CORONARY ARTERY DISEASE
This is the commonest cause of heart disease and the single most important cause
of death worldwide. It is almost always due to narrowing of the coronary arteries
by atherosclerosis, but sometimes may be caused by non- atherosclerotic
inflammatory CAD e.g. connective tissue disease.
Clinical manifestations and pathology:
• Stable angina: defined as reversible ischemia due to fixed atheromatous
obstruction of one or more coronary arteries.
• Unstable angina: ischemia caused by dynamic (transient) 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 myocardial infarction or ischemia
• Arrhythmia: altered conduction due to ischemia or infarction
• Sudden death: which is caused by ventricular arrhythmia, asystole, or massive
myocardial infarction
Chronic stable angina pectoris
Angina is a symptom complex caused by transient interruption of myocardial
blood flow. It is caused by a fixed obstruction to the coronary artery by coronary
atheroma, but may also occur in other conditions e.g. aortic stenosis and
hypertrophic cardiomyopathy, in which angina occurs despite the absence of
coronary stenosis.
Pathophysiology:
• Symptoms occur because of imbalance of myocardial oxygen supply and
demand.
• Factors determining myocardial oxygen demand include heart rate, myocardial
contractility, and left ventricular afterload
• Factors influencing myocardial oxygen supply (coronary blood flow) include
duration of diastole (heart rate), coronary perfusion pressure (Aortic _ coronary
sinus or RA pressure), coronary vasomotor tone, oxygen content of blood (i.e.
Hb concentration, oxygen tension).
Clinical Features: Symptoms
• Chest pain: usually, it is discomfort rather than pain. The site of the pain may
be the chest, back, upper abdomen, neck, shoulder, left arm, right arm, or lower
jaw.
It may be felt in any of the areas of radiation without being felt in the
chest. It is aggravated by
exercise, emotion, heavy meals, intercourse, or
exposure to cold. It is relieved by rest, or sublingual nitroglycerine. The pain is
described as oppressing, crushing, squeezing, or vice-like.
• Sometimes ischemia may manifest as exertional dyspnea (angina-equivalent
dyspnea).
Clinical Features: Signs
Physical examination is usually normal in between the attacks. It should focus on the
predisposing conditions and consequences, e.g. obesity, xanthomas and xanthelasma,
hypertension, valvular disease (aortic stenosis), anemia, thyrotoxicosis, LV
dysfunction (cardiomegaly, gallop rhythm), carotid bruits, and peripheral vascular
disease.
Differential Diagnosis:
Angina should be differentiated from the following conditions:
• Other forms of IHD: unstable angina, myocardial infarction
• Pericarditis
• Aortic dissection
• Pulmonary embolism
• Pneumothorax
• Extra-cardiac conditions: Esophageal spasm, peptic ulcer, cholelithiasis, etc.
Investigations:
These include resting ECG, exercise ECG, other stress testing, and coronary
angiography.
Resting ECG:
This is usually normal, even with the most severe forms of coronary artery
involvement. ECG features of angina include ST segment depression or elevation at
the time of exercise which revert to normal at rest. The pattern of ST depression is
unique to ischemia: it is horizontal or down-sloping.
Exercise Tolerance Test (ETT):
The test should be interpreted carefully. Not all positive tests indicate IHD (false
positive), on the other hand, a negative ETT does not always rule out IHD (false
negative). The result of the test should be interpreted in view of the likelihood of the
patient to have IHD.
Criteria of high risk ETT include:
– Low threshold for ischemia (early occurrence of ST segment changes)
– Fall in BP during exercise
– Widespread, marked or prolonged ischemic changes
– Exercise-induced arrhythmia
Other forms of stress testing:
These include myocardial perfusion scanning and stress echo (exercise echo and
dobutamine stress echo).
Coronary angiography:
Determines the anatomic nature of the disease i.e. the number of vessels involved, the
site of involvement, the extent of disease in each vessel, and the status of the left
ventricle. It is usually done for patients in whom mechanical intervention (i.e. CABG
or PCI) are contemplated, and is not done for all patients with chronic stable angina.
Indications for coronary angiography:
• When exercise testing gives high risk positive result
• In patients with stable angina who survive cardiac arrest
• In patients with serious ventricular arrhythmias
• Recurrence of angina after myocardial revascularization
• When non-invasive testing fails to identify the cause of atypical chest pain
Aims of management:
The aim of non interventional management is NOT to decrease the atheroma size
but to change its constituents so that the lipid core becomes smaller and the
fibrous cap thicker, thereby rendering the atheromatous plaque less liable for
rupture.
Management strategies:
• Treat and abolish symptoms
• Identify and treat risk factors
• Identify and treat other complications of atherosclerosis (e.g. cerebrovascular,
renovascular etc.)
• Select patients who should undergo mechanical intervention
Steps of Management:
• Exercise testing
• Life style modification
• Pharmacologic therapy:
– To control symptoms
– To control risk factors
• Intervention
Stress Testing: Should be performed in all patients with chronic stable angina to
identify the level of risk and to serve as a background against which to compare
during future assessment.
