f

2. Acute Coronary Syndromes
Dr/ Nouradden N. Al-Jaber ,Msc ,MD.
Associate prof. of Cardiology Sana,a Univ.

3. Disclosures
I have nothing to disclose.

4. ACS Overview
 Outline
 Definition
 Pathophysiology
 Risk Factors
 Clinical Features
 Assessment
 Management

5. Cost of Coronary Artery Disease (CAD )and
Cardiovascular Disease (CVD.)
• 17,600,000 Americans adults have a history of CAD.
• 8,500,000 American adults have a history of MI.
• 400,000 deaths annually (approx. 1 of every 6 deaths).
• 300,000 die from their initial ACS. event.
• 785,000 will have their initial cardiac event.
• 470,000 will have a recurrent event.
• 195,000 will have a silent cardiac event.
• Estimated direct & indirect costs for CVD.– $503.2 billion.
• Estimated direct & indirect costs for CAD.– $177.1 billion.
Historically,
Today…
AHA Heart Disease and Stroke Statistics 2010 Update. Circulation 2010;121:e41-e215.

6. Mortality from CVD and CHD
in selected countries
Rate per 100,000 population (Men aged 35–74 years)
0
500
1000
1500
Russia Finland England/
Wales
Italy Japan
CVD deaths CHD deaths
(Adapted from 1998 World Health Statistics)
Poland New
Zealand
USA Spain

7. Pathophysiology of Cardiovascular
Disease
Foam
Cells
Fatty
Streak
Intermediate
Lesion Atheroma
TCFA/Fibrous
Plaque
Lesion
Rupture
Adapted from Pepine CJ. Am J Cardiol. 1998;82(suppl 104).
Endothelial Dysfunction
Atherosclerotic Burden

8. Classifications of CVD.risk factors
*I-Exogenous OR Endogenous.
*II-Fixed (Non Modifiable )
And Modifiable.

9. Risk factors for CVD
Modifiable
– Smoking
– Dyslipidaemia
• raised LDL cholesterol
• low HDL cholesterol
• raised triglyceride
– Raised blood pressure
– Diabetes mellitus
– Obesity
– Dietary factors
– Thrombogenic factors
– Lack of exercise
– Excess alcohol consumption
Non-modifiable
– Personal history of CVD
– Family history of CVD
– Age
– Gender

10.  History of CAD/PAD
 Male Sex
 History of TIA/CVA
 Smoking
 Hypertension
 Diabetes Mellitus
 Dyslipidemia
– Low HDL < 40
– Elevated LDL / TG
 Family History - event in
first degree relative > 55
male, > 65 female
 Chronic Kidney Disease
 Obesity
 Lack of regular physical
activity
 Diet poor in fruits,
vegetables, and fiber
 Age > 45 male, > 55 female
Cardiovascular Disease Risk Factors

11. The Progression from CV Risk Factors to
Endothelial Injury and Clinical Events
Risk factors
Oxidative stress
Endothelial dysfunction
NO Local mediators Tissue ACE-Ang II
PAI-1 VCAM
ICAM cytokines
Endothelium Growth factors
matrix
Proteolysis
LDL-C BP Heart failure
Smoking
Diabetes
Vasoconstriction Vascular lesion
and remodelling
Plaque rupture
Inflammation
Thrombosis
Clinical endpoints
NO =Nitric oxide/PAI=plasminogen activator
inhibitor 1 /VCAM=vascular cell adhesion Molecule Gibbons GH, Dzau VJ. N Engl J Med 1994;330;1431-1438.

12. Clinical manifestations of atherosclerosis
 Coronary heart disease
– Angina pectoris, myocardial infarction, sudden cardiac death
 Cerebrovascular disease
– Transient ischaemic attacks, stroke
 Peripheral arterial disease
– Intermittent claudication, gangrene

13. Cardiovascular Disease
Cerebrovascular Disease (CVD)
Coronary Artery Disease (CAD)
Peripheral Artery Disease (PAD)

14. Death is inevitable but
premature death is not.
Sir Richard Doll

15. Treatments and Therapy

16. Moses Receiving The Tablets From God
ASA

17.  Antiplatelet agents
– Aspirin
– Clopidegrol .
 Lipid lowering agent
– High-dose Statin .
 Antihypertensive agent
– Beta blocker
– ACE-I/ARB
– Aldactone (as appropriate)
 Appropriate therapy for risk factors
Cardiovascular Medical Therapy

18. Cardiovascular Care

19.  Blood Pressure
– Goal < 135/85
– Maximize use of beta-blockers and ACE-I
 Lipids
– LDL < 100 (70) ; TG < 200
– Maximize use of statins; consider fibrates/niacin
first line for TG > 500; consider omega-3 fatty
acids, CoEnzyme Q10
 Diabetes
– HbA1c < 7%
Cardiovascular Care

20. Issues in Clinical Practice
Unfortunately, for healthcare providers and their
patients, most patients prefer the prescription of
pills to the proscription of harmful lifestyles.

