Download Atherosclerotic vascular disease (AVD)

Atherosclerotic vascular disease
AVD may manifest as:
Coronary artery disease.
2.
Cerebrovascular disease.
3.
Peripheral vascular disease.
Pathophysiology:
Early atherosclerosis:
Fatty streaks develop when inflammatory cells
predominantly monocytes migrate into the
intima,takeup oxidized LDL from the plasma and
become lipid laden foam cells or macrophages, when
these cells die and release their contents extra
cellular lipid pools appear. Smooth muscle cells then
migrate from the media into the intima in response to
cytokines &growth factors produced by activated
macrophages.
1.
The lipid core will be covered by smooth muscle
cells and matrix, producing a stable atherosclerotic
plaque which is asymptomatic until it becomes
large enough to obstruct arterial flow.
Advanced atherosclerosis:
 In an established atherosclerotic plaque
macrophages mediate inflammation & smooth
muscle cells promote repair, if inflammation
predominates, the plaque becomes active or
unstable & may be complicated by ulceration &
superadded thrombosis. Cytokines such as
interleukin-1, tumour necrosis-alpha, interferon
gamma, platelet derived growth factors, and matrix
metalloprotinases are released by activated
macrophages & may cause the initial smooth
muscle
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Cells overlying the plaque to become senescent
resulting in thinning of the protective fibrous cap,
may lead to erosion, fissuring or rupture of the
plaque surface, exposing its content to circulating
blood, & may trigger platelet aggregation &
thrombosis, may cause partial or complete
obstruction resulting in infarction or ischemia of
the affected organ.
Risk Factors
A. Fixed R. F
 Age
 Male sex
 Family history.
B. Modifiable R.F
 Smoking
- Sedentary lifestyle
 Hypertension
- Obesity
 Lipid disoder.
- Diet
 D.M
 Haemostatic variables
Primary Prevention
Population advice to prevent coronary disease;
 Do not smoke.
 Take regular exercise (minimum of 20 minutes
three times a week).
 Maintain ideal body weight .
 Eat a mixed diet rich in fresh fruit & vegetables.
 Aim to get no more than 30% of energy intake
from saturated fat.
Secondary prevention:
 Patients who already have evidence of
atheromatous vascular disease e.g M.I, are at high
risk of another vascular event, can be offered a
variety of treatment and measures to improve their
outlook (secondary prevention).
 Correction of risk factors
 Aspirin
 Beta blockers
 ACE Inhibitors
Coronary Heart Disease
It is the most common form of heart disease.
 Most important cause of premature death.
 In UK 1 in 3 men & 1 in 4 women die of CHD.
Clinical manifestation:
 Stable angina.
 Unstable angina.
 M.I
 Heart failure.
 Arrhythmia.
 Sudden death.
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Stable angina
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Angina pectoris is caused by transient myocardial
ischemia.
It may occur whenever there is an imbalance
between myocardial oxygen supply & demand.
Coronary atheroma is the most common cause.
Other causes include aortic valve disease &
hypertrophic cardiomyopathy.
Clinical features:
 The history is the most important factor in making
the diagnosis.
 Central chest pain, discomfort or breathlessness
that is precipitated by exertion or other forms of
stress, (heavy meal, cold exposure, intense
emotion, lying flat/ decubitus, vivid dreams/
nocturnal angina), and relieved by rest.
 Start up angina: the pain comes when they start
walking & that later it dose not return despite
greater effort.
 Physical examination is frequently negative, but
should include:
 Evidence of valve disease, important risk factors,
left ventricular dysfunction, features of arterial
disease e.g carotid bruits and untreated conditions
that may exacerbate angina e.g anemia,
thyrotoxicosis.
Investigations:
Resting ECG:
 Evidence of previous M.I, but may be normal.
 Occasionally T wave flattening or inversion.
 The most important ECG changes is reversible ST
segment depression or elevation with or without T
wave inversion at the time the patient is
experiencing symptoms.
Exercise ECG:
 Standard treadmill or bicycle ergometer protocol,
planar or down-sloping ST-segment depression of 1
mm or more is indicative of ischemia, up-sloping is
less specific & often occurs in normal individuals.
