American Heart Journal
Volume 144, Issue 6 , Pages 933-937, December 2002

Things ain't what they used to be: Impact of a new definition of myocardial infarction☆☆☆

Cardiology Department, Green Lane Hospital, Auckland, New Zealand

Article Outline

Abstract 

Am Heart J 2002;144:933-7.

 

See related articles on pages 957 and 981.

In September 2000 a new definition of myocardial infarction (MI) was promulgated by the Joint European Society of Cardiology/American College of Cardiology (ESC/ACC) Committee.1 The definition is based largely on rising and falling levels of the cardio-specific biomarkers, troponin T and troponin I, in the appropriate clinical context.

The ESC/ACC Committee has been criticized for changing the definition of MI, and some commentators have said there is little justification for adopting their recommendations at face value.2, 3, 4, 5, 6 The criticisms have largely focused on 2 issues. The first is the impact on epidemiology caused by difficulties in making comparisons with previous populations classified according to a different definition. With the change in definition, the number of patients receiving a diagnosis of MI will rise and the case fatality rates will fall, thus it will be difficult to compare prevalence trends over time. This means that audits of the prevalence of MI and patient outcomes will need to continue using previous definitions for a transition period in order to obtain comparative data. Notwithstanding the value of epidemiological studies such as the Monitoring Trends and Determinants in Cardiovascular Disease (MONICA) Project,7 new epidemiological studies using the new definition of MI are needed to provide comparative data for research in future years.

The second major criticism is the lack of attention given in the recommendations to the diagnosis of MI in situations where troponin levels cannot be determined. The release of troponins from the myocardial contractile apparatus in response to prolonged ischemia occurs slowly, and thus troponin levels in the blood do not rise for at least 3 to 4 hours after the onset of ischemia. The new definition of MI does not cater for patients who present very early, before their troponin levels have had time to rise, or who die before signs of myocardial necrosis have developed sufficiently to be detected at autopsy. Thus there is still a place for definitions of MI not based entirely on troponins. The diagnosis of MI should always take into account information obtained clinically and from imaging modalities such as angiography, echocardiography, radionuclide scanning or magnetic resonance imaging, which may show regional wall motion abnormalities with thinning of the myocardium.1

In this issue of the Journal, Newby et al8 describe the discussions and recommendations from a meeting held in January 2001 to consider the implications of the new definition. Three recommendations were made.

1.Any elevation of creatine kinase-MB (CK-MB) or troponin is associated with a worse prognosis and should be considered an event whether it occurs in the context of an acute coronary syndrome, percutaneous coronary intervention (PCI), or coronary artery bypass grafting (CABG).

2.Continuous measures of myocardial necrosis, rather than dichotomous measures, should be used.

3.The troponin assays currently available do not meet the recommendations defined by the ESC/ACC Committee, and need to be improved.

To these important and cogent recommendations I would add 4 further comments. First, although Europe and the United States are prominent on the international stage, they are not the whole world. The ESC/ACC recommendations have worldwide ramifications (including cost implications), which should have been considered, and the change in definition to a largely troponin-based one may not be possible to implement in Africa, Asia, South America, and many parts of Eastern Europe.

Second, the emphasis on troponins at a time when none of the available troponin assays had been shown to fulfil the Committee's recommendations of 10% precision and a 99th percentile coefficient of variation (ie, the detection limit) has been problematic. Many laboratories worldwide have not yet performed formal local reference range studies to determine whether they fulfil the recommended criteria for precision at the detection limit. They should do so as a matter of urgency, and should provide clinicians with supporting data for the particular assay they use. It is almost 2 years since the new definition was promulgated. Tests that are used for diagnosis and management of serious medical conditions must be accurate, and it would seem reasonable to set a time limit of 3 years after publication of the ESC/ACC recommendations for assays to achieve the recommended level of precision. Any assays that don't measure up should be withdrawn in the interests of patient care.

In an article accompanying the paper by Newby et al,8 Apple et al9 make further comments about implementation of the ESC/ACC recommendations. They make a number of recommendations, including using a cut-off value of ≤10% imprecision (which was above the 99th percentile of the reference range for all assays) until assays improve. This idea has considerable merit. They also make recommendations regarding the definition of MI associated with PCI, namely that an increase above the cut-off value determined at 10% imprecision should be considered an MI, and that an increase of ≥25% in cases where the troponin level was already increased should be defined as recurrent injury associated with PCI.

