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CORONARY
SYNDROME
Objectives
At the end of this lecture, the PGIs will be
able to:
identify, diagnose, treat and manage cases
of UA, NSTEMI AND STEMI
Pathophysiology
NSTE-ACS
- imbalance between oxygen
supply and oxygen demand
NSTE-ACS studied at
angiography
10% have stenosis of the left main coronary
artery
35% have three-vessel CAD
20% have two-vessel disease
20% have single-vessel disease
15 % have no apparent critical epicardial
coronary artery stenosis;
Clinical PRESENTATION
chest discomfort is severe and has at least one of three features:
(1) it occurs at rest (or with minimal exertion) lasting > 10 minutes
(2) it is of relatively recent onset
(3) it occurs with a crescendo pattern
evidence of myocardial necrosis - elevated levels of biomarkers of
cardiac necrosis
Anginal "equivalents"
- Dyspnea
- epigastric discomfort
- Nausea
- weakness may occur instead of chest pain
appear to be more frequent in women, the elderly and
patients with diabetes mellitus.
Electrocardiogram
ST -segment depression occurs in 20 to 25% of
patients
it may be transient in patients without
biomarker evidence of myocardial necrosis, but
may be persistent for several days in NSTEMI.
T -wave changes are common but are less
specific signs of ischemia, unless they are new
and deep T-wave inversions (> or =0.3 mV).
Cardiac Biomarkers
elevated biomarkers of necrosis - cardiac troponin I
or T
- are specific, sensitive, and the preferred markers
of myocardial
necrosis.
The MB isoform of creatine kinase (CK-MB)
- is a less sensitive alternative.
- distinguish patients with NSTEMI from those with
UA.
DIAGNOSTlC EVALUATION
3 major noninvasive tools:
- electrocardiogram(ECG)
- cardiac biomarkers
- stress testing
Treatment
MEDICAL TREATMENT
Patients should be placed at bed rest with continuous ECG monitoring for
ST-segment deviation and cardiac arrhythmias.
Ambulation is permitted if the patient shows no recurrence of ischemia
(symptoms or ECG changes) and does not develop an elevation of a
biomarker of necrosis for 12-24 hrs.
Medical therapy involves simultaneous anti-ischemic and antithrombotic
treatments and consideration of coronary revascularization.
ANTISCHEMIC TREATMENT
- To provide relief and prevention of recurrence of chest
pain
- initial treatment should include bed
rest nitrates beta adrenergic blockers and inhaled
oxygen in the presence of hypoxemia.
Nitrates
These should first be given sublingually or by buccal spray (0.3-0.6 mg)
If pain persists after three doses given 5 min apart
- intravenous nitroglycerin (5- 10 g/min using non-absorbing tubing)
- The rate of the infusion may be increased by 10 g/min every 3-5min until symptoms
are
relieved systolic arterial pressure falls to <100 m m Hg or the dose reaches 200
g/min
Topical or oral nitrates can be used when the pain has resolved or they may replace
intravenous nitroglycerin when the patient has been pain free for 12-24 hr.
The only absolute contraindications - hypotension or the use of sildenafil or other
phosphodiesterase-5 inhibitors within the previous 24-48 h
ANTITHROMBOTIC THERAPY
This is the second major cornerstone of
treatment.
There are two components of antithrombotic
therapy:
- antiplatelet drugs and anticoagulants
Antiplatelet Drugs
Aspirin
Initial treatment should begin with the platelet
cyclooxygenase inhibitor.
initial dose is 325 mg/d with lower doses (75- 100 mg/d)
Contraindications a reactive bleeding or aspirin intolerance.
"Aspirin resistance" has been noted in 2-8% of patients but
frequently has been related to noncompliance.
Clopidogrel
Platelet P2Y12 receptor blocker
In the absence of a high risk for bleeding patients with
NSTE-ACS irrespective of whether an invasive or
conservative strategy is selected
to inhibit platelet activation.
is an inactive prodrug that is converted into an active
metabolite that causes irreversible blockade of the platelet
P2Y12 receptor.
