J wave syndromes: Molecular and cellular mechanisms

An early repolarization (ER) pattern in the ECG, consisting of J point elevation, distinct J wave with or without ST segment elevation or slurring of the terminal part of the QRS, was long considered a benign electrocardiographic manifestation. Experimental studies a dozen years ago suggested that an ER is not always benign, but may be associated with malignant arrhythmias. Validation of this hypothesis derives from recent case–control and population-based studies showing that an ER pattern in inferior or infero-lateral leads is associated with increased risk for life-threatening arrhythmias, termed early repolarization syndrome (ERS). Because accentuated J waves characterize both Brugada syndrome (BrS) and ERS, these syndromes have been grouped under the heading of J wave syndromes. BrS and ERS appear to share common ECG characteristics, clinical outcomes, risk factors as well as a common arrhythmic platform related to amplification of I_to-mediated J waves. However, they differ with respect to the magnitude and lead location of abnormal J waves and can be considered to represent a continuous spectrum of phenotypic expression. Recent studies support the hypothesis that BrS and ERS are caused by a preferential accentuation of the AP notch in right or left ventricular epicardium, respectively, and that this repolarization defect is accentuated by cholinergic agonists. Quinidine, cilostazol and isoproterenol exert ameliorative effects by reversing these repolarization abnormalities. Identifying subjects truly at risk is the challenge ahead. Our goal here is to review the clinical and genetic aspects as well as the cellular and molecular mechanisms underlying the J wave syndromes.     

Some Controversies about Early Repolarization: The Haïssaguerre Syndrome

Controversy has followed the groundbreaking and cornerstone paper of Haïssaguerre et al. Much of this controversy has been due to the use of the term “early repolarization pattern” and possible waveform morphologies on the standard 12‐lead ECG ( it is 10 second strip) that could predict who will manifest the malignant arrhythmogenic syndrome described by Haïssaguerre et al. The standard ECG definition of early repolarization pattern (ERP) or early repolarization variant (ERV) since then has changed its clinical meaning for a surface electrocardiographic waveform from benign to malignant. The new definition of ERP/ERV contains only J wave but ST‐segment elevation is no more obligatory. In the old definition, early repolarization pattern (ERP) or early repolarization variant (ERV) 3 is a well‐recognized idiopathic electrocardiographic phenomenon considered to be present when at least two adjacent precordial leads show elevation of the ST segment, with values equal or higher than 1 mm. In the new electrocardiographic ERP concept, the ST segment may or may not be elevated and can be up‐sloping, horizontal or down‐sloping while in the old ERP/ERV concept it must be elevated at least 1 mm in at least two adjacent leads and the variant is characterized by a diffuse elevation of the ST segment of upper concavity, ending in a positive T wave of V₂ to V₄ or V₅ and prominent J wave and ST‐segment elevation predominantly in left precordial leads. The phenomenon constitutes a normal variant; it is almost a rule in athletes (present in 89% of the cases in this universe).     

Clinical Aspects of the Early Repolarization Syndrome: A 2011 Update

Recent studies suggest that the electrocardiographic (ECG) finding of J‐point ST‐elevation, the early repolarization syndrome, is not as benign as earlier believed. Three important articles published in 2008/2009 suggest that this finding in the inferolateral leads of the ECG may be representing a risk for subsequent ventricular fibrillation. Although these retrospective studies do justify a careful evaluation of persons with this electrocardiographic pattern, especially of those with syncope or ventricular arrhythmias and/or family history of sudden cardiac death, it seems to be unjustified to consider it today to be a marker for high risk for sudden cardiac deaths in a general population. Even in athletes, early repolarization was found to increase only minimally their arrhythmic risk. In spite of certain similarities with the Brugada syndrome, their association is far from being proved. Prospective studies and further electrophysiological and genetic information will help to clarify the clinical significance of this syndrome. Ann Noninvasive Electrocardiol 2011;16(2):192–195     

特发性异常J波与Brugada综合征的临床及心电图特征

目的探讨特发性异常J波与Brugada综合征的临床及心电学特点。方法对特发性异常J波与Brugada综合征各8例进行分析。结果①特发性异常J波在肢导联或(和)胸导联可见正向异常J波[除aVR(部分患者aVL)外],其波幅较低而分布较广,一般V1~V2导联不出现J波,若出现则JV1~V2R,TV1~V2(V3)倒置或直立。两者均易诱发多形性室性心动过速及/或心室颤动而致死。结论异常J波和Brugada综合征及Brugada样心电图象是具有不同临床及心电学特点的临床病症。     

Early repolarization syndrome and Brugada syndrome: is there any linkage?

