RESUMO
Early repolarization syndrome (ERS) is defined as occurring in patients with early repolarization pattern who have survived idiopathic ventricular fibrillation with clinical evaluation unrevealing for other explanations. The pathophysiologic basis of the ERS is currently uncertain. The objective of the present study was to examine the electrophysiological mechanism of ERS utilizing induced pluripotent stem cells (iPSCs) and CRISPR/Cas9 genome editing. Whole genome sequencing was used to identify the DPP6 (c.2561T > C/p.L854P) variant in four families with sudden cardiac arrest induced by ERS. Cardiomyocytes were generated from iPSCs from a 14-year-old boy in the four families with ERS and an unrelated healthy control subject. Patch clamp recordings revealed more significant prolongation of the action potential duration (APD) and increased transient outward potassium current (Ito) (103.97 ± 18.73 pA/pF vs 44.36 ± 16.54 pA/pF at +70 mV, P < 0.05) in ERS cardiomyocytes compared with control cardiomyocytes. Of note, the selective correction of the causal variant in iPSC-derived cardiomyocytes using CRISPR/Cas9 gene editing normalized the Ito, whereas prolongation of the APD remained unchanged. ERS cardiomyocytes carrying DPP6 mutation increased Ito and lengthen APD, which maybe lay the electrophysiological foundation of ERS.
RESUMO
Arrhythmias account for over 300,000 annual deaths in the United States, and approximately half of all deaths are associated with heart disease. Mechanisms underlying arrhythmia risk are complex; however, work in humans and animal models over the past 25 years has identified a host of molecular pathways linked with both arrhythmia substrates and triggers. This chapter will focus on select arrhythmia pathways solved by linking human clinical and genetic data with animal models.
Assuntos
Arritmias Cardíacas , Modelos Animais de Doenças , Animais , Humanos , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatologia , Arritmias Cardíacas/metabolismo , Transdução de Sinais/genéticaRESUMO
A 60-year-old man was referred to our hospital presenting with unconsciousness due to severe hyponatremia. The twelvelead ECG on admission exhibited prominent J waves in the inferolateral leads. During the treatment for hyponatremia, ventricular fibrillation (VF) occurred and the electrogram (ECG) after the VF incident exhibited marked ST elevation in the inferolateral leads. An Ach provocation test induced vasospasms in the right and left coronary arteries and J wave augmentation, suggesting a high risk for vasospastic angina. Finally, a subcutaneous implantable cardioverter defibrillator was implanted in the patient. We hereby discuss the possible contribution of hyponatremia to VF episodes in early repolarization syndrome based on the present case.
Assuntos
Vasoespasmo Coronário , Eletrocardiografia , Hiponatremia , Fibrilação Ventricular , Humanos , Masculino , Fibrilação Ventricular/etiologia , Fibrilação Ventricular/fisiopatologia , Fibrilação Ventricular/diagnóstico , Pessoa de Meia-Idade , Hiponatremia/etiologia , Vasoespasmo Coronário/fisiopatologia , Vasoespasmo Coronário/diagnóstico , Vasoespasmo Coronário/complicações , Desfibriladores Implantáveis , SíndromeRESUMO
Primary electrical heart diseases, often considered channelopathies, are inherited genetic abnormalities of cardiomyocyte electrical behavior carrying the risk of malignant arrhythmias leading to sudden cardiac death (SCD). Approximately 54% of sudden, unexpected deaths in individuals under the age of 35 do not exhibit signs of structural heart disease during autopsy, suggesting the potential significance of channelopathies in this group of age. Channelopathies constitute a highly heterogenous group comprising various diseases such as long QT syndrome (LQTS), short QT syndrome (SQTS), idiopathic ventricular fibrillation (IVF), Brugada syndrome (BrS), catecholaminergic polymorphic ventricular tachycardia (CPVT), and early repolarization syndromes (ERS). Although new advances in the diagnostic process of channelopathies have been made, the link between a disease and sudden cardiac death remains not fully explained. Evolving data in electrophysiology and genetic testing suggest previously described diseases as complex with multiple underlying genes and a high variety of factors associated with SCD in channelopathies. This review summarizes available, well-established information about channelopathy pathogenesis, genetic basics, and molecular aspects relative to principles of the pathophysiology of arrhythmia. In addition, general information about diagnostic approaches and management is presented. Analyzing principles of channelopathies and their underlying causes improves the understanding of genetic and molecular basics that may assist general research and improve SCD prevention.
