Spectrum of Acute

Coronary Syndrome
Milagros Estrada-Yamamoto,MD

Atherothombosis
Acute thrombosis occuring in the
presence of pre-existing atherosclerosis
producing acute ischemic strokes, acute
ischemic syndromes of peripheral arteries
and acute coronary syndrome including
unstable angina, myocardial infarction
(NSTEMI and STEMI) and sudden death.

Atherothrombosis
Maintenance of normal blood flow

Reparative process by an injury

Thrombosis: A Problem of Epidemic

Proportions
Over 400,000 deaths annually in Western
Europe
about 500,000 deaths annually in the
United States
Cardiovascular Disease - leading cause of
death in the Philippines today

Mechanism of Lesion Development

Endocrine
(DM)

Toxic
Toxic
(nicotine)

HyperHyperlipidemia
lipidemia

Mechanical
(HPN)

Genetic

Functional Impairment of Endothelium

Increased LDL or other lipid influx
Iniation of Inflammation
Monocyte Influx
Inadequate Wound Healing
Smooth
Smooth muscle
muscle cell
cell proliferation
proliferation
Matrix
Matrix Deposition
Deposition
Atheroma
Atheroma Formation
Formation
Thrombus
Thrombus Formation
Formation

Terminal Occlusion

Combination
of Factors

Atherosclerosis to Atherothrombosis

Thrombus
Fibrous
Cap
Lipid
Core

Lumen

Fibrous Cap
Lipid Core

Stable Plaque

Disrupted Plaque

Plaque Vulnerability
Thin fibrous cap (65 um
thick).
Atheromatous core size
greater
than 30%.
An increased
macrophage content.
Degree of inflammation
(systemic or local).
Coronary Artery with Plaque Rupture
and Thrombus

Occurrence of Plaque Complication

Rapid progression

Soft plaque

Malleable, plastic, sharp gradients of compliance

Slow progression

Hard plaque

Fixed, inflexible-rigid, fibrotic-calcified

Secondary rapid growth

Fragile plaque

Disruptible, fibrous cap dissolution, hemorrhage(?)

Interaction of Risk Factors, Triggers, and

Vulnerable Plaque
Triggers
Atherosclerosis
Chronic risk factors
Nonvulnerable
Nonvulnerable
plaque
plaque

Vulnerable
plaque
plaque

Acute risk factors:

Hemodynamic
Vasoconstrictive
Prothrombotic

Disruption,
Disruption,
thrombosis

Plaque progression

Unstable Angina
Angina
Myocardial Infarction
Sudden Cardiac Death

Ischemic Triggers
TRIGGER
Exercise
Assuming upright posture
Cigarette
Cigarette smoking
Cold exposure
MEDIATOR
Pulse pressure
Heart rate
Systolic BP
Increased vascular resistance
Catecholamine levels

Plaque fissure, Thrombin and platelet

activation,
and vasospasm

Possible Trigger for Myocardial Infarction

Burden of Acute Coronary

Syndrome

Significant Public Health Problem

both in Industrialized and
Developing Countries

Acute Coronary Syndrome

Unstable Angina
Non ST Elevation Myocardial Infarction
(NSTEMI)
1,433,000 hospitalizations in USA

National Center for Health

Statistics USA 1996

Acute Coronary Syndrome

ST Elevation Myocardial Infarction
(STEMI)
1,680,000 hospitalizations for ACS in 2001
Heart Disease and Stroke Statistics,2004
AHA Updates

30% of ACS patients have STEMI

500,000 STEMI events per year in USA
NRMI-4

Pathologic and Clinical Presentation of Acute

Coronary Syndromes

Unstable Angina and NSTEMI

Imbalance between Oxygen Demand and Supply
Non occlusive
Thrombus
Less severe Ischemia
and myocardial damage
Unstable Angina

Vasospasm

Severe Ischemia and

myocardial damage
NSTEMI

Hx : Severe localized chest or arm pain at rest or on minimal exertion >20mins,

crescendo pattern
PE : Pulmonary edema ; New or worsening MR; S3; New or worsening rales
ECG : Transient ST segment changes (> 0.05 mv) ; New Bundle branch Block;
Sustained Ventricular Tachycardia
Cardiac Markers

