Management of patients with STEMI

Raffaele Bugiardini

Myocardial Ischemia

• Spectrum of presentation– silent ischemia– exertion-induced angina– unstable angina– acute myocardial infarction

Acute Coronary Syndrome

• The spectrum of clinical conditions ranging from:– unstable angina– NSTEMI (non-Q wave MI)– STEMI (Q-wave MI)

• Characterized by the common pathophysiology of a disrupted atheroslerotic plaque

Unstable Angina - Definition

Clinical Circumstance

A—Develops in Presence of Extracardiac Condition That

Intensifies Myocardial Ischemia (Secondary UA)

B—Develops in Absence of Extracardiac Condition (Primary

UA)

C—Develops Within 2 wk of AMI

(Postinfarction UA)

I—New onset of severe angina or accelerated angina; no rest pain

II—Angina at rest within past month but not within preceding 48 h (angina at rest, subacute)

III—Angina at rest within 48 h (angina at rest, acute)

IA IB IC

IIA IIB IIC

IIIA IIIB IIIC

New definition: Myocardial Infarction(2000)

-------------------------------------------------------------------------

Acute, evolving or recent AMI

Established MI

-------------------------------------------------------------------------The Joint European Society of Cardiology/American Collegeof Cardiology Committee. JACC 2000, 36:959-69

---------------------------------------------------------------------------At least 2 of 3 criteria fulfilled:

1) POSITIVE CLINICAL HISTORY“Crushing” substernal chest with or withoutradiation to jaw or down the left arm

2) POSITIVE EKG

3) CARDIAC “ENZYME” ELEVATIONS---------------------------------------------------------------------------

INITIAL EVALUATION AND MANAGEMENT

Patients with suspected IHD must be evaluated rapidly

The physician then must place the evaluation in the context of 2 critical questions:

•Are the symptoms a manifestation of ACS?

•If so, what is the prognosis?

Are the symptoms a manifestation of ACS ?

If so, what is the prognosis ?

om:

Most of you are GP and frequently recive telephone calls from pts who are concerned that their symptoms may reflect haert disease. Most of these calls regarding chest disconfort do not rapresent an emergency,

some yes.

There are two critical questions:

om:

Most of you are GP and frequently recive telephone calls from pts who are concerned that their symptoms may reflect haert disease. Most of these calls regarding chest disconfort do not rapresent an emergency,

some yes.

There are two critical questions:

“The presence or absence of the traditional risk

factor ordinarily should not be used to determine

whether an individual patient should be admitted

or treated for ACS.

However, the presence of these risk factors does

apper to relate to poor outcomes in patients with

established ACS.”

ACC/AHA Practice Guidelines 2002

PERFORM

----------------------------------------------------------------------------

1) History2) Physical examination

Use this information to create ==> DIFFERENTIALDIAGNOSIS

----------------------------------------------------------------------------

What is in your differential diagnosis of chest pain?

Differential Diagnosis of Prolonged Chest Pain

• AMI• Aortic dissection• Pericarditis• Atypical angina pain

associate with hypertrophic cardiomyopathy

• Esophageal, other upper gastrointestinal, or biliary tract disease

• Pulmonary disease– pneumothorax– embolus with or without

infarction– pleurisy: infectious,

malignant, or immune disease-related

• Hyperventilation syndrome

• Chest wall– skeletal– neuropathic

• Psychogenic

High Likelihood Low LikelihoodIntermediate Likelihood

History

Examination

ECG

Cardiac Markers

Typical Angina CAD history

Transient MR Hypotension Diaphoresis, Pulmonary Edema

New ST-segment deviation or T-wave inversion

cardiac TnI, TnT or CK-MB

Typical Angina, Age >70 yrs, Sex M,

Diabetes Mellitus

Extracardiac vascular disease

Fixed Q waves Abnormal ST or T-waves not documented to be new

Normal

Probable ischemic symptoms

Recent cocaine use

T wave flattering

Normal

Likelihood that Signs and Symptoms Represent an Unstable Angina

Modified from Braunwald E et all 1994; AHCPR Pub. 94-0602

T wave flattering or inversion in laeds with dominant R

Chest disconfort by palpitation

Normal

Risk Stratification Non Invasive Stress Testing

• LOW RISK PTS • INTERMEDIATE RISK PTS

free of ischemia at rest and of CHF for a minimum

2 - 3 days12 - 24 hours

ACC/AHA Practice Guidelines 2002

Are the symptoms a manifestation of ACS ?

