ACS talk prepared Y2008 - emphasis on diagnosis of AMI and ACS via use of biomarkers.

1. Acute Coronary
Syndrome
Frank W Meissner, MD, RDMS, FACP, FACC, FCCP, CPHIMS, CCDS

2. Ruptured Plaque
Thrombus
Inflammatory
Cells
Few
SMCs
Activated
Macrophages

3. Sheer Force - Engine of Plaque Rupture
The Mattress Analogy
Jump from 10 ft Step Ladder
Box Mattress
Water Mattress
Unstable plaque has semi-liquid
cholesterol core

4. ACS Pathophysiology
Plaque rupture, thrombosis and microembolization
Plaque rupture Platelet-thrombin micro-emboli Inflammation, spasm
endothelial dysfunction
Thrombus
Cutoff TnT Curve
CK-MB
CK-MB Microvascular
CK-MB
1st 2nd 3rd Obstruction
embolus embolus embolus

5. ACS Risk Assessment
Effective Triage Tx to Tertiary Center
Early Risk
Assessment
Early Choice of
Revascularization Medical Therapy
Inform Patient and Family

6. Risk Stratification-ACS
Clinical Features
ECG
Troponin I or T
Inflammatory Markers
Renal Dysfunction
Novel Markers

7. High Risk Features I
Chest Pain
Prolonged rest pain >10 min
Recurrent Pain esp accelerated
tempo in preceding 48hrs
Rest angina not relieved by nitrates
Early post infarction angina

8. High Risk Features II
Hemodynamic Instability
(Systolic blood pressure <90mmHg,
cool periphery, diaphoresis)
Associated Heart Failure, Mitral
Regurgitation or Gallop Rhythm
Associated Syncope

9. High Risk Features III
Poor LV function
Previous Revascularisation (PCI,CABG)
Prior Aspirin Treatment
Diabetes
Renal Dysfunction

10. Killip Classification of AMI
I
No signs of heart failure or pump failure
II
Lung crackles, S3, elevated jugular venous pressure
III
Frank pulmonary edema
IV
Cardiogenic shock (BP <90 mmHg) + peripheral vasoconstriction
Killip T, and Kimball JT: Treatment of myocardial infarction in a coronary care unit: a two year experience of 250 patients.
American Journal of Cardiology 1967; 20: 457-464.

11. Low Risk Features
Nature of Pain
No Recurrence of Chest pain During
Observation
Exertional Symptoms Only
Few Risk Factors

12. Baseline ECG & Outcome
Six-Month Mortality
10%
ST ↓
8%
ST ↑
Mortality
6%
4% T-wave
2% inversion
0%
0 30 60 90 120 150 180
Days from Randomization

13. EKG High Risk Features
Dynamic ST changes esp ST depression
Transient ST Elevation
T inversion> 0.2 mv
Q waves
Bundle branch block
Ventricular Tachycardia

14. Value of EKG in ACS
(+) EKG = evidence of infarction, ischemia, or strain;
left ventricular hypertrophy; left bundle-branch block; or paced rhythm.

15. Troponin Structure/Function
•Troponin T (39.7 Kd) binds troponin complex to tropomyosin strand
•Troponin C (18 Kd) binds calcium and initiates contraction
•Troponin I (22.5 Kd) inhibits contraction in the resting state

16. Diagnostic Performance
Post
Troponin I CK-MB
AMI
Incr 4-6 hr 4-6 hr
Pk 14-24 hr 10-24 hr
Nml 5-7 d 2-3 d

17. Diagnostic Performance
Sensitivity Troponin I CK-MB Myo
0-2 hr 25% 7% 22%
2-4 hr 70% 12% 27%
4-6 hr - 73% 81%
6-8 hr 96% 90% 95%

18. Diagnostic Performance
Specificity Troponin I CK-MB Myo
0-2 hr 100% 100% 92%
2-4 hr 100% 93% 80%
4-6 hr - 95% 70%
6-8 hr 99% 90% 50%

19. Prognostic Value of Pos. Troponin T in ACS
est
RR 3.8
30.0
(2.6-5.5)
22.5
% RR 3.9
15.0
(2.9-5.3)
7.5
0 322
3634 1849 737
Death Death/MI
Neg
Column 1
Pos (Trop I + T)
Column 2

20. Cardiac Marker Release Patterns
50
Myoglobin
CK-MB
15 Troponin T or I
LD1
Multiples
of 10
Upper
Reference
5
Limit
Normal Range
0 1 2 3 4 5 6 7 10
Days After Onset of AMI
Wu, A. H., Journal of Clinical Immunoassay 1994;17, 45-48