Assuntos
Canalopatias , Síndrome do QT Longo , Humanos , Canalopatias/complicações , Arritmias Cardíacas/diagnóstico , Morte Súbita Cardíaca/etiologia , Morte Súbita Cardíaca/prevenção & controle , Fibrilação VentricularRESUMO
Despite early repolarization (ER) syndrome being usually considered benign, its association with severe/malignant ventricular arrhythmias (VA) was also reported. Microvolt T-wave alternans (MTWA) is an electrocardiographic marker for the development of VA, but its role in ER syndrome remains unknown. A 90-second 6-lead electrocardiogram from an ER syndrome patient, acquired with the Kardia recorder, was analyzed by the enhanced adaptive matched filter for MTWA quantification. On average, MTWA was 50 µV, higher than what was previously observed on healthy subjects using the same method. In our ER syndrome patient, MTWA plays a potential role in VA development in ER syndrome.
Assuntos
Morte Súbita Cardíaca , Desfibriladores Implantáveis , Humanos , Morte Súbita Cardíaca/etiologia , Eletrocardiografia/métodos , Arritmias Cardíacas/complicações , Arritmias Cardíacas/diagnóstico , Medição de Risco , Desfibriladores Implantáveis/efeitos adversosRESUMO
A 6-year-old girl presented with a difficult to control epilepsy syndrome. On evaluation, additional presyncope episodes associated with polymorphic ventricular tachycardia were also noted. A diagnosis of early repolarization syndrome (ERS) was made with an early repolarization pattern on electrocardiogram, documented VT episodes, and clinical presyncope (proposed Shanghai score 7). Paroxysmal atrial fibrillation (AF) was also noted on 24-h Holter recordings. The child was stabilized with isoprenaline infusion and was later discharged with arrhythmia control on quinidine and cilostazol. The genetic evaluation revealed a potassium channel KCND3 gene missense mutation. The case highlights the association of epilepsy syndrome and AF with ERS; the possible association of KCND3 gene mutation with a malignant phenotype; and management issues in a small child.
Assuntos
Fibrilação Atrial , Epilepsia , Síndromes Epilépticas , Fibrilação Atrial/diagnóstico , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/genética , China , Eletrocardiografia , Humanos , Mutação , Quinidina/uso terapêutico , Canais de Potássio Shal/genética , SíncopeRESUMO
Most causal genes for inherited arrhythmia syndromes (IASs) encode cardiac ion channel-related proteins. Genotype-phenotype studies and functional analyses of mutant genes, using heterologous expression systems and animal models, have revealed the pathophysiology of IASs and enabled, in part, the establishment of causal gene-specific precision medicine. Additionally, the utilization of induced pluripotent stem cell (iPSC) technology have provided further insights into the pathophysiology of IASs and novel promising therapeutic strategies, especially in long QT syndrome. It is now known that there are atypical clinical phenotypes of IASs associated with specific mutations that have unique electrophysiological properties, which raises a possibility of mutation-specific precision medicine. In particular, patients with Brugada syndrome harboring an SCN5A R1632C mutation exhibit exercise-induced cardiac events, which may be caused by a marked activity-dependent loss of R1632C-Nav1.5 availability due to a marked delay of recovery from inactivation. This suggests that the use of isoproterenol should be avoided. Conversely, the efficacy of ß-blocker needs to be examined. Patients harboring a KCND3 V392I mutation exhibit both cardiac (early repolarization syndrome and paroxysmal atrial fibrillation) and cerebral (epilepsy) phenotypes, which may be associated with a unique mixed electrophysiological property of V392I-Kv4.3. Since the epileptic phenotype appears to manifest prior to cardiac events in this mutation carrier, identifying KCND3 mutations in patients with epilepsy and providing optimal therapy will help prevent sudden unexpected death in epilepsy. Further studies using the iPSC technology may provide novel insights into the pathophysiology of atypical clinical phenotypes of IASs and the development of mutation-specific precision medicine.
