Download - I markers biochimici nelle CPU Learning Center Firenze 2 Ottobre 2001 Filippo Ottani, MD Bentivoglio
I markers biochimici nelle CPU
Learning CenterFirenze
2 Ottobre 2001
Filippo Ottani, MD Bentivoglio
Sospetta Ischemia Miocardica Acuta(sintomi + probabilità malattia)
ECG-12DST sopraslivellato
Ischemia ECG No Ischemia ECG
Ricovero UTIC(in base ad indicatori
clinici di rischio)
Possibile Ruolo dei Marcatori Biochimici nel Paziente con Dolore Toracico
riperfusione estensione necrosi
Ricovero Med
Marker - Marker + Marker -
Dimissione(in base a indicatoriclinico-strumentali)
Marcatori Biochimici nel Paziente con Sospetta Ischemia Miocardica
Acuta
• Diagnosi precoce di infarto miocardico acuto
• Riconoscimento rapido del paziente con angina instabile ad alto rischio
Vantaggi di una Strategia di Valutazione Basata su Marcatori
Biochimici
• Facilità di approccio al paziente
• Rapidità nella disponibilità del risultato
• Semplicità di interpretazione del dato ottenuto
• Adattabilità ad ogni contesto operativo(POC)
Marcatori Biochimici in Uso nella Diagnosi di I.M.A.
Marker PM(D)
Tempo diElevazione
(ore)
Tempo diNormalizzazione
(ore)
SpecificitàMiocardica
CK-MB 86 000 3-12 48-72 Relativa
Mioglobina 17 800 1-4 24 Assente
Isoforme CK-MB
86 000 2-6 ? (= CK-MB) Relativa
Troponina T 33 000 3-12 5-14 Assoluta
Troponina I 23 500 5-12 5-10 Assoluta
Cumulative Proportion of Patients with a Sample Above the
URL According to the Size of Infarction
De Winter et al, Circulation 1995
0
25
50
75
100
3 4 5 6 7 8 12 16 20 24
Large AMI
Mid-size AMI
Small AMI
CumulativeProportion
Time after T0 (hours)
Myo
0
25
50
75
100
3 4 5 6 7 8 12 16 20 24
Small AMI
Mid-size AMI
Large AMI
CK-MB mass
0
25
50
75
100
3 4 5 6 7 8 12 16 20 24
Small AMI
Mid-size AMI
Large AMI
cTnT
Negative Predictive Value of Several Biomarkers in a Group of Patients with Chets Pain and an AMI Probability
<75%
0
25
50
75
100
3 4 5 6 7 8 12 16 20 24
Myo
CK-MB mass
CK_MB act
cTnT
NPV
Time after T0 (hours)De Winter et al, Circulation 1995
Diagnosi Precoce di I.M.A.Diagnostic Marker Cooperative Study
995 pz con dolore toracico, 119 (12,5%) con IMAperformance diagnostica dei test a 6 ore dall’inizio dei sintomi
Zimmerman et al, Circulation 1999
0, 90 min 0, 90 min, 3 h
Sensitivity Specificity Sensitivity Specificity
Myo 84.6 (74–92) 73.0 (70–76) 84.6 (74–92) 71.1 (68–74)
CK-MB 83.1 (72–91) 83.0 (80–86) 89.2 (79–96) 81.6 (79–84)
cTnI 76.9 (65–86) 79.0 (76–82) 87.7 (77–94) 69.8 (66–73)
Myo/ CKmb 92.3 (83–98) 67.5 (64–71) 92.3 (83–98) 65.7 (62–69)
Myo/cTnI 96.9 (89–100) 59.7 (56–63) 96.9 (89–100) 53.1 (49–57)
-VE Predictive +VE Predictive -VE Predictive +VE Predictive
Value Value Value Value
Myo 98.2 (97–99) 21.4 (16–27) 98.3 (97–99) 20.4 (16–26)
CK-MB 98.3 (97–99) 29.8 (23–37) 98.9 (98–100) 29.9 (24–38)
