2. ACS: Definition
• A spectrum of clinical diagnoses
comprising unstable angina, Non-STEMI,
and STEMI that share similar pathological
features involving intracoronary thrombosis
4. Pathophysiology
• atherosclerosis with superimposed coronary thrombosis
• Slowly growing high-grade stenoses can progress to complete
occlusion but do not usually precipitate acute STEMI d/t collateral
circulation
• During development of plaques, abrupt transition can occur, resulting
in
• Platelet activation
• Thrombin generation
• Thrombus formation
• Blood flow occlusion leads to imbalance between supply and demand
and could lead to myocardial necrosis
• Pts with non-transmural infarction more likely to have more significan
stenosis in IRA
• Less severe stenosis with lipid-laden plaques and fragile caps more
likely to rupture and causing thrombsis and STEMI
5. Stable Angina
Pathophysiology
•Progressive
narrowing of coronary
lumen
•Stable fibrous cap
STEMI
•Minimal prior
Unstable narrowing of
coronary lumen
Angina •Acute rupture of thin
•Progressive fibrous cap
narrowing •Occlusive thrombus
•Acute worsening of formation
coronary lumen due •Acute injury pattern
to thrombus •Myocardial necrosis
formation
NSTEMI
•Acute worsening of
coronary lumen due to
thrombus formation
•Sub-occlusive/
transient coronary
thrombus with
myocardial necrosis
7. Angina
• Definition: Discomfort in the chest/ “choking,” that
characteristically comes on with exertion, relieved by rest
and/or NTG
Favors Ischemic Against
Origin Ischemic Origin
Character Constricting
Squeezing
Dull ache
Knife-like, sharp
Burning Jabs
Heaviness Pleuritic
Location Substernal
Anterior thorax
Left submammary area
Left hemithorax
Arms, shoulders
Neck, teeth,
Interscapular
Provoking Exertion Pain after completion
of exercise
Excitement
Factors Cold, meals, stress Pain with movement
8. Likelihood that signs & symptoms represent an ACS secondary to CAD
Feature High Intermediate Low
History Chest or left arm pain or Chest or left arm pain or Probable ischemic
discomfort as chief discomfort as chief symptoms in absence of
symptom reproducing prior symptom the intermediate likelihood
documented angina Age > 70 characteristics
Known history of CAD, Male gender Recent cocaine use
including MI Diabetes mellitus
Exam Transient MR, hypotension, Extracardiac vascular Chest discomfort
diaphoresis, pulmonary disease reproduced by palpation or
edema or rales respiration
EKG New or presumably new, Fixed Q waves T wave flattening or
transient ST segment Abnormal ST segments or inversion in leads with
deviation (≥0.05mV) or T T waves not documented to dominant R wave
wave inversion (≥0.2mV) be new Normal EKG
with symptoms
Cardiac Elevated cardiac TnI, TnT Normal Normal
Marker or CK-MB
Braundwald 1994 AHCPR Publication No. 94-0602
9. Chest Pain Classification
• Substernal
• Exertional
• Relieved with rest
• Interpretation
– Typical Angina: 3 criteria from above
– Atypical Angina: 2 criteria from above
– Non-Anginal Chest Pain: 1 or less criteria from
above
10. Classification of Angina
• STABLE vs UNSTABLE
• CCS Classification for STABLE Angina
– I: No symptoms, or angina with strenuous exertion
– II: Slight limitation of ordinary physical activity
• Walking more than two blocks, climbing more than
one flight of stairs brings on angina
– III: Marked limitation of ordinary physical activity
• Walking less than two blocks, climbing less than
one flight of stairs
– IV: Any physical activity brings on angina; angina at
rest
11. UA/NSTEMI
UA/NSTEMI 9/00
THREE PRINCIPAL PRESENTATIONS
Rest Angina* Angina occurring at rest and
prolonged, usually > 20 minutes
New-onset Angina New-onset angina of at least CCS
Class III severity
Increasing Angina Previously diagnosed angina that has
become distinctly more frequent,
longer in duration, or lower in
threshold (i.e., increased by > 1 CCS)
class to at least CCS Class III severity.
* Pts with NSTEMI usually present with angina at rest.