Prasugrel
A second P2Y12 blocker also a thienopyridine
achieves a more rapid onset and higher level of
platelet inhibition than clopidogrel.
for ACS patients following angiography in whom
PCI is planned.
a loading dose of 60 mg followed by 10mg/d for
up to 15 months.
TRITON-TIMI 38 trial
showed that relative to clopidogrel
prasugrel reduced the risk of cardiovascular
death MI or stroke significantly al beit
with an increase in major bleed ing.
Ticagrelor
is a novel potent reversible platelet P2Y12 inhibitor
has been shown in the PLATO trial to reduce the risk of cardiovascular
death MI or stroke compared with clopidogrel in ACS patients
who a retreated by either an invasive or a conservative strategy.
This agent reduced mortality but increased the risk of bleeding not
associated with coronary artery bypass grafting.
a loading dose of 180 mg and maintenance dose of 90 mg bid
Anticoagulants
Four options to be added to antiplatelet agents:
(1) unfractionated heparin (UFH) long the mainstay
of therapy;
(2) the low-molecular-weight heparin (LMWH)
enoxaparin
(3) bivalirudin
(4) the indirect factor Xa inhibitor, fondaparinux
Excessive bleeding
is the most important adverse effect of all
antithrombotic agents including both antiplatelet
agents and anticoagulants.
Therefore attention must be directed to the doses of
antithrombotic agents, accounting for body
weight creatinine clearance and a previous
history of excessive bleeding
Patients who have experienced a stroke are at higher
risk of intracranial bleeding with potent antiplatelet
agents and combinations of antithrombotic drugs
LONG.TERM MANAGEMENT
The time of hospital discharge - "teachable
moment" for the patient
Risk-factor modification is key
There is evidence of benefit with long-term therapy with five classes of drugs that are
directed at different components of the atherothrombotic process.
Beta blockers statins and ACE inhibitors or angiotensin receptor blockers - recommended
for long-term plaque stabilization.
Antiplatelet therapy now recommended to be the combination of low-dose (75-100 mg/d)
Aspirin and a P2Y12 inhibitor (clopidogrel prasugrel or ticagrelor) for 1 year with
aspirin continued thereafter prevents or reduces the severit of any thrombosis that would
occur if a plaque were to rupture
Registries have shown that women and racial minorities as well as patients with NSTE-ACS
at high risk including the elderly and patients with diabetes or chronic kidney disease are
less likely to receive evidence-based pharmacologic and interventional therapies with
resultant poorer clinical outcomes and quality of life. Special attention should be directed to
these groups.
Coronary angiography
demonstrates transient coronary spasm as the
diagnostic hallmark of PVA.
Hyperventilation or intracoronary acetylcholine
has been used to provoke focal coronary stenosis
on angiography or to provoke rest angina with ST
-segment elevation to establish the diagnosis.
Prognosis
Many patients with PVA pass through an acute active phase with frequent
episodes of angina and cardiac events during the first 6 months after
presentation.
Survival at 5 years is excellent (-90-95%).
Patients with no or mild fixed coronary obstruction tend to experience a more
benign course than do patients with associated severe obstructive lesions.
Nonfatal MI occurs in up to 20% of patients by 5 years.
Patients with PVA who develop serious arrhythmias during spontaneous episodes
of pain are at a higher risk for sudden cardiac death. In most patients who survive
an infarction or the initial 3- to 6-month period of frequent episodes there is a
tendency for symptoms and cardiac events to diminish over time.
PATHOPHYSIOLOGY: ROL E
OF ACUTE PLAQUE RUPTURE
usually occurs when coronary blood flow
decreases abruptly after a thrombotic occlusion
of a coronary artery previously affected by
atherosclerosis.
development of a rich collateral network over
time.
occurs when a coronary artery thrombus
develops rapidly at a site of vascular injury.