 Exercise ECG is used to diagnose angina, assess
severity & identifying high- risk individuals.
 False +ve: Digoxin, LVH, LBBB, WPW syndrome, the
accuracy is lower in women than men.
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Risk stratification in stable angina.
 High Risk; *post –infarct angina, *poor effort
tolerance, *ischemia at low workload, *left main or
three vessel disease, *poor LV function.
Low Risk:
 Predictable exertional angina, *good effort
tolerance, *ischemia only at high workload,
*single-vessel or minor two-vessel disease, *good
LV function.
Other forms of stress testing:
 Myocardial perfusion scanning: useful when
exercise test is not diagnostic, or patient can not
exercise, its accuracy is higher than exercise test.
The technique involve obtaining scintiscans of the
myocardium at rest and during stress after
administration of an i.v radioactive isotope e.g
thallium201, it is taken up by viable myocardium.
A perfusion defect present during stress but not rest
indicates reversible myocardial ischemia, whereas
persistent perfusion defect indicates previous M.I
Stress echocardiography:
It is alternative to perfusion scanning with similar accuracy.
Uses transthoracic echo to identify ischemic segments of
myocardium & area of infarction, the latter do not contract
at rest or during stress.
Coronary arteriography:
Shows the extent & nature of coronary artery disease, it may
be indicated when other investigations fail to diagnose the
cause of atypical chest pain.
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Management
 Assessment of the extent & severity of arterial
disease.
 Identification & control of significant risk factors
 Measures to control symptoms.
 Identification of high risk patients & application of
treatment to improve life expectancy.
Antiplatelet therapy:
Aspirin 75-150 mg reduce the risk of MI, Clopidogrel
75 mg daily equally effective but more expensive
can be used if the patient has dyspepsia.
Anti-anginal drugs:
 Nitrates: produces venous & arteriolar dilatation
 Decrease myocardial oxygen demand (lower
preload & afterload) & increase myocardial oxygen
supply.
 Sublingual glyceryl trinitrate (GTN), as aerosol 400
microgm or tablet 300-500 micro-gm sublingually
usually relieve angina in 2-3 minutes, side- effects
include headache, symptomatic hypotension &
syncope, the tablet should be replaced 8 weeks
after
the bottle has been opened.
 Nitrates can be used prophylactically before
exercise.
 GTN is subject to extensive first pass metabolism in
the liver, its ineffeective when swallowed.
 Nitrate free period of 6-8 hr. every day to avoid
tolerance.
Preparation
Peak action
Duration
Sublingual GTN
Buccal GTN
Transdermal GTN
Oral isosorbide dinitrate
Oral isosorbide mononitrate
4-8 mins
4-10 mins
1-3 hrs
45-120 mins
45-120 mins
10-30 mins
30-300 mins
up to 24 hrs
2-6 hrs
6-10 hrs
Beta-blockers
 Reduce myocardial oxygen demand by reducing heart rate, BP, and
myocardial contractility.
 Non-selective BB may exacerbate coronary spasm by blocking Beta 2
coronary adrenoceptors.
 Give once daily cardioselective preparation, atenolol 50-100 mg daily,
slow release metoprolol 200 mg daily, bisoprolol 5-10 mg daily.
 Ββ should not be withdrawn suddenly as this may cause arrhythmia,
more angina or MI.(ββ withdrawal syndrome).
Calcium antagonists:
 lower myocardial oxygen demand by reducing blood pressure and
myocardial contractility.
 Dihydropyridine calcium antagonists, such as nifedipine and
nicardipine, often cause a reflex tachycardia; it is often best to use
these drugs in combination with a β-blocker.
 In contrast, verapamil and diltiazem are particularly suitable for
patients who are not receiving a β-blocker because they inhibit
conduction through the AV node and tend to cause a bradycardia or
even atrioventricular block in susceptible individuals.
The calcium antagonists may reduce myocardial
contractility and can aggravate or precipitate heart
failure. Other unwanted effects include peripheral
oedema, flushing, headache and dizziness.
Potassium channel activators;
This class of drug has arterial and venous dilating
properties but does not exhibit the tolerance seen
with nitrates. Nicorandil (10-30 mg 12-hourly
orally) is the only drug in this class currently
available for clinical use.
 it is conventional to start therapy with low-dose
aspirin, sublingual GTN and a β-blocker, and then
add a calcium channel antagonist or a long-acting
nitrate later, if necessary.
