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Acute Coronary Syndrome (ACS)
“UAP, Acute Non-STEMI, STEMI”
Dr. Ilham Uddin, Sp JP (K), FIHA, FAsCC
Kariadi Hospital / RSND Hospital /
Diponegoro University
Semarang 02-2017
Coronary Heart Disease
• Anatomy Coroner
• Atherosclerosis
• Basic Physiology / Determinants of MVO2
• Autoregulatory Mechanisms / Coronary Flow
Reserve
• Pathophysiology of Coronary Ischemia
• Clinical Syndromes
– Stable Angina
– Acute Coronary Syndromes
• Unstable Angina
• Acute MI (UA, AMI)
Coronary Arteries Anatomy
Coronary arteries--anatomy
Coronary Heart Disease (CHD)
atherosclerosis
3
Atherosclerosis Time-line
Complicated
Foam Fatty Intermediate Fibrous Lesion/
Cells Streak Lesion Atheroma Plaque Rupture
Endothelial Dysfunction
From First From Third From Fourth
Decade Decade Decade
Silent ischemia
Clinical Presentations 2
Effect of Fixed Stenosis on Myocardial Blood Flow
6
Progression of coronary plaque over time Clinical Findings
Acute silent
Angina occlusive
pectoris process
Endothelial dysfunction
Atherogenic Thrombogenic
risk factors risk factors
Age
20 years 60 years 7
IHD – Clinical Spectrum
Chronic
Stable Angina
Silent Ischemia
Mixed Angina
Microvascular Angina
(Syndrome X)
Stunned & Hibernating
Acute
Unstable Angina
Acute Myocardial
Infarction (NSTEMI,
STEMI)
Sudden Cardiac Death
Prinzmetal Angina
8
Stable Angina Pectoris
(SAP)
Clinical Classification of Chest Pain
Typical angina (define) Canadian Cardiovascular Society
1.Substernal chest discomfort with a characteristic Classification ( CCSC)
quality and duration that is Class Activity Limits to
2.Provoked by exertion or emotional stress and evoking normal
3.Relieved by rest or nitroglycerin angina activity
Pxr
Wall Stress =
2h
4
Stable angina pectoris
(SAP)
definition:
acute and transient myocardial ischemia
and anoxaemia
usually caused by coronary insufficiency
during exertion
(SAP)
SAP Symptoms
• mid-substernal chest pain
• squeezing, pressure-like in quality (closed fist =
Levine’s sign)
• builds to a peak and lasts 2-20 minutes
• radiation to left arm, neck, jaw or back
• associated with shortness of breath, sweating, or
nausea
• exacerbated by exertion, cold, meals or stress
• relieved by rest, NTG
Stable angina pectoris
(SAP)
Pathology
in angiography
Significant coronary lesion with
diameter stenosis > 70% in 75% pts
• Metabolic abnormalities
- Lipids
• LDL< 100 mg/dl is optimal
- Esp for patients with multiple risk factors,
DM and established CAD
• HDL<40 mg/dl is an independent risk factor
• TG’s > 200 mg/dl should be treated (lifestyle)
- Glucose
• Impaired fasting glucose= 110-126 mg/dl
• DM = FBS > 126 mg/dl
- Others
– presence increase the risk of future CV events
– no consensus on routine measurement
-C-reactive protein; homocysteine; lipoprotein Lp(a)
What about non-invasive test?
