1-cardiovascular diseases lecturs - 1.pptx

CARDIOVASCULAR DISEASES
CHD
Dr. KHALID O.MOHSIN
D.M.C.A.B.M
INTERNAL MEDICINE DEPARTMENT
MISANUNIVERSITY /COLLEGE OF MEDICNE
ACADEMIC YEAR 2014-2015

CORONARY HEART DISEASE
• Coronary heart disease (CHD) is the
most common form of heart disease and
the single most important cause of
premature death in Europe, Russia,
North and South America, Australia and
New Zealand. By 2020 it is estimated
that it will be the major cause of death
in all regions of the world.

• In the UK (population 59 million), 1 in 3 men and 1
in 4 women die from CHD, an estimated 330 000
people have a myocardial infarct each year and
approximately 1.3 million people have angina.
• The death rates from CHD in the UK are amongst
the highest in Western Europe (more than 140 000
people) but are falling, particularly in younger age
groups; in the last 10 years CHD mortality has fallen
by 42% among UK men and women aged 16-64.

Coronary Artery Disease
• Coronary artery disease is one of the most common and
serious effects of aging. Fatty deposits build up in blood
vessel walls and narrow the passageway for the
movement of blood. The resulting condition, called
atherosclerosis often leads to eventual blockage of the
coronary arteries and a “heart attack”.

CHD
•Vascular disease is the common underlying
disease process for MI, ischemia and vascular
death.
•Acute coronary syndrome (ACS) is a classic
example of the progression of vascular disease
to an ischemic event.
•ACS (in common with ischemic stroke and
critical leg ischemia) is typically caused by
rupture or erosion of an atherosclerotic plaque
followed by formation of a platelet-rich
thrombus.

CHD
• Atherosclerosis is an ongoing process affecting mainly large and
medium-sized arteries, which can begin in childhood and
progress throughout a person’s lifetime.
• Stable atherosclerotic plaques may encroach on the lumen of
the artery and cause chronic ischemia, resulting in (stable)
angina pectoris or intermittent claudication, depending on the
vascular bed affected.
• Unstable atherosclerotic plaques may rupture, leading to the
formation of a platelet-rich thrombus that partially or
completely occludes the artery and causes acute ischemic
symptoms.

CHD
Acute coronary syndrome (ACS), stroke, and peripheral vascular
disease (PAD) are all caused by the same underlying disease
process—vascular disease.
[1] Acute coronary syndrome (ACS) is a classic example of the
progression of vascular disease to an ischemic event, with
platelets playing a central role in the development of the thrombi
and subsequent ischemic events. In ACS, rupture or erosion of an
atherosclerotic plaque leads to platelet adhesion, activation, and
aggregation, resulting in the formation of a platelet-rich
thrombus. Patients who have vascular disease in one vascular
bed have an increased lifetime risk for experiencing a thrombotic
event (eg, MI, stroke, and cardiovascular [CV] death)

CHD
Platelets play a central role in the
development of thrombi and subsequent
ischemic events. The process of platelet-
mediated thrombus formation involves
adhesion, activation, and aggregation.
Handin RI. Bleeding and thrombosis. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison’s Principles of Internal Medicine. Vol 1. 14th ed.
New York, NY: McGraw-Hill; 1998:339-345.
Schafer AI. Antiplatelet therapy. Am J Med. 1996;101:199-209.

CHD
Within seconds of injury, platelets adhere to collagen fibrils through glycoprotein
(GP) Ia/IIa receptors.
An adhesive glycoprotein, von Willebrand factor (vWF) allows platelets to stay
attached to the subendothelial vessel wall (via GP Ib) despite high shear forces.
Following adhesion, platelets are activated to secrete a variety of agonists including
thrombin, serotonin, adenosine diphosphate (ADP), and thromboxane A2 (TXA2).
These agonists, which further augment the platelet activation process, bind to
specific receptor sites on the platelets to activate the GP IIb/IIIa receptor complex,
the final common pathway to platelet aggregation. Once activated, the GP IIb/IIIa
receptor undergoes a conformational change that enables it to bind with
fibrinogen.[1,2]
Handin RI. Bleeding and thrombosis. In: Fauci AS, Braunwald E, Isselbacher KJ, et al, eds. Harrison’s Principles of Internal Medicine. Vol 1. 14th ed. New York, NY:
McGraw-Hill; 1998:339-345.
Schafer AI. Antiplatelet therapy. Am J Med. 1996;101:199-209.

