Abstract

INTRODUCTION

Electrocardiography is a low-cost, easy to perform method of investigation of the cardiovascular system with diagnostic and prognostic value and great clinical usefulness. Used in many different care provision contexts, from the Primary Care Unit to the Intensive Care Unit, the electrocardiogram (ECG) is a basic tool for several health professionals. Additionally, the progressive complexity and the increasing costs of modern medicine with invasive examinations reveal the need of a rational utilization of the available resources, prioritizing techniques and procedures that have a favorable cost-effectiveness ratio, like the ECG.¹⁵15. MacFarlane PW, Oosterom A, Pahlm O, Kligfield P, Janse M, Camm A, editors. Comprehensive electrocardiology. 2.ed. London: Springer; 2011.

The systematic utilization of the ECG in epidemiological studies began in the 1940s, with the first cardiovascular epidemiology cohorts.⁶6. Dawber TR, Kannel WB, Love DE, Streeper RB. The electrocardiogram in heart disease detection: a comparison of the multiple and single lead procedures. Circulation. 1952;5(4):559-66. However, it was soon verified that there were substantial difficulties in standardizing readings and coding, and these difficulties derived from variations between successive readings performed by different observers and also from the lack of an established coding, appropriate to epidemiological and population-based studies.⁴4. Blackburn H. The electrocardiogram in cardiovascular epidemiology: problems in standarized application. Ann N Y Acad Sci. 1965;126(2):882-905. The Minnesota Code was created in this context. Published in 1960,³3. Blackburn H, Keys A, Simonson E, Rautaharju P, Punsar S. The electrocardiogram in population studies: a classification system. Circulation. 1960;21:1160-75. it aimed to provide an objective, reproducible and safe system of electrocardiographic diagnoses that enabled the comparison of epidemiological studies carried out in different populations and countries. The code was validated in subsequent studies and has become the method chosen in epidemiological studies that use electrocardiography.¹⁹19. Prineas RJ, Crow RS, Zhang ZM. The Minnesota code manual of electrocardiographic findings. 2.ed. London: Springer; 2010.

In the following decades, countless papers were published on the use of ECG in population-based studies, showing the prognostic value of different electrocardiographic alterations to predict death and cardiac events.⁵5. Blackburn H, Taylor HL, Keys A. Coronary heart disease in seven countries. XVI. The electrocardiogram in prediction of five-year coronary heart disease incidence among men aged forty through fifty-nine. Circulation. 1970;41(4 Suppl):I154-61. ^{, 9}9. Kannel WB, Gordon T, Castelli WP, Margolis JR. Electrocardiographic left ventricular hypertrophy and risk of coronary heart disease. The Framingham study. Ann Intern Med. 1970;72(6):813-22. An aggregate analysis of data from eight population-based studies, published in 1978,¹⁷17. Pooling Project Research Group. Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: final report of the pooling project. J Chronic Dis. 1978;31(4):201-306. involved a total of 8,390 male individuals with an average follow-up of eight years. This study confirmed the importance of major ECG abnormalities (which included alterations related to myocardial ischemia, bundle branch blocks, atrial fibrillation and ventricular ectopy) as markers of subclinical cardiovascular disease and predictors of cardiac events, like myocardial infarction and sudden death. Subsequent population-based studies confirmed the prognostic importance of electrocardiographic alterations, including those originally classified as minor alterations.⁷7. Greenland P, Xie X, Liu K, Colangelo L, Liao Y, Daviglus ML, et al. Impact of minor electrocardiographic ST-segment and/or T-wave abnormalities on cardiovascular mortality during long-term follow-up. Am J Cardiol. 2003;91(9):1068-74. ^{, 16}16. Machado DB, Crow RS, Boland LL, Hannan PJ, Taylor Jr HA, Folsom AR. Electrocardiographic findings and incident coronary heart disease among participants in the Atherosclerosis Risk in Communities (ARIC) study. Am J Cardiol. 2006;97(8):1176-81. DOI:10.1016/j.amjcard.2005.11.036
https://doi.org/10.1016/j.amjcard.2005.1... ^{, 26}26. Zhang ZM, Prineas RJ, Eaton CB. Evaluation and comparison of the Minnesota Code and Novacode for electrocardiographic Q-ST wave abnormalities for the independent prediction of incident coronary heart disease and total mortality (from the Women's Health Initiative). Am J Cardiol. 2010;106(1):18-25. DOI:10.1016/j.amjcard.2010.02.007
https://doi.org/10.1016/j.amjcard.2010.0... ^{, 27}27. Zhang ZM, Prineas RJ, Soliman EZ, Baggett C, Heiss G. Prognostic significance of serial Q/ST-T changes by the Minnesota Code and Novacode in the Atherosclerosis Risk in Communities (ARIC) study. Eur J Prev Cardiol. 2012;19(6):1430-6. DOI:10.1177/1741826711426091
https://doi.org/10.1177/1741826711426091... In population-based studies, the ECG is also useful to define prevalent cases at baseline and to detect outcomes, such as silent myocardial infarctions, when it is performed in subsequent visits.

