.2 ± 11.8 vs. 49.6 ± 9.1, p = 0.018) and increased anxiety (9.9 ± 6.6 vs. 6.9 ± 7.7, p = 0.024) at T0; reduced resilience scores (3.69 ± 0.40 vs. 3.96 ± 0.55, p = 0.008) at T1; and reduced resilience (3.69 ± 0.35 vs. 3.96 ± 0.55, p = 0.019) and increased anxiety scores (16.4 ± 12.8 vs. 6.9 ± 7.7, p = 0.006) at T2. Relatives presented higher stress (17.63 ± 3.77 vs. 12.90 ± 6.0, p = 0.02) at T0 and higher anxiety scores at T0 (13.5 ± 7.6 vs. 6.9 ± 7.7, p < 0.001), T1 (12.0 ± 8.7 vs. 6.9 ± 7.7, p = 0.005), and T2 (16.4 ± 12.8 vs. 6.9 ± 7.7, p = 0.006) than controls. Female sex was significantly independently associated with worse mental QOL scores in patients at T0 (odds ratio = 0.10; 95% confidence interval = 0.05-0.94; p = 0.04). Conclusions: The diagnosis of BrS impairs the QOL and psychological status of patients and their relatives. Female sex is independently associated with worse mental QOL in patients at diagnosis.

Continuous Rhythm Monitoring With Implanted Loop Recorders in Children and Adolescents With Brugada Syndrome.

BACKGROUND: Young (<18 years of age) patients with Brugada syndrome (BrS) are often under-represented in BrS studies and their management, especially related to syncopal episodes, remains unclear. OBJECTIVES: This study sought to describe the arrhythmia prevalence among young patients with BrS undergoing continuous rhythm monitoring by implantable loop recorder (ILR) and to assess the etiology behind syncope of undetermined origin. METHODS: A total of 147 patients with BrS with ILR were enrolled in 12 international centers and divided into pediatric (age <12 years; n = 77, 52%) and adolescents (age 13-18 years; n = 70, 48%). RESULTS: Mean age was 11.3 years, 53 patients (36.1%) were female, and 31 (21.1%) had spontaneous type 1 electrocardiograms. Over a median follow-up of 3.6 years (Q1-Q3: 1.6-4.8 years), an arrhythmic event was recorded in 33 patients (22.4%), mainly of nonventricular origin: 15 atrial (10.2%) and 16 bradyarrhythmic events (10.9%). Ventricular arrhythmias occurred in 4 patients, all with spontaneous BrS, and were fever-related in one-half. Among all patients with recurrence of syncope during follow-up, true arrhythmic syncope was documented in 5 (17.8%), and it was due to bradyarrhythmias or atrial arrhythmias in 3 cases (60%). CONCLUSIONS: Continuous rhythm monitoring with ILRs in young patients with BrS detects a broad range of arrhythmias. Ventricular arrhythmias occur predominantly in patients with spontaneous type 1 electrocardiograms and during fever. Despite the young age, bradyarrhythmias and atrial arrhythmias are frequent and represent the cause of arrhythmic syncope in 60% of patients. Young patients with BrS with syncope of undetermined origin may benefit from ILR implant.

Genetics in Probands With Idiopathic Ventricular Fibrillation: A Multicenter Study.

BACKGROUND: Different genes have been associated with idiopathic ventricular fibrillation (IVF); however, there are no studies correlating genotype with phenotype. OBJECTIVES: The aim of this study was to define the genetic background of probands with IVF using large gene panel analysis and to correlate genetics with long-term clinical outcomes. METHODS: All consecutive probands with a diagnosis of IVF were included in a multicenter retrospective study. All patients had: 1) IVF diagnosis throughout the follow-up; and 2) genetic analysis with a broad gene panel. All genetic variants were classified as pathogenic/likely pathogenic (P+), variants of unknown significance (VUS) or no variants (NO-V), following current guidelines of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. The primary endpoint was occurrence of ventricular arrhythmias (VA). RESULTS: Forty-five consecutive patients were included. A variant was found in 12 patients, 3 P+ and 9 VUS carriers. After a mean follow-up time of 105.0 months, there were no deaths and 16 patients (35.6%) experienced a VA. NO-V patients had higher VA free survival during the follow-up, compared with both VUS (72.7% vs 55.6%, log-rank P < 0.001) and P+ (72.7% vs 0%, log-rank P = 0.013). At Cox analysis, P+ or VUS carrier status was a predictor of VA occurrence. CONCLUSIONS: In probands with IVF, undergoing genetic analysis with a broad panel, the diagnostic yield for P+ is 6.7%. P+ or VUS carrier status is a predictor of VA occurrence.

