Cardiac arrest occurs at rest or during sleep These patients may also display a high-risk ER pattern (J-point elevation >2 mm in the inferior or inferolateral leads or globally and/or horizontal or down sloping ST segment. (See 'Prognosis of ER pattern' above.) The ER pattern is not always identified on routine ECG due to the intermittent nature of ER. Bradycardia dependent and vagally dependent augmentation of ER has been reported [86]. However, no provocative test, such as pharmacologic augmentation of parasympathetic tone, is currently available and validated in this setting. Although the utility has not been studied systematically, tilt table testing may be of assistance to establish if vagal stimulation is associated with VF/syncope and/or if high-risk ER features are provoked. However, the diagnostic accuracy of this approach is unknown, and vasovagal syncope is far more common in comparison with VF due to ER syndrome. (See 'Prognostic variables' above and "Upright tilt table testing in the evaluation of syncope".) DIFFERENTIAL DIAGNOSIS ER versus Brugada syndrome Some individuals with Brugada syndrome (ECG findings of ST- segment elevation in leads V1 to V2 associated with SCD or sustained ventricular arrhythmia) also have ER (approximately 12 percent) as variants in genes encoding the L-type calcium channel, ATP-sensitive potassium channel, and sodium channels have been associated with both of these conditions [61,62,64,87-90]. Additionally, some ECG characteristics of ER resemble features of the Brugada ECG, including J waves, pause and bradycardia dependent accentuation, the dynamic nature of the ECG manifestations, short-coupled extra-systole-induced polymorphic ventricular tachycardia/ventricular fibrillation, and suppression of the ECG features and arrhythmia with isoproterenol and quinidine [8,82]. However, the provocation of the Brugada pattern by sodium channel blocker is not observed in ER [91]. In fact, sodium channel blockers in most patients with ER attenuate the J-point, whereas the J-point is augmented by sodium-channel blockers in the right precordial leads in patients with a Brugada ECG. Furthermore, a positive signal-averaged ECG and structural abnormalities in the RV outflow tract are not consistently observed and have not been reported in patients with ER, respectively [92-94]. (See "Brugada syndrome: Clinical presentation, diagnosis, and evaluation".) ER versus acute pericarditis As is seen in ER, there is J-point elevation with resultant ST segment elevation in patients with acute pericarditis. Symptom presentation is markedly https://www.uptodate.com/contents/early-repolarization/print 13/37 7/6/23, 3:25 PM Early repolarization - UpToDate different in the two conditions. Unlike ER, most patients with acute pericarditis have ST elevations diffusely in most or all limb and precordial leads. Additionally, patients with acute pericarditis often have deviation of the PR segment, which is not present in ER. (See "Acute pericarditis: Clinical presentation and diagnosis", section on 'Electrocardiogram'.) ER versus acute myocardial injury While patients with acute myocardial injury due to ST- elevation myocardial infarction (STEMI) can initially have elevation of the J point with concave ST- segment elevation, the ST-segment elevation typically becomes more pronounced and convex (rounded upward) as the infarction persists. However, the primary distinguishing factor between ER and acute myocardial injury is the presence of clinical symptoms such as chest pain or dyspnea. The distinction between the ECG findings of ER and acute MI are discussed in greater detail elsewhere. (See "Electrocardiogram in the diagnosis of myocardial ischemia and infarction", section on 'Early repolarization'.) TREATMENT Treatment of ER pattern As discussed above, the ER pattern is nearly always a benign incidental ECG finding, with no specific signs or symptoms attributed to it. In addition, there is no current risk stratification strategy for asymptomatic patients with ER pattern in the general population and within families with ER pattern that would allow for the identification of higher risk individuals with the ER pattern who might be candidates for treatment. The 2017 American Heart Association/American College of Cardiology/Heart Rhythm Society guideline for management of patients with ventricular arrhythmias and the prevention of SCD recommends observation with no treatment, and the 2015 European Society of Cardiology guidelines on the treatment of ventricular arrhythmias and prevention of SCD found that there was "insufficient evidence" to make a recommendation on the management of the ER pattern without associated symptomatic ventricular arrhythmias [12,95]. As such, for patients with the incidental finding of the ER pattern on their ECG, we recommend observation without therapy ( table 