Acute Coronary Syndrome

Clinical Manifestation of CAD

• Silent Ischemia/asymptomatic
• Stable Angina
• Acute Coronary Syndrome (Non-
STEMI/UA and STEMI)
• Arrhythmias
• Heart Failure
• Sudden Death
 Previously:

• WHO criteria for the diagnosis of

myocardial infarction ( at least 2/3):
1. Typical history of chest pain
2. Presence of ECG changes
3. Rise of biochemical markers
With the advent of troponins, which is more
sensitive biochemical marker, new
definition:
 ACS REDEFINED
Revised Criteria: Acute/Evolving/
Recent MI
( The Joint ESC-ACCF-AHA-WHF task force )

• Typical myocardial necrosis-associated rise & fall of Troponin or

CK-MBmass
PLUS
• One of:
• Cardiac Ischaemia symptoms
• Q waves on ECG
• ST segment changes indicative of ischaemia
• Coronary artery imaging (stenosis/obstruction)
• OR Pathologic ECG findings of an acute MI
 Typical chest pain

• Substernal pain/pressure radiating to

the jaws and down arms
• Exertional
• Relieved with rest
• Nausea
• Dyspnea
• Diaphoresis
 Typical Chest Pain
Considered to be unstable if presented
in any of the following three ways:

• Angina at rest lasting for more than 20

minutes
• New onset angina that markedly limits
physical activity
• Increasing angina that is more frequent,
lasts longer, or occurs with less exertion
than previous angina
 Atypical Chest Pain

• Only for Low Risk patiens

• For High Risk Patient ► all type of
chest pain must be exemined
ELECTROCARDIOGRAPHY
in ACS
 STEMI

• http://www.thrombosisadviser.com/html/images/library/atherothrombosis/stemi-and-
nstemi-ecg-illustration-PU.jpg
 STEMI ECG Criteria

• ≥ 2 mm of ST segment elevation in 2 contiguous

precordial leads in men (1.5 mm for women)
• ≥ 1mm in other leads (2 contiguous)
• An initial Q wave or abnormal R wave develops over
a period of several hours to days.
• Within the first 1-2 weeks (or less), the ST segment
gradually returns to the isoelectric baseline, the R
wave amplitude becomes markedly reduced, and the
Q wave deepens. In addition, the T wave becomes
inverted.
 STEMI ECG Criteria

• In addition to patients with ST elevation on the ECG,

two other groups of patients with an acute coronary
syndrome are considered to have an STEMI:
• those with new or presumably new left bundle
branch block
• those with a true posterior MI
• An elevation in the concentration of troponin or CK-
MB is required for the diagnosis of acute MI
Depresi ST pada iskemia miokard

a.Horizontal b.Landai ke bawah c.Landai

ke atas

Sunoto Pratanu, Buku Ajar ECG

edisi 2013
Inversi T pada iskemia miokard
a. Inversi T pada umumnya kurang spesifik untuk
iskemia
b. Inversi T yang berujung lancip dan simetris (seperti
ujung anak panah), spesifik untuk iskemia
Sunoto Pratanu, Buku Ajar
ECG edisi 2013
Sadapan ECG yang berkesesuaian
untuk Iskemia / Infark
• Daerah anteroseptal: V1-V4
• Daerah anterior ekstensif: V1-V6, I dan aVL
• Daerah anterolateral: V4-V6, I dan aVL
• Daerah anterior terbatas: V3-V5
• Daerah inferior: II, III dan aVF
• Daerah lateral tinggi: I dan aVL
• Daerah posterior murni: bayangan cermin dari
V1, V2, dan V3 terhadap garis horisontal

Sunoto Pratanu, Buku Ajar ECG edisi 2013

CARDIAC MARKERS
in ACS
 FEATURES OF AN IDEAL
CARDIAC MARKERS
They Should
• Be Heart Specific
• Be Highly Sensitive for Cardiac Damage
• Undetectable in Patients without Myocardial
Damage
• Be Able to Differentiate Reversible from
Irreversible Damage
• Allow The Monitoring of Reperfusion
• Be Able to Estimate Infarct Size And Prognosis
• Easy to Use (Can be measured in blood samples)
• And Cost Effective
CARDIAC MARKERS
• Cardiac Enzymes
1) CRATINE KINASE (CK)
2) LACTATE DEHYDROGENASE (LD)
3) ASPARTATE TRANSAMINASE (AST)
• Cardiac proteins
1) MYOGLOBIN
2) TROPONIN
• New Research Markers
1) GLYCOGEN PHOSPHORYLASE
2) HEART FATTY ACID BINDING PROTEIN
3) ISCHEMIA MODIFIED ALBUMIN
4) CARBONIC ANHYDRASE III
 BIOCHEMICAL MARKERS IN
MYOCARDIAL ISCHAEMIA / NECROSIS