21.  Smoking cessation
– Cessation-class, medications, counseling
 Physical activity
– Goal 30 - 60 minutes daily
– Risk assessment prior to initiation
 Diet
– DASH diet, Mediterranean diet, fiber,
omega-3 fatty acids
– <7% total calories from saturated fats
Cardiovascular Care

22. Smoking,

23. Smoking,

24. …and Smoking

26. Darwinism and Risk
of Cardiovascular Disease

27. Walking the Dog

28. Diet

29. Western Lifestyle

30. Double Cheeseburger,
Large Fries, Jumbo
Coffee.. Oh And An
Aspirin -Gotta Take
Care Of The Ticker
Y’Know.
Aspirin May
Reduce Risk Of
Heart Attack
New Yorker Magazine. 1988.

31. French Fries
How to burn* 400 calories:
Walk 2 hour 20 minutes
20 years ago Today
210 calories
2.4 ounces How many calories are
in these fries?
610 calories
6.9 ounces
Calorie difference: 400 Calories
*Based on 130-pound person.

32. High-risk for future cardiovascular disease?

33. High-risk for future cardiovascular disease?

34. Cardiovascular Diet

35. Established Risk Factors for CHD
Blood cholesterol
10%  = 20%-30%  in CHD
High blood pressure
5-6 mm Hg  = 42%  in Stroke
= 16%  in CHD
Cigarette smoking
Cessation = 50%-70%  in CHD
Body weight
BMI<25 vs BMI>27 = 35%-55%  in CHD
Physical activity
20-minute brisk walk daily = 35%-55%  in CHD

38. “We must all hang together, or
assuredly we shall all hang separately.”
– Benjamin Franklin
July 4, 1776

39. GOALS OF HEALTH CARE PROVIDERS
AND ACADEMIC RESEARCHERS
Maximize benefit and minimize risk which is not to be
confused with avoidance of risk.
Make clinical decisions based on the totality of evidence not
dependence on particular subgroups of particular studies.
Avoid misstatements of benefit to risk ratios which may
increase publicity, academic promotions and grant support
in the short run but confuse colleagues and frighten
patients and make it more difficult to conduct high quality
research
( COX-2 inhibitors and glitazones)

41. Goals of 2ry preventions among patient with
a known vascular disease.
Goals
Risk factors
140/90(130/85 if HF or RF.
Hypertension ( mmHg)
130/80 in DM)
LDL <100
Dyslipidaemia (mg/dl)
HDL >60
TG<100
30 min 3-4 x 1 week.
Physical activity.
<24.9 Kg/m2.
BMI
Near normal B.S (HbA1c<6.5%)
DM
Complete cessation.
Smoking.

42. Coronary artery Diseases (CAD ).
Ischaemic Heart Disease.(IHD ).
Coronary Heart Disease.(CHD ).

43. CAD CAUSES .
Type Comments
Atherosclerosis Most common cause. Risk factors: hypertension,
hypercholesterolemia, diabetes mellitus, smoking, family history
of atherosclerosis.
Spasm Coronary artery vasospasm can occur in any population but is
most prevalent in Japanese. Vasoconstriction appears to be
mediated by histamine, serotonin, catecholamines, and
endothelium-derived factors. Because spasm can occur at any
time, the chest pain is often not exertion-related.
Emboli Rare cause of coronary artery disease. Can occur from
vegetations in patients with endocarditis.
Congenital Congenital coronary artery abnormalities are present in 1 to 2%
of the population. However, only a small fraction of these
abnormalities cause symptomatic ischemia.
43
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:
http://www.accesspharmacy.com

44. Coronary artery Diseases.
 I- Angina pectoris (non Acute ).
 II- Acute coronary artery Disease
(syndrome ) (ACS)

45. 45
The Spectrum of
Myocardial Ischemia
Acute Coronary Syndromes
Thrombus present in the artery
Stable
Angina
Unstable
Angina
Non-ST
Elevated MI
(NSTEMI)
ST
Elevated MI
(STEMI)
Sudden
Death
Adapted from Contemporary Diagnosis and Management of Acute Coronary Syndromes, 2nd edition. Newtown, PA
Handbooks in Healthcare Co, 2008, p6.

46. Coronary artery Diseases.
 I- Angina pectoris (non Acute ).

47. Angina Pectoris
 Episode of chest pain or pressure due to
insufficient artery flow of oxygenated blood.
 Myocardial 02 demand exceeds 02 supply.
CAD is the most common cause.
 One coronary artery branch becomes
completely occluded; therefore, 02 is
not perfused to the myocardium,
resulting in transient ischemia and
subsequent retrosternal pain.

48. Angina Pectoris
Precipitating Factors: Warning Sign for MI
Clinical Signs & Symptoms:
*Do not occur until lumen is 75% narrowed.
*Sternal pain: mild to severe. May be described as heavy,
squeezing, pressing, burning, crushing or aching.
*Onset sudden or gradual.
*May radiate to L. shoulder and arm.
*Radiates less commonly to R. shoulder, neck, jaw.
*Pt may have weakness/numbness of wrist, arm, hands.
*Pain usually short duration and relieved by removal
precipitating factors,rest or NTG.
Can be gradual (CAD) or sudden(vasospasm)
Associated Symptoms:
Dyspnea, N & V, tachycardia, palpitations, fatigue,
diaphoresis, pallor, weakness, syncope, factors

49. Types of Angina
 Stable:
There is a stable pattern of onset, duration
and intensity of sx, pain is triggered by a
predictable degree of exertion or emotion.
 Variant Angina (Prinzmetal's)
Cyclical,may occur at rest.Ventricular arrhythmia,
brady arrhythmia and conduction disturbances
occur.Syncope ass.with arrhythmia may occur
 Nocturnal Angina
only at night.
Possible associated with REM sleep.
 Unstable Angina ACS.Pre infarction angina
Pain is more intense, lasts longer

50. Types of Angina
 Decubitus angina
when lying flat & improved by sitting
---bad prognosis >>> MI.
 Linked Angina
like with Gallbalder stone ,
or Hitus Hernia

51. Assesment
 1. Hx
 2. Physical Exam
 3. EKG
 4. Cardiac Enzymes.
 5. ECHO
 6. Exercise EKG
 7. Thallium Scan
 8. Coronary Angiography.

