Search

Background: Brugada syndrome (BrS) is caused by mutations in SCN5A gene in 15%-20% of cases. Previous studies showed worse prognosis in SCN5A mutation carriers (SCN5A+). To date, there are no data on genotype–phenotype correlation with electrocardiographic (ECG) imaging (ECGI) and high-density epicardial electroanatomic map. Objective: This study aimed to correlate SCN5A mutation with substrate severity in BrS assessed by ECGI and high-density electroanatomic map. Methods: All consecutive BrS patients undergoing ECGI and high-density epicardial electroanatomic map with HD Grid Mapping Catheter were retrospectively analyzed. On ECGI, the following parameters were analyzed before and after ajmaline administration: right ventricular outflow tract (RVOT) activation time (RVOT-AT) and RVOT recovery time (RVOT-RT). On electroanatomic map, the parameters analyzed before and after ajmaline were high-frequency potential activation time (HFPat), high-frequency potential duration (HFPd), high-frequency potential amplitude (HFPa), low-frequency potential activation time (LFPat), low-frequency potential duration (LFPd), and low-frequency potential amplitude (LFPa). Results: Thirty-nine BrS patients with ECGI were included. Eight patients (20.5%) were SCN5A+. At baseline ECGI map, mean RVOT-RT was longer in SCN5A+ (P = .024). After ajmaline administration, SCN5A+ patients showed longer RVOT-AT (125.6 vs 100.8 ms; P = .045) and longer RVOT-RT (426.4 vs 397 ms; P = .033). After ajmaline administration, SCN5A+ showed longer HFPat (164.1 vs 119.5 ms; P = .041); longer LFPat (272.7 vs 200.5 ms; P = .018); and longer LFPd (211.9 vs 151.2 ms; P = .033). Conclusion: In BrS, SCN5A+ patients compared with SCN5A– patients exhibit marked depolarization and repolarization abnormalities as assessed by ECGI and epicardial high-density electroanatomic map.

BACKGROUND: The pathogenesis of Brugada syndrome (BrS) and consequently of abnormal electrograms (aEGMs) found in the epicardium of the right ventricular outflow tract (RVOT-EPI) is controversial. OBJECTIVE: The purpose of this study was to analyze aEGM from high-density RVOT-EPI electroanatomic mapping (EAM). METHODS: All patients undergoing RVOT-EPI EAM with the HD-Grid catheter for BrS were retrospectively included. Maps were acquired before and after ajmaline, and all patients had concomitant noninvasive electrocardiographic imaging with annotation of RVOT-EPI latest activation time (RVOTat). High-frequency potentials (HFPs) were defined as ventricular potentials occurring during or after the far-field ventricular EGM showing a local activation time (HFPat). Low-frequency potentials (LFPs) were defined as aEGMs occurring after near-field ventricular activation showing fractionation or delayed components. Their activation time from surface ECG was defined as LFPat. RESULTS: Fifteen consecutive patients were included in the study. At EAM before ajmaline, 7 patients (46.7%) showed LFPs. All patients showed HFPs before and after ajmaline and LFPs after ajmaline. Mean HFPat (134.4 vs 65.3 ms, P

Background Abnormal delayed electrograms (EGMs) from the anterior wall of the right ventricular outflow tract (RVOT) epicardium have become the ablation target in Brugada syndrome (BrS). Objective The aim of this study was to analyze the safety, feasibility, and efficacy of a novel hybrid thoracoscopic approach to perform epicardial RVOT radiofrequency ablation in BrS. Methods Thirty-six patients with BrS (26 men (72.2%); mean age 36.6±15.8 years; range 3–63 years) who underwent hybrid thoracoscopic epicardial ablation of RVOT from January 2016 to April 2018 were included in this study. Two expert electrophysiologists analyzed the EGMs during ajmaline challenge and guided the surgeon to perform ablation. Ajmaline challenge was repeated after 1 month to assess the absence of the BrS electrocardiographic pattern. Patients were followed by remote monitoring and outpatient visits every 6 months. Results The elimination of all abnormal EGMs was achieved in 94.4% of patients. After a mean follow-up of 16 ± 8 months (range 6–30 months), freedom from ventricular arrhythmias was obtained in 7 (77.8%) patients in secondary prevention 9/36 (25%) and in 24 (100%) patients in primary prevention 24/36 (75%). Major complications were observed in 1 patient (2.8%), who experienced late cardiac tamponade. Conclusion Hybrid thoracoscopic epicardial RVOT ablation in BrS is a safe and feasible approach, allowing direct visualization of ablation during radiofrequency delivery. Because of ventricular arrhythmia recurrences, implantable cardioverter-defibrillator implantation is still mandatory in patients treated in secondary prevention and with high risk.