Braunwald
Braunwald
Circulation 80:410; 1989
Circulation 80:410; 1989
12. Pre-Test Likelihood of CAD
Nonanginal pain Atypical angina Typical angina
Age (y.) Men Women Men Women Men Women
30-39 4 2 34 12 76 26
40-49 13 3 51 22 87 55
50-59 20 7 65 31 93 73
60-69 27 14 72 51 94 86
Diamond and Forrester, NEJM, 1979
14. Troponin
• cTnT (33 kDa) binds to
tropomyosin to complex
molecule to thin filament
• cTnI (24kDa) inhibits
actin-myosin interactions
• cTnC binds Ca2+
• Generally not detectable
in plasma of normal
persons
15. Troponin
• TnT and TnI have different amino acid sequence in cardiac
vs. skeletal muscle
– Permits development of cardiac specific antibodies
• More sensitive and specific than CKMB
– Detects minimal amounts of cardiac necrosis (neg. CKMB)
• “minor myocardial damage/microinfarction”
– Elevated in MI (pos. CKMB)
– New guidelines suggest troponin is sufficient to dx MI
• Other situations assoc. with increased troponin:
• CHF
• ICU
• Renal failure
• CVA
• Myocarditis/other myocardial injury
16. TROPONIN I LEVELS PREDICT THE
Changes in Focus onIN UA/NSTEMI
RISK OF MORTALITY Heart Failure
Mortality at 42 Days (% of patients)
Mortality at 42 Days (% of patients) 7.5
7.5
8
8
6.0
6.0
6
6
3.7
3.7
4 3.4
3.4
4
1.7
1.7
2
2 1.0
1.0
831 174 148 134 50 67
0
0
0 to <0.4
0 to <0.4 0.4 to <1.0
0.4 to <1.0 1.0 to <2.0
1.0 to <2.0 2.0 to <5.0
2.0 to <5.0 5.0 to <9.0
5.0 to <9.0 >9.0
>9.0
Cardiac Troponin II (ng/ml)
Cardiac Troponin (ng/ml)
Risk Ratio
Risk Ratio 1.
1. 1.
1. 3.5
3.5 3.9
3.9 6.2
6.2 7.8
7.8
Antman N Engl J Med. 335:1342, 1996
Antman N Engl J Med. 335:1342, 1996
21. Management of UA/NSTEMI
• 8 medication
• Oxygen
• ASA , clopidogrel
• Anticoagulant: UFH, LMWH
• Nitrates for pain
– Nitropatch 0.4 mg/hr x 12 hours daily
– IV NTG
• Beta-blocker
– Metoprolol 25-50 mg PO BID
• + Calcium channel blocker
• ACEI for secondary prevention
• Statin
• Investigations:
– Serial cardiac enzymes
– Definitive in-hospital risk stratification.
22. Platelet Inhibitors in the ACS
• “A platelet GpIIb/IIIa receptor antagonist
should be administered, in addition to ASA
and UFH, to patients with continuing
ischemia or with other high risk features—”
• “Level of the evidence: A”
ACC/AHA Guideline Circulation 2000;102:1193-1209
23. DEATH OR MI AT 30 DAYS
18 16.7
Placebo GP IIb-IIIa Inhibitor
14.1
14
11.6
Percent of Patients
10.9
10.1 10.2
9
10
5.9
6 4.8
3.9
3.6
1.8
2
0
EPIC CAPTURE EPILOG EPISTENT PRISM-PLUS PURSUIT
ACC Slide
24. ANTIPLATELET Rx
Class I
Definite ACS with continuing
Possible ACS Likely/Definite ACS Ischemia or Other High-Risk
Features or planned PCI
Aspirin Aspirin Aspirin
+ +
Subcutaneous LMWH IV heparin
or +
IV heparin IV platelet GP IIb/IIIa antagonist
ACC Slide
25. Other Antiplatelet Agents: Clopidogrel
Primary efficacy endpoints in the CURE trial
Endpoint Clopidogrel Placebo Relative p value
risk
CV 9.3% 11.4% 0.80 <0.001
death/MI/stroke
CV 16.4% 18.8% 0.86 <0.001
death/MI/stroke/
refractory
ischemia
The CURE Investigators. N Engl J Med 2001;345: 494-502.
Role at this point in combination with 2b3a inhibitor .
unclear: a useful option in ASA allergic pt’
26. Effect of Clopidogrel in ACS: the CURE trial
Bleeding results
Endpoint Clopidogrel Placebo p value
Major bleeding 3.7% 2.7% 0.001
Life-threatening 2.1% 1.8% 0.13
bleeding
The CURE Investigators. N Engl J Med 2001;345: 494-502.
27. In Hospital Risk Stratification with
ACS: Principles
• Spectrum of risk
• Features associated with poor prognosis
(high probability of short term MI, etc.)