(SAP)
• ECG
- Resting ECG is normal in 50% patients
with stable angina
- Most common abnormality with chronic
CAD is non-specific ST-T wave changes
- Non specific changes also seen in
electrolyte abnormalities, LVH,
antiarrhythmic drugs
CHD----Diagnosis
(SAP)
Myocardial Coronary
ischemia stenosis
ST segment depression
Normal coronary
Normal
flow
Normal ST segment
Myocardial
infarction Coronary
occlusions
ST segment elevation
Stable Angina - Diagnosis (SAP)
Cardiac Echo
(SAP)
Soft or
‘Vulnerable’
Plaque
Imaging by
64 slice MSCT
(SAP)
1. General consideration:
rest,avoid provocative factors , risk factors
control
2. Drug therapy:
prevent MI and death
symptom relief and quality of life improvment
3. Coronary revascularization:
percutaneous coronary intervention (PCI)
Coronary artery bypass surgery (CABG)
SVG, LIMA
(SAP)
Stable angina pectoris
Drug therapy
antianginal and anti-ischemic therapy
Oxygen Oxygen
supply demand
a.nitrates
b.beta-adrenergic blockers
c.Calcium antagonists
d.Drugs improving metabolism
Drug therapy (SAP)
a.nitrates
•Nitroglycerin
•Isosorbide dinitrate 5 mg, 10 mg
•isosorbide 5-mononitrate (long-acting nitrates)
b. ß-blockers:
ß1-selective:metoprolol 50 mg, atenolol 50 mg,
bisoprolol 5 mg
c.Calcium antagonists:
Mis: Diltiazem, Verapamil
d. Drugs improving metabolism:
trimethazidine,selectively inhibit 3-KAT(),partly
inhibit FA oxidation,
Drug therapy (SAP)
a.antiplatelet angents:
ASA,75-325mg/d
clopidogrel; ticlopidine: ADP receptor- antagonists:
Cilostazol: phosphodiesterase inhititor,50-100mg bid
Stent
(ring?)
(SAP)
Acute Coronary Syndromes
(ACS)
Atherothrombosis: A Generalized and
Progressive Process
Thrombosis
Unstable
angina ACS
MI
Ischemic
stroke/TIA
Critical leg
Atherosclerosis ischemia
Intermitent
claudication
CV death
Stable angina/
Intermittent claudication
Adapted from Libby P. Circulation. 2001;104:365-372.
Spectrum of Chronic Coronary Syndrome
Risk Factors + Hypertension
Endothelial Dysfunction
Atherosclerosis
IHD/Angina Pectoris
Remodeling
Ventricular Dilation
Congestive Heart Failure
Dr.Sarma@works
Pathophysiology of ACS
Characteristics of Unstable and
Stable Plaque
Much
Less smooth inflammatory Much smooth Less
muscle cells cells muscle cells inflammatory
Thin fibrous Thick cells
cap fibrous cap
Eroded Integrated
endothelium endothelium
Active Foam cells
macrophage
Plaque
Rupture
Fuster V, et al. N Engl J Med. 1992;326:310-318.
Falk E, et al. Circulation. 1995:92:657-671.
Atherothrombosis: Thrombus Superimposed
on Atherosclerotic Plaque
PRIMARY
AGGREGATION
Fibrin
SECONDARY
COAGULATION Thrombin
Adapted from Ferguson JJ, et al. Antiplatelet Therapy in Clinical Practice. 2000:15-35.
Platelets Role in Thrombosis
1. Platelet Adhesion
Platelet
GP Ib 2. Platelet Activation
GP IIb/IIIa Inhibitors
Antithrombotic Thrombolysis
Therapy Primary PCI
ST-segment ST-segment
ECG Normal Depression Elevation
Markers – + – + +
Diagnosis Unstable
Rule-Out Acute MI
Angina
Anderson JL. J Am Coll Cardiol 2007;50:e1-157
Stable Unstable Non ST ST Elevation
Angina Angina Elevation MI MI
ECG – ST ↑
ECG - ST ↓
CK-MB
Troponin
CRP/BNP
.
Dynamic MVO2
Obstruction
Inflammation/
Infection
Mechanical
Thrombosis
Obstruction
.
Dynamic MVO2
Obstruction
Braunwald, Circulation Inflammation/
98:2219, 1998 Infection
Dr.Sarma@works
Unstable Angina Pectoris (UAP)
NSTEMI STEMI
Anginal •Rest angina - Rest or nocturnal Prolonged ( > 30 min )
Presentatio Angina ≥ 20 minutes occurring
ns within a week of presentation. crushing, strangling
•New onset angina - ( < 2 months chest pain more severe
) exertional angina progressing to and wider radiation
CCSA III
•Crescendo angina - < 2 moths
than usual angina
acceleration of previously stable
angina to at least CCSA III.