C L l N ICAL PRESENTAT I
ON
In up to one-half of cases a precipitating factor
appears to be present before STEMI such as vigorous
physical exercise emotional stress or a medical or
surgical illness.
Although STEMI may commence at any time of the day
or night circadian variations have been reported such
that clusters are seen in the morning within a few hours
of awakening.
Pain
is the most common presenting complaint in patients with STEMI
is deep and visceral; heavy squeezing and crushing
occasionally it is described as stabbing or burning
occurs at rest is usually more severe and lasts longer.
Typically the pain involves the central portion of the chest and/or
the epigastrium and on occasion it radiates to the arms.
It is often accompanied by weakness sweating
nausea vomiting anxiety and a sense of impending doom.
The pain may commence when the patient is at rest but when it
begins during a period of exertion it does not usually subside with
cessation of activity in contrast to angina pectors.
PHYSICAL FINDINGS
The combination of substernal chest pain persisting for
>30 min and diaphoresis strongly suggests STEMI.
Although many patients have a normal pulse rate and
blood pressure within the first hour of STEMI
about one-fourth of patients with anterior infarction have
manifestations of
sympathetic nervous system
hyperactivity (tachycardia and/or hypertension)
up to one-half with inferior infarction show evidence of
parasympathetic hyperactivity (bradycardia and/or
hypotension)
LABORATORY FINDINGS
ELECTROCARDIOGRAM
SERUM CARDIAC
BIOMARKERS
are released from necrotic heart muscle after
STEMI.
The rate of liberation of specific proteins differs
depending on their intracellular location their
molecular weight and the local blood and
lymphatic flow.
become detectable in the peripheral blood once
the capacity of the cardiac lymphatics to clear
the interstitium of the infarct zone is exceeded
and spillover into the venous circulation occurs.
Many hospitals are using cTnT or cTnl rather than CKMB as the routine serum cardiac marker for
diagnosis of STEMI although any of these analytes
remain clinically acceptable.
not cost -effective to measure both a cardiac-specific
troponin and CK-MB at all time points in every
patient.
While it has long been recognized that the total
quantity of protein released correlates with the size
of the infarct the peak protein con centration
correlates only weakly with infarct size.
CARDIAC IMAGIN G
Abnormalities of wall motion on two-dimensional echocardiography are almost universally present.
Although acute STEMI cannot be distinguished from an old myocardial scar or from acute severe
ischemia by echocardiography the ease and safety of the procedure make its use appealing as a
screening tool in the Emergency Department setting.
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 such as whether
the patient should receive reperfusion therapy (e.g. fibrinolysis or a percutaneous coronary
intervention [PCI] ) .
Echocardiographic estimation of left ventricular (L V) function is useful prognostically; detection of
reduced function serves as an indication for therapy with an inhibitor of the renin-angiotensinaldosterone system.
Echocardiography may also identify the presence of right ventricular (RV) infarction ventricular
aneurysm pericardial effusion and LV thrombus. In addition Doppler echocardiography is
useful in the detection and quantitation of a ventricular septal defect and mitral regurgitation
two serious compliations of STEMI.
INITIAL MANAGEMENT
PREHOSPITAL CARE
The prognosis in STEMI is largely related to the occurrence of two
general classes of complications:
( 1 ) electrical complications (arrhythmias)
(2) mechanical complications ("pump failure").
Most out of-hospital deaths from STEMI are due to the sudden
development of ventricular fibrillation. The vast majority of deaths
due to ventricular fibrillation occur within the first 24 h of the onset
of symptoms and of these over half 0ur in the first hour.
MANAGEMENT IN THE
EMERGENCY DEPARTMENT
In the Emergency Department
the goals with suspected STEMI
control of cardiac discomfort
rapid identification who are candidates for urgent reperfusion therapy
triage of lower-risk patients to the appropriate location in the hospital
avoidance of inappropriate discharge of patients with STEMI
The overarching goal is to minimize the time from first medical contact to
initiation of reperfusion therapy.
