New biomarker tests could slash heart attack diagnosis time

Medical Tribune October 2009 P7
David Brill

New-generation tests can rapidly accelerate the diagnosis of acute myocardial infarction (MI) – saving time, improving convenience and reducing costs in the emergency department, studies show.

High-sensitivity cardiac troponin assays can now rule MI in or out in patients presenting within the first hours of chest pain onset, thereby removing the delays associated with conventional tests and allowing for earlier transfer and treatment.

Testing for stress marker copeptin, meanwhile, can exclude MI with 99 percent certainty, thus saving many patients from unnecessary further testing.

Professor Christian Müller, reviewing the data, said that the new tests could answer an unmet clinical need in the assessment of chest pain, since current troponin tests have an undetectable “blind interval” of 3-4 hours after the onset of MI. Even if patients follow recommendations and present within 2 hours of chest pain, the test will be negative and electrocardiography monitoring will be required for 6 to 8 hours.

“The current-generation troponin tests are important but have important limitations in [making an] early diagnosis. There seem to be two approaches to solve this problem: either use troponin in combination with copeptin, or perhaps the approach now favored by many is the use of sensitive troponin assays,” said Müller, of the University Hospital Basel, Switzerland.

The new troponin assays were tested in two European multicenter trials, published recently in the New England Journal of Medicine. [2009;361:858-67; 2009;361:868-77]

German investigators tested 1,818 consecutive patients at admission and 3 and 6 hours later. Diagnostic accuracy at admission was higher with a sensitive troponin I test, as compared to a conventional troponin T test (area under the receiver-operated-characteristic curve [AUC] 0.96 versus 0.85). The new test had a clinical sensitivity of 90.7 percent and specificity of 90.2 percent, with accuracy unaffected by the time of chest pain onset.

The second study, led by Müller and colleagues, involved 718 consecutive patients – 123 of whom were ultimately diagnosed with acute MI. Four high-sensitivity assays were tested: all were superior to a conventional test (AUCs 0.95 – 0.96 versus 0.90) when performed at presentation. The difference was most marked in patients presenting within 3 hours of chest pain onset (AUCs 0.92 – 0.94 versus 0.76).

In an earlier study, Müller and colleagues tested 487 potential MI patients for copeptin, the C-terminal section of the vasopressin prohormone, which denotes endogenous stress. Combination with a conventional troponin T test yielded an AUC of 0.97, compared to 0.86 for the troponin test alone (P<0.001). Low levels of both copeptin (<14 pmol/l) and troponin T (≤0.01 μg/l) correctly excluded MI in the majority of cases (sensitivity 98.8 percent; negative predictive value 99.7 percent). [J Am Coll Cardiol 2009;54:60-8]