ACUTE CORONARY SYNDROME

Dr. ZAINUDDIN KHAN, SpJP. FIHA

TANJUNG PURA REGENCY HOSPITAL LANGKAT REGENCY

Acute Coronary Syndromes

Unstable Angina Non-ST-Segment

Similar pathophysiology
Similar presentation and early management rules STEMI requires evaluation for acute reperfusion intervention

Elevation MI (NSTEMI)
ST-Segment

Elevation MI (STEMI)

Scope of The 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

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

Fatty Intermediate Fibrous Complicated Atheroma Plaque Lesion/Rupture Streak Lesion

35-45 yrs 45-55 yrs Lipid accumulation Endothelial adhesion molecules injury (ICAM, VCAM)
nitric oxide endothelin-1 vasodilation 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)

Pathophysiology of Stable and Unstable Plaques

Thin fibrous cap Thrombus Thick fibrous cap Smooth muscle cells

Lipid rich core and macrophages

Unstable plaque

Media

Stable plaque

The Progressive Development of Cardiovascular Disease

Risk Factors Endothelial Dysfunction

Atherosclerosis
CAD Myocardial Ischemia

Coronary Thrombosis
Myocardial Infarction Arrhythmia & Loss of Muscle Remodeling Ventricular Dilation Congestive Heart Failure Endstage Heart Disease

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

Kematian Karena PJK & Stroke

1500

Gab PJK & Stroke

1000

Kematian PJK

500

0
Russia Poland Finland New England/ USA Zealand Wales Italy Spain Japan

(Adapted from 1998 World Health Statistics)

Atherothrombosis* merupakan penyebab kematian tertinggi sedunia

AIDS Pulmonary Disease Injuries Cancer Infectious Disease Atherothrombosis* 0 5 10 15 20 25 5.1 6 9 12 19 28 30

Mortality (%) *Ischemic heart disease, cerebrovascular disease, inflammatory heart disease and hypertensive heart disease Worldwide defined as Member States by WHO Region (African, Americas, Eastern Mediterranean, European, South-East Asia and Western Pacific)
1. The World Health Report, 2002, WHO Geneva, 2002.

Proses Terjadinya Atherosklerosis

Proses Tersumbatnya Pemb. Darah

Proses Penyempitan Pemb. Darah

FAKTOR RESIKO PJK DI INDONESIA INA MONICA 1993

Merokok

Hipertensi Hiperkolesterol D M

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
Non occlusive thrombus

NSTEMI
Occluding thrombus sufficient to cause tissue damage & mild myocardial necrosis ST depression +/T wave inversion on ECG Elevated cardiac enzymes

STEMI
Complete thrombus occlusion ST elevations on ECG or new LBBB Elevated cardiac enzymes More severe symptoms

Non specific ECG

Normal cardiac enzymes

Chest pain suggestive of ischemia

Immediate assessment within 10 Minutes
Initial labs and tests

Emergent care
IV access Cardiac monitoring Oxygen Aspirin Nitrates

History & Physical Establish diagnosis Read ECG Identify complications Assess for reperfusion

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

Targeted Physical
Examination Recognize factors that

Vitals Cardiovascular system Respiratory system Abdomen Neurological status

increase risk

Hypotension Tachycardia Pulmonary rales, JVD, pulmonary edema, New murmurs/heart sounds Diminished peripheral pulses Signs of stroke

ECG assessment ST Elevation or new LBBB STEMI

ST Depression or dynamic T wave inversions

NSTEMI
Non-specific ECG

Unstable Angina

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

Early Risk Stratification

TIMI Risk Score for STEMI
50 40 30 20

Historical Age 65-74 >75 DM/HTN/Angina Exam SBP < 100 mmHg HR > 100 bpm Killip II IV Weight < 67 kg

2pts 3pts 1pt 3pts 2pts 2pts 1 pt

Mortality at 30 d vs. STEMI TRS

23,4 16,1 12,4 2,2 2 4,4 7,3

35,9 26,8

10

0,8
0

1,6 1

Presentation Anterior STE or LBBB 1 pt Time to Rx > 4hr 1pt -----------------------------------Risk Score = Total (0-14)

>8

TIMI 17

Morrow DA, Circulation 2000;102:2031-7

Killip Classification of AMI

Clinical Evidence of LV Dysfunction
Class I Uncomplicated

Mortality

Absence of S3 gallop & rales

35%

Class II Mild to Mod HF

Mild to moderate orthopnea S3 gallop Bibasilar rales 50% of both lung fields Severe Respiratory Distress Rales over >50% of both lung fields X-ray:interstitial & alveolar edema
Hypotension (BP systolic <90mmHg) Tachycardia Signs of peripheral perfusion

6 10 %
20 30 %

Class III Pulmonary edema Class IV Cardiogenic Shock

>80 %

Cardiac markers
Troponin ( T, I)

CK-MB isoenzyme

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

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

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.

32

Non MI causes Elevation of Troponin

Defibrillator Discharged Renal insufficiency Left Ventricular failure Tachy-arrhythmias Myocarditis Pericaditis Pulmonary embolism

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

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

Low risk

Intermediate

risk

High risk

Chest Pain center

Conservative therapy

Invasive therapy

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