52. Perfusion
Abnormalities
Systolic Dysfunction
Δ ECG
Angina
Diastolic Dysfunction
Duration and severity of ischemia
Nuclear Imaging
Stress Echo/MRI
Stress ECG
Ischemic Cascade

53. Medications for Angina
1. Nitrates
Decrease myocardial 02 demand via
peripheral vasodilation and reverse coronary
artery spasm thus increase 02 supply to
myocardial tissue.
*Understanding how Nitrates Work:
peripheral Vasodilation results in:
-decreased 02 demand
-decreased venous return to heart
-decreased ventricular filling which results
in decreased wall tension and thus
-decreased 02 demand

54. NTG Forms:
• Sub Lingual (SL) (Nitrostat)
• Lingual Sprays - similar to SL in use (Nitrolingual)
• Sustained release capsules/tablets (Nitrobid)
• Ointments 2% (Nitrobid)- wear gloves when applying
• Transdermal Patch (Nitro-Dur)
• IV (Tridil) For attacks unresponsive to other tx

55. Side/Adverse Effects
Vascular HA (may be severe)
Hypotension (may be marked)
Tachycardia
Palpitations

56. Acute Angina Treatment
Goal: Enhance 02 supply to myocardium:
M- Morphine for pain
O- Oxygen 4-6L as ordered
N- NTG sublingual, repeat q5 minutes x3
A- Aspirin to prevent platelet aggregation
MONA

57. Angina Treatment
The focus is to relieve acute attacks
and prevent further attacks.
1-Activity/exercise tolerance : –
a regular exercise prescription is established
after stress testing and/or cardiac cath.
Baseline
Gradual increase
NTG before exercise

58. Angina Rx.-Patient education
2-Lifestyle modifications for controllable risk
factors. Support groups are helpful,
Example: Weight watchers,
3-Smoke-enders, stress workshops, cardiac
rehabilitation. Supply patients with
information, name of contact person and
phone numbers
4-Identify precipitating factors for Anginal pain
5-Medication compliance

59. Coronary artery Diseases.
 I- Angina pectoris (non Acute ).
 II- Acute coronary artery Disease
(syndrome ) (ACS)

60. Coronary artery Diseases.
 II- Acute coronary artery Disease
(syndrome ) (ACS)

61. ACS Definition
 Myocardial ischemia: insufficient blood supply
to the heart muscle that results from coronary
artery disease
 ACS: Any group of symptoms compatible with
myocardial ischemia.
 Represent a continuum of the same disease
process:
– Angina
– Unstable angina
– Non-ST elevation MI
– STEAMI

62. Epidemiology
 1.5 million American experience an ACS every year
 220,000 of those will die of an MI
 Chest discomfort:
2nd most frequent reason for ED visits
 CHD: leading cause of premature disability in the US
 2007 cost of CHD: ~$151.6 billion
62
Anderson JL, Adams CD, Antman EM, et al. ACC/AHA 2007, Guidelines for the management of patients with unstable angina/non
ST-elevation myocardial infarction: A report of the ACC/AHA Task Force on Practice Guidelines: Circulation 2007;116:803–877.
American Heart Association. Heart Disease and Stroke Statistics—2007, Update. Dallas, TX: American Heart Association, 2007.

63. Epidemiology
 In hospital death rates
– STE ACS: 4.6%
– NSTE ACS: 2.2%
 Lower mortality rates for patients treated with
reperfusion therapy (fibrinolytics or PCI)
 Mortality rates higher in women & elderly patients
63
American Heart Association. Heart Disease and Stroke Statistics—2007, Update. Dallas, TX: American Heart Association, 2007.

64. Diagnosis of Acute MI
STEMI / NSTEMI
 At least 2 of the following
 Ischemic symptoms
 Diagnostic ECG changes
 Serum cardiac marker elevations

65. ACS Pathophysiology
 All ACS - sudden
ischemia that cannot be
differentiated initially
 Three common events:
Plaque rupture
Thrombus formation
Vasoconstriction
Lipid Core
Fibrous Cap
Lumen

66. Pathophysiology of ACS/STEMI
‘Heart Attacks’
• 1980 DeWood et al. provided definitive Angiographic
and Histologic Evidence that intra-arterial
thrombosis was the inciting event for STEMI,
resulting in:
– Treatment with Antiplatelet and Antithrombotic therapies.
– The ‘Open Artery’ Theory, for AMI and patients with
hemodynamically significant CAD.