•Within 30 day post MI, PCI or
CABG
EKC initial Dynamic, transiet < 24 hours ST depression ST elevation (
findings T-wave inversion and/or ST seg and/pr T Wave and Q waves
depression inversion later)
NO YES
Neg: nonischemic
discomfort;low-risk UA/NSTEMI + UA/NSTEMI confirmed ADMIT
Outpatient follow-up
Dr.Sarma@works
Early Treatment: Class I Indications
Bedrest/chair with continuous ECG Monitoring
O2 therapy with saturation <90%, respiratory distress, or
other high-risk features for hypoxemia
SL NTG 0.4 mg q5min x3 then assessment of need for IV NTG
IV NTG indicated first 48 hours for treatment of persistent
ischemia, CHF or HTN; should not preclude tx with beta-
blockers or ACE
Oral Beta-Blocker in first 24 hours for pt who do not have
Signs of CHF
Low out-put state
Increased risk of cardiogenic shock
Contraindication to Beta blockers/heart block/COPD
If Beta-Blockers are contraindicated a nondihydropyridine
calcium channel blocker may be used if no LV dysfunction
Wright RS et al. Circ 2011;123;2022-2060.
ACC/AHA Guidelines
ACS Treatment Overview: UA/NSTEMI
Evaluation of LV
Function in pt Long-term medical management:
Clopidogrel, aspirin, β-blocker, ACEI,
with ischemia
statin
aIf possible, clopidogrel should be withheld for 5-7 days prior to the procedure.
Anderson JL, et al. Circulation. 2007;116:803-877.
Selection of Initial Treatment
1. Circulation 1994;89:81-88
Dr.Sarma@works 2. JAMA 1996;276:811-815
Unstable Angina
Anti-coagulant Therapy
• Low-molecular-weight heparin: Enoxaparine,
Fondaparinux
advantages over heparin:
– better bio-availability
– higher ratio (3:1) of anti-Xa to anti-IIa
activity
– longer anti-Xa activity, avoid rebound
– induces less platelet activation
– ease of use (subcutaneous - qd or bid)
– no need for monitoring
Dr.Sarma@works
STEMI (Myocardial Infarction)
Chest Pain Assessment
• ECG most important single source of
data .
• ECG findings in patients with acute
chest pain
- New ST-segment elevation of >=1 mm
• Probability of MI = 80%
- ST-segment depression or T-wave inversion no
know to be old
• Sensitivity = 90%; Specificity = 80%
Diagnosis of STEMI
History
• Tachycardia or bradycardia
• Extrasystoles
• S3 or S4, mitral regurgitation
murmur
• Lung rales
• Hypertension or hypotension
• Pallor, distress
Acute MI
Typical rise and gradual
fall (troponin) or more
rapid rise and fall of CK-
MB, markers of
myocardial necrosis,
with at least one of the
following:
•Ischemic symptoms
•EKG changes indicative
of ischemia (ST-seg
elevation or depression)
16
Cardiac Biomarkers “enzymes”
• Enzymes (cardiac biomarkers) diffuse into
the cardiac interstitium after MI and
become detectable in the blood within
hours.
• CK-MB detectable 4 hours after MI and up
to about 2 days
- Some CK-MB detectable in healthy patients
ST-seg ∆
Zone of ischemia
Path. Q waves
Zone of injury
Zone of necrosis
>0.03 seconds
Lateral
Septal Anterior >1/3 the total of
QRS
17
Inferior
Diagnosis of Acute MI : ECG
Defines location, extent, and prognosis of
infarction
• ST elevation diagnostic of coronary
occlusion
• Q-waves do NOT signify completed infarction
• ST depression or T inversion: unlikely total
coronary occlusion
• ST elevation in RV4 for RV infarction
• Observe up to 24 hrs for non-diagnostic ECG
• Differentiate from early repolarization in V1-2
18
19
20
If the clinical picture is consistent with acute STEMI
(including True Posterior MI) or new left bundle branch block
(LBBB) is present in EKG,
select and implement reperfusion therapy, Fibrinolysis or
PCI as quickly as possible within 12 hours of symptoms
onset to obtain and sustain optimal flow in the infarct-
related artery (IRA).
Do not wait for serum cardiac biomarkers result before
implementing reperfusion strategy !
