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J Wave Syndromes As a Cause of Sudden Arrhythmic Death

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J Wave Syndromes As a Cause of Sudden Arrhythmic Death Cardiogenetics 2013; volume 3:e2 J wave syndromes as a cause the ECG of animals and humans for over six decades,2 since Osborn’s observation in the Correspondence: Charles Antzelevitch, Masonic of sudden arrhythmic death early 1950s.3 In humans, the appearance of a Medical Research Laboratory, 2150 Bleecker prominent J wave in the ECG is considered Street, Utica, NY 13501, USA. Charles Antzelevitch pathognomonic of hypothermia,4-6 hypercal- Tel. +315.735.2217 - Fax: +315.735.5648. E-mail: [email protected] Masonic Medical Research Laboratory, cemia7,8 and more recently as a marker for a Utica, NY, USA substrate capable of generating life-threaten- Key words: cardiac arrhythmias, sudden cardiac ing ventricular arrhythmias.9 A distinct J wave death, early repolarization syndrome, brugada has been described in subjects completely syndrome, idiopathic ventricular fibrillation. recovered from hypothermia10,11 or those pre- Abstract disposed to idiopathic ventricular fibrillation Funding: Supported by grant HL47678 from (IVF), but is otherwise rarely observed in NHLBI, NYSTEM grant C026424 and Masons of humans under normal conditions. In animals, New York State, Florida, Massachusetts Accentuated J waves have been associated Maryland, Rhode Island Connecticut. a distinct J wave is commonly observed in the with idiopathic ventricular tachycardia and fib- ECG of some species, including Baboons and rillation (VT/VF) for nearly three decades. Conflict of interests: there are no conflict of inter- dogs, under baseline conditions and is greatly Prominent J waves characterize both Brugada ests to disclose. amplified under hypothermic conditions.12-14 and early repolarization syndromes leading to An elevated J point is commonly encountered Received for publication: 30 December 2011. their designation as J wave syndromes. An early in humans and some animal species under Revision received: 16 May 2013. repolarization (ER) pattern, characterized by J normal conditions. Accepted for publication: 17 May 2013. point elevation, slurring of the terminal part of An early repolarization (ER) pattern in the the QRS and ST segment elevation was consid- This work is licensed under a Creative Commons ECG has in recent years been shown to be ered to be a totally benign electrocardiographic Attribution NonCommercial 3.0 License (CC BY- associated with life-threatening arrhythmias, manifestation until a decade ago. Recent case- NC 3.0). earning the designation of ERS. Although BrS control and population-based association stud- and ERS differ with respect to lead location ©Copyright C. Antzelevitch, 2013 ies have advanced evidence that an ER pattern and magnitude of abnormal J wave manifesta- Licenseeonly PAGEPress, Italy in the inferior or infero-lateral leads is associat- tion, they have been proposed to represent a Cardiogenetics 2013; 3:e2 ed with increased risk for life-threatening continuous spectrum of phenotypic expression doi:10.4081/cardiogenetics.2013.e2 arrhythmias, named early repolarization syn- termed J wave syndromes.9 drome (ERS). ERS and Brugada syndrome An ER pattern, consisting of J point eleva-use (BrS) share similar electrocardiogram features, tion or a distinct J wave, a notch or slur of the clinical outcomes, risk factors as well as a com- reported that 60% of their IVF patients dis- terminal part of the QRS and an ST segment mon arrhythmic platform related to amplifica- played an ER pattern.29 Four of their patients elevation, is commonly found in healthy young tion of I -mediated J waves. Although BrS and presented with electrical storm (four or more to males and has long been considered to be ERS differ with respect to the magnitude and episodes of ventricular fibrillation in one day). benign.15,16 Our observation in 2000 that an lead location of abnormal J wave manifestation, Continuous electrocardiographic monitoring early repolarization pattern in the canine coro- they are thought to represent a continuous of the patients with electrical storm revealed a nary-perfused wedge preparation can convert spectrum of phenotypic expression, termed J unique electrocardiographic signature consist- to one in which phase 2 reentry gives rise to wave syndromes. A classification scheme for ing of an early repolarization pattern in the polymorphic ventricular tachycardia and fibril- ERS has been proposed: type 1, displaying an ER infero-lateral leads at baseline and dramatic lation (VT/VF), prompted the suggestion that pattern predominantly in the lateral precordial transient accentuation of the J waves in the ER may in some cases predispose to malignant leads, is considered to be largely benign; type 2, infero-lateral leads and the development of a arrhythmias in the clinic.9,17,18 A growing num- displaying an ER pattern predominantly in infe- marked J wave in the right precordial leads, ber of case