67. ACS Pathophysiology
Plaque rupture
Thrombus formation -
Fibrin cross-linking
Thrombus formation -
Platelet aggregation

68. Natural History of CAD : A story of remodeling

70. CAD is a diffuse process
with focal atherosclerotic
material (plaque).
Some plaques are
obstructive but not
thrombotic.
Others are potentially
thrombotic but not
obstructive.
Myocardial Infartion=
Death of myocardial cells.
Clinical MI = symptoms,
ECG and Biomarkers

71. Normal Atherosclerotic Plaque
CAD as a cause of Myocardial Ischemia and Infarction

72. Angiography vs. Pathology

73. 179
ACS
LAD
Angiography vs CTA for CAD
Motoyama et al. JACC 2007
Fibrous plaque
Positive remodeling
Soft plaque

74. •Acute Coronary Syndrome
•72 year-old Man
•Plaque crater, erosion
•Thrombus
•Calcific nodule

75. Risk Factors
 Hypertension
 Hyperlipidemia
 Diabetes mellitus
 Smoking
 Family history
 Males and post-menopausal
women
 Advancing age

76. Clinical Features
 Typical
 Atypical – 25% of all AMIs
– Pleuritic or sharp/stabbing CP
– Palpable CP (10-33% AMI)
– Arm pain only
– Indigestion
– SOB only (40% in elderly)
– “Dizziness” (5% AMI)
– Nausea
– Syncope

77. Chest pain
Discomfort in other areas of the
upper body
• One or both arms
• Back, neck or jaw
• Stomach
Shortness of breath
Other signs
• Cold sweat
• Nausea
• Lightheadedness
• Fatigue
Heart Attack Symptoms - MEN

78. As with men, chest pain or
discomfort
More likely- other
symptoms:
• Shortness of breath
• Nausea/vomiting
• Back or jaw pain
• Not feeling right
• Fatigue
• Palpitations
• Musculoskeletal complaints
• Hot flashes
Heart Attack Symptoms - WOMEN

79. Heart Attack Warning Signs
• Chest discomfort
– Pressure
– Squeezing
– Fullness
– Pain
• Discomfort in other areas of the upper body
– Arms
– Jaw
– Neck
– Back
– Stomach
• Shortness of Breath
• Cold sweat, nausea or lightheadedness
• **Women have atypical presentations!! Be more wary

80. Assessment – Examination
 Exam usually normal (85%)
 May have:
– Diaphoresis
– Extra heart sounds
(S3, S4 or rubs)
– Dysrhythmias
– Evidence of new or worsening
heart failure
– Hypotension

81. Targeted Physical
 Recognize factors that
increase risk
 Hypotension
 Tachycardia
 Pulmonary rales, JVD,
pulmonary edema,
 New murmurs/heart
sounds
 Diminished peripheral
pulses
 Signs of stroke
♥ Examination
♥ Vitals
♥ Cardiovascular system
♥ Respiratory system
♥ Abdomen
♥ Neurological status

82. Chest pain suggestive of ischemia
 12 lead ECG
 Obtain initial
cardiac enzymes
 electrolytes, cbc
lipids, bun/cr,
glucose, coags
 CXR
Immediate assessment within 10 Minutes
 Establish
diagnosis
 Read ECG
 Identify
complications
 Assess for
reperfusion
Initial labs
and tests
Emergent
care
History &
Physical
 IV access
 Cardiac
monitoring
 Oxygen
 Aspirin
 Nitrates

83. Assessment – investigations.
 ECG.
Biomarkers

84. Assessment – EKG
 12-lead EKG
– May be normal in ACS
– May be nonspecific: ST or T wave ischemic changes
– May be suspicious for injury.
– ST elevation (STEAMI)
– Fibrinolytic checklist

85. EKG - AMI Diagnosis
 AMI Diagnosis:
– At least 2 of 3 criteria
 Clinical history suggestive of AMI
 EKG criteria
 Laboratory diagnosis
 EKG criteria
– ST elevation 1 mm or more in 2 anatomically
contiguous leads
– OR BBB

86. EKG - Contiguous Leads
I aVR V1 V4
II aVL V2 V5
III aVF V3 V6
Limb Leads Chest Leads

87. Normal 12-lead ECG
http://www.uptodate.com/contents/image?imageKey=CARD%2F1617. Accessed Aug 6.
2011.
INFERIOR
ANTERIOR
LATERAL
LATERAL

88. EKG - AMI Imitators
 Causes of ST elevation
– AMI
– LVH
– BBB
– Ventricular beats – PVCs
– Pericarditis
– Early repolarization
– Others

89. Thygesen, K. et al. Circulation 2007;116:2634-2653
EKG - AMI Imitators

90. ECG assessment
ST Elevation or new LBBB
STEMI
Non-specific ECG
Unstable Angina
ST Depression or dynamic
T wave inversions
NSTEMI

91. Key Features of an ECG
P-R
T-P Interval
(continues to next heartbeat)
T-P Interval
(continued from
next heartbeat)
Marieb EN, Hoehn K. Human Anatomy and Physiology. 8th ed. San Francisco, CA:
Pearson Benjamin Cummings; 2010.

