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2. disease

Troponins and You
Brian Tiffany, MD, PhD, FACEP
Premier Emergency Medical Specialists
Evolution of the Cardiac Troponin (cTn) Assays
and Their Diagnostic Cutoffs
Vinay S. Mahajan, and Petr Jarolim Circulation.
2011;124:2350-2354
Copyright © American Heart Association, Inc. All rights reserved.
Cardiac troponin I (cTnI) levels in a healthy reference
population and in an acute coronary syndrome (ACS)
population.
Vinay S. Mahajan, and Petr Jarolim Circulation.
2011;124:2350-2354
One marker to rule the them, one
marker to find them . . . .
The Eye of Sauron the Plaintiff’s
Attorney is Upon You
Elevated Troponin =
Myocardial Necrosis, Right?
<crickets>, <crickets>
Cardiospecific, With One
Exception . . .
“Cytosolic” vs. “Structural”
Pools
Reversible Ischemia
u 
No elevation of troponins in stress testing induced
ischemia (Am J Cardiol 2002;89:224)
But WAIT!
u 
PROMPT-TIMI 35--Using ultra high sensitivity cTnI,
70/120 patients had detectable elevations during
reversible ischemia (Eur Heart J 2009;30:162)
Congestive Heart Failure
Figure 1 Comparison of cTnT and BNP Release Between Nonischemic HF Patients and Non-HF Group
ΔcTnT (CS-Ao) and ΔBNP (CS-Ao) levels were significantly higher in nonischemic HF patients than in nonHF group. Data are median and interquartile ranges.
JACC 2013;62:632
Stuff That Elevates Troponin
Ischemic Causes
Cardiac
Non-Cardiac
u 
Arrhythmia
u 
Shock
u 
Cocaine/meth
u 
Pulmonary embolus
u 
Variant angina
u 
Hypoxia
u 
Aortic dissection
u 
Vasculitis (SLE,
Kawasaki’s)
Stuff that Elevates Troponins
Non-ischemic Causes
Co-morbidities
Specific Identifiable
Precipitants
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Renal failure
u 
Extreme exertion
u 
Sepsis
u 
Cardiac contusion
u 
Infiltrative Diseases
u 
Burns > 30% BSA
u 
Respiratory Failure
u 
Electrical shock
u 
Stroke
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Takotsubo
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Subarachnoid
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Pericarditis/myocarditis
u 
Any cardiomyopathy
Troponin Predicts All Cause
Mortality . . .
NEJM 1996;335:1342
Even Small Elevations
Eur Heart J 2013;35:365
Troponin Predicts Mortality in
AFib
u 
Initial troponin within 8
hours of symptom onset
u 
Non-detectable <0.15
ng/ml
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Minor 0.15-0.65 ng/ml
u 
Positive >0.65ng/ml
u 
For this assay, 99%ile
URL was 0.65
Eur Heart J 2011;32:611
Eur Resp J 2011;41,S55:401
JACC 2003;41:2004
Troponin in Sepsis
Am J Respir Crit Care Med 2014;189:A3785
JACC 2011;60:2427
u 
“Sensitive and specific indicator of cardiac myonecrosis”
u 
“Non-specific relative to the etiology”
u 
“Should only be performed if clinically indicated for
suspected MI”
u 
“Must always be interpreted in the context of the clinical
presentation and pre-test likelihood that it represents MI”
u 
Recommends using 20% change in 6-9 hours for ESRD
patients as threshold for AMI diagnosis
u 
Acknowledges that any troponin elevation connotes risk of
badness
Bottom Line
u 
u 
Understand your tool
u 
99%ile URL for YOUR assay
u 
Elevations mean something, always
Use the right tool for the right job
u 
Don‘t order it without purpose
u 
Unnecessary troponins
u 
Cost money
u 
Make you look silly
u 
Make your cardiologists hate you
u 
Lead to unnecessary invasive testing and admissions
1990 Called.
It Wants Its Enzyme Back.
Are you really still ordering CK-MB?
Troponins are . . .
u 
More sensitive and specific than CK-MB for myocardial
infarction
u 
as good or better than CK-MB at infarct sizing
u 
Peak values of both cTnI and cTnT correlate well with
infarct size
u 
Better correlation than CK-MB
JACC 2006;48:2192
Clin Chem 2008;54:617
Myth of the ‘Discordant
Enzymes’
u 
u 
CRUSADE Registry in-hospital mortality (JACC 2006;47:312)
u 
2.7% CK-MB (-)/cTn (-)
u 
3.0% CK-MB (+)/cTn (-)
u 
4.5% CK-MB (-)/cTn (+)
u 
5.9% CK-MB (+)/cTn (+)
GRACE Registry in-hospital mortality (Am Heart J 2006;151:654)
u 
1.7% CK-MB (-)/cTn (-)
u 
2.3% CK-MB (+)/cTn (-)
u 
3.9% CK-MB (-)/cTn (+)
u 
7.7% CK-MB (+)/cTn (+)
“
It is difficult today to find any
situation in which CK-MB adds
anything other than cost to the
clinical utility of cTn if that
marker is properly used.
Saenger AK, Jaffe AS. Requim for a Heavyweight: the
demise of creatine kinase-MB. Circulation 2008;118:2000.
”
“
With contemporary
troponin assays, CK-MB
and myoglobin are not
useful for diagnosis of
ACS
III-A recommendation
2014 AHA/ACC NSTE-ACS Guidelines
”
Trop I, You Fools!!
Is Once Ever Enough?
or
How Low Can We Go?
JACC 2014;63:2569-2578
JACC 2014;63:2569-2578
14,636 patients
8,907 hscTnT <5ng/ml
JACC 2014;63:2569-2578
Bottom Line on Bandstein
JACC 2014;63:2569-2578
u 
8,883/14,636 (60.7%) patients were EKG/Initial hscTnT
negative
u 
15 (0.17%) of those had an MI in 30 days
u 
Authors assert ‘patient followup was complete because
followup data was obtained from national registers’
Arch Int Med 2012;172:1211
Arch Int Med 2012;172:1211
JACC 2012;59:2091
JACC 2012;59:2091
From: Validation of High-Sensitivity Troponin I in a 2-Hour Diagnostic Strategy to Assess 30-Day Outcomes in
Emergency Department Patients With Possible Acute Coronary Syndrome
J Am Coll Cardiol. 2013;62(14):1242-1249. doi:10.1016/j.jacc.2013.02.078
Recap
u 
Lots of things elevate troponin that aren’t ACS
u 
No such thing as a ‘false positive’ troponin
u 
Modern troponins have radically changed the
game for chest pain evaluation in the ED
u 
Order wisely
u 
Don’t turn off your brain