1

Cardiology

Coordinators
Antonio Martín Conejero
Miguel Sáez Alegre

Authors
Toni Soriano Colomé
Rafael Salguero Bodes
Alfonso Jurado Román
Roberto Martín Asenjo
David Filgueiras Rama
Javier de Juan Bagudá
Gerard Loughlin Ramírez
Sem Briongos Figuero
Felipe Díez del Hoyo

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 Card i o l ogy 1

Physical
point of maximal impact displaces down and left. LV aneurysms may
cause another ectopic focus (localization of aneurysm).

Examination
Chapter 01 Sometimes this apex beat can be displaced. For example, in hy-
pertrophic obstructive cardiomyopathy, a systolic double point of
maximal impact may be felt. When a systolic retraction of the apex
Some cardiac diseases present characteristic features when observed instead of an apical impulse is detected, constrictive pericarditis or
(Table 1). hypertrophy and RV displacing behind the LV must be suspected.

ILLNESS CARDIAC INVOLVEMENT OBSERVATION DATA

Sleep apnea- · Cor pulmonale · Obesity 1.2. Cardiac
hypopnea · Atrial fibrillation · Short neck
syndrome (SAHS) · Bradycardia and tachycardia · Daytime sleepiness Auscultation
Duchenne dystrophy Posterobasal left ventricular · Lower limbs pseudohypertrophy
dystrophy · Lumbar lordosis The first heart sound (S1) is produced by
· Gower’s sign the closing of the valves (mitral valve, more
Steinert myotonic · Infra-Hisian AV block · Inexpressive myopathic facies powerful, and tricuspid valve). The second
dystrophy syndrome · Ventricular tachycardia · Frontal baldness (S2) is produced by the closing of semilunar
· Cataracts valves (aortic, more powerful, and pulmo-
Kearn-Sayre Infra-Hisian AV block · Ophtalmoplegia nary, in this order).
syndrome · Unilateral ptosis
· Pigmentary retinopathy Murmurs
Marfan’s syndrome · Ascending aneurysm · Very tall. Enlarged limbs
· Aortic insufficiency · Aracnodactilia Murmurs are produced by turbulent flow
· Mitral prolapse · Upward lens dislocation through valves due to organic diseases or
· Pectum excavatum/carinatum to situations such as hyperflux in a valve or
Ehlers-Danlos Aneurysm or aortic dissection · Skin and joint hypermobility blood vessel.
syndrome · Detached retina
Rendu-Weber-Osler AV pulmonary fistulas Hemorrhagic telangiectasia in mucous According to the stage in which they
disease membranes appear, murmurs may be systolic, dia-
Carcinoid syndrome Pulmonary or tricuspid Flushing and edematous episodic stolic or continuous (systo-diastolic).
valvulopathy associated with hypotension Innocent murmurs (with no significant
organic disease) are mesosystolic. So,
Sarcoidosis · AV block Lachrymal glands hypertrophy
· Cor pulmonale by
in situations of hyperdinamia such as
pulmonary involvement temperature, anemia or pregnancy, it is
frequent to auscultate a mild mesosys-
Hypercholesterolemia Coronary artery disease · Xanthelasma
· Corneal arcus
tolic normal murmur due to blood tur-
· Tendon xanthomas bulence when rapidly entering the aorta
or pulmonary artery. Still’s murmur, very
Homocystinuria Systemic, pulmonary or Downward dislocation of the lens
frequent in children, is also reported.
coronary thrombosis
It appears from birth to adolescence
Infective endocarditis Endocarditis · Roth spots in retina and is heard in the pulmonic area. It is
· Osler nodes
thought to be produced by vibration of
· Petechiae in mucous membrane
the pulmonary valves. In the elderly, aor-
Acute rheumatic Rheumatic carditis Subcutaneous nodes in elbows, malleolus, tic sclerosis “innocent” murmur is very
fever and back of hands, feet or vertebra
frequent (without stenosis) by degen-
Table 1. Characteristic features of some diseases with cardiovascular manifestations erative fibrosis of aortic leaflets, becom-
ing more rigid and increasing vibration when blood flows through.
1.1. Palpation Gallavardin phenomenon is characteristic in this murmur and has
a harsh noisy sound heard in the aortic focus (due to blood turbu-
lence in the ascending aorta) and a musical sound in cardiac apex.
The apex beat or ‘apical impulse’ must be examined in the left lateral
decubitus position, better detected in forced expiration, and localized in A wider explanation of heart murmurs and its pathological correla-
a 2-3 cm diameter area normally located in the 5th intercostal space at tion will be made in ‘Valvular Heart Disease’ chapter.
the midclavicular line. A heart impulse, soft and short, or “unique move-
ment” will be felt. Other Heart Sound
Sometimes this apex beat can be displaced. For example, in concentric • Systolic sounds. Ejection sounds (opening or ejection sound) is
left ventricular hypertrophy, the point of maximal impact may be larger produced by the semilunar valves opening, when it is limited.
(more than 3 cm) and continuous during systole. In LV dilatation, the They are heard at the beginning of the systole in its correspon-

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 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

dent area (aortic or pulmonary). In mesosystole a mitral valve
prolapse might be heard, generally associated with a meso-tele-
systolic murmur.
• Diastolic sounds. The most typical one is the opening snap in the
mitral valve stenosis. Pericardical knock can be heard in protodia-
stole in some cases of constrictive pericarditis, or atrial myxoma
‘plop’ in which the tumor hits or occupies the atrioventricular canal.
Pericardial friction rub depends on the position of the patient (bet-
ter heard when the patient is bending forward) and is heard both in
systole and diastole.
by a notch or dicrotic notch (palpable at times) caused by the closure of
the aortic valve. With aging and arterial sclerosis, the initial wave tends
to be more abrupt reaching a higher peak.
Pulsus paradoxys consists in a decrease in systolic blood pressure >10
mmHg during inspiration. This is an magnification of a physiological
mechanism. During inspiration, pressure decreases inside the thorax
and increases venous return to the right heart. When the RV is filled
in diastole, the septum is displaced against the LV. During systole, since
the preload is lower, blood pressure cannot reach the same level as dur-
ing espiration.

Pulsus paradoxys is suggestive of RV diastolic failure, being typical of

Systole Diastole cardiac tamponade. It can appear in primary RV diseases and in lung
1S 2S Tumoral plop
1S diseases which cause right heart failure, but it is never present in dis-
3S 4S eases which exclusively affect LV.

The main anomalies of amplitude or waveform are described in Table 2

and Figure 2.

Click-
murmur
Opening snap
M T A P Pericardical knock M T

Figure 1. Principal sounds in heart auscultation Normal pulse Hypokinetic pulse Parvus et tardus pulse

1.3. Arterial Pulse

Celer et magnus/ Bisferiens pulse Dicrotic pulse
hyperkinetic pulse
Arterial pulse is evaluated in the main arteries such, generally when it
can be compressed against a bony structure (radial, brachial, popliteal,
posterior tibial, pedis and carotid pulses).

The wave of normal arterial pulse has a rapid climb (commonly called
Pulsus alternans
primary or percussion wave), with a detectable “anacrotic” notch (max-
imum aortic velocity) reaching a unique well defined rounded peak
(called ”pre-dicrotic” wave), followed by a slower decline, interrupted Figure 2. Abnormalities in arterial pulse

ARTERIAL PULSE ETIOLOGY CHARACTERISTICS

Celer et magnus Increase in cardiac output volume, decrease in peripheral · Strong and short heartbeat
hyperkinetic or resistance (aortic regurgitation, anemia, fever) · Wide differential pressure
collapsing

Hypokinetic Hypovolemia, LV failure (AMI, mitral stenosis) Amplitude-diminished heartbeat, possible tachycardia

Bisferiens Aortic regurgitation, HOCM Two systolic peaks

Dicrotic pulse · Dilated cardiomyopathy in low cardiac output Two peaks: one, systolic and the other, protodiastolic
· Generally associated with alternating pulse

Parvus et tardus Decrease in cardiac output volume (aortic stenosis) · Flat (weak) and prolonged wave
· Reduced differential pressure

Pulsus alternans In ventricular decompensation, with S3 and S4 Pulse amplitude variation

Bigeminus Ventricular premature contraction, digitalis intoxication Alternation of normal and extrasystole heartbeats

Paradoxic Cardiac tamponade, respiratory tract obstruction, poor blood More than 10 mmHg drop in systolic pressure during
return (sometimes, in constrictive pericarditis) inspiration
Table 2. Some abnormalities of arterial pulse

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1.4. Jugular Venous Pressure
Jugular veins pressure (JVP) is equivalent to the pressure in the right
atrium (central venous pressure). Its equivalent in the left side is the
pulmonary capilary wedge pressure, measured with the Swan Ganz
catheter. Pressure in the atrium during dyastole is the same as the pres-
sure in the ventricle.
Hepatojugular reflux (more correctly named abdominojugular reflux) is
tested by firmly pressing for 10-15 seconds over the center of the abdo-
men of the patient breathing normally so that they do not perform a
Valsalva maneuver. In healthy subjects, there is no evident elevation or
it is mild when compressing, whereas the test is considered to be posi-
tive if JVP visibly elevates during compression, sustained for 10-15 sec-
onds and falls more than 4 cm when pressure is released. This positivity
denotes hypofunction of the right ventricle.
Kussmaul’s sign consists of an increase in JVP on inspiration (which di-
minishes in physiologic conditions, since blood accumulated in jugular
veins is backed up into the RA due to negative pressure in thorax dur-
ing inspiration). It may appear in any severe right diastolic heart failure
since excessive blood volume reaching the right cavities on inspiration
produces an increased pressure, which is characteristic of constrictive
pericarditis, restrictive cardiomyopathy and RV infarction.
Electrocardiogram
Chapter 02
Standard surface electrocardiogram (ECG) has 12 vector views or leads,
6 of which are limb leads (I, II, III, aVR, aVL, aVF) and the other 6 are
precordial leads (V1 to V6). Each one represents cardiac electrical activ-
ity from different perspectives (Figure 3).
V9 V8
V7
aVR 150º
aVL 30º
I 0º
V4R
V3R
III 120º V2
II 60º V1
aVF 90º
Figure 3. Surface ECG standard leads
It is highly recommended to follow a systemic order when analyzing
electrocardiographic records.
Card i o l ogy 1
In normal resting patients, heart rate (HR) ranges from 60-100 bpm, but
can be lower in athletic young individuals. HR below 60 bpm constitute
bradycardia, and above 100 bpm, tachycardia.
It is necessary to differentiate “p” waves (atrial activation) from QRS
complexes (ventricular activation).
Specially in young people, a physiological respiratory sinus arrythmia can
appear. It consists on an inspiratory HR increase and an expiratory decrease.
Sometimes, there is a ‘wandering atrial pacemaker’ where the start of the
heart impulse is produced more caudal (closer to the AV node). This is rep-
resented in the ECG with negative or flattened P waves in the inferior leads.
In normal ECG, the paper moves forward 25 mm/sec. This is why 1 mm
equals 40 ms. In Figure 4, normal intervals are shown.
1 mm = 40 ms
P wave: 120 ms QRS: < 120 ms
PR: 120-200 ms QT: < 440 ms
QT
QT
Figure 4. Normal timing in surface ECG
Remember that QT interval depends on cardiac frequency: the faster the
heart rate, the shorter the interval. There are many forms to normalize or
V6 correct the absolute QT value: the normal QTc value is below 440 ms (450
V5 in women). Bazett’s is the most commonly used formula: Corrected QT =
measured QT/√ RR, where RR represents the time, in seconds, from the
V4 onset of one QRS complex to the onset of the new QRS complex, whose
QT is being measured.
V3
The electrical axis of any wave in ECG relies on the concept of a vector
which describes the motion in the frontal plane (expressed in degrees)
of such depolarization wave. Normal P, QRS and T point towards the
lower-right quadrant of the heart.
The normal QRS axis is between -30º and +150º. An axis beyond -30º is
a left -deviated axis (as in left anterior fascicular block [LAFB]), whereas
a right heart axis (beyond +150º) is deviated to the right (as in left pos-
terior fascicular block [LPFB]).
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 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

