9. 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, the Baltic states, 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, 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 140000 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.
 However, in Eastern Europe and much of
Asia, the rates of CHD are rapidly rising.

 Disease of the coronary arteries is almost
always due to atheroma and its
complications, particularly thrombosis.
 Occasionally, the coronary arteries are
involved in other disorders such as aortitis,
polyarteritis and other connective tissue
disorders.

 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.

 Coronary atheroma is by far the most
common cause of angina, although the
symptom may be a manifestation of other
forms of heart disease, particularly aortic
valve disease and hypertrophic
cardiomyopathy.

 The history is by far the most important factor
in making the diagnosis.
 Stable angina is characterized by central
chest pain, discomfort or breathlessness that
is precipitated by exertion or other forms of
stress, and is promptly relieved by rest.

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

 Physical examination is frequently
unremarkable but should include a careful
search for evidence of valve disease
(particularly aortic), important risk factors
(e.g. hypertension, diabetes mellitus), left
ventricular dysfunction (cardiomegaly, gallop
rhythm), other manifestations of arterial
disease (carotid bruits, peripheral vascular
disease) and unrelated conditions that may
exacerbate angina (anaemia, thyrotoxicosis).

1) Resting ECG:
 The ECG may show evidence of previous MI
but is often normal, even in patients with
severe coronary artery disease.
 Occasionally, there is T-wave flattening or
inversion in some leads, providing non-
specific evidence of myocardial ischaemia or
damage.

 The most convincing ECG evidence of
myocardial ischaemia is the demonstration of
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).

 An exercise tolerance test (ETT) is usually
performed using a standard treadmill or
bicycle ergometer protocol while monitoring
the patient’s ECG, BP and general condition.
 Planar or down-sloping ST segment
depression of ≥ 1mm is indicative of
ischaemia.

 Up-sloping ST depression is less specific and
often occurs in normal individuals.
 Exercise testing is also a useful means of
assessing the severity of coronary disease
and identifying high risk individuals.

 For example, the amount of exercise that can
be tolerated and the extent and degree of
any ST segment change provide a useful
guide to the likely extent of coronary disease.

 Exercise testing is not infallible and may
produce false positive results in the presence
of digoxin therapy, left ventricular
hypertrophy, bundle branch block or WPW
syndrome.

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

- 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.

 It entails obtaining scintiscans of the
myocardium at rest and during stress (either
exercise testing or pharmacological stress,
such as a controlled infusion of dobutamine)
after the administration of an intravenous
radioactive isotope, such as 99technetium
tetrofosmin.
 Thallium and tetrofosmin are taken up by
viable perfused myocardium.

 A perfusion defect
present during stress
but not at rest provides
evidence of reversible
myocardial ischaemia,
whereas a persistent
perfusion defect seen
during both phases of
the study is usually
indicative of previous
MI.

- Stress echocardiography:
 This is an alternative to myocardial perfusion
scanning and can achieve similar predictive
accuracy. It 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, and the
latter do not contract at rest or during stress.

 This provides detailed anatomical information
about the extent and nature of coronary
artery disease, and is usually performed with
a view to coronary artery bypass graft
(CABG) surgery or percutaneous coronary
intervention.

 In some patients, diagnostic coronary
angiography may be indicated when non-
invasive tests have failed to establish the
cause of atypical chest pain.
 The procedure is performed under local
anaesthesia and requires specialised
radiological equipment, cardiac monitoring
and an experienced operating team.

1) General measures:
 The management of angina pectoris
involves:
-a careful assessment of the likely extent and
severity of arterial disease.
-the identification and control of risk factors
such as smoking, hypertension and
hyperlipidaemia.

-the use of measures to control symptoms.
-the identification of high-risk patients for
treatment to improve life expectancy.

 Symptoms alone
are a poor guide to
the extent of
coronary artery
disease.
 Stress testing is
therefore advisable
in all patients who
are potential
candidates for
revascularisation.

 Management 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.

 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.

 Low-dose (75mg) aspirin reduces the risk of
adverse events such as MI and should be
prescribed for all patients with coronary
artery disease indefinitely.
 Clopidogrel (75mg daily) is an equally
effective antiplatelet agent that can be
prescribed if aspirin causes troublesome
dyspepsia or other side-effects.

 Five groups of drug are used to help relieve
or prevent the symptoms of angina: nitrates,
β-blockers, calcium antagonists, potassium
channel activators and an If channel
antagonist.

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

 Sublingual glyceryl trinitrate (GTN)
administered from a metered-dose aerosol
(400 μg per spray) or as a tablet (300 or 500
μg) will relieve an attack of angina in 2–3
minutes.
 Side-effects include headache, symptomatic
hypotension and, rarely, syncope.

 Patients should be encouraged to use the
drug prophylactically before taking exercise
that is liable to provoke symptoms.
 Sublingual GTN has a short duration of
action; however, a variety of alternative
nitrate preparations can provide a more
prolonged therapeutic effect.