1). Treatment of ER syndrome with idiopathic VF Among survivors of SCD due to idiopathic ventricular fibrillation (VF), the reported rate of recurrent VF ranges between 22 and 37 percent at two to four years [96-98]. Because these patients have no demonstrated structural heart disease, they have an excellent prognosis for long-term survival if VF is treated ( algorithm 1). As a result, such patients are best treated with an ICD [12,95-100]. (See "Secondary prevention of sudden cardiac death in heart failure and cardiomyopathy".) https://www.uptodate.com/contents/early-repolarization/print 14/37 7/6/23, 3:25 PM Early repolarization - UpToDate In patients with idiopathic VF, substrate and/or trigger ablation is feasible, safe, and effective in specialized centers [78,79]. In 43 patients undergoing ablation for recurrent VF episodes due to ER syndrome, two phenotypes were identified; one with late depolarization abnormalities predominantly in the epicardium of the RV outflow tract and RV inferolateral epicardium (group 1), and the other with VF triggers associated with Purkinje sites but without abnormal epicardial/endocardial depolarization substrates (group 2) [78]. Epicardial anterior RV, RV outflow tract, inferior RV, posterior and posterolateral LV and apical ablation guided by location of abnormal depolarization substrates +/- premature ventricular complex/contraction (PVC; also referred to a premature ventricular beats or premature ventricular depolarizations) triggers in group 1 and Purkinje PVC ablation in group 2 were effective with no VF recurrence in 91 percent at 31 +/- 26 months follow-up. Single procedure success was 67 percent. Ablation resulted in the disappearance of the ER pattern in 82 percent. Acute treatment of ER syndrome with VF storm For patients with ER syndrome and ongoing acute VF requiring frequent defibrillation, we suggest intravenous isoproterenol ( table 1). In a multicenter observational cohort study of 122 patients (90 males, mean age 37 12 years) with ER in the inferolateral leads and more than three episodes of idiopathic VF (including those with electrical storm), isoproterenol was effective for the acute suppression of VF, immediately suppressing electrical storms in seven of seven patients [101]. Theophylline has been described in a case report as eliminating ongoing malignant ventricular arrhythmias in spite of treatment with quinidine and high-rate ventricular pacing [102]. High-dose flecainide has also been reported to be effective at suppressing VF in ER syndrome in a case report [103]. In an experimental canine model of ER, quinidine, cilostazol, and milrinone, each administered individually, have been shown to suppress hypothermia-induced ventricular arrhythmias [104]. Furthermore in an ER syndrome wedge preparation, cilostazol and milrinone or isoproterenol were demonstrated to reverse the repolarization defects underlying the development of phase 2 reentry and VT/VF by inhibition of transient outward potassium current (Ito) and augmentation of L-type calcium current (Ica) [68]. Chronic treatment of ER syndrome Chronic treatment of the ER syndrome should include an ICD for rapid treatment of any recurrent VF ( table 1) [12,41]. Patients with frequent recurrent episodes of VF resulting in ICD shocks may require suppressive therapy with an antiarrhythmic drug and, rarely, ablation of a stereotypic initiating PVC. (See "Overview of catheter ablation of cardiac arrhythmias".) For patients with ER syndrome with prior resuscitated SCD due to VF, we recommend implantation of an ICD for secondary prevention of SCD. ICD therapy is highly effective in terminating ventricular arrhythmias in nearly all cases. https://www.uptodate.com/contents/early-repolarization/print 15/37 7/6/23, 3:25 PM Early repolarization - UpToDate Antiarrhythmic drug therapy is a therapeutic option for patients with recurrent VF following ICD implantation. For patients with ER syndrome and recurrent VF, we suggest the use of quinidine, a class IA antiarrhythmic drug, for chronic suppressive therapy. Class IA antiarrhythmic drugs have been shown to prevent reinduction of polymorphic ventricular arrhythmias both during electrophysiologic (EP) study and in long-term follow-up in patients with idiopathic VF [96,105]. The target dose should be 800 to 1600 mg per day, with a common target of 1200 to 1600 mg of quinidine sulfate divided in four doses. (See "Pharmacologic therapy in survivors of sudden cardiac arrest".) For patients with ER syndrome and prior idiopathic VF but no documented recurrent arrhythmias, we do not suggest chronic suppressive treatment with an antiarrhythmic drug as the frequency of recurrent VF attributed to ER syndrome is highly variable and not readily predicted. In an in vitro pharmacological model, the phosphodiesterase III inhibitors cilostazol or milrinone have been