Comparison of contemporary troponin assays with the novel biomarkers, heart fatty acid binding protein and copeptin, for the early confirmation or exclusion of myocardial infarction in patients presenting to the emergency department with chest pain

Collinson, Paul; Gaze, David; Goodacre, Steve

doi:10.1136/heartjnl-2013-304716

Cited by 45 publications

(52 citation statements)

References 31 publications

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“…6 In this research, we determined whether the detection of extremely low troponin concentrations by this assay at the time of arrival in the ED could be used immediately to exclude AMI in a proportion of patients. We found that the diagnostic performance of this assay at the conventional 99th percentile cut-off is comparable to that reported by Collinson et al 17 In a cohort of 850 patients, that group reported a sensitivity of 73.0%. Keller et al 6 reported a higher sensitivity of 90.2%.…”

Section: Discussionsupporting

confidence: 85%

Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a sensitive troponin I assay

et al. 2015

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Objective: With a high-sensitivity troponin assay, it may be possible to exclude acute myocardial infarction with a single blood test on arrival in the emergency department by using a novel 'rule out' cut-off set at the limit of detection of the assay. We aimed to determine whether this can also be achieved using a contemporary sensitive troponin assay that does not meet 'high-sensitivity' criteria. Methods: In a prospective diagnostic cohort study, we included patients presenting to the emergency department with suspected cardiac chest pain. For this secondary analysis, serum samples drawn on arrival were tested using a contemporary sensitive troponin I assay (s-cTnI; Siemens Ultra ADVIA Centaur, 99th percentile 40 ng/L, limit of detection 6 ng/ L). Acute myocardial infarction was adjudicated by two independent investigators based on reference standard troponin testing 512 h after symptom onset. Results: Of 414 participants, 70 (16.9%) had acute myocardial infarction and 205 (49.5%) had initial s-cTnI concentrations below the limit of detection. Using the limit of detection as a 'rule out' cut-off gave a sensitivity of 94.3% (95% CI 86.0-98.4%) for acute myocardial infarction. If only patients with s-cTnI below the limit of detection and no electrocardiogram ischaemia were considered to have acute myocardial infarction 'ruled out' (41.8% of the cohort, n ¼ 174), sensitivity would rise to 97.1% (90.1-99.7%) and negative predictive value to 98.8% (95.9-99.9%). Conclusions: Acute myocardial infarction cannot be excluded in patients with s-cTnI concentrations below the limit of detection using the contemporary sensitive assay evaluated. Future work with this assay should focus on serial sampling over 1-3 h and combination with clinical information and/or additional biomarkers.

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Section: Discussionsupporting

confidence: 85%

Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a sensitive troponin I assay

et al. 2015

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“…The increase in diagnostic sensitivity as a results of adding copeptin measurements to cTnI is 14% (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) in the meta-analysis, which is comparable to the 19.8% increase that we find in our study. 19 Two very recent reports, not included in the meta-analysis, that investigated the added value of copeptin on top of cTnI in the evaluation of chest pain patients have shown mixed results.…”

Section: Discussionsupporting

confidence: 83%

“…The first study by Maisel et al 15 shows clear advantages of adding copeptin to cTnI measurement and even suggests that the addition of copeptin has the potential to rule out AMI in 58% of patients with a baseline measurement. The second study, by Collinson et al, 20 however, does not show an added diagnostic value for copeptin measurements. To date, most studies seem to suggest that the addition of copeptin to cTnI measurements improves the early rule out of AMI in patients with chest pain.…”

Section: Discussionmentioning

confidence: 90%

Rapidly rule out acute myocardial infarction by combining copeptin and heart-type fatty acid-binding protein with cardiac troponin

et al. 2015

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Background: The rapid exclusion of acute myocardial infarction in patients with chest pain can reduce the length of hospital admission, prevent unnecessary diagnostic work-up and reduce the burden on our health-care systems. The combined use of biomarkers that are associated with different pathophysiological aspects of acute myocardial infarction could improve the early diagnostic assessment of patients presenting with chest pain. Methods: We measured cardiac troponin I, copeptin and heart-type fatty acid-binding protein concentrations in 584 patients who presented to the emergency department with acute chest pain. The diagnostic performances for the diagnosis of acute myocardial infarction and NSTEMI were calculated for the individual markers and their combinations. Separate calculations were made for patients presenting to the emergency department <3 h, 3-6 h and 6-12 h after chest pain onset. Results: For ruling out acute myocardial infarction, the net predictive values (95% CI) of cardiac troponin I, copeptin and heart-type fatty acid-binding protein were 90.4% (87.3-92.9), 84% (79.8-87.6) and 87% (83.5-90), respectively. Combining the three biomarkers resulted in a net predictive value of 95.8% (92.8-97.8). The improvement was most pronounced in the early presenters (<3 h) where the combined net predictive value was 92.9% (87.3-96.5) compared to 84.6% (79.4-88.9) for cardiac troponin I alone. The area under the receiver operating characteristic for the triple biomarker combination increased significantly (P < 0.05) compared to that of cardiac troponin I alone (0.880 [0.833-0.928] vs. 0.840 [0.781-0.898], respectively). Conclusions: Combining copeptin, heart-type fatty acid-binding protein and cardiac troponin I measurements improves the diagnostic performance in patients presenting with chest pain. Importantly, in patients who present early (<3 h) after chest pain onset, the combination improves the diagnostic performance compared to the standard cardiac troponin I measurement alone.

