J wave patterns in the normal population

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ScienceDirect Journal of Electrocardiology 46 (2013) 411 – 416 www.jecgonline.com

Prevalence of early repolarisation/J wave patterns in the normal population Philippe Maury, MD,⁎ Anne Rollin, MD University Hospital Rangueil, Toulouse, France

Whatever the terminology which will be further used, either early repolarization (ER), Haïssaguerre or J wave syndrome, it should never be forgotten that the ECG pattern associating various degrees of J point elevation, slurring or notching of the terminal part of the QRS and further ST elevation has been described well before the recent growing interest of electrophysiologists for this entity and was - and should be still considered – as a normal ECG variant, at least in the very largest part of the normal population. Although this introductive assumption is far from original, it is worth to be recalled, because we should never lose sight of a feature that is present in several percent of the normal population cannot be considered as abnormal. Historically, one can track the first description of this pattern as soon as 1936, 1 followed by some other reports over the last half of the previous century. 2–17 At this step, the pattern was essentially described as ST elevation with a distinct notch or slur on the downslope of the R wave and was described as a “normal variant”, “unusual RT segment deviation”, “normal RST elevation variant” related to a “persistent juvenile pattern”, reflecting the belief of lack of any harmful consequence carried by this ECG pattern at this time. The clinical relevance of the documentation of this ECG pattern in a given patient however is not negligible, since it may mimick pericarditis, acute myocardial infarction or hypothermia for example, and may be associated, although in a very limited subset of patients, to sudden death (see other chapters from this issue). If we now carefully look at the publications relying on the prevalence of “early repolarization" pattern in the normal population, we can see that very various rates have been observed (roughly 1–15% according to most of the studies compiled in Table 2). These rather large differences are believed to reflect some differences in the definition (ST elevation or J wave) or methods to diagnose the pattern (manual vs automatic analysis for example), as well as differences in the studied population. Moreover, for some authors the QRS possibly includes the J wave/slurring – so ⁎ Corresponding author. Cardiology, University Hospital Rangueil, 31059 Toulouse Cedex 09, France. E-mail address: [email protected] 0022-0736/$ – see front matter © 2013 Elsevier Inc. All rights reserved. http://dx.doi.org/10.1016/j.jelectrocard.2013.06.014

they locate the J point at the onset of the ST segment – while others possibly place the J point at the intersection between slur or J wave onset and the descending limb of the R wave, but these details are exceptionally available. Furthermore, because of the variability of ER pattern over time, true prevalence is probably higher than reported and may also explain the published variable prevalence rates. We should however acknowledge that some differences in the reported prevalence rates remain difficult to explain. One can classify the publications about ER prevalence into two periods of time: before and after the regain of interest for ER caused by the suspicious association between ER and idiopathic ventricular fibrillation. Some studies already had investigated the prevalence and characteristics of ER before this “new” area. Most of them were performed because of the ECG similarity to the acute myocardial infarction or pericarditis leading to possible challenges in clinical practice. ER was mostly defined as a simple ST elevation located in the precordial leads. The good prognosis said to be carried by ER came probably from the fact that the pattern was observed in a significant proportion of young healthy persons and that it was not apparently associated to an increased mortality in the few available studies from this time. 18 In 1936 probably the first study reporting the prevalence of ER in four-lead ECG in 200 subjects found 25% and 16% in men and women, respectively. 1 Following relatively small populations studies reported prevalences between 1% and 25% (see Table 1), till 1995, where Mehta and colleagues found 1% ER prevalence over 60000 subjects with a male preponderance and often younger than 50 years. ER was present as elevated, concave, ST segments, located most commonly in the precordial leads (73%), with notch and slur on R wave (56%), and normalized at exercise. 15 But the most frequently cited study in this area was published in 2003 by Klatsky and colleagues who reviewed 2081 nine-lead ECGs drawn from 73088 volunteer Californian adults (44% men, 55% white) and defined “early repolarization” as ≥ 1 mm ST elevation without any other specification. 19 Of note is that these ECG were not fully randomly selected (chosen among “normal variant” automatically coded ECG and matched to controls in a 2:1 ratio). The overall prevalence of ER was only 0.9% in this sample.