92. EKG changes with MI

93. Example of ST-segment Elevation (STEMI)
J point
STE

94. Example of ST-segment Depression
(UA/STEMI)
J point
STD

95. Example of T-wave Inversion (UA/STEMI)
T wave changes

96. Early-Stage Acute MI (STEMI)
ST-segment elevation ST-segment depression
T-wave inversion

97. 3-Day-Old MI (STEMI)
ST-segment elevation T-wave inversion

98. UA - NSTEMI
T-wave inversion

99. EKG Practice 1

100. EKG Practice 2

101. EKG Practice 3

102. EKG Practice 4

103. Spectrum of ACS
Accelerating/ New onset Angina
Unstable Angina, EKG-, Trop-
UA with Trop+ / NSTEMI / NQWMI
STEMI / QWMI

104. Non ST Elevation MI
ST Elevation MI

105. 105
The Spectrum of
Myocardial Ischemia
Acute Coronary Syndromes
Thrombus present in the artery
Stable
Angina
Unstable
Angina
Non-ST
Elevated MI
(NSTEMI)
ST
Elevated MI
(STEMI)
Sudden
Death
Adapted from Contemporary Diagnosis and Management of Acute Coronary Syndromes, 2nd edition. Newtown, PA
Handbooks in Healthcare Co, 2008, p6.

106. STEMI and ACS
Presumed prognosis: very
high risk of in-hospital
death
Treatment goal: prevent
death by restoring
coronary blood flow
Direct
PCI
Presumed prognosis: low risk of
in-hospital death, unless MI develops
Treatment goal: stabilize with aspirin
heparin +/-GIIb/IIIa & monitor for MI
development
+ Cardiac enzymes – Cardiac Enzymes
Scheduled
PCI
Manage
medically
Low -
risk
features
High-
risk
features
Fibrinolytic
therapy
STEMI NSTEMI/Unstable Angina

107. The Continuum
NSTEMI
Non-occlusive
thrombus
Non-specific
EKG
Normal cardiac
enzymes
Occluding thrombus
sufficient to cause
tissue damage & mild
myocardial necrosis
ST depression +/-
T wave inversion on
EKG
Elevated cardiac
enzymes
Complete thrombus
occlusion
ST elevations on
EKG or new LBBB
Elevated cardiac
enzymes
More severe
symptoms
STEMI
Unstable
Angina

108. Spectrum of ACS Presentations
Definition
Ischemia without
necrosis
Necrosis
(nontransmural)
Transmural necrosis
Diagnosis
Negative Biomarkers Positive biomarkers Positive biomarkers
No ECG ST-segment elevation
ECG ST-segment
elevation
Treatment Invasive or conservative depending on risk Immediate reperfusion
UA NSTEMI STEMI
Roger VL, Go AS, Lloyd-Jones DM, et al.. Circulation. 2011;123:e18-e209.

109. Thygesen K et al. Circulation 2007; available at:
http://circ.ahajournals.org.
New clinical classification of MI
Classification Description
1 Spontaneous MI due to coronary event, i.e. plaque erosion
and/or rupture, fissuring, or dissection
2 MI secondary to ischemia due to an imbalance of O2 supply
and demand, as from coronary spasm or embolism, anemia,
arrhythmias, hypertension, or hypotension
3 Sudden unexpected cardiac death, including cardiac arrest,
with new ST-segment elevation; new LBBB; or pathologic or
angiographic evidence of fresh coronary thrombus--in the
absence of reliable biomarker findings
4a MI associated with PCI
4b MI associated with documented in-stent thrombosis
5 MI associated with CABG surgery

110. Assessment – investigations.
 ECG.
Biomarkers

111. Biochemical Markers
 Evaluate troponin & CK MB to confirm MI
– released in response to myocardial necrosis
 3 measurements taken over the 1st 12 to 24 hrs
 MI diagnosis:
– > 1 one troponin value greater than MI decision limit set by lab
or
– 2 CK MB values greater than MI decision limit set by lab
111

112. Biochemical Markers
a - CK-MB
b - Troponin T
c - Troponin I
d - CRP , SAA
e - Myoglobin
f - Homocystein
g - Other inflammatory markers.

113. Troponin T
* Presents in the cardiac + skeletal muscles .
- early elevated ( 3 – 4 hours )
- last up to 14 days .
- not useful in evaluating recurrent damage .
* Its presence is associated with poor prognosis when
higher levels are present :
Troponin
(
‫خالل‬ ‫معايرة‬
24
‫ساعة‬
)
Risk MI , Death
( 5 months )
TT< 0.06 ug / L Low 4.3%
0.06-0.18 Intermediate 10.5%
> 0.18 High 16.1%

114. * Presents in the cardiac muscles only ( is not elevated after
muscular trauma )
Myoglobin :
* after 2 h .
* eliminated quickly from blood ( < 24 h )
* low specificity ,sensitivity is high ( 78 % ) .
Troponin I
After 3 – 4 hours
last up 7 – 10 days .

115. * acute phase reactant .
* with ACS : stable angina : 13%
unstable angina : 56%
AMI : 76%
* Provides prognostic information in NSTE-ACS :
> 3 mg/l high risk .
should be repeated in 3 weeks .
Other Biomarkers
CRP:
BNP:
Six fold increased risk for 30 days cardiac events .