Normal

Elevated ( Troponin I, Troponin T, CKMB)

ECG Changes in Unstable

Angina/NSTEMI
ST-segment depression (30%)
T-wave inversion (20%)
Transient ST-segment elevation (5%)

ST Elevation Myocardial Inarction

(STEMI)
TH
FC
LC

Total occlusion

Pathological Diagnosis
Coagulation necrosis
Prolonged Ischemia
Myocytolysis
Myocyte Death
Clinical Diagnosis
Hx - Accelerating Angina and rest pain ( >30 mins )
constricting,crushing,compressing,heaviness,choking
Retrosternal radiating to ulnar aspect of left arm
Atypical presentation
PE Soft S1, S3,S4 ; MR due to papillary muscle
dysfunction,pericardial friction rub
Hypotension, tachycardia,bradycardia
ECG ST segment Elevation, Q waves
Cardiac Markers Troponins ( cTnT,cTnI)
CK MB mass
Myoglobin

STEMI ECG Findings

Occlusion

Inferior infarct

ST segment elevation of at least

1 mm in two or more limb leads

STEMI ECG Findings

Occlusion

Anterior
Infarction

At least 2 mm ST segment elevation in

two or more precordial leads

Revised Definition of Myocardial

Infarction (MI)
Criteria for acute,evolving or
recent MI
Either 1 of the ff :
Typical rise and gradual fall
of troponin or rapid rise in
CKMB with at least 1 of ff :
Ischemic symptoms
Q waves on ECG
ST segment elevation or
depression
PCI

Criteria for Established MI

Either 1 of the ff :
Development of new
pathologic Q waves on
serial ECG
Pathologic findings of
healed or healing MI

Pathological findings

J Am Coll Cardio 2000

Cardiac Troponins in
Acute Myocardial
Infarction

Cardiac Troponin T
Cardiac Troponin I

Cut-Off Value : 0.04 ng/dl

Upper Reference Limit : 0.06 ng/dl

Time Course of Elevations of

Serum Markers After AMI

Likelihood That Signs and

Symptoms Represent Acute
Coronary Syndrome

Feature
History

High Likelihood
(any of the ff )
Chest/left arm pain
Known hx of CAD

Intermediate
Likelihood

Low Likelihood

Chest/left arm
pain
Age > 70
Male
DM

Probable
ischemic
symptoms with
no intermediate
characteristics
Recent cocaine
use

Extracardiac
vascular disease

Chest pain
elicited by
palpation

Examination

Transient MR,
hypotension,
diaphoresis,
pulmonary edema

ECG

New or presumably
Fixed Q waves
new ST seg deviation
Abnomal ST
(> 0.5 mv)
segment or T
T wave inversion > wave inversion
0.2 mv
not new

Cardiac
Markers

Elevated cTnI, cTnT,

CKMB

Normal

T wave
flattening or
inversion with
dominant R
waves
Normal ECG

Normal

Algorithm For Evaluation and Management of Acute

Coronary Syndrome (ACS) Suspect

Unstable Angina
Non ST Elevation MI
Acute Ischemia Pathway

Acute
Ischemia
Pathway
UA and
NSTEMI

Treatment Goals for Unstable

Angina and NSTEMI
To stabilize and passivate the acute
coronary lesion
To treat residual ischemia
To employ long term secondary prevention

General Measures for Unstable

Angina And NSTEMI
Admit to monitored bed
Bed rest
Supplemental oxygen
Relief of chest pain
Nitrates
Beta Blockers
Morphine ( 1-5mg/IV )

Antithrombotic therapy

Aspirin
Clopidogrel
Heparin ( UFH and LMWH )
GP IIb/IIIa inhibitors

Antithrombotic therapy
Prevents further thrombosis
Allow endogenous fibrinolysis
Long term therapy, to prevent progression to
complete occlusion
To reduce risk of developing future events

Aspirin
Clopidogrel
Heparin Unfractionated and LMWheparin
Glycoprotein IIb/IIa inhibitors

The Sequence of
Thrombotic Development
1. ADHESION
platelets adhere as a
monolayer to the damaged
site of the endothelium.