Assuntos
Arritmias Cardíacas/diagnóstico , Fibrilação Atrial/diagnóstico , Síndrome de Brugada/diagnóstico , Síndrome do QT Longo/diagnóstico , Arritmias Cardíacas/diagnóstico por imagem , Arritmias Cardíacas/genética , Arritmias Cardíacas/fisiopatologia , Fibrilação Atrial/diagnóstico por imagem , Fibrilação Atrial/genética , Fibrilação Atrial/fisiopatologia , Síndrome de Brugada/diagnóstico por imagem , Síndrome de Brugada/genética , Síndrome de Brugada/fisiopatologia , Eletrofisiologia Cardíaca , Morte Súbita Cardíaca/epidemiologia , Morte Súbita Cardíaca/prevenção & controle , Humanos , Síndrome do QT Longo/diagnóstico por imagem , Síndrome do QT Longo/genética , Síndrome do QT Longo/fisiopatologia , Fenótipo , Medicina de PrecisãoRESUMO
Previous studies demonstrated that variants in dipeptidyl aminopeptidase-like protein-6 (DPP6) are involved in idiopathic ventricular fibrillation. However, its role in early repolarization syndrome (ERS) remains largely elusive. The aim of this study is to determine whether the novel DPP6-L747P variant is associated with ERS, and explore the underlying mechanisms. In our study, whole genome sequencing was used to identify a genetic variant in 4 Chinese families with sudden cardiac arrest induced by ERS. Then, wild-type (WT) DPP6 or mutant (c.2240Tâ¯>â¯C/p.L747P) DPP6 were respectively expressed in HEK293â¯cells, co-expressed with KV4.3 and KChIP2. Western blotting, immunofluorescence, and whole-cell patch clamp experiments were performed to reveal possible underlying mechanisms. A novel missense variant (c.2240Tâ¯>â¯C/p.L747P) in DPP6 was identified in the 4 families. Both DPP6-WT and DPP6-L747P were mainly located on the cell membrane. Compared with DPP6-WT, the intensity of DPP6 protein bands was downregulated in DPP6-L747P. Functional experiments showed that macroscopic currents exhibited an increase in DPP6-L747P, and the current intensity of DPP6-L747P was increased more than that of DPP6-WT (63.1 ± 8.2 pA/pF vs.86.5 ± 15.1 pA/pF at +50 mV, Pâ¯<â¯0.05). Compared with DPP6-WT, the slope of the activation curve of DPP6-L747P was slightly decreased (15.49⯱â¯0.56â¯mV vs. 13.88⯱â¯0.54â¯mV, Pâ¯<â¯0.05), the slope of the inactivation curve was increased (13.65⯱â¯1.57â¯mV, vs. 24.44⯱â¯2.79â¯mV, Pâ¯<â¯0.05) and the recovery time constant was significantly reduced (216.81⯱â¯18.59â¯ms vs. 102.11⯱â¯32.03â¯ms, Pâ¯<â¯0.05). In conclusion, we identified a novel missense variant (c.2240Tâ¯>â¯C/p. L747P) in DPP6 in 4 Chinese families with sudden cardiac arrest induced by ERS. Patch clamp experiments revealed that this variant could generate a gain of function of Ito and affect the potassium current. These results demonstrated that changes caused by the variant may be the underlying mechanisms of malignant arrhythmias in the individuals with ERS.
Assuntos
Arritmias Cardíacas/genética , Povo Asiático/genética , Dipeptidil Peptidases e Tripeptidil Peptidases/genética , Mutação de Sentido Incorreto/genética , Proteínas do Tecido Nervoso/genética , Canais de Potássio/genética , Adolescente , Linhagem Celular , Membrana Celular/genética , Morte Súbita Cardíaca , Regulação para Baixo/genética , Família , Feminino , Células HEK293 , Humanos , MasculinoRESUMO
Objectives. Pericarditis, takotsubo cardiomyopathy and early repolarization syndrome (ERS) are well-known to mimic ST elevation myocardial infarction (STEMI). We aimed to study whether ECG findings of reciprocal ST depression, PR depression, ST-segment convexity or terminal QRS distortion can discriminate between ST elevation due to ischemia and non-ischemic conditions. Design. Eighty-five patients with STEMI and 94 patients with non-ischemic ST elevation were included. All patients had acute chest pain and at least 0.1 mV ST elevation. Presence of PR depression, ST-segment convexity, terminal QRS distortion or reciprocal ST depression was assessed in each ECG. Results. In anterior ST elevation, ST depression in lead II (≥0.025 mV) occurred in 40% of patients with STEMI but in none of the non-ischemic cases. In inferior ST elevation, ST depression in lead I (≥0.025 mV) was present in 83% of patients with STEMI but in none of the non-ischemic cases. Chest-lead PR depression was uncommon in STEMI (12%) compared to non-ischemic cases (38%; p < .001). Convex ST elevation occurred in 22% of STEMI cases and in 9% of non-ischemic cases (p = .01). Terminal QRS distortion was more prevalent in STEMI (40%) than in non-ischemic ST elevation (7%). In multivariable analysis, reciprocal ST depression was associated with an ischemic diagnosis, whereas ST depression in aVR and chest-lead PR depression were associated with a non-ischemic diagnosis. Conclusions. Identification of true STEMI among patients with different ST-elevation etiology may be improved by considering reciprocal ST depression, ST depression in aVR and chest-lead PR depression.
