The American Journal of Medicine
Volume 115, Issue 3 , Pages 237-240, 15 August 2003

Early repolarization: friend or foe?

  • Lauren Dowdy

      Affiliations

    • Duke Clinical Research Center (LD, GSW, PJ), Durham, North Carolina, USA
    • ,
  • Galen S Wagner, MD

      Affiliations

    • Duke Clinical Research Center (LD, GSW, PJ), Durham, North Carolina, USA
    • ,
  • Yochai Birnbaum, MD

      Affiliations

    • Division of Cardiology (YB), The University of Texas Medical Branch, Galveston, Texas, USA
    • ,
  • Peter Clemmensen, MD, PhD

      Affiliations

    • The Heart Center (PC), Rigshospitalet, University of Copenhagen, Copenhagen, Denmark
    • ,
  • Jocelyne Fayn, PhD

      Affiliations

    • Hôpital Louis Pradel (JF), Lyon, France
    • ,
  • Paul Rubel, PhD
    • ,
  • Sophia Zhou, PhD

      Affiliations

    • Advanced Algorithm Research Center (SZ), Philips Medical Systems, Oxnard, California, USA
    • ,
  • Per Johanson, MD, PhD

      Affiliations

    • Duke Clinical Research Center (LD, GSW, PJ), Durham, North Carolina, USA
    • Corresponding Author InformationRequests for reprints should be addressed to Per Johanson, MD, PhD, Duke University Medical Center, DCRI, P.O Box 17969, Durham, North Carolina 27705, USA

Article Outline

 

In the current issue of the Journal, Klatsky et al (1) address the possible risk of chronically having “normal” electrocardiographic (ECG) changes that may mimic the presence of an acute myocardial infarction. The authors compare the rates of hospital admissions for various conditions, and outpatient cardiovascular diagnoses, in patients with early repolarization and controls. The presence of “normal” early repolarization changes on the ECG could indeed be misinterpreted as signs of an acute thrombotic occlusion of a coronary artery, and lead to inappropriate and even potentially harmful reperfusion therapy.

Of the many people who present for emergency clinical evaluation with symptoms suggesting an acute coronary syndrome, only a small proportion have the thrombotic coronary occlusion for which immediate reperfusion therapy is indicated. The current European Society of Cardiology/American College of Cardiology guidelines suggest immediate reperfusion therapy only in patients with “ST elevation or presumably new left bundle branch block” (2). However, since ST elevation in the absence of myocardial infarction is common, the diagnostic threshold for such therapy yields low specificity. In the current paper, 30% of the subjects chronically had ST elevations ≥3 mm. Other studies 3, 4 also indicate that ST elevation above the commonly accepted threshold is not unusual, particularly in young men. Thus an individual’s age and gender should also be considered. Both female gender and older age are associated with lower amplitudes of all ECG waveforms, including the ST segment (3). The phenomenon associated with “normal” ST elevation has been termed “early repolarization” and pertains to the absence of a truly isoelectric ST segment between the QRS complex of ventricular depolarization and the T wave of repolarization.

The prevalence of early repolarization may be increased when the ST-segment changes are measured late after the J point, the heart rate is accelerated or there are conditions such as left ventricular hypertrophy or fascicular or bundle branch block that prolong the ventricular depolarization process (3).

The findings by Klatsky et al (1) support previous reports of a high prevalence of early repolarization in young men of African descent 5, 6, 7, 8, and in persons who engage regularly in “vigorous” exercise 9, 10. These findings also support the benign prognosis of this condition and even show nonsignificant trends toward lower use of health care. However, this study does not provide direct information on whether inappropriate and unnecessary therapy was administered as a result of misinterpretation of the early repolarization changes in patients who were admitted for in-hospital care.

Because ST elevation due to early repolarization may be interpreted as changes due to myocardial infarction, several noninvasive and practical approaches can be taken to minimize misinterpretation. This editorial considers the use of new algorithms for computerized analysis of an individual ECG; observations of the “stability” of the ST-segment changes on serial ECGs; and other non-ECG manifestations of ischemia, such as regional wall motion abnormalities assessed by echocardiography and myocardial perfusion defects via radionuclide measurements or contrast echocardiography.

