High Sensitivity Troponin
One year on in the South West
Charlotte Dawson
SpR Chemical Pathology / Metabolic Medicine
Bristol Royal Infirmary
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
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
Thygesen et al. Eur Heart J (2007) 28: 2525
hs-TnT (ng/L)
99th percentile
10% CV
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: 868-877
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
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
14 ng/L
0.5 ug/L
30 ng/L
hs-TnT
99%ile
NORMAL
ACS threshold
From 0.05 using TnI
INDETERMINATE
MI if clinical features exist
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
Timing of sampling using hs-Tn assays
8h post-pain onset
Reichlin et al. NEJM (2009) 361: 858
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
Patients with normal (<14 ng/L) or indeterminate (14-29 ng/L) TnT on adm
Indeterminate
83/303
Normal
220/303
Negative
predictive
value 89%
On admission
Positive
15/83
Normal
12/83
8h
Indet
20/220
Indet
56/83
Positive 2/56
Indet
25/56
8h
Normal
196/220
>12h
Not measured
28/56
Normal 1/56
Positive
4/220
>12h
Indet
8/20
Not measured
12/20
Time of admission after pain onset of all
patients with TnT > 30 ng/L during admission
TnT 26 32 (at 12h)
‘collapse’
TnT 28 30 (at 20h)
SOB, COPD, pulm
oedema, PPM.
Multiple adm TnT
25-45
30
No of patients
25
20
15
10
5
Positive on adm
0
n=88
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
Indet - positive
Normal - positive
STEMI
Time (h) after pain onset of adm TnT
1 patient-critical AS
2 patients-early presentation
No of patients
Patients with indeterminate – normal or normal - indeterminate
10
9
8
7
6
5
4
3
2
Indet - normal
1
0
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
Normal - indet
>8
7
6
6
5
No of patients
No of patients
Time after pain onset of adm TnT
5
4
3
2
1
0
14
15
16
17
18
19
20
21-25 26-29
Adm TnT (ng/L) indet – normal pts
4
3
2
1
0
14
15
16
17
18
19
20
21-25 26-29
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
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: 1210-1216
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:10.1136
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.
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