What is an acute myocardial infarction?

Russell V. Luepker
School of Public Health, University of Minnesota, Minneapolis, MN, USA

The accurate diagnosis of acute myocardial infarction (AMI) is crucial for many reasons. For the practicing physician, the diagnosis has clear and directive therapeutic implications. For the hospital administrator, it has important influences on resource allocation and quality assurance. For the clinical trialist, it defines outcomes in studies of new therapies. For the epidemiologist, case definitions are essential for understanding incidence and prevalence and for monitoring disease trends in the population. However, despite its importance, the definition of AMI is in flux, leading to ambiguity and confusion for clinicians, administrators, trialists and epidemiologists.

Common case-criteria for AMI developed in the 1960s from a need to establish heart disease registries. Most of these efforts focused on discharge diagnoses and retrospective surveillance. The criteria became the widely used 'World Health Organization (WHO) criteria' [1,2], and included a triad of elements: classical symptoms, enzyme elevation and electrocardiographic (ECG) changes, particularly the newly developed Q-waves. But these were ambiguous ‘criteria’, enabling clinicians and investigators to use them as they saw fit, and yet still claim to be using the WHO standard. This ambiguity meant that comparisons of AMI between centers and over time were difficult and often invalid.

The field advanced in the 1980s with the advent of large surveillance projects that developed explicit definitions for symptoms, enzyme levels and ECG patterns. The WHO MONICA (multinational MONItoring of trends and determinants in CArdiovascular disease) study and parallel efforts in the United States exemplified this advance [3,4].

Unfortunately, the discharge diagnoses approach and retrospective chart abstraction used in these trials did not allow for an immediate diagnosis, which is needed for acute therapy, where clinicians must make decisions with limited information. Furthermore, the changing presentation of AMI was not taken into account, and the various new biomarkers were not used.

Changing treatments
The emergence of acute reperfusion therapies implied a need for rapid diagnosis. Thrombolysis and percutaneous angioplasty, early treatment interventions designed to restore blood flow, were highly effective but only when performed within hours of the onset of symptoms.

New biomarkers
The advent of new biomarkers, specifically troponins, also dramatically altered the field. Troponins are highly sensitive and specific blood markers of cardiac myocyte damage [5-7]. In comparison with older enzyme markers such as lactate dehydrogenase (LDH), serum glutamic oxaloacetic transaminase (SGOT), creatine kinase (CK) and CK isoenzyme MB, they represent a ‘sea change’ in diagnosis, because they allow smaller infarcts to be detected - and to be detected more quickly.

Changing presentation
Finally, the presentation of the disease began to change as traditional Q-wave infarctions diminished and a more subtle form of ECG-based AMI became prevalent [8].

This combination of clinical needs, improved diagnostic technology and changes in the presentation led to widespread interest in revising the diagnostic criteria for AMI, resulting in a series of new and widely endorsed AMI definitions.

In 2000, a joint working group of the European Society of Cardiology and American College of Cardiology developed a statement on the redefinition of myocardial infarction [9]. It addressed both the need for a more rapid diagnosis and the advent of new biomarker technologies. It also suggested that diagnostic imaging would play a role in case definitions.

Later on, in 2003, an American Heart Association (AHA), WHO and US National Institutes of Health (NIH) group put forward definitions necessary for population surveillance of cardiovascular disease [10]. These epidemiological criteria focused on longer-term surveillance issues, in which consistency of case definition is crucial. The group also considered comparisons between modern and earlier enzyme-defined cases.

Most recently, in 2007, a combined group of all these organizations discussed a universal definition of myocardial infarction. It refined and better described a number of clinical situations in which myocardial infarction might be considered, including inadequate oxygen supply, trauma, and myocardial infarction associated with cardiac procedures [11].

The results of the technological advances and the new definitions are dramatic. A number of studies have demonstrated that the use of troponins can lead to substantial increases in the number of patients hospitalized with AMI. In one study, using troponin as a biomarker instead of CK or CK-MB resulted, respectively, in a 0-320% or 3.9-195% increase in AMI hospitalizations [12].

These differences are debated in the literature, but most investigators suggest that using troponin as a biomarker results in the detection of milder myocardial infarctions [13-15]. These ’small‘ AMIs nonetheless carry prognostic significance, because long-term follow-up demonstrates that even minor perturbations are associated with increased long-term mortality [16].

This trend will be enhanced by the advent of ultrasensitive cardiac troponin markers, which enable clinicians to reliably detect even lower levels of troponin [17]. One result of more sensitive markers is the revelation that a mild elevation in troponins is associated with other cardiac and non-cardiac diseases. These include a variety of pathologies, from heart failure to pulmonary embolisms and renal failure. In addition, extreme exertion is associated with a mild elevation in troponins [11]. These observations add confusion to the field.