RECENT
• CK-MB (mass) Traditional
• c.Troponins (I or T) • AST activity
• LDH activity
• Myoglobin
FUTURE: • LDH isoenzymes
• Ischaemia Modified Albumin
• CK-Total
• Glycogen Phosphorylase BB
• Fatty Acid binding Protein • CK-MB activity
• Highly sensitive CRP.
• CK-Isoenzymes
 ACS REDEFINED
Revised Criteria: Acute/Evolving/
Recent MI
( The Joint ESC-ACCF-AHA-WHF task force )

• Typical myocardial necrosis-associated rise & fall

of Troponin or CK-MBmass

PLUS
• One of:
• Cardiac Ischaemia symptoms
• Q waves on ECG
• ST segment changes indicative of ischaemia
• Coronary artery imaging (stenosis/obstruction)
• OR Pathologic ECG findings of an acute MI
 Release of Cardiac Troponins and CK-MB
in Acute MI

50
Cardiac troponin after
“classic” acute MI
20
CK-MB after acute MI
Multiples of 10
the upper
Cardiac troponin after
reference limit 5 “microinfarction”

2
Upper
1 reference
limit

0 1 2 3 4 5 6 7 8

Days after onset of acute MI

Antman EM. N Engl J Med. 2002;346:2079-82.
 BIOCHEMICAL MARKERS IN AMI
ASSESSMENT OF REPERFUSION

Successful • “Washout” phenomenon –

reperfusion enzymes & proteins have
direct vascular access
when occluded coronary
Marker Level

circulation becomes patent

Unsuccessful
• Peak concentrations earlier
reperfusion
& at higher levels if
reperfusion successful

Time

Due to short plasma half life (t½ = 10 min) Myoglobin is considered the
best re-perfusion marker
THE TROPONIN REGULATORY
COMPLEX
 Cardiac Biomarkers: Troponin
• Most specific for myocyte injury
• Rise @ 3 hours, elevated 7-10
days
• Not sensitive < 6 hours after onset
of pain
• Tn T skeletal muscle disease &
renal failure
• Tn I  preferred marker
• Predictor of outcome
• Single normal troponin does NOT
exclude ACS.
CARDIAC TROPONIN T (cTnT)
• After Onset of AMI
1) It Increases within A Few Hours
2) Peaks within 1 to 2 d
3) Return to Normal Levels within 5 to 10 d
• It Is Useful for
1) Diagnosis of AMI after 2 to 3 Days
2) Differential Diagnosis of Myocardial
Damage from Skeletal Muscle Damage
3) Estimation of Infarct Size
4) Monitoring after Reperfusion
CARDIAC TROPONIN I (cTnI)

• After Onset of AMI

1) It Increases within A Few Hours
2) Peaks within 1 to 2 d
3) Return to Normal Levels within 5 to
7d
• It Is Highly Specific for
Myocardium
• It Is A Very Sensitive Marker of
Cardiac Damage
 CK MB

• CK MB
• mostly in heart, can be increased in skeletal
muscle diseases
• low sensitivity early (< 3 hours from symptom
onset)
• Sensitivity increases with time
• Rise within 3-8 hours, peak 20 hours, decline
in 3 days
• Good for detecting early reinfarction by
noting repeat elevation in level after 2 days
 CK-MB ACTIVITY
• After Onset of chest Pain
1) It Increases within 4 to 6 h
2) Peaks within 24 h
3) Return to Normal Levels within 48 to 72 h
• It Is Valuable for Diagnosis of
AMI, But Have Several Limitations
:
1) Low Cardiac Specificity
2) Presence In Normal Serum
3) Low Cardiac Content
4) Its Cardiac Distribution Is Not Uniform
5) Technical Problems
 CK-MB MASS