Simultaneously, the evolution of signal processing techniques, with the use of microelectronics and computers, the miniaturization of devices, digitization of signals and automatic interpretation of ECGs, had a great impact on cardiovascular epidemiological studies.¹³13. MacFarlane PW. A brief history of computer-assisted electrocardiography. Methods Inf Med. 1990;29(4):272-81. ^{, 24}24. Savage DD, Rautaharju PM, Bailey JJ, Horton MR, Hadden W, LaCroix AZ, et al. The emerging prominence of computer electrocardiography in large population-based surveys. J Electrocardiol. 1987;20(Suppl):48-52. Systems that are capable of transmitting electrocardiographic tracings over the Internet and software packages that enable automatic analysis and coding of tracings have revolutionized the electrocardiography of population-based studies, enhancing its applications and allowing the study of large populations.

The Estudo Longitudinal de Saúde do Adulto (ELSA-Brasil - Brazilian Longitudinal Study for Adult Health) included more than 15 thousand participants aged 35-74 years at baseline. The aim was to monitor participants in order to identify outcomes related to the development and evolution of the main chronic diseases that affect adults, particularly cardiovascular diseases and diabetes. Baseline assessment (2008-2010) included detailed interviews and clinical and laboratory tests to obtain physiological data, especially concerning the cardiovascular system. The follow-up combines annual telephone contacts and re-tests and interviews every three to four years.²2. Aquino EM, Barreto SM, Bensenor IM, Carvalho MS, Chor D, Duncan BB, et al. Brazilian Longitudinal Study of Adult Health (ELSA-Brasil): objectives and design. Am J Epidemiol. 2012;175(4):315-24. DOI:10.1093/aje/kwr294
https://doi.org/10.1093/aje/kwr294...

The ECG is one of the methods performed at baseline in the ELSA-Brasil study, and it is repeated in the subsequent waves. In view of the complexity of its analysis and coding, it was decided to create a Centro de Leitura de ECG (CL-ECG - ECG Reading Center), so as to guarantee the quality of the records and the uniformity and comparability of coding. However, the specific literature describing basic requirements and difficulties related to the implementation of a CL-ECG is scarce.¹1. Anderson ST, Pahlm O, Bacharova L, Barbagelata A, Chaitman BR, Clemmensen P, et al. Standards for the function of an academic 12-lead electrocardiographic core laboratory. J Electrocardiol. 2001;34(1):41-7. DOI:10.1054/jelc.2001.22028
https://doi.org/10.1054/jelc.2001.22028... ^{, 18}18. Prineas RJ, Blackburn H. The Coronary Drug Project. Role and methods of the ECG Reading Center. Control Clin Trials. 1983;4(4):389-407. The implementation was preceded by a visit to two of the largest ECG reading centers in the world, EPICARE, which was coordinated at the time by Prof. Prineas, at Wake Forest University, in Winston-Salem, North Carolina, USA, and CARE, coordinated by Prof. MacFarlane, in Glasgow, University of Glasgow, Scotland. The present paper describes the process, difficulties and challenges concerning the implementation of the CL-ECG in the ELSA-Brasil.

EQUIPMENT

The centralized reading of the ECG is based on tracings obtained by different electrocardiographs, digital or analog, with the record of one, three or 12 simultaneous leads, with or without automatic interpretation. However, the best tracings are obtained by robust equipment that is exclusively dedicated to electrocardiography, with simultaneous acquisition of 12 high-frequency leads (>500 samples/s per channel), high-resolution thermal print head and automatic measurements of ECG deflections and intervals.

