TUKO SRIMULYO

Overview
Definition

Pathogenesis of ACS

Diagnosis
• Symptoms : Angina Pectoris
• Physical Examination
• Electrocardiogram
• Laboratory Findings
• Angiography

Treatment

Complications
 Definition 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 of Atherosclerosis
Endothelial
Dysfunction
•Foam •Fatty •Intermediate •Fibrous •Complicated
•Cells •Streak •Lesion •Atheroma •Plaque •Lesion/Rupture

•oxidized LDL
•homocysteine
•smoking
•aging
•hyperglycemia
•hypertension

35-45 yrs 45-55 yrs 55-65 yrs >65 yrs

•Endothelial •Lipid accumulation•Inflammation
injury •adhesion molecules •MMP's
(ICAM, VCAM) •continued macrophage/lipid
•nitric oxide accumulation •CRP (hepatic)
•monocyte adhesion
•endothelin-1 •leukocyte accumulation
•vasodilation •macrophage LDL
uptake •cytokines (IL-6,TNFa, IFNg)
Pathophysiology of
Stable and Unstable Plaques
Risk Factors of Coronary Heart
Disease
Non
Modifiable Novel
Modifiable
• Dyslipidemia (LDL • Advanced age • Homocysteine
,HDL) • Male gender (post • Lipoprotein (a)
• Tobacco smoking menopausal • CRP & other
• Hypertension women) inflammatory
• Diabetes Mellitus, • Family history (1st markers
Metabolic degree relatives
Syndrome <55 male or <65
• Lack of Physical female)
Activity
Diagnostic 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 E’s : 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 plaque: ACS
Adapted from Weissberg. Atherosclerosis. 1999;147:S3–S10
 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 Angina New-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 at rest. Circulation 2007;115;2549-2569
 Physical Examination
Myocardial
Ischemia

Papillary
Systolic Diastolic Sympathetic
muscle
function  compliance  tone 
dysfunction

Dyskinetic Diaphoresis
Pulmonary Mitral
apical S4
impulse
Congestion regurgitation HR ,BP 

Rales
Management of ACS

Compendium of Abridged ESC Guidelines 2008

 ACUTE CORONARY SYNDROME

No ST Elevation ST Elevation

UA / Non ST elevation MI ST elevation MI

ECG evolution of Acute STEMI
 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 of
NSTE-ACS
 Timing of Release of Various Biomarkers
After Acute Myocardial Infarction

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, 2007:773–80.
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5.
20
Timing of Release of Various Biomarkers
After Acute Myocardial Infarction

21
Comparison of Cardiac Biomarkers
Troponins for Evaluation and
Management of ACS
Advantages Disadvantages
• Risk Stratification • Low sens. early (< 6h)
• Sens/Spec > CKMB • Repeat at 8-12 h if neg.
• Detect Recent MI • Limited ability to
detect late minor reinfarction
• Selection of Rx
• Detect Reperfusion

Recommendation
• Useful as single test to efficiently Dx NSTEMI
• Clinicians should familiarize themselves with Dx “cutoffs” in local
lab
 Early Risk Stratification
One Point for
TIMI Risk Score for UA/NSTEMI each of:
• Age > 65 y
• > 3 CAD Risk
50 Factors
% D/MI/Urgent Revascularization Vs TRS 40.9 • Prior Stenosis
40 > 50 %
• ST deviation
30 26.2
19.9 • > 2 Anginal
events < 24 h
20 13.2 • ASA in last 7
8.3 days
10 4.7
• Elevated
0 Cardiac
Markers
0/1 2 3 4 5 6/7

TIMI 11B Antman EM, JAMA 2000;284:835-842

 Early Risk Stratification
Historical
TIMI Risk Score for STEMI Age 65-74 2pts
>75 3pts
DM/HTN/Angina 1pt
50
Exam
Mortality at 30 d vs. STEMI TRS SBP < 100 mmHg 3pts
40 35.9 HR > 100 bpm 2pts
Killip II – IV2pts
30 26.8 Weight < 67 kg 1 pt
23.4
Presentation
20 16.1 Anterior STE or
12.4 LBBB 1 pt
10 7.3 Time to Rx > 4hr 1pt
2.2 4.4 ------------------------------------
0.8 1.6
Risk Score = Total (0-14)
0

0 1 2 3 4 5 6 7 8 >8

TIMI 17 Morrow DA, Circulation 2000;102:2031-7

Killip Classification of AMI
Clinical Evidence of LV Dysfunction Mortality

Class I
• Absence of S3 gallop & rales 3–5%
Uncomplicated

Class II • Mild to moderate orthopnea

• S3 gallop 6 – 10 %
Mild to Mod HF • Bibasilar rales ≤ 50% of both lung fields

Class III • Severe Respiratory Distress

• Rales over >50% of both lung fields 20 – 30 %
Pulmonary
edema • X-ray:interstitial & alveolar edema

Class IV • Hypotension (BP systolic <90mmHg)

Cardiogenic • Tachycardia >80 %
Shock • Signs of  peripheral perfusion
Compendium of Abridged ESC Guidelines 2008
Management of Acute Coronary Syndrome

