Internal medicine:

cardiology

Educational book

Recommended by the Ministry of Education and Science of Ukraine

Sumy
Sumy State University
2013
УДК 616.12(075.8)
ББК 54.10я73
І-73
Composite author:
V. F. Orlovskyi, Doctor of Medical Sciences, professor of Sumy State
University;
L. N. Prystupa, Doctor of Medical Sciences, professor of Sumy State
University;
N. M. Kyrychenko, Candidate of Medical Sciences, assosiate professor
of Sumy State University;
O. S. Pogorelova, Candidate of Medical Sciences, assistant of Sumy State
University;
Yu. O. Ataman, Doctor of Medical Sciences, assosiate professor of Sumy
State University
Reviewers:
G. P. Pobedonna – Doctor of Medical Sciences, professor of Lugansk State
Medical University;
I. P. Katerentchuk – Doctor of Medical Sciences, professor of Ukrainian
Medical Stomatological Academy;
I. M. Fushtey – Doctor of Medical Sciences, professor of Zaporozhye
Medical Academy of Postgraduate Education

Recommended by the Ministry of Education and Science of Ukraine for the

English-speaking students of higher medical educational institutions
of III–IV levels accreditation
(letter № 1/11-13145 of 19.08.2013)

Internal medicine: cardiology : educational book /

I-73 V. F. Orlovskyi, L. N. Prystupa, N. M. Kyrychenko et al. – Sumy :
Sumy State University, 2013. – 243 р.
ISBN 978-966-657-489-6

This manual is intended for the students of medical higher educational institutions of IV
accreditation level, who study cardiology in English language.
Посібник рекомендований для студентів вищих медичних навчальних закладів IV
рівня акредитації, які вивчають кардіологію англійською мовою.

УДК 616.12(075.8)
ББК 54.10я73
© Orlovskyi V. F., Prystupa L. N.,
Kyrychenko N. M.,
Pogorelova O. S., Ataman Yu. O.,
2013
ISBN 978-966-657-489-6 © Sumy State University, 2013

3
 INTRODUCTION

The manual sets out the main issues of etiology, pathogenesis,

clinical symptoms, diagnostics and treatment of the most common
diseases of the circulatory system. It is recommended for the students
of the higher medical educational establishments of the IV-th
accreditation level.
Despite the considerable success of modern cardiology, the
number of patients with heart and blood vessels pathology increases
every year. It can be explained by the increase in life expectancy
(aging of the world's population), sedentary lifestyle, obesity,
addictions.
The manual presents the new classifications of diseases, modern
etiology, pathogenesis, diagnostics, treatment and prevention of the
heart and blood vessel diseases. The manual reflects extensive
material in the condensed statement.
We hope that this manual will help students, medical interns to
study the topic “Cardiology” and will be useful in the work of
medical practitioners.

4
 ARTERIAL HYPERTENSION

Arterial hypertension (AH) is frustration of cardiovascular

systems owing to primary dysfunction of vasoregulation centres and
subsequent neurohormonal and kidney mechanisms and is
characterized by arterial hypertension, functional and organic
disorder of kidneys, heart and central neurological system.

Table 1 – Classification of hypertension of blood pressure (BP)

levels (mmHg) (2003 ESH/ESC)

Category Systolic Diastolic

Optimal < 120 and < 80
Normal 120–129 and/or 80–84
High normal 130–139 and/or 85–89
Grade 1 hypertension 140–159 and/or 90–99
Grade 2 hypertension 160–179 and/or 100–109
Grade 3 hypertension ≥ 180 and/or ≥ 110
Isolated systolic
≥ 140 and < 90
hypertension

Total cardiovascular risk (factors influencing prognosis)

Risk factors (RF):
– levels of pulse pressure (in the elderly);
– age (M > 55 years; W > 65 years);
– smoking;
– dyslipidaemia: TC > 5.0 mmol/l (190 mg/dl) or LDL-C >
3.0 mmol/l (115 mg/dl) or HDL-C: M < 1.0 mmol/l (40 mg/dl), W <
1.2 mmol/l (46 mg/dl) or TG > 1.7 mmol/l (150 mg/dl);
– fasting plasma glucose 5.6–6.9 mmol/L (102–125 mg/dl);
– abnormal glucose tolerance test;
– abdominal obesity (waist circumference > 102 cm (M),
> 88 cm (W));
– family history of premature cardiovascular (CV) disease
(M < 55 years; W < 65 years).
Table 2 – Classification of arterial hypertension (1996)

5
 BP,
St. mmHg Organ damage
1 ≥ 140/90 Are absent
2 ≥ 140/90 Heart: ECG LVH (Sokolow-Lyon > 38 mm); Cornell
> 2440 mm/ms) or echocardiographic LVH (LVMI:
M ≥ 125 g/m2, W ≥ 110 g/m2).
Retinal: stenosis of vessels.
Kidney: microalbuminuria 30–300 mg/24 h or
increase in plasma creatinine: M: 115– 133 mmol/l
(1.3–1.5 mg/dl); W: 107–124 mmol/l (1.2–1.4 mg/dl);
low estimated glomerular filtration rate (< 60 ml/min).
Vessels: atherosclerosis (carotid wall thickening (IMT
> 0.9 mm) or plaque; carotid-femoral pulse wave
velocity > 12 m/s).
NS: encephalopathy.
3 ≥ 140/90 NS: cerebrovascular disease: ischaemic stroke;
cerebral haemorrhage; transient ischaemic attack.
Heart disease: myocardial infarction; angina;
coronary revascularization; heart failure.
Renal disease: diabetic nephropathy; renal impair-
ment (serum creatinine M > 133, W > 1.24 mmol/l);
proteinuria (> 300 mg/24 h).
Peripheral artery disease.
Advanced retinopathy: haemorrhages or exudates,
papilloedema
Note:
– the cluster of three out of 5 risk factors among abdominal obesity,
altered fasting plasma glucose, BP > 130/85 mmHg, low HDL- cholesterol
and high TG (as defined above) indicates the presence of metabolic
syndrome;
– St. – stage; M – men; W – women; CV – cardiovascular disease;
IMT – intima-media thickness; BP – blood pressure; TG – triglycerides;
C – cholesterol; risk maximal for concentric LVH (left ventricular
hypertrophy) increased LVMI (left ventricular hypertrophy) increased
LVMI (left ventricular mass index) with a wall thickness/radius ratio > 0.42.

High/very high risk subjects

1. BP ≥ 180 mmHg systolic and/or ≥ 110 mmHg diastolic.
2. Systolic BP > 160 mmHg with low diastolic BP (< 70 mmHg).

6
 3. Diabetes mellitus.
4. Metabolic syndrome.
5. ≥ 3 cardiovascular risk factors.
6. One or more of the following subclinical organ damages:
– electrocardiographic (particularly with strain) or
echocardiographic (particularly concentric) left ventricular
hypertrophy;
– ultrasound evidence of carotid artery wall thickening or
plague;
– increased arterial stiffness;
– moderate increase in serum creatinine;
– reduced estimated glomerular filtration rate or creatinine
clearance;
– microalbuminuria or proteinuria;
Established cardiovascular or renal disease.

Table 3 – Degree of risk of complications development

Presence of risk factors (RF), organ Degree of AH (mmHg)

damage and/or other pathology (2003ESH/ESC)
1 2 3
RF are absent (1) (2) (3)
1-2 of RF, except for (2) (4)
Diabetes mellitus (DM)
≥ 3 of FR or organ damage or DM (3) (4)
Other pathology (4)
Note:
(1) – low risk; (2) – moderate risk; (3) – high risk; (4) – very high risk.

The total 10-year risk of complications of AH (IHD, IM,

insultus, sudden heart death, etc.) is estimated as follows:
– low risk – less than 15% in the next 10 years;
– moderate risk – 15–20%;
– high risk – 20–30%;
– very high risk – more than 30% in the next 10 years.
Pathophysiology
The level of BP is determined by three homodynamic parameters:
1. The level of cardiac output (CO) (minute volume).
2. Total peripheral vascular resistance (TPR).
7
 3. Volume of blood circulations:
– abnormal Na transport;
– sympathetic stimulation of nervous system;
– renin-angiotensin-aldosterone system: renin catalyzes
conversion of angiotensinogen to angiotensin I. This inactive product
is cleaved by ACE to angiotensin II, a potent vasoconstrictor that
also stimulates autonomic centres in the brain to increase
sympathetic discharge and stimulates release of aldosterone and
ADH that causes Na and water retention, BP elevation. Aldosterone
also enhances K excretion; low plasma K (< 3.5 mEq/L) increases
vasoconstriction through closure of K channels;
– vasodilator deficiency: (bradykinin, nitric oxide).
Vasodilators and vasoconstrictors (mainly endothelin) are also
produced in endothelial cells. Therefore, endothelial dysfunction
greatly affects BP.
Diagnostic evaluation
Diagnostic procedures aim at:
– blood pressure levels establishing;
– identifying of secondary causes of hypertension;
– overall cardiovascular risk evaluating by searching for other
risk factors, target organ damage and concomitant diseases or
accompanying clinical conditions.
Diagnostic procedures comprise:
– repeated blood pressure measurements;
– medical history;
– physical examination;
– laboratory and instrumental investigations.
Blood pressure (BP) measurement
When measuring BP, care should be taken to:
– allow the patients to sit for several minutes in a quiet room
before beginning of BP measurements;
– take at least two measurements spaced by 1–2 minutes, and
additional measurements if the first two are quite different;
– use a standard bladder (12–13 cm long and 35 cm wide) but
have a larger and a smaller bladder available for fat and thin arms,
respectively. Use the smaller bladder in children;
– have the cuff at the heart level, whatever the position of the
patient;

8
 – use phase I and V (disappearance) of Korotkoff sounds to
identify systolic and diastolic BP, respectively;
– measure BP in both arms at first visit to detect possible
differences due to peripheral vascular disease. In this instance, take
the higher value as the reference one;
– measure BP 1 and 5 min after assumption of the standing
position in elderly subjects, diabetic patients, and in other conditions
in which postural hypotension be frequent or suspected;
– measure heart rate by pulse palpation (at least 30 sec) after the
second measurement in the sitting position.
Clinical signs of AH
– headache;
– discirculatory encephalopathy;
– cardiac pain;
– dyspnoea;
– oedema;
– vision disorder;
– kidney disorder.
Discirculatory encephalopathy: dizziness, infringements of
memory, noise in the head, irritability, fast fatigue, disorder of mood.
Cardiac pain: is located in the apex of the heart or in the left side
of the chest; arises at rest, at emotional pressure or BP increase;
usually is not provoked by physical activity; in some cases lasts long
enough (minute, hours); is not stopped by nitroglycerine.
Dyspnoea is a reason of HF of LV and diastolic dysfunction of
LV.
Oedema on legs may be at biventricular HF, with a delayed Na+
and water, hyperactivity of rennin-angiotensin system.
Vision disorder: functional – fog, flickering of “flies” before
eyes. Organic changes of the retina (trombosis of vessels,
haemorrhages, degenerative changes or amotio of retina) are
accompanied by significant decrease of sight, diplopia and even by
complete loss of sight.
Kidney disorder is a reason of KF.
Physical examination of the heart
– stage 1 of AH: borders are in norm;
– stage 2 of AH: concentric hypotrophy of LV will result in
amplification of apex push; eccentric hypotrophy of LV will result in

9
dilatation of LV.
Auscultation of the heart: I sound at the stages 1–2 of AH –
strengthening; at the stage 3 – weakening; II sound is aortic accent
(the reasons are increase of BP and sclerosis of Ao wall); occurrence
of IV sound at diastolic dysfunction of LV (at presence of concentric
hypotrophy of LV); III sound at eccentric hypotropfy of LV and
presence of volumetric overload of LV.
Cardiac murmurs: functional systolic murmur in the aorta
(II intercostal to the right of sternum). Its reasons are: aortectasia;
sclerosis of aorta. If systolic murmur at the apex, will be conducted
in the left axillary area and is combined with weakening of I sound
and increase of the sizes LA, it is mitral valve incompetence.
Pulse at AH: full pulse, tachycardia and arrhythmia are
frequent.
Registration a HELL by Korotkoff method
Systolic BP register at occurrence of the first sound above radial
artery (phase 1), and diastolic BP – at the moment of complete
disappearance of Korotkoff sounds (phase 5).
Investigations
Routine tests:
– fasting plasma glucose;
– serum total cholesterol;
– serum LDL-cholesterol;
– serum HDL-cholesterol;
– fasting serum triglycerides;
– serum potassium;
– serum uric acid;
– serum creatinine;
– estimated creatinine clearance (Cockroft-Gault formula) or
glomerular filtration rate (MDRD formula);
– haemoglobin and haematocrit;
– urinalysis (complemented by microalbuminuria via dipstick
test and microscopic examination);
– electrocardiogram.
Recommended tests: echocardiogram, carotid ultrasound,
quantitative proteinuria (if dipstick test is positive), ankle-brachial
BP index, fundoscopy, glucose tolerance test (if fasting plasma
glucose is > 5.6 mol/L (100 mg/dL), home and 24 h ambulatory BP

10
monitoring, pulse wave velocity measurement (if available).
Extended evaluation (domain of the specialist)
Further search for cerebral, cardiac, renal and vascular damage.
Mandatory in complicated hypertension.
Search for secondary hypertension when suggested by history,
physical examination or routine tests: measurement of renin,
aldosterone, corticosteroids, catecholamines in plasma and/or urine;
arteriographies; renal and adrenal ultrasound; computer-assisted
tomography; magnetic resonance imaging.
Position statement: searching for subclinical organ damage.
Due to the importance of subclinical organ damage as an
intermediate stage in the continuum of vascular disease and as a
determinant of total cardiovascular risk, signs of organ involvement
should be sought carefully by appropriate techniques:
1. Heart – electrocardiography should be a part of all routine
assessments of patients with high BP in order to detect left
ventricular hypertrophy, patterns of “strain”, ischaemia and
arrhythmias. Echocardiography is recommended when a more
sensitive detection of left ventricular hypertrophy is considered
useful. Geometric patterns can be defined echocardiographically, of
which concentric hypertrophy carries the worse prognosis. Diastolic
dysfunction can be evaluated by transmitral Doppler.
2. Blood vessels – ultrasound scanning of carotid arteries is
recommended when detection of vascular hypertrophy or
asymptomatic atherosclerosis is deemed useful. Large artery
stiffening (leading to isolated systolic hypertension in the elderly)
can be measured by pulse wave velocity. It might be more widely
recommended if its availability were greater. A low ankle-brachial
BP index signals advanced peripheral.
3. Kidney – diagnosis of hypertension-related renal damage is
based on a reduced renal function or an elevated urinary excretion of
albumin. Estimation from serum creatinine of glomerular filtration
rate (MDRD formula, requiring age, gender, race) or creatinine
clearance (Cockroft-Gault formula, requiring also body weight)
should be routine procedure. Urinary protein should be sought in all
hypertensives by dipstick. In dipstick negative patients low grade
albuminuria (microalbuminuria) should be determined in spot urine
and related to urinary creatinine excretion.

11
 4. Fundoscopy – examination of eye grounds is recommended in
severe hypertensives only. Mild retinal changes are largely
nonspecific except in young patients. Haemorrhages, exudates and
papilloedema, only present in severe hypertension, are associated
with increased CV risk
5. Brain – silent brain infarctions, lacunar infarctions, white matter
lesions and microbleeds are not infrequent in hypertensives, and can
be detected by MRI or CT. Availability and costs do not allow
indiscriminate use of these techniques. In elderly hypertensives,
cognitive tests may help to detect initial brain deterioration.
ECG: at ECG hypotrophy of LV, postinfarction cardiosclerosis,
signs of coronary insufficiency, disorders of rhythm and conductivity
can be revealed.
Roentgenological signs of LV hypertrophy: moderate dilatation
of LV (lengthening of an arch LV and its displacement downwards);
expressed of dilatation of LV (“aortic configuration” of heart).
Roentgenological signs of LV increase in the left anterior slanting
projection in – (circuit on I. H. Rabkin: I, II and III of a degree). The
arrow shows a back contour of heart shadow and disappearance of
retrocardial space.
Echocardiography: left parasternum access. Increase of
intraventriculus septum and posterior wall of LV, increase of LV cavity.
Ophthalmoscope: degrees of retina vessels disorder:
I degree – minimal narrowing of arterioles and non-uniformity of
their gleam. The signs of hypertensions retinopathy are absent.
II degree – expressed narrowing of arterioles with sites spasm and
expansion of venules at their chiasm with arteries (Salus`s and
Gvist`s symptoms). The signs of retinopathy are absent.
III degree – on a background of sharp spasm of arterioles and the
expansions of venules are determined by signs of hypertensive
retinopathy: oedema and moderate turbidity of the retina; multiple
haemorrhage in the retina; “floccular” exudates on the retina.
IV degree – any of set forth above signs + oedema of disk of a
visual nerve.
Complications of AH
Hypertensive crisis, impairment of cerebral circulation
(haemorrhagic or ischaemic insult), myocardial infarction,
nefrosclerosis (contracted kidney), heart failure, dissecting aortic

12
aneurysm, etc.
Treatment of AH
Positive lifestyle changes
The lifestyle measures that are widely recognized to lower BP or
cardiovascular risk, and that should be considered are: smoking
cessation, weight reduction (and weight stabilization), reduction of
excessive alcohol intake, physical exercise, reduction of salt intake,
increase in fruit and vegetable intake and decrease in saturated and
total fat intake.
Drugs treatment of AH
Groups of antihypertensive preparations: ACE inhibitors;
angiotensin receptor antagonists; b-blockers, Ca channel blockers,
α-blockers, diuretics.

Table 4 – ACE inhibitors and angiotensin II receptor blockers

ACE inhibitors Angiotensin II receptor blockers

Benazepril 5–40 mg once/day
Captopril12.5–150 mg tid
Fosinopril 10–80 mg once/day
Quinapril 5–80 mg once/day
Ramipril 1.25–20 mg once/day
Candesartan 8–32 mg once/day
Eprosartan 400–1200 mg once/day
Irbesartan 75–300 mg once/day
Losartan 25–100 mg once/day
Olmesartan 20–40 mg once/day
Telmisartan 20–80 mg once/day
Valsartan 80–320 mg once/day

β-blockers

Atenolol 25–100 mg once/day Metoprolol 50–400 mg once/day

Betaxolol 5–20 mg once/day
Bisoprolol 2.5–20 mg once/day
Carvedilol 6.25–25 mg tid
Carvedilol 20–80 mg once/day
Labetalol 100–900 mg tid
Metoprolol 25–150 mg tid
Nadolol 40–320 mg once/day
Penbutolol 10–20 mg once/day
Pindolol 5–30 mg tid
Propranolol 20–160 mg tid
Propranolol 60–320 mg once/day
Timolol 10–30 mg tid

Goals of the treatment:

– the primary goal of treatment is to achieve maximum
reduction in the long-term total risk of cardiovascular disease;
– BP should be reduced to at least below 140/90 mmHg

13
(systolic/diastolic) in all hypertensive patients;
– target BP should be at least < 130/80 mmHg in diabetics and
in high or very high risk patients, such as those with associated
clinical conditions (stroke, myocardial infarction, renal dysfunction,
proteinuria);
– in order to more easily achieve goal BP, antihypertensive
treatment should be initiated before significant cardiovascular
damage develops.
Ca channel blockers
Benzodiazepine derivatives:
Diltiazem, sustained release (60–180 mg tid); diltiazem, extended
release (120–360 mg once/day); selected adverse effects: headache,
dizziness, asthenia, flushing, oedema, negative inotropic effect;
possibly liver dysfunction; comments: contraindicated in heart
failure due to systolic dysfunction, in sick sinus syndrome, or in
greater than 1st degree atrioventricular block.
Diphenylalkylamine derivatives:
Verapamil (40–120 mg tid); verapamil, sustained release
(120–480 mg once/day); selected adverse effects: same as for
benzodiazepine derivatives, plus constipation; comments: same as
for benzodiazepine derivatives.
Dihydropyridines:
Amlodipine (2.5–10 mg once/day), isradipine (2.5–10 mg tid),
felodipine (2.5–20 mg once/day), nifedipine, extended release
(30–90 mg once/day).
Selected adverse effects: dizziness, flushing, headache, weakness,
nausea, heartburn, pedal oedema, tachycardia; comments:
contraindicated in heart failure, possibly except for amlodipine. Use
of short acting nifedipine is possibly associated with higher MI rate.
Diuretics
Thiazide type diuretics: chlorothiazide 62.5–500 mg tid
(max.:1000), chlorthalidone 12.5–50 mg once/day, indapamide
1.25–5 mg once/day.
K-sparing diuretics: amiloride 5–20 mg once/day, spironolactone
25–100 mg once/day, triamterene 25–100 mg once/day.
Adrenergic modifiers
α2-Agonists (central acting): clonidine 0.05–0.3 mg tid,
guanabenz 2–16 mg tid, guanfacine 0.5–3 mg once/day, methyldopa

14
250–1000 mg tid;
α-Blockers: doxazosin 1–16 mg once/day, prazosin 1–10 mg tid,
terazosin 1–20 mg once/day; peripheral-acting adrenergic blockers:
guanethidine 10–50 mg once/day, rauwolfia alkaloids 50–100 mg
once/day, reserpine 0.05–0.25 once/day.
Combination of drugs used for hypertension (mg/mg)
Diuretic/diuretic:
– triamterene/hydrochlorothiazide 37.5/25, 50/25, 75/50;
– spironolactone/hydrochlorothiazide 25/25, 50/50.
β-Blocker/diuretic:
– nadolol/bendroflumethiazide 40/5, 80/5;
– timolol/hydrochlorothiazide 10/25;
– bisoprolol/hydrochlorothiazide 2.5/6.25, 5/6.25, 10/6.25.
Adrenergic inhibitor/diuretic:
– guanethidine/hydrochlorothiazide 10/25;
– methyldopa/hydrochlorothiazide 250/15, 250/25, 500/30,
500/50.
ACE inhibitor/diuretic:
– enalapril/hydrochlorothiazide 5/12.5, 10/25;
– lisinopril/hydrochlorothiazide 10/12.5, 20/12.5, 20/25.
Angiotensin II receptor blocker/diuretic:
– valsartan/hydrochlorothiazide 80/12.5, 160/12.5;
– irbesartan/hydrochlorothiazide 75/12.5, 150/12.5, 300/12.5.
Ca channel blocker/ACE inhibitor:
– amlodipine/benazepril 2.5/10, 5/10, 5/20, 10/20;
– felodipine (extended-release)/enalapril 5/5.

Conditions favouring the use of some antihypertensive drugs

versus others
Thiazide diuretics: isolated systolic hypertension (elderly), heart
failure, hypertension in blacks.
Beta-blockers: angina pectoris, postmyocardial infarction, heart
failure, tachyarrhythmias, glaucoma, pregnancy.
Calcium antagonists (dihydropyridines): isolated systolic
hypertension (elderly), angina pectoris, LV hypertrophy,
carotid/coronary atherosclerosis, pregnancy, hypertension in blacks.
Calcium antagonists (verapamil/diltiazem): angina pectoris,
carotid atherosclerosis, supraventricular tachycardia.

15
 ACE inhibitors: heart failure, LV dysfunction, postmyocardial
infarction, diabetic nephropathy, non-diabetic nephropathy, LV
hypertrophy, carotid atherosclerosis, proteinuria/microalbuminuria,
atrial fibrillation, metabolic syndrome.
Angiotensin receptor antagonists: heart failure, postmyocardial
infarction, diabetic nephropathy, proteinuria/microalbuminuria,
atrial fibrillation, metabolic syndrome, ACEI-induced cough,
LV hypertrophy.
Diuretics (antialdosterone): heart failure, postmyocardial
infarction.
Loop diuretics: end stage renal disease, heart failure.

Table 5 – Antihypertensive treatment: preferred drugs

Clinical signs Drugs

Subclinical organ damage
LVH ACEI, CA, ARB
Asymptomatic atherosclerosis CA, ACEI
Microalbuminuria ACEI, ARB
Renal dysfunction ACEI, ARB
Clinical event
Previous stroke any BP lowering agent
Previous MI BB, ACEI, ARB
Angina pectoris BB, CA
diuretics, BB, ACEI, ARB,
Heart failure
antialdosterone agents
Atrial fibrillation
Recurrent ARB, ACEI
Permanent BB, non-dihydropiridine CA
ESRD/proteinuria ACEI, ARB, loop diuretics
Peripheral artery disease CA
Condition
ISH (elderly) diuretics, CA
Metabolic syndrome ACEI, ARB, CA
Diabetes mellitus ACEI, ARB
Pregnancy CA, methyldopa, BB
Blacks diuretics, CA
Abbreviations: LVH: left ventricular hypertrophy; ISH: isolated systolic
hypertension; ESRD: renal failure; ACEI: ACE inhibitors;

16
 ARB: angiotensin receptor antagonists; CA: calcium antagonists;
BB: β-blockers
Table 6 – Compelling and possible contraindications to
antihypertensive drugs use

Drugs Compelling Possible

Thiazide Gout Metabolic syndrome,
diuretics glucose intolerance,
pregnancy
Beta-blockers Asthma Peripheral artery disease,
A-V block (grade 2 or 3) metabolic syndrome,
glucose intolerance,
athletes and physically
active patients, chronic
obstructive pulmonary
disease
CA Tachyarrhythmias,
dihydropiridines heart failure
CA (verapamil, A-V block (grade 2 or 3),
diltiazem) heart failure
ACE inhibitors Pregnancy, angioneurotic
oedema, hyperkalaemia,
bilateral renal artery
stenosis
Angiotensin Pregnancy,
receptor hyperkalaemia,
antagonists bilateral renal artery
stenosis
Diuretics Renal failure,
(antialdosterone) hyperkalaemia

Causes of resistant hypertension

Poor adherence to therapeutic plan, failure to modify lifestyle
including weight gain heavy alcohol intake (NB: binge drinking).
Continued intake of drugs that raise blood pressure (licorice, cocaine,
glucocorticoids, non-steroid anti-inflammatory drugs, etc.).
Obstructive sleep apnoea. Unsuspected secondary cause. Irreversible
or scarcely reversible organ damage. Volume overload due to
inadequate diuretic therapy, progressive renal insufficiency, high
sodium intake, hyperaldosteronism. Causes of spurious resistant

17
hypertension: isolated office (white-coat) hypertension, failure to use
large cuff on large arm, pseudohypertension.
Treatment of associated risk factors
Lipid lowering agents
All hypertensive patients with established cardiovascular disease
or with type 2 diabetes should be considered for statin therapy
aiming at serum total and LDL cholesterol levels of, respectively,
< 4.5 mmol/l (175 mg/dl) and < 2.5 mmol/l (100 mg/dl), and lower,
if possible.
Hypertensive patients without overt cardiovascular disease but
with high cardiovascular risk (≥ 20% risk of events in 10 years)
should also be considered for statin treatment even if their baseline
total and LDL serum cholesterol levels are not elevated.
Antiplatelet therapy
Antiplatelet therapy, in particular low-dose aspirin, should be
prescribed to hypertensive patients with previous cardiovascular
events, provided that there is no excessive risk of bleeding.
Low-dose aspirin should also be considered in hypertensive
patients without a history of cardiovascular disease if older than
50 years, with a moderate increase in serum creatinine or with a high
cardiovascular risk. In all these conditions, the benefit-to-risk ratio of
this intervention (reduction in myocardial infarction greater than the
risk of bleeding) has been proven favourable.
To minimize the risk of haemorrhagic stroke, antiplatelet
treatment should be started after achievement of BP control.
Glycaemic control
Effective glycaemic control is of great importance in patients with
hypertension and diabetes.
In these patients dietary and drug treatment of diabetes should
aim at lowering plasma fasting glucose to values ≤ 6 mmol/l
(108 mg/dl) and glycated haemoglobin of < 6.5%.

Hypertensive crisis
Hypertensive crisis (HC) is a sudden sharp increase in BP. If it is
not treated promptly, it can lead to stroke, coma and even death.
Causes of hypertensive crisis
Chronic hypertension with acute exacerbation (most common):
1. Renovascular hypertension.

18
 2. Parenchymal renal disease:
– acute glomerulonephritis,
– renal infarction,
– vasculitis.
3. Sclerodermatous renal crisis.
4. Drug ingestion:
– tricyclic antidepressants,
– monoamine oxidase inhibitors,
– cocaine,
– amphetamines.
5. Antihypertensive drug withdrawal or failed compliance:
– centrally acting antihypertensives (e.g., clonidine),
– peripheral alpha blockers (e.g., prazosin),
– β-blocker acute withdrawal.
6. Preeclampsia and eclampsia.
7. Autonomic hyperactivity:
– Guillain-Barre syndrome,
– spinal cord injury.
8. Pheochromocytoma.
Signs of HC: sudden acute onset, high level of BP increase, blood
vessels and organs damage. HC depending on presence or absence of
the organ affection is divided into complicated and uncomplicated.
Features of complicated hypertensive crisis:
1. With acute progress of organ damage: heart attack and
myocardial infarction, transitory ischaemic attack and stroke, aortic
dissecting, unstable stenocardia, acute LV insufficiency (cardiac
asthma, pulmonale oedema), arrhythmia, eclampsia, bleeding, acute
hypertensive encephalopathy.
2. HC severe and potentially life-threatening increase in blood
pressure. These conditions require immediate in the course of the
1 hour BP reduction.
3. Treatment in ward of intensive therapy with the use of parental
drugs is necessary.
Parental therapy of complicated hypertensive crisis
Nitroglycerin
Highly effective in setting of coronary ischaemia, acute coronary
syndromes. The dose is 5–100 µg/min as IV infusion. Start
5–10 µg/min, then may be up to > 200 µg/min parenteral especially

19
in patients where Na nitroprusside is relatively contraindicated and in
patients with ischaemic heart disease, impaired renal or hepatic
function. Onset: immediate. Duration: 1–5 min. May cause headache,
tachycardia, vomiting, methemoglobinemia. Excellent for titrating
blood pressure in setting of coronary ischaemia.
Labetalol (trandate)
Mixed alpha/beta blocker, excellent for most hypertensive
emergencies. The dose is 20–80 mg IV bolus every 10 minutes or
0.5–2 mg/min infusion IV. Start 20 mg IV, then 20–80 mg q10 min
parenteral, or start with 0.5 mg/min infusion, then 1–2 mg/min (may
be up to 4 mg/min) IV infusion up to 300 mg/d max. Onset:
5–10 min. Duration: 1–5 min. May cause headache, tachycardia,
vomiting, methemoglobinemia. Excellent for titrating blood pressure
in setting of coronary ischaemia.
Avoid in patients with heart block, bradycardia, CHF, severe
asthma or bronchospasm. First or second line for eclampsia;
excellent in catecholamine surges.
Enalaprilat
Intravenous formulation of enalapril (ACE inhibitor). The dose is
1.25–5.0 mg q6 hour IV (duration of action is 6 hours). Onset of
action: in 15–30 minutes. Duration: 6 hours or more. Highly variable
response; precipitous BP drop in high-renin states, rarely
angioedema, hyperkalemia, or acute renal failure.
May be most useful in acute cardiogenic pulmonary oedema.
Avoid in acute myocardial infarction.
Sodium nitroprusside
Standard rapidly acting agent is effective in many cases. The dose
is 0.25–8 µg/kg/minute as IV infusion, start with 0.3–0.5 µg/kg/min
(about 20–50 µg/min), then 1–3 µg/kg/min IV (max:< 10 µg/kg/min)
(50 mg in 250 ml D5W). Onset: 0.5–1 min. Duration: 2–5 min.
Adverse effects: hypotension, N and V, apprehension, cyanide
(thiocyanate level > 10 mg/dl is toxic; > 20 mg/dl may be fatal)
toxicity convulsion, twitching, psychosis, dizziness, etc.
Nitroprusside has decreased efficacy in renal failure. Toxic levels
of cyanide build up rapidly in patients with renal failure. Nausea,
vomiting, muscle twitching and sweating can occur.
Diltiazem (cardizem)
Initial dose is 0.25 mg/kg over 2 min, followed by infusion of

20
0.35 mg/kg at an initial rate of 10 mg/hour. Onset: 3–30 min.
Adverse effects: excessive hypotension, flushing, rarely amblyopia.
Hydralazine (apresoline)
Indicated primarily for eclampsia. The dose is 10–50 mg IV or
IM titrate to effect (onset < 20 minutes, duration 3–8 hours).
Onset: 10–20 min. Duration: 3–8 h. Adverse effects: tachycardia,
flushing, contraindicated in angina or aortic dissection. Can be
given in IM as well, 10–50 mg (onset: 20–30 minutes).
Tachycardia, flushing, headache, vomiting, increased angina may
occur.
Nicardipine (cardene)
IV formulation is available, though not commonly used. The
dose is 5–15 mg/hr IV. Onset: 5–10 minutes. Duration: 1–4 hours.
Do not use in acute CHF or with coronary ischaemia. May be
most useful for hypertension in setting of subarachnoid
haemorrhage.
Esmololol (breviblock)
Very half life (2–4 minutes) nonselective ß-blockade. The dose
is 250–500 µg/kg/min for 1 minute, then 50–100 µg/kg for
4 minutes. Sequence may be repeated, and continuous drip may be
maintained. Onset of action is 1–2 minutes; 10–20 minute duration.
Mainly for acute aortic dissection, perioperatively, acute coronary
ischaemia. May be used with caution in acute MI with depressed
LV to modulate heart rate. Very close monitoring is required, and
fluid load is large with this agent.
Phentolamine
Mainly for catecholamine surges (pure alpha-adrenergic
blockade). The dose is 5–15 mg IV. Onset: in 1–2 minutes. Duration:
3–10 minutes. Tachycardia, flushing and headache may occur.

Features of uncomplicated hypertensive crisis:

1. Without progress of organ damage.
2. HC with potentially life-threatening increase in BP. Reduction
of BP is necessary in several hours. Symptoms of HC include: severe
chest pain, severe headache, stiff or sore neck, enlarged pupils, fast
or slow heartbeat, increased sensitivity of eyes to light, increased
sweating (possibly with fever or cold, clammy skin), nausea and
vomiting.

21
 3. Hospitalization is not obligatory with the use of per os PO and
intramuscular drugs.
Therapy of uncomplicated hypertensive crisis
Nifedipine
The dose is 10–20 mg may be under tongue. Adverse effects:
headache, tachycardia, angina pectoris, reddening of skin.
Clonidine (catapres)
PO 0.2 mg, followed by 0.1 mg/hr to total of 0.8 mg until the
diastolic BP is <110 mmHg, or reduction in diastolic BP of
20 mmHg or more. Onset: 30–120 min. Duration: 8–12 h. Adverse
effects: sedation, dry mouth, dizziness, orthostasis, bradycardia.
Contraindicated in patients with sinus bradycardia, sick sinus
syndrome or heart block.
Labetalol (trandate)
The dose is 200–300 mg PO, followed by 100–200 mg q8h.
Onset: in 1–2h; Duration: 12–24 h. Adverse effects: bradycardia.
Captopril
The dose is 12.5–50 mg. Adverse effects: arterial hypotensive
patients with bilateral renal artery stenosis.

SECONDARY HYPERTENSION

22
 Secondary hypertension (SH) is a type of hypertension which by
definition is caused by an identifiable underlying secondary cause. It
is much less common than the other type, called essential
hypertension, affecting only 5% of hypertensive patients. It has many
different causes including endocrine diseases, kidney diseases, and
tumours. It also can be a side effect of many medications. Simple
screening for secondary forms of hypertension can be obtained from
clinical history, physical examination and routine laboratory
investigations. Furthermore, SH is suggested by a severe blood
pressure elevation, sudden onset or worsening of hypertension and
blood pressure responding poorly to drug therapy. In these cases,
specific diagnostic procedures may become necessary, as outlined
below.
Classification of secondary hypertension
Kidney hypertension:
1. Renal parenchymal patology: glomerulonephritis, chronic
pyelonephritis, chronic nephritis, obstructive nephritis, polycystic
kidney disease, conductive tissue disease of kidney, diabetic
nephropathy, hydronephrosis, renal segmental hypoplasia
(Ask-Upmark kidney), affection of kidney.
2. Renovascular pathology: stenosis of the renal artery,
atherosclerosis of kidney arteries, fibromuscular dysplasia, vasculitis,
thromboembolism, aneurysm of kidney vessels, atresia and
hypoplasia of kidney arteries.
3. Hypertension after transplantation of kidney.
4. Cancer (tumours in kidney can operate in the same way as
kidney disease. More commonly, however, tumours cause inessential
hypertension by ectopic secretion of hormones involved in normal
physiological control of blood pressure).
Endocrine hypertension:
1. Pheochromocytoma – caused by an excessive secretion of
norepinephrine and epinephrine which promotes vasoconstriction.
2. Hyperaldosteronism (Crohn's syndrome) – idiopathic
hyperaldosteronism, Liddle's syndrome (also called
pseudoaldosteronism), glucocorticoid remediable aldosteronism.
3. Cushing's syndrome – an excessive secretion of
glucocorticoids causes the hypertension.
4. Hyperparathyroidism.

23
 5. Acromegaly.
6. Hyperthyroidism.
7. Hypothyroidism.
Haemodynamic disorders (at heart and vessels disorders)
hypertension:
1. Atherosclerosis of aorta.
2. Stenosis of carotid and vertebral arteries.
3. Aortic valve insufficiency.
4. Coarcation of the aorta.
5. Complete AV-block.
6. Hyperkinetic circulatory syndrome (hypertension in young, in
athletes, in anaemias).
7. Ischaemic and congestion hypertension (at blood circulation
failure, chronic obstructive pulmonary disease, mitral valve disease).
8. Rheology hypertension (in erythremia).
Hypertension in neurologic disordes:
1. Vessels change in brain.
2. Tumour in brain.
3. Inflammation of the brain (encephalitis, meningitis,
poliomyelitis.
4. Trauma of brain.
5. Polyneuritis.
6. Neurofibromatosis.
7. Obstructive sleep apnoea.
Other secondary hypertensions:
1. Drugs (hormonal contraceptives, adrenoreceptor stimulants,
steroid, erythropoietins).
2. White coat hypertension (i.e., elevated blood pressure in the
clinical setting but not in other settings, probably due to the anxiety
that some people experience during a visit to the clinic.
3. Perioperative hypertension is development of hypertension
just before, during or after surgery. (It may occur before surgery
during the induction of anaesthesia; intraoperatively, e.g., by pain-
induced sympathetic nervous system stimulation; in the early
postanaesthesia period, e.g., by pain-induced sympathetic
stimulation, hypothermia, hypoxia, or hypervolemia from excessive
intraoperative fluid therapy; and in 24 to 48 hours after the
postoperative period as fluid is mobilized from the extravascular

24
space. In addition, hypertension may develop perioperatively because
of discontinuation of long-term antihypertensive medication).
4. Under overweening using the salts, alcohol and licorice (when
consumed in excessive amounts).
Renal parenchymal disease
Renal parenchymal disease is the most common cause of SH. The
finding of bilateral upper abdominal masses at physical examination
is consistent with polycystic kidney disease and should lead to an
abdominal ultrasound examination. Renal ultrasound has now almost
completely replaced intravenous urography in the anatomical
exploration of the kidney. While the latter requires the injection of
potentially nephrotoxic contrast medium, ultrasound is non-invasive
and provides all the necessary anatomic data about kidney size and
shape, cortical thickness, urinary tract obstruction and renal masses.
Assessing the presence of protein, erythrocytes and leucocytes in the
urine, as well as measuring serum creatinine concentration, are the
appropriate functional screening tests for renal parenchymal disease.
These tests should be performed in all patients with hypertension.
Renal parenchymal disease may be excluded if urine analysis and
serum creatinine concentration are normal on repeated
determinations. The presence of erythrocytes and leucocytes should
be confirmed by microscopic examination of the urine. If the
screening tests for renal parenchymal hypertension are positive, a
detailed work-up for kidney disease should ensue.
Renovascular hypertension
Renovascular hypertension is the second most common cause of
SH, its prevalence being approximately 2% of adult patients with
blood pressure elevation. This is caused by one or more stenoses of
the extrarenal arteries which in the elderly population have
frequently an atherosclerotic nature. Fibromuscular dysplasia
accounts for up to 25% of total cases and is the most common variety
in young adults. There is hypertension of abrupt onset or worsening
as well as high BP. Signs of renal artery stenosis include abdominal
bruit with lateralization, hypokalaemia and progressive decline in
renal function. However, these signs are not present in many patients
with renovascular hypertension. Determination of the longitudinal
diameter of the kidney using ultrasound can be used as a screening
procedure. However, a difference of more than 1.5 cm in length

25
between the two kidneys, which is usually considered as being
diagnostic for renal artery stenosis is only found in 60–70% of the
patients with renovascular hypertension. Colour Doppler
ultrasonography is often able to detect stenosis of the renal artery.
The recommendations for patients with renovascular hypertension:
1) refractory hypertension (i.e. elevated BP values despite
administration of at least three drugs, including a diuretic at adequate
doses) as well as a progressive decline in renal function represent an
indication for revascularization; 2) although different opinions exist,
surgical revascularization is now performed less frequently and is
being progressively replaced by angioplasty; 3) angioplasty alone is
the treatment of choice in fibromuscular dysplasia in which it is
followed by a high rate of therapeutic success, i.e. persistent BP
normalization or reduction with values more responsive to drug
treatment. Success rate is less common in atherosclerotic disease,
which has a greater incidence of restenosis, but restenosis can be
reduced by stenting which is thus now almost regularly added to
angioplasty in renovascular stenoses of atherosclerotic nature;
4) because of the high risk of progression of atherosclerotic lesions,
their treatment consists of intense lifestyle modifications, low dose of
aspirin, statin and multiple antihypertensive drug administration. The
use should be made of a thiazide diuretic at appropriate doses and a
calcium antagonist with the possible addition of renin-angiotensin
blocker, except in the presence of bilateral renal artery stenosis.
Phaeochromocytoma is a very rare SH state (0.2–0.4% of all
cases of elevated BP) with an estimated annual incidence of 2–8 per
million population. It can be inherited or acquired. Hypertension
occurs in about 70% of all cases of phaeochromocytoma, being
stable or paroxysmal (presenting with symptoms such as headache,
sweating, palpitations and pallor) in approximately equal
proportions. The diagnosis is based on establishing an increase in
plasma or urinary catecholamines or their metabolites. When plasma
or urine values are only modestly elevated, despite there being a
strong clinical suspicion of phaeochromocytoma, then stimulation or
suppression tests with glucagon or clonidine. The glucagon test must
be performed after the patient has been effectively treated with an
a-adrenoreceptor antagonist to prevent marked blood pressure
increases after injection of the hormone. The clonidine suppression

26
test is regarded as negative when there is a marked reduction of
plasma catecholamines. After the diagnosis of phaeochromocytoma
has been made, localization of the tumour is mandatory. Ninety-five
per cent are located in or close to the adrenal glands and, since they
are often large tumours, they can sometimes be detected by
ultrasound. However, the most sensitive procedures (98–100%) are
CT and, particularly, magnetic resonance imaging (MRI), which,
however, has a low specificity (50%). Complementary to a CT scan
or MRI, isotopic scanning using meta-iodobenzylguanidine may be
useful in localizing extra-adrenal phaeochromocytomas and
metastases from the 10% of phaeochromocytomas. It is therefore
recommended to offer genetic tests to patients and their family
members, especially if phaeochromocytoma is associated with
hereditary syndromes. To date, germline mutations in five genes
have been described leading to familial disorders associated with
phaechromocytomas. Definite treatment requires excision of the
tumour. In advance of this the patient must be adequately prepared.
This requires the introduction of an adrenoreceptor blocker and, after
adequate treatment with this blocker, b-blockers can be introduced.
Surgical excision, these days often carried out laparoscopically, can
then follow, but after adequate fluid replacement had been effected.
This is necessary because protracted exposure to phaeochromocytoma
causes pressure natriuresis and venoconstriction with a marked
volume depletion.
Primary aldosteronism. 30% of cases of primary aldosteronism
are caused by adrenal adenomas which are commoner in women and
rarer in children. 70% of cases are caused by adrenal hyperplasia and
there are rare cases of adrenal carcinoma and the autosomal
dominant condition of glucocorticoid remediable aldosteronism. The
blood pressure profile is one of moderate or marked elevation
resistant to treatment. Glucocorticoid remediable hypertension
appears early in life and usually in childhood. There are associations
of primary aldosteronism with phaeochromocytoma,
hyperparathyroidism and acromegaly. It has been suggested that only
patients with unprovoked hypokalaemia or truly resistant
hypertension should be evaluated for primary aldosteronism. The
condition should be suspected in resistant hypertension and in
unprovoked hypokalaemia. It can be confirmed by the

27
fludrocortisone suppression test (failure of 4 day administration of
the hormone to reduce plasma aldosterone below its threshold value),
and measurement of aldosterone and renin under standardized
conditions. Imaging of the adrenal glands is now usually carried out
using CT, magnetic resonance imaging or isotopic techniques using
radio labelled cholesterol. The surgical technique for removal of a
suspected adenoma is laparoscopic adrenalectomy. Prior to surgery
or in the case of adrenal hyperplasia, treatment with an aldosterone
antagonist such as spironolactone is advised. However, this is
associated with side effects such as gynaecomastia which may reduce
its usefulness. In this case eplerenone may be considered, although at
recommendee doses its effect is less than that of spironolactone.
Cushing’s syndrome affects 0.1% of the total population.
Hypertension is a very common finding and is reported in about 80%
of such patients, with a 50% prevalence when the disease occurs in
children and adolescents. Usually, the syndrome is suggested by the
typical body habitus of the patient. The determination of 24-hour
urinary cortisol excretion is the most practical and reliable diagnostic
test and a value exceeding 110 mmol (40 mg) is highly suggestive of
Cushing’s syndrome. The diagnosis is confirmed by the 2-day, low-
dose dexamethasone suppression test (0.5 mg every 6 h for eight
doses) or the overnight dexamethasone suppression test (1 mg at
11.00 p.m.). In the 2-day test, urinary cortisol excretion higher than
27 mmol (10 mg) per day on day 2 indicates Cushing’s syndrome.
The same is true if plasma cortisol concentration is greater than
140 mmol/l (5 mg/dl) at 8.00 a.m. in the overnight test. A normal
result excludes the possibility of Cushing’s syndrome.
Obstructive sleep apnoea is characterized by recurrent episodes
of cessation of respiratory airflow caused by upper airway
inspiratory collapse during sleep, with a consequent decrease in
oxygen saturation. It is important to consider sleep apnoea in the
characterization of obese patients, especially those with hypertension
resistant to conventional drug therapy. Furthermore, hypertensive
patients, who are classifed as “non-dippers” on ambulatory pressure
measurements, should be investigated for obstructive sleep apnoea.
Signs and symptoms include daytime somnolence, impaired
concentration, unrefreshing and restless sleep, choking episodes
during sleep, witnessed apnoeas, nocturia, irritability and personality

28
changes, decreased libido and increased motor vehicle accidents.
Where suspected, one should use one of the validated questionnaires:
the Epworth Sleepiness Scale or the Berlin Questionnaire.
Polysomnography remains the “gold standard” diagnostic tool for
assessing sleep-disordered breathing. The apnoea-hypopnoea index
(i.e. the number of apnoeic and hypopnoeic events per hour) is used
as an index of the presence and severity of the syndrome. An
apnoea/hypopnoea index of 5 to 15 indicates mild apnoea; of 15 to
30, moderate apnoea; and of greater than 30, severe apnoea. Untreated
obstructive sleep apnoea may have direct and deleterious effects on
cardiovascular function and structure through several mechanisms,
including sympathetic activation, oxidative stress, inflammation and
endothelial dysfunction. The syndrome may contribute to the elevated
pressure in a large proportion of hypertensive patients, the pressor
effect being possibly generated by an impairment of reflex
cardiovascular regulation and endothelial dysfunction. Weight loss in
obese subjects ameliorates the syndrome, which is also improved by
using positive pressure breathing equipment.
Coarctation of aorta
Coarctation of aorta is a rare form of hypertension in children and
young adults. The diagnosis is usually evident from physical
examination. Midsystolic murmur, which may become continuous
with time, is heard over the anterior part of the chest and also over
the back. The femoral pulse is absent or delayed relative to the radial
pulse. Hypertension is found in the upper extremities concomitantly
with low or unmeasurable blood pressure in the legs. After repair or
stenting, especially in adults, hypertension may persist due to
haemodynamic and vascular effects, and many patients need to
continue antihypertensive therapy.
Drug-induced hypertension. Substances or drugs that can raise
blood pressure include: licorice, oral contraceptives, steroids,
nonsteroidal anti-infammatory drugs, cocaine and amphetamines,
erythropoietin, cyclosporins, tacrolimus. The patient should be asked
about their medication at the time their clinical history is taken, and
the use of drugs that can raise blood pressure should be monitored
carefully.