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

Patients with drug-induced Brugada syndrome (BS) are considered at a lower risk than those with a spontaneous type I pattern. Nevertheless, they can present arrhythmic events.The purpose of this study was to investigate their clinical characteristics, long-term prognosis and risk factors.A consecutive cohort of 343 patients with drug-induced BS was included and compared with 78 patients with a spontaneous type I pattern.The mean age was 40.7 ± 18.3 years. Sudden cardiac death (SCD) was the clinical presentation in 13 (3.8%) and syncope in 86 (25.1%); 244 (71.1%) were asymptomatic. Patients with drug-induced BS were less frequently men (180 (52.5%) vs 63 (80.8%); P .01), were more frequently asymptomatic (244 (71.1%) vs 44 (56.4%); P.01), and had less ventricular arrhythmias (VAs) induced during electrophysiology study (41 (13.2%) vs 31 (42.4%); P.01). An implantable cardioverter-defibrillator was implanted in 128 patients (37.3%). During a median follow-up of 62.5 months (interquartile range 28.9-115.6 months), 34 patients presented arrhythmic events. The event rate was 1.1% person-year (vs 2.3% person-year in patients with a spontaneous type I pattern; P.01). Presentation as SCD and inducible VAs were independent risk factors significantly associated with arrhythmic events (adjusted hazard ratio 22.0 and 3.5). Drug-induced BS was related to a better prognosis only in asymptomatic individuals.Drug-induced BS has a good prognosis if asymptomatic; however, SCD is possible. Clinical presentation as SCD and inducible VAs during electrophysiology study are independent risk factors for arrhythmic events. In asymptomatic patients, proband status and inducible VAs can help to identify patients at higher risk, but further evidence is needed.

Background The achievement of −40°C within the first 60 seconds during cryoenergy applications has proven to independently predict durable pulmonary vein (PV) isolation in the setting of second-generation cryoballoon (CB-A; Medtronic, Minneapolis, MN) ablation. Objective We sought to evaluate a strategy based on the attainment of the specific parameter of −40°C within the first 60 seconds during cryoenergy applications in the setting of CB-A ablation without the use of an inner lumen mapping catheter (Achieve, Medtronic) for the visualization of real-time recordings. Methods A total of 52 patients having undergone CB ablation for paroxysmal atrial fibrillation (AF) between 1 February 2015 and 30 June 2015 who underwent a temperature-guided approach based on achieving −40°C within 60 seconds without real-time recordings (wire group) were compared with a cohort of 52 propensity score–matched patients having undergone CB ablation performed with an inner lumen mapping catheter (Achieve group). All PVs were checked for electrical isolation at the end of the procedure with a circular mapping catheter in the wire group. Results Electrical isolation could be obtained in all patients in the Achieve group and in 99% of PVs in the wire group. Freedom from AF without antiarrhythmic drugs at a mean follow-up of 12.4 ± 3.0 months did not significantly differ between both groups (85% vs 88%, respectively; P = .56). Conclusion A temperature-guided approach based on achieving −40°C within 60 seconds is effective in producing PV isolation and affords freedom from AF at 12-month follow-up in 85% of patients affected by paroxysmal AF after a 3-month blanking period.

BACKGROUND: Phrenic nerve injury (PNI) is the most frequently observed complication during pulmonary vein (PV) isolation using the second-generation cryoballoon. OBJECTIVE: The purpose of this study was to analyze anatomic predictors based on preprocedural computed tomographic imaging data. METHODS: Forty-one patients with PNI during the procedure and 123 age-, gender-, and body mass index-matched controls were included. A total of 343 right PVs were evaluated for axial/coronal orientation, ostial diameters with cross-sectional area, ovality index, and branching pattern. External angle between the right superior pulmonary vein (RSPV) and the anterolateral wall of the left atrium (LA) was measured (RSPV-LA angle). Distance from this vertex to the superior vena cava (SVC) was considered the RSPV-SVC distance. RESULTS: For the RSPV, more anterosuperior orientation, larger dimensions, shorter RSPV-SVC distance, and more obtuse RSPV-LA angle (all P

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, SCOPUS: ar.j, info:eu-repo/semantics/published

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.

