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Background: Brugada syndrome (BrS) is characterized by a high risk of sudden cardiac death. The clinical value of deformation imaging in patients with BrS is unknown. We aimed to assess whether echocardiographic speckle tracking parameters differ between: 1) BrS patients and healthy controls, 2) BrS patients with and without life-threatening ventricular arrhythmias., Methods: Left ventricle (LV) and right ventricle (RV) longitudinal strain and mechanical dispersion (MD) were derived from echocardiography at inclusion. Clinical and ECG data were retrospectively assessed. A life-threatening ventricular arrhythmia was defined as an aborted cardiac arrest or sustained ventricular tachyarrhythmia., Results: We included 175 BrS patients and 82 controls. LV and RV longitudinal strain were lower (-18.1 ± 2.6% vs. -18.8 ± 2.0%, p = 0.01 and - 24.4 ± 5.4% vs. 25.6 ± 3.7%, p = 0.04), while MD was higher [38 ± 11 ms vs. 33 ± 8 ms, p = 0.001 and 15 (8-25) ms vs. 11 (6-19) ms, p = 0.03] in BrS patients compared to controls. BrS patients who experienced a life-threatening ventricular arrhythmia (n = 19) had higher LV MD compared to those without events (43 ± 11 ms vs. 37 ± 11 ms, p = 0.02). An LV MD ≥40 ms was optimally associated with life-threatening ventricular arrhythmias [odds ratio 4.62 (95%CI 1.58-13.50), p = 0.005]., Conclusions: BrS patients had lower longitudinal strain and more heterogeneous contractions than healthy controls. Furthermore, BrS patients with a history of life-threatening ventricular arrhythmia had more heterogeneous LV contractions than those without. Therefore, LV MD may be a risk marker in BrS and its evaluation in prospective studies is needed., (Copyright © 2019 Elsevier B.V. All rights reserved.)

Brugada syndrome is characterized by typical electrocardiogram changes and a high risk for sudden cardiac death (Priori et al., 2013). In addition to the well known electrical substrate, morphological and functional alterations appeared to be present in a subset of the Brugada syndrome patients (Catalano et al., 2009). Echocardiographic speckle tracking enables us to detect subtle contraction alterations (Smiseth et al.,2016). We performed transthoracic echocardiography with speckle tracking analysis in 82 healthy controls and 175 Brugada syndrome patients. Main findings are presented and discussed in the article "Contraction alterations in Brugada syndrome; association with life-threatening ventricular arrhythmias" (Scheirlynck et al., 2019). This related Data article contains segmental longitudinal strain values for RV and LV, and the comparison of echocardiographic parameters between Brugada syndrome patients with spontaneous and drug-induced type 1 pattern and between patients with and without ventricular arrhythmia inducibility during electrophysiological study.

Objectives: Non-dystrophic myotonia, periodic paralysis and, to a certain extent, myotonic dystrophies are rare hereditary skeletal muscle channelopathies, charactarized by myotonia or episodic muscle weakness. This review highlights the diagnostic challenges and treatment options., Results: Some of these rare skeletal muscle disorders are associated with a broad range of systemic and nonspecific muscle symptoms. Consequently, patients are often referred to the internist before seeing a neurologist. This article provides clinical clues to better diagnose an tackle these unique disorders., Conclusion: A increased knowledge will reduce the diagnostic delay, improve monitoring and treatment, and might even prevent potentially life-threatening conditions as seen in DM.

Background: Patients with Brugada syndrome (BrS) and a history of syncope or sustained ventricular arrhythmia have longer right ventricular ejection delays (RVEDs) than asymptomatic BrS patients. Different types ofSCN5Avariants leading to different reductions in sodium current (I Na ) may have different effects on conduction delay, and consequently on electromechanical coupling (i.e., RVED). Thus, we investigated the genotype-phenotype relationship by measuring RVED to establish whether BrS patients carrying more severeSCN5Avariants leading to premature protein truncation (T) and presumably 100%I Na reduction have a longer RVED than patients carrying missense variants (M) with different degrees ofI Na reduction.Methods and Results:There were 34 BrS patients (mean [±SD] age 43.3±12.9 years; 52.9% male) carrying anSCN5Avariant and 66 non-carriers in this cross-sectional study. Patients carrying aSCN5Avariant were divided into T-carriers (n=13) and M-carriers (n=21). Using tissue velocity imaging, RVED and left ventricular ejection delay (LVED) were measured as the time from QRS onset to the onset of the systolic ejection wave at the end of the isovolumetric contraction. T-carriers had longer RVEDs than M-carriers (139.3±15.1 vs. 124.8±11.9 ms, respectively; P=0.008) and non-carriers (127.7±17.3 ms, P=0.027). There were no differences in LVED among groups., Conclusions: Using the simple, non-invasive echocardiographic parameter RVED revealed a more pronounced 'electromechanical' delay in BrS patients carrying T variants ofSCN5A.