 GTN can be given transcutaneously as a
patch (5–10mg daily), or as a slow-release
buccal tablet (1–5mg 6-hourly).
 GTN undergoes extensive first-pass
metabolism in the liver and is ineffective
when swallowed.

 Other nitrates such as isosorbide dinitrate
(10–20mg 8-hourly) and isosorbide
mononitrate (20–60mg once or twice a day)
can be given by mouth.
 Headache is common but tends to diminish if
the patient perseveres with the treatment.

 Continuous nitrate therapy can cause
pharmacological tolerance.
 This can be avoided by a 6–8-hour nitrate-
free period, best achieved at night when the
patient is inactive.
 If nocturnal angina is a predominant
symptom, long-acting nitrates can be given
at the end of the day.

b) Beta-blockers:
 These lower myocardial oxygen demand by
reducing heart rate, BP and myocardial
contractility, but they may provoke
bronchospasm in patients with asthma.

 In theory, non-selective β-blockers may
aggravate coronary vasospasm by blocking
the coronary artery β2-adrenoceptors and so
a once-daily cardioselective preparation is
used (e.g. slow-release metoprolol 50–
200mg daily, bisoprolol 5–15mg daily).

 Beta-blockers should not be withdrawn
abruptly because this may have a rebound
effect and precipitate dangerous arrhythmias,
worsening angina or MI: the β-blocker
withdrawal syndrome.

c) Calcium channel 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 BP and myocardial
contractility.

 Dihydropyridine calcium antagonists, such as
nifedipine and nicardipine, often cause a
reflex tachycardia.
 This may be counterproductive and it is best
to use them in combination with a β-blocker.

 In contrast, verapamil and diltiazem are
particularly suitable for patients who are not
receiving a β-blocker (e.g. those with airways
obstruction) because they slow SA node
firing, inhibit conduction through the AV node
and tend to cause a bradycardia.

 Calcium channel antagonists reduce
myocardial contractility and can aggravate or
precipitate heart failure.
 Other unwanted effects include peripheral
oedema, flushing, headache and dizziness.

d) Potassium channel activators:
 These have arterial and venous dilating
properties but do not exhibit the tolerance
seen with nitrates.
 Nicorandil (10–30mg 12-hourly orally) is the
only drug in this class currently available for
clinical use.

:e) If channel antagonist
 Ivabradine is the first of this class of drug.
 It induces bradycardia by modulating ion
channels in the sinus node.
 In contrast to β-blockers and rate-limiting
calcium antagonists, it does not have other
cardiovascular effects.
 It appears to be safe to use in patients with
heart failure.

 Although each of these anti-anginal drugs is
superior to placebo in relieving the symptoms
of angina, there is little evidence that one
group is more effective than another.

 It is conventional to start therapy with low-
dose aspirin, a statin, sublingual GTN and a
β-blocker, and then add a calcium channel
antagonist or a long-acting nitrate later if
needed.
 The goal is the control of angina with
minimum side-effects and the simplest
possible drug regimen.

 There is little evidence that prescribing
multiple anti-anginal drugs is of benefit, and
revascularisation should be considered if an
appropriate combination of two or more
drugs fails to achieve an acceptable
symptomatic response.

a) 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.
 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.

 PCI provides an effective symptomatic
treatment but definitive evidence that it
improves survival in patients with chronic
stable angina is lacking.
 It 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.

 The technique is often used to provide
palliative therapy for patients with recurrent
angina after CABG.
 Coronary surgery is usually the preferred
option in patients with three-vessel or left
main stem disease, although recent trials
have demonstrated that PCI is also feasible
in such patients.

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

 The main long-term complication of PCI is
restenosis, 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.

 Stenting substantially reduces the risk of
restenosis, probably because it allows the
operator to achieve more complete dilatation
in the first place.
 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.

 There is an increased risk of late stent
thrombosis with drug-eluting stents, although
the absolute risk is small (< 0.5%).
 Recurrent angina (affecting up to 15–20% of
patients receiving an intracoronary stent at 6
months) may require further PCI or bypass
grafting.

 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.

 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 or contains acute
thrombus.

 In combination with aspirin and heparin,
adjunctive therapy with potent platelet
inhibitors, such as clopidogrel or glycoprotein
IIb/IIIa receptor antagonists, improves the
outcome of PCI, with lower short- and long-
term rates of death and MI.

b) Coronary artery bypass grafting (CABG):
 The internal mammary arteries, radial
arteries or reversed segments of the patient’s
own saphenous vein can be used to bypass
coronary artery stenoses.
 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.
 Approximately 90% of patients are free of
angina 1 year after CABG surgery, but fewer
than 60% of patients are asymptomatic after
5 or more years.

 Early postoperative 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.
 Late recurrence of angina may be due to
progressive disease in the native coronary
arteries or graft degeneration.
 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 led many surgeons to consider total
arterial revascularisation during CABG
surgery.

 Aspirin (75–150mg daily) and clopidogrel
(75mg daily) have both been shown to
improve graft patency, and one or other
should be prescribed indefinitely if well
tolerated.
 Intensive lipid-lowering therapy slows the
progression of disease in the native coronary
arteries and bypass grafts, and reduces
clinical cardiovascular events.