2.1. Main ECG Anomalies QRS right axis deviation appears (> 90º). In precordial leads, the vector
points towards V1 and V2 leads and instead of having a QRS complex
dominantly negative, QRS is dominantly positive with a dominant R
• P wave (better recorded in DII and V1). In RA hypertrophy, P wave pro- wave taller than S wave depth, along with aberrant secondary repolari-
duces a tall, peaked P in its first part (P pulmonale) in DII, increasing its zation (T-wave inversion and ST depression).
first positive component in V1. LA hypertrophy produces changes in the This is the traditional right ventricular hypertrophy or type “A”
second part of the wave, with a wide and uneven P in II (P mitral) and bi- growth. There exists a right ventricular hypertrophy type “C”,
phasic, prevailing the 2.nd negative component in V1. P wave disappears in characteristic of cor pulmonale, in which hypertrophy of the
atrial fibrillation (f waves) or in atrial flutter (F waves or ‘sawtooth waves’). right ventricle outflow tract causes a nondiscernible axis (iso-
P wave can also be inside the QRS complex in intranodal tachycardia or in diphasic complexes in all frontal leads). Acute right ventricular
ventricular tachycardia, being difficult to identify. P wave frequency is not volume overload (i.e. in pulmonary embolism) may cause these
related with QRS in an AV dissociation. alterations and the characteristic “SIQIIITIII” pattern (S in I, Q and
• PR Interval. It is enlarged in AV blocks, being sustained in 1.st degree AV negative T in III).
blocks, with a progressive enlargement in type I 2.nd degree AV blocks LV hypertrophy might deviate the QRS axis more to the left.
(Wenckebach) and variable in AV dissociation (as in complete 3rd degree However, it will produce high voltages in QRS, with aberrancies
AV block). It shortens in ventricular pre-excitation syndromes (Wolff- in repolarization (inversion of T wave and ST depression -espe-
Parkinson-White). PR interval depression is very specific (although in- cially in I, aVL, V5-V6 leads-). There are several ECG criteria to
frequent) of acute pericarditis. determine the existence of LV hypertrophy, although the exis-
• QRS complex. A Broad QRS complex (QRS > 120 ms) shows an ting different measure indexes generally show low sensibility
aberrant ventricular depolarization in which impulses are not but better specificity (Sokolov-Lyons, Cornell). This is why, at
triggered simultaneously in the His-Purkinje system. This occurs present, echocardiography is the first-choice test to prove hy-
when a His bundle branch block is present, when ventricular pre- pertrophy (even though cardiac magnetic resonance may be
excitation is produced by an accessory pathway with anterograde more precise; Figure 6).
conduction, under the influence of type I anti-
arrhythmic drugs which slow down the conduc-
tion, in hyperkalemia or when the impulse has a
ventricular origin (ventricular extrasystole, ven-
tricular tachycardia, infra-Hisian rhythm in com-
plete atrioventricular block, AIVR or pacemaker-
induced ventricular rhythm).
A bundle branch block is considered to be com-
plete if QRS is longer than 120 ms, or incomplete
if its length is less than 120 ms. QRS specific mor-
phology patterns enable differentiation of right
bundle branch block (RBBB) (rSR’ in V1-V2, wide
“s” wave in I and V5-V6) from left bundle branch
block (LBBB) (QRS is mainly negative in V1 as are
rS or QS and RR’ in V5-V6). In bundle branch block
the repolarization sequence is also affected (Figu-
re 5). RBBB appears in nearly 2% of the population
without any underlying heart disease. LBBB is less
frequent as a normal variation (0,1-0,7%) and fur-
ther investigations are required. Occasionally, BBB
are rate-dependent, appearing when a determi-
nate rate is reached and disappearing if the HR is
lower.
Normal q wave, a small physiologic wave appre-
ciated in leads I, II, III, aVF, aVL and V5-V6 indi-
cates depolarization of interventricular septum.
When Q wave is wider than 40 ms and deeper
than 2 mV (or 25% of depth of QRS complex), it
is considered a pathologic Q, which usually indi-
cates transmural infarction located in the area
explored by the lead in which the pathologic Q
wave appears. Sometimes, pathologic Q waves
are appreciated without infarction in hypertro-
phic cardiomyopathy or in Wolff-Parkinson-Whi-
te syndrome.
RV hypertrophy moves the ventricular depolariza-
Figure 5. Left bundle branch block (top) and Right bundle branch block characteristics
tion vector right and front. As a consequence, a in precordial leads

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Figure 6. ECG obtained from a patient suffering biventricular dilated
cardiomiopathy. Hypertrophic changes are remarkable as RBBB and
repolarization abnormalities
Alternating QRS amplitude, generally implies the existence of a sig-
nificant pericardial effusion. A low QRS voltage might also appear in
pericardial effusion as in obesity, emphysema, RV arrhythmogenic
dysplasia and in restrictive cardiomyopathy.
• ST segment. Elevated ST to values over 1 mm may indicate trans-
mural lesion current (upwards convex), ventricular aneurysm (if it
persists after acute myocardial infarction [AMI]), pericarditis (dif-
fuse upwards ST elevation), Brugada syndrome (elevation in V1-V3
with negative T and incomplete right bundle branch block) or often,
benign early repolarization (normal variant seen in young people
with dominant vagal hypertonia, with slight convex ST elevation and
notching of the J-point. This anomaly has been considered of no
clinical relevance for a long time, but recently, it has been more fre-
quently reported in patients with sudden cardiac death than in the
general population).
ST depression may also appear during ischemia episodes in stable/
unstable angina or subendocardial acute myocardial infarction. It
may also indicate ventricular overload (secondary to hypertrophy,
generally in a descending slope), digoxin effect or appear in bundle
branch block.
• T wave. It elevates with subendocardial ischemia, in hyperka-
lemia (“peaked T”), in the rare congenital short QT syndrome,
upon LV volume overload (dilated cardiomyopathy) or in some
cases of hypertrophic cardiomyopathy. T wave becomes nega-
tive in the presence of transmural ischemia (symmetrical and
deep), as a consequence of infarction accompanying Q wave,
in ventricular pre-excitation, upon ventricular overload (in ven-
tricular hypertrophy or dilation), in acute pericarditis progres-
sion, in apical hypertrophic cardiomyopathy (“giant” negative T
waves), and in V1-V3 leads in RV arrhythmogenic cardiomyopa-
thy. Negative T waves may be normal in V1-V3 leads, especially
Figure 7. Lead aVF ECG revealing characteristic signs of sinus dysfunction with significant sinus bradycardia
Card i o l ogy 1
in women and children (child pattern) and in III lead. Generally,
T wave is negative in aVR.
Occasionally, flat T waves are detected, defined as “unspecific
alteration of repolarization”, and they are usually a normal vari-
ant (especially frequent following cardiac surgery), though it is
recommended to rule out subjacent ischemia. Anxiety, physical
exercising (including ergometry), hyperventilation, sustained
tachycardia, postprandial period, orthostatism, acute pancreati-
tis (affecting DII, DIII and aVF), and acute CVA may flatten or even
invert T waves.
• QT Interval. Corrected QT interval shortens in hypercalcemia and,
occasionally, under digoxin treatment, as well as in congenital
short QT syndrome. It is enlarged in hypocalcemia, in hypokalemia
and other endocrine metabolic alterations, and in acute ischemia
because of the use of drugs prolonging QT interval (class IA and III
anti-arrhythmic drugs, macrolide and quinolone antibiotics, tricy-
clic antidepressants) or in congenital long QT syndrome. Negative
or inverted U wave may indicate underlying ischemia, although it
is not a frequent finding.
Arrhythmias
Chapter 03
3.1. Bradycardia
Underlying mechanisms in bradyarrhythmias (<60 bpm) may be re-
lated to many underlying circunstances such as a disturbance in the
impulse generation system (as in sick sinus syndrome, Figure 7), or to
a disturbance in the impulse conduction system. This forces a pace-
maker slower than sinus pacemakers to set the heart rhythm (the
more distal the block point the more severe it usually is (Figure 8). In
Figure 9, the pacemaker speed of the different conduction systems is
represented.
Complete supra-Hisian AV block (nodal)
Complete infra-Hisian AV block (His-Purkinje)
Figure 8. Influence of complete AV block point in escape rhythm
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 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

60-100 bpm
stimulation in patients with resynchronization usually reaches a nar-
rower fusion QRS than patients’ basal QRS.
Sinoatrial node

RBB 40-50 bpm

AV node
30-40 bpm
30-40 bpm

30-40 bpm LBB LPF

RBB 15-30 bpm

15-30 bpm
LAF

Figure 9. Heart conduction system
The most frequent reversible cause of bradycardia are drugs which slow
heart conduction. The most frequent irreversible cause is idiopathic de-
generative fibrosis of the conduction system.
Medical treatment usefulness is limited in acute transient manage-
ment; permanent pacemaker implantation is the required solution in
nonreversible cases (Table 3).
Figure 10. 12-lead ECG from a patient in sustained atrial fibrillation with
VVIR pacemaker implantation stimulating RV apex at 100 bpm
Chronic right apical pacing is harmful to contractile function in patients
with systolic dysfunction. In these cases, biventricular stimulation must
be considered (resynchronization).
Some conduction abnormalties
Sinus Node Disfunction

SITUATION
· Biphasic or triphasic block
· Sinus dysfunction
· First degree AV block
· Second degree Type I AV block
· Second degree Type II AV block
· “High degree” AV block
· Third degree AV block
· Alternating bundle branch
block
Other situations
INDICATION The etiology of this arrythmia remains unknown in the majority of cases.
It is related with degenerative changes in the elders. Some specific causes
· Only in case of symptoms
are rarer like sinus node ischemia, myocardial infiltrative process, Chagas’
secondary to bradycardia
disease, systemic diseases (hypothyroidism, advanced liver diseases…) or
(asthenia, syncope, or repetitive
presyncope) some drugs like ß-blockers, calcium antagonists, digoxin… When symp-
· Occasionally, to treat patients toms appear, the most frequent ones are extreme bradycardia related
with “blocker” drugs syncope and, sometimes, exercise intolerance (due to chronotropic in-
competence). Sometimes, sinus node dysfunction is associated with
ALWAYS
phases of atrial tachycardia (mostly AF), alternating with bradycardia
periods. This is known as the tachycardia-bradycardia syndrome (Figure
11). Asymptomatic sinus node dysfunction does not require treatment.
Pacemaker implantation might be considered in symptomatic cases to
relief symptoms. Sometimes atropine can be useful in acute episodes.
· Carotid sinus hypersensitivity
· Pure cardioinhibitory neurally
mediated syncope
· Ventricular arrhythmias
because of bradycardia
· Cardiac resynchronization
therapy

Table 3. General indications of pacemakers

Whenever in doubt of indication of permanent pacemaker implantation

(patients with syncope and bundle branch block or bifascicular block,
patients with 2:1 AV conduction ratio), an electrophysiologic evaluation
may be performed in order to evaluate the level of conduction disease,
whether infra-Hisian or supra-Hisian, as well as the sinus node dysfunc-
tion. If electrophysiologic study results are inconclusive and, mainly, if
syncope recurrence is very sporadic, a subcutaneously implanted Holter
may be useful.

Ventricular stimulation with pacemaker from the RV apex produces a Figure 11. Detail of the electrocardiographical monitoring of the ending
of an atrial flutter episode. Note the 3,7 seconds pause at the end of it,
QRS similar to that in left bundle branch block (Figure 10). Biventricular
and the start of a sinus node rhythm with atrial extrasystoles

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 Card i o l ogy 1
Atrial-ventricular Disturbances

AV conduction problems can be located in the AV node or in the Hiss-

Purkinje system. Most of the AV blocks occur in ancient patients, being
idiopathic in the majority of them. Other causes can be:
• Vagal tone increase.
• Coronary ischemia, mostly in the inferior area.
• Drugs:
ͳ AV nodal blocking drugs like digoxin, ß-blockers, verapamil, dil-
tiazem.
ͳ His-purkinje blocking drugs like group I antiarrhythmics, amio-
darone…

• Infeccions: Chagas, Lyme…

• Infiltrative myocardial diseases (amyloidosis).
• Tumors.
• Congenital AV blocks (normally supra-hisian).
• Other: ESL, Steinert myotonic dystrophy…
Figure 13. Second-degree AV block. Mobitz I (A) and Mobitz II (B)
Basic types of AV blocks:
• 1st degree AV block: PR interval >200ms. (Figure 12). A resume of bradyarrythmias can be found in Table 4 and Table 5.
• 2nd degree AV block (Figure 13). It is divided into two different categories:
ͳ Mobitz I (Wenckebach). It consists on a progressive enlarge-
ment of the PR interval until a P wave is not conducted. It is THIRD DEGREE NODAL INFRANODAL
physiological during sleeping time. AV BLOCK (SUPRA-HISIAN) (INFRA-HISIAN)
ͳ Mobitz II. A P wave is randomly not conducted and there is not
previous PR interval enlargement. Escape rhythm 40-60 bpm 20-40 bpm

Response to atropine + -
• High-degree AV block. Two or more P consecutive waves are not con-
ducted to the ventricle, but with a posterior normal conduction pattern. QRS Normal (< 0.12) Wide (> 0.12)
• 3rd degree AV block. It consists on the presence of an AV dissociation.
Prognosis Good Poor
P waves are not conducted to the ventricle and are present with a regu-
lar but independent rythm compared to the QRS (which is also regular). Table 4. Complete AV block

3.2. Tachycardia

Premature Beats
Figure 12. First-degree AV block See Table 6.

