Download Cardiac troponin assay-utility in early detection of CHD

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Transcript
By
Dr.Anup Bhandari
JR 1 ,Department of Pathology,
S.R.T.R.M.C.Ambajogai
• “A
is a substance used as
an indicator of a biologic state.
• It is a characteristic that is
objectively measured and
evaluated as an indicator of normal
biologic processes, pathogenic
processes, or pharmacologic
responses to a therapeutic
intervention.”
• --Wikipedia
• preexisting ST-segment
elevation because of
ventricular aneurysm or
by Q waves
• Gastroesophageal
disease
• pacemaker rhythm
• Pulmonary embolism
• or preexisting or newly
developed bundle
branch blocks (BBB).
• Aortic aneurism
• Pericarditis, pleuritis
• Chest wall syndromes
• Herpes zoster
• Diagnosing AMI/ACS
• Detecting myocardial damage whether due to AMI or
other cardiac process
• Risk-stratifying patients
• Commenting on Prognosis
– In ACS, pre and post PCI/reperfusion therapy
– Renal Disease
• Stressing interns, confusing residents and worrying
cardiology fellows
•
•
•
•
•
•
•
CK (CPK)
CK-MB
Troponin-I/T
LD (LDH)
Myoglobin
ALT/AST
Others
Test
Most cardiac specific
Normal Range
CK or CPK
Creatinine
Phosphokinase
Normal 25-170 U/L
CK-MB
< 5% MB
Myoglobin
Normal < 85 ng/ml
LDH
(Lactate
dehydrogenase)
Normal 100-200 U/L
LDH-1 -5
LDH- 1 is found primarily in
heart muscle and red blood
cells.
Troponin
cTnT
Normal < 0.01ng/ml
May be elevated by CRF
Troponin I
cTnI
Normal < 0.1 ng/ml
Not elevated by CRF
Timing Summary
TEST
ONSET
PEAK
DURATION
CK/CK-MB
3-12 hours
18-24 hours
36-48 hours
Troponins
3-12 hours
18-24 hours
Up to 10 days
Myoglobin
1-4 hours
6-7 hours
24 hours
LDH
6-12 hours
24-48 hours
6-8 days
• Typical rise and gradual fall (troponin) or
more rapid rise and fall (CK-MB) of
biochemical markers of myocardial necrosis
with at least one of the following:
• ischemic symptoms;
• development of pathologic Q waves on the
ECG;
• ECG changes indicative of ischemia (ST
segment elevation or depression);
• coronary artery intervention (e.g., coronary
angioplasty)
• Troponin is a complex of three regulatory
proteins that is integral to non-smooth
muscle contraction in skeletal as well as
cardiac muscle
• Troponin is attached to the tropomyosin
sitting in the groove between actin filaments
in muscle tissue
• three subunits, TnC, TnT, and TnI
– Troponin-C (calcium ions)
– Troponin-T (tropomyosin)
– Troponin-I (actin)
:
– Cutoff is set at 99th percentile of a
normal reference population,
variation of less than 10%
– Since troponin levels are virtually
undetectable in normal subjects,
this 99th percentile corresponds to
<0.01(cTn T) ,0.1(cTn I)
– -heparin in sample can result in
lowered values
Troponin
Early
Rise(hrs)
Peak (Hrs)
Duration
(Days)
Specficity
Sensitivity
Tn T
3-4
10-24
10-24
80%
>98%
Tn I
4-6
1-24
4-7
95%
>98%
• Therefore it has good utility for retrospectively
diagnosing AMI
• Remember, CK-MB returns to baseline by
detectable
levels
chronic disease
even if not acute
myocardial
damage
72-96 hour
peak TI
value
infarct size
time to peak
troponin >11
hours
a lower cardiac eventfree survival rate and
with increased risk
of reinfarction
heart failure, myocarditis and pericarditis,
cardiomyopathy, cardiac contusion, defibrillation and
internal or external cardioversion,cardiac procedures
critical illnesses such as sepsis, Several toxins and
venoms, Carbon monoxide poisoning , primary pulmonary
hypertension, pulmonary embolism and acute
exacerbations of chronic obstructive pulmonary disease
(COPD), Seizures, end-stage renal disease, Strenuous
endurance exercise
• SOS
• repeated at 2 and 72 hours later
• Assay times range from 5 to
30minutes
• TAT<60 min
• cTn T >0.1 ng/ml
• cTn I >1.0 ng/ml
An immunoassay is a biochemical test that
measures the concentration of a substance in
serum or urine, using the reaction of a
specific antibody (often monoclonal Ab) or
antibodies to bind to its antigen. To determine
a numerical result (as in cardiac biomarkers),
the response of the fluid being measured
must be compared to standards of a known
concentration. One of the most common
methods is to label either the antigen or the
antibody with an enzyme (EIA), radioisotope
(RIA), magnetic labels (MIA) or fluorescence
Falsepositive
Falsenegative
heterophile
antibodies
interference of
circulating IgGclass
autoantibodies
fibrin clots
microparticles
in specimens
analyzer
malfunctions
IMA
GPBB
MPO
• Increases within 6-10 min
• Used with ECG Or troponin
• Peaks earlier than CK-MB
• More sensitive early marker
• Released from WBC granules
• Atheromatous plaque instability
RBC GP1 • Inverse
activity relationship
PAPP-A
• Eroded or
ruptured plaque
Edge over other biomarkers
• improved time dependent sensitivity and
improved specificity
• first peak value 40 times the detection limit Vs
CK-MB only 6-9 times
• prognostic value of troponin in unstable
angina,reperfusion therapy
• Corelates with infarct size
• Reducing false positives