Penanganan Mutakhir Penyakit Jantung Koroner : Sindroma Koroner Akut

Prof. dr. Harmani Kalim, MPH,Sp.JP (K), FIHA, FASCC

Departemen Kardiologi dan Kedokteran Vaskuler FKUI Pusat Jantung Nasional-RS Jantung Harapan Kita

Epidemiologi

Survei Kesehatan Rumah Tangga (SKRT) Departemen Kesehatan menunjukkan, penyakit jantung memberikan kontribusi sebesar 19,8 % dari seluruh penyebab kematian pada tahun 1993. Angka tersebut meningkat menjadi 24,4 % pada tahun 1998 Hasil SKRT tahun 2001, PJK telah menempati urutan pertama dalam deretan penyebab utama kematian di Indonesia.

Atherosclerosis Timeline
Foam Cells Fatty Streak Intermediate Atheroma Lesion Fibrous Plaque Complicated Lesion/ Rupture

Endothelial Dysfunction From First Decade From Third Decade From Fourth Decade

Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 10A):23S-27S.

Pathogenesis of Atherosclerotic Plaques

Endothelial damage Protective response results in production of cellular adhesion molecules Monocytes and T lymphocytes attach to sticky surface of endothelial cells Migrate through arterial wall to subendothelial space Macrophages take up oxidised LDL-C Lipid-rich foam cells Fatty streak and plaque

The Activated Endothelium

endothelium cytokines (eg. IL-1, TNF-) chemokines (eg.MCP-1, IL-8) growth factors (eg. PDGF, FGF)
attracts monocytes and T lymphocytes which adhere to endothelial cells

activated

CELLULAR ADHESION MOLECULES

induces cell proliferation and a prothrombic state

Koenig W. Eur Heart J Suppl 1999;1(Suppl T);T1926.

Gambaran Robeknya Plak (Plaque) disertai Proses Trombosis

Unstable coronary artery disease

Thrombus Forms and Extends into the lumen

Thrombus

Lipid core

Adventitia

Acute Coronary Syndrome : Clinical Perspective

1772: Clinical description of progression of angina symptoms to myocardial infarction and death 1910: Pre-infarction angina 1971: Introduction of terminology of unstable angina 1988: Concept of acute coronary syndrome 1990-1995: Risk stratification-Troponins

Milestones in Management of Acute Coronary Syndrome

1983:Aspirin therapy 1985: Thrombolytic therapy 1988: Aspirin and heparin 1997: Low molecular weight heparin 1998: GPIIb/IIIa and aspirin and heparin 1999: Catheter based/ Invasive treatment (PCI/CABG) 2001: Clopidogrel with aspirin 2005: Whats new??

Sindroma Koroner Akut

Angina Pektoris terstabil Infark miokard non elevasi segmen ST (STEMI) Infark Miokard dengan elevasi segmen ST (NSTEMI)

Patofisiologi sama Persentasi sama Aturan2 pengelolaan awal sama STEMI perlu evaluasi untuk intervensi reperfusi akut

Clinical Classification of Myocardial Infarction: Expert Consensus

Type I Spontaneous MI related to ischemia due to a primary coronary event such as a plaque erosion and/or rupture, fissuring, or dissection Type 2 MI secondary to ischemia due to either O2 demand or decreased supply (coronary artery spasm, coronary embolism, anemia, HTN, hypotension, arrhythmia)

Thygesen, K. et.al. Circulation 2007; 116: 2634 2653.

Clinical Classification of Myocardial Infarction: Expert Consensus

Type 3 Sudden unexpected cardiac death, including cardiac arrest, often with symptoms suggestive of myocardial ischemia, accompanied by presumably new ST elevation, or new LBBB, or evidence of fresh thrombus in a coronary artery by angiography and/or at autopsy, but death occurring before blood tests could be obtained, or at a time before the appearance of cardiac biomarkers in the blood.

Thygesen, K. et.al. Circulation 2007; 116: 2634 2653.

Clinical Classification of Myocardial Infarction: Expert Consensus

Type 4a MI associated with PCI Type 4b MI associated with stent thrombosis as documented by angiography or at autopsy Type 5 MI associated with CABG

Thygesen, K. et.al. Circulation 2007; 116: 2634 2653.

Faktor Penentu Luas Infark

1.

1. 2. 3. 4.

