16
Diagnosis of AMI 1. Typical symptoms (may not be present) 2. Distinctive ECG (may not be present) 3. Abnormal blood tests Troponin-I “CK,” “CPK,” or “CK-Mb”

Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

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Page 1: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

Diagnosis of AMI

1 Typical symptoms (may not be present)

2 Distinctive ECG (may not be present)

3 Abnormal blood testsndash Troponin-Indash ldquoCKrdquo ldquoCPKrdquo or ldquoCK-Mbrdquo

Definition unstable angina

bull Unstable anginamdashan acute process of myocardial ischemia that is not of sufficient severity and duration to result in myocardial necrosis ndash Do not release biomarkers indicative of

myocardial necrosis into the blood

REQUISITI PER UN MARCATORE DI LESIONE DEL MIOCARDIO ldquoIDEALErdquo

Presente in elevate concentrazioni nel muscolo cardiaco

Contenuto unicamente nella cellula miocardica

(SPECIFICITArsquo ASSOLUTA)

Assenza dal circolo in condizioni di normalitagrave

(ESTREMAMENTE SENSIBILE E PRECISO)

Rilasciato dal muscolo cardiaco danneggiato rapidamente

in maniera completa ed in quantitarsquo proporzionale al

danno miocardico

Rilevabile nel plasma in una finestra diagnostica utile a

porre diagnosi sia precocemente che tardivamente

Validato dai trials clinici

Saggio ampiamente disponibile e poco costoso

A causa della loro scarsa sensibilitarsquo e specificitarsquo

le determinazioni di aspartato amminotransferasi (AST)

lattato deidrogenasi (LDH) totale e suoi isoenzimi

CK totale ed attivitarsquo catalitica del suo isoenzima MB

dovrebbero essere considerate come obsoletePanteghini M et al G Ital Cardiol 199929810

Tools Cardiac Markers for AMI DiagnosisCreatine Kinase MB isoenzyme (CK-MB)

Myocardial specific

4-10 hrs to achieve diagnostic performance

2-3 days to return to normal

Myoglobin 2-3 hrs to achieve diagnostic

performance24 hrs to return to normal

Not specific abundant in skeletal muscle

Troponin T or I (TnT TnI)Myocardiac specificUp to 12 hrs to achieve diagnostic

performance

Several days to return to normal

Myoglobin

Rapid riseNon-specificCannot be used alone to confirm MI

CPK-MB

15 of cardiac CPK small amount in skeletal muscle

MB-Mass Validated as marker for MIHowever Can increase after muscle injury muscular

diseases Can be found in tongue intestine

diaphragm uterus prostate

Le Troponine cardiacheLe Troponine cardiache

Sono costituite da un eterotrimero suddiviso

in 3 sub-unitagrave

bull Troponina C 18 kD deputata a legare ioni Ca++

bull Troponina I 22 kD con funzione inibitoria

bull Troponina T 37 kD con funzione di legame alla tropomiosina

Figure 1 Plot of the appearance of cardiac markers in blood vs time after onset of symptoms Peak A early release of myoglobin or CK-MB isoforms after AMI peak B cardiac troponin after AMI peak C CK-MB after AMI peak D cardiac troponin after unstable angina Data are plotted on a relative scale where 10 is set at the AMI cutoff concentration

New and old diagnostic criteria for MI

2 of 3

Elevated cardiac markers Trop or CK and CKMB

Evidence of myocardial damage as assessed by pathologic exam ECG or imaging modalityOne of

the following

WHO Criteria for Diagnosis of MI

ESC ACC Recommendations for diagnosis of MI

Chest pain

ECG changes

Serum markers

Alpert et al - ACC Consensus JACC 2000 36 959 - 969

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 2: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

Definition unstable angina

bull Unstable anginamdashan acute process of myocardial ischemia that is not of sufficient severity and duration to result in myocardial necrosis ndash Do not release biomarkers indicative of

myocardial necrosis into the blood

REQUISITI PER UN MARCATORE DI LESIONE DEL MIOCARDIO ldquoIDEALErdquo

Presente in elevate concentrazioni nel muscolo cardiaco

Contenuto unicamente nella cellula miocardica

(SPECIFICITArsquo ASSOLUTA)