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

•Anti-ischemic agents
•Anticoagulants
•Antiplatelet agents
•Coronary revascularization
•Long-term management
SELECTION OF INITIAL TREATMENT STRATEGY FOR
UAP/NSTEMI:
INITIAL INVASIVE VERSUS CONSERVATIVE STRATEGY
Invasive Recurrent angina/ischemia at rest with low-level activities despite
(12-48 hours) 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)
Reduced left ventricular function (LVEF < 40%)
Conservative Low risk score (e.g., TIMI, GRACE)
Patient/physician presence in the absence of high-risk features 34
Revascularization Options
Coronary Artery Disease Treatment Options

Left main disease CABG

Left main disease & not CABG Consider PCI
candidate
Three vessel disease with EF<50% CABG
Multivessel disease, including proximal CABG or PCI (most favor CABG)
LAD
Multivessel disease, including proximal PCI
LAD, EF>50%, no DM
One or two vessel disease without PCI or CABG
proximal LAD and large ischemia
One vessel proximal LAD PCI or CABG
Multiple SVG stenosis, including LAD CABG
graft
Focal SVG stenosis PCI (high embolization risk)
Management of AMI
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 embolus Boerhaave syndrome
Perforating ulcer (esophageal rupture with
mediastinitis)
 ED Evaluation of
Patients With STEMI
Differential Diagnosis of STEMI: Other Cardiovascular and
Nonischemic

Pericarditis LV hypertrophy with strain

Atypical angina Brugada syndrome
Early repolarization
Wolff-Parkinson-White Myocarditis
syndrome Hyperkalemia
Deeply inverted T-waves Bundle-branch blocks
suggestive of a central
nervous system lesion or Vasospastic angina
apical hypertrophic Hypertrophic
cardiomyopathy cardiomyopathy
 ED Evaluation of
Patients With STEMI
Differential Diagnosis of STEMI: Other Noncardiac

Gastroesophageal reflux Cervical disc or neuropathic

(GERD) and spasm pain
Chest-wall pain Biliary or pancreatic pain
Pleurisy Somatization and psychogenic
Peptic ulcer disease pain disorder

Panic attack
 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
contact–to- balloon) time for PCI can be kept within 90
minutes.
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 Fibrinolysis 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
 > 3 hours from symptom onset
Diagnosis of STEMI is in doubt
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
 > 1 hour vs fibrinolysis (fibrin-specific
agent) now
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
• Known bleeding diasthesis
Fibrinolytics : Which Agent ?
 Clinical Relevance of Clot Selectivity

Action of Clot-Selective Agents Action of Non-Clot-Selective

(TNK-tPA, staphylokinase, t-PA) Agents
(r-PA, SK, n-PA, UK)

Clot-selective Clot Blood Non-clot-selective Clot Blood

vessel vessel
plasminogen plasminogen
activators activators
Administration 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 mnt
 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.

 Increased biochemical markers of myonecrosis, including

myoglobin detected in bloodstream (“early peaking”)
Vascular Changes with
Reperfusion (Reperfusion Injury)

Prevention on Research : SOD derivatives (Gliadin & Glisodin)

Stunned and Hibernating Myocardium

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, PET

 DRUGS FOR ACS TREATMENT
Oxygen
 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
 Anti Ischemia
Nitrates
 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 IV 5 – 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
 Anti Coagulants
HEPARIN LMWH
 Bound to AT III •Depolimerization of UFH
 Inactivates thrombin with lower MW
No effect on factor Xa •SC injection/predictable
Benefit in UA/ rebound •90% bioavailability
Anti Xa : antithrombin = •Anti Xa : anti thrombin =
1:1 2-4 : 1
Prolongs APTT •FDA approves
enoxaparin / dalteparin for
ACS
Recommended Dose 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 after initiation
Target APTT 50-70 msec (1,5-2 x K)
 LMWH :
Enoxaparine : 1 mg/kg SC bid
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 β-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 contractility Electrical Tissue Pericardial

instability necrosis inflammation
Cardiogenic
shock
Embolism
Ischemia Hypotension Arrhythmias Pericarditis

Coronary
perfusion
pressure

Papillary Ventricular
muscle VSD rupture
infarction/
Complications of ACS ischemia

Mitral Cardiac
regurgitation tamponade

Congestive heart failure

 Management of Complications
LVF (After Swan Gantz • ACE inhibitors or ARBs
Cathetherization) • Diuretics, Nitrates

Ventricular Arrhythmias • Lidocaine

(symptomatic) • If refractory give procainamide or amiodarone

Supraventricular • Vagal procedures

Arrhythmias • Adenosine or verapamil or diltiazem or esmolol

• Acute angioplasty, Intra-aortic balloon

Cardiogenic Shock • Bypass surgery

• Fluids, inotropic support

RV Infarction • Avoid nitrates

Rupture of free wall, • Cardiac surgery

MV, IVS
• Switch OHO to insulin modified GIK regimen
Patient with NIDDM • Consider ACE inhibitor or ARB for all patients
Summary

 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