Furthermore, the electrocardiographs must communicate digitally with an ECG management and storage center, with a system that is capable of storing and organizing the tracings, enabling their editing and detailed analysis. Automatic coding and analyses of electrocardiographic parameters derived from computerized measurements depend on the availability of the tracings at such management and storage centers. Only a few companies have such systems, like GE, Philips, Mortara and Cardiac Science. Apart from these systems' intrinsic characteristics, the way in which tracing transmission is performed between the electrocardiographs and the storage center is relevant. With the current ubiquitous availability of the Internet, the best systems are the ones that send tracings electronically, in a network or using internet protocols.

In the ELSA-Brasil, the 12-lead ECG was recorded in a digital device (Atria 6100, Burdick, Cardiac Science Corporation, Bothel, WA, USA) with automatic reading of the heart rate; duration, amplitude and axes of the P, QRS and T waves; and also of the QT and QTC intervals and QT dispersion. The ECGs were transmitted from the Atria 6100 electrocardiograph to a server of the CL-ECG, located in the Centro de Investigação de Minas Gerais (CI MG - Investigation Center of Minas Gerais), where they were stored for subsequent analysis in a Pyramis ECG management system (version 6.2.b, Cardiac Science Corporation, Bothel, WA, USA), with the possibility of editing tracings and measuring intervals beat by beat.

PERSONNEL

The current guidelines indicate that a CL-ECG must have at least one physician experienced in clinical research or cohort studies and in electrocardiography, to assume the function of direction and coordination, with clinical and administrative responsibility. ¹1. Anderson ST, Pahlm O, Bacharova L, Barbagelata A, Chaitman BR, Clemmensen P, et al. Standards for the function of an academic 12-lead electrocardiographic core laboratory. J Electrocardiol. 2001;34(1):41-7. DOI:10.1054/jelc.2001.22028
https://doi.org/10.1054/jelc.2001.22028... ^{, 18}18. Prineas RJ, Blackburn H. The Coronary Drug Project. Role and methods of the ECG Reading Center. Control Clin Trials. 1983;4(4):389-407. The coordination activities can be shared with one or more coordinators, who supervise the technicians' activities, perform quality control and revise the coding.¹1. Anderson ST, Pahlm O, Bacharova L, Barbagelata A, Chaitman BR, Clemmensen P, et al. Standards for the function of an academic 12-lead electrocardiographic core laboratory. J Electrocardiol. 2001;34(1):41-7. DOI:10.1054/jelc.2001.22028
https://doi.org/10.1054/jelc.2001.22028... The technical team is composed of electrocardiography professionals who supervise the field activities, and primary and secondary ECG analysts, who are responsible for manual coding (primary analysts), when it is performed, and for reviewing abnormal codes, both in manual and in automatic coding (secondary analysts). ¹1. Anderson ST, Pahlm O, Bacharova L, Barbagelata A, Chaitman BR, Clemmensen P, et al. Standards for the function of an academic 12-lead electrocardiographic core laboratory. J Electrocardiol. 2001;34(1):41-7. DOI:10.1054/jelc.2001.22028
https://doi.org/10.1054/jelc.2001.22028... ^{, 18}18. Prineas RJ, Blackburn H. The Coronary Drug Project. Role and methods of the ECG Reading Center. Control Clin Trials. 1983;4(4):389-407. In addition, the CL-ECG needs to have administrative and information technology support.

The CL-ECG of the ELSA-Brasil had the administrative and information technology support that is provided for the other activities of the CI MG. General coordination (equivalent to the direction described above) was exercised by a senior medical researcher experienced in electrocardiography and clinical research, and the coordination of the works was performed by a cardiologist experienced in electrocardiography and in specific technical coordination, and by secondary analysts.

ELECTROCARDIOGRAM ACQUISITION PROCEDURES

Performing an ECG is a routine procedure in clinical practice and it is described in reference texts available in the medical literature. In the case of epidemiological studies, especially the multicenter ones, it is necessary to standardize procedures and ensure the quality of the resulting tracings, thus minimizing the chance of errors or loss of records. ECG performance in the ELSA-Brasil study followed a routine established in the Operations Manual (Figure), and the electrocardiography technicians of the ELSA ICs were trained and certified by the ECG Reading Center team. The configuration of the electrocardiograph was performed by the CL-ECG when the equipment was installed.

