1. High Sensitivity Troponin
One year on in the South West
Charlotte Dawson
SpR Chemical Pathology / Metabolic Medicine
Bristol Royal Infirmary

2. Troponin
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

3. 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 percentile
10% CV
Thygesen et al. Eur Heart J (2007) 28: 2525

4. Diagnosis of acute MI (AMI) after pain onset hs-Tn vs standard assay
= hs-TnT>14 ng/L
= TnI >0.05 ug/L
Keller et al NEJM (2009) 361:

5. Troponin I vs hs-Troponin T
Negative
(Normal, and ‘analytically
indistinguishable from normal’)
ACS threshold
(LOD with
10% CV)
Equivalent to WHO
definition of MI
standard TnI
0.05 ug/L
0.5 ug/L
14 ng/L
hs-TnT
99%ile
NORMAL
Myocardial infarction (MI) by new definition if clinical features exist

6. Troponin I vs hs-Troponin T MI if clinical features exist
Negative
(Normal, and ‘analytically
indistinguishable from normal’)
ACS threshold
(LOD with
10% CV)
Equivalent to WHO
definition of MI
standard TnI
0.05 ug/L
0.5 ug/L
14 ng/L
30 ng/L
hs-TnT
ACS threshold
From 0.05 using TnI
99%ile
NORMAL
INDETERMINATE
MI if clinical features exist

7. Causes of elevated troponin in the absence of overt ischaemic heart disease
Congestive heart failure—acute and chronic
Pulmonary embolism, severe pulmonary hypertension
Rhabdomyolysis with cardiac injury
Inflammatory diseases, e.g. myocarditis
Critically ill patients, especially with respiratory failure or sepsis
Renal failure
Cardiac contusion, or other trauma including surgery, ablation, pacing, etc
Aortic dissection
Aortic valve disease
Hypertrophic cardiomyopathy
Tachy- or bradyarrhythmias, or heart block
Acute neurological disease, including stroke or subarachnoid haemorrhage
Drug toxicity or toxins

8. Timing of sampling using hs-Tn assays
8h post-pain onset
Reichlin et al. NEJM (2009) 361: 858

10. 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

11. Adherence to Protocol - audit results
100% patients (303/303) with normal or indeterminate TnT on admission had repeat at 8 hr post pain / event
93% patients (182/196) with normal TnT at 8 hr did not have a repeat test at 12 hr
50% patients (36/76) with indeterminate result at 8 hr had repeat test at 12 hr

12. Patients with normal (<14 ng/L) or indeterminate (14-29 ng/L) TnT on adm
83/303
Normal
220/303
Negative
predictive
value 89%
On admission
Indet
20/220
Positive
4/220
Normal
12/83 8h
Positive
15/83 8h
Indet
56/83
Normal
196/220
Positive 2/56
>12h
>12h
Indet
25/56
Not measured
28/56
Indet
8/20
Not measured
12/20
Normal 1/56

13. Time of admission after pain onset of all patients with TnT > 30 ng/L during admission
TnT (at 12h)
‘collapse’
TnT (at 20h)
SOB, COPD, pulm oedema, PPM. Multiple adm TnT
25-45
No of patients
Positive on adm
Indet - positive
n=88
Normal - positive
Time (h) after pain onset of adm TnT
STEMI
1 patient-critical AS
2 patients-early presentation

15. Patients with indeterminate – normal or normal - indeterminate
No of patients
Indet - normal
Normal - indet
Time after pain onset of adm TnT
No of patients
No of patients
Adm TnT (ng/L) indet – normal pts
Max TnT (ng/L) normal - indet pts
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
? Distinct
prognostic gp

16. Survival of patients according to hs-Tn level
Improved survival of indeterminate patients once results start being reported (validation phase vs implementation phase)
Mills et al. JAMA (2011) 305:

17. Diagnosis of acute MI using hs-TnI – single vs serial measurements
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
Collinson PO J Clin Pathol (2011) doi:

18. Interval between hs-Tn measurements
1 hour
2 hours
Higher diagnostic accuracy for acute MI using absolute change of >50% of the 99th percentile value ie 7 ng/L.

19. 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