116. Biomarkers of Myocardial Damage

117. Timing of Release of Various Biomarkers After
Acute Myocardial Infarction
Shapiro BP, Jaffe AS. Cardiac biomarkers. In: Murphy JG, Lloyd
MA, editors. Mayo Clinic Cardiology: Concise Textbook. 3rd ed.
Rochester, MN: Mayo Clinic Scientific Press and New York:
Informa Healthcare USA, 2007:773–80.
Anderson JL, et al. J Am Coll Cardiol 2007;50:e1–e157, Figure 5.
Cardiac-specific troponins are
optimum biomarkers (Level IC)
For STEMI, reperfusion therapy
should be initiated as soon as
possible and is not contingent on
a biomarker assay (Level IC)

118. 118

119. Troponin Elevation and Likelihood for
Mortality
Antman EMl. N Engl J Med. 1996; 335: 1342-1349.
% mortality at
42 days
<0.4 <1.0 <2.0 <5.0 <9.0 9.0
2
4
6
8
0
Troponin levels

120. Non-MI Causes of Troponin Elevation
J Am Coll Cardiol. 2014;63(3):201-214

121. ACS Risk Stratification.
Based on initial
Evaluation, ECG, and
Cardiac markers

122. Risk Stratification
 Treat STEMI patients as fast as possible
 NST ACS patients stratified based on clinical
presentation, lab findings
– Risk categories
 high
 medium
 low
– TIMI: Thrombolysis In Myocardial Infarction
 Treatment based on TIMI score
122

123. TIMI Risk Score for Non–ST-Segment Elevation Acute Coronary Syndromes
Past Medical History Clinical Presentation
Age >65 years ST-segment depression (>0.5 mm)
>3 Risk factors for CAD >2 episodes of chest discomfort in the past 24 hrs
Hypercholesterolemia Positive biochemical marker for infarctiona
HTN
DM
Smoking
Family history of premature CHD
50% stenosis of coronary artery)
Use of aspirin within the past 7 days
Using the TIMI Risk Score
One point is assigned for each of the seven medical history and clinical presentation findings. The score (point) total is
calculated, and the patient is assigned a risk for experiencing the composite end point of death, myocardial infarction or urgent
need for revascularization as follows:
High Risk Medium Risk Low Risk
TIMI risk score 5–7 points TIMI risk score 3–4 points TIMI risk score 0–2 points
123
aTroponin I, troponin T, or creatinine kinase MB greater than the MI detection limit.
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:
http://www.accesspharmacy.com

124. TIMI Risk Score STEMI
Circulation 2000; 102:2031

125. Treatments and Therapy

126. Treatment Goals
♥ Restore blood flow to prevent infarct expansion & MI
♥ Prevent death, complications
♥ Prevent coronary artery reocclusion
♥ Relieve ischemic chest discomfort
♥ Maintain normoglycemia
126

127. •Reduce patient symptoms
•Decrease amount of myocardial necrosis
•Preserve heart function
•Prevent major adverse cardiac events
•Treat life threatening complications
TIME IS MUSCLE

128. Management – Prehospital
 Prehospital
– Oxygen
– ASA
– Nitro
– Morphine
– Dysrhythmia treatment
 Medication
 Defibrillation
– 12-lead EKG with notification
of receiving hospital
– Prehospital thrombolysis
– Triage to PCI facility

129. Management – Hospital
 Hospital
– Oxygen, ASA, Nitro,
Morphine
– Dysrhythmia management
– Anticoagulation - heparin
– Reperfusion
 Fibrinolysis
 PCI - percutaneous
coronary intervention

130. Medications in ACS.

131. 131
Discharge
Clinical Pathway for the At-Risk ACS Patient
ST elevation
MI
Non-cardiac
chest pain
Stable
angina
Unstable
angina
Non-ST
elevation MI
Serum markers Negative Positive
Thrombolysis
Primary PCI
Abciximab
ASA+GP IIb/IIIa inhibitor
Clopidogrel + Hep/LMWH
+ Anti-ischemic Rx
Early invasive Rx or
bivalirudin
Negative
Diagnostic
Rule out MI/ACS p/way
ECG ST-T wave
changes
ST
elevation
Negative
Risk assessment
Low
probability Medium-high risk STEMI
Low risk
ASA, Hep/LMWH/bival
+ clopidogrel
Anti-ischemic Rx
Early conservative
Clinical finding
Rest pain, Post-MI, DM,
Prior ASA
Exertional
pain
Atypical
pain
Ongoing
pain
Cannon C, Braunwald E, Heart Disease.
Positive

132. Pharmacotherapy for NSTE ACS
 Similar to STE ACS treatment with a few
exceptions
– fibrinolytic therapy contraindicated
– GP IIb/IIIa receptor blockers administered to high-risk
patients
– no established quality performance measures for
STE ACS patients with unstable angina
132

133. Rx. For STEMI- ACS
133

134. Performance Measure Description
1. Aspirin upon arrival STEMI and NSTE MI patients without aspirin contraindications who
received aspirin within 24 hours before or after hospital arrival
2. Aspirin prescribed at hospital
discharge
STEMI and NSTE MI patients without aspirin contraindications who
are prescribed aspirin at hospital discharge
3. β–Blocker upon hospital arrival β–Blocker STEMI and NSTE MI patients without β–blocker
contraindications who received a β–blocker within 24 hours after
hospital arrival
4. β–Blocker prescribed at hospital
discharge
STEMI and NSTE MI patients without β–blocker contraindications
who are prescribed a β–blocker at hospital discharge
5. LDL cholesterol assessment STEMI and NSTE MI patients with documentation of LDL cholesterol
level in the hospital record or documentation that LDL cholesterol
testing was done during the hospital stay or is planned for after
hospital discharge
6. Lipid-lowering therapy at hospital
discharge
STEMI and NSTE MI patients with elevated LDL cholesterol (100
mg/dL) who are prescribed lipid-lowering medicine at hospital
discharge
134
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:
http://www.accesspharmacy.com
STE and NSTE MI Performance Measures