Signs and Symptoms
• None: This is referred to as silent
ischemia. Blood to your heart may be
restricted due to CAD, but you don’t feel
any effects.
• Chest pain: If your coronary arteries can’t
supply enough blood to meet the oxygen
demands of your heart, the result may be
chest pain called angina.
• Shortness of breath: Some people may not
be aware they have CAD until they
develop symptoms of congestive heart
failure- extreme fatigue with exertion,
shortness of breath and swelling in their
feet and ankles.
• Heart attack: Results when an artery to
your heart muscle becomes completely
blocked and the party of your heart
muscles fed by that artery dies.
Signs &
Symptoms
None
Chest
Pain
Shortness
Of Breath
Heart
Attack

• Disease of the coronary arteries is almost always due
to atheroma and its complications, particularly
thrombosis; the common clinical manifestations and
pathological correlates of CHD are shown in (TABLE 5 ).
• Occasionally, the coronary arteries are involved in
other disorders such as
1-Aortitis
2-polyarteritis
3-Other connective tissue disorders.

TABLE 5 CORONARY HEART DISEASE: CLINICAL MANIFESTATIONS AND PATHOLOGY
Clinical problem Pathology
Stable angina Ischaemia due to fixed atheromatous
stenosis of one or more coronary arteries
Unstable angina Ischaemia caused by dynamic obstruction
of a coronary artery due to plaque rupture
with superimposed thrombosis and spasm
Myocardial infarction Myocardial necrosis caused by acute
occlusion of a coronary artery due to
plaque rupture and thrombosis
Heart failure Myocardial dysfunction due to infarction
or ischaemia
Arrhythmia Altered conduction due to ischaemia or
infarction
Sudden death Ventricular arrhythmia, asystole or
massive myocardial infarction

•Weak relationship between severity of pain and degree
of oxygen supply- there can be severe pain with minimal
disruption of oxygen supply or no pain in severe cases
•Four types:
Stable angina
Unstable angina
Microvascular angina
Prinzmetal’s angina

Stable angina:
•Also called “Effort Angina”
•Discomfort is precipitated by activity
•Minimal or no symptoms at rest
•Symptoms disappear after rest/cessation of activity

Unstable angina:
•Also called “Crescendo angina”
•Acute coronary syndrome in which angina worsens
•Occurs at rest
•Severe and of acute onset
•Crescendo pain- pain increases every time

Microvascular angina:
•Also called Syndrome X
•Cause unknown
•Probably due to poor functioning of the small blood
vessels of the heart, arms and legs
•No arterial blockage
•Difficult to diagnose because it does not have arterial
blockage
•Good prognosis

Prinzmetal’s angina
•Prinzmetal’s angina is a variant form of angina with
normal coronary vessels or minimal atherosclerosis
•It is probably caused by spasm of coronary artery

Angina pectoris
• Angina Defined
Angina pectoris is a clinical syndrome
• typically characterized by discomfort in the
• chest, jaw, shoulder, back or arm. Typically
• aggravated by exertion or emotional stress
• and relieved by nitroglycerine
• Typically occurs in patients with CAD
• involving at least one large epicardial artery

Angina Types
1-Chronic Stable Angina: - a chronic and predictable
development of chest pain upon exertion
2-Unstable Angina: - a critical condition characterized by the
*-unpredictable development of chest pain at rest or during
minimal exertion.
*- It is either accompanied by an increase in frequency and/or
severity of
*-pain within the recent (weeks to 1 or 2 months) past
3-Vasospastic Angina or Prinzmetal’s Angina:
- is characterized by the unprovoked coronary artery spasm
resulting in chest pain.

Angina Types
Chronic Stable Angina: -
*-a chronic and predictable development of
chest pain upon exertion
*- Patients rely on antianginal medication
degrees of activity however, may be prophylax
with sublingual nitrates based on anticipated
exertions

Angina Types
Unstable Angina (UA): - a critical condition
characterized by the
*- unpredictable development of chest pain at rest or during minimal
exertion. It is
*-either accompanied by an increase in frequency and/or severity of
pain within the recent (weeks to 1 or 2 months) past.
*-Patients with unstable angina are admitted to an acute care setting
and managed aggressively with nitrates, beta-blockers, CCBA’s,
*-antiplatelets and anticoagulants.
UA is part of the spectrum of acute coronary
syndromes (ACS) see ACS lectures)

Angina Types
• Vasospastic Angina or Prinzmetal’s Angina: -
*-is characterized by the unprovoked coronary
artery spasm resulting in chest pain.
*-Patients with this angina may be relatively
young and have few or even no cardiac risk
factors
*-the chest pain is often unpredictable and
cyclical in nature, sometimes reverting
spontaneously into remission.

Other Forms of Ischemia
Silent Myocardial Ischemia:
a phenomenon experienced by a large
percentage of patients with ischemic heart
disease who for various reasons do not
perceive chest pain despite EKG changes
onsistent with ischemic heart disease.
Usually diabetic Or elderly

STABLE ANGINA
• Angina pectoris is the symptom complex
caused by transient myocardial
ischaemia and constitutes a clinical
syndrome rather than a disease; it may
occur whenever there is an imbalance
between myocardial oxygen supply and
demand (TABLE 6).

