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Zainudd in Khan

SMF Kardiologi dan Kedokteran Vaskular

RSUD Tarakan, Jakarta

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Topics

Pathogenesis of ACS

Symptoms : Angina Pectoris Risk Factors Physical Examination Electrocardiogram Laboratory Findings Angiography

Diagnosis

Treatment

Prognosis & Complications

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Acute coronary syndrome encompasses aspectrum of coronary artery diseases :

- Unstable angina

- non ST-elevation myocardial infarction

(NSTEMI)

- ST-elevation myocardial infarction

(STEMI)

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Acute Coronary Syndromes

Similar pathophysiology

Similar presentationand early managementrules

STEMI requiresevaluation for acutereperfusion

intervention

Unstable Angina

Non-ST-SegmentElevation MI(NSTEMI)

ST-SegmentElevation MI(STEMI)

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Scope of Problem

CHD single leading cause ofdeath in United States 452,327 deaths in the U.S. in

2004

1,200,000 new & recurrentcoronary attacks per year

38% of those who withcoronary attack die within ayear of having it

Annual cost > $300 billion

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Endothelial

DysfunctionFoamCells

FattyStreak

IntermediateLesion Atheroma

FibrousPlaque

ComplicatedLesion/Rupture

Endothelialinjurynitric oxideendothelin-1vasodilation

Lipidaccumulationadhesion molecules(ICAM, VCAM)

monocyte adhesion

macrophage LDLuptake

Inflammationcontinued macrophage/lipidaccumulation

leukocyte accumulation

cytokines (IL-6,TNFa, IFNg)

MMP's

CRP(hepatic)

oxidized LDL

homocysteinesmokingaginghyperglycemiahypertension

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

Pathophysiology of Atherosclerosis

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Pathophysiology of

Stable and Unstable Plaques

Unstableplaque

Stable

plaque

Thin fibrous cap

ThrombusThick fibrous cap

Smooth muscle cells

Lipid rich coreand

macrophages

Media

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Risk Factors of Coronary Heart Disease

Modifiable

Dyslipidemia(LDL ,HDL)

Tobacco smoking Hypertension

Diabetes Mellitus,MetabolicSyndrome

Lack of PhysicalActivity

NonModifiable

Advanced age Male gender

(post menopausalwomen)

Family history (1stdegree relatives

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Diagnosis of Acute MI

STEMI / NSTEMI

At least 2 of the

following

Ischemic symptomsDiagnostic ECGchanges

Serum cardiac

marker elevations

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Diagnosis of Angina

Typical anginaAll three of thefollowing

Substernal chest discomfort

Onset with exertion or emotional stressRelief with rest or nitroglycerin

Atypical angina2 of the above criteria

Noncardiac chest pain1 of the above

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Assessing Chest Pain (Classic Angina)

Locat ion: usually retrosternalRadiat ion: neck, throat, lower jaw, teeth, ulnararm, left shoulder, interscapular, infrascapular,epigastricCharacter: Tightness,pressure,burning,heaviness, aching, strangling, compression Dull & deep

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Time of on set, du rat ion ,

f requencyExacerbat ing & al leviat ingfactors

4 Es : Exercise, Emotional

Stress, Exposure to Cold/Hothumid, EatingRelieved by : rest, relax,SL/NTGAssoc iated symptoms:breath shortness, sweating,dizziness, syncope, fatique

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Unstable

AnginaSTEMINSTEMI

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

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Chest pain suggestive of ischemia

12 lead ECG

Obtain initialcardiac enzymes

electrolytes, cbclipids, bun/cr,glucose,

CXR

Immediate assessment within 10 Minutes

Establishdiagnosis

Read ECG

Identifycomplications

Assess forreperfusion

Initial labs

and testsEmergent

care

History &

Physical

IV access Cardiac

monitoring

Oxygen

Aspirin

Nitrates

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Targeted Physical

Recognize factors

that increase riskHypotension

Tachycardia

Pulmonary rales, JVD,pulmonary edema,

New murmurs/heartsounds

Diminished peripheralpulses

Signs of stroke

Examination

Vitals

Cardiovascularsystem

Respiratorysystem

Abdomen Neurological

status

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ECG assessment

ST Elevation or new LBBB

STEMI

Non-specific ECG

Unstable Angina

ST Depression or dynamic

T wave inversions

NSTEMI

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ECG diagnosis of ACS

STEMI

New or presumablynew ST elevation, 2mm in V1-3 or 1 mm inother leads

Occurs in 2concomitant leads

Pathologic Q wave

(0,03 wide, 1 mm deep)in 2 concomitant leads New or presumably

new LBBB

NSTEMI/UAP

ST depression 0,5mm in 2 concomitantleads

Inverted T wave 1mm in 2 or moreconcomitant leads

Suspect UAP if ST

segment changes whilechest pain & normalwhile no complaints

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Normal or non-diagnostic EKG

