APPENDIX
Appendix I: Search Strategy
Medline Search Strategy
1. exp Syncope/
2. faint*.tw.
3. presyncop*.tw.
4. unconscious*.tw.
5. (drop adj1 attack*).tw.
6. syncop*.tw.
7. 1 or 2 or 3 or 4 or 5 or 6
8. Biological Markers/
9. exp Neuropeptides/
10. Myoglobin/
11. exp Creatine Kinase/
12. exp Troponin/
13. L-Lactate Dehydrogenase/
14. Natriuretic Peptide, Brain/
15. C-Reactive Protein/
16. (reactive adj1 oxidative adj1 metabolite*).tw.
17. Aldosterone/
18. Cystatin C/
19. Trans Fatty Acids/
20. (cardiac adj1 biomarker*).tw.
21. biomarker*.tw.
22. Adrenomedullin/
23. adrenomedullin.tw.
24. MRpro-ANP.tw.
25. exp Natriuretic Peptides/
26. NTpro-BNP.tw.
27. copeptin.tw.
28. CTproET-1.tw.
29. 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27 or 28
30. 7 and 29
Embase Search Strategy
1. exp faintness/
2. syncop*.tw.
3. unconscious*.tw.
4. (drop adj1 attack*).tw.
5. presyncop*.tw.
6. 1 or 2 or 3 or 4 or 5
7. biological marker/
8. neuropeptide/
9. myoglobin/
10. creatine kinase/
11. exp troponin/
12. lactate dehydrogenase/
13. brain natriuretic peptide/
14. C reactive protein/
15. (reactive adj1 oxidative adj1 metabolite*).tw.
16. aldosterone/
17. cystatin C/
18. trans fatty acid/
19. (cardiac adj1 biomarker*).tw.
20. adrenomedullin/
21. adrenomedullin.tw.
22. MRpro-ANP.tw.
23. natriuretic factor/
24. NTpro-BNP.tw.
25. copeptin/
26. CTproET-1.tw.
27. copeptin.tw.
28. 7 or 8 or 9 or 10 or 11 or 12 or 13 or 14 or 15 or 16 or 17 or 18 or 19 or 20 or 21 or 22 or 23 or 24 or 25 or 26 or 27
29. 6 and 28
Appendix II: Article Review Form for Inclusion/Exclusion during Phase II of the Systematic Review
Reviewer: ______
Identification
Article #:______
Title: ______
______
Study authors:______
Inclusion criteria:Yes No
Adult patients
Patients with syncope (not induced as part of investigations)
Research which incorporates quantitative or qualitative biomarker measurement for risk-stratification during acute management of syncope
Exclusion criteria:Yes No
Studies involving only children
Case report study design
Narrative reviews, Editorial or letters to the editor
STUDY INCLUDED IN THE REVIEW Yes No
If study included, please complete the data extraction form
If excluded, explain reason for exclusion:
Appendix III–Study Details for Included Studies
AuthorYear / Study Type / Study Population / Total Study Sample size / Number of Patients with Cardiac Biomarker Testing / Cut-off value / Outcome: Type and Duration of Follow-upAPPENDIX IV: Quality Assessment of Diagnostic Accuracy Studies (QUADAS) Scoring for Included Studies
Reviewer: ______
Article #:______
Title: ______
Study authors: ______
Item / Quality Assessment Item / Yes / No / Unclear1 / Was the spectrum of patients representative of the patients who will receive the testin practice?
2 / Were selection criteria clearly described?
3 / Is the reference standard likely to classify the target condition correctly?
4 / Is the period between reference standard and index test short enough to be reasonablysure that the target condition did not change between the two tests?
5 / Did the whole sample or a random selection of the sample, receive verification using areference standard of diagnosis?
6 / Did patients receive the same reference standard regardless of the index test result?
7 / Was the reference standard independent of the index test (i.e. the index test did not formpart of the reference standard)?
8 / Was the execution of the index test described in sufficient detail to permit replication ofthe test?
9 / Was the execution of the reference standard described in sufficient detail to permit itsreplication?
10 / Were the index test results interpreted without knowledge of the results of the reference standard?
11 / Were the reference standard results interpreted without knowledge of the results of theindex test?
12 / Were the same clinical data available when test results were interpreted as would beavailable when the test is used in practice?
13 / Were not interpretable/intermediate test results reported?
14 / Were withdrawals from the study explained?
Appendix V. Criteria for Classification of Troponin Assays and Type of Biomarker Used in the Included Studies
Contemporary troponin assay is defined as a troponin assay with a coefficient of variation between 10% and 20% at the 99th percentile of a healthy reference population and less than 50% of the healthy reference population is detectable by the assay.
High sensitive troponin assay is defined as one that can achieve a coefficient of variation of ≤10% at the 99th percentile of a healthy reference population and troponin levels can be quantitated in greater than 50% of the healthy reference population.
Contemporary Troponin Studies:
Hing 2005 – Roche Troponin T immunoassay; upper limit of normal 0.03µg/L
Chiu 2014 –Roche Diagnostics, cardiac troponin T assay, on the MODULAR Analytics E170 analyzer
Sun 2009 – TroponinI; normal range was <0.04 ng/nL
Reed 2010 –Abbott Architect STAT Troponin-I automated immunoassay; 99th percentile upper reference limit in a healthy population 0.012 ng/ml and coefficients of variation <10% for all troponin I values ≥0.20 ng/ml
Natriuretic Peptide Studies:
Reed 2007 and 2010 – Point of care B-type Natriuretic Peptide (BNP) assayusing Biosite triage point-of-care machine
Tanimoto 2004 – BNP Immunoradiometric assay (Shionoria BNP kit, Shionogi Co. Ltd, Tokyo Japan)
Pfister 2012 – ElecsysproBNP assay, Roche Diagnostics for measuring N-terminal proBNP (NT-proBNP) levels
High-Sensitive Troponin Studies:
Reed 2013 - Plasma troponin I concentrations were measuredusing the reformulated ARCHIECT STAT troponin I assay (Abbott Laboratories, Abbott Park, Illinois, USA). The assay was reformulated by the manufacturer to achieve a greater analytical sensitivity with a limit of detection of 0.01 ng/ml or less, a 10% coefficient of variation of 0.032 ng/ml, and a 99th percentile (male and female) of 0.028 ng/ml.
Lindner 2013 – High-sensitive troponin T was measured by Roche Modular E170, an electrochemiluminescence immunoassay
Christ 2014 – High-sensitive troponin was measured by cobas e411 (Roche Diagnostics, Germany).This assay has a limit of detection of 0.003µg/L, a 99th percentile cutoff point of 0.014 µg/L, and a coefficient of variation of <10% at 0.013µg/L