The ECG was performed according to a flow defined by the ICs, during the mornings, at an appropriate place that had low environmental noise and adequate lighting and temperature. Alcohol abstinence since the previous day was recommended; also, the participant should not smoke on the day of the test. The stages of the test were:

TRACE CODING SYSTEMS

The ECG coding system that is most frequently used in epidemiological and population-based studies, and also in clinical research, is the Minnesota Code.³ Divided into classifications that are grouped into nine groups, with rigidly defined criteria, the code has undergone only a few modifications since its initial description.¹⁹19. Prineas RJ, Crow RS, Zhang ZM. The Minnesota code manual of electrocardiographic findings. 2.ed. London: Springer; 2010. A published manual that is already in its second edition aids in the code application, with detailed explanations about how to perform the measurements and obtain the final coding.¹⁹19. Prineas RJ, Crow RS, Zhang ZM. The Minnesota code manual of electrocardiographic findings. 2.ed. London: Springer; 2010. The Minnesota code has been used in the majority of the large epidemiological, population-based studies and its prognostic value is already established. ⁵5. Blackburn H, Taylor HL, Keys A. Coronary heart disease in seven countries. XVI. The electrocardiogram in prediction of five-year coronary heart disease incidence among men aged forty through fifty-nine. Circulation. 1970;41(4 Suppl):I154-61. ^{, 7}7. Greenland P, Xie X, Liu K, Colangelo L, Liao Y, Daviglus ML, et al. Impact of minor electrocardiographic ST-segment and/or T-wave abnormalities on cardiovascular mortality during long-term follow-up. Am J Cardiol. 2003;91(9):1068-74. ^{, 9}9. Kannel WB, Gordon T, Castelli WP, Margolis JR. Electrocardiographic left ventricular hypertrophy and risk of coronary heart disease. The Framingham study. Ann Intern Med. 1970;72(6):813-22. ^{, 16}16. Machado DB, Crow RS, Boland LL, Hannan PJ, Taylor Jr HA, Folsom AR. Electrocardiographic findings and incident coronary heart disease among participants in the Atherosclerosis Risk in Communities (ARIC) study. Am J Cardiol. 2006;97(8):1176-81. DOI:10.1016/j.amjcard.2005.11.036
https://doi.org/10.1016/j.amjcard.2005.1... ^{, 17}17. Pooling Project Research Group. Relationship of blood pressure, serum cholesterol, smoking habit, relative weight and ECG abnormalities to incidence of major coronary events: final report of the pooling project. J Chronic Dis. 1978;31(4):201-306. ^{, 19}19. Prineas RJ, Crow RS, Zhang ZM. The Minnesota code manual of electrocardiographic findings. 2.ed. London: Springer; 2010. ^{, 26}26. Zhang ZM, Prineas RJ, Eaton CB. Evaluation and comparison of the Minnesota Code and Novacode for electrocardiographic Q-ST wave abnormalities for the independent prediction of incident coronary heart disease and total mortality (from the Women's Health Initiative). Am J Cardiol. 2010;106(1):18-25. DOI:10.1016/j.amjcard.2010.02.007
https://doi.org/10.1016/j.amjcard.2010.0... ^{, 27}27. Zhang ZM, Prineas RJ, Soliman EZ, Baggett C, Heiss G. Prognostic significance of serial Q/ST-T changes by the Minnesota Code and Novacode in the Atherosclerosis Risk in Communities (ARIC) study. Eur J Prev Cardiol. 2012;19(6):1430-6. DOI:10.1177/1741826711426091
https://doi.org/10.1177/1741826711426091... The Novacode classification system was developed from the Minnesota code, so as to be utilized in serial assessments, and since its conception it has been adapted to automated interpretation.²²22. Rautaharju PM, Calhoun HP, Chaitman BR. NOVACODE serial ECG classification system for clinical trials and epidemiologic studies. J Electrocardiol. 1992;24(Suppl):179-87. ^{, 23}23. Rautaharju PM, Park LP, Chaitman BR, Rautaharju F, Zhang ZM. The Novacode criteria for classification of ECG abnormalities and their clinically significant progression and regression. J Electrocardiol. 1998;31(3):157-87. In many aspects Novacode is comparable to the Minnesota code, both in terms of the coding system¹⁹ and concerning their prognostic impact.²⁶26. Zhang ZM, Prineas RJ, Eaton CB. Evaluation and comparison of the Minnesota Code and Novacode for electrocardiographic Q-ST wave abnormalities for the independent prediction of incident coronary heart disease and total mortality (from the Women's Health Initiative). Am J Cardiol. 2010;106(1):18-25. DOI:10.1016/j.amjcard.2010.02.007
https://doi.org/10.1016/j.amjcard.2010.0... ^{, 27}27. Zhang ZM, Prineas RJ, Soliman EZ, Baggett C, Heiss G. Prognostic significance of serial Q/ST-T changes by the Minnesota Code and Novacode in the Atherosclerosis Risk in Communities (ARIC) study. Eur J Prev Cardiol. 2012;19(6):1430-6. DOI:10.1177/1741826711426091
https://doi.org/10.1177/1741826711426091... The experience that has been accumulated with the Minnesota code, together with its greater simplicity, have made it become the standard coding system in modern epidemiological studies.

