1. RISK STRATIFICATION IN UA
AND NSTEMI :WHY AND HOW?
-Dr.DEV PAHLAJANI
MD,FACC,FSCAI
HOD INTERVENTIONAL CARDIOLOGY BREACH CANDY HOSPITAL,
CONS.CARDIOLOGIST B.NANAVATI HOPSITAL MUMBAI

2. ACS is an Important Manifestation of
Atherothrombosis1
Plaque
rupture
Stable UA Non- Q-wave
Old term angina Q-wave MI MI
New term Atherothrombosis UA/NSTEMI STEMI
Days– Minutes–
weeks hours
Antithrombotic Thrombolysis
therapy primary PCI
UA=unstable angina; NSTEMI=non-ST-segment elevation
myocardial infarction; PCI=percutaneous coronary intervention
1. Cannon CP. J Thromb Thrombolysis 1995; 2: 205–218.

3. Our current understanding of unstable coronary syndromes is that
they include a spectrum of disease and begin with a coronary
plaque rupture1
The degree of thrombus occlusion determines the severity of the
clinical syndrome, with total occlusion in ST-segment elevation MI
(STEMI) or severe (90%) stenosis in patients with non-ST-segment
elevation MI (NSTEMI) or unstable angina (UA)1
In addition, it is worthwhile to note that 99% of all plaque
ruptures are clinically silent. A small degree of rupture leads to a
small thrombus, which heals over, leading to the progression of a
plaque1
This current understanding of how atherosclerosis progresses
emphasizes the key role that acute and chronic antithrombotic
therapy plays in all patients with unstable coronary syndromes1
• Reference
• 1. Cannon CP. J Thromb Thrombolysis 1995; 2: 205−218.

4. Acute coronary syndromes:
Prognostic spectrum
 Unstable angina
• New onset exertional angina
• Progressive angina
• Rest pain without EKG changes
• Rest pain with EKG changes
• Rest pain troponin+
 Non ST elevation MI (NSTEMI)
 Acute ST segment elevation MI
Coronary
occlusion & short
term death Least Greatest

5. Objectives of stratification
 Can We Identify Patients At Low,
Intermediate And High Risk Of Short
Term And Long Term Macce?
 Will It Help To Guide Treatment For
Better Outcome?

6. The TIMI unstable angina risk score
7 possible risk factors:
• Age >= 65 years
• Prior known CAD
• >= 3 coronary risk factors ( HTN, Hchol, FH, DM, current
smoker)
• Aspirin use within 7 days
• ST segment deviation
• >= 2 episodes of angina within 24 hours
• Abnormal cardiac markers (MB or T)
Low risk = 0-2 risk factors
Intermediate risk = 4-3 risk factors Antman EM et al:
JAMA
High risk = 5-7 risk factors 2000;284:835-42

7. PURSUIT SCORE(0–18)
Age, separate points for enrolment diagnosis
Decade [UA (MI)]
50 18 (11)
60 19 (12)
70 11 (13)
80 12 (14)
Sex
Male 1
Female 0
Worst CCS-class in previous 6 weeks
No angina or CCS I/II 0
CCS III/IV 2
Signs of heart failure 2
ST-depression on presenting ECG 1
Eur Heart J (May 2005) 26 (9):865-872.

8. GRACE(0–258)
Age (years) Heart rate (bpm) Systolic BP (mmHg)
<40 0 <70 0 <80 63
40–49 18 170–89 7 180–99 58
50–59 36 190–109 13 100–119 47
60–69 55 110–149 23 120–139 37
70–79 73 150–199 36 140–159 26
≥80 91 >200 46 160–199 11
Creatinine (mg/dL) >200 0
Killip class 0.0- 0.39 2 Cardiac arrest at
Class I 0 0.4–0.79 5 admission 43
Class II 21 0.8–1.19 8 Elevated cardiac
Class III 43 1.2–1.59 11 markers 15
Class IV 64 1.6–1.99 14 ST-segment
0.2–3.99 23 deviation 30
>4 31 Eur Heart J (May 2005) 26 (9):865-872.