There are now several troponin assays available (eg, the Roche Diagnostics troponin T assay) that fulfil the ESC/ACC recommendations (personal communication). Several troponin I assays come close to fulfilling the recommendations. Apart from the precision of the assays themselves, it will be important for individual laboratories to show that they can achieve the required standards routinely.10

Another issue is that some laboratories may assay troponins only once a day or just several times a week. The ACC/American Heart Association (AHA) guidelines recommend that laboratories should provide cardiac biomarker results within 30 to 60 minutes,11 and the US National Academy of Clinical Biochemistry recommends bedside or point-of-care testing if laboratories cannot provide cardiac biomarker results consistently within 1 hour.12

Third, the ESC/ACC Committee did not give any recommendations for an implementation strategy. Many hospitals worldwide still do not perform troponin testing. For example, in a recent survey, only 70% of hospitals in Scotland had troponin testing available.13 Haphazard introduction of the new definition has already led to hospitals in the same community using different criteria for the diagnosis of MI. The transition might have been smoother if the introduction of the new definitions had been coordinated by national cardiac societies, the World Heart Federation and the World Health Organization. Major educational efforts are required to educate doctors and the public that there is now a new definition of what constitutes a heart attack, and national heart foundations should take a leading role in such initiatives. Many patients will now be told that they have had a heart attack who would not have been diagnosed as such previously. It is important that they are told that for most patients the future after a heart attack is excellent.

As the ESC/ACC Committee indicated, the new definition has had wide implications for patients and clinical practice. The Committee's recommendations affect driving and rehabilitation guidelines; sick leave and disability entitlements; employers' perceptions about employability; advice as to when patients can return to work or fly; pilot licensing; life, health and travel insurance; coding of diagnostic groups; epidemiology; clinical trials; and health funding and public policy.

In New Zealand the new definitions have already been accepted by the Land Transport Safety Authority, which governs driver licencing. Thus patients who have a positive troponin test (without elevation of other myocardial proteins) after PCI or in connection with a non-ST-elevation acute coronary syndrome are classified in the same way and must not drive a private vehicle for 2 weeks, and must not drive a commercial vehicle for 4 weeks.

The psychological impact of the diagnosis of MI on individuals and their families should not be underestimated, and the response—whether conscious or subconscious—will vary enormously. Of course, telling patients that they have had a heart attack should not be the only information given. Not all MIs are the same,14 and the implications for social activities, employment, and patients' prognoses will vary widely according to the extent of myocardial necrosis, evidence of inducible ischemia, predisposition to ventricular arrhythmias, the severity of coronary artery disease, whether revascularization has been performed, and the degree of impairment of left ventricular function. This information should be conveyed and discussed with patients and their families.

Fourth, the ESC/ACC Committee gave no recommendations as to the definition of MI in patients undergoing CABG, although a consensus conference in 1998 recommended that the CK-MB threshold should be 5 times the upper limit of normal.15 (The same conference recommended that the CK-MB threshold for PCI should be 3 times the upper limit of normal). Defining the troponin levels that correlate with increased risk after CABG is a different concept than defining the level at which to label an event “MI” based on an ischemic cause. In the setting of CABG, a positive troponin test signifies that myocyte necrosis has occurred, and patients should be risk-stratified according to their troponin level and other risk factors. There is clear evidence that patients with increased cardiac protein levels after CABG have worse outcomes. In the Arterial Revascularization Therapy (ARTS) Study,16 which compared multivessel stenting with CABG, elevated CK-MB levels were detected in 30.5% of patients treated with PCI and 62% of those treated with CABG. The 12-month mortality rate in the latter group increased significantly when CK-MB levels rose above 5 times normal (7% vs 0% in the 38% of patients without elevated CK-MB levels), and there was a trend towards a higher mortality rate in those with CK-MB levels above 3 times normal (5.4%). I believe that, as with periprocedural events associated with PCI, events associated with CABG should be reported separately in clinical trials.

A rise in troponin levels in patients with non-ST-elevation acute coronary syndromes clearly signifies an increased risk of death or MI. Meta-analysis has shown that elevated troponin levels are associated with a 9-fold increased risk of death or MI within the subsequent 30 days.17 Elevated troponin levels in patients with acute coronary syndromes have a prognostic value that is out of proportion to the extent of myocyte necrosis and left ventricular impairment, and probably indicate the occurrence of microinfarctions due to platelet microemboli from ulcerated, complex and unstable atheromatous coronary artery plaques (Figure 1).

  • View full-size image.
  • Fig. 1. 

    Microvascular obstruction after plaque rupture. Despite recurrent micro emboli, the levels of CK-MB do not reach the diagnostic threshold, whereas because of the long half life and higher sensitivity of the assays, the diagnostic threshold for troponin is reached. CK-MB, Creatine kinase-MB. Adapted with permission from: Goldman BU, Christenson RH, Hamm CW, et al. Implications of troponin testing in clinical medicine. Curr Control Trials Cardiovasc Med 2001;2:75-84.

Various different populations of patients develop elevated troponin levels (eg, after an acute coronary syndrome, PCI, or CABG). It is possible that similar degrees of troponin elevation are associated with similar outcomes irrespective of the etiology of myocardial necrosis. Another possibility is that these populations will have differing prognoses even though they have the same magnitude of troponin elevation (Figure 2).

  • View full-size image.
  • Fig. 2. 