 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 than those
who give up at surgery.

 CABG improves survival in symptomatic patients
with left main stem stenosis or three-vessel
coronary disease (i.e. involving LAD, CX and right
coronary arteries) or two-vessel disease involving
the proximal LAD coronary artery.

 Improvement in survival is most marked in
those with impaired left ventricular function or
positive stress testing prior to surgery and
those who have undergone left internal
mammary artery grafting.

 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.

 Symptoms are a poor guide to prognosis;
nevertheless, the 5-year mortality of patients
with severe angina (NYHA class III or IV) is
nearly double that of patients with mild
symptoms.

 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.

 In general, the prognosis of coronary artery
disease is related to the number of diseased
vessels and the degree of left ventricular
dysfunction.

 A patient with single-vessel disease and
good left ventricular function has an excellent
outlook (5-year survival > 90%), whereas a
patient with severe left ventricular
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.

 Approximately 10% of patients who report
stable angina on effort will 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.

 Vasospasm in coronary arteries may coexist
with atheroma, especially in unstable angina;
in < 1% of cases, 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).
 Calcium channel antagonists, nitrates and
other coronary vasodilators are the most
useful therapeutic agents but may be
ineffective.

 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.

 Acute coronary syndrome is a term that
encompasses both unstable angina and MI.
 Unstable angina is characterized by new-
onset or rapidly worsening angina
(crescendo angina), angina on minimal
exertion or angina at rest in the absence of
myocardial damage.

 In contrast, MI occurs when symptoms occur
at rest and there is evidence of myocardial
necrosis, as demonstrated by an elevation in
cardiac troponin or creatine kinase-MB
isoenzyme.
 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.
 This is a dynamic process whereby the
degree of obstruction may either increase,
leading to complete vessel occlusion, or
regress due to the effects of platelet
disaggregation and endogenous fibrinolysis.

 In acute MI, occlusive thrombus is almost
always present at the site of rupture or
erosion of an atheromatous plaque.
 The thrombus may undergo 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 20–30% of
patients.
 The process of infarction progresses over
several hours and most patients present
when it is still possible to salvage
myocardium and improve outcome.

 Pain is the cardinal symptom of an acute
coronary syndrome but breathlessness,
vomiting, and collapse 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.

 In acute MI, the pain can be excruciating,
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, MI may
pass unrecognised.
 Painless or ‘silent’ MI is particularly common
in older patients or those with diabetes
mellitus.

 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 VF or asystole, may
occur immediately and often within the first
hour.
 If the patient survives this most critical stage,
the liability to dangerous arrhythmias
remains, but diminishes as each hour goes
by.

 It is vital that patients know not to delay
calling for help if symptoms occur.
 The development of cardiac failure reflects
the extent of myocardial ischaemia and is the
major cause of death in those who survive
the first few hours.

 The differential diagnosis is wide and
includes most causes of central chest pain or
collapse.
 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.

 A 12-lead ECG is mandatory and defines the
initial triage, management and treatment.
 Patients with ST segment elevation or new
bundle branch block require emergency
reperfusion therapy.

 In patients with acute coronary syndrome
without ST segment elevation, the ECG may
show transient or persistent ST/T wave
changes including ST depression and T-
wave inversion.
 Approximately 12% of patients will die within
1 month and a fifth within 6 months of the
index event.

 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, recurrent ischaemia and
haemodynamic complications (e.g.
hypotension, mitral regurgitation) during
episodes of ischaemia.

 Risk stratification is important because it
guides the use of more complex
pharmacological and interventional
treatment.

1) Electrocardiography:
 The ECG is central to confirming the
diagnosis but may be difficult to interpret if
there is bundle branch block or previous MI.

 The initial ECG may be normal or non-
diagnostic in one-third of cases.
 Repeated ECGs are important, especially
where the diagnosis is uncertain or the
patient has recurrent or persistent symptoms.
 The earliest ECG change is usually ST-
segment deviation.

 With proximal occlusion of a major coronary
artery, ST-segment elevation (or new bundle
branch block) is seen initially with later
diminution in the size of the R wave, and in
transmural (full thickness) infarction,
development of a Q wave.

 Subsequently, the T wave becomes inverted
because of a change in ventricular
repolarisation; this change persists after the
ST segment has returned to normal.
 These sequential features are sufficiently
reliable for the approximate age of the infarct
to be deduced.

 In non-ST segment elevation acute coronary
syndrome, there is partial occlusion of a
major vessel or complete occlusion of a
minor vessel, causing unstable angina or
partial thickness (subendocardial) MI.
 This is usually associated with ST-segment
depression and T-wave changes.

 In the presence of
infarction, this may be
accompanied by some
loss of R waves in the
absence of Q waves.

 The ECG changes are best seen in the leads
that ‘face’ the ischaemic or 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 LV 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 RV.
 This may be identified by recording from
additional leads placed over the right
precordium.