– EKG features: dynamic ST depression
– Cardiac markers: increased troponin
• Risk stratification refers to identifying
patients at risk
29. Exercise Stress Testing
– Positive response: horizontal 1mm ST depression and
symptoms
– High risk response:
• Deep ST depression
• Poor exercise tolerance: unable to exercise past stage 2 (<6
mins)
• Exercise induced hypotension and dysrhythmias
– Uninterpretable:
• LBBB
• Digoxin
• LVH
– Contra-indications:
• Severe Aortic stenosis
• Aortic dissection
• MI/ACS within 24 h
• PE
30. Angiography
• Gold standard
– Defines anatomy: 1VD, 2VD, 3VD, LM
– Assesses LV function
– Guides treatment: PCI, CABG or medical therapy
• Indications
– UA/post MI with ongoing pain, ST depresssion
– Hemodynamic instability
– CHF, ventricular arrhythmias
– Previous PCI, CABG
– High risk non-invasive test
– Emerging as the strategy of choice for initial evaluation of most
ACS with elevated troponins or EKG changes
• Based on FRISC II, TACTICS trials
• Strategy needs to be individualized.
32. Indications for Invasive Risk
Stratification Strategy in UA/NSTEMI
• Class I
– Recurrent ischemia at rest despite medical Rx
– Elevated troponin I or T
– New ST depression
– High risk findings on non-invasive testing
– Depressed LV function
– Hemodynamic instability
– Sustained VT
– PCI within 6 months
– Prior CABG
• In the absence of the above, either non-invasive or
invasive strategy can be followed.
ACC/AHA Guidelines for Management of UA/NSTEMI 2002
33. SUMMARY: ER Evaluation of
Patient with Chest Pain
Symptoms
Suggestive of
Cardiac Origin?
NO YES
Consider
Alternative
Diagnosis
Stable Unstable
Early Risk Stratification in ER
34. SUMMARY: Management of UA/NSTEMI
HIGH RISK INTERM. RISK LOW RISK
(12-30%)* (4-8%) (<2%)
•Prolonged CP (>20 minutes •No high risk features but >=1 •No high or
or ongoing), plus:
•EKG: of: intermediated features
•Transient ST changes •Ongoing chest pain •Chest pain, single
*30 day rate of death or MI
•Sustained ST depr. •Crescendo angina episode, exertional
•Deep T wave inv. (>5 •Borderline positive •EKG: normal or
leads) troponin I (0.4-2.0) nonspecific or
•Biochemical markers: •Previous intervention: unchanged
•Troponin/CKMB PCI or CABG
abnormal •Increased baseline risk •May include previous
•Recurrent ischemia
•AMI in last 4 weeks (DM, elderly) hx of CAD or risk
•Hemodynamic compromise factors
•ASA + heparin/LMWH •ASA + clopidogrel •ASA
•GP IIb/IIIa •UFH or LMWH •No heparin
•Early cardiac cath •Cardiac cath lab •Observe/outpt tests
35. STEMI
• WHO defn: 2 of
– characteristic chest pain
– ECG changes – ST elevation
– Biochemical changes
• ACC + ESC
– Rise and fall of biochemical marker (Tn, CK-MB) +
one of
• ischemic symptoms
• development of pathological Q waves
• ECG changes suggestive of ischemia
• Coronary angiography
36. STEMI
• More than 1 million MI’s per year in US
• Fatal in 1/3 of pts, ½ of death occurs within
1 hr of symptoms (arrhythmias)
37. Symptoms
• prolonged pain > 30 min usually
• constricting, crushing, or compressing; heaviness or
squeezing
• can be choking, burning, knife-like
• retrosternal, radiating to L>R side of chest, ulnar sides of
arms L>R, shoulder, upper extremity, jaw, neck,
interscapular region sometimes epigastric
• pain usually implies ischemia
• other sx
– nausea/vomiting more common in inferior MI
– weakness
– dizziness
– palpitation
– cold perspiration
– sense of impending doom
38. STEMI
• Pre-hospital care
– EMS
• Dispatch, first response, EMS ambulance
• AED to first responders
• Relief of pain to reduce sympathetic tone
• Rapid transfer to hospital
– Prehosp fibrinolysis
• Some evidence suggesting improved mortality
39. STEMI
• ER Management
– Early recognition
• Ischemic type chest pain
• ECG signs
– ECG monitor rhythm
– IV access
– O2
– Reperfusion strategy will depend on
• Time since symptoms
• Risk assoc with STEMI
• Risk of lytics
• Time required for PCI
41. STEMI - Acute Rx
• ASA
– Block formation of thromboxane A2 in platelets by blocking cox