STABLE ANGINA
• Coronary atheroma is by far the most
common cause of angina; however, the
symptom may also be a manifestation of
other forms of heart disease, particularly
• aortic valve disease
• hypertrophic cardiomyopathy.
• Anemias

STABLE ANGINA
This Lecture describes the :
features of 'stable' angina
pectoris which occurs when
coronary perfusion is impaired
by fixed or stable atheroma of
the coronary arteries.

TABLE 6 FACTORS INFLUENCING MYOCARDIAL OXYGEN SUPPLY AND
DEMAND
Oxygen demand
•Cardiac work Heart rate
•Blood pressure
•Myocardial contractility
•Left ventricular hypertrophy
•Valve disease, e.g. aortic stenosis
Oxygen supply
•Coronary blood flow Duration of diastole
•Coronary perfusion pressure (aortic diastolic minus coronary sinus or right atrial diastolic
pressure)
•Coronary vasomotor tone
•Oxygenation
• Haemoglobin
• Oxygen saturation
N.B. Coronary blood flow occurs mainly in diastole

• Heart rate
• Contractility
• Preload
• Afterload
• Coronary flow
• Regional
myocardial blood
flow

O2
D
e
m
a
n
d

O2
S
u
p
p
l
y
-Blockers/Ca2+
channel blockers
Nitrates/Ca2+
channel
blockers
Nitrates/Ca2+
channel
blockers/antithrombotics/
statins
HEART

Clinical features
•The history is by far the
most important factor
in making the diagnosis.

Clinical features
• Stable angina is characterised by
• central chest pain, discomfort or
breathlessness that is precipitated
by exertion or other forms of stress
(Table 7),
• and is promptly relieved by rest

TABLE 7 ACTIVITIES PRECIPITATING ANGINA
Common
•Physical exertion
•Cold exposure
•Heavy meals
•Intense emotion
Uncommon
•Lying flat (decubitus angina)
•Vivid dreams (nocturnal angina)

Clinical features
• Some patients find that the
discomfort comes when they
start walking, and that later it
does not return despite greater
effort ('warm-up angina').

Clinical features
• Physical examination is
1- Frequently negative
2- But should include a careful search for evidence of valve
disease (particularly aortic)
3- Important risk factors (e.g. hypertension, diabetes)
4- Left ventricular dysfunction (e.g. cardiomegaly, gallop rhythm)
5- Other manifestations of arterial disease (e.g. carotid bruits,
peripheral vascular disease)
6- Unrelated conditions that may exacerbate angina (e.g.
anaemia, thyrotoxicosis).

Investigations
• Resting ECG
• The ECG may show evidence of previous
myocardial infarction but is often normal even
in patients with left main or severe three-
vessel coronary artery disease.
• Occasionally, there is T-wave flattening or
inversion in some leads, providing non-specific
evidence of myocardial ischaemia or damage.

• Figure 6
• Forms of exercise-induced ST depression.
Planar ST depression is usually indicative of
myocardial ischaemia.
Down-sloping depression also usually
indicates myocardial ischaemia.
Up-sloping depression, however, may be a
normal finding.

Figure 6 A positive exercise test.
• A positive exercise test. The resting 12-lead
ECG shows some minor T-wave changes in the
inferolateral leads but is otherwise normal.
After 3 minutes' exercise on a treadmill there
is marked planar ST depression in leads II, V4
and V5 (right offset). Subsequent coronary
angiography revealed critical three-vessel
coronary artery disease.

Figure 6 A positive exercise test. The resting 12-lead
ECG shows some minor T-wave changes in the
inferolateral leads but is otherwise normal. After 3
minutes' exercise on a treadmill there is marked
planar ST depression in leads II, V4 and V5 (right
offset). Subsequent coronary angiography revealed
critical three-vessel coronary artery disease.

TABLE 8 A GUIDE TO RISK STRATIFICATION IN STABLE
ANGINA
High risk Low risk
Post-infarct angina Predictable exertional angina
Poor effort tolerance Good effort tolerance
Ischaemia at low workload Ischaemia only at high workload
Left main or three-vessel
disease
Single-vessel or minor two-
vessel disease
Poor LV function Good LV function
N.B. Patients may fall between these categories.

STABLE ANGINA
• The most convincing ECG evidence of
myocardial ischaemia is obtained by
demonstrating reversible ST segment
depression or elevation, with or without
T-wave inversion, at the time the patient
is experiencing symptoms (whether
spontaneous or induced by exercise
testing).

STABLE ANGINA
• Exercise ECG
• An exercise tolerance test (ETT) is usually performed using a
standard treadmill or bicycle ergometer protocol
• while monitoring the patient's ECG, blood pressure and
general condition.
• Planar or down-sloping ST segment
depression of 1 mm or more is indicative of
ischaemia (Fig. 6);
• up-sloping ST depression is less specific and often occurs in
normal individuals.