2) PLASMA CARDIAC MARKERS:
 In unstable angina, there is no detectable
rise in cardiac markers or enzymes, and the
initial diagnosis is made from the clinical
history and ECG only.
 In contrast, MI causes a rise in the plasma
concentration of enzymes and proteins that
are normally concentrated within cardiac
cells.

 These biochemical markers are creatine
kinase (CK), a more sensitive and
cardiospecific isoform of this enzyme (CK-
MB), and the cardiospecific proteins,
troponins T and I.
 Admission and serial (usually daily)
estimations are helpful because it is the
change in plasma concentrations of these
markers that confirms the diagnosis of MI.

 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,
particularly in older people, 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.

3) OTHER BLOOD TESTS:
 A leucocytosis is usual, reaching a peak on
the first day.
 The erythrocyte sedimentation rate (ESR)
and C-reactive protein (CRP) are also
elevated.

4) 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.

5) ECHOCARDIOGRAPHY:
 This is useful 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.

 Patients should be admitted urgently to
hospital because there is a significant risk of
death or recurrent myocardial ischaemia
during the early unstable phase, and
appropriate medical therapy can reduce the
incidence of these by at least 60%.

 Patients are usually managed in a dedicated
cardiac unit where the necessary expertise,
monitoring and resuscitation facilities can be
concentrated.
 If there are no complications, the patient can
be mobilised from the second day and
discharged from hospital after 3–5 days.

 Adequate analgesia is essential not only to
relieve distress, but also to lower adrenergic
drive and thereby reduce vascular
resistance, BP, infarct size and susceptibility
to ventricular arrhythmias.

 Intravenous opiates (initially morphine
sulphate 5–10 mg or diamorphine 2.5–5 mg)
and antiemetics (initially metoclopramide
10mg) should be administered and titrated by
giving repeated small aliquots until the
patient is comfortable.

 Intramuscular injections should be avoided
because the clinical effect may be delayed by
poor skeletal muscle perfusion, and a painful
haematoma may form following thrombolytic
or anti-thrombotic therapy.

- Antithrombotic therapy:
a) Antiplatelet therapy:
 In patients with acute coronary syndrome,
oral administration of 75–300mg aspirin daily
improves survival, with a 25% relative risk
reduction in mortality.
 The first tablet (300mg) should be given
orally within the first 12 hours and therapy
should be continued indefinitely if there are
no side-effects.

 In combination with aspirin, the early (within 12
hours) use of clopidogrel 600 mg, followed by 150
mg daily for 1 week and 75mg daily thereafter,
confers a further reduction in ischaemic events.

 In patients with an acute coronary syndrome
with or without ST-segment elevation,
ticagrelor (180 mg followed by 90 mg 12-
hourly) is more effective than clopidogrel in
reducing vascular death, MI or stroke, and
all-cause death without affecting overall
major bleeding risk.

 Glycoprotein IIb/IIIa receptor antagonists,
such as tirofiban and abciximab, block the
final common pathway of platelet
aggregation and are potent inhibitors of
platelet-rich thrombus formation.

 They are of particular benefit in patients with
acute coronary syndromes who undergo PCI,
those with recurrent ischaemia and those at
particularly high risk, such as patients with
diabetes mellitus or an elevated troponin
concentration.

b) Anticoagulants:
 Anticoagulation reduces the risk of thromboembolic
complications, and prevents reinfarction in the
absence of reperfusion therapy or after successful
thrombolysis.

 Anticoagulation can be achieved using
unfractionated heparin, fractioned (low
molecular weight) heparin or a
pentasaccharide.
 Comparative clinical trials suggest that the
pentasaccharides (subcutaneous
fondaparinux 2.5mg daily) have the best
safety and efficacy profile, with low molecular
weight heparin (subcutaneous enoxaparin
1mg/kg 12-hourly) being a reasonable
alternative.

 Anticoagulation should be continued for 8
days or until discharge from hospital or
coronary revascularisation.
 A period of treatment with warfarin should be
considered if there is persistent atrial
fibrillation or evidence of extensive anterior
infarction, or if echocardiography shows
mobile mural thrombus, because these
patients are at increased risk of systemic
thromboembolism.

 Sublingual glyceryl trinitrate (300–500 μg) is
a valuable first-aid measure in unstable
angina or threatened infarction, and
intravenous nitrates (GTN 0.6–1.2mg/hour or
isosorbide dinitrate 1–2mg/hour) are useful
for the treatment of left ventricular failure and
the relief of recurrent or persistent ischaemic
pain.

 Intravenous β-blockers (e.g. atenolol 5–10mg
or metoprolol 5–15mg given over 5mins)
relieve pain, reduce arrhythmias and improve
short-term mortality in patients who present
within 12 hours of the onset of symptoms.
 However, they should be avoided if there is
heart failure (pulmonary oedema),
hypotension (systolic BP < 105mmHg) or
bradycardia (heart rate < 65/min).

