Acute Coronary Syndrome

- ()
- Cardillogy Fellowship, Western General Hospital, Edinburgh and
Freeman Hospital, Newcastle upon Tyne, U.K.
- Members of Royal College of Physicians of England (MRCP)

- Bachelor of Medicine and Bachelor of Surgery All India institute
of Medical Sciences New Delhi, India
- Internship .
- Internal Medicine Residency, University of Illinois, Chicago, USA.
- Cardiology Fellowship, University of Chicago, Chicago, USA.
- Cardiac and Peripheral Intervention Fellowship, Lahey Clinic/
Beth Isreal Deaconess Hospital, Boston, USA.
- American Board of Internal Medicine
- American Board of Cardiovascular Disease
- American Board of Interventional Cardiovascular Disease

3
unstable angina (UA), non-ST elevation myocardial
infarction (NSTEMI) acute ST-elevation
myocardial infarction (STEMI)

3
acute coronary syndrome (ACS)
( 1)
ACS STEMI STEMI

ACS
UA
myocardial oxygen demand
supply 4 1
1. Occlusive or non-occlusive thrombus on
pre-existing plaque :
ACS atherosclerosis plaque
thrombus formation
thrombus

2. Dynamic obstruction (coronary spasm)
: Prinzmetals angina
vasospasm hypercontractility
vascular smooth muscle endothelial
dysfunction
3. Progressive mechanical obstruction :
atherosclerosis
progressive/worsening angina plaque
rupture vasospasm
4. Secondary causes :
stable coronary artery disease

1 ACS

106


occlusive thrombus
STEMI NSTEMI UA
non-occlusive thrombus
spontaneous reperfusion
spontaneous clot lysis

myocardial oxygen
delivery
ACS
plague rupture
ACS

ACS 3

1. Rest angina:
angina
2. New-onset angina:
angina 2

Canadian Cardiovascular Society
(CCS) class III
3. Progressive angina:
angina 2

ACS : The Vulnerable Plaque

ACS /
plaque (plaque rupture) plaque
(plaque erosion)
coagulation system extrinsic
intrinsic pathway (thrombus)
Plaque
(vulnerable plaque) ( 2) (mild
to moderate stenosis) vulnerable
plaque fibrous cap lipid core,
macrophage T-lymphocyte
Inflammatory cells enzymes
fibrous cap

2 vulnerable plaque inflammatory process foam cell metalloprotienase enzyme

collagen fibrous cap

107


CCS class III

prognosis Classification Braunwald
Classification ( 1)
3 1.
2. 3.

Classification UA
ACS spectrum

1

Braunwalds Classification

unstable angina (Braunwald s Classification)

Class I:
New-onset, severe, or accelerated angina
Patients with angina of less than 2 months duration, severe or occurring three or more
times per day, or angina that is distinctly more frequent and precipitated by distinctly less
exertion. No rest pain in the last 2 months.
Class II:
Angina at rest. Sub acute
Patients with one or more episodes of angina at rest during the preceding month but not
within the preceding 48 hr.
Class III:
Angina at rest. Acute
Patient with one or more episodes at rest within the preceding 48 hr.

Class A:
Secondary unstable angina
A clearly identified condition extrinsic to the coronary vascular bed that intensified
myocardial ischemia, e.g. anemia, infection, fever, hypotension, tachyarrhythmia,
thyrotoxicosis, hypoxemia secondary to respiratory failure.
Class B:
Primary unstable angina
Class C:
Post infarction unstable angina (within 2 weeks of documented MI)

1.
Absence of treatment or minimal treatment
2.
Occurring in presence of standard therapy for chronic stable angina (conventional doses of oral
beta-blockers, nitrates, and calcium antagonists)
3.
Occurring despite maximally tolerated doses of all three categories of oral therapy, including
intravenous nitroglycerin

108

1. ACS
obstructive CAD 2
2.
non-fatal MI 3

(Risk Stratification)

ACS high risk
intracoronary thrombus


aggressive monitor

TIMI III Registry 2
UA/NSTEMI 1416 1
MI 1
ECG
( 3)
1. Left bundle-branch block (LBBB) relative risk
2.8

ACS
2
2 obstructive CAD

3 UA/NSTEMI non fatal MI

109

2. ST depression 1.0 .
dealth/MI 11% (relative risk
1.89)
3. T-wave inversion death/MI 6.8%
symmetrical deep Twave inversion precardial
leads V1-V4 proximal mid