cTnI 97.5 (96–99) 24.2 (18–31) 98.5 (97–99) 20.2 (16–25)
Myo/ CKmb 99.0 (98–100) 19.7 (15–25) 99.0 (98–100) 19.0 (15–24)
Myo/cTnI 99.6 (98–100) 17.3 (14–22) 99.5 (98–100) 15.2 (12–19)
90’ Exclusion of AMI by Use of POC Testing of Myoglobin And Troponin I
McCord, Circulation 2001; 104: 1483
SMARTT Trial: Sensitivity and Specificity for Serum Markers for AMI
Gibler WB et al, JACC 2000;36:1500
Marker Sensistivity%
Specificity %
Myoglobin 64.1 90.2
CK-MB 52.6 96.7Either myoglobin
orCK-MB
72 88.5
Survival During 30 Days Follow UP According to Troponin Status:Death or Nonfatal MI
0
60
80
90
100
70
0 10 20 30
Days
Eve
nt-
free
S
urv
ival
(%
)
Troponin I negative
Troponin T negative
Troponin I positive
Troponin T positive
ST-Segment Depression
Hamm CW, NEJM 1997;337:1648
Le Troponine nei Pazienti con Sospetta Ischemia Miocardica
Acuta(considerazioni basate sui dati di Hamm et al,
NEJM 1997)
Quesito: Risposta Motivazione
I pazienti positividevono esserericoverati in UTIC?
SI L’incidenza di morte+ IMA non-fatale è19% a 30 gg, 12%durante la degenza
I pazienti negativipossono esseremandati a casa?
NO Più del 50% deinegativi sono statiricoverati, il 30% diquesti in UTIC
Incidenza di Eventi Cardiaci Maggiori Entro 72 Ore in Pazienti con Dolore Toracico
Polanczyk et al, JACC 1998
All Pts(n=1047)
Pts with MI(n=142)
Pts withUA (n=385)
Pts withNo MI or
UA (n=520)
1 major cardiacevent
94 (9%) 37 (26%) 56 (15%) 1 (0.2%)
Cardiac arrest 7 (0.7%) 1 (0.7%) 5 (1.3%) 1 (0.2%)
High degree AVblock
1 (0.1%) 0 1 (0.3%) 0
Intubation 5 (0.5%) 2 (1.4%) 3 (0.8%) 0
IABP 26 (2%) 17 (12%) 9 (6%) 0
Coronary revasc 80 (8%) 32 (23%) 48 (13%) 0
Performance Diagnostica di Troponina I e CK-MB in Pazienti con Dolore Toracico
Polanczyk et al, JACC 1998
All Pts Pts With No MI
CTnI CK-MB CTnI CK-MB
Sensitivity 47%
(44/99)
38%
(36/94)
26%
(15/57)
5%
(3/57)
Specificity 80%(763/953)
87%(827/953)
88%(749/848)
98%(827/848)
PPV 19%(44/234)
22%(36/162)
8%
(3/38)
13%
(3/24)
NPV 94%(763/813)
93%(827/885)
95%(749/791)
94%(827/881)
RR 3.1 3.4 2.6 2.1
Uso dei Marcatori Biochimici nei Pazienti con Dolore Toracico
Polanczyk et al, Am J Cardiol 1999
Chest PainStudy Population
(n=1051)
Elevated CK-MB massST elevation on ECG
ECG with changes consistent with ischemia
Elevated troponin I
GROUP A85% (145/170)
Yes(n=170)
No (n=881)
GROUP B26% (9/35)
GROUP C13% (19/150)
GROUP D4% (26/696)
No(n=696)
Yes (n=35) No (n=150)
VALORE COMBINATO DI TROPONINA E IMAGING PERFUSIONALE
Kontos et al, Circulation 1999
92
8175
82
90
17 17
45
97
26 26
53
101010
30
0
10
20
30
40
50
60
70
80
90
100
MI Revasc Sig Dis MI or SD
67
74 74 76
96 98 98 9894 96 96 97
0
10
20
30
40
50
60
70
80
90
100
MI Revasc Sig Dis MI or SD
Tc MIBI Adm TnI TnI >2.0 TnI >1.0
SENSITIVITY SPECIFICITY