If so, what is the prognosis ?

om:

Most of you are GP and frequently recive telephone calls from pts who are concerned that their symptoms may reflect haert disease. Most of these calls regarding chest disconfort do not rapresent an emergency,

some yes.

There are to critical questions:

om:

Most of you are GP and frequently recive telephone calls from pts who are concerned that their symptoms may reflect haert disease. Most of these calls regarding chest disconfort do not rapresent an emergency,

some yes.

There are to critical questions:

0 2 4 6 8 10 12 14

15

20

25

30

35

40

10

5

Heparin

Enoxaparin

Time since enrollment (months)

Combined Endopoint

Goodman SG, J AM Coll Cardiol 2000;36:693-8

The ESSENCE Study

TIMI risk score

1- age > 65 yrs

2- > 3 coronary risk factors

3- more that 2 angina events within 24 hrs

4- prior angiographic obstruction

5- aspirin (in the 7 prior days)

6- ST-segment deviation

7- elevated cardiac markers

Antman EM et al. JAMA 2000;284:835-42

15

20

25

30

35

40

10

5

Validation of TIMI Risk Score and Assessment of Treatment Effect According to Score in ESSENCE

Antman E, JAMA 2000;284:835-42

45

0/1 2 6/73 4 5

7.27.311.6

9.5

15.8

12

16.8

12.4

31

18.3

38.1

20

Rat

e of

Com

posi

te E

nd P

oint

%

No. of Risk Factors

Unfractionated Heparin (n=1564)

Enoxaparin (n=1607)

Tools for risk stratificationinitial management

• Age and History

• Symptoms

• Standard ECG

• Biochemical Markers

• Continous ECG

Q waveQ waveInverted T waveInverted T wave

Types of lesions: Inferior

• Often RCA• Potential involvement of

RV dx

Lateral

• Often LCX

Septal

• Certainly LAD

Anterior

Posterior ! no ST ELEVATION

• Derivazioni destre

• Sospettato coinvolgimento del ventricolo destro in infarto POSTERIORE

Up to you ….

Right Side Chest leads

Acute?

Q waves inlateral wallmyocardialinfarction

Example:

ECG alone is not sufficient for

diagnosis!

The pazient had MI in 1989 , and subsequent evolution in aneurysm

of the LV!

CARDIAC MARKERS:------------------------------------------------------------------------------

Cardiac enzymescreatine kinase (CK)aspartate aminotransferase (AST)lactate dehydrogenase (LD)

Structural proteinscardiac troponin T (cTnT) cardiac troponin I (cTnI)

Oxygen-binding proteinsmyoglobin

-----------------------------------------------------------------------------

0

1

2

3

4

3.1

1.7

2.4

1.4

4

2.6

3.7

2.5

0.4 0.5

1.00.8

All Pts All Pts All PtsNo CK-MB Elevation

No CK-MB Elevation

No CK-MB Elevation

Enrolled 0 to 6 hr

after Pain Onset Enrolled > 6 to 24 hr

after Pain Onset Enrolled 0 to 24 hr

after Pain Onset

Risk Ratio

95% Confidence Interval

1.8

0.6-5.5

1.8

0.4-7.6

9.5

2.2-4146

5.5

1.1-29.7

3.8

1.7-8.5

3.0

0.97-9.2

Mortality Rates at 42 Days According to the Time From Onset of Pain to Study Enrollment and the Baseline Cardiac Troponin I

Troponin I 0.4 ng/mlTroponin I <0.4 ng/ml

P<0.05P<0.01

Antman EM N Engl J Med 1996; 335:1342-49

0% 20% 40% 60% 80% 100%

1%

2%

3%

4%

5%

Patients with Ischemia on ECG

Mor

tali

ty

Negative TnINegative TnT

Relation between initial negative Troponin and ECG

Heidenreich J Am Coll Cardiol 2001;38:478-85

NORMAL REST ECG

Normal LVEF 98 %

Abnormal LVEF 2%

Am Heart J 2000: 139:584

Dea

th o

r M

I %

0 60 120 180 240 300 360

ST Elevation and Depression n=78

ST Depression Only n=216

ST Elevation Only n=93

T Wave Inversion Only n=287

No ST or T Wave Change n=237

Life table of cumulative risk and time of MI or death during 1 year of follow-up with regard to different types of ST-T segment change