demonstrated to diminish ER manifestations and prevent the hypothermia-induced phase 2 reentry and ventricular tachycardia (VT)/VF [104]. Quinidine also demonstrated similar effects in this model. Patients with ER syndrome who participate in competitive athletics require further evaluation and appropriate precautions prior to returning to competition [106]. SOCIETY GUIDELINE LINKS Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Inherited arrhythmia syndromes" and "Society guideline links: Ventricular arrhythmias".) SUMMARY AND RECOMMENDATIONS Early repolarization (ER) is defined as either a sharp well-defined positive deflection or notch immediately following a positive QRS complex at the onset of the ST segment, or the presence of slurring at the terminal part of the QRS complex (since the J-wave or J-point elevation may be hidden in the terminal part of the QRS complex, resulting in the slurring of the terminal QRS complex) ( waveform 1). Most literature defines ER as being present on the ECG when there is J-point elevation of 0.1 mV in two adjacent leads with either a slurred or notched morphology. (See 'ECG findings' above.) https://www.uptodate.com/contents/early-repolarization/print 16/37 7/6/23, 3:25 PM Early repolarization - UpToDate ER is an ECG finding. Two terms, distinguished by the presence or absence of symptomatic arrhythmias, have been used to describe patients with this ECG finding (see 'ER pattern versus ER syndrome' above): The ER pattern describes the patient with appropriate ECG findings in the absence of symptomatic arrhythmias. The ER syndrome applies to the patient with both appropriate ECG findings and symptomatic arrhythmias (cardiac arrest). The mere presence of ER pattern on ECG should not lead to a classification of ER syndrome in the absence of symptoms or documented ventricular fibrillation (VF). Several population studies have estimated that the prevalence of ER ranges from 5 to 13 percent of persons. The perception that ER was a benign finding has changed, with numerous studies suggesting a two- to threefold increased risk of death in those with ER versus those without ER. While ER appears to increase one's risk of sudden cardiac death (SCD), the absolute risk of SCD remains exceedingly low in otherwise healthy people. (See 'Prevalence' above and 'Arrhythmic risk' above.) The genetic basis of ER continues to be elucidated, with the evidence restricted to either case reports or preliminary studies that fall short of clearly identifying the genetic basis of ER. (See 'Genetic basis and inheritance of ER' above.) The purported mechanisms of ER and idiopathic VF reflect either an imbalance in the ion channel currents responsible for the terminal portion of depolarization or the early portion of repolarization and/or abnormal epicardial RV depolarization abnormalities with conduction delay. (See 'Mechanism of ER and idiopathic ventricular fibrillation' above.) Given its relatively high prevalence in the general population in comparison with the incidence of idiopathic VF, the ER pattern is almost always an incidental ECG finding. The diagnosis of ER syndrome, however, should be considered in a survivor of SCD with ECG evidence of ER and VF and an apparently structurally normal heart following extensive testing. (See 'ER pattern' above and 'ER syndrome' above.) For patients with the incidental finding of the ER pattern on their ECG, we recommend observation without therapy (Grade 1A). (See 'Treatment of ER pattern' above.) For patients with ER and ongoing acute VF (VF storm) requiring frequent defibrillation, we suggest intravenous isoproterenol (Grade 2C). (See 'Acute treatment of ER syndrome with VF storm' above.) https://www.uptodate.com/contents/early-repolarization/print 17/37 7/6/23, 3:25 PM Early repolarization - UpToDate For patients with ER syndrome with prior resuscitated SCD due to VF, we recommend implantation of an implantable cardioverter-defibrillator (ICD) for secondary prevention of SCD (Grade 1A). (See 'Chronic treatment of ER syndrome' above.) For patients with ER syndrome and recurrent VF, we suggest the use of quinidine, a class IA antiarrhythmic drug, for chronic suppressive therapy (Grade 2C). (See 'Chronic treatment of ER syndrome' above.) Catheter ablation targeting epicardial substrates and/or Purkinje premature ventricular complex (PVC) triggers is appropriate in patients with recurrent VF not responding to quinidine. (See "Overview of catheter ablation of cardiac arrhythmias".) Patients with ER syndrome who have had an ICD placed but who have had no documented recurrent arrhythmias do not require chronic antiarrhythmic drug treatment. (See 'Chronic treatment of ER syndrome' above.) Use of UpToDate is subject to the Terms of Use. REFERENCES 1. Rautaharju PM, Surawicz B, Gettes LS, et al. AHA/ACCF/HRS recommendations for the standardization and interpretation of the electrocardiogram: part IV: the ST segment, T and U waves, and the QT interval: a scientific statement from the American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; the American College of Cardiology Foundation; and the Heart Rhythm Society: endorsed by the International Society for Computerized Electrocardiology. Circulation 2009; 119:e241. 