STABLE ANGINA
• Exercise testing can be used to
confirm or refute a diagnosis of
angina and is also a useful means of
assessing the severity of coronary
disease and identifying high-risk
individuals
• (Table8).

STABLE ANGINA
• For example, the amount of
exercise which can be tolerated
and the extent and degree of any
ST segment change (Fig. 7)
provide a useful guide to the
likely extent of coronary disease.

Figure 7 A positive exercise test. The resting 12-lead ECG
shows some minor T-wave changes in the inferolateral leads
but is otherwise normal. After 3 minutes' exercise on a
treadmill there is marked planar ST depression in leads II, V4
and V5 (right offset). Subsequent coronary angiography
revealed critical three-vessel coronary artery disease.

STABLE ANGINA
Exercise testing is not infallible and may
produce false positive results in the presence
of
Digoxin therapy
Left ventricular hypertrophy
Left bundle branch block
Wolff-Parkinson-White syndrome.

STABLE ANGINA
The predictive accuracy of exercise testing
is lower in women than men.
The test should be classed as inconclusive
(and not negative) if the patient cannot
achieve an adequate level of exercise
because of locomotor or other non-
cardiac problems.

STABLE ANGINA
Other forms of stress
testing Myocardial
perfusion scanning

Myocardial perfusion scanning
• This may be helpful in the
evaluation of patients with an
equivocal or uninterpretable
exercise test and those who are
unable to exercise; its predictive
accuracy is higher than that of
the exercise ECG.

• The technique involves obtaining scintiscans of
the myocardium at rest and during stress after
the administration of an inravenous
radioactive isotope such as 99
technetium
tetrofosmin.
• It may be used in conjunction with
conventional exercise testing or some form of
pharmacological stress such as a controlled
infusion of dobutamine.

• Thallium and tetrofosmin are taken up by
viable perfused myocardium.
• A perfusion defect present during stress but
not rest provides evidence of reversible
myocardial ischaemia (Fig. 8), whereas a
persistent perfusion defect seen during both
phases of the study is usually indicative of
previous myocardial infarction.

Figure 8 A technetium scan showing reversible anterior myocardial ischaemia. The images
are cross-sectional tomograms of the left ventricle. The resting scans (right) show even
uptake of technetium and look like doughnuts; during stress (in this case a dobutamine
infusion) there is reduced uptake of technetium, particularly along the anterior wall (arrows),
and the scans look like crescents (left).

• Stress echocardiography
• This is an alternative to myocardial perfusion scanning and
can achieve similar predictive accuracy (superior to
exercise ECG).
• The technique uses transthoracic echocardiography to
identify ischaemic segments of myocardium and areas of
infarction.
• The former characteristically exhibit reversible defects in
contractility during exercise or pharmacological stress with
a dobutamine infusion; the latter typically do not contract
at rest or during stress.

Coronary Arteriography
Coronary arteriography
In contrast to the functional information
provided by stress testing, coronary
arteriography provides detailed
anatomical information about the
extent and nature of coronary artery
disease (Fig. 9),

Figure 9 Coronary angiogram from a patient
with stable angina. There is severe stenosis of
the left main stem (arrow).

Coronary Arteriography
Usually performed with a view to coronary bypass grafting
or percutaneous coronary intervention (PCI).
In some patients, diagnostic coronary angiography may be
indicated when non-invasive tests have failed to
elucidate the cause of atypical chest pain.
The procedure is performed under local anaesthesia and
requires
specialised radiological equipment
cardiac monitoring
an experienced operating team.

Management
• The management of angina pectoris involves:
• a careful assessment of the likely extent and severity
of arterial disease
• the identification and control of significant risk
factors (e.g. smoking, hypertension,
hyperlipidaemia)
• the use of measures to control symptoms
• the identification of high-risk patients and
application of treatments to improve life expectancy.

Management
Symptoms alone are a poor guide to the extent
of coronary artery disease; exercise or
pharmacological stress testing is therefore
advisable in all patients who are potential
candidates for revascularisation.
An algorithm for the investigation and
treatment of patients with stable angina is
shown in Figure 10.

Figure 10 A scheme for the investigation and treatment of stable angina on effort. (PCI = percutaneous
coronary intervention; CABG = coronary artery bypass grafting)

Management
Treatment should start with a careful
explanation of the problem and a
discussion of the potential lifestyle
and medical interventions that may
relieve symptoms and improve
prognosis (Table 8).

Management
Anxiety and misconceptions often contribute to
disability; for example, some patients avoid all
forms of exertion because they believe that
each attack of angina is a 'mini heart attack'
that results in permanent damage.
Effective management of these psychological
factors can make a huge difference to the
patient's quality of life.