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They found that ER pattern was significantly related to male gender, a younger age, African or Asian descent, and sportive activity. This was not associated to any morbidity or mortality. Subjects with ER had lower mean heart rates, more ample T waves and QRS complexes. ER was more evident in the limb leads, the majority showing “marked” ST elevations and 29% showing slurred R-wave downslope. Interestingly, some subgroups demonstrated significantly less arrhythmias when ER was present. 19 Such a low prevalence was probably biased by the lack of detection of subjects with J waves without ST elevation both by the automatic initial coding process and the manual ECG reviewing. Finally, further analysis of the control group revealed that half showed in fact ER, 20 possibly explaining the lack of prognosis role of ER. The reviving interest in ER came after the first reports of sudden death in healthy subjects with inferolateral ER and the evocation of a possible link between ER and malignant ventricular arrhythmias. 21 Case control studies were then published, comparing patients with idiopathic VF and ER to control groups from the normal population (Table 2). All demonstrated that ER pattern in survivors of idiopathic VF was more prevalent than in matched controls. The first report by Haïssaguerre et al. found a prevalence of 5% in 412 control subjects (66% males, mean age 36 years), 23 while ER prevalence was 13% for Rosso in 124 controls (mean 38 years) 24 and 3.5% for Nam in 1395 Korean subjects, 25 using the same definition of J waves (≥ 1 mm J point elevation in at least two inferior or lateral ECG leads, either as QRS slurring – a smooth transition from the QRS segment to the ST segment – or notching – a positive J deflection inscribed on the S wave, the J point being defined by the QRS–ST junction). Abe and colleagues found a 1.9% prevalence of subjects showing a J wave ≥ 1 mm over 6657 control subjects (mean 45 years, 51% males). 30 Reanalyzing ECG of 200 unselected control subjects having been identified as “normal” ER from a large ECG database, Merchant and colleagues found that only 31% had ≥ 1 mm J point elevation in ≥ 2 contiguous ECG leads. 26

Table 1 Listing of studies on the prevalence of early repolarization in normal populations as historically published before the awareness of a possible link of ER to sudden death. Author Shipley

Year 1

Definition Nb

1936 _

Grusin5

1954 ST +

Seriki11

1966 ST + ≥ 2 mm 1986 _ 1995 ST + ± notch/slur 1998 ST + 2001 ST + and notch 2003 ST +

Akhmedov14 Mehta15 Vitelli16 Mansi17 Klatsky19

% ER

Prognosis

200

25% (men) 15% _ (women) 159/50 25% (patients)/4% _ (control women) 300 34% _ 1306 60000

4.5% 1%

_ _

2686 597

1% 3.5%

_ _

2081

0.9%

none

Population-based studies were then performed for determining the prevalence of ER in large unselected populations (Table 2). The landmark paper in this area came from the group of Huikuri and colleagues in 2009. 29 They reviewed ECG from 10864 subjects from 30 to 59 years of age (52% men, mean age 44 years) representative of the middle-aged Finnish population. Defining ER as ≥ 1 mm or ≥ 2 mm J point elevation with either notched (positive J deflection inscribed on the S wave) or slurred (smooth transition from QRS to STsegment) in at least two consecutive inferior or lateral leads, they found a global prevalence of ER of 5.8% (≥ 1 mm) and 0.6% (≥ 2 mm). Of the subjects with early repolarisation undergoing repeated ECG at an average of 5 years later, the pattern was still present in 82%. They also demonstrated that ER pattern in the inferior leads was associated with an independent increased risk for cardiac and sudden death especially when J point elevation was ≥ 2 mm. 29 In 2010, Sinner et al. performed a large prospective population-based case-cohort study (German MONICA/ KORA study) comprising individuals of Central European descent. In 6213 participants (49% males, aged 35–74 years, mean 52) they found a 13% prevalence of ER (similarly defined). ER was correlated to an older age and male gender and was associated with increased cardiac and all-cause mortality. 31 In 2011, Olson et al. report their results on a prospective population-based cohort study designed to investigate the etiology and natural history of cardiovascular disease (ARIC study). They enrolled 15141 subjects (44% males, 27% black, aged 45–64) residing in four US communities. A Jpoint elevation ≥ 0.1 mV in any ECG lead – as automatically coded and manually confirmed – was found in 12% of the population. Subjects with J point elevation had lower heart rate and J point elevation was also significantly correlated to a younger age, to the male gender and to race (24% in blacks vs 8% in whites). J point elevation was more frequently observed in the inferior vs lateral leads. J point elevation was independently linked to sudden cardiac death over the 17 years of follow-up in whites or in women. 32 On the same year, Perez and colleagues performed a retrospective visual analysis of computerized ECG from 29281 outpatients believed to be devoid of apparent cardiovascular disease (mean age 55 years, 13% female, 13% AfroAmericans). They found 2.3% of patients with inferior or lateral ≥ 1 mm ST elevation. This pattern was correlated to a younger age, a slower heart rate, male gender and the AfricanAmerican descent (6.2% vs 1.7%). While ST elevation in whites was independently associated with cardiovascular death, it was not in African Americans. Interestingly, ST slope in African Americans was higher compared to that in non-African Americans and was inversely correlated with cardiovascular death in the whole population. 33 In 2011, Uberoi et al, reanalyzing ECG from a subgroup of 4041 subjects from the same population, showed that J wave or QRS slurring were present in 14% and was not associated with cardiovascular mortality. Finally, in the whole population, all patterns and components of ER were associated with decreased cardiovascular mortality, but this was not significant after adjustment for age. 34