3. Brain natriuretic peptide (BNP)

32 amino acid polypeptide
ventricle volume
expansion pressure overload
cardiac marker
UA/
NSTEMI BNP

3 ECG
1

4 Troponin I
(TIMI IIIB study)

7
4. Makers fibrinogen, fibrinopeptide,
amyloid A, Interleukin-6, VCAM-1

AMI reinfarction
sudden cardiac death

1. : Bedrest, oxygen therapy,
sedation analgesic drug morphine
correct precipitating factors
anemia, infection, arrhythmia, thyrotoxicosis
2. 3
2.1 Anti-ischemic drugs : Nitrates, Betablockers, Calcium- blockers
2.2 Antiplatelets

left anterior descending coronary artery

stenosis
4. Normal ECG
death/MI 8.2%
serologic markers
1. Cardiac troponin T troponin I
cardiac marker
myocardial necrosis
cardiac events
UA
Troponin T I
CK-MB
Troponin T / I
5 ( 4)
2. C-reactive protein (CRP)
marker inflammation
CRP
non fatal MI sudden
cardiac death
110

2.3 Anticoagulants
3. mechanical revascularization

nitrates ACS
nitrates
8, 9

Nitrates

Beta-blockers
Beta-blockers
myocardial infarction
ACS

LV


50-60
beta

Nitrates
vasodilator
vein artery cardiac preload
Homodynamic
Nitrates UA/
NSTEMI contraindication
hypotension

( 4)
4 Nitrates

5 Beta - blockers

111

blockers intrinsic sympathetic activity (ISA)

Pindolol Acebutolol heart rate

(AMI) 48
51 160-325 .
75-325 . 11
aspirin UA/NSTEMI



aspirin
anaphylaxis shock

Calcium-channel blockers (CB)

calciumchannel blockers
AMI 10
CB
angina
Nitrates Beta-blockers CB
Nitrates Beta-blockers
angina
CB
CB 6
(
Antiplatelet therapy (Aspirin , Ticlopidine ,
Clopidogrel )
1. Aspirin
Aspirin platelet aggregation
Cyclooxygenase (COX-1)
thromboxane A2
aspirin ACS

2. Thienopyridine group (Ticlopidine

Clopidogrel)
2.1 Ticlopidine
platelet aggregation
ADP antagonist
ticlopidine UA cardiovascular death 47 nonfatal
MI 46 6
10 12
aspirin
ticlopidine 250 . 2
neutropenia

6 Calcium-channel blockers

112

thrombocytopenia 1
CBC platelet count 2
thrombotic thrombocytepenic purpura (TTP) 0.02%
2.2 Clopidogrel
Clopidogrel thienopyridine
derivative ticlopidine
platelet aggregation
adenosine diphosphate receptor
platelet (ADP antogonist) CURE 13
clopidogrel aspirin
UA/NSTEMI aspirin
clopidogrel aspirin
, MI
stroke 20 (P = 0.00005)
1
clopidogrel
aspirin clopidogrel 300 .
75 .
(CURE
study) 3 -12
Clopidogrel ticlopidine

loading dose 2
neutropenia 0.1%
TTP 0.0004%
Anticoagulants
ACS platelet aggregation
coagulation plaque rupture
thrombus formation
aspirin heparin inhibit platelet
aggregation coagulation UA/NSTEMI
AMI sudden death
aspirin
anticoagulation unfractionated
heparin (UFH) Low -molecular-weight heparin
(LMWH)

Unfractionated heparin (UFH)

meta-analysis UA/
NSTEMI UFH aspirin
aspirin
recurrent ischemia
MI 2-12 33 UA
intermediate high risk heparin

UFH 1 60-70 /
bolus
12-15 //
aPTT 6
heparin
heparin aPTT ratio 1.5-2
baseline aPTT 50-70
3-5
Low-molecular-weight-heparin ( LMWH )
LMWH
UFH
- anti-Xa antithrombotic

- Plasma protein binding

bioavailability predict anticoagulant
response
- monitor aPTT
- Heparin-induced thrombocytopenia
- bioavailability

rebound effect UFH

Pharmacokinetic safety profile LMWH
UFH Enoxaparin
UFH 14 LMWH
check
aPTT UFH

113

 7 LMWH UA/NSTEMI

Antixa : IIa

Dalteparin(Fragnin)

2.7

6000

Nadrapaine(Fraxiparine) 3.6

4500

Enoxaparin(Clexane)