Assuntos
Potenciais de Ação , Arritmias Cardíacas/diagnóstico , Eletrocardiografia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Pericardite/diagnóstico , Cardiomiopatia de Takotsubo/diagnóstico , Adulto , Idoso , Arritmias Cardíacas/fisiopatologia , Diagnóstico Diferencial , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pericardite/fisiopatologia , Valor Preditivo dos Testes , Estudos Retrospectivos , Cardiomiopatia de Takotsubo/fisiopatologia , Fatores de Tempo , Adulto JovemRESUMO
While a KCND3 V392I mutation uniquely displays a mixed electrophysiological phenotype of Kv4.3, only limited clinical information on the mutation carriers is available. We report two teenage siblings exhibiting both cardiac (early repolarization syndrome and paroxysmal atrial fibrillation) and cerebral phenotypes (epilepsy and intellectual disability), in whom we identified the KCND3 V392I mutation. We propose a link between the KCND3 mutation with a mixed electrophysiological phenotype and cardiocerebral phenotypes, which may be defined as a novel cardiocerebral channelopathy.
Assuntos
Fibrilação Atrial/genética , Canalopatias/genética , Epilepsias Parciais/genética , Deficiência Intelectual/genética , Canais de Potássio Shal/genética , Adolescente , Morte Súbita Cardíaca , Eletrocardiografia , Eletroencefalografia , Feminino , Humanos , Pessoa de Meia-Idade , Mães , Mutação , Linhagem , Irmãos , Síncope/genética , Adulto JovemRESUMO
BACKGROUND: Recent studies have revealed that mutation in KCNE1, ß-subunits of cardiac potassium channel, involved in ventricular fibrillation. Whereas its role in early repolarization syndrome (ERS) is less well understood. OBJECTIVE: To study whether mutant in KCNE1 is associated with ERS and explore the possible underlying molecular mechanisms. METHODS: Whole genome from four unrelated families with ERS was amplified and sequenced. Wild-type (WT) KCNE1 and/or KCNE1-S38G (S38G) were expressed in HEK293 cells with KCNQ1. Functional studies included whole-cell patch-clamp, western blot and immunofluorescence were performed to reveal the possible underlying mechanisms. RESULTS: The co-expression of KCNE1-S38G and KCNQ1 decreased tail current density of IKs but had little effect in modulation channel kinetics of IKs. Compared with KCNE1-WT, the expression and membrane location of KCNE1-S38G decreased. Co-expression of KCNE1-WT and KCNE1-S38G partially rescued the function of IKs channel. CONCLUSIONS: The S38G mutation induced a loss-of-function of IKs due to decreasing of KCNE1 protein expression and defecting in KCNE1 protein membrane trafficking. Our findings suggested that KCNE1 may be one of the possible modulatory genes associated to ERS.