DISEASE ECG MANIFESTATIONS TREATMENT

Sinus nodal There may exist: Pacemaker in (DDD/R):
dysfunction · Bradycardia (< 55 bpm) · Symptoms
· Bradycardia–tachycardia · Symptomatic daytime
>6 s pauses
A-V CONDUCTION ALTERATIONS
(Pacemaker of choice DDD/R. In AF, the indication is VVIR)
First-degree block PR > 0.20 sec (pacemaker indication DDD/R. In Consider pacemaker
AF, the indication is VVIR) according to PR > 0.3 s ASSOCIATION LOCATION
and symptoms
Second-degree Repeating cycles with progressive PR increase Pacemaker if symptomatic Inferior AMI. Drugs AV node
block (Mobitz I) until a P wave block, and then restarting the cycle

Second-degree Failure in the conduction of some impulses Pacemaker Anterior AMI His bundle
block (Mobitz II) (P not followed by QRS)
Third-degree block A-V Dissociation Pacemaker
Table 5. Characteristics and treatment of bradyarrhythmias

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 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

ATRIAL
PREMATURE BEATS
VENTRICULAR
PREMATURE BEATS
Atrial Fibrillation
ECG · Premature P wave · Premature QRS
Atrial fibrillation (AF) is the most common type of arrhythmia after pre-
alterations · Normal QRS · Wide QRS
mature beats and also the most frequent sustained chronic arrhyth-
Subsequent Noncompensatory Compensatory
mia. ECG reveals a disorganized atrial activity without P waves, which
pause (usually)
are replaced with irregular waves of the T-QRS complex (“f” waves, at
Prevalence Present in 60% of adults
350-600 bpm) showing variable and irregular ventricular conduction
Consequences Usually few · Few in the absence of heart (ventricular response; Figure 15).
disease
· Clinical importance,
especially in ischemic heart
disease, if they are frequent,
complex or with R-on-T
phenomenon (in which the
premature beat matches
with the T wave of the
previous QRS beat)
Treatment · Remove excitants · Remove excitants
· β-blockers if · β-blockers if discomfort
discomfort in patients with no heart
· Consider ablation disease
in special cases · Patients with underlying
Figure 15. Atrial fibrillation
heart disease and premature
ventricular beats should be
treated with ß-blockers AF is classified into first episode (first documented AF episode of the pa-
· In some special cases (like tient, regardless of duration), paroxysmal (with spontaneous cardiover-
tachycardiomyopathy induced sion during the first week, usually within first 24-48 hours), persistent (it
by frequent premature beats), does not cardiovert spontaneously within seven days, although it may
radiofrequency ablation can be attempted) or permanent (chronic, it does not cardiovert spontane-
be useful ously nor is it pursued). Just as any other arrhythmia, it is called recur-
Table 6. Types of premature beats rent when there is more than one episode and sustained when it lasts
for more than 30 seconds.

Sinus Tachycardia
It consists on a sinus rhythm with a rate of over 100 bpm, with identical
P waves to the sinus ones (Figure 14). This arrhythmia starts and finishes
gradually, and its frequency may be slowed temporarily with vagal ma-
neuvers.
There are multiple causes, since in most cases it is the result of stress,
anxiety, fever, anemia, hypovolemia, hypotension, exercise, thyrotoxicosis,
hypoxemia, heart failure, pulmonary embolism, adrenergic stimulus. Rare
inappropriate sinus tachycardia, common among female health workers.
does not have a recognizable triggering factor, and may require the use of
β-blockers, calcium antagonists or ivabradine.
AF may appear both in people with structural heart disease and in
“healthy” people. Among its causes, the following are found: emotional
stress, post-surgery, acute alcohol intake, hypoxemia, fever, hypercap-
nia, metabolic or hemodynamic alterations, hyperthyroidism, valvulop-
athies, hypertensive heart disease, almost any structural heart disease,
chronic obstructive pulmonary disease, sleep apnea, constituting a part
of the bradycardia-tachycardia syndrome...
AF may range from asymptomatic to result in hemodynamic intolerance
with syncope or acute pulmonary edema. Arrhythmia management in-
volves assuming that its presence indicates a steep increase in stroke
risks, especially (although not exclusively) caused by the formation of
clots in the left atrial appendages. It is thus necessary to assess in all
cases the need for anticoagulant treatment, which will be necessary for
almost every patient with heart disease or underlying prosthetic cardiac
valves, as well as when suggested according to the CHADS-VASc score of
calculated risk (Table 7).

Currently, there are two potential treatment strategies for atrial fibrillation:
• Rate control strategy. It does not aim to restore sinus rhythm but to miti-
gate potential complications which may result from a permanent AF.
• Rhythm control strategy. Aimed at restoring sinus rhythm and sus-
taining it for the longest possible time.

Figure 14. 12-lead ECG of patient with sinus tachycardia and no
structural heart disease
Various clinical trials have shown that neither strategy is better than the
other in terms of mortality, but recent studies have shown that rhythm
control might be beneficial in terms of survival and thromboembolic
risk reduction. Hence, The strategy will be selected based on patient
characteristics and arrhythmia tolerance.

10
 Card i o l ogy 1

CHA2DS2-
ANNUAL
ADJUSTED
Atrial Flutter
FACTOR POINTS
VASC SCORE STROKE RISK
RATE (%) The common typical flutter in an atrial tachycardia caused by a macro-
C (congestive heart failure 1 0 0 reentry around the tricuspid annulus, which cycles at 250-350 bpm (in a
or ventricular dysfunction counter-clockwise direction in the common type, clockwise in the reverse
with EF < 40%) type) and from which atrial depolarization takes place, showing in the
H (hypertension) 1 1 1.3 ECG saw-toothed regular atrial activity (F waves, positive in V1 and nega-
A2 (age > 75) 2 2 2.2 tive in inferior leads) with little mechanical activity (Figures 17 and 18).
D (diabetes mellitus) 1 3 3.2
S2 (prior stroke or TIA or 2 4 4.0
Common flutter is very frequent among patients with COPD or sleep
thromboembolism) apnea. There are atypical flutter circuits around other obstacles, which
V (coronary, aortic or 1 5 6.7 are less frequent (foramen ovale, cava veins, post-surgery scars; Figure
peripheral vascular disease) 19). Ventricular rate is usually half of the atrial one, due to 2:1 conduc-
A (age 65-74) 1 6 9.8 tion (around 150 bpm).
Sc (female gender) 1 7 9.6
The most effective treatment is synchronized electrical cardioversion,
8 6.7 which usually requires low energy. Anti-arrhythmic drugs are very in-
9 15.2 effective, except dibutilide and dofetilide, which shows only moderate
Table 7. Stroke risk calculation in atrial fibrillation according to score efficacy.
system CHA2DS2-VASc • Although stroke risk seems somewhat lower, anticoagulation treat-
ment must be conducted as analogous to AF. AV node “slowers” are
Figure 16 shows general management of a patient with atrial fibrillation. less effective than in AF to control ventricular response.

Atrial fibrillation

Asymptomatic
Heart rate control strategy or minimum symptoms, Symptomatic episode or,
especially when over 65 in general, first episode
in young people

Assess need for drugs Thromboembolic Rhythm control strategy

for HR control prophylaxis

Drugs for HR control < 48 hours or chronic > 48 hours

oral anticoagulant
- β-blockers
- Calcium antagonists Unknown Consider
- Digoxine duration HR control
Electrical or pharmacologic
cardioversion Consider electrical cardioversion
Chronic oral anticoagulation.
guided by transesofageal
Antistroke treatment The use of novel oral · ECV: 200-360 J monophasic echocardiography findings
instructions in AF anticoagulant (NOAC) is (150-200 J biphasic) versus anticoagulation
preferred, except in cases · Pharmacologic: group IC for three to four weeks and then
· Heart valve prosthetics of valvular AF (INR 2-3 anti-arrhythmic drugs show electrical cardioversion
· Mitral stenosis except mechanical highest success note
· Other severe structural heart Yes prosthetics: 2,5-3,5) (flecainide, propafenone);
diseases: amiodarone if underlying
- Hypertrophic cardiomyopathy heart disease
- Complex congenital heart disease
Yes Secondary AF prevention and stroke prevention
No

CHADS2VASc score ≥ 1 (male)

or CHADS2VASc score ≥ 2 (female) If there is recurrence risk (AF was not secondary to a temporary cause):
Anticoagulant treatment
No · If there are no stroke risk factors, OAC (oral anticoagulation)
may be discontinuated after three to four weeks
· If there are stroke risk factors, act IS if it was permanent
No treatment
Anti-arrhythmic treatment
· Consider anti-arrhythmic drugs to prevent recurrences:
IC, dronedarone (avoid in case of heart failure),
sotalol. If there is severe structural heart diesease or heart failure,
amiodarone (most effective)
· Consider ablation in case of recurrent, symptomatic episodes,
if at least one anti-arrhythmic fails to maintain sinus rhythm

Figure 16. Clinical management of atrial fibrillation

11
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Pulmonary veins
• For recurrence prevention, drugs are also very limited, thus with recur- Upper cava
ring common or reverse flutters, or in a poorly tolerated first episode,
the procedure of choice is radiofrequency ablation of the cavotricuspid
isthmus (part of the reentry circuit), with a success rate of over 90% in
common flutter. In atypical cases, ablation efficacy is lower.

Right
atrium Left
atrium

Mitral ring
Coronary sinus

Tricuspid ring
Lower cava

Common flutter

Figure 17. Anatomic reconstruction with nonfluoroscopic navigation

system of atrium and right atrial appendage (blue), cava veins (brown)
and coronary sinus (purple). A diagnostic catheter can be seen around
the tricuspid ring, as well as radiofrequency lesions (orange spots)
performed on the cavotricuspid isthmus for common flutter circuit
ablation

Common flutter

V1

Atypical flutter over

a surgical atriotomy scar

aVF Figure 19. Common and atypical flutter circuits: atrial layout representing
the placement of atrial macroreentry in common flutter
and atypical flutter because of atriotomy scar

Atypical flutter Atrioventricular Nodal Reentrant

V1 Tachycardia (AVNRT)
It is the most common paroxysmal supraventricular tachycardia (Figure
20).

aVF In atrioventricular reentrant tachycardia (AVNRT), it is speculated that a

Figure 18. ECG of common flutter and atypical flutter in leads V1 and aVF
double pathway between the atrium and AV node exists (although this
phenomenon is also present in subjects with no tachycardia), a slow
pathway (α, with short refractory period) and a fast pathway (β, with
long refractory period), which may establish a reentrant circuit between
them (Figure 21).

12
 Card i o l ogy 1
Tachycardia starts and finishes abruptly, and
may cause palpitations, hypotension, syncope.
It is prevalent among middle-aged women.

ECG outside of crisis periods is normal, and dur-

ing tachycardia it shows a retrograde P wave
almost simultaneous to QRS thus altering their
final portions (“pseudo S” in inferior leads or
“pseudo R” in V1; Figure 22).

The close match between atrial and ventricular

contractions causes “cannon” a-waves in the
jugular venous pulse, regular in all tachycardia
beats (“frog’s sign”), and the patient frequently
refers neck palpitations.

Electrical cardioversion is the treatment of

choice, if there is severe hemodynamic com-
promise. If there is no compromise, maneuvers
are adopted to block the AV node to interrupt
the tachycardia: vagal maneuvers (carotid sinus
Figure 20. Paroxysmal supraventricular tachycardia (AV nodal reentrant tachycardia)
massage), intravenous infusion of drugs such
as adenosine or verapamil. It is best to con-
duct the treatment under electrocardiographic
monitoring, since the use of adenosine may
cause atrial fibrillation (less than 10%).