2. Patton KK, Ellinor PT, Ezekowitz M, et al. Electrocardiographic Early Repolarization: A Scientific Statement From the American Heart Association. Circulation 2016; 133:1520. 3. Macfarlane PW, Antzelevitch C, Haissaguerre M, et al. The Early Repolarization Pattern: A Consensus Paper. J Am Coll Cardiol 2015; 66:470. 4. Ha ssaguerre M, Derval N, Sacher F, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008; 358:2016. 5. Tikkanen JT, Anttonen O, Junttila MJ, et al. Long-term outcome associated with early repolarization on electrocardiography. N Engl J Med 2009; 361:2529. 6. Antzelevitch C, Yan GX. J wave syndromes. Heart Rhythm 2010; 7:549. 7. Antzelevitch C, Yan GX, Viskin S. Rationale for the use of the terms J-wave syndromes and early repolarization. J Am Coll Cardiol 2011; 57:1587. https://www.uptodate.com/contents/early-repolarization/print 18/37 7/6/23, 3:25 PM Early repolarization - UpToDate 8. Nam GB, Ko KH, Kim J, et al. Mode of onset of ventricular fibrillation in patients with early repolarization pattern vs. Brugada syndrome. Eur Heart J 2010; 31:330. 9. Surawicz B, Macfarlane PW. Inappropriate and confusing electrocardiographic terms: J-wave syndromes and early repolarization. J Am Coll Cardiol 2011; 57:1584. 10. Wilde AA. "J-wave syndromes" bring the ATP-sensitive potassium channel back in the spotlight. Heart Rhythm 2012; 9:556. 11. Derval N, Simpson CS, Birnie DH, et al. Prevalence and characteristics of early repolarization in the CASPER registry: cardiac arrest survivors with preserved ejection fraction registry. J Am Coll Cardiol 2011; 58:722. 12. Priori SG, Blomstr m-Lundqvist C, Mazzanti A, et al. 2015 ESC Guidelines for the management of patients with ventricular arrhythmias and the prevention of sudden cardiac death: The Task Force for the Management of Patients with Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death of the European Society of Cardiology (ESC). Endorsed by: Association for European Paediatric and Congenital Cardiology (AEPC). Eur Heart J 2015; 36:2793. 13. Rosso R, Kogan E, Belhassen B, et al. J-point elevation in survivors of primary ventricular fibrillation and matched control subjects: incidence and clinical significance. J Am Coll Cardiol 2008; 52:1231. 14. Sinner MF, Reinhard W, M ller M, et al. Association of early repolarization pattern on ECG with risk of cardiac and all-cause mortality: a population-based prospective cohort study (MONICA/KORA). PLoS Med 2010; 7:e1000314. 15. Haruta D, Matsuo K, Tsuneto A, et al. Incidence and prognostic value of early repolarization pattern in the 12-lead electrocardiogram. Circulation 2011; 123:2931. 16. McNamara DA, Bennett AJ, Ayers C, et al. Early Repolarization Pattern Is Associated With Increased Left Ventricular Mass: Insights From the Dallas Heart Study. JACC Clin Electrophysiol 2019; 5:395. 17. Olson KA, Viera AJ, Soliman EZ, et al. Long-term prognosis associated with J-point elevation in a large middle-aged biracial cohort: the ARIC study. Eur Heart J 2011; 32:3098. 18. Abe A, Ikeda T, Tsukada T, et al. Circadian variation of late potentials in idiopathic ventricular fibrillation associated with J waves: insights into alternative pathophysiology and risk stratification. Heart Rhythm 2010; 7:675. 19. Sugao M, Fujiki A, Nishida K, et al. Repolarization dynamics in patients with idiopathic ventricular fibrillation: pharmacological therapy with bepridil and disopyramide. J Cardiovasc Pharmacol 2005; 45:545. https://www.uptodate.com/contents/early-repolarization/print 19/37 7/6/23, 3:25 PM Early repolarization - UpToDate 20. Sahara M, Sagara K, Yamashita T, et al. J wave and ST segment elevation in the inferior leads: a latent type of variant Brugada syndrome? Jpn Heart J 2002; 43:55. 21. Kalla H, Yan GX, Marinchak R. Ventricular fibrillation in a patient with prominent J (Osborn) waves and ST segment elevation in the inferior electrocardiographic leads: a Brugada syndrome variant? J Cardiovasc Electrophysiol 2000; 11:95. 22. Aizawa Y, Tamura M, Chinushi M, et al. Idiopathic ventricular fibrillation and bradycardia- dependent intraventricular block. Am Heart J 1993; 126:1473. 23. Siebermair J, Sinner MF, Beckmann BM, et al. Early repolarization pattern is the strongest predictor of arrhythmia recurrence in patients with idiopathic ventricular fibrillation: results from a single centre long-term follow-up over 20 years. Europace 2016; 18:718. 24. Rosso R, Glikson E, Belhassen B, et al. Distinguishing "benign" from "malignant early repolarization": the value of the ST-segment morphology. Heart Rhythm 2012; 9:225. 