Lama oklusi (Ingat: door to balloon < 90 menit dan door to needle < 30 menit ) Kolateral Tingkat konsumsi oksigen miokard Keadaan metabolik Keseimbangan fibrinolitik

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

Diagnosis of Unstable Angina

Patients with typical angina - An episode of angina

Increased in severity or duration Has onset at rest or at a low level of exertion Unrelieved by the amount of nitroglycerin or rest that had previously relieved the pain

Patients not known to have typical angina

First episode with usual activity or at rest within the previous two weeks Prolonged pain at rest

Diagnosis of Acute MI STEMI / NSTEMI

At least 2 of the following

Ischemic

symptoms Diagnostic ECG changes Serum cardiac marker elevations

Unstable Angina
Non occlusive thrombus Non specific ECG Normal cardiac enzymes

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

Sasaran Perawatan Kardiak

1. 2. 3.

4.

5.

Mengurangi luasnya infark Mempertahankan fungsi ventrikel kiri Mencegah kejadian kardiak atau komplikasi major Mengatasi komplikasi yang mengancam jiwa Mulai melakukan pencegahan sekunder

Acute Management

Initial evaluation & stabilization Efficient risk stratification Focused cardiac care

Evaluation

Efficient & direct history Initiate stabilization interventions

Occurs simultaneously

Plan for moving rapidly to indicated cardiac care Directed Therapies

are Time Sensitive!

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, coags CXR

Focused History

Aid in diagnosis and rule out other causes

Palliative/Provocative factors Quality of discomfort Radiation Symptoms associated with discomfort Cardiac risk factors Past medical history especially cardiac

Reperfusion questions

Timing of presentation ECG c/w STEMI Contraindication to fibrinolysis Degree of STEMI risk

Targeted Physical

Examination

Vitals Cardiovascular system Respiratory system Abdomen Neurological status

Recognize factors that increase risk

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

Rekaman EKG harus secepatnya dilakukan dan diinterpretasi saat pasien tiba di IGD Standar waktu 10 menit

Hamm Lancet 358:1533,2001

Presentation Working Dx

Ischemic Discomfort Acute Coronary Syndrome

Davies MJ Heart 83:361, 2000

ECG

No ST Elevation NSTEMI

ST Elevation

Biochem. Marker Final Dx Unstable Angina

Myocardial Infarction NQMI Qw MI

Normal or non-diagnostic EKG

ST Depression or Dynamic T wave Inversions

ST-Segment Elevation MI

New LBBB

QRS > 0.12 sec L Axis deviation Prominent S wave V1-V3 Prominent R wave 1, aVL, V5-V6

Use of Cardiac Markers in ACS

URL = 99th %tile of Reference Control Group

50
Multiples of the URL

20 10 5 2 1 0 1
Upper reference limit

Cardiac troponin after classical AMI CK-MB after AMI Cardiac troponin after microinfarction

2 3 4 5 6 Days After Onset of AMI

Modified from: ESC/ACC Comm MI redefined JACC 36: 959,2000 Wu AH et al. Clin Chem 1999;45:1104.

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 3648 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

Prognosis with Troponin

8 7
Mortality at 42 Days

7.5 % 6.0 % 3.4 % 1.0 %

831

6 5 4 3 2 1 0

3.7 %

1.7 %
174 148 134 50 67
9.0

0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 Cardiac troponin I (ng/ml)

SPEKTRUM KLINIS SKA

Current definitions and prognosis of ACS

12hr serum troponin T concentration (ug/L) < 0.01 BCS ESC/ACC WHO 30-day mortality 6-month mortality ACS with unstable angina Unstable angina Unstable angina 4.5% 8.6% 0.1 and < 1.0 ACS with myocyte necrosis MI Unstable angina 10.4% 18.7% 1.0 ACS with clinical MI MI MI 12.9% 19.2%

Acute Coronary Syndrome No ST Elevation ST Elevation

Risk Stratification
Purposes Triage / Transfer for Tertiary Care Resource Allocation Selection of Rx Strategy Prognosis

Continuous Process Presentation: History, ACS features, Biomarkers, PEx In Hospital: Events, Response to Rx Discharge: LV Function, Arrhythmias, Ischemia

Risk Stratification
STEMI Patient?
Based on initial Evaluation, ECG, and Cardiac markers

YES

NO

- Assess for reperfusion

- Select & implement reperfusion therapy - Directed medical therapy

UA or NSTEMI - Evaluate for Invasive vs. conservative treatment - Directed medical therapy