Back to Article Outline

New ecg interpretive algorithms 

The development of computerized algorithms for classifying ST-elevation myocardial infarction (STEMI) is complicated by conditions such as acute pericarditis and “normal” early repolarization, which can mimic its diagnosis.

The ST elevation thresholds of 0.2 mV in leads V1 to V3 and 0.1 mV in the other leads, as suggested by the European Society of Cardiology/American College of Cardiology (2), are not sufficient for this purpose, as was demonstrated by Klatsky et al. Hence, adjustments for known age- and gender-dependent differences in ST amplitude (4) have been incorporated. A computer system programmed to identify both magnitude and “contour” of the ST-segment elevation typical of STEMI has been reported to attain a sensitivity of 52% and a specificity of 98% (11). Optimally, a computer system should have capabilities to differentiate STEMI not only from noninfarction in general, but from its mimics such as acute pericarditis and normal early repolarization. In a recent study, patients with presenting symptoms suggesting acute coronary syndromes were allocated to the following groups by serial ECG and non-ECG criteria: STEMI (n = 321), pericarditis (n = 115) and early repolarization (n = 153). A new algorithm for detection of STEMI demonstrated an improvement in sensitivity to 87% and an extremely high specificity of 99%. An algorithm for the detection of early repolarization had a sensitivity of 76% and specificity of 98% (12).

Back to Article Outline

Serial ecg comparison 

It is well recognized that serial ECG analysis could considerably improve the overall diagnostic accuracy of ECGs. Comparing patients' current and previous recordings improves the understanding of the diagnostic information content of the ECG (13). Serial ECG comparison is highly recommended for enhancing the accuracy of myocardial infarction or ischemia detection, and for distinguishing early repolarization from acute epicardial injury (14).

However, timely retrieval of previous ECGs may be difficult in an emergency situation, especially if that ECG must be sent from another institution. Retrieving paper copies is time consuming, and most of the ECG management systems use proprietary archiving and compression formats. Recent progress in computerized electrocardiography and information and communication technologies may, however, facilitate easy retrieval of high-quality digital ECG recordings for reanalysis and serial comparison 15, 16. By such means, ECGs may be collected from regional hospitals that have databases obtained during hospital visits or sent by primary care physicians. In addition, patients with a known abnormal baseline ECG could even carry an image of their ECG either in electronic format (which will enable direct computerized comparison) or on a card.

Progress achieved during the last decade in computerized electrocardiography and in information and communication technologies offers the opportunity to easily retrieve previous, high quality digital ECG recordings for their reanalysis for serial comparison 17, 18, 19. The “Personal Electronic Health Record” is becoming a reality in several countries. The development of personal portable devices of professional quality and low cost allows ECG recordings from any location, at the time the first symptoms occur, and their digital transmission to an application server (20). This system can achieve sophisticated serial ECG analysis in almost real time of the serial changes of standard measurements, and of specialized methods such as the Novacode or Minnesota code 21, 22. It also facilitates the stratification of the spatiotemporal changes of the QRS and T waveforms, which have been shown to be more robust and to convey additional information to ST segment changes alone 23, 24.

Serial observation of ST-segment evolution, minute by minute during ST-elevation or non–ST-elevation myocardial infarction, is becoming one of the cornerstones for risk stratification (25) and for evaluation of myocardial reperfusion (26) as a measurement of treatment efficacy. Such serial observations have also been shown to be very useful for the early diagnosis of these conditions (27), especially in the presence of confounding factors such as repolarization changes due to left or right bundle branch block 28, 29 or of initially nondiagnostic ECG changes (30). If the ST elevation on the presenting ECG increases or decreases significantly on serial recordings, the diagnosis of myocardial infarction is more likely. Dynamic changes in ST elevation caused by early repolarization can appear over time (31), and such elevation has been shown to resolve during mild exercise (32). However, there are no definitive studies of the short-term consistency of “normal” early repolarization.