Brugada syndrome 2012.

Brugada syndrome (BS) is a cardiac disorder characterized by typical ECG alterations, and it is associated with a high risk for sudden cardiac death (SCD), affecting young subjects with structurally normal hearts. The prevalence of this disorder is still uncertain, presenting marked geographical differences. The syndrome has a genetic basis, and several mutations have been identified in genes encoding subunits of cardiac sodium, potassium, and calcium channels, as well as in genes involved in the trafficking or regulation of these channels. Most BS patients are asymptomatic, but those who develop symptoms present with syncope and/or SCD secondary to polymorphic ventricular tachycardia and/or ventricular fibrillation. Risk stratification is still challenging, especially in cases of asymptomatic BS patients. This is a brief review of recent advances in our understanding of the genetic and molecular bases of BS, arrhythmogenic mechanisms and clinical course, as well as an update of the tools for risk stratification and treatment of the condition.

Preparation for pacemaker or implantable cardiac defibrillator implants in patients with high risk of thrombo-embolic events: oral anticoagulation or bridging with intravenous heparin? A prospective randomized trial.

AIMS: Current guidelines recommend stopping oral anticoagulation (OAC) and starting heparin infusion before implanting/replacing a pacemaker/implantable cardioverter-defibrillator (ICD) in patients with high risk for thrombo-embolic events. The aim of this study was to demonstrate that the maintenance of OAC during device implantation/replacement is as safe as bridging to intravenous heparin and shortens in-hospital stay. METHODS AND RESULTS: A cohort of 101 consecutive patients with high risk for embolic events and indication for implant/replacement of a pacemaker/ICD were randomized to two anticoagulant strategies: bridging from OAC to heparin infusion (n = 51) vs. maintenance of OAC to reach an INR = 2 +/- 0.3 at the day of the procedure (n = 50). Haemorrhagic and thrombo-embolic complications were evaluated at discharge, 15 and 45 days after the procedure. A total of 4/51 patients (7.8%) from heparin group and 4/50 (8.0%) from the OAC group developed pocket haematoma following the implant (P = 1.00). One haematoma in each group required evacuation (1.9 vs. 2%, P = 1.00). No other haemorrhagic events or embolic complications developed during the follow-up. Duration of the hospital stay was longer in the heparin group [median of 5 (4-7) vs. 2 (1-4) days; P < 0.001]. CONCLUSION: Implant of devices maintaining OAC is as safe as bridging to heparin infusion and allows a significant reduction of in-hospital stay.

Rendered OCT Imaging of an Impressive Stent Malapposition in the Left Main Coronary Artery.

This case emphasizes the need to use intravascular imaging to optimize stent implantation in the left main coronary artery. Despite recommendations, intravascular imaging is still widely under-utilized. The recently developed stent apposition OCT software (OPTIS Stent Optimization Software; Abbott Vascular) confirmed its usefulness in optimizing stent implantation in unprotected left main PCI.

Nonvalvular atrial fibrillation in high-hemorrhagic-risk patients: state of the art of percutaneous left atrial appendage occlusion.

