A C U TE C O R O N A R Y

SYN D R O M E

O verview
Definition
Pathogenesis of ACS
Diagnosis

Symptoms : Angina Pectoris

Physical Examination
Electrocardiogram
Laboratory Findings
Angiography

Treatment
Complications

D efi
nition of ACS
ACS refer to a constellation of clinical

symptoms and findings that represent

acute myocardial ischemia.
Common pathophysiological origins related
to coronary plaque progression, instability,
or rupture with or without luminal
thrombosis and vasospasm
ACS Classification :
ST-elevation myocardial infarction (STEMI)
Non-ST-elevation ACS (NSTE-ACS) : NSTEMI and UA

American Heart Association Heart Disease and Stroke Statistics-2008 Update

Hurst's The Heart, 12th Edition, Mayo clinic cardiology 3rd edition

Pathophysiology ofAtherosclerosis
Foam
Cells

Endothelial
Dysfunction

Fatty Intermediate
Fibrous Complicated
Streak Lesion Atheroma Plaque
Lesion/Rupture

oxidized LDL
homocystein
e
smoking
aging
hyperglycemi
a
hypertension

35-45 yrs
45-55 yrs
Endothelia Lipid
accumulation
l injury
nitric oxide
endothelin-1
vasodilation

55-65 yrs

>65 yrs

Inflammatio
adhesion moleculesn
(ICAM, VCAM)
continued
monocyte adhesionmacrophage/lipid
macrophage LDL accumulation
leukocyte accumulation
uptake

MMP's
CRP
(hepatic)

Pathophysiology of
Stable and Unstable Plaques

Risk Factors ofCoronary H eart D isease

Modifiable
Dyslipidemia
(LDL ,HDL)
Tobacco
smoking
Hypertension
Diabetes
Mellitus,
Metabolic
Syndrome
Lack of Physical
Activity

Non
Modifiable
Advanced age
Male gender
(post
menopausal
women)
Family history
(1st degree
relatives <55
male or <65
female)

Novel
Homocysteine
Lipoprotein (a)
CRP & other
inflammatory
markers

D iagnostic Tools
Clinical symptom and physical

examination
ECG
Cardiac Biochemical markers
Echocardiography
Imaging of the coronary anatomy

Assessing Chest Pain (Classic Angina)

Location : usually retrosternal
Radiation : neck, throat, lower jaw,

teeth, ulnar arm, left shoulder,

interscapular, infrascapular, epigastric
Character :
Tightness,pressure,burning, heaviness,
aching, strangling, compression Dull &
deep
Time of onset, duration, frequency
Exacerbating & alleviating factors
4 Es : Exercise, Emotional Stress,
Exposure to Cold/Hot humid, Eating
Relieved by : rest, relax, SL/NTG
Associated symptoms : breath
shortness, sweating, dizziness, syncope,
fatique

Angina Pectoris
SUPPLY

DEMAND

Stable : There is no substantial deterioration in

symptoms over several weeks. Stability or

quiescence of an atherosclerotic plaque;
depending on increased oxygen demand
Unstable : symptom pattern worsen abruptly
without an obvious caused of increased oxygen
consumption, decreased supply . Unstable
Adaptedplaque:
from Weissberg.ACS
Atherosclerosis. 1999;147:S3S10

Variant/Printzmetal Angina : focal coronary artery

spasm without overt atherosclerotic lesions (may

involve endothelial dysfunction-vasodilator response
low & increased symphatetic activity)
Syndrome X : typical symptoms of angina without
evidence of significant coronary stenoses (due to
inadequate vasodilator reserve of coronary
resistance vessels, microvascular dysfunction,
vasospasm or hypersensitive pain perception

UA/NSTEMI
THREE PRINCIPAL PRESENTATIONS
Rest Angina*

Angina occurring at rest and

prolonged, usually > 20 minutes

New-onset AnginaNew-onset angina (de novo) of

at

least CCS Class III severity

Increasing (Crescendo) Angina

Previously diagnosed angina that has
become distinctly more frequent,
longer in duration, or lower in
threshold (i.e., increased by > 1 CCS)
class to at least CCS Class III severity.
Alexander et al