135. Performance Measure Description
7. ACE inhibitor or ARB for LVSD at
discharge
STEMI and NSTE MI patients with LVSD and without ACE inhibitor
and ARB contraindications who are prescribed an ACE inhibitor or
ARB at hospital discharge
8. Time to fibrinolytic therapy Median time from arrival to administration of fibrinolytic therapy
in patients with STE or LBBB on the ECG performed closest to
hospital arrival time
STEMI or LBBB patients receiving fibrinolytic therapy during the
hospital stay and having a time from hospital arrival to fibrinolysis
of 30 minutes or less
9. Time to PCI Median time from arrival to PCI in patients with STE or LBBB on
the ECG performed closest to hospital arrival time
STEMI or LBBB patients receiving PCI during the hospital stay with
a time from hospital arrival to PCI of 90 minutes or less
10. Reperfusion therapy STEMI patients with STE on the ECG performed closest to the
arrival who receive fibrinolytic therapy or primary PCI
11. Adult smoking cessation advice
counseling
STEMI and NSTE MI patients with a history of smoking cigarettes
who are given smoking cessation advice or counseling during
hospital stay
135
STE and NSTE MI Performance Measures
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:
http://www.accesspharmacy.com

136. Fibrinolytics
 Indicated in STEMI patients who present within
12 hours of symptom onset & have > 1 mm of
STE on EKG (Class 1)
– not indicated in NSTE ACS
 CI in patients with high bleeding risk
 Fibrinolytic therapy controversial in patients >
75 yr
136

137. Contraindications to
Fibrinolysis
 Absolute contraindications:
– active internal bleeding (not including menses)
– previous intracranial hemorrhage at any time
– ischemic stroke within 3 months
– intracranial neoplasm
– structural vascular lesion (e.g., arteriovenous
malformation)
– suspected aortic dissection
– significant closed head or facial trauma within 3
months
137

138. Contraindications to
Fibrinolysis
 Relative contraindications:
– uncontrolled HTN (BP > 180/110 mm Hg)
– ischemic stroke > 3 months
– dementia
– intracranial pathology
– current anticoagulant use
– bleeding diathesis
– traumatic or prolonged CPR (> 10 min)
– major surgery (< 3 wks)
138

139. Contraindications to
Fibrinolysis
 Relative contraindications:
– noncompressible vascular puncture
 recent liver biopsy
 carotid artery puncture
– recent internal bleeding (within 2 to 4 wks)
– for streptokinase administration, previous
streptokinase use (> 5 days) or prior allergic reaction
– pregnancy
– active peptic ulcer
– history of severe, chronic, poorly controlled HTN
139

140. Comparison of Fibrinolytic Agents
Agent Fibrin
Specificity
TIMI-3
Blood Flow
Complete
Perfusion
at 90
Minutes
Systemic
Bleeding
risk/ICH
Risk
Administration AWP Other Approved Uses
Streptokinase
(Streptase)
+ 35% +++/+ Infusion over 60
minutes
$563 Pulmonary embolism,
DVT, clearance of an
occluded arteriovenous
catheter, intraplueral
administration for
clearance of pulmonary
effusion
Alteplase
(rt-PA)
(Activase)
+++ 50-60% ++/++ Bolus followed by
infusions over 90
minutes, weight
based dosing
$3,826 Pulmonary embolism,
acute ischemic stroke,
clearance of an occluded
arteriovenous catheter
Reteplase (rPA)
(Retavase)
++ 50-60% ++/++ Two bolus doses,
30 minutes apart
$2,896
Tenecteplase
(TNK-tPA)
(TNKase)
++++ 50-60% +/++ Single bolus dose,
weight-based
dosing
$2,918
140
DiPiro JT, Talbert RL, Yee GC, Matzke GR, Wells BG, Posey LM: Pharmacotherapy: A Pathophysiologic Approach, 7th Edition:
http://www.accesspharmacy.com

141. Nonpharmacologic Therapy
 STEMI patients should receive either fibrinolysis
or primary PCI within 3 hrs of symptom onset
– PCI: preferred treatment in capable centers
 High risk NST ACS patients may undergo PCI
or CABG
– “early invasive strategy”
141

142. 58 yo Man,
Chest pain
after lunch on
the way to
car.
Bad sushi?

