Zainuddin Khan

SMF Kardiologi dan Kedokteran Vaskular

RSUD Tarakan, Jakarta


Topics

Pathogenesis of ACS
Symptoms : Angina Pectoris
Risk Factors
Physical Examination
Electrocardiogram
Laboratory Findings
Angiography
Diagnosis

Treatment
Prognosis & Complications
Acute coronary syndrome encompasses a
spectrum of coronary artery diseases :
- Unstable angina
- non ST-elevation myocardial infarction
(NSTEMI)
- ST-elevation myocardial infarction
(STEMI)

Acute Coronary Syndromes

Similar pathophysiology

Similar presentation
and early management
rules

STEMI requires
evaluation for acute
reperfusion
intervention

Unstable Angina

Non-ST-Segment
Elevation MI
(NSTEMI)

ST-Segment
Elevation MI
(STEMI)
Scope of Problem
CHD single leading cause of
death in United States
452,327 deaths in the U.S. in
2004

1,200,000 new & recurrent
coronary attacks per year

38% of those who with
coronary attack die within a
year of having it

Annual cost > $300 billion

Endothelial
Dysfunction
Foam
Cells
Fatty
Streak
Intermediate
Lesion

Atheroma
Fibrous
Plaque
Complicated
Lesion/Rupture
Endothelial
injury
nitric oxide
endothelin-1
vasodilation
Lipid
accumulation
adhesion molecules
(ICAM, VCAM)
monocyte adhesion
macrophage LDL
uptake
Inflammation
continued macrophage/lipid
accumulation
leukocyte accumulation
cytokines (IL-6,TNFa, IFNg)
MMP's
CRP
(hepatic)
oxidized LDL
homocysteine
smoking
aging
hyperglycemia
hypertension
35-45 yrs 45-55 yrs 55-65 yrs >65 yrs
Pathophysiology of Atherosclerosis
Pathophysiology of
Stable and Unstable Plaques
Unstable
plaque
Stable
plaque
Thin fibrous cap
Thrombus
Thick fibrous cap

Smooth muscle cells

Lipid rich core
and
macrophages

Media
Risk Factors of Coronary Heart Disease
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 (1
st

degree relatives
<55 male or <65
female)
Novel
Homocysteine
Lipoprotein (a)
CRP & other
inflammatory
markers
Diagnosis of Acute MI
STEMI / NSTEMI
At least 2 of the
following
Ischemic symptoms
Diagnostic ECG
changes
Serum cardiac
marker elevations
Diagnosis of Angina
Typical anginaAll three of the
following
Substernal chest discomfort
Onset with exertion or emotional stress
Relief with rest or nitroglycerin

Atypical angina
2 of the above criteria

Noncardiac chest pain
1 of the above
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

Unstable
Angina
STEMI
NSTEMI
Non occlusive
thrombus

Non specific
ECG

Normal cardiac
enzymes

Occluding thrombus
sufficient to cause
tissue damage & mild
myocardial necrosis

ST depression +/-
T wave inversion on
ECG

Elevated cardiac
enzymes

Complete thrombus
occlusion

ST elevations on
ECG or new LBBB

Elevated cardiac
enzymes

More severe
symptoms
Chest pain suggestive of ischemia

12 lead ECG
Obtain initial
cardiac enzymes
electrolytes, cbc
lipids, bun/cr,
glucose,
CXR

Immediate assessment within 10 Minutes
Establish
diagnosis
Read ECG
Identify
complications
Assess for
reperfusion
Initial labs
and tests
Emergent
care
History &
Physical
IV access
Cardiac
monitoring
Oxygen
Aspirin
Nitrates
Targeted Physical
Recognize factors
that increase risk
Hypotension
Tachycardia
Pulmonary rales, JVD,
pulmonary edema,
New murmurs/heart
sounds
Diminished peripheral
pulses
Signs of stroke

Examination
Vitals
Cardiovascular
system
Respiratory
system
Abdomen
Neurological
status