 A dihydropyridine calcium channel antagonist
(e.g. nifedipine or amlodipine) can be added
to the β-blocker if there is persistent chest
discomfort but may cause an unwanted
tachycardia if used alone.
 Because of their rate-limiting action,
verapamil and diltiazem are the calcium
channel antagonists of choice if a β-blocker
is contraindicated.

a) Non-ST segment elevation acute coronary
syndrome:
 Immediate emergency reperfusion therapy has no
demonstrable benefit in patients with non-ST
segment elevation MI and thrombolytic therapy may
be harmful.
 Selected medium- to high-risk patients do benefit
from in-hospital coronary angiography and
coronary revascularisation but this does not need to
take place in the first 12 hours.

b) ST segment elevation acute coronary
syndrome:
 Immediate reperfusion therapy restores
coronary artery patency, preserves left
ventricular function and improves survival.
 Successful therapy is associated with pain
relief, resolution of acute ST elevation and
sometimes transient arrhythmias (e.g.
idioventricular rhythm).

Primary percutaneous coronary intervention
(PCI):
 This is the treatment of
choice for ST segment
elevation MI.
 Outcomes are best
when it is used in
combination with
glycoprotein IIb/IIIa
receptor antagonists
and intracoronary stent
implantation.

 In comparison to thrombolytic therapy, it is
associated with a greater reduction in the risk of
death, recurrent MI or stroke.

 The universal use of primary PCI has been
limited by availability of the necessary
resources to provide this highly specialised
emergency service.
 Thus, intravenous thrombolytic therapy
remains the first-line reperfusion treatment in
many hospitals, especially those in rural or
remote areas.

 When primary PCI cannot be achieved within
2 hours of diagnosis, thrombolytic therapy
should be administered.

Thrombolysis:
 The appropriate use of thrombolytic therapy
can reduce hospital mortality by 25–50% and
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:
‘minutes mean muscle’.

 Alteplase (human tissue plasminogen
activator or tPA) is a genetically engineered
drug that is given over 90 minutes (bolus
dose of 15mg, followed by 0.75mg/kg body
weight, but not exceeding 50mg, over
30mins and then 0.5mg/kg body weight, but
not exceeding 35mg, over 60mins).

 Its use is associated with better survival rates
than other thrombolytic agents, such as
streptokinase, but carries a slightly higher
risk of intracerebral bleeding (10 per 1000
increased survival, but 1 per 1000 more non-
fatal stroke).

 Analogues of tPA, such as tenecteplase and
reteplase, have a longer plasma half-life than
alteplase and can be given as an intravenous
bolus.
 Tenecteplase (TNK) is as effective as
alteplase at reducing death and MI whilst
conferring similar intracerebral bleeding
risks.

 However, other major bleeding and
transfusion risks are lower and the practical
advantages of bolus administration may
provide opportunities for prompt treatment in
the emergency department or in the pre-
hospital setting.

 Reteplase (rPA) is administered as a double
bolus and also produces a similar outcome to
that achieved with alteplase, although some
of the bleeding risks appear slightly higher.

 An overview of all the large randomised trials
confirms that thrombolytic therapy reduces
short-term mortality in patients with 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 > 1 mm in the limb leads or 2 mm
in the chest leads.

 Thrombolysis appears to be of little net
benefit and may be harmful in those who
present more than 12 hours after the onset of
symptoms and in those with a normal ECG
or ST depression.

 In patients with ST elevation or bundle
branch block, the absolute benefit of
thrombolysis plus aspirin is approximately 50
lives saved per 1000 patients treated within 6
hours and 40 lives saved per 1000 patients
treated between 7 and 12 hours after the
onset of symptoms.
 The benefit is greatest for patients treated
within the first 2 hours.

 The major hazard of thrombolytic therapy is
bleeding.
 Cerebral haemorrhage causes 4 extra
strokes per 1000 patients treated and the
incidence of other major bleeds is between
0.5% and 1%.
 Accordingly, the treatment should be withheld
if there is a significant risk of serious
bleeding.

 For some patients, thrombolytic therapy is
contraindicated or fails to achieve coronary
arterial reperfusion.
 Early emergency PCI may then be
considered, particularly where there is
evidence of cardiogenic shock.

 Complications are seen in all forms of acute
coronary syndrome, although the frequency
and extent vary with the severity of
ischaemia and infarction.
 Major mechanical and structural
complications are only seen with significant,
often transmural, MI.

 Many patients with acute coronary syndrome
have some form of arrhythmia.
 In the majority of cases this is transient and
of no haemodynamic or prognostic
importance.
 Pain relief, rest and the correction of
hypokalaemia may help prevent them.

a) Ventricular fibrillation:
 This occurs in about 5–10% of patients who
reach hospital and is thought to be the major
cause of death in those who die before
receiving medical attention.
 Prompt defibrillation will usually restore sinus
rhythm and is lifesaving.

 The prognosis of patients with early
ventricular fibrillation (within the first 48
hours) who are successfully and promptly
resuscitated is identical to that of patients
who do not suffer ventricular fibrillation.

b) Atrial fibrillation:
 This is common but frequently transient, and
usually does not require emergency
treatment.
 However, if the arrhythmia causes a rapid
ventricular rate with hypotension or
circulatory collapse, prompt cardioversion by
immediate synchronised DC shock is
essential.

