1. Acute Coronary Syndrome #2
July 26, 2013

2. Class of Recommendation
Level of Evidence A
Class I: Benefit >>> Risk
Class IIa: Benefit >> Risk
Class IIb: Benefit ≥ Risk
Class III: Risk ≥ Benefit
Data from randomized clinical trials or meta-analysis
Procedure or treatment should be performed B
It is reasonable to perform procedure or treatment
Data from single randomized trial or nonrandomized studies
It is reasonable to consider procedure or treatment C
Consensus of opinion of experts, case studies or standard of care
Procedure or treatment should not be performed

3. Percutaneous Coronary Intervention (PCI)
Facilitated PCI: Strategy of full or half dose fibrinolytic therapy with or without IIb/IIIa receptor antagonist with immediate transfer or planned PCI within 90 to 120 minutes.
Rescue PCI: Transfer for PCI of patients who failed reperfusion with fibrinolytic therapy.
2013 ACCF/AHA Guideline for STEMI, JACC 2013:61:

4. Fibrinolysis Primary PCI
Coronary Angioplasty VS Fibrinolytic Therapy in Acute Myocardial Infarction
Fibrinolysis
Door-to-Needle or FMC to Needle
< 30 mins
Not PCI
capable
EMS Transport
PCI
capable
Primary PCI
Door-to-Balloon or FMC to Balloon ≤ 90 mins

5. Door-to-Balloon or FMC to Balloon ≤ 120 mins
Coronary Angioplasty VS Fibrinolytic Therapy in Acute Myocardial Infarction
DIDO
30 mins
Not PCI
capable
EMS Transport
2013 STEMI Guideline
PCI
capable
PCI
Door-to-Balloon or FMC to Balloon ≤ 120 mins

6. PCI + Thrombolytic Therapy
IIa
IIb
III
2007 ACC/AHA STEMI Guideline B
A planned strategy using full dose fibrinolytic therapy followed by immediate PCI is not recommended and may be harmful.

7. Use of IIb/IIIa antagonists in STEMI
Abciximab (Reopro)
Eptifibatide (Integrilin)
Tirofiban (Aggrastat)

8. IIb/IIIa Antagonists in STEMI
2009 ACC/AHA STEMI Guideline
Facilitated PCI B
The usefulness of IIb/IIIa receptor antagonists (as part of a preparatory pharmacologic strategy for STEMI patients prior to arrival in cardiac catheterization lab for angiography and PCI) is uncertain.

9. Use of Thienopyridines in STEMI
Also called P2Y12 receptor inhibitors
Clopidogrel (Plavix)
Prasugrel (Effient)
Ticagrelor (Brilinta)

10. Use of Thienopyridines in STEMI
IIa
IIb
III C
Clopidogrel during PCI
2007 STEMI guidelines 600 mg loading dose
2009 STEMI guidelines at least 300 to 600 mg
Prasugrel during PCI
2009 STEMI guidelines 60 mg loading dose
Ticagrelor during PCI 180 mg loading dose once followed by 90 mg bid. ASA 325 mg then <100 mg maintenance dose

11. Use of Thienopyridines in STEMI
IIa
IIb
III C
Clopidogrel with fibrinolytic therapy
2013 STEMI guidelines
≤ 75 y = 300 mg loading dose
> 75 y = no loading dose

12. IIb/IIIa Antagonists in STEMI
LOE: I
IIa
IIb
III
A: Abciximab
2007 ACC/AHA STEMI Guideline AB
B: Tirofiban
Integrilin
It is reasonable to start treatment with IIb/IIIa receptor antagonist at the time of primary PCI (with or without stenting) in selected patients with STEMI.

13. MKSAP Item #82
A 55 year old man is evaluated for a 2-month history of dyspnea on exertion without chest pain. Medical history is significant for type 2 diabetes mellitus, hypertension and hyperlipidemia. Medications are metformin, lisinopril, pravastatin and aspirin.
On physical exam, BP is 110/75 mm Hg and pulse rate is 60/min. BMI is 35. Jugular venous distention is noted, and trace lower extremity edema is present.