Assenza dal circolo in condizioni di normalitagrave

(ESTREMAMENTE SENSIBILE E PRECISO)

Rilasciato dal muscolo cardiaco danneggiato rapidamente

in maniera completa ed in quantitarsquo proporzionale al

danno miocardico

Rilevabile nel plasma in una finestra diagnostica utile a

porre diagnosi sia precocemente che tardivamente

Validato dai trials clinici

Saggio ampiamente disponibile e poco costoso

A causa della loro scarsa sensibilitarsquo e specificitarsquo

le determinazioni di aspartato amminotransferasi (AST)

lattato deidrogenasi (LDH) totale e suoi isoenzimi

CK totale ed attivitarsquo catalitica del suo isoenzima MB

dovrebbero essere considerate come obsoletePanteghini M et al G Ital Cardiol 199929810

Tools Cardiac Markers for AMI DiagnosisCreatine Kinase MB isoenzyme (CK-MB)

Myocardial specific

4-10 hrs to achieve diagnostic performance

2-3 days to return to normal

Myoglobin 2-3 hrs to achieve diagnostic

performance24 hrs to return to normal

Not specific abundant in skeletal muscle

Troponin T or I (TnT TnI)Myocardiac specificUp to 12 hrs to achieve diagnostic

performance

Several days to return to normal

Myoglobin

Rapid riseNon-specificCannot be used alone to confirm MI

CPK-MB

15 of cardiac CPK small amount in skeletal muscle

MB-Mass Validated as marker for MIHowever Can increase after muscle injury muscular

diseases Can be found in tongue intestine

diaphragm uterus prostate

Le Troponine cardiacheLe Troponine cardiache

Sono costituite da un eterotrimero suddiviso

in 3 sub-unitagrave

bull Troponina C 18 kD deputata a legare ioni Ca++

bull Troponina I 22 kD con funzione inibitoria

bull Troponina T 37 kD con funzione di legame alla tropomiosina

Figure 1 Plot of the appearance of cardiac markers in blood vs time after onset of symptoms Peak A early release of myoglobin or CK-MB isoforms after AMI peak B cardiac troponin after AMI peak C CK-MB after AMI peak D cardiac troponin after unstable angina Data are plotted on a relative scale where 10 is set at the AMI cutoff concentration

New and old diagnostic criteria for MI

2 of 3

Elevated cardiac markers Trop or CK and CKMB

Evidence of myocardial damage as assessed by pathologic exam ECG or imaging modalityOne of

the following

WHO Criteria for Diagnosis of MI

ESC ACC Recommendations for diagnosis of MI

Chest pain

ECG changes

Serum markers

Alpert et al - ACC Consensus JACC 2000 36 959 - 969

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 3: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

REQUISITI PER UN MARCATORE DI LESIONE DEL MIOCARDIO ldquoIDEALErdquo

Presente in elevate concentrazioni nel muscolo cardiaco

Contenuto unicamente nella cellula miocardica

(SPECIFICITArsquo ASSOLUTA)

Assenza dal circolo in condizioni di normalitagrave

(ESTREMAMENTE SENSIBILE E PRECISO)

Rilasciato dal muscolo cardiaco danneggiato rapidamente

in maniera completa ed in quantitarsquo proporzionale al

danno miocardico

Rilevabile nel plasma in una finestra diagnostica utile a

porre diagnosi sia precocemente che tardivamente

Validato dai trials clinici

Saggio ampiamente disponibile e poco costoso

A causa della loro scarsa sensibilitarsquo e specificitarsquo

le determinazioni di aspartato amminotransferasi (AST)

lattato deidrogenasi (LDH) totale e suoi isoenzimi

CK totale ed attivitarsquo catalitica del suo isoenzima MB

dovrebbero essere considerate come obsoletePanteghini M et al G Ital Cardiol 199929810

Tools Cardiac Markers for AMI DiagnosisCreatine Kinase MB isoenzyme (CK-MB)