29
Figure 1 – Algorithm of the differential diagnostics

ATHEROSCLEROSIS

30
 Atherosclerosis (dyslipidemia) is elevation of plasma cholesterol,
triglycerides (TG), or both, or a low high density lipoprotein level
that contributes to the development of atherosclerosis. Causes may
be primary (genetic) or secondary. Diagnosis is by measuring plasma
levels of total cholesterol, TG, and individual lipoproteins. Treatment
is dietary changes, exercise, and lipid-lowering drugs.
Coronary heart disease (CHD) affects approximately 12.9 million
Americans and is the primary cause of death in both men and
women. In 2000, 681,100 people (more than one in five) died as a
result of CHD. Dyslipidemia is one of the most important modifiable
risk factors for CHD. Many patients with CHD or who are at risk for
CHD have more than one lipid abnormality, each of which increases
cardiovascular risk. In one study of men with CHD, 87% had low-
density lipoprotein-cholesterol (LDL-C) levels of 100 mg/dl or more,
64% had high-density lipoprotein-cholesterol (HDL-C) below
40 mg/dl, and 33% had triglyceride levels above 200 mg/dl. Of the
58% of patients with CHD who were not definite candidates for
lipid-modifying therapy (LDL-C below 130 mg/dl), 41% had HDL-C
levels below 35 mg/dl.
Low HDL-C levels (below 40 mg/dl in men and below 50 mg/dl
in women) were the second most common metabolic abnormality (in
35% of men and in 39% of women), after abdominal obesity, found
in adults over the age of 20 living in the U.S. Cardiovascular risk is
independently increased by abnormalities in low-density and high-
density lipoprotein-cholesterol and triglycerides.
Clinical trial results have indicated that for every 1% reduction in
LDL-C, the risk of CHD is reduced by 1%.
Risk factors of atherosclerosis:
– abdominal obesity (waist circumference: M > 102 cm,
W > 88 cm);
– smoking;
– drink;
– lowering of physical activity;
– atherogenic dyslipidemia (low HDL-C, elevated triglycerides,
and incise LDL-C);
– hypertension;
– insulin resistance and diabetes mellitus;

31
 – prothrombotic (hypercoagylation);
– proinflammatory states (↑ C-protein);
– elderly age;
– men;
– presence of diseases caused by atherosclerosis in the relatives
(in the age of up to 55 years in men and 65 years in women).

Table 7 – Classification of LDL-cholesterol, HDL-cholesterol,

total cholesterol, and triglyceride levels

LDL-cholesterol
< 100 mg/dl (< 2,6 mmol/l) Optimal
100–129 mg/dl (2.6–3.3 mmol/l) Near or above optimal
130–159 mg/dl (3.3–4.1 mmol/l) Borderline
160–189 mg/dl (4.1–4.9 mmol/l) High
≥ 190 mg/dl (> 4.9 mmol/l) Very high
Total cholesterol
< 200 mg/dl (< 5.2 mmol/l) Desirable
200–239 mg/dl (5.2–6.2 mmol/l) Borderline high
≥ 240 mg/dl (> 6.2 mmol/l) High
HDL-cholesterol
< 40 mg/dl (< 1.0 mmol/l) High
> 60 mg/dl (> 1.6 mmol/l) Low
Triglycerides (TG)
< 150 mg/dl (< 1.7 mmol/l) Normal
150–199 mg/dl (1.7–2.2 mmol/l) Borderline high
200–499 mg/dl (2.2–5.6 mmol/l) High
≥ 500 mg/dl (> 5.6 mmol/l) Very high
LDL = low-density lipoprotein; HDL = high-density lipoprotein;
TG = triglycerides

Treatment
Five classes of drugs are available for the treatment of
dyslipidemia, each with different effects on the various lipid and
lipoprotein parameters.
1. Statins are the most potent drugs available for reducing
LDL-C. They bring about moderately lower triglyceride levels and
modestly increase HDL-C levels. Most of the lowering effect of
statins on LDL-C can be obtained with relatively low doses with less

32
 incremental benefit as doses are increased.
2. Bile acid sequestrants mainly affect LDL-C. They have
minimal effects on HDL-C and little or no effect on triglyceride
concentrations. These drugs are a good option for patients who are
intolerant of statins or whose condition is refractory to them.
3. Of the available agents, niacin (vitamin B3) has the most
powerful effect on HDL-C levels; it is the only agent that improves
all components of the lipid profile. It moderately lowers LDL-C and
triglyceride levels and increases LDL particle size. Niacin is the only
drug that decreases lipoprotein(a) levels, which the ATP III
guidelines recognize as an emerging risk factor for CHD. Niacin is
recommended for patients with isolated low HDL-C levels and
atherogenic dyslipidemia.
4. Fibrates exert their greatest effects on triglyceride levels, have
moderate effects on HDL-C and mild effects on LDL-C, and increase
LDL particle size. Fibrates are recommended for patients with
hypertriglyceridemia and atherogenic dyslipidemia.
5. Cholesterol absorption inhibitors are a new class of lipid-
modifying agents. They lower LDL-C concentrations by almost 20%,
regardless of concurrent therapy, and have a modest effect on HDL-C
and triglycerides. Ezetimibe (Zetia), the first agent approved in this
class, might be a good option for patients who do not tolerate or
respond to statin therapy. This product is contraindicated in patients
with active liver disease and in patients with hypersensitivity to any
component of the drug.

Table 8 – Classification of lipoprotein patterns (Fredrickson

phenotypes, 1970)

Pheno- Elevated Elevated lipids

type lipoprotein(s)
I Chylomicrons TG
IIa LDL Cholesterol
IIb LDL and VLDL TG and cholesterol
III VLDL and chylomicron remnants TG and cholesterol
IV VLDL TG
V Chylomicrons and VLDL TG and cholesterol
Table 9 – Lipid and lipoprotein effects

33
 Drug class or LDL- HDL- Triglycerides
agent cholesterol cholesterol
Statins ↓ 18–55% ↑ 5–15% ↓ 7–30%
Bile acid ↓ 15–30% ↑ 3–5% No change or
sequestrants increase
Niacin ↓ 5–25% ↑ 15–35% ↓ 20–50%
Fibric acid ↓ 5–20% ↑ 10–20% ↓ 20–50%
Cholesterol ↓ 17–19% ↑ 1–4% ↓ 0–6%
absorption
Inhibitors

Table 10 – Lipid-lowering drugs

Drugs Adult doses Comments

LDL-C lowering (primary),
Statins HDL-C increase, TG lowering
(secondary)
Atorvastatin 10–80 mg po No renal excretion, long half-
once/day life.
Dose necessary to achieve
recommended 30–40% reduction
of LDL-C: 10 mg
Pravastatin 10–80 mg po Dose necessary to achieve
once/day recommended 30–40% reduction
of LDL-C: 40 mg
Simvastatin 5–80 mg po Dose necessary to achieve
once/day in the recommended 30–40% reduction
evening of LDL-C: 20–40 mg
Rosuvastatin 5–40 mg po Most potent, long half-life.
once/day Dose necessary to achieve
recommended 30–40% reduction
of LDL-C: 5–10 mg
Fluvastatin Immediate release: Least potent, no renal excretion.
20–80 mg po Dose necessary to achieve
once/day at recommended 30–40% reduction
bedtime. of LDL-C: 40–80 mg
Extended release:
80 mg once/day
Table 10 continuation

34
 Drugs Adult doses Comments
Nicotinic acid (niacin)
Immediate release: Increases HDL, lowers TG (low
500 mg bid – doses), LDL-C (higher doses),
1000 mg po tid and Lp(a) (secondary)
Extended release: Frequent adverse effects:
500–2000 mg po flushing, impaired glucose
once/day at tolerance, increased uric acid;
bedtime Aspirin and administration with
food minimize flushing
LDL-C lowering (primary),
slight HDL increase
Bile acid sequestrants (secondary), TG increase is
possible
Cholestyr- 4 g po 1–6 times
amine per day with meals
Colestipol 5–30 g po once/day
with a meal
Colesevelam 2.4–4.5 g po once a
day with a meal
TGs and VLDL lowering,
HDL increase, LDL-C
Fibrates
increase is possible (in patients
with high TG)
Bezafibrate 200 mg po tid or Decreased dose required in
400 mg po renal insufficiency.
once/day Not available in US
Fenofibrate 67–201 mg po Decreased dose required in
once/day renal insufficiency. May be
safest fibrate for use with statins
Gemfibrozil 600 mg po bid Decreased dose required in
renal insufficiency
Lowers LDL-C (primary),
Cholesterol absorption inhibitor
minimally increases HDL-C
Ezetimibe 10 mg po once/day
Dietary supplements
Omega-3 acid 3–4 g daily TG lowering only
ethylesters (4 capsules)
Table 10 continuation

35
 Drugs Adult doses Comments
Combination products Combined effects of 2 drugs
Ezetimibe Ezetimibe 10 mg + Not recommended as initial
+ simvastatin simvastatin 10, 20, therapy
40, or 80 mg po
once/day
Niacin Niacin 500 mg +
extended lovastatin 20 mg po
release once/day; niacin
+ lovastatin 2000 mg + lovastatin
40 mg po once/day
Niacin Niacin 500 mg +
extended simvastatin mg po
release once/day at bedtime
+ simvastatin (starting dose) or
niacin 750 or 1000
mg + simvastatin
20 mg po once/day at
bedtime
HDL = high density lipoprotein; HDL-C = HDL-cholesterol; LDL = low
density lipoprotein; LDL-C = LDL-cholesterol; Lp(a) = lipoprotein a;
TG = triglyceride

Statins have proved to be very safe in most patients, but

myopathy remains a concern (table 10), especially when statins are
used in combination with other drugs. Adverse hepatic effects have
also been a concern with statin therapy.
Table 11 – Muscle-related adverse effects associated with statin
therapy

Condition Definition
Myopathy Any disease of the muscles
Myalgia Muscle aches or weakness without elevations in CK
Myositis Muscle aches or weakness with elevations in CK
Rhabdomyolysis Muscle symptoms with marked elevations in CK
(usually greater than 10 times the ULN)
CK = creatine kinase; ULN = upper limit of normal
ISHAEMIC HEART DISEASE

36
 Cardiovascular diseases are presently the leading causes of death
in industrialized countries and expected to become so in emerging
countries by 2020. Among these, coronary artery disease (CAD) is
the most prevalent manifestation and is associated with high
mortality and morbidity. The clinical presentations of ischaemic
heart disease (IHD) include silent ischaemia, stable angina pectoris,
unstable angina, myocardial infarction (MI), heart failure, and
sudden death. Patients with chest pain represent a very large
proportion of all acute medical hospitalizations in Europe.

Acute Coronary Syndrome

Acute coronary syndromes (ACS) – is the group of clinical

signs and symptoms IHD, which give the basis to suspect developing
acute MI or unstable stenocardia, in which basis lays uniform
pathophysiology process – thrombosis of various degrees, formed
above the area of rupture of atherosclerotic patch or damage
(erosion) of endothela.
ACS results from acute obstruction of the coronary artery.
Consequences depend on degree and location of obstruction and
range from unstable angina to:
– unstable stenocardia;
– ST-segment elevation MI (STEMI) or new or for the first time
arising of left bundle-branch block (LBBB);
– non-ST-segment elevation MI (NSTEMI);
– sudden cardiac death.
Symptoms are similar in each of these syndromes (except sudden
death) and include chest discomfort with or without dyspnoea,
nausea, and diaphoresis. Diagnosis is by ECG and the presence or
absence of serologic markers. Treatment is antiplatelet drugs,
anticoagulants, nitrates, β-blockers, and, for STEMI, emergency
reperfusion via fibrinolytic drugs, percutaneous intervention, or,
occasionally, coronary artery bypass graft surgery.
ACS with ST-segment elevation MI or new or for the first
time arising of LBBB:
– these patients have very serious prognosis;

37
 – proof elevation of a segment RS-T is in parameter widespread
and “deep”, transmural, myocardial ischaemia, which is caused by
the termination of coronary circulation in coronary arteries;
– the reason is blood clot with complete occlusion of artery, or
combination of not completely occlusion of artery of a blood clot and
long spasm of coronary arteries.

Acute
Acutecoronary syndromes
coronary syndromes

non-ST-segment
non-ST-segment ST-segment
ST-segment Provisional
elevation
elevation elevation or LBBB
elevation or LBBB diagnosis

1/2 1/2 2/3

Final
Unstable Q negative Q positive diagnosis
stenocardia MI MI

Figure 2 – Characteristics of acute coronary syndromes

Pathophysiology
Atherosclerosis is a chronic, multifocal immunoinflammatory,
fibroproliferative disease of medium-sized and large arteries mainly
driven by lipid accumulation.
Vulnerable plaque
Atherosclerosis is not a continuous, linear process but rather a
disease with alternate phases of stability and instability. Sudden and
unpredictable changes in symptoms appear to be related to plaque
disruption. The plaque erosion is another underlying mechanism in
ACS. Macrophage infiltration has been consistently demonstrated in
pathological studies; the proportion of macrophages is six to nine
times greater in ruptured than in stable plaques and is characterized
by the presence of activated T lymphocytes at the site of plaque
rupture that can release various cytokines that activate macrophages
and promote smooth muscle cell proliferation.

38
 Coronary thrombosis plays the central role in the development
of ACS. Thrombosis is induced at the site of plaque rupture or
erosion and may lead to rapid changes in the severity of stenosis that
may cause subtotal or total vessel occlusion. The thrombus is fibrin-
rich and completely occlusive in STEMI, whereas it is platelet-rich
and partially or intermittently occlusive in NSTE-ACS.
Vulnerable patient
Hypercholesterolaemia, tobacco smoking, and increased
fibrinogen levels have been reported to contribute to instability in
these patients, leading to thrombotic complications.
Endothelial vasodilatory dysfunction
Minor changes in coronary tone may greatly affect myocardial
blood supply and thus cause insufficient flow at rest or during the
exercise. Vasospasm most frequently occurs at the site of
atherosclerotic plaques in which local vasoconstricting substances,
such as serotonin, thromboxane A2, and thrombin, are released
locally by platelets and intracoronary thrombi. It has been shown that
the endothelium is a multifunctional organ, the integrity of which is
essential for normal tone modulation. Endothelial dysfunction is
linked to prognosis and is unmasked by vasoconstriction induced by
acetylcholine and methacholine.
Accelerated atherosclerosis
Severe endothelial injury appears to be the critical initiating event
that causes smooth muscle cell proliferation in accelerated
atherosclerosis. This is followed by intense platelet activation and
thrombus formation leading to rapidly progressive coronary narrowing.
Secondary mechanisms
A number of extracardiac mechanisms can cause a critical
increase in myocardial oxygen consumption to treble the supply, and
thus elicit an ACS episode with or without a pre-existing coronary
stenosis. The mechanisms related to an increase in myocardial
oxygen consumption are fever, tachycardia, thyrotoxicosis,
hyperadrenergic state, sudden emotional stress, and increased left
ventricular (LV) afterload (hypertension, aortic stenosis), whereas
those related to reduced myocardial oxygen delivery are anaemia,
methaemoglobinaemia, and hypoxaemia. Triggers such as emotional
upset, vigorous physical exercise, lack of sleep, or overeating have
been shown to precipitate the onset of ACS.

39
 Clinical presentation and history of NSTE-ACS
The clinical presentation of NSTE-ACS encompasses a wide
variety of symptoms. Traditionally, several clinical presentations
have been distinguished:
– prolonged (20 min) anginal pain at rest;
– new onset (de novo) severe angina (class III of the Canadian
Cardiovascular Society classification);
– recent destabilization of previously stable angina with at least
CCS III angina characteristics (crescendo angina);
– post-MI angina.
Prolonged pain is observed in 80% of patients, whereas de novo
or accelerated angina is observed in only 20%. It is important to note
that a reliable distinction between ACS with or without ST-elevation
cannot be based on symptoms. The typical clinical presentation of
NSTE-ACS is retrosternal pressure or heaviness (“angina”) radiating
to the left arm, neck, or jaw, which may be intermittent (usually
lasting several minutes) or persistent. These complaints may be
accompanied by other symptoms such as diaphoresis, nausea,
abdominal pain, dyspnoea, and syncope. However, atypical
presentations of NSTE-ACS are not uncommon.
These include epigastric pain, recent-onset indigestion, stabbing
chest pain, chest pain with some pleuritic features, or increasing
dyspnoea. Atypical complaints are often observed in younger
(25–40 years) and older (> 75 years) patients, in women, and in
patients with diabetes, chronic renal failure, or dementia. Absence of
chest pain leads to under-recognition of the disease and
undertreatment. The diagnostic and therapeutic challenges arise
especially when the ECG is normal or nearly normal, or conversely
when the ECG is abnormal at baseline due to underlying conditions
such as intraventricular conduction defects or LV hypertrophy.
Physical examination
The physical examination is frequently normal. Signs of heart
failure or haemodynamic instability must prompt the physician to
expedite the diagnosis and treatment of patients. An important goal
of the physical examination is to exclude noncardiac causes of chest
pain and non-ischaemic cardiac disorders (e.g., pulmonary
embolism, aortic dissection, pericarditis, valvular heart disease), or
potentially extracardiac causes, such as acute pulmonary diseases

40
(pneumothorax, pneumonia, pleural effusion). In this regard,
differences in blood pressure between the upper and lower limbs, an
irregular pulse, heart murmurs, friction rub, pain on palpation, and
abdominal masses are physical findings that may suggest a diagnosis
other than NSTE-ACS. Other physical findings such as pallor,
increased sweating, or tremor may orientate towards precipitating
conditions, such as anaemia and thyrotoxicosis.
ECG: the finding of persistent (> 20 min) ST-elevation; ST-
segment depression > 0.5 mm (0.05 mV); T-wave inversion
(> 1 mm). Particularly, ischaemia in the territory of the circumflex
artery frequently escapes the common 12-lead ECG, but may be
detected in lead V4R and V3R as well as in leads V7–V9. Transient
episodes of bundle branch block occasionally occur during ischaemic
attacks.
Biochemical markers:
Markers of myocardial injury: cTnT or cTnI are the preferred
markers of myocardial injury, because they are more specific and
more sensitive than the traditional cardiac enzymes such as
creatinine kinase (CK) or its isoenzyme MB (CK-MB).
Markers of inflammatory activity: (increased ESR, moderately
elevated WBC with a shift to the left, increased C-reactive protein).
Markers of neurohumoral activation: neurohumoral activation
of the heart can be monitored by measurements of systemic levels of
natriuretic peptides secreted from the heart. Natriuretic peptides,
such as brain type (B-type natriuretic peptide (BNP)) or its
N-terminal prohormone fragment (NT-proBNP), are highly sensitive
and fairly specific markers for the detection of LV dysfunction.
Markers of renal function: impaired renal function is a strong
independent predictor for long-term mortality in ACS patients.
Serum creatinine concentration is a less reliable indicator of renal
function than creatinine clearance (CrCl) or glomerular filtration rate
(GFR), because it is affected by a multitude of factors, including age,
weight, muscle mass, race, and various medications.
Novel biomarkers: these include markers of oxidative stress
(myeloperoxidase), markers of thrombosis and inflammation (soluble
CD40 ligand), or markers involved more upstream in the
inflammation cascade, i.e. markers specific of vascular inflammation.
Echocardiography: LV systolic function is an important

41
prognostic variable in patients with IHD. In experienced hands,
transient localized hypokinesia or akinesia in segments of the left
ventricle wall may be detected during ischaemia, with normal wall
motion on resolution of ischaemia. Furthermore, differential
diagnoses such as aortic stenosis, aortic dissection, pulmonary
embolism, or hypertrophic cardiomyopathy may be identified.
Coronary angiography is the gold standard in diagnostics.
Patients with multiple vessel disease as well as those with left main
stenosis are at the highest risk of serious cardiac events.

Recommendations for diagnosis and risk stratification

1. Diagnosis and short-term risk stratification of NSTE-ACS
should be based on the combination of clinical history, symptoms,
ECG, biomarkers, and risk score results (IB).
2. The evaluation of the individual risk is a dynamic process that
is to be updated as the clinical situation evolves.
– A 12-lead ECG should be obtained within 10 min after first
medical contact and immediately read by an experienced physician
(IC). Additional leads (V3R and V4R, V7–V9) should be recorded.
ECG should be repeated in the case of recurrence of symptoms, and
at 6 and 24 h and before hospital discharge (IC).
– Blood must be drawn promptly for troponin (cTnT or cTnI)
measurement. The result should be available within 60 min (IC). The
test should be repeated after 6–12 h if the initial test is negative (IA).
– Established risk scores (such as GRACE) should be
implemented for initial and subsequent risk assessment (IB).
– An echocardiogram is recommended to rule in/out differential
diagnoses (IC).
– In patients without recurrence of pain, normal ECG findings,
and negative troponins tests, a non-invasive stress test for inducible
ischaemia is recommended before discharge (IA).
3. The following predictors of long-term death or MI should be
considered in risk stratification (IB).
– Clinical indicators: age, heart rate, blood pressure, Killip class,
diabetes, previous MI/CAD.
– ECG markers: ST-segment depression.
– Laboratory markers: troponins, GFR/CrCl/cystatin C,
BNP/NT-proBNP, hsCRP.

42
 – Imaging findings: low EF, main stem lesion, three-vessel
disease.
– Risk score result.
Treatment
The treatment options described in this section are based on
evidence from numerous clinical trials or meta-analyses. Four
categories of acute treatment are discussed: anti-ischaemic agents,
anticoagulants, antiplatelet agents, and coronary revascularization.
Anti-ischaemic agents. These drugs decrease myocardial oxygen
consumption (decreasing heart rate, lowering blood pressure, or
depressing LV contractility) and/or induce vasodilatation:
β-blockers, nitrates, calcium channel blockers.
Recommendations for anti-ischaemic drugs:
1. B-blockers are recommended in the absence of
contraindications, particularly in patients with hypertension or
tachycardia (IB).
2. Intravenous or oral nitrates are effective for symptom relief in
the acute management of anginal episodes (IC).
3. Calcium channel blockers provide symptom relief in patients
already receiving nitrates and beta-blockers; they are useful in
patients with contraindications to beta-blockade and in the subgroup
of patients with vasospastic angina (IB).
4. Nifedipine, or other dihydropyridines, should not be used
unless combined with beta-blockers (IIIB).
Anticoagulants: unfractionated heparin (UFH) as intravenous
infusion; low molecular weight heparin (LMWH) as subcutaneous
injection; fondaparinux as subcutaneous injection; direct thrombin
inhibitors (DTIs) as intravenous infusion; vitamin K antagonists
(VKAs) as oral medication.
Recommendations for anticoagulation:
1. Anticoagulation is recommended for all patients in addition to
antiplatelet therapy (IA).
2. Anticoagulation should be selected according to the risk of
both ischaemic and bleeding events (I-B).
3. Several anticoagulants are available, namely UFH, LMWH,
fondaparinux, and bivalirudin. The choice depends on the initial
strategy (IB).
4. In an urgent invasive strategy, UFH (I-C), enoxaparin (IIa, B),

43
or bivalirudin (IB) should be immediately started.
5. In nonurgent situation, as long as a decision between an early
invasive or conservative strategy is pending:
– fondaparinux is recommended on the basis of the most
favourable efficacy/safety profile (IA);
– enoxaparin with a less favourable efficacy/safety profile than
fondaparinux should be used only if the bleeding risk is low (IIa, B);
– as the efficacy/safety profile of LMWH (other than
enoxaparin) or UFH relative to fondaparinux is unknown, these
anticoagulants cannot be recommended over fondaparinux (IIa, B);
– at PCI procedures, the initial anticoagulant should also be
maintained during the procedure regardless of whether this treatment
is UFH (IC), enoxaparin (IIa,B), or bivalirudin (IB), whereas
addititional UFH in standard dose (50–100 IU/kg bolus) is necessary
in the case of fondaparinux (IIa, C);
– anticoagulation can be stopped within 24 h after an invasive
procedure (IIa, C). In a conservative strategy, fondaparinux,
enoxaparin, or other LMWH may be maintained up to hospital
discharge (IB).
Antiplatelet agents: acetylsalicylic acid (aspirin); both
ticlopidine and clopidogrel.
Glycoprotein IIb/IIIa receptor inhibitors
Three GP IIb/IIIa inhibitors have been approved for clinical use,
namely abciximab, eptifibatide, and tirofiban.
Recommendations for oral antiplatelet drugs:
1. Aspirin is recommended for all patients presenting with
NSTE-ACS without contraindication at an initial loading dose of
160–325 mg (non-enteric) (IA), and at a maintenance dose of
75–100 mg long-term (IA).
2. For all patients, an immediate 300 mg loading dose of
clopidogrel is recommended, followed by 75 mg clopidogre daily
(IA). Clopidogrel should be maintained for 12 months unless there is
an excessive risk of bleeding (IA).
3. For all patients with contraindication to aspirin, clopidogrel
should be given instead (IB).
4. In patients considered for an invasive procedure/PCI, a loading
dose of 600 mg of clopidogrel may be used to achieve more rapid
inhibition of platelet function (IIa, B).

44
 5. In patients pretreated with clopidogrel who need to undergo
CABG, surgery should be postponed for 5 days for clopidogrel
withdrawal if clinically feasible (IIa, C).
Recommendations for glycoprotein IIb/IIIa inhibitors:
1. In patients at intermediate to high risk, particularly patients
with elevated troponins, ST-depression, or diabetes, either
eptifibatide or tirofiban for initial early treatment is recommended in
addition to oral antiplatelet agents (IIa, A).
2. The choice of combination of antiplatelet agents and
anticoagulants should be made in relation to risk of ischaemic and
bleeding events (IB).
3. Patients who receive initial treatment with eptifibatide or
tirofiban prior to angiography should be maintained on the same drug
during and after PCI (IIa, B).
4. In high-risk patients not pretreated with GP IIb/IIIa inhibitors
and proceeding to PCI, abciximab is recommended immediately
following angiography (IA). The use of eptifibatide or tirofiban in
this setting is less well established (IIa, B).
5. GP IIb/IIIa inhibitors must be combined with an anticoagulant
(IA).
6. Bivalirudin may be used as an alternative to GP IIb/IIIa
inhibitors plus UFH/LMWH (IIa, B).
7. When anatomy is known and PCI planned to be performed
within 24 h with GP IIb/IIIa inhibitors, most secure evidence is for
abciximab (IIa, B).

Clinical use of antithrombotic therapy

Oral antiplatelet therapy
Aspirin initial dose: 160–325 mg non-enteric formulation,
followed by 75–100 mg daily; clopidogrel 75 mg/day after a loading
dose of 300 mg (600 mg when rapid onset of action is wanted).
Anticoagulants
Fondaparinuxa 2.5 mg subcutaneously daily, enoxaparina
1 mg/kg subcutaneously every 12 h, dalteparina 120 IU/kg every
12 h, nadroparina 86 IU/kg every 12 h. UFH intravenous bolus
60–70 U/kg (maximum 5000 IU) followed by infusion of
12–15 IU/kg/h (maximum 1000 U/h) titrated to aPTT 1.5–2.5 times
control, bivalirudina intravenous bolus of 0.1 mg/kg and infusion of

45
0.25 mg/kg/h. Additional intravenous bolus of 0.5 mg/kg and
infusion increased to 1.75 mg/kg/h before PCI.
GP IIb/IIIa inhibition
Abciximab 0.25 mg/kg intravenous bolus followed by infusion of
0.125 mg/kg/min (maximum 10 mg/min) for 12–24 h.
Eptifibatide 180 mg/kg intravenous bolus (second bolus after
10 min for PCI) followed by infusion of 2.0 mg/kg/min for 72–96 h.
Tirofiban 0.4 mg/kg/min intravenously for 30 min followed by
infusion of 0.10 mg/kg/min for 48–96 h. A high-dose regimen (bolus
25 mg/kg þ 0.15 mg/kg/min infusion for 18h) is tested in clinical
trials.
Coronary revascularization
Invasive coronary angiography remains pivotal in determining
suitability for percutaneous and/or surgical revascularization.
Recommendations for invasive evaluation and
revascularization:
1. Urgent coronary angiography is recommended in patients with
refractory or recurrent angina associated with dynamic ST-deviation,
heart failure, life-threatening arrhythmias, or haemodynamic
instability (IC).
2. Early (< 72 h) coronary angiography followed by
revascularization (PCI or CABG) in patients with intermediate to
high-risk features is recommended (IA).
3. Routine invasive evaluation of patients without intermediate to
high-risk features is not recommended (IIIC), but non-invasive
assessment of inducible ischaemia is advised (IC).
4. PCI of nonsignificant lesions is not recommended (IIIC).
5. After critical evaluation of the risk–benefit ratio, and
depending on known comorbidities and potential need for noncardiac
surgery in the short/medium term (e.g., planned intervention or other
conditions) requiring temporary withdrawal of dual antiplatelet
therapy, consideration should be given to the type of stent to be
implanted (BMS or DES) (IC).
Long-term management:
1. Weight reduction.
2. Blood pressure control. The goal is to achieve blood pressure
< 140/90 mmHg in nondiabetic patients and < 130/80 mmHg in
patients with diabetes or chronic renal dysfunction.

46
 3. Management of diabetes (HbA1c levels ≤ 6.5%).
4. Interventions on lipid profile. Recommendations for lipid-
lowering therapy:
a) statins are recommended for all NSTE-ACS patients (in the
absence of contraindications), irrespective of cholesterol levels,
initiated early (within 1–4 days) after admission, with the aim of
achieving LDLc levels < 100 mg/dL (< 2.6 mmol/L) (IB);
b) intensive lipid-lowering therapy with target LDLc levels
< 70 mg/dL (< 1.81 mmol/L) initiated within 10 days after admission
is advisable (IIa, B);
5. Antiplatelet agents and anticoagulants.
6. Beta-blockers. Recommendations for use of β-blockers:
should be given to all patients with reduced LV function (IA).
7. ACE inhibitors. Recommendations for the use of ACEI: ACEI
are indicated long-term in all patients with LVEF ≤ 40% and in
patients with diabetes, hypertension, or CKD, unless contraindicated
(IA). ACEI should be considered for all other patients to prevent
recurrence of ischaemic events (IIa, B). Agents and doses of proven
efficacy are recommended (IIa, C).
8. Angiotensin-2 receptor blockers (ARBs). Recommendations
for the use of ARBs: ARBs should be considered in patients who are
intolerant to ACEI and/or who have heart failure or MI with LVEF <
40% (IB).
9. Aldosterone receptor antagonists. Recommendations for
aldosterone receptor antagonists: aldosterone blockade should be
considered in patients after MI who are already treated with ACE
inhibitors and beta-blockers and who have an LVEF < 40% and
either diabetes or heart failure, without significant renal dysfunction
or hyperkalaemia (IB).
10. Rehabilitation and return to physical activity.
Recommendations for rehabilitation and return to physical activity:
after NSTE-ACS, assessment of functional capacity is recommended
(IC). Every patient after NSTE-ACS should undergo an ECG-guided
exercise test (if technically feasible) or an equivalent non-invasive
test for ischaemia, within 4–7 weeks after discharge (IIa, C). On the
basis of cardiovascular status and the results of functional physical
capacity assessment, patients should be informed about the timing of
resumption and the recommended level of physical activity,

47
including leisure, work, and sexual activities (IC).
Complications and their management
Bleeding complications
Recommendations for bleeding complications:
1. Assessment of bleeding risk is an important component of the
decision-making process. Bleeding risk is increased with higher or
excessive doses of antithrombotic agents, length of treatment,
combinations of several antithrombotic drugs, switch between
different anticoagulant drugs, as well as with older age, reduced renal
function, low body weight, female gender, baseline haemoglobin,
and invasive procedures (IB).
2. Bleeding risk should be taken into account when deciding on a
treatment strategy. Drugs, combination of drugs, and
nonpharmacological procedures (vascular access) known to carry a
reduced risk of bleeding should be preferred in patients at high risk
of bleeding (IB).
3. Minor bleeding should preferably be managed without
interruption of active treatments (IC).
4. Major bleeding requires interruption and/or neutralization of
both anticoagulant and antiplatelet therapy, unless bleeding can be
adequately controlled by specific haemostatic intervention (IC).
5. Blood transfusion may have deleterious effects on outcome
and should therefore be considered individually, but withheld in
haemodynamically stable patients with haematocrit > 25% or
haemoglobin level > 8 g/L (IC).
Thrombocytopenia
Recommendations for thrombocytopenia:
1. Significant thrombocytopenia (< 100 000 mL-1or > 50% drop
in platelet count) occurring during treatment with GP IIb/IIIa
inhibitors and/or heparin (LMWH or UFH) requires the immediate
interruption of these drugs (IC).
2. Severe thrombocytopenia (< 10 000 mL -1) induced by GP
IIb/IIIa inhibitors requires platelet transfusion with or without
fibrinogen supplementation with fresh-frozen plasma or
cryoprecipitate in case of bleeding (IC).
3. Interruption of heparin (UFH or LMWH) is warranted in case
of documented or suspected HIT. In case of thrombotic
complications, anticoagulation can be achieved with DTI (IC).

48
 4. Prevention of HIT can be achieved with the use of
anticoagulants devoid of risk of HIT, such as fondaparinux or
bivalirudin, or by brief prescription of heparin (UFH or LMWH) in
cases where these compounds are chosen as anticoagulant (IB).
Special populations and conditions
Recommendations for the elderly:
1. Elderly patients (> 75 years old) often have atypical
symptoms. Active screening for NSTE-ACS should be initiated at
lower levels of suspicion than among younger (< 75 years old)
patients (IC).
2. Treatment decisions in the elderly should be tailored according
to estimated life expectancy, patient wishes, and comorbidities to
minimize risk and improve morbidity and mortality outcomes in this
frail but high-risk population (IC).
3. Elderly patients should be considered for routine early
invasive strategy, after careful evaluation of their inherent raised risk
of procedure-related complications, especially during CABG (IB).
Gender. Recommendations for women: women should be
evaluated and treated in the same way as men, with special attention
to comorbidities (IB).
Recommendations for diabetes mellitus:
1. Tight glycaemic control to achieve normoglycaemia as soon as
possible is recommended in all diabetic patients with NSTE-ACS in
the acute phase (IC).
2. Insulin infusion may be needed to achieve normoglycaemia in
selected NSTE-ACS patients with high blood glucose levels at
admission (IIa, C).
3. An early invasive strategy is recommended for diabetic
patients with NSTE-ACS (IA).
4. Diabetic patients with NSTE-ACS should receive intravenous
GP IIb/IIIa inhibitors as part of the initial medical management
which should be continued through the completion of PCI (IIa, B).
Recommendations for patients with chronic kidney disease
(CKD):
1. CrCl and/or GFR should be calculated for every patient
hospitalized for NSTE-ACS (I-B). Elderly people, women, and low
body weight patients merit special attention as near normal serum
creatinine levels may be associated with lower than expected CrCl

49
and GFR levels (IB).
2. Patients with CKD should receive the same first-line treatment
as any other patient, in the absence of contraindications (IB).
3. In patients with CrCl < 30 mL/min or GFR <
30 mL/min/1.73 m2, a careful approach to the use of anticoagulants is
recommended, since dose adjustment is necessary with some, while
others are contraindicated (IC).
4. UFH infusion adjusted according to aPTT is recommended
when CrCl < 30 mL/min or GFR < 30 mL/min/1.73 m2 (IC).
5. GP IIb/IIIa inhibitors can be used in the case of renal failure.
Dose adaptation is needed with eptifibatide and tirofiban. Careful
evaluation of the bleeding risk is recommended for abciximab (IB).
6. Patients with CKD with CrCl < 60 mL/min are at high risk of
further ischaemic events and therefore should be submitted to
invasive evaluation and revascularization whenever possible (IIa, B).
7. Appropriate measures are advised in order to reduce the risk of
CIN (IB).
Recommendations for anaemia:
1. Low baseline haemoglobin is an independent marker of the
risk of ischaemic and bleeding events at 30 days. It should be taken
into consideration in assessing initial risk (IB).
2. All necessary measures should be taken during the course of
initial management to avoid worsening of anaemia by bleeding (IB).
3. Well-tolerated anaemia at baseline in patients with NSTE-
ACS should not lead to systematic blood transfusion which should
be considered only in the case of compromised haemodynamic status
(IC).

Management strategies
First step: initial evaluation
The initial step is to assign the patient without delay to a working
diagnosis on which the treatment strategy will be based. The criteria
are the following: quality of chest pain and a symptom-oriented
physical examination; assessment of the likelihood of CAD (e.g.,
age, risk factors, previous MI, CABG, PCI); ECG (ST-deviation or
other ECG abnormalities).
On the basis of these findings which should be available within
10 min after first medical contact, the patient can be assigned to one

50
of the three major working diagnoses: STEMI requiring immediate
reperfusion; NSTE-ACS; ACS (highly) unlikely.
Second step: diagnosis validation and risk assessment
After the patient is assigned to the group NSTE-ACS, intravenous
and oral treatments will be started according to the first-line,
treatment should be made up of at least nitrates, beta-blockers,
aspirin, clopidogrel, and anticoagulation, the type depending on the
management strategy, i.e. urgent invasive, early invasive, or
conservative (see third step).
Primary therapeutic measures
1. Oxygen insufflation (4–8 L/min) if oxygen saturationis <
90%.
2. Nitrates sublingually or intravenously (caution if systolic
blood pressure < 90 mmHg).
3. Aspirin initial dose of 160–325 mg non-enteric formulation
followed by 75–100 mg/day (intravenous administration is
acceptable).
4. Clopidogrel loading dose of 300 mg (or 600 mg for rapid
onset of action) followed by 75 mg daily.
5. Anticoagulation choice between different options depends on
strategy: UFH intravenous bolus 60–70 IU/kg (maximum 5000 IU)
followed by infusion of 12–15 IU/kg/h (maximum 1000 IU/h)
titrated to aPTT 1.5–2.5 times control; fondaparinux 2.5 mg/daily
subcutaneously; enoxaparin 1 mg/kg twice daily subcutaneously;
dalteparin 120 IU/kg twice daily subcutaneously, nadroparin
86 IU/kg twice daily subcutaneously; bivalirudin 0.1 mg/kg bolus
followed by 0.25 mg/kg/h.
6. Morphine 3–5 mg intravenously or subcutaneously, depending
on pain severity.
7. Oral beta-blocker, particularly if tachycardia or hypertension
without sign of heart failure.
8. Atropine 0.5–1 mg intravenously in bradycardia or vagal
reaction.
The further management will be based on additional
information/data: routine clinical chemistry, particularly troponins
(on presentation and after 6–12 h) and other markers according to
working diagnoses (e.g., D-dimers, BNP, NT-proBNP); repeat,
preferably continuous, ST-segment monitoring (when available);

51
echocardiogram, MRI, CT, or nuclear imaging for differential
diagnoses; responsiveness to antianginal treatment; risk score
assessment; bleeding risk assessment.
Third step: invasive strategy
Cardiac catheterization is advised to prevent early complications
and/or to improve long-term outcome. Accordingly, the need for and
timing of an invasive strategy has to be tailored according to the
acuteness of risk into three categories: conservative, early invasive,
or urgent invasive.
Conservative strategy: no recurrence of chest pain; no signs of
heart failure; no abnormalities in the initial ECG or second ECG
(6–12 h); no elevation of troponins (arrival and in 6–12 h).
Urgent invasive strategy. These patients are characterized by:
refractory angina (e.g., evolving MI without ST-abnormalities);
recurrent angina despite intense antianginal treatment associated with
ST-depression (> 2 mm) or deep negative T waves; clinical
symptoms of heart failure or haemodynamic instability (“shock”);
life-threatening arrhythmias (ventricular fibrillation or ventricular
tachycardia).
Early invasive strategy: most patients initially respond to the
antianginal treatment, but are at increased risk and need early
angiography. The timing depends on the local circumstances, but it
should be performed within 72 h. The following features indicate
patients who should undergo routine early angiography: elevated
troponin levels; dynamic ST or T wave changes (symptomatic or
silent) (≥ 0.5 mm); diabetes mellitus; reduced renal function
(GFR,60 mL/min/1.73 m2); depressed LVEF,40%; early post-MI
angina; PCI within 6 months; previous CABG; intermediate to high
risk according to a risk score.
Fourth step: revascularization modalities.
If the angiogram shows no critical coronary lesions, patients will
be referred for medical therapy. The diagnosis of NSTE-ACS may be
reconsidered and particular attention should be paid to other possible
reasons for symptoms at presentation before the patient is
discharged. However, the absence of critical coronary lesions does
not rule out the diagnosis if clinical presentation was suggestive of
ischaemic chest pain and if biomarkers were positive. In this
situation, patients should receive treatment according to

52
recommendations in NSTE-ACS.
Fifth step: discharge and post-discharge management.

Myocardial Infarction

Myocardial infarction (MI) is the myocardial necrosis resulting from

abrupt reduction in coronary blood flow to part of the myocardium.
Infarcted tissue is permanently dysfunctional; however, there is a
zone of potentially reversible ischaemia adjacent to infarcted tissue.
In the US, about 1.5 million MIs occur annually; MI results in
death for 400,000 to 500,000 people, with about half dying before
they reach the hospital. The term “myocardial infarction” reflects cell
death of cardiac myocytes caused by ischaemia, which is the result of
a perfusion imbalance between supply and demand. Ischaemia in a
clinical setting most often can be identified from the patient’s history
and from the ECG. Possible ischaemic symptoms include various
combinations of chest, upper extremity, jaw, or epigastric discomfort
with exertion or at rest. The discomfort associated with acute
myocardial infarction usually lasts at least 20 min. Often, the
discomfort is diffuse, not localized, not positional, not affected by
movement of the region, and it may be accompanied by dyspnoea,
diaphoresis, nausea, or syncope.
These symptoms are not specific to myocardial ischaemia and can
be misdiagnosed and thus attributed to gastrointestinal, neurological,
pulmonary, or musculoskeletal disorders. Myocardial infarction may
occur with atypical symptoms, or even without symptoms, being
detected only by ECG, biomarker elevations, or cardiac imaging.
Criteria for acute myocardial infarction (MI)
Any of the following criteria meets the diagnosis for MI:
1. Detection of elevated values of cardiac biomarkers (preferably
troponin) above the 99th centile of the upper reference limit (URL)
together with evidence of myocardial ischaemia with at least one of
the following: ischaemic symptoms; ECG changes indicative of new
ischaemia (new ST-T changes or new left bundle branch block
(LBBB)); development of pathological Q waves in the ECG;
imaging evidence of new loss of viable myocardium or new regional
wall motion abnormality.
2. Sudden unexpected cardiac death, including cardiac arrest,

53
with symptoms suggestive of myocardial ischaemia, accompanied by
new ST elevation, or new LBBB, or definite new thrombus by
coronary angiography but dying before blood samples could be
obtained, or in the lag phase of cardiac biomarkers in the blood.
3. For percutaneous coronary interventions (PCI) in patients with
normal baseline values, elevations of cardiac biomarkers above the
99th centile URL are indicative of periprocedural myocardial
necrosis. By convention, increases of biomarkers greater than 3 × 99th
centile URL have been designated as defining PCI related MI.
4. For coronary artery bypass grafting (CABG) in patients with
normal baseline values, elevations of cardiac biomarkers above the
99th centile URL are indicative of periprocedural myocardial
necrosis. By convention, increases of biomarkers greater than 5 × 99th
centile URL plus either new pathological Q waves or new LBBB, or
angiographically documented new graft or native coronary artery
occlusion, or imaging evidence of new loss of viable myocardium
have been designated as defining CABG related MI.
5. Pathological postmortem findings of acute MI.
Criteria for prior MI
Any of the following criteria meets the diagnosis for prior MI:
1. Development of new pathological Q waves with or without
symptoms.
2. Imaging evidence of a region of loss of viable myocardium
that is thinned and fails to contract, in the absence of a non-
ischaemic cause.
3. Pathological postmortem findings of a healed or healing MI.
Pathology
Myocardial infarction is defined by pathology as myocardial cell
death due to prolonged ischaemia. Cell death is categorized
pathologically as coagulation and/or contraction band necrosis,
which usually evolves through oncosis, but can result to a lesser
degree from apoptosis. After the onset of myocardial ischaemia, cell
death is not immediate but takes a finite period to develop (as little as
20 min or less in some animal models). It takes several hours before
myocardial necrosis can be identified by macroscopic or microscopic
postmortem examination. Complete necrosis of all myocardial cells
at risk requires at least 2–4 h or longer depending on the presence of
collateral circulation to the ischaemic zone, persistent or intermittent

54
coronary arterial occlusion, the sensitivity of the myocytes to
ischaemia, preconditioning, and/or, finally, individual demand for
myocardial oxygen and nutrients.
Classification of MI
– by size: microscopic (focal necrosis), small (< 10% of the left
ventricular (LV) myocardium), moderate (10–30% of the LV
myocardium), and large (> 30% of the LV myocardium);
– MI can be defined pathologically as acute, healing, or healed.
Myocardial infarctions can be classified temporally from clinical and
other features, as well as according to the pathological appearance, as
evolving (< 6 h), acute (6 h – 7 days), healing (7–28 days), and
healed (29 days and beyond);
– by the character of the disease course;
– by localization of MI (anteroseptal, anteroapexal, anterolateral,
aneriobasal, inferiodiaphragmatic, inferiolateral, inferiobasal, gross
inferior, gross anterior (septal, apex, lateral), MI of right ventricle);
– by presence of MI complications.
By the character of the disease course:
Primary MI is diagnosed at absence of MI signs in the past.
Repeated MI – when the patient, which had MI in the past, has
signs of the new necrosis centre, formed in other coronary arteries in
terms exceeding 28 days from the moment of occurrence of the
previous MI.
At relapsing MI the clinical and laboratory signs of formation of
the new centres of necrosis occur in terms from 72 h (3 days) about
28 days after MI development.
Clinical classification of different types of MI
Type 1. Spontaneous myocardial infarction related to ischaemia
due to primary coronary event such as plaque erosion and/or rupture,
fissuring, or dissection.
Type 2. Myocardial infarction secondary to ischaemia due to
either increased oxygen demand or decreased supply, e.g., coronary
artery spasm, coronary embolism, anaemia, arrhythmias,
hypertension, or hypotension.
Type 3. Sudden unexpected cardiac death, including cardiac
arrest, often with symptoms suggestive of myocardial ischaemia,
accompanied by presumably new ST elevation, or new LBBB, or
evidence of fresh thrombus in a coronary artery by angiography

55
and/or at autopsy, but death occurring before blood samples could be
obtained, or before the appearance of cardiac biomarkers in the
blood.
Type 4a. Myocardial infarction associated with PCI.
Type 4b. Myocardial infarction associated with stent thrombosis
as documented by angiography or at autopsy.
Type 5. Myocardial infarction associated with coronary artery
bypass grafting (CABG).
Two classifications of the severity of heart failure in the
context of acute MI:
1. Killip’s classification
Designed to provide clinical estimation of the severity of
circulatory derangement in the treatment of acute MI.
Stage 1. No heart failure. No clinical signs of cardiac
decompensation.
Stage 2. Heart failure. Diagnostic criteria include rales, S3
gallop, and pulmonary venous hypertension. Pulmonary congestion
with wet rales in the lower half of the lung fields.
Stage 3. Severe heart failure. Frank pulmonary oedema with rales
throughout the lung fields.
Stage 4. Cardiogenic shock. Signs include hypotension (SBP <
90 mmHg), and evidence of peripheral vasoconstriction such as
oliguria, cyanosis and sweating.
2. Forrester’s classification
Designed to describe clinical and haemodynamic status in acute
MI.
1. Normal perfusion and pulmonary wedge pressure (PCWP –
estimation of the left atrial pressure).
2. Poor perfusion and low PCWP (hypovolaemic).
3. Near normal perfusion and high PCWP (pulmonary oedema).
4. Poor perfusion and high PCWP (cardiogenic shock).
Clinical variants of MI
– painful (anginosus) variant of the onset (status anginosus);
– asthmatic variant (status asthmaticus);
– abdominal variant (status abdominalis);
– arhythmical variant;
– cerebrovascular variant;
– asymptomatic onset of MI.