Given these recent changes, what are reasonable recommendations? It is apparent that the contemporary diagnosis of AMI is driven by biomarkers, specifically troponins. Using these markers in combination with symptoms will result in the diagnosis of AMI even in the setting of negative cardiograms. For the emergency reperfusion situation, a single biomarker and/or cardiographic changes might be all that is available and adequate to make a diagnosis for reperfusion treatment. For monitoring disease trends and for trials, multiple markers - at least 2 - in an ascending or descending pattern in association with symptoms are essential for making the diagnosis.

Conclusions
In the future, we will see a continuing evolution of the definition of AMI as more sensitive measures of myocardial damage emerge. Disease rates will rise in the setting of milder cases, as a result of more-sensitive measures. These changes should provide direction for clinicians to implement the most effective therapies for their patients, based on an improved understanding of the underlying pathophysiology. For those interested in disease outcomes, a continuing evolution of data-based criteria is needed.

References

1. Weinstein BJ, Epstein FH. Comparability of criteria and methods in the epidemiology of cardiovascular disease. Report of a survey. Circulation 1964;30:643-653.
2. World Health Organization. Working group on the establishment of ischaemic heart disease registers: Report of the fifth working group. 1971; WHO Report No. Eur 8201(5); Copenhagen.
3. Gillum RF, Folsom A, Luepker RV, et al. Sudden death and acute myocardial infarction in a metropolitan area, 1970-1980. The Minnesota Heart Survey. N Engl J Med 1983;309:1353-1358.
4. Tunstall-Pedoe H, Kuulasmaa K, Amouyel P, et al. Myocardial infarction and coronary deaths in the World Health Organization MONICA Project. Registration procedures, event rates, and case-fatality rates in 38 populations from 21 countries in four continents. Circulation 1994;90:583-612.
5. Apple FS. Cardiac troponin monitoring for detection of myocardial infarction: Newer generation assays are here to stay. Clinica Chimica Acta 2007;380:1-3.
6. Apple FS, Jesse RL, Newby LK, et al. National Academy of Clinical Biochemistry and IFCC Committee for Standardization of Markers of Cardiac Damage Laboratory Medicine Practice Guidelines: Analytical issues for biochemical markers of acute coronary syndromes. Clin Chem 2007;53:547-551.
7. Saenger AK, Jaffe AS. Requiem for a heavyweight: the demise of creatine kinase-MB. Circulation 2008;118:2200-2206.
8. Crow RS, Hannan PJ, Jacobs DR Jr, et al. Eliminating diagnostic drift in the validation of acute in-hospital myocardial infarction - implication for documenting trends across 25 years: the Minnesota Heart Survey. Am J Epidemiol 2005;161:377-388.
9. Alpert JS, Thygesen K, Antman E, Bassand JP. 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.
10. Luepker RV, Apple FS, Christenson RH, et al. Case definitions for acute coronary heart disease in epidemiology and clinical research studies: a statement from the AHA Council on Epidemiology and Prevention; AHA Statistics Committee; World Heart Federation Council on Epidemiology and Prevention; the European Society of Cardiology Working Group on Epidemiology and Prevention; Centers for Disease Control and Prevention; and the National Heart, Lung, and Blood Institute. Circulation 2003;108:2543-2549.
11. Thygesen K, Alpert JS, White HD; Joint ESC/ACCF/AHA/WHF Task Force for the Redefinition of Myocardial Infarction. Universal definition of myocardial infarction. Eur Heart J 2007;28:2525-2538.
12. White HD. Evolution of the definition of myocardial infarction: What are the implications of a new universal definition? Heart 2008;94:679-684.
13. Polanczyk CA, Schneid S, Imhof BV, et al. Impact of redefining acute myocardial infarction on incidence, management and reimbursement rate of acute coronary syndromes. Int J Cardiol 2006;107:180-187.
14. Salomaa V, Ketonen M, Koukkunen H, et al. The effect of correcting for troponins on trends in coronary heart disease events in Finland during 1993-2002: the FINAMI study. Eur Heart J 2006;27:2394-2399.
15. Salomaa V, Koukkunen H, Ketonen M, et al. A new definition for myocardial infarction: what difference does it make? Eur Heart J 2005;26:1719-1725.
16. Hochholzer W, Buettner HJ, Trenk D, et al. New definition of myocardial infarction: impact on long-term mortality. Am J Med 2008;121:399-405.
17. Casals G, Filella X, Auge JM, Bedini JL. Impact of ultrasensitive cardiac troponin I dynamic changes in the new universal definition of myocardial infarction. Am J Clin Pathol 2008;130:964-968.