Relazione ATB '97

1
CK-MB mass assay
AMI redefined
RIA for myoglobin
cTnT in UA
INH for CK-MB
cTnI in AMI
WHO criteria for AMI
electrophoresis for CK and LD isoenzymes
cTns for risk stratific.
cTnT in AMI
AST in AMI
CK in AMI
cTns to guide therapy
1950
1960
1970
1980
1990
2000
2
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
3
GdS Intersocietario ANMCO-SIBioC-SIMeL
Marcatori di lesione miocardica
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.
Panteghini M et al. G Ital Cardiol 199929810
4
MYOCARDIAL INFARCTION REDEFINED
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
5
Elevation of Cardiac Troponins in Patients
without Overt Ischemic Heart Disease

• Trauma (including contusion,ablation,pacing,firin
  g, 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

6
Committee on Standardization of Markers of
Cardiac Damage
Use of Biochemical Markers in Acute Coronary
Syndromes
Sampling frequency
marker admission 4h 8 h 12h or next
morning early e.g. myoglobin X X (X) troponin
X X X X (X) indicates optional determination
7
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 1999371097
8
Zaninotto M et al., 1999
9
TWO MARKERS PROTOCOL- OUTCOME DATA -(Caragher
et al., Arch Pathol Lab Med 2000)
10
TWO MARKERS PROTOCOL- OUTCOME DATA -
ACS-Negative Patients
ACS-Positive Patients
Caragher et al., Arch Pathol Lab Med 2000
11
Gruppo di Studio Intersocietario ANMCO-SIBioC-SIMe
L Marcatori di lesione miocardica
Limpiego del marcatore precoce, sebbene di
principio consigliabile, può essere comunque
valutato in funzione del reale impatto che
linformazione da esso fornita (elevato valore
predittivo negativo 4 h dopo lammissione del
paziente) può ottenere sulle decisioni cliniche
relative al paziente stesso (dimissione vs
osservazione).
Panteghini M et al., G Ital Cardiol 1999
12
Committee on Standardization of Markers of
Cardiac Damage
Use of Biochemical Markers in Acute Coronary
Syndromes
Sampling frequency
For hospitals without an area for rapid ruling
out of chest pain patients (decisions are not
made within the first few hours after admission),
the following protocol is recommended marker
admission 6 h 12h or next
morning cardiac troponin X X X
13
Troponin T role in altering patient management
and enabling earlier discharge from a district
general hospital
Unstable angina pts Median length of stay
Median cost Test group 4 days
910 Control group 5 days
1125 Non-ischemic chest pain pts Test group 2
days 235 Control group 9 days
1125 Control indicates use of the
traditional enzymatic approach. Test indicates
use of cardiac troponin T protocol.
Owen A et al., Ann Clin Biochem 2001
14
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
15
Question
Answer
How much necrosis is needed to make diagnosis of
MI?
In the purest physiologic sense, any detectable
necrosis is a MI.
16
Lindahl B et al., 1996
17
FRISC-2 Study
cTnT,
g/L
lt0.01
0.01
lt0.03
0.03
lt0.10
0.10
m
³
³
³
n541
n1615
n656
n1500
n892
n1264
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
16.9

ns
P lt0.001 P lt0.01 ns not significant
Lindahl B et al., 2000
18
Risk of Death or MI at 43 Days
Baseline cTnI ?0.10 ?g/L
RR (95 CI)
Immuno-1 2.2 (1.3 - 3.6)
ACS180 2.8 (1.5 - 5.1)
RxL 3.0 (1.5 - 5.7)
Lower Risk
Higher Risk
Morrow DA et al., Clin Chem 2000
19
P lt 0.0001
P 0.0002
P 0.006
P 0.0004
P 0.0001
Events () at 43 days
P 0.009
P 0.08
P NS
P NS
ACS180
Dimension RxL
Immuno 1
20
MYOCARDIAL INFARCTION REDEFINED
An increased value for cardiac troponin should
be defined as a measurement exceeding the 99th
percentile of a reference control group.
The Joint European Society of Cardiology/ American
College of Cardiology Committee, Sept 2000
21
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
22
Imprecision around the Diagnostic Cutoff of
Troponin Assays
Assay Troponin,mg/L CV,
Abbott AxSYM
2.90
10.0
Bayer ACS180
1.33
4.1
Bayer ACSCentaur
0.52
13.0
Bayer Immuno 1
1.00
4.9
Beckman Access 2nd gen.
0.09
10.0
Biosite Triage
0.34
19.5
Dade Dimension RxL 2 gen.
0.14
11.4
Dade Opus 2nd gen.
1.70
25.6
Dade Stratus CS
0.08
14.0
BioMerieux Vidas
0.27
8.4
DPC Immulite
1.00
9.8
First Medical Alpha Dx
0.30
7.4
Ortho-Clinical Diagn. Vitros
0.35
10.0
Roche Cardiac Reader
0.33
18.0
Roche Elecsys 3rd gen.
0.11
3.6
23
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.
24
99th URL
25
Implication of troponin assay imprecision for AMI
diagnosis
Calculated
Concentration associated

th
Assay
99
URL
with a 10 CV
(AMI cutoff)
Abbott AxSYM
0.50
g/L
2.90
g/L (5.8 x URL)
m
m
0.15
g/L
1.40
m
g/L (9.3 x URL)
Bayer ACSCentaur
m
0.05
g/L
0.40
g/L (8 x URL)
Dade Behring Dimension
m
m
0.40
g/L
1.20
g/L (3 x URL)
DPC Immulite
m
m
0.10
g/L
0.35
g/L (3.5 x URL)
Ortho Vitros
m
m
Roche Elecsys
0.01
g/L
0.03
g/L (3 x URL)
m
m
Panteghini M, 2001
26
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.

27

• Firenze, 10 ottobre 2001

Incontro Nazionale su La nuova definizione di
infarto miocardico Obiettivo ottimizzare luso
dei marcatori di danno miocardico attraverso il
raggiungimento di un consenso nei comportamenti
nella pratica clinica, anche per favorire
lintroduzione della nuova definizione di IM