Effects of Early Repolarization on Electrocardiography and Long-term Cardiovascular Outcomes: A 15-Year Population-Based Cohort Study
-
Masoumeh Sadeghi
,
Erfan Sheikhbahaei
,
Mohammad Talaei
,
Ali Gholamrezaei
,
Seyed Vahid Sharif
,
Hamidreza Roohafza
Abstract
Background: We aimed to investigate the association between persistent early repolarization (ER) in healthy individuals and long-term cardiovascular events and mortality rates in a large cohort study.
Methods: Demographic characteristics, medical records, 12-lead electrocardiograms (ECGs), and laboratory data were retrieved and analyzed from the Isfahan Cohort Study. The participants were followed up biannually via telephone interviews and 1 live structured interview in between until 2017. Individuals who had ER in all their ECGs were considered persistent ER cases. Study outcomes were cardiovascular events (unstable angina, myocardial infarction, stroke, and sudden cardiac death), cardiovascular-related mortality, and all-cause mortality. The independent t test, the χ2 test, the Mann-Whitney U test, and the Cox regression models were used for statistical analyses.
Results: The study population consisted of 2696 subjects (50.5% female). Persistent ER was found in 203 subjects (7.5%), with a higher frequency in men (6.7% vs 0.8%; P<0.001). Cardiovascular events, cardiovascular-related mortality, and all-cause mortality occurred in 478 (17.7%), 101 (3.7%), and 241 (8.9%) individuals, respectively. After controlling for known cardiovascular risk factors, we found an association between ER and cardiovascular events (adjusted hazard ratio [95% confidence interval] =2.36 [1.19–4.68], P=0.014), cardiovascular-related mortality (4.97 [1.95–12.60], P=0.001), and all-cause mortality (2.50 [1.11–5.58], P=0.022) in women. No significant association was found between ER and any study outcomes in men.
Conclusion: ER is common in young men with no apparent long-term cardiovascular risks. In women, ER is relatively rare, but it could be associated with long-term cardiovascular risks.
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2. WASSERBURGER RH, ALT WJ. The normal RS-T segment elevation variant. Am J Cardiol 1961;8:184-192.
3. Haïssaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, Pasquié JL, Nogami A, Babuty D, Yli-Mayry S, De Chillou C, Scanu P, Mabo P, Matsuo S, Probst V, Le Scouarnec S, Defaye P, Schlaepfer J, Rostock T, Lacroix D, Lamaison D, Lavergne T, Aizawa Y, Englund A, Anselme F, O'Neill M, Hocini M, Lim KT, Knecht S, Veenhuyzen GD, Bordachar P, Chauvin M, Jais P, Coureau G, Chene G, Klein GJ, Clémenty J. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008;358:2016-2023.
4. Obeyesekere MN, Klein GJ, Nattel S, Leong-Sit P, Gula LJ, Skanes AC, Yee R, Krahn AD. A clinical approach to early repolarization. Circulation 2013;127:1620-169.
5. Rosso R, Kogan E, Belhassen B, Rozovski U, Scheinman MM, Zeltser D, Halkin A, Steinvil A, Heller K, Glikson M, Katz A, Viskin S. J-point elevation in survivors of primary ventricular fibrillation and matched control subjects: incidence and clinical significance. J Am Coll Cardiol 2008;52:1231-1238.
6. Walsh JA 3rd, Ilkhanoff L, Soliman EZ, Prineas R, Liu K, Ning H, Lloyd-Jones DM. 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;61:863-869.
7. Ilkhanoff L, Soliman EZ, Prineas RJ, Walsh JA 3rd, Ning H, Liu K, Carr JJ, Jacobs DR Jr, Lloyd-Jones DM. 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;7:392-399.
8. Uberoi A, Jain NA, Perez M, Weinkopff A, Ashley E, Hadley D, Turakhia MP, Froelicher V. Early repolarization in an ambulatory clinical population. Circulation. 2011;124:2208-2214.
9. Benito B, Guasch E, Rivard L, Nattel S. Clinical and mechanistic issues in early repolarization of normal variants and lethal arrhythmia syndromes. J Am Coll Cardiol 2010;56:1177-1186.
10. Junttila MJ, Sager SJ, Tikkanen JT, Anttonen O, Huikuri HV, Myerburg RJ. Clinical significance of variants of J-points and J-waves: early repolarization patterns and risk. Eur Heart J 2012;33:2639-2643.
11. Tikkanen JT, Anttonen O, Junttila MJ, Aro AL, Kerola T, Rissanen HA, Reunanen A, Huikuri HV. Long-term outcome associated with early repolarization on electrocardiography. N Engl J Med 2009;361:2529-2537.