56
 Diagnosis of MI
– serial ECGs;
– serial cardiac markers;
– emergent coronary angiography for those with STEMI or
complications (e.g., persistent chest pain, markedly elevated cardiac
markers, unstable arrhythmias);
– delayed angiography (24 to 48 h) for those with NSTEMI or
unstable angina.
Electrocardiographic detection of MI
ECG manifestations of acute myocardial ischaemia (in
absence of LVH and LBBB)
ECG is the most important test and should be done within 10 min
of presentation. It is the centre of the decision pathway because
fibrinolytics benefit patients with STEMI but may increase risk for
those with NSTEMI. Also, emergent cardiac catheterization is
indicated for patients with acute STEMI but not for those with
NSTEMI.
For STEMI, initial ECG is usually diagnostic, showing ST-
segment elevation ≥ 1 mm in 2 or more contiguous leads subtending
the damaged area.
ST elevation
New ST elevation at the J-point in two contiguous leads with the
cut-off points: ≥ 0.2 mV in men or ≥ 0.15 mV in women in leads
V2–V3 and/or ≥ 0.1 mV in other leads.
ST depression and T wave changes
New horizontal or down-sloping ST depression ≥ 0.05 mV in two
contiguous leads; and/or T inversion ≥ 0.1 mV in two contiguous
leads with prominent R wave or R/S ratio > 1.
ECG changes associated with prior MI
– any Q wave in leads V2–V3 ≥0.02 s or QS complex in leads
V2 and V3;
– Q wave ≥ 0.03 s and ≥ 0.1 mV deep or QS complex in leads I,
II, aVL, aVF, or V4–V6 in any two leads of contiguous lead
grouping (I, aVL,V6;V4–V6; II, III, and aVF);
– R wave ≥ 0.04 s in V1–V2 and R/S ≥ 1 with a concordant
positive T wave in the absence of a conduction defect.
Conditions that confound the ECG diagnosis of MI
A QS complex in lead V1 is normal. Q wave < 0.03 s and < 1/4 of

57
the R wave amplitude in lead III is normal if the frontal QRS axis is
between 30 and 0°. Q wave may also be normal in aVL if the frontal
QRS axis is between 60 and 90 °. Septal Q waves are small
nonpathological Q waves < 0.03 s and < 1/4 of the R wave amplitude
in leads I, aVL, aVF, and V4–V6. Pre-excitation, obstructive or
dilated cardiomyopathy, LBBB, RBBB, left anterior hemiblock, left
and right ventricular hypertrophy, myocarditis, acute cor pulmonale,
or hyperkalaemia may be associated with Q/QS complexes in the
absence of MI.
ECG abnormalities that simulate myocardial ischaemia or
infarction are:
False positives (benign early repolarization, LBBB, pre-
excitation, Brugada syndrome, peri-/myocarditis, pulmonary
embolism, subarachnoid haemorrhage, metabolic disturbances such
as hyperkalaemia, failure to recognize normal limits for J-point
displacement, lead transposition or use of modified Mason–Likar
configuration, cholecystitis).
False negatives (prior MI with Q waves and/or persistent, ST
elevation, paced rhythm, LBBB).
Elevations of troponin in the absence of overt ischaemic heart
disease: cardiac contusion, or other trauma including surgery,
ablation, pacing, etc.; congestive heart failure – acute and chronic
aortic dissection; aortic valve disease; hypertrophic cardiomyopathy;
tachy- or bradyarrhythmias, or heart block; apical ballooning
syndrome; rhabdomyolysis with cardiac injury; pulmonary
embolism, severe pulmonary hypertension; renal failure; acute
neurological disease, including stroke or subarachnoid haemorrhage;
infiltrative diseases, e.g., amyloidosis, haemochromatosis,
sarcoidosis, and scleroderma; inflammatory diseases, e.g.,
myocarditis or myocardial extension of endo-/pericarditis; drug
toxicity or toxins; critically ill patients, especially with respiratory
failure or sepsis; especially if affecting > 30% of body surface area;
extreme exertion.
Laboratory data
Cardiac markers. Cardiac markers are cardiac enzymes (CPK-
MB) and cell contents (troponin I, troponin T, myoglobin) that are
released into the bloodstream after myocardial cell necrosis. The
markers appear at different times after injury and decrease at

58
different rates.
Relative timing and levels of cardiac markers in blood after
acute MI.
Other tests. Routine laboratory tests are nondiagnostic but, if
obtained, show nonspecific abnormalities compatible with tissue
necrosis (increased ESR, moderately elevated WBC with a shift to
the left). A fasting lipid profile should be obtained within the first
24 h for all patients hospitalized with ACS.
Troponin is the preferred biomarker for diagnosis.
Troponins have the greatest sensitivity and specificity in detecting
MI. The test result is both diagnostic as well as prognostic of
outcome. Troponin is a contractile protein that normally is not found
in serum. It is released only when myocardial necrosis occurs.
For early detection of myocardial necrosis, sensitivity of this
laboratory test is superior to that of the creatine kinase-MB (CK-
MB). Troponin I is detectable in serum 3–6 hours after an AMI and
its level remains elevated for 14 days.
Troponin is also the optimum biomarker for the evaluation of
patients with MI who have coexistent skeletal muscle injury.
Creatine kinase – MB level
CK-MB levels begin to rise within 4 hours after injury, peak at
18–24 hours, and subside over 3–4 days. A level within the reference
range does not exclude myocardial necrosis.
Occasionally, very small infarctions can be missed by CK-MB;
therefore, a troponin level should be measured for patients suspected
of having had MI who have negative serial CK-MBs.
Myoglobin levels
Myoglobin, a low-molecular-weight heme protein found in
cardiac and skeletal muscle, is released more rapidly from infarcted
myocardium than troponin and CK-MB and may be detected as early
as 2 hours after MI. Myoglobin levels rise early in the course of MI.
The marker has high sensitivity but poor specificity. When
performed in conjunction with other studies, it may be useful for the
early detection of MI.
Complete blood count (CBC)
CBC is indicated if anaemia is suspected as a precipitant.
Transfusion with packed red blood cells may be indicated.
Leukocytosis may be observed within several hours after an

59
AMI. It peaks in 2–4 days and returns to levels within the reference
range within 1 week.
Chemistry profile
Potassium and magnesium levels should be monitored and
corrected.
Creatinine levels must be considered before using an angiotensin-
converting enzyme (ACE) inhibitor.
C-reactive protein (CRP) is a marker of acute inflammation.
Patients without biochemical evidence of myocardial necrosis but
with elevated CRP level are at increased risk of a subsequent
ischaemic event.
Erythrocyte sedimentation rate (ESR) rises above reference range
values within 3 days and may remain elevated for weeks.
Serum lactate dehydrogenase (LDH) level rises above the
reference range within 24 hours of MI, reaches a peak within
3–6 days, and returns to the baseline within 8–12 days.
Echocardiography: zone hypokinesis or akinesis.
Technetium-99m sestamibi scan
Technetium-99m is a radioisotope that is taken up by the
myocardium in proportion to the blood flow and is only minimally
redistributed after initial uptake. This allows for time delay between
injection of the isotope and imaging.
It has potential use in identifying infarction in patients with
atypical presentations or in patients with ECGs that are not
interpretable.
Normal scan findings are associated with an extremely low risk of
subsequent cardiac events.
Thallium scanning: Thallium accumulates in the viable
myocardium.
Treatment of MI
Specific prehospital care includes the following:
– intravenous access, supplemental oxygen, pulse oximetry;
– immediate administration of aspirin en route;
– nitroglycerin for active chest pain, given sublingually or by
spray;
– telemetry and prehospital ECG, if available.
Medication
Antithrombotic agents

60
 – aspirin (anacin, bayer buffered aspirin, ecotrin) aspirin
(75–325 mg/d) if not contraindicated;
– heparin;
– enoxaparin (lovenox). The heparin-antithrombin III complex
binds to and inactivates activated factor X (Xa) and factor II
(thrombin). Does not actively lyse but is able to inhibit further
thrombogenesis.
Vasodilators: nitroglycerin (minitran, nitrogard, nitrol,
nitrolingual, nitrostat, nitro-dur); β-blockers (metoprolol (lopressor),
esmolol (brevibloc)). Loading dose: 500 mcg/kg/min IV over 1 min.
Optional loading dose: 0.5 mg/kg slow IV infusion. Average
maintenance dose: 50 mcg/kg/min IV over 4 min.
Thrombolytic agents
These agents prevent recurrent thrombus formation and rapid
restoration of haemodynamic disturbances. In addition, they remove
pathologic intraluminal thrombus or embolus not yet dissolved by
the endogenous fibrinolytic system. When given within 12 h of
symptom onset, they restore patency of occluded arteries, salvage
myocardium, and reduce morbidity and mortality rates of AMI.
Thrombolytic treatment should be started within 30 min of arrival
(door-drug time). Maximum benefit occurs when administered
within 1–3 h of symptom onset.
Alteplase (activase)
Fibrin-specific agent with a brief half-life of 5 min. Adjunctive
therapy with IV heparin is necessary to maintain patency of arteries
recanalized by tPA, especially during the first 24–48 h. Heparin may
be administered during tPA infusion.
15 mg IV bolus; 0.75 mg/kg IV over 30 min; not to exceed
50 mg; followed by 0.5 mg/kg over 60 min, up to 35 mg; not to
exceed 100 mg.
Tenecteplase (TNKase). Give IV bolus over 5 s using body
weight; not to exceed 50 mg < 60 kg: 30 mg (6 mL); 60–70 kg:
35 mg (7 mL); 70–80 kg: 40 mg (8 mL); 80–90 kg: 45 mg (9 mL);
> 90 kg: 50 mg (10 mL).
Anistreplase (eminase) 30 U IV over 2–5 min.
Streptokinase (kabikinase, streptase) 1.5 million U in 50 mL
D5W IV over 60 min.
Reteplase (retavase) 10.8 U IV over 2 min; repeat in 30 min.

61
 Clopidogrel (plavix)
Selectively inhibits adenosine diphosphate (ADP) binding to
platelet receptor and subsequent ADP-mediated activation of
glycoprotein GPIIb/IIIa complex, thereby inhibiting platelet
aggregation.
Antagonist of the platelet glycoprotein (GP) IIb/IIIa receptor that
reversibly prevents von Willebrand factor, fibrinogen, and other
adhesion ligands from binding to the GP IIb/IIIa receptor, thereby
inhibiting platelet aggregation: eptifibatide (integrilin) 180 mcg/kg
IV load; followed by 2 mcg/kg/min IV for 72 h. Tirofiban (aggrastat)
0.4 mcg/kg/min IV for 30 min; followed by 0.1 mcg/kg/min.
Analgesics
These agents reduce pain, which decreases sympathetic stress.
They may provide some preload reduction. Analgesics ensure patient
comfort, promote pulmonary toilet, and have sedating properties,
which are beneficial for patients who experience chest discomfort
resulting from myocardial infarction.
Morphine sulfate (duramorph, astramorph, MS contin) 1–3 mg
IV; repeat and titrate to pain relief.

Table 12 – Fibrinolytic Therapy for STEMI

Criteria Specifics
ECG criteria ST-segment elevation in ≥ 2 contiguous leads
Typical symptoms and left bundle branch block not
known to be old
Strictly posterior MI (large R wave in V1 and ST
depression in V1–V4

Absolute contraindications at fibrinolytic therapy for STEMI:

aortic dissection, previous haemorrhagic stroke (at any time),
previous ischaemic stroke within 1 yr, active internal bleeding (not
menses), intracranial tumour, pericarditis.
Relative contraindications at fibrinolytic therapy for STEMI:
BP > 180/110 mm Hg after initial, antihypertensive therapy, trauma
or major surgery within 4 wk, active peptic ulcer, pregnancy,
bleeding diathesis, noncompressible vascular puncture, current
anticoagulation (INR > 2).

62
 Complications of MI
Ischaemic complications of MI
Infarction extension
Infarction extension is a progressive increase in myocardial
necrosis within the infarction zone of the original MI. This may
present as an infarction that extends and involves the adjacent
myocardium or as a subendocardial infarction that becomes
transmural.
Reocclusion of infarction-related arteries (IRAs) occurs in 5 to
30% of patients after fibrinolytic therapy. These patients tend to have
a poorer outcome. Reinfarction is more common in patients with
diabetes mellitus or prior MI.
Recurrent infarction
Infarction in a separate territory (recurrent infarction) may be
difficult to diagnose in the first 24 to 48 hours after the initial event.
Multivessel coronary artery disease is common in patients presenting
with acute MI. In fact, angiographic evidence of complex or
ulcerated plaques in non-IRAs is present in up to 40% of patients
with acute MI.
Postinfarction angina
Angina that occurs within a few hours to 30 days after acute MI is
defined as postinfarction angina. The incidence of postinfarction
angina is greatest in patients with non-ST-segment elevation MI
(approximately 25%) and in those treated with fibrinolytics,
compared with mechanical revascularization.
Mechanical complications of acute MI include:
– ventricular septal rupture (VSR), cardiac free wall rupture;
– papillary muscle rupture or dysfunction (causing mitral
regurgitation);
– LV failure with cardiogenic shock, right ventricular (RV)
failure;
– ventricular pseudoaneurysm and aneurysm;
– dynamic LV outflow tract (LVOT) obstruction.
Cardiac tamponade is life-threatening, slow or rapid
compression of the heart due to the pericardial accumulation of fluid,
pus, blood, clots, or gas, as a result of effusion, trauma, or rupture of
the heart.
Pseudoaneurysm

63
 Pseudoaneurysm is caused by a contained rupture of the LV free
wall. The outer walls are formed by the pericardium and mural
thrombus. The pseudoaneurysm communicates with the body of the
left ventricle through a narrow neck, the diameter of which is less
than 50% of the diameter of the fundus.
Ventricular aneurysm
Typical ECG findings include: ST elevation, which persists
despite reperfusion therapy, and Q waves. ST elevations that persist
for more than 6 weeks suggest a chronic ventricular aneurysm.
Arrhythmical complications:
– ventricular dysrhythmia;
– supraventricular arrhythmias;
– bradyarrhythmias, including AV block and sinus bradycardia,
occur most frequently with inferior MI;
– transvenous pacing is indicated in patients who present with
asystole, Mobitz type II, second-degree AV block, or with complete
AV block.
Embolic complications
Most embolic complications arise from the left ventricle as a
result of wall motion abnormalities or aneurysms. Atrial fibrillation
may also contribute to systemic embolic complications.
Pericarditis
The pathogenesis of acute pericarditis is an inflammatory reaction
in response to necrotic tissue. As such, acute pericarditis develops
more often in patients with transmural MI. The pathogenesis of
Dressler's syndrome is not known, but an autoimmune mechanism
has been suggested. It is characterized by fever, pericarditis with a
friction rub, pericardial effusion, pleurisy, pleural effusions,
pulmonary infiltrates, and joint pain.

Secondary prevention
Aspirin
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
is a suitable alternative.
Beta-blockers
Continuous treatment with an oral β-blocker has been shown to

64
reduce long-term mortality by approximately 25% among the
survivors of acute MI (see EBM panel). Unfortunately, a significant
minority of patients do not tolerate β-blockers because of
bradycardia, heart block, hypotension, overt cardiac failure, asthma,
chronic obstructive airways disease or peripheral vascular disease.
Secondary prevention after MI – use of β-blockers
ACE inhibitors
Several clinical trials have shown that long-term treatment with
an ACE inhibitor (e.g., captopril 50 mg 8-hourly, enalapril 10 mg
12-hourly or ramipril 2.5–5 mg 12-hourly) can counteract ventricular
remodelling, prevent the onset of heart failure, improve survival and
reduce hospitalization.
The benefit of treatment is the greatest in those with overt heart
failure (clinical or radiological) but extends to patients with
asymptomatic LV dysfunction. This form of therapy should therefore
be considered in any patient who has sustained a myocardial
infarction complicated by transient heart failure or poor residual left
ventricular function (e.g., LV ejection fraction < 40%). Caution must
be exercised in hypovolaemic or hypotensive patients because the
introduction of an ACE inhibitor may exacerbate hypotension and
impair coronary perfusion.
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
infarction. Giving up smoking is the single most effective
contribution a patient can make to his or her own future.
Hyperlipidaemia
Convincing evidence from large-scale randomized clinical trials
has demonstrated the importance of lowering plasma cholesterol
following MI. The aim is to reduce total cholesterol to less than
5.0 mmol/l and/or low-density lipoprotein (LDL) cholesterol to less
than 3.0 mmol/l. Lipids should be measured within 24 hours of
presentation because there is often a transient and unrepresentative
fall in blood cholesterol in 3 months following infarction. Dietary
advice should be given but is often ineffective. HMG CoA reductase
enzyme inhibitors (“statins”) can produce marked reductions in total
(and LDL) cholesterol and have been shown to reduce the

65
subsequent risk of death, reinfarction, stroke and the need for
revascularization.
Other risk factors
Maintaining an ideal body weight, taking regular exercise, and
achieving good control of hypertension and diabetes may all improve
the long-term outlook.
Mobilisation and rehabilitation
There is histological evidence that the necrotic muscle of an acute
myocardial infarction takes 4–6 weeks to become replaced with
fibrous tissue and it is conventional to restrict physical activities
during this period. When there are no complications the patient can
sit in a chair on the second day, walk to the toilet on the third day,
return home in 5–7 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; however, in the UK vocational (e.g.,
heavy goods and public service vehicle) driving licence holders
require special assessment.
Emotional problems such as denial, anxiety and depression are
common, and must be recognised and dealt with accordingly. Many
patients are severely and even permanently incapacitated as a result
of the psychological rather than the physical effects of MI, 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.
Prognosis
In almost a quarter of all cases of MI death occurs within a few
minutes without medical care. Half the deaths from MI 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 80%.

66
 Early death is usually due to an arrhythmia but later on the
outcome is determined by the extent of myocardial damage.
Unfavourable features include poor left ventricular function, heart
block and persistent ventricular arrhythmias. The prognosis is worse
for anterior than for inferior infarctions. Bundle branch block and
high enzyme levels both indicate extensive myocardial damage. Old
age, depression and social isolation are also associated with a higher
mortality. In the absence of unfavourable features, the outlook is as
good for those who survive ventricular fibrillation as for the others.
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.

Stable Angina

The diagnosis of chronic stable angina pectoris includes

predictable and reproducible left anterior chest discomfort after
physical activity, emotional stress, or both; symptoms are typically
worse in cold weather or after meals and are relieved by rest or
sublingual nitroglycerin. The presence of one or more obstructions in
major coronary arteries is likely; the severity of stenosis is usually
greater than 70%.
Pathophysiology
As the plaque burden increases, the atherosclerotic mass tends to
stay external to the lumen, which allows the diameter of the lumen to
be maintained; this is known as Glagov’s effect, or positive
remodeling. As plaque encroaches into the lumen, the coronary
artery diameter decreases. Myocardial ischaemia results from a
discordant ratio of coronary blood supply to myocardial oxygen
consumption. Luminal narrowing of more than 65 to 75% may result
in transient ischaemia and angina. In acute coronary syndromes,
vulnerable plaque is a more important factor than the degree of
stenosis; acute coronary events result from ulceration or erosion of
the fibrous cap, with subsequent intraluminal thrombosis. Vulnerable
plaque within the vessel wall may not be obstructive and thus may
remain clinically silent until it causes rupture and associated
consequences.
Classification of angina pectoris

67
 Chest pain is characterized as classic, or typical, angina; as
atypical angina, which includes symptoms that have some but not all
the features of angina; and as nonanginal chest pain, which has none
of the features of angina. Chest pain that occurs during rest or at
night is well described in persons with chronic stable angina,
particularly women.
Classic (typical): sensations in chest of squeezing, heaviness,
pressure, weight, vise-like aching, burning, tightness; radiation to
shoulder, neck, jaw, inner arm, epigastrium (can occur without chest
component); band-like discomfort; relatively predictable; lasts
3–15 min; abates when stressor is gone or nitroglycerin is taken.
Atypical, noncardiac: pain is pleuritic, acute, pricking, knife-
like, pulsating, lancinating, choking; involves chest wall; is
positional, tender to palpation; can be inframammary; radiation
patterns are highly variable; random onset; lasts seconds, minutes,
hours, or all day; variable response to nitroglycerin.
Classification and severity of angina
Class I. No angina with ordinary physical activity (e.g., walking,
climbing stairs). Angina with strenuous or prolonged exertion.
Class II. Early-onset limitation of ordinary activity (e.g., walking
rapidly or walking > 2 blocks; climbing stairs rapidly or climbing
> 1 flight); angina may be worse after meals, in cold temperatures, or
with emotional stress.
Class III. Marked limitation of ordinary activity.
Class IV. Inability to carry out any physical activity without chest
discomfort. Angina occurs during rest.
Common stress-testing procedures for the evaluation of chest
pain
Standard treadmill or bicycle exercise
Protocol: patient is able to perform adequate amount of physical
activity. Baseline ECG is normal or near normal (e.g., minimal ST-
segment depression). Should not be used if patient has left bundle-
branch block or electronic pacemaker.
Positive result: new horizontal or downsloping ST-segment
depression ≥ 1 mm or ≥ 2 mm in presence of baseline repolarization
abnormality.
Comments: blood-pressure response, exercise duration,
ventricular arrhythmias, Duke treadmill score, and heart rate

68
recovery should also be assessed. Functional capacity and Duke
treadmill score have significant prognostic value. Specificity –
70–75%.
Exercise stress echocardiography
Protocol: patient is able to perform physical activity. Two-
dimensional echocardiogram immediately after exercise.
Positive result: one or more new segmental wall-motion
abnormalities (hypokinesis, akinesis, or dyskinesis), left ventricular
dilation, or both.
Comments: useful for abnormal baseline ECG (should not be
used if patient has left bundle-branch block or electronic pacemaker).
Technically high-quality echocardiogram is essential.
Estimated specificity – 80–85%.

Drugs for coronary artery disease

ACE inhibitors (benazepril, captopril, enalapril, fosinopril,
lisinopril, moexipril, perindopril, quinapril, ramipril, trandolapril);
dosage: variable. Use: all patients with CAD, especially those with
large infarctions, heart failure, hypertension, and diabetes.
Contraindications include hypotension, renal failure, bilateral renal
artery stenosis, and known allergy.
Angiotensin II receptor blockers (candesartan, irbesartan,
losartan, telmisartan, valsartan). Dosage: variable. Use: an effective
alternative for patients who cannot tolerate ACE inhibitors (because
of cough). Not currently 1st-line treatment after MI.
Contraindications include hypotension, renal failure, bilateral renal
artery stenosis, and known allergy.
Anticoagulants
Argatroban, dosage: 350 μg/kg (bolus) followed by
2–5 μg/kg/min; bivalirudin, dosage: 0.75 mg/kg (bolus) followed by
1.75 mg/kg/h. Use: patients with ACS and a known or suspected
history of heparin-induced thrombocytopenia as an alternative to
heparin. Fondaparinux, dosage: 2.5 mg sc q 24 h; enoxaparin,
dosage: 30 mg IV (bolus) followed by 1 mg/kg sc q 12 h (maximum,
100 mg). Use: patients with unstable angina or NSTEMI, patients
< 75 yr receiving tenecteplase, almost all patients with STEMI as an
alternative to unfractionated heparin (unless PCI is indicated and can

69
be done in < 90 min). Drug continued until PCI or CABG is done or
patient is discharged.
Unfractionated heparin, dosage: 60–70 units/kg IV (maximum,
5000 units; bolus), followed by 12–15 units/kg/h (maximum,
1000 units/h) for 3 to 4 days or until PCI is complete 60 units/kg IV
(maximum, 4000 units; bolus) given when alteplase, reteplase, or
tenecteplase is started, then followed by 12 units/kg/h (maximum,
1000 units/h) for 48 h or until PCI is complete. Use: patients with
unstable angina or NSTEMI as an alternative to enoxaparin, patients
who have STEMI and undergo urgent angiography and PCI or
patients > 75 yr receiving tenecteplase.
Warfarin, dose adjusted to maintain INR of 2.5–3.5 mg. Use: may
be useful long-term in patients at high risk of systemic emboli (i.e.,
with large anterior MI, known LV thrombus, or atrial fibrillation).
Antiplatelet drugs
Aspirin dosage: for stable angina: 75 or 81 mg po once/day
(enteric-coated). For ACS: 160–325 mg po chewed (not enteric-
coated) on arrival at emergency department and once/day thereafter
during hospitalization 81 mg po once/day long-term after discharge.
Use: all patients with CAD or at high risk of developing CAD, unless
aspirin is not tolerated or is contraindicated. Long-term use.
Clopidogrel dosage: 75 mg po once/day. For patients undergoing
PCI: 300–600 mg po once, then 75 mg po once/day for 1 to 12 mo.
Use: used with aspirin or, in patients who cannot tolerate aspirin,
alone. For patients undergoing percutaneous intervention (PCI),
clopidogrel loading dose to be administered only in cardiac
catheterization laboratory after angiography has confirmed that
coronary anatomy is amenable to PCI (so as not to delay CABG if
indicated). Maintenance therapy required for at least 1 mo for bare-
metal stents and for at least 12 mo for drug-eluting stents.
Ticlopidine dosage: 250 mg po bid. Use: rarely used routinely
because neutropenia is a risk and WBC count must be monitored
regularly.
Glycoprotein IIb/IIIa inhibitors, IV for 24–36 h. Use: some
patients with ACS, particularly those who are having prothrombotic
conditions. Abciximab 0.25 µg/kg bolus, then 10 µg/min or
eptifibatide 180 µg/kg bolus, then 2 µ/kg/min or tirofiban
0.4 µg/kg/min for 30 min, then 0.1 µg/kg/min. Use: PCI with stent

70
placement and high-risk patients with unstable angina or NSTEMI.
Therapy started at least 6 h before PCI and continued for 18 to 24 h
thereafter.
β-blockers
Atenolol 50 mg po q 12 h acutely, then 50–100 mg po bid long-
term; metoprolol 1–3 boluses of 5 mg given 2–5 min apart as
tolerated (up to 15 mg); then 25–50 mg po q 6 h, beginning 15 min
after last IV dose and continued for 48 h; then 100 mg bid or 200 mg
once/day given long term. Use: all patients with ACS, unless
β-blocker is not tolerated or is contraindicated, especially in high-
risk patients. Long-term use.
Calcium channel blockers
Amlodipine 5–10 mg po once/day, diltiazem (extended-release)
180–360 mg po once/day, felodipine 2.5–20 mg po once/day,
nifedipine (extended-release) 30–90 mg po once/day, verapamil
(extended-release) 120–360 mg po once/day. Use: patients with
stable angina, if symptoms persist despite nitrates use or if nitrates
are not tolerated.
HMG-CoA reductase inhibitors (statins) (atorvastatin,
fluvastatin, lovastatin, pravastatin, rosuvastatin, simvastatin).
Dosage: variable. Use: patients with CAD to achieve a targert LDL
cholesterol level of 70 mg/dL.
Short-acting nitrates
Sublingual nitroglycerin (tablet or spray) 0.3–0.6 mg q 4–5 min
up to 3 doses. Use: all patients for immediate relief of chest pain.
Used as needed. Nitroglycerin as continuous IV drip. Dosage: started
at 5 µg/min and increased 2.5–5.0 µg every few minutes until
required response occurs. Use: selected patients with ACS: during
the first 24 to 48 h, in patients with heart failure (unless
hypotension is present), large anterior MI, persistent angina, or
hypertension (BP is reduced by 10–20 mm Hg but not to
< 80–90 mm Hg systolic). For longer use, in patients with recurrent
angina or persistent pulmonary congestion.
Long-acting nitrates
Isosorbide dinitrate 10–20 mg po bid; can be increased to 40 mg
bid, isosorbide dinitrate (sustained-release) 40–80 mg po bid
(typically given at 8 am and 2 pm), isosorbide mononitrate 20 mg po
bid, with 7 h between the 1st and 2nd doses, isosorbide mononitrate

71
(sustained-release) 30 or 60 mg once/day, increased to 120 mg or,
rarely, 240 mg, nitroglycerin patches 0.2–0.8 mg/h applied between
6:00 and 9:00 am and removed 12 to 14 h later to avoid tolerance,
nitroglycerin ointment 2% preparation (15 mg/2.5 cm) dosage:
1.25 cm spread evenly over upper torso or arms q 6 to 8 h and
covered with plastic, increased to 7.5 cm as tolerated, and removed
for 8–12 h each day to avoid tolerance. Use: patients who have
unstable angina or persisternt severe angina and continue to have
anginal symptoms after the β-blocker dose is maximized. A nitrate-
free period of 8–10 h (typically at night) is recommended to avoid
tolerance.
Opioids
Morphine 2–4 mg IV, repeated as needed. Use: all patients with
chest pain due to ACS to relieve pain (but ischaemia may persist).
Best used after drug therapy has been started or the decision to do
revascularization procedure has been made.

Table 13 – Recommendations on the use of antiplatelet agents in

different clinical presentations of vascular disease

Clinical setting Recommendation Specifications

IHD; chronic stable Aspirin, clopidogrel As an alternative to
angina (IA) aspirin
ACS without per- Aspirin or clopidogrel More effective than
sistent ST-segment + aspirin (IA). aspirin alone peri-
elevation with PCI; procedural use.
without PCI Aspirin More effective than
clopidogrel+aspirin aspirin alone tirofiban
i.v. GPIIb/IIIa or eptifibatide.
ST elevation AMI inhibitors. Abciximab
with primary PCI Aspirin.
i.v. GPIIb/IIIa
inhibitors
Prior MI Aspirin, clopidogrel As an alternative to
(IA) aspirin
After coronary Aspirin (IA)
bypass surgery
Elective PCI Aspirin (IA);
clopidogrel (IA); In case of stent
ticlopidine (IA); application;

72
 i.v. GPIIb/IIIa in case of stent
inhibitors (IIA) application;
grade 2 in stable
patients
Acute ischaemic Aspirin (IA)
stroke/TIA
Prior stroke/TIA Aspirin, clopidogrel As an alternative to
(IA) aspirin
Table 13 continuation

Clinical setting Recommendation Specifications

Primary prevention Aspirin
in high-risk groups,
diabetes mellitus, (IIB),
hypertension (IIA)
Atrial fibrillation Aspirin (IA) In intermediate-risk
subjects or in high-risk
patients not candidate
to warfarin
Valve disease Aspirin (IB) Rheumatic mitral valve
disease in patients not
candidate to warfarin
Valve surgery Aspirin (IIB) In combination with
warfarin in patients
with mechanical valves

Antiplatelet drugs that may prevent atherothrombosis

Approximately 20 different agents have been shown to inhibit
platelet aggregation through different mechanisms of action.
However, inhibition of platelet aggregation as measured ex vivo
does not necessarily translate into prevention of atherothrombosis.
Antiplatelet drugs that have been successfully tested against
placebo in adequately large randomized clinical trials include aspirin,
ticlopidine and clopidogrel for chronic oral dosing, and abciximab,
tirofiban and eptifibatide for short-term intravenous administration.
Patients that may benefit from antiplatelet therapy
Allocation of high-risk patients to a prolonged course of
antiplatelet therapy reduced the combined outcome of nonfatal

73
myocardial infarction, nonfatal stroke or vascular death (“serious
vascular events”) by about 25%.
Absolute reductions in the risk of having a serious vascular event
were 36 per 1000 treated for 2 years, among patients with previous
myocardial infarction; per 1000 patients treated for 1 month among
patients with acute myocardial infarction; 36 per 1000 treated for
2 years among those with previous stroke or transient ischaemic
attack (TIA); nine per 1000 treated for 1 month among those with
acute ischaemic stroke; and per 1000 treated for 2 years among other
high-risk patients, including those with stable angina, peripheral
arterial disease and atrial fibrillation.
In each of these high-risk categories, the absolute benefits
substantially outweighed the absolute risks of major bleeding
complications.
Clinical trial evidence in patients with ischaemic heart disease
Both ticlopidine and clopidogrel have been tested against aspirin
in patients with recent myocardial infarction, and both trials showed
nonsignificantly lower rates of serious vascular events in the aspirin-
treated arm, including a smaller number of vascular deaths.
In patients with chronic stable angina, aspirin (75 mg daily)
significantly reduced the occurrence of the primary end-point
(myocardial infarction or sudden death) by 34% after a median
duration of follow-up of 50 months, with no evidence of attenuation
of the benefit over such an extended period of observation.
Both aspirin and ticlopidine have been shown to reduce by
approximately 50% the rate of MI and death in randomized trials of
patients with unstable angina, and the benefit of aspirin has been
demonstrated in a wide range of daily doses, i.e., 75 to 1300 mg, in
four different placebo-controlled trials.
Blockade of platelet COX-1 with aspirin and of the platelet ADP
receptor P2Y12 with clopidogrel produced additive effects in
patients with acute coronary syndromes without ST-segment
elevation, by reducing the rate of the first primary outcome
(a composite of cardiovascular death, nonfatal MI, or stroke) by 20%
as compared to aspirin alone, with no evidence of attenuation of the
additional benefit over 12 months of follow-up.
The efficacy and safety of this combined antiplatelet strategy is
currently being tested in patients with acute MI, a clinical setting

74
where aspirin alone (162.5 mg started within 24 h of the onset of
symptoms) reduced the primary end-point of vascular death by 23%
and nonfatal vascular events by 50%.
Recommendations concerning individual antiplatelet agents
Aspirin
Aspirin once daily is recommended in all clinical conditions in
which antiplatelet prophylaxis has a favourable benefit/risk profile.
Because of GI toxicity and its potential impact on compliance,
physicians are encouraged to use the lowest dose of aspirin that was
shown to be effective in each clinical setting.
The available evidence supports daily doses of aspirin in the
range of 75–100 mg for the long term prevention of serious vascular
events in high-risk patients (i.e., ≥ 3% per annum).
In clinical situations where an immediate antithrombotic effect is
required (such as in acute coronary syndromes or in acute ischaemic
stroke), a loading dose of 160 mg should be given at diagnosis in
order to ensure rapid and complete inhibition of TXA2-dependent
platelet aggregation.
No test of platelet function is recommended to assess the
antiplatelet effect of aspirin in the individual patient.
The routine use of proton pump inhibitors or cytoprotective
agents is not recommended in patients taking daily doses of aspirin
in the range of 75–100 mg, because of lack of randomized trials
demonstrating the efficacy of such protective strategies in this
setting.
Nonsteroidal anti-inflammatory drugs (NSAIDs) have been
investigated inadequately in terms of their potential cardiovascular
effects. Thus, physicians prescribing these drugs to arthritic patients
with prior vascular complications should not discontinue treatment
with low-dose aspirin.
Because of potential pharmacodynamic interactions between
traditional NSAIDs (e.g., ibuprofen) and aspirin, patients treated
with low-dose aspirin requiring NSAID therapy may benefit from the
use of selective COX-2 inhibitors.
Ticlopidine
The role of ticlopidine in the present therapeutic armamentarium
is uncertain. Now that ticlopidine is available as a generic drug in

75
many countries, its lower cost as compared to clopidogrel is being
emphasized within a broad cost-containment strategy.
Although there are no large head-to-head comparisons between
the two thienopyridines, indirect comparisons are highly suggestive
of a lower burden of serious bone-marrow toxicity with clopidogrel
as compared to ticlopidine.
In contrast to clopidogrel, ticlopidine does not have an approved
indication for patients with a recent myocardial infarction.
Clopidogrel
Although clopidogrel may be slightly more effective than aspirin,
the size of any additional benefit is statistically uncertain and the
drug has not been granted a claim of superiority vs aspirin by
regulatory authorities.
Clopidogrel, 75 mg daily, is an appropriate alternative for high-
risk patients with coronary, cerebrovascular or peripheral arterial
disease who have a contraindication to low-dose aspirin.
The results of the CURE trial have led to approval of a new
indication for clopidogrel in patients with acute coronary syndromes
without ST-segment elevation. A loading dose of 300 mg clopidogrel
should be used in this setting followed by 75 mg daily. Revision of
the existing guidelines will need a consensus agreement by the
experts with respect to timing of percutaneous coronary intervention,
length of clopidogrel treatment, and combination with GPIIb/IIIa
antagonists.
Dipyridamole
Although the combination of low-dose aspirin and extended-
release dipyridamole (200 mg bid) is considered an acceptable option
for initial therapy of patients with non-cardioembolic cerebral
ischaemic events, there is no basis to recommend this combination in
patients with ischaemic heart disease.
Abciximab, eptifibatide, and tirofiban
The benefit/risk profile of currently available GPIIb/IIIa
antagonists is substantially uncertain for patients with acute coronary
syndromes who are not routinely scheduled for early
revascularization.
In contrast, for patients undergoing percutaneous coronary
intervention, intensification of antiplatelet therapy by adding an

76
intravenous GPIIb/IIIa blocker is an appropriate strategy to reduce
the risk of procedure-related thrombotic complications.
Other antiplatelet drugs
Indobufen, triflusal and picotamide are commercially available in
a few European countries, based on relatively limited evidence for
efficacy and safety.
Because of substantial statistical uncertainty surrounding the
direct randomized comparisons of these antiplatelet agents vs aspirin
and inadequate statistical power of the studies to assess reliably any
difference in serious vascular events, the use of indobufen, triflusal
or picotamide instead of aspirin is not recommended.
Differential Diagnosis of Chest Pain

Epidemiology
The prevalence of chest pain or chest discomfort varies in
different parts of Europe. A large proportion of people in the
community have been reported to suffer from some type of chest
discomfort. In a British study of 7735 men, angina pectoris or a
history of possible acute MI was reported in 14% and a further 24%
suffered from atypical chest pain. The ischaemic origin of calls about
chest pain is much more frequent at dispatch centres. About 25% of
all emergency calls to a dispatch centre are initiated because of chest
pain. Among such patients, 40% are reported to have confirmed
myocardial ischaemia or infarction, and 66% either confirmed or
possible MI or infarction as the cause of their pain.

Table 14 – Aetiology to chest pain in various clinical settings

Aetiology General Dispatch Ambu- Emergenc

practitio- centre lance y
ner (1–3)% (4)% crew (5)% depart-
ment (6)%
Cardiac 20 60 69 45
Musculoskeletal 43 6 5 14
Pulmonary 4 4 4 5
Gastrointestinal 5 6 3 6
Psychiatric 11 5 5 8
Other 16 19 18 26

77
 Ischaemic cardiac pain.
Non-ischaemic chest pain. Aetiology to chest pain in various
clinical settings: cardiac, musculoskeletal, gastrointestinal,
pulmonary, psychiatric, etc.
Clinical classification of chest pain
1. Typical angina (definite) meets three of the following
characteristics:
– substernal chest discomfort of characteristic quality and
duration;
– provoked by exertion or emotional stress;
– relieved by rest and/or GTN.
2. Atypical angina (probable) meets two of these characteristics.
3. Noncardiac chest pain meets one or none of the
characteristics.
Table 15 – Non-ischaemic causes of chest pain

Disease Differentiating symptoms and signs

Reflux No ECG changes, heartburn; worsening in
oesophagitis, recumbent position, but also during strain, such as
oesophageal spasm angina pectoris; a common cause of chest pain
Pulmonary Tachypnoea, hypoxaemia, hypocarbia.
embolism No pulmonary congestion on chest X-ray.
May resemble inferior wall infarction: ST
elevation (II, III, aVF).
Hyperventilation.
PaO2 and PaCO2 decreased
Hyperventilation The main symptom is dyspnoea, as in pulmonary
embolism.
Often a young patient.
Tingling and numbness of the limbs, dizziness.
PaCO2 decreased, PaO2 increased or normal.
An organic disease may cause secondary
hyperventilation
Spontaneous Dyspnoea is the main symptom.
pneumothorax Auscultation and chest X-ray.
One sided pain and bound to respiratory
movements
Aortic dissection Severe pain with changing localization.

78
 In type A dissection sometimes coronary ostium
obstruction, usually right coronary with signs of
inferoposterior infarction.
Sometimes broad mediastinum on chest X-ray.
New aortic valve regurgitation
Pericarditis Change of posture and breathing influence the
pain.
Friction sound may be heard.
ST-elevation but no reciprocal ST depression
Pleuritis Jabbing pain when breathing.
Cough is the most common symptom.
Chest X-ray
Costochondral Palpation tenderness.
Movements of chest influence the pain
Table 15 continuation

Disease Differentiating symptoms and signs

Early herpes zoster No ECG changes.
Rash.
Localized paraesthesia before rash
Ectopic beats Transient, in the area of the apex
Peptic ulcer, Clinical examination (inferior wall ischaemia may
cholecystitis, resemble acute abdomen)
pancreatitis
Depression Continuous feeling of heaviness in the chest.
No correlation to exercise.
Normal ECG
Alcohol-related Young man in emergency room, inebriated

79
 Symptom from the chest:
Intensity?
Duration?
Localization?
Referred pain?
Changes with posture/movement?
Influenced by food/fluid intake?
Reaction to nitroglycerin?

Cutaneous pain Visceral pain

Cardiac Non-cardiac

Ischemic Non-ischemic

Muscle AMI, Myocarditis Lung

Skeleton ACS Cardiomyopathy GI
Skin Pericarditis Aorta
Mediastinum
Psychiatric

Figure 3 – Algorithm for the diagnosis of acute chest pain

Diagnostic tests in acute chest pain
The diagnostic procedure in patients with acute chest pain should
serve two major purposes: (1) to identify high risk patients quickly
for the fast track and (2) to delineate patients in whom there is little
or no suspicion of a life-threatening disease.
The ECG
The presence of ST-segment elevation or ST-depressions
indicates myocardial ischaemia but the power to identify an ongoing
MI is poor and only about 50% of patients with such changes will
eventually develop acute MI.
Symmetrical T-wave inversions are nonspecific sign which might
indicate various disorders including myocardial ischaemia,
myocarditis, and pulmonary embolism. About one third of patients
with chest pain and such changes on the hospital admission ECG will

80
eventually develop acute MI. Newly developed Q waves on the
admission ECG among patients with acute chest pain are diagnostic of
acute MI, and about 90% of these patients have an evolving acute MI.
About one third of patients admitted to the emergency department
with acute chest pain have a normal ECG. Yet, among such patients,
5–40% have an evolving acute MI.
Biochemical markers
Biochemical markers in serum are measured to detect or exclude
myocardial necrosis. Troponin T and troponin I, myoglobin and
creatine kinase (CK) MB, are the most often used. For ruling out
acute myocardial infarction, myoglobin is a better marker from 3 h
until 6 h after the onset of symptoms compared to CK MB mass and
troponin T, but the maximal negative predictive value of myoglobin
reaches only 89% during this time-frame. Within the first 6 h after
acute MI, CK MB subforms appear to be both more sensitive and
more specific than CK MB mass activity or even the troponins.
However, in one study of rapid assays for troponins T and I, 94% of
773 patients without ST-segment elevations subsequently developing
an acute MI had a positive test for troponin T and all patients had a
positive test for troponin I within 6 h after the onset of chest pain.
From 7 h after onset of symptoms, CK MB and troponin T seem
to have a higher negative predictive value than myoglobin.
Measurements of troponin T or I has been shown to be a more
sensitive and more specific marker of acute MI than CK MB.
Cardiac Arrhythmias

Cardiac arrhythmia is a term for any of a large and

heterogeneous group of conditions in which there is abnormal
electrical activity in the heart. The heart beat may be too fast or too
slow, and may be regular or irregular.
Some arrhythmias are life-threatening medical emergencies that
can result in cardiac arrest and sudden death. Others cause
aggravating symptoms such as abnormal awareness of heart beat
(palpitations), and may be merely annoying. Others may not be
associated with any symptoms at all, but predispose toward
potentially life threatening stroke or embolism.
Some arrhythmias are very minor and can be regarded as
normal variants. In fact, most people will sometimes feel their

81
heart skip a beat, or give an occasional extrastrong beat – neither of
which is usually a cause for alarm.
However, some asymptomatic arrhythmias are associated with
adverse events. Examples include increase in risk of blood clotting
within the heart, and also an insufficient amount of blood is
transported to the heart because of weak heart beat, and thus
increases the risk of pulmonary embolism and stroke, or increase in
the risk of heart failure, or increase in the risk of sudden cardiac
death.
Some, but not all, cardiac arrhythmias are related to
pathologic lesions of the cardiac conduction system. Common
atrial arrhythmias and first-degree atrioventricular block rarely
are explained on the basis of anatomic lesions in specific sites of
the conduction system or its blood supply. Second-degree
atrioventricular block of Mobitz type II, which may be a
precursor of complete (third-degree) heart block, commonly, is
associated with pathological lesions of uncertain aetiology in the
branching part of the bundle of His or the bundle branches.
Ischaemic lesions are found less often, and other pathologic
processes rarely are present. Chronic complete heart block most
often results from nonspecific, fibrotic interruption of the distal
bundle of His, or of the first parts of the bundle branches after
their origins. Ischaemic lesions are uncommonly the cause of
chronic block. High-grade AV block complicating acute
myocardial infarction may be associated with infarction of the
AV conduction, but often morphologic evidence of ischaemia
cannot be identified. Congenital variants in anatomy of the
conduction system are responsible for some relatively uncommon
arrhythmias.
Classification of cardiac arrhythmias
I. Infringement of the impulse formation:
A. Infringement of SA node automatism (nomotopic
arrhythmia):
1. Sinusal tachycardia.
2. Sinusal bradycardia.
3. Sinusal arrhythmia.
4. Sick sinus syndrome.

82
 B. Ectopic (heterotropic) rhythm which is caused by
prevalence of automatism of the ectopic centres:
1. Slow (replacing) sliding complexes and rhythms:
a) atrial;
b) with AV node;
c) ventricular.
2. The accelerated ectopic rhythms (not paroxyshmal
tachycardia):
a) atrial;
b) with AV node;
c) ventricular.
3. Migration of supraventricular driver of the rhythm.
C. Ectopic (heterotropic) rhythm which is caused by
mechanism of reentry:
1. Extrasystole:
a) atrial;
b) with AV node;
c) ventricular.
2. Paroxysmal tachycardia:
a) atrial;
b) with AV node;
c) ventricular.
3. Atrial flutter.
4. Atrial fibrillation.
5. Ventricular flutter and fibrillation.
II. Infringement of conductivity:
1. Sinoatrial block.
2. Intra-atrial block.
3. AV block:
a) I degree;
b) II degree;
c) III degree.
4. Bundle branch block:
a) one branches (monofascicular);
b) two branches (bifascicular);
c) three branches (trifascicular).
5. Asystolia of ventriculus.
6. Syndrome of premature excitation of ventriculus:

83
 a) WPW syndrome;
b) syndrome of the short interval P–Q(R) (Clerk-Levy-
Critesco’s syndrome).
III. The combined infringements of a rhythm.
1. Parasystolia.
2. Ectopic rhythms with blockade of an exit.
3. AV dissociations.
General mechanisms of supraventricular arrhythmia:
Specialized atrial tissue: the SA node is a collection of
morphologically and electrically distinct cells (22–28). The central
portion of the sinus node, which houses the dominant pacemaking
function, contains cells with longer action potentials and faster rates
of phase 4 diastolic depolarization than other cardiac cells.
Cellular recordings support the existence of distinct populations
of cells in the mammalian AV node. Ovoid cells have a nodal (N- or
NH-type) action potential configuration (i.e., action potentials with
slow (Ca channel-dependent) phase 0 upstrokes and prominent phase
4 diastolic depolarization). In contrast, rod-shaped cells have action
potentials more similar to action potentials recorded in atrial
myocytes (AN-type) with rapid Na channel-dependent upstrokes and
little phase 4 diastolic depolarization. Differences in ion channel
expression underlie the differences in the electrophysiological
behaviour of each of the cell types. Variation in cell phenotype and
intercellular connectivity cause differences in tissue-level conduction
velocity, refractory period, and automaticity.
General mechanisms
The most common arrhythmia mechanism is re-entry. Indeed,
the first proven re-entry circuit in humans was that composed of the
atrium, AV node, ventricle, and accessory pathway in patients with
AV re-entry tachycardia.
Re-entry may occur in different forms. In its simplest form, it
occurs as repetitive excitation of a region of the heart and is a result
of conduction of an electrical impulse around a fixed obstacle in a
defined circuit. This is referred to as re-entrant tachycardia, and there
are several requirements for its initiation and maintenance. Initiation
of re-entrant tachycardia requires unidirectional conduction block in
one limb of a circuit. Unidirectional block may occur as a result of
acceleration of the heart rate or block of a premature impulse that

84
impinges on the refractory period of the pathway. Slow conduction is
usually required for both initiation and maintenance of re-entrant
tachycardia.
In the case of orthodromic AV re-entry (i.e., anterograde
conduction across the AV node with retrograde conduction over an
accessory pathway), slowed conduction through the AV node allows
for recovery of, and retrograde activation over, the accessory
pathway. A requirement for the maintenance of such a tachycardia is
that the wavelength of the tachycardia (i.e., the product of the
conduction velocity and the refractory period) must be shorter than
the pathlength of the circuit over which the impulse travels. Too long
a wavelength or too short a pathlength will result in the extinction of
the tachycardia as the activation wavefront impinges on the
inexcitable refractory tail terminating propagation. The amount by
which the pathlength exceeds the wavelength represents the excitable
gap.
Antiarrhythmic drugs may interrupt re-entrant tachycardia by
altering the relationship between the pathlength and the wavelength.
Drugs with class III action prolong refractoriness and, therefore, the
wavelength, thereby eliminating the excitable gap. Alternatively,
drugs with class I action may interfere with conduction, often in the
region of slow conduction-producing bidirectional block and
inability to initiate or maintain the tachycardia.
Re-entry is the mechanism of tachycardia in SVTs such as
AVRT, AVNRT, and atrial flutter (AF).
Predisposing or precipitating factors for patients with
palpitations
Noncardiac causes: nicotine, alcohol, caffeine; physical or
mental stress; hyperthyroidism; premenstrual or menstrual;
electrolyte disturbance; certain drugs (antiarrhythmic, antidepressant,
antibiotic drugs; stimulants; antihistamines; appetite suppressants);
anaemia; anxiety or hypovolemia; fever, infection; lack of sleep.
Cardiac causes: coronary artery disease; old myocardial
infarction, especially for ventricular tachycardias; congestive heart
failure; cardiomyopathy; valvular disease; congenital heart disease;
other conditions that may cause myocardial scarring (i.e.,
sarcoidosis, tuberculosis); primary electrical disorders (i.e., long QT
syndrome, Brugada syndrome); accessory pathways.