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The goal is the control of angina with minimum
side-effects and the simplest possible drug
regimen. There is little or no evidence that
prescribing multiple anti-anginal drugs is of
benefit, and revascularisation should be considered
if an appropriate combination of two drugs fails to
achieve a symptomatic response.
Invasive treatment The most widely used invasive
options for the treatment of ischaemic heart
disease include percutaneous coronary intervention
(PCI; including percutaneous transluminal coronary
angioplasty, PTCA) and coronary artery bypass
graft (CABG) surgery.
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UNSTABLE ANGINA
is a clinical syndrome that is characterised by newonset or rapidly worsening angina (crescendo angina),
angina on minimal exertion or angina at rest.
The condition shares common pathophysiological
mechanisms with acute myocardial infarction,
the term 'acute coronary syndrome' is used to
describe these disorders collectively.
These entities comprise a spectrum of disease that
encompasses ischaemia with no myocardial damage,
ischaemia with minimal myocardial damage, partial
thickness (non-Q wave) myocardial infarction, and full
thickness (Q wave) myocardial infarction .
An acute coronary syndrome may present as a new
phenomenon or against a background of chronic
stable angina.
 The culprit lesion is usually a complex ulcerated or
fissured atheromatous plaque with adherent
platelet-rich thrombus and local coronary artery
spasm .
Diagnosis and risk stratification
 The assessment of acute chest pain depends
heavily on an analysis of the character of the pain
and its associated features, evaluation of the ECG,
and serial measurements of biochemical markers of
cardiac damage, such as troponin I and T.
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A 12-lead ECG is mandatory and is the most useful
method of initial triage.
Evolving transmural infarction is characterised by
persistent ST elevation, new Q waves or new left
bundle branch block
In patients with unstable angina or partial
thickness (non-Q wave or non-ST elevation)
myocardial infarction, the ECG may show ST/T
wave changes including ST depression, transient ST
elevation and T-wave inversion; the T-wave
changes are sometimes prolonged.
Approximately 12% of patients with wellcharacterised unstable angina or non-ST segment
elevation myocardial infarction progress to acute
infarction or death, and almost one-third will suffer
a recurrence of severe ischaemic pain, within 6
months of the index event.
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The risk markers that are indicative of an adverse
prognosis include :
recurrent ischaemia,
extensive ECG changes at rest or during pain,
the release of biochemical markers (creatine
kinase or troponin),
arrhythmias and haemodynamic complications
(e.g. hypotension, mitral regurgitation) during
episodes of ischaemia
those who experience unstable angina following
acute myocardial infarction are also at increased
risk.
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Risk stratification is important because it
guides the use of more complex
pharmacological and interventional
treatment .
High risk:
Clinical:
 Post-infarct angina
Recurrent pain at rest
Heart failure
ECG:
 Arrhythmia
ST depression
Transient ST elevation
Persistent deep T-wave inversion
 Biochemistry:Troponin T > 0.1 μg/l
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Low risk:
Clinical
 No history of MI
 Rapid resolution of symptoms
ECG:
Minor or no ECG changes
Biochemistry:
 Troponin T < 0.1 microgm/ l
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The initial treatment should include
 bed rest,
 antiplatelet therapy (aspirin 300 mg followed by
75-325 mg daily long-term and clopidogrel 300 mg
followed by 75 mg daily for 12 months,
 anticoagulant therapy (e.g. unfractionated or
fractionated heparin)
 β-blocker (e.g. atenolol 50-100 mg daily or
metoprolol 50-100 mg 12-hourly
 A dihydropyridine calcium antagonist (e.g.
nifedipine or amlodipine) can be added to the βblocker, but may cause an unwanted tachycardia if
used alone; verapamil or diltiazem is therefore the
calcium antagonist of choice if a β-blocker is
contraindicated
An intravenous infusion of unfractionated heparin
(with dose adjusted according to the activated
partial thromboplastin time) or weight-adjusted
subcutaneous low molecular weight heparin (e.g.
enoxaparin 1 mg/kg 12-hourly) should be given
 If pain persists or recurs, infusions of intravenous
nitrates (e.g. GTN 0.6-1.2 mg/hr or isosorbide
dinitrate 1-2 mg/hr) or buccal nitrates may help,
but such patients should also be considered for
early revascularisation.