Assuntos
Mutação/genética , Canais de Potássio de Abertura Dependente da Tensão da Membrana/genética , Adulto , Idoso , Predisposição Genética para Doença , Células HEK293 , Humanos , Masculino , Moduladores de Transporte de Membrana/metabolismo , Pessoa de Meia-Idade , Linhagem , Potássio/metabolismoRESUMO
BACKGROUND: Abnormal cardiac ion channels current, including transient outward potassium current (Ito ), is associated with early repolarization syndrome (ERS). Previous studies showed that mutations in SCN1Bß both to increase the Ito current and to decrease the sodium current. Yet its role in ERS remains unknown. OBJECTIVE: To determine the role of mutations in the SCN1Bß subunits in ERS. METHODS: We screened for mutations in the SCN1B genes from four families with ERS. Wild-type and mutant SCN1Bß genes were co-expressed with wild-type KCND3 in human embryonic kidney cells (HEK293). Whole-cell patch-clamp technique and co-immunoprecipitation were used to study the electrophysiological properties and explore the underlying mechanisms. RESULTS: S248R and R250T mutations in SCN1Bß were detected in 4 families' probands. Neither S248R nor R250T mutation had significant influence on the sodium channel current density (INa ) when co-expressed with SCN5A/WT. Co-expression of KCND3/WT and SCN1Bß/S248R or SCN1Bß/R250T increased the transient outward potassium current Ito by 27.44% and 199.89%, respectively (P < 0.05 and P < 0.01, respectively) when compared with SCN1Bß/WT. Electrophysiological properties showed that S248R and R250T mutations decreased the steady-state inactivation and recovery from inactivation of Ito channel. Co-immunoprecipitation study demonstrated an increased association between SCN1Bß mutations and Kv4.3 compared with SCN1Bß/WT (P < 0.05 and P < 0.01, respectively). CONCLUSION: The S248R and R250T mutations of SCN1Bß gene caused gain-of-function of Ito by associated with Kv4.3, which maybe underlie the ERS phenotype of the probands.
Assuntos
Morte Súbita Cardíaca/patologia , Coração/fisiopatologia , Canais de Potássio Shal/genética , Subunidade beta-1 do Canal de Sódio Disparado por Voltagem/genética , Adulto , Idoso , Animais , Eletrofisiologia , Feminino , Predisposição Genética para Doença , Células HEK293 , Coração/diagnóstico por imagem , Humanos , Masculino , Potenciais da Membrana , Mutação/genética , Técnicas de Patch-Clamp , TransfecçãoRESUMO
BACKGROUND/AIMS: Early repolarization syndrome (ERS) has been recently recognized as early repolarization pattern with idiopathic ventricular fibrillation. However, the genetic background of ERS has not been fully understood. METHODS: A Chinese family with sudden cardiac death associated with ERS was investigated. Direct sequencing of ERS susceptibility genes was performed on the proband and family members. Whole-cell patch-clamp methods were used to characterize the mutant channel expressed in HEK 293 cells. RESULTS: One missense mutation (p. K801T) was found in the hERG (KCNH2 gene) by the direct sequencing of candidate genes. Whole cell voltage clamp studies of the K801T mutation in HEK 293 cells demonstrated a 1.5-fold increase in maximum steady state current (37.2±7.3 vs 20.3±4.4 pA/pF) that occurred at a 20 mV more positive potential compared to the wild type channels. The voltage dependence of inactivation was significantly shifted in the positive voltage direction (WT -59.5±1.4 vs K801T -44.3±1.2 mV). Kinetic analysis revealed slower inactivation rates of K801T, but faster rates of activation and deactivation. The hERG channel blockers tested inhibited K801T-hERG channel in concentration response, and the potencies of these drugs can be rank-ordered as follows: quinidine> disopyramide> sotalol> flecainide. CONCLUSION: Our study indicated that the K801T mutation caused the gain of function of hERG channels that may account for the clinical phenotype of ERS. Quinidine and disopyramide could improve the function of K801T-hERG mutant channel, and may be therapeutic options for patients with the K801T hERG mutation.
Assuntos
Canal de Potássio ERG1/genética , Mutação de Sentido Incorreto , Fibrilação Ventricular/genética , Adulto , Morte Súbita Cardíaca/etiologia , Células HEK293 , Heterozigoto , Humanos , Masculino , Linhagem , Fibrilação Ventricular/complicaçõesRESUMO
The J wave syndromes, including the Brugada (BrS) and early repolarization (ERS) syndromes, are characterized by the manifestation of prominent J waves in the electrocardiogram appearing as an ST segment elevation and the development of life-threatening cardiac arrhythmias. BrS and ERS differ with respect to the magnitude and lead location of abnormal J waves and are thought to represent a continuous spectrum of phenotypic expression termed J wave syndromes. Despite over 25 years of intensive research, risk stratification and the approach to therapy of these two inherited cardiac arrhythmia syndromes are still rapidly evolving. Our objective in this review is to provide an integrated synopsis of the clinical characteristics, risk stratifiers, as well as the molecular, ionic, cellular, and genetic mechanisms underlying these two syndromes that have captured the interest and attention of the cardiology community over the past two decades.
