J-wave syndromes. from cell to bedside

The J wave, a deflection that follows the QRS complex of the surface electrocardiogram, is usually partially buried in the R wave in humans, appearing as a J-point elevation. An early repolarization (ER) pattern characterized by J-point elevation, slurring of the terminal part of the QRS, and ST-segment elevation has long been recognized and considered to be totally benign. Recent studies have presented evidence demonstrating that an ER pattern in inferior leads or inferolateral leads is associated with increased risk for life-threatening arrhythmias, named early repolarization syndrome. Early repolarization syndrome and Brugada syndrome share similar electrocardiographic characteristics, clinical outcomes, risk factors, as well as a common arrhythmic platform related to amplification of I_to-mediated J waves. Although Brugada syndrome and early repolarization syndrome differ with respect to the magnitude and lead location of abnormal J wave manifestation, they can be considered to represent a continuous spectrum of phenotypic expression, termed J-wave syndromes. Early repolarization syndrome has been proposed to be divided into 3 subtypes: type 1, displaying an ER pattern predominantly in the lateral precordial leads, is prevalent among healthy male athletes and rarely seen in ventricular fibrillation survivors; type 2, displaying an ER pattern predominantly in the inferior or inferolateral leads, is associated with a higher level of risk; whereas type 3, displaying an ER pattern globally in the inferior, lateral, and right precordial leads, is associated with the highest level of risk for development of malignant arrhythmias and is often associated with ventricular fibrillation storms.     

Brugada综合征和特发性J波的临床分析

目的：了解Brugada综合征和特发性J波的临床和心电图特点及其异同点,方法：对收集的10例Brugada综合征和8例特发性J波患者临床和心电图资料进行对比并结合文献。结果：两病有 相似的临床和心电图表现,但心电图表现仍有一定区别,Brugada综合征R’波大于R波,多见于V1－V3导联,伴ST段持续抬高,T波倒置,图形较恒定,特发性J波中J波小于R波,在Ⅱ,Ⅲ,aVF和V4－V6导联多见,无T波倒置,J波可因药物,运动等原因在短时间内明显改变。结论：Brugada综合征和特发性J波临床表现相似,可能有相同的发病机制,只是影响的部位不同,其区别主要在心电图表现。     

Depolarization versus repolarization abnormality underlying inferolateral J-wave syndromes: New concepts in sudden cardiac death with apparently normal hearts

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Early repolarization syndrome: A cause of sudden cardiac death

Early repolarization syndrome (ERS), demonstrated as J-point elevation on an electrocardiograph, was formerly thought to be a benign entity, but the recent studies have demonstrated that it can be linked to a considerable risk of life - threatening arrhythmias and sudden cardiac death (SCD). Early repolarization characteristics associated with SCD include high - amplitude J-point elevation, horizontal and/or downslopping ST segments, and inferior and/or lateral leads location. The prevalence of ERS varies between 3% and 24%, depending on age, sex and J-point elevation (0.05 mV vs 0.1 mV) being the main determinants. ERS patients are sporadic and they are at a higher risk of having recurrent cardiac events. Implantable cardioverter-defibrillator implantation and isoproterenol are the suggested therapies in this set of patients. On the other hand, asymptomatic patients with ERS are common and have a better prognosis. The risk stratification in asymptomatic patients with ERS still remains a grey area. This review provides an outline of the up-to-date evidence associated with ERS and the risk of life - threatening arrhythmias. Further prospective studies are required to elucidate the mechanisms of ventricular arrhythmogenesis in patients with ERS.     

J wave elevation to monitor quinidine efficacy in early repolarization syndrome

We present the case of a 14-year-old female with early repolarization syndrome who presented with recurrent ventricular fibrillation and ICD shocks which were refractory to multiple drugs and catheter ablation. Treatment with quinidine, an Ito blocker, resulted in a normalization of J waves and suppression of VF. Interestingly, J wave amplitude correlated with the ventricular arrhythmia susceptibility and quinidine levels. The case highlights the importance of quinidine for management of ventricular arrhythmias in the context of early repolarisation and suggests that J wave amplitude may be an important indicator of therapeutic drug levels and arrhythmia susceptibility.     

