Results of Expert Meetings: Diagnosis of Myocardial Infarction Vienna, Virginia January 25-27, 2001

Changing the diagnosis of acute myocardial infarction: Implications for practice and clinical investigations☆,☆☆,★,★★

Each year, a large number of patients are seen in the Emergency Department with presentations necessitating investigation for possible acute myocardial infarction. Patients can be stratified by symptoms, risk factors and electrocardiogram results but cardiac biomarkers also have a prime role both diagnostically and prognostically. This review summarizes both the history of cardiac biomarkers as well as currently available (established and novel) assays. Cardiac troponin, our current “gold standard” biomarker criterion for the diagnosis of myocardial infarction has high sensitivity and specificity for this diagnosis and therapies instituted in patients with elevated troponin have been shown to influence outcomes. Other markers of myocardial necrosis, inflammation and neurohormonal activity have also been shown to have either diagnostic or prognostic utility, but none have been shown to be superior to troponin. The measurement of multiple biomarkers and the use of point of care markers may accelerate current diagnostic protocols for the assessment of such patients.

The aim of this study was to evaluate the distribution of cardiac troponin I (cTnl) values, measured by the ADVIA Tnl-Ultra method in a multi-ethnic group and to determine the imprecision of the assay.

The study population comprised 234 men and 208 women and the age range was 18–73 years. Recruitment was aimed at enrolling different races and comprised 186 Malays, 136 Chinese and 120 Indians. We evaluated the analytical performance the ultra sensitive cardiac troponin I (cTnI) assay.

The mean values for cTnl for male and female were 0.011 μg/L and 0.010 μg/L respectively. No significant difference was noted between male and female populations (p > 0.05). The 99th percentile for ADVIA Tnl-Ultra was 0.061 μg/L. The mean values of cTn in Malay, Chinese and Indian groups were 0.011, 0.011 and 0.011 μg/L, respectively. There was no significant difference between the different ethnic populations (p > 0.05). The assay imprecision was less than 10% at concentrations higher than 0.036 μg/L.

ADVIA TnI-Ultra assay showed no difference in the troponin values among different ethnic groups and between males and females. Hence a single cut-off value based on the 99th percentile can be used.

In patients with known or suspected myocardial infarction (MI), cardiovascular magnetic resonance (CMR) provides a comprehensive, multifaceted view of the heart. The data, including that from a recent multicenter clinical trial, indicate that delayed-enhancement cardiac magnetic resonance imaging (DE-CMR) is a well-validated, robust technique that can be easily implemented on scanners that are commonly available worldwide, with an effectiveness that clearly rivals the best available imaging techniques for the detection and assessment of acute and chronic MI. When patients present outside the diagnostic window of cardiac troponins, DE-CMR may be especially useful. Moreover, because DE-CMR can uniquely differentiate between ischemic and various nonischemic forms of myocardial injury, it may be helpful in cases of diagnostic uncertainty, such as in patients with classical features of MI in whom coronary angiography does not show a culprit lesion. Even after the diagnosis of MI has been made, CMR provides clinically relevant information by identifying residual viability, microvascular damage, stunning, and right ventricular infarction. In addition, post-MI sequelae, including left ventricular thrombus and pericarditis, are easily identified. Given that quantification of infarct size by DE-CMR is highly reproducible, this technique may provide a useful surrogate end point for clinical trials with appreciable reductions in sample size compared with alternative methods.

While more sensitive cardiac troponin (cTn) assays may overcome current limitations in diagnosing acute coronary syndrome (ACS), clinicians and laboratorians are concerned about the clinical impact of higher rates of cTn positivity.

We collected statistics on test volume and positivity rates before and after the implementation of a more sensitive assay. We divided patients into 6 groups based on their cardiac troponin I (cTnI) results and utilized additional laboratory test results to determine the impact of the new assay. In addition, we assessed the clinical significance of low-positive cTnI results (0.05–0.10 µg/l).

Lowering the diagnostic cutoff from 0.10 to 0.04 µg/l increased the number of positive test results by 44.2% hospital-wide and 114.4% in the emergency department without significantly changing test volume. In some patients, low-positive results were part of the typical rise and fall of cTnI consistent with myocardial damage. Diagnosis was more challenging in patients with consistently low-positive results. Patients in this group were significantly more likely to have impaired renal function than those with cTnI elevations > 0.10 µg/l.

More sensitive cTn assays will increase the number of positive results and allow for earlier detection of cardiac injury while also detecting non-ACS related pathologies.

To measure the agreement between the newer European Society of Cardiology–American College of Cardiology (ESC-ACC) definition of acute myocardial infarction (AMI) and the traditional definition established by the World Health Organization (WHO).

All adult ED patients admitted to our institution with at least one abnormally elevated cardiac biomarker were determined to have had an AMI by either or both definitions. The degree of agreement and the frequency of the reasons for disagreement between these 2 definitions were measured.

A final study population consisted of 339 patients; 196 (58%) had an AMI by one or both definitions. Among them, 126 (64%; 95% confidence interval [CI], 57-71) were discordant for these 2 definitions: 104 (53%; 95% CI, 46-60) met only the ESC-ACC, whereas 22 (11%; 95% CI, 6-16) met only the WHO definition. Among those who met only the ESC-ACC definition, 37 (36%; 95% CI, 27-45) met none of the 3 traditional WHO criteria.

More patients are discordant than concordant for the 2 standard definitions of AMI. Among them, a large majority meet only the new ESC-ACC definition.

The use of cardiac troponin allows the identification of additional patients developing myocardial necrosis during an acute coronary syndrome. Novel guidelines of European and American cardiac societies recommend labeling these events as myocardial infarction. Our study evaluated the long-term mortality in the group of patients with non-ST segment elevation myocardial infarction not meeting the older World Health Organization (WHO) criteria (creatine phosphokinase) but additionally identified by the novel definition of myocardial infarction.

This cohort study included 1024 consecutive patients with non-ST segment elevation acute coronary syndrome classified into “unstable angina,” myocardial infarction according to the WHO definition (“WHO criteria”), and myocardial infarction additionally identified by the novel definition (“additional criteria”). All patients were treated with an early invasive strategy. The primary end point was all-cause mortality during follow-up of up to 36 months.

During long-term follow-up (median 16 months, interquartile range 6-29 months), 67 deaths occurred. Kaplan-Meier analysis showed cumulative 3-year mortality rates of 5.6% in patients with “unstable angina,” 9.1% in patients identified by “WHO criteria,” and 17.5% in patients identified by “additional criteria” (P <.001). Cox regression analysis confirmed the “additional criteria” as a significant predictor of mortality (hazard ratio 3.1; 95% confidence interval, 1.9-5.0; P <.001).

The new definition of myocardial infarction based on cardiac troponin testing identifies a high-risk group of additional patients with acute coronary syndrome that is, therefore, appropriately classified as myocardial infarction. In fact, long-term mortality in “additional criteria” patients is higher than in “WHO criteria” patients.