Prediction of Cardiac Events by Troponin I in Patients with Chest Pain
58 61
77
41 43
0 1
18 1712
0
10
20
30
40
50
60
70
80
90
cTnI +VE
cTnI -VE
%
MI MI/D MI/D/Sig CAD
Sig CAD Sig Comp
Kontos, JACC 2000; 36: 1818
Performance Diagnostica di Troponina I in Pazienti con Dolore Toracico
All Pts Nonischemic ECGonly
Sensitivity Specificity Sensitivity Specificity
MI 96%
(92-98)
93%
(92-94)
97%
(92-99)
94%
(93-95)
MI or death 92%
(87-95)
92%
(87-95)
90%
(84-94)
94%
(93-95)
MI/D or CAD 43%
(39-48)
95%
(94-96)
40%
(35-45)
95%
(94-96)
Complications 20%
(15-25)
96%
(95-97)
19%
(14-25)
95%
(94-96)
CAD 14%
(11-18)
95%
(94-96)
12%
(8.8-17)
95%
(94-96)
Kon
tos,
JA
CC
200
0; 3
6: 1
818
CHECKMATE30-Day Outcomes
Circ 103(14):1832, 2001 CP1000342-4
Positive Negative Positive Negative Positive Negativen=149 n=641 P n=114 n=684 P n=44 n=807 P
No. % No. % No. % No. % No. % No. %
Baseline testing
Death 3 2.0 0 0.007 2 1.8 1 0.2 0.055 0 4 0.5 1.000
MI 17.5 3.0 0.001 21.1 3.1 0.001 13.6 5.1 0.029
Revasc 14.8 5.7 0.001 18.4 5.5 0.001 25.0 7.3 <0.001
Death or MI 18.8 3.0 0.001 21.9 3.2 0.001 13.6 5.5 0.038
Death, MI, or 27.5 7.3 0.001 33.3 7.3 0.001 36.4 10.3 0.001revasc
Serial testing
Death 3 1.3 1 0.1 0.045 2 1.1 2 0.3 0.163 1 1.2 3 0.3 0.308
MI 18.0 1.7 0.001 20.0 2.2 0.001 55.3 0.9 0.001
Revasc 14.5 4.9 0.001 17.8 4.7 0.001 32.1 5.1 0.001
Death or MI 18.9 1.8 0.001 20.6 2.5 0.001 55.3 1.3 0.001
Death, MI, or 27.6 5.8 0.001 31.1 6.3 0.001 67.1 5.9 0.001
MMS-1 MMS-2 LL single marker
n=228 n=725 n=180 n=775 n=85 n=883
CHECKMATEPredictors of Death or Myocardial Infarction at 30 Days
* Log-likelihood
Circ 103(14):1832, 2001 CP1000342-5
Odds ratioWald 2 P (95% CI) Model 2* C-index
Baseline testing models
MMS-1 62.2 0.804
MMS-1 status 25.1 0.0001 5.4 (2.8-10.40)
Prior infarction 7.6 0.0060 2.7 (1.3-5.5)
Female sex 6.6 0.0104 0.38 (0.18-0.80)
Abnormal ECG 4.2 0.0396 2.0 (1.0-4.0)
MMS-2 69.9 0.823
MMS-2 status 27.6 0.0001 5.9 (3.0-11.4)
Prior infarction 8.6 0.0033 2.9 (1.4-6.0)
Female sex 8.7 0.0032 0.31 (0.14-0.68)
Diabetes 5.0 0.0247 2.3 (1.1-4.9)
Abnormal ECG 4.0 0.0446 2.0 (1.0-4.0)
CHECKMATEPredictors of Death or Myocardial Infarction at 30 Days
* Log-likelihood
Circ 103(14):1832, 2001 CP1000342-6
Odds ratioWald 2 P (95% CI) Model 2* C-index
Serial testing models
MMS-1 87.4 0.848
MMS-1 status 42.3 0.0001 9.6 (4.9-19.0)
Female sex 5.6 0.0177 0.45 (0.23-0.87)
Prior anginal pain 5.0 0.0257 2.0 (1.1-3.7)
Abnormal ECG 4.5 0.0345 2.0 (1.1-3.7)
MMS-2 80.5 0.839
MMS-2 status 42.6 0.0001 7.8 (4.2-14.4)
Female sex 6.8 0.0090 0.41 (0.21-0.80)
Prior anginal pain 6.5 0.0110 2.2 (1.2-4.0)
Abnormal ECG 5.9 0.0152 2.2 (1.2-4.1)
CHECKMATEChest Pain Duration by Baseline Marker Status
Data are median (25th, 75th percentiles)Circ 103(14):1832, 2001 CP1000342-7