9. TIMI, PURSUIT, and GRACE risk
scores: sustained prognostic value
and interaction with
revascularization in NSTE‐ACS
Pedro de Araújo Gonçalves,
Jorge Ferreira,
Carlos Aguiar and
Ricardo Seabra-Gomes
Eur Heart J (May 2005) 26 (9):865-872.

10. Objective
• Compare the prognostic value
• Ability to predict benefit from myocardial
revascularization performed during initial
hospitalization
Eur Heart J (May 2005) 26 (9):865-872 .

11. Study Endpoint
• Follow up
1 year OR
Until major event
• Endpoint
All-cause mortality OR
 Non-fatal MI
• Analysis
 30 days
 1 year.
Eur Heart J (May 2005) 26 (9):865-872.

12. Interaction between the admission score and
the prognostic impact of myocardial
revascularization performed during initial
hospital stay.
Eur Heart J (May 2005) 26 (9):865-872.

13. Comparison of the predictive
accuracy of the risk scores
30 days 1 year
Δ P-value Δ P-value
PURSUIT vs.
TIMI 0.064 0.288 0.044 0.319
GRACE vs.
PURSUIT 0.057 0.332 0.086 0.04
GRACE vs. TIMI 0.121 0.054 0.130 0.004
Eur Heart J (May 2005) 26 (9):865-872.

14. Conclusions
RSs developed from
Databases of clinical trials (PURSUIT and TIMI) or
Registries (GRACE)
• At 30 days the risk stratification by all 3 scores for
patients with NSTE-ACS
 has fair to good discriminatory accuracy
in predicting major adverse cardiac events
at both 30 days and 1 year.
• The GRACE RS was the best for predicting the
risk of death or MI at 1 year after admission.
Eur Heart J (May 2005) 26 (9):865-872.

15. The TIMI unstable angina risk score
7 possible risk factors:
• age >= 65 years
• >= coronary risk factors (like HTN, Hchol, FH, DM, current
smoker)
• Aspirin use within 7 days
• ST segment deviation
• >= 2 episodes of angina within 24 hours
• Abnormal cardiac markers (MB or T)
Low risk= 0-2 risk factors
Intermediate risk= 3-4 risk factors
High risk = 5-7 risk factors
Antman EM et al. JAMA
2000:284:835-42

16. Prognostic value of recurrent ischemia in
ACS
Armstrong PW et al. Circulation 1998:98:1860-1868

17. Troponin T and ST segment depression are
independent predictors of adverse cardiac
events at FU in ACS
Univariate OR( 95% Cl) Multivariate OR (95% Cl)
ST segment depression
1 mm 1.56[1.02-2.40] 1.34[0.86-2.09]
2mm 2.64 [1.57-4.44] 1.91 [1.10-3.32]
Troponin T
0.01-0.047 ng/ml 2.45 [1.25-4.82] 2.43 [1.22-4.85]
0.048-0.277 ng/mg 3.23[1.89-5.16] 3.18 [1.83-5.53]
0.278- 8.37 ng/ml 3.91 [2.32-6.61] 3.86 [2.24-6.66]
Kaul et al.JACC 2002

18. TIMI Risk Score: 1oEP at 6 mos
OR=0.55
CONS INV CI (0.33, 0.91)
35 OR=0.75 30.6
Death/MI/ACS Rehosp (%)
30 CI (0.57, 1.00)
25
20.3 19.5
20 16.1
15 11.8 12.8
10
5
0
Low 0-2 Intermed. 3-4 High 5-7
TIMI Risk Score
% of Pts: 25% 60% 15%

19. TACTICS TIMI 18
Troponin T : Primary endpoint
Death / MI / rehospitalization for ACS at 6 months
OR = 0.53 p<0.001
30 Conservative Invasive Interaction p<0.001
24.5
Incidence (%)
25
P=NS
20 16.9 TnT cut point = 0.001
14.5 14.2 ng/ml (54 % of patients
15
were Troponin T
10 positive)
5
0
TnT negative TnT positive

20. TACTICS-TIMI 18: Invasive vs. Cons.
Troponin T >0.01 ng/dl
Primary Endpoint: Death/MI/Rehosp ACS
TnT +, CONS
24.2%
TnT -, INV
14.8%
TnT +, INV
TnT -, CONS
Morrow DA, et al. JAMA 2001;286:2405-2412.

