Analytically false or true positive elevations of high sensitivity cardiac troponin: a systematic approach

Cardiac troponin (cTn) is a regulatory protein of the myofibrillar thin filament of striated muscle regulating excitation–contraction coupling in the heart.w1 Among the three subunits (T, I, and C), only cardiac troponin T (cTnT) and I (cTnI) are expressed in cardiac muscle and released into blood following myocardial cell death. Several distinct pathobiological mechanisms leading to elevated troponin values have been suggested, not all of which involve myocyte necrosis.w2 cTnT or cTnI are routinely used in emergency units as the preferred biomarkers for the diagnosis of acute myocardial infarction (MI). According to joint criteria for the diagnosis of acute MI by the European Society of Cardiology/American College of Cardiology/American Heart Association/World Heart Federation Task Force, an acute MI should be diagnosed in patients with symptoms of myocardial ischaemia and detection of a rise and/or fall of cardiac biomarkers (preferentially troponins) with at least one value above the 99th percentile of the upper reference limit.1 Use of high sensitivity troponin assays allows more accurate and earlier detection of MI.2 w3 Higher analytical sensitivity increases the number of patients with analytically true positive cTn results due to non-ST elevation MI (NSTEMI) but also due to numerous acute or chronic diseases in the absence of overt ischaemic heart disease (box 1).3 w4 Box 1 ### Elevations of cardiac troponin values because of myocardial injury Injury related to primary myocardial ischaemia Plaque rupture Intraluminal coronary artery thrombus formation Injury related to supply/demand imbalance of myocardial ischaemia Tachy-/bradyarrhythmias Aortic dissection or severe aortic valve disease Hypertrophic cardiomyopathy Cardiogenic, hypovolaemic, or septic shock Severe respiratory failure Severe anaemia Hypertension with or without left ventricular hypertrophy Coronary spasm Coronary embolism or vasculitis Coronary endothelial dysfunction without significant coronary artery disease Injury not related to myocardial ischaemia Cardiac contusion, surgery, ablation, pacing, or …