Topics

Pathogenesis of ACS

Diagnosis Symptoms : Angina Pectoris Electrocardiogram Laboratory Findings Angiography

Treatment

Prognosis & Complications

Epidemiology of ACS
Incidence: 1.1 million people/y in the

United States Of these:

At least one half die within 1 hour of symptom

onset or before reaching the hospital 24% of men and 42% of women die within 1 year 66% fail to achieve full recovery 21% of men and 30% of women develop congestive heart failure within 6 years

A 1% reduction in mortality would save

3,400 lives per year

American Heart Association. Available at http://www.americanheart.org/statistics/07other.html. Accessed February 2000.

Pathophysiology of Atherosclerosis
Endothelial Dysfunction
Foam Cells
oxidized LDL homocysteine smoking aging hyperglycemia hypertension

Fatty Intermediate Fibrous Complicated Streak Lesion Atheroma Plaque Lesion/Rupture

35-45 yrs

Endothelial injury
nitric oxide endothelin-1 vasodilation

45-55 yrs Lipid accumulation

adhesion molecules (ICAM, VCAM) monocyte adhesion macrophage LDL uptake

55-65 yrs

>65 yrs
MMP's CRP (hepatic)

Inflammation
continued macrophage/lipid accumulation leukocyte accumulation cytokines (IL-6,TNFa, IFNg)

Diagnosis ACS
Simptomp EKG Enzim marker

Klinis Nyeri dada

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

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 (1st degree relatives <55 male or <65 female)

Novel
Homocysteine Lipoprotein (a) CRP & other inflammatory markers

Angina Pectoris
SUPPLY DEMAND

Adapted from Weissberg. Atherosclerosis. 1999;147:S3S10

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:S3S10

UA/NSTEMI THREE PRINCIPAL PRESENTATIONS

Rest Angina*
New-onset Angina
Angina occurring at rest and
prolonged, usually > 20 minutes New-onset angina 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 at least CCS Class III severity. * Pts with NSTEMI usually present withto angina at rest.
Braunwald Circulation 80:410; 1989

STEMI Unstable angina KARDIAK NYERI DADA NON KARDIAK Stable angina Cari Etiologi Dyspepsia, dll Non STEMI

 Stable angina : nyeri reversibel / iskemik

reversibel Proses sklerotik bukan ACS UAP/NSTEMI obstruksi sub total proses obsttruksi ACS STEMI obstruksi total kematian otot jantung infark

EKG dari ACS

ECG diagnosis of ACS

STEMI NSTEMI/UAP

New or presumably new ST elevation, 2 mm in V13 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

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

Coronary Anatomy
Conduction Pathway Primary arterial supply

SA node
AV node Bundle of His RBB LBB Left anterior fascicle Left posterior fascicle

RCA (70% patients)

RCA (85% patients) LAD (septal branches) Proximal by LAD Distal by RCA LAD LAD & PDA

Dominance : (PAD inferior&posterior) Right Dominant (85%) Left Dominant (8%) Codominant (7%)

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

MARKER ENZIM JANTUNG

Timing of Release of Various Biomarkers After Acute Myocardial Infarction

29

TATALAKSANA

Options for Transport of Patients With STEMI and Initial Reperfusion Treatment
Hospital fibrinolysis: Door-to-Needle within 30 min.

Not PCI capable

Onset of symptoms of STEMI 9-1-1 EMS Dispatch

EMS on-scene
Encourage 12-lead ECGs. Consider prehospital fibrinolytic if capable and EMS-to-needle within 30 min.

InterHospital Transfer

5 min. Patient

GOALS

PCI capable

8 EMS Transport min.

EMS Prehospital fibrinolysis EMS transport EMS-to-needle EMS-to-balloon within 90 min. within 30 min. Patient self-transport Hospital door-to-balloon within 90 min.

Dispatch 1 min.

Golden Hour = first 60 min.

Total ischemic time: within 120 min.