2. ACTIVATION
agonists (ADP, Epinephrine,
Thrombin, TxA2) are
secreted.

3. AGGREGATION
GP IIb/IIIa receptors bind
fibrinogen to form a bridge
between other platelets
(platelet plug)

Mechanisms of action of antiplatelet therapies

Antiplatelet Therapy
Aspirin
Block formation of thromboxane A2 in platelets by
cyclooxygenase inhibition
Initial dose : 162 to 325 mg tab to be chewed
Maintenance dose : 75 to 325 mg/day

Clopidogrel
Adenosine Diphosphate (ADP) antagonists
Inhibit platelet aggregation
Given to patients who are unable to tolerate ASA
( hypersensitivity or GI contraindications,PUD,Gastritis)
Initial dose : 300mg loading dose
Maintenance dose : 75 mg daily

UFH Loading dose :

75U/kg IV bolus with
maintenance infusion of
1250 U/hr titrated to
aPTT of 1.5 to 2x
control for 2-3 days
LMWH dose :
1mg/kg SC BID x 2-8
days

Mechanisms of inhibitory action of unfractionated heparin

(heparin) and low-molecular-weight heparin (LMWH)

Role of GP IIb/IIIa Receptor

in Platelet Aggregation
Facilitates platelet aggregation
by binding with fibrinogen
Used as an adjunct to primary
PCI or thrombolysis
Class II a indication of use
during primary PCI for STEMI
Abciximab / Eptifibatide/ Tirofiban
Prevention of restenosis
0.25mg/kg IV bolus in 10-60mins
before PCI followed by
0.125mcg/kg/min infusion x 12hrs
UA not responsive to medical tx
0.25mg/kg IV bolus followed by 18-24
hrs IV infusion 10mg/min

Agonists for Platelet Activation and

Antiplatelet Agents

Beta Blockers

Anti Ischemic Therapy

Reduce myocardial oxygen demand
Prevent Plaque rupture

Beta Blockers
Nitrates
Calcium Antagonists

Coronary and
Venodilation
SL NTG 0.4
mg q 5 mins
for chest
pain

Mechanism of action of nitrates

IV NTG
1mg/hr to be
titrated until
relief of
chest pain

Beta Blockers

O2 Demand

O2 Supply

Effects of Beta Blockers on the ischemic heart

Beta Blocker Use In ACS

Contraindications ?

Yes

Avoid use of beta blockers

HR < 50-60 bpm

Systolic BP < 90-100mmHg
Severe HF
Cardiogenic Shock

Metoprolol / Atenolol

Asthma or reactive airway

disease

Initial dose
Atenolol 25mg BID

2 or 3 degree AV block
No
nd

rd

Precautions ?
Heart failure
COPD
Diabetes mellitus
Peripheral vascular disease
1 degree AV block
st

Metoprolol 50-100mg BID

Titration : weekly
No

Target dose
Atenolol 25mg BID
Metoprolol 50-100 mg BID

Do not abruptly discontinue use !

(Reduce dose gradually in 1-2 weeks)

ACE Inhibitors / A2 Receptor Antagonist

Attenuation of
Ventricular remodelling
Reduction in recurrent
MI and ischemia
Decrease in
sympathetic activity
Improvement in
endothelial function
Improving
hypercoagulable state
by decreasing PAI -1

Apical STEMI

Oval
Spherical

Progressive Ventricular
Remodelling
To be started within 24 hours of MI
Initial dose :
Captopril 6.25mg q6-8 max of 50mg TID
Enalapril 2.5mg/day max of 20mg BID
Lisinopril 2.5mg/day max of 10mg/day

ST Elevation Myocardial
Infarction (STEMI)
Occlusion

Anterolateral
Infarct

Hemodynamic Consequences and Complications of Acute MI

Algorithm For Evaluation and Management of Acute

Coronary Syndrome (ACS) Suspect

General Treatment Measures for

STEMI
Timely reperfusion of infarcted area
Fibrinolysis
Percutaneous Catheter Intervention (PCI)