ADVICE TO PATIENTS WITH STABLE ANGINA
*Do not smoke
• Aim at ideal body weight
• Take regular exercise (exercise up to, but not
beyond, the point of chest discomfort is beneficial
and may promote collateral vessels)
• Avoid severe unaccustomed exertion, and vigorous
exercise after a heavy meal or in very cold weather
• Take sublingual nitrate before undertaking
exertion that may induce angina

Antiplatelet therapy
• Low-dose (75-150 mg) aspirin
• reduces the risk of adverse events
• such as myocardial infarction
• and should be prescribed for all
patients with coronary artery
disease indefinitely .

Antiplatelet therapy
• Clopidogrel (75 mg daily) is an equally effective antiplatelet
agent that can be prescribed if aspirin causes troublesome
dyspepsia or other side-effects.
• Anti-anginal drug treatment
• Four groups of drugs are used to help relieve or prevent the
symptoms of angina:
• Nitrates
• β-blockers
• Calcium antagonists
• Potassium channel activators.

Nitrates
• Nitrates
• These drugs act directly on vascular smooth
muscle to produce venous and arteriolar
dilatation; their beneficial effects in angina are
due to a reduction in myocardial oxygen
demand (lower preload and afterload) and an
increase in myocardial oxygen supply
(coronary vasodilatation).

Nitrates
• Sublingual glyceryl trinitrate (GTN) administered
from a metered-dose aerosol (400 μg per spray) or as
a tablet (300 or 500 μg) allowed to dissolve under the
tongue or crunched and retained in the mouth will
usually relieve an attack of angina in 2-3 minutes.
• Unwanted side-effects include headache (which may
be more distressing than the angina), symptomatic
hypotension and, rarely, syncope. To avoid these
symptoms the tablet may be spat out as soon as the
angina is relieved.

Nitrates
Patients often need to be reassured that GTN is not habit-
forming and will not lose its effect if used repeatedly.
They should also be encouraged to use the drug
prophylactically before engaging in exercise that is liable to
provoke symptoms.
Sublingual GTN has a short duration of action (Table 11)
however, a variety of alternative nitrate preparations can
provide a more prolonged therapeutic effect.
GTN can be given transcutaneously as a patch (5-10 mg
daily), or as a slow-release buccal tablet (1-5 mg 6-hourly).

Nitrates
GTN is subject to extensive first-pass metabolism
in the liver and is therefore virtually ineffective
when swallowed;
however, other nitrates such as isosorbide
dinitrate (10-20 mg 8-hourly) and isosorbide
mononitrate (20-60 mg once or twice a day) can
be given by mouth.
Headache is common but tends to diminish if the
patient perseveres with the treatment.

Nitrates
Continuous nitrate therapy causes pharmacological
tolerance and this should be avoided by using a regimen
that includes a nitrate-free period of 6-8 hours every day.
A variety of once-daily proprietary preparations with a
built-in nitrate-free period are available.
It is usually advisable to schedule the medication so that
drug levels are low during the night when the patient is
inactive; however, if nocturnal angina is a prominent
symptom, long-acting nitrates can be given at the end of
the day instead.

TABLE 11 DURATION OF ACTION OF SOME NITRATE PREPARATIONS
Preparation Peak action Duration of
action
Sublingual GTN 4-8 mins 10-30 mins
Buccal GTN 4-10 mins 30-300 mins
Transdermal GTN 1-3 hrs Up to 24 hrs
Oral isosorbide
dinitrate
45-120 mins 2-6 hrs
Oral isosorbide
mononitrate
45-120 mins 6-10 hrs

Beta-blockers
• Beta-blockers
• These drugs lower myocardial oxygen
demand by reducing heart rate, blood
pressure and myocardial contractility.
• Unfortunately, they can exacerbate the
symptoms of peripheral vascular disease and
may provoke bronchospasm in patients with
obstructive airways disease.

Beta-blockers
In theory, non-selective β-blockers may
aggravate coronary vasospasm by blocking the
coronary artery β2-adrenoceptors and it is
usually advisable to use a once-daily
cardioselective preparation (e.g. atenolol 50-
100 mg daily, slow-release metoprolol 50-200
mg daily, bisoprolol 5-10 mg daily).

Beta-blockers
A β-blocking drug should not be withdrawn
abruptly because this may have a
rebound effect and precipitate
dangerous arrhythmias, worsening
angina or myocardial infarction (the β-
blocker withdrawal syndrome).

CALCIUM ANTAGONISTS (CCB)
• Calcium antagonists
• These drugs inhibit the slow inward current
caused by the entry of extracellular calcium
through the cell membrane of excitable cells,
particularly cardiac and arteriolar smooth
muscle, and lower myocardial oxygen demand
by reducing blood pressure and myocardial
contractility.

CALCIUM ANTAGONISTS
• Dihydropyridine calcium antagonists, such as
nifedipine and nicardipine, often cause a reflex
tachycardia; this may be counterproductive and 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.