 In other situations, digoxin or a β-blocker is
usually the treatment of choice.
 Atrial fibrillation (due to acute atrial stretch) is
often a feature of impending or overt left
ventricular failure, and therapy may be
ineffective if heart failure is not recognised
and treated appropriately.
 Anticoagulation is required if atrial fibrillation
persists.

c) Bradycardia:
 This does not usually require treatment, but if
there is hypotension or haemodynamic
deterioration, atropine (0.6–1.2mg i.v.) may
be given.
 AV block complicating inferior infarction is
usually temporary and often resolves
following reperfusion therapy.

 If there is clinical deterioration due to
second-degree or complete AV block, a
temporary pacemaker should be considered.
 AV block complicating anterior infarction is
more serious because asystole may
suddenly supervene; a prophylactic
temporary pacemaker should be inserted.

 Patients who develop recurrent angina at
rest or on minimal exertion following an acute
coronary syndrome are at high risk and
should be considered for prompt coronary
angiography with a view to revascularisation.

 Patients with dynamic ECG changes and
ongoing pain should be treated with
intravenous glycoprotein IIb/IIIa receptor
antagonists.
 Patients with resistant pain or marked
haemodynamic changes should be
considered for intra-aortic balloon
counterpulsation and emergency coronary
revascularisation.

 Post-infarct angina occurs in up to 50% of
patients treated with thrombolysis.
 Most patients have a residual stenosis in the
infarct-related vessel despite successful
thrombolysis, and this may cause angina if
there is still viable myocardium downstream.

 For this reason, all patients who have
received successful thrombolysis should be
considered for early (within the first 6–24
hours) coronary angiography with a view to
coronary revascularisation.

 Acute circulatory failure usually reflects
extensive myocardial damage and indicates
a bad prognosis.
 All the other complications of MI are more
likely to occur when acute heart failure is
present.

 This only occurs following infarction and is
particularly common on the second and third
days.
 The patient may recognise that a different
pain has developed, even though it is at the
same site, and that it is positional and tends
to be worse or sometimes only present on
inspiration.

 A pericardial rub may be audible.
 Opiate-based analgesia should be used.
 Non-steroidal and steroidal anti-inflammatory
drugs may increase the risk of aneurysm
formation and myocardial rupture in the early
recovery period, and so should be avoided.

 The post-MI syndrome (Dressler’s syndrome)
is characterised by persistent fever,
pericarditis and pleurisy, and is probably due
to autoimmunity.
 The symptoms tend to occur a few weeks or
even months after the infarct and often
subside after a few days; prolonged or
severe symptoms may require treatment with
high-dose aspirin, NSAIDs or even
corticosteroids.

Part of the necrotic muscle in a fresh infarct
may tear or rupture, with devastating
consequences:
a) Rupture of the papillary muscle can cause
acute pulmonary oedema and shock due to
the sudden onset of severe mitral
regurgitation, which presents with a
pansystolic murmur and third heart sound.

 In the presence of severe valvular
regurgitation, the murmur may be quiet or
absent.
 The diagnosis is confirmed by
echocardiography and emergency mitral
valve replacement may be necessary.
 Lesser degrees of mitral regurgitation due to
papillary muscle dysfunction are common
and may be transient.

b) Rupture of the interventricular septum
causes left-to-right shunting through a
ventricular septal defect.
 This usually presents with sudden
haemodynamic deterioration accompanied
by a new loud pansystolic murmur radiating
to the right sternal border, but may be difficult
to distinguish from acute mitral regurgitation.

 However, patients with an acquired
ventricular septal defect tend to develop right
heart failure rather than pulmonary oedema.
 Doppler echocardiography and right heart
catheterisation will confirm the diagnosis.
 Without prompt surgery, the condition is
usually fatal.

c) Rupture of the ventricle may lead to
cardiac tamponade and is usually fatal,
although it may rarely be possible to support
a patient with an incomplete rupture until
emergency surgery is performed.

 Thrombus often forms on the endocardial
surface of freshly infarcted myocardium.
 This can lead to systemic embolism and
occasionally causes a stroke or ischaemic
limb.
 Venous thrombosis and pulmonary embolism
may occur but have become less common
with the use of prophylactic anticoagulants
and early mobilisation.

 Acute transmural MI is often followed by
thinning and stretching of the infarcted
segment (infarct expansion).
 This leads to an increase in wall stress with
progressive dilatation and hypertrophy of the
remaining ventricle (ventricular remodelling).

 As the ventricle dilates, it becomes less
efficient and heart failure may supervene.
 Infarct expansion occurs over a few days and
weeks but ventricular remodelling can take
years.
 ACE inhibitor therapy reduces late ventricular
remodelling and can prevent the onset of
heart failure.

 A left ventricular aneurysm develops in
approximately 10% of patients with MI and is
particularly common when there is persistent
occlusion of the infarct-related vessel.
 Heart failure, ventricular arrhythmias, mural
thrombus and systemic embolism are all
recognised complications of aneurysm
formation.