Early repolarization syndrome (ERS) is characterized by the presence, in most cases in mid-to-lateral precordial leads, of a J wave on the downsloping portion of the QRS complex, followed by an elevation of the ST-segment with upward concavity. ERS is considered a benign electrocardiographic pattern of ventricular repolarization and, thus far, clinical interest in this syndrome has been confined to its differential diagnosis from myocardial infarction and pericarditis. Brugada syndrome (BS), an inherited cardiac disease first described in 1992, exhibits a characteristic electrocardiographic pattern consisting of a J wave mimicking a right bundle branch block with typical ST-segment elevation in the right precordial leads. Believed to be a normal repolarization variant for more than three decades, the syndrome is now known instead to be associated with a high incidence of life-threatening ventricular tachyarrhythmias and is responsible for a number of sudden deaths in young adults worldwide. Although clinical findings seem to differentiate the two syndromes, similarities between BS and ERS in terms of response to heart rate, pharmacologic agents, and neuromodulation could suggest a linkage in their pathophysiological mechanism. The authors review the clinical and experimental data in order to test this hypothesis.     

Early Repolarization: A Rare Primary Arrhythmic Syndrome and Common Modifier of Arrhythmic Risk

Despite longstanding beliefs, early repolarization is not always a benign electrocardiographic observation. Its association with increased arrhythmic events has been observed in 2 strikingly different groups of individuals, retrospectively in young subjects with idiopathic ventricular fibrillation and in long‐term cohort studies from the general population. This form of primary electrical disease is now referred to as the early repolarization syndrome and has mechanistically been demonstrated to occur secondary to a transmural gradient of early cellular repolarization, resulting in the presence of an ST‐elevation pattern and J‐waves merged within or offset from the terminal QRS complex. In addition to creating a milieu of increased arrhythmic risk in isolation, an increasing number of studies have highlighted that the presence of early repolarization and J‐waves may provide a baseline electrical substrate that modifies the risk of malignant arrhythmias in other clinical settings, such as acute myocardial ischemia. The challenge ahead lies in discerning when early repolarization may represent an ominous ECG marker, as opposed to a benign entity.     

Ventricular Fibrillation with Prominent Early Repolarization Associated with a Rare Variant of KCNJ8/KATP Channel

Background: Early repolarization in the inferolateral leads has been recently recognized as a frequent syndrome associated with idiopathic ventricular fibrillation (VF). We report the case of a patient presenting dramatic changes in the ECG in association with recurrent VF in whom a novel genetic variant has been identified.
Case Report: This young female (14 years) was resuscitated in 2001 following an episode of sudden death due to VF. All examinations including coronary angiogram with ergonovine injection, MRI, and flecainide or isoproterenol infusion were normal. The patient had multiple (>100) recurrences of VF unresponsive to beta-blockers, lidocaine/mexiletine, verapamil, and amiodarone. Recurrences of VF were associated with massive accentuation of the early repolarization pattern at times mimicking acute myocardial ischemia. Coronary angiography during an episode with 1.2 mV J/ST elevation was normal. Isoproterenol infusion acutely suppressed electrical storms, while quinidine eliminated all recurrences of VF and restored a normal ECG over a follow-up of 65 months. Genomic DNA sequencing of K_ATP channel genes showed missense variant in exon 3 (NC_000012) of the KCNJ8 gene, a subunit of the K_ATP channel, conferring predisposition to dramatic repolarization changes and ventricular vulnerability.     

Early repolarization syndrome: clinical characteristics and possible cellular and ionic mechanisms

Early repolarization syndrome (ERS) has traditionally been regarded as benign. In the electrocardiogram (ECG), it is characterized by a diffuse upward ST-segment concavity ending in a positive T wave in leads V2-V4 (5). Clinical interest in this ECG phenomenon has recently been rekindled because of similarities with the electrocardiographic manifestations of the highly arrhythmogenic Brugada syndrome and the potential for misdiagnosis. This article addresses the clinical characteristics and cellular and ionic basis for ERS. In experimental models, the ECG signature of ERS can be converted to that of the Brugada syndrome, raising the possibility that ERS may not be as benign as generally thought, and that under certain conditions known to predispose to ST-segment elevation, patients with ERS may be at greater risk. Further clinical and experimental data are clearly required to test these hypotheses, and the characteristics of ERS need to be more fully delineated within the framework of what has been learned about the Brugada syndrome in recent years.     

