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Medicine II 4.03b 1 Sem/A.Y. 2015-2016

Acute Coronary Syndrome
Rodney M. Jimenez, M.D. January 12, 2017

OUTLINE ! The vulnerable plaque is not a stable plaque, not yet

A. Pathophysiology solidified. These are not seen upon stress test or executive
B. Signs & Symptoms check-ups because they are not stenosis, they don't cause
C. Physical Findings angina upon stress. However, it is prone to rupture and so
D. Diagnosis some people who don’t have angina will suddenly develop
E. Management MI. It is usually seen upon autopsy.

ACUTE CORONARY SYNDROME

A. PATHOPHYSIOLOGY
• Acute coronary syndrome (ACS) refers to a spectrum of
clinical presentations ranging from:
o ST-segment elevation myocardial infarction (STEMI)
o Non–ST-segment elevation myocardial infarction
(NSTEMI)
o Unstable angina
! These three all have the same pathophysiology.
! STEMI: The worst type because there is a complete
obstruction of the lumen by the thrombus, so there is no
chance of oxygenating the myocardium anymore. There
will be a lot of pain, and a bigger area of the myocardium
will be affected.
! NSTEMI: Partial obstruction
! Unstable Angina: Partial obstruction; there is no infarction,
there is no evidence of myocardial apoptosis/necrosis;
there is no elevation of biochemical myocardial markers
• In terms of pathology, ACS is almost always associated
with rupture of an atherosclerotic plaque and partial or
complete thrombosis of the infarct-related artery
• In some instances, however, stable coronary artery
disease (CAD) may result in ACS in the absence of plaque
rupture and thrombosis, when physiologic stress (eg,
Figure 1: Plaque rupture, thrombosis, and healing. (A) Arterial
trauma, blood loss, anemia, infection, tachyarrhythmia)
remodeling during atherogenesis. (B) Rupture of the plaque’s fibrous
increases demands on the heart cap causes thrombosis (C) When the clot overwhelms the endogenous
fibrinolytic mechanisms, it may propagate and lead to arterial occlusion
(D) The subsequent thrombin-induced fibrosis and healing causes a
Myocardial Infarction subtypes: fibroproliferative response that can lead to a more fibrous lesion that
o Type 1: a spontaneous MI related to ischemia from a can produce an eccentric plaque that causes a hemodynamically
primary coronary event (e.g., plaque rupture, significant stenosis.
thrombotic occlusion)
o Type 2: secondary to ischemia from a supply-and-
demand mismatch (the oxygen supply cannot sustain
the oxygen demand. e.g. stress, marathon)
o Type 3: MI resulting in sudden cardiac death.
o Type 4a: MI associated with percutaneous coronary
intervention
o Type 4b: associated with in-stent thrombosis.
o Type 5: MI associated with coronary artery bypass
surgery

• The diagnosis of acute myocardial infarction in this setting
requires a finding of the typical rise and fall of biochemical
markers of myocardial necrosis in addition to at least one
of the following: Figure 2: Stages of atherosclerosis. Plaque formation -> Plaque
o Ischemic symptoms progression -> Plaque rupture (This will come out in the exam!
o Development of pathologic Q waves on ECG Memorize the order). See appendix for larger image.
o Ischemic ST-segment changes on electrocardiogram
(ECG) or in the setting of a coronary intervention § This event is followed by platelet activation and aggregation,
• Acute coronary syndrome (ACS) is caused primarily by activation of the coagulation pathway, and vasoconstriction
atherosclerosis § This process culminates in coronary intraluminal thrombosis
• Most cases of ACS occur from disruption of a previously and variable degrees of vascular occlusion
non-severe lesion (an atherosclerotic lesion that was
previously hemodynamically insignificant yet vulnerable to
rupture)
• The vulnerable plaque is typified by a large lipid pool,
numerous inflammatory cells, and a thin, fibrous cap

2018-A GALICIA, GAITOS, GARCIA, GARCIA 1OF5

Medicine II 4.03b Acute Coronary Syndrome
• Cool, clammy skin and diaphoresis in patients with
cardiogenic shock
• A third heart sound (S3) and, frequently a fourth heart
sound (S4)
• A systolic murmur related to dynamic obstruction of the
left ventricular outflow tract
• Rales on pulmonary examination (suggestive of left
ventricular dysfunction or mitral regurgitation)

D. DIAGNOSIS
• In the emergency setting, electrocardiography (ECG) is the
most important diagnostic test for angina. ECG changes
that may be seen during angina episodes include the
following:
o Transient ST-segments elevations
o Dynamic T-wave changes: Inversions,
normalizations, or hyperacute changes
o ST depressions: may be junctional, downsloping,
or horizontal
• Cardiac Biomarkers:
o Creatine kinase isoenzyme MB (CK-MB) levels
Figure 3: Acute coronary syndromes. Following disruption of a o Cardiac troponin levels
vulnerable plaque, patients experience ischemic discomfort resulting
from a reduction of flow through the affected epicardial coronary artery. E. MANAGEMENT
The flow reduction may be caused by a completely occlusive thrombus
(right) or subtotally occlusive thrombus (left). Patients with ischemic
discomfort may present with or without ST-segment elevation. Of A. Initial therapy
patients with ST-segment elevation, the majority (wide red arrow) • Stabilizing the patient’s condition
ultimately develop a Q wave on the ECG, while a majority (thin red • Relieving ischemic pain
arrow) do not develop Q wave. Patients who present without ST-
segment elevation are suffering from either unstable angina or a non-
• Providing antithrombotic therapy
ST-segment elevation MI (NSTEMI) (wide green arrows), a distinction
that is ultimately made on the presence or absence of a serum cardiac
marker such as CKMB or a cardiac troponin detected in the blood.