control and population-based stud- rior or infero-lateral leads, is associated with a ies as well asexperimental studies have sug- where it had not appeared before, just before higher level of risk; whereas type 3, displaying gested a critical role for the J wave in the the development of electrical storm, which was an ER pattern globally in inferior, lateral and pathogenesis of IVF.19-27 A conclusive associa- precipitated by relatively short-coupled prema- right precordial leads, is associated with the 29 Non-commercialtion between ER and IVF was presented in the ture ventricular beat. The accentuated J highest level of risk for development of malig- form of two studies published in the New waves and VF could be suppressed with quini- nant arrhythmias and is often associated with England Journal of Medicine in 2008.28,29 These dine and isoproterenol or with pacing at VF storms. were followed by another study from Viskin increasingly rapid rates. Interestingly, unlike and co-workers30 that same year and large pop- in patients BrS, the electrocardiographic and ulation-based association studies in 2009 and arrhythmic abnormalities could not be pro- 31-35 voked with intravenous flecainide in these Evolution of the J wave 2010. In a case-control study of 206 patients who type 3 ERS patients. syndromes survived an episode of IVF and 412 matched Several case-control studies followed confirm- control subjects, Haissaguerre and co-workers ing the association between ER and IVF.30,36-40 A Early repolarization syndrome (ERS) and demonstrated that 31% of the IVF group, com- recent case-control study explored the prognos- Brugada syndrome (BrS) share similar elec- pared to 5% of the controls displayed an early tic significance of ER among chronic coronary trocardiogram (ECG) features, clinical out- repolarization pattern consisting of a J point disease patients with implantable cardioverter- comes, risk factors as well as a common elevation (>0.1 mV), slurring of the terminal defibrillator (ICD).41 The prevalence of inferior arrhythmic platform related to amplification of part of the QRS and ST segment elevation in ER was significantly greater among patients 1 31 Ito-mediated J waves. the inferior and/or lateral ECG leads. who had appropriate ICD therapy for ventricular Also referred to as the Osborn wave, the J In the same issue of the New England arrhythmias than in patients who were arrhyth- wave or elevated J point has been described in Journal of Medicine, Nam and co-workers mia-free (28% vs 8%, P=0.011), irrespective of [page 8] [Cardiogenetics 2013; 3:e2] Review their ejection fraction. Rgwy noted that ER bomb survivors in the Nagasaki region of ple). BrS represents a fourth variant in which prevalence was much greater among young Japan40 reported that in subjects followed over ER is limited to the right precordial leads. males compared to females and that the higher a period of 46 years, a stable ER pattern was prevalence in males declines rapidly with age, found in 650 subjects resulting in a prevalence suggesting a potential influence of testosterone of 29.3%. Mortality rates in subjects with ER as a modifier of J-wave or ER manifestation. did not show an increased risk for all-cause Mechanisms underlying This male predominance is observed with all of mortality or cardiac death, but the risk for sud- the inscription of the 9 the J wave syndromes, including Brugada syn- den unexpected death was significantly higher electrocardiogram J wave and drome.42 among ER subjects, as in the other studies. The prevalence and prognosis of inferior or Based on a review of published clinical data, associated arrhythmogenesis infero-lateral ER have also been studied in sev- we recently suggested a classification scheme The cellular basis for the J wave was first eral general population studies.31,32,34,35,40 In a for ER.9 An ER pattern appearing exclusively in identified in 1996.20 Transmural distribution of study of 10,864 middle-aged Fins enrolled in a the lateral precordial leads was designated as the transient outward current (I )-mediated population-based study of coronary heart dis- type 1; this form is prevalent among healthy to ease between (1966-1972) with a mean follow- male athletes and is thought to be associated action potential notch was shown to be respon- up of 30±11 years, the prevalence of inferolat- with a relatively low level of risk for arrhythmic sible for the inscription of the electrocardio- 20,44,45 eral ER at entry was 5.8%. Inferior ER was events. ER pattern in the inferior or infero-lat- graphic J wave. The ventricular epicardial associated with increased risk of cardiac mor- eral leads was designated as type 2; this form action potential, particularly in the right ven- tality [relative risk (RR) 1.28, P=0.03], and appears to be associated with a moderate level tricle, displays a prominent Ito-mediated notch inferior ER patterns with J-point elevations of risk. Finally, an ER pattern manifest globally or spike and dome morphology.
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