25. Wu SH, Lin XX, Cheng YJ, et al. Early repolarization pattern and risk for arrhythmia death: a meta-analysis. J Am Coll Cardiol 2013; 61:645. 26. Tikkanen JT, Junttila MJ, Anttonen O, et al. Early repolarization: electrocardiographic phenotypes associated with favorable long-term outcome. Circulation 2011; 123:2666. 27. Serra-Grima R, Do ate M, lvarez-Garc a J, et al. Long-term follow-up of early repolarization pattern in elite athletes. Am J Med 2015; 128:192.e1. 28. Barbosa EC, Bomfim Ade S, Benchimol-Barbosa PR, Ginefra P. Ionic mechanisms and vectorial model of early repolarization pattern in the surface electrocardiogram of the athlete. Ann Noninvasive Electrocardiol 2008; 13:301. 29. Quattrini FM, Pelliccia A, Assorgi R, et al. Benign clinical significance of J-wave pattern (early repolarization) in highly trained athletes. Heart Rhythm 2014; 11:1974. 30. Klatsky AL, Oehm R, Cooper RA, et al. The early repolarization normal variant electrocardiogram: correlates and consequences. Am J Med 2003; 115:171. 31. Rollin A, Maury P, Bongard V, et al. Prevalence, prognosis, and identification of the malignant form of early repolarization pattern in a population-based study. Am J Cardiol 2012; 110:1302. 32. Ilkhanoff L, Soliman EZ, Prineas RJ, et al. Clinical characteristics and outcomes associated with the natural history of early repolarization in a young, biracial cohort followed to middle age: the Coronary Artery Risk Development in Young Adults (CARDIA) study. Circ Arrhythm Electrophysiol 2014; 7:392. 33. Cheng YJ, Lin XX, Ji CC, et al. Role of Early Repolarization Pattern in Increasing Risk of Death. J Am Heart Assoc 2016; 5. https://www.uptodate.com/contents/early-repolarization/print 20/37 7/6/23, 3:25 PM Early repolarization - UpToDate 34. Pargaonkar VS, Perez MV, Jindal A, et al. Long-term prognosis of early repolarization with J- wave and QRS slur patterns on the resting electrocardiogram: a cohort study. Ann Intern Med 2015; 163:747. 35. Roten L, Derval N, Maury P, et al. Benign vs. malignant inferolateral early repolarization: Focus on the T wave. Heart Rhythm 2016; 13:894. 36. Yoon N, Hong SN, Cho JG, et al. Experimental verification of the value of the Tpeak -Tend interval in ventricular arrhythmia inducibility in an early repolarization syndrome model. J Cardiovasc Electrophysiol 2019; 30:2098. 37. Karim Talib A, Sato N, Sakamoto N, et al. Enhanced transmural dispersion of repolarization in patients with J wave syndromes. J Cardiovasc Electrophysiol 2012; 23:1109. 38. Cristoforetti Y, Biasco L, Giustetto C, et al. J-wave duration and slope as potential tools to discriminate between benign and malignant early repolarization. Heart Rhythm 2016; 13:806. 39. Holkeri A, Eranti A, Haukilahti MAE, et al. Impact of age and sex on the long-term prognosis associated with early repolarization in the general population. Heart Rhythm 2020; 17:621. 40. Nunn LM, Bhar-Amato J, Lowe MD, et al. Prevalence of J-point elevation in sudden arrhythmic death syndrome families. J Am Coll Cardiol 2011; 58:286. 41. Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS expert consensus statement on the diagnosis and management of patients with inherited primary arrhythmia syndromes: document endorsed by HRS, EHRA, and APHRS in May 2013 and by ACCF, AHA, PACES, and AEPC in June 2013. Heart Rhythm 2013; 10:1932. 42. Merchant FM, Noseworthy PA, Weiner RB, et al. Ability of terminal QRS notching to distinguish benign from malignant electrocardiographic forms of early repolarization. Am J Cardiol 2009; 104:1402. 43. Cheng YJ, Li ZY, Yao FJ, et al. Early repolarization is associated with a significantly increased risk of ventricular arrhythmias and sudden cardiac death in patients with structural heart diseases. Heart Rhythm 2017; 14:1157. 44. Walsh JA 3rd, Ilkhanoff L, Soliman EZ, et al. Natural history of the early repolarization pattern in a biracial cohort: CARDIA (Coronary Artery Risk Development in Young Adults) Study. J Am Coll Cardiol 2013; 61:863. 45. Perez MV, Uberoi A, Jain NA, et al. The prognostic value of early repolarization with ST- segment elevation in African Americans. Heart Rhythm 2012; 9:558. 46. Rosso R, Adler A, Halkin A, Viskin S. Risk of sudden death among young individuals with J waves and early repolarization: putting the evidence into perspective. Heart Rhythm 2011; https://www.uptodate.com/contents/early-repolarization/print 21/37 7/6/23, 3:25 PM Early repolarization - UpToDate 8:923. 47. Patel RB, Ilkhanoff L, Ng J, et al. Clinical characteristics and prevalence of early repolarization associated with ventricular arrhythmias following acute ST-elevation myocardial infarction. Am J Cardiol 2012; 110:615. 48. Patel RB, Ng J, Reddy V, et al. Early repolarization associated with ventricular arrhythmias in patients with chronic coronary artery disease. Circ Arrhythm Electrophysiol 2010; 3:489. 