ECG assessment
ST Elevation or new LBBB
STEMI
Non-specific ECG
Unstable Angina
ST Depression or dynamic
T wave inversions
NSTEMI
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
NSTEMI/UAP
ST depression 0,5
mm in 2 concomitant
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 or non-diagnostic EKG
ST Depression or Dynamic T wave
Inversions
ST-Segment Elevation MI
New LBBB
TIMI 17
TIMI Risk Score for STEMI
Mortality at 30 d vs. STEMI TRS
Morrow DA, Circulation 2000;102:2031-7
Historical
Age 65-74 2pts
>75 3pts
DM/HTN/Angina 1pt
Exam
SBP < 100 mmHg 3pts
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 (0-14)
0.8
1.6
2.2
4.4
7.3
12.4
16.1
23.4
26.8
35.9
0
10
20
30
40
50
0 1 2 3 4 5 6 7 8 >8
Early Risk Stratification
Killip Classification of AMI
Absence of S3 gallop & rales
Class I
Uncomplicated
Mild to moderate orthopnea
S3 gallop
Bibasilar rales 50% of both lung
fields
Class II
Mild to Mod HF
Severe Respiratory Distress
Rales over >50% of both lung fields
X-ray:interstitial & alveolar edema
Class III
Pulmonary
edema
Hypotension (BP systolic
<90mmHg)
Tachycardia
Signs of peripheral perfusion
Class IV
Cardiogenic
Shock
Clinical Evidence of LV Dysfunction Mortality
3 5 %
6 10 %
20 30 %
>80 %
Cardiac markers
Troponin ( T, I)

Very specific and more
sensitive than CK
Rises 4-8 hours after
injury
May remain elevated
for up to two weeks
Can provide
prognostic information
Troponin T may be
elevated with renal dz,
poly/dermatomyositis

CK-MB isoenzyme

Rises 4-6 hours after
injury and peaks at 24
hours
Remains elevated 36-48
hours
Positive if CK/MB > 5%
of total CK and 2 times
normal
Elevation can be
predictive of mortality
False positives with
exercise, trauma,
muscle dz, DM, PE
Timing of Release of Various Biomarkers
After Acute Myocardial Infarction
27
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.
Comparison of Cardiac Biomarkers
Non MI causes Elevation of Troponin
Defibrillator Discharged
Renal insufficiency
Left Ventricular failure
Tachy-arrhythmias
Myocarditis
Pericaditis
Pulmonary embolism

Reperfusion
Approach
Aspirin
Heparin
(UFH/LMWH)
Clopidogrel
Reperfusion
method :
A.Fibrinolytic
B.Primary PCI
(+GPIIb/IIIa
inhibitor)
All patients
General :
Pain control
(morphine)
Oxygen
Anti ischemic :
blocker
Nitrates
+/- Ca blocker
Additional :
ACE inhibitor
Statins
Antithrombotic
Approach
Aspirin
Heparin
(UFH/LMWH)
Clopidogrel
For high risk
patients :
GP IIb/IIIa
inhibitor
Cardiac cath
STEMI
UAP/NSTEMI
Cardiac Care Goals

Decrease amount of myocardial
necrosis
Preserve LV function
Prevent major adverse cardiac events
Treat life threatening complications
STEMI cardiac care
STEP 1: Assessment
Time since onset of symptoms
90 min for PCI / 12 hours for fibrinolysis

Is this high risk STEMI?
KILLIP classification
If higher risk may manage with more invasive rx

Determine if fibrinolysis candidate
Meets criteria with no contraindications

Determine if PCI candidate
Based on availability and time to balloon rx

Fibrinolysis indications
ST segment elevation >1mm in two
contiguous leads
New LBBB
Symptoms consistent with ischemia
Symptom onset less than 12 hrs prior to
presentation

Doses and Administration of
Thrombolytic Agents
Streptokinase (SK)
- 1.5 millions unit in 100 ml normal saline IV over
1 hour
- No indication for routine heparinization after SK
Recombinant Tissue-type plasminogen
activator (rTPA, alteplase)
- 15 mg bolus IV then 0.75 mg/ kg over 30
minutes (not to exceed 50 mg), then 0.5 mg/
kg over 60 minutes (not to exceed 35 mg)
Reteplase
- Two IV bolus doses of 10 units 10 minutes
apart
Tenectaplase
- As injection over 10 seconds at 30 50 mg
according to body weight
- Maximum dose is 50 mg
APSAC (Anistreplase)
- IV bolus of 30 mg over 2 5 minutes
Absolute contraindications for fibrinolysis
therapy in patients with acute STEMI