TIME IS MUSCLE

Symptom Recognition

Call to Medical System

PreHospital

ED

Cath Lab

Increasing Loss of Myocytes

Delay in Initiation of Reperfusion Therapy

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

STEMI
Reperfusion Approach
Aspirin Heparin (UFH/LMWH) Clopidogrel Reperfusion method :
A.Fibrinolytic B.Primary PCI (+GPIIb/IIIa inhibitor)

UAP/NSTEMI
All patients
General :
Pain control (morphine) Oxygen

Antithrombotic Approach
Aspirin Heparin (UFH/LMWH) Clopidogrel For high risk patients :
GP IIb/IIIa inhibitor Cardiac cath

Anti ischemic :
blocker Nitrates +/- Ca blocker

Additional :
ACE inhibitor Statins

Reperfusion
The medical system goal is to facilitate rapid recognition and treatment of patients with STEMI such that doorto- needle (or medical contactto-needle) time for initiation of fibrinolytic therapy can be achieved within 30 minutes or that door-to-balloon (or medical contactto- balloon) time for PCI can be kept within 90 minutes. The goals of reperfusion therapy are : Early patency 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

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,

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

increased risk of bleeding and ICH

Late presentation > 3 hours from symptom onset Diagnosis of STEMI is in doubt

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 ?

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)

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.

Anti Coagulants
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

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

Kesimpulan
1. ACS kematian tertinggi harus tahu 2. ACS :

UAP NSTEMI STEMI Klinis EKG Enzim

3. ACS : (2 dari 3 kriteria)

4. Klinis nyeri dada :

Non Kardiak Kardiak : Stable angina Unstable angina Door to EKG 10 min (diagnose made) Obat oral (MONA, CPG, b bloker) STEMI reperfusi (medical, PCI) NSTEMI/ UAP antikoagulan mencegah terjadi ACS berikutnya.

5. IGD treatment :

6. A. Yani enzim jantung (-), streptokinase (-), Antikoagulan (-) rujuk saja?????

UDAH AH STOP DULU

Angina Pectoris
SUPPLY DEMAND

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 coronaty resistance vessels, microvascular dysfunction, Adapted from Weissberg. Atherosclerosis. 1999;147:S3S10 vasospasm or hypersensitive pain perception

ED Evaluation of Patients With STEMI

Differential Diagnosis of STEMI: Life-Threatening
Aortic dissection Pulmonary embolus Perforating ulcer Tension pneumothorax Boerhaave syndrome (esophageal rupture with 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 T-waves 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
Pleurisy Peptic ulcer disease Panic attack

Biliary or pancreatic pain

Somatization and psychogenic pain disorder

Angiography Fails to Depict Coronary Arterial Remodeling

3.1 mm

3.1 mm

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%) Conservativ e Low risk score (e.g., TIMI, GRACE) Patient/physician presence in the absence of high-risk features
57

Glasgovs Coronary Remodeling Hypothesis

Progression Compensatory expansion maintains constant lumen Expansion overcome: lumen narrows

Normal vessel

Minimal CAD

Moderate CAD Regression

Severe CAD

Glagov et al. N Engl J Med 1987; 316:1371-5.

Conditional on PCI Related Delay (DB-DN)(min) The Advantage of PCI Compared with Fibrinolysis Covariates Decreases as the After PCI Adjusting Related for Delay Increases
2.0

Odds of Death with Fibrinolysis

Better Better Fibrinolysis PCI Effect Treatment Estimated

1.5 1.25

1.0

0.8

0.5 60 75 90 105 114 120 135 150 165 180

PCI Related (DB-DN) (min) PCI Related Delay Delay (DB-DN) (min)
Pinto DS Gibson CM, Circulation 2006

PCI-Related Time Delay vs Mortality Benefit in 22 Randomized Studies of PCI vs Fibrinolytic Therapy
15

10

23 RCTs N= 7419

For every 10 min delay to PCI: 1 % reduction in Mortality Difference Between PCI & Lysis

DANAMI: on site PCI 90 DB 50 DN = 40 min delay DANAMI: with transfer 110 DB 50 DN = 60 min delay USA AMI with transfer: 171 DB 32 DN = 139 min delay

p=0.006

-5 0 20 40 60 80 PCI-Related Time Delay (min) 100

Nallamothu and Bates, AJC 2003

Clinical Relevance of Clot Selectivity

Action of Clot-Selective Agents

(TNK-tPA, staphylokinase, t-PA)

Action of Non-Clot-Selective Agents

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

Clot-selective vessel plasminogen activators

Clot

Blood

Non-clot-selective vessel plasminogen activators

Clot

Blood

Vascular Changes with Reperfusion (Reperfusion Injury)

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