A 12-year-old girl, known to have MYH7 gene–associated hypertrophic cardiomyopathy, presented in the emergency room with acute onset of chest pain. The pain was situated at the centre and left side of the thorax and was described as intermittent piercing pain, increased by movement, inspiration, and expiration. The patient had not been ill, and no trauma had occurred prior to the onset of symptoms. Furthermore, signs of hyperventilation and palpitations were absent. The patient was on verapamil and carvedilol. Sublingually administered nitroglycerine had no effect, but after paracetamol 500 mg, the pain slightly improved. At presentation, the heart rate was 70 b.p.m., blood pressure 110/70 mmHg, breathing frequency 17/min, and transcutaneous saturation 97%. Upon heart auscultation, a previously documented grade 2–3/6 systolic ejection murmur was heard, loudest at the left sternal border. The chest pain could be provoked by palpating the sternum. Transthoracic echocardiography was performed and was similar to earlier transthoracic echocardiography (; see, ): significant hypertrophy of both ventricles (left ventricle peripheral wall thickness in diastole of 14.7 mm and interventricular septal thickness in diastole of 17.3 mm), decreased systolic function (fractional shortening of 10%, tricuspid annular plane systolic excursion 1.1 cm), diastolic dysfunction, no regional wall movement disorders, and no pericardial effusion. Blood tests revealed elevated cardiac enzymes (reference values in brackets): cTnT 558 ng/L (<14 ng/L), N-terminal brain natriuretic pro-peptide (NT-pro-BNP) 1322 ng/L (<125 ng/L), creatinine kinase (CK) 285 U/L (<145 U/L), creatinine kinase muscle/brain isoenzyme (CK-MB) activity 199 U/L (<25 U/L), CK-MB mass 15.53 μg/L (<3 U/L), lactate dehydrogenase (LDH) 1198 U/L (<247 U/L), blood urea nitrogen 5.6 mmol/L (2.5–7.5 mmol/L), creatinine 56 μg/L (in women 50–90 μmol/L), and estimated glomerular giltration rate 121 mL/min/1.73 m2, all measured on cobas CE modules (Roche Diagnostics, Mannheim, Germany). In addition to cTnT, cTnI, a similar but biochemically different cardiac marker, was also elevated (36 823 pg/mL; reference value for adults: 25.1–34.4 pg/mL; measured on the Lumipulse immunoanalyzer, Fujirebio Inc., Tokyo, Japan). C-reactive protein was low at 0.6 mg/L (<10 mg/L). shows the laboratory findings over the course of time. Anamnesis and physical examination led to a low suspicion of a heart-related cause. However, the high cardiac enzymes seemed unfitting for such a diagnosis. The patient was not on any medication, such as checkpoint inhibitors or monoclonal antibodies, which could interfere in cTn analysis. Due to this discrepancy, the patient was admitted for observation and additional investigations were performed. Viral serology was negative, and C-reactive protein remained low. Thoracic X-ray showed no abnormalities besides cardiomegaly. Computed tomography angiography showed a normal origin and course of the coronary arteries and no pulmonary embolism. Magnetic resonance imaging shows hypertrophy () and no signs of myocarditis and a normal pericardium. Myocardial perfusion scintigraphy did not show signs of ischaemia. After additional investigation, doubts were raised concerning the unexpectedly and disproportionally high cTnT and subsequent cTnI values. Therefore, a laboratory specialist was consulted, and it was concluded that these results could be explained by the following: (i) an analytical error, (ii) an interference of endogenous antibodies like human anti-mouse antibodies (HAMA) and/or heterophilic antibodies in immunoassays, or (iii) the presence of macrotroponins. The first hypothesis was rejected since both cTn assays were increased, even after reanalysis. For the second hypothesis, the presence of these antibodies was investigated using heterophilic blocking tubes (Scantibodies Laboratory Inc., CA, USA) and dilution with a negative plasma sample. Percentage recovery of cTnI and cTnT appeared unaffected (recovery of 104 and 109%, respectively). Therefore, the influence of endogenous interfering antibodies was excluded. Finally, the third hypothesis was investigated by using a 25% (w/v) polyethylene glycol (PEG) pre-treatment. The summary figure is a schematic representation of the macrotroponin investigation using PEG. In a sample drawn on Day 4, a total cTnT of 1224 ng/L was found with a recovery of 21.7% after PEG precipitation; in addition, a total cTnI of 44 175 ng/L with a recovery of 0.2% was found. To be able to interpret these recovery percentages, 10 different randomly chosen residual anonymized samples with different cTnT and cTnI values were similarly pre-treated with PEG. Recovery rates for cTnT and cTnI ranged from 96–136% to 74.5–109.5%, respectively (). From these data, it can be concluded that the markedly elevated cTnT and cTnI values from our patient can be explained by the presence of macrotroponin T as well as macrotroponin I. Since no alternative diagnosis other than musculoskeletal pain could be ascertained and the chest pain spontaneously subsided after 7 days, the patient was discharged from the hospital after 9 days with declining but still elevated cardiac enzymes. In the months following the patient’s hospital discharge, cTnT values remained high. Again, macrotroponin T was investigated in a sample drawn 5 months after hospital admission. The cTnT concentration was 803 ng/L, whereas after PEG precipitation, only 15% of the initial cTn could be recovered.