 Other clinical features include a paradoxical
impulse on the chest wall, persistent ST
elevation on the ECG, and sometimes an
unusual bulge from the cardiac silhouette on
the chest X-ray.
 Echocardiography is usually diagnostic.
 Surgical removal of a left ventricular
aneurysm carries a high morbidity and
mortality but is sometimes necessary.

 Simple clinical tools can be used to identify
medium-to high-risk patients.
 The GRACE score is a simple method of
calculating early mortality that can help guide
which patients should be selected for
intensive therapy, and specifically early
inpatient coronary angiography.

 The prognosis of patients who have survived
an acute coronary syndrome is related to the
extent of residual myocardial ischaemia, the
degree of myocardial damage and the
presence of ventricular arrhythmias.

Left ventricular function:
 The degree of left ventricular dysfunction can
be crudely assessed from physical findings
(tachycardia, third heart sound, crackles at
the lung bases, elevated venous pressure
and so on), ECG changes and chest X-ray
(size of the heart and presence of pulmonary
oedema).
 However, formal assessment with
echocardiography should be undertaken in
the early recovery phase.

Ischemia:
 Patients with early ischaemia following an
acute coronary syndrome should undergo
coronary angiography with a view to
revascularisation.
 Low-risk patients without spontaneous
ischaemia should undergo an exercise
tolerance test approximately 4 weeks after
the acute coronary syndrome.

 This will help to identify those individuals with
residual myocardial ischaemia who require
further investigation and may help to boost
the confidence of the remainder.
 If the exercise test is negative and the patient
has a good effort tolerance, the outlook is
good, with a 1–4% chance of an adverse
event in the next 12 months.

 In contrast, patients with residual ischaemia
in the form of chest pain or ECG changes at
low exercise levels are at high risk, with a
15–25% chance of suffering a further
ischaemic event in the next 12 months.

Arrhythmias:
 The presence of ventricular arrhythmias
during the convalescent phase of acute
coronary syndrome may be a marker of poor
ventricular function and may herald sudden
death.

 Although empirical anti-arrhythmic treatment
is of no value and even hazardous, selected
patients may benefit from
electrophysiological testing and specific anti-
arrhythmic therapy (including implantable
cardiac defibrillators).

 Recurrent ventricular arrhythmias are
sometimes manifestations of myocardial
ischaemia or impaired left ventricular function
and may respond to appropriate treatment
directed at the underlying problem.

 Smoking:
 The 5-year mortality of patients who continue
to smoke cigarettes is double that of those
who quit smoking at the time of their acute
coronary syndrome.

 Giving up smoking is the single most
effective contribution a patient can make to
his or her future.
 The success of smoking cessation can be
increased by supportive advice and
pharmacological therapy.

Hyperlipidaemia:
 The importance of lowering serum
cholesterol following acute coronary
syndrome has been demonstrated in large-
scale randomised clinical trials.
 Lipids should be measured within 24 hours of
presentation because there is often a
transient fall in blood cholesterol in the 3
months following infarction.

 HMG CoA reductase enzyme inhibitors
(‘statins’) can produce marked reductions in
total (and LDL) cholesterol and reduce the
subsequent risk of death, reinfarction, stroke
and the need for revascularisation.

 Irrespective of serum cholesterol
concentrations, all patients should receive
statin therapy after acute coronary
syndrome, but those with serum LDL
cholesterol concentrations > 3.2mmol/L
(∼120mg/dL) benefit from more intensive
lipid-lowering, such as atorvastatin 80mg
daily.

Other risk factors:
 Maintaining an ideal body weight, eating a
Mediterranean-style diet, taking regular
exercise, and achieving good control of
hypertension and diabetes mellitus may all
improve the long-term outlook.

 The necrotic muscle of an acute myocardial
infarct takes 4–6 weeks to be replaced with
fibrous tissue and it is conventional to restrict
physical activities during this period.
 When there are no complications, the patient
can mobilise on the second day, return home
in 3–5 days and gradually increase activity
with the aim of returning to work in 4–6
weeks.

 The majority of patients may resume driving
after 4–6 weeks, although in most countries
vocational driving licence holders (e.g. heavy
goods and public service vehicles) require
special assessment.
 Emotional problems, such as denial, anxiety
and depression, are common and must be
addressed.

 Many patients are severely and even
permanently incapacitated as a result of the
psychological rather than the physical effects
of acute coronary syndrome, and all benefit
from thoughtful explanation, counselling and
reassurance at every stage of the illness.

 Many patients mistakenly believe that ‘stress’
was the cause of their heart attack and may
restrict their activity inappropriately.
 The patient’s spouse or partner will also
require emotional support, information and
counselling.

 Formal rehabilitation programmes based on
graded exercise protocols with individual and
group counselling are often very successful,
and in some cases have been shown to
improve the long-term outcome.

a) Aspirin and clopidogrel:
 Low-dose aspirin therapy reduces the risk of
further infarction and other vascular events
by approximately 25% and should be
continued indefinitely if there are no
unwanted effects.

