Combined testing of copeptin and high-sensitivity cardiac troponin T at presentation in comparison to other algorithms for rapid rule-out of acute myocardial infarction.

BACKGROUND: We aimed to directly compare the diagnostic and prognostic performance of a dual maker strategy (DMS) with combined testing of copeptin and high-sensitivity (hs) cardiac troponin T (cTnT) at time of presentation with other algorithms for rapid rule-out of acute myocardial infarction (AMI). METHODS: 922 patients presenting to the emergency department with suspected AMI and available baseline copeptin measurements qualified for the present TRAPID-AMI substudy. Diagnostic measures using the DMS (copeptin <10, <14 or < 20 pmol/L and hs-cTnT≤14 ng/L), the 1 h-algorithm (hs-cTnT<12 ng/L and change <3 ng/L at 1 h), as well as the hs-cTnT limit-of-blank (LoB, <3 ng/L) and -detection (LoD, <5 ng/L) were compared. Outcomes were assessed as combined end-points of death and myocardial re-infarction. RESULTS: True-negative rule-out using the DMS could be achieved in 50.9%-62.3% of all patients compared to 35.0%, 45.3% and 64.5% using LoB, LoD or the 1 h-algorithm, respectively. The DMS showed NPVs of 98.1%-98.3% compared to 99.2% for the 1 h-algorithm, 99.4% for the LoB and 99.3% for the LoD. Sensitivities were 93.5%-94.8%, as well as 96.8%, 98.7% and 98.1%, respectively. Addition of clinical low-risk criteria such as a HEART-score ≤ 3 to the DMS resulted in NPVs and sensitivities of 100% with a true-negative rule-out to 33.8%-41.6%. Rates of the combined end-point of death/MI within 30 days ranged between 0.2% and 0.3% for all fast-rule-out protocols. CONCLUSION: Depending on the applied copeptin cut-off and addition of clinical low-risk criteria, the DMS might be an alternative to the hs-cTn-only-based algorithms for rapid AMI rule-out with comparable diagnostic measures and outcomes.

Efficacy of High-Sensitivity Troponin T in Identifying Very-Low-Risk Patients With Possible Acute Coronary Syndrome.

Importance: Physicians need information on how to use the first available high-sensitivity troponin (hsTnT) assay in the United States to identify patients at very low risk for 30-day adverse cardiac events (ACE). Objective: To determine whether a negative hsTnT assay at 0 and 3 hours following emergency department presentation could identify patients at less than 1% risk of a 30-day ACE. Design, Setting, and Participants: A prospective, observational study at 15 emergency departments in the United States between 2011 and 2015 that included individuals 21 years and older, presenting to the emergency department with suspected acute coronary syndrome. Of 1690 eligible individuals, 15 (no cardiac troponin T measurement) and 320 (missing a 0-hour or 3-hour sample) were excluded from the analyses. Exposures: Serial hsTnT measurements (fifth-generation Roche Elecsys hsTnT assay). Main Outcomes and Measures: Serial blood samples from each patient were collected after emergency department presentation (once identified as a potential patient with acute coronary syndrome) and 3 hours, 6 to 9 hours, and 12 to 24 hours later. Adverse cardiac events were defined as myocardial infarction, urgent revascularization, or death. The upper reference level for the hsTnT assay, defined as the 99th percentile, was established as 19 ng/L in a separate healthy US cohort. Patients were considered ruled out for acute myocardial infarction if their hsTnT level at 0 hours and 3 hours was less than the upper reference level. Gold standard diagnoses were determined by a clinical end point committee. Evaluation of assay clinical performance for acute myocardial infarction rule-out was prespecified; the hypothesis regarding 30-day ACE was formulated after data collection. Results: In 1301 healthy volunteers (50.4% women; median age, 48 years), the upper reference level was 19 ng/L. In 1600 patients with suspected acute coronary syndrome (48.4% women; median age, 55 years), a single hsTnTlevel less than 6 ng/L at baseline had a negative predictive value for AMI of 99.4%. In 974 patients (77.1%) with both 0-hour and 3-hour hsTnT levels of 19 ng/L or less, the negative predictive value for 30-day ACE was 99.3% (95% CI, 99.1-99.6). Using sex-specific cutpoints, C statistics for women (0.952) and men (0.962) were similar for acute myocardial infarction. Conclusions and Relevance: A single hsTnT level less than 6 ng/L was associated with a markedly decreased risk of AMI, while serial levels at 19 ng/L or less identified patients at less than 1% risk of 30-day ACE.

High sensitivity cardiac troponin T in patients not having an acute coronary syndrome: results from the TRAPID-AMI study.