This may involve transfer from a non-PCI hospital to one that is PCI capable
with a goal of initiating PCI within 120 min of first medical contact
Aspirin
is essential in the management of patients with suspected
STEMI and is effective across the entire spectrum of acute coronary
syndromes (Fig. 295- 1 ) . Rapid inhibition of cyclooxygenase- 1 in
platelets
followed by a reduction of thromboxane A2 levels is achieved by
buccal absorption of a chewed 160-325-mg tablet in the Emergency
Department. This measure should be followed by daily oral adminis
tration of aspirin in a dose of 75- 162 mg.
CONTROL OF
DISCOMFORT
Sublingual nitroglycerin
can be given safely to most patients with STEMI.
Up to three doses of 0.4 mg should be administered at about 5-min
intervals.
nitroglyerin may be capable of both decreasing myocardial oxygen
demand (by lowering preload) and increasing myocardial oxygen supply
(by dilating infarct-related coronary vessels or collateral vessels).
In patients whose initially favorable response to sublingual nitroglyerin is
followed by the return of chest discomfort particularly if accompanied
by other evidence of ongoing ischemia such as further ST-segment or Twave shifts the use of intravenous nitroglycerin should be considered.
Contraindications
low systolic arterial pressure (<90 mmHg)
clinical suspicion of RV infarction (inferior infarction on
ECG elevated jugular venous pressure clear lungs and
hypotension).
phosphodiesterase-5 inhibitor for erectile dysfunction within the
preceding 24h (hypotensive effects of nitrates)
An idiosyncratic reaction to nitrates consisting of sudden marked
hypotension sometimes occurs but can usually be reversed
promptly by the rapid administration of intravenous atropine
Morphine
Metoprolol
5 mg every 2-5 min for a total of three doses
provided the patient has a heart rate >60 beats/min
systolic pressure > 100 mmHg
a PR interval <0.24 s
and rales that are no higher than 10 cm up from the
diaphragm
Fifteen minutes after the last intravenous dose an oral
regimen is initiated of 50 mg every 6 h for 48 h followed
by 1 00 mg every 12 h.
Calcium antagonists
evidence that short-acting dihydropyridines may
be associated with an increased mortality risk
MANAG E M E N T
STRATEG I ES
The primary tool for screening patients and
making triage decisions
initial 12-lead ECG.
LIMITATION OF INFARCT
SIZE
The quantity of myocardium - necrotic as a
consequence of a coronary artery occlusion
While the central zone of the infarct contains
necrotic tissue that is irretrievably lost the
fate of the surrounding ischemic myocardium
(ischemic penumbra) may be improved
PRIMARY PERCUTANEOUS
CORONARY INTERVENTION
PCI ( angioplasty and/or stenting without
preceding fibrinolysis)
is effective in restoring perfusion in STEMI
when carried out on an emergency basis in the
first few hours of MI.
patients who have contraindications to
fibrinolytic therapy
FIBRINOLYSIS
tPA rPA and TNK are more effective than streptokinase at restoring full
perfusion
The current recommended regimen of tPA
- 15-mg bolus followed by 50 mg intravenously over the first 30
min followed by
35 mg over the next 60 min.
Streptokinase is administered as 1.5 million units (MU) intravenously over 1h.
rPA
- 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
- single weight-based intravenous bolus of 0.53 mg/kg over 10s.
In addition to the fibrinolytic agents discussed earlier pharmacologic
reperfusion typically involves adjunctive antiplatelet and antithrombotic
drugs as discussed subsequently.