Background: Noncompaction cardiomyopathy (NCCM) is considered to be the result of an arrest in the normal myocardial embryogenesis. The histological, developmental, and electrophysiological explanation of ventricular arrhythmias in NCCM is still unknown. The aim of this study was to determine the origin of premature ventricular contractions (PVCs) in NCCM and to identify any predominant arrhythmic foci., Methods: Retrospective data from our NCCM registry including 101 patients were analyzed. A total number of 2069 electrocardiograms (ECGs) were studied to determine the origin of PVCs. Echocardiographic data were analyzed in patients with PVCs in all 12 leads. Segments affected by noncompaction (NC) were compared with the origin of PVCs., Results: PVCs were documented in 250 ECGs from 55 (54%) patients. Thirty-five ECGs recorded PVCs on all 12 leads and the origin of 20 types of PVCs could be determined. Ninety-five percent of PVCs did not originate from left ventricular NC myocardial areas and two PVCs (10%) had a true myocardial origin. All other PVCs originated from structures such as the outflow tracts (8/20), the fascicles (7/20), especially the posteromedial fascicle (6/20), and the mitral and tricuspid annulus (3/20)., Conclusions: Our data suggest that PVCs in NCCM mainly originate from the conduction system and related myocardium., (© 2016 Wiley Periodicals, Inc.)

Background: After the introduction of the Biotronik Linox S/SD high-voltage lead, several cases of early failure have been observed., Objective: The purpose of this article was to assess the performance of the Linox S/SD lead in comparison to 2 other contemporary leads., Methods: We used the prospective Erasmus MC ICD registry to identify all implanted Linox S/SD (n = 408), Durata (St. Jude Medical, model 7122) (n = 340), and Endotak Reliance (Boston Scientific, models 0155, 0138, and 0158) (n = 343) leads. Lead failure was defined by low- or high-voltage impedance, failure to capture, sense or defibrillate, or the presence of nonphysiological signals not due to external interference., Results: During a median follow-up of 5.1 years, 24 Linox (5.9%), 5 Endotak (1.5%), and 5 Durata (1.5%) leads failed. At 5-year follow-up, the cumulative failure rate of Linox leads (6.4%) was higher than that of Endotak (0.4%; P < .0001) and Durata (2.0%; P = .003) leads. The incidence rate was higher in Linox leads (1.3 per 100 patient-years) than in Endotak and Durata leads (0.2 and 0.3 per 100 patient-years, respectively; P < .001). A log-log analysis of the cumulative hazard for Linox leads functioning at 3-year follow-up revealed a stable failure rate of 3% per year. The majority of failures consisted of noise (62.5%) and abnormal impedance (33.3%)., Conclusion: This study demonstrates a higher failure rate of Linox S/SD high-voltage leads compared to contemporary leads. Although the mechanism of lead failure is unclear, the majority presents with abnormal electrical parameters. Comprehensive monitoring of Linox S/SD high-voltage leads includes remote monitoring to facilitate early detection of lead failure., (Copyright © 2016. Published by Elsevier Inc.)

SCN5A mutations involving the α-subunit of the cardiac voltage-gated muscle sodium channel (NaV1.5) result in different cardiac channelopathies with an autosomal-dominant inheritance such as Brugada syndrome. On the other hand, mutations in SCN4A encoding the α-subunit of the skeletal voltage-gated sodium channel (NaV1.4) cause non-dystrophic myotonia and/or periodic paralysis. In this study, we investigated whether cardiac arrhythmias or channelopathies such as Brugada syndrome can be part of the clinical phenotype associated with SCN4A variants and whether patients with Brugada syndrome present with non-dystrophic myotonia or periodic paralysis and related gene mutations. We therefore screened seven families with different SCN4A variants and non-dystrophic myotonia phenotypes for Brugada syndrome and performed a neurological, neurophysiological and genetic work-up in 107 Brugada families. In the families with an SCN4A-associated non-dystrophic myotonia, three patients had a clinical diagnosis of Brugada syndrome, whereas we found a remarkably high prevalence of myotonic features involving different genes in the families with Brugada syndrome. One Brugada family carried an SCN4A variant that is predicted to probably affect function, one family suffered from a not genetically confirmed non-dystrophic myotonia, one family was diagnosed with myotonic dystrophy (DMPK gene) and one family had a Thomsen disease myotonia congenita (CLCN1 variant that affects function). Our findings and data suggest a possible involvement of SCN4A variants in the pathophysiological mechanism underlying the development of a spontaneous or drug-induced type 1 electrocardiographic pattern and the occurrence of malignant arrhythmias in some patients with Brugada syndrome.