85
 Supraventricular arrhythmia
General evaluation of patients without documented
arrhythmia
Clinical history and physical examination: patients with
paroxysmal arrhythmias are most often asymptomatic at the time
of evaluation. Arrhythmia-related symptoms include palpitations;
fatigue; lightheadedness; chest discomfort; dyspnoea; presyncope;
or, more rarely, syncope.
Diagnostic investigations: a resting 12-lead ECG should be
recorded and evaluated for the presence of abnormal rhythm, pre-
excitation, prolonged QT interval, sinus tachycardia, segment
abnormalities, or evidence of underlying heart disease.
An echocardiographic examination should be considered in
patients with documented sustained SVT to exclude the possibility
of structural heart disease.
An ambulatory 24-hour Holter recording can be used in
patients with frequent (i.e., several episodes per week) but transient
tachycardias.
Management: nature of the symptoms. If the surface ECG is
normal and the patient reports a history consistent with premature
extrabeats, then precipitating factors, such as excessive caffeine,
alcohol, nicotine intake, recreational drugs, or hyperthyroidism,
should be reviewed and eliminated. Benign extrasystoles are often
manifested at rest and tend to become less common with exercise.
If symptoms and the clinical history indicate that the arrhythmia
is paroxysmal in nature and the resting 12-lead ECG gives no clue
for the arrhythmia mechanism, then further diagnostic tests for
documentation may not be necessary before referral for an invasive
electrophysiological study and/or catheter ablation. Patients should
be taught to perform vagal maneuvers. A beta-blocking agent may
be prescribed empirically provided that significant bradycardia
(less than 50 bpm) have been excluded. Due to the risk of
proarrhythmia, antiarrhythmic treatment with Class I or Class III
drugs should not be initiated without a documented arrhythmia.
General evaluation of patients with documented
arrhythmia:
Diagnostic evaluation: whenever possible, a 12-lead ECG

86
should be taken during tachycardia but should not delay immediate
therapy to terminate arrhythmia if there is haemodynamic
instability. At a minimum, a monitor strip should be obtained from
the defibrillator, even in cases with cardiogenic shock or cardiac
arrest, before direct current (DC) cardioversion is applied to
terminate arrhythmia.
Differential diagnosis for narrow QRS-complex
tachycardia: if ventricular activation (QRS) is narrow (less than
120 ms), tachycardia is almost always supraventricular and the
differential diagnosis relates to its mechanism. If no P waves or
evidence of atrial activity is apparent and the RR interval is
regular, AVNRT is most commonly the mechanism. Responses of
narrow QRS-complex tachycardias to adenosine or carotid
massage may aid in the differential diagnosis. A 12-lead ECG
recording is desirable during the use of adenosine or carotid
massage. If P waves are not visible, the use of oesophageal pill
electrodes can also be helpful.
Differential diagnosis for wide QRS-complex tachycardia: if
the QRS is wide (greater than 120 ms), it is important to
differentiate between SVT and ventricular tachycardia (VT).
Intravenous medications given for the treatment of SVT,
particularly verapamil or diltiazem, may be deleterious because
they may precipitate haemodynamic colapse for a patient with VT.
Stable vital signs during tachycardias are not helpful for
distinguishing SVT from VT. If the diagnosis of SVT cannot be
proven or cannot be made easily, the patient should be treated as if
VT were present. Wide-QRS tachycardia can be divided into three
groups: SVT with bundle-branch block (BBB) or aberration, SVT
with AV conduction over an accessory pathway, and VT.
Differentiating of VT from SVT:
– RS (from the initial R to the nadir of S) interval longer than
100 ms in any precordial lead is highly suggestive of VT;
– QRS pattern with negative concordance in the precordial
leads is diagnostic for VT (“negative concordance” means that the
QRS patterns in all of the precordial leads are similar, and with QS
complexes). Positive concordance does not exclude antidromic
AVRT over a left posterior accessory pathway;
– the presence of ventricular fusion beats indicates a

87
ventricular origin of the tachycardia;
– QR complexes indicate a myocardial scar and are present in
approximately 40% of patients with VTs after MI.
Management
The most effective and rapid means of terminating any
haemodynamically unstable narrow or wide QRS-complex
tachycardia is DC cardioversion.
Acute management of narrow QRS-complex tachycardia: in
regular narrow QRS-complex tachycardia, vagal maneuvers (i.e.,
Valsalva, carotid massage, and facial immersion in cold water),
should be initiated to terminate arrhythmia or to modify AV
conduction. If this fails, IV antiarrhythmic drugs should be
administered for arrhythmia termination in haemodynamically
stable patients. Adenosine or nondihydropyridine calcium-channel
antagonists are the drugs of choice. The advantage of adenosine
relative to IV calcium-channel or beta-blockers relates to its rapid
onset and short half-life. Intravenous adenosine is, therefore, the
preferred agent except for patients with severe asthma.
Acute management of wide QRS-complex tachycardia:
immediate DC cardioversion is the treatment for
haemodynamically unstable tachycardias. If tachycardia is
haemodynamically stable and definitely supraventricular, the
management is as described for narrow QRS-complex
tachycardias. For pharmacologic termination of stable wide QRS-
complex tachycardia, IV procainamide and/or sotalol are
recommended on the basis of randomized but small studies.
Amiodarone is also considered acceptable. Amiodarone is
preferred, compared to procainamide and sotalol, in patients with
impaired left ventricular (LV) function or signs of heart failure.

Drugs for arrhythmias

Class I: Na channel blockers (membrane-stabilizing drugs)
block fast Na channels, slowing conduction in fast-channel tissues
(working atrial and ventricular myocytes, His-Purkinje system). In
the ECG, this effect may be reflected as widening of the P wave,
widening of the QRS complex, prolongation of the PR interval, or
combination.
Class II: class II drugs are β-blockers, which affect

88
predominantly slow-channel tissues (SA and AV nodes), where
they decrease rate of automaticity, slow conduction velocity, and
prolong refractoriness. Thus, heart rate is slowed, the PR interval is
lengthened, and the AV node transmits rapid atrial depolarizations
at a lower frequency.
Class III: class III drugs are primarily K channel blockers,
which prolong action potential duration and refractoriness in slow-
and fast-channel tissues. Thus, the capacity of all cardiac tissues to
transmit impulses at high frequencies is reduced, but conduction
velocity is not significantly affected. Because the action potential
is prolonged, rate of automaticity is reduced. The predominant
effect on the ECG is QT-interval prolongation.
Class IV: class IV drugs are the nondihydropyridine Ca
channel blockers, which depress Ca-dependent action potentials in
slow channel tissues and thus decrease rate of automaticity, slow
conduction velocity, and prolong refractoriness. Heart rate is
slowed, the PR interval is lengthened, and the AV node transmits
rapid atrial depolarizations at a lower frequency.
Devices and procedures
Direct-current (DC) cardioversion-defibrillation
A transthoracic DC shock of sufficient magnitude depolarizes
the entire myocardium, rendering the entire heart momentarily
refractory to repeat depolarization. Thereafter, the most rapid
intrinsic pacemaker, usually the SA node, reassumes control of
heart rhythm. Thus, DC cardioversion-defibrillation very
effectively terminates tachyarrhythmias that result from reentry.
Pacemakers sense electrical events and respond when necessary by
delivering electrical stimuli to the heart. Permanent pacemaker
leads are placed via thoracotomy or transvenously, but some
temporary emergency pacemaker leads can be placed on the chest
wall.
Implantable cardioverter-defibrillators (ICDs)
ICDs cardiovert or defibrillate the heart in response to VT or
VF. Contemporary tiered-therapy ICDs also provide
antibradycardia pacing and antitachycardia pacing (to terminate
responsive atrial or ventricular tachycardias) and store intracardiac
electrograms. ICDs are implanted subcutaneously or subpectorally,
with electrodes inserted transvenously or, rarely, via thoracotomy.

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 Radiofrequency (RF) ablation
If tachyarrhythmia depends on a specific pathway or ectopic
site of automaticity, the site can be ablated by low-voltage, high-
frequency (300 to 750 MHz) electrical energy, applied through an
electrode catheter. This energy heats and necroses an area < 1 cm
in diameter and up to 1 cm deep. Before energy can be applied,
the target site or sites must be mapped at an electrophysiologic
study.
Success rate is > 90% for reentrant tachycardias (via the AV
node or an accessory pathway), focal atrial tachycardia and flutter,
and focal idiopathic VTs (right ventricular outflow tract, left septal,
or bundle branch reentrant VT). RF ablation is sometimes
successful in patients with VT refractory to drugs and with
ischaemic heart disease.
RF ablation is safe; mortality is <1/2000. Complications include
valvular damage, embolism, cardiac perforation, tamponade (1%),
and unintended AV node ablation.
Surgery
Surgery to remove a focus of tachyarrhythmia is becoming less
necessary as the less invasive RF ablation techniques evolve. But it
is still indicated when arrhythmia is refractory to RF ablation or
when another indication requires a cardiac surgical procedure,
most commonly when patients with AF require valve replacement
or repair or when patients with VT require revascularization or
resection of a left ventricular aneurysm.
Antiarrhythmic drugs (Vaughan-Williams classification)
CLASS IA uses: APB and VPB suppression, SVT and VT
suppression, AF or atrial flutter, and VF suppression.
Drug: disopyramide.
Dosage: IV: initially, 1.5 mg/kg over > 5 min, followed by an
infusion of 0.4 mg/kg/h. Oral immediate release: 100 or 150 mg q
6 h; oral controlled release: 200 or 300 mg q 12 h.
Adverse effects: anticholinergic effects (glaucoma, dry mouth,
urinary retention, blurred vision, intestinal upset), hypoglycemia,
torsades de pointes, ventricular tachycardia; negative inotropic
effects (which may worsen heart failure or hypotension), torsade
de pointes, ventricular tachycardia.
Comments: drug should be used cautiously in patients with

90
impaired LV function. Dosage should be decreased in patients with
renal insufficiency. Adverse effects may contribute to
nonadherence. If QRS interval widens or if QTc interval is
prolonged > 550 msec, infusion rate or dosage should be decreased
or drug stopped.
Drug: procainamide.
Dosage: IV: 10–15mg/kg bolus at 25–50 mg/min, followed by
a constant IV infusion of 1–4 mg/min. Oral: 250–625 mg (rarely,
up to 1 g) q 3 or 4 h.
Adverse effects: hypotension (with IV infusion), serologic
abnormalities (especially ANA) in almost 100% taking drug for
> 12 mo, drug-induced lupus (arthralgia, fever, pleural effusions)
in 15–20%, agranulocytosis in < 1%, torsades de pointes,
ventricular tachycardia.
Comments: sustained-release preparations obviate the need for
frequent dosing. If QRS interval widens or if QTc interval is
prolonged > 550 msec, infusion rate or dosage should be decreased
or drug stopped.
Drug: quinidine.
Dosage: oral: 200–400 mg q 4–6 h.
Adverse effects: diarrhoea, colic, flatulence, fever,
thrombocytopenia, liver function abnormalities, torsades de
pointes, ventricular tachycardia; overall adverse effect rate
of 30%.
Comments: if QRS interval widens or if QTc interval is
prolonged > 550 msec, infusion rate or dosage should be decreased
or drug stopped.
CLASS IB uses: suppression of ventricular arrhythmias
(VPB, VT,VF)
Drug: lidocaine.
Dosage: IV: 100 mg over 2 min, followed by continuous
infusion of 4 mg/min (2 mg/min in patients > 65); 5 min after first
dose, a 2nd 50 mg bolus is given.
Adverse effects: tremor, seizures; if administration is too rapid,
there is drowsiness, delirium, paresthesias; possibly increased risk
of bradyarrhythmias after acute MI.
Comments: to reduce toxicity risk, dosage or infusion rate
should be reduced to 2 mg/min after 24 h. Extensive first-pass

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hepatic metabolism occurs.
Drug: mexiletine.
Dosage: oral immediate release: 100–250 mg po q 8 h. Oral
slow release: 360 mg po q 12 h.
IV: 2 mg/kg at 25 mg/min, followed by 250 mg infusion over
1 h, 250 mg infusion over next 2 h, and maintenance infusion of
0.5 mg/min.
Adverse effects: nausea, vomiting, tremor, seizures.
Comments: oral slow-release and IV forms are not available in
the US.
CLASS IC uses: APB and VPB suppression, SVT and VT
suppression, AF or atrial flutter, and ventricular fibrillation
suppression.
Drug: propafenone.
Dosage: oral: initially, 150 mg tid, titrated up to 150–300 mg
tid. IV: 2-mg/kg bolus, followed by 2 mg/min infusion.
Adverse effects: β-blocking activity, possible worsening of
reactive airway disorders; occasionally, GI upset.
Comments: pharmacokinetics is nonlinear; increases in dose
should not exceed 50% of previous dose. Bioavailability and
protein binding vary; drug has saturable first-pass metabolism. IV
form is not available in the US.
Drug: flecainide.
Dosage: oral: 100 mg q 8 or 12 h. IV: 1–2 mg/kg over 10 min.
Adverse effects: occasionally, blurred vision and paresthesias.
Comments: IV form is not available in US. If QRS complex
widens, dose must be decreased or drug stopped.
CLASS II β-blockers uses: supraventricular.
Tachyarrhythmias (APB, ST, SVT, AF, atrial flutter) and
ventricular arrhythmias (often in a supportive role).
Drug: atenolol.
Dosage: oral: 50–100 mg once/day.
Adverse effects: GI disturbances, insomnia, nightmares,
lethargy, erectile dysfunction, possible AV block in patients with
AV node dysfunction.
Comments: these drugs are contraindicated in patients with
bronchospastic. Airway disorders.
Drug: carvedilol.

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 Dosage: oral: initially, 6.25 mg bid, followed by titration to
25 mg bid.
Drug: bisoprolol.
Dosage: oral: 5–10 mg once/day.
Drug: metoprolol.
Dosage: oral: 50–100 mg bid IV: 5 mg q 5 min up to 15 mg.
Drug: nadolol.
Dosage: oral: 60–80 mg once/day.
Drug: timolol.
Dosage: oral:10–20 mg bid.
CLASS III membrane stabilizing drugs uses: any
tachyarrhythmia except torsades de pointes VT.
Drug: amiodarone.
Dosage: oral: 600–1200 mg/day for 7–10 days, then
400 mg/day for 3 wk, followed by a maintenance dose (ideally,
200 mg/day).
IV: 150–450 mg over 1–6 h (depending on urgency), followed
by a maintenance dose of 0.5–2.0 mg/min.
Adverse effects: pulmonary fibrosis; QTc prolongation;
torsades de pointes; bradycardia; gray or blue discolouration of
sunexposed skin; sun sensitivity; hepatic abnormalities; peripheral
neuropathy; corneal microdeposits; changes in thyroid function.
Comments: drug has noncompetitive β-blocking, Ca channel
blocking, and Na channel blocking effects, with a long delay in
onset of action.
CLASS IV Ca channel blockers uses: termination of SVT
and slowing of rapid AF or atrial flutter.
Drug: diltiazem.
Dosage: oral: 120 mg to 360 mg once/day.
IV: 5–15 mg/h for up to 24 h.
Adverse effects: possible precipitation of VF in patients with
VT, negative inotropy.
Comments: IV form is most commonly used to slow
ventricular response rate to AF or atrial flutter.
Drug: verapamil.
Dosage: oral: 40–120 mg tid or, for sustained-release form,
180 mg once/day to 240 mg bid; prophylaxis: 40–120 mg tid.
IV: 5–15 mg over 10 min.

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 Adverse effects: possible precipitation of VF in patients with
VT, negative inotropy.
Comments: IV form is used to terminate narrow complex
tachycardias involving the AV node (success rate, almost 100%
with 5–10 mg IV over 10 min).
Other antiarrhythmics
Drug: adenosine.
Dosage: 6 mg rapid IV bolus, repeated twice at 12 mg if
needed; flush bolus with additional 20 mL saline.
Adverse effects: transient dyspnoea, chest discomfort, and
flushing (in 30–60%), transient bronchospasm.
Comments: drug slows or blocks AV nodal conduction.
Duration of action is extremely short. Contraindications include
asthma and high-grade heart block. Dipyridamole potentiates
effects.
Drug: digoxin.
Dosage: IV loading dose: 0.5 mg. Oral maintenance dose:
0.125–0.25 mg/day.
Adverse effects: anorexia, nausea, vomiting, and often serious
arrhythmias (VPBs, VT, APBs, atrial tachycardia, 2nd-degree or
3rd-degree AV block, combinations of these arrhythmias).
Comments: contraindications include antegrade conduction
over an accessory AV connection pathway (manifest
Wolff-Parkinson-White syndrome) because if AF occurs,
ventricular responses may be excessive (digoxin shortens
refractory periods of the accessory connection).
Emergency care for arrhythmia
Ventricular fibrillation:
1. Precordial blow.
2. If there is no effect – to begin cardiopulmonary resuscitation,
defibrillation is allowed.
3. Epinephrine 1 mg intravenously every 3–5 minutes (3 times).
4. Lidocaine 1.5 mg/kg intravenously once.
5. Novokainamid 1 g intravenously once.
6. Magnesium sulfate 2 g intravenously once.
If pulmonary oedema or cardiogenic shock developed due to
tachyarrhythmia:
1. Carrying oxygen therapy.

94
 2. If the patient's condition allows – premedication is conducted
(fentanyl 0.05 mg or 10 mg intravenously promedol).
3. Providing medication sleep (diazepam 5 mg intravenously and
2 mg every 1–2 minutes to fall asleep).
4. Conducting cardioversion.
Paroxysm of supraventricular tachycardia:
1. Carotid sinus massage.
2. No effect – to enter the ATP 10 mg IV bolus.
3. No effect – in 2 minutes verapamil 2.5–5 mg intravenously.
4. No effect – within 15 minutes of verapamil 5.10 mg
intravenously.
5. No effect – in 20 minutes novokainamid 1000 mg (up to
17 mg/kg) intravenously at a rate of 50–100 mg/min.
Paroxysm of atrial fibrillation:
1. Novokainamid (as in a paroxysm of supraventricular
tachycardia).
2. When high baseline heart rate (more than 120/min), it is
recommended initially to be administered intravenously 0.25–0.5 mg
digoxin.
3. Verapamil 2.5–5 mg intravenously.
Paroxysm of ventricular tachycardia:
1. Lidocaine 80–120 mg (1–1.5 mg/kg) and every 5 minutes to
40–60 mg intravenously to effect or achieve a total dose of 3 mg/kg.
2. No effect – either novokainamid or amiodarone 300 mg
(5 mg/kg).
3. No effect – cardioversion.
Severe bradyarrhythmia:
1. When asystole – to provide cardiopulmonary resuscitation.
2. Lay the patient with raised at an angle of 20 degrees lower
extremities (if not stagnation is expressed in the lungs).
3. Oxygen therapy.
4. If necessary (depending on the patient) – closed cardiac
massage or rhythmic effleurage on sternum.
5. Atropine intravenously every 3–5 minutes for 1 mg to effect or
until a total dose of 0.04 mg/kg.
6. No effect – immediate percutaneous endocardial
elektrocardiostimulation.

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 7. No effect – the slow intravenous infusion of 240–480 mg
aminophylline.
8. No effect – dopamine 100 mg or 1 mg epinephrine in 200 mL
of 5% glucose solution intravenously, gradually increasing the
infusion rate to the lowest adequate heart rate.
9. Continuously monitor heart rhythm and conduction.

CONGENITAL HEART VALVULAR DISEASE

Atrial Septal Defect

An atrial septal defect is one or more openings in the interatrial

septum, producing a left-to-right shunt, pulmonary hypertension, and
heart failure.
Atrial septal defects (ASDs) account for about 6 to 10% of cases
of congenital heart disease. Most cases are isolated and sporadic, but
some are a part of the genetic syndrome (e.g., mutations of
chromosome 5, Holt-Oram syndrome).

96
 Pathophysiology
In unaffected individuals, the chambers of the left side of the
heart are under higher pressure than the chambers of the right side of
the heart. This is because the left ventricle has to produce enough
pressure to pump blood throughout the entire body, while the right
ventricle only has to produce enough pressure to pump blood to the
lungs.
In the case of a large ASD (> 9 mm), which may result in a
clinically remarkable left-to-right shunt, blood will shunt from the
left atrium to the right atrium. This extra blood from the left atrium
may cause a volume overload of both the right atrium and the right
ventricle. If untreated, this condition can result in enlargement of the
right side of the heart and ultimately heart failure.
Any process that increases the pressure in the left ventricle can
cause worsening of the left-to-right shunt. This includes
hypertension, which increases the pressure that the left ventricle has
to generate in order to open the aortic valve during ventricular
systole, and coronary artery disease which increases the stiffness of
the left ventricle, thereby increasing the filling pressure of the left
ventricle during ventricular diastole.
The right ventricle will have to push out more blood than the left
ventricle due to the left-to-right shunt. This constant overload of the
right side of the heart will cause an overload of the entire pulmonary
vasculature. Eventually pulmonary hypertension may develop.
Pulmonary hypertension will cause the right ventricle to face
increased afterload in addition to the increased preload that the
shunted blood from the left atrium to the right atrium caused. The
right ventricle will be forced to generate higher pressures to try to
overcome pulmonary hypertension. This may lead to right
ventricular failure (dilatation and decreased systolic function of the
right ventricle) or elevations of the right sided pressures relative to
left sided pressures.
When the pressure in the right atrium rises to the level in the left
atrium, there will no longer be a pressure gradient between these
heart chambers, and the left-to-right shunt will diminish or cease.
If left uncorrected, the pressure in the right side of the heart will
be greater than the left side of the heart. This will cause the pressure
in the right atrium to be higher than the pressure in the left atrium.

97
This will reverse the pressure gradient across the ASD, and the shunt
will reverse; a right-to-left shunt will exist. This phenomenon is
known as Eisenmenger's syndrome.
ASDs can be classified by location: ostium secundum (defect in
the fossa ovalis – in the central (or middle) part of the atrial septum),
sinus venosus (defect in the posterior aspect of the septum, near the
superior vena cava or inferior vena cava), or ostium primum (defect
in the anteroinferior aspect of the septum, a form of endocardial
cushion defect).
In ASD, shunting is left to right initially. Most small ASDs close
spontaneously during the 1st few years of life. However, persistent,
large shunts result in right atrial and ventricular volume overload,
pulmonary artery hypertension, elevated pulmonary vascular
resistance, and right ventricular hypertrophy. Atrial fibrillation may
occur later. Ultimately, the increase in right-sided pressure may
result in a bidirectional atrial shunt with cyanosis during adulthood.
Symptoms
Most small ASDs are asymptomatic. Symptoms: exercise
intolerance, dyspnoea during exertion, fatigue, atrial arrhythmias
sometimes with palpitations, cerebral or systemic thromboembolic
disorders.
Rarely, when an ASD is undiagnosed or untreated, Eisenmenger's
syndrome develops.
Physical examination: (ejection systolic) murmur at the upper left
sternal border; split, fixed S2 at the upper left sternal border; a low-
pitched diastolic murmur (due to increased tricuspid flow) at the left
lower sternal border.
Diagnosis
Diagnosis is suggested by cardiac examination, chest X-rays, and
ECG and confirmed by 2-dimensional echocardiography with colour
flow and Doppler studies.
ECG: may show right axis deviation, right ventricular
hypertrophy, or right bundle branch block (with rSR′ pattern in V1).
Chest X-rays: show cardiomegaly with dilation of the right
atrium and right ventricle, prominent main pulmonary artery
segment, and increased pulmonary vascular markings.
Treatment

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 Most small ostium secundum ASDs (< 3 mm) close
spontaneously; about 80% of those between 3 mm and 8 mm close
spontaneously by age 18 mo. However, ostium primum and sinus
venosus ASDs do not close spontaneously.
Asymptomatic children with a small shunt require annual
echocardiography. Because these children are at risk of paradoxical
systemic embolization, some centres recommend a catheter-delivered
closure device even for small ASDs. However, these devices are not
suitable for primum or sinus venosus defects because these defects
are near important structures.
Patients with moderate to large defects (e.g., pulmonary to
systemic flow ratio > 1.5:1) should have ASD closed, typically
between age 2 to 6 yr. Before repair, patients with large shunts and
heart failure should be treated with diuretics, digoxin, and ACEI.
Patients with primum ASD require endocarditis prophylaxis;
those with secundum or sinus venosus ASD do not.

Ventricular Septal Defect

A ventricular septal defect is one or more openings in the

interventricular septum, producing a shunt between ventricles.
VSDs are classified by location: membranous
(perimembranous), trabecular muscular, outlet (supracristal or
subpulmonary), or inlet defects.
Pathophysiology
During ventricular contraction, or systole, some of the blood from
the left ventricle leaks into the right ventricle, passes through the
lungs and reenters the left ventricle via the pulmonary veins and left
atrium. This has two net effects. First, the circuitous refluxing of
blood causes volume overload on the left ventricle. Second, because
the left ventricle normally has a much higher systolic pressure
(~120 mm Hg) than the right ventricle (~20 mm Hg), the leakage of
blood into the right ventricle therefore elevates right ventricular
pressure and volume, causing pulmonary hypertension with its
associated symptoms (elevated pulmonary artery vascular resistance,
right ventricular pressure overload, and right ventricular
hypertrophy). Ultimately, the increased pulmonary vascular
resistance causes shunt direction to reverse (from the right to the left

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ventricle), leading to Eisenmenger's syndrome.
Small defects produce a relatively small left-to-right shunt; the
pulmonary artery pressure is normal or only slightly increased. Heart
failure (HF) and Eisenmenger's syndrome do not develop.
Symptoms
Symptoms depend on defect size and magnitude of the left-to-
right shunt. Children with a small VSD are typically asymptomatic
and grow and develop normally.
In those with a larger defect, symptoms of HF: poor weight gain,
fatigue after feeding, tachypnoea, dyspnoea with feeding. Eventually,
untreated patients may develop symptoms of Eisenmenger's syndrome.
Physical examination: holosystolic murmur (with or without
thrill) at the lower left sternal border; it is audible shortly after birth.
S2 is usually narrowly split with an accentuated pulmonary
component; gallop; crackles; hepatomegaly.
Diagnosis
Diagnosis is suggested by clinical examination, supported by
chest X-ray and ECG, and established by echocardiography.
Chest X-ray: shows cardiomegaly and increased pulmonary
vascular markings.
ECG: shows left ventricular hypertrophy or combined ventricular
hypertrophy and, occasionally, left atrial hypertrophy. ECG and
chest X-ray are typically normal if the VSD is small.
Echocardiography: reveals pulmonary arterial and RV and RA
dilatation with abnormal (paradoxical) ventricular septal motion in
the presence of a significant right heart volume overload. The atrial
septal defect may be visualized directly by two-dimensional imaging,
colour flow imaging, or echocontrast.
Treatment
Small VSDs, particularly muscular septal defects, often close
spontaneously during the 1st few years of life. A small defect that
remains open does not require medical or surgical therapy.
Moderate-sized defects are less likely to close spontaneously.
Diuretics, digoxin, and ACE inhibitors are indicated before surgery if
HF develops. If infants do not respond to medical treatment or have
large shunts (with pulmonary to systemic flow ratio ≥ 2:1), surgical
repair may be done during the 1st few months of life.

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 All patients with a VSD, regardless of size, should be given
endocarditis prophylaxis with antibiotics before dental or surgical
procedures that are likely to produce bacteraemia.

Patent Ductus Arteriosus

Patent ductus arteriosus (PDA) is a persistence of the foetal

connection (ductus arteriosus) between the aorta and pulmonary
artery after birth, resulting in a left-to-right shunt.
Patent ductus arteriosus (PDA) accounts for 5 to 10% of
congenital heart anomalies; the male:female ratio is 1:3.
Pathophysiology
In the developing fetus, the ductus arteriosus (DA) is the vascular
connection between the pulmonary artery and the aortic arch that
allows most of the blood from the right ventricle to bypass the fetus'
fluid-filled compressed lungs. During foetal development, this shunt
protects the right ventricle from pumping against the high resistance
in the lungs, which can lead to right ventricular failure if the DA
closes inutero.
When the newborn takes its first breath, the lungs open and
pulmonary vascular resistance decreases. After birth, the lungs
release bradykinin to constrict the smooth muscle wall of the DA and
reduce bloodflow through the DA as it narrows and completely
closes, usually within the first few weeks of life.
In normal newborns, the DA is substantially closed within
12–24 hours after birth, and is completely sealed after three weeks.
The primary stimulus for the closure of the ductus is the increase in
neonatal blood oxygen content. Withdrawal from maternal
circulating prostaglandins also contributes to ductal closure. The
residual scar tissue from the fibrotic remnants of DA, called the
ligamentum arteriosum, remains in the normal adult heart.
The ductus arteriosus is a normal foetal blood vessel that closes
soon after birth. In a patent ductus arteriosus (PDA) the vessel does
not close and remains “patent” resulting in irregular transmission of
blood between two of the most important arteries close to the heart,
the aorta and the pulmonary artery. In patent ductus arteriosus,
pulmonary blood flow, LA and LV volumes, and ascending AO
volume are increased.

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 Physiologic consequences depend on ductal size. A small ductus
rarely produces symptoms. A large (and short) ductus causes a large
left-to-right shunt. Over time, a large shunt results in pulmonary
artery hypertension and elevated pulmonary vascular resistance,
ultimately leading to Eisenmenger's syndrome.
Symptoms
Clinical presentation depends on PDA size and gestational age at
delivery. Infants and children with a small PDA are generally
asymptomatic; infants with a large PDA present with signs of HF.
Physical examination:
1. Most children with a small PDA have normal heart sounds and
peripheral pulses.
2. A grade 1 to 3/6 continuous machinery murmur is heard best
in the upper left sternal border.
3. A gallop rhythm may be audible if HF develops.
4. Left subclavicular thrill.
Diagnosis
Diagnosis is suggested by clinical examination, supported by
chest X-rays and ECG, and established by 2-dimensional
echocardiography with colour flow and Doppler studies.
Chest X-ray and ECG are typically normal if the PDA is small.
If the shunt is significant it show prominence of the left atrium, left
ventricle, and ascending aorta and increased pulmonary vascular
markings. ECG may show left ventricular hypertrophy.
Treatment
In premature infants with compromised respiratory status, the
PDA can sometimes be closed by using a prostaglandin synthesis
inhibitor (e.g., indomethacin IV q 12 h for 3 doses; or ibuprofen
10 mg/kg po followed by 2 doses of 5 mg/kg at 24-h intervals) with
or without fluid restriction. If this treatment is ineffective, surgical
ligation is indicated.
In full-term infants, indomethacin is usually ineffective. For a
large PDA, surgical ligation and division are typically done
electively at age 6 mo to 3 yr. If HF develops, surgery can be done
earlier after medical management for HF.

Coarctation of Aorta

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 Coarctation of aorta is localized narrowing of the aortic lumen.
Coarctation of aorta accounts for 8 to 10% of congenital heart
anomalies. It occurs in 10 to 20% of patients with Turner's
syndrome. The male:female ratio is 2:1.
Pathophysiology
There are three types:
Preductal coarctation. The narrowing is proximal to the ductus
arteriosus. Blood flow to the aorta that is distal to the narrowing is
dependent on the ductus arteriosus; therefore severe coarctation can
be life-threatening. Preductal coarctation results when an intracardiac
anomaly during foetal life decreases blood flow through the left side
of the heart, leading to hypoplastic development of the aorta. This is
the type seen in approximately 5% of infants with Turner’s
syndrome.
Ductal coarctation. The narrowing occurs at the insertion of the
ductus arteriosus. This kind usually appears when the ductus
arteriosus closes.
Postductal coarctation. The narrowing is distal to the insertion
of the ductus arteriosus. Even with an open ductus arteriosus blood
flow to the lower body can be impaired. This type is most common
in adults. It is associated with notching of the ribs (because of
collateral circulation), hypertension in the upper extremities, and
weak pulses in the lower extremities.
Postductal coarctation is most likely the result of the extension
of a muscular artery (ductus arteriosus) into an elastic artery (aorta)
during foetal life, where the contraction and fibrosis of the ductus
arteriosus upon birth subsequently narrows the aortic lumen.
Physiologic consequences include increased left ventricular
pressure overload, left ventricular hypertrophy, overperfusion of the
upper part of the body including the brain, and malperfusion of the
abdominal organs and lower extremities.
Symptoms
If coarctation is significant, circulatory shock with renal
insufficiency (oliguria or anuria) and metabolic acidosis may develop
during the neonatal period and may mimic findings of other systemic
disorders such as sepsis.
Less severe coarctation may be asymptomatic during infancy.
Patients may have such symptoms:

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 – headache;
– chest pain;
– fatigue;
– leg claudication during physical activities.
Physical examination: hypertension in the upper extremities,
diminished or delayed femoral pulses, low or unobtainable arterial
BP in the lower extremities; a grade 2 to 3/6 ejection systolic
murmur is best heard in the left interscapular area.
Diagnosis
Diagnosis is suggested by clinical examination (including BP
measurement in all 4 extremities), supported by chest X-rays and
ECG, and established by 2-dimensional echocardiography with
colour flow and Doppler studies or with CT or MR angiography.
Chest X-ray: shows coarctation as a “3” sign in the upper left
mediastinal shadow. Heart size is normal unless HF supervenes.
Dilated intercostal collateral arteries may erode the 3rd to 8th ribs,
making the ribs notched, but notching is seldom seen before age 5 yr.
ECG: shows left ventricular hypertrophy but may be normal.
ECG usually shows right ventricular hypertrophy or right bundle
branch block rather than left ventricular hypertrophy.
Treatment
Symptomatic neonates require cardiopulmonary stabilization with
infusion of prostaglandin E1 (0.05 to 0.10 μg/kg/min – may titrate
up to 0.4 μg/kg/min, then back down to lowest effective dose) to
reopen the constricted ductus arteriosus. Then, pulmonary artery
blood can perfuse the descending aorta through the ductus,
improving systemic perfusion and reversing metabolic acidosis.
Short-acting inotropic drugs (e.g., dopamine, dobutamine),
diuretics, and O2 are used to treat HF.
Before surgery, hypertension may be treated with β-blockers;
ACE inhibitors should be avoided. After surgery, hypertension can
be treated with β-blockers, ACE inhibitors, or angiotensin II receptor
blockers.
The preferred definitive treatment is controversial. Some centres
prefer balloon angioplasty with or without stent placement, but
others prefer surgical correction and reserve the balloon procedure
for recoarctation after surgical correction.

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 Surgical options include resection and end-to-end anastomosis,
patch aortoplasty, and left subclavian flap aortoplasty. Choice
depends on anatomy and centre preference. All patients should be
given endocarditis prophylaxis before dental or surgical procedures
that are likely to produce bacteraemia, regardless of whether surgical
correction has been done.

HEART VALVULAR DISEASE

Aortic Regurgitation

Aortic regurgitation is incompetency of the aortic valve causing

flow from the aorta into the left ventricle during diastole. Causes
include idiopathic valvular degeneration, rheumatic fever,
endocarditis, myxomatous degeneration, congenital bicuspid aortic

105
valve, aortic root dilatation or dissection, and connective tissue or
rheumatologic disorders.
Aetiology: aortic regurgitation (AR) may be acute or chronic.
The primary causes of acute AR are: infective endocarditis and
dissection of the ascending aorta; idiopathic degeneration of the
aortic valves or root, rheumatic fever, infective endocarditis,
myxomatous degeneration (in patients with Marfan’s or Ehlers-
Danlos’ syndromes); trauma. In children, the most common cause is
a ventricular septal defect with aortic valve prolapse.
Symptoms: acute AR causes symptoms of HF and cardiogenic
shock. Chronic AR is typically asymptomatic for years.
Signs: progressive exertional dyspnoea, orthopnoea, paroxysmal
nocturnal dyspnoea, palpitations. Chest pain (angina pectoris) affects
only about 5% of patients.
Physical examination:
– large-volume pulse with rapid rise and fall (slapping, water-
hammer, or collapsing pulse);
– systolic apical or carotid thrill;
– LV impalce displaced downward and laterally, with systolic
depression of the entire left parasternal area;
– systolic BP increases while diastolic BP decreases.
Auscultatory findings: normal 1st heart sound (S1); nonsplit,
loud, sharp or slapping 2nd heart sound (S2); diastolic murmur is
blowing, high-pitched, and decrescendo, beginning soon after the
aortic component of S2 (A2). The murmur is heard best when the
patient is leaning forward, with breath held at end-expiration.
Diastolic murmur heard near the axilla or mid left thorax
(Cole-Cecil murmur); mid-to-late diastolic rumble heard at the
apex (Austin Flint murmur); sharp sound heard over the femoral
pulse (pistol-shot sound, or Traube's sign); femoral systolic bruit
distal and a diastolic bruit proximal to arterial compression
(Duroziez's murmur).
Visible signs include:
– head bobbing (Musset's sign);
– pulsation of the fingernail capillaries (Quincke's sign, best
seen with slight pressure) or uvula (Müller's sign);
– pulsation of the carotid arteries (Corrigan's sign);
– pulsation of the retinal arteries (Becker's sign);

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 – pulsation of the liver (Rosenbach's sign);
– pulsation of the spleen (Gerhard's sign).
Diagnosis is suspected based on history and physical examination
and confirmed by echocardiography.
Doppler echocardiography: is the test of choice to detect and
quantify the magnitude of regurgitant blood flow. Two-dimensional
echocardiography can quantify aortic root size and anatomy and LV
function.
Echocardiography: can also assess severity of pulmonary
hypertension secondary to LV failure, detect vegetations or
pericardial effusions (e.g., in aortic dissection), and provide
information about prognosis.
Radionuclide imaging: may be used to determine LVEF if
echocardiographic results are borderline abnormal or if
echocardiography is technically difficult.
An ECG: may show repolarization abnormalities with or without
QRS voltage criteria of LV hypertrophy, left atrial enlargement, and
T-wave inversion with ST-segment depression in precordial leads.
Chest X-ray: may show cardiomegaly and a prominent aortic
root in patients with chronic progressive AR. If AR is severe, signs
of pulmonary oedema and HF may also be present. Exercise testing
may help assess functional capacity and symptoms in patients with
documented AR and equivocal symptoms.
Coronary angiography: should be considered before surgery,
even if no angina is present, because about 20% of patients with
severe AR have significant CAD, which may need concomitant
coronary artery bypass graft surgery.
Treatment
Treatment of chronic AR varies by symptoms and degree of LV
dysfunction. Patients with symptoms precipitated by normal daily
activity or during exercise testing require aortic valve replacement;
patients who prefer to avoid surgery may be treated with vasodilators
(e.g., long-acting nifedipine 30 to 90 mg po once/day or ACE
inhibitors). Also, diuretics or nitrates to reduce preload may be
beneficial for severe AR. Patients who do not meet these criteria
should be reevaluated by physical examination, echocardiography,
and possibly rest-exercise radionuclide cineangiography to measure
LV contractility q 6 to 12 mo.

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 Antibiotic prophylaxis against endocarditis is indicated before
procedures that can result in bacteraemia.
Nitroprusside and inotropic agents (dopamine or dobutamine)
may be used before surgery in patients with poorly tolerated acute
AR to stabilize their clinical condition. In patients with chronic
severe AR and heart failure, ACE-inhibitors are the treatment of
choice when surgery is contraindicated or in cases with persistent
postoperative LV dysfunction. In asymptomatic patients with high
blood pressure, the indication for antihypertensive treatment with
vasodilators such as ACE-inhibitors or dihydropyridine calcium
channel blockers is warranted.
The role of vasodilators in the asymptomatic patients without
high blood pressure in order to delay surgery is unproved.
In patients with Marfan’s syndrome, beta-blockers slow the
progression of the aortic dilatation and should also be given after
operation. In patients with severe AR, the use of beta-blockers
should be very cautious because the lengthening of diastole increases
the regurgitant volume. However, they can be used in patients with
severe LV dysfunction. Recently, enalapril has also been used to
delay aortic dilatation in patients with Marfan’s syndrome. Whether
the same beneficial effect occurs in patients with bicuspid aortic
valves is not known. Patients with AR should be educated on
endocarditis prevention and antibiotic prophylaxis.
Indications for surgery
In symptomatic acute AR, urgent intervention is indicated (aortic
valve replacement).
In chronic AR, the goals of the operation are to improve outcome,
to diminish symptoms, to prevent the development of postoperative
heart failure and cardiac death, and to avoid aortic complications in
patients who present with aortic aneurysm. Surgery should be
considered in asymptomatic patients with severe AR and impaired
LV function at rest (resting EF 50% and/or LV end-diastolic diameter
70 mm and/or end-systolic diameter 50 mm (or 25 mm/m² BSA))
since the likelihood of early development of symptoms is high,
perioperative mortality is low, and postoperative results are excellent.
Indications for surgery in aortic regurgitation: severe AR;
symptomatic patients (dyspnoea, NYHA class II, III, IV or angina)
(IB); asymptomatic patients with resting LVEF ≤ 50% (IB); patients

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undergoing CABG or surgery of ascending aorta, or on another valve
(IC); asymptomatic patients with resting LVEF > 50% with severe
LV dilatation; end-diastolic dimension > 70 mm or (IIa, C); ESD >
50 mm (or > 25 mm/m2 BSA) (IIa, C); whatever the severity of AR;
patients who have aortic root disease with maximal aortic diameter: ≥
45 mm for patients with Marfan's syndrome (IC); ≥ 50 mm for patients
with bicuspid valves (IIa, C); ≥ 55 mm for other patients (IIa, C).

Aortic Stenosis

Aortic stenosis (AS) is narrowing of the aortic valve obstructing

blood flow from the left ventricle to the ascending aorta during
systole. Causes include a congenital bicuspid valve, idiopathic
degenerative sclerosis with calcification, and rheumatic fever.
Aetiology and pathophysiology
The most common cause of AS in patients < 70 yr is a congenital
bicuspid aortic valve. Congenital AS affects more males.
Causes include: congenital bicuspid valve, idiopathic
degenerative sclerosis with calcification, rheumatic fever.
The left ventricle (LV) gradually hypertrophies in response to AS.
Significant LV hypertrophy causes diastolic dysfunction and, with
progression, may lead to decreased contractility, ischaemia, or
fibrosis, any of which may cause systolic dysfunction and heart
failure (HF). LV chamber enlargement is a late finding unless there
is coexisting MI. Patients with AS have a higher incidence of GI
bleeding (called Heyde's syndrome) because the high shear stress of
stenotic valves makes multimeric von Willebrand's factor more
susceptible to cleavage by a plasma metalloprotease and may
increase platelet clearance. GI bleeding may also be due to
angiodysplasia.
Symptoms
Congenital AS is usually asymptomatic until at least age 10 or
20 yr, when symptoms may begin to develop insidiously: exertional
syncope, angina, dyspnoea (SAD triad); ventricular fibrillation
leading to sudden death, exertional or nonexertional syncope,
exertional angina pectoris.
Physical examination: carotid and peripheral pulses that are
reduced in amplitude and slow rising (pulsus parvus, mollus et

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tardus); the LV impulse may become displaced; systolic BP may be
high with mild or moderate AS and falls as AS becomes more
severe; systolic thrill, which felt best at the left upper sternal border;
S1 is normal and S2 is single because aortic valve closing is delayed
and merges with the pulmonic (P2) component of S2. Ejection
murmur, heard best at the right and left upper sternal border when a
patient who is sitting upright leans forward. The murmur typically
radiates to the right clavicle and both carotid arteries
But in elderly patients, vibration of the unfused cusps of calcified
aortic valve leaflets may transmit a louder, more high-pitched,
“cooing” or musical sound to the cardiac apex, with softening or
absence of the murmur parasternally (Gallavardin's phenomenon),
thereby mimicking mitral regurgitation.
Diagnosis: diagnosis is suspected clinically and confirmed by
echocardiography.
Two-dimensional transthoracic echocardiography: is used to
identify a stenotic aortic valve and possible causes, to quantify LV
hypertrophy and degree of diastolic or systolic dysfunction, and to
detect coexisting valvular heart disorders (aortic regurgitation, mitral
valve disorders) and complications (e.g., endocarditis).
Doppler echocardiography is used to quantify degree of stenosis
by measuring aortic valve area, jet velocity, and transvalvular
systolic pressure gradient. A valve area of 0.5 to 1.0 cm² or a mean
gradient > 45 to 50 mm Hg represents severe stenosis.
Cardiac catheterization is necessary to determine whether
coronary artery disease (CAD) is the cause of angina and,
occasionally, to resolve differences between clinical and
echocardiographic findings.
An ECG is obtained. ECG typically shows changes of LV
hypertrophy with or without an ischaemic ST- and T-wave pattern.
Chest X-ray findings may include calcification of the aortic
cusps (seen on the lateral projection or on fluoroscopy) and evidence
of HF. Heart size may be normal or only mildly enlarged.
Treatment
Asymptomatic patients with gradients of 25 to 50 mm Hg or
valve area < 1.0 cm² are at higher risk of developing symptoms in the
next 2 yr, but generally elective valve replacement is not required in
the absence of symptoms. Valve replacement is indicated for patients

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who have moderate or severe AS and primarily require CABG.
Surgery may be indicated for patients who become hypotensive
during exercise treadmill testing and for those with LV ejection
fraction < 50%. Patients with ventricular arrhythmias and severe
LV hypertrophy are also often referred for surgery, but benefits are
less clear. Recommendations for patients without any of these
qualifying conditions include more frequent monitoring for
progression of symptoms, LV hypertrophy, gradients, and valve area
with medical management as needed. It is unclear whether statins
reduce the progression of AS. Other drugs may be detrimental,
especially those that can cause hypotension. Small studies suggest
that perhexilene maleate may decrease symptoms. Nitroprusside has
been used as a temporizing measure to reduce afterload in patients
with decompensated HF in the hours before valve replacement, but
because this drug can have the same effect as rapid-acting nitrates,
it must be used cautiously and monitoring is required.
Symptomatic patients should undergo valve replacement or
balloon valvotomy. Valve replacement is indicated for virtually all
who can tolerate surgery. In younger patients, the patient's own
pulmonic valve can be used, providing good durability; a
bioprosthesis is then used to replace the pulmonic valve (Ross
procedure). Most often, the aortic valve is replaced with a
mechanical or bioprosthetic valve. Preoperative evaluation for CAD
is indicated so that CABG and valve replacement, if indicated, can
be done during the same procedure.
Balloon valvotomy is used primarily in children and very young
adults with congenital AS. In older patients who are unfit for
surgery, balloon valvuloplasty can provide temporary relief of
symptoms, perhaps for 6 to 12 mo, and can be repeated in selected
patients.
Although several retrospective reports have shown beneficial
effects of statins and ACE-inhibitors, data are still conflicting and
the only randomized trial assessing the effect of statin therapy is
negative. It is, therefore, too early for treatment recommendations.
Symptomatic patients require early surgery, as no medical therapy
for AS is able to delay the inevitability of surgery. However,
patients who are unsuitable candidates for surgery may be treated
with digitalis, diuretics, ACE-inhibitors, or angiotensin receptor

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blockers if they are experiencing heart failure. Beta-blockers should
be avoided in these circumstances. In selected patients with
pulmonary oedema, nitroprusside can be used under haemodynamic
monitoring.
Indications for aortic valve replacement in aortic stenosis:
patients with severe AS and any symptoms IB; patients with severe
AS undergoing coronary artery bypass surgery, surgery of the
ascending aorta, or on another valve (IC); asymptomatic patients
with severe AS and systolic LV dysfunction (LVEF < 50%) unless
due to other cause (IC); asymptomatic patients with severe AS and
abnormal exercise test showing symptoms on exercise (IC);
asymptomatic patients with severe AS and abnormal exercise test
showing fall in blood pressure below baseline (IIa, C); patients with
moderate AS undergoing coronary artery bypass surgery, surgery of
the ascending aorta or another valve (IIa, C); asymptomatic patients
with severe AS and moderate-to-severe valve calcification, and a rate
of peak velocity progression ≥ 0.3 m/s per year (IIa, C); AS with low
gradient (< 40 mmHg) and LV dysfunction with contractile reserve
(IIa, C); asymptomatic patients with severe AS and excessive LV
hypertrophy ( ≥ 15 mm) unless this is due to hypertension (IIb, C);
AS with low gradient (< 40 mmHg) and LV dysfunction without
contractile reserve (IIb, C); asymptomatic patients with severe AS
and abnormal exercise test showing complex ventricular arrhythmias
(IIb, C).

Mitral Regurgitation

Mitral regurgitation (MR) is incompetency of the mitral valve

causing flow from the left ventricle (LV) into the left atrium during
systole.
Aetiology and pathophysiology
MR may be acute or chronic. Causes of acute MR include:
ischaemic papillary muscle dysfunction or rupture; infective
endocarditis; acute rheumatic fever; spontaneous, traumatic, or
ischaemic tears or rupture of the mitral valve leaflets or subvalvular
apparatus; acute dilation of the LV due to myocarditis or ischaemia;
mechanical failure of a prosthetic mitral valve.

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 Common causes of chronic MR include: those of acute MR;
myxomatous degeneration of the mitral leaflets or chordae tendineae;
mitral valve prolapse (MVP); mitral annular enlargement;
nonischemic papillary muscle dysfunction; calcification of the mitral
annulus (mainly in elderly women).
Acute MR may cause acute pulmonary oedema and biventricular
failure with cardiogenic shock or sudden cardiac death.
Symptoms: acute MR causes the same symptoms and signs as
acute heart failure and cardiogenic shock.
Most patients with chronic MR have dyspnoea, fatigue (due to
heart failure), orthopnoea, and palpitations (often due to AF).
Physical examination: LV impulse that is sustained, enlarged,
and displaced downward and to the left; diffuse precordial lift occurs
with severe MR because the LA enlarges, causing anterior cardiac
displacement; diffuse precordial lift; regurgitant murmur (or thrill)
may also be palpable in severe cases.
On auscultation: the 1st heart sound (S1) may be soft (or
occasionally loud). The 3rd heart sound (S3) is at the apex;
(pansystolic) murmur, heard best at the apex when the patient is in
the left lateral decubitus position. The murmur radiates toward the
left axilla.
Diagnosis is suspected clinically and confirmed by
echocardiography.
Doppler echocardiography is used to detect regurgitant flow
and help quantify its severity; 2-dimensional echocardiography is
used to determine the cause of MR and to detect pulmonary
hypertension.
If endocarditis or valvular thrombi are suspected,
transoesophageal echocardiography (TEE) can provide a more
detailed view of the mitral valve and LA. TEE is also indicated when
mitral valve repair instead of replacement is being considered to
confirm the anatomy in more detail.
An ECG shows LA enlargement and LV hypertrophy with or
without ischaemia. Sinus rhythm is usually present when MR is
acute because the atria have not had time to stretch and remodel.
Chest X-ray in acute MR may show pulmonary oedema;
abnormalities in cardiac silhouette are not evident unless an
underlying chronic disorder is also present. Chest X-ray in chronic

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MR may show LA and LV enlargement. It may also show pulmonary
vascular congestion and pulmonary oedema with heart failure.
Cardiac catheterization is done before surgery, mainly to
determine whether coronary artery disease (CAD) is present. A
prominent systolic c-v wave is seen on pulmonary artery occlusion
pressure (pulmonary capillary wedge pressure) tracings during
ventricular systole. Ventriculography can be used to quantify MR.
Treatment
Acute MR requires emergency mitral valve repair or replacement;
patients with ischaemic papillary muscle rupture may also require
coronary revascularization. Pending surgery, nitroprusside or
nitroglycerin infusion may be used to reduce afterload, thus
improving forward stroke volume and reducing ventricular and
regurgitant volume.
Indications for surgery in severe chronic organic mitral
regurgitation: symptomatic patients with LVEF > 30% and ESD
< 55 mm (IB); asymptomatic patients with LV dysfunction (ESD >
45 mm and/or LVEF ≤ 60%) (IC); asymptomatic patients with
preserved LV function and atrial fibrillation or pulmonary
hypertension (systolic pulmonary artery pressure > 50 mm Hg at
rest) (IIa, C); patients with severe LV dysfunction (LVEF < 30%
and/or ESD > 55 mm) refractory to medical therapy with high
likelihood of durable repair, and low comorbidity (IIa, C);
asymptomatic patients with preserved LV function, high likelihood
of durable repair, and low risk for surgery (IIb, B); patients with
severe LV dysfunction (LVEF < 30% and/or ESD > 55 mm)
refractory to medical therapy with low likelihood of repair and low
comorbidity (IIb, C).
Definitive treatment of chronic MR is also mitral valve repair or
replacement, but patients with asymptomatic or mild chronic MR
and no pulmonary hypertension or AF may do well with periodic
monitoring. ACE inhibitors or angiotensin receptor blockers are
used to decrease left ventricular preload and afterload. They are used
in patients with moderate mitral insufficiency to delay dilation of the
LV. Loop diuretics such as furosemide are helpful in patients with
exertional or nocturnal dyspnoea. Digoxin may reduce symptoms in
patients with atrial fibrillation or those in whom valve surgery is not
appropriate. The ideal timing for surgery is uncertain, but

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intervention before ventricular decompensation (defined as
echocardiographic end-diastolic dimension > 70 mm, end-systolic
dimension > 45 mm, and ejection fraction < 60%) improves
outcomes and decreases the chance of worsening LV function. After
decompensation, ventricular function becomes dependent on the
afterload reduction of MR, and in about 50% of decompensated
patients, valve replacement causes a markedly depressed ejection
fraction. Antibiotic prophylaxis is indicated before procedures that
can cause bacteraemia.