In recent years, advances in information technology and in the knowledge that has been acquired about automatic interpretation of the ECG have enabled the development of programs for the automatic coding of tracings through the Minnesota code.¹¹11. Kors JA, Crow RS, Hannan PJ, Rautaharju PM, Folsom AR. Comparison of computer-assigned Minnesota Codes with the visual standard method for new coronary heart disease events. Am J Epidemiol. 2000;151(8):790-7. ^{, 12}12. Kors JA, van Herpen G. The coming of age of computerized ECG processing: can it replace the cardiologist in epidemiological studies and clinical trials? Stud Health Technol Inform. 2001;84(Pt 2):1161-7. DOI:10.3233/978-1-60750-928-8-1161
https://doi.org/10.3233/978-1-60750-928-... ^{, 14}14. MacFarlane PW, Latif S. Automated serial ECG comparison based on the Minnesota code. J Electrocardiol. 1996;29(Suppl):29-34. ^{, 19}19. Prineas RJ, Crow RS, Zhang ZM. The Minnesota code manual of electrocardiographic findings. 2.ed. London: Springer; 2010. Such methods have proved to be particularly attractive to be used in population-based studies, which started to have increasingly large samples. Comparisons between the manual and automatic methods have shown that automatic coding presents lower variability and greater accuracy and it has been recommended for epidemiological studies.¹¹11. Kors JA, Crow RS, Hannan PJ, Rautaharju PM, Folsom AR. Comparison of computer-assigned Minnesota Codes with the visual standard method for new coronary heart disease events. Am J Epidemiol. 2000;151(8):790-7. ^{, 12}12. Kors JA, van Herpen G. The coming of age of computerized ECG processing: can it replace the cardiologist in epidemiological studies and clinical trials? Stud Health Technol Inform. 2001;84(Pt 2):1161-7. DOI:10.3233/978-1-60750-928-8-1161
https://doi.org/10.3233/978-1-60750-928-... ^{, 14}14. MacFarlane PW, Latif S. Automated serial ECG comparison based on the Minnesota code. J Electrocardiol. 1996;29(Suppl):29-34. ^{, 19}19. Prineas RJ, Crow RS, Zhang ZM. The Minnesota code manual of electrocardiographic findings. 2.ed. London: Springer; 2010.

At the CL-ECG, the automatic coding system developed at the University of Glasgow by Prof. MacFarlane¹⁴ was adopted. The software was installed by Cardiac Science in the Pyramis system (version 6.2.b) available at the CL-ECG. The resulting codes were extracted and reviewed by secondary coders, to confirm the results. Next, the records were transferred to the ELSA-Brasil Datacenter. In 382 cases, there was a failure in the transmission of the ECG from the IC to the CL-ECG. In these cases, manual coding was performed at the University of Glasgow, under the supervision of Prof. MacFarlane.