Assuntos
Arritmias Cardíacas/etiologia , Doença do Sistema de Condução Cardíaco/complicações , Síndrome de Brugada/complicações , Síndrome de Brugada/fisiopatologia , Doença do Sistema de Condução Cardíaco/genética , Doença do Sistema de Condução Cardíaco/fisiopatologia , Doença do Sistema de Condução Cardíaco/terapia , Eletrocardiografia , HumanosRESUMO
The voltage-gated cardiac sodium channel (Nav1.5) is a mega-complex comprised of a pore-forming α subunit and 4 ancillary ß-subunits together with numerous protein partners. Genetic defects in the form of rare variants in one or more sodium channel-related genes can cause a loss- or gain-of-function of sodium channel current (INa) leading to the manifestation of various disease phenotypes, including Brugada syndrome, long QT syndrome, progressive cardiac conduction disease, sick sinus syndrome, multifocal ectopic Purkinje-related premature contractions, and atrial fibrillation. Some sodium channelopathies have also been shown to be responsible for sudden infant death syndrome (SIDS). Although these genetic defects often present as pure electrical diseases, recent studies point to a contribution of structural abnormalities to the electrocardiographic and arrhythmic manifestation in some cases, such as dilated cardiomyopathy. The same rare variants in SCN5A or related genes may present with different clinical phenotypes in different individuals and sometimes in members of the same family. Genetic background and epigenetic and environmental factors contribute to the expression of these overlap syndromes. Our goal in this chapter is to review and discuss what is known about the clinical phenotype and genotype of each cardiac sodium channelopathy, and to briefly discuss the underlying mechanisms.
Assuntos
Arritmias Cardíacas/etiologia , Mutação , Canal de Sódio Disparado por Voltagem NAV1.5/genética , Animais , Síndrome de Brugada/etiologia , Humanos , Síndrome do QT Longo/etiologia , Canal de Sódio Disparado por Voltagem NAV1.5/fisiologiaRESUMO
INTRODUCTION: Brugada syndrome (BrS) and early repolarization syndrome (ERS) are termed the J-wave syndrome. In most cases of J-wave syndrome, ventricular fibrillation (VF) often occurs around midnight or in the early morning when parasympathetic tone is augmented. OBJECTIVE: The purpose of this study was to clarify the relationship between VF and autonomic nervous activity in patients with J-wave syndrome. METHODS AND RESULTS: We enrolled 28 consecutive patients with J-wave syndrome (20 BrS and 8 ERS) in whom implantable cardioverter defibrillators (ICDs) were implanted between January 2002 and December 2014. Eleven patients (39%) experienced ICD shock delivery due to VF recurrence after ICD implantation (recurrent-VF group). We investigated baroreflex sensitivity (BRS) using the phenylephrine method, heart rate variability (HRV) with Holter electrocardiography, plasma levels of norepinephrine, and cardiac 123 I-metaiodobenzylguanidine (MIBG) scintigraphy to estimate autonomic nervous function. Upon measurement of HRV, plasma levels of norepinephrine, and 123 I-MIBG testing, there was no significant difference between recurrent-VF and nonrecurrent-VF groups. However, BRS was significantly higher in the recurrent-VF group than in the nonrecurrent-VF group (P = 0.03). Kaplan-Meier curves suggested that high-BRS patients had higher VF recurrence than those with nonhigh-BRS (P = 0.04). Cox proportional hazards regression analyses showed that high BRS was associated independently with VF recurrence (P = 0.002). CONCLUSIONS: Our results suggest that exaggerated reactivity of parasympathetic nerves, as represented by increased BRS, may underlie VF in patients with J-wave syndrome.
