False-Positive Cardiac Troponin Elevations in Skeletal Muscle Disease: Clinical Relevance, Mechanisms, and Laboratory Approaches

Cardiac troponins are indispensable biomarkers for the diagnosis of acute myocardial infarction, but false-positive elevations that contradict the clinical picture remain a significant challenge in laboratory medicine. Analytical interferences may arise from macrotroponins, heterophile or anti-troponin antibodies, and the limited cardiac specificity of high-sensitivity troponin T (hs-cTnT) in skeletal muscle disease. Recent studies show that hs-cTnT is elevated in up to two-thirds of patients with myopathies, while high-sensitivity troponin I (hs-cTnI) is largely unaffected, underscoring the diagnostic advantage of hs-cTnI in this setting. A pragmatic diagnostic approach should combine clinical plausibility with stepwise laboratory testing. First, preanalytical factors such as sample mislabeling, fibrin clots, or hemolysis must be excluded and the measurement repeated. If the results remain incongruent, an alternative assay – ideally hs-cTnI – should be performed. Further evaluation may include heterophile-blocking reagents, polyethylene glycol precipitation to screen for macro-analytes, and, where available, confirmatory techniques such as gel filtration chromatography or immunoglobulin depletion (protein A/G). Although these strategies can help identify assay interference, there is no universally accepted gold standard. Awareness of false-positive elevations, careful interpretation of discordant troponin results, and effective collaboration between laboratories and clinicians are essential to prevent misdiagnosis and unnecessary interventions. Clear documentation of confirmed interferences further ensures safe patient management and provides guidance on which assays are reliable for future tests.