4200

3.8

120 IU/kg IV 12 .
( 10,000 IU twice daily
86 anti-Xa IU/Kg IV
86 antiXa IU SC 12
30 mg IV bolus
1 mg/kg sc 12

cardiac
troponin positive
eptifibatide
tirofiban abciximab
GUSTO IV - ACS abciximab setting
placebo
2. UA/NSTEMI
PCI 24
GP IIb/IIIa inhibitors

3 tirofiban, eptifibatide
abciximab abciximab

(Mechanical Revascularization)


coronary anatomy
(culprit lesion)
setting
balloon
(stent) acute closure
(restenosis)

creatinine clearance < 30 ml/min

LMWH
7

Glycoprotein (GP) IIb/IIIa inhibitors

antiplatelet aspirin,
thienopyridine group
pathways pathways
platelet
aggregation GP IIb/IIIa inhibitors
GP IIb/IIIa receptor final
common pathway platelet aggregation

oral form intravenous

form oral form
meta-analysis oral form


intravenous GP
IIb/IIIa Inhibitors
UA/NSTEMI
coronary angioplasty 3 abciximab,
eptifibatide tirofiran


1. UA/NSTEMI high risk
feature ongoing pain , hemodynamic
compromise, refractory ischemia

conservative invasive
strategy
UA/NSTEMI 2

114

1. Early conservative strategy

recurrent angina / failed
medical therapy noninvasive
stress test positive EST, stress
radionuclide / echocardiography
coronary angiography revascularization
recurrent ischemia, hemodynamic
instability/shock
noninvasive stress test
adverse cardiac events

- New or presumably new ST-segment

depression
- Recurrent angina/ischemia with CHF
symptoms, an S3 gallop, pulmonary
edema, worsening rales, or new or
worsening MR
- High-risk findings on noninvasive stress
testing
- Depressed LV systolic function (EF < 0.40
on noninvasive study)
- Homodynamic instability
- Sustained ventricular tachycardia
- PCI within 6 months or prior CABG

2. Early invasive strategy

Early invasive strategy
ACS coronary angiography 2448 revascularization of culprit lesion strategy

TACTIC-TIMI 18 UA/NSTEMI high
risk intermediate risk GP IIb/IIIa
inhibitors tirofiban early
invasive strategy primary endpoint (death,
myocardial infarction, rehospitalization)
conservative strategy

ACS 15
1

- , rule out noncoronary cause valvular heart disease,
hypertrophic cardiomyopathy, pulmonary
disease ACS
- 2 ECG
ST-segment elevation group non-ST
segment elevation group
- cardiac marker
troponin T I sensitivity
specificity CK CK-MB
hemoglobin anemia
(secondary cause of UA)
- ACS without ST segment
elevation
Aspirin 160-325 . 11 clopidogrel
aspirin
LMWH UFH , beta-blockers oral
intravenous nitrate persistent/
recurrent chest pain , calcium channel
blockers Beta-

non invasive
test
ACC/AHA Practice Guideline UA/
NSTIMI 2002
early invasive
- Recurrent angina/ischemia at rest or with
low-level activities despite intensive antiischemic therapy
- Elevated TnT or TnI
115

blocker Beta-blockers
oxygen morphine pain
2

ECG cardiac
marker 2
high/intermediate risk low risk

High/intermediate risk

- coronary angiography
(early invasive strategy)
- LMWH/UFH
coronary angiography
- GP IIb /IIIa inhibitors
clopidogrel abciximab 12
angioplasty eptifibatide
tirofiban 24 angioplasty
Low risk LMWH
aspirin clopidogrel beta
blocker / nitrate, calcium-channel blockers
noninvasive stress test

adverse cardiac events
significant ischemia
coronary angiography revascularization

3.

4.

5.

6.

7.

8.

9.

10.

References
1. Braunwald E, Antman EM, Beasley JW, Califf RM, Cheitlin
MD, Hochman JS, Jones RH, Kereiakes D, Kupersmith J,
Levin TN, Pepine CJ, Schaeffer JW, Smith EE III, Steward
DE, Theroux P. ACC/AHA guideline update for the
management of patients with unstable angina and non
ST- segment elevation myocardial infarction: a report of
the American College of Cardiology/American Heart
Association Task force on Practice Guidelines [Committee
on the Management of Patients With Unstable Angina].
2002.
2. Cannon CP, McCabe CH, Stone PH, et al. The
electrocardiogram predicts one-year outcome of patients
with unstable angina and non-Q wave myocardial infarction

11.