Days

Nyman N, J Intern Med 1993;234:293-301

Dea

th o

r M

I %

Recurrent angina

Duration of anginal episodes> 15 min

Pain-free interval < 1 h

Duration of TMI 60 min/24h

Duration of TMI 60 min/24h and high risk coronary lesion

High risk coronary lesion

88

37

24

83

88

80

32

92

92

75

59

89

46

75

67

68

58

83

80

69

65

87

88

88

Sensitivity Specificity

Positive predictive

value

Negative predictive

value(%) (%) (%) (%)

Prognostic Significance of different Clinical, ECG and Angiographic Variables for Identifying High Risk Pts with UA

Bugiardini R, J Am Coll Cardiol 1995; 25:597-604

180

160

140

120

100

80

60

30

0

Symptoms Predictive of coronary events

Dur

atio

n of

TM

I at a

dmis

sion

(m

in/2

4 hr

s)

Relations among prognosis, duration of ischemia at admission and symptoms

Over 180

Yes YesNo No

Unfavorable clinical

Outcome Favorable clinical

Outcome Fatal or Non fatal MIOther clinical outcome

Bugiardini R, J Am Coll Cardiol 1995; 25:597-604

Simplified TIMI risk score

CLASSES

Low Risk 0-

1

Intermediate Risk 2

High Risk 3

CRITERIA

a - age > 65 yrs

b- ST deviation > 0.5 mm

c- CK > 2 times normal

or TnT high

Holper EM et al Am J Cardiol 2001;87:1008-10

Low (0/1) Inter (2) High (3)

1514.1

20.5

17.9

29.6

24.8

802 870 848 797 307 286

30

25

20

15

10

5

0

Unfractionated heparinEnoxaparin

Holper EM, Am J Cardiol 2001;87:1008-13

Eve

nt r

ate

at d

ay 4

3

Simplified TIMI risk score

Chronic Stable Angina

Unstable Angina

0 100 200 300 400 500 600 700.5

1.0

.9

.8

.7

.6

Days

Eve

nt-f

ree

surv

ival

Florenciano-Sandez R. J Am Coll Cardiol 2001;38:1974-9

Prognostic value of low risk exercise test

Duration (min)

% TMHR

Rate-pressure product

Positive clinical response

Positive ECG response

Positive result

Duke index

92 74

8013 7711

21,4817,079 20,9025,835

17 (16%) 40 (46%)

34 (32%)

41 (39%)

57 (66%)

64 (74%)

55 06

Patients With UA (n=105)

Patients With CSA (n=86)

p Value

0.0001

0.0001

0.0001

0.0001

0.0001

NS

NS

RESULTS OF THE EXERCISE TEST

Florenciano-Sandez R. J Am Coll Cardiol 2001;38:1974-9

In patients with suspected ACS and negative

ECG-Exercise Stress Test, physycians should

proceede to pharmacological stress or cardiac

scintigraphy.

100%

80%

60%

40%

20%

SPECT

Stress-Echo

Sensitivity Specificity

90%

81%

72%

89%

Comparison of Stress Echocardiography and Stress Myocardial Perfusion Scintigraphy for CAD

O’Keefe J Am J Cardiol 1995;75:25D-34D

Do not judge yourself harshly.

Without mercy for ourselves we cannot

love the world.

The Buddha

Key Assumptions

• The euros available for health care are limited

• The medical profession must play a significant role in the critical evaluation of the use of diagnostic procedures and therapies

PURSUIT Trial Investigator

0,9

0,91

0,92

0,93

0,94

0,95

0,96

0,97

0,98

0,99

1

30 60 90 120 150 180

Pro

b. o

f su

rviv

al

Days

N Engl J Med 1998;339:436-43

280

210

180

150

120

90

60

30

0

280

210

180

150

120

90

60

30

0

(+) (o) (+) (o)

(+) (o)

In hospital adverse outcome

Complex morphology

Dur

atio

n of

TM

I at a

dmis

sion

(m

in/2

4 hr

s)