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Table 2 Listing of studies on the prevalence of early repolarization in normal populations (case control and population bases studies) as published after the awareness of a possible link of ER to sudden death. Author

Year

Definition of ER

Nb

% ER

Prognosis

Kui22 Haïssaguerre23 Rosso24 Nam25 Merchant26 Vinsonneau27 Castellant28 Huikuri29 Abe30 Sinner31 Olson32 Perez33 Uberoi34 Noseworthy35 Haruta36 Reinhard37 Roukoz38 Stavrakis39 Rollin40 Hisamatsu41 Hisamatsu42 Walsh43

2007 2008 2008 2008 2009 2009 2009 2009 2010 2010 2011 2011 2011 2011 2011 2011 2011 2012 2012 2013 2013 2013

J N0.05 mV J N0.1 mV J N0.1 mV J N0.1 mV J N0.1 mV ST + and slurring or J N 0.05 mV ST + and slurring or J N 0.05 mV J N0.1 mV J N0.1 mV J N0.1 mV J N0.1 mV ST + J or QRS slurring J N0.1 mV J N0.1 mV J N0.1 mV ST + J N0.1 mV J N0.1 mV J N0.1 mV J N0.1 mV J point elevation N0.1 or 0.2 mV + upward ST + notch/slur

1817 412 124 1395 200 “normal ER” 128 women 146 AFib/213 controls 10864 6657 6213 15141 29281 4041 9444 5976 1877 11424 852 ER 1161 7630 4248 men 5069

7% 5% 13% 3.5% 31% 17% 18%/12% 5% 1.9% 13% 12% 2.3% 14% 4.5% 24% 7.7% 0.9% NA 13% 3.5% 7.8% 18%

_ _ _ _ _ _ _ yes _ yes yes none none _ yes _ _ yes yes yes yes _

In 2011, Noseworthy and colleagues reviewed ECG of 9444 subjects from the Framingham Heart Study (USA) and Health 2000 Survey (Finland). ER pattern, again similarly defined, was present in 6.1% and 3.3% of each population, respectively (4.5% overall). There was an independent association of ER with male sex, younger age, and higher Sokolow-Lyon voltage, while siblings of individuals with ER had an ER prevalence of 11.6% (odds ratio 2.22). 35 Heritability of ER was further studied by Reinhard and colleagues in 2011. In 1877 individuals from the British general population, prevalence of similarly defined ER was 7.7%: 5.9% in parents and 9.6% in offspring (2.5-fold increased risk for presenting with ER for offspring of individuals with ER). 37 In 2012, Stavrakis et al. found 852 patients (essentially males, mean age 49 years) with ER (J-point elevation ≥ 0.1 mV in inferior or lateral leads) from a large ECG database of inpatients and outpatients. ER was associated with increased mortality compared to a sample of subjects without ER and some more risky ECG features were pointed such as an older age, non-African American descent, prolonged corrected QT (QTc) and higher ER amplitude. 39 Very recently, Hisamatsu and colleagues found a J-point elevation ≥ 0.1 mV in 3.5% of 7630 individuals (41% men, mean age 52 years) (which was associated with an increased risk of cardiac death and death from coronary artery disease) and in 7.8% of 4348 men (mean age 49 years) here again correlated to cardiac death, 41,42 while 18% of 5069 subjects (mean age 25) display “definite” ER (defined as ST-J elevation N 1 or 2 mm + upward ST segment and distinct notch or slur in V3 to V6) according to Walsh, most of them regressing by middle-age. 43 Finally, we also recently report on the prevalence of ER in 1161 middle-aged subjects from the MONICA study (35–

