UnsTAble angina AND

NON-ST-ELEVATION
MYOCARDIAL INFARCTION

FEU-NRMF Medical Center

Department of Medicine
ISCHEMIC HEART DISEASE
• Two large groups
1. Stable angina
2. Acute coronary
syndromes (ACS)
a. STEMI
b. Unstable angina
c. NSTEMI
 Stable Angina
• Chest pain or arm
discomfort
• Reproducibly associated
with physical exertion
or stress
• Relieved within 10-15
minutes by rest and/or
sublingula nitroglycerin
Unstable Angina
• At least one of three
features:
1. Occurs at rest (or with
minimal exertion), usually
lasting for >10 minutes
2. Severe and of new onset
(within the prior 4-6
weeks)
3. Crescendo pattern
(distinctly more severe,
prolonged, or frequent
than previously)
Non-ST-Segment Elevation Myocardial
Infarction

• Clinical features of UA
• There is evidence of
myocardial necrosis as
reflected in elevated
cardiac biomarkers
 Pathophysiology
1. Plaque rupture or erosion with a superimposed
nonocclusive thrombus

2. Dynamic obstruction [e.g., coronary spasm, as in

Prinzmetal's variant angina

3. Progressive mechanical obstruction [e.g., rapidly

advancing coronary atherosclerosis or restenosis
following percutaneous coronary intervention (PCI)]

4. UA secondary to increased myocardial oxygen demand

and/or decreased supply (e.g., tachycardia, anemia)
 Pathophysiology
• “Culprit Lesion”
– Eccentric stenosis with
scalloped or overhanging
edges and a narrow neck
on angiography
– Angioscopy
• ‘White” (platelet-rich)
thrombi
Clinical Presentation
• Chest pain
– Clinical hallmark
– Substernal region or in the
epigastrium radiating to the
neck, left shoulder, and/or
left arm

• Anginal equivalents
– Dyspnea
– Epigastric discomfort

• Diaphoresis; pale cool skin;

ST; 3rd or 4th heart sound;
basilar rales; hypotension
 Electrocardiogram
• ST-segment depression
• Transient ST-segment
elevation
• T-wave inversion
– Sensitive but less
specific, unless new,
deep T-wave inversions
(≥0.3 mV)
 Cardiac Biomarkers
• CK-MB and troponin (more specific and sensitive
marker of MI)
– Elevated levels of these markers distinguis patients
with NSTEMI from those with UA

• Conditions with minor elevated troponin other

than MI
1. CHF
2. Myocarditis
3. Pulmonary embolism
Factors associated with high likelihood
of ACS

1. Prior history of stable angina

2. CAD by angiography
3. Prior MI
4. CHF
5. New ECG changes
6. Elevated cardiac biomarkers
 Diagnostic Pathways
1. Clinical history
2. ECG
3. Cardiac markers
– Obtained at baseline and at 4-6 h and 12 h after presentation
4. Stress testing
5. Coronary imaging (emerging option)

 GOALS:
 Recognize or exclude MI (using cardiac markers)
 Evaluate for rest ischemia (using serial or continuous ECGs)
 Evaluate for significant CAD (using provocative stress testing).
 Risk Stratification and Prognosis
• TIMI Trial (Independent Risk Factors)
1. ≥ 65 years old
2. 3 or more risk factors for CAD
3. Documented CAD on catheterization
4. Development of UA/UNSTEMI while on ASA
5. >2 episodes of angina within the preceding 24h
6. ST deviation ≥0.5 mm
7. Elevated cardiac biomarkers
 Treatment
• Involves simultaneous
anti-ischemic treatment
and antithrombotic
treatment