Dur

atio

n of

TM

I at a

dmis

sion

(m

in/2

4 hr

s)

Bugiardini R et al Am J Cardiol 1991;67:460-464

Relations among complex stenosis morphology, transient myocardial ischemia, and in-hospital outcome in pts with UA

0 50 100 150 200 250 300 350

0.85

0.85

0.90

0.95

1.00

No ST Shift

ST Shift

P=0.0226

Days from Randomization

Eve

nt-f

ree

Sur

viva

l (P

ropo

rtio

n)

The Canadian ESSENCE ST Segment Monitoring Substudy

Goodman SG J Am Coll Cardiol 2000;36:1507-13

Age > 65 years

Hypertension

Transient ischemia

Severe recurrent pain

4.66

7.10

11.87

0.00046.82

9.47

3.33

Multivessel disease

Complex lesion morphology

IC thrombus

0.03

0.0003

0.04

0.09

Independent predictors of multivessel disease, complex lesion morphology, intracoronary thrombus or either of

latter two

Patel DJ Eur Heart J 2001; 22:1991-96

Complex lesion or IC thrombus

Odds ratio p Value Odds ratio p Value Odds ratio p Value Odds ratio p Value

0.02

If exercise ECG is so bloody good, why is it

abnormal so infrequently during

dobutamine echocardiography when

ischemia (inducible wall motion

abnormality) is present ?

0.0

2.0

4.0

6.0

8.0

10.0

0.5

2.93.5

0.6

5.3

7.1

1.4

3.2

9.0H

ard

Eve

nt R

ate

per

Yea

r (%

)

Low Intermadiate High

Normal

Mild Abnl

Mod-Sev Abnl

Duke Treadmill Score

Rates of hard events per years as a function of the result of stress SPECT in pts with low, intermediate, and high Duke treadmill scores groups

Hachamovitch R, Circulation 2002; 105:823-829

Clinical suspicion of ACS

Physical examination, echocardiogram, ECG monitoring, blood samples

Persistent ST-segment elevation

No Persistent ST-segment elevation

Thrombolysis

PCI

Aspirin, clopidogrel, LMW heparin, Beta-blockers, nitrates

High Risk Low Risk

Second troponin measurement

Glycoprotein IIb/IIIa, coronary angiography

Positive Negative

Stress Test, coronary angiography

Hamm CW Lancet 2001;358:1533-38

•Early Conservative Strategy?

•Early Invasive Strategy?

25%

20%

15%

10%

5%

0%

At Discharge At 1 Month At 1 Year

Comparison of Outcomes (death or MI in non-Q-wave MI) in VANQWISH

7.8%

3.3%

10.4%

5.7%

24%

18.6%

V Conservative (n=458)V Invasive (n=462)

Boden H, N Engl J Med 1998; 339:1091-9

0 60 120 180 240 300 360

0.06

0.08

0.10

0.12

0.14

0.16

0.04

0.02

Non-invasive group

Time since start of open-label dalteparin (days)

FRISC II TRIAL

Wallentin L, Lancet 2000;356:9-16

Invasive groupProb

abil

ity

of d

eath

or

myo

card

ial i

nfar

ctio

n

Early Invasive Strategy

• Recurrent angina-ischemia at rest or with low level activities despite intensive anti-ischemic therapy

• Elevated TnT or TnI

• New or presumably new ST-segment depression

• Recurrent angina/ischemia with CHF symptoms

• High-risk findings on noninvasive stress testing

• Depressed LV systolic function

• Hemodynamic Instability

• Sustained Ventricular Tachycardia

• PCI within 6 months

• Prior CABG ACC/AHA Practice Guidelines 2002

coronary angiographyclass I - Level Evidence A

Early Conservative Strategy

Coronary angiography is reserved for patients with:

• Evidence of recurrent ischemia

- angina at rest or with minimal activity - dynamic ST-segment changes

• Strongly positive stress-test (despite vigorous medical therapy)

ACC/AHA Practice Guidelines 2002

Early Invasive Strategy

• Recurrent angina-ischemia at rest or with low level activities despite intensive anti-ischemic therapy