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“…Three studies used hsTnI, 19,20,22 four used hsTnT 15,16,21 and one assayed both. 17 The analyser for hsTnT was produced by Roche Diagnostics in all (99% cut-off 14 ng/L), while hsTnI was measured using the Beckman-Coulter AccuTnI Enhanced (cut-off 40 ng/L) in one study, 17 Siemens TnI-Ultra assay (99% cut-off 40 ng/L) in two, 17,22 and the Abbott-Architect assay (99% cut-off: 28 and 32 ng/ L, respectively) in the remainder. 19,20 Four studies analysed their HT FABP with Randox immunoturbidimetric assay, [16][17][18]22 one by enzyme-linked immunosorbent assay (ELISA) provided by Dainippon Pharmaceutical, Osaka, Japan, 20 one with QuickSenshFABP assay, 21 one by Hycult Biotech, 15 and the last with Innotrac Aiol Immunoanalyser.…”

Section: Resultsmentioning

confidence: 99%

“…When HT FABP was compared specifically with hsTnT, [15][16][17][18]21 the pooled sensitivity (60.3%, 95% CI: 55.5-64.9%) was much worse (P ¼ 0.001) though the specificity (86.9%, 95% CI: 85.4-88.3%) did not differ significantly (P ¼ 0.34). The AUC of 0.86 (SE 0.04) is significantly worse than hsTnT (P < 0.01).…”

Section: Heart-type Fatty Acid Binding Protein (Figure 2)mentioning

confidence: 97%

Heart-type fatty acid binding protein in early diagnosis of myocardial infarction in the era of high-sensitivity troponin: a systematic review and meta-analysis

Liou

2014

Ann Clin Biochem

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Introduction: Heart-type fatty acid binding protein (HT FABP) is an emerging biomarker of ischaemic myocardial necrosis. While previous studies have demonstrated its additive value when compared to contemporary troponin assays in the diagnosis of acute myocardial infarction (AMI), its utility in the era of high-sensitivity troponin (hsTn) assays remains undetermined. Methodology: A systematic review and meta-analysis of relevant studies was performed comparing the diagnostic performance of HT FABP both alone and in conjunction with hsTn in the early diagnosis and exclusion of AMI. Results: A systematic literature search yielded eight eligible studies including 3395 patients. Of these, 716 patients (21.1%) were eventually diagnosed with AMI. The pooled sensitivity and specificity for hsTn on admission was 82.5% (95% confidence interval [CI]: 79.8-85.0%) and 89.7% (95% CI: 88.7-90.6%), respectively, while the area under the curve (AUC) for the summary receiver operating characteristics (ROC) curve is 0.92 (SE 0.02). While the pooled specificity (84.6%, 95% CI: 83.2-85.9%) of admission HT FABP is similar to hsTn for the early diagnosis of AMI (P ¼ 0.07), its pooled sensitivity (63.5%, 95% CI: 59.9-67.1%, P < 0.001) is significantly worse. Accordingly, the AUC of the summary ROC curve for HT FABP (0.79, SE 0.03) is inferior to hsTn (P < 0.0001). The addition of HT FABP to hsTn resulted in no improvement in the sensitivity (P ¼ 0.058) and worsened the specificity (P ¼ 0.001) in the early diagnosis of AMI compared to hsTn alone. Conclusion: HT FABP does not appear to improve the diagnostic accuracy of hsTn, and consequently its routine use currently cannot not be recommended.

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Comparison of contemporary troponin assays with the novel biomarkers, heart fatty acid binding protein and copeptin, for the early confirmation or exclusion of myocardial infarction in patients presenting to the emergency department with chest pain

Abstract: High-sensitivity cardiac troponin is the best single marker. Addition of HFABP to high-sensitivity troponin increased diagnostic sensitivity. Additional measurement of copeptin is not useful in the chest pain population.

Cited by 45 publications

References 31 publications

Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a sensitive troponin I assay

Rapid exclusion of acute myocardial infarction in patients with undetectable troponin using a sensitive troponin I assay

Rapidly rule out acute myocardial infarction by combining copeptin and heart-type fatty acid-binding protein with cardiac troponin

Heart-type fatty acid binding protein in early diagnosis of myocardial infarction in the era of high-sensitivity troponin: a systematic review and meta-analysis

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