• Measured By Monoclonal Anti-CK2

Antibody
• Is Rapid
• Is More Specific
• Is Detectable Earlier (About 1 h)
BIOCHEMICAL MARKERS IN ACS
CURRENT RECOMMENDATIONS
• AMI – Routine diagnosis : Troponins (CK-
MBmass)
• Retrospective diagnosis : Troponins
• Skeletal muscle pathology : Troponins
• Reinfarction : Mb, CK-MBmass
• Reperfusion : Mb, Tn, CK-Mbmass

• Infarct size : Troponins

• Risk stratification in UA : Troponins
 Atherosclerosis: A Progressive Disease

Plaque rupture

Adhesion Macrophage
molecule Oxidized
Monocyte LDL-C LDL-C

Foam cell
CRP

Smooth muscle
cells

Plaque instability
Endothelial dysfunction Inflammation Oxidation
and thrombus

Libby P. Circulation. 2001;104:365-372; Ross R. N Engl J Med. 1999;340:115-126.

 Evolution Process of Atherosclerosis

Foam Fatty Intermediate Fibrous Complicated

Cells Streak Lesion Atheroma Plaque Lesion/Rupture

Type I Type II Type III Type IV Type V Type VI

November 14, 2018

33
Unstable Plaque
Platelets aggregate at
site of rupture/erosion

Lipid core

Adventitia

34
 Unstable Plaque
Thrombus forms and
extends into the
lumen and the plaque
Thrombus

Lipid core

Adventitia

35
 Pathogenesis of ACS
Inflammation and/or infection
Platelet aggregation Incomplete occlusion
Thrombus formation Distal embolization
Vasospasm

Unstable angina
Plaque rupture
NSTE MI
(55-80%)

Exertion
BP, HR
Vasoconstriction
Vulnerable Plaque
Complete occlusion

STEMI
38
Hyperacute phase of extensive
anterior-lateral myocardial
infarction
Admission CHEST PAIN

Working
Suspicion of Acute Coronary Syndrome ( ACS )
Diagnosis

Persistent Normal /
ECG ST-Elevation
ST/T-abnormalities
Undetermined ECG

Biochemistry Troponin (+) Troponin 2x (-)

Risk High Risk Low Risk

Stratification

Diagnosis STEMI NSTEMI UA

Treatment Reperfusion Invasive Non-Invasive

Guideline for the diagnosis and treatment of NSTEMI ACS, ESC Guidelines June 14th, 2007
 ESC : Management Strategy in ACS Patients
Clinical suspicion of ACS

Physical examination
ECG monitoring, blood samples

Persistent No persistent Undetermined

ST-segment elevation ST-segment elevation diagnosis

Thrombolysis ASA, Fonda/Enox/UHF ASA

PCI clopidogrel*, beta-blockers, nitrates

*Omit clopidogrel if
the patient is likely to High risk Low risk
go to CABG within 5 Second troponin measurement
days GPIIb/IIIa,
coronary angiography
Positive Twice negative

PCI, CABG or medical management Stress test,

depending upon clinical and angiographic features coronary angiography

1. Bertrand ME et al. Eur Heart J 2002; 23; 18091840.

 Early Assessment

Unstable Angina
Clinical concern alone

NSTEMI
Clinical concern
Positive cardiac marker
Absence of ST elevation

STEMI
Clinical concern
Positive cardiac marker
ST elevation on ECG
 MANAGEMENT of STEMI

• Management of STEMI is time sensitive, early

revascularization  reduction of infarct size,
better myocardial function, lower mortality
• In the
Patient callsoptimal
a central EMSsituation;
as soon as possible after the onset of chest pain.

Fully equipped ambulance with personnel trained to perform and

interpret a 12-lead ECG
ECG : ST-segment elevation or new LBBB

Nearest PCI hospital is informed

Catheterization laboratory is prepared and staff summoned Lim et al, 2013;

Steg et al, 2012
 REPERFUSION THERAPY
• Restoring coronary flow and myocardial tissue reperfusion

Mechanical (PCI)

Pharmacological (Fibrinolytic)

• Coronary artery being occluded  Half of salvageable

myocardium is lost within 1 h, and two-thirds are lost
within 3 h
• Should be performed as early as possible for patient :

