Citations

Abstract BACKGROUND Initial reports suggest that concentrations of high-sensitivity cardiac troponin T (hs-cTnT) (Roche Diagnostics Elecsys®) below the limit of blank (LoB) (3 ng/L) or limit of detection (LoD) (5 ng/L) of the assay have almost 100% negative predictive value (NPV) for acute myocardial infarction (AMI), particularly among patients without electrocardiograph (ECG) evidence of ischemia. We aimed to prospectively validate those findings. METHODS We included adults presenting to the emergency department with suspected cardiac chest pain. Standard troponin T (cTnT) and hs-cTnT (both Roche Elecsys) were tested in samples drawn on arrival. The primary outcome was AMI, adjudicated by 2 investigators on the basis of clinical data and ≥12-h cTnT testing. We also evaluated diagnostic performance when AMI was readjudicated on the basis of hs-cTnT (≥12-h) concentrations. RESULTS Of 463 patients included, 79 (17.1%) had AMI. Twenty-four patients (5.2%) had hs-cTnT concentrations below the LoB, although none had AMI. Ninety-six patients (20.7%) had hs-cTnT concentrations below the LoD, 1 of whom had AMI. Thus, diagnostic sensitivity was 98.7% (95% CI 87.5%–98.6%) and NPV was 99.0% (95% CI 94.3%–100.0%). Of the 17.3% (n = 80) patients with hs-cTnT below the LoD and no ECG ischemia, none had AMI. Thus, diagnostic sensitivity was 100.0% (95% CI 95.4%–100.0%) and NPV was 100.0% (95% CI 95.5%–100.0%). Sensitivity and NPV were maintained when AMI was readjudicated on the basis of hs-cTnT. CONCLUSIONS Our findings confirm that patients with nonischemic ECG and undetectable hs-cTnT at presentation have a very low probability of AMI, although the proportion of patients affected was smaller than in previous research.

AbstractObjectivesChest pain is a common complaint to emergency departments (EDs) and clinical risk factors are used to predict which patients are at risk for worse outcomes and mortality. The goal was to assess the novel biomarker midregional proadrenomedullin (MR‐proADM) in prediction of mortality and major adverse cardiac events (MACE).MethodsThis was a subanalysis of the CHOPIN study, a 16‐center prospective trial that enrolled 2,071 patients presenting with chest pain within 6 hours of onset. The primary endpoint was 6‐month all‐cause mortality and the secondary endpoint was 30‐day and 6‐month MACE: ED visits or hospitalization for acute myocardial infarction, unstable angina, reinfarction, revascularization, and heart failure.ResultsMR‐proADM performed similarly to troponin (cTnI; c‐statistic = 0.845 and 0.794, respectively) for mortality prediction in all subjects and had similar results in those with noncardiac diagnoses. MR‐proADM concentrations were stratified by decile, and the cohort in the top decile had a 9.8% 6‐month mortality risk versus 0.9% risk for those in the bottom nine deciles (p < 0.0001). MR‐proADM, history of coronary artery disease (CAD), and hypertension were predictors of short‐term MACE, while history of CAD, hypertension, cTnI, and MR‐proADM were predictors of long‐term MACE.ConclusionsIn patients with chest pain, MR‐proADM predicts mortality and MACE in all‐comers with chest pain and has similar prediction in those with a noncardiac diagnosis. This exploratory analysis is primarily hypotheses‐generating and future prospective studies to identify its utility in risk stratification should be considered.