CALCIUM ANTAGONISTS
• The calcium antagonists may reduce
myocardial contractility and can
aggravate or precipitate heart failure.
• Other unwanted effects include
peripheral oedema, flushing,
headache and dizziness.

CCB
• The dosage and some of the
distinguishing features of these drugs
are listed Table 12.

TABLE 12 CALCIUM ANTAGONISTS USED FOR THE
TREATMENT OF ANGINA
Drug Dose Feature
Nifedipine 5-20 mg 8-hourly* May cause marked
tachycardia
Nicardipine 20-40 mg 8-hourly May cause less
myocardial depression
than the other drugs in
this group
Amlodipine 2.5-10 mg daily Ultralong-acting skin
allergy
* Once- or twice-daily slow-release preparations are
available.

TABLE 12 CALCIUM ANTAGONISTS USED FOR THE
TREATMENT OF ANGINA
Drug Dose Feature
Verapamil 40-80 mg 8-hourly* Commonly causes
constipation; useful
anti-arrhythmic
properties
Diltiazem 60-120 mg 8-
hourly*
Similar anti-
arrhythmic
properties to
verapamil
* Once- or twice-daily slow-release preparations are available.

Potassium channel activators
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.

Drugs in stable angina pectoris
• Although each of these groups of drug has
been shown to be superior to placebo in
relieving the symptoms of angina, there is little
convincing evidence that one group is more
effective than another.
• Moreover, many commonly used
combinations of anti-anginal drugs have not
been evaluated in well-controlled clinical trials.

• Nevertheless, it is conventional to start therapy
with
• Low-dose aspirin
• Sublingual GTN
• A β-blocker
• Then add a calcium channel antagonist
or a long-acting nitrate later, if necessary.

• 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
1-Percutaneous coronary intervention
(PCI) including percutaneous
transluminal coronary angioplasty,
PTCA)
2-Coronary artery bypass graft (CABG)
surgery.

Invasive treatment
• Percutaneous coronary intervention (PCI)
• This is performed by passing a fine
guidewire across a coronary stenosis
under radiographic control and using it to
position a balloon which is then inflated
to dilate the stenosis ( Fig. 11).

Figure 11 Percutaneous coronary intervention. A sequence of images from a 58-
year-old woman with stable angina. Severe stenosis of the circumflex artery
(arrow). A balloon has been advanced into the stenosis, over a guidewire, and has
been inflated. (Note the waisting caused by the lesion.) Residual stenosis and
dissection (tramline shadow-arrow) after balloon dilatation. A stent is deployed
on a balloon. The stent is visible on plain fluoroscopy (arrow). Angiogram after
stenting. A short balloon is used to dilate the stent at high pressure. Final result.

Figure 11 Percutaneous coronary intervention. A sequence of images from a 58-
year-old woman with stable angina. Severe stenosis of the circumflex artery
(arrow). A balloon has been advanced into the stenosis, over a guidewire, and
has been inflated. (Note the waisting caused by the lesion.) Residual stenosis
and dissection (tramline shadow-arrow) after balloon dilatation. A stent is
deployed on a balloon. The stent is visible on plain fluoroscopy (arrow).
Angiogram after stenting. A short balloon is used to dilate the stent at high
pressure. Final result.

Figure 11 Percutaneous coronary intervention. A sequence of images from a 58-year-old woman with
stable angina. Severe stenosis of the circumflex artery (arrow). A balloon has been advanced into the
stenosis, over a guidewire, and has been inflated. (Note the waisting caused by the lesion.) Residual
stenosis and dissection (tramline shadow-arrow) after balloon dilatation. A stent is deployed on a balloon.
The stent is visible on plain fluoroscopy (arrow). Angiogram after stenting. A short balloon is used to
dilate the stent at high pressure. Final result.

Invasive treatment
• A coronary stent is a piece of coated metallic
'scaffolding' that can be deployed on a balloon
and used to maximise and maintain dilatation
of a stenosed vessel.
• The routine use of stents in appropriate
vessels reduces both acute complications and
the incidence of clinically important restenosis
(Table 13).

Invasive treatment
• PCI provides an effective
symptomatic treatment but there
is no evidence that it improves
survival in patients with chronic
stable angina.

Invasive treatment
PCI is mainly used in single or two-vessel
disease; stenoses in bypass grafts can be
dilated as well as those in the native
coronary arteries, and the technique is
often used to provide palliative therapy
for patients with recurrent angina after
CABG.

Invasive treatment
Coronary surgery is usually the preferred option
in patients with
Three-vessel
Left main disease
although recent trials have demonstrated
that PCI is also feasible in such patients.