Myocardial specific

4-10 hrs to achieve diagnostic performance

2-3 days to return to normal

Myoglobin 2-3 hrs to achieve diagnostic

performance24 hrs to return to normal

Not specific abundant in skeletal muscle

Troponin T or I (TnT TnI)Myocardiac specificUp to 12 hrs to achieve diagnostic

performance

Several days to return to normal

Myoglobin

Rapid riseNon-specificCannot be used alone to confirm MI

CPK-MB

15 of cardiac CPK small amount in skeletal muscle

MB-Mass Validated as marker for MIHowever Can increase after muscle injury muscular

diseases Can be found in tongue intestine

diaphragm uterus prostate

Le Troponine cardiacheLe Troponine cardiache

Sono costituite da un eterotrimero suddiviso

in 3 sub-unitagrave

bull Troponina C 18 kD deputata a legare ioni Ca++

bull Troponina I 22 kD con funzione inibitoria

bull Troponina T 37 kD con funzione di legame alla tropomiosina

Figure 1 Plot of the appearance of cardiac markers in blood vs time after onset of symptoms Peak A early release of myoglobin or CK-MB isoforms after AMI peak B cardiac troponin after AMI peak C CK-MB after AMI peak D cardiac troponin after unstable angina Data are plotted on a relative scale where 10 is set at the AMI cutoff concentration

New and old diagnostic criteria for MI

2 of 3

Elevated cardiac markers Trop or CK and CKMB

Evidence of myocardial damage as assessed by pathologic exam ECG or imaging modalityOne of

the following

WHO Criteria for Diagnosis of MI

ESC ACC Recommendations for diagnosis of MI

Chest pain

ECG changes

Serum markers

Alpert et al - ACC Consensus JACC 2000 36 959 - 969

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 4: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

A causa della loro scarsa sensibilitarsquo e specificitarsquo

le determinazioni di aspartato amminotransferasi (AST)

lattato deidrogenasi (LDH) totale e suoi isoenzimi

CK totale ed attivitarsquo catalitica del suo isoenzima MB

dovrebbero essere considerate come obsoletePanteghini M et al G Ital Cardiol 199929810

Tools Cardiac Markers for AMI DiagnosisCreatine Kinase MB isoenzyme (CK-MB)

Myocardial specific

4-10 hrs to achieve diagnostic performance

2-3 days to return to normal

Myoglobin 2-3 hrs to achieve diagnostic

performance24 hrs to return to normal

Not specific abundant in skeletal muscle

Troponin T or I (TnT TnI)Myocardiac specificUp to 12 hrs to achieve diagnostic

performance

Several days to return to normal

Myoglobin

Rapid riseNon-specificCannot be used alone to confirm MI

CPK-MB

15 of cardiac CPK small amount in skeletal muscle

MB-Mass Validated as marker for MIHowever Can increase after muscle injury muscular

diseases Can be found in tongue intestine

diaphragm uterus prostate

Le Troponine cardiacheLe Troponine cardiache

Sono costituite da un eterotrimero suddiviso

in 3 sub-unitagrave

bull Troponina C 18 kD deputata a legare ioni Ca++

bull Troponina I 22 kD con funzione inibitoria

bull Troponina T 37 kD con funzione di legame alla tropomiosina

Figure 1 Plot of the appearance of cardiac markers in blood vs time after onset of symptoms Peak A early release of myoglobin or CK-MB isoforms after AMI peak B cardiac troponin after AMI peak C CK-MB after AMI peak D cardiac troponin after unstable angina Data are plotted on a relative scale where 10 is set at the AMI cutoff concentration

New and old diagnostic criteria for MI

2 of 3

Elevated cardiac markers Trop or CK and CKMB

Evidence of myocardial damage as assessed by pathologic exam ECG or imaging modalityOne of

the following

WHO Criteria for Diagnosis of MI

ESC ACC Recommendations for diagnosis of MI

Chest pain

ECG changes

Serum markers

Alpert et al - ACC Consensus JACC 2000 36 959 - 969

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 5: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

Tools Cardiac Markers for AMI DiagnosisCreatine Kinase MB isoenzyme (CK-MB)

