Transcript Document

1. What is the acute coronary
syndrome? How big a health
problem is the acute coronary
syndrome?
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Progression to MI
Troponin released follows necrosis
Fatty Streak
Ruptured plaque with thrombosis
MI - Thrombus completely 2
blocking vessel
ACS Overview
AGE
Plaque Accumulation
Fatty streaks
Acute Coronary Syndromes
Troponin I or T
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Classification of different types of MI
Major Focus in Emergency Department
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Acute Coronary Syndromes
Evidence of a Major Health Problem
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500,000 CHD deaths per year
250,000 sudden deaths per year
700,000 hospitalized MIs per year
1.25 million MIs per year
6 million patients with CHD
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2. What is the preferred test for diagnosis
of myocardial infarction?
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Necrosis Biomarkers Timeline
Guidelines
sensitive
cTn Assays Highly
sensitive
cTn Assays
CK-MB
RIA
LD & CK
in MI
AST in
MI
1950
cTnT in
cTnI/cTnT
Electrophoresis WHO criteria
MI
Risk
cTnI
CK and LD
MI
Stratification
Standardization
Myoglobin
CK-MB
CK
CK-MB
Redefinition
RIA
Mass
cTnI in
isoenzymes in MI
of MI
MI
1960
1970
1980
1990
2000
2010
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Myoglobin Characteristics
Sensitivity = 90%
(95%CI: 87.8% to 93.1%)
NPV = 96%
(95%CI: 94.9% to 96.8%)
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B B
M M
Skeletal Muscle
Brain
Epitope 1
M
B
M
Hybrid
B
Epitope 2
Creatine
+
Phosphate
M B
Creatine
Phosphate
ACTIVITY
ASSAY
MASS
ASSAY
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When troponin is increased think heart
Cardiac isoforms in blood
=
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Universal Definition of Myocardial Infarction
Joint ESC/ACCF/AHA/WHF Task Force
Circulation. 2007 Nov 27;116(22):2634-53.
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3. What is the difference between
clinical performance of CK-MB and
cardiac troponin?
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CK-MB mass Metaanalysis
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Comparison of CK-MB and
Cardiac Troponin
Table 5. Studies of CK-MB and Troponin (cTn) Comparison
Positive CK-MB
Positive cTn
Characteristics
n (% )
n (% )
Acute myocardial ischemia
admissions
216 (27)
289 (36)
Possible myocardial ischemia in
emergency ward
15 (5)
34 (12)
MI discharge diagnosis plus
biomarker, ECG and pain
algorithm
4157 (28)
4661 (32)
All ACS admissions
373 (22)
430 (25)
All ACS admissions except with
diagnostic ECG of MI
23 (29)
32 (40)
% cTn
cTn/CK-MB
+ 34%
+ 127%
+ 12%
+ 15%
+ 39%
ACS indicates acute coronary syndrome
Circulation 2003;108:2543-2549
Single Biomarker Test for MI
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NACB Clinical Guidelines for ACS
2007 Clin Chem and Circulation
Class I
1. A Cardiac troponin is the preferred marker for the
diagnosis of MI. CK-MB by mass assay is an
acceptable alternative when cardiac troponin is
not available (Level of Evidence: A).
2. In patients with a clinical syndrome consistent with ACS, a
maximal (peak) concentration exceeding the 99th
percentile of values for a reference control
group should be considered indicative of increased risk
of death and recurrent ischemic events (Level of Evidence: A).
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NACB Clinical Guidelines for ACS
2007 Clin Chem and Circulation
Class I
1. Patients with suspected ACS should undergo early risk stratification
based upon an integrated assessment of symptoms,
physical exam findings, ECG findings, and
biomarkers (Level of Evidence: C).
2. Blood should be obtained for testing on hospital presentation followed
by serial sampling with timing of sampling based on the clinical
circumstances. For most patients, blood should be obtained
for testing at hospital presentation, and at 6 to 9
hours (Level of Evidence: B).
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4. How should cardiac troponin be interpreted
for diagnosis of myocardial infarction
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“Definition of MI. Criteria for acute, evolving or
recent MI.”
Typical rise and gradual fall (troponin) or
more rapid rise and fall (CK-MB) of
biochemical markers for myocardial
necrosis with at least one of the following:
– Ischemic symptoms
– Development of pathologic Q waves on ECG
– ECG changes indicative of ischemia (ST or
ST)
Thygesen K, et al, JACC 2000;36:959-969. Note: Joint ESC/ACC
Consensus Committee.