12. Sinner MF, Reinhard W, Müller M, Beckmann BM, Martens E, Perz S, Pfeufer A, Winogradow J, Stark K, Meisinger C, Wichmann HE, Peters A, Riegger GA, Steinbeck G, Hengstenberg C, Kääb S. 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.
13. Patel RB, Ng J, Reddy V, Chokshi M, Parikh K, Subacius H, Alsheikh-Ali AA, Nguyen T, Link MS, Goldberger JJ, Ilkhanoff L, Kadish AH. Early repolarization associated with ventricular arrhythmias in patients with chronic coronary artery disease. Circ Arrhythm Electrophysiol 2010;3:489-495.
14. Pei J, Li N, Gao Y, Wang Z, Li X, Zhang Y, Chen J, Zhang P, Cao K, Pu J. The J wave and fragmented QRS complexes in inferior leads associated with sudden cardiac death in patients with chronic heart failure. Europace 2012;14:1180-1187.
15. Talaei M, Sarrafzadegan N, Sadeghi M, Oveisgharan S, Marshall T, Thomas GN, Iranipour R. Incidence of cardiovascular diseases in an Iranian population: the Isfahan Cohort Study. Arch Iran Med 2013;16:138-144.
16. Rautaharju PM, Surawicz B, Gettes LS, Bailey JJ, Childers R, Deal BJ, Gorgels A, Hancock EW, Josephson M, Kligfield P, Kors JA, Macfarlane P, Mason JW, Mirvis DM, Okin P, Pahlm O, van Herpen G, Wagner GS, Wellens H; American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; American College of Cardiology Foundation; Heart Rhythm Society. 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. J Am Coll Cardiol 2009;53:982-991.
17. Sarrafzadegan N, Talaei M, Sadeghi M, Kelishadi R, Oveisgharan S, Mohammadifard N, Sajjadieh AR, Kabiri P, Marshall T, Thomas GN, Tavasoli A. The Isfahan cohort study: rationale, methods and main findings. J Hum Hypertens 2011;25:545-553.
18. Rollin A, Maury P, Bongard V, Sacher F, Delay M, Duparc A, Mondoly P, Carrié D, Ferrières J, Ruidavets JB. Prevalence, prognosis, and identification of the malignant form of early repolarization pattern in a population-based study. Am J Cardiol 2012;110:1302-1328.
19. Olson KA, Viera AJ, Soliman EZ, Crow RS, Rosamond WD. Long-term prognosis associated with J-point elevation in a large middle-aged biracial cohort: the ARIC study. Eur Heart J 2011;32:3098-3106.
20. Klatsky AL, Oehm R, Cooper RA, Udaltsova N, Armstrong MA. The early repolarization normal variant electrocardiogram: correlates and consequences. Am J Med 2003115:171-177.
21. Reinhard W, Kaess BM, Debiec R, Nelson CP, Stark K, Tobin MD, Macfarlane PW, Tomaszewski M, Samani NJ, Hengstenberg C. Heritability of early repolarization: a population-based study. Circ Cardiovasc Genet 2011;4:134-138.
22. Noseworthy PA, Tikkanen JT, Porthan K, Oikarinen L, Pietilä A, Harald K, Peloso GM, Merchant FM, Jula A, Väänänen H, Hwang SJ, O'Donnell CJ, Salomaa V, Newton-Cheh C, Huikuri HV. The early repolarization pattern in the general population: clinical correlates and heritability. J Am Coll Cardiol 2011;57:2284-2289.
23. Junttila MJ, Tikkanen JT, Kenttä T, Anttonen O, Aro AL, Porthan K, Kerola T, Rissanen HA, Knekt P, Huikuri HV. Early repolarization as a predictor of arrhythmic and nonarrhythmic cardiac events in middle-aged subjects. Heart Rhythm 2014;11:1701-1706.
24. Shulman E, Aagaard P, Kargoli F, Hoch E, Biase LD, Fisher J, Gross J, Kim S, Palma E, Ferrick KJ, Krumerman A. The Prognostic Value of Early Repolarization with ST-Segment Elevation by Age and Gender in the Hispanic Population. Pacing Clin Electrophysiol 2015;38:1396-1404.
25. Trenkwalder T, Rübsamen N, Schmitt VH, Arnold N, Kaess BM, Sinning CR, Zeller T, Beutel ME, Schmidtmann I, Nickels S, Pfeiffer N, Leuschner A, Münzel T, Lackner KJ, Hengstenberg C, Blankenberg S, Wild PS, Reinhard W, Schnabel R. Left ventricular geometry and function in early repolarization: results from the population-based Gutenberg Health Study. Clin Res Cardiol 2019;108:1107-1116.