The year-to-year ECG variations in early repolarization in normal adults have been compared to the day-to-day variations (33). The early literature 34, 35 indicates that ST-segment variability exists, but the amplitudes of the day-to-day and year-to-year variations have not been measured and statistically analyzed. To further improve the efficacy of serial ECG comparison the stability of the ST-segment in patients with “normal” early repolarization needs further investigation.

Back to Article Outline

Non-ECG Methods 

According to the European Society of Cardiology/American College of Cardiology guidelines, a therapeutic decision concerning reperfusion therapy should be effective within 30 minutes of presentation to the emergency department. This decision is usually based on the clinical information and ECG, and may be delayed if there are confounding factors on the ECG. At this early time point, when biochemical cardiac markers may be either positive or negative and are therefore of limited help, the clinician may use myocardial imaging techniques to confirm or refute the presence of either acute regional ischemia or infarction.

The use of two-dimensional echocardiography may add diagnostic information to the ECG and clinical information in patients with symptoms suggestive of myocardial infarction. However, regional wall motion abnormalities found by echocardiography do not differentiate acute ischemia from prior infarction (36). The use of a handheld echo device for the evaluation of patients with chest pain might become feasible, and this could even be employed by nonechocardiographers with minimal training. Thus, integrated information from the ECG and echocardiogram may well provide readily available early assessment of diagnostic information in the emergency department.

Use of single photon emission computed tomographic imaging yields reliable negative predicative values for the absence of myocardial infarction and has been recommended in the prevention of unnecessary hospitalizations for moderate-risk patients with ongoing chest pain and nondiagnostic ECG changes (37). As with echocardiography, positive findings of perfusion defects do not differentiate acute ischemia from previous myocardial infarction. Nuclear imaging is not routinely feasible in the emergency setting; however, small portable devices have been shown to be promising for bedside evaluations (38), and these might be used in the future in a similar way as the handheld echo.

Contrast echocardiography provides another possibility of obtaining very accurate evaluations of myocardial perfusion (26). However, this method requires much experience and, until recently, even coronary artery access for contrast administration. In some instances, acute coronary catheterization may be indicated as an emergency diagnostic procedure. Recent studies have shown that less than completely occluded coronary arteries (varying from “normal” to subtotally occluded), can be the “culprit site” in some of the patients with STEMI (39)

Back to Article Outline

Conclusion 

In conclusion, chronic ST elevation caused by early repolarization appears to be rather “friendly” and benign, and associated, as in the current study, with fitness, lower cholesterol values, and trends toward lower use of health care resources. It may indeed be associated with lower rather than higher mortality or morbidity. Still, despite this “friendly” aspect, early repolarization can be a “foe” leading to the unjustified use of potentially harmful reperfusion therapy that has been shown to be overadministered to this group of patients. The possibility of early repolarization should be considered by application of new computer algorithms to the presenting ECG, by pursuing serial ECGs and by performing additional tests for acute ischemia or infarction. However, taking such care in diagnosis must be balanced against delaying justified and life-saving reperfusion therapy.