Clinical presentation of STEMI within 12 h of

symptom onset
(with persistent ST-segment elevation or new or
presumed new LBBB) Gray et al, 2013;
Steg et al, 2012
Primary PCI
• An emergent percutaneous catheter intervention in the
setting of STEMI, without previous fibrinolytic treatment.
• The preferred reperfusion strategy in STEMI.
• RCTs show PPCI is superior to fibrinolysis in patients with
STEMI

Hospitals with an established interventional

cardiology programme (available 24/7) should
use primary PCI as a routine treatment

Within 60*-90 minutes

*Steg et al, 2012;
O’Gara et al. 2013
• Manual thrombus PPCI
aspiration : improved
tissue perfusion, more
complete ST resolution.
• PCI noninfarct artery :
considered in patients with
cardiogenic shock due to
pump failure.
• DES implantation ↓
restenosis rates and the
need for reintervention, but
does not definitely reduce
rates of death or
reinfarction. DES

BMS O’ Gara et al, 2013; Steg et al,

2012
Fibrinolysis
• Fibrinolysis is an important reperfusion strategy 
when primary PCI cannot be offered to STEMI
patients.
• Should be given to patients with STEMI and onset of
ischemic symptoms < 12 hours. within 30 min

Steg et al, 2012; O’ Gara

et al, 2013
 Thrombolytic agents

STREPTASE • ALTEPLASE UF
H

• Non fibrin selective • Tissue Plasminogen Activator

• Immunogenic • Binds to fibrin >> than

• Inexpensive streptokinase or urokinase

• Two thirds of the total dose of
• Infusion 1.5 million IU in
100 ml of normal saline 100 mg , first 30 minutes :
(30 – 60 min). o initial bolus of 15 mg 
o 50mg over 30 minutes 
• Side effects : bleeding
and allergic reaction. o 35 mg over 1 hour.

Fox et al, 2009; Gogo et al, 2010

TIMI phase 1 trial (1985), GISSI trial, ISSIS trial : tPA is
superior to SK

O’Gara et al, 2013;

Gogo et al, 2010

Absolute
Previous ICH or stroke of unknown
origin at any time
Ischaemic stroke in the preceding 6
months
Central nervous system damage or
neoplasms or AVM
Recent major trauma/surgery/head
injury (within the preceding 3 weeks)
Gastrointestinal bleeding within the past
month
Known bleeding disorder (excluding
menses)
Aortic dissection
Non-compressible punctures in the past
24 h (e.g. liver biopsy, lumbar puncture)
Contradindication
Relative
Transient ischaemic attack in the
preceding 6 months
Oral anticoagulant therapy
Pregnancy or within 1 week postpartum
Refractory hypertension (systolic blood
pressure >180 mmHg and/or diastolic
blood pressure >110 mmHg)
Advanced liver disease
Infective endocarditis
Active peptic ulcer
Prolonged or traumatic resuscitation
Steg et al, 2012
 ADJUVANT THERAPY
Antiplatelet
ADP receptor inhibitor
Aspirin
Loading dose given Clopidogrel
orally (preferably 150– PPCI 1x75 mg
600 mg
300 mg) including
chewing Prasugrel
1x 10 mg
60 mg

Ticagrelor
2 x 90 mg
180 mg

Fibrinolyti Clopidogre
Aspirin 162 - 325 mg c l
loading dose  Age 75 y: 300-mg
loading dose
and continued indefinitely  Age > 75 y: 75 mg (no
loading dose)
In PPCI setting Clopidogrel was
limited 300 mg

• Loading dose 600

mg /150 mg is
superior than
300mg/75 mg.
OASIS 7
• Clopidogrel 600
mg reach maximal
inhibition within 2
hours, (300 mg  Prasugrel is contraindicated in
patients with prior Stroke/TIA
need 24-48 hours)  And not recommended in
patients aged ≥75 years or with
low er body w eight (<60 kg)
Steg et al, 2012
 Cangrelor

• Novel i.v, fast-acting, potent,

and direct-acting ADP
inhibitor, has rapid
reversible effects.
• Half-life 3-5 minutes.
• CHAMPION PHOENIX trial :
30 μg/kg  4 μg/kg/min at
least 2 hours (or duration
procedure)
Reduced rate of
ischemic events, stent
thrombosis during PCI
Ticagrelor may cause transient
dyspnoea, asymptomatic bradicardy vs clopidogrel

Steg et al, 2012 Bhatt et al, 2013

Steg et al, 2012
 Anti coagulant

Anticoagulant options for primary PCI include unfractionated

heparin (UFH), enoxaparin and bivalirudin.