For prophylaxis of new episodes, drugs of

choice are those “slowers” of the fast pathway
of the AV node, such as β-blockers, verapamil
or diltiazem. Anti-arrhythmic agents may be
useful as a second choice, especially those in
the Ic group. However, if episodes are frequent,
Figure 21. Lewis diagram showing the start of common AV nodal reentrant tachycardia
recurrent or sustained, or if the patient prefers
V1 during sinus rhythm V1 during common AVRNT a radiofrequency ablation of the slow pathway
may be performed, with a success rate over
90% with minimum complications (the risk of
causing complete AV block is 0.4%, and it is usu-
DII during sinus rhythm DII during common AVRNT ally temporary, although it may require pace-
makers on occasions).

Focal Atrial Tachycardia

Figure 22. ECG of the same patient in V1 and DII during sinus rhythm and common AV nodal Regular episodic tachycardia which usually
reentrant tachycardia, showing image of “pseudoR” in V1 and “pseudoS” in DII starts and finishes abruptly, although more
gradually than AVRNT or orthodromic, where
before each QRS complex there is a P wave
originating at some point of the atria other
than the sinus node, with a different morphol-
ogy than the sinus (depending on the location
of the focus) and a usually prolonged PR. On oc-
casion, the AV node does not “tolerate” such a
high rate and some of the P waves cannot be
conducted to the ventricles, even though the
tachycardia remains (Figure 23).

It may respond to β-blockers or calcium an-

tagonists (which also stop the AV node and
obtain a slower ventricular response during
Figure 23. Lewis diagram showing focal atrial tachycardia with irregular conduction to ventricles
because of varying block degrees in AV node tachycardia).

13
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)
Multifocal Atrial Tachycardia
There are at least three P waves with different morphology (of different
focuses) during tachycardia, with a variable ventricle conduction degree.
It is frequent among patients with worsened bronchopathy, especially un-
der treatment with theophylline or beta-agonists. It frequently evolves into
atrial fibrillation.
Treatment consists in improving the patient’s pulmonary condition (ox-
ygenation) and removing, if possible, theophylline and beta-agonists.
Calcium antagonists or magnesium sulfate may be useful.
Pre-excitation Syndromes
This occurs when there is a congenital
accessory conductive pathway for elec-
tric communication between atria and
ventricles which, in sinus, causes early
depolarization of ventricles (it pre-ex-
cites them), causing a shortened PR, a
“slurred” upstroke to the QRS complex
(the ‘delta wave’, showing the fragment
of ventricles depolarized through the ac-
cessory conductive pathway, and a broad
QRS (Figure 24).
There may be evident pre-excitation (es-
pecially the right pathways close to the
sinus node) or be “inapparent” in the
ECG (especially in the left pathways fur-
ther from the sinus node).
Accessory pathways may be bidirectional,
only retrograde (concealed pathways) or
Figure 24. ECG in Wolff-
only antegrade. Conduction velocity and Parkinson-White syndrome
refraction vary with each pathway.
The combination of pre-excitation and paroxysmal tachycardia is called
Wolff-Parkinson-White (WPW) syndrome. It may be related to Ebstein’s
disease (birth defect most frequently related to WPW) and, maybe, with
mitral valve prolapse and hypertrophic cardiomyopathy.
There are two types of paroxysmal tachycardia by AV reentry related to
WPW (Figure 25):
Accesory pathway
AV node
His bundle His bundle
Orthodromic mechanism
Figure 25. Reentry circuits in orthodromic and antidromic tachycardia
14
• Orthodromic. There is anterograde conduction through AV node
and retrograde conduction through the accessory pathway.
They are the most frequent, and QRS during tachycardia is narrow
(with the exception of bundle branch blocks); the second most fre-
quent is supraventricular paroxysmal tachycardia.
• Antidromic. Anterograde conduction is through the accessory path-
way, and retrograde conduction through AV node, therefore QRS is
wide (a “maximum preexcitation”). It is very rare.
The treatment of acute tachycardia episodes because of AV reentrant
is similar to AVNRT.
Pre-excited Atrial Fibrillation
When an AF appears with WPW syndrome (or a flutter or other quick
atrial tachycardia) and the pathway performs a fast anterograde con-
duction it is a medical emergency, since an excessively fast conduction
through the accessory pathway may result in ventricular fibrillation (VF).
Treatment involves electrical cardioversion. If it is well tolerated, electri-
cal cardioversion will be performed or anti-arrhythmic drugs from the
Ic group or procainamide will be applied. Intravenous administration
of digoxin, calcium antagonists (and probably amiodarone) is contra-
indicated, since by slowing node conduction and/or causing vasodila-
tion with increased in sympathetic tone they may facilitate conduction
through the accessory pathway and VF.
Definitive treatment of accessory pathways is percutaneous cath-
eter ablation of the accesory pathway, which is more effective than
anti-arrhythmic drugs and has low risk, and is therefore the treatment
of choice for patients with tachycardia episodes. In subjects with as-
ymptomatic pre-excitation, clinical observation is advisable, except
for hazardous-activity professionals (professional drivers, sport play-
ers, etc.) or according to the patient’s wishes, when ablation is recom-
mended.
Nonparoxysmal Junctional Tachycardia
It is a very rare type of tachycardia, caused by an increase in automatism
or triggered activity in the AV node. QRS is the same as the patient’s
basal and there is frequently AV dissociation or VA conduction. It starts
and ends gradually and heart rate varies with maneuvers affecting the
autonomic nervous system (increased with vagolytic drugs, exercise or
catecholamines and decreased with vagal maneuvers or β-blockers).
Carotid sinus massage may transiently stop tachycardia, but does not
make it disappear.
Accesory pathway
AV node
Antidromic mechanism

It is characteristic of digitalis toxicity, catecholamines increase, acute
lower myocardial infarction or myocarditis. Treatment is aimed at the
root cause; electrical cardioversion should not be attempted, especially
if the cause is digitalis toxicity, since it is not effective as far as it is not
caused by reentrant.
Card i o l ogy 1
Other diseases causing intramyocardial scars (dilated cardiomyopathy,
right ventricular dysplasia, Chagas disease, etc.) may likewise present
monomorphic ventricular tachycardia during their clinical course.

Ventricular Tachycardia
Ventricular tachycardia (VT) involves the presence of three or more
consecutive beats originating in the ventricles at over 100 bpm. A
wide QRS tachycardia is shown in the ECG (≥ 0.12 seconds), with AV
dissociation (there can be some retrograde P waves). A wide QRS
tachycardia has a high probability of being a VT, representing 98% of
the tachycardias in patients with underlying heart disease (specially
MI) (Figure 26).

It is said to be sustained if it lasts for more than 30 seconds or if it causes

circulatory collapse.

Nonsustained VT (< 30 seconds) may also be associated with underly-

ing heart diseases, although less frequently than sustained VT. Nonsus-
tained VT is usually asymptomatic.

The following are distinguished according to QRS morphology:

• Monomorphic VT. QRS morphology is the same for all beats.
• Polymorphic VT. QRS morphology varies from one beat to the Scar from prior acute
other. myocardial infarction
• Bidirectional VT. Direction of QRS axes alternates. It is associated
Figure 27. Intramyocardial ventricular tachycardia mechanism layout
with digoxin intoxication.

The most frequent etiology of monomorphic VT is reentry through vi-
able tissue channels located inside or on the edges of a prior acute myo-
cardial infarction scar (Figure 27).
In the acute phase of the acute myocardial infarction, which does not
yet have a scar, arrhythmias are the result of myocardial irritability due
to ischemia, i.e., ventricular premature beats, ventricular fibrillation or
accelerated idioventricular rhythm associated with reperfusion.
In the acute phase of the acute myocardial infarction, which does not
yet have a scar, arrhythmias are the result of myocardial irritability due
to ischemia, i.e., ventricular premature beats, ventricular fibrillation or
accelerated idioventricular rhythm associated with reperfusion.
Other diseases causing intramyocardial scars (dilated cardiomyopathy,
right ventricular dysplasia, Chagas disease, etc.) may likewise present
monomorphic ventricular tachycardia during their clinical course.

Figure 26. Monomorphic ventricular tachycardia

15
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Other monomorphic VT, called idiopathic, appear in patients without Channelopathies

structural heart diseases (they comprise 10% of VT and have better
prognosis), such as right ventricular outflow tract VT (sensitive to ad- A modern term which comprises a group of arrhythmic syndromes
enosine and β-blockers or fascicular ventricular tachycardia (sensitive caused by dysfunction of ion channels located in the membranes of car-
to verapamil). diac cells in patients without structural heart diseases.
• Long QT syndrome (LQTS: most frequent channelopathy). It is a con-
Faced with a common tachycardia with wide QRS, a differential genital or acquired disorder whereby membrane ion currents length-
diagnosis between monomorphic sustained VT and supraventricu- en the duration of the action potential, shown in the ECG as a pro-
lar tachycardia with bundle branch block (aberrancy) is important, longed QT interval, which facilitates the appearance of afterpotentials
since prognosis is different. Verapamil should not be used to distin- (premature beats) that are transmitted to the rest of the myocardium
guish them, since it could cause shock or even cardiac arrest in a VT with functional reentrant phenomena causing polymorphic ventric-
(Table 8). ular tachycardia with twisting of the points (Torsades de Pointes or
helicoidal ventricular tachycardia), where QRS are polymorphic, i.e.,
they vary in width and duration, causing an oscillation pattern on the
SUPRAVENTRICULAR TACHYCARDIA basal line similar to a helix (Figures 28 and 29). These tachycardia
If the bundle branch block is equal to the block prior to tachycardia episodes are very fast and cause syncope if self-contained, although
they may evolve into VF and cause sudden death.
VENTRICULAR TACHYCARDIA
If QRS > 0.14 s
If there is AV dissociation or variable retrograde conduction
Upper QRS axis
All precordial QRS of the same sign (+ or -)
QRS > 0.12 s and does not match with structured or typical RBBB or
LBBB
Figure 28. Helicoidal tachycardia
Time to R wave peak in DII ≥ 50 ms + absence of RS in precordial
Table 8. Data for the ventricular or supraventricular origin The most frequent cause of acquired LQTS is the use of drugs which
of wide QRS tachycardia interfere with repolarizing ion currents (especially IKr), usually in pre-
disposed subjects (women with hypertensive ventricular hypertrophy
Treatment of sustained monomorphic VT with poor clinical tolerance is or perhaps certain genetic polymorphisms which predispose to pro-
electrical cardioversion. When the patient is hemodynamically stable, a longed QT). Other causes of prolonged QT intervals are those listed
choice can be made between electrical cardioversion or drugs (intrave- in Table 9.
nous procainamide -more effective- or amiodarone).
Myocardial infarction or other acute coronary
Recurrence prevention. β-blockers are used, which should be taken by ISCHEMIA
syndromes
all patients with prior acute myocardial infarction. Amiodarone may be
· Hypocalcemia
useful in specific cases to decrease recurrence risk, although it does ELECTROLYTIC
· Hypokalemia
not improve survival. Other anti-arrhythmic drugs are contraindicated ALTERATIONS
· Hypomagnesemia
when there is structural heart disease. ANTI-ARRHYTHMIC · Class Ia
DRUGS · Class III
In patients with normal or near normal systolic function (LVEF > 40%) · Tricyclic antidepressants
and good clinical tolerance during monomorphic VT, it is possible to PSYCHIATRIC DRUGS · Haloperidol
conduct radiofrequency ablation of the reentrant circuit causing the VT. · Phenothiazine
INTRACRANIAL Subarachnoid hemorrhage, intracranial
However, it is necessary to consider implanting an automatic defibrilla- PROCESSES hypertension
tor or ICD, with capability to apply painless therapies of overstimulation OTHER DRUGS Macrolides, quinolones, antihistamines.
or internal electric shocks to restore sinus rhythm, both for secondary BRADYARRHYTHMIA Third degree AV block.
prevention (if systolic function is impaired or arrhythmia tolerance is · Jervell-Large-Nielsen syndrome (autosomal
bad) and for primary prevention in patients with LVEF ≤ 35% after at CONGENITAL recessive, deafness)
least 40 days following a myocardial infarction and under optimized LONG QT · Romano-Ward syndrome (autosomal
medical treatment. ICD implantation is contraindicated when life expec- dominant, not deafness)
tancy is less than 1 year or in patients with NYHA class IV. Table 9. Long QT syndrome etiology

Figure 29. Torsades de Pointes episode in patient with severe sinus bradycardia, secondary long QT and ventricular premature beat with probable
afterpotentials that start the episode (evolved into VF and required defibrillation)

16
 Card i o l ogy 1
Congenital LQTS (less frequent) is a genetic disorder due to mutations 30% of patients present recognizable mutations. Nevertheless,
affecting ion channels, with two classic phenotypical expressions: Ro- up to eight different genes (including calcium and potassium
mano-Ward syndrome (autosomal dominant) and Jervell-Lange-Nielsen channels) have been known to be involved in some cases of this
syndrome (autosomal recessive linked to congenital deafness and due syndrome.
to a potassium channel defect).
These patients present a typical ECG with an incomplete right bun-
Up to 12 genetic types LQTS are reported according to the affected gene dle branch block, a J point above 2 mm and a descending ST seg-
(named from 1 through 12), the first three being the most frequent (Ta- ment (coved-type) with a negative T wave in V1-V3 (this is a diagno-
ble 10). sis ECG, denominated type I). A pharmacologic test can be carried
out on patients with uncertains ECGs, consisting in the intravenous
infusion of flecainide, ajmaline or other sodium inhibiting drugs to
SUBTYPE
MUTATION
T WAVE TRIGGER TREATMENT
force the type I pattern to manifest itself in actually affected pa-
EFFECT tients (Figure 30).
LQTS 1 ↓ Activity K · Exercise β-blocker ± ICD
channels · Stress
· Swimming
LQTS 2 ↓ Activity K · Waking up β-blocker ± ICD
channels · Noises K+ supplements?

