High Sensitivity TroponinOne year on in the South West
Charlotte DawsonSpR Chemical Pathology / Metabolic Medicine
Bristol Royal Infirmary
2000 • 1st generation troponin assays routinely replaced cardiac
marker panels (CK, CK-MB, myoglobin) as diagnostic test for acute coronary syndrome (ACS)
• Specific for myocardial injury measured >12h after onset of chest pain– STEMI: confirms diagnosis and estimates infarct size– Normal or equivocal ECGs: distinguishes between NSTEMI and other
causes of chest pain where myocardial injury has not occurred
• Limitation was poor sensitivity in the first few hours after pain onset– Delayed treatment– Delayed discharge from A&E / hospital
Troponin
High Sensitivity Troponin (hs-Tn)
2007
• ESC-ACCF-AHA-WHF and IFCC Task Force recommends use of a high sensitivity troponin assay
• Requirements were detection of hs-Tn at the 99th percentile of an apparently healthy reference population with <10% variability
• New definition of myocardial infarction: hs-Tn >99th percentile (hs-TnT >14 ng/L) with clinical features
hs-TnT (ng/L)
99th percentile10% CV
Thygesen et al. Eur Heart J (2007) 28: 2525
Diagnosis of acute MI (AMI) after pain onset hs-Tn vs standard assay
Keller et al NEJM (2009) 361: 868-877
= hs-TnT>14 ng/L
= TnI >0.05 ug/L
Troponin I vs hs-Troponin T
standard TnI
hs-TnT
0.05 ug/L 0.5 ug/L
14 ng/L
99%ile
NORMAL Myocardial infarction (MI) by new definition if clinical features exist
Equivalent to WHO definition of MI
Negative (Normal, and ‘analytically
indistinguishable from normal’)
ACS threshold(LOD with 10% CV)
hs-TnT
0.05 ug/L 0.5 ug/L
30 ng/L14 ng/L
99%ile
ACS thresholdFrom 0.05 using TnI
NORMAL INDETERMINATE MI if clinical features exist
Equivalent to WHO definition of MI
Negative (Normal, and ‘analytically
indistinguishable from normal’)
ACS threshold(LOD with 10% CV)
Troponin I vs hs-Troponin T
standard TnI
Causes of elevated troponin in the absence of overt ischaemic heart disease
Congestive heart failure—acute and chronicPulmonary embolism, severe pulmonary hypertensionRhabdomyolysis with cardiac injuryInflammatory diseases, e.g. myocarditis Critically ill patients, especially with respiratory failure or sepsisRenal failureCardiac contusion, or other trauma including surgery, ablation, pacing, etc Aortic dissectionAortic valve diseaseHypertrophic cardiomyopathyTachy- or bradyarrhythmias, or heart blockAcute neurological disease, including stroke or subarachnoid haemorrhageDrug toxicity or toxins
Study aims
• Audit adherence to protocol
• Establish whether time of second measurement can be earlier than 8 hours
• Monitor troponin outcome of patients admitted with ‘indeterminate’ result
Adherence to Protocol- audit results
1. 100% patients (303/303) with normal or indeterminate TnT on admission had repeat at 8 hr post pain / event
2. 93% patients (182/196) with normal TnT at 8 hr did not have a repeat test at 12 hr
3. 50% patients (36/76) with indeterminate result at 8 hr had repeat test at 12 hr
Normal220/303
Indeterminate83/303
Patients with normal (<14 ng/L) or indeterminate (14-29 ng/L) TnT on adm
Normal196/220
Indet20/220
Positive4/220
Indet 56/83
Normal 12/83
Positive 15/83
Not measured28/56
Indet25/56
Normal 1/56
Positive 2/56
8h
>12h
8h
>12h
On admission
Negative predictive value 89%
Not measured12/20
Indet8/20
Time (h) after pain onset of adm TnT
TnT 26 32 (at 12h)‘collapse’
TnT 28 30 (at 20h)SOB, COPD, pulm oedema, PPM. Multiple adm TnT 25-45
Positive on adm
Indet - positive
Normal - positive
0
5
10
15
20
25
30
0-0.9 1.0-1.9 2-2.9 3-3.9 4-4.9 5-5.9 6-6.9 7-7.9
No
of
patie
nts
Time of admission after pain onset of all patients with TnT > 30 ng/L during admission
n=88
STEMI
1 patient-critical AS2 patients-early presentation
Patients with indeterminate – normal or normal - indeterminate
Time after pain onset of adm TnT
No
of
patie
nts
0
1
2
3
4
5
6
7
8
9
10
0-0.9 1.0-1.9 2-2.9 3-3.9 4-4.9 5-5.9 6-6.9 7-7.9 >8 Normal - indet
Indet - normal
0
1
2
3
4
5
6
7
14 15 16 17 18 19 20 21-25 26-29
Adm TnT (ng/L) indet – normal pts
No
of
patie
nts
0
1
2
3
4
5
6
14 15 16 17 18 19 20 21-25 26-29
Max TnT (ng/L) normal - indet pts
No
of
patie
nts
• Indet – normal patients are not presenting later• Normal – indet patients are not presenting earlier• Majority have indeterminate levels at the lower end of the range
? Distinctprognostic gp
Improved survival of indeterminate patients once results start being reported (validation phase vs implementation phase)
Survival of patients according to hs-Tn level
Mills et al. JAMA (2011) 305: 1210-1216
• Intra individual variation 15-21% for hs-TnT (9.7% for hs-TnI)
• Based on 10% CV at 95% probability, studies suggest increase of 90% for hs-TnT (46% for hs-TnI) is a significant increase = acute MI
• Optimal increase may be 235 – 245%
• In clinical practice recommend• rise in troponin to > 99th percentile AND• doubling of hs-TnT
Diagnosis of acute MI using hs-TnI – single vs serial measurements
Collinson PO J Clin Pathol (2011) doi:10.1136
Higher diagnostic accuracy for acute MI using absolute change of >50% of the 99th percentile value ie 7 ng/L.
1 hour 2 hoursInterval between hs-Tn measurements
Summary
• hs-Tn allows for more rapid diagnosis of MI • Optimal timing for ruling out acute MI uncertain -
4 – 6 hours after pain onset
• Identifies ‘indeterminate’ patients in a poor prognostic group and need further investigation
• Change in troponin level may be informative in identifying acute MI in this group – more work needed