21. Through 14 days in the un fractionated heparin (UFH) and
enoxaparin (ENOX) treatment groups in the pooled (TIMI) 11B
and (ESSENCE) trial populations, with patients stratified by
TIMI risk score
J Am Coll Cardiol. 2003;41(4s1):S89-S95.

22. High TIMI score is associated with
coronary thrombus in ACS
Subanalysis of PRISM-PLUS (n=1491)
D.A Morrow et al, AHA
2001

23. Evaluation of B-Type Natriuretic Peptide for
Risk Assessment in Unstable Angina/Non-ST-
Elevation
Myocardial Infarction
B-Type Natriuretic Peptide and
Prognosis in Tactics-TIMI 18
David A. Morrow, MD, MPH, James A. de Lemos, MD,
Marc S. Sabatine, MD, MPH, Sabina A. Murphy, MPH,
Laura A. Demopoulos, MD, Peter M. Dibattiste, MD,
Carolyn H. McCabe, BS, C. Michael Gibson, MD, MS, Christopher P. Cannon,
MD, Eugene Braunwald, MD
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.

24. Mortality Risk Stratified by B-Type Natriuretic Peptide Levels
Over Range of 40 to 160 pg/ml: UA/NSTEMI
14
12
6 Month Mortality (%)
10.9 11.1
10
8 7.1
6
3.6
4
1.7 1.9
2
0
BNP (pg/ml) >80-
≤ 40 >40- ≤80 >100- ≤120 >120- ≤160 >160
≤100
BNP Threshold >40 >80 >100 >120 >160
% Positive - 38% 19% 14% 11% 7%
OR - 1.9 3.7 4.0 3.7 2.4
X2 - 3.8 13.8 16.2 14.1 5.9
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.

25. Combination of cTnI, CRP, BNP in ACS
OPUS-TIMI 16 TACTICS-TIMI 18
6 14
N=1635
30-Day Mortality Relative Risk
30-Day Mortality Relative Risk
N=450 Validation
5 12
P = 0.014 P < 0.0001
10
4
8
3
6
2
4
1
2
0 0
0 1 2 3 0 1 2 3
N= 67 150 155 78 N = 504 717 324 90
# of Elevated Cardiac Biomarkers # of Elevated Cardiac Biomarkers
Sabatine MS et al. Circulation. 2002;105:1760-3.

26. Conclusions
• UA and NSTEMI Patients have varied anatomy
and pathology
• Need to be stratified to determine urgency
and modality of treatment either invasive or
conservative
• Simple bed side score like TIMI score can
stratify patients in low, intermediate and high
risk patients

27. Multimarker Data
N= 3461
80
72.0
70
60
Percent of Cases
50
40
30
20 16.0
10 6.8 5.9
0
0 1 2 3
Number or Markers Positive
Kontos MC, Garg R, Anderson FP, Roberts CS, Tatum JL, Ornato JP, Jesse RL. A multimarker strategy predicts short- and long-
term mortality n patients admitted for the exclusion of myocardial infarction. J Am Coll Cardiol 2005;45(3):217A.

28. Risk of Death or MI at 30 Days Stratified by BNP and
cTnI: UA/NSTEMI
10 Death Death/MI
BNP >80 7.9
8 BNP <80
7.5
6.4
6 5.4
4.5
%
4
2
2 1.4
0.7
0
cTnI NEG cTnI POS cTnI NEG cTnI POS
P=0.004 P<0.001 P=0.008 P=0.4
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.