LQTS 3 ↑ Activity · Tiredness ICD

Na+ · Fever Group I drugs?
channels
Table 10. Characteristics of main congenital long QT syndrome subtypes

Treatment of Torsades de Pointes is immediate electrical cardioversion.

During the acute phase it is essential to treat the triggering cause (ion
correction, discontinue drugs, treat the ischemia or bradycardia, etc);
it is also possible to use magnesium sulphate or other actions in order
to produce tachycardia (because this reduces QT interval and recurrent
episodes) such as isoproterenol (only in acquired long QT syndrome be-
cause in congenital cases this is contraindicated) or implanting tempo-
rary pacemakers.

Drugs and situations which prolong QT should be avoided to prevent

recurrence. Further, β-blockers should be used with congenital LQTS
(although they cause bradycardia, they decrease the risk of Torsades
de Pointes), which are very effective in type 1 and also very useful in
type 2.
In type 3, the benefit of β-blockers is less clear and anti-arrthymic drugs
from group I could be used, such as mexiletine or flecainide, to reduce
ICD shock episodes. If syncope or ventricular arrhythmia persists in
spite of β-blocker treatment or if it is not effective, an ICD is prescribed
to reduce sudden death risks.
• Congenital short QT syndrome. It is a very rare genetic disorder,
caused by the presence of different mutations in potassium chan-
nels which increase the repolarizing currents and shorten the action
potential in different ways, predisposing the subject to supraven-
tricular arrhythmias (atrial fibrillation) or ventricular arrhythmias
(self-limiting polymorphic tachycardia causing syncope or ventricu-
lar fibrillation, and sudden death). The corrected QT is lower than
320 ms and the T is very high and spiky.
These are patients without structural heart diseases and, given the
risk of sudden death, the implantation of an ICD is recommended.
The use of quinidine may help in some cases.
• Brugada syndrome (BS). It is a genetic disorder which mainly af-
fects the gene SCN5A, in charge of codifying the cardiac sodium
channel, causing a hypofunction of the sodium channel. Only
Figure 30. Effect of flecainide infusion on the ECG of a patient with
Brugada syndrome. Nondiagnostic basal ECG
The arrhythmia associated with Brugada syndrome is a polymorphic
VT which may cause a ventricular fibrillation, usually during sleep,
fever of after using group I anti-arrhythmic agents or other drugs
blocking sodium currents, such as tricyclic antidepressants. There-
fore, it is a common cause of sudden death. It is more lethal in males
and more common in Southeast Asia.
The treatment of symptomatic patients (syncope or sudden
death) consists in avoiding any triggering events and implanting
an ICD. Whether or not an ICD must be implanted in all asymp-
tomatic patients remains a controversial issue, especially when
dealing with relatives of patients with an ECG pattern that can
only be unmasked with drugs, since the risk of long term effects
is not high.
• Catecholaminergic polymorphic ventricular tachycardia. Presents
itself mainly as the result of mutations in the ryanodine receptor
gene (RyR2). Ryanodine is a protein in charge of transporting cal-
cium from the sarcoplasmic reticulum. It causes polymorphic VT

17
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

episodes triggered by physical exercise or stress. The bidirectional
VT is also common in this syndrome. β-blockers may be useful in
these cases, although they usually require the implantation of an
ICD.
Accelerated Idioventricular Rhythm
The accelerated idioventricular rhythm (AIVR) is a ventricular rhythm
resulting from myocardial irritability with ectopic automaticity. The fre-
quency of which usually oscillates between 60 and 120 bpm. It usually
occurs in the context of an AMI and is frequently a sign of reperfusion.
It is usually transitory and only produces major symptoms or hemody-
namic alterations under exceptional circumstances, therefore it gen-
erally requires no treatment. In cases with hemodynamic instability it
must be treated with atropine.
Sudden Cardiac Death
This is defined as a cardiopulmonary arrest occurred within the first
hour following the onset of symptoms of the disease. It is most fre-
quently caused by an ischemic cardiomyopathy (70-80% of the cases).
Other important diseases that may cause a sudden death are the di-
lated and hypertrophic cardiomyopathies (this is deemed to be the
most frequent cause of sudden death among competition athletes,
even though data has been collected in Europe suggesting that right
ventricular dysplasia can be at least as important as the hypertrophic
cardiomyopathy, or more), arrhythmogenic right ventricular cardiomy-
opathy, channelopathies, or WPW syndrome. Figure 32 shows the main
causes of sudden death.

Flutter and Ventricular Fibrillation

These kinds of arrhythmias cause an immediate loss of consciousness
and, if not treated shortly thereafter, death (Figure 31).

Figure 31. 12-lead ECG of a ventricular fibrillation. The rhythm strip

(lower section) shows the recovery of sinus rhythm after a discharge
of the defibrillator implanted on the patient

It is most frequently caused by myocardial ischemia, either during

the acute phase (primary VF) or as the result of the degeneration of
a sustained monomorphic VT in a patient who has suffered a previ-
ous acute myocardial infarction. It is traditionally understood that
a primary VF during the acute phase of the AMI does not affect the
long-term prognosis of the patient, since the risk of a relapse is low
if no other episodes of ischemia occur. Nevertheless, some data link
this to higher mortality rates in the short term, not as the result of Figure 32. Main causes of sudden death
the arrhythmia itself, but because this is more usually present in pa-
tients with larger infractions, with more severe ventricular dysfunc- The treatment for sudden death is immediate cardiopulmonary resusci-
tion and hemodynamic alteration, and who respond less to reperfu- tation (CPR). When this originates in the heart (most cases), recent data
sion therapies. reveal that thoracic compression maneuvers and access to immediate
defibrillation must be prioritized over other therapeutic measures (in-
When this occurs long after an AMI, it does entail a poor long-term cluding mouth to mouth resuscitation) during basic CPR.
prognosis. In all other cases recurrence is frequent and a definite etho-
logic treatment must be scheduled or, when this is not possible, a defi- Therapeutic hypothermia may improve the brain prognosis of some pa-
brillator must be implanted. tients resuscitated after a sudden death event.

18
 Card i o l ogy 1
The implanted cardioverted defibrillator (ICD) is a very useful tool to prevent is based on the idea that many patients are at risk of suffering symptom-
arrhythmic sudden death. The current indications are detailed in Table 11. atic heart failure which may be prevented or alleviated with adequate
cardiovascular prevention measures. There is also a stage classification
described in Table 12.
CLINICAL STATUS
Secondary Aborted sudden Documented VF or VT because of
prevention death irreversible causes High risk of heart failure. Unidentified structural or
STAGE A
functional anomaly without signs or symptoms
Sustained SMVT with hemodynamic
monomorphic compromise or in patients with Structural heart disease clearly developed as the result of
STAGE B
ventricular ventricular dysfunction (LVEF a heart failure, but without signs or symptoms
tachycardia (SMVT) < 40%) Symptomatic heart failure associated with an underlying
STAGE C
Primary Nonsustained NVT in patients with ischemic structural disease
prevention Ventricular ventricular dysfunction (LVEF Advanced structural heart disease and symptoms of heart
Tachycardia (NVT) < 40%) with induced SMVT or VF STAGE D failure at rest despite receiving the maximum allowed
in the electrophysiology study medical treatment
Systolic heart Consider ICD in patients with EF
Table 12. Stage classification by the American Heart Association/
failure < 35% and functional class II-III
American College of Cardiology
of the NYHA classification despite
an optimal medical treatment
The reference to the nature of the predominant functional disorder
Special Channelopathies · Symptoms (syncope or aborted enables researchers to differentiate between systolic HF and diastol-
cases sudden death) ic HF, even though the current trend is to replace “systolic HF” and
· Congenital long QT where the
“diastolic HF” with “HF with reduced LVEF” (HFrEF) and “HF with a
patient suffers a syncope despite
the use of β-blockers preserved LVEF” (HFpEF). In the last few years, patients who have a
LVEF between this two groups (40-49%) are now defined as HF with
Hypertrophic Several sudden death risk factors mid-range LVEF (HFmrEF). This difference is essential when it comes
cardiomyopathy (see the applicable chapter) to deciding on the appropriate treatment for each patient (Table 13).
Dilated Syncope, sustained VT or aborted
cardiomyopathy sudden death
Table 11. Indications for the implantation of an ICD HF WITH HF WITH
REDUCED LVEF PRESERVED LVEF
Prevalence Greater (descending) Lower (increasing,
especially in the

Heart Failure LVEF < 40%

elderly)
> 50%
Left ventricular Yes No
Chapter 04 dilatation
Left ventricular Scarce Frequent
hypertrophy
Treatment · Diuretics (were not proven · β-blockers
The concept of heart failure (HF) encompasses all conditions in which to improve prognosis) · Verapamil or
the heart is not capable of supplying all of the blood the body needs · ACE inhibitors, ARBs, diltiazem
at a given time or does so at the expense of causing high ventricular sacubitril/valsartan or · Careful preload
hydralazine + nitrates and afterload
pressures. Thus, cardiac output is insufficient to cover all of the body’s
· β-blockers management
metabolic needs or this is achieved by the generation of diastolic pres- · Spironolactone, eplerenone (diuretics and
sures that can produce symptoms by retrograde congestion. · Consider digoxin, ICD and vasodilators)
CRT · CRF control and
· Avoid verapamil, comorbidities
diltiazem and anti-
4.1. Classification arrhythmic agents (except
amiodarone)
· Ivabradine (sinus rhythm
and HR > 70)
A classification by the American Heart Association/American College of Usual · Ischemic cardiomyopathy · Hypertrophic
Cardiology and very broadly used nowadays consists of graduating HF etiologies · Dilated cardiomyopathy cardiomyopathy
· Valvular heart disease · Restrictive
states. This provides an idea of how the disease evolves, different from
· Myocarditis cardiomyopathy
the functional classification of heart failure (New York Heart Association · Hypertension and
(NYHA). Class I: no symptoms and no limitation in ordinary physical ac- diabetes
tivity. Class II: mild symptoms and slight limitation during ordinary activ- · Pericardial disease
ity. Class III: marked limitation in activity because of symptoms. Class IV: Table 13. Differences between heart failure with depressed systolic
severe limitations and symptoms even while at rest). This classification function and heart failure with preserved systolic function

19
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

4.2. Pathophysiology and hepatic, splanchnic and lower extremities congestion in the right-
sided CHF. If both signs and symptoms appear, we call it biventricular
and Clinical Characteristics CHF (Table 14).