• Elevated demand can produce ACS in the presence of a

high-grade fixed coronary obstruction, due to increased
myocardial oxygen and nutrition requirements, such as
those resulting from exertion, emotional stress, or
physiologic stress (e.g., from dehydration, blood loss,
hypotension, infection, thyrotoxicosis, or surgery)
! These are the people with stable angina (chest pain) who
still exert a lot of stress in their body (e.g running) or those
who does not feel any chest pain (diabetics), it can cause
ischemia even if there’s no rupture

B. SIGNS AND SYMPTOMS

• Palpitations
• Pain, which is usually described as pressure, squeezing,
or a burning sensation across the precordium and may
radiate to the neck, shoulder, jaw, back, upper abdomen,
Figure 4: Algorithm for risk stratification and treatment of patients
or either arm with suspected coronary artery disease.
• Exertional dyspnea that resolves with pain or rest
• Diaphoresis from sympathetic discharge B. Anti-Ischemic Therapy
• Nausea from vagal stimulation • Pharmacologic anti-ischemic therapy includes the
• Decreased exercise tolerance following:
o Nitrates (for symptomatic relief)
C. PHYSICAL FINDINGS o Beta blockers (e.g. metoprolol): these are indicated
• Hypotension: indicates ventricular dysfunction due to in all patients unless contraindicated (e.g., if a
myocardial ischemia, myocardial infarction, or acute patient has pulmonary congestion or edema, beta
valvular dysfunction blockers is contraindicated since it can cause
• Hypertension: may precipitate angina or reflect elevated bronchoconstriction)
catecholamine levels due to anxiety or to exogenous
sympathomimetic stimulation C. Beta-blockers
• Diaphoresis • Beta-blockers reduce oxygen demand and ventricular
• Pulmonary edema and other signs of left heart failure wall tension
• Extracardiac vascular disease • Decrease mortality and adverse cardiovascular events
• Jugular venous distention