22
“ Time is muscle”
myocardium
Mild injured
severe
impairment
Management: onset of STEMI
CHD –Sudden death (arrhythmia)
Ventriclar Tachycardia
Ventricular flutter
Ventricular fibrillation
Initial Management in ED
• Initial evaluation with 12-lead ECG in < 10 minutes
– targeted history (for AMI inclusion, thrombolysis
exclusion)
– vital signs, focused examination
• Continual ECG, automated BP, HR monitoring
• IV access
• Draw blood for serum cardiac markers, electrolytes,
magnesium, hematology, lipid profile panel
Dr.Sarma@works
Initial Management in ED
• Aspirin165-325 mg (chew and swallow)
• Sublingual NTG unless SBP <90 or HR <50 or >100:
test for prinzmetal’s angina, reversible spasm, anti-
ischemic, antihypertensive effects
• O2 by nasal prolongs, first 2-3 h in all; continue if PaO2
<90%
• Analgesia: small doses of morphine (2-4 mg) as needed
• Fibrinolysis or PCI if ST elevation > 1mV or LBBB
(Goal: door-needle < 30 min or door-dilatation < 60-90
min)
Dr.Sarma@works
Management of Patients with ST
Elevation
ST elevation
Aspirin
Beta-blocker
12 h > 12 h
No Yes
Primary
Fibrinolytic therapy
PTCA or CABG
Other medical therapy: Consider
ACE inhibitors Reperfusion
? Nitrates Therapy
Anticoagulants
Dr.Sarma@works Modified from Antman EM. Atlas of Heart Disease, VIII; 1996
Comparison of Fibrinolytic Agents
Streptokinase Anistreplase Alteplase
Reteplase
Absolute Contraindications:
• Previous hemorrhagic stroke at any time: other strokes or
cerebrovascular events within one year
• Known intracranial neoplasm
• Active internal bleeding (does not include menses)
• Suspect aortic dissection
Dr.Sarma@works
ContraindicatIons and Cautions for
Fibrinolytic Used in STEMI
Cautions / Relative Contraindications
• Severe uncontrolled HTN on • Noncompressible vascular
presentation (BP >180/110 punctures
mmHg) • Recent (within 2-4 weeks)
• History of prior CVA or known internal bleeding
intra-cerebral pathology not • For streptokinase/anistreplase:
covered in contraindications prior exposure (especially
• Current use of anticoagulants in within 5d-2 yrs) or prior allergic
therapeutic doses (INR 2-3); reaction
no bleeding diathesis • Pregnancy
• Recent trauma (within 2-4 • Active peptic ulcer
weeks) including head trauma • History of chronic hypertension
Dr.Sarma@works
Primary Percutaneous
Coronary Intervention (PCI) Recommendations
Class I Recommendations
1. As an alternative to fibrinolytic therapy if:
– ST segment elevation or new or presumed new LBBB
– Within 12 hrs of symptoms or > 12 hrs of persistent pain
– In a timely fashion (90 30 min)
– By experienced operators
– In appropriate environment
2. In cardiogenic shock patients < 75 yrs or within 36 hrs of AMI and
revascularization can be performed within 18 hrs of onset of shock
Class IIa Recommendations
1. As reperfusion strategy in candidates for reperfusion who have
contraindications to fibrinolytic therapy
Dr.Sarma@works
Primary Percutaneous
Coronary Intervention (PCI) Recommendations
Class IIb Recommendations
1. In patients with AMI who do not present with ST elevation but who
have reduced (< TIMI grade 2) flow of the infarct-related artery and
when angioplasty can be performed within 12 hrs of onset of
symptoms
Class III Recommendations
1. This classification applies to patients with AMI who:
• undergo elective angioplasty in the non-infarct-related artery at the time of
AMI
• are beyound 12 hrs after the onset of symptoms and have no evidence of
myocardial ischemia
• have received fibrinolytic therapy and have no symptoms of myocardial
ischemia
• are fibrinolytic-eligible and are undergoing primary angioplasty by and
Dr.Sarma@works
unskilled operator in a laboratory that does not have surgical capability
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
Dr.Sarma@works
Primary PCI of STEMI
Primary PCI of STEMI
Advantages of Primary PTCA
• Higher initial reperfusion rates
• Lower recurrence rates of ischemia / infarction
• Less residual stenosis
• Less intracranial bleeding
• Defines coronary anatomy and LV function
• Utility when fibrinolysis contraindicated
Dr.Sarma@works
Pharmacologic Management of Patients with
MI
Heparin Recommendations