 Clopidogrel should be given in combination
with aspirin for at least 3 months.
 If patients are intolerant of long-term aspirin,
clopidogrel is a suitable alternative.

b) Beta-blockers:
 Continuous treatment with an oral β-blocker
reduces long-term mortality by approximately
25% among the survivors of acute MI.
 Unfortunately, a minority of patients do not
tolerate β-blockers because of bradycardia,
AV block, hypotension or asthma.

 Patients with heart failure, irreversible
chronic obstructive pulmonary disease or
peripheral vascular disease derive similar, if
not greater secondary preventative benefits
from β-blocker therapy if they can tolerate it,
so it should be tried.
 The secondary preventative role of β-
blockers in patients with unstable angina is
unknown.

c) ACE inhibitors:
 Several clinical trials have shown that long-
term treatment with an ACE inhibitor (e.g.
enalapril 10mg 12-hourly or ramipril 2.5–5mg
12-hourly) can counteract ventricular
remodelling, prevent the onset of heart
failure, improve survival, reduce recurrent MI
and avoid rehospitalisation.

 The benefits are greatest in those with overt
heart failure (clinical or radiological) but
extend to patients with asymptomatic left
ventricular dysfunction and those with
preserved left ventricular function.
 They should therefore be considered in all
patients with acute coronary syndrome.

 Caution must be exercised in hypovolaemic
or hypotensive patients because the
introduction of an ACE inhibitor may
exacerbate hypotension and impair coronary
perfusion.
 In patients intolerant of ACE inhibitor therapy,
angiotensin receptor blockers (e.g. valsartan
40–160mg 12-hourly or candesartan 4–16mg
daily) are suitable alternatives and are better
tolerated.

 Patients with acute MI and left ventricular
dysfunction (ejection fraction < 35%) and
either pulmonary oedema or diabetes
mellitus further benefit from additional
aldosterone receptor antagonism (e.g.
eplerenone 25–50mg daily).

 Most low-risk patients stabilise with aspirin,
clopidogrel, anticoagulation and anti-anginal
therapy, and can be rapidly mobilised.
 In the absence of recurrent symptoms, low-
risk patients do not benefit from routine
coronary angiography.

 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 or urgent CABG.
 In these cases coronary revascularisation is
associated with short- and long-term
benefits, including reductions in MI and
death.

 Implantable cardiac defibrillators are of
benefit in preventing sudden cardiac death in
patients who have severe left ventricular
impairment (ejection fraction ≤ 30%) after MI.

 In almost one-quarter of all cases of MI,
death occurs within a few minutes without
medical care.
 Half the deaths occur within 24 hours of the
onset of symptoms and about 40% of all
affected patients die within the first month.

 The prognosis of those who survive to reach
hospital is much better, with a 28-day
survival of more than 85%.
 Patients with unstable angina have a
mortality approximately half those with MI.
 Early death is usually due to an arrhythmia
and is independent of the extent of MI.

 However, late outcomes are determined by
the extent of myocardial damage and
unfavourable features include poor left
ventricular function, AV block and persistent
ventricular arrhythmias.

 The prognosis is worse for anterior than for
inferior infarcts.
 Bundle branch block and high cardiac marker
levels both indicate extensive myocardial
damage.
 Old age, depression and social isolation are
also associated with a higher mortality.

 Of those who survive an acute attack, more
than 80% live for a further year, about 75%
for 5 years, 50% for 10 years and 25% for 20
years.

CARDIAC RISK OF NON-
CARDIAC SURGERY

 Non-cardiac surgery, particularly major
vascular, abdominal or thoracic surgery, can
precipitate serious perioperative cardiac
complication such as MI and death in
patients with coronary artery and other forms
of heart disease.

 Careful pre-operative cardiac assessment
may help to determine the balance of benefit
versus risk on an individual basis, and
identify measures that minimise the operative
risk.

 A hypercoagulable state is part of the normal
physiological response to surgery, and may
promote coronary thrombosis leading to an
acute coronary syndrome in the early post-
operative period.
 Patients with a history of recent PCI or acute
coronary syndrome are at greatest risk and,
whenever possible, elective non-cardiac surgery
should be avoided for 3 months after such an
event.

 Antiplatelet agents, statins and β-blockers
reduce the risk of perioperative MI in patients
with coronary artery disease and, where
possible, should be prescribed throughout
the perioperative period.

 Careful attention to fluid balance during and
after surgery is particularly important in
patients with impaired left ventricular function
and valvular heart disease because
antidiuretic hormone is released as part of
the normal physiological response to surgery,
and in these circumstances the overzealous
administration of intravenous fluids can
easily precipitate heart failure.

 Patients with severe valvular heart disease,
particularly aortic stenosis and mitral
stenosis, are also at increased risk because
they may not be able to increase their
cardiac output in response to the stress of
surgery.

 Atrial fibrillation may be triggered by hypoxia,
myocardial ischaemia or heart failure, and is
a common postoperative complication in
patients with pre-existing heart disease.
 It usually terminates spontaneously when the
precipitating factors have been eliminated,
but digoxin or β-blockers can be prescribed
to control the heart rate.

9. coronary heart disease

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9. coronary heart disease