1950196019701980 1990 2000 ast in ami ck in ami electrophoresis for ck and ld isoenzymes inh for...
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1950
1960
1970
1980
1990
2000
AST in
AMI
CK in AMI
electrophoresis for CK
and LD isoenzymes
INH for CK-MB
RIA for myoglobin
WHO criteria for AMI
CK-MB mass assay
cTnT in AMI
cTnT in UA
cTnI in AMI
cTns to guide therapy
cTns for risk stratific.
AMI redefined
Biochemical Markers for Detecting Myocardial Necrosis
1) Maximal concentration of troponin T or I exceeding the 99th percentile of the reference values on at least one occasion during the first 24 h after the clinical event.
2) Maximal value of CK-MB (preferably CK-MB mass) exceeding the 99th percentile of the reference values on two successive samples, or maximal value exceeding twice the upper reference limit on one occasion during the first hours after the clinical event. Values for CK-MB should rise and fall.
The Joint European Society of Cardiology/American College of Cardiology Committee, September 2000
A causa della loro scarsa sensibilita’ e specificita’,
le determinazioni di aspartato amminotransferasi (AST),
lattato deidrogenasi (LDH) totale e suoi isoenzimi,
CK totale e attivita’ catalitica del suo isoenzima MB
dovrebbero essere considerate come obsolete.
GdS Intersocietario ANMCO-SIBioC-SIMeL “Marcatori di lesione miocardica”
Panteghini M et al. G Ital Cardiol 1999;29:810
MYOCARDIAL INFARCTION MYOCARDIAL INFARCTION REDEFINEDREDEFINED
MYOCARDIAL INFARCTION MYOCARDIAL INFARCTION REDEFINEDREDEFINED
The term “Myocardial
Infarction” should be used
when evidence of cardiac
damage exists, as detected by
cardiac proteins in a clinical
setting consistent with
myocardial ischemia.The Joint European Society of Cardiology/American College of Cardiology Committee, Sept 2000
Trauma (including contusion,ablation,pacing,firing, cardioversion,cardiac surgery)
Congestive heart failure Hypertension Hypotension, often with arrhythmias Postoperative non-cardiac surgery Chronic renal failure Critically ill patients, esp. with diabetes Hypothyroidism Myocarditis Post percutaneous coronary interventions Pulmonary embolism Sepsis Amyloidosis Cardiotoxicity from cancer therapy
Elevation of Cardiac Troponins in Patients without Overt Ischemic Heart Disease
Use of Biochemical Markers in Acute Coronary Syndromes
Sampling Sampling frequencyfrequency
marker marker admissionadmission +4h+4h +8 h +8 h +12h +12h or next morningor next morning
early early e.g. myoglobine.g. myoglobin XX XX (X)(X)
troponin troponin XX XX XX XX
(X) indicates optional determination(X) indicates optional determination
Committee on Standardization of Markers of Cardiac Damage
“Myoglobin is at present the most sensitive marker for
excluding early AMI with an optimum timing of sampling at
patient presentation and approx. 4 h later.”