    Increasing risk in different clinical scenarios with the same troponin level. ACS, Acute coronary syndrome; CABG, coronary artery bypass grafting; LAD, left anterior descending coronary artery; LV, left ventricular; PCI, percutaneous coronary intervention.

For example, a patient with an occluded branch artery after PCI, such as a small diagonal or obtuse marginal branch, may have an excellent prognosis based on factors other than those associated with myocyte necrosis, whereas a patient presenting with a non-ST-elevation acute coronary syndrome with a thrombus-rich, fissured and unstable plaque in the left anterior descending coronary artery is likely to have an unstable clinical course and a poor prognosis even though the rise in troponin levels may be no greater.

The prognostic importance of troponin elevations after PCI was shown in the Sibrafiban versus aspirin to Yield Maximum Protection from ischemic Heart events post-acute corONary sYndromes (SYMPHONY) trial, in which 82% of patients underwent PCI with stenting. Forty-eight percent had elevated troponin I levels, whereas only 29% had elevated CK-MB levels.18 Twenty-six percent of patients who tested negative for troponins before the procedure tested positive after the procedure, and these patients had a combined hazard ratio (HR) for death or MI within 90 days of 4.3 (95% CI 1.4-13.5) versus those without elevated troponin levels. Multivariate analysis including baseline characteristics and procedural variables showed that troponin I (entered as a continuous variable) was an independent predictor of the time to death or MI (P = .0001). In a recent meta-analysis of 2605 patients who were followed up for 1.5 to 77 months after PCI, those with elevated troponin levels (measured using a variety of troponin assays and a variety of cutpoints) after the procedure were found to have double the rates of mortality (HR 2.09, CI 1.42-3.08) and MI (HR 2.27, CI 1.62-3.16).19 Troponin elevations occur more frequently after stenting and are higher than after PCI without stenting, but because stenting produces better outcomes, the risk gradient may not be so pronounced and may be concentrated in patients with the greatest troponin elevations.20

The mechanism for the increase in adverse events associated with troponin elevations after PCI is unclear. Small myocardial scars resulting from plaque or platelet emboli may act as a focus for arrhythmogenesis and sudden death. The impaired prognosis could also be due to an underlying unifying factor, such as inflammation.15 Alternatively, it is possible that the troponin elevation is not the cause of a poor prognosis, but rather the result of diffuse coronary disease with an increased plaque burden.

Elevated troponin levels are found in most patients after CABG, but some patients may have only small increases (eg, those undergoing off-pump CABG).21 Troponin levels have been shown to be superior to CK-MB levels as a predictor of inhospital death or MI after CABG.21 As with PCI, it is likely that outcomes will vary according to the etiology of the troponin rise—but whatever the cause, such a rise signifies that myocyte necrosis has occurred, and the prognosis will be worse than if it had not occurred. There are a number of reasons why cardiac protein levels may rise after CABG, such as ischemic causes, anesthetic factors, atrial cannulation, aortic cross-clamping, handling of the heart,22 suturing of heart muscle, inadequate myocardial protection, and factors related to graft patency, including plaque and platelet embolism, spasm and thrombosis.

Where the resources are available, troponin testing should be considered mandatory for prognostic evaluation of patients with non-ST-elevation acute coronary syndromes, diagnosis of MI, and treatment selection (also taking into account other clinical information and tests).23, 24, 25, 26 Use of the new definitions of MI may actually reduce costs because the greater precision of troponin testing for risk assessment should mean that unnecessary hospitalization and drug usage can be reduced in low-risk patients, while those with elevated troponin levels should be more likely to receive appropriate antithrombotic therapy, revascularization,27, 28 and secondary preventative measures such as aspirin and statins.

A heart attack in 2002 is not the same as a heart attack in previous years. I believe that the new definition will lead to improved patient care and consequently better patient outcomes. There is much work to be done to ensure that assays are of an appropriate standard and to educate the public that, as the old Ted Parsons song says, “Things ain't what they used to be.”

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References 

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☆ Reprint requests: Harvey White, DSc, Cardiology Department, Green Lane Hospital, Private Bag 92-189, Auckland 1030, New Zealand.

☆☆ E-mail: harveyw@adhb.govt.nz

PII: S0002-8703(02)00216-8

doi:10.1067/mhj.2002.129780

Refers to article:

  • Changing the diagnosis of acute myocardial infarction: Implications for practice and clinical investigations

    L.Kristin Newby, Joseph S. Alpert, E.Magnus Ohman, Kristian Thygesen, Robert M. Califf
    American Heart Journal December 2002 (Vol. 144, Issue 6, Pages 957-980)

  • European Society of Cardiology and American College of Cardiology guidelines for redefinition of myocardial infarction: How to use existing assays clinically and for clinical trials

    Fred S. Apple, Alan H.B. Wu, Allan S. Jaffe
    American Heart Journal December 2002 (Vol. 144, Issue 6, Pages 981-986)

American Heart Journal
Volume 144, Issue 6 , Pages 933-937, December 2002

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