2018-A GAITOS, GALICIA, GARCIA JR, GARCIA MC 2OF5

Medicine II 4.03b Acute Coronary Syndrome
• These drugs may prevent mechanical complications of • Aside from the possible medical benefits of using LMWH
myocardial infarction, including rupture of the papillary in place of unfractionated heparin, advantages of LMWH
muscle, left ventricular free wall, and ventricular septum include ease of administration, absence of need for
• Beta-blockers meliorate dynamic obstruction of the left anticoagulation monitoring, and potential for overall cost
ventricular outflow tract in patients with apical infarct and savings
hyperdynamic basal segments • Although 3 LMWHs are approved for use in the United
• Beta-blockers should not be used acutely in patients with States, only ENOXAPARIN is currently approved for
cardiogenic shock or signs of heart failure on use in unstable angina
presentation • Pharmacologic anticoagulant therapy includes the
following:
D. Anti-Platelets o Unfractionated heparin (UFH)
• Pharmacologic antithrombotic therapy includes the o Low-molecular-weight heparin (LMWH)
following: § Dalteparin
o Aspirin - main antiplatelet and could be combined § Nadroparin
with or be replaced by the following depending on § Enoxaparin
the indication o Factor Xa inhibitors
o Clopidogrel § Rivaroxaban
o Prasugrel § Fondaparinux
o Ticagrelor
[See Appendix for Drugs commonly used in Intensive Medical
E. Aspirin Management of Unstable Angina and Non-ST Segment
• Aspirin permanently impairs the cyclooxygenase Elevation MI]
pathway of thromboxane A2 production in platelets, in
this way inhibiting platelet function J. Additional Management for STEMI
• Aspirin reduces morbidity and mortality and is continued • Primary percutaneous coronary intervention (preferred
indefinitely treatment for ST elevation MI over thrombolysis)
• Thrombolysis
F. Clopidogrel (thienopyridine)
o Prehospital thrombolysis allows eligible patients
• Inhibits adenosine 5'-diphosphate (ADP)-dependent to receive thrombolysis 30-60 minutes sooner
activation of the glycoprotein IIb/IIIa complex, a than if treatment were given in the ED; however,
necessary step for platelet aggregation
prehospital thrombolysis is still under
• This process results in intense inhibition of platelet
investigation and has not become a trend, as a
function, particularly in combination with aspirin. In the
CURE trial, thienopyridine reduced the rate of result of unproven benefit
myocardial infarction by 20% o Although PCI is the preferred treatment for
• Clopidogrel is a class I recommendation for patients STEMI, the distance to primary PCI centers and
when an early noninterventional approach is planned in the inherent time delay in delivering primary PCI
therapy for at least 1 month and ideally up to 1 year limits widespread use of this treatment
o Prehospital electrocardiographic (ECG)
G. Ticagrelor diagnosis and direct referral for primary PCI
• Ticagrelor (Brilinta) was approved by the US Food and enables patients with STEMI living far from a
Drug Administration in July 2011, and is the first PCI center to achieve a system delay
reversible oral P2Y receptor antagonist comparable to patients who are closer to a PCI
• Results from the randomized PLATO (PLATelet center
inhibition and patient Outcomes) trial showed that
ticagrelor provides faster, greater, and more consistent GUIDE QUESTIONS
ADP-receptor inhibition than clopidogrel 1. J.K. is a 60 year-old male who sees his cardiologist for his recurrent
chest pain which he claims as chest heaviness felt behind the
H. Prasugrel sternum. There are times when he feels the pain even at rest and
would last for 3-5 minutes. Sometimes it would occur upon climbing
• Like clopidogrel, prasugrel is a thienopyridine ADP stairs hurriedly. His treadmill test was negative at 10 METS. It goes
receptor inhibitor that inhibits platelet aggregation. It has away with nitroglycerin. J.K. is probably suffering
been approved in the United States and has been shown from which of the following?
to reduce new and recurrent myocardial infarctions a. Typical angina
• The loading dose is 60 mg PO once and maintenance is b. Unstable angina
10 mg PO qd (given with aspirin 75-325 mg/d) c. Prinzmetal angina
d. Pericarditis
• Prasugrel is indicated for the reduction of thrombotic
cardiovascular events (including stent thrombosis) with 2. When treating a patient with a non-ST-segment elevation MI, risk
ACS that is managed with PCI stratification and timely administration of anti-ischemic and anti-
thrombotic therapies are paramount. For a patient with unstable
I. Low Molecular Weight Heparins angina with negative biomarkers, which medication regimen is most
• Indicated for treatment of ST-segment elevation appropriate as initial treatment?
a. Aspirin, B blocker, spironolactone, HMG CoA reductase inhibitor
myocardial infarction (STEMI) managed medically or with (statin)
subsequent PCI b. Aspirin, clopidogrel, nitroglycerin, B blocker, heparin In the
• It is also indicated as prophylaxis for ischemic mentos
complications caused by unstable angina and non-Q- c. Aspirin, nitroglycerin, B blocker, heparin, glycoprotein IIB/IIIa
wave myocardial infarction inhibitor
d. Aspirin, morphine, oxygen, nitrates

2018-A GAITOS, GALICIA, GARCIA JR, GARCIA MC 3OF5

Medicine II 4.03b Acute Coronary Syndrome

3. A 52 year old man with a history of stable angina presents to the 4. This medication is an example of a class of medication that works by
hospital with 30 min of chest pain. He reports that over the past 2 reducing transmembrane flux of calcium via calcium channels.
weeks he has developed typical symptoms of chest pressure Cause smooth muscle relaxation, resulting in peripheral arterial
radiating to his jaw and left arm with progressively less exertion. He vasodilation and afterload reduction. Indicated when symptoms
has been using sublingual nitroglycerin more frequently. His other persist despite treatment with B blockers or when B blockers are
medication includes a B blocker, aspirin and atorvastatin. On the day contraindicated. Also indicated in patients with prinzmetal angina
of admission he developed pain at rest that was not relieved with 3 with or without nitrates.
nitroglycerin tablets. On examination, he is anxious and short of a. atorvastatin
breath. His vital signs are notable for a BP of 140/88, HR of 110 and b. bisoprolol
RR of 25. He has bilateral crackles halfway up both lung fields and c. terazocin
has a 3/6 systolic murmur that radiates to the axilla. His d. diltiazem
echocardiogram shows 3mm ST segment depression in leads V3-V5.
In addition to his outpatient medication, all of the following therapies
are indicated EXCEPT. Answer Key:
a. cardiac catheterization 1) C
b. clopidogrel 2) B
c. enoxaparin 3) D
d. tissue plasminogen activator 4) D

APPENDIX

Table 1. Drugs commonly used in intensive medical management of unstable angina and non-ST segment elevation MI.

2018-A GAITOS, GALICIA, GARCIA JR, GARCIA MC 4OF5

 st
Medicine II 4.03b 1 Sem/A.Y. 2015-2016
Acute Coronary Syndrome
Rodney M. Jimenez, M.D. January 12, 2017

Figure 1. Stages of atherosclerosis. Activation à aggregation à activation of the coagulation pathway and vasoconstriction (This will come out in the
exam! Memorize the order).

Figure 2. Options for transportation with STEMI and initial reperfusion treatment.

2018-A GALICIA, GAITOS, GARCIA, GARCIA 5OF5