TABLE 13 ANGIOPLASTY AND INTRACORONARY
STENTS IN ANGINA
'In comparison with simple balloon
angioplasty, intracoronary stents
afford superior acute and long-term
clinical and angiographic results with
lower rates of
Restenosis (e.g. 17% vs 40%)
Recurrent angina (13% vs 30%).'

TABLE 14 PERCUTANEOUS CORONARY INTERVENTION
VS MEDICAL THERAPY IN STABLE ANGINA
'PCI is more effective than medical therapy for
Alleviating angina pectoris
Improving exercise tolerance
Does not reduce mortality.
It carries risks of
Procedure-related myocardial infarction,
Emergency coronary artery bypass grafting
Repeat procedures for restenosis

PCI
• The main acute complications of PCI are
• occlusion of the target vessel or a side branch by
thrombus or a loose flap of intima (coronary artery
dissection), and consequent myocardial damage.
• This occurs in about 2-5% of procedures and can
often be corrected by deploying a stent; however,
emergency CABG is sometimes required.

PCI
• Minor myocardial damage, as
indicated by elevation of
sensitive intracellular markers
(troponins), occurs in up to
10% of cases.

PCI
The main long-term complication of PCI is
restenosis (Table 14), which occurs in up
to one-third of cases; this is due to a
combination of
elastic recoil and smooth muscle
proliferation (neo-intimal hyperplasia)
and tends to occur within 3 months.

PCI
• Drug-eluting stents can reduce this
risk even further by allowing an
antiproliferative drug, such as
sirolimus or paclitaxel, to elute slowly
from the coating and prevent neo-
intimal hyperplasia and in-stent
restenosis.

PCI
• Recurrent angina (affecting up
to 15-20% of patients receiving
an intracoronary stent at 6
months) may require further
PCI or bypass grafting.

PCI
The risk of complications and the likely
success of the procedure are closely
related to the morphology of the
stenoses, the experience of the operator
and the presence of important
comorbidity (e.g. diabetes, peripheral
arterial disease).

PCI
A good outcome is less likely if the target lesion is
Complex
Long
Eccentric or calcified
Lies on a bend or within a tortuous vessel
Involves a branch
Contains acute thrombus.

PCI
In combination with Aspirin and Heparin
adjunctive therapy with Potent platelet
inhibitors, such as clopidogrel or
glycoprotein IIb/IIIa receptor antagonists
has been shown to improve the outcome of
PCI, with lower short- and long-term rates of
death and myocardial infarction.

CABG
Coronary artery bypass grafting (CABG)
The internal mammary arteries
(LIMA), radial arteries or reversed
segments of the patient's own
saphenous vein (SVG) can be used to
bypass coronary artery stenoses (Figs 12
and 13).

Figure 12 Coronary artery bypass graft surgery. Narrowed or stenosed
arteries are bypassed using saphenous vein grafts connected to the
aorta, or by utilising the internal mammary artery.

Figure 13 Three-dimensional reconstruction of multislice computed tomography of the heart.
The image shows the patent saphenous vein grafts (SVG) to the right coronary artery (RCA),
obtuse marginal branch (OM) and diagonal branch (LADD), and left internal mammary artery
graft (LIMA) to the left anterior descending (LAD) coronary artery.

CABG
This usually involves major surgery under
cardiopulmonary bypass, but in some cases,
grafts can be applied to the beating heart: 'off-
pump' surgery.
The operative mortality is approximately 1.5%,
but risks are higher in elderly patients, those
with poor left ventricular function and those
with significant comorbidity, such as renal
failure.

TABLE 15 CORONARY ARTERY BYPASS GRAFTING
(CABG) FOR STABLE ANGINA
'CABG is superior to medical treatment
for at least 10 years after surgery in
terms of survival.
Greatest benefit occurred in those with
Asignificant stenosis in the left main
coronary artery
Those with three-vessel disease
Impaired ventricular function.

CABG
• Approximately 90% of patients are free of
angina 1 year after surgery, but fewer than
60% of patients are asymptomatic 5 or more
years after CABG.
• Early post-operative angina is usually due to
graft failure arising from technical problems
during the operation or poor 'run off' due to
disease in the distal native coronary vessels.

CABG
Late recurrence of angina may
be due to
Progressive disease in the
native coronary arteries
Graft degeneration.

CABG
• Less than 50% of vein grafts are patent 10
years after surgery.
• However, arterial grafts have a much better
long-term patency rate with more than 80%
of internal mammary artery grafts patent at
10 years.
• This has lead many surgeons to consider
total arterial revascularisation (TAR) during
CABG surgery.

CABG
• Aspirin (75-150 mg daily) and clopidogrel (75 g
daily) have both been shown to improve graft patency,
and one or other should be prescribed indefinitely if well
tolerated.
• Intensive lipid-lowering therapy has also been
shown to slow the progression of disease in the native
coronary arteries and bypass grafts, and to reduce clinical
cardiovascular events;
• Serum LDL cholesterol concentrations should
therefore be reduced below 3.2 mmol/l ( 120 mg/dl).
∼

CABG
• There is substantial excess cardiovascular
morbidity and mortality in patients who
continue to smoke after bypass grafting.
• Persistent smokers are twice as likely to
die in the 10 years following surgery
compared with those who give up at
surgery.