14. MKSAP Item #82
The point of maximal impulse is normal. Cardiac exam reveals a regular rate and rhythm and the chest is clear to auscultation.
Laboratory studies show a serum B-type naturetic peptide level of 110 pg/mL.
The EKG is shown. Echocardiogram shows inferior wall hypokinesis and ejection fraction of 35%.

15. MKSAP Item #82

16. MKSAP Item #82
Which of the following is the most appropriate diagnostic test to perform next?
Adenosine thallium stress test
Cardiac magnetic resonance imaging
Cardiopulmonary exercise test
Coronary angiography

17. MKSAP Item #64
A 64-year old woman is evaluated in the ED for chest pain and SOB. The chest pain began earlier in the day after she received news that her younger sister had died in a motor vehicle accident. She reports no similar episodes of chest pain before today. She takes no meds.
On PE, temperature is C, BP is 150/80 mm Hg, pulse rate is 90/min, and respiration rate is 11/min. BMI is 24. A normal carotid upstroke without carotid bruits is noted, jugular venous pulsations are normal, and normal S1 and S2 are heard without murmurs.

18. MKSAP Item #64 Serum troponin level is 1.4 ng/mL.
EKG displays sinus rhythm at 90/min, 1-mm ST elevation in leads V1 through V4, and no Q waves. Echo shows reduced wall motion of the anterior and apical portion of the heart, hyperdynamic wall motion of the basal segments, no significant valvular disease, and no pericardial effusion. She undergoes emergent coronary angiography, which shows normal coronary arteries. Ventriculography shows no movement of the apical portion of the heart and hyperdynamic wall motion of the basal segments of the heart.

19. MKSAP Item #64 Which of the following is the most likely diagnosis?
Non-ST elevation MI
Pericarditis
ST elevation MI
Stress cardiomyopathy

20. Item 68
A 56-year old man is admitted to the hospital with new onset substernal chest pressure. Medical history is remarkable for hyperlipidemia. He is a cigarette smoker. His medications are aspirin and atorvastatin; upon admission to the hospital, he began receiving metoprolol, clopidogrel and IV heparin.
On PE, the patient is afebrile, BP is 132/78 mm HG, pulse rate is 82/min and regular, and respiration rate is 14/min. No jugular venous distention is note, the lungs are clear to auscultation, no murmur or gallop is heard and no peripheral edema is noted.

21. Item 68 (con’t)
On admission, cardiac troponin I level was 1.2 ng/mL; on hospital day 2, it peaks at 8.4 ng/mL. ECG on arrival to the ED demonstrated nonspecific ST-T wave abnormality, but no ST segment elevation or depression. Cardiac catheterization demonstrates overall preserved LV systolic function with diffuse severe disease of the distal portion of all three major epicardial vessels. No catheterization based intervention is performed.

22. Item 68 (con’t)
Which of the following is the most appropriate management of this patient’s clopidogrel therapy?
Stop clopidogrel
Continue clopidogrel for 2 weeks
Continue clopidogrel therapy for 1 year
Continue clopidogrel therapy lifelong.

23. Hospitalizations in the US due to ACS
Acute Coronary Syndromes
1.57 Million Hospital Admissions
79%
21%
UA/NSTEMI
STEMI
Approximately 2.3 million Americans will present to the emergency department with chest pain due to acute coronary syndrome.[1] Of these patients, twice as many (1.43 million) will be admitted and diagnosed with unstable angina (UA) or non–ST-segment elevation myocardial infarction (NSTEMI; also known as non–Q-wave MI) compared with 829,000 patients who will be diagnosed with ST-segment elevation MI (STEMI; also known as Q-wave MI).[1]
According to the American Heart Association, 1.1 million new or recurrent coronary attacks (defined as MI or coronary heart disease) will occur this year.[2] Of these cases, 650,000 will be first cases and 450,000 will be recurrent cases. Additionally, about 150,000 new cases of UA will be diagnosed.[2]
National Center for Health Statistics National Hospital Discharge Survey: Annual Summary with Detailed Diagnosis and Procedure Data. Hyattsville, Maryland: US Dept of Health and Human Services; 2001: Series 13, No. 151.
American Heart Association Heart and Stroke Statistical Update
0.33 million admissions
1.24 million admissions
0.57 million NSTEMI
0.67 million UA
Heart Disease and Stroke Statistics 2007 Update
Circulation 2007;115:69-171
ACC/AHA 2009 Joint STEMI/PCI Guidelines Focused Update 23

24. Atherosclerotic plaque
Acute Coronary Syndromes
Pathophysiology
Large Fissure
Small Fissure
Mural thrombus (unstable angina/ non-ST elevation MI)
Occlusive thrombus (ST Elevation MI)
Thrombus
Lipid Pool
Macrophages
Stress, tensile, internal
Shear forces, external
Atherosclerotic plaque
Fissure
Plaque rupture
Fuster V et al. NEJM. 1992; 326:
Davies MJ et al. Circulation. 1990; 82 (Suppl II): II-38, II-46.