Assuntos
Síndrome de Brugada/fisiopatologia , Frequência Cardíaca , Ventrículos do Coração/inervação , Sistema Nervoso Parassimpático/fisiopatologia , Fibrilação Ventricular/fisiopatologia , 3-Iodobenzilguanidina/administração & dosagem , Potenciais de Ação , Adulto , Barorreflexo , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/terapia , Distribuição de Qui-Quadrado , Ritmo Circadiano , Desfibriladores Implantáveis , Intervalo Livre de Doença , Cardioversão Elétrica/instrumentação , Eletrocardiografia Ambulatorial , Feminino , Humanos , Radioisótopos do Iodo/administração & dosagem , Estimativa de Kaplan-Meier , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Modelos de Riscos Proporcionais , Compostos Radiofarmacêuticos/administração & dosagem , Recidiva , Fatores de Risco , Sistema Nervoso Simpático/fisiopatologia , Fatores de Tempo , Resultado do Tratamento , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/terapia , Adulto JovemRESUMO
AIMS: Idiopathic ventricular fibrillation (iVF) accounts for up to 14% of VF incidence. Data regarding long-term outcome and clinical risk markers of arrhythmia recurrence are scarce. The objective of our study was to describe a long-term follow-up (FU) of a cohort of iVF survivors in our centre during the past 20 years, and to investigate the influence of clinical parameters, e.g. presence of an early repolarization pattern (ERP), on recurrence rate of arrhythmias. METHODS AND RESULTS: Thirty-five iVF survivors were identified and retrospectively analysed regarding recurrent implantable cardioverter-defibrillator (ICD) interventions and covariates potentially influencing arrhythmia recurrence. Appropriate ICD interventions occurred in 15 patients (43%) after a median of 6.6 years during a median FU period of 8.8 years. Two patients (13%) received the first appropriate therapy after an assumed average ICD battery longevity of 7 years, while in all other patients, the first therapy occurred within the first ICD period. Appropriate interventions were observed more often and earlier in patients with ERP (HR 3.9; 1.4-11.0; P = 0.01), whereas all other covariates failed to predict subsequent events. A high incidence of inappropriate ICD therapies (67 interventions in 14 patients) could be attributed to the occurrence of atrial fibrillation (66% of all inappropriate therapies). CONCLUSION: The recurrence rate of ventricular arrhythmias in iVF survivors is high and recurrence might occur delayed (>7 years after the initial event). ERP seems to be highly predictive with respect to early arrhythmia recurrence. Our results highlight that better pathophysiologic understanding of ERP might facilitate a better risk stratification before and an optimal treatment after an iVF event. The high rate of AF and ERP in iVF survivors might indicate an underlying heart disease or myocardial electrical disorder not apparent at the index event.
Assuntos
Morte Súbita Cardíaca/epidemiologia , Desfibriladores Implantáveis/efeitos adversos , Fibrilação Ventricular/diagnóstico por imagem , Fibrilação Ventricular/terapia , Adulto , Idoso , Morte Súbita Cardíaca/etiologia , Ecocardiografia , Eletrocardiografia , Feminino , Seguimentos , Alemanha , Humanos , Imageamento por Ressonância Magnética , Masculino , Pessoa de Meia-Idade , Recidiva , Estudos Retrospectivos , Fatores de RiscoRESUMO
The pro-arrhythmic triggers in Brugada and early repolarization syndromes (BrS, ERS) have not been analyzed systematically except for case reports. We clinically investigated the circumstances which precede/predispose to arrhythmic events in these syndromes during long-term follow-up. A detailed history from the patients/witnesses was taken to investigate the antecedent events in the last few hours that preceded syncope/ventricular fibrillation (VF); medical records, ECG and blood test from the emergency room (ER) were reviewed. 19 patients that fulfilled the investigation criteria were followed up for 71 ± 49 months (34-190 months). Prior to the event (syncope/VF), the patients were partaking different activities in the following decreasing order; drinking alcoholic beverage, having meal, and getting up from sleep, exercise. 3 patients reported mental/physical stress prior to the event and 2 patients developed VF several days after starting oral steroid for treatment of bronchial asthma. In the ER, elevated J-wave amplitude (0.27 ± 0.15 mV) was found with 58 % of the patients having hypokalemia. After electrolyte correction and cessation of steroids, the following day plasma K+ (4.2 ± 0.3 mEq/L, P < 0.001) was significantly increased and J-wave amplitude (0.13 ± 0.1 mV, P < 0.001) was remarkably reduced. Three patients were kept on oral spironolactone/potassium supplements. During follow-up for 71 ± 49 (34-190) months, among 4 patients with VF recurrence, one patient developed VF after taking oral steroid. In ERS and BrS, hypokalemia and corticosteroid therapy add substantial pro-arrhythmic effects, but potentially treatable. Stopping steroid therapy and avoiding hypokalemia had excellent long-term outcome.