64 years, 52% males, mean age 50 years). Prevalence of ER was 13%, was higher in men and decreased with age but only in the male population. Subjects with ERP had an increased hazard ratio of all-cause and cardiovascular mortality. 40 Preferential ECG location of the ER varied considerably according to the studies, from 0.6% to 7.6% in the inferior leads and from 0.4% to 9% in the lateral leads (average ratio inferior/lateral 1.4).

Influence of gender, age and race Gender The higher prevalence of ER in males was reliably found in most if not all these studies (from 1.8% to 21% compared 0.2% to 10% in women, average ratio 3.7). Only Vinsonneau and colleagues found 17% ER in 128 healthy women. 27 Physiologically, a J point elevation N 0.1 mV and ST angle N 20° in V1–V4 are present in 90% of males while a J point b 0.1 mV is observed in 80% of females. 44 Ito has been shown to be more prominent in males 36 and testosterone may increase the outward repolarizing potassium currents such as IK1, IKr, IKs and Ito while inhibiting inward L-type calcium current. 45 Age From many of the above mentioned works, it also appears that ER prevalence was also dependent on age, decreasing as age increased. Interestingly, the age-dependant decrease in ER prevalence seems mainly significant in males. 35,40,44 It should be also mentioned that ER prevalence has not been reliably evaluated in children. Experientially, there is an age associated decrease in peak Ito density, 46 which, together

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with changes in autonomic tone, may explain this age-related prevalence of ER. Race The influence of race has also been largely mentioned. As soon as 1954, Grusin found a 25% ST elevation in the precordial leads of 159 African medical patients, 5 while ≥ 2 mm ST segment elevation in the precordial leads was found by Seriki et al. in 34% of 300 students and children in Nigeria, increasing with age and occurring more commonly in males. 11 Akhmedov et al. studied ECG from 1306 17–30 year-old student from Asia, Africa and Latin America. ER was noted in 4.5%, significantly more frequently in the Africans (9.1%), as compared to the Asiatics (2.6%) and Latin Americans (2.2%). 14 Reddy et al. compared ST heights in 4612 AfricanAmerican, Chinese, Hispanic, and non-Hispanic white men and women aged 45–84 years in the Multiethnic Study of Atherosclerosis (MESA). ST height, measured at the J point and 60 ms after the J point in leads I, II and V1–V6, was significantly different across all ethnic groups at both time points for most leads both in men and women. 47 ST height was lower for non-Hispanic whites while Chinese and African American had the highest ST heights. Vitelli and colleagues examined ECG tracings of 2,686 healthy, middle-aged African-American and white men and women (30% men, around 50 years old) who participated in the Atherosclerosis Risk in Communities Study. 16 The ageadjusted prevalence of ST elevation was significantly higher in African-Americans, while the J-point amplitude in leads V2 and V5 was significantly greater in African-Americans than in whites. 15% of African-American men had ST elevation versus 1% of white men, 0.2% and 0% of AfricanAmerican and white women; however the prevalence of J wave was not determined. Recently, Roukoz and colleagues found in 11424 subjects (52% men) a 0.9% prevalence of 1–3 mm ST elevation ending in an inverted T wave in midprecordial leads. 38 This pattern was essentially seen in black population (3.7% in men and 1% in women) while particularly rare in white subjects (1 out of 5099). It seems to be evenly distributed