Back to Article Outline

References 

  1. Klatsky AL, Ohem R, Cooper RA, Udaltsova N, Armstrong MA. The early repolarization normal variant electrocardiogram (correlates and consequences). Am J Med. 2003;115:171–177
  2. The Joint European Society of Cardiology/American College of Cardiology Committee . Myocardial infarction redefined. A consensus document of the Joint European Society of Cardiology/American College of Cardiology Committee for the redefinition of myocardial infarction. J Am Coll Cardiol. 2000;36:959–969
  3. In:  MacFarlane PW,  Lawrie TD editor. Comprehensive Electrocardiography (Theory and Practice in Health and Disease). New York, New York: Pergamon Press; 1989;
  4. MacFarlane PW. Age, sex, and the ST amplitude in health and disease. J Electrocardiol. 2001;34(suppl):235–241
  5. Goldman MJ. Normal variants in the electrocardiogram leading to cardiac invalidism. Am Heart J. 1950;59:71–77
  6. Grushin H. Pecularities of the African's electrocardiogram and the changes observed in serial studies. Circulation. 1954;9:860–867
  7. Seriki O, Smith AJ. The electrocardiogram of young Nigerians. Am Heart J. 1966;72:153–157
  8. 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;77:441–459
  9. Balady GJ, Cadigan JB, Ryan TJ. Electrocardiogram of the athlete (an analysis of 289 professional football players). Am J Cardiol. 1984;53:1339–1343
  10. Hanne-Paparo N, Drory Y, Schoenfield Y, et al.  Common ECG changes in athletes. Cardiology. 1976;61:267–278
  11. Kudenchuk PJ, Ho MT, Weaver WD, et al.  Accuracy of computer-interpreted electrocardiography in selecting patients for thrombolytic therapy. J Am Coll Cardiol. 1991;17:1486–1491
  12. Zhou S, Helfenbein E, Clifton J, Selvester R, Wagner GS. Classification of ST elevation acute myocardial infarction, acute pericarditis, and benign early repolarization. J Electrocardiol. 2000;33(Suppl):251
  13. Schlant RC, Adolph RJ, DiMarco JP, et al.  Guidelines for electrocardiography. A report of the American College of Cardiology/American Heart Association Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on Electrocardiography). J Am Coll Cardiol. 1992;19:473–481
  14. Kadish AH, Buxton AE, Kennedy HL, et al.  ACC/AHA clinical competence statement on electrocardiography and ambulatory electrocardiography (a report of the ACC/AHA/ACP–ASIM Task Force on Clinical Competence (ACC/AHA Committee to Develop a Clinical Competence Statement on Electrocardiography and Ambulatory Electrocardiography)). Circulation. 2001;104:3169–3178
  15. Rubel P, Fayn J, Willems JL. Future prospects in ECG signal interpretation. In:  Barahona P,  Christensen JP editor. Knowledge and Decisions in Health Telematics. Amsterdam, The Netherlands: IOS Press; 1994;p. 173–180
  16. Assanelli D, Lazzari S, Moretti M, et al.  Comparison of 12-lead repolarization parameters during follow-up study in middle-aged sportsmen and in patients during acute myocardial infarction. J Electrocardiol. 1996;29(suppl):73–77
  17. CEN/TC251 ENV 1064. Medical Informatics—Standard communications protocol—computer assisted electrocardiography. June 1993
  18. Rubel P, Fayn J, Willems JL. Future Prospects in ECG Signal Interpretation. In:  Barahona P,  Christensen JP editor. Knowledge and Decisions In Health Telematics. Amsterdam: IOS Press; 1994;p. 173–180
  19. Fayn J, Rubel P, Mohsen N. An improved method for the precise measurement of serial ECG changes in QRS duration and QT interval (Performance assessment on the CSE noise testing database and on a healthy 720-case-set-population). J Electrocardiol. 1992;24(suppl):123–127
  20. Rubel P, Gouaux F, Fayn J, et al.  Towards intelligent and mobile systems for early detection and interpretation of cardiological syndromes. In:  Murray A,  Swiryn S editor. Computers in Cardiology. 28:Piscataway, NJ: IEEE Computer Society; 2001;p. 193–196
  21. Rautaharju PM, Park LP, Chaitman BR, et al.  The Novacode criteria for classification of ECG abnormalities and their clinically significant progression and regression. J Electrocardiol. 1998;31(3):157–187