ETHICAL AND PRACTICAL ASPECTS RELATED TO THE DELIVERY OF REPORTS

The literature documents the existence of a strong controversy about the pertinence and need of delivering test results to participants in epidemiological and clinical studies, and also about the way in which the results are delivered.²⁵25. Shalowitz DI, Miller FG. Communicating the results of clinical research to participants: attitudes, practices, and future directions. PLoS Med. 2008;5(5):e91. DOI:10.1371/journal.pmed.0050091
https://doi.org/10.1371/journal.pmed.005... On the one hand, the majority of participants want to receive the results, which can be useful to the early diagnosis of treatable conditions. On the other hand, the meaning of asymptomatic alterations obtained through casual tests is questionable, even regarding established methods such as the ECG.⁸8. Greenland P. Should the resting electrocardiogram be ordered as a routine risk assessment test in healthy asymptomatic adults? JAMA. 2012;307(14):1530-1. DOI:10.1001/jama.2012.441
https://doi.org/10.1001/jama.2012.441... ^{, 25}25. Shalowitz DI, Miller FG. Communicating the results of clinical research to participants: attitudes, practices, and future directions. PLoS Med. 2008;5(5):e91. DOI:10.1371/journal.pmed.0050091
https://doi.org/10.1371/journal.pmed.005...

The ELSA-Brasil decided to deliver tests and reports on complementary tests whose clinical use is established, such as the ECG. The reports were made by an experienced cardiologist and both the tracing and the report were delivered to the participants. The results were handed personally, by doctors or qualified health professionals, who provided explanations based on the report. In specific situations, the participant was advised to make an appointment with his/her private doctor in order to follow the propedeutics. In case the ECG result was normal and the participant wanted to receive the report at home, it would be sent by mail.

QUALITY CONTROL

Quality control is an essential aspect of the centralized reading of ECGs, as it guarantees the accuracy and reliability of the performed tests. Quality control at the CL-ECG of the ELSA-Brasil included the following activities, based on recommendations found in the literature: :¹1. Anderson ST, Pahlm O, Bacharova L, Barbagelata A, Chaitman BR, Clemmensen P, et al. Standards for the function of an academic 12-lead electrocardiographic core laboratory. J Electrocardiol. 2001;34(1):41-7. DOI:10.1054/jelc.2001.22028
https://doi.org/10.1054/jelc.2001.22028... ^{, 18}18. Prineas RJ, Blackburn H. The Coronary Drug Project. Role and methods of the ECG Reading Center. Control Clin Trials. 1983;4(4):389-407. ^{, 19}19. Prineas RJ, Crow RS, Zhang ZM. The Minnesota code manual of electrocardiographic findings. 2.ed. London: Springer; 2010. ^{, 21}21. Rautaharju PM, Broste SK, Prineas RJ, Eifler WJ, Crow RS, Furberg CD. Quality control procedures for the resting electrocardiogram in the Multiple Risk Factor Intervention Trial. Control Clin Trials. 1986;7(3 Suppl):46S-65S. ^{, 25}25. Shalowitz DI, Miller FG. Communicating the results of clinical research to participants: attitudes, practices, and future directions. PLoS Med. 2008;5(5):e91. DOI:10.1371/journal.pmed.0050091
https://doi.org/10.1371/journal.pmed.005...

DIFFICULTIES AND CHALLENGES

The process of creating the CI-ECG underwent a series of difficulties and challenges. We listed below some critical aspects of the creation of the CL, briefly discussing the difficulties.

FINAL REMARKS

In the present study, we described the implementation of an ECG reading center in Brazil, discussing the difficulties and challenges that were faced. It is an original report, for as far as we know, there is no other reading center of academic nature in Brazil or in other Latin American countries that has followed the international recommendations for its implementation.

We would like to emphasize the utilization of a totally digitized system and the automatic coding of the ECGs through an internationally accepted protocol. The CL-ECG of ELSA-Brasil has become one of the few centers in the world that has a software that allows automatic coding by the Minnesota code, guaranteeing that its results are reliable and ensuring comparability with studies carried out in other parts of the world. The results of the ECGs analyzed in the baseline by the ELSA-Brasil study will enable to define the reference parameters for the Brazilian population, the study of the relationship between cardiovascular risk factors and prevailing diseases - such as hypertension - and ECG alterations in the Brazilian population. As the ECG will be repeated in the subsequent waves of the ELSA study, the results will help to understand the natural history of cardiovascular diseases in the Brazilian population.

References

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