 Refractory cases or those with haemodynamic
compromise should be considered for a
glycoprotein IIb/IIIa receptor antagonist (e.g.
abciximab, tirofiban or eptifibatide), intra-aortic
balloon pump or emergency coronary angiography .
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Most low-risk patients stabilise with aspirin,
clopidogrel, heparin and anti-anginal therapy, and
can be gradually mobilised. If there are no
contraindications,
exercise testing may be performed prior to or
shortly following discharge.
Coronary angiography should be considered with a
view to revascularisation in all patients at
moderate or high risk, including those who fail to
settle on medical therapy, those with extensive
ECG changes, those with an elevated plasma
troponin and those with severe pre-existing stable
angina.
This often reveals disease that is amenable to PCI ;
however, if the lesions are not suitable for PCI the
patient should be considered for urgent CABG.
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MYOCARDIAL INFARCTION
 Myocardial infarction (MI) is almost always due to
the formation of occlusive thrombus at the site of
rupture or erosion of an atheromatous plaque in a
coronary artery.
 The thrombus often undergoes spontaneous lysis
over the course of the next few days, although by
this time irreversible myocardial damage has
occurred.
 Without treatment the infarct-related artery
remains permanently occluded in 30% of patients.
 The process of infarction progresses over several
hours and therefore most patients present when it
is still possible to salvage myocardium and improve
outcome.
CLINICAL FEATURES
 Pain is the cardinal symptom of MI, but
breathlessness, vomiting, and collapse or syncope
are common features.
 The pain occurs in the same sites as angina but is
usually more severe and lasts longer;
 It is often described as a tightness, heaviness or
constriction in the chest. At its worst, the pain is
one of the most severe which can be experienced
and the patient's expression and pallor may vividly
convey the seriousness of the situation
 Most patients are breathless and in some this is the
only symptom. Indeed, some myocardial infarcts
pass unrecognised.
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Painless or 'silent' myocardial infarction is
particularly common in older or diabetic patients.
If syncope occurs, it is usually due to an
arrhythmia or profound hypotension. Vomiting and
sinus bradycardia are often due to vagal
stimulation and are particularly common in patients
with inferior MI.
Nausea and vomiting may also be caused or
aggravated by opiates given for pain relief.
Sometimes infarction occurs in the absence of
physical signs.
Sudden death, from ventricular fibrillation or
asystole, may occur immediately, and many deaths
occur within the first hour.
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If the patient survives this most critical stage, the
liability to dangerous arrhythmias remains, but
diminishes as each hour goes by.
The development of cardiac failure reflects the
extent of myocardial damage and is the major
cause of death in those who survive the first few
hours of infarction.
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Physical signs
Signs of sympathetic activation
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Signs of vagal activation
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Hypotension, oliguria, cold peripheries
Narrow pulse pressure
Raised jugular venous pressure
Third heart sound
Quiet first heart sound
Diffuse apical impulse
Lung crepitations
Signs of tissue damage
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Vomiting, bradycardia
Signs of impaired myocardial function
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Pallor, sweating, tachycardia
Fever
Signs of complications, e.g. mitral regurgitation,
pericarditis
INVESTIGATIONS :
 Electrocardiography The ECG is usually helpful in
confirming the diagnosis; however, it may be
difficult to interpret if there is bundle branch block
or evidence of previous MI.
 Only rarely is the initial ECG entirely normal, but in
up to one-third of cases the initial ECG changes
may not be diagnostic.
 The earliest ECG change is usually ST elevation;
later on there is diminution in the size of the R
wave, and in transmural (full thickness) infarction
a Q wave begins to develop.
 Subsequently, the T wave becomes inverted, this
change persists after the ST segment has returned
to normal.
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In contrast to transmural lesions, partial thickness
or subendocardial infarction causes ST/T wave
changes, without Q waves or prominent ST
elevation; this is often accompanied by some loss
of the R waves in the leads facing the infarct and is
also known as non-Q wave or non-ST elevation
myocardial infarction.