25. Non-ST elevation - coronary artery is not completely occluded
Myocardial Ischemia
Blood Supply
Oxygen Demand
TIMI 1 or 2 Flow
Heart Rate
Blood Pressure
Inotropicity
Non-ST elevation - coronary artery is not completely occluded

26. Mortality Rates According to Level of Cardiac Troponin
Troponin Levels Predict Risk of Mortality in ACS at 42 days in TIMI III B 8
7.5 7
6.0 6 5
Mortality at 42 days (Percentage of Patients) 4
3.7
3.4 3 2
1.7
1.0 1
831
174
148
134 50 67
0-0.4
0.4-<1.0
1.0 -<2.0
2.0 -<5.0
5.0 -<9
>9.0
Cardiac Troponin (ng/ml)
Circulation 2011;123:e451
NEJM 1996;335:1342-9

27. Non-ST Elevation MI/Unstable Angina

28. Non-ST Elevation MI/Unstable Angina

29. Diagnostic and Therapeutic Pathways in Patients With and Without Persistent ST-Segment Elevation
Acute Coronary Syndrome
ECG
Persistent ST-segment elevation
ACS, No ST-segment elevation
Thrombolysis, PCI
Aspirin, clopidogrel, UFH or LMWH,
b-blockers, nitrates
Hamm CW et al. Lancet. 2001;358:
2002 ACC/AHA UA/NSTEMI Guideline Update. Available at:

30. Myocardial Ischemia
Blood Supply
Oxygen Demand
TIMI 1 or 2 Flow
Heart Rate
Blood Pressure
Inotropicity
Non-ST elevation ACS indicates that there is coronary blood flow, but not adequate to supply enough oxygen to the myocardium

31. Coronary angiography only if Continuing ischemia or (+) Stress test
Diagnostic and Therapeutic Pathways in Patients With non-ST Segment Elevation
UA/NSTEMI
ASA/Clopidogrel/Heparin
Nitrates/Beta blockers
Conservative Therapy
Aggressive Therapy
Low risk
High risk
Medical Therapy Only Stress Test
Coronary angiography within hours
Coronary angiography only if
Continuing ischemia or (+) Stress test
2007 ACC/AHA Guidelines for the Management of Patients with Unstable angina/NSTEMI.

32. NSTEMI/Unstable Angina
High Risk Markers (Invasive Strategy)
Elevated troponins
Recurrent angina/ischemia at rest or with low level activities
New or presumably new ST segment depression
Recurrent angina/ischemia with CHF, S3 gallop, rales, MR
High risk findings on noninvasive stress testing
Depressed LVF (EF <0.40)
Hemodynamic instability
Sustained VT
PCI within 6 months
Prior CABG
High GRACE or TIMI Risk Score
Low Risk (Conservative Strategy)
2011 ACCF/AHA UA/Non-STEMI Guidelines. Circulation 2011;123 e458

33. TIMI Risk Score NSTEMI/Unstable Angina
7 Variables (One Point Each)
Age 65 years or older
At least 3 risk factors for CAD
Prior coronary stenosis of 50% or more
ST segment deviation on ECG presentation
At least 2 anginal events in prior 24 hours
Use of aspirin in prior 7 days
Elevated serum cardiac biomarkers
JAMA 2000;284:

34. TIMI Risk Score TIMI Risk Score JAMA 2000;284:835-842
All Cause Mortality, New or Recurrent MI or Severe Recurrent Ischemia Requiring Urgent Revascularization Through 14 days after Randomization (%)
TIMI Risk Score
0-1
4.7% 2
8.3% 3
13.2% 4
19.9% 5
26.2%
6-7
40.9%
JAMA 2000;284:

35. GRACE Prediction Score Card
Medical History
Age in years (0-100 points)
History of congestive heart failure (24 points)
History of myocardial infarction (12 points)
Findings at initial hospital presentation
Resting heart rate (0-43 points)
Systolic blood pressure (0-24 points)
ST depression (11 points)
Findings during hospitalization
Initial serum creatinine (1 to 20 points)
Elevated cardiac enzymes (15 points)
No in-hospital percutaneous coronary intervention (14 points)
JAMA 2004:291;

36. Medical History Age in years Points History of CHF 24 History of MI 12
≤29
30-39
40-49 18
50-59 36
60-69 55
70-75 73
80-89 91
≥90
100
JAMA 2004:291;

37. Findings at Initial Hospital Presentation
4. Resting HR BPM Points
≤49.9 3 9 14 23 35
≥200 43
5. Systolic BP (mm Hg)
≤79.9 43 22 18 14 10 4
≥200 4
6. ST Segment Depression

38. Findings During Hospitalization
7. Initial Serum Creatinine Points
0-0.39 1 3 5 7 9 15 ≥4 20
8. Elevated Cardiac Enzyme
9. No In-hospital PCI
JAMA 2004:291;

39. GRACE Prediction Score Card
Points
JAMA 2004:291;
1. _______
0.50
2. _______
3. _______
0.40
4. _______
5. _______
0.30
Mortality Risk
Probability (All Cause Mortality 6 Mos)
6. _______
0.20
7. _______
8. _______
0.10
9. _______
Total Score _____ 70 90
110
130
150
170
190
210
Mortality Risk from Plot __________
Total Risk Score = No. of Points

40. NSTEMI/Unstable Angina
High Risk Markers (Invasive Strategy)
Elevated troponins
Recurrent angina/ischemia at rest or with low level activities
New or presumably new ST segment depression
Recurrent angina/ischemia with CHF, S3 gallop, rales, MR
High risk findings on noninvasive stress testing
Depressed LVF (EF <0.40)
Hemodynamic instability
Sustained VT
PCI within 6 months
Prior CABG
High GRACE or TIMI Risk Score
Low Risk (Conservative Strategy)
2011 ACCF/AHA UA/Non-STEMI Guidelines. Circulation 2011;123 e458

41. STRIVE TM

42. Invasive Strategy for UA/NSTEMI
ASA (If ASA intolerant Clopidogrel)
Invasive Strategy
Anticoagulant therapy (Enoxaparin or UFH Bivaluridin or Fondaparinux)
Prior to Angiography
Initiate one or both of the following
Clopidogrel /IV IIb/IIIa inhibitor
Give both if there is Delay to Angiography, High Risk Features, Early recurrent ischemic discomfort

43. Conservative Strategy for UA/NSTEMI
ASA (If ASA intolerant Clopidogrel)
Conservative Strategy
Anticoagulant therapy (Enoxaparin or UFH or Fondaparinux but enoxaparin and fondaparinus are preferable)
Initiate Clopidogrel
Consider adding IV eptifibatide or tirofiban
Continue ASA indefinitely Continue clopidogrel >1 year D/C IIb/IIIA if started D/C anticoagulant therapy
May need angio if LVEF <40%, Stress test or there is Ischemia (Induced or Spontaneous)

44. Acute Coronary Syndrome Non-ST Segment Elevation
Aspirin
Clopidogrel
Heparin
2B/3A Antagonists
Nitrates/Oxygen/Morphine
Beta Blockers
ACE Inhibitors/ARB’s
Statins
Aldosterone antagonist (EF <40%)

45. Medication/Intervention STEMI
Non-STEMI/ Unstable Angina
Medication/Intervention
STEMI
Aspirin
Yes
Yes
Clopidogrel
Yes
Yes
Heparin
Yes
Yes
10 PCI – No
tPa (thrombolytic agent) No
No PCI – Yes
PCI – Yes
10 PCI – Yes
IIb/IIIa antagonists
No PCI – High Risk only -Yes
No PCI – No
Beta Blockers
Yes
Yes
ACE Inhibitors/ARB
Yes
Yes
LV Dysfunction
Aldosterone Antagonists
Yes
Yes
Statins
Yes
Yes