BACKGROUND: A left common pulmonary vein (LCPV) accounts as the most frequent PV variation. The use of the cryoballoon (CB) for isolating these veins, is still debatable. To date, no data are available regarding the feasibility, acute PV isolation, and clinical outcome of the second-generation CB (CB-A) in this setting. OBJECTIVE: To investigate the performance of the CB-A in patients with LCPVs. METHODS: In a total cohort of 433 patients having undergone CB-A ablation for drug-refractory atrial fibrillation (AF) together with pre-procedural CT-scanning, 146 patients presented a LCPV. Measurement of ostial area and trunk distance was performed, together with analysis of procedural and fluoroscopic data in order to determine the ablation strategy. The latter 146 LCPV+ were compared for outcome with a cohort of 146 propensity-score matched LCPV- patients. RESULTS: Electrical isolation could be achieved in all left-sided veins. A long left common trunk (>15mm) was found in 25% (37/146) of the LCPV+ patients. LCPVs treated with a single-shot freeze strategy presented a longer trunk (22 ± 5 mm vs 9 ± 4, P < 0,001) and smaller ostial area (305 ± 109 mm(2) vs 400 ± 108 mm(2), P < 0,001) compared to LCPV patients where a segmental (superior and inferior) freeze was delivered. AF-free survival was similar between LCPV+ and LCPV- patients during follow-up (mean 19 ± 10 months) (log rank, P = 0.33). CONCLUSION: CB-A ablation in LCPV+ patients is effective and showed no difference in clinical outcome compared to LCPV- patients.

Item does not contain fulltext BACKGROUND: Phrenic nerve palsy (PNP) is the most frequently observed complication during cryoballoon ablation (CB; Arctic Front, Medtronic, MN) occurring in roughly 7%-9% of the cases. The new second-generation cryoballoon ablation Arctic Front Advance (CB-A) (Arctic Front) has recently been launched in the market. OBJECTIVE: To evaluate the incidence of right PNP with the new CB-A in comparison with the first-generation balloon in a series of consecutive patients that underwent pulmonary vein isolation with this modality. METHODS: The study was designed as an observational study with a prospective follow-up. In total, 121 consecutive patients were included: 80 patients with the CB (group 1) and 41 with the CB-A (group 2). RESULTS: Mean procedural times, fluoroscopic times, and time to pulmonary vein isolation documented by real-time recordings were significantly lower in group 2 (P

Background The transient outward current I to is of critical importance in regulating myocardial electrical properties during the very early phase of the action potential. The auxiliary β subunit KCNE2 recently was shown to modulate I to . Objective The purpose of this study was to examine the contributions of KCNE2 and its two published variants (M54T, I57T) to I to . Methods The functional interaction between Kv4.3 (α subunit of human I to ) and wild-type (WT), M54T, and I57T KCNE2 , expressed in a heterologous cell line, was studied using patch-clamp techniques. Results Compared to expression of Kv4.3 alone, co-expression of WT KCNE2 significantly reduced peak current density, slowed the rate of inactivation, and caused a positive shift of voltage dependence of steady-state inactivation curve. These modifications rendered Kv4.3 channels more similar to native cardiac I to . Both M54T and I57T variants significantly increased I to current density and slowed the inactivation rate compared with WT KCNE2 . Moreover, both variants accelerated the recovery from inactivation. Conclusion The study results suggest that KCNE2 plays a critical role in the normal function of the native I to channel complex in human heart and that M54T and I57T variants lead to a gain of function of I to , which may contribute to generating potential arrhythmogeneity and pathogenesis for inherited fatal rhythm disorders.

Background Type 3 long-QT syndrome (LQT-3) is caused by gain-of-function mutations in the SCN5A encoding the cardiac sodium channel. Familial atrial fibrillation (AF), previously considered a potassium channelopathy, has recently been related to sodium genetic variants, both in isolated forms and in patients with underlying heart disease. Objective The purpose of this study was to describe the first family associating LQT-3 and AF due to a gain-of-function mutation in SCN5A and assess the usefulness of the sodium blocker flecainide in individuals with both phenotypes. Methods Complete family screening was performed after identifying a proband showing paroxysmal AF and a long QT interval suggestive of LQT-3. Secondary causes of AF were ruled out in all individuals. Flecainide was used in two patients for LQT-3 diagnosis and therapeutic treatment of AF. Genetic screening was performed by direct sequencing of the exons and exon-intron boundaries of SCN5A. Results We identified a three-generation family (eight members), all of them showing long QT intervals. Paroxysmal AF initiated between 20 and 35 years of age in all three adults. The flecainide test led to shortening of the QTc interval. Flecainide was also effective in acutely restoring sinus rhythm. A Y1795C mutation was identified in all members. Conclusion This is the first report showing an association of familial AF and LQT-3 due to a mutation in SCN5A. This finding provides further evidence of the role of SCN5A in AF. We also confirm the usefulness of flecainide in this particular complex phenotype, both as a diagnostic tool for LQT-3 and as an acute treatment for AF.