Any prior ICH (intracranial haemorrhage)
Known structural cerebral vascular lesion (e.g., AVM)
Known malignant intracranial neoplasm
(primary or metastatic)
Ischemic stroke within 3 months EXCEPT acute
ischemic stroke within 3 hours
Suspected aortic dissection
Active bleeding or bleeding diathesis (excluding
menses)
Significant closed-head or facial trauma within 3
months
Relative contraindications for fibrinolysis
therapy in patients with acute STEMI
History of chronic, severe, poorly controlled
hypertension
Severe uncontrolled hypertension on
presentation (SBP greater than 180 mm Hg or
DBP greater than 110 mmHg)
History of prior ischemic stroke greater than 3
months, dementia, or known intracranial
pathology not covered in contraindications
Traumatic or prolonged (greater than 10
minutes) CPR or major surgery (less than 3
weeks)

Recent (within 2-4 weeks) internal bleeding
Noncompressible vascular punctures
For streptokinase/anistreplase: prior exposure
(more than 5 days ago) or prior allergic reaction to
these agents
Pregnancy
Active peptic ulcer
Current use of anticoagulants: the higher the INR,
the higher the risk of bleeding
STEMI cardiac care
STEP 2: Determine preferred reperfusion strategy
Fibrinolysis preferred
if:
<3 hours from onset
PCI not available/delayed
door to balloon >
90min
door to balloon minus
door to needle > 1hr
Door to needle goal
<30min
No contraindications

PCI preferred if:
PCI available
Door to balloon < 90min
Door to balloon minus
door to needle < 1hr
Fibrinolysis
contraindications
Late Presentation > 3 hr
High risk STEMI
Killup 3 or higher
STEMI dx in doubt

Medical Therapy
MONA + BAH
Morphine (class I, level C)
Analgesia
Reduce pain/anxietydecrease sympathetic tone,
systemic vascular resistance and oxygen demand
Careful with hypotension, hypovolemia, respiratory
depression

Oxygen (2-4 liters/minute) (class I, level C)
Up to 70% of ACS patient demonstrate hypoxemia
May limit ischemic myocardial damage by
increasing oxygen delivery/reduce ST elevation

Nitroglycerin (class I, level B)

Analgesiatitrate infusion to keep patient
pain free
Dilates coronary vesselsincrease blood
flow
Reduces systemic vascular resistance and
preload
Careful with recent ED meds, hypotension,
bradycardia, tachycardia, RV infarction

Aspirin (160-325mg chewed & swallowed) (class I,
level A)

Irreversible inhibition of platelet aggregation
Stabilize plaque and arrest thrombus
Reduce mortality in patients with STEMI
Careful with active PUD, hypersensitivity,
bleeding disorders
Beta-Blockers (class I, level A)

14% reduction in mortality risk at 7 days at
23% long term mortality reduction in STEMI
Approximate 13% reduction in risk of
progression to MI in patients with
threatening or evolving MI symptoms
Be aware of contraindications (CHF, Heart
block, Hypotension)
Reassess for therapy as contraindications
resolve


ACE-Inhibitors / ARB (class I, level A)

Start in patients with anterior MI, pulmonary
congestion, LVEF < 40% in absence of
contraindication/hypotension
Start in first 24 hours
ARB as substitute for patients unable to
use ACE-I
Clopidodrel (class I, level B)
Irreversible inhibition of platelet aggregation
Used in support of cath / PCI intervention or if
unable to take aspirin
3 to 12 month duration depending on scenario

Glycoprotein IIb/IIIa inhibitors
(class IIa, level B)
Inhibition of platelet aggregation at final
common pathway
In support of PCI intervention as early as
possible prior to PCI
Heparin (class I, level C to class IIa, level C)
LMWH or UFH (max 4000u bolus, 1000u/hr)
Indirect inhibitor of thrombin
less supporting evidence of benefit in era of
reperfusion
Adjunct to surgical revascularization and
thrombolytic / PCI reperfusion
24-48 hours of treatment
Coordinate with PCI team (UFH preferred)
Used in combo with aspirin and/or other platelet
inhibitors
Changing from one to the other not recommended