29. 30-day and 1-year endpoint rates for
PURSUIT score
Eur Heart J (May 2005) 26 (9):865-872.

30. 30-day and 1-year endpoint rates for
the TIMI score.
Eur Heart J (May 2005) 26 (9):865-872.

31. 30-day and 1-year endpoint rates for
the GRACE score.
Eur Heart J (May 2005) 26 (9):865-872.

32. Through 30 days in the heparin alone and tirofiban
plus heparin treatment groups in (PRISM-PLUS), with
patients stratified by (TIMI) trial risk score
J Am Coll Cardiol. 2003;41(4s1):S89-S95.

33. Through six months in the invasive (INV) and
conservative (CONS) treatment strategy arms
in (TACTICS TIMI)-18 trial, with patients
stratified by TIMI risk score
J Am Coll Cardiol. 2003;41(4s1):S89-S95.

34. Acute Evaluation of ACS
Presentation Chest Pain or Short of Breath
ST-Segment ST-Segment
ECG Normal Depression Elevation
Blood Marker Panel – + – + +
Diagnosis Unstable
Rule-Out Acute MI
Angina
Adapted from Braunwald E, et al. Available at:
http://www.americanheart.org/downloadable/heart/1022188973899unstable_may8.pdf.
Adapted from Antman EM, et al. Circulation.2004 Aug 31;110(9):e82-292.

35. Clinical Utilization of Cardiac Troponin
and Natriuretic Peptides in ACS and CHF
Consultant Cardiologist and Chief, Division of Nutrition and Preventive
Medicine Clinical Professor, Oakland University School of Allied
Health Sciences, William Beaumont Hospital, Royal Oak, Michigan,
USA

36. Troponin i levels predict the risk of mortality
Changes in Focus on Heart Failure
in ua/nstemi
7.5
8
Mortality at 42 Days (% of patients)
6.0
6
3.7
4 3.4
1.7
2
1.0
831 174 148 134 50 67
0
0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 >9.0
Cardiac Troponin I (ng/ml)
Risk Ratio 1.0 1.8 3.5 3.9 6.2 7.8
Antman
N Engl J Med. 335:1342, 1996

37. BNP Elevation in ACS
• Pre-existing or concurrent HF
• Large zone of myocardial ischemia
– Left main disease
– Multivessel disease
• Large zone of infarction
• Delayed presentation
• Renal dysfunction
McCullough, PA, ACC 2007

38. Kaplan-Meier Estimates of the
Probability of Death Through 6 Months: UA/NSTEMI
BNP at baseline in 1,676 patients
10 BNP > 80 pg/ml with non-ST-elevation ACS
BNP ≤ 80 pg/ml
Probability of Death (%)
6 months 8.4%
5 vs. 1.8% p<0.001
0
0 50 100 150 180
Days since enrollment
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.

39. Probability of Death or Congestive Heart
Failure Through 6 Months: UA/NSTEMI
20 BNP > 80 pg/ml
BNP ≤ 80 pg/ml
Probability of Death or CHF (%)
15
10 6 months 16.3%
vs. 3.6%
p<0.0001
5
0
0 30 60 90 120 150 180
Days since enrollment
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.

40. Risk of CHF at 30 Days Stratified by BNP and
cTnI: UA/NSTEMI
12 CHF Death/CHF
10.4
10 BNP >80 9
BNP <80
8
6.2
6
%
4.5
4 2.9
2 1.5
0.8
0.2
0
cTnI NEG cTnI POS cTnI NEG cTnI POS
P<0.0001 P<0.0001 P<0.0001 P<0.0001
Morrow DA et al. J Am Coll Cardiol. 2003;41:1264-72.