Mitral Stenosis

Mitral stenosis (MS) is narrowing of the mitral orifice impeding

blood flow from the left atrium to the left ventricle.
Aetiology and pathophysiology
Rheumatic fever, less common causes include bacterial
endocarditis, SLE, atrial myxoma, RA malignant carcinoid syndrome
with an atrial right-to-left shunt.
Occasionally, MS is congenital.
The normal area of the mitral valve orifice is 4 to 5 cm². An area
of 1 to 1.5 cm² reflects moderate MS and often causes exertional
symptoms. An area < 1 cm² represents severe stenosis and may cause
symptoms during rest. However, the relationship between the area of
the valve orifice and symptoms is not always reliable. Left atrial
(LA) size and pressure increase progressively to compensate for MS;
pulmonary venous and capillary pressures also increase and may
cause secondary pulmonary hypertension, leading to right ventricular
(RV) heart failure and tricuspid and pulmonic regurgitation. Rate of
progression varies.
LA enlargement predisposes to atrial fibrillation (AF), a risk
factor for thromboembolism. The faster heart rate and loss of atrial
contraction with onset of AF often leads to sudden worsening of
symptoms.
Symptoms: symptoms correlate poorly with disease severity
because the disease often progresses insidiously and patients reduce
their activity without being aware of it. Many patients are
asymptomatic until they become pregnant or AF develops.

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 Initial symptoms are usually those of heart failure. They typically
do not appear until 15 to 40 yr after an episode of rheumatic fever.
Less common symptoms include haemoptysis due to rupture of
small pulmonary vessels and pulmonary oedema.
Physical examination: classic mitral facies, a plum-coloured
malar flush; palpable 1st and 2nd heart sounds (S1 and S2). S1 is
best palpated at the apex, and S2 at the upper left sternal border;
evident pulmonic component of S2 (P2); RV impulse (heave)
palpable at the left sternal border; auscultatory findings include: loud
S1, it is heard best at the apex; diastolic murmur, heard best with the
bell of the stethoscope at the apex (or over the palpable apex beat) at
end-expiration when the patient is in the left lateral decubitus
position. Austin Flint murmur (a low-pitched mid-diastolic murmur
heard at the apex due to AR); Graham Steell's murmur (a soft
decrescendo diastolic murmur heard best along the left sternal border
and caused by pulmonic regurgitation secondary to severe pulmonary
hypertension).
Diagnosis is suspected clinically and confirmed by
echocardiography.
Two-dimensional echocardiography provides information about
the degree of valvular calcification and stenosis and LA size.
Doppler echocardiography provides information about the
transvalvular gradient and pulmonary artery pressure.
Transoesophageal echocardiography can be used to detect or
exclude small LA thrombi, especially those in the LA appendage.
ECG show LA enlargement, right axis QRS deviation, and tall R
waves in V1 suggest RV hypertrophy.
Chest X-ray shows straightening of the left cardiac border due to
a dilated LA appendage, and widening of the carina. With barium in
the oesophagus, the lateral chest X-ray will show the dilated LA
displacing the oesophagus posteriorly. The main pulmonary artery
(trunk) may be prominent; the descending right pulmonary artery
diameter is ≥ 16 mm if pulmonary hypertension is significant. The
upper lobe pulmonary veins may be dilated. A double shadow of an
enlarged LA may be seen along the right cardiac border. Horizontal
lines in the lower posterior lung fields (Kerley B lines) indicate
interstitial oedema associated with high LA pressure.

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 Cardiac catheterization indicated only for perioperative
assessment of coronary artery disease (CAD) before surgical repair,
can confirm elevated LA and pulmonary artery pressures, mitral
gradient and valve area.
Treatment
Asymptomatic patients require only prophylaxis against recurrent
rheumatic fever (e.g., with IM injections of benzathine penicillin G
1.2 million units q 3 or 4 wk) until age 25 to 30 and prophylaxis
against endocarditis before high-risk procedures.
Mildly symptomatic patients usually respond to diuretics and, if
sinus tachycardia or AF is present, to β-blockers or Ca channel
blockers, which can control ventricular rate. Anticoagulants are
indicated to prevent thromboembolism. All patients should be
encouraged to continue at least low levels of physical exercise
despite exertional dyspnoea.
Indications for percutaneous mitral commissurotomy in
mitral stenosis with valve area < 1.5 cm2: symptomatic patients
with favourable characteristics for PMC (IB); symptomatic patients
with contraindication or high risk for surgery (IC); as initial
treatment in symptomatic patients with unfavourable anatomy but
otherwise favourable clinical characteristics (IIa, C); asymptomatic
patients with favourable characteristics and high thromboembolic
risk or high risk of haemodynamic decompensation; previous history
of embolism (IIa, C); dense spontaneous contrast in the left atrium
(IIa, C); recent or paroxysmal atrial fibrillation (IIa, C); systolic
pulmonary pressure > 50 mmHg at rest (IIa, C); need for major non-
cardiac surgery (IIa, C); desire of pregnancy (IIa, C).
More severely symptomatic patients and patients with evidence of
pulmonary hypertension require valvotomy, commissurotomy, or
valve replacement.
Patients with severe subvalvular disease, valvular calcification, or
LA thrombi may be candidates for surgical commissurotomy, in
which fused mitral valve leaflets are separated using a dilator passed
through the LV (closed commissurotomy) via thoracotomy, or by
direct vision (open commissurotomy) via sternotomy. Choice of
procedure is based on surgeon's experience and the morphology of
the valve, although closed valvotomy is now performed less
frequently in Western countries.

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 Valve replacement is confined to those with severe morphologic
changes that make the valve unsuitable for balloon or surgical
valvotomy.
Common complications are pulmonary hypertension, atrial
fibrillation, and thromboembolism.

Tricuspid Regurgitation

Tricuspid regurgitation (TR) is insufficiency of the tricuspid

valve causing blood flow from the right ventricle to the right atrium
during systole.
Aetiology: TR is most commonly caused by dilation of the right
ventricle (RV) with malfunction of a normal valve, as occurs in
pulmonary hypertension, RV dysfunction induced heart failure (HF),
and pulmonary outflow tract obstruction. Less commonly from
infective endocarditis in IV drug abusers, carcinoid syndrome, chest
or abdominal injury, rheumatic fever, idiopathic myxomatous
degeneration, ischaemic papillary muscle dysfunction, congenital
defects (e.g., cleft tricuspid valve, endocardial cushion defects),
Ebstein's anomaly, Marfan syndrome, use of certain drugs (e.g.,
ergotamine, fenfluramine, phentermine).
Symptoms and signs: TR usually causes no symptoms, but some
patients experience neck pulsations due to elevated jugular pressures.
Acute or severe TR may cause symptoms of RV dysfunction induced
HF. Patients may also develop symptoms of AF or atrial flutter.
Physical examination: jugular venous distention, pedal oedema;
ascites; hepatomegaly; systolic hepatic pulsation and an RV impulse
at the left lower sternal border.
On auscultation: the 2nd heart sound (S2) may be split;
holosystolic murmur heard best at the left middle or lower sternal
border or at the epigastrium when the patient is sitting upright or
standing. The murmur varies with respiration, becoming louder with
inspiration (Carvallo's sign).
Diagnosis
Mild TR is most often detected on echocardiography done for
other reasons. Doppler echocardiography. ECG is usually normal
but, in advanced cases, may show tall peaked P waves caused by

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right atrial enlargement, a tall R or QR wave in V1 characteristic of
RV hypertrophy, or AF.
Chest X-ray is usually normal but, in advanced cases with RV
hypertrophy or RV dysfunction-induced HF, may show an enlarged
superior vena cava, an enlarged right atrial or RV silhouette (behind
the upper sternum in the lateral projection), or pleural effusion.
Treatment
Surgical options include: annuloplasty, valve repair, and valve
replacement. If endocarditis has damaged the tricuspid valve and
cannot be cured with antibiotics, the valve may be totally excised and
not replaced until 6 to 9 mo later; this procedure is well tolerated.

Tricuspid Stenosis

Tricuspid stenosis (TS) is narrowing of the tricuspid orifice that

obstructs blood flow from the right atrium to the right ventricle.
Aetiology: TS is almost always due to rheumatic fever; rare
causes of TS include SLE, right atrial (RA) myxoma, congenital
malformations, metastatic tumours.
The RA becomes hypertrophied and distended, and sequelae of
right heart disease-induced heart failure develop but without right
ventricular (RV) dysfunction; the RV remains underfilled and small.
Uncommonly, atrial fibrillation occurs.
Symptoms: fluttering discomfort in the neck (due to giant a
waves in the jugular pulse), fatigue and cold skin (due to low cardiac
output), right upper quadrant abdominal discomfort (due to an
enlarged liver), peripheral oedema, ascites.
On auscultation: TS may produce a soft opening snap and a mid-
diastolic rumble with presystolic accentuation. The murmur becomes
louder and longer with maneuvers that increase during inspiration.
Diagnosis is suspected based on history and physical examination
and confirmed by Doppler echocardiography.
Two-dimensional echocardiography shows thickened leaflets
with reduced movement and RA enlargement.
ECG and chest X-ray are often obtained. ECG may show RA
enlargement out of proportion to RV hypertrophy and tall, peaked P
waves in inferior leads and V1.

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 Chest X-ray shows a dilated superior vena cava and RA
enlargement, indicated by an enlarged right heart border.
Liver enzymes are elevated because of passive hepatic
congestion.
Cardiac catheterization is rarely indicated for evaluation of TS.
When catheterization is indicated (e.g., to evaluate coronary
anatomy), findings include elevated RA pressure with a slow fall in
early diastole and a diastolic pressure gradient across the TV.
Treatment
Evidence to guide treatment is scarce. For all symptomatic
patients, treatment should include a low-salt diet, diuretics, and
aldosterone antagonists. Patients with hepatic congestion leading to
cirrhosis or severe systemic venous congestion and effort limitation
may benefit from interventions such as balloon valvotomy or valve
repair or replacement.
Indications for intervention in tricuspid valve disease: severe
TR in a patient undergoing left-sided valve surgery (IC); severe
primary TR and symptoms despite medical therapy without severe
right ventricular dysfunction (IC); severe TS (±TR), with symptoms
despite medical therapy (IC); severe TS (±TR) in a patient
undergoing left-sided valve intervention (IC); moderate organic TR
in a patient undergoing left-sided valve surgery (IIa, C); moderate
secondary TR with dilated annulus (> 40 mm) in a patient
undergoing left-sided valve surgery (IIa, C); severe TR and
symptoms, after left-sided valve surgery, in the absence of left-sided
myocardial, valve, or right ventricular dysfunction and without
severe pulmonary hypertension (systolic pulmonary artery pressure
> 60 mmHg) (IIa, C); severe isolated TR with mild or no symptoms
and progessive dilation or deterioration of right ventricular function
(IIb, C).

INFECTIVE ENDOCARDITIS

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 Infective endocarditis (IE). If not to treat it, it is a fatal disease.
The achievements of last years in diagnostics and treatment have
improved that the prognosis of the patients with IE is poor. The
reason of high mortality in IE is later establishment of the diagnosis
or later treatment. Therefore it is very important that: 1) the
opportunity of IE occurrence was considered (examined) at early
stages of inspection of each patient having a fever or septicemia and
cardiac murmur; 2) urgently carried out cardiography to each patient
with suspicion on IE; 3) to ensure (supply) cooperation of
cardiologists, microbiologists and cardiosurgeons at suspicion on IE
or at establishment of this diagnosis.
Densities of IE in structure of the acquired defects have increased
8 times for last ten years. The reason of such increase is the growth
of narcomania. At those who introduce drugs intravenously, IE arises
30 times more often, than in people in general and 4 times is more
often, than in patients with rheumatic heart defects. In 1–4% of the
patients with prosthetic valves IE arises in the first year after the
operation. At 10% IE arises after the realization of diagnostic and
medical manipulations.
The men are sick for IE 2–3 times more often, than the women. In
the industrialized countries the tendency to “aging” IE is marked for
last 30 years. The average age of such patients is 50 years and 25%
of the patients are older than 60 years.
Definitions. IE is an endovascular, microbial infection of
intracardiac structures facing the blood including infections of the
large intrathoracic vessels and of intracardiac foreign bodies. The
early characteristic lesion is a variably sized vegetation, although
destruction, ulceration or abscess formation may be seen earlier by
echocardiography.
Aetiology and pathophysiology
The normal heart is relatively resistant to infection. Bacteria and
fungi do not easily adhere to the endocardial surface, and constant
blood flow helps prevent them from settling on endocardial
structures. Thus, 2 factors are generally required for endocarditis:
predisposing abnormality of the endocardium and
microorganisms in the bloodstream (bacteraemia). Rarely,
massive bacteraemia or particularly virulent microorganisms cause
endocarditis on normal valves.

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 Endocardial factors:
– Endocarditis usually involves the heart valves. Major
predisposing factors are congenital heart defects, rheumatic valvular
disease, bicuspid or calcific aortic valves, mitral valve prolapse, and
hypertrophic cardiomyopathy. Prosthetic valves are a particular risk.
Occasionally, mural thrombi, ventricular-septal defects, and patent
ductus arteriosus sites become infected. The actual nidus for
infection is usually a sterile fibrin-platelet vegetation formed when
damaged endothelial cells release tissue factor.
– Infective endocarditis occurs most often on the left side (mitral
or aortic valve). About 10 to 20% of cases are right-sided (tricuspid
or pulmonic valve). IVDA have a much higher incidence of right-
sided endocarditis (about 30 to 70%).
Microorganisms:
– Microorganisms that infect the endocardium may originate
from distant infected sites (cutaneous abscess, inflamed or infected
gums) or have obvious portals of entry such as a central venous
catheter or a drug injection site. Almost any implanted foreign
material (ventricular or peritoneal shunt, prosthetic device) is at risk
of bacterial colonization, thus becoming a source of bacteraemia and
hence endocarditis. Endocarditis also may result from asymptomatic
bacteraemia, such as typically occurs during invasive dental,
medical, or surgical procedures. Even toothbrushing and chewing
can cause bacteraemia (usually due to streptococci viridans) in
patients with gingivitis.
– Causative microorganisms vary by site of infection, source of
bacteraemia, and host risk factors (IVDA), but overall, streptococci
and Staphylococcus aureus cause 80 to 90% of cases. Enterococci,
gram-negative bacilli, HACEK organisms (Cardiobacterium
hominis, Kingella kingae, Actinobacillus actinomycetemcomitans,
Eikenella corrodens, Haemophilus sp. are included in the group), and
fungi cause most of the rest. Why streptococci and staphylococci
frequently adhere to vegetations and why gram-negative aerobic
bacilli seldom adhere are unclear. However, the ability of S. aureus
to adhere to fibronectin may play a role, as may dextran production
by streptococci viridans.
Table 16 – Terminology for infective endocarditis

122
 Acti- Recur- Diagnos- Patho- Anato- Microbi-
vity rence tic termi- logy mical ology
nology site
Active Mitral Micro-
Heale organism
d Aortic culture,
Tri negative
First Relaps- cus-pid
episodea ing Mu Serologi-
ra-letic cally
Recur- negative
Definite rent Suspected
a
PCR
Possible negative
Early
Nativea prosthe- Histolo-
tic gically
valves; negative
late
prosthe-
tic
valves;
IVDA
(b)

a) if the columns ‘recurrence’, ‘diagnostic terminology’, and/or

pathology’ are without text, they signify the first episode of IE (not
relapsing or recurrent), ‘definite’ IE (not suspected or possible) and
involvement of a native cardiac valve;
b) intravenous drug abuse.

Examples: Active mitral valve IE due to Enterococcus faecalis;

healed recurrent prosthetic aortic valve endocarditis due to
Staphylococcus epidermidis; suspected culture-negative late
prosthetic mitral valve endocarditis.

Pathophysiology:
– damage of endothelia and formation of micro blood clots;
– colonization of micro thrombus by microorganisms;
– repeated deposit of thrombocytes and fibrin on a surface;
– formation of vegetation;

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 – formation of vegetation on cusp of the valve.

Table 17 – Frequency of revealing aetiology agents of IE in the

USA, Canada and advanced countries of Europe (by
W. М. Sheld, М. А. Sand, 1995)

Activators of disease Frequency of revealing, %

- Streptococcus: Streptococcus 60–80: 30–40, 5–18, 15–25;
viridans, Enterococcus and others
Streptococcus;
- Staphylococcus: St. aureus and 20–35: 10–27, 1–3;
others St.;
- gram-negative bacilli; 13–15;
- HACEK organisms; less than 5;
- fungi; 2–4;
- infection of polymicroorganism 1–2

Consequences: endocarditis has local and systemic

consequences.
Local consequences include:
– formation of myocardial abscesses;
– severe valvular regurgitation may develop suddenly, causing
heart failure and death (usually due to mitral or aortic valve lesions);
– aortitis may result from contiguous spread of infection;
– prosthetic valve infections are particularly likely to involve
valve ring abscesses, obstructing vegetations, myocardial abscesses,
and mycotic aneurysms manifested by valve obstruction, dehiscence,
and conduction disturbances.
Systemic consequences include:
1. Immunological change as cellular and humoral infringements
of immunity and not specific system of protection:
– an oppression of Т-system lymphocytes and hyperactivation of
B-system (high IgМ and IgG titre);
– high autoantibody titre (cryoglobulins, rheumatoid factor, anti-
myocardial antibodies, etc.);
– decrease of the contents compliment;
– formation of circulating immune complexes (CIC).
2. Immunopathological reaction of basal membranes in internal
organs on antibodies and CIC:

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 – glomerulonephritis;
– myocarditis;
– arthritis;
– vasculitis, etc.
3. Occurrence of thromboembolic complication in arterial vessels
of lungs, heart, brain, intestine, spleen, and other organs.
4. The combination of these pathological changes determines a
clinical picture of IE.
Classification
Infective endocarditis may have an indolent, subacute course or a
more acute, fulminant course with greater potential for rapid
decompensation.
– Subacute bacterial endocarditis (SBE), although
aggressive, usually develops insidiously and progresses slowly (i .e.,
over weeks to months). Often, no source of infection or portal of
entry is evident. SBE is caused most commonly by streptococci
(especially viridans, microaerophilic, anaerobic, and
nonenterococcal group D streptococci and enterococci) and less
commonly by S. aureus, Staphylococcus epidermidis, Gemella
morbillorum, Abiotrophia defectiva, Granulicatella sp, and
fastidious Haemophilus sp. SBE often develops on abnormal valves
after asymptomatic bacteraemia due to periodontal, GI, or GU
infections.
– Acute bacterial endocarditis (ABE) usually develops
abruptly and progresses rapidly (i.e., over days). A source of
infection or portal of entry is often evident. When bacteria are
virulent or bacterial exposure is massive, ABE can affect normal
valves. It is usually caused by S. aureus, group A haemolytic
streptococci, pneumococci, or gonococci.
– Prosthetic valvular endocarditis (PVE) develops in 2 to 3%
of patients within 1 yr after valve replacement and in 0.5%/yr
thereafter. It is more common after aortic than after mitral valve
replacement and affects mechanical and bioprosthetic valves equally.
Early-onset infections (< 2 mo after surgery) are caused mainly by
contamination during surgery with antimicrobial-resistant bacteria
(e.g., S. epidermidis, diphtheroids, coliform bacilli, Candida sp,
Aspergillus sp). Late-onset infections are caused mainly by
contamination with low-virulence organisms during surgery or by

125
transient asymptomatic bacteraemias, most often with streptococci;
S. epidermidis; diphtheroids; and the fastidious gram-negative
bacilli, Haemophilus sp, Actinobacillus actinomycetemcomitans, and
Cardiobacterium hominis.
Criteria that should raise suspicion of IE:
1. High clinical suspicion (urgent indication for
echocardiographic screening and possibly hospital admission):
– new valve lesion/(regurgitant) murmur;
– embolic event(s) of unknown origin (esp. cerebral and renal
infarction);
– sepsis of unknown origin;
– haematuria, glomerulonephritis, and suspected renal
infarction;
– “fever” plus: prosthetic material inside the heart, other high
predispositions for IE, newly developed ventricular arrhythmias or
conduction disturbances, first manifestation of CHF, positive BCs (if
the organism identified is typical for NVE/PVE), cutaneous (Osler,
Janeway) or ophthalmic (Roth) manifestations, multifocal/rapid
changing pulmonic infiltrations (right heart IE), peripheral abscesses
(renal, splenic, spine) of unknown origin predisposition and recent
diagnostic/therapeutic interventions known to result in significant
bacteraemia.
2. Low clinical suspicion:
– fever plus none of the above.
Revised Duke clinical diagnostic criteria for IE
Major criteria:
– two positive blood cultures for organisms typical of
endocarditis;
– three positive blood cultures for organisms consistent with
endocarditis;
– serologic evidence of Coxiella burneti;
– echocardiographic evidence of endocardial involvement:
oscillating intracardiac mass on a heart valve, on supporting
structures, in the path of regurgitant jets, or on implanted material
without another anatomic explanation; cardiac abscess; new
dehiscence of prosthetic valve; or new valvular regurgitation.
Minor criteria:
– predisposing heart disorder;

126
 – IV drug abuse;
– fever ≥ 38° C;
– vascular phenomena: arterial embolism, septic pulmonary
embolism, mycotic aneurysm, intracranial haemorrhage, conjunctival
petechiae or Janeway lesions;
– immunologic phenomena: glomerulonephritis, Osler's nodes,
Roth's spots, or rheumatoid factor;
– microbiologic evidence of infection consistent with but not
meeting major criteria;
– serologic evidence of infection with organisms consistent with
endocarditis.
For definite clinical diagnosis: 2 major criteria or 1 major and 3
minor criteria or 5 minor criteria.
For possible clinical diagnosis: 1 major and 1 minor criteria or 3
minor criteria.
For disconfirmation of diagnosis:
Firm alternative diagnosis explaining the findings of infective
endocarditis, resolution of symptoms and signs after antimicrobial
therapy for ≤ 4 days, no pathologic evidence of infective endocarditis
found during surgery or autopsy, or failure to meet the clinical
criteria for possible endocarditis.
Symptoms and signs
SBE. Initially, symptoms are vague: low-grade fever (< 39° C),
night sweats, fatigability, malaise, and weight loss. Chills and
arthralgias may occur. Symptoms and signs of valvular insufficiency
may be the first clue. Initially, ≤ 15% of patients have fever or
murmur, but eventually almost all develop both. Physical
examination may be normal or include pallor, fever, change in a
preexisting murmur or development of a new regurgitant murmur,
and tachycardia.
Retinal emboli can cause round or oval haemorrhagic retinal
lesions with small white centres (Roth's spots). Cutaneous
manifestations include petechiae (on the upper trunk, conjunctivae,
mucous membranes, and distal extremities), painful erythematous
subcutaneous nodules on the tips of digits (Osler's nodes), nontender
haemorrhagic macules on the palms or soles (Janeway lesions), and
splinter haemorrhages under the nails. About 35% of patients have
CNS effects, including transient ischaemic attacks, stroke, toxic

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encephalopathy, and, if a mycotic CNS aneurysm ruptures, brain
abscess and subarachnoid haemorrhage. Renal emboli may cause
flank pain, and, rarely, gross haematuria. Splenic emboli may cause
left upper quadrant pain. Prolonged infection may cause
splenomegaly or clubbing of fingers and toes.
ABE and PVE. Symptoms and signs are similar to those of SBE,
but the course is more rapid. Fever is almost always present initially,
and patients appear toxic; sometimes septic shock develops. Heart
murmur is present initially in about 50 to 80% and eventually in >
90%. Rarely, purulent meningitis occurs.
Right-sided endocarditis. Septic pulmonary emboli may cause
cough, pleuritic chest pain, and sometimes haemoptysis. A murmur
of tricuspid regurgitation is typical.
Palpation and percussion of heart:
1. Conducting in a clinical picture of IE, alongside with fever and
intoxication symptom, are the diseases of heart caused by formation
of heart defect, myocarditis and (sometimes) by defeat of coronary
vessels (embolism, vasculitis).
2. At acute course of IE, sudden break of tendinous ailment of
MV or ТV develops acute LV or RV insufficiency.
3. АV lesion is more often (in 55–65% of the patients), МV
insufficiency is less often (in 15–40% of the patients). Combined АV
and МV defeat comes to light in 13% of cases. Isolated ТV
insufficiency meets in 1–5% of cases, though at narcomaniac this
localization of a defeat (in 45–50% of the patients) prevails.
4. The data palpation and percussion of heart are determined by
localization of an infectious lesion (АV, МV, ТV), and also presence
of an accompanying pathology, on which background IE was
developed.
5. The signs of LV expansion and its hypertrophy are observed in
most cases: displacement to the left of apical push and left border of
relative dullness of heart, amplification of apical push.
Аuscultation of heart:
1. Аuscultation signs of formed heart defect usually begin to be
shown in 2–3 months of the feverish period. At affected АV I and II
heart tones are weaken. Silent diastolic murmur after II tone occurs
in II intercostal to the right sternum and in Botkin point. The murmur
has decrescendo character and will be carried over the apex of the

128
heart. At affected МV there is an easing of I heart tone and rough
systolic murmur occurs on the apex, which will be carried over the
left axillary area.
2. ТV defeat is characterized by systolic murmur TV
insufficiency, which is maximum located in V intercostal to the left
of sternum.
Аrterial pulse and arterial pressure (AP):
1. It is important always to compare auscultation data with the
research of properties of arterial pulse and changes in AP. Diastolic
murmur occurs at formation of АV insufficiency, which associates
with the changes of pulse for a type pulsus celer, altus et magnus,
and also with decrease of diastolic AP and tendency to increase
systolic AP.
2. At MV insufficiency there is a poorly expressed tendency to
decrease systolic and diastolic AP.
Laboratory data
Сlinical blood examination: normochromic anaemia; increase of
erythrocyte sedimentation rate; displacement of leukogram to the
left.
Biochemical blood examination: increase of alanine
aminotranspherase, lactate dehydrogenase, creatine phosphokinase,
α2- and γ-globulin, cialic acid, fibrinogen, seromucoid, haptoglobin,
C-reactive protein, rheumatoid factor.
Immunologic examination: increase of titre of circulating
immune complex, C3 and C4 complements.
Standard blood culture techniques:
1. Three or more blood cultures (BC) should be taken
irrespective of body temperature at least 1 h apart. If the patient has
been on short-term antibiotics, one should wait, if possible, at least
for 3 days after discontinuing of antibiotic treatment before new BCs
are taken. Blood cultures after long-term antibiotic treatment may not
become positive after treatment has been discontinued for 6–7 days.
2. One BC consists of one aerobic and one anaerobic bottle, each
containing approximately 50 ml of medium (less in pediatric BC
bottles). Venous blood, minimally 5 ml and better 10 ml in adults
and 1–5 ml in children should be added to each bottle. Minimum
inhibitory concentrations should be determined for the drugs of
choice.

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 Culture-negative endocarditis (CNE):
1. The most frequent cause of CNE is previous antimicrobial
treatment. If traditional (non-automatic) BC systems are used, longer
incubation periods (> 6 days) are required when organisms of the
HACEK group, Propionibacterium spp., Neisseria spp., Brucella,
Abiotrophia spp., or Campylobacter spp. are suspected. Especially in
CNE all material excised during cardiac surgery for active IE should
also be cultured and examined.
2. The value of serology has been proven for IE due to
Bartonella, Legionella, Chlamydia (immunofluorescence) and
Coxiella burnetii.
3. The use of broad-spectrum polymerase chain reaction (PCR)
provides a significant improvement in the capability to detect
difficult-to-culture organisms and even dead bacteria.

Figure 4 – Algorithm for the use of transthoracic (TTE) and

transoesophageal echocardiography (TEE) in suspected IE. N.B. TTE
“positive” indicates finding of typical IE (e.g., fresh vegetation or abscess
formation)
Echocardiography
Any patient suspected of having NVE by clinical criteria should
be screened by transthoracic echocardiography (TTE). When images

130
are of good quality and prove to be negative and there is only a low
clinical suspicion of IE, endocarditis is unlikely and other diagnoses
are to be considered. If there is high suspicion of IE, TEE should be
performed in all TTE-negative cases, in suspected PVE, and if TTE
is positive but complications are suspected or likely and before
cardiac surgery during active IE. If TEE remains negative and there
is still suspicion, it should be repeated within one week. A repeatedly
negative study should virtually exclude the diagnosis.

Figure 5 – Echocardiographic sings of vegetation on cusp of the MV

a) One-dimensional echocardiogram (circuit);

b) Two-dimensional echocardiogram (fragment);
c) Two-dimensional echocardiogram from apical position of four-
chamber heart
Three echocardiographic findings are considered to be major
criteria in the diagnosis of IE:

131
 1. Mobile, echodense mass attached to the valvular or the mural
endocardium or to implanted prosthetic material.
2. Demonstration of abscesses or fistulas.
3. New dehiscence of a valve prosthesis, especially when
occurring late after implantation.
ECG: decrease of T wave or ST segments, downward T wave,
upward ST segments, atrioventricular block, extrasystole, auricular
fibrillation or flutter.
Treatment

Table 18 – Decision making for antibiotic treatment of native

(NVE) and prosthetic valve endocarditis (PVE) due to
streptococci

Regimen (A) NVE; full susceptibility to penicillin (MIC 0.1mg/l)

Patient, 65 years, normal Penicillin G 12–20 million units/24 h IV,
serum creatinine levels divided into 4–6 doses for 4 weeks plus
gentamicin 3 mg/kg/24 h IV (maximum
240 mg/day), divided into 2–3 doses for
2 weeks
The same conditions as Penicillin G 12–20 million units/24 h IV,
above with uncomplicated divided into 4–6 doses for 2 or 4 weeks
courses and rapid clinical with ambulatory treatment after 7 days
response to therapy treatment in hospital
Patient, 65 years, and/or Penicillin G adapted to renal function for
elevated serum creatinine 4 weeks or ceftriaxone 2 g/24 h IV single
levels or allergy to penicillin dose for 4 weeks
Patients allergic to penicillin Vancomycin 30 mg/kg/24 h IV divided
and cephalosporins into two doses for 4 weeks
Regimen (B) susceptibility to penicillin (MIC 0.1 mg/l–0.5 mg/l) or
PVE
– penicillin G 20–24 million units/24h IV divided into 4–6 doses or
ceftriaxone 2 g/24 h IV as single dose both for 4 weeks plus gentamicin
3 mg/kg/24 h IV, divided into 2–3 doses for 2 weeks, followed by
ceftriaxone 2 g/24 h IV for additional 2 weeks;
– vancomycin as single drug treatment for 4 weeks (dosage see above)
Regimen (C) resistance to penicillin; MIC > 0.5 mg/ld
Table 19 – Decision making for antibiotic treatment of IE due to
staphylococci

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 Regimen (A) native valve endocarditis
Methicillin-susceptible Oxacillin 8–12 g/24 h IV, divided into
S. aureus, no allergy to 3–4 doses for at least 4 weeks plus gentamicin
penicillin 3 mg/kg/24 h IV (maximum 240 mg/day),
divided into 2–3 doses for the first 3–5 days of
treatment
Methicillin-susceptible Vancomycin 30 mg/kg/24 h IV divided into
S. aureus, allergy to two doses for 4–6 weeks, plus gentamicin
penicillin 3 mg/kg/24 h IV (maximum 240 mg/day)
divided into 2–3 doses for the first 3–5 days of
treatment
Methicillin-resistant Vancomycin 30 mg/kg/24 h IV divided into
S. Aureus two doses for 6 weeks
Regimen (B) Endocarditis involving prosthetic material/cardiac
valve prostheses
Methicillin-susceptible Oxacillinb 8–12 g/24 h IV, divided into
S. aureus 3–4 doses plus rifampicin 900 mg/24 h IV
divided into three doses, both for 6–8 weeks,
plus gentamicin 3 mg/kg/24 h IV (maximum
240 mg/day) divided into 2–3 doses for the
first 2 weeks of treatment
Methicillin-resistant S. Vancomycin 30 mg/kg/24 h IV divided into
aureus. Coagulase- two doses for 6 weeks, plus rifampicin
negative staphylo- 900 mg/24 h IV divided into three doses, plus
cocci. In oxacillin- gentamicin 3 mg/kg/24 h IV (maximum
susceptible CONS 240 mg/day) divided into 2–3 doses, all for
vancomycin should be 6–8 weeks
replaced by oxacillin.
For resistant staphylo-
cocci treatment with
oxazolidinone may be
an option but should
be initiated only after
advice from a
reference centre has
been taken.

Table 20 – Decision making for antibiotic treatment of IE due to

enterococci and penicillin-resistant streptococci

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 Penicillin MIC 8 mg/l and for
gentamicin MIC < 500 mg/l
Penicillin-allergic patients with
penicillin/gentamicin
susceptible enterococcal isolates
Penicillin-resistant strains, MIC
> 8 mg/l
Vancomycin-resistant strains
including strains with low
resistance to vancomycin (MIC
4–16 mg/l) or high resistance to
gentamicina
Penicillin G, 16–20 million units in
4–6 divided doses plus gentamicin
3 mg/kg, IV, divided in two doses for
4 weeks
Vancomycin 30 mg/kg/day IV in two
divided doses plus gentamicin
(dosage as above) for 6 weeks
Vancomycin plus gentamicin (dosage
as above) for 6 weeks
Assistance of an experienced
microbiologist is mandatory. If
antimicrobial therapy fails, valve
replacement should be considered
early

Table 21 – Antimicrobial treatment in CNE or if therapy is

urgent and the causative organism unidentified

NVE PVE
Vancomycin 15 mg/kg i.v. every Vancomycin 15 mg/kg i.v. every
12 h 4–6 weeks 12 h 4–6 weeks
+ gentamicin 1.0 mg/kg i.v. every + rifampicin 300–450 mg p.o.
8 h 2 weeks every 8 h 4–6 weeks
+ gentamicin 1.0 mg/kg i.v. every
8 h 2 weeks

Management of complications
Rapid and effective antimicrobial treatment may help to prevent
embolism. If the patient is on long-term oral anticoagulation,
coumarin therapy should be discontinued and replaced by heparin
immediately after the diagnosis of IE has been established.
After embolic complication, the risk for recurrent episodes is
high. After manifestation of cerebral embolism, cardiac surgery to
prevent a recurrent episode is not contraindicated if performed early
(best within 72 h) and cerebral haemorrhage has been excluded by
cranial computed tomography immediately before the operation. If
surgery is not performed early, it is advisable to be postponed for 3–
4 weeks.
Surgery for active NVE

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 The following indications for urgent valve surgery are accepted:
– heart failure due to acute aortic regurgitation;
– heart failure due to acute mitral regurgitation;
– persistent fever and demonstration of bacteraemia for more
than 8 days despite adequate antimicrobial therapy;
– demonstration of abscesses, pseudoaneurysms, abnormal
communications like fistulas or rupture of one or more valves,
conduction disturbances, myocarditis or other findings indicating
local spread (locally uncontrolled infection);
– involvement of microorganisms which are frequently not
cured by antimicrobial therapy (e.g., fungi; Brucella and Coxiella) or
microorganisms which have a high potential for rapid destruction of
cardiac structures (e.g., S. lugdunensis).
If vegetations are larger than 10 mm on the mitral valve or if they
are increasing in size despite antibiotic therapy or if they represent
mitral kissing vegetations, early surgery should also be considered.
The prognosis of right-sided IE is favourable. Surgery is necessary if
tricuspid vegetations are larger than 20 mm after recurrent
pulmonary emboli.
Surgery for active PVE
The following indications are accepted:
– early PVE (less than 12 months after surgery);
– late PVE complicated by prosthesis dysfunction including
significant perivalvular leaks or obstruction, persistent positive blood
cultures, abscess formation, conduction abnormalities, and large
vegetations, particularly if staphylococci are the infecting agents.
Cardiac conditions in which antimicrobial prophylaxis is
indicated:
– prosthetic heart valves;
– complex congenital cyanotic heart diseases;
– previous infective endocarditis;
– surgically constructed systemic or pulmonary conduits;
– acquired valvular heart diseases;
– mitral valve prolapse with valvular regurgitation or severe
valve thickening;
– non-cyanotic congenital heart diseases (except for secundum
type ASD) including bicuspid aortic valves;
– hypertrophic cardiomyopathy.

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 Patient-related noncardiac conditions:
– older age;
– conditions: promoting nonbacterial thrombotic vegetation;
compromising host defence; compromising local non-immune
defence mechanisms; and increased risk/frequency/amount of
bacteraemia are considered patient-related, noncardiac risk
conditions.
Diagnostic and therapeutic interventions likely to produce
bacteraemia: bronchoscopy (rigid instrument), cystoscopy during
urinary tract infection, biopsy of urinary tract/prostate, dental
procedures with the risk of gingival/mucosal trauma, tonsillectomy
and adenoidectomy, instrumentation of obstructed biliary tracts,
oesophageal dilation/sclerotherapy, transurethral resection of
prostate, urethral instrumentation/dilation, lithotripsy, gynaecological
procedures in the presence of infection.
Prophylaxis is not recommended for cardiac catheterization.
Prophylactic antibiotic regimens
Prophylaxis aims primarily at viridans streptococci and HACEK
organisms before dental, oral, respiratory, and oesophageal
procedures, and at enterococci and Streptococcus bovis before
gastrointestinal and genitourinary procedures.
Prognosis
Untreated, infective endocarditis is always fatal. Even with
treatment, death is more likely and the prognosis is generally poorer
for older people and people who have infection with resistant
organisms, an underlying disorder, or a long delay in treatment. The
prognosis is also poorer for people with aortic or multiple valve
involvement, large vegetations, polymicrobial bacteraemia,
prosthetic valve infections, mycotic aneurysms, valve ring abscess,
and major embolic events. The mortality rate for viridans
streptococcal endocarditis without major complications is < 10% but
is virtually 100% for Aspergillus endocarditis after prosthetic valve
surgery.
The prognosis is better with right-sided than left-sided
endocarditis because tricuspid valve dysfunction is tolerated better,
systemic emboli are absent, and right-sided S. aureus endocarditis
responds better to antimicrobial therapy.
Table 22 – Prophylactic antibiotic regimens

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 Dental, oral, respiratory, and oesophageal procedures (Р)
Not allergic to Amoxillin 2.0 g (children 50 mg/kg) p.o.1 h
penicillin before P unable to take oral medication:
amoxicillin or ampicillin 2.0 g (children
50 mg/kg) i.v. – 1 h before P
Allergic to penicillin Clindamycin 600 mg (children 20 mg/kg) or
azithromycin/clarithromycin 500 mg (children
15 mg/kg) 1 h before P
Genitourinary and gastrointestinal procedures (P)
Not allergic to Ampicillin or amoxicillin 2.0 g i.v. plus
penicillin, high-risk gentamicin 1.5 mg/kg i.v. – 1 h before P; 6 h
group later, ampicillinor amoxicillin 1.0 g p.o.
Not allergic to Ampicillin or amoxicillin 2.0 g i.v. (children
penicillin, moderate- 50 mg/kg) – 1 h before P; or amoxicillin 2.0 g
risk group (children 50 mg/kg) p.o. 1 h before P
Allergic to penicillin, Vancomycin 1.0 g (children 20 mg/kg) over
high-risk group 1–2 h before P plus gentamicin 1.5 mg/kg i.v.
or i.m.
Allergic to penicillin, Vancomycin (see above) without gentamicin
moderate-risk group

MYOCARDITIS

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 Myocarditis is an inflammation of myocardium, disease with
infectious or noninfectious aetiology.
Сlassification of myocarditis
According to aetiology:
1. Infectious:
– viral (Coxsackie A, B; influenza A,B, measles, infectious
mononucleosis, hepatitis B and C, chickenpox, cytomegalovirus;
Epstein-Barr virus; acquired immunodeficiency syndrome);
– bacterial (Corynebacterium diphtheriae, Staphylococcus,
Streptococcus β-haemolytic, Mycoplasma pneumoniae, Salmonella,
Meningococcus, Gonococcus, etc.;
– rickettsial (Coxiella burnetii – Q fever; Rickettsia rickettsii –
Rocky mountain spotted fever);
– spirochetal (Borrelia burgdorferi – Lyme disease; recurrent
fever; syphilis; leptospirosis);
– protozoal (Trypanosoma cruzi – Chagas disease; Toxoplasma
gondii);
– methazoal (Trichinellosis; Echinococcosis);
– fungous (Candidiasis; Cryptococcosis).
2. Noninfectious:
a) allergic (immunologic):
– medicament (serum sickness, antibiotics, sulfanilamides,
methyldopa, etc.);
– at system diseases of connective tissue;
– asthma;
– transplantation illness;
– brush.
b) toxic (uremia; radiation; phenothiazines; industrial exposure to
toxic chemicals; cobalt, alcohol, narcotic, etc.).
According to the course:
– acute;
– latent;
– chronic;
– recurring;
According to prevalence:
– focal;
– diffusive;

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 According to form of disease:
– mild (the size of heart is not changed);
– moderate (coming cardiomegaly; HI is not present);
– severe (cardiomegaly, HI, system and lung tromboembolism);
According to clinical displays:
– oligosymptomatic;
– pseudocoronary;
– decompensation;
– arrhythmic;
– pseudovalval;
– thromboembolic;
– mixed.
Clinical and laboratory data
Mild form of disease
Complaints: moderately expressed general weakness, constant
stabbing and aching pain in heart, palpitation and fault in heart, small
dyspnoea at physical activity.
Objective inspection: general state of the patient is satisfactory,
oedema, cyanosis, dyspnoea is not present. Pulse is in norm or a little
accelerated, sometimes it is not rhythmical. Arterial pressure is in
norm. Cardiomegaly is absent, I sound is slightly weakened, low
amplitude systolic murmur is on apex of heart
Laboratory data. Clinical blood examination is in norm or
there is low erythrocyte sedimentation rate (ESR). Biochemical
blood examination: small increase of alanine aminotranspherase,
lactate dehydrogenase, creatine phosphokinase, α2- and γ-globulin,
cialic acid, seromucoid, haptoglobin. Antibodies credits to activators
are increased.
ECG: decrease of T wave or ST segments, increase of PQ
interval.
Roentgenological and echocardiography examination shows
no pathology.
Moderate form of disease
Complaints: expressed weakness, constant stabbing and anginal
pain in heart, palpitation and fault in heart, dyspnoea at rest and
physical activity, subfebrile temperature.
Objective inspection: general state of the patient is of moderate
severity. Acrocyanosis, oedema, and dyspnoea are not present. Rapid

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pulse, not rhythmical. Arterial pressure is in norm. Heart border is
extended to the left, I sound is weakened, systolic heart murmur,
sometimes friction rub.
Laboratory data. Clinical blood examination: increase of
erythrocyte sedimentation rate (ESR), displacement of leukogram to
the left, at virus myocarditis – leukopenia. Biochemical blood
examination: increase of alanine aminotranspherase, lactate
dehydrogenase, creatine phosphokinase, α2- and γ-globulin, cialic
acid, seromucoid, haptoglobin, C-reactive protein. Immunologic
examination: ↑ antibody titre to myocardium, detection of
antibodies to myosin, actin, myolemma
ECG: decrease of T wave or ST segments, downward T wave,
upward ST segments, atrioventricular block, extrasystole, auricular
fibrillation or flutter.
Roentgenological and echocardiography examination shows
cardiac dilatation and increase of the heart chamber.
Severe form of disease
Complaints: dyspnoea at rest and physical activity, tachycardia,
cardiac arrhythmia, and pain in heart, pain in the right
hypochondrium, oedema on legs, cough.
Objective inspection: general state of the patient is severe.
Acrocyanosis. Forced patient’s position, orthopnoea, oedema on
legs, dyspnoea. Swift pulse, weak pulse, not rhythmic pulse. Arterial
pressure is low. Cardiomegaly heart sound is quiet, “gallop” rhythm,
systolic heart murmur, friction rub.
Auscultation of lungs: pulmonary congestion and crepitation as
a symptom of acute LV insufficiency.
Increase of the liver, oedema, ascites. There is occurrence of
tricuspid heart disease and tromboembolic complications at
expressed cardiomegaly.
Laboratory data. Clinical blood examination: increase of
erythrocyte sedimentation rate (ESR), displacement of leukogram to
the left, at virus myocarditis – leukopenia. Biochemical blood
examination: increase of alanine aminotranspherase, lactate
dehydrogenase, creatine phosphokinase, α2- and γ-globulin, cialic
acid, seromucoid, haptoglobin, C-reactive protein. Immunologic
examination: ↑ antibody titre to myocardium, detection of
antibodies to myosin, actin, myolemma.

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 ECG: decrease of T wave or ST segments, downward T wave,
upward ST segments, atrioventricular and intraventricular blocks,
extrasystole, auricular fibrillation or flutter.
Roentgenological and echocardiography examination shows
cardiac dilatation and increase of the heart chamber.
Auscultation of heart
Weakening of the I and II heart sound, sometimes quiet and
inaudible heart sounds. Protodiastolic “gallop” rhythm testifies
decrease of systolic LV function. Cardiac arrhythmia.
Systolic murmur at myocarditis is caused by the defeat of
papillary muscles or by expansion of fibrous ring of mitral valve
with development of mitral valve incompetence. The dilatation of
right ventricle promotes occurrence of pulmonary artery stenosis,
then systolic murmur in II-III intercostal to the left of sternum arises.
Diastolic murmur auscultation at the patients expressed dilatation
of LV, that promotes formation of left atrioventricular aperture.

Figure 6 – Example of ECG: the amplitude of ECG waves is reduced,

splitting of the I sound and occurrence of pathological III sound. The short
systolic murmur, which has arisen in result of dysfunction of valvular
apparatus.

Complications: cardiac arrhythmia (extrasystole, paroxysmal

tachycardia, ventricular tachycardia, atrial fibrillation, etc.); heart
block (intraventricular and intra-auricular blocks); intraventricular
thrombosis and thromboembolis; sudden heart death.
Diagnosis
ECG: the changes of processes repolarization of ventricles are
most constantly registered: upward or depression of ST segments,
downward T wave.
Heart block: intraventricular and atrioventricular block (AV
block) of II degree (tape of Mobitz II).
Cardiac arrhythmia: extrasystole, auricular fibrillation or flutter,
paroxysmal ventricular and atrial tachycardia, ventricular fibrillation.