Panteghini M et al.The sensitivity of cardiac markers: an evidence-based
approach.Clin Chem Lab Med 1999;37:1097
Disease Prevalence
0.0 0.2 0.4 0.6 0.8 1.0
Perf
orm
ance
Mea
sure
Val
ue
0.0
0.2
0.4
0.6
0.8
1.0
Disease Prevalence
0.0 0.2 0.4 0.6 0.8 1.0Pe
rfor
man
ce M
easu
re V
alue
0.0
0.2
0.4
0.6
0.8
1.0CK-MB Myoglobin +
Troponin
Pos Predictive Value
Neg Predictive Value
Accuracy
Zaninotto M et al., 1999
TWO MARKERS PROTOCOL- OUTCOME DATA -
(Caragher et al., Arch Pathol Lab Med 2000)
Number of patients discharged in <24 h
Control group Test group 20 of 71 41 of 81 28% 50.6% P = 0.0048
Number of patients discharged in <12 h
Control group Test group 16 of 71 30 of 81 22% 37% P = 0.0522
TWO MARKERS PROTOCOL- OUTCOME DATA -
Group Age Sex LOS # LabProc
TotalCost
LabCost
Control 64.4 M, 35F, 38
2.02 14.7 $ 2019 $ 189
Test 63.8 M, 39F, 42
1.62 12.3 $ 1635 $ 158
Control 69.0 M, 10F, 9
5.69 36.0 $ 7425 $ 462
Test 74.4 M, 7F, 8
4.56 23.6 $ 5164 $ 303
ACS-Negative Patients
ACS-Positive Patients
Caragher et al., Arch Pathol Lab Med 2000
L’impiego del marcatore precoce, sebbene di principio
consigliabile, può essere comunque valutato in funzione
del reale impatto che l’informazione da esso fornita
(elevato valore predittivo negativo 4 h dopo l’ammissione
del paziente) può ottenere sulle decisioni cliniche relative
al paziente stesso (dimissione vs osservazione).
Gruppo di Studio IntersocietarioANMCO-SIBioC-SIMeL “Marcatori di lesione miocardica”
Panteghini M et al., G Ital Cardiol 1999
Use of Biochemical Markers in Acute Coronary Syndromes
Sampling Sampling frequencyfrequency
Committee on Standardization of Markers of Cardiac Damage
For hospitals without an area for rapid ruling out of For hospitals without an area for rapid ruling out of chest pain patients (decisions are not made within chest pain patients (decisions are not made within the first few hours after admission), the following the first few hours after admission), the following protocol is recommended:protocol is recommended:
marker marker admission admission +6 h +6 h +12h +12h or next morning or next morning
cardiac troponin cardiac troponin X X X X XX
Owen A et al., Ann Clin Biochem 2001
Troponin T: role in altering patient management and enabling earlier discharge from a district general
hospital
Unstable angina pts Median length of stay Median costTest group 4 days £ 910Control group 5 days £ 1125
Non-ischemic chest pain ptsTest group 2 days £ 235Control group 9 days £ 1125
“Control” indicates use of the traditional enzymatic approach.“Test” indicates use of cardiac troponin T protocol.
Rate of inaccurate estimation
of interval between onset of
symptoms and admission in
patients with AMI = 15%
Bholasingh R, De Winter RJ, Nieuwenhuijs AB, Sanders GT. Proceedings of “The Challenge of Acute Coronary Syndromes” - The Lancet Conference. Copenhagen, 1999
Question
How much necrosis is needed to make diagnosis of MI?
In the purest physiologic sense, any detectable necrosis is a MI.
Answer
Cardiac death or MI, %
Time from inclusion (days)
Troponin T, g/L
> 0.62< 0.62
< 0.18
< 0.06
160140120100806040200
48
121620
24
Lindahl B et al., 1996
FRISC-2 StudyFRISC-2 Study
Lindahl B et al., 2000
cTnT, g/L <0.01 0.01 <0.03 0.03 <0.10 0.10
n=541 n=1615 n=656 n=1500 n=892n=1264
12-m death, % 1.7 5.9 * 2.7 5.7 ** 3.4 5.9 **
12-m death/AMI, % 8.5 18.0 * 10.2 17.9 * 13.8 16.9ns
* P <0.001; ** P <0.01; ns = not significant
0.1 1 10
Morrow DA et al., Clin Chem 2000
Risk of Death or MI at 43 Days
Lower Risk Higher Risk
Immuno-1 2.2 (1.3 - 3.6)
ACS:180 2.8 (1.5 - 5.1)
RxL 3.0 (1.5 - 5.7)
RR (95% CI)
Baseline cTnI 0.10 g/L
0
5
10
15
20
Dea
th MI
D o
r M
I
Dea
th MI
D o
r M
I D
MI
D o
r M
I
cTnI Negative
cTnI Positive
Dimension RxL
ACS:180 Immuno 1
Even
ts (
%)
at
43 d
ays
P = NS
P = 0.0001
P = 0.0002
P = 0.08
P = 0.0004
P < 0.0001
P = NS
P = 0.009
P = 0.006
“An increased value for cardiac
troponin should be defined as a
measurement exceeding the
99th percentile of a reference
control group.”