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

Absolute contraindications for fibrinolysis therapy in patients with acute STEMI

Any prior ICH 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

Advantages of Fibrinolytic Therapy

More universal access Shorter time to treatment Greater clinical trial evidence of:

reduction in infarct size improvement of LV function

Results less dependent on physician experience Lower system costs

42

Advantages of primary PCI over thrombolysis

Clinical indices Event rate Thrombolysis Short term mortality (4-6weeks) Long term mortality (6-18months) Stroke Re-infarction Recurrent ischaemia Death or non-fatal re-infarction Need for CABG 8% 8% 2% 8% 18% 12% 13% PCI 5% 5% <1% 3% 7% 7% 8% Absolute RR 3% 3% 2% 5% 11% 5% 5% Relative RR 36% 38% 64% 59% 59% 44% 38% NNT

33 33 50 20 20 20 20

Comparing outcomes

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

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 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

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 Reassess for therapy as contraindications resolve ACE-Inhibitors / ARB (class I, level A) Start in patients with anterior MI, pulmonary congestion, LVEF < 40% Start in first 24 hours ARB as substitute for patients unable to use ACE-I

Heparin (class I, level C to class IIa, level C) LMWH or UFH (max 4000u bolus, 1000u/hr) Indirect inhibitor of thrombin 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

STEMI care CCU

Monitor for complications:

recurrent ischemia, cardiogenic shock, ICH, arrhythmias

Review guidelines for specific management of complications & other specific clinical scenarios

PCI after fibrinolysis, emergent CABG, etc

Decision making for risk stratification at hospital discharge and/or need for CABG

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 High

Intermediate

High Risk ACS (UA/NSTEMI)

Elevated cardiac markers New or presumed new ST depression Recurrent ischemia despite therapy Recurrent ischemia with heart failure High risk findings on non-invasive stress test Depressed systolic left ventricular function Hemodynamic instability Sustained Ventricular tachycardia PCI with 6 months Prior Bypass surgery

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) Serial ECGs Serial Markers

Surveillence in hospital

Medication Use at Discharge and 1-year Mortality

After adjusting for age, previous MI, CHF, Killip class, abnormal biomarker, ST deviation/BBB on presentation, the discharge use of the following medications was associated with lower 1-year mortality *: ASA [OR=0.48 (0.36 to 0.63), P<0.001] Beta-blocker [OR=0.72 (0.56 to 0.92), P<0.01] ACE inhibitor [OR=0.76 (0.60 to 0.96), P=0.02] Lipid lowering agent [OR=0.72 (0.57 to 0.92), P<0.01]
* OR= odds ratio (95% confidence interval)

Comprehensive Medical Therapy For 2nd Prevention for Patients with CHD or Other Vascular Disease
Risk Reduction

ASA* Beta Blockers* ACE inhibitors* Statins* Smoking Cessation

20-30% 20-35% 22-25% 25-42% 50%

*The four medications every atherosclerosis patient should be treated with, unless contraindications exist and are documented

Pencegahan Sekunder
A : ASA, antikoagulan, ACE-I/ARB (LVD, HF, HTN, DM) B : Beta-blocker, BW reduction, BP Control (BP< 130/80 mmHg) C : Cigarette smoking cessation Cholesterol control (K-LDL<70 mg/dl) D : Diet ( AHA step 2 diet ) Diabetes management ( Ac<7%) E : Exercise regularly Education F : Family Support G : Go to Hospital

Secondary Prevention of Coronary Disease

Secondary Prevention
CAD
Non-Coronary Atherosclerosis

Primary Prevention

Subclinical Atherosclerosis Multiple Risk Factors Environmental, Genetic Factors that Produce Risk

Population Wellness

Prevention news
From 1994 to 2004 the death rate from coronary heart disease declined33%... But the actual number of deaths declined only18%

Getting better with treatment But more patients developing disease need for primary prevention focus

Kesimpulan

SKA mencakup APTS, NSTEMI, dan STEMI Fokus penatalaksanaan - penilaian dan intervensi segera ( MONA + BAH ) - stratifikasi resiko ( APTS/NSTEMI VS STEMI ) - reperfusi cepat pada STEMI (Fibrinolitik vs PCI ) - strategi konservatif vs invasif dini pada APTS/ NSTEMI Pencegahan sekunder agresif pada pasien SKA - BB, ACE-1/ARB, ASA, statin