Background: The prognostic value of electrophysiological investigations in individuals with Brugada syndrome remains controversial. Different groups have published contradictory data. Long-term follow-up is needed to clarify this issue., Methods and Results: Patients presenting with spontaneous or drug-induced Brugada type I ECG and in whom programmed electric stimulation was performed at our institution were considered eligible for this study. A total of 403 consecutive patients (235 males, 58.2%; mean age, 43.2±16.2 years) were included. Ventricular arrhythmias during programmed electric stimulation were induced in 73 (18.1%) patients. After a mean follow-up time of 74.3±57.3 months (median 57.3), 25 arrhythmic events occurred (16 in the inducible group and 9 in the noninducible). Ventricular arrhythmias inducibility presented a hazard ratio for events of 8.3 (95% confidence interval, 3.6-19.4), P<0.01., Conclusions: Programmed ventricular stimulation of the heart is a good predictor of outcome in individuals with Brugada syndrome. It might be of special value to guide further management when performed in asymptomatic individuals. The overall accuracy of the test makes it a suitable screening tool to reassure noninducible asymptomatic individuals., (© 2015 American Heart Association, Inc.)

Background and Objectives: Right ventricular (RV) conduction delay has been suggested as an underlying pathophysiological mechanism in Brugada syndrome (BS). In this cross-sectional study we non-invasively assessed the value of echocardiographic markers reflecting ventricular ejection delay to further assess electromechanical abnormalities in BS and to identify patients at risk for life-threatening arrhythmic events. Furthermore, we sought to assess differences in ejection delays between genders because male BS patients demonstrate a more malignant clinical phenotype., Methods: 124 BS patients (57.3% males) and 62 controls (CTR) (48.4% males) were included. Using Tissue Velocity Imaging, the ejection delay, determined as the time from QRS onset to the onset of the sustained systolic contraction, was measured for both RV free wall (RVED) and lateral LV wall (LVED). From these parameters, the interventricular ejection delay between both walls (IVED) was calculated., Results: BS patients had longer RVEDs and IVEDs compared to the CTR. BS patients with a previous history of syncope or spontaneous ventricular arrhythmia showed the longest RVEDs and IVEDs. Male BS patients demonstrated longer RVEDs and IVEDs than females. Male BS patients with malignant events had the longest delays. No significant differences regarding LVED were observed between BS patients and CTR., Conclusions: We demonstrated that a previous history of malignant events was associated with longer RVEDs. Our findings supported the RV conduction delay mechanism behind BS and demonstrated for the first time that the predominant malignant male Brugada phenotype might also be the result of a more delayed RV conduction in males., (Copyright © 2015 Elsevier Ireland Ltd. All rights reserved.)

Background: Brugada syndrome (BrS) is an inheritable cardiac disease associated with syncope, malignant ventricular arrhythmias and sudden cardiac death. The largest proportion of mutations in BrS is found in the SCN5A gene encoding the α-subunit of cardiac sodium channels (Nav1.5). Causal SCN5A mutations are present in 18-30% of BrS patients. The additional genetic diagnostic yield of variants in cardiac sodium channel β-subunits in BrS patients was explored and functional studies on 3 novel candidate variants were performed., Methods and results: TheSCN1B-SCN4B genes were screened, which encode the 5 sodium channel β-subunits, in a SCN5A negative BrS population (n=74). Five novel variants were detected; in silico pathogenicity prediction classified 4 variants as possibly disease causing. Three variants were selected for functional study. These variants caused only limited alterations of Nav1.5 function. Next generation sequencing of a panel of 88 arrhythmia genes could not identify other major causal mutations., Conclusions: It was hypothesized that the studied variants are not the primary cause of BrS in these patients. However, because small functional effects of these β-subunit variants can be discriminated, they might contribute to the BrS phenotype and be considered a risk factor. The existence of these risk factors can give an explanation to the reduced penetrance and variable expressivity seen in this syndrome. We therefore recommend including the SCN1-4B genes in a next generation sequencing-based gene panel.