49. Furukawa Y, Yamada T, Morita T, et al. Early repolarization pattern associated with sudden cardiac death: long-term follow-up in patients with chronic heart failure. J Cardiovasc Electrophysiol 2013; 24:632. 50. Watanabe H, Makiyama T, Koyama T, et al. High prevalence of early repolarization in short QT syndrome. Heart Rhythm 2010; 7:647. 51. Panicker GK, Manohar D, Karnad DR, et al. Early repolarization and short QT interval in healthy subjects. Heart Rhythm 2012; 9:1265. 52. Caliskan K, Ujvari B, Bauernfeind T, et al. The prevalence of early repolarization in patients with noncompaction cardiomyopathy presenting with malignant ventricular arrhythmias. J Cardiovasc Electrophysiol 2012; 23:938. 53. Laksman ZW, Gula LJ, Saklani P, et al. Early repolarization is associated with symptoms in patients with type 1 and type 2 long QT syndrome. Heart Rhythm 2014; 11:1632. 54. Sugrue A, Rohatgi RK, Bos M, et al. Clinical Significance of Early Repolarization in Long QT Syndrome. JACC Clin Electrophysiol 2018; 4:1238. 55. T l men E, Schulze-Bahr E, Zumhagen S, et al. Early repolarization pattern: a marker of increased risk in patients with catecholaminergic polymorphic ventricular tachycardia. Europace 2016; 18:1587. 56. Kaneko Y, Horie M, Niwano S, et al. Electrical storm in patients with brugada syndrome is associated with early repolarization. Circ Arrhythm Electrophysiol 2014; 7:1122. 57. Hasegawa Y, Watanabe H, Ikami Y, et al. Early repolarization and risk of lone atrial fibrillation. J Cardiovasc Electrophysiol 2019; 30:565. 58. McNair PW, Benenson DM, Ip JE, et al. Prevalence of early repolarization pattern in patients with lone atrial fibrillation. J Electrocardiol 2017; 50:545. 59. Mahida S, Derval N, Sacher F, et al. Role of electrophysiological studies in predicting risk of ventricular arrhythmia in early repolarization syndrome. J Am Coll Cardiol 2015; 65:151. 60. Ha ssaguerre M, Chatel S, Sacher F, et al. Ventricular fibrillation with prominent early repolarization associated with a rare variant of KCNJ8/KATP channel. J Cardiovasc Electrophysiol 2009; 20:93. https://www.uptodate.com/contents/early-repolarization/print 22/37 7/6/23, 3:25 PM Early repolarization - UpToDate 61. Watanabe H, Nogami A, Ohkubo K, et al. Electrocardiographic characteristics and SCN5A mutations in idiopathic ventricular fibrillation associated with early repolarization. Circ Arrhythm Electrophysiol 2011; 4:874. 62. Medeiros-Domingo A, Tan BH, Crotti L, et al. Gain-of-function mutation S422L in the KCNJ8- encoded cardiac K(ATP) channel Kir6.1 as a pathogenic substrate for J-wave syndromes. Heart Rhythm 2010; 7:1466. 63. Barajas-Mart nez H, Hu D, Ferrer T, et al. Molecular genetic and functional association of Brugada and early repolarization syndromes with S422L missense mutation in KCNJ8. Heart Rhythm 2012; 9:548. 64. Burashnikov E, Pfeiffer R, Barajas-Martinez H, et al. Mutations in the cardiac L-type calcium channel associated with inherited J-wave syndromes and sudden cardiac death. Heart Rhythm 2010; 7:1872. 65. Noseworthy PA, Tikkanen JT, Porthan K, et al. The early repolarization pattern in the general population: clinical correlates and heritability. J Am Coll Cardiol 2011; 57:2284. 66. Reinhard W, Kaess BM, Debiec R, et al. Heritability of early repolarization: a population- based study. Circ Cardiovasc Genet 2011; 4:134. 67. Gourraud JB, Le Scouarnec S, Sacher F, et al. Identification of large families in early repolarization syndrome. J Am Coll Cardiol 2013; 61:164. 68. Patocskai B, Barajas-Martinez H, Hu D, et al. Cellular and ionic mechanisms underlying the effects of cilostazol, milrinone, and isoproterenol to suppress arrhythmogenesis in an experimental model of early repolarization syndrome. Heart Rhythm 2016; 13:1326. 69. Ji CC, Yao FJ, Cheng YJ, et al. A novel DPP6 variant in Chinese families causes early repolarization syndrome. Exp Cell Res 2019; 384:111561. 70. Cheng YJ, Yao H, Ji CC, et al. A Heterozygous Missense hERG Mutation Associated with Early Repolarization Syndrome. Cell Physiol Biochem 2018; 51:1301. 71. Takayama K, Ohno S, Ding WG, et al. A de novo gain-of-function KCND3 mutation in early repolarization syndrome. Heart Rhythm 2019; 16:1698. 72. Teumer A, Trenkwalder T, Kessler T, et al. KCND3 potassium channel gene variant confers susceptibility to electrocardiographic early repolarization pattern. JCI Insight 2019; 4. 73. Chauveau S, Janin A, Till M, et al. Early repolarization syndrome caused by de novo duplication of KCND3 detected by next-generation sequencing. HeartRhythm Case Rep 2017; 3:574. 