In a robust clinical study, researchers have determined the precise magnitude of change in cardiac troponin levels required for early diagnosis of a heart attack (myocardial infarction (MI)), thus improving the already FDA-cleared blood test.

Beckman Coulter Diagnostics (Brea, CA, USA) announced publication of the large, multicenter study, which utilized its “Access AccuTnI+3” troponin-I blood test designed to aid in MI diagnosis. It is the only troponin assay currently cleared by the US Food and Drug Administration (FDA) that is directly aligned with the agency’s October 2010 guidance to manufacturers of troponin tests. The precise magnitude of change in the post-market cardiac troponin study data were not evaluated by FDA as part of the product’s 510(k) clearance.

The test is a paramagnetic particle, chemiluminescent immunoassay for the quantitative determination of cardiac troponin-I (cTnI) levels in human serum and plasma using the Access 2 Immunoassay System or UniCel DxI Access Immunoassay System. 

Troponin is released from damaged heart cells and detected in blood. Current guidelines require demonstration of a delta detected for levels of troponin measured for samples collected in sequence following presentation to the Emergency Department. However, the guidelines do not quantify what a clinically significant delta is. Without a defined delta, physicians do not have a consistent approach for diagnosing MI.

Previous studies suggested a percentage-change in troponin levels as the appropriate change criteria for determining if a patient has had a heart attack. However, this method has proven not sufficiently reliable and more recent publications have suggested that absolute values may perform better. This new study recommends moving away from a percentage-change reading and rather to using an absolute difference by ng/mL change.

The prospective multicenter trial study consisted of nearly 2,000 patients enrolled at 14 institutions and reports representative diagnostic performance that would be observed in clinical practice for early rule-in and rule-out of MI. It demonstrated that absolute changes (0.01 or 0.02 ng/mL) performed better than relative (percentage) changes at all time intervals after Emergency Department admission.

“Study results suggest that the majority of patients with MI can be identified at earlier observation times, and support consensus recommendations for an optimal blood sampling protocol with troponin measurement on admission and 3 hours later,” said principal investigator and lead author Alan B. Storrow, MD, vice chairman for Research and Academic Affairs, Department of Emergency Medicine, Vanderbilt University, “Another key finding of the study is that rule-out (correct identification of patients without a heart attack) was nearly 100% when baseline troponin was less than the diagnostic threshold of 0.03 ng/mL and absolute delta troponin was less than 0.01 ng/mL.”

“As troponin values rose, the probability of MI increased. Baseline troponin values greater than 0.20 ng/mL were associated with nearly 90% probability of MI. Earlier rule-in and rule-out may potentially save patient lives,” said Paula Southwick, PhD, coauthor and principal clinical research scientist at Beckman Coulter Diagnostics.

The study was published as two companion articles, by Storrow AB et al., in a special cardiac biomarkers issue, March 2015, of the journal Clinical Biochemistry.