12.

13.

116

: results of the TIMI III Registry ECG Ancillary Study. J

Am Coll Cardiol 1997;30:133-40.
Savonitto S, Ardissino D, Granger CB, et al. Prognostic
value of the admission electrocardiogram in acute coronary
syndromes. JAMA 1999;281:707-13.
Hyde TA, French JK, Wong CK, et al. Four-year survival of
patients with acute coronary syndromes without STsegment elevation and prognostic significance of 0.5- mm
ST-Segment depression. Am J Cardiol 1999;84:379-385.
Antman EM, Tanasijevic MJ, Thompson B, et al. Cardiacspecific troponin I levels to predict the risk of mortality in
patients with acute coronary syndromes. N Eng J Med
1996;335:1342-9.
Haverkate F, Thompson SG, Pyke SDM, Gallimore JR, Pepys
MB, for the European Concerted Action on Thrombosis
and Disabilities Angina Pectoris Study Group. Production
of C-reactive protein and risk of coronary events in stable
and unstable angina. Lancet 1997;349:462-6.
de Lemos JA, Morrow DA, Bentley JH, et al. The prognostic
value of B-type natriuretic peptide in patients with acute
coronary syndromes. N Eng J Med 2001;345:1014-21.
Gruppo Italiano per Io studio della sopravvivenza nellnfarto
Miocardio. GISSI-3: effect of lisinopril and transdermal
glyceryl trinitrate singly and together on 6-week mortality
and ventricular function after acute myocardial infarction.
Lancet 1994;343:1115-22.
ISIS-4 Collaborative Group. ISIS-4 : randomized factorial
trial assessing early oral captopril, oral mononitrate, and
intravenous magnesium sulphate in 58,050 patients with
suspected acute myocardial infarction. Lancet 1995;354:66985.
Held PH, Yusuf S, and Furberg CD. Calcium channel
blockers in acute myocardial infarction and unstable angina
: An overview. Br Med J 1989;299:1187-92.
Antiplatelet Trialists Collaborative overview of randomized
trials of antiplatelet therapy. Prevention of death, myocardial
infarction,and stroke by prolonged antiplatelet therapy in
various categories of patients. BMJ 1994;308:81-106.
Balsano F, Rizzon P, Violi F, et al. Antiplatelet treatment
with ticlopidine in unstable angina : A controlled
multicenter clinical trial : The Studio Della Ticlopidina Nell
Angina Instable Group. Circulation 1990;82:17-26.
The Clopidogrel in Unstable Angina To Prevent Recurrent
Events [CURE] Trial Investigators. Effect of Clopidogrel in
Addition to Aspirin in Patients with Acute Coronary
Syndromes without ST-Segment Elevation. N Eng J Med
2001;345:494-502.

14. Antman EM, McCabe CH, Gurfinkel EP, et al. Enoxaparin

prevents death and cardiac ischemic events in unstable
angina / non-Q wave myocardial infarction : results of the
Thrombolysis In Myocardial Infarction [TIMI] 11B trial.
Circulation 1999;100:1593-601.
15. Michel EB, Maarten LS, Keith A AF, Lars CW, Christian
WH, Eugene M, Pim J DF, Giuseppe S, Witold R.

Management of acute coronary syndromes in patients

presenting without persistent ST-segment elevation : The
Task Force on the Management of Acute Coronary
Syndromes of the European Society of Cardiology. Eur Heart
J 2002;23:1809-40.

. Non-Q wave MI
. ST elevation MI
.
4. acute coronary syndrome


. aspirin
. B-blocker
. Nitrate
. Thrombolytics
.

1.

. plaque
(plaque rupture)
.

. (vasospasm)
.

5. ST elevation MI
. (revascularization)

. balloon
angioplasty + stent
thrombolytic
. Aspirin STEMI
thrombolytic
. Heparin STEMI
contra indication heparin
.

2. non ST
elevation MI
. Aspirin
. Beta-blocker
. Clopidogrel
. Nitrates
. Thrombolytics
3. acute coronary syndrome syndrome
?
. Unstable angina
. Non-ST elevation MI
117


Acute Coronary Syndrome
1.
2.
3.

Multiple choice-one best answer 5 3

CME 1
31 2547
19
.
71/3
. 10400

3-23-606-9500-0409
- _____________________________________________________________
_______________________________________________
______________________________________________________
__________________________________________________________________________

ANSWER
1

Acute Coronary Syndrome

3-23-606-9500-0409

3
4
5

118