False-positive troponin elevation due to an immunoglobulin-G-cardiac troponin T complex: a case report

Abstract

Background Troponin is a crucial biomarker for the diagnosis of an acute coronary syndrome (ACS). It rises in response to myocardial injury from significant acute myocardial ischaemia caused by obstructive coronary artery disease [‘classical’ myocardial infarction (MI)]. However, raised levels have also been noted in conditions not recognized as classical ACS. This may include MI with non-obstructed coronary arteries such as takotsubo cardiomyopathy and other acute or chronic conditions such as pulmonary embolus or chronic kidney disease. This is commonly labelled as a ‘falsely elevated’ troponin although there is some myocardial strain to explain the rise, such as an increase in cardiac oxygen demand. True ‘falsely elevated’ troponin, characterized by a persistent elevation in the absence of cardiac injury does occur and thought to be secondary to an immunoglobulin-troponin complex (macrotroponin). Case summary A 53-year-old gentleman with a background of diabetes, hypertension, hypercholesterolaemia, and hepatitis B was admitted with chest pain and persistently elevated cardiac troponin T (cTnT) levels. Investigations revealed unobstructed coronary arteries and a structurally normal, well-functioning heart. Subsequent biochemical analysis found the persistently elevated cTnT secondary to macrotroponin T. Discussion Macrotroponin, an immunoglobulin-troponin bound complex should be considered as a differential diagnosis when the biochemistry is not reflective of the clinical picture. Early recognition requires effective collaboration with the biochemistry laboratory for accurate diagnosis.

“Troponinosis”, the Cardiologist’s Curse—When Clinic–Laboratory Interaction Unveils the Mystery: A Case Report

“…In our case, it was not possible to confirm the presence of the analytical interference in cTnI concentrations before AMI, but it is equally true that it cannot be excluded that it occurred secondary to the cardiac ischemic injury. Although mainly anecdotal cases are reported in the literature [ 13 ], evidence has recently become available regarding the prevalence and clinical impact of troponin macroforms. Warner et al report the presence of a high-molecular-weight immunoglobulin-cTnI complex in 5% of patients with elevated cTnI concentrations [ 14 ].…”

Circulating biomarkers in the diagnosis and prognosis of immune checkpoint inhibitor-related myocarditis: time for a risk-based approach

“…The phenomenon of macrotroponin (macroTn) indicating formation of immunoglobulin-troponin complexes, is also coming to attention in the ICI population, where immune activation may result in autoantibody binding to circulating cTn, forming a macrocomplex. Initially considered a spurious cTn result finding, macroTn has been reported with all cTn assays and has been associated with myocarditis and cardiomyopathy (40)(41)(42). While clinical implications of macroTn in ICI-myocarditis remain an area of active investigation, elevated cTn must always be interpreted in conjunction with clinical context.…”

Role of Antitroponin Antibodies and Macrotroponin in the Clinical Interpretation of Cardiac Troponin

“…The overall prevalence of antitroponin antibodies and macrotroponin remains elusive, because they are usually assessed only in extreme cases of clinical and biological discordance and not routinely or systematically. 10 Previous studies have showed that the involvement of macrotroponin could range between 5% and ~50% in patients with an increased cTn result depending on the context and the assays. 8 , 54 MI with nonobstructive coronary arteries is a recently defined heterogeneous clinical entity characterized by nonobstructive coronary arteries on coronary artery angiogram (≤50% stenosis) and without an overt cause for the MI, such as cardiac trauma or injury.…”

“… 7 Macrotroponin has become more of a challenge since the use of hs‐cTn (high‐sensitivity cTn) assays, 8 and several cases of misinterpreted troponin elevation related to antibodies and macrotroponin have been reported. 10 , 11 , 12 Thus, although cTn is a powerful and recognized marker of myocardial injury, cTn results are not undisputable and should always be interpreted within the clinical context, especially in case of mismatch between the clinical scenario and the result of the cTn assay (Figure 1 ).…”