21. Etiologies for Troponin Elevation
TROPONIN
False +ve
AMI NSTEMI (e.g. heterophilic antibodies)
Clinical Chemistry 44: 2212-2214, 1998.
False Increase of Cardiac Troponin I with Heterophilic Antibodies. Fitzmaurice, TF et al.
Pericarditis
Iatrogenic
Pulmonary Embolism
•Cardiac Surgery
Sepsis Shock
•PCI
Acute LVF
•Cardioversion
Trauma
•Cardiotoxin Drugs
Hypertension/Hypotension
•EP Ablation
Drug T oxicity
Jeremias A & Gibson M. Narrative Review: Alternative Causes for Elevated Cardiac Troponin Levels when Acute
Coronary Syndromes Are Excluded. Ann Int Med. 142(9); 786-791. 2005

22. Diagnosis MI?
Biomarker indicators of MI
Troponin is preferred biomarker for Dx of MI
cTnT or cTnI > 99th %ile on any determination
CK-MB > 99th %ile on two successive
measurements or > 2X ULN on any sample
ESC/ACC Consensus – J Am Coll Cardiol 2000; 36: 959-69

23. Pulmonary Embolism Troponin T
Time-Release Curve
Time-release curve of cTnT (µg/L) in nine
patients with confirmed PE who developed a
cTnT ≥0.1 µg/L (A) and 6 patients with
microinfarction (B)
Muller-Bardorff et al. Clin
Chem 48 (4): 673

24. Troponin Level & Survival
Three-year Kaplan-
Meier curves for
group 1 versus group
2 patients
Perna et al. Am Heart J 2002:143: 814-20

25. Prob of Death ƒ(creaClr & Troponin T level)
Aviles et al. N Engl J Med 2002;346:2047-2052

26. CRP & outcome by quartiles
15.00 N=272
*χ2 for trend <0.001
N=287
11.25
*
N=263 14.5%
7.50
11.5%
N=262
3.75 8.0% *2.6%
5.3%
0.3%
0
<0.3mg/dL 0.3-0.5mg/dL 0.5-1.1mg/dL >1.1mg/dL
Death Death/MI

27. “Time is Myocardium”
Ischemia Infarction
Ischemia
Necrosis
AMI = Ischemia + Necrosis
100%
Acute chest pain
Remaining
% Muscle
Lost Muscle
Infarct
50%
Shortness of breath
ECG changes 0%
Before Infarct After Infarct

28. “Time is Myocardium”
Ischemia Infarction
Ischemia
Necrosis
AMI = Ischemia + Necrosis
100%
Acute chest pain
Remaining
% Muscle
Lost Muscle
Infarct
50%
Shortness of breath
ECG changes 0%
Before Infarct After Infarct

29. What is IMA?
Human Serum Albumin (HSA) is
a circulating protein in blood with a metal
binding site at the N-terminus.
The N-terminus is damaged during an ischemic event, resulting
in Ischemia Modified Albumin (IMA™). IMA is unable to bind
metals at the N-terminus.
Bar Or et al, European Journal of Biochemistry, 2001

30. BNP & ACS
Natriuretic peptides in unstable coronary artery disease: Review
Jernberg T, et al., European Heart Journal; 17(25): 1486-93, 2004.

31. Lethal Chest Pain I
AMI
Unstable Angina
Pulmonary Embolism
Critical Aortic Stenosis
IHSS
Pericarditis with Tamponade
Aortic Dissection

32. Lethal Chest Pain II
Spontaneous Tension Pneumothorax
Pneumomediastinum
Decompression Sickness (‘Chokes’)
Lymphoma
1° PAH
Oncological Disease - Met to T-spine

33. Lethal Chest Pain III
Boerhauve’s Syndrome
Acute Cholecystitis
Acute Pancreatitis
Perforated Gastric Ulcer
Ruptured Viscus
Bowel Infarction

34. Non-life Threatening
Barlowe’s Syndrome
Pericarditis without tamponade
Pleurisy - viral or rheumatological
Tietze’s Syndrome (costochondritis)
“Floating rib syndrome”, “slipping rib
syndrome”, Cyriax or Davies- Colley’s
Syndrome

35. Non-life threatening
Herpes Zoster
Cervical or Thoracic Disk Disease
Thoracic outlet syndromes
Rib fracture
Shoulder pain/injury
Peptic ulcer disease
“Nutcracker esophagus”

36. Non-life threatening
Non-surgical GB colic
Splenic flexure syndrome
Irritable bowel syndrome
SBO
Dental disease or TMJ

37. Non-life threatening
Hyperventilation syndrome
Panic Disorder
Depression
Somatization disorder
Conversion reaction
Factitious chest pain

38. If the Troponin is Normal
The Hard Work Has Just Begun!
R/O MI is not a diagnosis
Patient’s do not care what they do not have,
they want to know what they have