Hs cTn Research Articles

P363 HIGH–SENSITIVITY TROPONINS FOR OUTCOME PREDICTION IN THE GENERAL POPULATION: A SYSTEMATIC REVIEW AND META–ANALYSIS

Abstract Background High–sensitivity (hs) assays allow to measure cardiac troponin T and I (cTnT/I) even in healthy individuals. The higher hs–cTn values, the higher the ongoing cardiomyocyte damage, and then reasonably the risk of developing symptomatic cardiac disease. Methods We retrieved all studies evaluating the prognostic value of hs–cTnT or I in the general population. We calculated pooled hazard ratio (HR) values for all–cause and cardiovascular death, cardiovascular events and heart failure (HF) hospitalization. Results We included 24 studies for a total of 203,202 subjects; 11 studies assessed hs–cTnT and 14 hs–cTnI. One standard deviation (SD) increase in baseline hs–cTn was associated with a 23% higher risk of all–cause death (HR 1.226, 95% CI 1.083–1.388, p < 0.001, I2=88.5%); all these studies measured hs–cTnI. In an exploratory analysis on 3 studies with 25,760 subjects, hs–cTn predicted cardiovascular death (HR 1.822, 95% CI 1.241–2.674, p = 0.002, I2=87.2%). After synthesizing 9 studies with 58,565 subjects, hs–cTn predicted cardiovascular events (HR 1.328, 95% CI 1.167–1.513, p < 0.001, I2=93.8%). Both hs–cTnT (HR 1.627, 95% CI 1.145–2.311, p < 0.001) and hs–cTnI (HR 1.260, 95% CI 1.115–1.423, p < 0.001; p for interaction <0.001). Furthermore, in 10 studies with 61,467 subjects, hs–cTn predicted HF hospitalization (HR 1.493, 95% CI 1.368–1.630, p < 0.001, I2=76.6%). Both hs–cTnT (HR 1.566, 95% CI 1.303–1.883, p < 0.001) and hs–cTnI (HR 1.467, 95% CI 1.321–1.628, p < 0.001) were associated with HF hospitalization (p for interaction <0.001). Conclusions Hs–cTn values hold strong prognostic value in subjects from the general population, predicting the risk of all–cause and cardiovascular mortality, cardiovascular events, and HF hospitalization.

High sensitivity Troponins In Patients with elevated prohormone of beta natriuretic peptide and acute heart failure (HIGH TRIP Trial)

In patients presented to emergency rooms, Pro hormone of Natriuretic Peptide (Pro BNP) essay is overly sensitive test to rule out heart failure but less specific in predicting outcomes in follow-ups, in this study we ought to find the added value of High Sensitivity cardiac Troponin I (Hs-cTn I), in patients presented acutely with heart failure and its impact on mortality when Pro BNP is highly elevated. Prospective cohort study, inclusion criteria were age above 18 and clearly positive NT Pro BNP > 1000 pg/ml, with 12 months follow up period, primary end point was mortality from heart failure, secondary endpoint was need for rehospitalization. 95 patients were enrolled, divided into overt and non-overt pulmonary edema groups. Mean (Pro BNP) was 6184 and 5927 pg/ml and mean (Hs-cTn I) were 19.27 and 0.17 ng/ml respectively, Mean Ejection fraction was 48 ± 7 and 47 ± 7 for each group sequentially. Mortality rate was 4 (13%) in the higher Hs-c Tn I group, and 1 (1.6%) in the low troponin level group p = .03, odd ratio was 8.5, 95% CI (0.9–80). Need for re-hospitalization was present in 12 (38%) Vs 7 (8%) patients, p = .0081, odd ratio 4.8, 95% CI (1.7–14.2). In COX proportional hazard analysis, only Hs-cTn I was a significant predictor of poor outcome in this high-risk cohort with p = 0.0001. Adding (Hs-cTrop I) assay to the panel of laboratory testing, in patients presented to ER with acute heart failure and with high Pro-BNP > 1000, may further predicts mortality and rehospitalization rate.

Analytical and clinical characterization of a novel high-sensitivity cardiac troponin assay in a United States population

BackgroundCardiac troponin (cTn) is the keystone for diagnosis of acute myocardial infarction (AMI). We examined the analytical and clinical diagnostic characteristics of the ACCESS hsTnI assay in a United States (US) population. MethodsAll measurements and studies were conducted using a lithium heparin matrix. Sex-specific 99th percentile upper reference limits (URLs) were determined for 1089 healthy women (54.6%) and men using non-parametric statistics. High-sensitivity (hs) performance was assessed to determine if the total CV was ≤10% at sex-specific URLs, and if ≥50% of cTnI values for each sex exceeded the assay’s limit of detection (LoD). Precision, analytical measurement range, high-dose hook effect, and endogenous/exogenous interferences were examined with CLSI guidance. Clinical characterization included serial sampling of 1854 suspected AMI subjects presenting to 14 US Emergency Departments. AMI was adjudicated by a panel of expert cardiologists. The study’s only exclusion was end stage renal disease. Results99th percentile URLs were 11.6-, 19.8- and 17.5-ng/L for respective female, male and all-subject populations. Total %CV was <8% from 6.8 to 19,000 ng/L, and <6% at sex-specific 99th percentiles; ≥99% of ACCESS hsTnI values for each sex exceeded the LoD. No high-dose hook effect or endogenous/exogenous interferences were identified. A comparison of Baseline samples collected at ≤1 h and any-time after presentation, found 4% lower sensitivity for AMI than with earlier sampling. For 1–9 h post presentation, the sensitivity was >90%, specificity >85%; and negative and positive predictive value were ≥99% and >60%, respectively. ConclusionAnalytical and clinical performance of the ACCESS hsTnI assay meets the definition of a hs cTn method. The ACCESS hsTnI assay has good precision over a wide range, no significant interferences, and sensitivity >90% and NPV ≥99%. Performance is appropriate for aiding in AMI diagnosis.