The ECG changes are best seen in the leads that
'face' the infarcted area.
When there has been anteroseptal infarction,
abnormalities are found in one or more leads from
V1 to V4
while anterolateral infarction produces changes
from V4 to V6, in aVL and in lead I.
Inferior infarction is best shown in leads II, III and
aVF, while at the same time leads I, aVL and the
anterior chest leads may show 'reciprocal' changes
of ST depression
 Infarction of the posterior wall of the left ventricle
does not cause ST elevation or Q waves in the
standard leads, but can be diagnosed by the
presence of reciprocal changes (ST depression and
a tall R wave in leads V1-V4).
 Some infarctions (especially inferior) also involve
the right ventricle; this may be identified by
recording from additional leads placed over the
right precordium.
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The serial evolution of ECG changes in full thickness
myocardial infarction.
A. Normal ECG complex.
B. Acute ST elevation ('the current of injury').
C. Progressive loss of the R wave, developing Q wave,
resolution of the ST elevation and terminal T wave
inversion.
D. Deep Q wave and T wave inversion.
E. Old infarction
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Plasma biochemical markers
The biochemical markers that are most widely used
in the detection of MI are creatine kinase (CK), a
more sensitive and cardiospecific isoform of this
enzyme (CK-MB), and the cardiospecific proteins,
troponins T and I
The troponins are also released, to a minor degree,
in unstable angina with minimal myocardial
damage Serial (usually daily) estimations are
particularly helpful because it is the change in
plasma concentrations of these markers that is of
diagnostic value.
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CK starts to rise at 4-6 hours, peaks at about 12
hours and falls to normal within 48-72 hours.
CK is also present in skeletal muscle, and a modest
rise in CK (but not CK-MB) may sometimes be due
to an intramuscular injection, vigorous physical
exercise or, in old people particularly, a fall.
Defibrillation causes significant release of CK but
not CK-MB or troponins. The most sensitive
markers of myocardial cell damage are the cardiac
troponins T and I, which are released within 4-6
hours and remain elevated for up to 2 weeks.
Other blood tests A leucocytosis is usual, reaching a
peak on the first day. The erythrocyte
sedimentation rate (ESR) becomes raised and may
remain so for several days. C-reactive protein
(CRP) is also elevated in acute MI.
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Chest X-ray
This may demonstrate pulmonary oedema that is
not evident on clinical examination The heart size
is often normal but there may be cardiomegaly due
to pre-existing myocardial damage.
Echocardiography
This can be performed at the bedside and is a very
useful technique for assessing left and right
ventricular function and for detecting important
complications such as mural thrombus, cardiac
rupture, ventricular septal defect, mitral
regurgitation and pericardial effusion.
EARLY MANAGEMENT OF ACUTE MYOCARDIAL
INFARCTION
Provide facilities for defibrillation
Immediate measures:
 High-flow oxygen
 I.v. access
 ECG monitoring
 12-lead ECG
 I.v. analgesia (opiates) and antiemetic
 Aspirin 300 mg
Reperfusion
 Primary PCI or thrombolysis
Detect and manage acute complications
 Arrhythmias
 Ischaemia
 Heart failure
 Patients are usually managed in a dedicated
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cardiac unit because this offers a convenient way of
concentrating the necessary expertise, monitoring
and resuscitation facilities.
If there are no complications, the patient can be
mobilised from the second day and discharged from
hospital on the fifth or sixth day.
Analgesia
 Adequate analgesia is essential not only to
relieve severe distress, but also to lower
adrenergic drive and thereby reduce
pulmonary and systemic vascular resistance
and susceptibility to ventricular
arrhythmias.
 Intravenous opiates (initially morphine
sulphate 5-10 mg or diamorphine 2.5-5 mg)
and antiemetics (initially metoclopramide
10 mg) should be administered through an
intravenous cannula.
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Acute reperfusion therapy
Thrombolysis:
 Coronary thrombolysis helps restore coronary
patency, preserves left ventricular function and
improves survival.
 Successful thrombolysis leads to reperfusion with
relief of pain, resolution of acute ST elevation and
sometimes transient arrhythmias (e.g.
idioventricular rhythm).