Genetic, molecular and cellular mechanisms underlying the J wave syndromes

An early repolarization (ER) pattern in the ECG, distinguished by J-point elevation, slurring of the terminal part of the QRS and ST-segment elevation has long been recognized and considered to be a benign electrocardiographic manifestation. Experimental studies conducted over a decade ago suggested that some cases of ER may be associated with malignant arrhythmias. Validation of this hypothesis was provided by recent studies demonstrating that an ER pattern in the inferior or inferolateral leads is associated with increased risk for life-threatening arrhythmias, termed ER syndrome (ERS). Because accentuated J waves characterize both Brugada syndrome (BS) and ERS, these syndromes have been grouped under the term "J wave syndromes". ERS and BS share similar ECG characteristics, clinical outcomes and risk factors, as well as a common arrhythmic platform related to amplification of I(to)-mediated J waves. Although BS and ERS 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. Although most subjects exhibiting an ER pattern are at minimal to no risk, mounting evidence suggests that careful attention should be paid to subjects with "high risk" ER. The challenge ahead is to be able to identify those at risk for sudden cardiac death. Here I review the clinical and genetic aspects as well as the cellular and molecular mechanisms underlying the J wave syndromes.     

恶性快速性室性心律失常致心脏骤停的临床观察

目的探讨恶性快速性室性心律失常致心脏骤停的原因与高危心电表现。方法分析45例在入院时或入院后至少发生1次心脏骤停患者的原因及其发作时与发作前后的常规12导联心电图或持续心电监视心电图形。结果45例恶性快速性心律失常致心脏骤停最常见的基本原因为冠心病急性或陈旧性心肌梗死,次为特发性及继发性巨大异常J波、扩张型心肌病;低钾血症是最常见的诱因;最常见的恶性快速性室性心律失常类型是心室颤动。其高危心电图表现:①复杂性室性早搏;②异常J波;③继发性长Q-T间期综合征;④Brugada综合征;⑤广泛前壁心肌梗死伴墓碑样ST段抬高。上述各种原因心脏骤停者有各自不同的临床及心电学特征。结论恶性快速性室性心律失常所致心脏骤停存在多种原因及高危心电图表现。     

Clinical characteristics of patients with spontaneous or inducible ventricular fibrillation without apparent heart disease presenting with J wave and ST segment elevation in inferior leads

INTRODUCTION: The clinical characteristics of three patients with spontaneous or inducible ventricular fibrillation (VF) without apparent heart disease, who presented with J wave and ST segment elevation in inferior leads, are described. METHODS AND RESULTS: All patients were male and experienced syncope. Their symptoms occurred at night or early in the morning. Holter ECG revealed infrequent premature ventricular complexes. Injection with disopyramide 2 mg/kg augmented ST segment elevation. CONCLUSION: These characteristics were very similar to those of patients with Brugada syndrome. These three patients with these specific features might have a variant of Brugada syndrome.     

Early repolarization pattern: Innocent finding or marker of risk?

The presence of early repolarization (ER) pattern in the 12-lead ECG, defined as elevation of the QRS–ST junction (J point) often associated with a late QRS slurring or notching (J wave), is a common finding in the general population, particularly in the inferior and precordial lateral leads. In young and healthy individuals, particularly in males, blacks and athletes, this pattern has commonly been considered to represent an innocent finding. However, experimental studies, case reports and studies on healthy subjects surviving a cardiac arrest or with primary ventricular fibrillation (VF) have suggested an association between J-point elevation and/or QRS slurring in the inferior and lateral ECG leads and the risk of VF. On the other hand, in recent epidemiological studies on large general population no significant association between ER patterns and cardiac mortality was found. In athletes, changes of the QRS–ST segment are frequent. We found that in a selected group of 21 young competitive athletes, without underlying heart disease, who experienced cardiac arrest, the prevalence of J wave and/or QRS slurring in the inferior and lateral (V4 to V6) leads was significantly higher in cases than in 365 control athletes. Following sport discontinuation, during the 36-month follow-up arrhythmia recurrences did not differ between subgroups with and without J wave or QRS slurring. Recently, other studies showed that among different patterns of ER rapidly ascending ST segment after the J point seems to be almost universally benign. The conflicting data regarding the prognostic role of ER patterns can be partly due to different definitions of ER used. This emphasizes the need for standardized methods of measurements of QRS end–J point–ST segment and for detailed definitions. The knowledge of the true significance in clinical setting of the various aspects of ER is still unclear and warrants prospective, long-term epidemiological studies.     