FarahMutiaraSariHarmani

Objectives

Define & delineate acute coronary syndrome Review Management Guidelines

Unstable Angina / NSTEMI STEMI

Review secondary prevention initiatives

Acute Coronary Syndromes

Unstable Angina Non-ST-Segment Elevation MI (NSTEMI) ST-Segment Elevation MI (STEMI)

Similar pathophysiology

Similar presentation and early management rules

STEMI requires evaluation for acute reperfusion intervention

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

Diagnosis of Unstable Angina

Patients with typical angina - An episode of angina

Increased in severity or duration Has onset at rest or at a low level of exertion Unrelieved by the amount of nitroglycerin or rest that had previously relieved the pain

Patients not known to have typical angina

First episode with usual activity or at rest within the previous two weeks Prolonged pain at rest

Unstable Angina
Non occlusive thrombus Non specific ECG Normal cardiac enzymes

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

Acute Management

Initial evaluation & stabilization Efficient risk stratification Focused cardiac care

Efficient & direct history Occurs Initiate stabilization interventions simultaneousl

y

Evaluation

Plan for moving rapidly to indicated cardiac care

Directed Therapies are Time Sensitive!

Chest pain suggestive of ischemia

Immediate assessment within 10 Minutes
Initial labs and tests

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

Emergent care IV access Cardiac monitoring Oxygen Aspirin Nitrates

History & Physical

Establish diagnosis Read ECG Identify complicatio ns Assess for reperfusion

Focused History

Aid in diagnosis and rule out other causes

Palliative/Provocative factors Quality of discomfort Radiation Symptoms associated with discomfort Cardiac risk factors Past medical history -especially cardiac

Reperfusion questions

Timing of presentation ECG c/w STEMI Contraindication to fibrinolysis Degree of STEMI risk

Targeted Physical

Examination

Vitals Cardiovascular system Respiratory system Abdomen Neurological status

Recognize factors that increase risk

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

Modified from Libby P Circ 104:365,2001

Acute Coronary Syndrome

Superficial Erosion

Ruptured Fibrous Cap

Hamm Lancet 358:1533,2001

Presentation Working Dx

Ischemic Discomfort Acute Coronary Syndrome

Davies MJ Heart 83:361, 2000

ECG

No ST Elevation NSTEMI

ST Elevation

Biochem. Marker Final Dx Unstable Angina

Myocardial Infarction NQMI Qw MI

URL = 99th %tile of Reference Control Group

Use of Cardiac Markers in ACS

50 20 10 5 2 1 0 1
Upper reference limit

Multiples of the URL

Cardiac troponin after classical AMI CK-MB after AMI Cardiac troponin after microinfarction

2 3 4 5 6 Days After Onset of AMI

Modified from: ESC/ACC Comm MI redefined JACC 36: 959,2000 Wu AH et al. Clin Chem 1999;45:1104.

Acute Coronary Syndrome No ST Elevation ST Elevation

Risk Stratification
Purposes Triage / Transfer for Tertiary Care Resource Allocation Selection of Rx Strategy

Prognosis

Continuous Process Presentation: History, ACS features, Biomarkers, PEx In Hospital: Events, Response to Rx Discharge: LV Function, Arrhythmias, Ischemia

Symptoms suggestive of ACS

Rapid Triage Obtain Biomarkers

Assess 12 lead ECG

Goal = 10 min

Non Cardiac Diagnosis

Chronic Stable Angina

Possible ACS ASA

Definite ACS

As Per Other Dx

Medical Rx

Antithrombin Beta Blocker ACS Protocol

Symptoms Suggestive of ACS Possible ACS No ST elev. < 12h Lytic eligible Lytic
(D-N < 30 m)

Definite ACS ST elev. > 12h Not a reperfusion candidate

Consider Reperfusion for Symptoms

Lytic ineligible PCI*

(D-B < 90)
Consider: GP IIb/IIIa + stent

Medical Rx
(ACEI)

*Skilled Oper./Team Rapidly Available

Symptoms Suggestive of ACS

Possible ACS No ST elev. Definite ACS ST elev. Evaluate for reperfusion

Non dx ECG Neg. card. markers Observe f/u studies Neg Neg Outpt f/u Stress Pos Pos

ST-Tw changes Ongoing pain Positive card markers Hemodynamic abnl.

