A 16-year-old girl who was an avid triathlete was transferred to our hospital with a working diagnosis of persistent myopericarditis. Her medical history was unremarkable and she had not received a vaccine against SARS-CoV-2. She had initially presented to an emergency department with atypical chest pain. Her vital signs and cardiac examination were normal. Serial electrocardiograms (ECGs) showed normal sinus rhythm (Figure 1A). A high-sensitivity assay (Dimension Vista 1500, Siemens Healthineers) showed elevated cardiac troponin I (cTnI), with an initial result of 872 ng/L (99th percentile upper limit of normal [ULN] in women 54 ng/L). A transthoracic echocardiogram and a ventilation-perfusion lung scan were normal. The patient was discharged with a presumptive diagnosis of myopericarditis and was prescribed naproxen and colchicine. Her cTnI level remained elevated at an outpatient visit 7 days later (Figure 1B). Cardiac magnetic resonance imaging showed no evidence of myocardial inflammation. Because of the possibility of persistent myopericarditis, a short course of prednisone was started.
One month later, the patient was readmitted to hospital following a repeat episode of atypical chest pain with very elevated cTnI (3165 ng/L, Dimension Vista 1500). Her physical symptoms were nonspecific and included exertional dyspnea and fatigue. The referring cardiologist resumed anti-inflammatory therapy (Figure 1B) for a short period. Considering her unusual clinical course and the unexpected increase in troponin levels (Figure 1B), the patient was transferred to our centre for further investigations.
At our hospital, laboratory testing showed no evidence of systemic inflammation (normal levels of white blood cells, erythrocyte sedimentation rate and C-reactive protein). Renal and liver function were normal. Results from serial ECGs, 7-day telemetry monitoring, exercise treadmill testing and signal-averaged ECGs were unremarkable. Additional cardiac imaging--including transthoracic echocardiography with strain analysis (Figure 1C), repeat cardiac resonance imaging, coronary magnetic resonance angiography (to exclude anomalous coronary arteries) and fluorodeoxyglucose positron emission tomography (to exclude cadiac inflammation, such as sarcoidosis)--was normal. The patient had no evidence of any inflammatory, autoimmune or infectious disease after testing for rheumatoid factor, antinuclear antibodies, SARS-CoV-2, Epstein-Barr virus and HIV. Genetic testing for hereditary cardiomyopathies was negative.
These negative findings on an extensive workup for myocardial injury made us suspicious that the results of the cTnI assays were false positives, a suspicion supported by normal levels of creatine kinase-MB at less than 1.0 (ULN 8.0) [micro]g/L and of cardiac troponin T (cTnT) at 12 (ULN 14) ng/L from a high-sensitivity assay (Cobas, Roche Diagnostics). We therefore undertook additional biochemical testing. Analysis of cTnI with another method (Vitros 5600, Ortho Clinical Diagnostics) was close to normal at 11 (ULN 9) ng/L. To assess the possibility of circulating macrotroponin, we conducted a precipitation test with polyethylene glycol (PEG), which showed an initial recovery of 31%, followed by 21% after dilution (the recovery threshold for a positive test has been suggested as < 40%). (1) Therefore, we concluded that the presence of circulating macrotroponin likely caused false-positive TnI results on the Siemens' Dimension Vista 1500 assays.
Reviewing the patient's entire clinical course, we considered that the most...