Symptom onset tobaseline sample (hr)
MyoglobinPositive 4.4 (1.9, 12.5)Negative 5.5 (2.5, 11.0)
CK-MBPositive 5.6 (2.9, 11.1)Negative 5.4 (2.4, 11.6)
Troponin IPositive 6.4 (3.0, 14.3)Negative 5.3 (2.4, 11.0)
CHECKMATE-PROBLEMS•A multi-marker strategy with sensitive cut points was compared to local CKMB with ? cut points; troponin was only used if CKMB was not available. In 31 patients total CK was relied upon.
•The gold standard was CKMB elevation - no rising and falling pattern, new Q waves or if doctor diagnosed.
•Sampling was at zero, 3 and 6 hours after onset of symptoms andbeyond if in hospital - no results of those measurements.
•Myoglobin testing identified 35 ? MIs (23%) and one death.
•Troponin testing early added 2 deaths and 70 MIs and might have added more had the late data on the 4 patients with negative CKMBs who died been added.
CHECKMATE - CONCLUSIONS
•Troponin is substantially better than CKMB for diagnosis of MI and for defining prognosis.
•Cut points chosen for sensitivity work better for early detection.
•Myoglobin may identify patients with MI earlier.
Prevalenza e Significato Diagnostico delle Alterazioni ECG nel Multicenter Chest Pain Study
ECG Finding % of TotalPopulation(n=7115)
% of Patientswith MI
(n=1024)
1 mm ST or Q waves >2leads
9% (605) 45% (461)
New ischemia 1 mm, ST2 leads
7% (531) 20% (203)
Other new ST or T changes<1 mm
10% (693) 14% (147)
Old MI or ischemia 9% (644) 5% (50)
Other new or oldabnormality
16% (1147) 5% (56)
Nonspecific ST-T changes 20% (1433) 7% (72)
Normal 29 % (2062) 4% (35)
Rouan et al, AJC 1989
Relations between cTnT and CK-MB results Occurrence of long-term adverse events
de Filippi et al., JACC 35, 7; 2000:1827-34
1-year Prognosis in Patients with Chest Pain and Absence of Electrocardiographic Ischemia According
to Troponin Status
de Filippi et al., JACC 35, 7; 2000:1827-34
CONCLUSIONI• I marker biochimici permettono una valutazione rapida,
universalmente praticabile, del paziente con sospetta ischemia miocardica acuta
• La dimostrazione precoce di danno miocardico consente di individuare i pazienti con I.M.A. e la maggioranza di quelli con A.I. ad alto rischio di morte e I.M.A. non-fatale
• L’esclusione del danno miocardico non è da sola sufficiente a decidere la dimissione del paziente, dal momento che anche in assenza di danno miocardico si possono verificare complicanze gravi e diventare necessaria la rivascolarizzazione
Prognostic Value of Troponin T, Myoglobin, and CK-MB mass in Emergency Room Patients with Chest
Pain
1.00
0.75
0.500 60 180120
1.00
0.75
0.500 60 180120
1.00
0.75
0.500 60 180120
Time (d)
Time (d) Time (d)
Normal CK-MB Abnormal CK-MB Normal Myo Abnormal Myo
Normal cTnT Abnormal cTnT
% o
f E
ve
nt-
fre
e S
urv
iva
l
De Winter Heart 1996; 75:235