Unstable angina/NSTEMI cardiac care
Evaluate for conservative vs. invasive
therapy based upon:
Risk of actual ACS
TIMI risk score
ACS risk categories per AHA guidelines

Low
Intermediate
High
Assessment
Findings indicating
HIGH likelihood of ACS
Findings indicating
INTERMEDIATE
likelihood of ACS in
absence of high-
likelihood findings
Findings indicating
LOW likelihood of ACS
in absence of high- or
intermediate-likelihood
findings
History
Chest or left arm pain or
discomfort as chief
symptom
Reproduction of previous
documented angina
Known history of coronary
artery disease, including
myocardial infarction
Chest or left arm pain or
discomfort as chief
symptom
Age > 50 years
Probable ischemic
symptoms
Recent cocaine use
Physical
examination
New transient mitral
regurgitation,
hypotension, diaphoresis,
pulmonary edema or rales
Extracardiac vascular
disease
Chest discomfort
reproduced by palpation
ECG
New or presumably new
transient ST-segment
deviation (> 0.05 mV) or T-
wave inversion (> 0.2 mV)
with symptoms
Fixed Q waves
Abnormal ST segments or
T waves not documented
to be new
T-wave flattening or
inversion of T waves in
leads with dominant R
waves
Normal ECG
Serum cardiac
markers
Elevated cardiac troponin
T or I, or elevated CK-MB
Normal Normal
Risk Stratification to Determine the Likelihood of
Acute Coronary Syndrome
Low
risk
High
risk
Conservative
therapy
Invasive
therapy
Chest Pain
center
Intermediate
risk
Invasive therapy option
UA/NSTEMI
Coronary angiography and
revascularization within 12 to 48 hours
after presentation to ED
For high risk ACS (class I, level A)
MONA + BAH (UFH)
Clopidogrel
20% reduction death/MI/Stroke CURE trial
1 month minimum duration and possibly up to 9
months
Glycoprotein IIb/IIIa inhibitors
Conservative Therapy for UA/NSTEMI
Early revascularization or PCI not planned
MONA + BAH (LMW or UFH)
Clopidogrel
Glycoprotein IIb/IIIa inhibitors
Only in certain circumstances (planning PCI, elevated
TnI/T)
Surveillence in hospital
Serial ECGs
Serial Markers
Complications of ACS
Acute cardiac failure
Cardiogenic shock
Post-infarct or refractory unstable angina
Arrhythmias : Tachycardias and Bradycardias
Myocardial rupture
Cardiac tamponade
Ventricular septal defect
Papillary muscle rupture
Pericarditis

Factors Associated with a poor
prognosis
Age > 70 years
Previous MI or chronic stable angina
Anterior MI or right ventricular infarction
Left ventricular failure at presentation
Hypotension (and sinus tachycardia) at
presentation
Acute mitral regurgitation
Ventricular septal defect
Secondary Prevention
Disease
HTN, DM, HLP

Behavioral
smoking, diet, physical activity, weight

Cognitive
Education, cardiac rehab program
Secondary Prevention
disease management
Blood Pressure
Goals < 140/90 or <130/80 in DM /CKD
Maximize use of beta-blockers & ACE-I

Lipids
LDL < 100 (70) ; TG < 200
Maximize use of statins; consider
fibrates/niacin first line for TG>500; consider
omega-3 fatty acids

Diabetes
A1c < 7%

Secondary prevention
behavioral intervention
Smoking cessation
Cessation-class, meds, counseling

Physical Activity
Goal 30 - 60 minutes daily
Risk assessment prior to initiation

Diet
DASH diet, fiber, omega-3 fatty acids
<7% total calories from saturated fats
Secondary prevention
cognitive
Patient education
In-hospital discharge outpatient
clinic/rehab

Monitor psychosocial impact
Depression/anxiety assessment & treatment
Social support system
Medication Checklist
after ACS
Antiplatelet agent
Aspirin* and/or Clopidorgrel
Lipid lowering agent
Statin*
Fibrate / Niacin / Omega-3

Antihypertensive agent
Beta blocker*
ACE-I*/ARB
Aldactone (as appropriate)

Summary
ACS includes UA, NSTEMI, and STEMI

Management guideline focus
Immediate assessment/intervention (MONA+BAH)
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