Dx of ACS confirmed Admit to hospital Acute ischemia pathway

Development of atherosclerosis and vulnerable plaque

Chronology of Atherosclerotic Vascular Disease Process

Acute Coronary Syndrome Secondary Prevention

Ischemic Heart Disease Cerebrovascular Disease Peripheral Vascular Disease

Modified from Libby P Circ 104:365,2001

Troponins for Evaluation and Management of ACS

Advantages

Disadvantages

Risk Stratificaton Sens/Spec > CKMB Detect Recent MI Selection of Rx Detect Reperfusion

Low sens. early (< 6h) Repeat at 8-12 h if neg. Limited ability to detect late minor reinfarction

Recommendation Useful as single test to efficiently Dx NSTEMI Clinicians should familiarize themselves with Dx cutoffs in local lab

ECG assessment
ST Elevation or new LBBB STEMI
ST Depression or dynamic T wave inversions

NSTEMI
Non-specific ECG

Unstable Angina

Normal or non-diagnostic EKG

ST Depression or Dynamic T wave Inversions

ST-Segment Elevation MI

New LBBB

QRS > 0.12 sec L Axis deviation Prominent R wave V1-V3 Prominent S wave 1, aVL, V5-V6 with t-wave inversion

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

Prognosis with Troponin

8 7 Mortality at 42 Days 6 5 4 3 2 1 0

7.5 % 6.0 % 3.4 % 1.0 %

831

3.7 %

1.7 %
174 148 134 50 67
9.0

0 to <0.4 0.4 to <1.0 1.0 to <2.0 2.0 to <5.0 5.0 to <9.0 Cardiac troponin I (ng/ml)

Risk Stratification
STEMI Patient?
Based on initial Evaluation, ECG, and Cardiac markers

YES

NO

- Assess for reperfusion

- Select & implement reperfusion therapy - Directed medical therapy

UA or NSTEMI - Evaluate for Invasive vs. conservative treatment - Directed medical therapy

Cardiac Care Goals

Decrease

necrosis Preserve LV function Prevent major adverse cardiac events Treat life threatening complications

amount of myocardial

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 Based on availability and time to balloon rx

Determine if PCI candidate

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

Absolute contraindications for fibrinolysis therapy in patients with acute STEMI

Any prior ICH 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)

Relative contraindications for fibrinolysis..

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

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

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

Comparing outcomes

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 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

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 Reassess for therapy as contraindications resolve ACE-Inhibitors / ARB (class I, level A) Start in patients with anterior MI, pulmonary congestion, LVEF < 40% Start in first 24 hours ARB as substitute for patients unable to use ACE-I

Heparin (class I, level C to class IIa, level C) LMWH or UFH (max 4000u bolus, 1000u/hr) Indirect inhibitor of thrombin 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

Additional medication therapy

Aldosterone blockers (class I, level A)

Post-STEMI patients
no significant renal failure (cr < 2.5 men or 2.0 for women) No hyperkalemis > 5.0 LVEF < 40% Symptomatic CHF or DM

STEMI care CCU

Monitor for complications:

recurrent ischemia, cardiogenic shock, ICH, arrhythmias

Review guidelines for specific management of complications & other specific clinical scenarios

PCI after fibrinolysis, emergent CABG, etc

Decision making for risk stratification at hospital discharge and/or need for CABG

Unstable angina/NSTEMI care

cardiac

Evaluate for conservative vs. invasive therapy based upon:

Risk

of actual ACS TIMI risk score ACS risk categories per AHA guidelines Low Intermediate High

Predicts risk of death, new/recurrent MI, need for urgent revascularization within 14 days

TIMI Risk Score

ACS risk criteria (UA/NSTEMI)

Low Risk ACS
No intermediate or high risk factors <10 minutes rest pain Non-diagnositic ECG Non-elevated cardiac markers Age < 70 years

Intermediate Risk ACS

Moderate to high likelihood of CAD >10 minutes rest pain, now resolved T-wave inversion > 2mm Slightly elevated cardiac markers

High Risk ACS (UA/NSTEMI)

Elevated cardiac markers New or presumed new ST depression Recurrent ischemia despite therapy Recurrent ischemia with heart failure High risk findings on non-invasive stress test Depressed systolic left ventricular function Hemodynamic instability Sustained Ventricular tachycardia PCI with 6 months Prior Bypass surgery

Low risk

Intermediate

risk

High risk

Chest Pain center

Conservative therapy

Invasive therapy

Secondary prevention behavioral intervention

Smoking cessation

Cessation-class, meds, counseling Goal 30 - 60 minutes daily Risk assessment prior to initiation DASH diet, fiber, omega-3 fatty acids <7% total calories from saturated fats

Physical Activity

Diet

Or maybe just move.