The pathophysiology underlying a heart failure is showed in Figure 33. LEFT-SIDED CHF RIGHT-SIDED CHF
Symptoms due to low cardiac output (anterograde)
Peripheral tissue hypoperfusion Lung hypoperfusion symptoms
Ischemic C., signs (with consequently lower are rare. Arterial hypotension
cardiomyopathies, oxygen and nutrients tissue
etc. supply): oliguria, asthenia,
Hypertrophy weakness, insomnia, memory
apoptosis loss… being able to reach
fibrosis
cardiogenic shock and multiple
Myocardial lesion
organ failure
Activation Symptoms due to tissue congestion (retrograde)
of neurohormonal Lung congestion: dyspnea, Fluid retention symptoms:
Lower O2 inflow systems and inflammation
Increased O2 to tissues paroxysmal nocturnal dyspnea, pitting peripheral edemas,
requirement (anterograde orthopnea, acute pulmonary painful hepatomegaly, ascites,
· Renin-angiotensin
symptoms) aldosterone edema pleural effusion, protein-losing
· Endothelin enteropathy, oliguria
· ADH
Physical exam
Increased · Sympathetic system
postload Lung crackles, wheezes (cardiac Jugular vein distention,
asthma), pink frothy sputum, hepatojugular reflux,
S3 gallop, S4, pulsus alternans, hepatomegaly, elevated central
Perfusion - Natriuretic
pressure Hydrosaline peptides elevated pulmonary capillary venous pressure
retention pressure
Table 14. Clinical features of HF

Clinical features that happen as a result of HF are summarized in Fig-

preload
ure 34.
(retrograde
symptoms)

Figure 33. Pathophysiology of heart failure

In patients with HFrEF the onset of the symptoms is due to a failure in

the contractile capacity of the myocardium, generally with progressive
ventricular dilation. The most frequent causes are ischemic cardiomy-
opathy and dilated cardiomyopathy. It is the most frequent situation,
and the type of HF in which medical treatment has a higher benefit.
On the other hand, patients with HFpEF have an alteration in myocar-
dial distensibility. There is a higher prevalence between woman, obese
patients and in the elderly, as well as in hypertension and AF patients.

There is also a distinction between acute and chronic HF:

• Acute HF. AMI and its mechanical complications are the paradigm
of acute HF. In this case, there is an abrupt increase in the preload,
afterload or a remarkable decrease in the myocardial functioning
mass. Here, the predominant symptoms are lung congestion and
those due to low cardiac output.
• Chronic HF. It is the most common form of this disease. Patients gen-
erally are on a stable situation, with a variable limitation on their func-
tional capacity. They can present exacerbations during the disease
development, mainly due to myocardial function progressive decline
or to some triggering factors (some of the most frequent ones are in-
fections, treatment discontinuation, NSAIDs use or a high salt intake).

A differentiation between right-sided and left-sided congestive HF

can also be made. This classification refers to symptoms driven by
the predominant failure of one of the two ventricles (mainly due to
Figure 34. Clinical symptoms of congestive heart failure
retrograde congestion): pulmonary congestion in the left-sided CHF

20

4.3. Diagnosis
HF diagnosis is made based on the presence of typical signs and symp-
toms which will guide the supplementary tests:
• ECG can reveal nonspecific alterations or alterations suggesting
the etiology of the clinical condition (Q waves demonstrating pre-
vious AMI, cavity enlargement, supraventricular arrhythmia such
as atrial fibrillation, bundle branch blocks, ventricular arrhythmias,
etc.).
• Chest x-ray (Rx) can show cardiomegaly and signs of pulmonary
venous hypertension, such as vascular redistribution, signs of a
peribronchial, perivascular and alveolar edema, a pleural or inter-
cisural effusion. In accute pulmonary edema, a butterfly-shaped
diffuse perihiliar bilateral pattern of alveolar infiltrate appears
(Figure 35).
Figure 35. Radiology of acute pulmonary edema (APE): butterfly-shaped
alveolar infiltrates
• Echocardiography. It must be performed on all patients with clini-
cal symptoms suggesting a heart failure (first episode), since this
frequently helps in the assess of the etiology and provides useful
data for prognosis purposes. The echocardiography must be con-
ducted to find global or segmental structural heart abnormalities
causing the failure, and to determine global systolic function by esti-
mating the LVEF. The presence of abnormalities in the regional wall
contraction is very common among patients with an ischemic etiol-
ogy. Other elements frequently observed are the dilation and in-
creased sphericity of the ventricles (especially the left ventricle), mi-
tral and tricuspid regurgitation secondary to the dilation of the rings
and various data depending on the etiology (serious hypertrophy in
patients with high blood pressure, aneurysms in some patients with
previous AMI). Diastolic function may be analyzed through different
echocardiographic-Doppler techniques, the most common one of
which is analysis of mitral inflow.
• MRI. A magnetic resonance of the heart enables a more precise
detection of morphologic alterations compared to an echocardio-
Card i o l ogy 1
gram, and enables estimation of masses, volumes and LVEF with the
outmost exactitude.
• Blood test. A dilutional hyponatremia is usually a late sign of a heart
failure, and is therefore usually associated with a poor prognosis.
Anemia and iron deficiency are frequent in advanced stages of the
disease and are also associated with a poor functional capacity and
higher mortality. Increased troponin levels indicate cell necrosis
and, therefore, a worsened prognosis.
Brain natriuretic peptide (BNP) can be used for diagnostic and prog-
nostic purposes. Natriuretic peptides are released as the result of an
increase in ventricular dyastolic pressure. These peptides increase so-
dium and water excretion (by inhibiting its reabsorption in the proximal
tube), and also produce arteriolar and venous vasodilation (countering
the effects of angiotensin II, vasopressin and sympathetic stimulation),
therefore lowering peripheral vascular resistance.
A normal or low BNP value in a non-previously treated patient makes
unlikely that the patient symptoms could be explained by the diagno-
sis of HF. However, increased levels support the diagnosis but do not
confirm it. A clinical test can directly determine this factor or the NT-
pro-BNP, with a longer half-life, being therefore more stable. Certain
conditions, such as those present in the female organism, renal failure,
an COPD, a pulmonary embolism, or old age can increase the BNP level,
and obesity can lower it.
4.4. Chronic Heart Failure
Treatment
HF treatment must be initiated, when possible, by correcting the
underlying cause (AMI, valvular disease, constrictive pericardi-
tis…). Besides, general therapeutic measurements must be imple-
mented:
• Instruct the patient to participate actively in the treatment and
comment on the importance of completing all therapeutic re-
gimes.
Patients can be taught to modify the treatment, especially the dosa-
ge of diuretics depending on their volume state.
• Restrict the intake of salt. Restrict the intake of fluids to less than
1.5-2 litres a day.
• IMC <30. Daily weight.
• Limit consumption of alcohol to 10-20 g/day (strictly forbidden if
enolic ethiology).
• Daily physical activity and exercise adapted to their functional situ-
ation.
• Vaccination against influenza and pneumococcus.
• CVRF control.
• Sleep apnea/hypopnea must be investigated and treated when
present.
• The use of NSAIDs and COX-2 inhibitors, corticosteroids, type I anti
-arrhythmic agents, calcium antagonists (such as verapamil, dil-
tiazem or nifedipine), tricyclic anti-depressants and lithium salts
should be avoided.
Treatment objectives are to alleviate symptoms and signs, reduce hos-
pitalization and improve survival.
21
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Treatment of HF With Reduced LVEF rates in patients with HFrEF (preventing both sudden death and the
death resulting from the progression of the HF). Drugs on which
Therapeutic measures which have shown to have an impact in mortality conclusive data has been obtained are carvedilol, metoprolol, biso-
are ACE inhibitors and ARBs, beta-blockers, MRAs, sacubitril/valsartan, prolol and nebivolol.
hydralazine + nitrates, ivabradine, implantable defibrillator and RCT. • Treatment must be initiated with low doses which are to be in-
Treatment of HFrEF is summarized in Figure 36. creased slowly since, given that these are negative inotropic drugs,
they can initially worsen HF. Their use is admitted for all of the func-
Angiotensin-converting enzyme (ACE) inhibitors tional classes reported by the NYHA, provided the patient is eu-
volemic, which can usually be obtained by means of a concomitant
and angiotensin II receptor blockers (ARBs) treatment with diuretics. Patients who are admitted because of an
exacerbation who are chronically treated with beta-blockers should
They reduce mortality, improve functional class and reduce disease pro- not suspend their use except in life threatening situations (acute
gression in asymptomatic patients with LVEF disfunction. pulmonary edema and cardiogenic shock).
• ACE inhibitors are vasodilators, modify myocardial remodeling af- • They are contraindicated in asthma patients, patients with AV blocks
ter AMI and reduce myocardial hypertrophy and vessel fibrosis and and in Prinzmetal’s angina.
hipertrophy. They improve vessel distensibility and suppress coro-
nary vasoconstriction. In the kidney, they reduce efferent arteriole Mineralocorticoid receptor antagonists
vasoconstriction and mesangial proliferation, and improve renal
blood flow. Given that these are mixed vasodilators (arterial and ve- (spironolactone and eplerenone)
nous), they lower preload and afterload, and favor an increased out-
put of the heart. These drugs are contraindicated in bilateral kidney • Spironolactone is a potassium-sparing diuretic, acting in the
artery stenosis and during pregnancy. Their main adverse events distal convoluted and collecting tubules antagonizing the aldo-
are cough, kidney injury, angioedema, and hyperkalemia (specially sterone effect (it secretes sodium and absorbs potassium and
in diabetic patients and when combining with MRAs). protons). Their beneficial effects on patients with HF is not the
• ARBs have not shown to be superior to ACE inhibitors, so these are result of the diuretic effect, but the antagonism of the delete-
reserved to patients developing intolerance to ACE inhibitors (main- rious effects of high aldosterone levels: vascular fibrosis, sym-
ly cough or angioedema). The concomitant use of an ARB, an ACE pathetic tone activation, reduction in arterial distensibility, in-
inhibitor and an MRA is contraindicated. creased sodium in the body… Its use at low doses has shown to
increase survival rate.
Beta-blockers • They should not be prescribed if creatinine values are over 2.5 mg/
dL or potassium levels are above 5,5 mEq/L, due to the high risk of
• Several studies have shown beta-blockers improve LVEF and func- hyperkalemia. This is especially important when associating them
tional class, lower hospitalization rates, and increase the survival with ACE inhibitors and ARBs.

Symptomatic HF
with LVEF<40%

ACEi & BB

Symptomatic No
ICD in primary prevention (LVEF <35 despite OMT)

LVEF≤35%?
Diuretics whether congestion signs/symptoms

Yes
or secondary (symptomatic VT/VF)

MRAs

Symptomatic No
LVEF≤35%?
Yes

Tolerates ACEi/ARBs QRS ≥130ms SR y HR ≥70bpm

Sacubitril-valsartan CRT Ivabradine

Symptomatic
Yes LVEF≤35%? No
HDLZ/NT, No more actions.
digoxine, VAD, HT Reduce diuretic?

Figure 36. Current guidelines HFrEF treatment summary (ACEi: angiotensin-converting enzyme inhibitors; BB: beta-blockers; MRAs: mineralocorticoid
receptor antagonists; ARBs: angiotensin II receptor blockers; CRT: cardiac resynchronization therapy; SR: sinus rhythm; HR: heart rate; OMT: optical medical
treatment; HDLZ/NT: hydralazine + nitrates; ICD: implantable cardioverter-defibrillator; VAD: ventricular assist device; HT: Heart transplant)

22

• Eplerenone (a more selective inhibitor to aldosterone) has
been shown to increase survival rates in patients who have suf-
fered an AMI and present a LVEF≤40% and clinical signs of HF or
diabetes. In patients with a NYHA functional class ≥II, eplere-
none appears to be useful to lower the combined cardiovascular
mortality endpoint or hospital admission as a result of HF exac-
erbation. Its main advantage as compared to spironolactone is
that it causes a lower gynecomastia rate, even though it is more
expensive.
Card i o l ogy 1
• In digital intoxication, the earliest symptoms are gastrointestinal,
visual (“xanthopsia” or vision of a yellow halo) and confusion. It
can also induce heart arrhythmias; most frequent ones are ven-
tricular premature beats and sinus bradycardia or AV blocks.
Non-paroxysmal auricular tachycardia with variable AV block, ac-
celerated nodal rhythm or bidirectional ventricular tachycardia
are really specific. ST segment depression is not a sign of digoxin
intoxication.

Neprilysin inhibitor and MRBs (sacubitril/valsartan)

Digoxin toxicity
Sacubtitril is an inhibitor of neprilysin, the enzyme responsible for the
degradation of BNP and, therefore it increases the BNP circulating lev-
els. Its association with a MRBs (valsartan) has shown to reduce both
mortality and HF hospital admission rates in patients with symptomatic
HF (NYHA II-IV) when comparing with an ACE inhibitor. Therefore, pa-  Digoxinemia No digoxinemia
tients who are still symptomatic despite the use of an ACE inhibitor/
Renal failure K+, Mg2+, O2,
MRBs, a beta-blocker and MRA should replace the ACE inhibitor/MRB Drugs  pH,  thyroids,
for a neprilysin inhibitor. It is being discussed whether the use of nepri- Ca2+
lysin inhibitor as a first line treatment in newly diagnosed HF patients is
an adequate option, but clinical guidelines do not include it yet for this
indication.
Gastrointestinal Electrical
Hydralazine + nitrates Nausea, vomiting, diarrhea · More frequent: ventricular extrasystoles
· Atrioventricular block
· More specific: supraventricular tachycardia
Hydralazine is a potent arterial vasodilator. When associated to nitrates
with variable AV block
(predominantly venous vasodilators) it has shown to increase survival rate · Accelerated nodal rhythm
against placebo in patients with HFrEF, especially in African American pa- · Bidirectional tachycardia
tients. They can be associated or an alternative to ACE inhibitors/MRBs.