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ST Depression or Dynamic T wave

Inversions

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ST-Segment Elevation MI

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New LBBB

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TIMI 17

TIMI Risk Score for STEMI

Mortality at 30 d vs. STEMI TRS

Morrow DA, Circulation 2000;102:2031-7

HistoricalAge 65-74 2pts

>75 3ptsDM/HTN/Angina 1pt

Exam

SBP < 100 mmHg 3pts

HR > 100 bpm 2ptsKillip IIIV 2ptsWeight < 67 kg 1 pt

Presentation

Anterior STE orLBBB 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

23.426.8

35.9

0

10

20

30

40

50

0 1 2 3 4 5 6 7 8 >8

Early Risk Stratification

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Killip Classification of AMI

Absence of S3 gallop & ralesClass I

Uncomplicated

Mild to moderate orthopnea

S3 gallop Bibasilar rales 50% of both lung

fields

Class IIMild to Mod HF

Severe Respiratory Distress Rales over >50% of both lung fields X-ray:interstitial & alveolar edema

Class III

Pulmonaryedema

Hypotension (BP systolic80 %

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Cardiac markers

Troponin ( T, I)

Very specific and moresensitive than CK

Rises 4-8 hours after

injury May remain elevated

for up to two weeks Can provide

prognostic information

Troponin T may beelevated with renal dz,poly/dermatomyositis

CK-MB isoenzyme

Rises 4-6 hours afterinjury and peaks at 24hours

Remains elevated 36-48hours Positive if CK/MB > 5%

of total CK and 2 timesnormal

Elevation can bepredictive of mortality False positives with

exercise, trauma,muscle dz, DM, PE

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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 rded. Rochester, MN:Mayo Clinic Scientific Press and New York: Informa Healthcare USA, 2007:77380.

Anderson JL, et al. J Am Coll Cardiol2007;50:e1e157, Figure 5.

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Comparison of Cardiac Biomarkers

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Non MI causes Elevation of Troponin

Defibrillator Discharged

Renal insufficiency

Left Ventricular failure

Tachy-arrhythmias

Myocarditis

Pericaditis

Pulmonary embolism

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ReperfusionApproach

Aspirin Heparin

(UFH/LMWH) Clopidogrel Reperfusion

method :A.FibrinolyticB.Primary PCI(+GPIIb/IIIainhibitor)

All patients

General : Pain control(morphine)

Oxygen

Anti ischemic : blocker Nitrates +/- Ca blocker

Additional : ACE inhibitor Statins

AntithromboticApproach

Aspirin Heparin

(UFH/LMWH) Clopidogrel For high risk

patients : GP IIb/IIIa

inhibitor Cardiac cath

STEMI UAP/NSTEMI

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Cardiac Care Goals

Decrease amount of myocardialnecrosis

Preserve LV functionPrevent major adverse cardiac events

Treat life threatening complications

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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

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Fibrinolysis indications

ST segment elevation >1mm in twocontiguous leads

New LBBB

Symptoms consistent with ischemia

Symptom onset less than 12 hrs prior topresentation

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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)

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Reteplase

- Two IV bolus doses of 10 units 10 minutesapart

Tenectaplase

-As injection over 10 seconds at 3050 mgaccording to body weight

- Maximum dose is 50 mg

APSAC (Anistreplase)- IV bolus of 30 mg over 25 minutes

Absolute contraindications for fibrinolysis

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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 acuteischemic stroke within 3 hours

Suspected aortic dissection

Active bleeding or bleeding diathesis (excludingmenses)

Significant closed-head or facial trauma within 3months

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Relative contraindications for fibrinolysis

therapy in patients with acute STEMI

History of chronic, severe, poorly controlledhypertensionSevere uncontrolled hypertension onpresentation (SBP greater than 180 mm Hg orDBP greater than 110 mmHg)History of prior ischemic stroke greater than 3months, dementia, or known intracranialpathology not covered in contraindications

Traumatic or prolonged (greater than 10minutes) CPR or major surgery (less than 3weeks)

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Recent (within 2-4 weeks) internal bleedingNoncompressible vascular puncturesFor streptokinase/anistreplase: prior exposure(more than 5 days ago) or prior allergic reaction tothese agentsPregnancy

Active peptic ulcerCurrent use of anticoagulants: the higher the INR,the higher the risk of bleeding

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STEMI cardiac care

STEP 2: Determine preferred reperfusion strategy

Fibrinolysispreferredif: 90min

door to balloon minus

door to needle > 1hr Door to needle goal

3 hr High risk STEMI

Killup 3 or higher

STEMI dx in doubt

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Medical Therapy

MONA + BAH

Morphine(class I, level C)Analgesia

Reduce pain/anxietydecrease sympathetic tone,

systemic vascular resistance and oxygen demandCareful with hypotension, hypovolemia, respiratorydepression