• To provide relief and

prevention of recurrenc
of chest pain

• Initial treatment should

include bed rest, nitrates,
and beta-blockers
 Nitrates
• First be given SL or by buccal spray (0.3-0.6 mg)
• If chest pain persists after 3 doses given 5 min apart, IV
nitroglycerin (5-10 ug/min) using nonabsorbing tubing)
is recommended
– Rate of infusion may be increased by 10 ug/min every 3-5
min until symptoms are relieved or SBP falls to <100 mmHg
• Topical or oral nitrates can be used once chest pain has
resolved or pain-free for 12-24h
• Absolute contraindication
– Hypotension
– Use of sildenafil or other drugs within the same class
within the previous 24-48h
 Beta Adrenergic Blockers
• Other mainstay of anti-ischemic treatment
– Oral beta blockade targeted to a heart rate of 50–
60 beats/min is recommended as first-line
treatment
– A caution has been raised in the new ACC/AHA
guidelines for use of intravenous beta blockade in
patients with any evidence of acute heart failure,
where they could increase the risk of cardiogenic
shock
 Calcium Channel Blockers
• Recommended for patients who have
persistent or recurrent symptoms after
treatment with full-dose nitrates and beta
blockers and in patients with contraindications
to beta blockade
– Diltiazem
– Verapamil
 Other Anti-ischemic Drugs
• Angiotensin-converting enzyme (ACE)
inhibition and HMG-CoA reductase inhibitors
(statins) for long-term secondary prevention
– Early administration of intensive statin therapy
(e.g., atorvastatin 80 mg) prior to percutaneous
coronary intervention (PCI) has been shown to
reduce complications
 Anti-Thrombotic Therapy
• Initial treatment should begin with the
platelet cyclooxygenase inhibitor ASA
– Initial dose of 375 mg/d
– Long-term use of 75-162 mg/d
– "Aspirin resistance" has been noted in 5–10% of
patients and more frequently in patients treated
with lower doses of aspirin, but frequently has
been related to noncompliance
 Anti-Thrombotic Therapy
• Clopidogrel
– A thienopyridine which is inactive prodrug that is
converted into an active metabolite blocking the
platelet P2Y12 component or ADP receptor
– Loading dose of 300-600 mg/d
– Maintenance dose of 75 mg/d
– CURE trial
– OASIS trial
 Anti-Thrombotic Therapy
• Prasugrel
– A thienopyridine
– More rapid onset than clopidogrel
– Loading dose of 60 mg/d
– Maintenance dose of 10/d for 15 months
– Contraindicated with prior stroke or TIA
– TRITON TIMI trial
 Anticoagulant therapy
• Unfractionated heparin (UFH)
– Mainstay of treatment
• LMWH (Enoxaparin)
– More superior to UFH in reducing recurrent
cardiac event
• Indirect Factor Xa inhibitor (Fondaparinux)
– Lower risk of major bleeding
• Direct thrombin inhibitor (Bivalirudin)
• Adverse effect: excessive bleeding
 Invasive Strategy
• Coronary arteriography is carried out within
48 h of admission, followed by coronary
revascularization (PCI or coronary artery
bypass grafting), depending on the coronary
anatomy
Prinzmetal’s Angina
• Transient ST-segment
elevation with rest pain
• Coronary angiography
shows transient coronary
spasm
– Diagnostic hallmark
• Atherosclerotic plaque is
seen in at least 1 proximal
coronary artery (spasm
usually within 1 cm of the
plaque)
– Right coronary artery
 Prinzmetal’s Angina
• Nitrates and calcium channel blockers
– Main agents to treat acute episodes and to abolish
recurrent episodes
• ASA
– Increase severity of ischemic episodes due to
sensitivity of coronary tone to modest changes in
the synthesis of prostacyclin
 ST-ELEVATION
MYOCARDIAL INFARCTION

GHERALD R. BERMUDEZ, M.D.