Figure 37. Digitalis toxicity

Ivabradine

It acts as a selective blocker of the If current in the sinus node. In pa-

tients in sinus rhythm, with HR>70 bpm, with a LVEF ≥35% and NYHA
class ≥II, have shown to reduce the combinate outcome of cardiovascu-
lar death or HF hospital admissions.
Digoxin
• It has been traditionally used to treat combinations of atrial fibril-
lation (mainly in the acute phase) and heart failure, even though
no clinical trials have proven its effects on survival rates. It has also
not been proven to increase survival rates in sinus rhythm but does
reduce hospitalization rates in cases of heart failure.
• It has a narrow therapeutic range, so it is common for drug toxic-
ity to occur. There are many factors that can modify blood levels.
In some situations, these levels can be increased like in kidney
failure (most frequent cause of intoxication) and in the adminis-
tration of certain drugs (quinidine, amiodarone, verapamil, dil-
tiazem, propafenone, macrolides, itraconazole, cyclosporin…).
Besides, many situations increase toxicity without changing di-
goxin blood levels as in hypokalemia, hypomagnesemia, hypox-
emia, anemia, acidosis, amyloidosis, elder or hypothyroidism.
On the other hand, some factors may decrease digital activity.
Administration of enzyme inducer drugs (barbiturates, rifampi-
cine or diphenylhydantoin), situations or drugs which reduce its
absorption (HF, antacids, antidiarrheals, metoclopramide, cole-
stiramine) or hyperthyroidism are examples of factors which de-
crease its activity (Figure 37).
Diuretics
Diuretics have not shown to increase survival; therefore, their use must
be restricted to the minimal dose needed to improve symptoms. They
can increase asthenia and produce hydroelectrolytic disorders (hypoka-
lemia and hyponatremia). The main groups and main characteristics are
summarized in Table 15 and Figure 38.
Iron
Intravenous administration in patients with iron deficiency has shown a
beneficial effect improving symptoms, quality of life, and reducing hos-
pital admissions.
Diabetes
The use of sodium/glucose cotransporter 2 (SGLT2) inhibitors (dapa-
gliflozine, empagliflozine, canagliflozine...) might reduce hospitalization
rate in patients with heart failure, even in patients without diabetes.
Antiarrhythmic drugs
They are contraindicated in sudden death primary prevention. In
secondary prevention, when patients already have arrhythmias,
amiodarone, dofetilide and mainly ß-blockers (improve survival
rate).

23

DIURETIC
Thiazides (chlorothiazide,
xipamide, indapamide)
Loop diuretics (frusemide,
etacrynic acid, bumetanide,
indacrinone)
K+ sparing agents
1. Aldosterone antagonists
(spironolactone)
2. Amiloride, triamterene
24
A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)
ACTION MECHANISM INDICATIONS CONTRAINDICATION COLLATERAL EFFECTS
Inhibition of Na/Cl · Mild or moderate heart When GF < 25 mL/min. · Hypo K
channels in distal failure · Hyperuricemia
convolute tubule · Hypertension · Increased glucose and lipids
Inhibition of the · Refractory edema · Anuria · Hypo K
Na+-K+-2Cl- symporter · Serious acute edemas · Pregnancy · Hypo Na
(cotransporter) in the · GF < 25 mL/min. · Hypersensitivity · Hyperuricemia
thick ascending limb · Serious HTN · Hypo Mg
of the loop of Henle · Cytotoxicity
Blocks the action of · Associated with other · Hyper K · Impotence, gynecomastia
aldosterone in distal diuretics with edemas or HTN · Renal failure · Hyper K
convolute tubule · Hyperaldosteronism not · Treatment with K
correctible with surgery supplements
· Edemas with
hyperaldosteronism
(nephrotic syndrome, CHF,
cirrhosis)
Blocks the absorption · Same as above Hyper K
of Na+ in distal · Liddle’s syndrome
convolute tubule
Table 15. Main characteristics of main diuretic types
Figure 38. Site of action and mechanism of diuretics

Implantable cardioverter-defibrillator (ICD)
It has become a device widely used in patients at high risk of sudden
death, especially for ischemic heart disease. ICD should be indicated
in:
• Patients with HF who have been resuscitated from cardiac arrest
(secondary prevention)
• Patients that present symptoms (usually syncope or pre-syncope)
related to ventricular arrhythmias (secondary prevention).
• Patients with LVEF ≤35% and NYHA class II-III despite of optimal
medical treatment (primary prevention).
• Patients, regardless of NYHA class, with LVEF ≤30% despite of opti-
mal medical treatment (primary prevention).
Generally, they should be indicated to patients with a life expectancy >1
year (thus, it is not indicated in NYHA class IV).
Cardiac resyncronization therapy (CRT)
It aims to improve the mechanical asynchrony which appears in a
high percentage of patients with advanced systolic dysfunction re-
sponsible for a substantial ventricular contraction inefficiency. This
therapy is based on the use of a pacemaker that stimulates both
ventricles simultaneously, in order to maintain a synergy in the con-
traction of the left ventricle walls, thus obtaining a more effective
pumping. This is accomplished by placing one stimulating lead in the
apex of the RV and lead in the lateral or posterolateral epicardium of
the LV, generally through the coronary venous system. It has shown
to increase survival rate, functional class, exercise tolerance and
quality of life in patients with (patient must accomplish the three
statements):
• Severe ventricular dysfunction (LVEF below 35%).
• Symptomatic (NYHA class II-IV) despite an adequate medical treat-
ment.
• With confirmed asynchrony (QRS wider than 150 ms [especially in
case of a left bundle branch block, LBBB]).
Indications for ICD and CRT frequently overlap; therefore, the current
trend is to implant an CRT-ICD (Figure 39).
Figure 39. Cardiac resynchronization therapy device
Card i o l ogy 1
Cardiac rehabilitation units
Cardiac rehabilitation units have demonstrated to reduce HF hospital
admissions and mortality. Regular aerobic exercise improves functional
capacity, reduce symptoms and HF hospital admissions.
Verapamil and diltiazem are contraindicated in patients with HFrEF.
Treatment of HF With Preserved LVEF
Despite HF with preserved LVEF treatment:
• Until now, no treatment has demonstrated to reduce morbidity in HF-
pEF. Thus, treatment must be directed to reduce symptoms, controlling
BP (vasodialtors), myocardial ischemia, evading tachycardia (BB, digox-
in, calcium channel blockers…), favoring sinus rhythm (atrial fibrillation
reduces auricular filling phase), and reducing congestion.
• In contrast with HFrEF, the use of verapamil and diltiazem is not con-
traindicated.
• Diuretics and vasodilators must be used carefully, because it is neces-
sary to maintain an adequate preload in order not to reduce cardiac
output.
4.5. Acute Heart Failure
Treatment
Acute Cardiogenic Pulmonary Edema
Cardiogenic pulmonary edema is a medical emergency that requires
careful monitoring in order to maintain blood pressure, heart rate
and urine output and, occasionally, the pressure of the pulmonary
vessels by means of a Swan-Ganz catheter. Treatment is to be quickly
commenced:
• High-flow oxygen. Noninvasive or invasive mechanical ventilation
could be performed if necessary.
• The patient should be seated, if possible, legs dangling.
• Morphine sulfate improves the symptoms because of vasodilatory
and central sedative effects.
• Potent diuretics should be used, such as furosemide, which also has
a vasodilatory effect.
• Vasodilators should be used when blood pressure is higher than 90
mmHg. Intravenous nitroglicerin is the drug of choice.
• Arterial hypotension may be treated with an intravenous positive
inotropic agent, such as dopamine, dobutamine or levosimendan.
• An intra-aortic balloon pump may be useful in some cases, espe-
cially when blood pressure is low.
Note that the use of sympathetic agonist drugs tends to worsen the
situation if the underlying heart disease is a condition with pure dia-
stolic dysfunction, such as mitral stenosis or hypertrophic obstruc-
tive cardiomyopathy, whether the triggering agent of the acute pul-
monary edema is atrial fibrillation with rapid ventricular response
(a relatively frequent event). Nevertheless, beta blockers or calcium
channel blockers may be useful, as they prolong diastolic time by
slowing conduction through the AV node and have lusotropic ef-
fects. However, an urgent electrical cardioversion is usually indicat-
ed in this case.
25
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Severe Myocardial Failure Treatment
Intra-aortic Balloon Pump
It is an effective percutaneous assisted circulation technique that can be
implanted in conscious patients. A catheter with a balloon is introduced
in the femoral artery and pushed towards the thoracic aorta, placing
the balloon immediately distal to the left subclavian artery.
The balloon is inflated during diastole and deflated during systole.
ECG signal and invasive pressure should be monitored in order to
synchronize the inflation and deflation. Correct use of this procedure
results in decreased systolic blood pressure and increased diastolic
blood pressure (thus raising mean blood pressure).
With these devices, patients may be discharged in order to wait for their
heart transplant at home, or they may serve as therapy for patients not
eligible for transplantation. Nonetheless, their long-term use is associ-
ated with a significant risk of complications like bleeding, embolism and
infection (Figure 41).
Another alternative mechanical support for patients with very severe
cardiac insufficiency is extracorporeal membrane oxygenation (ECMO),
which involves the removal of nonoxygenated blood from the superior
vena cava, its oxygenation inside the device and its reinfusion to the
inferior vena cava (veno-venous ECMO, respiratory support only) or to
the arterial territory (veno-arterial ECMO, respiratory and circulatory
support).

Contraindications: significant aortic insufficiency (AI), aortic dissection,

and access problems because of peripheral vascular disease.

An IABP is mainly indicated for patients in cardiogenic shock, patients

that present low cardiac output after cardiac surgery, those with unsta-
ble angina resistant to medical treatment in preparation for emergency
coronary angiography, those facing mechanical complications after
acute myocardial infarction and in very ill patients as a bridge to heart
transplantation, but its systematical use is controversial (Figure 40).

Figure 40. Intra-aortic balloon pump

Ventricular Assistances and “Artificial Heart”

Ventricular assist devices provide myocardial support. For that purpose,

blood is drawn from an atrium or vein and sent through the correspond-
ing artery (this may be a pulmonary or aortic artery, and it may con-
sist of right ventricular assistance, left ventricular assistance, or both at
once). They are implanted in operating rooms and are indicated upon
cardiogenic shock after surgery, as a bridge to heart transplantation and
in some cases of severe acute myocarditis until actual recovery.

Different models with different types of operation exist. Some devices

are fully implantable inside the body, and placed in a preperitoneal po-
sition which, by means of a percutaneous connection, which enables
battery recharge (“artificial heart”). Figure 41. Ventricular assistance

26

Heart Transplantation
This is a very effective therapy for the treatment of end-stage heart
failure. Results are good, not only regarding survival but also regarding
lifequality. Most of the patients who undergo a heart transplant are pa-
tients with ischemic or idiopatic dilated cardiomyopathy. Most frequent
indications are summarized in Table 16.
Ergospirometry is the best tool to asses functional class and to correlate
prognosis. Guidelines assess a peak O2 value ≤14ml/kg/min as the cutoff
to indicate heart transplantation. Currently, it is preferred not to talk
about contraindications but comorbidities that increase morbimorbid-
ity after transplantation (Table 17).
Card i o l ogy 1
There are different anatomopathological transplant rejection de-
grees:
• Hyperacute. It is currently rare, and it consists in a severe endothe-
lial lesion due to the presence of preformed antibodies against MHC
or AB0 systems.
• Acute. It usually occurs after the first week and before the first year,
consisting in a lymphocytic infiltration. The most common immuno-
suppression combination therapy used to prevent this to happen is
tacrolimus, mycophenolate and corticosteroids.
Graft vascular disease seems to be favored by repeated rejection epi-
sodes, CMV infection and hyperlipidemia. Angina is exceptional (donor
heart is denervated) and might appear as sudden death or as a silent
myocardial infarction.