The use of soluble cardiac biomarkers such as N‐terminal pro‐brain natriuretic peptide (NT‐proBNP) and troponin has revolutionized prognostication for patients with AL amyloidosis. Soluble ST2 (sST2) and galectin‐3 have also been reported to have prognostic value in other cardiac patient populations. We identified 502 patients with AL amyloidosis, who provided a research sample and consent to review their medical records between 1/1/2006‐12/31/2010 within 90 days of their diagnosis. Samples were assayed for sST2 and galectin‐3. Within this AL amyloidosis population, overall survival (OS) was 25.5 months (95% CI 18, 35.7 months). Receiver operating curve analyses were done to detect the best cut‐points for sST2 and galectin‐3 to predict both 1‐ and 5‐year OS. The respective cut points for sST2 were 30 and 29.7 ng/mL, while the median sST2 for the entire population was 31 ng/mL (IQR 19.8, 53.6). The respective cut points for galectin‐3 were 11 and 10.4 ng/mL while the median for the entire population was 16.6 ng/mL (IQR 11.5, 24.0). Although on univariate analysis, both sST2 and galectin‐3 were prognostic, upon multivariate analysis, only sST2 was independent of troponin, NT‐proBNP, serum immunoglobulin free light chain, and blood pressure. Not only did sST2 add to previously reported prognostication systems, but a novel prognostication 5‐point system including sST2 was possible. The addition of sST2 – but not galectin‐3 – to existing prognostication systems for patients with AL amyloidosis strengthens the ability to predict for death. Am. J. Hematol. 90:524–528, 2015. © 2015 Wiley Periodicals, Inc.

Abstract BACKGROUND N-terminal pro B-type natriuretic peptide (NT-proBNP) has strong prognostic value for all-cause mortality in the general population. High-sensitivity assays now allow detection of cardiac troponins even in asymptomatic populations. We examined the association between NT-proBNP, high-sensitivity cardiac troponin T (hs-cTnT), and hs-cTnI and all-cause mortality in older adults. METHODS We conducted a longitudinal cohort study [Activity and Function in the Elderly in Ulm (ActiFE Ulm)] including 1506 community-dwelling adults ≥65 years old with NT-proBNP, hs-cTnT, and hs-cTnI measured at baseline. We evaluated the associations between log-transformed biomarker concentrations and 4-year total mortality, accounting for possible confounders, with Cox proportional hazards models. RESULTS We observed 125 deaths among 1422 participants (median follow-up 4 years). We detected effect modification by sex for all biomarkers (all P values &lt;0.05) expressed as hazard ratio (HR) for death per 1-unit increment of ln(biomarker concentration) in women (n = 618, 37 deaths) compared with men (n = 804, 88 deaths): HR 2.97 (95% CI 2.04–4.33) vs 1.73 (1.40–2.13) for NT-proBNP; 3.67 (2.31–5.81) vs 2.15 (1.61–2.87) for hs-cTnT; and 3.32 (2.13–5.18) vs 1.92 (1.55–2.38) for hs-cTnI. Among 777 participants with undetectable hs-cTnT (&lt;5 ng/L), hs-cTnI remained associated with all-cause mortality in age- and sex-adjusted analysis. CONCLUSIONS NT-proBNP, hs-cTnT, and hs-cTnI were independently associated with all-cause mortality in older adults. The strength of these associations varied between men and women, emphasizing the need for additional sex-specific research among older people.

Abstract BACKGROUND Aggressive LDL cholesterol (LDL-C)-lowering strategies are recommended for primary and secondary prevention of cardiovascular events. A newly derived equation for LDL-C estimation was recently published that addressed limitations in the commonly used Friedewald LDL-C calculation method. The novel method was reported to classify patients with superior concordance to measured LDL-C compared to the Friedewald method, particularly in patients with LDL-C &lt;70 mg/dL. METHODS We evaluated the performance of the novel method within an independent cohort of 23 055 patients with LDL-C measured by the gold standard β-quantification reference method. RESULTS Overall Friedewald underestimated and the novel method overestimated measured LDL-C. Both estimations significantly deviated from the reference method when LDL-C was &lt;70 mg/dL. Overall, the Friedewald and novel calculations correctly classified 77% and 78% of patients, respectively. The largest discrepancy in classification was observed in individuals with measured LDL-C &lt;70 mg/dL. For this group the novel calculation would reclassify 8.7% of patients as &gt;70 mg/dL compared to the Friedewald equation. CONCLUSIONS We compared both novel and Friedewald estimated LDL-C against the LDL-C reference method; in contrast, the prior study relied on validation of a subset of samples by β-quantification to allow the use of the vertical autoprofile method for LDL-C measurement. We conclude that the novel method has some benefits but it is unclear whether improvements over the Friedewald calculation are substantive enough to justify making the change in routine clinical practice and to improve patient outcomes.