Transition of the ST segment from a J wave to a coved-type elevation before ventricular fibrillation induced by coronary vasospasm in the precordial leads

We describe the case of a 63-year-old man whose electrocardiogram showed transition of the ST segment from a J wave to a coved-type elevation in precordial leads before ventricular fibrillation induced by right coronary artery vasospasm. Simultaneously, the ST segment in inferior leads was gradually depressed with a J wave. Considering the sudden death of his son, induced ventricular fibrillation by programmed electrical stimulation, and modulations of the ST segment in the precordial and inferior leads by pilsicainide, some abnormalities in repolarization associated with Brugada syndrome or early repolarization syndrome might have caused these atypical ST-segment manifestations.     

Early repolarization syndrome: is it always benign?

Early repolarization syndrome is a well-recognized idiopathic electrocardiographic phenomenon characterized by prominent J wave and ST-segment elevation predominantly in left precordial leads. The syndrome shares remarkable cellular, ionic, and electrocardiographic similarities with the Brugada syndrome and idiopathic ventricular fibrillation (a variant of the Brugada syndrome with ST-segment elevation in inferior leads). Although early repolarization syndrome is considered a benign entity, its arrhythmogenic potential still remains unknown. We report the case of a 39-year-old male with a family history of sudden death and an electrocardiogram consistent with early repolarization syndrome. Diagnostic dilemmas are discussed.     

Intravenous administration of class I antiarrhythmic drugs induced T wave alternans in a patient with Brugada syndrome

A 71-year-old man who experienced aborted sudden death was referred to our hospital. Coronary artery disease and cerebral accident were ruled out by conventional tests. The 12-lead ECG obtained at rest showed a right bundle branch block pattern and ST segment elevation in leads V1 to V3. Double ventricular extrastimuli at coupling intervals >180 msec induced ventricular fibrillation (VF) twice during electrophysiologic study. Intravenous administration of procainamide accentuated ST segment elevation in leads V1 to V3, and visible T wave alternans was induced in leads V2 and V3 at a dose of 450 mg. Initiation of T wave alternans was not associated with changes of the cardiac cycle or development of premature beats. When procainamide infusion was discontinued, T wave alternans disappeared before the elevated ST segment returned to the control level. Pilsicainide also accentuated ST segment elevation and induced similar T wave alternans in leads V2 and V3. Class I antiarrhythmic drug-related T wave alternans has been reported rarely in Brugada syndrome, but it may represent enhanced arrhythmogenicity of VF. We need to monitor closely and study the clinical implications of T wave alternans in Brugada syndrome.     

ECG Repolarization Waves: Their Genesis and Clinical Implications

The electrocardiographic (ECG) manifestation of ventricular repolarization includes J (Osborn), T, and U waves. On the basis of biophysical principles of ECG recording, any wave on the body surface ECG represents a coincident voltage gradient generated by cellular electrical activity within the heart. The J wave is a deflection with a dome that appears on the ECG after the QRS complex. A transmural voltage gradient during initial ventricular repolarization, which results from the presence of a prominent action potential notch mediated by the transient outward potassium current (I_to) in epicardium but not endocardium, is responsible for the registration of the J wave on the ECG. Clinical entities that are associated with J waves (the J‐wave syndrome) include the early repolarization syndrome, the Brugada syndrome and idiopathic ventricular fibrillation related to a prominent J wave in the inferior leads. The T wave marks the final phase of ventricular repolarization and is a symbol of transmural dispersion of repolarization (TDR) in the ventricles. An excessively prolonged QT interval with enhanced TDR predisposes people to develop torsade de pointes. The malignant “R‐on‐T” phenomenon, i.e., an extrasystole that originates on the preceding T wave, is due to transmural propagation of phase 2 reentry or phase 2 early afterdepolarization. A pathological “U” wave as seen with hypokalemia is the consequence of electrical interaction among ventricular myocardial layers at action potential phase 3 of which repolarization slows. A physiological U wave is thought to be due to delayed repolarization of the Purkinje system.     