PURPOSE: To describe the baseline, 1 hr and delta high sensitivity cardiac troponin (hs-cTnT) values in patients with suspected acute myocardial infarction (AMI) but without a final acute coronary syndrome (ACS) diagnosis. MATERIALS AND METHODS: hs-cTnT assay for RAPID rule out of acute myocardial infarction (TRAPID-AMI) was a prospective diagnostic trial that enrolled emergency department (ED) patients with suspected AMI. Final patient diagnoses were adjudicated by a clinical events committee and subjects placed in different clinical groups: AMI, unstable angina, non-ACS cardiac, non-cardiac and unknown origin. The baseline, 1 hr and delta hs-cTnT values were analysed in the 902 non-ACS patients. RESULTS: Amongst the 1282 studied the patient groups were 213 (17%) AMI, 167 (13%) unstable angina, 113 (9%) non-ACS cardiac, 288 (22%) non-cardiac and 501 (39%) unknown origin. The hs-cTnT values in the non-cardiac and unknown origin groups were combined. The median hs-cTnT values (ng/L) were higher (p < 0.001) in the non-ACS cardiac compared to the non-cardiac/unknown origin group at baseline (11.8, <5) and 1 hr (12.3, <5). Their negative predictive values were 0.955 (baseline) and 0.954 (1 hr) for predicting non-ACS cardiac versus non-cardiac/unknown origin diagnoses. CONCLUSIONS: Hs-cTnT may help predict whether non-ACS ED patients have a final non-ACS cardiac or non-cardiac/unknown origin diagnoses.

Serial Sampling of High-Sensitivity Cardiac Troponin T May Not Be Required for Prediction of Acute Myocardial Infarction Diagnosis in Chest Pain Patients with Highly Abnormal Concentrations at Presentation.

BACKGROUND: Guidelines for diagnosing acute myocardial infarction (AMI) recommend adding kinetic changes to the initial cardiac troponin (cTn) blood concentration to improve AMI diagnosis. We hypothesized that kinetic changes may not be required in patients presenting with highly abnormal cTn. METHODS: Patients presenting with suspected AMI to the emergency department were enrolled in a prospective diagnostic study. We assessed the positive predictive value (PPV) of initial high-sensitivity cardiac troponin T (hs-cTnT) blood concentrations alone and in combination with kinetic changes for AMI. Predefined relative changes (δ change of ≥20%) and absolute changes (Δ change ≥9.2 ng/L) within different time intervals (1 h, 2 h, and 4-14 h after presentation) were assessed. The final diagnosis was adjudicated by 2 independent cardiologists. RESULTS: Among 1282 patients, 213 (16.6%) patients had a final diagnosis of AMI. For AMI prediction, PPVs increased from 48.8% for an initial hs-cTnT >14 ng/L to 87.2% for >60 ng/L, whereas PPVs remained unchanged for higher hs-cTnT concentrations at baseline (87.1% for both >80 ng/L and >100 ng/L). With addition of 20% relative Δ change, PPVs were not further improved in patients with baseline hs-cTnT >80 ng/L using the 1-h (84.0%) and 2-h (88.9%) intervals, and only minimally when extending the interval to 4-14 h (91.2% for >80 ng/L and 90.4% for >100 ng/L, respectively). Similar findings were observed when applying absolute changes. CONCLUSIONS: In chest pain patients with highly abnormal hs-cTnT concentrations at presentation, subsequent blood draws may not be required, as they do not provide incremental diagnostic value for prediction of AMI diagnosis.

Soluble fms-Like Tyrosine Kinase-1-to-Placental Growth Factor Ratio and Time to Delivery in Women With Suspected Preeclampsia.

OBJECTIVE: To assess the association of a serum soluble fms-like tyrosine kinase 1-to-placental growth factor (sFlt-1-to-PlGF) ratio of greater than 38 with time to delivery and preterm birth. METHODS: Secondary analysis of an observational cohort study that included women 18 years of age or older from 24 to 36 6/7 weeks of gestation at their first study visit with suspected (not confirmed) preeclampsia. Participants were recruited from December 2010 to January 2014 at 30 sites in 14 countries. A total of 1,041 women were included in time-to-delivery analysis and 848 in preterm birth analysis. RESULTS: Women with an sFlt-1-to-PlGF ratio greater than 38 (n=250) had a 2.9-fold greater likelihood of imminent delivery (ie, delivery on the day of the test) (Cox regression hazard ratio 2.9; P<.001) and shorter remaining time to delivery (median 17 [interquartile range 10-26] compared with 51 [interquartile range 30-75] days, respectively; Weibull regression factor 0.62; P<.001) than women with an sFlt-1-to-PlGF ratio of 38 or less, whether or not they developed preeclampsia. For women who did not (n=842) and did develop preeclampsia (n=199), significant correlations were seen between an sFlt-1-to-PlGF ratio greater than 38 and preterm birth (r=0.44 and r=0.46; both P<.001). Among women who did not develop preeclampsia, those who underwent iatrogenic preterm delivery had higher median sFlt-1-to-PlGF ratios at their first visit (35.3, interquartile range 6.8-104.0) than those who did not (8.4, interquartile range 3.4-30.6) or who delivered at term (4.3, interquartile range 2.4-10.9). CONCLUSIONS: In women undergoing evaluation for suspected preeclampsia, a serum sFlt-1-to-PlGF ratio greater than 38 is associated with a shorter remaining pregnancy duration and a higher risk of preterm delivery.