Clear contraindications
history of cerebrovascular hemorrhage at any time
a nonhemorrhagic stroke or other cerebrovascular
event within the past year
Marked hypertension (systolic arterial pressure >
180mmHg and/or a diastolic pressure >110mmHg)
at any time during the acute presentation
suspicion of aortic dissection
active internal bleeding (excluding menses)
Relative contraindications
current use of anti coagulants (international normalized ratio
2) a recent (<2 weeks)
invasive or surgical procedure
prolonged (> 10 min) cardiopulmonary Resuscitation
known bleeding diathesis pregnancy a hemorrhagic
ophthalmic condition (e.g. hemorrhagic diabetic
retinopathy) active peptic ulcer disease and a history of
severe hypertension that is currently adequately controlled
risk of an allergic reaction streptokinase not used if
received within the preceding 5 days to 2 years.
INTEGRATED
REPERFUSION STRATEGY
Cardiac catheterization and coronary angiography
should be carried out after fibrinolytic therapy if there is evidence of either
(1) failure of reperfusion (persistent chest pain and ST -segment elevation >90min) in which
case a rescue PCI should be considered;
(2) coronary artery reocclusion (re-elevation of ST segments and/or recurrent chest pain) or the
development of recurrent ischemia (such as recurrent angina in the early hospital course or a
positive exercise stress test before discharge) in which case an urgent PCI should be
considered.
Routine angiography and elective PCI even in asymptomatic patients following administration of
fibrinolytic therapy are used with less frequency given the numerous technologic advances
that have occurred in the catheterization laborator and the increasing number of skilled
interventionalists.
Coronary artery bypass surgery should be reserved for patients whose coronary anatomy is
unsuited to PCI but in whom revascularization appears to be advisable because of extensive
jeopardized myocardium or recurrent ischemia.
HOSPITAL PHASE
MANAGEMENT
CORONARY CARE U N ITS
routinely equipped with a system that permits
continuous monitoring of the cardiac rhythm of each
patient and hemodynamic monitoring in selected
patients. Defibrillators respirators noninvasive
transthoracic paemakers and facilities for
introducing pacing catheters and flow-directed
balloon-tipped catheters are also usually available.
Activity Factors that increase the work of the heart during the initial
hours of infarction may increase the size of the infarct.
kept at bed rest for the first 6- 12 h.
encourage under supervision to resume an upright posture by
dangling their feet over the side of the bed and sitting in a chair
within the first 24 h reduction in the pulmonar capillary wedge
pressure
absence of hypotension and other complication
by the 2nd or 3rd day patients typically are ambulating in their
room with increasing duration and frequency and they may shower
or stand at the
sink to bathe
by day 3 after infarction, increasing their ambulation
progressively to a
goal of 185 m (600 ft) at least three times a day.
Sedation
to withstand the period of enforced inactivity
with tranquility.
Diazepam (5 mg) oxazepam ( 1 5-30 mg)
or lorazepam (0.5-2 mg) given three to four
times daily
An additional dose - at night to ensure
adequate sleep.
PHARMACOTHERAPY
ANTI THROMBOTIC AGENTS
initial phase of STEMI thrombosis plays an important role in the
pathogenesis
The primary goal to maintain patency of the infarct-related artery in
conjunction with reperfusion strategies.
A secondary goal to reduce the patient' s tendency to thrombosis and
the likelihood of mural thrombus formation or deep venous thrombosis
pulmonary embolization
The degree to which antiplatelet and anticoagulant therapy achieves these
goals partly determines how effectively it reduces the risk of mortality from
STEMI.
aspirin is the standard antiplatelet agent for patients with STEMI.
COM P L lCAT I O N S A N D
THE I R MANAG E M E N T
VENTRICULAR DYSFU NCTION
H EMODYNAMIC
ASSESSMENT
Pump failure is now the primary cause of inhospital death from STEMI
HYPOVOLEMIA
CARDIOG E N IC SHOCK
RIGHT VENTRICULAR I N
FARCTION
Approximately one-third of patients with inferior infarction demonstrate
at least a minor degree of RV necrosis. An occasional patient with
inferoposterior L V infarction also has extensive RV infarction and rare
patients present with infarction limited primarily to the RV.
Clinically significant RV infarction causes signs of severe RV failure
(19u1ar venous distention Kussmaul's sign hepatomegaly [Chap.