Background: Propofol is an anesthetic drug with a very attractive pharmacokinetic profile, which makes it the induction agent of choice, especially in day-case surgery. Data on its potential proarrhythmic effects in patients with Brugada syndrome (BS) patients are still lacking. The aim of our study was to investigate whether a single dose of propofol triggered any adverse events in consecutive high-risk patients with BS., Methods: All consecutive patients with BS having undergone an implantable cardiac defibrillator implantation under general anesthesia were eligible for this study. The anesthetic chart of each patient was reviewed, and the occurrence of malignant arrhythmic events as well as the need for defibrillation during induction and maintenance of anesthesia was investigated. Further monitoring of the patient comprised five-lead electrocardiogram (ECG), pulse oxymetry, and continuous carbon dioxide monitoring through side sampling from the ventilator tubes. Anesthesia was induced with propofol and sufentanyl. Injection of propofol occurred in a single-shot bolus-as often performed by most anesthetists-over a few seconds. Anesthesia was maintained with volatile anesthetics (sevoflurane or desflurane) in an oxygen-air mixture., Results: From 1996 to 2011, 57 high-risk patients with BS (35 males; mean age: 43 ± 16 years) underwent an automated implantable cardioverter defibrillator implantation at our center using propofol as induction drug of general anesthesia. Three patients had a history of spontaneous type I ECG, three had aborted sudden death, and 51 had a history of recurrent or unexplained syncope. The induction dose ranged between 0.8 mg/kg and 5.0 mg/kg (2.2 ± 0.7 mg/kg). Only one case received propofol to maintain anesthesia. The surgical procedure involved an anesthetic period of 75 ± 25 minutes. No patient developed a malignant rhythm during induction and maintenance of anesthesia. All patients were then safely discharged from the postanesthetic care unit after 1 hour. No adverse events were noticed during the recovery phase. In our study, administration of a single-dose propofol in patients with BS was safe. Nevertheless, extreme caution is still recommended when conducting general anesthesia in patients with BS, especially if BS patients are sedated with propofol for longer periods., (©2013, The Authors. Journal compilation ©2013 Wiley Periodicals, Inc.)

Atrial fibrillation (AF) can be the first manifestation of latent Brugada syndrome (BS). The aim of our study was to assess the prevalence of AF as the first clinical diagnosis in patients with BS and their demographic and clinical characteristics and diagnosis management in a large cohort of patients. The patient group consisted of 611 patients with BS. The data from those with a diagnosis of AF previous to the identification of BS were analyzed (n = 35). Eleven cases were unmasked after the initiation of a class I antiarrhythmic drug and one during the establishment of general anesthesia. In the remaining population, BS was diagnosed using an ajmaline test performed mainly because of younger age in patients with lone AF (n = 13), previous syncope or sudden cardiac death (n = 3), or a clinical history of sudden cardiac death in the family (n = 5). The mean patient age was 49 ± 15 years, 21 were male patients, 14 had a family history of sudden death, 15 had had previous syncope, and 4 had survived cardiac arrest. Concomitant electrical disorder was found in 13 patients. Remarkably, 21 patients had normal findings on the baseline electrocardiogram. In conclusion, AF could be one of the first clinical manifestations of latent BS in a considerable number of patients. This identification is crucial because the treatment of these patients is subject to relevant changes. The ajmaline test plays an essential role, mainly in young patients with a family history of sudden death, despite having normal findings on a baseline electrocardiogram., (Copyright © 2013 Elsevier Inc. All rights reserved.)

It has long been assumed that the ventilation heterogeneity associated with lung disease could, in itself, affect the measurement of carbon monoxide transfer factor. The aim of this study was to investigate the potential estimation errors of carbon monoxide diffusing capacity (Dl(CO)) measurement that are specifically due to conductive ventilation heterogeneity, i.e., due to a combination of ventilation heterogeneity and flow asynchrony between lung units larger than acini. We induced conductive airway ventilation heterogeneity in 35 never-smoker normal subjects by histamine provocation and related the resulting changes in conductive ventilation heterogeneity (derived from the multiple-breath washout test) to corresponding changes in diffusing capacity, alveolar volume, and inspired vital capacity (derived from the single-breath Dl(CO) method). Average conductive ventilation heterogeneity doubled (P < 0.001), whereas Dl(CO) decreased by 6% (P < 0.001), with no correlation between individual data (P > 0.1). Average inspired vital capacity and alveolar volume both decreased significantly by, respectively, 6 and 3%, and the individual changes in alveolar volume and in conductive ventilation heterogeneity were correlated (r = -0.46; P = 0.006). These findings can be brought in agreement with recent modeling work, where specific ventilation heterogeneity resulting from different distributions of either inspired volume or end-expiratory lung volume have been shown to affect Dl(CO) estimation errors in opposite ways. Even in the presence of flow asynchrony, these errors appear to largely cancel out in our experimental situation of histamine-induced conductive ventilation heterogeneity. Finally, we also predicted which alternative combination of specific ventilation heterogeneity and flow asynchrony could affect Dl(CO) estimate in a more substantial fashion in diseased lungs, irrespective of any diffusion-dependent effects.