 The sooner the patient is treated, the better the
results will be; any delay will only increase the
extent of myocardial damage-'minutes mean
muscle'.
Clinical trials have shown that the
appropriate use of these drugs can reduce
the hospital mortality of myocardial
infarction by 25%-50% and follow-up
studies have demonstrated that this
survival advantage is maintained for at least
10 years.
 The benefit is greatest in those patients
who receive treatment within the first few
hours, and choice of agent is less important
than speed of treatment.
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Streptokinase, 1.5 million U in 100 ml of saline
given as an intravenous infusion over 1 hour, is a
widely used regimen. Streptokinase is antigenic
and occasionally causes serious allergic
manifestations. It may also cause hypotension,
which can often be managed by stopping the
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slower rate.
Circulating neutralising antibodies are formed
following treatment with streptokinase and may
persist for 5 years or more.
These antibodies can render subsequent infusions
of streptokinase ineffective so it is advisable to use
another non-antigenic agent if the patient requires
further thrombolysis in the future.
Alteplase (human tissue plasminogen activator or
tPA) is a genetically engineered drug that is not
antigenic and seldom causes hypotension. The
standard regimen is given over 90 minutes (bolus
dose of 15 mg, followed by 0.75 mg/kg body
weight, but not exceeding 50 mg, over 30 minutes
and then 0.5 mg/kg
body weight, but not exceeding 35 mg, over 60
minutes).
 There is evidence that tPA may produce better
survival rates than streptokinase, particularly
among high-risk patients (e.g. large anterior
infarct), but with a slightly higher risk of
intracerebral bleeding (10 per 1000 increased
survival, but 1 per 1000 more non-fatal stroke).
 Newer-generation analogues of tPA have been
generated that have a longer plasma half-life and
can be given as an intravenous bolus. Large-scale
trial data have demonstrated that tenecteplase
(TNK) is as effective as alteplase at reducing death
and MI whilst conferring similar intracerebral
bleeding risks.
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Reteplase (rPA) is administered as a double bolus
and trial data indicate a similar outcome to that
achieved with alteplase, although some of the
bleeding risks appear slightly higher. The double
bolus administration may provide practical
advantages over the infusion of alteplase.
An overview of all the large randomised trials
confirms that thrombolytic therapy significantly
reduces short-term mortality in patients with
suspected MI if it is given within 12 hours of the
onset of symptoms and the ECG shows bundle
branch block or characteristic ST segment elevation
of greater than 1 mm in the limb leads or 2 mm in
the chest leads.
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Thrombolysis appears to be of little net benefit, and
may be harmful in other patient groups, specifically
those who present more than 12 hours after the
onset of symptoms and those with a normal ECG or
ST depression.
The major hazard of thrombolytic therapy is
bleeding.
RELATIVE CONTRAINDICATIONS TO THROMBOLYTIC
THERAPY (POTENTIAL CANDIDATES FOR PRIMARY
ANGIOPLASTY)
 Active internal bleeding
 Previous subarachnoid or intracerebral
haemorrhage
 Uncontrolled hypertension
 Recent surgery (within 1 month)
 Recent trauma (including traumatic resuscitation)
 High probability of active peptic ulcer
 Pregnancy
Primary percutaneous coronary intervention (PCI)
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In institutions that are able to offer rapid access
(within 3 hours) to a 24-hour catheter laboratory
service, percutaneous coronary intervention is the
treatment of choice.
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In comparison to thrombolytic therapy, it is
associated with a 50% greater reduction in the risk
of death, recurrent myocardial infarction or stroke.
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The widespread use of PCI has been limited by the
availability of the resources necessary to achieve
this highly specialized emergency service.
As a consequence, intravenous thrombolytic
therapy remains the first-line reperfusion
treatment in many hospitals.
For some patients, thrombolytic therapy is
contraindicated or fails to achieve coronary arterial
reperfusion. Early emergency PCI (within 6 hours
of symptom onset) may be considered under such
circumstances, particularly where there is evidence
of cardiogenic shock.
Acute right
Coronary art.
Occlusion.
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Initial angio: Filling defect
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Complete resolution of flow following insertion of stent