Myocardial specific

4-10 hrs to achieve diagnostic performance

2-3 days to return to normal

Myoglobin 2-3 hrs to achieve diagnostic

performance24 hrs to return to normal

Not specific abundant in skeletal muscle

Troponin T or I (TnT TnI)Myocardiac specificUp to 12 hrs to achieve diagnostic

performance

Several days to return to normal

Myoglobin

Rapid riseNon-specificCannot be used alone to confirm MI

CPK-MB

15 of cardiac CPK small amount in skeletal muscle

MB-Mass Validated as marker for MIHowever Can increase after muscle injury muscular

diseases Can be found in tongue intestine

diaphragm uterus prostate

Le Troponine cardiacheLe Troponine cardiache

Sono costituite da un eterotrimero suddiviso

in 3 sub-unitagrave

bull Troponina C 18 kD deputata a legare ioni Ca++

bull Troponina I 22 kD con funzione inibitoria

bull Troponina T 37 kD con funzione di legame alla tropomiosina

Figure 1 Plot of the appearance of cardiac markers in blood vs time after onset of symptoms Peak A early release of myoglobin or CK-MB isoforms after AMI peak B cardiac troponin after AMI peak C CK-MB after AMI peak D cardiac troponin after unstable angina Data are plotted on a relative scale where 10 is set at the AMI cutoff concentration

New and old diagnostic criteria for MI

2 of 3

Elevated cardiac markers Trop or CK and CKMB

Evidence of myocardial damage as assessed by pathologic exam ECG or imaging modalityOne of

the following

WHO Criteria for Diagnosis of MI

ESC ACC Recommendations for diagnosis of MI

Chest pain

ECG changes

Serum markers

Alpert et al - ACC Consensus JACC 2000 36 959 - 969

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 6: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

Myoglobin

Rapid riseNon-specificCannot be used alone to confirm MI

CPK-MB

15 of cardiac CPK small amount in skeletal muscle

MB-Mass Validated as marker for MIHowever Can increase after muscle injury muscular

diseases Can be found in tongue intestine

diaphragm uterus prostate

Le Troponine cardiacheLe Troponine cardiache

Sono costituite da un eterotrimero suddiviso

in 3 sub-unitagrave

bull Troponina C 18 kD deputata a legare ioni Ca++

bull Troponina I 22 kD con funzione inibitoria

bull Troponina T 37 kD con funzione di legame alla tropomiosina

Figure 1 Plot of the appearance of cardiac markers in blood vs time after onset of symptoms Peak A early release of myoglobin or CK-MB isoforms after AMI peak B cardiac troponin after AMI peak C CK-MB after AMI peak D cardiac troponin after unstable angina Data are plotted on a relative scale where 10 is set at the AMI cutoff concentration

New and old diagnostic criteria for MI

2 of 3

Elevated cardiac markers Trop or CK and CKMB

Evidence of myocardial damage as assessed by pathologic exam ECG or imaging modalityOne of

the following

WHO Criteria for Diagnosis of MI

ESC ACC Recommendations for diagnosis of MI

Chest pain

ECG changes

Serum markers

Alpert et al - ACC Consensus JACC 2000 36 959 - 969

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 7: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

CPK-MB

15 of cardiac CPK small amount in skeletal muscle

MB-Mass Validated as marker for MIHowever Can increase after muscle injury muscular

diseases Can be found in tongue intestine

diaphragm uterus prostate

Le Troponine cardiacheLe Troponine cardiache

Sono costituite da un eterotrimero suddiviso

in 3 sub-unitagrave

bull Troponina C 18 kD deputata a legare ioni Ca++

bull Troponina I 22 kD con funzione inibitoria

bull Troponina T 37 kD con funzione di legame alla tropomiosina

Figure 1 Plot of the appearance of cardiac markers in blood vs time after onset of symptoms Peak A early release of myoglobin or CK-MB isoforms after AMI peak B cardiac troponin after AMI peak C CK-MB after AMI peak D cardiac troponin after unstable angina Data are plotted on a relative scale where 10 is set at the AMI cutoff concentration

New and old diagnostic criteria for MI

2 of 3

Elevated cardiac markers Trop or CK and CKMB

Evidence of myocardial damage as assessed by pathologic exam ECG or imaging modalityOne of

the following

WHO Criteria for Diagnosis of MI

ESC ACC Recommendations for diagnosis of MI

Chest pain

ECG changes

Serum markers

Alpert et al - ACC Consensus JACC 2000 36 959 - 969

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
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  • Slide 11
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  • Slide 15
  • Slide 16
Page 8: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