26. Tadros R, Ton AT, Fiset C, Nattel S. Sex differences in cardiac electrophysiology and clinical arrhythmias: epidemiology, therapeutics, and mechanisms. Can J Cardiol 2014;30:783-792.
27. Adler A, Gollob MH. A practical guide to early repolarization. Curr Opin Cardiol 2015;30:8-16.
28. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C. 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;10:1932-1963.
2. WASSERBURGER RH, ALT WJ. The normal RS-T segment elevation variant. Am J Cardiol 1961;8:184-192.
3. Haïssaguerre M, Derval N, Sacher F, Jesel L, Deisenhofer I, de Roy L, Pasquié JL, Nogami A, Babuty D, Yli-Mayry S, De Chillou C, Scanu P, Mabo P, Matsuo S, Probst V, Le Scouarnec S, Defaye P, Schlaepfer J, Rostock T, Lacroix D, Lamaison D, Lavergne T, Aizawa Y, Englund A, Anselme F, O'Neill M, Hocini M, Lim KT, Knecht S, Veenhuyzen GD, Bordachar P, Chauvin M, Jais P, Coureau G, Chene G, Klein GJ, Clémenty J. Sudden cardiac arrest associated with early repolarization. N Engl J Med 2008;358:2016-2023.
4. Obeyesekere MN, Klein GJ, Nattel S, Leong-Sit P, Gula LJ, Skanes AC, Yee R, Krahn AD. A clinical approach to early repolarization. Circulation 2013;127:1620-169.
5. Rosso R, Kogan E, Belhassen B, Rozovski U, Scheinman MM, Zeltser D, Halkin A, Steinvil A, Heller K, Glikson M, Katz A, Viskin S. J-point elevation in survivors of primary ventricular fibrillation and matched control subjects: incidence and clinical significance. J Am Coll Cardiol 2008;52:1231-1238.
6. Walsh JA 3rd, Ilkhanoff L, Soliman EZ, Prineas R, Liu K, Ning H, Lloyd-Jones DM. 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;61:863-869.
7. Ilkhanoff L, Soliman EZ, Prineas RJ, Walsh JA 3rd, Ning H, Liu K, Carr JJ, Jacobs DR Jr, Lloyd-Jones DM. 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;7:392-399.
8. Uberoi A, Jain NA, Perez M, Weinkopff A, Ashley E, Hadley D, Turakhia MP, Froelicher V. Early repolarization in an ambulatory clinical population. Circulation. 2011;124:2208-2214.
9. Benito B, Guasch E, Rivard L, Nattel S. Clinical and mechanistic issues in early repolarization of normal variants and lethal arrhythmia syndromes. J Am Coll Cardiol 2010;56:1177-1186.
10. Junttila MJ, Sager SJ, Tikkanen JT, Anttonen O, Huikuri HV, Myerburg RJ. Clinical significance of variants of J-points and J-waves: early repolarization patterns and risk. Eur Heart J 2012;33:2639-2643.
11. Tikkanen JT, Anttonen O, Junttila MJ, Aro AL, Kerola T, Rissanen HA, Reunanen A, Huikuri HV. Long-term outcome associated with early repolarization on electrocardiography. N Engl J Med 2009;361:2529-2537.
12. Sinner MF, Reinhard W, Müller M, Beckmann BM, Martens E, Perz S, Pfeufer A, Winogradow J, Stark K, Meisinger C, Wichmann HE, Peters A, Riegger GA, Steinbeck G, Hengstenberg C, Kääb S. 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.
13. Patel RB, Ng J, Reddy V, Chokshi M, Parikh K, Subacius H, Alsheikh-Ali AA, Nguyen T, Link MS, Goldberger JJ, Ilkhanoff L, Kadish AH. Early repolarization associated with ventricular arrhythmias in patients with chronic coronary artery disease. Circ Arrhythm Electrophysiol 2010;3:489-495.
14. Pei J, Li N, Gao Y, Wang Z, Li X, Zhang Y, Chen J, Zhang P, Cao K, Pu J. The J wave and fragmented QRS complexes in inferior leads associated with sudden cardiac death in patients with chronic heart failure. Europace 2012;14:1180-1187.
15. Talaei M, Sarrafzadegan N, Sadeghi M, Oveisgharan S, Marshall T, Thomas GN, Iranipour R. Incidence of cardiovascular diseases in an Iranian population: the Isfahan Cohort Study. Arch Iran Med 2013;16:138-144.