1ST Year Resident
Internal Medicine
FEU-NRMF Medical Center
ST-Elevation MI
• ECG
– pivotal diagnostic and
triage tool because it is at
the center of the decision
pathway for management
– it permits distinction of
those patients presenting
with ST-segment elevation
from those presenting
without ST-segment
elevation
 ST-Elevation MI
• Cradiac Biomarkers
– It distinguish unstable
angina (UA) from non-
ST-segment MI (NSTEMI)
– It assess the magnitude
of an ST-segment
elevation MI (STEMI)
 Pathophysiology
• Coronary blood flow decreases abruptly after a
thrombotic occlusion of a coronary artery
previously affected by atherosclerosis
• Coronary artery thrombus develops rapidly at a
site of vascular injury
– Smoking, hypertension, lipid accumulation
• Occurs when the surface of an atherosclerotic
plaque becomes disrupted (exposing its contents
to the blood) and conditions (local or systemic)
favor thrombogenesis
Pathophysiology
• Histology
– Coronary plaques prone
to disruption are those
with a rich lipid core and
a thin fibrous cap
 Pathophysiology
• Activation of platelets by agonists promotes a
conformational change in the glycoprotein
IIb/IIIa receptor
– Once converted to its functional state, this
receptor develops a high affinity for soluble
adhesive proteins (i.e., integrins) such as
fibrinogen
• Cross-linking and platelet activation
• Coagulation cascade
 Risk Factors
a. Multiple coronary risk factors
b. Unstable angina
c. Hypercoagulability
d. Collagen vascular diseases
e. Cocaine abuse
f. Intracardiac thrombi
g. Masses producing coronary emboli
 Clinical Presentation
• Precipitating factors
– Smoking, emotional stress, surgical illness
• Pain
– Vigorous physical activity, emotional stress, surgical illness
– Deep and visceral
– Heavy, squeezing, crushing, stabbing, burning
– Usually occurs at rest
– Central portion of the chest
– Radiates as high as the occiput but not below the umbilicus
• Sudden onset of breathlessness, LOC, confusion, profound
weakness, arryhtmia, unexplained drop in arterial pressure
Physical Findings
• Anxious and restless
• Pallor with perspiration and
coolness of extremities
• Substernal pain persisting for
>30 mins
• Diaphoresis
• The precordium is usually
quiet, and the apical impulse
may be difficult to palpate
– Fourth and third heart sounds,
decreased intensity of the first
heart sound, and paradoxical
splitting of the second heart
sound
 Temporal Stages

1. Acute (first few

hours–7 days)
2. Healing (7–28 days)
3. Healed (29 days)
 Laboratory Findings
• ECG
– Total occlusion of an epicardial coronary artery
produces ST-segment elevation
– Q waves on the ECG
• A small proportion of patients initially presenting with ST-
segment elevation will not develop Q waves when the
obstructing thrombus is not totally occlusive, obstruction is
transient, or if a rich collateral network is present
• development of a Q wave on the ECG is more dependent on
the volume of infarcted tissue rather than the transmurality
of infarction
 Laboratory Findings
• Serum cardiac biomarkers
1. Troponin
– may remain elevated for 7–10
days after STEMI
2. CK
– rises within 4–8 h and
generally returns to normal
by 48–72 h
– CKMB is more specific
– A ratio (relative index) of
CKMB mass: CK activity 2.5
suggests but is not diagnostic
of a myocardial rather than a
skeletal muscle source for the
CKMB elevation
 Laboratory Findings
• Cardiac imaging
– When the ECG is not diagnostic of STEMI, early
detection of the presence or absence of wall
motion abnormalities by echocardiography can
aid in management decisions
– Echocardiographic estimation of left ventricular
(LV) function is useful prognostically; detection of
reduced function serves as an indication for
therapy with an inhibitor of the renin-
angiotensin–aldosterone system
Emergency Management
• Goals
1. Control of cardiac
discomfort
2. Rapid identification of
patients who are
candidates for urgent
reperfusion therapy
3. Triage of lower-risk
patients to the
appropriate location in
the hospital
4. Avoidance of
inappropriate discharge
of patients with STEMI
 Emergency Management
• Aspirin is essential in the management of patients
with suspected STEMI and is effective across the
entire spectrum of acute coronary syndromes
– Loading dose: 160-325 mg/tablet
– Maintenance dose: 75-162 mg/tablet OD
• When hypoxemia is present, O2 should be
administered by nasal prongs or face mask (2–4
L/min) for the first 6–12 h after infarction; the
patient should then be reassessed to determine if
there is a continued need for such treatment
 Emergency Management
• Control of discomfort
A. Nitroglycerin
• Up to three doses of 0.4 mg should be administered at about
5-min intervals
• Capable of both decreasing myocardial oxygen demand (by
lowering preload) and increasing myocardial oxygen supply
(by dilating infarct-related coronary vessels or collateral
vessels)
• Should not be administered to patients who have taken the
phosphodiesterase-5 inhibitor sildenafil for erectile
dysfunction within the preceding 24 h, because it may
potentiate the hypotensive effects of nitrates
 Emergency Management
• Control of discomfort
B. Morphine
• Very effective analgesic for the pain associated with
STEMI
• May reduce sympathetically mediated arteriolar and
venous constriction, and the resulting venous pooling
may reduce cardiac output and arterial pressure
– TX: elevation of legs; volume expansion
• Has a vagotonic effect and may cause bradycardia or
advanced degrees of heart block, particularly in
patients with inferior infarction
– TX: atropine (0.5 mg intravenously)
 Emergency Management
• Control of discomfort
C. IV beta-blockers
• Control pain by diminishing myocardial O2 demand and
hence ischemia
• Reduce the risks of reinfarction and ventricular fibrillation
• Oral beta-blocker therapy should be initiated in the first 24 h
for patients who do not have any of the following:
1) signs of heart failure
2) evidence of a low-output state
3) increased risk for cardiogenic shock
4) other relative contraindications to beta blockade (PR interval
greater than 0.24 seconds, second- or third-degree heart block,
active asthma, or reactive airway disease).
 Management Strategies
 The primary tool for screening patients and
making triage decisions is the initial 12-lead ECG