Le Troponine cardiacheLe Troponine cardiache

Sono costituite da un eterotrimero suddiviso

in 3 sub-unitagrave

bull Troponina C 18 kD deputata a legare ioni Ca++

bull Troponina I 22 kD con funzione inibitoria

bull Troponina T 37 kD con funzione di legame alla tropomiosina

Figure 1 Plot of the appearance of cardiac markers in blood vs time after onset of symptoms Peak A early release of myoglobin or CK-MB isoforms after AMI peak B cardiac troponin after AMI peak C CK-MB after AMI peak D cardiac troponin after unstable angina Data are plotted on a relative scale where 10 is set at the AMI cutoff concentration

New and old diagnostic criteria for MI

2 of 3

Elevated cardiac markers Trop or CK and CKMB

Evidence of myocardial damage as assessed by pathologic exam ECG or imaging modalityOne of

the following

WHO Criteria for Diagnosis of MI

ESC ACC Recommendations for diagnosis of MI

Chest pain

ECG changes

Serum markers

Alpert et al - ACC Consensus JACC 2000 36 959 - 969

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 9: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

Figure 1 Plot of the appearance of cardiac markers in blood vs time after onset of symptoms Peak A early release of myoglobin or CK-MB isoforms after AMI peak B cardiac troponin after AMI peak C CK-MB after AMI peak D cardiac troponin after unstable angina Data are plotted on a relative scale where 10 is set at the AMI cutoff concentration

New and old diagnostic criteria for MI

2 of 3

Elevated cardiac markers Trop or CK and CKMB

Evidence of myocardial damage as assessed by pathologic exam ECG or imaging modalityOne of

the following

WHO Criteria for Diagnosis of MI

ESC ACC Recommendations for diagnosis of MI

Chest pain

ECG changes

Serum markers

Alpert et al - ACC Consensus JACC 2000 36 959 - 969

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 10: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

New and old diagnostic criteria for MI

2 of 3

Elevated cardiac markers Trop or CK and CKMB

Evidence of myocardial damage as assessed by pathologic exam ECG or imaging modalityOne of

the following

WHO Criteria for Diagnosis of MI

ESC ACC Recommendations for diagnosis of MI

Chest pain

ECG changes

Serum markers

Alpert et al - ACC Consensus JACC 2000 36 959 - 969

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 11: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

Cardiac Analyzer 2nd and 3rd Specimens 6hrs and 12hrs

Second or third specimen

Measure CKMB

Previous

Troponin gt

99th percentile

Measure

troponin

Troponin

gt 30 ngml

Cancel remaining tests

Continue

test algorithm

No

Yes

Yes

Delta

CKMB gt 20

No Measure

troponin

Yes

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 12: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

The Future

bull Early indicators of plaque instability

bull Early indicators of thrombotic activity

bull Markers for IIbIIIa sensitivity

bull Indicators of cytokine activation

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 13: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

Technology in the Future Family of Near-Patient Diagnostic Sensors

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 14: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

Human protein P05413 - Fatty acid-binding protein heart (H-FABP) (Heart-type fatty acid- binding protein) (Muscle fatty acid-binding protein) (M-FABP) (Mammary-derived growth inhibitor) (MDGI) EMBL

Normalized expression distribution for tissue type Top ten

Tissue Normalized

Expression () Cluster Clones

Tissue clones Heart 3995 1335504

Muscle 2162 1890826

Lung 814 17227901

Uterus 594 7128533

Peripheral_Nervous_System 519 121019

Testis 507 5107669

Kidney 287 3113979

Brain 239 7319574

Bone 213 151252

Prostate 113 196523

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16
Page 15: Diagnosis of AMI 1.Typical symptoms (may not be present) 2.Distinctive ECG (may not be present) 3.Abnormal blood tests –Troponin-I –“CK,” “CPK,” or “CK-Mb”

Tools FABP in AMI Diagnosis

FABP CharacteristicsSmall cytoplasmic protein abundant in heart and muscle

Cardiac specific isoforms

Normal levels below 1ngml

Most sensitive early cardiac marker

lt3 hrs to achieve diagnostic performance

12-24 hrs to return to normal

  • Slide 1
  • Slide 2
  • Slide 3
  • Slide 4
  • Slide 5
  • Slide 6
  • Slide 7
  • Slide 8
  • Slide 9
  • Slide 10
  • Slide 11
  • Slide 12
  • Slide 13
  • Slide 14
  • Slide 15
  • Slide 16