* Pts with NSTEMI usually present with angina atCirculation

rest.
2007;115;2549-2569

PhysicalExam ination
Myocardial
Ischemia

Systolic
function

Dyskinetic
apical
impulse

Pulmonary
Congestion

Rales

Diastolic
compliance

Papillary
muscle
dysfunctio
n

Sympatheti
c tone

S4

Mitral
regurgitati
on

Diaphoresi
s
HR ,BP

M anagem ent ofACS

Compendium of Abridged ESC Guidelines 2008

A C U TE C O R O N A R Y
SYN D R O M E
No ST Elevation

UA / Non ST elevation MI

ST Elevation

ST elevation MI

ECG evolution of Acute STEM I

A = Normal
B = Acute
ST elevation/tall T

C = Hours
ST elevation
R wave, Q wave begins

D = Day 1-2
T wave inversion
Deeper Q wave

E = Days later
ST normalizes
T wave inverted

F = Weeks later
ST & T normal
Q wave persists

ECG diagnosis of ACS

STEMI
New or presumably
new ST elevation, 2
mm in V1-3 or 1 mm
in other leads
Occurs in 2
concomitant leads
Pathologic Q wave
(0,03 wide, 1 mm
deep) in 2
concomitant leads
New or presumably
new LBBB

NSTE-ACS/UAP
ST depression 0,5
mm in 2 contiguous
leads
Inverted T wave 1
mm in 2 or more
concomitant leads
Suspect UAP if ST
segment changes
while chest pain &
normal while no
complaints
Normal ECG does not
exclude the possibility

Tim ing ofRelease ofVarious Biom arkers

After Acute M yocardialInfarction

Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3 rd ed.
Rochester, MN: Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:77380.
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1e157, Figure 5.

20

Tim ing ofRelease ofVarious Biom arkers

After Acute M yocardialInfarction

21

Com parison of Cardiac Biom arkers

Troponins for Evaluation and

M anagem ent ofACS
Disadvantages

Advantages

Risk Stratification
Sens/Spec > CKMB
Detect Recent MI
Selection of Rx
Detect Reperfusion

Low sens. early (< 6h)

Repeat at 8-12 h if neg.
Limited ability to
detect late minor reinfarction

Recommendation

Useful as single test to efficiently Dx NSTEMI

Clinicians should familiarize themselves with Dx cutoffs in local
lab

Early Risk Stratification

TIMI Risk Score for UA/NSTEMI

One Point for

each of:

% D/MI/Urgent Revascularization Vs
TRS

TIMI 11B

Antman EM, JAMA

2000;284:835-842

Age > 65 y
> 3 CAD
Risk Factors
Prior
Stenosis >
50 %
ST
deviation
> 2 Anginal
events < 24
h
ASA in last
7 days
Elevated
Cardiac
Markers

Early Risk Stratification

TIMI Risk Score for STEMI
Mortality at 30 d vs. STEMI TRS

Historical
Age 65-74
2pts
>75 3pts
DM/HTN/Angina 1pt
Exam
SBP < 100 mmHg3pts
HR > 100 bpm
2pts
Killip II IV 2pts
Weight < 67 kg 1 pt
Presentation
Anterior STE or
LBBB
1 pt
Time to Rx > 4hr 1pt
----------------------------------Risk Score = Total (014)

TIMI 17

Morrow DA, Circulation

Killip Classifi
cation of AM I
Clinical Evidence of LV Dysfunction Mortality
35%

6 10
%

20 30
%

>80 %

Compendium of Abridged ESC Guidelines 2008

M anagem ent ofAcute Coronary Syndrom e

S TEM I

U A P /N S TEM
I

Therapeutic O ption N STE-ACS

(U A/N STEM I)
Anti-ischemic agents
Anticoagulants
Antiplatelet agents
Coronary revascularization
Long-term management

S ELEC TIO N O F IN ITIA L TR EATM EN T S TR ATEG Y FO R

U A P /N S TEM I:
IN ITIA L IN VA S IV E V ER S U S C O N S ER VATIV E S TR ATEG Y
Invasive
(12-48
hours)

Recurrent angina/ischemia at rest with low-level activities

despite intensive medical therapy
Elevated cardiac biomarkers (TnT or TnI)
New/presumably new ST-segment depression
Signs/symptoms of heart failure or new/worsening mitral
regurgitation
High-risk findings from noninvasive testing
Hemodynamic instability
Sustained ventricular tachycardia
PCI within 6 months
Prior CABG
High risk score (e.g., TIMI, GRACE)
34

Revascularization O ptions
Coronary Artery Disease

Treatment Options

Left main disease

CABG

Left main disease & not CABG

candidate

Consider PCI

Three vessel disease with

EF<50%

CABG

Multivessel disease, including

proximal LAD

CABG or PCI (most favor CABG)

Multivessel disease, including

proximal LAD, EF>50%, no DM

PCI

One or two vessel disease

without proximal LAD and large
ischemia

PCI or CABG

One vessel proximal LAD

PCI or CABG

Multiple SVG stenosis, including

LAD graft

CABG

Focal SVG stenosis

PCI (high embolization risk)

M anagem ent ofAM I

Emergency Care
Initial diagnosis of AMI
Relief of pain, breathlessness, and anxiety
In-hospital care

PCI
Fibrinolytic therapy
Heparin co-therapy
Therapy for pump failure and shock
Routine prophylaxis therapy