267] ) with or without hypotension. ST -segment elevations of right
sided precordial ECG leads particularly lead V4R are frequently
present in the first 24 h in patients with RV infarction. Two-dimensional
echocardiography is helpful in determining the degree of RV
dysfunction. Catheterization of the right side of the heart often reveals a
distinctive hemodynamic pattern resembling constrictive pericarditis
(steep right atrial "y" descent and an early diastolic dip and plateau in
RV waveforms) (Chap. 288). Therapy consists of volume expansion to
maintain adequate RV preload and efforts to improve L V performance
ARRHYTHMIAS
The incidence of arrhythmias after STEMI is higher in patients seen
ea a r the onset of symptoms.
The mechanisms responsible for infarction-related arrhythmias
include autonomic nervous system imbalance electrolyte
disturbances ischemia and slowed conduction in zones of
ischemic myocardium. An arrh hmia can usually be managed
successfully if trained personnel and appropriate equipment are
available when it develops. Since most deaths from arrh hmia
occur during the first few hours after infarction the effectiveness
of treatment relates directly to the speed with which patients come
under medical observation. The prompt management of
arrhythmias constitutes a significant advance in the treatment of
STEMI.
OTHER COMPLlCATIONS
Recurrent Chest Discomfort - recurrent or persistent
ischemia often heralds extension of the original infarct
or reinfarction in a new myocardial zone and is
associated with a near tripling of mortality after
STEMI
patients with these symptoms should be referred for
prompt coronary arteriography and mechanical
revascularization
Administration of a fibrinolytic agent is an alternative
to early mechanical revascularization.
Pericarditis
Pericardial friction rubs and/or pericardial pain are frequently
encountered in patients with STEMI involving the epicardium.
managed with aspirin (650 mg four times daily).
failure to recognize it may lead to the erroneous diagnosis of recurrent
ischemic pain and/or infarct extension with resulting inappropriate use
of anticoagulants nitrates beta blockers or coronary arteriography.
complaints of pain radiating to either trapezius muscle is helpful
because such a pattern of discomfort is typical of pericarditis but rarely
occurs with ischemic discomfort.
Anticoagulants potentially could cause tamponade in the presence of
acute pericarditis (as manifested by either pain or persistent rub) and
therefore should not be used unless there is a compelling indication.
Thromboembolism
complicates STEMI in -10% of cases but embolic lesions are found in 20% of patients
in necropsy series suggesting that thromboembolism is often clinically silent.
contributing cause of death in 25% of patients with STEMI who die after admission to the
hospital.
Arterial emboli originate from L V mural thrombi while most pulmonary emboli arise in
the leg veins
typically occurs in association with large infarcts (especially anterior) CHF and an LV
thrombus detected by echocardiography.
The incidence of arterial embolism from a clot originating in the ventricle at the site of
an infarction is small but real.
Two-dimensional echocardiography reveals L V thrombi in about one-third of patients
with anterior wall infarction but in few patients with inferior or posterior infarction.
presents as a major complication such as hemiparesis when the cerebral circulation is
involved or hypertension if the renal circulation is compromised.
SECONDARY
PREVENTION
Long-term treatment with an antiplatelet agent (usually aspirin) after
STEMI - - 25% reduction in the risk of recurrent infarction stroke or
cardiovascular mortality (36 fewer events for every 1000 patients
treated).
An alternative antiplatelet agent that may be used for secondary
prevention in patients intolerant of aspirin is clopidogrel (75 mg orally
daily).
ACE inhibitors or ARBs and in appropriate patients aldosterone
antagonists should be used indefinitely by patients with clinically evident
heart failure a moderate decrease in global ejection fraction or a
large regional wall motion abnormality to prevent late ventricular
remodeling and recurrent ischemic events.
The chronic routine use of oral beta-adrenoceptor blockers for at least 2
years after STEMI is supported by well-conducted placebo controlled
trials.