throughout the age and normalized in all cases during treadmill test. In 2007, 1817 Chinese healthy subjects (mean 46 years, 62% men) were screened. 22 A ≥ 0.5 mm J wave in the inferior, right or left precordial leads was present in 7% of this population. The presence of J wave was correlated to male gender and increased with age in this population. In 2011, Haruta and colleagues identified 24% of 5976 Japanese atomic bomb survivors (44% males, all age classes) showing ER (defined according to Haissaguerre and Huikuri), which was associated with the male gender and a higher risk of unexpected death and a lower risk of cardiac and all-cause death. 45 However other works did not find the same results: ER incidence in Caucasians was as common as in blacks according to Mehta, but ER was defined as concave ST elevation. 15 In 597 healthy adults (58% men, 15–60 years), Mansi et al. found 3.5% with an ECG pattern of early repolarization (upward ST segment elevation and QRS notching), without difference among ethnic groups (Arabians, Indians and Caucasians). 17 In this study however, isolated ST segment elevation (without QRS notching) occurred in the most important part of the subjects.

Early repolarisation and sportive activity ER has also repetitively said to be more prevalent in athletes and sportsmen. Variable high prevalences have been reported (Table 3) and seem therefore clearly higher than in unselected populations (see Table 2) or matched controls. 48,50 This may be explained by the definitions used (ST elevation in many publications), by the lower heart rate and higher vagal tone induced by the practice of intensive physical activity and also by the low number of women included in these studies. Furthermore ethnical differences are here particularly marked, black athletes showing more ER than whites, 55–57 while prevalence clearly differ according to the sport (see Ref. [49]) and is lower in amateur athletes. 51 Of note, the pattern of ER in athletes is ascending in most cases. 55 The prognosis role of ER in athletes was just once addressed: even if J wave and/or QRS slurring were more

Table 3 Listing of studies on the prevalence of early repolarization in athletes and sportsmen. Author

Year

Definition

Nb

% ER

Sharma Peliccia49 Bianco50 Pelliccia51 Rosso24 Crouse52 Capatto53 Junttila54 Tikkanen55 Papadakis56 Di Paolo57

1999 2000 2001 2007 2008 2009 2010 2011 2011 2011 2012

1000 vs 300 controls 1005 155 vs 50 controls 32652 amateur athletes 121 77 365 503 62 Finnish/503 US athletes 904 black/1819 white athletes 154 black/vs 62 white athletes

Schmied58

2013

ST + ST + ≥ 0.2 mV ST + ≥0.1 mV J wave and ST elevation J N0.1 mV ST + J wave/slurring N0.05 mV Slurring or notch ≥0.1 mV J ≥0.1 mV ST + ≥0.1 mV ST + ≥0.1 mV J ≥0.1 mV ST + ≥0.1 mV

43% vs 24% 24% 89% vs 36% 7% 22% 34% 8% 30% 44% vs 30% 63% vs 26% 91% vs 56% 18% vs 13% 71%