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NACB Clinical Guidelines for ACS
2007 Clin Chem and Circulation
Class I
1. A cardiac troponin is the preferred marker
for risk stratification and, if available, should
be measured in all patients with suspected
ACS. In patients with a clinical syndrome
consistent with ACS, a maximal (peak)
concentration exceeding the 99th
percentile of values for a reference
control group should be considered
indicative of increased risk of death and
recurrent ischemic events (Level of Evidence:
A).
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Universal Definition of Myocardial Infarction
Joint ESC/ACCF/AHA/WHF Task Force
Circulation. 2007 Nov 27;116(22):2634-53.
RISE AND/OR FALL OF CARDIAC BIOMARKERS (PREFERALY TROPONIN)
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5. What are some of the diagnostic specificity
problems with cardiac troponin?
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Elevated Troponin in Patients without ACS or Heart
Failure
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Acute Disease
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Cardiac and Vascular
Acute Aortic dissection
Cerebrovascular accident
Ischemic Stroke
Intracerebral Hemorrhage
Subarachnoid Hemorrhage
Medical ICU Patients
Gastrointestinal bleeding
Respiratory
Acute pulmonary embolism
ARDS
Cardiac Inflammation
Endocarditis
Myocarditis
Pericarditis
Muscular Damage
Infectious
Sepsis
Viral Ilness
Other Acute Causes of Troponin Elevation
Kawasaki disease
Apical ballooning syndrome
TTP
Rhabdomyolysis
Birth Complications in Infants
Extreme Low Birth Weight
Preterm Delivery
Acute Complications of
Inherited Disorders
Neurofibromatosis
Duchenne Muscular Dystrophy
Klippel-Feil syndrome
Environmental Exposure
Carbon Monoxide
Hydrogen Sulfide
Colchicine exposure
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Chronic Disease
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ESRD
Cardiac infiltrative disorders
Amyloidosis
Sarcoidosis
Hemochromatosis
Scleroderma
Hypertension
Diabetes
Hypothyroidism
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Iatrogenic
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Invasive Procedures
Heart Transplantation
Congenital defect repair
Radio Frequency Catheter Ablation
Lung Resection
ERCP
Non-Invasive Procedures
Cardioversion
Lithotripsy
Pharmacologic sources
Chemotherapy
Other Medications
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Myocardial Injury
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Blunt Chest Injury
Endurance athletes
Envenomation
Snake
Jellyfish
Spider
Centipede
Scorpion
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cTn at Presentation
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6. What are the differences in
performance for the between
cardiac troponin methods?
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Are All Cardiac Troponin
Assays Created Equal?
1000
NO
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Single Biomarker Test for MI
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NACB Analytical Guidelines for ACS
2007 Clin Chem and Circulation
Class I (Level of Evidence C)
Identification of antibody/epitope recognition
sites for each biomarker.
Assays for cardiac biomarkers should strive for a total imprecision
(%CV) of <10% at the 99th percentile reference limit.
Cardiac biomarker assays must be characterized with respect to potential
interferences, including rheumatoid factors, human anti-mouse
antibodies, and heterophile antibodies.
Stability (over time and across temperature ranges) for each
acceptable specimen type
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Six commercial (Hytest) mAbs evaluated
for use in a 1 x 1 “reference “immunoassay
Epitope 1
cTnC
cTnI
Epitope 2
cTnT
mAb M18
mAb 3C7
mAb 19C7
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AD GS S D A A R E P RP A P A P I R RR S S N Y RA YA T E P H A K K K S K I S A S RK L Q L K T
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L L L Q I A K Q E L E R E A E E R RG E K G R A L S T RC Q P L E L A G L G F A E L Q D L C RQ L H
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A R VD K VD E E R YD I E A K V T K N I T E I A D L TQ K I F D L RGK F K RP T L RR V R I S A
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D A MM Q A L L G A R A K E S L D L R A H L K Q V K K E D T E K E N R E V GD WR K N I D A L S GM
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EG RK K K F E S
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mAb 560
mAb 267
mAb MF4
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From IFCC Website: Accessed 7-15-09
<http://www.ifcc.org/index.asp?cat=Scientific_Activities&scat=Committees&suba=Standardisation_of_Markers_of_Cardiac_Damage_(C-SMCD)&zip=1&dove=1&numero=53>
Analytical characteristics of commercial cardiac troponin I and T assays as stated by manufacturer (version October 2008)
Company/platform/assay (generation)
LoD µg/L
99thcentile
µg/L
10% CV µg/L
Epitopes recognized by antibodies
Abbott AxSYM ADV (2nd)
0.02
0.04
0.16
C 87-91, 41-49; D 24-40
Abbott Architect
0.009
0.012
0.032
C 87-91, 24-40: D: 41-49
Abbott i-STAT
0.02
0.08#
0.10
C: 41-49, 88-91; D: 28-39,62-78
Beckman Access AccuTnI (2nd)
0.01
0.04
0.06
C; 41-49; D: 24-40.