16. Rautaharju PM, Surawicz B, Gettes LS, Bailey JJ, Childers R, Deal BJ, Gorgels A, Hancock EW, Josephson M, Kligfield P, Kors JA, Macfarlane P, Mason JW, Mirvis DM, Okin P, Pahlm O, van Herpen G, Wagner GS, Wellens H; American Heart Association Electrocardiography and Arrhythmias Committee, Council on Clinical Cardiology; American College of Cardiology Foundation; Heart Rhythm Society. 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. J Am Coll Cardiol 2009;53:982-991.
17. Sarrafzadegan N, Talaei M, Sadeghi M, Kelishadi R, Oveisgharan S, Mohammadifard N, Sajjadieh AR, Kabiri P, Marshall T, Thomas GN, Tavasoli A. The Isfahan cohort study: rationale, methods and main findings. J Hum Hypertens 2011;25:545-553.
18. Rollin A, Maury P, Bongard V, Sacher F, Delay M, Duparc A, Mondoly P, Carrié D, Ferrières J, Ruidavets JB. Prevalence, prognosis, and identification of the malignant form of early repolarization pattern in a population-based study. Am J Cardiol 2012;110:1302-1328.
19. Olson KA, Viera AJ, Soliman EZ, Crow RS, Rosamond WD. Long-term prognosis associated with J-point elevation in a large middle-aged biracial cohort: the ARIC study. Eur Heart J 2011;32:3098-3106.
20. Klatsky AL, Oehm R, Cooper RA, Udaltsova N, Armstrong MA. The early repolarization normal variant electrocardiogram: correlates and consequences. Am J Med 2003115:171-177.
21. Reinhard W, Kaess BM, Debiec R, Nelson CP, Stark K, Tobin MD, Macfarlane PW, Tomaszewski M, Samani NJ, Hengstenberg C. Heritability of early repolarization: a population-based study. Circ Cardiovasc Genet 2011;4:134-138.
22. Noseworthy PA, Tikkanen JT, Porthan K, Oikarinen L, Pietilä A, Harald K, Peloso GM, Merchant FM, Jula A, Väänänen H, Hwang SJ, O'Donnell CJ, Salomaa V, Newton-Cheh C, Huikuri HV. The early repolarization pattern in the general population: clinical correlates and heritability. J Am Coll Cardiol 2011;57:2284-2289.
23. Junttila MJ, Tikkanen JT, Kenttä T, Anttonen O, Aro AL, Porthan K, Kerola T, Rissanen HA, Knekt P, Huikuri HV. Early repolarization as a predictor of arrhythmic and nonarrhythmic cardiac events in middle-aged subjects. Heart Rhythm 2014;11:1701-1706.
24. Shulman E, Aagaard P, Kargoli F, Hoch E, Biase LD, Fisher J, Gross J, Kim S, Palma E, Ferrick KJ, Krumerman A. The Prognostic Value of Early Repolarization with ST-Segment Elevation by Age and Gender in the Hispanic Population. Pacing Clin Electrophysiol 2015;38:1396-1404.
25. Trenkwalder T, Rübsamen N, Schmitt VH, Arnold N, Kaess BM, Sinning CR, Zeller T, Beutel ME, Schmidtmann I, Nickels S, Pfeiffer N, Leuschner A, Münzel T, Lackner KJ, Hengstenberg C, Blankenberg S, Wild PS, Reinhard W, Schnabel R. Left ventricular geometry and function in early repolarization: results from the population-based Gutenberg Health Study. Clin Res Cardiol 2019;108:1107-1116.
26. Tadros R, Ton AT, Fiset C, Nattel S. Sex differences in cardiac electrophysiology and clinical arrhythmias: epidemiology, therapeutics, and mechanisms. Can J Cardiol 2014;30:783-792.
27. Adler A, Gollob MH. A practical guide to early repolarization. Curr Opin Cardiol 2015;30:8-16.
28. Priori SG, Wilde AA, Horie M, Cho Y, Behr ER, Berul C, Blom N, Brugada J, Chiang CE, Huikuri H, Kannankeril P, Krahn A, Leenhardt A, Moss A, Schwartz PJ, Shimizu W, Tomaselli G, Tracy C. 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;10:1932-1963.
| Files | ||
| Issue | Vol 17 No 4 (2022): J Teh Univ Heart Ctr | |
| Section | Original Article(s) | |
| DOI | https://doi.org/10.18502/jthc.v17i4.11606 | |
| Keywords | ||
| Early repolarization Arrhythmia Myocardial infarction sudden cardiac death Mortality | ||
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How to Cite
1.
Sadeghi M, Sheikhbahaei E, Talaei M, Gholamrezaei A, Sharif SV, Roohafza H. Effects of Early Repolarization on Electrocardiography and Long-term Cardiovascular Outcomes: A 15-Year Population-Based Cohort Study. J Tehran Heart Cent. 2022;17(4):195-201.
