According to the Fourth Universal Definition of Myocardial Infarction, myocardial infarction (MI) can be classified into 5 different groups. Particularly, type 1 MI (T1MI) - which is related to atherosclerotic plaque rupture or erosion with resulting thrombus in a coronary artery leading to a decreased myocardial blood flow and resulting in cardiomyocyte necrosis - and type 2 MI (T2MI) - defined as an imbalance between myocardial oxygen supply and demand in presence or absence of coronary artery disease (CAD) causing ischemia and permanent myocardial damage – are of increasing interest [[1], [2], [3]].

Patients presenting with suspicion of T1MI usually undergo immediate invasive management and treatment, while those who experience a T2MI are considered to have other underlying causes of troponin elevation and eventually also an increased risk for invasive diagnostic procedures and antithrombotic therapy [[3], [4], [5]]. Due to a frequently similar clinical presentation of both types, differentiation between T1MI and T2MI remains a challenge in routine clinical practice, as it may require time- and facility-consuming diagnostic measures in order to discriminate between these two entities [6,7]. In order to assure a quick and appropriate diagnosis and treatment according to its underlying pathophysiology, the need to distinguish T1MI from T2MI as early as possible by use of biomarkers is of high clinical relevance.

First attempts using delta troponin concentrations showed that cTnI changes were unable to differentiate between both MI subtypes [8]. In another study using high-sensitivity cTn (hs-cTnI) assays with sex-specific 99th percentile cutoffs, it was demonstrated that T1MI had significantly higher initial and maximum hs-cTnI mean concentrations; however, its limited sample size and low outcome events did not allow for a clear distinction between these MI types [9]. Also biomarker combinations were used to differentiate between both MI types, as Nowak et al. used an N-terminal pro B-type natriuretic peptide (NT-proBNP)/cTnT generation 5 ratio. In this small sample size study (25 T1MI, 18 T2MI) significantly higher ratios were found in T2MI [10].

Other recent studies investigating biomarkers reflecting cardiomyocyte necrosis and endothelial dysfunction such as creatine kinase-myocardial band, heart-type fatty acid-binding protein, midregional pro-A-type natriuretic peptide, myeloperoxidase, placental growth factor, procalcitonin or C-terminal proendothelin-1 have not been able to differentiate T1MI from T2MI [11,12].

Copeptin, a surrogate marker for vasopressin and therefore a marker for acute stress, has already been tested for early rule-out of non-ST-segment elevation acute coronary syndrome (NSTE-ACS) in combination with troponin [[13], [14], [15], [16]]. Copeptin has also be found to be elevated in some diseases/conditions contributing to T2MI such as decompensated heart failure, atrial fibrillation, cardiac inflammation, syncope, pneumonia and pulmonary embolism [14,[17], [18], [19], [20]]. The usefulness of copeptin to differentiate T1MI from T2MI has also been tested in a few studies, though with contradictory results [11,[21], [22], [23]].

The aim of the study was to evaluate the ability of the dual marker strategy, copeptin in combination with hs-cTnI to distinguish T1MI from T2MI and myocardial injury.