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 QRS complex changes: low amplitude of R waves, pathological
Q waves.
Roentgenological investigation
Cardiomegaly signs:
– increase of the cross size of the cardiac shadow up to 15.5 cm
and more in men and up to 14.5 cm and more in women;
– increase of cardiothorax index (relation of the cross size of the
heart shadow to internal cross size of thorax) up to 50% and more;
– roentgenological signs of heart chambers dilatation on the
background of effective treatment considerably decrease or disappear
absolutely.
Endomyocardial biopsy (Dallas criterion (USA, 1986))
The detection in biopsy of two morphological signs is considered
necessary and sufficient:
1) inflammatory cellular infiltrate;
2) necrosis or damage of cardiomyocytes.
At virus myocarditis lymphocytes prevail in infiltrate, at bacterial
myocarditis – neutrophiles, at allergic – eosinophiles. Gigantocytes
infiltrate is characteristic for myocarditis of the most severe course
with lethal outcome.
In real clinical conditions the indication for lifetime
endomyocardial biopsy can be served by the most severe course of
disease, refractory to medicament therapy, when there is a problem
of differential diagnosis between severe diffusive myocarditis and
dilatation cardiomyopathy (DCM) and the problem of heart
transplantation is solved.
Diagnostic criteria. The recommendations (New York Heart
Association – NYHA).
Major criteria
Combination of eatiological factors with occurrence of
symptoms:
1. Cardiomegaly.
2. Cardiac insufficiency.
3. Cardiogenic shock.
4. Morgani-Adams-Stokes syndrome.
5. Pathological changes of ECG.
6. Increase of cardiospecific ferments activity: creatine
phosphokinase, lactate dehydrogenase, increase of antibody titre to

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myocardium, detection of antibodies to myosin, actin, myolemma,
troponins.
Minor criteria
1. Laboratory confirmation of the transmitted infection (e.g.,
high credits of antiviral antibodies).
2. Weakening of the heart sound.
3. Protodiastolic “gallop” rhythm.
Myocarditis is diagnosed on the basis of presence of
chronological combination of signs of the transmitted infection
(allergy, toxic, etc.):
– with two “large” criteria myocarditis;
– with one “large” + two “small” criteria.
Idiopathic Abramov-Fiedler myocarditis (AFM)
The most severe form is nonrheumatic myocarditis of unknown
aetiology, which proceeds with expressed diffusion with defeats of
heart muscle.
Clinical symptoms of AFM
– expressed HF;
– expressed cardiomegaly;
– arterial pressure is low;
– intraventricular thrombosis and thromboembolis;
– ECG: decrease of T wave or ST segments, downward T wave,
upward ST segments, pathological Q waves, arrhythmia and blocks.
Мorphologic signs of AFM
– myocardial hypertrophy, especially papillary muscle,
subendomyocardial layers of myocardium;
– presence of the large myolysis fields with replacement of
muscle with fibrous tissue;
– presence of intracavitary thrombus;
– presence of vasculitis of coronary arteries fine vessels;
– inflammatory cellular infiltrate on a course of vessels.
Laboratory, roentgenological, and echocardiographic data of
idiopathic AFM correspond to severe form of myocarditis.
Treatment of myocarditis
Medical programme:
– correction of haemodynamic infringements;
– therapy of the basic disease;
– correction of immune status and immunopathologic reactions;

143
 – treatment and preventive maintenance of infringements of the
cordial rhythm and conductivity;
– treatment and prevention of thromboembolic complications.
1. Treatment of HF:
– restriction of physical activity;
– restriction of salt consumption up to 2–3 gr per day;
– restriction of liquid consumption up to 1.0–1.2 l per day (but is
not less 0.8 l per day);
– prescription of potassium and magnesium in a diet.
Pharmacologic therapy:
– diuretics;
– ACE inhibitors;
– beta blockers;
– digitalis;
– spironolactone, etc.
2. Anti-inflammatory therapy:
Aminochinolinae group (delagil, rezochin, chlorochin)
0.25–0.5 gr per day. The application of placvenil (0.4 gr per day) is
possible. These preparations apply to treatment of myocarditis during
6–9 months, and at recurring course – up to 1 year.
Acetylsalicylic acid – in a doze up to 3 gr per day within
4–5 weeks.
Indometacin – in a doze 75–100 gr per day within 4–6 weeks.
Movalis, diclofenac (voltaren)
Pyrazolinae derivatives (butadionum, brufen, ibuprofenum) are
poorly effective.
Antibacterial therapy is shown only in case of widespread of
bacterial infection, on the background of which myocarditis
develops. Efficiency of application of antiviral preparations at viral
myocarditis is studied now.
3. Glucocorticoid. Indications for prescription at myocarditis:
– at acute course with the expressed allergic component or
immunology by infringements;
– long and recurring course;
– at myocarditis, accompanying pericarditis;
– expressed painful syndrome at severe gigantocellular
myocarditis, and also in the patients with acquired
immunodeficiency syndrome.

144
 In these cases prednisolonum is nominated usually in a doze of
0.4–0.75 mg/kg of body weight per day. The duration of reception is
1.5–2 months with gradual decrease of a doze and cancellation of a
preparation.
4. Heparinum:
Nominate at the severe forms of myocarditis subcutaneously with
the expressed clinical and laboratory activity. In a doze
5000–10 000 IM 4 times per day for 7 days. Then reduce dosage,
continuing injections up to 10–14 days. In subsequent nominate
indirect anticoagulant or antiaggregant.
5. Metabolic preparations.
Myocarditis prognosis
– recovery with absence of changes on ECG;
– recovery with presence of changes on ECG;
– progressing decrease of systole function of heart and
transformation in dilated cardiomyopathy.

CARDIOMYOPATHY

145
 Dilated Cardiomyopathy (DCM)

DCM is myocardial dysfunction producing heart failure in which

ventricular dilation and systolic dysfunction predominate. Symptoms
include dyspnoea, fatigue, and peripheral oedema. Diagnosis is
clinical and by chest X-ray and echocardiography. Treatment is
directed at the cause; heart transplantation may be needed.

Aetiology of DCM (acute or chronic)

– chronic diffuse myocardial ischaemia (coronary artery
disease);
– infections (acute or chronic): bacteria, spirochetes, rickettsia,
viruses (including HIV), fungi, protozoa, helminths;
– granulomatous diseases: sarcoidosis, granulomatous or giant
cell myocarditis, Wegener's granulomatosis;
– metabolic disorders: nutritional disorders (beriberi, selenium
deficiency, carnitine deficiency, kwashiorkor), familial storage
disorders, uremia, hypokalemia, hypomagnesemia, hyperthyroidism,
hypothyroidism, hypophosphatemia, diabetes mellitus, acromegaly,
pheochromocytoma, morbid obesity;
– drugs and toxins: ethanol, cocaine, anthracyclines, cobalt,
psychotherapeutic drugs (tricyclic and quadricyclic antidepressants,
phenothiazine), catecholamines, cyclophosphamide, radiation;
– tumours;
– connective tissue disorders;
– isolated familial (mendelian dominant);
– hereditary neuromuscular and neurologic disorders
(Friedreich's ataxia);
– pregnancy (peripartum period).
In some patients, DCM is believed to start with acute myocarditis
(probably viral in most cases), followed by a variable latent phase, a
phase with diffuse necrosis of myocardial myocytes (due to an
autoimmune reaction to virus-altered myocytes), and chronic
fibrosis. Regardless of the cause, the remaining myocardium dilates,
thins, and hypertrophies in compensation, often leading to functional
mitral or tricuspid regurgitation and atrial dilation. The disorder

146
affects both ventricles in most patients, only the left ventricle (LV) in
a few, and only the right ventricle (RV) rarely.
Pathophysiology:
– systolic dysfunction.
Clinical examination:
– LV and RV failure;
– cardiomegaly;
– functional AV valve regurgitation of the 3rd heart sound and
4th heart sound.
ECG: nonspecific ST- and T-wave abnormalities; Q waves ±
BBB.
Echocardiography: dilated hypokinetic ventricles ± mural
thrombus. Low EF.
X-ray: cardiomegaly. Pulmonary venous congestion.
Haemodynamics: normal or high EDP, low EF, diffusely dilated
hypokinetic ventricles ± AV valve regurgitation. Low CO.
Prognosis: 70% patients with DCM 5-yr mortality.

Figure 7 – Heart systolic and diastolic dysfunction

Treatment

147
 Diuretics, ACE inhibitors, angiotensin II receptor blockers,
β-blockers, spironolactone or eplerenone (inspra), internal
cardioverter-defibrillator, biventricular pacing, inotropic drugs,
anticoagulants.

Hypertrophic Cardiomyopathy (HCM)

HCM is a complex and relatively common genetic cardiac

disorder (about 1:500 in the general adult population) that has been
the subject of intense scrutiny and investigation for over 40 years.
HCM affects men and women equally and occurs in many races and
countries, although it appears to be under-diagnosed in women,
minorities, and under-served populations. HCM is a particularly
common cause of sudden cardiac death in young people
(including trained athletes) and may cause death and disability in
patients of all ages, although it is also frequently compatible with
normal longevity.
Hypertrophic cardiomyopathy is a congenital or acquired disorder
characterized by marked ventricular hypertrophy with diastolic
dysfunction but without increased afterload (valvular aortic stenosis,
coarctation of aorta, systemic hypertension). Symptoms include chest
pain, dyspnoea, syncope, and sudden death. A systolic murmur,
increased by Valsalva maneuver, is typically present in the
hypertrophic obstructive type. Diagnosis is by echocardiography.
Treatment is with β-blockers, verapamil, disopyramide, and
sometimes chemical reduction or surgical removal of outflow tract
obstruction.
Aetiology and pathophysiology of HCM
Autosomal dominant inheritance, pheochromocytoma,
acromegaly, neurofibromatosis.
Pathophysiology: diastolic dysfunction ± outflow obstruction.
Clinical examination: angina, exertional dyspnoea, syncope,
sudden death; ejection ± mitral regurgitation murmurs S 4; Bifid
carotid pulse with a brisk upstroke and rapid downstroke.
ECG: LV hypertrophy and ischaemia; deep septal Q waves.
Echocardiography: hypertrophied ventricle ± mitral systolic
anterior motion ± asymmetric hypertrophy ± LV gradient.
X-ray: no cardiomegaly.

148
 Haemodynamics: high EDP (end-diastolic pressure), high EF ±
outflow subvalvular gradient ± mitral regurgitation. Normal or low
CO.
Prognosis: 4% patients with HCM 1-yr mortality.
Treatment
Reduced contractility with β-blockers ± verapamil, ±
disopyramide, ± septal myotomy, ± catheter alcohol ablation; AV
pacing.

Figure 8 – Clinical presentation and treatment strategies for patient

subgroups within the broad clinical spectrum of hypertrophic
cardiomyopathy (HCM)

Note: AF – atrial fibrillation; DDD – dual-chamber; ICD – implantable

cardioverter-defibrillator; SD – sudden death.
Risk factors for sudden death in HCM
Major: cardiac arrest (ventricular fibrillation); spontaneous

149
sustained ventricular tachycardia; family history of premature sudden
death; unexplained syncope; LV thickness greater than or equal to
30 mm; abnormal exercise blood pressure; nonsustained ventricular
tachycardia (Holter).
Possible in individual patients: atrial fibrillation; myocardial
ischaemia; LV outflow obstruction; high-risk mutation; intense
(competitive) physical exertion.

Restrictive Cardiomyopathy (RCM)

RCM is characterized by noncompliant ventricular walls that

resist diastolic filling; one or both ventricles, most commonly the
left, may be affected. Symptoms include fatigue and exertional
dyspnoea. Diagnosis is by echocardiography. Treatment is often
unsatisfactory and is best directed at the cause. Surgery is sometimes
useful.

Aetiology and pathophysiology of RCM

Amyloidosis, diffuse systemic sclerosis, fibroelastosis,
endocardial fibrosis, Fabry's disease, Gaucher's disease,
haemochromatosis, Löffler's syndrome, sarcoidosis, hypereosinophilia
syndrome, tumours.
Pathophysiology: diastolic dysfunction.
Clinical examination: exertional dyspnoea and fatigue LV ± RV
failure; functional AV valve regurgitation.
ECG: LV hypertrophy or low voltage.
Echocardiography: increased wall thickness ± cavity
obliteration LV diastolic dysfunction asymmetry.
X-ray: no or mild cardiomegaly.
Hemodynamics: high EDP, dip and plateau diastolic LV pressure
curve; normal or low CO.
Prognosis: 70% patients with RCM 5-yr mortality.
Treatment
– phlebotomy for haemochromatosis;
– endocardial resection;
– hydroxyurea for hypereosinophilia.
Table 23 – Diagnostic criteria for arrhythmogenic right
ventricular cardiomyopathy (ARVC)

150
 Major criterion
Severe dilation and reduction of
right ventricular ejection fraction
with no (or only mild) left
ventricular impairment
Localized right ventricular
aneurysms (akinetic or dyskinetic
areas with diastolic bulging)
Severe segmental dilation of the
right ventricle; fibrofatty
replacement of myocardium on
endomyocardial biopsy
Epsilon waves or localized
prolongation (> 110 ms) of the
QRS complex in right precordial
leads (V1–V3)
Familial disease confirmed at
necropsy or surgery
PERICARDITIS
Minor criterion
Mild global right ventricular
dilation and/or ejection fraction
reduction with normal LV
Mild segmental dilation of the right
ventricle
Regional right ventricular
hypokinesia, inverted T waves in
right precordial leads (V2 and V3)
(people older than 12 years of age;
in the absence of right bundle
branch block)
Late potentials (signal averaged
electrocardiogram)
Left bundle branch block type
ventricular tachycardia (sustained
and nonsustained) (electro-
cardiogram, Holter monitor,
exercise testing); frequent
ventricular extrasystoles (> 1000/
24 h) on Holter monitor; familial
history of premature sudden death
(< 35 years of age) due to suspected
ARVC; familial history (clinical
diagnosis based on present criteria)
151
 Pericarditis (pericardial syndromes) is inflammation of the
pericardium, often with fluid accumulation. Pericarditis may be
caused by many disorders but is often idiopathic.
In progressive human immunodeficiency virus (HIV) the
incidence of echocardiographically detected pericardial effusion is up
to 40%. Purulent pericarditis in adults is rare, but always fatal if
untreated. Mortality rate in treated patients is 40%, mostly due to
cardiac tamponade, toxicity, and constriction. In the last decade TBC
pericarditis in the developed countries has been primarily seen in
immunocompromised patients (AIDS). The mortality rate in
untreated acute effusive TBC pericarditis approaches 85%.
Pericardial constriction occurs in 30–50%.
Blunt chest trauma is the major risk of car accidence. The
deceleration force can lead to myocardial contusion with
intrapericardial haemorrhage, cardiac rupture, pericardial rupture, or
herniation. Transoesophageal echocardiography in the emergency
room or immediate computed tomography should be performed.
Pericardial laceration and partial extrusion of the heart into the
mediastinum and pleural space may also occur after injury.
In dissection of the ascending aorta (pericardial effusion can be
found in 17–45% of the patients and in 48% of the autopsy cases. In
a clinical series of aortic dissection, pericardial tamponade was found
by CT, MRI, or echocardiography in 17–33% of patients with type I
dissection and 18–45% in type II dissection and 6% in type III
dissection.
Pericardial constriction may happen in up to 20% of patients with
radiation-induced pericarditis, requiring pericardiectomy. The
operative mortality is high (21%) and the postoperative five years
survival rate is very low (1%) mostly due to myocardial fibrosis.
Classifications
According to aetiology of the causative agent:
1. Infectious:
– viral (Coxsackie A9, B1-4, Echo 8, mumps, EBV, CMV,
varicella, rubella, HIV, parvo B19...). Incidence is 30–50%1;
– bacterial (pneumo-, meningo-, gonococcosis, haemophilus,
treponema pallidum, borreliosis, chlamydia, tuberculosis...).
Incidence is 5–10%1;
– fungal (candida, histoplasma...) – rare1;

152
 – parasitary ( entameba histolytica, echinococcus, toxoplasma...)
– rare1.
2. Pericarditis in systemic autoimmune diseases
Systemic lupus erythematosus – incidence is 30%2; rheumatoid
arthritis – 30%2; spondylitis ankylosans – 1%2; systemic sclerosis –
> 50%2; dermatomyositis – rare2; periarteritis nodosa – rare2; Reiter’s
syndrome – 2%; familial mediterranean fever – 0.7%2.
3. Type 2 (auto)immune process
Rheumatic fever – incidence is 20–50%2; postcardiotomy
syndrome – 20%2 (10–14 days after surgery); postmyocardial
infarction syndrome – 1–5%2; autoreactive (chronic) pericarditis –
23.1%2.
4. Pericarditis and pericardial effusion in diseases of
surrounding organs
Acute MI (P. Epistenocardica) – incidence is 5–20%2 (1–5 days
after transmural MI); myocarditis – 30%2; paraneoplastic pericarditis
– frequent2; aortic aneurysm – rare2; lung infarction – rare2
pneumonia – rare2; oesophageal diseases – rare2; hydropericardium
in CHF – rare2.
5. Pericarditis in metabolic disorders
Renal insufficiency (uraemia) – frequent2; myxedema – 30%2;
Addison’s disease – rare2; diabetic ketoacidosis – rare2; cholesterol
pericarditis – very rare2.
6. Pregnancy – rare
7. Traumatic pericarditis
Direct injury (penetrating thoracic injury, oesophageal
perforation, foreign bodies) – rare2; indirect injury (nonpenetrating
thoracic injury, mediastinal irradiation) – rare.
8. Neoplastic pericardial disease – 35%1
Primary tumours – rare2; secondary metastatic tumours –
frequent2.
9. Idiopathic – 3.5 – 50%1
10. Congenital defects of the pericardium (congenital defects
of the pericardium (1/10.000 autopsies)):
– comprise partial left (70%2);
– right (17%2);
– total bilateral (extremely rare2) pericardial absence.
Note:

153
 1
- Marburg pericarditis registry 1988–2001;
2
- percentage related to the incidence of pericarditis in the specific
population of patients.
Clinical-morphological classification
1. Acute pericarditis:
a) dry;
b) fibrinous;
c) effusive:
– with cardiac tamponade;
– without cardiac tamponade.
2. Chronic pericardial (inflammation (> 3 months)):
– effusive;
– adhesive;
– constrictive forms.
3. Recurrent pericarditis:
– intermittent type (widely varying symptom-free interval
without therapy);
– incessant type (discontinuation of anti-inflammatory therapy
always ensures a relapse).
Acute pericarditis
Acute pericarditis is either dry, fibrinous or effusive, independent
from its aetiology. A prodrome of fever (usually < 39 ºC), malaise,
and myalgia is common, but elderly patients may not be febrile.
Major symptoms are retrosternal or left precordial chest pain
(radiates to the trapezius ridge, can be pleuritic or simulate
ischaemia, and varies with posture), nonproductive cough, and
shortness of breath.
Auscultation: pericardial rub (mono-, bi-, or triphasic).
ECG:
Stage I: anterior and inferior concave ST segment elevation. PR
segment deviations opposite to P polarity.
Early stage II: ST junctions return to the baseline, PR deviated.
Late stage II: T waves progressively flatten and invert.
Stage III: generalized T wave inversions.
Stage IV: ECG returns to prepericarditis state.
Typical lead involvement: I, II, aVL, aVF, and V3-V6. The ST
segment is always depressed in VR, frequently in V1, and
occasionally in V2.

154
 Echocardiography: effusion types B-D (Horowitz); signs of
tamponade.
Blood analysis:
– ↑ ESR, CRP, LDH, leukocytes (inflammation markers);
– troponin I, CK-MB (markers of myocardial lesion).
Chest X-ray: ranging from normal to “water bottle” heart
shadow. Revealing additional pulmonary/mediastinal pathology.
Pericardiocentesis and drainage (mandatory in tamponade
(indication class I), optional in large/recurrent effusions or if
previous tests inconclusive (indication class IIa) in small effusions
(indication class IIb)): PCR and histochemistry for aetiopathogenetic
classification of infection or neoplasia.

Type A: no effusion.
Type B: separation of epicardium
and peri-cardium (3–16 ml).
Type C 1: systolic and diastolic
separation of epicardium and
pericardium (small effusion > 16 ml).
Type C 2: systolic and diastolic
separation of epicardium and
pericardium with attenuated
pericardial motion.
Type D: pronounced separation of
epicardium and pericardium with
large echo-free space.
Type E: pericardial thickening
(> 4 mm)

Figure 9 – Horowitz classification of pericardial effusions (Copyrights

American Heart Association)

Optional or if previous tests are inconclusive (IIa):

– CT – effusions, peri-, and epicardium;
– MRI – effusions, peri-, and epicardium;
– pericardioscopy, pericardial biopsy – establishing the specific
aetiology.
Treatment

155
 Hospitalization is warranted for most patients to determine the
aetiology, observe for tamponade, and start anti-inflammatory and
symptomatic treatment.
1. Specific therapy depending on the aetiology factor.
2. Nonsteroidal anti-inflammatory drugs (NSAID)(IB):
– ibuprofen is preferred for its rare side effects, favourable effect
on the coronary flow and the large dose range.
– ibuprofen 300–800 mg every 6–8 h may be initially required
and can be continued for days or weeks, best until the effusion has
disappeared.
– gastrointestinal protection must be provided in all patients.
3. Colchicine (0.5 mg bid) (IIa, B).
4. Systemic corticosteroid therapy should be restricted to connective
tissue diseases, autoreactive or uremic pericarditis (IIa, B).
Pericardiocentesis
Indication:
– pericardiocentesis is life saving in cardiac tamponade (IB);
– in effusions > 20 mm in echocardiography in diastole or for
diagnostic purposes.
Contraindication:
– aortic dissection;
– relative contraindications include uncorrected coagulopathy,
anticoagulant therapy, thrombocytopenia < 50,000/mm³, small,
posterior, and loculated effusions;
– pericardiocentesis in acute traumatic haemopericardium and
purulent pericarditis is probably less appropriate than surgical
drainage.
Pericardiocentesis guided by fluoroscopy is performed in the
cardiac catheterisation laboratory with ECG monitoring. Direct ECG
monitoring from the puncturing needle is not an adequate safeguard.
Right-heart catheterisation can be performed simultaneously, allowing
exclusion of constriction. It is prudent to drain the fluid in < 1 steps
to avoid the acute right-ventricular dilatation. The subxiphoid
approach has been used most commonly, with a long needle with a
mandrel (Tuohy or thin-walled 18-gauge) directed towards the left
shoulder at a 30° angle to the skin. This route is extrapleural and
avoids the coronary, pericardial, and internal mammary arteries.

156
 Echocardiographic guidance of pericardiocentesis is technically
less demanding and can be performed at the bedside.
Echocardiography should identify the shortest route where the
pericardium can be entered intercostally (usually in the sixth or
seventh rib space in the anterior axillary line). Prolonged pericardial
drainage is performed until the volume of effusion obtained by
intermittent pericardial aspiration (every 4–6 h) fall to < 25 ml per
day. The feasibility is high (93%) in patients with anterior effusion
≥ 10 mm while the rate of success is only 58% with small,
posteriorly located effusions.
Complications of pericardiocentesis are:
– laceration and perforation of the myocardium and the coronary
vessels;
– air embolism, pneumothorax, arrhythmias (usually vasovagal
bradycardia), and puncture of the peritoneal cavity or abdominal
viscera;
– internal mammary artery fistulas, acute pulmonary oedema,
and purulent pericarditis were rarely reported.
Chronic pericarditis
Chronic (> 3 months) pericarditis includes effusive (inflammatory
or hydropericardium in heart failure), adhesive, and constrictive
forms.
Symptoms are usually mild (chest pain, palpitations, fatigue),
related to the degree of cardiac compression and pericardial
inflammation. The diagnostic algorithm is similar as in acute
pericarditis. The detection of the curable causes (e.g., tuberculosis,
toxoplasmosis, myxedema, autoimmune, and systemic diseases)
allows successful specific therapy.
Symptomatic treatment and indications for pericardiocentesis are
as in acute pericarditis. For frequent and symptomatic recurrences
balloon pericardiotomy or pericardiectomy should be considered
(IIb, nB).
Recurrent pericarditis
The term “recurrent pericarditis” encompasses:
– intermittent type (symptom – free intervals without therapy);
– incessant type (discontinuation of anti-inflammatory therapy
ensures a relapse). Massive pericardial effusion, overt tamponade or
constriction are rare.

157
 Evidence for an immunopathological process include:
– latent period lasting for months;
– presence of antiheart antibodies;
– quick response to steroid treatment and the similarity and co-
existence of recurrent pericarditis with other autoimmune conditions
(lupus, serum sickness, polyserositis, postpericardiotomy/
postmyocardial infarction syndrome, celiac disease, dermatitis
herpetiformis, frequent arthralgias, eosinophilia, allergic drug
reaction, and history of allergy);
– genetic disorders were also reported: autosomal dominant
inheritance with incomplete penetrance and sex-linked inheritance
(recurrent pericarditis associated with ocular hypertension).
Symptomatic management relies on exercise restriction and the
regimen used in acute pericarditis. The colchicine – recommended
dose is 2 mg/day for one or two days, followed by 1 mg/day (I, B).
Corticosteroids should be used only in patients with poor general
condition or in frequent crises (IIa, C). The recommended regimen is:
prednisone 1–1.5 mg/kg, for at least one month. If patients do
not respond adequately, azathioprine (75–100 mg/day) or
cyclophosphamide can be added. Corticoids should be tapered over a
three-month period. If symptoms still recur, return to the last dose
that suppressed the manifestations, maintain that dose for 2–3 weeks
and then recommence tapering. Towards the end of the taper,
introduce anti-inflammatory treatment with colchicine or NSAID.
Renewed treatment should continue for at least three months.
Pericardiectomy is indicated only in frequent and highly
symptomatic recurrences resistant to medical treatment (Iia, B).
Before pericardiectomy, the patient should be on a steroid-free
regimen for several weeks.
Pericardial effusion and cardiac tamponade
Pericardial effusion may appear as transudate (hydropericardium),
exudate, pyopericardium or haemopericardium.
Large effusions are common with neoplastic, tuberculous,
cholesterol, uremic pericarditis, myxedema, and parasitoses. Effusions
that develop slowly can be remarkably asymptomatic, while rapidly
accumulating smaller effusions can present with tamponade.
Loculated effusions are more common when scarring has
supervened (e.g., postsurgical, posttrauma, purulent pericarditis).

158
 Massive chronic pericardial effusions are rare (2–3.5% of all
large effusions).
Cardiac tamponade is the decompensated phase of cardiac
compression caused by effusion accumulation and the increased
intrapericardial pressure. In “surgical” tamponade intrapericardial
pressure is rising rapidly, in the matter of minutes to hours (i.e.,
haemorrhage), whereas a low-intensity inflammatory process is
developing days to weeks before cardiac compression occurs
(“medical” tamponade).
Clinical presentation: orthopnoea, cough and dysphagia,
occasionally with episodes of unconsciousness can be observed.
Elevated systemic venous pressure, hypotension, pulsus paradoxus,
tachycardia, dyspnoea or tachypnoea with clear lungs. Insidiously
developing tamponade may present with the signs of its
complications (renal failure, abdominal plethora, shock liver and
mesenteric ischaemia). Heart sounds are distant.
Determination of pulsus paradoxus
Pulsus paradoxus is defined as a drop in systolic blood pressure
> 10 mmHg during inspiration whereas diastolic blood pressure
remains unchanged. It is easily detected by feeling the pulse. During
inspiration, the pulse may disappear or its volume diminishes
significantly. Clinically significant pulsus paradoxus is apparent
when the patient is breathing normally. When present only in deep
inspiration it should be interpreted with caution. The magnitude of
pulsus paradoxus is evaluated by sphygmomanometry. If the pulsus
paradoxus is present, the first Korotkoff sound is heard only during
expiration. The blood pressure cuff is therefore inflated above the
patient's systolic pressure. During deflation, the first Korotkoff
sound is intermittent. Correlation with the patient's respiratory cycle
identifies a point at which the sound is audible during expiration, but
disappears in inspiration. As the cuff pressure drops, another point is
reached when the first blood pressure sound is audible throughout
the respiratory cycle. The difference is the measure of pulsus
paradoxus.
Electrocardiography may demonstrate diminished QRS and
T-wave voltages, PR-segment depression, ST-T changes, bundle
branch block, and electrical alternans (rarely seen in the absence of
tamponade).

159
 In chest radiography: enlarged cardiac silhouette with clear
lungs. The separation of pericardial layers can be detected in
echocardiography, when the pericardial fluid exceeds 15–35 ml.
The size of effusions can be graded as:
1. small (echo-free space in diastole < 10 mm);
2. moderate (10–20 mm);
3. large (≥ 20 mm);
4. very large (≥ 20 mm and compression of the heart).
At the M mode/2D echocardiogram: diastolic collapse of the
anterior RV free wall, RA collapse, LA and very rarely LV collapse,
increased LV diastolic wall thickness “pseudohypertrophy”, VCI
dilatation (no collapse in inspirium), “swinging heart”.
Doppler:
1. Tricuspid flow increases and mitral flow decreases during
inspiration (reverse in expiration).
2. Systolic and diastolic flows are reduced in systemic veins in
expirium and reverse flow with atrial contraction is increased.
Cardiac catheterisation:
1. Confirmation of the diagnosis and quantification of the
haemodynamic compromise; RA pressure is elevated (preserved
systolic x descent and absent or diminished diastolic y descent);
intrapericardial pressure is also elevated and virtually identical to RA
pressure (both pressures fall in inspiration); RV mid-diastolic
pressure elevated and equal to the RA and pericardial pressures (no
dip-and-plateau configuration); pulmonary artery diastolic pressure
is slightly elevated and may correspond to the RV pressure;
pulmonary capillary wedge pressure is also elevated and nearly equal
to intrapericardial and right atrial pressure; LV systolic and aortic
pressures may be normal or reduced.
2. Documenting that pericardial aspiration is followed by
haemodynamic improvement.
3. Detection of the coexisting haemodynamic abnormalities (LV
failure, constriction, pulmonary hypertension).
4. Detection of associated cardiovascular diseases
(cardiomyopathy, coronary artery disease).
RV/LV angiography: atrial collapse and small hyperactive
ventricular chambers.
Coronary angiography: coronary compression in diastole.

160
 Computer tomography: no visualisation of subepicardial fat
along both ventricles, which show tube-like configuration and
anteriorly drawn atrias.
Treatment
Pericardiocentesis is not necessary when the diagnosis can be
made otherwise or the effusions are small or resolving under anti-
inflammatory treatment. Haemodynamic compromise and cardiac
tamponade is an absolute indication for drainage. Treatment should
be aimed at the underlying aetiology. Even in idiopathic effusions
extended pericardial catheter drainage (3±2 days, range 1–13 days)
was associated with a lower recurrence rates (6% vs. 23%) than in
those without catheter drainage during the follow-up of 3.8±4.3 years.
Resistant neoplastic processes require intrapericardial treatment,
percutaneous balloon pericardiotomy or rarely pericardiectomy.
Surgical approach is recommended only in patients with very large
chronic effusion in whom repeated pericardiocentesis and/or
intrapericardial therapy were not successful.
Constrictive pericarditis
Constrictive pericarditis is a rare but severely disabling
consequence of the chronic inflammation of the pericardium, leading
to an impaired filling of the ventricles and reduced ventricular
function. Until recently, increased pericardial thickness has been
considered an essential diagnostic feature of constrictive pericarditis.
However, in the large surgical series from the Mayo clinic
constriction was present in 18% of the patients with normal
pericardial thickness. Tuberculosis, mediastinal irradiation, and
previous cardiac surgical procedures are frequent causes of the
disease, which can present in several pathoanatomical forms.
Clinical presentation: severe chronic systemic venous
congestion associated with low cardiac output, including jugular
venous distension, hypotension with a low pulse pressure, abdominal
distension, oedema and muscle wasting.
ECG: can be normal, or reveal low QRS voltage, generalized
T-wave inversion/flattening, LA abnormalities, atrial fibrillation,
atrioventricular block, intraventricular conduction defects, or rarely
pseudoinfarction pattern.
M mode/2D echocardiogram: pericardial thickening and
calcificationsa as well as the indirect signs of constriction: RA and

161
LA enlargement with normal appearance of the ventricles, and
normal systolic function, early pathological outward and inward
movement of the interventricular septum (“dip-plateau
phenomenon”), flattering waves at the LV posterior wall, LV
diameter is not increasing after the early rapid filling phase, VCI and
the hepatic veins are dilated with restricted respiratory fluctuations.
Chest X-ray: pericardial calcifications, pleural effusions.
Doppler: restricted filling of both ventricles with respiratory
variation > 25% over the AV-valves).

Figure 10 – Pathoanatomical forms of constrictive pericarditis vs. restrictive

cardiomyopathy

(a) Annular form of pericardial constriction with bilateral thickening of the

pericardium along the atrial ventricular grooves with normal configuration
of both ventricles and enlargement of both atria.
(b) Left-sided form of pericardial constriction with thickened pericardium
along the left ventricle and right sided bending of the interventricular
septum with tube-like configuration of mainly left ventricle and
enlargement of both atria (lateral sternotomy and partial pericardiectomy is
indicated).
(c) Right-sided form of pericardial constriction with thickened pericardium
along the right ventricle and left sided bending of the interventricular
septum with tube-like configuration of mainly right ventricle and
enlargement of both atria (median sternotomy and partial pericardiectomy is
indicated).
(d) Myocardial atrophy and global form of pericardial constriction with
bilateral thickening of the pericardium along both ventricles separated from
the right myocardial wall by a thin layer of subepicardial fat. Tube-like

162
configuration of both ventricles and enlargement of both atria, however,
thinning of the interventricular septum and posterolateral wall of the left
ventricle below 1 cm is suggesting myocardial atrophy (pericardiectomy is
contraindicated).
(e) Perimyocardial fibrosis and global form of pericardial constriction
with bilateral thickening of the pericardium along both ventricles, however,
the right-sided thickened pericardium cannot be separated from the wave-
like thin form of right-sided ventricular wall suggesting perimyocardial
fibrosis (pericardiectomy is contraindicated).
(f) Global form of pericardial constriction with bilateral thickening of the
pericardium along both ventricles separated from the right myocardial wall
by a thin layer of subepicardial fat. Tube-like configuration of both
ventricles and enlargement of both atria (median sternotomy and
pericardiectomy is indicated).
(g) Restrictive cardiomyopathy with normal thin pericardium along both
ventricles that show normal configuration and with enlargement of both
atria.

Transoesophageal echocardiography: measurement of the

pericardial thickness.
CT/MRI: thickened and/or calcified pericardium, tube-like
configuration of one or both ventricles, narrowing of one or both
atrioventricular grooves, congestion of the caval veins enlargement
of one or both atria.
Cardiac catheterisation: “dip and plateau” or “square route”
sign in the pressure curve of the right and/or left ventricle;
equalisation of LV/RV end-diastolic pressures in the range of
5 mmHg or less.
RV/LV angiography: the reduction of RV&LV size and increase
of RA&LA size, during diastole a rapid early filling with stop of
further enlargement (“dip-plateau”).
Coronary angiography: in all patients over 35 years and in
patients with a history of mediastinal irradiation, regardless of the age.
Treatment
Pericardiectomy is the only treatment for permanent constriction.
The indications are based upon clinical symptoms, echocardiography
findings, CT/MRI, and heart catheterisation.
Specific forms of pericarditis
Viral pericarditis

163
 Viral pericarditis is the most common infection of the
pericardium. Inflammatory abnormalities are due to direct viral
attack, the immune response (antiviral or anticardiac), or both.
Various viruses cause pericarditis (entero-, echo-, adeno-,
cytomegalovirus, Ebstein Barr, herpes simplex, influenza, parvo B19,
hepatitis C, HIV, etc.). Attacks of enteroviral pericarditis follow the
seasonal epidemics of Coxsackie virus A+B and Echovirus
infections. Cytomegalovirus pericarditis has an increased incidence
in immunocompromised and HIV infected hosts. Infectious
mononucleosis may also present with pericarditis. The diagnosis of
viral pericarditis is not possible without the evaluation of pericardial
effusion and/or pericardial/epicardial tissue, preferably by PCR or in-
situ hybridisation (Ia, B). A four-fold rise in serum antibody levels is
suggestive but not diagnostic for viral pericarditis (Ib, B).
Treatment of viral pericarditis is directed to resolve symptoms
(see acute pericarditis), prevent complications, and eradicate the
virus. In patients with chronic or recurrent symptomatic pericardial
effusion and confirmed viral infection the following specific
treatment is under investigation:
– сytomegalovirus pericarditis: hyperimmunoglobulin – 1 time
per day 4 ml/kg on day 0, 4, and 8; 2 ml/kg on day 12 and 16;
– Coxsackie B pericarditis: interferon alpha or beta 2.5 Mio.
IU/m2 surface area s.c. 3 x per week;
– adenovirus and parvovirus B19 perimyocarditis: immuno-
globulin treatment: 10 g intravenously at day 1 and 3 for 6–8 hours.
Pericardial manifestation of human immunodeficiency virus
(HIV) infection can be due to infective, non-infective and neoplastic
diseases (Kaposi’s sarcoma and/or lymphoma). Infective
(myo)pericarditis results from the local HIV infection and/or from
the other viral (cytomegalovirus, herpes simplex), bacterial
(S. aureus, K. pneumoniae, M. avium, and M. tuberculosis) and
fungal coinfections (Cryptococcus neoformans). During the treatment
with retroviral compounds, lipodystrophy can develop with intense
paracardial fat deposition leading to heart failure. Treatment is
symptomatic, while in large effusions and cardiac tamponade
pericardiocentesis is necessary. The use of corticoid therapy is
contraindicated except in patients with secondary tuberculous
pericarditis (I, A).

164
Table 24 – Differential diagnosis of the specific forms of
pericarditis

Viral Bacterial Tuberculous Autoreactive

Cardio- Entero-, echo-, Staphylo-, Myco- Autoimmune
tropic adeno-, pneumo-, bacterium process in the
microbial cytomegalo- strepto- tuberculosis absence of
agents virus, Epstein cocci, viral and
Barr, herpes Neisseria, bacterial
simplex, proteus, agents
influenza, gram nega-
parvo B19, tive rods,
hepatitis A, B, legionella
C virus, HIV
Aetiologi- PCR or in-situ Gram stain, Ziehl- Ig-binding to
cal hybridisation bacterial Neelsen, peri- and
evidence (IIa, B) culture, auramin 0 epicardium,
PCR for stain, culture,
negative
Borrelia PCR (IB) PCR for
and cardiotropic
chlamydia agents,
pneumo- epicarditis
niae (IB) (IIa, B)
Incidence 30 5–10.5 < 4 (more in 20–30
(%) in per Africa and
Western 100,000 South
countries patients America)
Male: 3:1 1:1 1:1 1:1
female
ratio
Predis- Unknown Chronic Alcohol Association
position alcohol abuse, to
abuse, HIV autoimmune
immuno- infection disorders
suppression
Clinical Identical to Spiking Subfebrile, Subfebrile,
features acute fever, chronic chronic
pericarditis, fulminant,
often tachycardia,
subfebrile pericardial

165
 rubs
Table 24 continuation

Viral Bacterial Tuberculous Autoreactive

Effusion Variable, Variable Variable, Variable
size mostly small mostly large
Tamponade Infrequent 80% Frequent Infrequent
Sponta- Frequent None None Rare
nious
remission
Recurrence 30–50% Rare Frequent Frequent;
rate > 25%
Aspect of Serous/sero- Purulent Sero- Serous
PE sanguinous sanguinous
Protein > 3 g/dL High High/inter- Intermediate
content mediate
Leukocyte > 5000/ml >10000/ml Intermediate Intermediate
count (PE) > 8000 < 5000
Pericardial Activated Granulo- Granulocytes Activated
fluid lymphocytes cytes and and macro- lymphocytes
analysis and macro- macro- phages and macro-
phages. phages (intermediate) phages
Adenosindea- (massive) ADA (sparse)
minase ADA- positive ADA-
(ADA)- negative (> 40 U/ml) negative
negative
Peri- and Lymphocytic Leukocytic Caseous Lymphocytic
epicardial peri-/ epicarditis granuloma, peri-/
biopsy epicarditis, PCR epicarditis,
PCR positive PCR negative
for cardio-
tropic virus
Mortality if Depending 100% 85% In untreated
untreated on agent and tamponade
tamponade
Intraperi- Drainage, if Drainage Drainage, Drainage, i.p.
cardial needed, no and rinsing if needed triamcinolon
treatment intraper- (saline) (IIa, B)
cardial gentamycin
corticoids 80 mg i.p.

166
Table 24 continuation

Viral Bacterial Tuberculous Autoreactive

Peri- Rarely Promptly Rarely Rarely
cardiotomy/ needed needed needed needed
pericardi- (evidence
ectomy level B,
indication I)
Systemic I.V.immuno- I.V. Tuberculo- NSAIDs,
treatment globulins, antibiotics static colchicine,
IFN (in +prednisone prednisolone/
enteroviral azathioprin
pericarditis)
Constriction Rare Frequent Frequent Rare
(30–50%)
Bacterial pericarditis
It is usually a complication of an infection originating elsewhere
in the body, arising by contiguous spread or haematogenous
dissemination. Predisposing conditions are pericardial effusion,
immunosuppression, chronic diseases (alcohol abuse, rheumatoid
arthritis, etc.), cardiac surgery and chest trauma. The disease appears
as an acute, fulminant infectious illness with short duration.
Percutaneous pericardiocentesis must be promptly performed.
Obtained pericardial fluid should undergo urgent Gram, acid-fast and
fungal staining (I, B).
Pericarditis in renal failure
Renal failure is a common cause of pericardial disease, producing
large pericardial effusions in up to 20% of patients. Two forms have
been described:
1. Uremic pericarditis – in 6–10% of patients with advanced
renal failure (acute or chronic) before dialysis has been instituted or
shortly thereafter. It results from inflammation of the visceral and
parietal pericardium and correlates with the degree of azotemia
(BUN > 60 mg/dl).
2. Dialysis-associated pericarditis – in up to 13% of patients on
maintenance haemodialysis, and occasionally with chronic peritoneal
dialysis due to inadequate dialysis and/or fluid overload.
The clinical features may include fever and pleuritic chest pain
but many patients are asymptomatic. Pericardial rubs may persist

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even in large effusions or may be transient. Due to autonomic
impairment in uremic patients, heart rate may remain slow
(60–80 beats/min) during tamponade, despite fever and hypotension.
Anaemia, due to induced resistance to erythropoietin may worsen the
clinical picture. The ECG does not show the typical diffuse ST/T wave
elevations observed with other causes of acute pericarditis due to the
lack of the myocardial inflammation. If the ECG is typical of acute
pericarditis, intercurrent infection must be suspected. Most patients
with uremic pericarditis respond rapidly to haemo- or peritoneal
dialysis with resolution of chest pain and pericardial effusion.
Autoreactive pericarditis and pericardial involvement
in systemic autoimmune diseases
Pericarditis occurs in systemic autoimmune diseases. The
diagnosis of autoreactive pericarditis is established using the
following criteria:
– increased number of lymphocytes and mononuclear cells
> 5000/mm3 (autoreactive lymphocytic), or the presence of
antibodies against heart muscle tissue (antisarcolemmal) in the
pericardial fluid (autoreactive antibody-mediated);
– inflammation in epicardial/endomyocardial biopsies by
≥ 14 cells/mm2;
– exclusion of active viral infection both in pericardial effusion
and endomyocardial/epimyocardial biopsies (no virus isolation, no
IgM-titre against cardiotropic viruses in pericardial effusion, and
negative PCR for major cardiotropic viruses);
– tuberculosis, Borrelia burgdorferi, Chlamydia pneumoniae,
and other bacterial infection excluded by PCR and/or cultures;
– neoplastic infiltration absent in pericardial effusion and biopsy
samples;
– exclusion of systemic, metabolic disorders, and uraemia.
Postcardiac injury syndrome: postpericardiotomy syndrome
Postcardiac injury syndrome develops within days to months after
cardiac, pericardial injury or both. It resembles the postmyocardial
infarction syndrome, both appearing to be variants of a common
immunopathic process. Unlike postmyocardial infarction syndrome,
postcardiac injury syndrome acutely provokes a greater antiheart
antibody response (antisarcolemmal and antifibrillary).

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 Symptomatic treatment is as in acute pericarditis (NSAIDs or
colchicine for several weeks or months, even after disappearance of
effusion). Long term (3–6 months) oral corticoids or preferably
pericardiocentesis and intrapericardial instillation of triamcinolone
(300 mg/m²) are therapeutic options in refractory forms.
Postinfarction pericarditis
Two forms of postinfarction pericarditis can be distinguished:
1. “Early” form (pericarditis epistenocardica).
2. “Delayed” form (Dressler's syndrome).
Epistenocardiac pericarditis, caused by direct exudation, occurs in
5–20% of transmural myocardial infarctions but is clinically
discovered rarely. Dressler's syndrome occurs from one week to
several months after clinical onset of myocardial infarction with
symptoms and manifestations similar to the postcardiac injury
syndrome. Its incidence is 0.5–5% and is still lower in patients
treated with thrombolytics (< 0.5%), but was more frequent in cases
of pericardial bleeding after antithrombotic treatment. Of note, ECG
changes are often overshadowed by myocardial infarction changes.
Stage I ECG changes are uncommon and suggest “early”
postmyocardial infarction syndrome whereas failure to evolve or
“resurrection” of previously inverted T waves strongly suggest
myocardial infarction pericarditis. Postinfarction pericardial effusion
> 10 mm is most frequently associated with haemopericardium, and
two thirds of these patients may develop tamponade/free wall
rupture. Urgent surgical treatment is life saving.
Treatment
Ibuprofen, which increases coronary flow, is the agent of choice.
Aspirin, up to 650 mg every 4 hours for 2 to 5 days has also been
successfully applied. Other nonsteroidal agents risk thinning the
infarction zone. Corticosteroid therapy can be used for refractory
symptoms only but could delay myocardial infarction healing (Ia, B).
Neoplastic pericarditis
Primary tumours of the pericardium are 40 times less common
than the metastatic ones. Mesothelioma, the most common of the
primary tumours, is almost always incurable. The most common
secondary malignant tumours are lung cancer, breast cancer,
malignant melanoma, lymphomas, and leukemias. Effusions may be
small or large with an imminent tamponade (frequent recurrences) or

169
constriction. It even may be the initial sign of malignant disease. With
small malignant effusions most patients are asymptomatic. The onset
of dyspnoea, cough, chest pain, tachycardia, jugular venous
distension is observed when the volume of fluid exceeds 500 ml. The
analyses of pericardial fluid, pericardial or epicardial biopsy are
essential for the confirmation of malignant pericardial disease (I, B).
Rare forms of pericardial disease
Fungal pericarditis
Fungal pericarditis occurs mainly in immunocompromised
patients or in the course of endemic-acquired fungal infections.The
clinical picture comprises the full spectrum of pericardial diseases
including fungal myocarditis. Fungal pericarditis is mainly due to
endemic fungi (Histoplasma, Coccidioides), or nonendemic –
opportunistic fungi (Candida, Aspergillus, Blastomyces) and
semifungi (Nocardia, Actinomyces). Diagnosis is obtained by
staining and culturing pericardial fluid or tissue. Antifungal
antibodies in serum are helpful in establishing the diagnosis of fungal
infection.
Antifungal treatment with fluconazole, ketoconasole, itraconasole,
amphotericin B is indicated (I, B). Corticosteroids and NSAIDs can
support the treatment with antifungal drugs (Iia, C). Patients with
pericarditis in the course of histoplasmosis do not need antifungal
therapy, but respond to nonsteroidal anti-inflammatory drugs given
during 2–12 weeks. Sulfonamides are the drugs of choice for a
nocardiosis infection. Combination of three antibiotics including
penicillin should be given for actinomycosis (I, C).
Pericardiocentesis or surgical treatment is indicated for
haemodynamic impairment. Pericardiectomy is indicated in fungal
constrictive pericarditis (I, C).
Chylopericardium
Chylopericardium refers to a communication between the
pericardial sac and the thoracic duct, as a result of trauma, congenital
anomalies, or as a complication of open-heart surgery, mediastinal
lymphangiomas, lymphangiomatous hamartomas, lymphangiectasis,
and obstruction or anomalies of the thoracic duct. The chylous nature
of the fluid is confirmed by its alkaline reaction, specific gravity
between 1010 and 1021, Sudan III stain for fat, high concentrations
of triglycerides (5–50 g/l) and protein (22–60 g/l). Treatment

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depends on the aetiology and the amount of chylous accumulation.
Chylopericardium after thoracic or cardiac operation is preferably
treated by pericardiocentesis and diet (medium chain triglycerides)
and surgical treatment (I, B).
Radiation pericarditis
The probability to develop radiation-induced pericarditis is
influenced by the applied source, dose, its fractionation, duration,
radiation exposed volume, form of mantel field therapy, and the age
of the patients. Radiation induced pericarditis may occur already
during the therapy or months and years later – with latency of up to
15–20 years. The effusion may be serous or haemorrhagic, later on
with fibrinous adhesions or constriction, typically without tissue
calcification. The symptoms may be masked by the underlying
disease or the applied chemotherapy.
Drug- and toxin-related pericarditis
Pericardial reactions to drugs are rare. However, several
medications and toxic substances can induce pericarditis, tamponade,
adhesions, fibrosis, or constriction. Mechanisms include drug
induced: drug-induced lupus erythematosus (procainamide,
hydralazine, methyldopa, mesalazine, isoniazid, hydantoins);
hypersensitivity reaction (penicillins, tryptophan, cromolyn sodium);
idiosyncratic reaction or hypersensitivity (amiodarone, streptokinase,
thiazides, streptomycin, thiouracils, cyclophosphamide,
cyclosporine, mesalazine), 5-fluorouracil, vaccines (smallpox,
yellow fever, cytarabine); serum sickness (foreign antisera (e.g.,
antitetanus), blood products); venom (scorpion fish sting); foreign-
substance reactions (direct pericardial application) (silicones,
tetracycline/other sclerosants, iron in ß-thalasssemia, asbestos);
Secondary pericardial bleeding/haemopericardium (anticoagulants,
thrombolytic agents); polymer fumes fever – inhalation of the
burning fumes of polytetrafluoroethylene (teflon).
Pericardial effusion in thyroid disorders
Pericardial effusion occurs in 5–30% of patients with
hypothyroidism. Fluid accumulates slowly and tamponade occurs
rarely. In some cases cholesterol pericarditis may be observed. The
diagnosis of hypothyroidism is based on serum levels of thyroxin and
thyroid stimulating hormone. Therapy with thyroid hormone
decreases pericardial effusion (I, B).