48

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frequently recorded in athletes presenting with sudden death than in control athletes, recurrences of arrhythmia did not differ between the subgroups with and without ER. 53 Moreover, ST elevation was much less commonly observed in athletes victims of sudden death. 53 References 1. Shipley RA, Hallaran WR. The four-lead electrocardiogram in two hundred men and women. Am Heart J 1936;11:325. 2. Littmann D. Persistence of the juvenile pattern in the precordial leads of healthy adult Negroes, with report of electrocardiographic survey on three hundred Negro and two hundred white subjects. Am Heart J 1946;32:370. 3. Myers GB, Klein HA, et al. Normal variations in multiple precordial leads. Am Heart J 1947;34:785. 4. Goldman MJ. RS-T segment elevation in mid- and left precordial leads as a normal variant. Am Heart J 1953;46:817. 5. Grusin H. Peculiarities of the African's electrocardiogram and the changes observed in serial studies. Circulation 1954;9:860. 6. Gottschalk CW, Craige E. A comparison of the precordial S-T and T waves in the electrocardiograms of 600 healthy young Negro and white adults. South Med J 1956;49:453. 7. Goldman MJ. Normal variants in the electrocardiogram leading to cardiac invalidism. Am Heart J 1960;59:71. 8. Thomas J, Harris E, Lassiter G. Observations on the T wave and S-T segment changes in the precordial electro-cardiogram of 320 young Negro adults. Am J Cardiol 1960;5:468. 9. Wasserburger RH. The normal RS-T segment elevation variant. Am J Cardiol 1961;8:184. 10. Fenichel NN. A long term study of concave RS-T elevation – a normal variant of the electrocardiogram. Angiology 1962;13:360. 11. Seriki O, Smith AJ. The electrocardiogram of young Nigerians. Am Heart J 1966;72:153. 12. Walker RP, Walker BF. The bearing of race, sex, age, and nutritional state on the precordial electrocardiograms of young South African Bantu and Caucasian subjects. Am Heart J 1969;77:441. 13. Kambara H, Phillips J. Long-term evaluation of early repolarization syndrome (normal variant RS-T segment elevation). Am J Cardiol 1976;38:157. 14. Akhmedov NA. Early ventricular repolarization syndrome and heart function in the inhabitants of Asia, Africa and Latin America. Kardiologiia 1986;26:63. 15. Mehta MC, Jain AC. Early repolarization on scalar electrocardiogram. Am J Med Sci 1995;309:305. 16. Vitelli LL, Crow RS, Shahar E, Hutchinson RG, Rautaharju PM, Folsom AR. Electrocardiographic findings in a healthy biracial population. Atherosclerosis Risk in Communities (ARIC) study investigators. Am J Cardiol 1998;81:453. 17. Mansi IA, Nash IS. Ethnic differences in the ST segment of the electrocardiogram: a comparative study among six ethnic groups. Am J Emerg Med 2001;19:541. 18. Liu X, Shah A, Sacher F, et al. Clinical frontiers in electrocardiographic early repolarization syndrome: does a good guy turn bad now? Chin Med J (Engl) 2010;123:1459. 19. Klatsky AL, Oehm R, Cooper RA, Udaltsova N, Armstrong MA. The early repolarization normal variant electrocardiogram: correlates and consequences. Am J Med 2003;115:171. 20. 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;8:923. 21. Gussak I, Antzelevitch C. Early repolarization syndrome: clinical characteristics and possible cellular and ionic mechanisms. J Electrocardiol 2000;33:299. 22. Kui C, Congxin H, Xi W, et al. Characteristic of the prevalence of J wave in apparently healthy Chinese adults. Arch Med Res 2008;39:232. 23. Haïssaguerre M, Derval N, Sacher F, et al. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008;358:2016.

415

24. 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. 25. 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. 26. Merchant FM, Noseworthy PA, Weiner RB, Singh SM, Ruskin JN, Reddy VY. Ability of terminal QRS notching to distinguish benign from malignant electrocardiographic forms of early repolarization. Am J Cardiol 2009;104:1402. 27. Vinsonneau U, Brondex A, Vergez-Larrouget C, et al. Prevalence of the early repolarization aspect in a healthy women population (abstract). Eur Heart J 2009;30(S):167. 28. Castellant P, Blanc JJ, Valls-Bertault V, et al. Prevalence of early repolarization aspect in young patients with paroxysmal atrial fibrillation (abstract). Eur Heart J 2009;30(S):818. 29. Tikkanen JT, Anttonen O, Junttila MJ, et al. Long-term outcome associated with early repolarization on electrocardiography. N Engl J Med 2009;361:2529. 30. 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. 31. Sinner MF, Reinhard W, Müller 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. 32. Olson KA, Viera AJ, Soliman EZ, Crow RS, Rosamond WD. Longterm prognosis associated with J-point elevation in a large middle-aged biracial cohort: the ARIC study. Eur Heart J 2011;32:3098. 33. Perez MV, Uberoi A, Jain NA, Ashley E, Turakhia MP, Froelicher V. The prognostic value of early repolarization with ST-segment elevation in African Americans. Heart Rhythm 2012;9:558. 34. Uberoi A, Jain NA, Perez M, et al. Early repolarization in an ambulatory clinical population. Circulation 2011;124:2208. 35. 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. 36. Di Diego JM, Cordeiro JM, Goodrow RJ, et al. Ionic and cellular basis for the predominance of the Brugada syndrome phenotype in males. Circulation 2002;106:2004. 37. Reinhard W, Kaess BM, Debiec R, et al. Heritability of early repolarization: a population-based study. Circ Cardiovasc Genet 2011;4:134. 38. Roukoz H, Wang K. ST elevation and inverted T wave as another normal variant mimicking acute myocardial infarction: the prevalence, age, gender, and racial distribution. Ann Noninvasive Electrocardiol 2011;16:64. 39. Stavrakis S, Patel N, Te C, et al. Development and validation of a prognostic index for risk stratification of patients with early repolarization. Ann Noninvasive Electrocardiol 2012;17:361. 40. 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. 41. Hisamatsu T, Ohkubo T, Miura K, et al, For The Nippon Data90 Research Group. Association between J-point elevation and death from coronary artery disease. Circ J 2013;77:1260. 42. Hisamatsu T, Miura K, Ohkubo T, et al, for the NIPPON DATA80 Research Group. Interaction between dietary marine-derived n-3 fatty acids intake and J-point elevation on the risk of cardiac death: a 24-year follow-up of Japanese men. Heart 2013;99:1024. 43. Walsh JA, 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. 44. Surawicz B, Parikh SR. Prevalence of male and female patterns of early ventricular repolarization in the normal ECG of males and females from childhood to old age. J Am Coll Cardiol 2002;40:1870. 45. 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. 46. Walker KE, Lakatta EG, Houser SR. Age associated changes in membrane currents in rat ventricular myocytes. Cardiovasc Res 1993;27:1968.