ETT should be repeated routinely every year to follow
up the patient. Also, it should be repeated in case of any exacerbation of ymptoms
or change in angina pattern.
Life Style Modification: cessation of smoking, control of obesity, sticking to a
healthy diet (rich in fibers and low-fat dairy products, deficient in saturated fat and
cholesterol), and regular exercise short of the point that produces angina: this may
promote the development of collaterals, it should never be continued if angina
develops. Severe unaccustomed exercise should be avoided, as is exercise after
heavy meal or in the cold.
Pharmacologic Therapy of Angina:
• Antiplatelet agents: Aspirin, clopidogrel
• Statins
• Anti-anginal drugs: nitrates, beta blockers, calcium channel blockers.
Antiplatelet Therapy:
• Asprin: low dose (75-100 mg/day) should be administered for life.
• Clopidogrel: may be an alternative to ASA in patients who develop side effects
Statins:
Administered to keep LDL level ≤ 100 mg/dl (2.5 mmol/L). They should be
administered at night. Side effects include hepatic injury and myositis.
Anti-anginal Drugs:
Nitrates: these include:
• Short acting nitrates: glyceryl trinitrate (GTN) preparations:
– Sublingual tablets
– Sublingual spray
– Buccal
– Transdermal GTN
• Long acting nitrates:
– isosorbide dinitrate
– Isosorbide mononitrate
Side Effects of Nitrates:
• Headache: usually subsides with continuation of treatment.
• Nitrate tolerance:
– Loss of action when nitrates are continuously administered throughout
the day
– Avoided by allowing 6-8 hours nitrate-free interval
• Pronounced hypotension:
– Especially in patients who have taken sildenafil (Viagra)
– Nitrates should never be administered within 24 hours of ingesting
Viagra
• May cause syncope
Anti-anginal Drugs: β-Blockers:
• Cardio-selective β-blockers: e.g. atenolol, metoprolol, bisoprolol. They block
β-1 but not β-2 adrenergic receptors, and have less extracardiac side effects
(e.g. asthma)
• Non-cardioselective β-blockers: e.g. propranolol, nadolol, carvedilol
• Β-blockers with intrinsic sympathetic activity: e.g. pindolol, oxprenolol: not to
be used in angina
• Mechanism of Action in Angina: reduce myocardial oxygen consumption by
reducing heart rate, blood pressure, and myocardial contractility.
Side Effects of β-blockers
• Cardiovascular: Bradycardia and heart block, hypotension, worsening of heart
failure, and possible exacerbation of peripheral vascular disease.
• Extracardiac side effects: bronchospasm: especially with non-selective forms
Implementation of β-blockers
• Should be introduced in a dose sufficient to reduce the heart rate (50-60/min at
rest)
• They should not be withdrawn abruptly from the patient as this may precipitate
myocardial infarction
• Some β-Blockers are useful in the presence of LV systolic dysfunction e.g.
bisoprolol, carvedilol, metoprolol
Anti-anginal Drugs: Calcium Channel Blockers (Calcium antagonists)
Two major groups:
• Dihydropyridines e.g. nifedipine, amlodipine
• Non-dihydropyridines: verapamil, diltiazem
Mechanism of action:
They act by inhibiting the slow calcium influx into excitable tissue of vascular
smooth muscle cells and myocardium causing relaxation:
• Reduce blood pressure
• Reduce myocardial contractility
• Non-dihydropyridines also reduce heart rate
Side Effects of Calcium Antagonists:
• Non-dihydropyridine group may cause severe bradycardia and congestive
failure
• Dihydropyridine group may cause reflex tachycardia but have minimal effect
on contractility
• Other S.E: headache, flushing, constipation, edema, polyruia
Strategy in Antianginal Therapy:
• First, a short-acting GTN is used
• Then, a β-blocker is added
• If symptoms persist, either a calcium antagonist (preferably non-
dihydropyridine) or a long-acting nitrate is added
Mechanical Intervention
• Percutaneous Coronary Intervention (PCI), also called percutaneous
transluminal coronary angioplasty (PTCA)
• Coronary Artery Bypass Grafting (CABG)
PCI:
• Provides effective symptomatic treatment
• There is no evidence that it prolongs survival in patients with chronic stable
angina
• Patients with 3-vessel disease or LMCA are increasingly treated by PCI
• The main problem is recurrence of stenosis.
CABG
• Usually through a midline sternotomy incision
• Grafts are liable for degeneration or recurrence of atherosclerosis
• Arterial conduits survive longer than venous ones
Prognosis of Stable Angina
This is determined by:
• The patient’s performance on exercise testing
• The number of vessels involved
• The status of LV function
Accordingly,
• The patient with angina & negative ETT has 1% four-year mortality
• Strongly positive ETT is associated with >20% four-year mortality
• Single vessel disease with good LV: > 90% five-year survival
• Three vessel disease with poor LV: < 30% five-year survival without
revascularization.