Review Article http://dx.doi.org/10.4070/kcj.2016.46.5.601 Print ISSN 1738-5520 • On-line ISSN 1738-5555 Korean Circulation Journal J Wave Syndromes: History and Current Controversies Tong Liu, MD1, Jifeng Zheng, MD2, and Gan-Xin Yan, MD3,4 1Tianjin Key Laboratory of Ionic-Molecular Function of Cardiovascular disease, Department of Cardiology, Tianjin Institute of Cardiology, The Second Hospital of Tianjin Medical University, Tianjin, 2Department of cardiology, The Second Hospital of Jiaxing, Jiaxing, China, 3Lankenau Institute for Medical Research and Lankenau Medical Center, Wynnewood, Pennsylvania, USA, 4The First Affiliated Hospital, Medical School of Xi'an Jiaotong University, Xi'an, China The concept of J wave syndromes was first proposed in 2004 by Yan et al for a spectrum of electrocardiographic (ECG) manifestations of prominent J waves that are associated with a potential to predispose affected individuals to ventricular fibrillation (VF). Although the concept of J wave syndromes is widely used and accepted, there has been tremendous debate over the definition of J wave, its ionic and cellular basis and arrhythmogenic mechanism. In this review article, we attempted to discuss the history from which the concept of J wave syndromes (JWS) is evolved and current controversies in JWS. (Korean Circ J 2016;46(5):601-609) KEY WORDS: Brugada syndrome; Sudden cardiac death; Ventricular fibrillation. Introduction History of J wave and J wave syndromes The concept of J wave syndromes was first proposed in 2004 The J wave is a positive deflection seen at the end of the QRS by Yan et al.1) for a spectrum of electrocardiographic (ECG) complex; it may stand as a distinct “delta” wave following the QRS, manifestations of prominent J waves that are associated with a or be partially buried inside the QRS as QRS notching or slurring. The potential to predispose affected individuals to ventricular fibrillation earliest description of the ECG changes representing J wave (QRS (VF). Although the concept of J wave syndromes is widely used and slurring or notching) in healthy young individuals was by Shipley accepted, there has been tremendous debate over the definition of and Hallaran in 1936.2) In 1953, Osborn published a landmark paper J wave, its ionic and cellular basis and arrhythmogenic mechanism. for hypothermia-induced “current of injury” that manifested more In this review article, we attempted to discuss the history from prominent J wave in dogs.3) Therefore, J wave is also termed as which the concept of J wave syndromes (JWS) is evolved and Osborn wave. current controversies in JWS. Ionic and cellular basis of J wave remained unclear until 1996 when Yan and Antzelevitch developed a novel experimental preparation, i.e. an arterially-perfused canine ventricular wedge, in which transmembrane action potentials from epicardium, endocardium and midmyocardium (M cells) could be recorded 4) Received: January 29, 2016 simultaneously with a transmural ECG. They demonstrated that Revision Received: March 14, 2016 a prominent action potential notch in the epicardium mediated by Accepted: March 17, 2016 transient outward current (I ) is responsible for the appearance Correspondence: Gan-Xin Yan, MD, Lankenau Medical Center and to Lankenau Institute for Medical Research, 100 Lancaster Avenue, of J wave on the ECG under a normal activation sequence from Wynnewood, PA 19096, USA the endocardium to the epicardium (Fig. 1). Therefore, J wave is Tel: 1-484-476-2687, Fax: 1-484-476-8019 an ECG manifestation an Ito-mediated repolarization component, Email: [email protected] and its property is determined by the features of Ito which can help • The authors have no financial conflicts of interest. to distinguish J wave from depolarization abnormalities resembling This is an Open Access article distributed under the terms of the Creative J wave (pseudo J wave).5)6) In this landmark study, they pointed Commons Attribution Non-Commercial License (http://creativecommons. out that the so-called “right bundle branch block” in cases of VF org/licenses/ by-nc/3.0) which permits unrestricted non-commercial use, 7) distribution, and reproduction in any medium, provided the original work by Brugada brothers in 1992 was in fact a prominent J wave. is properly cited. Since then, J wave has not been simply viewed as a hallmark of Copyright © 2016 The Korean Society of Cardiology 601 602 J Wave Syndromes common mechanism underlying the VF development.1)11)12) 50 Epi mV In 2008, Haïssaguerre et al reported that J point elevation in two consecutive leads in a group of 206 case subjects with idiopathic VF is more common than that in a control group of 412 healthy 13) 50 individuals. Since then, JWS has become one of the hottest topics Endo mV in basic and clinical electrophysiological research.5)6)14)15) However, they redefined J wave or J point elevation to be at least 1 mm (0.1 mV) above the baseline level in two