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 Pericardial effusion in pregnancy
There is no evidence that pregnancy affects susceptibility to
pericardial disease. However, many pregnant women develop a
minimal to moderate clinically silent hydropericardium by the third
trimester. Cardiac compression is rare. ECG changes of acute
pericarditis in pregnancy should be distinguished from the slight
ST-segment depressions and T-wave changes seen in normal
pregnancy. Occult constriction becomes manifest in pregnancy due to
the increased blood volume. Most pericardial disorders are managed
as in nonpregnant.

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 SYNDROME OF CHRONIC CARDIAC FAILURE

Much is now known about the epidemiology of heart failure (HF).

The ESC represents countries with a population of > 900 million, and
there are at least 15 million patients with HF in those 51 countries.
The prevalence of asymptomatic ventricular dysfunction is similar,
so that HF or asymptomatic ventricular dysfunction is evident in ~4%
of the population. The overall prevalence of HF is increasing because
of the ageing of the population. The prevalence of HF is between 2
and 3% and rises sharply at ~75 years of age, so the prevalence in 70-
to 80-year-old people is between 10 and 20%. In younger age groups
HF is more common in men because the most common cause,
coronary heart disease, occurs in earlier decades. In the elderly, the
prevalence is equal between the sexes.
In some countries the age-adjusted mortality from HF is falling at
least in part due to modern treatment. The mean age of patients with
HF in the community in developed countries is 75 years. HFPEF is
more common in the elderly, women, and those with hypertension or
diabetes. HF is the cause of 5% of acute hospital admissions, is present
in 10% of patients in hospital beds, and accounts for ~2% of national
expenditure on health, mostly due to the cost of hospital admissions.
The outlook is, in general, gloomy, although some patients can
live for many years. Overall 50% of patients are dead at 4 years.
Forty per cent of patients admitted to hospital with HF are dead or
readmitted within 1 year.
HF should never be the only diagnosis.
Definition
1) symptoms of heart failure (SHF) (at rest or during
exercise);
2) objective evidence (preferably by echocardiography) of
cardiac dysfunction (systolic and/or diastolic) (at rest) and (in cases
where the diagnosis is in doubt);
3) response to treatment directed towards heart failure.
Criteria I and II should be fulfilled in all cases.
HF is characterized by overflow and congestion of blood in
venous system because of infringement of process:
– contraction and expel of the oxygenation of blood in vascular
channel in systole;

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 – relaxations and fillings of veins with blood in diastole.
Classification of HF
According to aetiology:
1. Coronarogenic: IHD.
2. Noncoronarogenic: arterial hypertension, valvular disease,
myocarditis, endocarditis, pericarditis, infringement of heart rate,
neoplasm, cor pulmonale.
According to the course:
1. Acute: pulmonary oedema and cardiogenic shock.
2. Chronic (CHF).
According to the degree:
– asymptomatic;
– symptomatic;
– refractory.
According to the tolerance to physical activity: I-IV FC
(NYHA, 1964).
New York heart association (NYHA,1964)
classification of HF
I FC – patients have no palpitation, dyspnoea, fatigue or attacks
of angina at usual physical loadings.
II FC – patients with cardiovascular pathology have palpitation,
dyspnoea, fatigue or attacks of angina at usual physical loadings. At
rest clinical signs are absent.
III FC – patients with cardiovascular pathology at which the
physical activity is considerably limited. They have palpitation,
dyspnoea, fatigue or attacks of angina at minimal physical loadings.
At rest clinical signs are expressed а little or absent.
IV FC – patients with cardiovascular pathology, which can not
carry out any physical loading. They have clinical symptoms of heart
insufficiency at rest. Any physical loading results in deterioration of
health state.
Types of CHF
1. Leftcardiac CHF – characterized by transient or constant
hypervolemia of pulmonary circulation, caused by pump
insufficiency of the left part of heart.
2. Rightcardiac CHF – characterized by transient or constant
hypervolemia of systemic circulation, caused by pump insufficiency
of the right part of heart.

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 3. Combined (total) – combination of the above stated criteria.
Table 25 – Classification of HF by structural abnormality
(ACC/AHA), or by symptoms relating to functional capacity
(NYHA)

ACC/AHA stages of heart failure NYHA functional classification

(Stage of HF based on structure and (Severity based on symptoms and
damage to heart muscle) physical activity)
Stage A. At high risk for Class I. No limitation of physical
developing HF. No identified activity. Ordinary physical
structural or functional abnorma- activity does not cause undue
lity; no signs or symptoms fatigue, palpitation, or dyspnoea
Stage B. Developed structural heart Class II. Slight limitation of
disease that is strongly associated physical activity. Comfortable at
with the development of HF, but rest, but ordinary physical activity
without signs or symptoms results in fatigue, palpitation, or
dyspnoea
Stage C. Symptomatic heart failure Class III. Marked limitation of
associated with underlying physical activity. Comfortable at
structural heart disease rest, but less than ordinary
activity results in fatigue,
palpitation, or dyspnoea
Stage D. Advanced structural heart Class IV. Unable to carry on any
disease and marked symptoms of physical activity without
heart failure at rest despite maximal discomfort. Symptoms at rest. If
medical therapy any physical activity is
undertaken, discomfort is
increased

Variants of CHF
1. Systolic – infringement of haemodynamics is caused by
insufficient ventricular systolic function (is characteristic for
inflammations of myocardium defeats, dilated cardiomyopathy,
postinfarction cardiosclerosis with LV dilatation, decompensation of
valves regurgitations).
The basic criterion is fraction of reduced LV emission (< 45–50%).
2. Diastolic – infringement of haemodynamics is caused by
insufficient ventricular diastolic function (is characteristic for
hypertrophy and restrictive cardiomyopathy, constrictive pericarditis,
cardiac hypertension, compensated aortic stenosis).

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 The basic criterion:
– pulmonary oedema, cardiac asthma or X-rays signs of
pulmonary congestion at the LV emission fraction is more than 50 %;
– reduction of the size (volume) of ventricular cavity.
3. Combined – combination of the above stated criteria. Is
characteristic for ischaemic heart disease, myocardiosclerosis,
decompensation of heart hypertension, combined valvular disease.
The pathophysiology cause of SHF development
1. Damage of myocardium:
1) primary damage:
– physical (trauma of myocardium, electric trauma, radioactive
radiation);
– chemical (toxic effect of neurohormones, medicinal and not
medicinal substances);
– biological (toxin, viruses, parasites and microorganisms);
– not specified and/or genetic determination (cardiomyopathy);
2) secondary damage (ischaemic heart disease, diseases of
endocrine system, connective tissue, heredity myopathy, deficiency
of vitamins and enzyme, etc.).
2. The increased haemodynamic loading on myocardium
results in:
– overloads by pressure (arterial hypertension, primary vascular
pulmonary hypertension, stenosis of aorta or pulmonary artery);
– overloads by volume (incompetence of mitral, aortic, and
tricuspid valves, some inherent defects of heart);
– combined overload.
3. Infringement of heart rate (tachycardia, bradycardia).
4. Age changes (aging).
5. Extracardiac reasons (compression of heart with exudates or
tumour, changes in pericardium, cardiac tamponade, infringement of
endocrine organs function, e.g., in case of hypothyrosis, diabetes
mellitus, etc.).
Neurohumoral activation in case of SHF:
1. Activation of sympathoadrenal system (SAS).
2. Increased secretion of natriuretic peptide.
3. Activation of renin-angiotensin-aldosterone system (RAAS).
4. Secretion of prostaglandin E2 and prostacyklin I2.
5. Secretion of antidiuretic hormone.

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 6. Secretion of NO and endoteline-1.
Table 26 – Negative effects of long SAS activation

Negative effect Consequence

Vasoconstriction. Increase of before and
Retention of Na+ and liquors. post loading
Activation of other neurohumoral systems
(RAAS)
Increase of heart wall pressure. Increase of needs in O2
Increase of myocardial ischaemia and energy
Straight cardiotoxic effect of catecholamines
Infringement receptor of the device: Infringement of normal
– desensetization (or tachyphylaxis) function separate
postsynaptic adrenoreceptors (mainly β1); cardiomyocytes and
– change of activity and expression of myocardium as a whole
protein-G.
Infringement outputs, return capture and
concentration noradrenaline.
Remodeling of myocardium.
Stimulations of pathological myocardial
hypertrophy
Decrease of threshold of ventricular Development of
fibrillation ventricles rhythm

Table 27 – Atrials natriuretic peptide (ANUP)

Favourable effect Consequence

Increase of baroreceptor sensitivity Decrease of SAS activation
Decreased noradrenaline release from Decrease of vasoconstriction
nervous synapses effect of SAS
Suppression of renin and angiotensin Decrease of vasoconstriction
II development
Decrease of aldosterone and Decrease of vasoconstriction,
vasopressin development diuretic effect

Cardial mechanisms of compensations:

1. Frank-Starling mechanism – tonogenesis dilatation of heart
ventricle (factor of immediate adaptation).
2. Remodeling of the left ventricle – set changes of its form,
size of cavity and weight of myocardium, that is clinically shown in

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its hypertrophy, dilatation, and geometrical deformation.

Figure 11– Scheme of activation of renin-angiotensin-aldosterone system

Table 28 – Effects of angiotensin II

Organs Effects
Acute Chronic
Heart Inotropic effect – myocardial hypertrophy;
– increased collagen synthesis
Artery Vasoconstriction Remodeling of vessels
Kidney – vasoconstriction of
efferent arteriole;
– increased synthesis of
prostaglandin;
– increased reabsortion
of Na and water
Adrenal – aldosterone secretion; Hypertrophy of adrenal gland
gland – catecholamines
secretion
Encepha- – stimulation of thirst;
lon – increase of vasopressin
secretion;

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 – stimulation of SAS
Diagnosis
Breathlessness, tiredness, and fatigue are the characteristic
symptoms, but elicitation and assessment of these symptoms requires
experience and skill particularly in the elderly. The clinical signs of
HF (table 29) should be assessed in a careful clinical examination,
including observation, palpation, and auscultation. The signs of early
HF can be difficult to interpret both in the elderly and in the obese.
Clinical picture of CHF:
– orthopnoea;
– dyspnoea at rest or at physical loading;
– general weakness or increased fatigue;
– night cough (cough in the laying position);
– delay of liquid in organism (peripheral oedema, swelling veins
of neck, ascites);
– cardiomegaly;
– additional III and protodiastolic heart sound;
– murmur in heart at development of dilatation of heart cavities;
– pulmonary congestion;
– hepatomegalya;
– nycturia.

Table 29 – Symptoms and signs of HF

Dominant
Symptom Sign
clinical feature
Peripheral Breathlessness, Peripheral oedema, raised jugular
oedema/ venous pressure, hepatomegaly,
congestion tiredness, pulmonary oedema, ascites, fluid
fatigue, overload (congestion), cachexia
anorexia
Pulmonary Severe breath- Crackles or rales over lungs,
oedema lessness at rest effusion, tachycardia, tachypnoea
Cardiogenic Confusion, Poor peripheral perfusion.
shock (low output weakness, SBP < 90 mmHg.
syndromes) cold periphery Anuria or oliguria
High BP Breathlessness Usually raised BP, LV
(hypertensive HF) hypertrophy, and preserved EF
Right HF Breathlessness, Evidence of RV dysfunction.

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 fatigue Raised JVP, peripheral oedema,
hepatomegaly, gut congestion
There is a poor relationship between symptoms and the severity
of cardiac dysfunction. Symptoms relate more closely to prognosis if
persistent after therapy and can then be used to classify the severity
of HF and to monitor the effects of therapy.
The severity of heart failure is most often classified using the
NYHA functional classification. A more recent classification is
based on both the structure of the heart and symptoms. In the context
of MI, two other classifications of HF severity, Killip’s and
Forrester’s classifications, are used.
ECG:
– normal electrocardiogram (ECG) suggests that the diagnosis of
CHF should be carefully reviewed;
– sinus tachycardia (causes decompensated HF, anaemia, fever,
hyperthyroidism);
– sinus bradycardia (causes β-Blockade, digoxin,
antiarrhythmics, hypothyroidism, sick sinus syndrome);
– atrial tachycardia/flutter/fibrillation (causes hyperthyroidism,
infection, mitral valve diseases, decompensated HF, infarction);
– ventricular arrhythmias (cause ischaemia, infarction,
cardiomyopathy, myocarditis hypokalaemia, hypomagnesaemia,
digitalis overdose);
– ischaemia/infarction (causes coronary artery disease);
– the presence of pathological Q-waves may suggest myocardial
infarction as the cause of cardiac dysfunction;
– LV hypertrophy (causes hypertension, aortic valve disease,
hypertrophic cardiomyopathy);
– AV block (causes infarction, drug toxicity, myocarditis,
sarcoidosis, Lyme disease);
– microvoltage (causes obesity, emphysema, pericardial
effusion, amyloidosis);
– QRS width > 120 ms suggests that cardiac desynchronization
may be present.
Chest X-ray is an essential component of the diagnostic work-up
in heart failure. It permits assessment of pulmonary congestion and
may demonstrate important pulmonary or thoracic causes of
dyspnoea. Chest X-ray (in two planes) is useful to detect:

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 – cardiomegaly (causes dilated LV, RV, atrial
pericardial effusion);
– ventricular hypertrophy (causes hypertension, aortic stenosis,
hypertrophic cardiomyopathy);
– normal pulmonary findings (cause pulmonary congestion
unlikely);
– pulmonary venous congestion and interstitial oedema (cause
elevated LV filling pressure);
– pleural effusions (cause elevated filling pressures, HF likely if
bilateral, pulmonary infection, surgery, or malignant effusion);
– Kerley B lines (cause increased lymphatic pressures);
– hyperlucent lung fields (cause emphysema or pulmonary
embolism);
– pulmonary infection (causes pneumonia may be secondary to
pulmonary congestion);
– pulmonary infiltration (causes systemic disease).

Table 30 – Common echocardiographic abnormalities in heart failure

Measurement Abnormality Clinical implication

LV ejection Reduced Systolic dysfunction
fraction (< 45–50%)
LV function, Akinesis, hypo- MI/ischaemia, myocarditis,
global and focal kinesis, dyskinesis cardiomyopathy
End-diastolic Increased Volume overload, HF likely
diameter (> 55–60 mm)
End-systolic Increased Volume overload, HF likely
diameter (> 45 mm)
Fractional Reduced (< 25%) Systolic dysfunction
shortening
Left atrial size Increased Increased filling pressures,
(> 40 mm) MV-dysfunction, AF
Left ventricular Hypertrophy Hypertension, hypertrophic
thickness (> 11–12 mm) cardiomyopathy, aortic
stenosis
Valvular Valvular stenosis or May be primary cause of HF
structure and regurgitation or complicating factor, assess
function (especially aortic haemodynamic consequences,
stenosis and mitral assess gradients and
insufficiency) regurgitant fraction, consider

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 surgery
Table 30 continuation

Measurement Abnormality Clinical implication

Mitral diastolic Abnormalities of Indicates diastolic dysfunction
flow profile the early and late and suggests mechanism
diastolic filling
patterns
Tricuspid Increased (> 3 m/s) Increased right ventricular
regurgitation systolic pressure, suspect
peak velocity pulmonary hypertension
Pericardium Effusion, Consider tamponade, uraemia,
haemopericardium, malignancy, systemic disease,
thickening acute or chronic pericarditis,
constrictive pericarditis
Aortic outflow Reduced (< 15 cm) Reduced low stroke volume
velocity time
integral
Inferior vena Dilated retrograde Increased right atrial
cava flow pressures, hepatic congestion,
right ventricular dysfunction

Table 31 – Common laboratory test abnormalities in heart

failure

Abnormality Cause Clinical implication

Increased serum Renal disease Calculate GFR, consider
creatinine ACEI/ARB, reducing ACEI/ARB, or
(> 150 µmol/L) aldosterone blockade aldosterone blocker dose,
check potassium and
BUN
Anaemia CHF, haemodilution, Diagnostic work-up,
(< 13 g/dL in iron loss or poor consider treatment
men, tilization, renal
< 12 in women) failure, chronic
disease
Hyponatraemia Chronic HF, AVP Consider water restriction,
(< 135 mmol/L) release, diuretics, reducing diuretic dosage,
haemodilution ultrafiltration, vasopressin
antagonist

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 Hypernatraemia Hyperglycaemia. Assess water intake,
(> 150 mmol/L) Dehydratation diagnostic work-up
Table 31 continuation

Abnormality Cause Clinical implication

Hypokalaemia Diuretics, secondary Risk of arrhythmia,
(< 3.5 mmol/L) hyperaldosteronism ACEIs/ARB, consider
potassium supplements,
aldosterone blockers
Hyperkalaemia Renal failure, Stop potassium-sparing
(>5.5 mmol/L) potassium treatment, (ACEIs/ARB,
supplement, aldosterone blockers),
renin-angiotensin- assess renal function and
aldosterone system pH, risk of bradycardia
blockers
Hyperglycaemia Diabetes, Evaluate hydration, treat
(> 6.5 mmol/L) insulin resistance glucose intolerance
Hyperuricaemia Diuretic treatment, Allopurinol.
(> 500 µmol/L) gout, malignancy Reduce diuretic dose
BNP > 400 Increased ventricular HF likely, indication for
pg/mL, wall stress echo, consider treatment
NT-proBNP-
> 2000 pg/mL
BNP < 100 Normal wall stress Re-evaluate diagnosis of
pg/mL, HF unlikely if untreated
NT-proBNP-
< 400 pg/mL
Albumin high Dehydratation, Rehydrate
(> 45 g/L) myeloma
Albumin low Poor nutrition, renal Diagnostic work-up
(< 30 g/L) loss
Transaminase Liver dysfunction. Diagnostic work-up.
increase Right heart failure. Liver congestion.
Drug toxicit Reconsider therapy
Troponin I or T Acute coronary An elevated troponin is a
syndrome, episodes of strong prognostic marker
HF decompensation, in HF, especially in the
acute myocarditis presence of elevated
natriuretic peptides
Elevated Myocyte necrosis, Evaluate pattern of

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 troponins prolonged ischaemia, increase (mild increases
pulmonary embolism, common in severe HF),
myocarditis, sepsis, coronary angiography,
renal failure, severe evaluation for
HF revascularization
Table 31 continuation

Abnormality Cause Clinical implication

Abnormal thyroid Amiodarone. Treat thyroid abnormality
tests Hyper-/hypothyroidis
m
Urinalysis Proteinuria, Diagnostic work-up.
glycosuria, bacteria Rule out infection
INR > 2.5 Anticogulant Evaluate anticoagulant
overdose, dosage, assess liver
liver congestion function, assess
anticoagulant dose
CRP > 10 mg/L, Infection, Diagnostic work-up
neutrophilic inflammation
leukocytosis
Hyperkalaemia Renal failure, potas- Stop potassium-sparing
(> 5.5 mmol/L) sium supplement, treatment (ACEIs/ARB,
renin-angiotensin- aldosterone blockers),
aldosterone system assess renal function and
blockers pH, risk of bradycardia

Laboratory tests
A routine diagnostic evaluation of patients with suspected HF
includes a complete blood count (haemoglobin, leukocytes, and
platelets), serum electrolytes, serum creatinine, estimated glomerular
filtration rate (GFR), glucose, liver function tests, and urinalysis.
Additional tests should be considered according to the clinical picture
(table 31). Marked haematological or electrolyte abnormalities are
uncommon in untreated mild to moderate HF, although mild
anaemia, hyponatraemia, hyperkalaemia, and reduced renal function
are common, especially in patients treated with diuretics and
ACEI/ARB/aldosterone antagonist therapy. Appropriate laboratory
monitoring is essential during the initiation, titration, and follow-up
phases in patients receiving drug therapy for HF.

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 Treatment
Nonpharmacological management:
1. Weight monitoring (I, C)
Increases in body weight are often associated with deterioration
of HF and fluid retention. In the case of a sudden unexpected
weight gain of > 2 kg in 3 days, patients may increase their diuretic
dose.
Weight reduction in obese (body mass index (BMI) > 30 kg/m²)
persons with HF should be considered in order to prevent the
progression of HF, decrease symptoms, and improve well-being.
2. Diet and nutrition (IIa, C)
Sodium restriction is recommended in symptomatic HF to prevent
fluid retention.
3. Fluid restriction (IIb, C) of 1.5–2 L/day may be considered in
patients with severe symptoms of HF especially with hyponatraemia.
4. Alcohol (IIa, C) intake should be limited to 10–20 g/day
(1–2 glasses of wine/day).
5. Smoking (I, C)
It is recommended that patients receive support and advice and be
motivated to stop smoking.
6. Traveling.
7. Rest and exercise.
Objectives of treatment in chronic heart failure
1. Prognosis:
– reduce mortality.
2. Morbidity:
– relieve symptoms and signs;
– improve quality of life;
– eliminate oedema and fluid retention;
– increase exercise capacity;
– reduce fatigue and breathlessness;
– reduce need for hospitalization;
– provide for end of life care.
3. Prevention:
– occurrence of myocardial damage;
– progression of myocardial damage;
– remodelling of the myocardium;
– reoccurrence of symptoms and fluid accumulation;

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 – hospitalization.
Pharmacological management:
– angiotensin-converting enzyme inhibitors
(ACEIs) (I, A);
– β-Blockers (I, A);
– aldosterone antagonists (I, B);
– angiotensin receptor blockers (ARBs) (I, A);
– hydralazine and isosorbide dinitrate (H-ISDN)
(IIa, B);
– digitalis (I, C);
– diuretics (I, B);
– anticoagulants (vitamin K antagonists) (I, A);
– antiplatelet agents (IIb, B);
– HMG CoA reductase inhibitors (‘statins’) (IIb,
B).
Angiotensin-converting enzyme inhibitors (ACEIs)
Indications, based upon the patients enrolled in the RCTs:
LVEF ≤ 40%, irrespective of symptoms. Treatment with an ACEI
improves ventricular function and patient well-being, reduces
hospital admission for worsening HF, and increases survival. In
hospitalized patients, treatment with ACEI should be initiated
before discharge.
Contraindications: history of angioedema, bilateral renal artery
stenosis, serum potassium concentration > 5.0 mmol/L, serum
creatinine > 220 µmol/L (~2.5 mg/dL), severe aortic stenosis.
Initiation of ACEI: check renal function and serum electrolytes,
recheck renal function and serum electrolytes within 1–2 weeks of
starting treatment.
Dose up-titration: consider dose up-titration after 2–4 weeks. Do
not increase dose if significant worsening of renal function or
hyperkalaemia. Recheck renal function and serum electrolytes 1 and
4 weeks after dose increasing. Recheck renal function and serum
electrolytes 1, 3, and 6 months after achieving maintenance dose and
6 monthly thereafter.

Table 32 – Recommended ACE-inhibitor maintenance dose

Drug Initiating dose Maintenance dose

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 Captopril 6.25 mg t.i.d. 50–100 mg t.i.d.
Enalapril 2.5 mg b.i.d. 10–20 mg b.i.d.
Lisinopril 2.5–5 mg o.d. 20–35 mg o.d.
Ramipril 2.5 mg o.d. 5 mg b.i.d.
Trandolapril 0.5 mg o.d. 4 mg o.d.

Potential adverse effects: worsening of renal function,

hyperkalaemia, symptomatic hypotension, cough.
β-Blockers
Indications: LVEF ≤ 40%; mild to severe symptoms (NYHA
functional class II–IV); patients with asymptomatic LV systolic
dysfunction after MI also have an indication for a β-blocker.
Contraindications: asthma (chronic obstructive pulmonary
disease (COPD) is not a contraindication); second- or third-degree
heart block, sick sinus syndrome (in the absence of a permanent
pacemaker), sinus bradycardia (< 50 b.p.m.).
Dose up-titration: visits every 2–4 weeks to up-titrate the dose
of β-blocker (slower dose up-titration may be needed in some
patients). Do not increase dose if there are signs of HF worsening,
symptomatic hypotension (e.g., dizziness), or excessive bradycardia
(pulse rate < 50/min) at each visit.
Table 33 – Recommended β-blockers maintenance dose

Drug Initiating dose Maintenance dose

Bisoprolol 1.25 mg o.d. 10 mg o.d.
Carvedilol 3.125 mg b.i.d. 25–50 mg b.i.d.
Metoprolol succinate 12.5/25 mg o.d. 200 mg o.d.
Nebivolol 1.25 mg o.d. 100 mg o.d.

Potential adverse effects: symptomatic hypotension, HF

worsening, excessive bradycardia.
Aldosterone antagonists
Indications: LVEF ≤ 35%; moderate to severe symptoms
(NYHA functional class III-IV); optimal dose of β-blocker and ACEI
or ARB (but not ACEI and ARB).
Contraindications: serum potassium concentration

187
> 5.0 mmol/L; serum creatinine > 220 µmol/L (~2.5 mg/dL);
concomitant potassium sparing diuretic or potassium supplements;
combination of ACEI and ARB.
Initiation of spironolactone (or eplerenone): check renal
function and serum electrolytes; starting dose: spironolactone 25 mg
o.d. (or eplerenone 25 mg o.d.). Recheck renal function and serum
electrolytes 1 and 4 weeks after starting treatment.
Table 34 – Recommended aldosterone antagonist maintenance
dose

Drug Initiating dose Maintenance dose

Eplerenone 25 o.d. 50 o.d.
Spironolactone 25 o.d. 25–50 o.d.

Dose up-titration: сonsider dose up-titration after 4–8 weeks. Do

not increase dose in case of renal function worsening or
hyperkalaemia.
Recheck renal function and serum electrolytes 1 and 4 weeks after
increasing dose.
In absence of the above-mentioned problems, aim for evidence-
based target dose – spironolactone 50 mg o.d. or eplerenone
50 mg o.d. – or maximum tolerated dose.
Recheck renal function and serum electrolytes 1, 2, 3, and 6
months after achieving maintenance dose, and 6 monthly thereafter.
Potential adverse effects: hyperkalaemia, worsening renal
function – if creatinine rises to > 220 µmol/L (~2.5 mg/dL) halve
dose of spironolactone, breast tenderness and/or enlargement.
Angiotensin receptor blockers (ARBs)
Treatment with ARB improves ventricular function and patient
well-being, and reduces hospital admission for HF worsening.
Treatment reduces the risk of death from cardiovascular causes.
Indications: LVEF ≤ 40% and either; as an alternative in patients
with mild to severe symptoms (NYHA functional class II–IV) who
are intolerant of ACEI, or in patients with persistent symptoms
(NYHA functional class II–IV) despite treatment with ACEI and
β-blocker; ARBs may cause worsening of renal function,
hyperkalaemia, and symptomatic hypotension with an incidence

188
similar to ACEI. They do not cause cough.
Contraindications: as with ACEIs, with exception of
angioedema; patients treated with ACEI and aldosterone antagonist;
ARB should only be used in patients with adequate renal function and
normal serum potassium concentration; serial monitoring of serum
electrolytes and renal function is mandatory, especially if ARB is
used in conjunction with ACEI.
Initiation of an ARB: check renal function and serum
electrolytes; starting dose: either candesartan 4–8 mg o.d. or
valsartan 40 mg b.i.d.; recheck renal function and serum electrolytes
within 1 week of starting treatment.
Dose up-titration: consider dose up-titration after 2–4 weeks. Do
not increase dose in case of renal function worsening or
hyperkalaemia. Recheck renal function and serum electrolytes 1 and
4 weeks after dose increasing.
In absence of the above-mentioned problems, aim for evidence-
based target dose – candesartan 32 mg o.d. or valsartan 160 mg b.i.d.
– or maximum tolerated dose.
Recheck renal function and serum electrolytes 1, 3, and 6 months
after achieving maintenance dose, and 6 monthly thereafter.
Table 35 – Recommended ARBs maintenance dose

Drug Initiating dose Maintenance dose

Candesartan 4 or 8 o.d. 32 o.d.
Valsartan 40 b.i.d. 160 b.i.d.

Potential adverse effects: as with ACEIs except for cough.

Hydralazine and isosorbide dinitrate (H-ISDN)

In symptomatic patients with LVEF ≤ 40%, the combination of
H-ISDN may be used as an alternative if there is intolerance to both
ACEI and ARB. Adding the combination of H-ISDN should be
considered in patients with persistent symptoms despite treatment
with ACEI, β-blocker, and ARB or aldosterone antagonist.
Indications: an alternative to ACEI/ARB when both of the latter
are not tolerated; as add-on therapy to ACEI if ARB or aldosterone
antagonist is not tolerated; evidence is the strongest in patients of
African-American descent.

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 Contraindications: symptomatic hypotension; lupus syndrome;
severe renal failure (dose reduction may be needed).
Initiation: starting dose: hydralazine 37.5 mg and ISDN 20 mg tid.

Dose up-titration: consider dose up-titration after 2–4 weeks. Do

not increase dose with symptomatic hypotension.
If tolerated, aim for evidence-based target dose – hydralazine
75 mg and ISDN 40 mg t.i.d. – or maximum tolerated dose.
Potential adverse effects: symptomatic hypotension (e.g.,
dizziness) – often improves with time; consider reducing dose of other
hypotensive agents (except ACEI/ARB/β-blocker/aldosterone
antagonist). Asymptomatic hypotension does not require intervention.
Arthralgia/muscle aches, joint pain or swelling,
pericarditis/pleuritis, rash or fever – consider drug-induced lupus-like
syndrome; check ANA, discontinue H-ISDN.
Digoxin
Indications:
– atrial fibrillation: with ventricular rate at rest > 80 b.p.m., at
exercise > 110–120 b.p.m.
– sinus rhythm: LV systolic dysfunction (LVEF ≤ 40%); mild to
severe symptoms (NYHA functional class II–IV); optimal dose of
ACEI or/and ARB, β-blocker and aldosterone antagonist, if indicated.
Contraindications: second- or third-degree heart block (without
a permanent pacemaker); caution if suspected sick sinus syndrome;
pre-excitation syndromes; previous evidence of digoxin intolerance.
Initiation of digoxin: starting dose: loading doses of digoxin are
generally not required in stable patients with sinus rhythm. A single
daily maintenance dose of 0.25 mg is commonly employed in adults
with normal renal function. In the elderly and in those with renal
impairment, reduced dose of 0.125 or 0.0625 mg o.d. should be used.
Digoxin concentration should be checked early during chronic
therapy in those with normal renal function. Steady state may take
longer to be achieved in those with renal impairment. There is no
evidence that regular digoxin concentration measurements confer
better outcomes. The therapeutic serum concentration should be
between 0.6 and 1.2 ng/mL, lower than previously recommended.
Certain drugs may increase plasma digoxin levels (amiodarone,
diltiazem, verapamil, certain antibiotics, quinidine).

190
 Potential adverse effects: sinoatrial and AV block; atrial and
ventricular arrhythmias, especially in the presence of hypokalaemia
(digoxin-specific Fab antibody fragments should be considered for
ventricular arrhythmias caused by toxicity); signs of toxicity include:
confusion, nausea, anorexia, and disturbance of colour vision.
Diuretics
Diuretics are recommended in patients with HF and clinical signs
or symptoms of congestion.
Table 36 – Practical considerations in treatment of heart failure
with loop diuretics (management of diuretic resistance)

Problem Suggested action

Hypokalaemia/ – increase ACEI/ARB dosage;
hypomagnesaemia – add aldosterone antagonist;
– potassium supplements;
– magnesium supplements
Hyponatraemia Fluid restriction:
– stop thiazide diuretic or switch to loop diuretic,
if possible;
– reduce dose/stop loop diuretics, if possible;
– consider AVP antagonist, e.g., tolvaptan, if
available;
– i.v. inotropic support;
– consider ultrafiltration
Hyperuricaemia/ Consider allopurinol:
gout – for symptomatic gout use colchicine for pain
relief ;
– avoid NSAIDs
Hypovolaemia/ Assess volume status:
dehydration – consider diuretic dosage reduction
Insufficient Check compliance and fluid intake:
response or – increase dose of diuretic;
diuretic resistance – consider switching from furosemide to
bumetanide or torasemide;
– add aldosterone antagonist;
– combine loop diuretic and thiazide/
metolazone;
– administer loop diuretic twice daily or on empty
stomach;

191
 – consider short-term i.v. infusion of loop
diuretic
Renal failure Check for hypovolaemia/dehydration:
(excessive rise – exclude the use of other nephrotoxic agents,
in urea/BUN e.g., NSAIDs, trimethoprim;
and/or creatinine) – withhold aldosterone antagonist;
– if using concomitant loop and thiazide diuretic,
stop thiazide diuretic;
– consider reducing dose of ACEI/ARB;
– consider ultrafiltration
Initiation of diuretic therapy
Check renal function and serum electrolytes. Most patients are
prescribed loop diuretics rather than thiazides due to the higher
efficiency of induced diuresis and natriuresis.
Diuretic dosages (table 37)
Start with a low dosage and increase until clinical improvement of
the symptoms and signs of congestion.
Dose must be adjusted, particularly after restoration of dry body
weight, to avoid the risk of renal dysfunction and dehydration. Aim to
maintain “dry weight” with the lowest achievable dose.
Self-adjustment of diuretic dose based on daily weight
measurements and other clinical signs of fluid retention should be
encouraged in HF outpatient care. Patient’s education is required.

Table 37 – Diuretic dosages in patients with heart failure

Diuretic Initial dose (mg) Usual daily dose (mg)

Loop diuretics*
Furosemide 20–40 40–240
Bumetanide 0.5–1.0 1–5
Torasemide 5–10 10–20
Thiazides**
Bendroflumethiazide 2.5 2.5–10
Hydrochlorothiazide 25 12.5–100
Metolazone 2.5 2.5–10
Indapamide1 2.5 2.5–5
Potassium-sparing diuretics***
+ ACEI/ – ACEI/ +ACEI/ –ACEI/
ARB ARB ARB ARB

192
 Spironolactone/ 12.5–25 50 50 100–200
Eplerenone
Amiloride 2.5 5 20 40
Triamterene 25 50 100 200
*Dose might need to be adjusted according to volume status/weight;
excessive doses may cause renal impairment and ototoxicity.
**Do not use thiazides if eGFR < 30 mL/min, except when prescribed
synergistically with loop diuretics.
***Aldosterone antagonists should always be preferred to other
potassium-sparing diuretics.
1
Indapamide is not-thiazides sulphonamide.
Anticoagulants (vitamin K antagonists)
Warfarin (or an alternative oral anticoagulant) is recommended in
patients with HF and permanent, persistent, or paroxysmal AF
without contraindications to anticoagulation. Adjusted dose
anticoagulation reduces the risk of thromboembolic complications
including stroke.
Antiplatelet agents
Antiplatelet agents are not as effective as warfarin in reducing the
risk of thromboembolism in patients with AF. In a pooled analysis of
two small trials comparing warfarin and aspirin in patients with HF,
the risk of HF hospitalization was significantly greater in aspirin-
treated, compared with warfarin-treated, patients. There is no
evidence that antiplatelet agents reduce atherosclerotic risk in patients
with HF.
HMG CoA reductase inhibitors (“statins”)
In elderly patients with symptomatic chronic HF and systolic
dysfunction caused by CAD, statin treatment may be considered to
reduce cardiovascular hospitalization.

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 COR PULMONALE

Cor pulmonale is right ventricular enlargement secondary to a

lung disorder that produces pulmonary artery hypertension. It results
from a disorder of the lung or its vasculature or deformation of chest.
Cor pulmonale is estimated to account for 6–7% of all types of
adult heart disease in the United States, with chronic obstructive
pulmonary disease (COPD) due to chronic bronchitis or emphysema
causative factor in more than 50% of cases. At present, cor
pulmonale accounts for 10–30% of decompensated heart failure
related admissions in the United States. Acute massive pulmonary
thromboembolism is the most common cause of acute life-
threatening cor pulmonale in adults. In the United States, 50,000
deaths are estimated to occur per year from pulmonary emboli and
about half occur within the first hour due to acute right heart failure.
Development of cor pulmonale as a result of a primary pulmonary
disease usually heralds a poorer prognosis. For example, patients
with COPD who develop cor pulmonale have a 30% chance of
surviving for 5 years. In haemodynamically stable patients with
pulmonary embolism, the following factors may be independent
predictors of inhospital mortality: age over 65 years, bed rest for
longer than 72 hours, chronic cor pulmonale, sinus tachycardia,
tachypnoea.
Pathophysiology
Lung disorders cause pulmonary hypertension by several
mechanisms:
1. Loss of capillary beds (due to bullous changes in COPD or
thrombosis in pulmonary embolism);
2. Vasoconstriction caused by hypoxia, hypercapnia, or both;
3. Increased alveolar pressure (COPD, during mechanical
ventilation);
4. Medial hypertrophy in arterioles (often a response to
pulmonary hypertension due to other mechanisms).

194
 These pathogenetic mechanisms include (1) pulmonary
vasoconstriction due to alveolar hypoxia or blood acidemia, (2)
anatomic compromise of the pulmonary vascular bed secondary to
lung disorders (e.g., emphysema, pulmonary thromboembolism,
interstitial lung disease), (3) increased blood viscosity secondary to
blood disorders (e.g., polycythemia vera, sickle cell disease,
macroglobulinemia), and (4) idiopathic primary pulmonary
hypertension. The result is increased pulmonary arterial pressure.
Causes of cor pulmonale
Acuity: massive pulmonary embolization; injury due to
mechanical ventilation (most commonly for acute respiratory
distress syndrome).
Chronic: COPD, extensive loss of lung tissue due to surgery or
trauma, chronic, unresolved pulmonary emboli, pulmonary veno-
occlusive disorders, scleroderma, pulmonary interstitial fibrosis,
kyphoscoliosis, obesity with alveolar hypoventilation, neuromuscular
disorders involving respiratory muscles; idiopathic alveolar
hypotension.
Symptoms
Physical findings may reflect the underlying lung disease or
pulmonary hypertension, RVH, and RV failure.
On inspection, an increase in chest diameter, labored respiratory
efforts with retractions of the chest wall, distended neck veins with
prominent A or V waves, and cyanosis may be seen. Initially, cor
pulmonale is asymptomatic, although patients usually have
significant symptoms due to the underlying lung disorder (dyspnoea,
exertional fatigue). Later, as RV pressures increase, physical signs
commonly include a left parasternal systolic lift, a loud pulmonic
component of the 2nd heart sound, and murmurs of functional
tricuspid and pulmonic insufficiency. Later, RV gallop rhythm (3rd
and 4th heart sounds) augmented during inspiration, distended
jugular veins (with a dominant A wave unless tricuspid regurgitation
is present), hepatomegaly, and lower-extremity oedema may occur.
Clinical manifestations of cor pulmonale generally are
nonspecific:
1. The patient may complain of fatigue, tachypnoea, exertional
dyspnoea, and cough.
2. Anginal chest pain also can occur and may be due to right

195
ventricular ischaemia (it usually does not respond to nitrates) or
pulmonary artery stretching.
3. Haemoptysis may occur because of rupture of the dilated or
atherosclerotic pulmonary artery.
4. Rarely, the patient may complain of hoarseness due to
compression of the left recurrent laryngeal nerve by a dilated
pulmonary artery.
5. A variety of neurologic symptoms (syncope) may be seen due
to decreased cardiac output and hypoxemia.
6. In advanced stages, passive hepatic congestion secondary to
severe right ventricular failure may lead to anorexia, right upper
quadrant abdominal discomfort, and jaundice.
7. Peripheral oedema.
Diagnosis test
Laboratory investigations are directed toward defining the
potential underlying aetiologies as well as evaluating complications
of cor pulmonale. In specific instances, appropriate laboratory
studies may include the following: hematocrit for polycythemia,
which can be a consequence of underlying lung disease but which
can also increase pulmonary arterial pressure by increasing viscosity;
serum alpha1-antitrypsin, if deficiency is suspected; antinuclear
antibody level for collagen vascular disease, such as scleroderma;
coagulations studies to evaluate hypercoagulability states (e.g.,
serum levels of proteins S and C, antithrombin III, factor V Leyden,
anticardiolipin antibodies, homocysteine).
ECG: right axis deviation, right ventricular hypertrophy, p
pulmonale pattern low-voltage QRS, incomplete or complete right
bundle branch bock.
Chest X-ray: right-sided cardiac enlargement, enlargement of
pulmonary arteries, oligemic peripheral lung fields, right-sided
pleural effusion.
Echocardiography: evidence of abnormal right ventricular
structure and/or function. Evidence of increased pulmonary pressure.
Septal flattening during systole.
CT scan of the chest and cardiac catheterization
Treatment
1. Elimination of the cause is the most important intervention.
Smoking must be stopped, exposure to dust, flames, household

196
smoke, and cold weather is avoided. If there is evidence of
respiratory infection, it should be treated with appropriate antibiotics
after culture and sensitivity.
2. Diuretics for RVF.
3. In pulmonary embolism, thrombolysis (enzymatic dissolution
of the blood clot) is advocated by some authorities if there is
dysfunction of the right ventricle, and is otherwise treated with
anticoagulants. In COPD, long-term oxygen therapy may improve
cor pulmonale. Cor pulmonale may lead to congestive heart failure
(CHF), with worsening of respiration due to pulmonary oedema,
swelling of the legs due to peripheral oedema and painful congestive
hepatomegaly (enlargement of the liver due to tissue damage as
explained in the Complications section. This situation requires
diuretics (to decrease strain on the heart), sometimes nitrates
(to improve blood flow), phosphodiesterase inhibitors such as
sildenafil or tadalafil and occasionally inotropes (to improve heart
contractility). CHF is a negative prognostic indicator in cor
pulmonale. Oxygen is often required to resolve shortness of breath.
Plus, oxygen to the lungs also helps relax the blood vessels and eases
right heart failure. Oxygen is given at the rate of 2 litres per minute.
Excess oxygen can be harmful to patients because hypoxia is the
main stimulus to respiration. If such hypoxia is suddenly corrected
by overflow of oxygen, such stimulus to the respiratory centre is
suddenly withdrawn and respiratory arrest occurs.
4. When wheezing is present, majority of the patients require
bronchodilators. A variety of drugs have been developed to relax the
blood vessels in the lung. Calcium channel blockers are used but
work only in a few cases. Other novel medications that need to be
inhaled or given intravenously include prostacyclin derivatives.
5. Cases of COPD with chronic cor pulmonale present with
secondary polycythemia, if severe, it may increase the blood
viscosity and contribute to pulmonary hypertension. If hematocrit
(PCV) is above 60%, it is better to reduce the red blood cell count by
phlebotomies.
6. Mucolytic agents like bromhexine and carbocisteine help bring
out excessive bronchial secretions more easily by coughing.
7. All patients with pulmonary heart disease are maintained on
blood thinning medications to prevent formation of blood clots.

197
 8. When medical therapy fails, one may require a transplant.
However, since the lungs are damaged, both the heart and lungs need
to be transplanted. With a shortage of donors this therapy is only
done 10–15 times a year in North America.
PULMONARY EMBOLISM

Acute pulmonary embolism (PE) is a major cause of

complications and death associated with surgery, injury, and medical
illnesses, and it may occur after long-distance air travel. Venous
thromboembolism is responsible for up to 15% of all in-hospital
deaths, and it also accounts for 20 to 30% of deaths associated with
pregnancy and delivery in the United States and Europe. Overall, the
annual incidence of pulmonary embolism has been reported to range
between 23 and 69 cases per 100,000 population. Case fatality rates
vary widely depending on the severity of the disease; at an average
case fatality rate within 2 weeks of diagnosis of approximately 11%,
the Surgeon General estimates that venous thromboembolism
accounts for at least 100,000 deaths each year.
Classification of PE:
– massive (shock and/or hypotension (defined as a systolic
blood pressure < 90 mmHg or a pressure drop of ≥ 40 mmHg for
> 15 min if not caused by new-onset arrhythmia, hypovolaemia or
sepsis));
– submassive (markers of RV hypokinesia);
– not massive (RV function is not changed).
Epidemiology
1. The patient may have annual incidence of deep vein
thrombosis. DVT and PE is estimated at 1.0 and 0.5 per 1000 in the
Western world, respectively.
2. DVT and PE are both part of one entity: venous
thromboembolism (VTE).
3. Both acquired and inherited risk factors have been identified.
Risk factors for venous thromboembolism
Primary: antithrombin deficiency, protein C deficiency,
congenital dysfibrinogenemia, factor V Leiden (APC-R),
thrombomodulin, plasminogen deficiency, hyperhomocysteinemia,
dysplasminogenemia, anticardiolipin antibodies, protein S

198
deficiency, excessive plasminogen activator inhibitor, factor XII
deficiency, prothrombin 20210A mutation.
Secondary: trauma/fractures, surgery, stroke, immobilisation,
advanced age, malignancy±chemotherapy, central venous catheters,
obesity, chronic venous insufficiency, heart failure, smoking, long
distance travel, pregnancy/puerperium, oral contraceptives, Crohn’s
disease, lupus anticoagulant, nephrotic syndrome, prosthetic surface,
hyperviscosity (polycythemia, Waldenstrom’s macroglobulinemia),
platelet abnormalities.
Strong predisposing factors: fracture (hip or leg), hip or knee
replacement, major general surgery, major trauma, spinal cord injury.
Moderate predisposing factors:
– arthroscopic knee surgery, central venous lines, chemotherapy,
chronic heart;
– respiratory failure, hormone replacement therapy, malignancy,
oral contraceptive therapy, paralytic stroke, pregnancy/postpartum,
previous VTE, thrombophilia.
Weak predisposing factors: bed rest > 3 days, immobility due to
sitting (e.g., prolonged car or air travel), increasing age, laparoscopic
surgery (e.g., cholecystectomy), obesity, pregnancy/antepartum,
varicose veins.
Pathophysiology
The consequences of acute PE are primarily haemodynamic and
become apparent when > 30–50% of the pulmonary arterial bed is
occluded by thromboemboli. The contribution of reflex or humoral
pulmonary vasoconstriction is less important in humans.

Table 38 – The consequences of pulmonary embolism

Change Haemodynamic consequence

of PE
(A) Changes of pulmonary haemodynamics
Precapillary hypertension Reduced vascular bed
Bronchoconstriction
Arteriolar vasoconstriction
Development of collateral vessels Bronchopulmonary arterial
Anastomoses
Pulmonary arteriovenous shunts
Blood flow changes Flow redistribution

199
 Flow resumption (lysis, etc.)
(B) Changes of systemic circulation and cardiac function
Arterial hypotension
Tachycardia
RV overload and dilation
Table 38 continuation

Change Haemodynamic consequence

of PE
Increased central venous pressure
LV geometrical changes
(C) Changes of coronary circulation
Reduced transcoronary Aortic hypotension
pressure gradient
Right atrial hypertension
Reduced flow per myocardial unit
Relative hypoperfusion of RV
subendocardium
Change Respiratory consequence of PE
(A) Changes of respiratory dynamics
Hyperventilation Pulmonary arterial hypertension
Reduced compliance
Atelectasis
Increased airway resistance Local hypocapnia
Chemical mediators
(B) Changes of alveolar ventilation
Alveolar hyperventilation (hypocapnia, alkalemia) or relative alveolar
hypoventilation
(C) Changes of respiratory mechanics
Reduced dynamic compliance Decreased surfactant
Atelectasis
Bronchoconstriction
(D) Changes of diffusing capacity
Reduced capillary blood volume
Reduced membrane permeability
(E) Changes of ventilation/perfusion ratio

Haemodynamic consequences of PE are directly related to the

size and number of emboli and the pre-existing cardiac and
respiratory status.