Primary prevention of vascular events

Aspirin
Clopidogrel

Control of Cardiac pain

Oxygen
Nitrates
Beta Blockers
Analgesic ( Morphine )

Prevent Ventricular remodelling

Reperfusion
ACE inhibitors

Primary Goal for STEMI : Timely Reperfusion

Pharmacological dissolution of thrombus in

infarct-related artery
FIBRINOLYSIS

Fibrinolytic Agents
Braunwald, 2005

Primary Goal for STEMI : Timely Reperfusion

Percutaneous Catheter Intervention (PCI)

Correlation of
TIMI flow grade
and mortality

Assessment of Reperfusion
Options for STEMI Patients
Assess time and risk
Time since onset of symptoms
Risk of STEMI
Risk of Fibrinolysis
Time required for transport to a skilled PCI lab

Determine if Fibrinolysis or PCI is

preferred
( If presentation < 3 hours and no delay to PCI,
there is no preference for either strategy )
ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, 2004

Fibrinolysis
Preferred if :
Early presentation (< 3 hrs from symptom
onset and delay to PCI )
Invasive strategy is not an option
PCI lab occupied or not available
Vascular access difficulties
Lack of success to a skilled PCI lab

Delay to Invasive strategy

Prolonged transport
(Door to Balloon) (Door to Needle) > 1hr
Medical contact to balloon > 90 min

CONTRAINDICATIONS TO
FIBRINOLYTIC TREATMENT
Absolute Contraindications :
Known bleeding disorder
Suspected aortic
dissection
Prolonged, traumatic CPR
Altered consciousness
Active internal bleeding
Recent head trauma, spinal
or intracranial surgery
Previous hemorrhagic CVA
Major trauma or surgery
w/in the previous 2 weeks
Persistent HPN > 200 / 120
mm Hg
Pregnancy

Relative Contraindications :
Active PUD
History of ischemic or embolic
stroke in the last 6 months
Major trauma or surgery
during the previous 2 weeks
to 2 months
Current use of anticoagulation
Chronic HPN w/ diastolic BP >
100 mm Hg
Subclavian or internal jugular
cannulation

Percutaneous Catheter
Intervention
Preferred if :
Skilled PCI lab available with surgical backup
High risk from STEMI
Cardiogenic shock
Killips class > 3

Contraindications to Fibrinolysis including

increased risk of bleeding and ICH
Late presentation
Symptom onset > 3 hr ago

Diagnosis of STEMI is in doubt

Time delay between onset of infarction and

restoration of flow in the infarct-related artery
ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, 2004

Transportation of STEMI patients and initial

reperfusion treatment
ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, 2004

Patient self-transport
ACC/AHA Guidelines for the Management of Patients with ST-Elevation Myocardial Infarction, 2004

Patient with ischemic type discomfort

Rapid triage to urgent care room
Aspirin 150-325 mg chewed
Goal=10 min
Obtain baseline cardiac marker levels
Assess initial 12-lead EKG

ST elevation

Initiate reperfusion
strategy

ECG strongly suspicious for ischemia

ST depression Tw inversion
Nondiagnostic ECG

Admit
Initiate antiischemic therapy

Thrombolysis
PCI

Continue evaluation in
ED or short-term
observation unit
Obtain follow-up serum
cardiac markers
Consider 2 D echo

Evidence of ischemia/infarction
Yes
Routine blood tests to be
obtained on admission
CBC
Lipid profile
Electrolyte levels

No

Admit
Initiate reperfusion strategy
Discharge
if ST elevation develops

(Goal=6-12 h)

Recommendations
We could reduce the burden of ACS
through :
Education of patients and relatives about the
disease and its attendant risk factors and
complications
Train healthcare workers and physicians on
how to recognize the clinical spectrum of ACS
and to be able to administer timely therapeutic
strategies following guidelines and protocols

Recommendations
Facility and capability improvement for
hospitals and health institutions so that early
recognition, observation of symptom
progression and prompt delivery of accurate
management may be carried out in the
Emergency Department, Chest Pain Clinics,
Urgency Care Units, Critical Care Units,
Cardiac Catheterization and Interventional
Units.

Timi
Is
of
ng the

Essen
ce