CABG
CABG has been shown to improve survival in patients with
1- Left main coronary stenosis
2- Symptomatic patients with three-vessel
coronary disease (i.e. involving left anterior
descending, circumflex and right coronary
arteries, Table 15)
3- Two-vessel disease involving the proximal
left anterior descending coronary artery.

CABG
Improvement in survival is most marked in those
with
1- Impaired left ventricular function
2- Positive stress testing prior to
surgery
3- Those who have undergone left
internal mammary artery grafting.

CABG
Neurological complications are common, with a
1-5% risk of perioperative stroke.
Between 30% and 80% of patients develop short-
term cognitive impairment that is often mild
and typically resolves within 6 months.
There are also reports of long-term cognitive
decline that may be evident in more than 30%
of patients at 5 years.

Table 16 COMPARISON OF PERCUTANEOUS CORONARY INTERVENTION
(PCI) AND CORONARY ARTERY BYPASS GRAFTING (CABG)
PCI CABG
Death < 0.5% < 1.5%
Myocardial infarction* 2% 10%
Hospital stay 12-36 hrs 5-8 days
Return to work 2-5 days 6-12 weeks
Recurrent angina 15-20% at 6 months 10% at 1 year
Repeat revascularisation 10-20% at 2 years 2% at 2 years
Neurological
complications
Rare Common (see text)
Other complications Emergency CABG
Vascular damage related to
access site
Diffuse myocardial damage
Infection (chest, wound)
Wound pain
* Defined as CK-MB > 2 ×normal

TABLE17 COMPARISON OF PERCUTANEOUS CORONARY INTERVENTION (PCI)
VS CORONARY ARTERY BYPASS GRAFT (CABG) SURGERY IN STABLE ANGINA
'Systematic reviews and meta-analyses have found
similar rates of death, Myocardial infarction and
Quality of life.
PCI is associated with a greater need for
repeat procedures, although this has been
halved by the introduction of intracoronary
stent implantation.
For patients with multi-vessel disease or
diabetes, CABG appears to confer better
survival rates at 4-5 years.

Prognosis
1-Symptoms are a poor guide to prognosisn
2-Nevertheless, the 5-year mortality of patients
with severe angina (NYHA class III or IV ) is nearly
double that of patients with mild symptoms.
3-Exercise testing and other forms of stress testing
are much more powerful predictors of mortality;
for example, in one study, the 4-year mortality of
patients with stable angina and a negative
exercise test was 1%, compared to more than
20% in those with a strongly positive test.

Prognosis
In general, the prognosis of coronary
artery disease is related to the
1-Number of diseased vessels (one-,
two- or three-vessel coronary artery
disease)
2-The degree of left ventricular
dysfunction.

Prognosis
• A patient with single-vessel disease and good LV
function has an excellent outlook (5-year
survival > 90%)
• whereas a patient with severe LV dysfunction
and extensive three-vessel disease has a poor
prognosis (5-year survival < 30%) without
revascularisation.
• Spontaneous symptomatic improvement due to
the development of collateral vessels is
common.

ANGINA WITH NORMAL CORONARY
ARTERIES
• Approximately 10% of patients who report
stable angina on effort will be found to have
angiographically normal coronary arteries.
• Many of these patients are women and the
mechanism of their symptoms is often difficult
to establish.
• It is important to review the original diagnosis
and explore other potential causes.

ARTERIES
• Coronary artery spasm
• Vasospasm in coronary arteries may coexist with
atheroma, especially in unstable angina
• occasionally (< 1% of all cases of angina), however,
vasospasm may occur without angiographically
detectable atheroma.
• This form of angina is sometimes known as variant
angina and may be accompanied by spontaneous and
transient ST elevation on the ECG (Prinzmetal's
angina).

ARTERIES
• Calcium antagonists, nitrates and
other coronary vasodilators (e.g.
nicorandil) are the most useful
therapeutic agents but may be
ineffective.

ARTERIES
• Syndrome X
• The constellation of typical angina on effort,
objective evidence of myocardial ischaemia on
stress testing, and angiographically normal
coronary arteries is sometimes known as
syndrome X.
• This disorder is poorly understood but carries a
good prognosis and may respond to treatment
with anti-anginal therapy.

Worldwide Statistics
Each year:
• > 4 million patients are admitted
with unstable angina and acute MI
• > 900,000 patients undergo PTCA
with or without stent

PROGNOSIS
Of those who survive an acute attack
More than 80% live for a further year
About 75% for 5 years
50% for 10 years
25% for 20 years.

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