Background The second-generation cryoballoon Advance (CB-A) recently launched on the market has technical modifications designed to significantly improve procedural outcome with respect to the first-generation device. Objective The purpose of this study was to evaluate the overall incidence of complications in a large sample of patients having undergone pulmonary vein (PV) isolation with CB-A technology. Methods All consecutive patients who underwent PV isolation procedures using CB-A technology between June 2012 and February 2015 were considered. Exclusion criteria were presence of an intracavitary thrombus, uncontrolled heart failure, moderate or severe valvular disease, left atrial diameter ≥55 mm, and contraindications to general anesthesia. Results During the study period, 500 consecutive patients (67% male, age 57.6 ± 12.9 years) were enrolled. Major complications occurred in 10 patients (2.0%): vascular complications at the puncture site in 6 (1.2%), and thromboembolic events, cardiac tamponade, persisting phrenic nerve palsy, and retroperitoneal hematoma all occurred in a single patient respectively (0.2%). Phrenic nerve palsy occurred in 36 patients (7.2%) and did not revert in only 1 patient at final follow-up of 20 months. No deaths related to the procedure occurred. No predictors of major complication were found. Conclusion The present findings highlight that PV isolation using CB-A technology can be safely performed with a low incidence of adverse events. The incidence of major complications after atrial fibrillation ablation procedures using CB-A technology was 2% in our study. The most frequent complication consisted of vascular complications at the puncture site. No deaths related to the procedure occurred.

BACKGROUND: Sustained ventricular arrhythmias (sVA), such as polymorphic ventricular tachycardia or ventricular fibrillation, can complicate ajmaline challenge in patients with Brugada syndrome (BS). OBJECTIVE: Aim of this study was to assess the incidence of life-threating sVA during ajmaline administration in a large series of patients with BS. In addition, clinical characteristics as well as prognosis of these patients were evaluated. METHODS: All consecutive patients with ajmaline-induced diagnosis of BS were eligible for this study. RESULTS: A total of 503 patients were included. Nine patients (1.8%) (44% male, mean age: 26±18 years) experienced a life-threating sVA during ajmaline challenge. Three patients were children and 2 individuals (22%) experienced sVA refractory to the first external defibrillation. One patient underwent veno-arterial extracorporeal membrane oxygenation to restore the sinus rhythm. Age at the time of ajmaline challenge was significantly lower in the group of patients developing sVA as compared to patients without sVA (26±18 vs 41±18 years, p=0.01). Moreover, patients with sVA presented more frequently with sinus node dysfunction as compared to patients with normal response to ajmaline (22.2% vs 1.4%, P=0.01). After a mean follow-up time of 29±8 months, none of the patients having experienced sVA during ajmaline challenge died suddenly or experienced further life-threating ventricular arrhythmias. CONCLUSION: Sustained VA during ajmaline challenge is not a rare event in BS occurring in 1.8% of patients. Despite its challenging acute treatment, the occurrence of ajmaline-induced sVA in patients with BS might not identify a category at higher risk for further arrhythmic events.

Background Arrhythmogenic right ventricular cardiomyopathy (ARVC) is an inherited heart muscle disease carrying a risk of sudden death. Information about the clinical features during childhood and the age at disease onset is scanty. Objective The aim of the study was to describe the ARVC phenotype as its initial clinical manifestation in a pediatric population (14 years (42%). At the end of follow-up (9 ± 7 years), 21 (40%) fulfilled the 1994 diagnostic criteria (mean age 16 ± 4 years). By using the 2010 criteria in subjects aged ≤18 years, 53% were unaffected, versus 62% by using the traditional criteria. More than two-thirds of affected subjects had moderate-severe forms of the disease. Contrast-enhanced CMR was performed in 21 (40%); of 13 unaffected gene mutation carriers, six showed ARVC morphological and/or tissue abnormalities. Conclusion In pediatric ARVC mutation carriers, a diagnosis was achieved in 40% of cases, confirming that the disease usually develops during adolescence and young adulthood. The 2010 modified criteria seem to be more sensitive than the 1994 ones in identifying familial pediatric cases. Contrast-enhanced CMR can provide diagnostic information on gene mutation carriers not fulfilling either traditional or modified criteria. Management of asymptomatic gene mutation carriers remains the main clinical challenge.

Background\ud There is limited information on ethnic differences between patients with Brugada syndrome (BrS) and arrhythmic events (AEs).\ud \ud Objective\ud The purpose of this study was to compare clinical, electrocardiographic (ECG), electrophysiological, and genetic characteristics between white and Asian patients with BrS and AEs.\ud \ud Methods\ud 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.\ud \ud Results\ud 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.\ud \ud Conclusion\ud 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.