MYOCARDIAL INFARCTION REDEFINEDMYOCARDIAL INFARCTION REDEFINEDMYOCARDIAL INFARCTION REDEFINEDMYOCARDIAL INFARCTION REDEFINED
The Joint European Society of Cardiology/American College of Cardiology Committee, Sept 2000
Committee on Standardization of Markers of Cardiac Damage
Recommendation: A total CV of less than
10% at the myocardial infarction
decision limit is recommended. This
should provide an objective target for
manufacturers of instruments and kits in
the construction of new assays.Panteghini M et al., Quality specifications for
cardiac troponin. Clin Chem Lab Med 2001
Imprecision around the Diagnostic Cutoff of Troponin Assays
Assay Troponin,g/L CV,% Abbott AxSYM 2.90 10.0
Bayer ACS:180 1.33 4.1Bayer ACS:Centaur 0.52 13.0Bayer Immuno 1 1.00 4.9
Beckman Access 2nd gen. 0.09 10.0Biosite Triage 0.34 19.5
Dade Dimension RxL 2 gen. 0.14 11.4Dade Opus 2nd gen. 1.70 25.6Dade Stratus CS 0.08 14.0 BioMerieux Vidas 0.27 8.4DPC Immulite 1.00 9.8First Medical Alpha Dx 0.30 7.4Ortho-Clinical Diagn. Vitros 0.35 10.0Roche Cardiac Reader 0.33 18.0Roche Elecsys 3rd gen. 0.11 3.6
In the context of clinical
practice:
For troponin assays that cannot meet the 10% CV recommendation at the 99th percentile, a predetermined higher concentration that meets the goal of 10% imprecision should be used as AMI cutoff until the goal of a 10% CV can be achieved at the 99th percentile.
0
10
20
30
40
0 0.01 0.02 0.03 0.04 0.05 0.06 0.07 0.08 0.09 0.1
Cardiac troponin concentration
CV,
%
Assay AAssay B
99th URL
Implication of troponin assay imprecision for AMI diagnosis
Assay
Calculated
99th URL
(AMI cutoff)
Concentration associated
with a 10% CV
Abbott AxSYM 0.50 g/L 2.90g/L (5.8 x URL)
Bayer ACS:Centaur 0.15 g/L 1.40 g/L (9.3 x URL)
Dade Behring Dimension 0.05 g/L 0.40 g/L (8 x URL)
DPC Immulite 0.40 g/L 1.20 g/L (3 x URL)
Ortho Vitros 0.10 g/L 0.35 g/L (3.5 x URL)
Roche Elecsys 0.01 g/L 0.03 g/L (3 x URL)
Panteghini M, 2001
BIOCHEMICAL MARKERS IN ST-SEGMENT ELEVATION MYOCARDIAL INFARCTION
In these patients, biochemical markers may be useful:
1. to qualitatively estimate the MI size,
2. for early stratification of the subsequent risk, 3. to predict rate of failed primary PCI,
4. to detect the presence of complications such as re-infarction,
5. to monitor thrombolytic therapy.
These applications are however optional and not definitively supported by scientific evidence.
Firenze, 10 ottobre 2001
Incontro Nazionale su “La nuova
definizione di infarto miocardico”
Obiettivo: ottimizzare l’uso dei marcatori di
danno miocardico attraverso il
raggiungimento di un consenso nei
comportamenti nella pratica clinica, anche
per favorire l’introduzione della nuova
definizione di IM