: Atrial fibrillation is the most common cardiac arrhythmia and its prevalence is constantly increasing. The main complications related to atrial fibrillation are death and major stroke. Oral anticoagulant therapy is the cornerstone of management of atrial fibrillation patients at increased stroke risk. Unfortunately, a significant proportion of patients do not receive adequate anticoagulant therapy due to increased or prohibitive hemorrhagic risk. The observation that most thrombi are generated in the left atrial appendage (LAA) had led to the consideration of surgical or percutaneous occlusion as an alternative. During recent years, the WATCHMAN percutaneous occlusion device has proven to be not inferior to anticoagulant therapy for the prevention of thromboembolic events, with the added benefit of a lower rate of hemorrhagic events. Numerous data showed the same results for the AMPLATZER cardiac plug and Amulet devices. Left atrial appendage occlusion (LAAO) often represents the only therapeutic strategy in this group of patients. We describe the current state of the art of percutaneous LAAO in atrial fibrillation patients with a high hemorrhagic risk.

QRS Variations During Arrhythmias: Mechanisms and Substrates. Toward a Precision Electrocardiology.

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.

Predictors of arrhythmia recurrence in patients with lone atrial fibrillation.

AIMS: The need for antiarrhythmic drugs (AAD) after a first episode of atrial fibrillation (AF) is determined by the probability of recurrence. The aim of this study was to asses the probability of relapse and the predictors of recurrence in patients with idiopathic AF. METHODS AND RESULTS: A cohort of 98 consecutive patients younger than 65 years admitted at the emergency room because of an episode of symptomatic idiopathic (lone) AF was included in this study. On admission, a complete medical history was taken, and an echocardiogram and 24-h Holter monitoring were performed. Patients were seen at 3 and 6 months after the index episode. There were 35 (35.7%) patients with a new-onset AF episode and 63 (64.3%) with a recurrent AF episode. A majority of them were male (71%), with a mean age of 48+/-11 years. Patients with new-onset AF episodes did not receive AAD. At 6 month follow-up, 57% of all patients suffered at least one symptomatic AF relapse. Patients with AF relapses belong more often to the recurrent group vs. new-onset group of AF (65.1 vs. 34.9%, respectively, P = 0.03); they had larger LA diameter indexed for body surface area (BSA) (22.6+/-3.7 vs. 19.8+/-3.2 mm/m(2), P = 0.001), larger left ventricular end-systolic diameter (18.4+/-3.1 vs. 17.2+/-2.5 mm/m(2), P = 0.05) and a tendency towards a higher proportion of atrial tachycardia runs on Holter (66.7 vs. 50%, P = 0.09). Logistic regression analysis showed that the presence of previous episodes of AF (OR: 3.2; 95% CI; 1.0-8.0, P = 0.04) and a larger anteroposterior LA diameter (OR: 1.3; 95% CI; 1.1-1.6, P = 0.001) were independent predictors of AF recurrences at 6 months. CONCLUSIONS: The recurrence rate in lone AF patients is high. The presence of previous episodes and a mildly enlarged anteroposterior LA diameter increase the probability of relapse of lone AF.

Integration of "Omics" Strategies for Biomarkers Discovery and for the Elucidation of Molecular Mechanisms Underlying Brugada Syndrome.

PURPOSE: The Brugada syndrome (BrS) is a severe inherited cardiac disorder. Given the high genetic and phenotypic heterogeneity of this disease, three different "omics" approaches are integrated in a synergic way to elucidate the molecular mechanisms underlying the pathophysiology of BrS as well as for identifying reliable diagnostic/prognostic markers. EXPERIMENTAL DESIGN: The profiling of plasma Proteome and MiRNome is perfomed in a cohort of Brugada patients that were preliminary subjected to genomic analysis to assess a peculiar gene mutation profile. RESULTS: The integrated analysis of "omics" data unveiled a cooperative activity of mutated genes, deregulated miRNAs and proteins in orchestrating transcriptional and post-translational events that are critical determining factors for the development of the Brugada pattern. CONCLUSIONS AND CLINICAL RELEVANCE: This study provides the basis to shed light on the specific molecular fingerprints underlying BrS development and to gain further insights on the pathogenesis of this life-threatening cardiac disease.

Patients With Brugada Syndrome and Implanted Cardioverter-Defibrillators: Long-Term Follow-Up.

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.