Diagnostic value of circulating microRNAs compared to high-sensitivity troponin T for the detection of non-ST-segment elevation myocardial infarction

Abstract

Aims To assess the diagnostic value of microRNAs (miRNAs) for the detection of non-ST-segment elevation myocardial infarction (NSTEMI). Methods and results A total of 1042 patients presenting between August 2014 and April 2017 to the emergency department with the suspected acute coronary syndrome were included. Non-ST-segment elevation myocardial infarction was diagnosed per criteria of the fourth Universal definition of myocardial infarction (UDMI) using high-sensitivity troponin T (hs-cTnT). Expression levels of eleven microRNAs (miR-21, miR-22, miR-29a, miR-92a, miR-122, miR-126, miR-132, miR-133, miR-134, miR-191, and miR-423) were determined using RT-qPCR. Discrimination of NSTEMI was assessed for individual and a panel of miRNAs compared to the hs-cTnT reference using C-statistics and reclassification analysis. NSTEMI was diagnosed in 137 (13.1%) patients. The area under the curve (AUC) of the hs-cTnT based reference was 0.937. In a multivariate model, three miRNAs (miR-122, miR-133, and miR-134) were found to be associated with NSTEMI with AUCs between 0.506 and 0.656. A panel consisting of these miRNAs revealed an AUC of 0.662 for the diagnosis of NSTEMI. The AUC of the combination of the miRNA panel and troponin reference was significantly lower than the reference standard (AUC: 0.897 vs. 0.937, P = 0.006). Despite a significant improvement of NSTEMI reclassification measured by IDI and NRI, miRNAs did not improve the specificity of hs-cTnT kinetic changes for the diagnosis of NSTEMI (ΔAUC: 0.04). Conclusion Although single miRNAs are significantly associated with the diagnosis of NSTEMI a miRNA panel does not add diagnostic accuracy to the hs-cTnT reference considering baseline values and kinetic changes as recommended by the fourth version of UDMI. Clinical Trials Identifier NCT02116153

Marathon-Induced Cardiac Strain as Model for the Evaluation of Diagnostic microRNAs for Acute Myocardial Infarction

“…These findings emphasize that miRNAs owe the potential of improving the current strategy of MI-diagnostics, which incorporates the evaluation of serial cTn’s concentrations and their kinetic [ 3 ]. In contrast, it has been recently demonstrated that single miRNAs and a signature of best performing miRNAs can fail adding diagnostic accuracy to cTn serial measurements for detection of NSTEMI [ 32 ]. Both studies show relevant differences in terms of study design [ 32 , 72 ], wherefore miRNAs potential for clinical implementation still remains unclear.…”

“…In contrast, it has been recently demonstrated that single miRNAs and a signature of best performing miRNAs can fail adding diagnostic accuracy to cTn serial measurements for detection of NSTEMI [ 32 ]. Both studies show relevant differences in terms of study design [ 32 , 72 ], wherefore miRNAs potential for clinical implementation still remains unclear.…”

“…Nevertheless, similar to cTn, some potential diagnostic serum miRNAs for MI lack diagnostic-specificity [ 31 ]. Furthermore, some studies have questioned their diagnostic ability and superiority compared to conventional cardiac biomarkers [ 32 , 33 ]. Therefore, their clinical implementation as single miRNA assays still appears uncertain.…”

Peripheral blood RNA biomarkers for cardiovascular disease from bench to bedside: a position paper from the EU-CardioRNA COST action CA17129

“… 6 , 7 However, they currently do not improve the diagnosis of acute MI on top the currently available methods and the turnaround time is long. 8 Therefore, RNAs in ischaemic heart disease may be more informative to guide therapies after the acute phase, e.g. to improve the prediction of left ventricular (LV) dysfunction post-MI, predict recurrent ischaemic events, and eventually guide new cardioprotective therapies.…”

Current Knowledge of MicroRNAs (miRNAs) in Acute Coronary Syndrome (ACS): ST-Elevation Myocardial Infarction (STEMI)

“…In consideration of their roles, steadily growing research in life science of the expression pattern of cardiac tissue reveals that microRNAs (miRNAs/miR) are up-or downregulated during myocardial injury, showing their potential as biomarkers for AMI and ischemia-reperfusion injury (I/R) [17,18]. Accordingly, the gamut of new evidence lays out the potential role of miRNAs as novel biomarkers in acute and chronic cardiovascular diseases such as stable CAD [17,[19][20][21][22], acute coronary syndromes (NSTEMI/STEMI) [23][24][25][26], or heart failure (HF) and cardiac remodeling secondary to MI [27,28].…”