Secondary prevention cognitive

Patient education

In-hospital discharge outpatient clinic/rehab Depression/anxiety assessment & treatment Social support system

Monitor psychosocial impact

Antiplatelet agent

Medication Checklist after ACS

Aspirin* and/or Clopidorgrel Statin* Fibrate / Niacin / Omega-3 Beta blocker* ACE-I*/ARB Aldactone (as appropriate)

Lipid lowering agent

Antihypertensive agent

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

Cardiovascular disease and diabetes

~65% of deaths are to CV disease due

Coronary heart disease deaths 2- to 4-fold

Cardiovascular complications of T2DM

Stroke risk 2- to 4-fold

Heart failure 2- to 5-fold

T2DM = type 2 diabetes mellitus
Bell DSH. Diabetes Care. 2003;26:2433-41. Centers for Disease Control (CDC). www.cdc.gov.

Abnormal glucose metabolism in CAD

n = 2107 inpatients with acute CAD; n = 2854 outpatients with stable CAD
Known diabetes OGTT* 58 51

60

60

Total patients (%)

40

32

30

Patients* (%)

40

20

20

0 Inpatients Outpatients

0 Inpatients
IGT IFG

Outpatients
New DM

*n = 1920 without known diabetes OGTT = oral glucose tolerance test; IGT = impaired glucose tolerance; IFG = impaired fasting glucose

Bartnik M et al. Eur Heart J. 2004;25:1880-90.

New-onset hyperglycemia linked to highest rate of in-hospital mortality

N = 2030 hospital patients
40 30 Mortality 20 (%) 10 0 Normoglycemia Known diabetes New hyperglycemia

ICU patients
*P < 0.01 vs normoglycemia and known diabetes

Non-ICU patients

Umpierrez GE et al. J Clin Endocrinol Metab. 2002;87:97882.

Stress hyperglycemia in AMI: Association with mortality risk in patients without known diabetes
Reference OSullivan 1991 Lewandowicz 1979 Soler 1981 Oswald 1986 Bellodi 1989 Ravid 1975 Sewdarsen 1989 Pooled 0 1 2 3 4 5 6 7 8 9 10 11 12 13
Hyperglycemia definition (mg/dL)

>144 121 110 144 >121 >121 144

Unadjusted RR of in-hospital mortality after MI*

*vs patients with normoglycemia
Capes SE et al. Lancet. 2000;355:773-8.

Baseline fasting plasma glucose levels predict HF hospitalization in high-risk patients

ONTARGET/TRANSCEND; N = 31,546 with CVD or DM + end-organ damage
0.06 0.05 0.04 Proportion with incident HF hospitalization 0.03 0.02 0.01 0.0 0 200 400 600 800 1000 1200 Follow-up (days)
Log rank P < 0.001
Held C et al. Circulation. 2007;115;1371-5.

Normal low Normal high IFG New DM DM

23% in HF hospitalization per 18 mg/dL glucose in patients with no known diabetes

Admission glucose and glucose change within 24 hours predict mortality risk
N = 1469 with AMI (n = 1219 without DM)
12 10 30-day mortality (%) 8 6 4 2 0 0 <125 125<140 140<170 Baseline glucose (mg/dL) 170 9% in 30-day mortality per 11 mg/dL glucose in first 24 hr (P = 0.002)*

Glucose (24 hr vs baseline) 30 mg/dL decrease No change to <30 mg/dL decrease

*Multivariate analysis

Increase

Goyal A et al. Eur Heart J. 2006;27:1289-97.

Modified from Libby P Circ 104:365,2001

Acute Coronary Syndrome

Superficial Erosion

Ruptured Fibrous Cap

Hamm Lancet 358:1533,2001

Presentation Working Dx

Ischemic Discomfort Acute Coronary Syndrome

Davies MJ Heart 83:361, 2000

ECG

No ST Elevation NSTEMI

ST Elevation

Biochem. Marker Final Dx Unstable Angina

Myocardial Infarction NQMI Qw MI

Troponins for Evaluation and Management of ACS

Advantages

Disadvantages

Risk Stratificaton Sens/Spec > CKMB Detect Recent MI Selection of Rx Detect Reperfusion

Low sens. early (< 6h) Repeat at 8-12 h if neg. Limited ability to detect late minor reinfarction