Increased Dispersion of Repolarization Time Determined by Monophasic Action Potentials in Two Patients with Familial Idiopathic Ventricular Fibrillation

Increased Dispersion of RT in Familial Idiopathic VF. Introduction: The role of increased dispersion of repolarization in the genesis of torsades de pointes in patients with long QT syndrome has been clarified, but its role in the genesis of idiopathic ventricular fibrillation (VF) is not yet known. To investigate the pathogenesis of VF, we recorded monophasic action potentials (MAPs) from two siblings (48- and 36-year-old males) with familial idiopathic VF. Methods and Results: The elder brother (patient I) showed a late r’ wave in lead V¹ and ST segment elevation in leads V¹ through V³. The younger brother (patient 2) had late r’ waves and ST segment elevation in leads II, III, and aVF, and the configurations were very similar to those of patient I. MAPs were recorded from several sites in the right ventricular (RV) and left ventricular (LV) endocardium during constant right atrial pacing. The repolarization time (RT) was defined as the sum of the activation time (AT) and action potential duration (APD) at 90% repolarization. In patient 1, marked prolongation of the AT (140 msec) and the RT (380 msec) was recorded in the RV septum of the outflow tract, and the RT dispersion was markedly increased (125 msec). In contrast, patient 2 showed prolongation of the AT (80 msec) and RT (310 msec), and fractionated electrograms in the RV floor of the inflow tract. The RT dispersion was also increased (80 msec). VF and nonsustained polymorphic ventricular tachycardia were induced by double premature stimulation in patients 1 and 2, respectively. Chronic amiodarone therapy decreased the RT dispersion and suppressed the induction of ventricular tachyarrhythmias in patient 2, although late r’ waves and slight ST segment elevation were unmasked in leads V₁, and V₂. Conclusion: Our data suggest that the increased dispersion of the RT, which was due mainly to a localized conduction delay in the RV, created an arrhythmogenic substrate in the two patients with familial idiopathic VF.     

Epsilon‐Like Electrocardiographic Pattern in a Patient with Brugada Syndrome

Both Brugada syndrome (BrS) and arrhythmogenic right ventricle dysplasia/cardiomyopathy (ARVD/C) can cause repolarization abnormalities in right precordial leads and predispose to sudden cardiac death (SCD) due to ventricular arrhythmias. Although there is controversy over whether BrS is distinct from ARVD/C, it is believed that both are different clinical entities with respect to both the clinical presentation and the genetic predisposition. The coexistence of these two relatively rare clinical entities is also reported, but, some hypothesized that it is more possible that disease of the right ventricular muscle might accentuate the Brugada electrocardiographic pattern. In clinic practice, there may be cases where the dividing line is not so clear. We report a 33‐year‐old male presenting with recurrent syncope, who has a peculiar pattern of coved‐type ST‐segment elevation (ST‐SE) with epsilon‐like wave in right precordial leads.     

Das Oberflächen-EKG in der Diagnostik von Arrhythmien

The surface electrocardiogram (ECG) is a simple noninvasive method to assess the electrical activity of the heart and provides important information to identify patients with cardiac arrhythmias and increased arrhythmic risk. This brief review highlights cardiac conditions in which the right precordial leads recorded on the surface ECG during sinus rhythm or tachycardia are of important diagnostic and prognostic value. Epsilon waves seen in the right precordial ST segments are the electrocardiographic hallmark of arrhythmogenic right ventricular cardiomyopathy. The diagnosis of Brugada syndrome and risk stratification of affected patients are based on a coved-type >or=2 mm ST-segment elevation in the right precordial leads. This typical ECG pattern may be present persistently, intermittently or only after administration of sodium-channel blockers. The early repolarization syndrome, most commonly seen in healthy young individuals, is characterized by a ST-segment elevation of 1 to 4 mm in the mid-precordial leads with a notched and elevated J point in lead V4. The precordial ECG T-wave repolarization pattern may be helpful in identifying the genotype in patients with suspected long QT syndrome. In patients with overt preexcitation, the surface leads V1 and V2 play a key role in localizing the site of bypass-tract insertion. Finally, the right precordial lead V1 is often crucial in the diagnosis of narrow and broad QRS-complex tachycardias.     

Lambda-like ST segment elevation in acute myocardial infarction - a new risk marker for ventricular fibrillation? Three case reports

Sudden cardiac death (SCD) is responsible for almost 50% of all cardiac deaths in the U.S. The most common underlying cause of SCD is coronary artery disease, especially acute myocardial infarction (AMI). There are no publications concerning the shape of ST segment elevation in AMI and the risk of ventricular fibrilation (VF) or SCD. We present three cases with AMI and atypical ST segment elevation - 'lambda-wave-like' pattern, complicated with episodes of VF. This ECG pattern resembles the ST segment elevation shape in the type 1C Brugada syndrome. The 'lambda-like' ST segment elevation in AMI may identify patients with increased risk of VF or SCD.