 When ST-segment elevation of at least 2 mm in 2

contiguous precordial leads and 1 mm in 2
adjacent limb leads is present, a patient should
be considered a candidate for reperfusion therapy

 In the absence of ST-segment elevation,

fibrinolysis is not helpful, and evidence exists
suggesting that it may be harmful
 Management Strategies
Glucocorticoids and nonsteroidal anti-
inflammatory agents, with the exception of
aspirin, should be avoided in patients with
STEMI
They can impair infarct healing and increase the
risk of myocardial rupture, and their use may
result in a larger infarct scar
They can increase coronary vascular resistance,
thereby potentially reducing flow to ischemic
myocardium.
 Primary Percutaneuos Coronary Intervention

• Angioplasty and/or
stenting without
preceding fibrinolysis
• Generally preferred when
the diagnosis is in doubt,
cardiogenic shock is
present, bleeding risk is
increased, or symptoms
have been present for at
least 2–3 h when the clot
is more mature and less
easily lysed by fibrinolytic
drugs
 Fibrinolysis
• If no contraindications are present fibrinolytic therapy
should ideally be initiated within 30 min of
presentation
• The principal goal of fibrinolysis is prompt restoration
of full coronary arterial patency
• Act by promoting the conversion of plasminogen to
plasmin, which subsequently lyses fibrinthrombi
– Tissue plas minogen activator (tPA), streptokinase,
tenecteplase (TNK), and reteplase (rPA)
– TNK and rPA are referred to as bolus fibrinolytics since
their administration does not require a prolonged
intravenous infusion
 Fibrinolysis
• Thrombolysis in myocardial infarction
(TIMI)grading system
– grade 0 indicates complete occlusion of the infarct-
related artery
– grade 1 indicates some penetration of the contrast
material beyond the point of obstruction but without
perfusion of the distal coronary bed
– grade 2 indicates perfusion of the entire infarct vessel
into the distal bed, but with flow that is delayed
compared with that of a normal artery
– grade 3 indicates full perfusion of the infarct vessel
with normal flow
 Fibrinolysis
• Patients treated within 1–3 h of the onset of
symptoms generally benefit most
– Remains of benefit for many patients seen 3–6 h
after the onset of infarction, and some benefit
appears to be possible up to 12 h, especially if
chest discomfort is still present and ST segments
remain elevated
 Fibrinolysis
• Generally the preferred reperfusion strategy:
a. for patients presenting in the first hour of
symptoms
b. if there are logistical concerns about
transportation of the patient to a suitable PCI
c. there is an anticipated delay of at least 1 h
between the time that fibrinolysis could be
started versus implementation of PCI
 Fibrinolysis
• tPA
 15-mg bolus followed by 50 mg intravenously over the first
30 min, followed by 35 mg over the next 60 min
• Streptokinase
 1.5 million units (MU) intravenously over 1 h
• rPA
 administered in a double-bolus regimen consisting of a 10-
MU bolus given over 2–3 min, followed by a second 10-MU
bolus 30 min later
• TNK
 given as a single weight-based intravenous bolus of 0.53
mg/kg over 10 s
 Clear Contraindications
1. a history of cerebrovascular hemorrhage at any
time
2. a nonhemorrhagic stroke or other