– Chew 160-325 mg to allow for buccal absorption
• Pain control
– Try to decrease sympathetic activity
– Analgesics
– Nitrates
• Coronary vasodilation, decrease preload by increasing venous
capacitance
• Avoid if suspect RV infarct
– Beta blockers
• Reduce HR, decrease myocardial oxygen demand
• Reduce pain
• Reduce the need for analgesics
• Reduce infarct size
– Oxygen
42. STEMI - Reperfusion
• “Time is muscle”
• Increased mortality with delay in reperfusion
regardless of strategy
• Less time:
– Recovery of LV systolic fxn
– Improved diastolic dysfxn
– Reduced mortality
– Post ischemic contractile dysfxn can occur after
reperfusion
– Myocardial stunning
43. STEMI - Lytics
• Benefits
– Recanalize thrombotic occlusion
– Restores coronary flow
– Reduce infarct size
– Improves myocardial function
– Improves survival
– May result in microvascualr damage and
reperfusion injury
– STR strong predictor of reperfusion
44. STEMI - lytics
• GISSI first trial to demonstrate benefit of
streptokinase
• Other fibrinolytics
– Alteplase (t-PA)
• GUSTO I
– Reteplace (rtPA)
• GUSTO III (equivalence)
– Tenecteplase (TNK)
• ASSENT II (equiv with t-PA)
50. Choosing a Fibrinolytic
• Patients in whom t-PA is proven superior to SK:
– Age < 75
– Anterior MI, presenting within 4 hours
– High risk/extensive MI at other site within 4 hours
– Cardiogenic shock
– Previous SK exposure
• TNK = rtPA > tPA
– Easy administration
– Lower chance of med error
– Less non-cerebral bleeds
• Patients in whom SK appears to be equivalent to t-PA:
– Inferior, posterior or lateral MI
– MI at any site after 6 hours
– Age > 75 years
51. Bleeding complications with Lytics
• Major bleeding 0.5-2%
• Minor bleeding: 10-20 %
• Intracranial hemorrhage: 0.5-2%
• Management:
– D/C thrombolytic
– Cryoprecipitate (fibrinogen enriched)
– If heparin, give protamine sulfate
52. Indications for Primary PCI
• Class I
– Alternative to thrombolytic if performed in a timely fashion by
skilled individuals
– Patients within 36 hours of AMI, with cardiogenic shock, <75
years
• Class IIa
– Contraindication to thrombolysis
• Class IIb
– NSTEMI within 12 hours, with less than TIMI II flow in infarct
related artery
• Class III
– Elective PCI of non-IRA at time of AMI
– Beyond 12 hours of symptoms, no evidence of ischemia
– Successful thrombolysis
From ACC/AHA Guidelines, 2000
53. STEMI -PCI
• Meta analyis shows improved clinical
endpoints favoring PCI
– Factors to consider
• Time to treatment
• Risk of STEMI
• Cardiogenic shock
• Kilip class >= II
• Risk of bleeding
• Time to transport to skilled PCI center
54. STEMI – Other Rx
• ASA
– ISIS-2
• Thienpyridines
– Clopidogrel
• CLARITY
– Ticlopidine
• Inhibit binding to adenosine diphosphate receptor
• GPIIb/IIIa inhibitors
– Abciximab
– Tirofiban
– Eptifibatide
• GUSTO V
– rtPA vs 1/2rtPA and abciximab
– similar efficace endpoints but increased bleeds with IIb/IIIa
64. Discharge Planning
• usually 5 days post STEMI
• counseling
– ambulation but avoid heavy lifting
– graded activity (symptom limited)
– Rehabilitation
Here the slide set introduces the evidence that the GpIIb/IIIa anti-platelet drugs are highly effective in minimizing those adverse outcomes for what are referred to as well defined outcomes, mortality or MI. They show the consistent studies of various drugs. Notably, they omit GUSTO IV, presumably because they consider it an outlier that is not valid. The slide clearly makes the case that the use of these drugs is highly effective.
This slide emphasizes that aspirin should be given liberally, but, one should reserve the use of Gpii//IIIa drugs for definitie ACS. Therein lies a tale! Troponin positivity, in the appropriate chest pain patient, is what makes the diagnosis “definite.” This is the essence of the newly revised definition of MI from the joint U.S. and European societies. As you can see, troponin is central to the decision to treat although this slide makes that an indirect connection.