41. TACTICS-TIMI 18 Study Design
PCI/ CABG
Early
Angio
Invasive
Medical Rx
UA/ ASA, Hep,
NSTEMI Tirofiban Endpoints
Baseline Early
Medical Rx ETT
Troponin Conservative
+ischemia
+ischemia
+ischemia
Chest Cath/ PCI/ CABG
pain Randomize
-24 Hour 4- 48 108 6 mos
0 hrs hrs
hrs
Cannon CP et al. Am J Cardiol 1998;82:731-6.

42. Primary Endpoint
Death, MI, Rehosp for ACS at 6 Months
20 19.4%
16 15.9%
% Patients
12
O.R 0.78
8 95% CI (0.62, 0.97)
p=0.025
4
CONS
0 INV
0 1 2 3 4 5 6
Time (months)
Cannon CP, et al. N Engl J Med. 2001;344:1879-87.

43. Troponin Substudy: 6 Month Results
INV CONS
1O Composite (%) (%)
< 0.01 16.9 14.5
0.01 – 0.1 P=0.01 10.1 23.0
> 0.1 P<0.001 15.7 24.6
Death/MI
< 0.01 4.3 5.3
0.01 – 0.1 P=0.06 5.9 13.3
> 0.1 9.0 12.0
TnT
0 0.5 1 1.5 2.0
Invasive Better Conserv. Better

44. Subgroups: Primary Endpoint
Death, MI, Rehosp ACS at 6 Months
CONS INV
1 Endpoint
O
%Pts (%) (%)
Men (66%) 19.4 15.3
Women (34%) 19.6 17.0
Age < 65 yrs (57%) 17.8 14.9
Age > 65 yrs (43%) 21.7 17.1
Diabetes (28%) 27.7 20.1
No diabetes (72%) 16.4 14.2
ST ∆ * (38%) 26.3 16.4
No ST ∆ (62%) 15.3 15.6
19.4 15.9
Total Population
*Interaction P=0.006 0 0.5 1 1.5
others P=NS INV Better CONS Better

45. Benefit of INV in TnT+ Women
Death, MI, Rehosp for ACS
1.00
OR=0.56
Invasive Log rank p=0.03
0.90
Event Free Survival
0.80
Conservative
0.70
Glaser et al
ACC 2002 0 50 !00 150 200
Time (days)

46. ESC Guidelines for UA/NSTEMI
Clinical suspicion ACS
PE, ECG, Bloods
No ST elevation High-risk
↑ Troponin GP IIb/IIIa inhibitor
Rec. Ischemia, DM
Aspirin Coronary Angio
Hemodyn. Instability
Nitrates Early Post MI angina
B-blockers
Heparin Low-Risk Stress Test
Normal Troponin Before or
Clopidogrel After
on admission Discharge
and 12 h later
Bertrand, presented ESC 2002, Eur Heart J Sept 2000

47. UNSTABLE ANGINA
TIMI - 3B
CIRC. 1994, 89 : 1545-1556
1473 PATIENTS WITH REST ANGINA,
ECG CHANGES OR NON Q INF.
1473 PATIENTS RANDOMISED TO Tpa
OR PLACEBO
SECOND RANDOMISATION TO EARLY
CATH VS CONSERVATIVE CARE
NO DIFFERENCE IN DEATH OR MI
EARLIER DISCHARGE, FEWER ADMISSIONS
AND ↓ NEED FOR ANTIANGINAL DRUGS
IN INVASIVE STRATEGY

48. TIMI- IIIB
42 days (1 degree EP*) Invasive Conservative P value
N 740 733
Death(%) 2.4 2.5 NS
MI (%) 5.1 5.7 NS
D/MI/ +ETT (%) * 16.2 18.1 NS
LOS(days) 10.2 10.9 <0.001
Rehosp angina (%) 7.8 14.1 <0.001
>= 2 anginal meds (%) 44 52 0.02
D/MI/Rehosp (%) 15 22 0.007
# days rehosp 365 930 < 0.001
D/MI at 1 year (%) 10.8 12.2 NS
Anderson HV et al.JACC 1995;26:1643-50

