New Immunoassay Specifically Measures Heart Attack-linked Blood Troponin Levels

A recently developed immunoassay for measurement of intact troponin molecules in the blood is able to differentiate patients suffering from myocardial infarction (MI) from those with other transient or chronic conditions.

Measurement of blood levels of cardiac troponins (cTnT) is an important cornerstone in the diagnostics of heart attack, but the result may be elevated also due to other transient or chronic conditions, such as renal insufficiency, atrial fibrillation, or strenuous physical exercise. This may happen because troponins are released to the circulation in MI as large molecules, while in other conditions they are found in the blood as small fragments. Furthermore, currently used commercial troponin tests recognize the combined amount of both large and small troponin molecules.

Image: Ribbon representation of the human cardiac troponin (cTnT) core complex (Photo courtesy of Wikimedia Commons)

To resolve this situation, investigators at University of Turku (Finland) developed a novel, simple time-resolved fluorescence-based immunoassay that measures only large troponin molecules.

For this assay, the investigators used a cocktail of monoclonal antibodies. The binding antibody recognized the C-terminal part of cTnT, while the three test antibodies bound to different areas of the central part of cTnT. Thus, the test detected only intact and very mildly truncated forms of the molecule.

The new test was compared to a commercial assay produced by Roche-Diagnostics (Risch-Rotkreuz, Switzerland), which detects intact, mildly truncated, and heavily truncated short forms of cTnT (i.e. total cTnT). For the study, the investigators collected and tested heparin plasma samples from 46 patients with non-ST-segment MI elevation, 71 patients with ST-segment MI elevation, and 40 patients with end-stage renal disease (ESRD).

A troponin ratio was calculated by dividing the level of large troponin molecules, determined by the new test, by the level of all troponin molecules, determined by the commercial assay. This troponin ratio was remarkably higher in MI patients than in renal insufficiency patients, although the results of the commercial troponin test were similar in both groups.

“More than half of the small troponin elevations detected in emergency department patients are due to causes other than heart attack. The developed test seems to separate very well the small troponin elevations caused by threatening MI from more benign transient troponin elevations,” said first author Dr. Juhani Airaksinen, professor of internal medicine at the University of Turku.

Senior author Dr. Saara Wittfooth, assistant professor of life technologies at the University of Turku, said, “A special feature of the test we have developed is that it would be possible to implement it in automated analysis systems in the hospital laboratories, similarly as the commercial troponin tests currently at use in the hospital laboratories,”

The new troponin assay was described in the October 31, 2022, online edition of the journal Circulation.

Related Links:
University of Turku
Roche-Diagnostics