BioMerieux Vidas TnI-Ultra (2nd)
0.01
0.01
NA
NA
Innotrac Aio!
0.012
0.023
0.036
C: 41-49,190-196; D: 137-149
<0.05 = 68%
NA
41-49 AA region0.05=11/16
Inverness Biosite Triage
C: NA; D: 27-40
Mitsubishi Chemical
0.008
0.029
NA
C: 41-49; D:71-116, 163-209
Ortho Vitros ECi (2nd)
0.012
0.034
0.034
C 24-40, 41-49; D 87-91
Response Biomedical
0.03
<0.01
0.21
NA
Roche* E170 (4th)
0.01
<0.01
0.03
C: 125-131; D: 136-147
Roche* Elecsys 2010 (4th)
0.01
<0.01
0.030
81-93
AA
region
=8/16
=
50%
Siemens Centaur TnI-Ultra (2 )
C: 125-131; D: 136-147
0.006
0.04
0.03
C; 41-49, 87-91; D: 27-40
Siemens Dimension RxL (2nd)
0.04
0.07
0.14
C: 27-32; D: 41-56
Siemens Immulite 2500 STAT
0.1
0.2
0.42
C: 87-91:D: 27-40
Siemens Immulite 1000 Turbo
0.15
NA
0.64
C: 87-91:D: 27-40
Siemens Stratus CS (2nd)
0.03
0.07
0.06
C: 27-32; D: 41-56
Siemens VISTA (2nd)
0.015
0.045
0.04
C: 27-32; D: 41-56
Tosoh AIA 21 (2nd)
0.06
<0.06
0.09
NA
nd
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NACB Analytical Guidelines for ACS
2007 Clin Chem and Circulation
Class I (Level of Evidence C)
Identification of antibody/epitope recognition sites for each
biomarker.
Assays for cardiac biomarkers should strive for
a total imprecision (%CV) of <10% at the 99th
percentile reference limit.
Cardiac biomarker assays must be characterized with respect to potential
interferences, including rheumatoid factors, human anti-mouse
antibodies, and heterophile antibodies.
Stability (over time and across temperature ranges) for each
acceptable specimen type
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Recommended Precision of Troponin
Assays at 99th Percentile Cutoff
J Am Coll Cardiol 2000;36;959-969
CV  10%
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NACB Analytical Guidelines for ACS
2007 Clin Chem and Circulation
Class I (Level of Evidence C)
Identification of antibody/epitope recognition sites for each
biomarker.
Assays for cardiac biomarkers should strive for a total imprecision
(%CV) of <10% at the 99th percentile reference limit.
Cardiac biomarker assays must be characterized with respect to
potential interferences, including rheumatoid factors,
human anti-mouse antibodies, and heterophile
antibodies.
Stability (over time and across temperature ranges) for each
acceptable specimen type
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7. Are there other conditions
where cardiac troponin is clinically
useful?
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Acute Infarction
(Hours)
Infarct Expansion
(Hours to Days)
Global Remodeling
(Days to Months)
Adapted from: Atlas of Heart Failure, 2nd Edition, Current Science, Inc, Philadelphia, PA
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Heart Failure is Huge Healthcare Issue
 Most common discharge Dx in patients > 65
years
 400,000 - 700,000 new cases yearly
 10% of individuals over 65 years
 4.7 million patients
 50% of patients are asymptomatic
 11 million office visits each year
 3.5 million hospitalizations
 250,000 deaths
 Cost exceeds 56 billion dollars
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Incidence of detectable troponin in
acute and chronic HF
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<3.00 ng/L
>12.94 ng/L
Categories
1. <3.00
2. 3.00 - 5.44 3. 5.44 - 8.16
4. 8.17 – 12.94
5. >12.94
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Conclusions
As investigators begin to understand the
relationship of detectable cTn to HF outcome…
more insight may be gained into….the transition
from chronic compensated to acute
decompensated HF. Ultimately, this information
might allow physicians to guide therapy… and
improve HF outcomes.
(J Am Coll Cardiol 2010;56:1071–8)
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