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

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Nitroglycerin (class I, level B)

Analgesiatitrate infusion to keep patientpain free

Dilates coronary vesselsincrease bloodflow

Reduces systemic vascular resistance andpreload

Careful with recent ED meds, hypotension,

bradycardia, tachycardia, RV infarction

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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

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Beta-Blockers(class I, level A)

14% reduction in mortality risk at 7 days at23% long term mortality reduction in STEMI

Approximate 13% reduction in risk ofprogression to MI in patients withthreatening or evolving MI symptoms

Be aware of contraindications (CHF, Heart

block, Hypotension)Reassess for therapy as contraindicationsresolve

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

Start in patients with anterior MI, pulmonarycongestion, LVEF < 40% in absence of

contraindication/hypotensionStart in first 24 hours

ARB as substitute for patients unable touse ACE-I

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Clopidodrel (class I, level B)Irreversible inhibition of platelet aggregation

Used in support of cath / PCI intervention or ifunable 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 pathwayIn support of PCI intervention as early aspossible prior to PCI

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Heparin(class I, level C to class IIa, level C)

LMWH or UFH(max 4000u bolus, 1000u/hr)Indirect inhibitor of thrombinless supporting evidence of benefit in era ofreperfusion

Adjunct to surgical revascularization andthrombolytic / PCI reperfusion

24-48 hours of treatment

Coordinate with PCI team (UFH preferred)

Used in combo with aspirin and/or other plateletinhibitors

Changing from one to the other not recommended

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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

LowIntermediate

High

Risk Stratification to Det

ermine the Likelihood of

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Assessment Find ings ind icatingHIGHlikel ihood of ACS

Find ings ind icating

INTERMEDIATE

l ikel ihood o f ACS inabsence of high-

l ikel ihood f ind ings

Findings indicating

LOW l ikel ihood of ACS

in absence of high- orintermediate-l ikel ihood

f ind ings

History Chest or left arm pain ordiscomfort as chief

symptomReproduction of previous

documented anginaKnown history of coronary

artery disease, including

myocardial infarction

Chest or left arm pain or

discomfort as chief

symptomAge > 50 years

Probable ischemic

symptomsRecent 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 newtransient ST-segment

deviation (> 0.05 mV) or T-

wave inversion (> 0.2 mV)

with symptoms

Fixed Q wavesAbnormal ST segments or

T waves not documented

to be new

T-wave flattening or

inversion of T waves in

leads with dominant R

wavesNormal 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

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Low

risk

High

risk

Conservative

therapy

Invasive

therapy

Chest Pain

center

Intermediate

risk

I i h i

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Invasive therapy option

UA/NSTEMI

Coronary angiography andrevascularization within 12 to 48 hoursafter presentation to ED

For high risk ACS (class I, level A)

MONA + BAH(UFH)

Clopidogrel 20% reduction death/MI/StrokeCURE trial

1 month minimum duration and possibly up to 9months

Glycoprotein IIb/IIIa inhibitors

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Conservative Therapy for UA/NSTEMI

Early revascularization or PCI not planned

MONA + BAH(LMW or UFH)

ClopidogrelGlycoprotein IIb/IIIa inhibitors Only in certain circumstances (planning PCI, elevated

TnI/T)

Surveillence in hospital Serial ECGs

Serial Markers

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Complications of ACS

Acute cardiac failure

Cardiogenic shock

Post-infarct or refractory unstable angina

Arrhythmias : Tachycardias and Bradycardias

Myocardial rupture

Cardiac tamponade

Ventricular septal defectPapillary muscle rupture

Pericarditis

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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) atpresentation

Acute mitral regurgitationVentricular septal defect

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Secondary Prevention

Disease

HTN, DM, HLP

Behavioral smoking, diet, physical activity, weight

Cognitive

Education, cardiac rehab program


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disease management

Blood Pressure Goals < 140/90 or 500; consider

omega-3 fatty acids

DiabetesA1c < 7%

S d ti

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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

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Secondary prevention

cognitive

Patient education

In-hospitaldischargeoutpatientclinic/rehab

Monitor psychosocial impact

Depression/anxiety assessment & treatment

Social support system

Medication Checklist

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Medication Checklist

after ACS

Antiplatelet agentAspirin*and/or Clopidorgrel

Lipid lowering agent Statin* Fibrate / Niacin / Omega-3

Antihypertensive agent Beta blocker*

ACE-I*/ARBAldactone (as appropriate)

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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 initiativesfor ACS patients

Beta blocker, ASA, ACE-I, Statin

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Documents

ACS , Zai