Beat-to-beat variations of the electrocardiogram in survivors of sudden death without structural heart disease

Aim

We sought to determine whether survivors of sudden death without structural heart disease have beat-to-beat electrocardiographic (ECG) characteristics at the microvolt and at the millisecond level that differ from normal subjects.

Methods

We studied patients at our implantable cardioverter defibrillator clinic who had been resuscitated from ventricular fibrillation with no evidence of underlying structural heart disease. Continuous 10-minute high-resolution unfiltered digital surface ECGs at 1000-Hz sampling rate were acquired in these subjects and in a group of healthy volunteers. We then analyzed different parameters of beat-to-beat variations in duration, amplitudes and vectors of the QRS complex, and the T wave using a locally developed program (Comparative Analysis of ECGs, Vectocardiograms, and their Interpretation with Auto-Reference to the patient) and compared them between the 2 groups.

Results

Thirteen patients (7 men; age, 46 ± 16 years) were studied. Standard ECGs were unremarkable in 7 patients and suggestive of Brugada syndrome in the 6 others. The control group consisted of 23 age- and sex-matched subjects (13 men; age, 41 ± 10 years). Although the QRS parameters showed only few differences between the 2 groups, there were several differences in parameters evaluating repolarization.

Conclusion

High-resolution ECGs show distinct beat-to-beat variations in parameters of repolarization in survivors of sudden death without structural heart disease, as compared with normal subjects. These findings may reflect increased electrical instability and should be evaluated for stratifying arrhythmic risk in asymptomatic individuals.     

Ionic and cellular mechanisms underlying the development of acquired Brugada syndrome in patients treated with antidepressants

Antidepressant‐Induced Brugada Syndrome. Introduction: Tricyclic antidepressants are known to induce cardiac arrhythmias at therapeutic or supratherapeutic doses. The tricyclic antidepressant, amitriptyline, is reported to induce ST segment elevation in the right precordial electrocardiogram (ECG) leads, thus unmasking Brugada syndrome (BrS). The mechanism by which antidepressants induce the BrS phenotype and associated sudden death is not well established. Methods and Results: Action potentials (AP) were simultaneously recorded from epicardial and endocardial sites of isolated coronary‐perfused canine right ventricular wedge preparations, together with a transmural pseudo‐ECG. Amitriptyline alone (0.2 μM–1 mM) failed to induce a BrS phenotype. NS5806 (8 μM), a transient outward potassium channel current (I_to) agonist, was used to produce an outward shift of current mimicking a genetic predisposition to BrS. In the presence of NS5806, a therapeutic concentration of amitriptyline (0.2 μM) accentuated the epicardial AP notch leading to ST‐segment elevation of the ECG. All‐or‐none repolarization at some epicardial sites but not others gave rise to phase‐2‐reentry and polymorphic ventricular tachycardia (VT) in 6 of 9 preparations. Isoproterenol (100 nM) or quinidine (10 μM) reversed the effects of amitriptyline aborting phase 2 reentry and VT (4/4). Using voltage‐clamp techniques applied to isolated canine ventricular myocytes, 0.2 μM amitriptyline was shown to produce use‐dependent inhibition of sodium channel current (I_Na), without significantly affecting I_to (n = 5). Conclusions: Our data suggest that amitriptyline‐induced inhibition of I_Na unmasks the Brugada ECG phenotype and facilitates development of an arrhythmogenic substrate only in the setting of a genetic predisposition by creating repolarization heterogeneities that give rise to phase 2 reentry and VT.     