Detecting cardiac events - state-of-the-art.

Cardiac biomarker measurement currently addresses two key questions in patient management: the differential diagnosis of chest pain and the differential diagnosis of the patient with breathlessness. There are currently three major themes in the strategies for the differential diagnosis of chest pain. The first is to undertake troponin measurement in patients selected to be at lower risk, hence to have a low prior probability of disease. The second is the introduction of high-sensitivity cardiac troponin (hs cTn) assays into routine clinical use with measurement at 0 and 3 h from admission. Two other approaches that utilize the diagnostic characteristics of these assays have also been suggested. The first is to use the limit of detection or limit of blank of the assay as the diagnostic discriminant. The second approach is to use the low imprecision of the assay within the reference interval and combine a discriminant value with an absolute rate of change (delta value). The third is the use of additional biomarkers to allow early discharge from the emergency department. The concept is to measure high-sensitivity cardiac troponin plus the extra marker on admission. The role of measurement of B-type natriuretic peptide or its N-terminal prohormone, N-terminal pro-B-type natriuretic peptide, has been accepted and incorporated into guidelines for chronic heart failure for some time. More recently, guidelines for acute heart failure can also recommend a single measurement of B-type natriuretic peptide or N-terminal pro-B-type natriuretic peptide in people presenting with new suspected acute heart failure.

Interpretation of mild elevation of high-sensitivity cardiac troponins

Measurements of cardiac troponins (cTn) are yet considered the gold standard method in patients with chest pain. Very recently, high-sensitivity (hs)cTn emerged and allow to measure very low concentrations of cTn. The aim of these assays was the better detection of patients with acute myocardial infarction (AMI). The threshold value should be the 99th percentile of the method, which corresponds to the concentration obtained from 99% of a reference population. These assays improve the detection of patients with elevated cTn concentrations. All patients with increased hs-cTn concentration above the 99th percentile should be considered at high risk of future clinical event when compared to patients with lower concentration. However, these elevated concentrations are not necessarily related to AMI due to coronary artery plaque rupture and superimposed thrombus. In order to understand adequately cTn measurement, the physician should base his interpretation on the context, the cTn concentration, variations during serial sampling, and the possible existence of a coexistent disease characterized by increased cTn concentrations.

THE PROGNOSTIC VALUE OF ABSOLUTE AND RELATIVE CHANGES IN CARDIAC TROPONIN CONCENTRATIONS AMONG NON-ACUTE MYOCARDIAL INFARCTION PATIENTS

It is unknown whether high sensitive cardiac troponin (hs cTn) at baseline and early changes carry long term mortality prognosis among chest pain patients presenting to emergency department, diagnosed with non acute myocardial infarction (AMI). In a prospective, international multicenter study, hs

High-Sensitivity Cardiac Troponin Assays: What Analytical and Clinical Issues Need to Be Addressed before Introduction into Clinical Practice?

The guidelines of the Global Task Force for the Universal Definition of Myocardial Infarction (MI)1 and the complementary laboratory medicine practice guidelines of the National Academy of Clinical Biochemistry (NACB), both published in 2007, established cardiac troponin (cTn) as the standard biomarker for the diagnosis of MI. Ongoing improvements in technology over the past several years have advanced the analytical detection of low concentrations of cTn (I and T) in blood, serum, and plasma. “Contemporary” assays demonstrate excellent diagnostic accuracy for detection of MI by using the recommended 99th percentile concentration as the medical decision cutoff value in specimens obtained at presentation. Optimal accuracy is seen with these assays in samples obtained 6 or more hours after presentation. However, there are 2 important biomarker issues mentioned in these guidelines that will be critical in defining the next and possibly final generation of high-sensitivity (hs) cTn assays. (1) In both guidelines, total assay imprecision is recommended but not required to be ≤10% at the 99th percentile. As previously shown and discussed in the literature, cTn assay imprecision ≤20% CV at the 99th percentile value does not lead to substantial increases in false-positive or -negative misclassifications. (2) Whereas study of a normal reference population is advocated in both guidelines for calculation of the 99th percentile before assay implementation in clinical practice, the specifications of that population (age, sex, ethnicity, race) and the number of individuals that should be included in the “normal” group have not been clearly stipulated. An opinion paper recently published in this journal suggested that hs-cTn assays need to have a total imprecision ≤10% at the 99th percentile and that >95% of apparently healthy subjects need to have measurable concentrations for the assay to be “guideline acceptable.” An assay with an imprecision between >10% and ≤20% was deemed …