The tale of a rabbit and pitfalls in MI diagnosis, an EHJ case report

In patients presenting with clinical and ECG signs of myocardial ischaemia, cardiac troponin concentration is the cornerstone in establishing a diagnosis of acute coronary syndrome (ACS). An interesting case report from European Heart Journal aims to remind the clinicians about the possibility of false-positive troponin levels due to laboratory analytical interference caused by heterophile antibodies.

Lakusic et al have reported a case of a 53-year-old woman presenting with chest pain for 3 hours before coming to the emergency room, which she characterized as chest discomfort, tightness and heaviness in rest, without radiation, with no progression in physical activity, that regressed gradually (did not respond to nitroglycerine spray), but the patient was hospitalized due to elevated troponin I of 1359 ng/L with a diagnosis of non-ST-elevation myocardial infarction (NSTE-ACS). There was no change in troponin concentration on the second day of treatment. Echocardiography showed normal left ventricular ejection fraction and no regional wall motion abnormalities. Coronary angiography was then performed that revealed a borderline 70% lesion in the proximal left circumflex artery (LCx). This lesion was stented and the patient was later discharged.

Three weeks later, she was hospitalized because of recurrent chest pain which had the same characteristics as the first time. There were no ischaemic changes on the ECG, but due to significant elevation of troponin I, urgent coronary angiography was performed. There was no in-stent thrombosis/restenosis in LCx and no stenosis of LAD and RCA. Troponins remained elevated throughout the hospitalization. The patient was then referred for cardiac rehabilitation. On the fifth day of rehabilitation, after a disturbing telephone conversation with her family, the patient had chest pain similar to the previous hospitalizations. Troponin I was significantly elevated (1111 ng/L). When measured again, three hours later and the next morning, troponin I was at a similar, 'plateau' elevated level. In view of these findings, the patient's stable clinical state the authors suspected the existence of heterophile antibodies in the patient's serum causing a chronic elevation of troponin.

Next day, the concentration of hs-troponin I was 1254 ng/L while hs-troponin T from the same sample was within the normal range 0.007 µg/L (normal value <0.1 µg/L). With such laboratory findings and the occupational history that patient breeds rabbits, a diagnosis of false positive hs-troponin I caused by heterophile antibodies was made.

The further course of rehabilitation went without complications, and the patient's discharge medical records emphasized the presence of chronically elevated troponin caused by heterophile antibodies which is extremely important for further monitoring and evaluation.

Heterophile antibodies are an under-recognized cause of false-positive troponin. These are weak antibodies produced against poorly defined antigens. Heterophile antibodies simultaneously create complexes with 'capture' and 'label' antibodies of the analyte in sandwich ELISA technique—thus "bridging" and giving a false-positive result (Figure).

The article serves to remind the clinicians about the possibility of false-positive troponin elevation caused by heterophile antibodies. It is important to emphasize that there is no characteristic dynamics of troponin, as is in the ACS.

"Since heterophile antibodies are generally poorly mentioned or even not mentioned at all in cardiology guidelines, we wanted to remind the clinicians of the possibility of this scenario for purpose of avoiding unnecessary invasive procedures and overtreatment of these 'patients'.", concluded the authors.

Source: European Heart Journal : Case reports. Nenad L, Ivana S, Daren L et al, Heterophile antibodies, false-positive troponin, and acute coronary syndrome: a case report indicating a pitfall in clinical practice, European Heart Journal - Case Reports, Volume 5, Issue 2, February 2021, ytab018, https://doi.org/10.1093/ehjcr/ytab018