cerebrovascular event within the past year
3. marked hypertension (a reliably determined
systolic arterial pressure >180 mmHg and/or a
diastolic pressure >110 mmHg) at any time
during the acute presentation
4. suspicion of aortic dissection
5. active internal bleeding (excluding menses)
 Relative Contraindications
1. current use of anticoagulants (international
normalized ratio 2)
2. a recent (<2 weeks) invasive or surgical procedure or
prolonged (>10 min) cardiopulmonary resuscitation
3. known bleeding diathesis
4. Pregnancy
5. a hemorrhagic ophthalmic condition (e.g.,
hemorrhagic diabetic retinopathy)
6. active peptic ulcer disease
7. a history of severe hypertension that is currently
adequately controlled
Complications
1. Hemorrhage
– the most frequent and
potentially the most
serious complication
– Hemorrhagic stroke is
the most serious
complication
2. Allergic reactions
 Hospital Phase Management
 Coronary Care Units
 Activity
 Bed rest for the first 12 h
 In the absence of complications, resume an
upright posture by dangling their feet over the
side of the bed and sitting in a chair within the
first 24 h
 By day 3 after infarction, increase ambulation
progressively to a goal of 185 m (600 ft) at least 3
times a day
 Hospital Phase Management
 Diet
Nothing or only clear liquids by mouth for the first 4–
12 h
 Bowel management
Bed rest and the effect of the narcotics used for the
relief of pain often lead to constipation
Stool softener such as dioctyl sodium sulfosuccinate
(200 mg/d) are recommended
 Sedation
Diazepam (5 mg), oxazepam (15–30 mg), or lorazepam
(0.5–2 mg), given 3–4 times daily
 Pharmacotherapy
• Antithrombotic agents
– Goals
1. To maintain patency of the infarct-related artery, in
conjunction with reperfusion strategies

2. Reduce the patient's tendency to thrombosis and,

thus, the likelihood of mural thrombus formation or
deep venous thrombosis, either of which could result
in pulmonary embolization
 Pharmacotherapy
• Antithrombotic agents
– Aspirin is the standard
antiplatelet agent for
patients with STEMI
– Inhibitors of the P2Y12
ADP receptor prevent
activation and
aggregation of platelets
• Clopidogrel
• Prasugrel
 Pharmacotherapy
• Antithrombotic agents
– LMWH
• High bioavailability permitting administration
subcutaneously, reliable anticoagulation without
monitoring, and greater antiXa:IIa activity
– Fondaparinux
• Its relative efficacy and safety compared with UFH is
less certain
– Bivalirudin (direct anti-thrombin)
• Associated with a lower rate of bleeding
 Pharmacotherapy
• Inhibition of RAAS
– ACE inhibitors reduce the mortality rate after
STEMI
• Causes reduction in ventricular remodeling after
infarction with a subsequent reduction in the risk of
CHF
– Angiotensin receptor blockers (ARBs) should be
administered to STEMI patients who are intolerant
of ACE inhibitors and who have either clinical or
radiological signs of heart failure
 Pharmacotherapy
• Inhibition of RAAS
– Long-term aldosterone blockade should be
prescribed for :
1. STEMI patients without significant renal dysfunction
(creatinine 2.5 mg/dL in men and 2.0 mg/dL in
women)
2. Hyperkalemia (potassium 5.0 mEq/L) who are already
receiving therapeutic doses of an ACE inhibitor
3. LV ejection fraction 40 percent
4. Either symptomatic heart failure or diabetes mellitus