UFH/ Heparin
• PCI :
• bolus 70–100 U/kg when no glycoprotein (GP) IIb/IIIa inhibitor
• 50–60 U/kg when the use of GP IIb/IIIa inhibitors is expected
• Fibrinolysis :
(at
• Bolus 60 IU/kg (max 4000 IU)  12 IU/kg/h (max 1000 IU)
least 48 hours after fibrinolysis or until
revascularization)
Steg et al, 2012;
Kern et al, 2013
 LMWH

PPCI :
• Enoxaparin (with or without
routine GP IIb/IIIa blocker)
preferred over UFH
• Dose : 0.5 mg/kg iv bolus

Fibrinolysis, or without
reperfusion :
 30 mg iv bolus, followed 1
mg/kg s.c every 12 h
 elderly (without bolus iv)
 0,75 mg/kg s.c every 12
h O’Gara et al, 2013
 FONDAPARINUX GP IIb/IIIa inhibitor
• Should not be used as • Abciximab (ReoPro),
the sole anticoagulant Tirofiban (Aggrastat),
Eptifibatide (Integrilin)
in PPCI  risk of
catheter thrombosis. • Current role of routine
use of GP IIb/IIIa
• Initial dose 2.5 mg iv, inhibitors in primary PCI
then 2.5 mg sc 1x/day still unclear.
• As bailout therapy 
• Contraindicated if CrCl evidence of large
< 30 mL/min thrombus, slow or no-
reflow

Yusuf et al, 2009; Fox et al,

2009; Steg et al, 2012
 ROUTINE MEDICAL THERAPY

Beta Blocker ARB/ACEI

• Oral: All patients • ACEI : evidence of heart
without failure, LV systolic
contraindication dysfunction, diabetes
• IV: Patients with or an anterior infarct.
refractory hypertension • ARB : For patients
or ongoing ischemia intolerant of ACE
without inhibitors
contraindication

O’ Gara et al, 2013; Fox et al,

2009
 Statins
• All patients without
contraindications
CCB
• Recommendation : High-
• May be useful, however, dose atorvastatin 80 mg
to relieve ischemia, daily
lower BP, or control the
ventricular response
rate to AF patients Nitrate
• Indication : Ongoing chest pain,
• Caution : LV systolic Hypertension and HF
dysfunction.
• Should not be given to patients
with hypotension, marked
bradycardia or tachycardia, RV
infarction
O’ Gara et al, 2013; Fox et al, 2009; Man et al,
2010; Antman & Morrow, 2012
 Prosedur Terapi trombolitik

• Check list thrombolytic (adakah

kontraindikasi)
• Informed consent (jelaskan yg
terburuk, tanda tangan persetujuan
maupun penolakan, tidak ada istilah
penundaan
• Pemberian bisa di UGD, ICCU, ICU,
ROI
• Pasang monitor
• Siapkan defibrilator
• Pasang 2 iv line
• Ekg sblm trombolitik, 1 jam post
trombolitik
• Streptokinase 1.5 juta unit dlm D5
100 cc dlm 30 menit
• Atau alteplase bolus 15 mg, drp 50
mg dlm 30 menit, 35 mg dlm 1 jam
 Komplikasi
• Perdarahan
• Hipotensi
• Aritmia
• Alergi
• Demam
 ESC : Management Strategy in ACS Patients
Clinical suspicion of ACS

Physical examination
ECG monitoring, blood samples

Persistent No persistent Undetermined

ST-segment elevation ST-segment elevation diagnosis

Thrombolysis ASA, Fonda/Enox/UHF ASA

PCI clopidogrel*, beta-blockers, nitrates

*Omit clopidogrel if
the patient is likely to High risk Low risk
go to CABG within 5 Second troponin measurement
days GPIIb/IIIa,
coronary angiography
Positive Twice negative

PCI, CABG or medical management Stress test,

depending upon clinical and angiographic features coronary angiography

1. Bertrand ME et al. Eur Heart J 2002; 23; 18091840.

NSTE- ACS