416

P. Maury, A. Rollin / Journal of Electrocardiology 46 (2013) 411–416

47. Reddy VK, Gapstur SM, Prineas R, Colangelo LA, Ouyang P, Kadish AH. Ethnic differences in ST height in the multi-ethnic study of atherosclerosis. Ann Noninvasive Electrocardiol 2008;13:341. 48. Sharma S, Whyte G, Elliott P, et al. Electrocardiographic changes in 1000 highly trained junior elite athletes. Br J Sports Med 1999;33:319. 49. Pelliccia A, Maron BJ, Culasso F, et al. Clinical significance of abnormal electrocardiographic patterns in trained athletes. Circulation 2000;102:278. 50. Bianco M, Bria S, Gianfelici A, Sanna N, Palmieri V, Zeppilli P. Does early repolarization in the athlete have analogies with the Brugada syndrome? Eur Heart J 2001;22:504. 51. Pelliccia A, Culasso F, Di PFM, et al. Prevalence of abnormal electrocardiograms in a large, unselected population undergoing preparticipation cardiovascular screening. Eur Heart J 2007;28:2006. 52. Crouse SF, Meade T, Hansen BE, Green JS, Martin SE. Electrocardiograms of collegiate football athletes. Clin Cardiol 2009;32:37. 53. Cappato R, Furlanello F, Giovinazzo V, et al. J wave, QRS slurring, and ST elevation in athletes with cardiac arrest in the absence of heart

54.

55.

56.

57.

58.

disease: marker of risk or innocent bystander? Circ Arrhythm Electrophysiol 2010;3:305. Junttila MJ, Sager SJ, Freiser M, McGonagle S, Castellanos A, Myerburg RJ. Inferolateral early repolarization in athletes. J Interv Card Electrophysiol 2011;31:33. Tikkanen JT, Junttila MJ, Anttonen O, et al. Early repolarization: electrocardiographic phenotypes associated with favorable long-term outcome. Circulation 2011;123:2666. Papadakis M, Carre F, Kervio G, et al. The prevalence, distribution, and clinical outcomes of electrocardiographic repolarization patterns in male athletes of African/Afro-Caribbean origin. Eur Heart J 2011; 32:2304. Di Paolo FM, Schmied C, Zerguini YA, et al. The athlete's heart in adolescent Africans: an electrocardiographic and echocardiographic study. J Am Coll Cardiol 2012;59:1029. Schmied C, Di Paolo FM, Zerguini AY, Dvorak J, Pelliccia A. Screening athletes for cardiovascular disease in Africa: a challenging experience. Br J Sports Med 2013;47:579.