74. Li N, Wang R, Hou C, et al. A heterozygous missense SCN5A mutation associated with early repolarization syndrome. Int J Mol Med 2013; 32:661. https://www.uptodate.com/contents/early-repolarization/print 23/37 7/6/23, 3:25 PM Early repolarization - UpToDate 75. Yao H, Ji CC, Cheng YJ, et al. Mutation in KCNE1 associated to early repolarization syndrome by modulation of slowly activating delayed rectifier K+ current. Exp Cell Res 2018; 363:315. 76. Sinner MF, Porthan K, Noseworthy PA, et al. A meta-analysis of genome-wide association studies of the electrocardiographic early repolarization pattern. Heart Rhythm 2012; 9:1627. 77. Yan GX, Antzelevitch C. Cellular basis for the electrocardiographic J wave. Circulation 1996; 93:372. 78. Nademanee K, Haissaguerre M, Hocini M, et al. Mapping and Ablation of Ventricular Fibrillation Associated With Early Repolarization Syndrome. Circulation 2019; 140:1477. 79. Ha ssaguerre M, Nademanee K, Hocini M, et al. Depolarization versus repolarization abnormality underlying inferolateral J-wave syndromes: New concepts in sudden cardiac death with apparently normal hearts. Heart Rhythm 2019; 16:781. 80. Voskoboinik A, Hsia H, Moss J, et al. The many faces of early repolarization syndrome: A single-center case series. Heart Rhythm 2020; 17:273. 81. Koncz I, Gurabi Z, Patocskai B, et al. Mechanisms underlying the development of the electrocardiographic and arrhythmic manifestations of early repolarization syndrome. J Mol Cell Cardiol 2014; 68:20. 82. Roten L, Derval N, Sacher F, et al. Heterogeneous response of J-wave syndromes to beta- adrenergic stimulation. Heart Rhythm 2012; 9:1970. 83. Maury P, Sacher F, Rollin A, et al. Ventricular fibrillation in loop recorder memories in a patient with early repolarization syndrome. Europace 2012; 14:148. 84. Krahn AD, Healey JS, Chauhan V, et al. Systematic assessment of patients with unexplained cardiac arrest: Cardiac Arrest Survivors With Preserved Ejection Fraction Registry (CASPER). Circulation 2009; 120:278. 85. Aizawa Y, Chinushi M, Hasegawa K, et al. Electrical storm in idiopathic ventricular fibrillation is associated with early repolarization. J Am Coll Cardiol 2013; 62:1015. 86. Mizumaki K, Nishida K, Iwamoto J, et al. Vagal activity modulates spontaneous augmentation of J-wave elevation in patients with idiopathic ventricular fibrillation. Heart Rhythm 2012; 9:249. 87. Letsas KP, Sacher F, Probst V, et al. Prevalence of early repolarization pattern in inferolateral leads in patients with Brugada syndrome. Heart Rhythm 2008; 5:1685. 88. Sarkozy A, Chierchia GB, Paparella G, et al. Inferior and lateral electrocardiographic repolarization abnormalities in Brugada syndrome. Circ Arrhythm Electrophysiol 2009; 2:154. https://www.uptodate.com/contents/early-repolarization/print 24/37 7/6/23, 3:25 PM Early repolarization - UpToDate 89. Antzelevitch C, Pollevick GD, Cordeiro JM, et al. Loss-of-function mutations in the cardiac calcium channel underlie a new clinical entity characterized by ST-segment elevation, short QT intervals, and sudden cardiac death. Circulation 2007; 115:442. 90. Hong K, Berruezo-Sanchez A, Poungvarin N, et al. Phenotypic characterization of a large European family with Brugada syndrome displaying a sudden unexpected death syndrome mutation in SCN5A:. J Cardiovasc Electrophysiol 2004; 15:64. 91. Kawata H, Noda T, Yamada Y, et al. Effect of sodium-channel blockade on early repolarization in inferior/lateral leads in patients with idiopathic ventricular fibrillation and Brugada syndrome. Heart Rhythm 2012; 9:77. 92. Nam GB, Kim YH, Antzelevitch C. Augmentation of J waves and electrical storms in patients with early repolarization. N Engl J Med 2008; 358:2078. 93. Roten L, Derval N, Sacher F, et al. Ajmaline attenuates electrocardiogram characteristics of inferolateral early repolarization. Heart Rhythm 2012; 9:232. 94. Nademanee K, Veerakul G, Chandanamattha P, et al. Prevention of ventricular fibrillation episodes in Brugada syndrome by catheter ablation over the anterior right ventricular outflow tract epicardium. Circulation 2011; 123:1270. 95. Al-Khatib SM, Stevenson WG, Ackerman MJ, et al. 2017 AHA/ACC/HRS Guideline for Management of Patients With Ventricular Arrhythmias and the Prevention of Sudden Cardiac Death: A Report of the American College of Cardiology/American Heart Association Task Force on Clinical Practice Guidelines and the Heart Rhythm Society. J Am Coll Cardiol 2018; 72:e91. 96. Viskin S, Belhassen B. Idiopathic ventricular fibrillation. Am Heart J 1990; 120:661. 97. Wever EF, Hauer RN, Oomen A, et al. Unfavorable outcome in patients with primary electrical disease who survived an episode of ventricular fibrillation. Circulation 1993; 88:1021. 98. Marcus FI. Idiopathic ventricular fibrillation. J Cardiovasc Electrophysiol 1997; 8:1075. 99. Survivors of out-of-hospital cardiac arrest with apparently normal heart. Need for definition and standardized clinical evaluation. Consensus Statement of the Joint Steering Committees of the Unexplained Cardiac Arrest Registry of Europe and of the Idiopathic Ventricular Fibrillation Registry of the United States. Circulation 1997; 95:265. 