  22. MacFarlane PW, Latif S. Automated serial ECG comparison based on the Minnesota code. J Electrocardiol. 1996;29(suppl):29–34
  23. Fayn J, Forlini MC, Behlouli H, et al.  Typological characterization of the spatial QRS and ST-T changes during acute myocardial ischemis evoked byPTCA. J Electrocardiol. 1999;32(suppl):101
  24. Fayn J, Rubel P, Forlini MC, et al.  How to improve the identification of the coronary artery occlusion site in acute myocardial ischemia using computerized ECG analysis methods. Eur Heart J. 2003;24(Suppl):
  25. Johanson P, Jernberg T, Gunnarsson G, Lindahl B, Wallentin L, Dellborg M. Prognostic value of ST-segment resolution—when and what to measure. Eur Heart J. 2003;24:337–345
  26. Santoro GM, Valenti R, Buonamici P, et al.  Relation between ST-segment changes and myocardial perfusion evaluated by myocardial contrast echocardiography in patients with acute myocardial infarction treated with direct angioplasty. Am J Cardiol. 1998;82:932–937
  27. Fesmire FM, Hughes AD, Fody EP, et al.  The Erlanger chest pain evaluation protocol (a one-year experience with serial 12-lead ECG monitoring, two-hour delta serum marker measurements, and selective nuclear stress testing to identify and exclude acute coronary syndromes). Ann Emerg Med. 2002;40:584–594
  28. Eriksson P, Gunnarsson G, Dellborg M. Diagnosis of acute myocardial infarction in patients with chronic right bundle-branch block using standard 12-lead electrocardiogram compared with dynamic vector cardiography. Cardiology. 1998;90:58–62
  29. Gunnarsson G, Eriksson P, Kallstrom G, Eriksson M, Dellborg M. Vectorcardiographic monitoring of patients with left bundle branch block and clinical suspicion of acute myocardial infarction. Eur Heart J. 2001;22(suppl):110
  30. Gustafsson G, Dellborg M, Lindahl B, Wallentin L. Dynamic vectorcardiography for early diagnosis of acute myocardial infarction compared with 12-lead electrocardiogram. BIOMACS Study Group. Coron Artery Dis. 1996;7:871–876
  31. Brady WJ, Chan TC. Electrocardiographic manifestations (benign early repolarization). J Emerg Med. 1999;17:473–478
  32. Spratt KA, Borans SM, Michelson EL. Early repolarization (normalization of the electrocardiogram with exercise as a clinically useful diagnostic feature). J Invasive Cardiol. 1995;7:238–242
  33. McManus CD, Doyle JT, Pipberger HV. Year-to-year variation of the orthogonal electrocardiogram and vectorcardiogram among 243 normal white males. J Electrocardiol1984;17(2):107–114.
  34. Kambara H, Phillips J. Long term evaluation of early repolarization syndrome (normal variant RS-T segment elevation). Am J Cardiol1976;38:157–161.
  35. Fenichell NN. A long term study of concave RS-T elevation—a normal variant of the electrocardiogram. Angiology1962;13:360–366
  36. Sabia P, Afrookteh A, Touchstone DA, Keller MW, Esquivel L, Kaul S. Value of regional wall motion abnormality in the emergency room diagnosis of acute myocardial infarction (a prospective study using two-dimensional echocardiography). Circulation. 1991;84(suppl I):85–92
  37. Stowers SA, Eisenstein EL, Wackers FJ, et al.  An economic analysis of an aggressive diagnostic strategy with single photon emission computed tomography myocardial perfusion imaging and early exercise stress testing in emergency department patients who present with chest pain but nondiagnostic electrocardiograms (results from a randomized trial). Ann Emerg Med. 2000;35:17–25
  38. Lindhardt TB, Kelbaek H, Madsen JK, et al.  Continuous monitoring of global left ventricular ejection fraction during percutaneous transluminal coronary angioplasty. Am J Cardiol. 1998;81:853–859
  39. Madsen JK, Grande P, Saunamaki K, et al. Danish Multicenter Randomized Study of Invasive Versus Conservative Treatment in patients with inductable ischemia after thrombolysis in acute myocardial infarction (DANAMI). Circulation1997;96(3):748–755

PII: S0002-9343(03)00370-X

doi:10.1016/S0002-9343(03)00370-X

The American Journal of Medicine
Volume 115, Issue 3 , Pages 237-240, 15 August 2003

Article Tools