Early repolarisation and J wave syndromes

J wave syndrome has emerged as a significant cause of Idiopathic ventricular fibrillation (IVF) responsible for sudden cardiac death. A large body of data is now available on genesis, genetics and ionic mechanisms of J wave syndromes. Two of these viz., Early repolarization syndrome (ER) and Brugada syndrome (BrS) are fairly well characterized enabling correct diagnosis in most patients. The first part of repolarization of ventricular myocardium is governed by Ito current i.e., rapid outward potassium current. The proposed mechanism of ventricular fibrillation (VF) and ventricular tachycardia (VT) storms is the faster I_to current in the epicardium than in the endocardium results in electrical gradient that forms the substrate for phase 2 reentry. Prevention of Ito current with quinidine supports this mechanism. Majority of ER patterns in young patients are benign. The key issue is to identify those at increased risk of sudden cardiac death. Association of both ER syndrome and Brugada syndrome with other disease states like coronary artery disease has also been reported. Individuals resuscitated from VF definitely need an implantable cardiac defibrillator (ICD) but in others there is no consensus regarding therapy. Role of electrophysiology study to provoke ventricular tachycardia or fibrillation is not yet well defined. Radiofrequency ablation of epicardial substrate in right ventricle in Brugada syndrome is also under critical evaluation. In this review we shall discuss historical features, epidemiology, electrocardiographic features, ionic pathogenesis, clinical features and current status of proposed treatment of ER and BrS.     

Clinical and mechanistic issues in early repolarization of normal variants and lethal arrhythmia syndromes

Early repolarization, involving ST-segment elevation and, sometimes, prominent J waves at the QRS-ST junction, has been considered a normal electrocardiographic variant for over 60 years. A growing number of case reports and case-control studies indicate that in some instances, early repolarization patterns are associated with increased risk of idiopathic ventricular fibrillation. Epidemiological evidence indicates a dose effect for the risk of cardiac and sudden death with the extent of J-point elevation. This paper reviews present knowledge regarding the epidemiology, presentation, therapeutic response, and mechanisms characteristic of early repolarization. We highlight major unanswered questions relating to our limited ability to determine which individuals with this common electrocardiographic variant are at risk for sudden death, our incomplete understanding of underlying mechanisms, the inadequate information regarding genetic determinants and therapeutic responses, and the unclear relationship between early repolarization and other conditions involving accelerated repolarization and sudden arrhythmic death such as Brugada and short-QT syndromes. This review paper intends to inform the practicing physician about important clinical issues and to stimulate investigators to address the many unresolved questions in this rapidly evolving field.     

Épidémiologie de la repolarisation précoce chez le jeune maghrébin

An early repolarization variant (ERV) in inferolateral leads has recently been associated with vulnerability to ventricular fibrillation. These studies have been conducted in the occidental countries. The prevalence of ERV in the population of the Maghreb is unknown. The aim of this study was to evaluate the prevalence and risk factors of ERV in a young population from Algeria.MethodsWe assessed the prevalence of ERV within a population of 441 healthy subjects (mean age 25 years) using 12-lead electrocardiography. ERV was stratified by three independent cardiologists according to the J-point elevation (≥ 0.1 mV) in the inferior, apicolateral or both leads with QRS slurring or notching.ResultsThe inferolateral ERV pattern was present in 55 subjects (12.4%). A malign ERV (> 2 mm) was present in 5 subjects (9% of ER) and ER in inferior and lateral leads in 40% of ER. An ERV pattern was more frequently associated with young age, male, bradycardia and T wave in V1 lead.ConclusionAn ERV is a common finding in a healthy Algerian young population. This prevalence seems to be more important than other studies due to young age and not to a racial difference. Our population were more at risk that other studies, and we found more T waves in V1 lead in this people, due to an ethnic particularities or a phenotypic association with the Brugada syndrome.     

The Brugada Syndrome

The Brugada syndrome is a genetically determined disease caused by mutations of the cardiac sodium channel. The disease affects mainly males in their forties and causes sudden cardiac death because of polymorphic ventricular tachycardia. These patients have a structurally normal heart. The electrocardiogram of this syndrome shows, spontaneously or after Class 1 antiarrhythmic drugs, ST segment elevation in leads V₁ to V₃ and a pattern resembling a right bundle branch block. Phase 2 reentry between epi‐ and endocardiac layers is responsible for the arrhythmias. The only effective treatment at present is implantation of a cardioverter defibrillator. A.N.E. 2000;5(1):88–91