consecutive leads as “early 1 ECG mV repolarization (ER)” in the study.13) Such a deviation in definition from the traditional ER description has caused confusion in both 200 ms research and clinical practice involving JWS A 200 ms B 50 Epi mV J wave and Early Repolarization: Vaguely Defined Terms and Concepts 2) 50 When Shipley and Hallaran described J wave in 1936, they also Endo mV described ST elevation as a normal variant but did not specify if the elevation was related to J wave. In 1961, Wasserburger and Alt16) ECG 0.5 clearly defined ER as a ‘normal precordial RS-T segment elevation mV variant’. In their definition, ER was characterized as: (1) an elevated C 200 ms 200 ms take-off of the S-T segment at the J junction of the QRS complex, Fig. 1. The sequence of ventricular activation influences the appearance of varying from 1 to 4 mm, relative to the succeeding T-P interval; (2) J wave in a transmural ECG recorded from coronary-perfused canine left ventricular wedge preparation. (A) Stimulation of the endocardial (Endo) a downward (should be “upward”, the authors might use a wrong surface causes the epicardial (Epi) surface to be activated last. In such case word) concavity of the S-T segment; and (3) symmetrically limbed the J wave is aligned with Ito-mediated epicardial AP notch. (B) Stimulation T waves with a large amplitude. This pattern is usually seen in the of the epicardial surface activates it before the endocardial surface. This mid- and left precordial leads V -V . The authors also indicated causes the epicardial AP notch to occur simultaneously with the QRS, 3 5 hiding the J wave. Reproduced from Yan and Antzelevitch4) with accelerated ventricular repolarization was considered as the permission. (C) Endocardial activation at different locations can cause the J mechanism of this ECG pattern. In a review article by Gussak and wave to occur at the end of the QRS, manifesting as slurred (left panel) or Antzelevitch in 2000, ER syndrome is defined as a diffuse upward notched (right panel) QRS. Reproduced from Badri et al.5) with permission. 17) ST-segment concavity ending in a positive T wave in leads V2-V4. In other words, J wave and ER were historically considered as two hypothermia, but also linked to VF. distinguished ECG manifestations. In early 2000s, there were a few of case reports that J wave Haissagueree et al.13) in 2008 defined ER as an elevation in inferior leads were associated with idiopathic VF.8-10) Intrinic of the QRS–ST junction (J point) in at least two consecutive connection via the underlying ionic and cellular basis between leads, excluding right precordial leads. Since then, a number of the Brugada syndrome (BrS) and idiopathic ventricular fibrillation publications, including the consensus statement on the diagnosis with a prominent J wave in inferior leads was then discussed.8) and management of primary inherited arrhythmia syndromes from The concept of JWS was introduced by Yan et al. in 2004 and HRS/EHRA/APHRS18) and a recent expert consensus paper on ER,19) 2005.1)11)12) In Yan’s initial proposal, JWS are a spectrum of ECG have adopted this new definition. In contrast to the traditional manifestations of prominent J waves that are associated with a ER definition, the upwardly concave ST segment elevation is no risk for the development of VF or sudden cardiac death, including longer included in the new ER definition (Table 1). This shift in ECG BrS, idiopathic VF with prominent J waves in inferior leads and definition of “early repolarization” from traditional one, which early repolarization (ER) syndrome by the traditional definition (see primarily focused on ST segment elevation, to QRS terminal J point below). The ionic and cellular basis linking the ECG manifestations elevation including Ito-mediated J wave has generated tremendous of BrS, the idiopathic VF and ER syndrome is Ito-mediated epicardial confusion in almost aspects in basic research as well as in clinical action potential notch and phase 2 reentry that severs as the practice.14)20)21) http://dx.doi.org/10.4070/kcj.2016.46.5.601 www.e-kcj.org Tong Liu, et al. 603 Table 1. The difference between traditional and modern ER Traditional ER definition Modern ER definition Time of firstly proposed 1961 2008 Major difference in diagnosis Upwardly concave ST segment Elevation An elevation of the QRS–ST junction AP plateau depression in the epicardium related to Mechanisms Ito-mediated AP notch and IVCD Ito-mediated AP notch 12 lead ECG recognition ER can be easily identified in 12 lead ECG ER can be often confused with IVCD in 12 lead ECG Depending on J wave amplitude and related changes in ST Risk for VF Rare, considering benign and T wave Prevalence lower higher ER: early repolarization, AP: action potential, ECG: electrocardiography, VF: ventricular fibrillation, IVCD: intraventricular conduction delay Firstly, the traditional ER and modern ER (an elevation of the idiopathic VF.