Prospective validation of an acoustic-based system for the detection of obstructive coronary artery disease in a high-prevalence population.

Recent guidelines recommend a risk-adjusted, non-invasive work-up in patients presenting with chest discomfort to exclude coronary artery disease (CAD). However, a risk-adjusted diagnostic approach remains challenging in clinical practice. An acoustic detection device for analyzing micro-bruits induced by stenosis-generated turbulence in the coronary circulation has shown potential for ruling out CAD in patients with low-to-intermediate likelihood. We examined the diagnostic value of this acoustic detection system in a high-prevalence cohort. In total, 226 patients scheduled for clinically indicated invasive coronary angiography (ICA) were prospectively enrolled at two centers and examined using a portable, acoustic detection system. The acoustic analysis was performed in double-blinded fashion prior to quantitative ICA and following percutaneous coronary intervention (PCI). An acoustic detection result (CAD score) was obtained in 94% of all patients. The mean baseline CAD score was 41.2 ± 11.9 in patients with obstructive CAD and 33.8 ± 13.4 in patients without obstructive CAD (p < 0.001). ROC analysis revealed an AUC of 0.661 (95% CI 0.584-0.737). Sensitivity was 97.6% (95% confidence interval (CI) 91.5-99.7%), specificity was 14.5% (CI 9.0-21.7%), negative predictive value was 90.5% (CI 69.6-98.8%), and positive predictive value was 41.7% (CI 34.6-49.0%). Following PCI, the mean CAD score decreased from 40.5 ± 11.2 to 38.3 ± 13.7 (p = 0.039). Using an acoustic detection device identified individuals with CAD in a high-prevalence cohort with high sensitivity but relatively low specificity. The negative predictive value was within the predicted range and may be of value for a fast rule-out of obstructive CAD even in a high-prevalence population.

Myeloid-related protein 8/14 and high-sensitivity cardiac troponin I to differentiate type 2 myocardial infarction.

Myocardial infarction (MI) not only defines acute MI with obstructed coronary arteries (T1MI) but also myocardial necrosis caused by myocardial oxygen supply/demand mismatch as type 2 MI (T2MI); only T1MI patients benefit from an early invasive management. Myeloid-related protein(MRP)-8/14 is a biomarker described in various inflammatory diseases and in MI patients. Here we evaluate the potential of MRP-8/14 and high-sensitivity troponin I (hs-cTnI) to differentiate T2MI from T1MI. Patients with final diagnosis NSTEMI (n = 254; 33.1% female) enrolled in a prospective biomarker registry between 08/2011 and 10/2016 were analysed. Median baseline MRP-8/14 levels were higher in T2MI (n = 55; 3.37(1.88-6.48)µg/mL) than in T1MI (n = 199; 2.4 [1.4-3.79]µg/mL) (p = .013) patients, in contrast to hs-cTnI (T2MI:52[11.65-321.4]ng/L vs. T1MI:436.5 [61.25-1973.8]ng/L; p < .001). To detect the strength of this association odds ratios(OR) were calculated with MRP-8/14 yielding 2.13(1.16-3.92; p = .015) to predict T2MI and 0.47(0.26-0.87; p = .015) for T1MI. As expected, hs-cTnI yielded an OR of to predict T2MI 0.34(0.17-0.65; p = .001) and 2.98(1.53-5.81; p = .001) for T1MI. Both markers show comparable and independent results if adjust to hs-cTnI/MRP-8/14, TIMI risk score and CRP. T2MI is associated with higher MRP-8/14 and lower hs-cTnI concentrations than T1MI. Our data suggest that MRP-8/14 as a marker of inflammation might provide usable discriminatory information complementing hs-cTnI in a diagnostic procedure evaluating the type of MI directly upon hospital admission.

Identification of Periprocedural Myocardial Infarction Using a High-Sensitivity Troponin I Assay in Patients Who Underwent Transcatheter Aortic Valve Implantation.

Periprocedural myocardial infarction (MI), a rare complication after transcatheter aortic valve implantation (TAVI), is associated with worse outcome. According to the Valve Academic Research Consortium (VARC-2), MI is defined by an increase in cardiac troponin (cTn) and creatine kinase MB (CK-MB) levels; however, many patients show periprocedurally elevated cTn without clinical evidence of MI. The aims of this study were to establish reference values of cardiac troponin I measured with a high-sensitivity assay (hs-cTnI) and to assess the periprocedural diagnostic value of this biomarker in patients who underwent TAVI. Hs-cTnI and CK-MB levels were assessed before and up to 3 days after transfemoral (TF) or transapical (TA) TAVI in 515 patients. A high proportion (61.2%) of patients had elevated hs-cTnI at baseline. According to VARC-2 criteria, almost all TA-patients (99.5%) showed an MI based on hs-cTnI compared with 4.2% based on CK-MB. In TF-patients, 81.1% had an MI based on hs-cTnI compared with 9.0% based on CK-MB. Only 10 patients (2%), however, had a type 1 MI. The ninety-ninth percentile for hs-cTnI was 285 ng/L in the TAVI cohort. After applying a TAVI-specific cutoff the frequency of MI was lower and more realistic (TF: 5% vs 81.1%; p <0.001; TA: 22.2% vs 99.5%; p <0.001). In conclusion, the VARC-2 definition leads to an overestimation of periprocedural MI. Our new TAVI-specific reference values yield a more realistic estimation of the myocardial ischemic risk. hs-cTnI, however, does not seem to be the biomarker of choice for MI detection in this setting.

High-sensitivity cardiac troponin T and copeptin assays to improve diagnostic accuracy of exercise stress test in patients with suspected coronary artery disease.

BACKGROUND: The average diagnostic sensitivity of exercise stress tests (ESTs) is lower than that of other non-invasive cardiac stress tests. The aim of the study was to examine whether high-sensitivity cardiac troponin T (hs-cTnT) or copeptin concentrations rise in response to inducible myocardial ischaemia and may improve the diagnostic accuracy of ESTs. METHODS AND RESULTS: An EST was performed stepwise on a bicycle ergometer by 383 consecutive patients with suspected or progression of coronary artery disease (CAD). In addition venous blood samples for measurement of hs-cTnT and copeptin were collected prior to EST, at peak exercise, and 4 h after EST. Coronary angiography was assessed for all patients. Patients with significant CAD (n = 224) were more likely to be male and older compared to patients with non-significant CAD (n = 169). Positive EST was documented in 125 (55.8%) patients with significant CAD and in 69 (43.4%) patients with non-significant CAD. Copeptin and hs-cTnT concentrations at baseline were higher in patients with significant CAD (copeptin: 10.8 pmol/l (interquartile range (IQR) 8.1-15.6) vs 9.4 pmol/l (IQR 7.1-13.9); p = 0.04; hs-cTnT: 3.0 ng/l (IQR <3.0-5.4) vs <3.0 ng/l (IQR <3.0); p = 0.006). Hs-cTnT improved sensitivity (61.6% vs 55.8%), specificity (67.7% vs 56.6%) and the positive predictive value (PPV) (72.3% vs 64.4%) and negative (55.2% vs 47.6%) predictive value (NPV) of EST. Copeptin could not improve sensitivity (55.4% vs 55.8%) and reduced specificity, PPV and NPV. CONCLUSIONS: The measurement of hs-cTnT during EST improves sensitivity, specificity, and positive and negative predictive values. In contrast, measurement of copeptin does not improve diagnostic sensitivity and reduces specificity.