49. The detrimental role of platelet derived
soluble CD40L * in cardiovascular disease
Inflammation
Induces production/ release of
pro inflammatory cytokines
from vascular and atheroma
cells
Thrombosis
Stabilizes platelet rich
thrombi
Restenosis
Prevents re-endothelialization
of the injured vessel
*sCD40L= Soluble CD40L Contributes to activation and
proliferation of smooth muscle
cells

50. )
Death or nonfatal myocardial infarction
during six months of follow up
According to base line level of soluble CD40 ligand in placebo
group (544 patients) and the Abcximab group (544 patients

51. GP II b/IIIa in ACS: Intention to treat analysis
Death or MI at 30 days
The PRISM-Plus investigators. Nejm 1998; The PURSUIT Investigators. NEJM
338:1488-87 1998; 339:436-43

52. PRISM: Death/MI at 30 days

53. FRISC II: 1 year death or MI

54. One year outcomes TAXUS in ACS
TAXUS(n= 237) Control P value
(n=213)
Cardiac death 2.5 2.0 0.63
MI 3.8 6.2 0.27
CABG 1.7 6.1 0.05
PCI 5.2 13.0 0.0049

55. In-Hospital Death or Recurrent Myocardial
Infarction
(GRACE + EUR. HEART SURVEY)
In-Hospital Death Reinfarction
Type of Disease GRACE EHS-ACS GRACE EHS-ACS
(%) (%) (%) (%)
STEMI 7 7 3 2.7
NSTEMI 6 2.4 2 1.4
UA 3 - - -
Undetermined - 11.8 - 1.7
ECG
Eur. H.J. 2002, 23, 1179
Eur. H.J. 2002, 23, 1190

56. Outcomes of Percutaneous Intervention in Five Trials
Characteristic FRISC II TACTICS VINO RITA – 3 ICTUS
(N = 2457) (N = 2220) (N = 1131) (N = 1810) (N = 1200)
(1222/1235) (1114/1106) (64 / 67) (895/915) (604/596)
Mean age (year) 65 62 66 63 62
Men (%) 70 66 61 62 62
Diabetes (%) 12 28 25 13 14
Previous MI (%) 22 39 26 39 23
Mean follow up (mo) 24 6 6 24 12
Invasive / selective
revascularization
At end FU 78/43 61/44 73/39 57/28 79/54
PCI at FU 44/21 42/29 52/13 36/16 61/40
CABG at FU 38/23 22/16 35/30 22/12 18/14

57. TACTICS – TIMI - 18
Treat Angina with Aggrastat and Determine Cost of
Therapy with an Invasive or Conservative Strategy
New Engl. J. Med, June 2001, 344, 25 1879
ACS patients : Randomised
1114 Invasive Strategy
1106 Conservative Strategy
Similar demographic features
Standard treatment with ASP, Hep, BB &
Tirofiban 48 to 108 hours

58. Results of the ISAR-REACT 2 Trial, Comparing
Abciximab with Placebo
Abciximab Placebo
P = .02
20 18.3
P = .03
13.1
11.9
10 8.9
P = .98
4.6 4.6
0
All Patients High-risk Low-risk
Troponin + Troponin -
(N = 2022) (N = 1049) (N = 1049)

59. ACS
Incidence of Early (in-hospital)
Revascularization in Several Trials
80 76
71 73
70
60
60
50 44
39 40
40 36
%
30
20
9 10
10
0
FRISC-II TACTICS VINO RITA-3 ICTUS
Early Invasive Conservative

60. ACS
Incidence of Mortality or Nonfatal MI at the end
follow-up in several trials
Early Invasive Conservative
25 22.4
20
15
15 14.1
% 10.4
9.5 10
10 7.3 7.6 8.3
6.3
5
0
FRISC-II TACTICS VINO RITA-3 ICTUS
FU (months) 12 6 6 12 12