Rehabilitation and secondary

prevention

ED Evaluation of
Patients With STEMI

Differential Diagnosis of STEMI: Life-Threatening

Aortic dissection

Tension pneumothorax

Pulmonary

Boerhaave syndrome

embolus

(esophageal rupture with

Perforating ulcer

mediastinitis)

ED Evaluation of
Patients With STEMI
Differential Diagnosis of STEMI: Other
Cardiovascular and Nonischemic
Pericarditis
Atypical angina
Early repolarization
Wolff-Parkinson-White
syndrome
Deeply inverted Twaves suggestive of
a central nervous
system lesion or
apical hypertrophic
cardiomyopathy

LV hypertrophy with
strain
Brugada syndrome
Myocarditis
Hyperkalemia
Bundle-branch blocks
Vasospastic angina
Hypertrophic
cardiomyopathy

ED Evaluation of
Patients With STEMI
Differential Diagnosis of STEMI: Other Noncardiac
Gastroesophageal
reflux (GERD) and
spasm

Cervical disc or
neuropathic pain

Chest-wall pain

Somatization and
psychogenic pain
disorder

Pleurisy
Peptic ulcer disease
Panic attack

Biliary or pancreatic pain

Reperfusion
Indicated for STEMI with onset < 12 hours.
The medical system goal is to facilitate rapid
recognition and treatment of patients with STEMI
such that door-to- needle (or medical contact
to-needle) time for initiation of fibrinolytic
therapy can be achieved within 30 minutes
or that door-to-balloon (or medical contacttoThe goals
of PCI
reperfusion
therapy
balloon)
time for
can be kept
within are
90 :
Early patency
minutes.
Increased myocardial salvage
Preservation of LV function
Lower mortality
Improves remodeling, enhance electrical
stability
Potential of collateral

If presentation is < 3 hours and there is no delay to an

invasive strategy, there is no preference for either
strategy.

Invasive strategy generally

preferred
Skilled PCI lab with surgical
backup
Door-to-balloon < 90
minutes
High Risk from STEMI
Cardiogenic shock, Killip
class 3
Contraindications to fibrinolysis,
increased risk of bleeding and
ICH
Late presentation

Fibrinolysis generally
preferred
Early presentation ( 3 hours
from
onset and delay to invasive
strategy)
Cath lab occupied or not
available
Vascular access difficulties
No access to skilled PCI lab
Prolonged transport
Door-to-balloon > 90
minutes

Fibrinolytics :Contraindications
Absolute Contraindications
Prior intracranial
hemorrhage
Suspected aortic
dissection
History of intracranial
neoplasm
Active internal
hemorrhage

Relative Contraindications
Stroke within 1 year
Marked elevated BP
>180/100 mmHg
Recent major surgery (< 3
weeks)
Recent internal
hemorrhage
Recent trauma (<2-4
weeks)
Prolonged CPR (>10 min)
Active peptic ulcer
Noncompressible
puncture
Pregnancy
Chronic severe
hypertension
Current use of
anticoagulant

Fibrinolytics : W hich Agent ?

ClinicalRelevance of Clot Selectivity

Action of Clot-Selective
Agents

(TNK-tPA, staphylokinase, t-PA)

Action of Non-ClotSelective Agents

(r-PA, SK, n-PA, UK)

Clot-selective
vessel
plasminogen
activators

Clot

Blood

Non-clot-selective
Blood vessel
plasminogen
activators

Clot

Adm inistration of Fibrinolytics

Streptokinase ( Streptase )

1.5 million unit in 100 ml D5W or 0,9%

saline in 30-60 minutes
without heparin : inferior MCI
with heparin
: anterior MCI
tPA (Alteplase)
15 mg IV bolus then 0,75 mg/kg for 30
mnt, continued 0,5 mg/kg for next 60

Assessment of Reperfusion
I IIa IIb III

It is reasonable to monitor the pattern of ST

elevation,
cardiac rhythm and clinical symptoms over the 60
to 180
minutes after initiation of fibrinolytic therapy.
Noninvasive findings suggestive of reperfusion
include:
Relief of symptoms
Maintenance and restoration of hemodynamic
and/or electrical instability
Reduction of 50% of the initial ST-segment
elevation pattern on follow-up ECG 60 to 90
minutes after initiation of therapy.