100. Meissner MD, Lehmann MH, Steinman RT, et al. Ventricular fibrillation in patients without significant structural heart disease: a multicenter experience with implantable cardioverter- defibrillator therapy. J Am Coll Cardiol 1993; 21:1406. https://www.uptodate.com/contents/early-repolarization/print 25/37 7/6/23, 3:25 PM Early repolarization - UpToDate 101. Ha ssaguerre M, Sacher F, Nogami A, et al. Characteristics of recurrent ventricular fibrillation associated with inferolateral early repolarization role of drug therapy. J Am Coll Cardiol 2009; 53:612. 102. Perrin T, Guieu R, Koutbi L, et al. Theophylline as an adjunct to control malignant ventricular arrhythmia associated with early repolarization. Pacing Clin Electrophysiol 2018; 41:444. 103. Ahn J, Roh SY, Lee DI, et al. Effect of flecainide on suppression of ventricular fibrillation in a patient with early repolarization syndrome. Heart Rhythm 2016; 13:1724. 104. Gurabi Z, Koncz I, Patocskai B, et al. Cellular mechanism underlying hypothermia-induced ventricular tachycardia/ventricular fibrillation in the setting of early repolarization and the protective effect of quinidine, cilostazol, and milrinone. Circ Arrhythm Electrophysiol 2014; 7:134. 105. Belhassen B, Viskin S, Fish R, et al. Effects of electrophysiologic-guided therapy with Class IA antiarrhythmic drugs on the long-term outcome of patients with idiopathic ventricular fibrillation with or without the Brugada syndrome. J Cardiovasc Electrophysiol 1999; 10:1301. 106. Ackerman MJ, Zipes DP, Kovacs RJ, Maron BJ. Eligibility and Disqualification Recommendations for Competitive Athletes With Cardiovascular Abnormalities: Task Force 10: The Cardiac Channelopathies: A Scientific Statement From the American Heart Association and American College of Cardiology. J Am Coll Cardiol 2015; 66:2424. Topic 83199 Version 27.0 https://www.uptodate.com/contents/early-repolarization/print 26/37 7/6/23, 3:25 PM Early repolarization - UpToDate GRAPHICS Expert consensus recommendations regarding early repolarization from the HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes Expert consensus statement on diagnosis 1. ER syndrome is diagnosed in the presence of J-point elevation 1 mm in 2 contiguous inferior and/or lateral leads of a standard 12-lead ECG in a patient resuscitated from otherwise unexplained VF/polymorphic VT. 2. ER syndrome can be diagnosed in an SCD victim with a negative autopsy and medical chart review with a previous ECG demonstrating J-point elevation 1 mm in 2 contiguous inferior and/or lateral leads of a standard 12-lead ECG. 3. ER pattern can be diagnosed in the presence of J-point elevation 1 mm in 2 contiguous inferior and/or lateral leads of a standard 12-lead ECG. Expert consensus statement on therapeutic intervention CLASS I 1. ICD implantation is recommended in patients with a diagnosis of ER syndrome who have survived a cardiac arrest. CLASS IIa 2. Isoproterenol infusion can be useful in suppressing electrical storms in patients with a diagnosis of ER syndrome. 3. Quinidine in addition to an ICD can be useful for secondary prevention of VF in patients with a diagnosis of ER syndrome. CLASS IIb 4. ICD implantation may be considered in symptomatic family members of ER syndrome patients with a history of syncope in the presence of ST-segment elevation >1 mm in 2 inferior or lateral leads. 5. ICD implantation may be considered in asymptomatic individuals who demonstrate a high-risk ER ECG pattern (high J-wave amplitude, horizontal/descending ST segment) in the presence of a strong family history of juvenile unexplained sudden death with or without a pathogenic mutation. CLASS III 6. ICD implantation is not recommended in asymptomatic patients with an isolated ER ECG pattern. ECG: electrocardiogram; VF: ventricular fibrillation; VT: ventricular tachycardia; ER: early repolarization; SCD: sudden cardiac death; ICD: implantable cardioverter defibrillator. https://www.uptodate.com/contents/early-repolarization/print 27/37 7/6/23, 3:25 PM Early repolarization - UpToDate Priori SG, Wilde AA, Horie M, et al. HRS/EHRA/APHRS Expert Consensus Statement on the Diagnosis and Management of Patients with Inherited Primary Arrhythmia Syndromes. Heart Rhythm 2013; 10:1932. Table used with the permission of Elsevier Inc. All rights reserved. Graphic 93392 Version 2.0 https://www.uptodate.com/contents/early-repolarization/print 28/37 7/6/23, 3:25 PM Early repolarization - UpToDate Early repolarization end-QRS notch and slur terminology (A) Illustration of the amplitudes J onset (Jo), J peak (Jp), and J termination (Jt), as well as durations D and D , in relation to an end-QRS notch, as defined in the text. 1 2 (B) Illustration of Jp and Jt, as well as D , in relation to an end-QRS slur. 2