61. FRISC – II
CONCLUSIONS
After one year in 100 patients invasive strategy :
1) Saves 1.7 lives
2) Prevents 2 non fatal MI
3) Prevents 20 readmissions
4) Better symptoms relief
5) Lower cost
6) Preferred strategy for ischaemia with ECG
changes and raised serum enzymes

62. Prognostic value of recurrent
ischemia in ACS
Armstrong PW et al. Circulation 1998:98:1860-1868

63. High TIMI score is associated with coronary
thrombus in ACS
Sub analysis of PRISM-PLUS (n=1491)
D.A Morrow et al, AHA 2001

64. Timing of Intervention in Patients with
NSTEMI Acute Coronary Syndrome in
the CRUSADE Registry
Timing of Catheterization
In-Hospital Events 46.3 Hours 23.4 Hours
(n = 10,804) (n = 45,548) P Value
Death (%) 4.4 4.1 .23
Recurrent MI (%) 2.9 3.0 .36
Death / MI (%) 6.6 6.6 .86

65. Outcomes of the CRUSADE Trial :
In-Hospital Death or Myocardial Infarction
Outcome No Early Invasive Early Invasive Management
( Management (n = 9889 ( (n = 9889
Mortality (%) 6.2 2.0
Post-admission MI (%) 3.7 3.1
Death or MI (%) 8.9 4.7

66. Troponin I Levels Predict the Risk
of Mortality in ACS
0.08 7.5%
0.07
6.0%
Mortality at 42 Days
0.06
0.05
0.04 3.7%
3.4%
0.03
0.02 1.7%
1.0%
0.01 831
174 148 134 50 67
0
0 - <0.4 0.4 - <1.0 1.0 - <2.0 2.0 - <5.0 5.0 - < 9.0 ≥ 9.0
Cardiac Troponin I (ng/ml)
Antman EM et al. N Engl J Med. 1996;335:1342-9.

67. Minor Troponin Elevations and Mortality
• 34,227 patients admitted from ED
over a 3 yr. period who had at
least 1 TnI sampled (48% of all pts 10 9.4
admitted) In-hospital Mortality, %
• Pts classified based on degree
of elevation 7.5
– 0 not detected
– Negative 0–0.08 (99%) 5
5
– Indeterminant 0.09-0.2 (10% CV)
3.3
– Positive > 0.21
• Significant increase in mortality 2.5 1.8
with increasing TnI
• Results same if analyzed
0
– Patients with ACS
0 Neg Indeterm Pos
– Patient who had serial sampling
Waxman DA. JACC. 2006;48:1755-62.

68. Cardiac Troponin
Limitations
 Not an early marker
 Currently there is no standardization across
Troponin I assays from different manufacturers
 Diagnostic accuracy at the low end is variable
 Sporadic elevations from non-atherothrombotic myocardial
damage may confuse interpretation
 A low level troponin is not benign!

69. FRISC – II
FRAGMIN AND FAST REVASCULARISATION DURING INSTABILITY
IN CORONARY ARTERY DISEASE TRIAL (FRISC-II)
LANCET 2000 : 356:9-16
Object :
Compare Invasive And Non Invasive Strategy For
Coronary Intervention In Patients With Unstable
Coronary Artery Disease
 Design :
Prospective Randomised Multicentre Trial With
Parallel Groups (58 Scandinavian Centres)

70. FRISC – II
Inclusion criteria
 Symptoms of ischaemia
 ECG changes > 0.1 mV DEP OR T WAVE
 Inversion Or
 CPKMB > 6 µ g/l
 Troponin T > 0.1 µ g/l
 More than 3000 patients randomised
 1 year data available in 1222 invasive
 And 1234 non invasive group

71. Multimarker Data and All-Cause Mortality
N= 3461 P < 0.05 for all pairwise comparisons
25 25.0
20 20.0
Mortality
15 13.7
12.7
10 30 Day
6.6 6.8 1-Year
5 3.7
1.0
0
0 1 2 3
Number or Markers Positive
Kontos MC, Garg R, Anderson FP, Roberts CS, Tatum JL, Ornato JP, Jesse RL. A multimarker strategy predicts short- and long-term mort
n patients admitted for the exclusion of myocardial infarction. J Am Coll Cardiol 2005;45(3):217A.