• Elevated TnT or TnI

• New or presumably new ST-segment depression

• Recurrent angina/ischemia with CHF symptoms

• High-risk findings on noninvasive stress testing

• Depressed LV systolic function

• Hemodynamic Instability

• Sustained Ventricular Tachycardia

• PCI within 6 months

• Prior CABG ACC/AHA Practice Guidelines 2002

coronary angiographyclass I - Level Evidence A

Angina

ECG

Cardiac Markers

IMA UA Possible UA

+ + +/- + + + - ?+ + - -

Reperfusion Therapy

CCU CPU Pharmacological test

Initial Clinical Presentation

0.1 1 10 100Clinical TrialsAntmanHamm

OhmanLuscherSummary

Cohort StudiesGokhan CinHamm

HammMockel

PettijohnRavkilde

StubbsSummary

Ravkilde

The odds ratio for increased mortality with a positive troponin T for clinical trials and cohort studies

Heidenreich J Am Coll Cardiol 2001;38:478-85

Age, by decade

Gender, female

S3 or rales

ST segment depression

Complicated angina

CK-MB < 5 IU/ml

CTnI, by category

1.51 (1.3,1.9)

0.9 (0.7, 1.5)

3.4 (1.2, 9.2)

2.0 (1.4, 3.0)

1.5 (1.0, 2.3)

1.4 (0.9, 2.0)

1.1 (0.8, 1.5)

Crude Relative Risk OR (95% CI)

Adjusted Relative Risk OR (95% CI)

p Value

0.0001

0.0004

0.03

0.2

0.5

0.02

0.9

Crude and adjusted Relative Risk of Death or Myocardial Infarction by 42 Days

CRP, by category 1.0 (0.9, 1.1) 0.3

1.5 (1.2, 1.8)

1.5 (0.3, 0.7)

1.6 (1.1, 2.5)

1.8 (1.2, 2.8)

1.3 (0.9, 2.0)

_

_

_

p Value

0.0004

0.03

0.004

0.2

0.6

_

_

_

Salomon J Am Coll Cardiol 2001;38:969-79

Why are the guidelines so misleading?

• Composition of members

• Selection bias

• Peer pressure

The purpose of this study was to compare the effects of

nitrates and calcium channel blockers on

electrocardiografic (ECG) ischemia during exercise in a

group of women admitted to our laboratories because of

the occurrence of effort angina associated with ST

depression. The results of this investigation demonstrate

that simply acquired ECG variables during exercise stress

testing on drugs contain diagnostic information, and may

reflect the underlying pathogenetic substrate of angina.

16

18

20

22

24

26

28

Before ISDN After ISDN16

18

20

22

24

26

28

Before V After V

16

18

20

22

24

26

28

Before ISDN After ISDN16

18

20

22

24

26

28

Before V After V

NCA

CAD

RP

P (

103 U

) A

T 0

.1 m

V S

T

RP

P (

103 U

) A

T 0

.1 m

V S

T

p<0.001

p<0.001p<0.001

ST

ST

RPP (103 U)

Baseline EST

EST on drug

RPP (103 U)

(mV)

(mV)

ISDN VerapamilNCA Patients

CAD Patients

2827262524232221201918

0.0

0.1

0.2

0.3

2827262524232221201918

0.0

0.1

0.2

0.3

28272625242322212019181716

0.0

0.1

0.2

0.3

2827262524232221201918

0.0

0.1

0.2

0.3

200

300

400

500

600

700

Before ISDN After ISDN

NCACAD

Tim

e of

exe

rcis

e (s

ec)

Tim

e of

exe

rcis

e (s

ec)

200

300

400

500

600

700

Before V After V

200

300

400

500

600

700

Before ISDN After ISDN

200

300

400

500

600

700

Before V After V

p<0.001

p<0.001p<0.001

PURSUIT Trial Investigator

0,9

0,91

0,92

0,93

0,94

0,95

0,96

0,97

0,98

0,99

1

30 60 90 120 150 180

Pro

b. o

f su

rviv

al

Days

N Engl J Med 1998;339:436-43

TIMI Risk Score

0

5

10

15

20

25

30

35

40

45

0/1 2 3 4 5 6/7

4,7

8,3

13,2

19,9

26,2

40,9

N° of Risk Factors

Rat

e of

com

posi

te e

nd p

oint

%

Antman EM et al. JAMA 2000;284:835-42