Assuntos
Síndrome de Brugada/etiologia , Sistema de Condução Cardíaco/fisiopatologia , Frequência Cardíaca , Síncope/etiologia , Fibrilação Ventricular/etiologia , Potenciais de Ação , Corticosteroides/efeitos adversos , Adulto , Idoso , Antiarrítmicos/uso terapêutico , Biomarcadores/sangue , Síndrome de Brugada/diagnóstico , Síndrome de Brugada/tratamento farmacológico , Síndrome de Brugada/fisiopatologia , Eletrocardiografia , Feminino , Seguimentos , Sistema de Condução Cardíaco/efeitos dos fármacos , Frequência Cardíaca/efeitos dos fármacos , Humanos , Hipopotassemia/sangue , Hipopotassemia/complicações , Hipopotassemia/terapia , Masculino , Pessoa de Meia-Idade , Potássio/sangue , Prognóstico , Estudos Prospectivos , Fatores de Risco , Síncope/diagnóstico , Síncope/tratamento farmacológico , Síncope/fisiopatologia , Fatores de Tempo , Fibrilação Ventricular/diagnóstico , Fibrilação Ventricular/tratamento farmacológico , Fibrilação Ventricular/fisiopatologia , Adulto JovemRESUMO
A 21-year-old man developed ventricular fibrillation (VF) while drinking alcohol and was admitted to our hospital. An electrocardiogram (ECG) on admission revealed remarkably prominent slurs on the terminal part of QRS complexes in the left precordial leads and a coved type ST elevation at higher intercostal spaces. After hypothermia therapy, he underwent implantation of an implantable cardioverter-defibrillator (ICD). Standard twelve-lead follow-up ECGs revealed early repolarization pattern and an intermittent coved type ST elevation. When the coved type ST elevation appeared, the early repolarization pattern in the inferior and left precordial leads was attenuated. Prominent early repolarization pattern was the most likely trigger of the VF storm in this Brugada patient.
Assuntos
Síndrome de Brugada/complicações , Síndrome de Brugada/diagnóstico , Eletrocardiografia/métodos , Fibrilação Ventricular/complicações , Fibrilação Ventricular/diagnóstico , Síndrome de Brugada/terapia , Diagnóstico Diferencial , Humanos , Masculino , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Fibrilação Ventricular/terapia , Adulto JovemRESUMO
OBJECTIVE: To evaluate the preoperative prevalence of each type of J-wave syndrome electrocardiographic pattern and its association with perioperative cardiac events. DESIGN: Retrospective study. SETTING: Single hospital university study. PARTICIPANTS: The study evaluated 930 patients who underwent gynecologic, abdominal, neurosurgical, orthopedic, and urologic surgeries. INTERVENTIONS: Preoperative standard 12-lead electrocardiogram (ECG) monitoring was performed, and each type of J-wave syndrome ECG pattern-types 1, 2, and 3 and Brugada syndrome-type-was evaluated. Incidence of perioperative cardiac events was investigated up to 1 year postoperatively using an electronic medical record system. MEASUREMENTS AND MAIN RESULTS: Data from 789 patients were included in the final study. Of these, 16 patients (2.0%) had J-wave syndrome: 7 patients (0.9%) had type-1 patterns; 5 patients (0.6%) had type-2 patterns; 2 patients (0.3%) had type-3 patterns; and 2 patients (0.3%) had Brugada syndrome-type ECG patterns. A J-point elevation≥0.2 mV, which is considered to be more dangerous, was found in only 2 patients with Brugada syndrome-type ECG patterns, both of whom suffered perioperative lethal arrhythmias. CONCLUSION: Patients with J-wave syndrome ECG patterns, even dangerous patterns, are not necessarily associated with a higher risk of perioperative cardiac events. However, Brugada syndrome type ECG patterns should be carefully monitored.