144. Percutaneous Coronary Intervention
(PCI) for ACS and STEMI

145. STEMI PCI

146. NSTEMI PCI

147. Unstable Angina PCI

148.  History/Assessment
 Risk factors
 EKG
 Medical Management
ACS Management Summary

149. Early Invasive Initial
Conservative
Braunwald E et al. Available at: www.acc.org.
Bowen WE, McKay RG. N Engl J Med. 2001;344:1939-1942.
* Also known as Q-wave MI
† Also known as non-Q-wave MI
Treatment of Acute Coronary Syndrome

150. Early Invasive Initial
Conservative
Braunwald E et al. Available at: www.acc.org.
Bowen WE, McKay RG. N Engl J Med. 2001;344:1939-1942.
* Also known as Q-wave MI
† Also known as non-Q-wave MI
Treatment of Acute Coronary Syndrome

151. PCI vs Fibrinolysis in STEMI
Systematic Overview
Short term (4-6 weeks)
Keeley EC et al. Lancet. 2003;361:13-20.
P=0.0002
P=0.0003 P<0.0001
P<0.0001
P=0.0004
(23 RCTs, n=7,739)
8.5
7.3 7.2
22.0
2.0
7.2
4.9
2.8
6.8
1.0
0.0
5.0
10.0
15.0
20.0
25.0
D eath D eath
SH OC K
excl.
R einfarction R ecurrent
ischem ia
Stroke
Percent
(%)
Lysis
PC I

152. Importance of Rapid Reperfusion in STEMI
30-minute delay = 8% increase in 1-year mortality
Rathore SS, Curtis JP, Chen J, et al. BMJ. 2009;338:b1807.
Antman E. ST-segment elevation myocardial infarction: Management. In: Bonow RO, Mann DL, Zipes P, et al,
eds. Braunwald's Heart Disease. 9th ed. Philadelphia, PA: Elsevier Saunders; 2011a:1087-1110.

153. 48 yo Man,
Chest pain
after lunch
while walking
to car.

154. 48 yo M, HBP with Chest pain while walking

155. TIMI Risk Score (n=7)
TIMI Risk Score Calculator
Age ≥65 years? Yes (+1)
≥3 Risk Factors for CAD? Yes (+1)
Known CAD (stenosis ≥50%)? Yes (+1)
ASA Use in Past 7d Yes (+1)
Severe angina (≥2 episodes w/in 24 hrs)? Yes (+1)
ST changes ≥0.5 mm? Yes (+1)
+ Cardiac Marker? Yes (+1)
Total Score pts
Antman EM, Cohen M, Bernink PJ, et al. JAMA. 2000;284:835-842.
TIMI Study Group. TIMI Risk Score Calculator. http://www.timi.org/?page_id=294. Updated 2011.
Accessed July 7, 2011.

156. What does TIMI RISK mean?
Increasing TIMI RISK 0/1 to 5/7
increases risk of death, MI,
urgent revascularization within
14 days 5% to 41%.
Antman EM et al. TIMI 11B, JAMA 2000;284:835-842

157. Nursing
Diagnosis

158. Nursing Interventions
Remember: MONA and Oh Batman
 Obtain EKGs
 Monitor mentation
 Assess heart sounds
 Assess lungs
 Assess peripheral circulation/skin
 Assess urinary output
 Assess GI function
 Assess pain

159. OH BATMAN!
 O =O2
 H =Heparin
 B =B.Block
 A =Aspirin
 T =Thromboltic
 M =Morphin
 A =ACI or ARB.
 N =Nitrate

160. Nursing Interventions
 Activity
 Safety
 Reduce anxiety
 Patient Education
 Nutrition

161. Differential Dx for ACS Chest Pain
Syndromes (beyond STEMI, NSTEMI, UA)
• Aortic dissection
• Pulmonary embolus
• Perforating ulcer
• Pericarditis
• GERD (Gastroesophageal reflux disease)
• Heart failure, Pneumonia, Pneumothorax

162. Complications of MI
Early
 Acut CHF
 Shock
 Sudden death.
 Acut Mitral Valve
Insufficiency
 VSD.
 Dysrhythmias
 Thromboembolic
Complications
 Rupture of Ventricular Wall
Late
 Delayed CHF
 Ventricular aneurysm .
 Dysrhythmias
 Pericarditis Dressler,s
syndrome.
 Post Infarction MI
 Thromboembolic
Complications
 Frozen shoulder syndrome.
 Complications of

163. Acute Coronary Syndromes (ACS)
Van de Werf F. Throm Haemost. 1997; 78(1):210-213.
Unstable Angina
Coronary
Arterial
Thrombosis
Non-ST-Elevation
Myocardial
Infarction
ST-Elevation
Myocardial
Infarction

164. End-stage heart disease
Congestive heart failure
Ventricular dilation
Remodeling
Arrhythmia & loss of muscle
Myocardial infarction
Myocardial ischemia
IHD/angina pectoris
Atherosclerosis
Endothelial dysfunction
Risk factors + hypertension
Coronary thrombosis
Chronic
Coronary
Syndrome
Acute
Coronary
Syndrome
Baroldi G. The Etiopathogenesis of Coronary Heart Disease. 2nd ed. 2004.
Spectrum of Chronic Coronary Syndrome
IHD = ischemic heart disease.

165. Secondary Prevention
 Disease
* HTN, DM, HLP
 Behavioral
* smoking, diet, physical activity, weight
 Cognitive
* Education, cardiac rehab program

166. Rx. At discharge.
 All patients at discharge:
– ASA
– β-blocker
– statin/lipid lowering therapy
– ACE inhibitor or ARB
 Select patients:
– Aldosterone antagonists
– Clopidogrel
– Warfarin
166

167. Prevention news…
From 1994 to 2004 the death rate from
coronary heart disease declined 33%...
But the actual number of deaths declined
only 18%
Getting better with treatment…
But more patients developing disease –
need for primary prevention focus

168. 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

169. Questions ?

170. Thanks