200
 Pulmonary infarction is a relatively rare complication.
Diagnosis
Clinical presentation. Clinical signs, symptoms and routine
laboratory tests do not allow the exclusion or confirmation of acute
PE but increase the index of its suspicion.
Table 39 – Signs, symptoms, and findings in suspected PE

PE confirmed PE excluded
(n = 219) (n = 546)
Symptoms
Dyspnoea 80% 59%
Chest pain (pleuritic) 52% 43%
Chest pain (substernal) 12% 8%
Cough 20% 25%
Haemoptysis 11% 7%
Syncope 19% 11%
Signs
Tachypnoea (≥ 20/min) 70% 68%
Tachycardia (> 100/min) 26% 23%
Signs of DVT 15% 10%
Fever (>38.58C) 7% 17%
Cyanosis 11% 9%
Chest X-ray
Atelectasis or infiltrate 49% 45%
Pleural effusion 46% 33%
Pleural-based opacity 23% 10%
(infarction)
Elevated diaphragm 36% 25%
Decreased pulmonary 36% 6%
vascularity
Amputation of hilar 36% 1%
artery
Blood gases
Hypoxaemia 75% 81%
Electrocardiogram
Right ventricular 50% 12%
overload

201
 Clinical evaluation makes it possible to classify patients into
probability categories corresponding to an increasing prevalence of
PE, whether assessed by implicit clinical judgement or by a validated
prediction rule.
Table 40 – The most frequently used clinical prediction rule is the
Canadian rule, by Wells et al. (2000) and revised Geneva score
(2006)

Revised Geneva score Wells score

Variable Point Variable Point
Predisposing factor +1 Predisposing factor
Age > 65 years +3
Previous DVT or PE +2 Previous DVT or PE +1.5
Surgery or fracture +2 Recent surgery or +1.5
within 1 month immobilization
Active malignancy
Symptom Symptom
Unilateral lower limb +3
pain
Haemoptysis +2 Haemoptysis +1
Clinical sign Clinical sign
Heart rate Heart rate
75–94 beats/min +3 >100 beats/min +1.5
≥ 95 beats/min +5
Pain on lower limb deep +4 Clinical signs of DVT +3
vein at palpation and
unilateral oedema
Clinical judgement
Alternative diagnosis less +3
likely than PE
Clinical probability Total Clinical probability Total
(3 levels)
Low 0–3 Low 0–1
Intermediate 4–10 Intermediate 2–6
High ≥ 11 High ≥7
Clinical probability
(2 levels)
PE unlikely 0–4
PE likely >4

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 D-dimer
Plasma D-dimer, a degradation product of crosslinked fibrin.
D-dimer levels are elevated in plasma in the presence of an acute clot
because of simultaneous activation of coagulation and fibrinolysis.
The specificity of fibrin for VTE is poor because fibrin is produced
in a wide variety of conditions, such as cancer, inflammation,
infection, necrosis, dissection of the aorta, and the positive predictive
value (PPV) of D-dimer is low. Therefore, D-dimer is not useful for
confirming PE. A negative D-dimer result in a highly sensitive assay
safely excludes PE in patients with a low or moderate clinical
probability. D-dimer is most useful in emergency ward patients. In
elderly or inpatients, D-dimer retains a high negative predictive
value, but it is normal (D-dimer < 500 mg/l) in less than 10% of
patients.
Lung scintigraphy
Approximately 25% of patients with suspected PE will have the
diagnosis refuted by a normal perfusion lung scan and anticoagulants
may be safely withheld.
Around 25% of patients with suspected PE will have a high
probability lung scan and anticoagulant therapy may be instituted.
The remaining patients will require further diagnostic tests as a
part of a wider diagnostic strategy.
Pulmonary angiography
The safety of pulmonary angiography has improved over the past
decade.
Pulmonary angiography is the reference method, but should be
reserved for patients in whom non-invasive diagnostic tests remain
indeterminate.
It is safe to withhold anticoagulant therapy in patients with
suspected PE and normal angiogram.
Indirect signs of PE on angiography have not been validated.
Spiral computed tomography
Spiral CT is more accurate in the demonstration of central or
lobar PE than segmental PE.
A normal sCT does not rule out isolated subsegmental PE.
The safety of withholding anticoagulant therapy in patients with a
normal sCT angiogram needs further confirmation.
Echocardiography

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 Echocardiography is useful in patients with suspected massive
PE.
Whether echocardiography may identify patients who could
benefit from thrombolytic therapy in the absence of systemic
hypotension or shock remains to be confirmed in prospective studies.
Echocardiographic criteria: RV hypokinesis and dilatation, RVD,
RV > 30 mm or tricuspid insufficiency > 2.8 m/s. At least one of the
following: RV > 30 mm or RV/LV > 1; paradox septal systolic
motion, acceleration time of right ventricular ejection (AcT) < 90 ms
or tricuspid insufficiency peak gradient (TIPG) > 30 mmHg.
Detection of deep vein thrombosis
Ultrasonography shows a proximal DVT in 50% of patients with
proven PE.
A normal ultrasonography exam of the leg veins does not rule out
PE.
Serial leg testing may replace angiography in patients with non-
diagnostic lung scan findings. However, its practical use seems
limited.
Diagnostic strategies
Principal markers useful for risk stratification in acute
pulmonary embolism
1. Clinical markers: shock; hypotension (defined as a systolic
blood pressure < 90 mmHg or a pressure drop of ≥ 40 mmHg for >
15 min if not caused by new-onset arrhythmia, hypovolaemia or
sepsis).
2. Markers of RV dysfunction: RV dilatation, hypokinesis or
pressure overload on echocardiography; RV dilatation on spiral
computed tomography; brain natriuretic peptide (BNP) or
N-terminal-proBNP elevation; elevated right heart pressure at right
heart catheterization (RHC).
3. Markers of myocardial injury: cardiac troponin T or I positive.
Suspected high-risk PE
In high-risk PE, as indicated by the presence of shock or
hypotension, mergency CT or bedside echocardiography (depending
on availability and clinical circumstances) is recommended for
diagnostic purposes.
Suspected non-high-risk PE
Low clinical probability:

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 – normal D-dimer level using either a highly or moderately
sensitive assay excludes PE (I, A);
– normal perfusion lung scintigraphy excludes PE (I, A);
– non-diagnostic (low or intermediate probability) ventilation-
perfusion scintigraphy (V/Q scan) may exclude PE (IIa, B);
particularly when combined with negative proximal CUS (IA);
– negative multidetector coputer tomography (MDCT) safely
excludes PE (I, A);
– negative single-detector CT excludes PE when combined with
negative proximal compression venous ultrasonography (CUS) (I,
A);
– high-probability V/Q scan may confirm PE (IIa, B);
– further testing may be considered in selected patients to
confirm PE (IIb, B);
– CUS showing a proximal DVT confirms PE (I, B);
– if CUS shows only a distal DVT, further testing should be
considered to confirm PE (IIa, B);
– SDCT or MDCT showing a segmental or more proximal
thrombus confirms PE (I, A);
– further testing should be considered to confirm PE if SDCT or
MDCT shows only subsegmental clots (IIa, B).
Intermediate clinical probability:
– normal D-dimer level using a highly sensitive assay excludes
PE (I, A);
– further testing should be considered if D-dimer level is normal
when using a less sensitive assay (IIa, B);
– normal perfusion lung scintigraphy excludes PE (I, A);
– in case of a non-diagnostic V/Q scan, further testing is
recommended to exclude or confirm PE (I, B);
– negative MDCT excludes PE (I, A);
– negative SDCT only excludes PE when combined with
negative proximal CUS (I, A);
– high-probability ventilation-perfusion lung scintigraphy
confirms PE (I, A);
– CUS showing a proximal DVT confirms PE (I, B);
– if CUS shows only a distal DVT, further testing should be
considered (IIa, B);

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 – SDCT or MDCT showing a segmental or more proximal
thrombus confirms PE (I, A);
– further testing may be considered in case of subsegmental
clots to confirm PE (IIb, B).
High clinical probability:
– D-dimer measurement is not recommended in high clinical
probability patients as a normal result does not safely exclude PE
even when using a highly sensitive assay (III, C);
– in patients with a negative CT, further tests should be
considered in selected patients to exclude PE (IIa, B);
– high-probability ventilation-perfusion lung scintigraphy
confirms PE (I, A);
– CUS showing a proximal DVT confirms PE (I, B);
– if CUS shows only a distal DVT, further testing should be
considered (IIb, B);
– SDCT or MDCT showing a segmental or more proximal
thrombus confirms PE (I, A);
– further testing may be considered where there are
subsegmental clots, to confirm PE (IIb, B).

Treatment
Haemodynamic and respiratory support:
1. Haemodynamic and respiratory support is necessary in
patients with suspected or confirmed PE presenting with shock or
hypotension.
2. Dobutamine and dopamine may be used in patients with PE,
low cardiac index and normal blood pressure.
3. Vasopressive drugs may be used in hypotensive patients with PE.
4. Monitored oxygen therapy is beneficial in patients with PE
and hypoxaemia.
5. The usefulness of fluid challenge is controversial and should
not exceed 500 ml.
Thrombolytic treatment:
1. Thrombolytic therapy is indicated in patients with massive PE.
Thrombolytic therapy is the first-line treatment in patients with high-
risk PE presenting with cardiogenic shock and/or persistent arterial
hypotension, with very few absolute contraindications.
2. Routine use of thrombolysis in non-high-risk patients is not

206
recommended, but may be considered in selected patients with
intermediate-risk PE and after thorough consideration of conditions
increasing the risk of bleeding.
3. Thrombolytic therapy should be not used in patients with low-
risk PE.
Table 41 – Approved thrombolytic regimens for pulmonary
embolism

Streptokinase 250 000 IU as a loading dose over 30 min, followed by

100 000 IU/h over 12–24 h.
Accelerated regimen: 1.5 million IU over 2 h
Urokinase 4400 IU/kg as a loading dose over 10 min, followed by
4400 IU/kg/h over 12–24 h.
Accelerated regimen: 3 million IU over 2 h
rtPA 100 mg over 2 h
or 0.6 mg/kg over 15 min (maximum dose 50 mg)
rtPA = recombinant tissue plasminogen activator

Table 42 – Contraindications to fibrinolytic therapy

Absolute contraindication Relative contraindication

Haemorrhagic stroke or stroke of
unknown origin at any time
Ischaemic stroke in preceding
6 months
Central nervous system damage
or neoplasms
Recent major trauma/surgery/
head injury (within preceding
3weeks)
Gastrointestinal bleeding within
the last month
Known bleeding
Transient ischaemic attack in
preceding 6 months
Oral anticoagulant therapy
Pregnancy or within 1 week post
partum
Noncompressible punctures
Refractory hypertension (systolic
blood pressure > 180 mmHg)
Traumatic resuscitation
Advanced liver disease
Infective endocarditis
Active peptic ulcer

Surgical embolectomy

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 With current surgical techniques pulmonary embolectomy is a
valuable therapeutic option in patients with high-risk PE in whom
thrombolysis is absolutely contraindicated or has failed.
Percutaneous catheter embolectomy and fragmentation
Catheter embolectomy or fragmentation of proximal pulmonary
arterial clots may be considered as an alternative to surgical
treatment in high-risk PE patients when thrombolysis is absolutely
contraindicated or has failed.
Anticoagulant therapy
Anticoagulation with unfractionated heparin, low-molecular-
weight heparin (LMWH) or fondaparinux should be initiated without
delay in patients with confirmed PE and those with a high or
intermediate clinical probability of PE while the diagnostic workup
is still ongoing. Except for patients at high risk of bleeding and those
with severe renal dysfunction, subcutaneous LMWH or fondaparinux
rather then intravenous unfractionated heparin should be considered
for initial treatment.

Table 43 – Adjustment of intravenous unfractionated heparin

dosage based on the activated partial thromboplastin time

Activated partial Change of dosage

thromboplastin time
< 35 s (< 1.2 times control)
35–45 s (1.2–1.5 times control)
46–70 s (1.5–2.3 times control)
71–90 s (2.3–3.0 times control)
> 90 s (> 3.0 times control)
80 U/kg bolus; increase infusion
rate by 4 U/kg/h
40 U/kg bolus; increase infusion
rate by 2 U/kg/h
No change
Reduce infusion rate by 2 U/kg/h
Stop infusion for 1 h, then reduce
infusion rate by 3 U/kg/h

Table 44 – Subcutaneous regimens of low molecularweight

heparins and fondaparinux approved for the treatment of
pulmonary embolism

Dose Interval
Enoxaparin 1.0 mg/kg Every 12 h,

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 or 1.5 mg/kg once daily
Tinzaparin 175 U/kg Once daily
Fondaparinux 5 mg (body weight < 50 kg); Once daily
7.5 mg (body weight 50–100 kg);
10 mg (body weight >100 kg)
Therapeutic strategies
High-risk pulmonary embolism
1. Anticoagulation with unfractionated heparin should be
initiated without delay in patients with high-risk PE (I, A).
2. Systemic hypotension should be corrected to prevent
progression of RV failure and death due to PE (I, C).
3. Vasopressive drugs are recommended for hypotensive patients
with PE (I, C).
4. Dobutamine and dopamine may be used in patients with PE,
low cardiac output and normal blood pressure (IIa, B).
5. Aggressive fluid challenge is not recommended (III, B).
6. Oxygen should be administered in patients with hypoxaemia
(I, C).
7. Thrombolytic therapy should be used in patients with high-risk
PE presenting with cardiogenic shock and/or persistent arterial
hypotension (I, A).
8. Surgical pulmonary embolectomy is a recommended
therapeutic alternative in patients with high-risk PE in whom
thrombolysis is absolutely contraindicated or has failed (I, C).
9. Catheter embolectomy or fragmentation of proximal
pulmonary arterial clots may be considered as an alternative to
surgical treatment in high-risk patients when thrombolysis is
absolutely contraindicated or has failed (IIb, C).
Non-high-risk pulmonary embolism
1. Anticoagulation should be initiated without delay in patients
with high or intermediate clinical probability of PE while diagnostic
workup is still ongoing (I, C).
2. Use of LMWH or fondaparinux is the recommended form of
initial treatment for most patients with non-high-risk PE (I, A).
3. In patients at high risk of bleeding and in those with severe
renal dysfunction, unfractionated heparin with an aPTT target range
of 1.5–2.5 times normal is a recommended form of initial
treatment (I, C).

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 4. Initial treatment with unfractionated heparin, LMWH or
fondaparinux should be continued for at least 5 days and (I, A) may
be replaced by vitamin K antagonists (VKA) only after achieving
target INR levels for at least 2 consecutive days (I, C).
5. Routine use of thrombolysis in non-high-risk PE patients is
not recommended, but it may be considered in selected patients with
intermediate-risk PE (IIb, B).
6. Thrombolytic therapy should be not used in patients with low-
risk PE (III, B).
Long-term anticoagulation and secondary prophylaxis
1. For patients with PE secondary to a transient (reversible) risk
factor, treatment with a VKA is recommended for 3 months (I, A).
2. For patients with unprovoked PE, treatment with a VKA is
recommended for at least 3 months (I, A).
3. Patients with a first episode of unprovoked PE and low risk of
bleeding, and in whom stable anticoagulation can be achieved, may
be considered for long-term oral anticoagulation (IIb, B).
4. For patients with a second episode of unprovoked PE, long-
term treatment is recommended (I, A).
5. In patients who receive long-term anticoagulant treatment, the
risk/benefit ratio of continuing such treatment should be reassessed
at regular intervals (I, C).
6. For patients with PE and cancer, LMWH should be considered
for the first 3–6 months (IIa, B) after this period, anticoagulant
therapy with VKA or LMWH should be continued indefinitely or
until the cancer is considered cured (I, C).
7. In patients with PE, the dose of VKA should be adjusted to
maintain a target INR of 2.5 (range 2.0–3.0) regardless of treatment
duration (I, A).
Venous filters
Recommendations:
– IVC filters may be used when there are absolute
contraindications to anticoagulation and a high risk of VTE
recurrence (IIb, B);
– the routine use of IVC filters in patients with PE is not
recommended (III, B).

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 NEUROCIRCULATORY DYSTONIA

As it is known, neurocirculatory dystonia (NCD) is defined as a

condition characterized by disturbance of the normal activity of the
autonomous nervous system due to the change in the tone of its
sympathetic and parasympathetic parts, and prevalence of the ton of
one of those.
Causes
The NCD, vasoneurosis has the functional nature. Disorders of
neuroendocrinal regulation of cardiovascular system activity are
characteristic for it. At teenagers and young men NCD is caused by a
mismatch of physical development and degree of maturity of the
excitatory-endocrine apparatus more often. At other age dystonia
development can be promoted by psychological attrition in an
outcome of acute and chronic infectious diseases and intoxications,
by sleep loss, overfatigue, and irregular diets, to sexual life, physical
activity (lowered or too intensive).
The causes of dystonia are not yet known or understood;
however, they are categorized as follows on the theoretical basis:
Primary dystonia is suspected to be caused by a pathology of the
central nervous system, likely originating in those parts of the brain
concerned with motor function, such as the basal ganglia, and the
GABA (gamma-aminobutyric acid) producing Purkinje neurons. The
precise cause of primary dystonia is unknown. In many cases it may
involve some genetic predisposition towards the disorder combined
with environmental conditions.
Secondary dystonia refers to dystonia brought on by some
identified cause, usually involving brain damage, or by some
unidentified cause such as chemical imbalance. Some cases of
(particularly focal) dystonia are brought on after trauma, are induced
by certain drugs (tardive dystonia), or may be the result of diseases
of the nervous system such as Wilson's disease.
Environmental and task-related factors are suspected to trigger

211
the development of focal dystonias because they appear
disproportionately in individuals who perform high precision hand
movements such as musicians, engineers, architects, and artists. At
adults disturbance of regulatory functions of the vegetative nervous
system sometimes proceeds in the form of attacks – vegetative crises.
Classification
Types of dystonia:
– generalized;
– focal;
– segmental;
– intermediate;
– acute dystonic reaction.
Generalized dystonias:
– normal birth history and milestones;
– autosomal dominant;
– childhood onset;
– starts in lower limbs and spreads upwards;
– also known as “idiopathic torsion dystonia” (old terminology
“dystonia musculorum deformans”).
Focal dystonias
Symptoms vary according to the kind of dystonia involved. In
most cases, dystonia tends to lead to abnormal posturing, particularly
on movement. Many sufferers have continuous pain, cramping and
relentless muscle spasms due to involuntary muscle movements.
Early symptoms may include loss of precision muscle coordination
(sometimes first manifested in declining penmanship, frequent small
injuries to the hands, dropped items and a noticeable increase in
dropped or chipped dishes), cramping pain with sustained use and
trembling. Significant muscle pain and cramping may result from
very minor exertions like holding a book and turning pages. It may
become difficult to find a comfortable position for arms and legs
with even the minor exertions associated with holding arms crossed
causing significant pain similar to restless leg syndrome.
Affected persons may notice trembling in the diaphragm while
breathing, or the need to place hands in pockets, under legs while
sitting or under pillows while sleeping to keep them still and to
reduce pain. Trembling in the jaw may be felt and heard while lying
down, and the constant movement to avoid pain may result in the

212
grinding and wearing down of teeth. The voice may crack frequently
or become harsh, triggering frequent throat clearing. Swallowing can
become difficult and accompanied by painful cramping.
Electrical sensors (EMG) inserted into affected muscle groups,
while painful, can provide a definitive diagnosis by showing
pulsating nerve signals being transmitted to the muscles even when
they are at rest. The brain appears to signal portions of fibers within
the affected muscle groups at a firing speed of about 10 Hz causing
them to pulsate, tremble and contort. When called upon to perform
an intentional activity, the muscles fatigue very quickly and some
portions of the muscle groups do not respond (causing weakness)
while other portions over-respond or become rigid (causing micro-
tears under load). The symptoms worsen significantly with use,
especially in the case of focal dystonia, and a “mirror effect” is often
observed in other body parts: use of the right hand may cause pain
and cramping in that hand as well as in the other hand and legs that
were not being used. Stress, anxiety, lack of sleep, sustained use and
cold temperatures can worsen symptoms.
Direct symptoms may be accompanied by secondary effects of
the continuous muscle and brain activity, including disturbed sleep
patterns, exhaustion, mood swings, mental stress, difficulty
concentrating, blurred vision, digestive problems and short temper.
People with dystonia may also become depressed and find great
difficulty adapting their activities and livelihood to a progressing
disability. Side effects from treatment and medications can also
present challenges in normal activities.
In some cases, symptoms may progress and then plateau for
years, or stop progressing entirely. The progression may be delayed
by treatment or adaptive lifestyle changes, while forced continued
use may make symptoms progress more rapidly. In others, the
symptoms may progress to total disability, making some of the more
risky forms of treatment worth considering.
An accurate diagnosis may be difficult because of the way the
disorder manifests itself. Sufferers may be diagnosed as having
similar and perhaps related disorders including Parkinson's disease,
essential tremor, carpal tunnel syndrome, TMD, Tourette's
syndrome, or other neuromuscular movement disorders.

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 These are the most common dystonias and they tend to be
classified as follows:
1. Cervical dystonia (spasmodic torticollis) affects the muscles of
the neck, causing the head to rotate to one side, to pull down towards
the chest, or back, or a combination of these postures.
2. Blepharospasm affects the muscles around the eyes. The
sufferer experiences rapid blinking of the eyes or even their forced
closure causing effective blindness.
3. Oculogyric crisis is an extreme and sustained (usually) upward
deviation of the eyes often with convergence causing diplopia. It is
frequently associated with backwards and lateral flexion of the neck
and either widely opened mouth or jaw clenching. Frequently it is a
result of antiemetics such as neuroleptics or metoclopramide.
4. Oromandibular dystonia affects the muscles of the jaw and
tongue, causing distortions of the mouth and tongue.
5. Spasmodic dysphonia/laryngeal dystonia affects muscles of
the larynx, causing the voice to sound broken or reducing it to a
whisper.
6. Focal hand dystonia (also known as musician's or writer's
cramp) affects a single muscle or small group of muscles in the hand.
It interferes with activities such as writing or playing a musical
instrument by causing involuntary muscular contractions. The
condition is sometimes “task-specific”, meaning that it is generally
only apparent during certain activities. Focal hand dystonia is
neurological in origin, and is not due to normal fatigue. The loss of
precise muscle control and continuous unintentional movement
results in painful cramping and abnormal positioning that makes
continued use of the affected body parts impossible.
The combination of blepharospasmodic contractions and
oromandibular dystonia is called cranial dystonia or Meige's
syndrome. There is a group called myoclonus dystonia or myoclonic
dystonia, where some cases are hereditary and have been associated
with a missense mutation in the dopamin-D2 receptor. Some of these
cases have responded remarkably to alcohol.
Segmental dystonias affect two adjoining parts of the body:
1. Hemidystonia affects arm and leg on one side of the body.
2. Multifocal dystonia affects many different parts of the body.

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 3. Generalized dystonia affects most of the body, frequently
involving legs and back.
Treatment
Treatment has been limited to minimizing the symptoms of the
disorder as there is no successful treatment for its cause. Reducing
the types of movements that trigger or worsen dystonic symptoms
provides some relief, as does reducing stress, getting plenty of rest,
moderate exercise, and relaxation techniques. Various treatments
focus on sedating brain functions or blocking nerve communications
with the muscles via drugs, neurosuppression or denervation. All
current treatments have negative side effects and risks.
The prevention of a vascular dystonia should begin with
tempering at children's and youthful age, the organization of a
rational regimen of work and rest. It is necessary to avoid the
excitatory overstrains, at disease carefully to observe a regimen and
other appointments of the doctor.
Mainly not medicament methods: normalization of the mode of
life, tempering procedures, employment by physical culture and
some kinds of sports (swimming, track, and field athletics). The
physiotherapy, a balneotherapy, sanatorium treatment is used. At
irritability, sleep disorders – preparations of valeriana, leonurus,
valocordin, sometimes tranquilizers. At a hypotensive type –
physiotherapy exercises, belloidum, caffeine, phethanolum. At a
hypertensive type – beta adrenoblockers, rauwolfia preparations. The
balanced regimen of day, sleep – the best rest (8–10 hours).
Adequate physical activity. Only teenagers from a BP 140–90
and above are engaged in preparatory sports bunch, the others –
basically. Good effect is given by employment pool render, run, skis,
aerobics, dances, skis. It is possible to use a bicycle.
A diet containing all necessary ingredients, vitamin-rich, the
products keeping salts of a potassium – a potato, eggplants, cabbage,
prunes, apricots, raisin, a fig, a green peas, parsley, tomatoes, a
rhubarb, a beet, fennel, a string bean, a dock are shown. A part of
animal adepses to change vegetative (corn, olive). With the raised BP
– the products keeping salts of magnesium buckwheat, oat, wheaten
groats, nuts, a soya, a string bean, carrots, a dogrose are necessary.
Patients need to exclude from pickle nutrition, marinades, to confine
salt to 4–5g. Strong tea, coffee, and chocolate are contraindicative.

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 Psychotherapy: relaxation methods, a combination of autogenic
training and direct suggestion, the permission of a psychologic
problem. The purpose of psychotherapy is to normalise the attitude
of the person to associates, putting off of psychologic intensity.
Massage of a head, collar region С1–С4, backs. Duration of sessions
of 8–10–15 minutes, a course 18–20 of procedures. With the lowered
BP massage of a trunk, extremities brushes.
Phytotherapy: valeriana, viburnum red, a peony, leonurus, a
basis a sedation, possess the same action and the soft diuretic a
quince, a birch mushroom, a poppy, almonds, carrots, mint, a
parsnip, a liquorice. In the absence of BP normalisation add agents
about reserpinum similar and beta adrenoblocking action: a running
myrtle, a butter-bur, a vervain, a dragonhead, a magnolia, rauwolfia,
a black mountain ash, an arnica, a Labrador tea, the shepherd's ascus.
In the absence of effect from the described actions it is necessary
to pass to medicamental therapy.
Treatment of a NCD – complex with application of medicines and
physiotherapeutic procedures, is spent on doctor's orders. With a
view of improvement of patients physiotherapy exercises, country
walks, tourism, sanatorium treatment, the normalisation of a mode of
life tempering procedures are widely applied. At irritability, sleep
disorders – preparations of valeriana, leonurus, valocordin,
sometimes tranquilizers. At hypotensive type – physiotherapy
exercises, belloidum, caffeine, phethanolum. At hypertensive type –
beta adrenoblockers, rauwolfia preparations.
Physicians may prescribe a series of different medications on a
trial basis in an effort to find a combination that is effective for a
specific patient. Not all patients will respond well to the same
medications. Drugs that have had positive results in some patients
include antiparkinsonian agents trihexyphenidyl, trihexyphenidyl-
hydrochloride (pakisonal), muscle relaxers (valium), keppra, and
beta-blockers including “off-label” uses for some blood pressure
medications.
Drugs such as anticholinergics, which act as inhibitors of the
neurotransmitter acetylcholine, may provide some relief.
Clonazepam, an antiseizure medicine, is also sometimes prescribed.
However, for most sufferers their effects are limited and side effects

216
like mental confusion, sedation, mood swings, and short-term
memory loss occur.
Botulinum toxin injections into affected muscles have proved
quite successful in providing some relief for around 3–6 months,
depending on the kind of dystonia. Botox injections have the
advantage of ready availability (the same form is used for cosmetic
surgery) and the effects are not permanent. There is a risk of
temporary paralysis of the muscles being injected or the leaking of
the toxin into adjacent muscle groups causing weakness or paralysis
in them. The injections have to be repeated as the effects wear off
and around 15% of recipients will develop immunity to the toxin.
There is a Type A and Type B toxin approved for treatment of
dystonia; often those that develop resistance to Type A may be able
to use Type B. Surgery, such as the denervation of selected muscles,
may also provide some relief; however, the destruction of nerves in
the limbs or brain is not reversible and should only be considered in
the most extreme cases. Recently, the procedure of deep brain
stimulation has proven successful in a number of cases of severe
generalised dystonia. DBS as treatment for medication-refractory
dystonia, on the other hand, may increase the risk of suicide in
patients. Reference data of patients without DBS therapy are lacking.
One type of dystonia, dopamine-responsive dystonia, can be
completely treated with regular doses of L-DOPA in a form such as
Sinemet (carbidopa/levodopa). Although this doesn't remove the
condition, it does alleviate the symptoms most of the time.
In the case of Oculogyric crisis, benadryl may be administered
with excellent results. Symptoms subside in a matter of minutes.
A baclofen pump has been used to treat patients of all ages
exhibiting muscle spasticity along with dystonia. The pump delivers
baclofen via a catheter to the thecal space surrounding the spinal
cord. The pump itself is placed in the abdomen. It can be refilled
periodically by access through the skin.
Physical therapy can sometimes help with focal dystonia. A
structured set of exercises is tailored to help the affected area.
Some focal dystonias have been proven treatable through
movement retraining in the Taubman approach, particularly in the
case of musicians. However other focal dystonias may not respond
and may even be made worse by this treatment.

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 In the case of acute dystonic reaction, diphenhydramine
(benadryl) 25–50 mg IV push is often used in the prehospital and
emergency department setting to relieve to muscle contractions
associated with dystonic reactions. Although antihistamine,
diphenhydramine also possesses some anticholinergic properties.
Although diphenhydramine (benadryl) is used to treat this reaction, it
is not an allergic reaction to the medication. The patient should be
informed of this distinction.
QUESTIONS

Тopic 1. Arterial hypertension

1. A 50-year-old male with a history of diabetes mellitus

presents for a routine clinic visit. He has been feeling well and has
no complaints. He has been exercising regularly and dieting as
instructed for his diabetes. His medications include metformin and
glypizide. His blood pressure is 180/90, heart rate – 70, and
respirations – 20. His physical examination is normal. Which of the
following is the most appropriate management at this time?
A. Continue diet and lifestyle modifications only.
B. Start lisinopril and hydrochlorothiazide.
C. Start amlodipine.
D. Start hydrochlorothiazide.
E. Start spironolactone.

2. A 29-year-old female with a history of hypertension presents

for a routine clinic visit without any physical complaints. Her
blood pressure is 180/100 which she admits it has been at home as
well. Physical examination reveals normal lung sounds, regular
rhythm with hyperdynamic apical impulse and S4 heart sound,
abdominal bruit is heard, there is no lower extremity oedema. Her
pulses are 2+ in upper and lower extremities. Her blood pressure
medications include lisinopril, amlodipine, atenolol,
hydrochlorothiazide, hydralazine, and clonidine which she states
she takes regularly. Screening for secondary causes of
hypertension thus far has been negative which has included
electrolytes, a complete blood count, creatinine, urinary and serum
catecholamines, AM cortisol levels, renin/aldosterone levels,

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thyroid stimulating hormone levels, and dexamethasone
suppression test. Which of the following tests should be ordered
next?
A. CT aortogram of the thoracic aorta.
B. Serum erythropoietin levels.
C. CT scan of the adrenal glands.
D. Magnetic resonance angiography of the renal arteries.

Topic 2. Atherosclerosis

3. A 55-year-old male with a history of hypertension has the

following fasting lipid profile: total cholesterol 240 mg/dL, LDL
cholesterol 98 mg/dL, HDL cholesterol 35 mg/dL, triglycerides
140 mg/dL. Which of the following is the most appropriate treatment?
A. Diet and lifestyle modifications.
B. Start niacin.
C. Start gemfibrozil.
D. Start HMG-CoA reductase inhibitor.
E. No therapy is needed.

Topic 3. Ischaemic heart disease

4. A 72-year-old female with a history of diabetes mellitus and

no history of heart disease presents to the emergency department
with chest pains at rest intermittently for the past 4 hours. She has
associated shortness of breath and diaphoresis. Her heart rate is 59,
blood pressure – 134/72, respiratory rate – 20, and oxygen saturation
is 95% on room air. Physical examination reveals normal lung
sounds and S4 gallop. Her ECG reveals ST segment depression in
leads V1 to V3. She is given aspirin immediately. Her troponin
levels remain negative. She is currently chest pain free. Which of the
following is the correct diagnosis?
A. Stable angina.
B. Unstable angina.
C. Non-ST segment elevation myocardial infarction.
D. ST segment elevation myocardial infarction.

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 5. A 48-year-old male with a history of hypertension presents to
the emergency room with chest pain. He is diaphoretic and also
complaining of shotness of breath. His temperature is 37.1 ºC, blood
pressure – 120/82, heart rate – 82, and respirations – 20. His physical
examination is significant for S4 heart sound. ECG reveals an
inferior wall ST elevation myocardial infarction and appropriate
treatment is undertaken. He is discharged home and was doing well.
Two months later he develops acute chest pain worse with laying flat
radiating to his left neck. He returns to his cardiologist and his
temperature is 38.5 C, blood pressure – 118/82, heart rate – 80, and
respirations – 18. Physical examination is normal. ECG reveals ST
segment elevation in leads I, II, III, aVF, aVL, and V1-V4 as well as
PR depression in lead II. What is the most likely diagnosis at this
time?
A. Left ventricular rupture.
B. Anterior myocardial infarction.
C. Dressler's syndrome.
D. Early repolarization.

6. A 58-year-old male with a history of hypertension and

diabetes presents to the emergency room with chest pain at rest. He
states the pain is substernal, pressure-like, and associated with
diaphoresis and shortness of breath. He is afebrile, blood pressure is
110/70, heart rate – 70, and respirations – 18. Physical examination
reveals normal lung sounds, normal jugular venous pressure, and S4
heart sound. Laboratory studuies are initially normal. His ECG is
below. What is the appropriate diagnosis?

Figure 12 – Patient’s ECG

A. Unstable angina with anterior ischaemia.

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 B. Posterior wall myocardial infarction.
C. Inferior wall myocardial infarction.
D. Noncardiac chest pain.

Тopic 4. Congenital heart disease

7. A 18-year-old male with no significant past medical history

presents to his primary care physcician for a routine physical
examination. He has no physical complaints. His blood pressure is
115/85, heart rate – 80, respirations – 12, and he is afebrile. His
physical examination reveals normal lung sounds, V/VI holosystolic
murmur with a thrill at the left lower sternal border and no change in
intensity with inspiration, no gallops or extra heart sounds, and
normal jugular venous pressures. His ECG and laboratory studies are
normal. What is his most likely diagnosis?
A. Mitral regurgitation.
B. Patent ductus arteriosis.
C. Tricuspid regurgitation.
D. Ventricular septal defect.

8. A 36-year-old female with no past medical history presents to

her primary care office a complaint of chest pains for the past few
months. She states that intermittently she has a feeling that she is
going to die and develops severe chest pains and palpitations. The
pain is substernal, pressure-like, and radiating to her left arm. It can
last for minutes or hours at a time. Her blood pressure is 120/80,
heart rate – 80, and respirations – 20. Physical examination reveals
normal lung sounds, no murmurs, and a mid-systolic click that
moves to early systole with standing from a squatting position. Her
ECG is normal. Which of the following is the most likely diagnosis?
A. Mitral valve regurgitation.
B. Myocardial ischaemia.
C. Mitral valve prolapse.
D. Mitral valve stenosis.

Тopic 5. Heart valvular disease

9. A 27-year-old female with no significant past medical history

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is 40 weeks pregnant and labor has just begun. She begins to
complain of shortness of breath, which worsens throughout delivery
to the point of requiring intubation. She had never previously
complained of any dyspnoea or chest pains. Her temperature is
37.0 ºC, blood pressure – 90/50, heart rate – 130, respirations – 26,
and oxygen saturation – 100% on 60% FiO2 on the ventilator.
Physical examination reveals diffuse pulmonary rales, II/IV early
diastolic murmur, and no lower extremity oedema. Laboratory
studies are normal. ECG shows sinus tachycardia and left atrial
enlargement. Her chest X-ray has significant pulmonary oedema.
Which of the following is the most likely diagnosis?
A. Aortic dissection.
B. Coronary artery dissection.
C. Aortic valve stenosis.
D. Mitral valve stenosis.
10. A 27-year-old female with no significant past medical history
is 40 weeks pregnant and labor has just begun. She begins to
complain of shortness of breath, which worsens throughout delivery
to the point of requiring intubation. She had never previously
complained of any dyspnoea or chest pains. Her temperature is
37.0 ºC, blood pressure – 90/50, heart rate – 130, respirations – 26,
and oxygen saturation – 100% on 60% FiO2 on the ventilator.
Physical examination reveals diffuse pulmonary rales, II/IV early
diastolic murmur, and no lower extremity oedema. Laboratory
studies are normal. ECG shows sinus tachycardia and left atrial
enlargement. Her chest X-ray has significant pulmonary oedema.
Which of the following is the most likely diagnosis?
A. Aortic dissection.
B. Coronary artery dissection.
C. Mitral valve stenosis.
D. Aortic valve stenosis.
Тopic 6. Infective endocarditis
11. A 62-year-old male with a history of mitral valve prolapse,
rhematoid arthritis, and colon cancer presents to the emergency room
with increased dyspnoea on exertion, lower extremity swelling, and
fevers slowly worsning over the past month. His temperature is

222
38.0 ºC, blood pressure – 95/65, heart rate – 80, respirations – 20,
and oxygen saturation – 92% on room air. Physical examination
reveals normal breath sounds, II/VI holosystolic murmur at the apex,
and 1+ bilateral lower extremity pitting oedema. Laboratory studies
show a WBC count of 20 thousand and an ESR of 100.
Echocardiogram reveals 8 mm mobile vegitation on the anterior
leaflet of the mitral valve. Which of the following is the most likely
pathogen?
A. Staphylococcus aureus.
B. Pseudomonas auriginosa.
C. Candida albicans.
D. Streptococcus bovis.

Тopic 7. Мyocarditis and cardiomyopathy

12. A 17-year-old male with no significant past medical history

pasess out while running. He states that he was feeling a little dizzy
prior to the event, but no chest pains or palpitations. His blood
pressure is 115/85, heart rate – 80, respirations – 12, and he is
afebrile. His physical examination reveals normal lung sounds, II/VI
mid-sytolic creshendo-decreshndo murmur is heard at the right upper
sternal border which increases in intensity with Valsalva, S4 heart
sound is also present. Laboratory studies are normal. What is his
most likely diagnosis?
A. Congenital pulmonic valve stenosis.
B. Hypertrophic obstructive cardiomyopathy.
C. Congential aortic valve stenosis.
D. Commotio cordis.
E. Atrial setpal defect.

Тopic 8. Pericarditis

13. A 71-year-old female with a history of tobacco use, diabetes

mellitus, rheumatoid arthritis, breast cancer is seen by her primary
care physician for a routine follow-up visit. She has been feeling
gerenally weak. She can only walk about 1/2 block before getting
short of breath and dizzy. She denies chest pain. Her blood pressure
is 90/60, heart rate – 90, respirations – 20, and she is afebrile. Her

223
physical examination reveals normal breath sounds and no cardiac
murmurs but heart sounds are distant. Her chest X-ray is below.
What is her most likely diagnosis?
A. Pericardial effusion.
B. Congestive heart failure.
C. Pulmonary hypertension.
D. Mitral valve stenosis.

Figure 13 – Patient’s X-ray

14. A 68-year-old female with a history of hypertension, diabetes,

coronary artery disease treated with coronary artery bypass grafting
20 years ago, presents to the emergency room with increasing
shortness of breath and lower extremity oedema. She denies any chest
pains and does not drink alcohol. Her temperature is 37.0 ºC, blood
pressure – 110/70, heart rate – 110, and respirations – 20. Physical
examination reveals a cachectic appearance, marked jugular venous
distension worse with inspiration, decreased breath sounds at the left
base, pulmonary rales throughout the lung fields, a regular rhythm
with extrasystolic heart sound, hepatomegaly with ascites, and 3+
pitting lower extremity oedema above the knees. ECG is normal.
Laboratory studies reveal elevated AST, ALT, and total bilirubin.
Hepatitis profile is normal. Which of the following is the most likely
diagnosis?
A. Restrictive cardiomyopathy.
B. Systolic congestive heart failure.
C. Tricuspid regurgitation.
D. Cardiac tamponade.
E. Constrictive pericarditis.

224
 15. A 32-year-old male with no significant past medical history
presents to the emergency room with 3 hours of chest pain at rest. He
recently has had an upper respiratory tract infection for which he has
been taking over the counter medications for symptoms relief. His
blood pressure is 120/80, heart rate – 80, and respirations – 20. Physical
examination is normal. Laboratory and chest X-ray is normal. His
ECG is below. Which of the following is the most likely diagnosis?
A. Dilated cardiomyopathy.
B. Pericarditis.
C. Constrictive pericarditis.
D. Myocardial ischaemia.

Figure 14 – Patient’s ECG

Тopic 9. Arrhythmias and conduction disorders

16. A 22-year-old college student with no prior past medical
history presents to the emergency room with complaints of
palpiations and dizziness. He states he was at a party recently and
had been drinking heavily when he noted the symptoms. No chest
pains or shortness of breath. His blood pressure is 90/60, heart rate –
160, respirations – 20, and oxygen saturation – 95% on room air. A
portion of his ECG is below. What is his most likely diagnosis?
A. Multifocal atrial tachycardia.
B. Ventricular tachycardia.

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 C. Atrial fibrillation.
D. Atrial flutter.

Figure 15 – Patient’s ECG

17. A 82-year-old male with a history of recent aortic valve
replacement, hypertension, and diabetes presents to the emergency
department with fevers for 5 days. No chest pains or shortness of
breath. His medications include lisinopril, hydrochlorothiazide,
aspirin, and coumadin. His temperature is 38.4 ºC, blood pressure is
160/60, heart rate – 100, respirations – 20, and oxygen saturation –
99% on room air. Physical examination reveals normal lung sounds,
II/IV early diastolic decrescendo murmur, and a very soft 1st heart
sound. Laboratory studies reveal a white blood cell count of
15 thousand and an ESR of 110. A portion of his ECG is below.
Which of the following is causing his abnormal finding on his ECG?

Figure 16 – Patient’s ECG

A. Aortic valve endocarditis.

B. Aortic valve regurgitation.
C. Aortic valve annular abscess.
D. Aortic valve stenosis.

18. A 67-year-old male with a history of severe chronic

obstructive pulmonary disease (COPD), hypertension, and
congestive heart failure presents to the emergency room with
increasing shortness of breath over the past week. He denies any
chest pains or fevers. His temperature is 37.0 ºC, blood pressure –
130/70, heart rate – 120, respirations – 24, and oxygen saturation –

226
87% on room air. Physical examination reveals diffuse expiratory
wheezing without rales, heart sounds are normal without murmurs
and in irregularly irregular rhythm is noted. There is trace lower
extremity pitting oedema. Laboratory studies reveal a mildly
elevated b-type naturatic peptide and an elevated white blood cell
count. His chest X-ray shows hyperexpanded lungs and no evidence
of pulmonary oedema. His ECG is below. What is the appropriate
treatment for his heart rhythm disorder?
A. Propranolol.
B. Verapamil.
C. Amiodarone.
D. No specific medication treatment.

Figure 17 – Patient’s ECG

19. A 82-year-old male with a history of benign prostatic

hypertrophy and osteoarthritis presents to the emergency room with
an episode of syncope while watching TV. He has felt generally
weak for the past 5 days. He denies any chest pains, shortness of
breath, or fevers. His medications include tamsulosin and celecoxib.
His blood pressure is 115/65, heart rate – 40, respirations – 12, and
he is afebrile. His physical examination reveals normal lung sounds,
a regular, bradycardic rhythm with varying intensities of the S1 heart
sound, and intermittent large cannon A waves in the jugular venous

227
pulsation. His laboratory studies are normal. His ECG is below.
What is the appropriate treatment?

Figure 18 – Patient’s ECG

A. No treatment needed.
B. Discontinue tamsulosin.
C. Permanent pacemaker implantation.
D. Defibrillator implantation.

20. A 55-year-old male has complains of weakness, dyspnoea

during exertion and sometimes at rest, cough, has periodical
palpitation and arrythmia. Anamnesis: myocardial infarction 2 years
ago. During examination: pale skin, central cyanosis. Auscultation:
inspiratory basilar crackles in lungs, loud S2. Pansystolic murmur at
the apex, accentuated pulmonic component (P2) of the 2nd heart
sound (S2). Irregular heart rate – 92/min, BP – 120/80. Palpation of
the abdomen is painless, enlargerment of liver – absent. Peripheral
oedema is absent. Which condition has this patient?
A. Left-sided failure.
B. Right-sided failure.
C. Biventricular failure.
D. Cor pulmonale.

Figure 19 – Patient’s ECG

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 Answers

№ of question 1 2 3 4 5 6 7 8 9 10
Correct answer D B A B C B D C D C
№ of question 11 12 13 14 15 16 17 18 19 20
Correct answer D B A E B C C D C A
ECG Quiz

ECG 1

ECG 2

229
ECG 3

ECG 4

230
ECG 5

ECG 6

231
ECG 7

ECG 8

232
ECG 9

ECG 10

233
ECG 11

ECG 12

234
ECG findings include:
ECG 1:
1. Atrial fibrillation with rapid ventricular rate.
2. Old inferior MI.
3. Poor R-wave progression.
4. ST-segment abnormality, consider myocardial ischaemia
(lateral in leads V6, I, and VL).
ECG 2:
1. Atrial fibrillation.
2. Ventricular pacing.
ECG 3:
1. Sinus bradycardia.
2. Old inferior MI.
3. Left ventricular hypertrophy.
4. Poor R-wave progression.
ECG 4:
1. Atrial fibrillation with rapid ventricular response.
2. RBBB.
ECG 5: Ventricular tachycardia (VT).
ECG 6:
1. Normal sinus rhythm.
2. Right ventricular hypertrophy with strain pattern.
3. Left atrial enlargement.
4. Right atrial enlargement.
ECG 7:
1. Normal sinus rhythm.
2. Old inferior myocardial infarction.
3. Old anterior myocardial infarction.
4. Non-specific ST-T-wave changes.
ECG 8:
1. Normal sinus rhythm.
2. Left atrial enlargement.
3. Premature ventricular contractions in a pattern of ventricular
bigeminy.
ECG 9: inferior localization of myocardial infarction (acute
coronary syndrome with ST segment elevation).

235
ECG 10: anterior localization of Q-wave infarction.
ECG 11:
1. Sinus rhythm.
2. Left axis deviation (deep S waves in leads II and III).
3. Wide QRS complex (duration 160 ms).
4. RSR pattern in lead V.
5. Second degree (2:1) block with left anterior hemiblock and
RBBB.
ECG 12:
1. Sinus rhythm.
2. LBBB.

LIST OF REDUCTIONS
ACEIs – angiotensin-converting enzyme inhibitors
ACS – acute coronary syndrome
AF – atrial flutter
Af – atrial fibrillation
AFM – Abramov-Fiedler myocarditis
AH – arterial hypertension
ANA – antinuclear antibody
AP – arterial pressure
APB – arterial premature beat
AR – aortic regurgitation
ARB – angiotensin receptor antagonists
AS – aortic stenosis
AT – atrial tachycardia
AV – aortic valve

236
AVNRT – atrioventricular nodal reciprocating tachycardia
AVRT – atrioventricular reciprocating tachycardia
BB – β-blockers
BBB – bundle branch block
BC – blood cultures
BMI – body mass index
BP – blood pressure
BSA – body surface area
CA – calcium antagonists
CABG – coronary artery bypass grafting
CHD – coronary heart disease
CHF – chronic heart failure
CIC – circulating immune complexes
CK – creatine kinase
CNE – culture negative endocarditis
CO – cardiac output (minute volume)
CrCl – creatinine clearance
CRP – c-reactive protein
CT – computer tomography
cTnT (cTnI) – troponins T or I
CVD – cardiovascular disease
CUS – compression venous ultrasonography
DCM – dilatation cardiomyopathy
DVT – deep vein thrombosis
ECG – electrocardiogram
EF – ejection fraction
ESD – end-systolic dimension
ESRD – end-stage renal disease
GI – gastrointestinal
GU – genitourinary
HCM –hypertrophic cardiomyopathy
HDL-C – high-density lipoprotein cholesterol
HF – heart failure
IE – infective endocarditis
IHD – ischaemic heart disease
IMT – intima-media thickness
ISH – isolated systolic hypertension
IV – intravenous

237
IVDA – intravenous drug abuse
IVS – interventricular septum
LA – left atrium
LBBB – left bundle branch block
LDH – lactate dehydrogenase
LDL-C – low-density lipoprotein cholesterol
LMWH – low-molecular-weight heparin
LV – left ventricle
LVH – left ventricular hypertrophy
LVMI – left ventricular mass index
M – men
MB – myoglobin
MI – myocardial infarction
MV – mitral valve
NCD – neurocirculatory dystonia
NSTEMI – non ST-segment elevation MI
NVE – native valve endocarditis
P – procedures
PCI – percutaneous coronary intervention
PCR – polymerase chain reaction
PE – pulmonary embolism
PMC – percutaneous mitral commissurotomy
PO – per os
PVE – prosthetic valve endocarditis
QTc – QT interval corrected for heart rate
RA – right atrium
RAAS – renin-angiotensin-aldosterone system
RCM – restrictive cardiomyopathy
RF – risk factors
RV – right ventricle
SAS – sympathoadrenal system
SBP – systolic blood pressure
SES – speed of erythrocyte sedimentation
SHF – symptoms of heart failure
STEMI – ST-segment elevation MI
SVT – supraventricular tachycardia
TEE – transesophageal echocardiography
TG – triglycerides

238
TIA – transient ischaemic attack
TPR – total peripheral vascular resistance
TR – tricuspid regurgitation
TS – tricuspid stenosis
TTE – transthoracic echocardiography
TV – tricuspid valve
VF – ventricular fibrillation
VPB – ventricular premature beat
VT – ventricular tachycardia
VTE – venous thromboembolism
W – women

Levels of evidence
Level of evidence A – data derived from multiple randomized
clinical trials or meta-analyses.
Level of evidence B – data derived from a single randomized
clinical trials or multiple trials with etherogeneous results.
Level of evidence C – consensus of opinion of the experts and/or
small studies, retrospective studies, registries.

Grading using classes of recommendation

Class I – evidence and/or general agreement that a given diagnostic
procedure/treatment is beneficial, useful and effective.
Class II – conflicting evidence and/or a divergence of opinion about
the usefulness/efficacy of the treatment.
Class IIa – weight of evidence/opinion is in favour of
usefulness/efficacy.
Class IIb – usefulness/efficacy is less well established by
evidence/opinion.
Class III – evidence or general agreement that the treatment is not
useful/effective and in some cases may be harmful. Use of Class III
is discouraged by the European Society of Cardiology.

239
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CONTENTS P.
Introduction………………………………………………………...3
Arterial hypertension……………………………………………....4
Secondary hypertension…………………………………………..22
Atherosclerosis …………………………………………………....30
Ischaemic heart disease…………………………………………...36
Acute coronary syndrome…………………………….……36
Myocardial infarction………………………………………
52
Stable angina ………………………………………...
…….66
Differential diagnosis of chest pain ……………………….76
Cardiac arrhythmias …………………………………….…
80

244
Congenital heart valvular disease………..
……………………….95
Atrial septal defect………………………………………....95
Ventricular septal defect…………………………………...97
Patent ductus arteriosus……………………………………99
Coarctation of aorta ……………………………….
……...101
Heart valvular disease…………………………………………...104
Aortic
regurgitation……………………………………….104
Aortic stenosis ………………………………..……….
….107
Mitral regurgitation………………………………...
……..110
Mitral
stenosis…………………………………………….113
Tricuspid regurgitation…………………………………...116
Tricuspid stenosis..……………………………………….117
Infective endocarditis……………………………………...…….119
Myocarditis…………………………………………………….....136
Cardiomyopathy ……………………………… ………………..144
Pericarditis………………………………………...……………..150
Syndrome of chronic cardiac failure…………………………...171
Cor pulmonale …………………………………………………...192
Pulmonary embolism…………………………………………….196
Neurocirculatory dystonia ……………………………………..209
Questions……….………………………………………………...216
List of reductions………………………………………………...234
References………………………………………………………..238

245