Refining diagnostic microRNA signatures by whole-miRNome kinetic analysis in acute myocardial infarction.

BACKGROUND: Alterations in microRNA (miRNA) expression patterns in whole blood may be useful biomarkers of diverse cardiovascular disorders. We previously reported that miRNAs are significantly dysregulated in acute myocardial infarction (AMI) and applied machine-learning techniques to define miRNA subsets with high diagnostic power for AMI diagnosis. However, the kinetics of the time-dependent sensitivity of these novel miRNA biomarkers remained unknown. METHODS: To characterize temporal changes in the expressed human miRNAs (miRNome), we performed here the first whole-genome miRNA kinetic study in AMI patients. We measured miRNA expression levels at multiple time points (0, 2, 4, 12, 24 h after initial presentation) in patients with acute ST-elevation myocardial infarction by using microfluidic primer extension arrays and quantitative real-time PCR. As a prerequisite, all patients enrolled had to have cardiac troponin T concentrations <50 ng/L on admission as measured with a high-sensitivity assay. RESULTS: We found a subset of miRNAs to be significantly dysregulated both at initial presentation and during the course of AMI. Additionally, we identified novel miRNAs that are dysregulated early during myocardial infarction, such as miR-1915 and miR-181c*. CONCLUSIONS: The present proof-of-concept study provides novel insights into the dynamic changes of the human miRNome during AMI.

Conference on clinical use of troponin T high sensitive (TnThs) on September 8, 2009 at the airport conference center, Frankfurt/Main.

With the redefinition of myocardial infarction in 2000, cardiology associations ESC and ACC require the use of the 99th percentile of a healthy population at a coefficient of variation (CV) of less than 10 % for Troponin values in diagnosing myocardial infarction. With a new Troponin T high sensitive (TnThs) assay as an advancement, it is now possible to fulfill these requirements. A panel of experts from laboratories and cardiologists discussed how to use this new assay in daily routine. Their experience confirms the excellent correlation between the upper measuring range of the new, highly sensitive Troponin T high sensitive test and the values obtained for Troponin T (4th generation). The Troponin T high sensitive test will identify more patients with myocardial infarction when using Troponin Ths above the 99t percentile (14 pg/mL). To diagnose myocardial infarction, one Troponin T value above the 99th percentile, a rise or fall within hours, and symptoms of ischemia need to be applied. Patients with elevated Troponin T levels but without myocardial infarction are supposed to have myocardial damage due to other reasons and have a rather poor prognosis. Is one of the criteria is not fulfilled, a myocardial infarction is less probable and differential diagnosis needs to be conducted.

Biological variation of high sensitive Troponin T in stable heart failure patients with ischemic or dilated cardiomyopathy.

INTRODUCTION: High sensitive Troponin (hsTn) assays enable detection of minimal marker elevation in heart failure patients previously deemed Troponin negative. Biovariability, reference change values (RCV), and index of individuality (II) have not been previously described for hsTnT although serial testing is important in interpreting low concentrations. For these values, a difference between ischemic heart disease (IHD) and dilated cardiomyopathy (dCMP) appears conceivable. METHODS: Change in hsTnT was determined alongside with clinical variables in 41 patients with stable chronic systolic dysfunction at 2-week-, 1-month-, 2-month-, and 3-month-intervals (IHD n = 17; dCMP n = 24). RESULTS: HsTnT was detectable in all patients. Individual hsTnT-variations at 2-week, 1-month, 2-month, and 3-month follow-up were 7.2, 22.6, 28.9, and 15.7%, respectively, corresponding to RCVs of 20.1, 62.5, 80.0, and 43.3%, respectively, for crude values. For log-normalised values, individual variations were 3.2, 2.8, 2.7, and 3.5%, respectively, corresponding to RCVs of 8.8, 7.9, 7.6, and 9.7%, respectively. The II was 0.03 to 0.33 according to interval. Aetiology of heart failure was not a consistent determinant of variation (p = 0.28; p = 0.07; p = 0.98; p = 0.03 for 2-week, 1-month, 2-month, and 3-month follow-up, respectively). CONCLUSION: While short-term biological variation of hsTnT is low, it becomes relatively more important for intermediate follow-up. It is not related to aetiology of heart failure. The corresponding indices of individuality indicate high individuality of values.