Vascular Changes w ith

Reperfusion (Reperfusion Injury)

Prevention on Research : SOD derivatives (Gliadin &

Stunned and H ibernating M yocardium

Stunned Myocardium : prolonged postischemic

dysfunction of viable tissue salvaged by
reperfusion
Hibernating Myocardium : function promptly
improved when blood flow is restored
Distinguished by : dobutamine echo, thallium-201,

D RU G S FO R ACS TREATM EN T

O xygen

O2 is given to pts w/ desaturated O2 ( SaO2 < 90% )

May limit myocardial injury or decreasing ST

elevation

Pain Killer
Morphine : 2,5 5 mg slow IV
Caution in inferior MCI, Asthma, Bradycardia
Pethidine : 12,5 25 mg IV

Anti-platelets
Aspirin : 81-325 mg p.o/day
Clopidogrel : 300-600 mg loading dose then 75

mg/day
Ticlopidine : 2 x 250 mg
Gp IIb / IIIa inhibitor

AntiIschem ia
N itrates
Benefit : venodilation, preload, coronary perfusion
Caution : Inferior MI with RV involvement
Sublingual : ISDN 2,5-15 mg ; NTG 0,3-0,6 mg max 1,5 mg
Oral : ISDN 5-80 mg/2-3 x daily ; ISMO 2 x 20 mg/day
IV : Initial dose 5 mcg/min titrated every 5 min according to

clinical presentation & ECG

Beta Blockers
Benefit : myocardial demand, negative inotrope, HR
Metoprolol PO 2 x 25-100 mg IV5 15 mg
Atenolol
PO 1 x 25-100 mg
Propanolol PO 3 x 20-80 mg
Bisoprolol PO 1 x 5 10 mg
Carvedilol PO 1 x 25 mg

AntiCoagulants
HEPARIN
Bound to AT III
Inactivates
thrombin
No effect on factor
Xa
Benefit in UA/
rebound
Anti Xa :
antithrombin = 1:1
Prolongs APTT

LMWH
Depolimerization of
UFH with lower MW
SC
injection/predictable
90% bioavailability
Anti Xa : anti
thrombin = 2-4 : 1
FDA approves
enoxaparin /
dalteparin for ACS

Recom m ended D ose for Anticoagulants

UFH : Initial IV bolus 60 UI/kg max 4000

UI
Infusion 12 15 UI/kg/hour max 1000
UI/jam
APTT monitoring: 3, 6, 12, 24 hours
LMWH :
after initiation
Target APTT 50-70
Enoxaparine : 1 mg/kg SC bid
msec (1,5-2 x K)
Nadroparine : 0,1 ml/10kg bid
Fondaparinux: 2,5 mg

Secondary Prevention
Life style modification

STOP SMOKING!
Class I Level C
Glycemic control in diabetes
Class I Level B
Blood Pressure control in hipertension Class I Level C
Diet
Class I Level B
Fish oil supplement
Class I Level B

Pharmacological
Aspirin 75-160 mg daily
Class I Level A
Or clopidogrel 75 mg daily
Class IIb Level C
Or oral anticoagulant
Class IIa Level B
Oral -Blocker (no contraindication)
Class I Level A
ACE-Inhibitor
Class I Level A
Statins (if LDL >115mg/dL)
Class I Level A
Ca-antagonist (verapamil or diltiazem) Class IIb Level B
Nitrate without angina
Class III Level A

Myocardial Infarction
Ventricular thrombus

Embolism

contractilit
y
Cardiogeni
c shock

Ischemia

Electrical
instabilit
y

Hypotensio
n
Coronar
y
perfusio
n
pressure

Com plications of ACS

Tissue
necrosi
s

Pericardit
is

Arrhythmia
s

Papillary
VSD
muscle
infarction
/ischemi
a

Pericardial
inflammatio
n

Ventricula
r rupture

Mitral
regurgitatio
n
Congestive heart failure

Cardiac
tampona
de

M anagem ent of Com plications

LVF (After Swan
Gantz
Cathetherization)
Ventricular
Arrhythmias
(symptomatic)
Supraventricular
Arrhythmias
Cardiogenic Shock
RV Infarction
Rupture of free
wall, MV, IVS
Patient with NIDDM

ACE inhibitors or ARBs

Diuretics, Nitrates
Lidocaine
If refractory give procainamide or amiodarone
Vagal procedures
Adenosine or verapamil or diltiazem or esmolol
Acute angioplasty, Intra-aortic balloon
Bypass surgery
Fluids, inotropic support
Avoid nitrates
Cardiac surgery
Switch OHO to insulin modified GIK regimen
Consider ACE inhibitor or ARB for all patients

Sum m ary
ACS includes UA, NSTEMI, and STEMI
Management guideline focus

Immediate assessment/intervention
Risk stratification (UA/NSTEMI vs. STEMI)
RAPID reperfusion for STEMI (PCI vs. Thrombolytics)
Conservative vs Invasive therapy for UA/NSTEMI

Aggressive attention to secondary prevention

initiatives for ACS patients

Beta blocker, ASA, ACE-I, Statin

Thank You

Action Sites of Antithrom botics & Fibrinolytics