Cardiovascular Biomarkers in the Early Discrimination of Type 2 Myocardial Infarction

Abstract

IMPORTANCERapid and accurate noninvasive discrimination of type 2 myocardial infarction (T2MI), which is because of a supply-demand mismatch, from type 1 myocardial infarction (T1MI), which arises via plaque rupture, is essential, because treatment differs substantially. Unfortunately, this is a major unmet clinical need, because even high-sensitivity cardiac troponin (hs-cTn) measurement provides only modest accuracy.OBJECTIVE To test the hypothesis that novel cardiovascular biomarkers quantifying different pathophysiological pathways involved in T2MI and/or T1MI may aid physicians in the rapid discrimination of T2MI vs T1MI. DESIGN, SETTING, AND PARTICIPANTSThis international, multicenter prospective diagnostic study was conducted in 12 emergency departments in 5 countries (Switzerland, Spain, Italy, Poland, and the Czech Republic) with patients presenting with acute chest discomfort to the emergency departments. The study quantified the discrimination of hs-cTn T, hs-cTn I, and 17 novel cardiovascular biomarkers measured in subsets of consecutively enrolled patients against a reference standard (final diagnosis), centrally adjudicated by 2 independent cardiologists according to the fourth universal definition of MI, using all information, including cardiac imaging and serial measurements of hs-cTnT or hs-cTnI. RESULTS Among 5887 patients, 1106 (18.8%) had an adjudicated final diagnosis of MI; of these, 860 patients (77.8%) had T1MI, and 246 patients (22.2%) had T2MI. Patients with T2MI vs those with T1MI had lower concentrations of biomarkers quantifying cardiomyocyte injury hs-cTnT (median [interquartile range (IQR)], 30 (17-55) ng/L vs 58 (28-150) ng/L), hs-cTnI (median [IQR], 23 [10-83] ng/L vs 115 [28-576] ng/L; P < .001), and cardiac myosin-binding protein C (at presentation: median [IQR], 76 [38-189] ng/L vs 257 [75-876] ng/L; P < .001) but higher concentrations of biomarkers quantifying endothelial dysfunction, microvascular dysfunction, and/or hemodynamic stress (median [IQR] values: C-terminal proendothelin 1, 97 [75-134] pmol/L vs 68 [55-91] pmol/L; midregional proadrenomedullin, 0.97 [0.67-1.51] pmol/L vs 0.72 [0.53-0.99] pmol/L; midregional pro-A-type natriuretic peptide, 378 [207-491] pmol/L vs 152 [90-247] pmol/L; and growth differentiation factor 15, 2.26 [1.44-4.35] vs 1.56 [1.02-2.19] ng/L; all P < .001). Discrimination for these biomarkers, as quantified by the area under the receiver operating characteristics curve, was modest (hs-cTnT, 0.

Clinical and prognostic implications of high-sensitivity cardiac troponin T concentrations in type 2 non-ST elevation myocardial infarction

“…Even previous data demonstrated that cTn only provides limited discriminative value [4] , [5] , [8] , [9] . Some studies have suggested that this could be enhanced by the consideration of clinical findings and/or other biomarkers [10] , [11] , [12] , [13] . However, none of these approaches is generally acknowledged, and the differentiation of both NSTEMI types will likely remain cumbersome, in particular in patients with critical illness or known CAD.…”

Diagnostic and prognostic performance of the ratio between high-sensitivity cardiac troponin I and troponin T in patients with chest pain

“…Previous data have demonstrated that hs-cTn concentrations themselves only provide limited discriminative value [ 23 , 30 – 32 ]. This could be enhanced by combinations with other cardiovascular biomarkers or advanced statistical modelling [ 23 , 30 , 31 , 33 ], none of which currently used in routine practice.…”

“…Our data also suggest that the hs-cTn I/T ratio may be a clue for the clinically challenging distinction of type 2 MI from type 1 MI. Previous data have demonstrated that hs-cTn concentrations themselves only provide limited discriminative value [23,[30][31][32]. This could be enhanced by combinations with other cardiovascular biomarkers or advanced statistical modelling [23,30,31,33], none of which currently used in routine practice.…”

L-Carnitine Alleviates the Myocardial Infarction and Left Ventricular Remodeling through Bax/Bcl-2 Signal Pathway

“…cTnT is unique to the myocardium and mainly exists in myofibrillar thin filaments. High levels of cTnT are closely related to myocardial hypoxia, ischemia, necrosis, and cardiac function decline, and the detection of cTnT has the advantages of high sensitivity and specificity, both in the early intervention and prognosis of acute MI have important value [ 35 ]. NT-proBNP is a cardiogenic neurohormone synthesized by ventricular myocytes.…”