Recommendation Useful as single test to efficiently Dx NSTEMI Clinicians should familiarize themselves with Dx cutoffs in local lab

Acute Coronary Syndrome No ST Elevation ST Elevation

Risk Stratification
Purposes Triage / Transfer for Tertiary Care Resource Allocation Selection of Rx Strategy

Prognosis

Continuous Process Presentation: History, ACS features, Biomarkers, PEx In Hospital: Events, Response to Rx Discharge: LV Function, Arrhythmias, Ischemia

Symptoms suggestive of ACS

Rapid Triage Obtain Biomarkers

Assess 12 lead ECG

Goal = 10 min

Non Cardiac Diagnosis

Chronic Stable Angina

Possible ACS ASA

Definite ACS

As Per Other Dx

Medical Rx

Antithrombin Beta Blocker ACS Protocol

Symptoms Suggestive of ACS Possible ACS No ST elev. < 12h Lytic eligible Lytic
(D-N < 30 m)

Definite ACS ST elev. > 12h Not a reperfusion candidate

Consider Reperfusion for Symptoms

Lytic ineligible PCI*

(D-B < 90)
Consider: GP IIb/IIIa + stent

Medical Rx
(ACEI)

*Skilled Oper./Team Rapidly Available

Symptoms Suggestive of ACS

Possible ACS No ST elev. Definite ACS ST elev. Evaluate for reperfusion

Non dx ECG Neg. card. markers Observe f/u studies Neg Neg Outpt f/u Stress Pos Pos

ST-Tw changes Ongoing pain Positive card markers Hemodynamic abnl.

Dx of ACS confirmed Admit to hospital Acute ischemia pathway

Development of atherosclerosis and vulnerable plaque

Chronology of Atherosclerotic Vascular Disease Process

Acute Coronary Syndrome Secondary Prevention

Ischemic Heart Disease Cerebrovascular Disease Peripheral Vascular Disease

Modified from Libby P Circ 104:365,2001

Electrocardiographic Changes

129

Causes of ST segment Elevation

Acute myocardial infarction Benign early repolarization Left bundle branch block Left ventricular hypertrophy Ventricular aneursym Coronary vasospasm Pericarditis Brugada Syndrome Subarachnoid hemorrhage
130

Initial Management in ED
1. 2. 3. 4. 5. 6. 7.

Initial evaluation with ECG in < 10 min O2 by nasal prongs, IV access, continual ECG Sublingal NTG unless SBP<90 or HR <50 or >100 Analgesia (morphine or meperidine) Aspirin (325 mg po chewed) Lipid panel, electrolytes, magnesium, CIPs Thrombolysis or PCI if ST >1mV or LBBB (door-needle < 30 min or door-balloon < 90 min)

Thrombolytics
Mechanism of Action
Streptokinase Proactivator Activator Plasminogen tPA Reteplase Tenecteplase Plasmin

Activates plasminogen that is bound to fibrin

Fibrin

Fibrin degradation products

Thrombolytics
Mechanism of Action
Streptokinase Proactivator Activator Plasminogen tPA Reteplase Tenecteplase Plasmin

Activates plasminogen that is bound to fibrin

Fibrin

Fibrin degradation products

Thrombolytics

Absolute Contraindications

Precautions

Previous hemorrhagic stroke at any time; or other strokes within one year Known intracranial neoplasm Active internal bleeding Suspected aortic dissection

Severe uncontrolled HTN (BP>180/100mmHg) Current use of anticoagulants in therapeutic dose (INR 2-3) Recent trauma (within 2-4 weeks), including head trauma or traumatic or prolonged CPR or major surgery(<3 weeks) Noncompressible vascular punctures Recent internal bleeding (within 2-4 weeks) Active PUD H/O chronic severe HTN

Thrombolytics

Monitoring Parameters

EKG BP Sites of bleeding CBC (H/H, platelets)

Pivotal Thrombolytic Clinical Trials

GISSI-1
(1986)

GISSI-2
(1990)

ASSENT-2
(1999)

ASSENT-3
(2001)

ISIS-2
(1988)

GUSTO-I
(1993)

GUSTO-III
(1997)

GUSTO-V
(2001)

136

Advantages of Fibrinolytic Therapy

More universal access Shorter time to treatment Greater clinical trial evidence of:

reduction in infarct size improvement of LV function

Results less dependent on physician experience Lower system costs

137

Comparing outcomes