72. FRISC – II
CONCLUSIONS
After one year in 100 patients invasive strategy :
1) Saves 1.7 lives
2) Prevents 2 non fatal MI
3) Prevents 20 readmissions
4) Better symptoms relief
5) Lower cost
6) Preferred strategy for ischaemia with ECG
changes and raised serum enzymes

73. TROPONIN T LEVELS
IN ACS & CARDIAC DEATH
1506 Patients
FRISC – Circ. 1996, 93 : 1651

74. SABATINE AND ANTMAN
TIMI RISK SCORE FOR UA/NSTEMI
6-7
pulation 4.3 17.3 32.0 29.3 13.0 3.4
Antman RM et al JAMA 2000, 284, 835

75. Annual Admissions for Acute
Coronary Syndrome (ACS)
~ 2.0 MM Patients Admitted
to CCU or Telemetry Annually
600,000 1.4 Million
ST-Segment Elevation MI Non-ST-Segment
Elevation ACS
Antman EM, et al. Circulation. 2004;110:588-636.
Braunwald E, et al. Circulation. 2000;102:1193-1209.

76. Conclusion
In NSTE-ACS population,
• TIMI risk score can be widely applied
• At 30-day PURSUIT are better than others in
the high-risk group
• GRACE is superior at long term follow-up in
high risk group
Heart 2012;98(S 2): E1–E319

77. UNSTABLE ANGINA NSTEMI
• Ischemic discomfort • Ischemic discomfort
• At rest or with minimal • Rest or with minimal
exertion exertion
• Occurs in a crescendo • Occurs in a crescendo
pattern or is severe pattern or is severe
• New onset with or no • New onset
ECG changes
• With cardiac
biomarkers of necrosis
 creatine kinase-MB
iso enzyme [CK-MB]
 cardiac troponin)

78. Chest Pain in the
Emergency Department (ED)
100 million visits annually (US)
~6 million chest pain visits
Discharged Admitted
2,000,000 Non 4,000,000
Cardiac Suspected or Actual Cardiac
24,000 1,360,000
Missed ACS Non Cardiac
(1.2%) (34%)
910,000
Non-Ischemic Cardiac (23%)
900,000
Unstable Angina (23%)
830,000
Myocardial Infarct (20%)
NCHS, Hospital Discharge Data, 2002
Pope et al, NEJM, 2000

79. Acute ischaemic coronary syndromes
Global Practice Pattern (OASIS) (1)
Source : Organisation to Assess Strategies
For Ischaemic Syndromes Registry
(OASIS)
8000 Patients
Acute Myocardial Infarction
No ST Elevation
Predischarge Coronary Angio :
Performed in Brazil 70 %, USA 60 %, Hungary 20 %
Holland 7 %, Canada, Aust. Intermediate
PTCA, CABG : More Widespread Differences Between Countries
Circ. 1997, 96 (Suppl.) 1-40

80. Prognostic value of baseline Troponins in ACS
GUSTO-IIA: 30 Day mortality
Ohman EM et al. NEJM 1996;335:1331-4

81. TIMI Risk Score
Thrombolysis In Myocardial Infarction
Characteristics Points
Historical
Age ≥65 yrs 1
≥3 Risk factors for CAD 1
Known CAD (stenosis ≥50%) 1
Aspirin use in past 7 days 1
Presentation
Recent (≤24 h) severe angina 1
ST-segment deviation ≥0.5 mm 1
↑Cardiac markers 1
Risk Score = Total Points (0–7)
Eur Heart J (May 2005) 26 (9):865-872.