The Use of Very Low Concentrations of High‐sensitivity Troponin T to Rule Out Acute Myocardial Infarction Using a Single Blood Test

Abstract

BackgroundRecent single‐center and retrospective studies suggest that acute myocardial infarction (AMI) could be immediately excluded without serial sampling in patients with initial high‐sensitivity cardiac troponin T (hs‐cTnT) levels below the limit of detection (LoD) of the assay and no electrocardiogram (ECG) ischemia. ObjectiveWe aimed to determine the external validity of those findings in a multicenter study at 12 sites in nine countries. MethodsTRAPID‐AMI was a prospective diagnostic cohort study including patients with suspected cardiac chest pain within 6 hours of peak symptoms. Blood drawn on arrival was centrally tested for hs‐cTnT (Roche; 99th percentile = 14 ng/L, LoD = 5 ng/L). All patients underwent serial troponin sampling over 4–14 hours. The primary outcome, prevalent AMI, was adjudicated based on sensitive troponin I (Siemens Ultra) levels. Major adverse cardiac events (MACE) including AMI, death, or rehospitalization for acute coronary syndrome with coronary revascularization were determined after 30 days. ResultsWe included 1,282 patients, of whom 213 (16.6%) had AMI and 231 (18.0%) developed MACE. Of 560 (43.7%) patients with initial hs‐cTnT levels below the LoD, four (0.7%) had AMI. In total, 471 (36.7%) patients had both initial hs‐cTnT levels below the LoD and no ECG ischemia. These patients had a 0.4% (n = 2) probability of AMI, giving 99.1% (95% confidence interval [CI] = 96.7% to 99.9%) sensitivity and 99.6% (95% CI = 98.5% to 100.0%) negative predictive value. The incidence of MACE in this group was 1.3% (95% CI = 0.5% to 2.8%). ConclusionsIn the absence of ECG ischemia, the detection of very low concentrations of hs‐cTnT at admission seems to allow rapid, safe exclusion of AMI in one‐third of patients without serial sampling. This could be used alongside careful clinical assessment to help reduce unnecessary hospital admissions.

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

“…The NPVs (0.956 at baseline, 0.953 at 1 hr) remained similar when the LoD (!5 ng/L) was used in the ROC analysis. Just as very low baseline hs-cTnT levels (below the LoD) strongly suggest the absence of AMI (Body et al 2016) it appears that similar values < LoD at baseline and 1 hr also suggest the absence of any alternative other non-ACS cardiac diagnoses. Patients with hscTnT levels below the LoD at either baseline or 1 hr are very unlikely to have a non-ACS cardiac diagnosis as the cause of the symptoms that brought them to the ED for evaluation, especially if they have no comorbidities that are associated with chronic troponin elevations.…”

“…The LoD is defined as the LoB plus 1.645 standard deviation of results obtained from a low concentration sample and is thus the lowest troponin concentration that might reasonably be distinguished from the LoB (Armbruster and Pry 2008). The hscTnT assay has been reported in recent clinical trials to be useful in the ruling out of AMI using a single baseline draw if the result is below the LoD with no associated ECG ischemia (Carlton et al 2015, Body et al 2016. Additionally, the use of the baseline, 1 hr and resultant delta hs-cTnT measurements have been shown to be helpful in the very early rule in and out of AMI (Reichlin et al 2012, Mueller 2012, Roffi et al 2015.…”

“…TRAPID-AMI was undertaken to externally validate the diagnostic accuracy of the hs-cTnT baseline and 1-hr algorithm for rapid rule in and out of AMI and thereby confirm its suitability for routine clinical use in the ED (Reichlin et al 2012, Body et al 2016.…”

Fast track protocols using highly sensitive troponin assays for ruling out and ruling in non-ST elevation acute coronary syndrome

“…Considering a diagnostic strategy including only hsTn determination at patient admission, a negative PV >99% can be reached when the diagnostic sensitivity is close to 100%. This is achievable by setting the limit of blank (LOB) (defined as the highest measurement result that is likely to be observed for a sample that contains no troponin ['blank sample']) [14] of hsTn as decision threshold, even if some studies have proposed as an alternative the hsTn limit of detection (LOD) (defined as the lowest amount of troponin in a biological sample that can reliably be detected by that method) as rule-out cut-off, but without any substantial difference in diagnostic performance [15][16][17][18][19]. However, if by applying the hsTn LOB (or LOD) cut-off at admission only less than one patient with NSTEMI in 100 consecutive ED patients is missed, an undetectable hsTn value in patients admitted to ED with chest pain is relatively rare, and thus a very early rule-out may concern only a minority of subjects presenting to the ED with a paltry effect on the workload.…”

Use of the HEART Pathway with high sensitivity cardiac troponins: A secondary analysis

“…Recent studies suggest that hs-cTn measures should be used within the context of an ADP [5, 6]. However, the impact of integrating hs-cTn measures into the HEART Pathway has yet to be determined.…”