Class I Recommendations
1. In patients undergoing percutaneous or surgical revascularization
Class IIa Recommendations
1. Intravenously in patients undergoing reperfusion therapy with
alteplase/reteplase (note change in recommendations)
1999 1996
Bolus Dose 60 U/kg 70 U/kg
Maintenance ~12 U/kg/hr ~15 U/kg/hr
Maximum 4000 U bolus None
1000 U/h if >70kg
aPTT 1.5-2.0 x control 1.5-2.0 x control
(50-70 sec) for 48 hrs (50-70 sec) for 48
hrs
Dr.Sarma@works
Pharmacologic Management of Patients with
MI
Heparin Recommendations
Class IIa Recommendations (continued)
2. Intravenous unfractionated heparin (UFH) or low molecular weight
heparin (LMWH) subcutaneously for patients with non-ST elevation
MI
3. Subcutaneous UFH (eg, 7,500 U b.I.d.) or low molecular weight
heparin (eg, enoxaparin 1 mg/kg b.I.d.) in all patients not treated with
fibrinolytic therapy who do not have a contraindication to heparin. In
patients who are at high risk for systemic emboli (large or anterior MI,
AF, previous embolus, or known LV thrombus), intravenous heparin is
prefered
4. Intravenously in patients treated with nonselective fibrinolytic agents
(streptokinase, anistrplase, urokinase) who are at high risk for systemic
emboli (large or anterior MI, AF, previous embolus, or known LV
thrombus)
Dr.Sarma@works
MI Management in 1st 24 Hours
• Limited activity for 12 hours, monitor 24 hours
• No prophylactic antiarrhythmics
• IV heparin if: a) large anterior MI; b) PTCA; c) LV
thrombus; or d) alteplase/reteplase use (for ~48 hours)
• SQ heparin for all other MI (7,500 u b.I.d.)
• Aspirin indefinitely
• IV NTG for 24-48 hrs if no / HR or BP
• IV beta-blocker if no contraindications
• ACE inhibitor in all MI if no hypotension
Dr.Sarma@works
Therapeutics--patients with ACS
Anti-ischemic therapy
• Nitrates
- relieve pain and ischemia, given sublingually or IV acutely
• Morphine sulfate
- Relieve pain, decreases agitation and decreases preload
(decreased venous congestion)
• B- Blockers
- Decreases myocardial oxygen demand, decreases heart
rate, stabilizes membranes thereby decreasing
arrhythmia risk
Do not use short acting Calcium channel
blockers (nifedipine)
Therapeutics--patients with ACS
Antiplatelet and anticoagulant therapy
• Antiplatelets
- ASA
• Give promptly
- Clopridogel
• Give promptly
• Anticoagulants
- Heparin – LMWH or unfractionated
RE-vascularization (thrombolytics or PTCA
with stent) in patients with STEMI
Treatment Strategy for
Right Ventricular Ischemia/Infarction
• Maintain right ventricular preload
– Volume loading (IV normal saline)
– Avoid use of nitrates and diuretics
– Maintain AV synchrony (AV sequential pacing for
symptomatic high-degree heart block unresponsive to
atropine)
– Prompt cardioversion for hemodynamically significant SVT
• Inotropic support
– Dobutamine (if cardiac output fails to increase after volume
loading)
Dr.Sarma@works
Treatment Strategy for
Right Ventricular Ischemia/Infarction
• Reduced right ventricular afterload with LV dysfunction
– Intra-aortic balloon pump
– Arterial vasodilators (sodium nitroprusside, hydralazine)
– ACE inhibitors
• Reperfusion
– Fibrinolytic agents
– Primary PTCA
– CABG (in selected patients with multivessel disease)
Dr.Sarma@works
Complications of Ml
24
COMPLICATIONS OF INFARCTION
25
Ventricular Free Wall Rupture
ACS Treatment
Revascularization
Mechanical: PCI, CABG
Pharmacologic: Thrombolytics
Stabilization of Vulnerable Plaque Aspirin
Antithrombotics
Beta-Blockers
ACE-Inhibitors
Lipid-Lowering Agents (+stantins)
Antioxidants
Aggressive Risk Factors Modifications
23
Take Home Messages
Atherosclerosis is the leading cause of death and
disability, also the main cause of CHD
Risk factors and prevention of atherosclerosis
CHD is due to the imbalance between myocardial oxygen
supply and demand
Two large groups of CHD: chronic(stable angina pectoris)
and ACS
ACS composed of UAP/NSTEMI and STEMI, resulting
from the plaque rupture or erosion, with differing degree
of thrombosis and distal embolization, with different
obstruction of the coronary artery.
reperfusion either by fibrinolysis or primary PCI is the
mainstay of therapy of STEMI
Thanks!