FACTORS WHICH INCREASE MORBIMORBIDITY Most frequent cancer types are skin and lymphomas (mainly non-Hodg-
AFTER HEART TRANSPLANTATION kin B-type, extranodal, related with EB infection).

· Non controlled active infection About patients’ follow-up:

· Peripherical or cerebrovascular arterial disease • Endomyocardial biopsy. It is the most accurate test to monitor graft
· Non-reversible pulmonary hypertension, despite medical rejection. In heart transplanted patients, endomyocardial biopsies are
treatment performed periodically to detect early stages of this complication. They
· Cancer are normally preformed in the left ventricle through a venous access.
· Diabetes with severe organic disfunction • Echocardiography. It is the first-choice test to assess graft function.
· Chronic kidney disease with creatinine clearance < 30ml/min
· Systemic multiorgan disease
· BMI >35 before heart transplantation
· Smoking, drinking or drug use
· Poor social support

Table 17. Comorbidities which increase morbimorbidity after heart

Cardiomyopathies
transplantation (possible contraindications)
Chapter 05

A relative age limit for heart transplantation has been stated in 70 years
old. The most used surgical technique is the bicaval one.
Mortality causes vary depending on the moment they occur. Primary
graft failure is the most frequent death cause in the first year after the
procedure, particularly in the first month (after the first month infec-
tions are the main cause). After the first year, vascular graft disease is
the main death cause, followed by cancer.
Cardiomyopathies are a wide group of diseases characterized by a struc-
tural and functional myocardial alteration in the absence of hemody-
namical overload or coronary artery disfunction to justify it. Therefore,
myocardial affectation in patients with coronary artery disease, valvo-
pathies or hypertension are not considered as patients with cardiomy-
opathy. Table 18 summarizes the main types of cardiomyopathy and
its etiology.

ABSOLUTE RELATIVE INSUFFICIENT

(Suitable patients in advanced functional class)
· Refractory cardiogenic shock · Peak oxygen consumption from 11 · Severely depressed LVEF
· Documented dependence on intravenous to 14 mL/kg/min (or below 55% of predicted) · Functional class III to IV
inotropic support to maintain adequate tissue in advanced functional class
· Peak oxygen consumption above
perfusion · Persistent ischemia incurable by any other 15 mL/kg/min (or above 55%
· Peak oxygen consumption below 10 mL/kg/min intervention of predicted)
once the anaerobic threshold has been reached · Recurrent instability in hydrosaline balance,
· Uncontrollable ventricular arrhythmias despite adequate therapeutic treatment
despite all possible therapeutic measures
· Constraining ischemic symptoms, refractory
to therapeutic treatments (which include
revascularization)
· Patients with congenital heart disease
in advanced functional class ineligible
for surgical correction
Table 16. Indications for heart transplantation

27
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

GROUP TYPE CAUSES

Hypertrophic cardiomyopathy
Dilated cardiomyopathy
Restrictive cardiomyopathy
Arrhythmogenic right
ventricular cardiomyopathy
Nonclassifiable cardiomyopathy
Familial/genetic · Mutations affecting sarcomeric protein genes
· Friedreich’s ataxia
· Noonan syndrome
· Glycogen storage disease (Pompe disease)
· Lysosomal disease (Anderson-Fabry disease)
Nonfamilial/nongenetic · Obesity
· Infant of diabetic mother
· Overtraining syndrome
Familial/genetic Mutations affecting cytoskeletal, sarcomeric or Z band
protein genes
Nonfamilial/nongenetic · Infectious myocarditis: Coxsackievirus B, HIV, diphtheria,
Chagas disease
· Alcoholic cardiomyopathy
· Arrhythmias (tachycardiomyopathy)
· Kawasaki disease
· Pregnancy (peripartum cardiomyopathy)
· Chemicals and drugs (anthracyclines, cyclophosphamide)
· Endocrinopathies (Myxedema)
· Nutritional deficiencies (carnitine, thiamine: beriberi;
selenium: Keshan disease)
Familial/genetic · Familial amyloidosis (transthyretin)
· Desminopathies
· Pseudoxanthoma Elasticum
· Hemochromatosis
· Glycogen storage disease (Pompe disease)
Nonfamilial/nongenetic · Amyloid Light-chain (AL) amyloidosis
· Scleroderma
· Carcinoid syndrome
· Postradiation damage
· Endomyocardial fibrosis:
- Idiopathic
- Hypereosinophilic syndrome (Loeffler)
- Drugs: serotonin, ergotamine, methysergide, mercurial
agents, busulfan
· Metastasis
Familial/genetic Mutations affecting desmosomal protein genes
Nonfamilial/nongenetic Not reported
Familial/genetic Spongiform cardiomyopathy (Noncompaction
cardiomyopathy)
Nonfamilial/nongenetic Tako-tsubo cardiomyopathy (Apical transient dyskinesia,
apical ballooning) or stress cardiomyopathy
Table 18. Etiologic classification of cardiomyopathies

The different characteristics of three classic cardiomyopathies (hyper-

trophic, dilated and restrictive), are summarized in Table 19. 5.1. Hypertrophic Cardiomyopathy
HYPERTROPHIC DILATED RESTRICTIVE
LV volume ↓↓↓ ↑↑↑ =/↑/↓ Concept
↑↑↑ = or ↓ (slight) = or ↑ (slight)
LV thickness
and Fisiopathology
Dysfunction Diastolic Systolic Diastolic
Ejection fraction =/↑ ↓ =/↓ (slight)
Defined as an increase in ventricular wall thick-
Clinical observations · Asymptomatic · Heart failure · Effort dyspnea ness in the absence of abnormal hemodinami-
· “SAD” symptoms: symptoms · Right heart failure cal circumstances (such as high blood pres-
- Syncope and · Mural thrombus · Strokes
sure, congenital cardiomyopathies or heart
sudden death strokes
- Angina · Arrhythmias valve diseases) sufficient to cause the anomaly
- Dyspnea (Figure 42). Its prevalence is around 1/500
adults, being the most frequent genetical car-
Table 19. Differences among hypertrophic, dilated and restrictive cardiomyopathy
diac disorder.

28

Figure 42. Layout of hypertrophic cardiomyopathy with septal
predominant
The most important pathophysiologic alteration is diastolic dysfunction
causing structural changes to the myocardium. It increases left filling
pressures, which explains pulmonary congestion and its most frequent
symptom: dyspnea.
Increased oxygen demand and anomalies in associated intramural coro-
nary arteries, among other reasons, result in predisposition to ischemia.
Approximately 5% to 10% of the patients show late progress towards
thinning and myocardial dilation imitating dilated cardiomyopathy.
Septal hypertrophy may result in flow acceleration of the left ventricle
outflow tract causing a Venturi effect which, associated with abnormal
location of mitral valve papillary muscles, forces the valves into systolic
anterior motions (SAM) and to move towards the septum. This causes dy-
namic left ventricular outflow tract obstruction which occurs, at rest, in
one-third of patients. Another third of patients does not present obstruc-
tion at rest, but does with Valsalva-type maneuvers (dynamic obstruc-
tion), and the remaining third does not present any significant dynamic
obstruction (> 30 mmHg). SAM is characteristic, but not pathognomonic
of hypertrophic cardiomyopathy. It usually associates a variable degree of
mitral valve regurgitation, proportional to the obstruction size.
Pathology
At an ultrastructural level, in addition to hypertrophy, there is a variable
degree of fibrosis and disorganization of myocardial histology adopting
a disarrayed pattern, as well as changes into the intramural coronary
arteries that show wall thickening and facilitate the appearance of myo-
cardial ischemia.
At macroscopic level, it is common to find significant asymmetric hypertro-
phy (> 15 mm), which is, in most of the cases, septal. However, there are
other hypertrophy patterns, such as apical hypertrophic cardiomyopathy
(Yamaguchi’s disease, frequent in Japan), with giant inverted T-waves in the
precordial lead (Figure 43) or cases of concentric hypertrophy.
Card i o l ogy 1
Figure 43. Echocardiographic image (apical four-chamber view) with
echo-enhancer (an increased echogenicity may be noted inside the
heart chambers because of contrast) of a patient with hypertrophic
cardiomyopathy with apical predominance (arrows)
Etiology
In 60-70% of the cases, hypertrophic cardiomyopathy is a genetic dis-
ease with dominant autosomal inheritance and variable penetrance. It
affects mainly to sarcomeric proteins (being ß-myosin heavy chain the
most frequent one, besides myosin binding protein C, α-tropomyosin,
T and I troponins…), also characterized by an earlier and more severe
onset. Another 5-10% of the patients with genetic hypertrophic cardio-
myopathy are related with neuromuscular and deposit diseases (see
Table 19). In approximately 25% of the patients, the underlying cause
cannot be identified.
Clinical History
Most patients remain asymptomatic or have mild symptoms. The most
frequent symptom is dyspnea, followed by angina. Fatigue, lighthead-
edness and syncope (because of various mechanisms, from neural me-
diation to other severe, caused by left ventricular outflow tract obstruc-
tion or ventricular arrhythmias) are also present. Frequently, symptoms
are heightened by exercise or during postprandial periods. Atrial fibrilla-
tion is frequent during clinical course and usually results in a significant
worsening of symptoms. In some cases, disease onset occurs as heart
failure or even sudden death.
Examination may be normal except for the presence of a fourth sound
and, occasionally, a double, prominent apical impulse.
In patients with left ventricular outflow tract obstruction a hard systolic
murmur is heard, located in the apex and left sternal border, which may
irradiate to the heart’s base but not to the carotids (unlike aortic valve
murmur).
Likewise, an initially intense, bisferiens pulse is usually present and, if
the obstruction is severe, there is a double inverted splitting of the sec-
ond heart sound.
29
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Whatever decreases preload (Valsalva maneuver, sudden standing, ar-
rhythmias) and/or afterload (vasodilators, exercise) or increases con-
tractility (positive inotropes, physical exercise), increases the outflow
tract obstructive gradient and the murmur’s intensity. On the other
hand, the murmur’s intensity decreases with increased preload (squat-
ting, raising lower limbs, and volemia expansion) and/or afterload (va-
soconstrictors such as phenylephrine, squatting) (Figure 44).
An echocardiogram is the most important study to be performed, since
it assesses the magnitude and distribution of ventricular hypertrophy
(normal septum diastolic thickness in adults is lower than 12 mm), the
presence of SAM (which enhaces dynamic obstruction), and enables
quantitation of basal outflow tract gradient and after Valsalva-type ma-
neuvers; a frosted appearance of the ventricular septum is a common
feature (Figure 46).

Increases murmur
A
↑ Ventricle contractility ↓ Preload (less volume to send ↓ Afterload RV
(contraction with more strength) with more strength) (less flow resistance) SEPTUM
· Exercise · Valsava
· Sudden standing · Arterial vasodilators
· Isoprenaline · Exercise
· Digital · Tachycardia
· Nitroglycerin

· Calcium antagonists · Volume expansion · Squatting Ao

· β-blockers · ↑ Venous return
· Raised legs
· Phenylephrine LV

↓ Contractility ↑ Preload ↑ Afterload

Decreases murmur
RA

Figure 44. Murmur variations in hypertrophic cardiomyopathy

Diagnosis
The ECG usually shows certain changes, such as variable degrees of left
ventricular hypertrophy and left atrial growth. Abnormal Q waves in the
left precordial lead are characteristic in the absence of previous myocar-
dial infarction. In apical form, inverted “giant” T waves may be noticed B
in the precordial leads (Figure 45).
SEPTUM

RV

LV

Figure 46. Echocardiographic image in parasternal long axis (A) and short
axis (B) of a patient with asymmetric septal hypertrophic cardiomyopathy,
showing excessive thickness of intraventricular septum (arrows)

Enhancement (increase) of post-extrasystole gradient and murmur is

Figure 45. 12-lead ECG of a patient with hypertrophic cardiomyopathy
with apical predominance. Note they are in atrial fibrillation, the elevated
voltages of QRS complex in precordial leads and “giant” inverted T-waves in
left precordial leads.
Heart shape on chest x-ray is usually normal or with mild cardiomegaly,
especially at the expense of the left atrium when it is dilated.
very frequent. In apical forms, ventriculography has the morphology of
an ‘’ace-of-spades’’.
Nowadays, finding the causal mutation has little effect in the patient
management. However, identifying the mutation in the “index” case,
enables to do the familiar screening. Therefore, if a mutation has been
described in a patient, first degree family members must also be tested

30

for this mutation. Family members in which that mutation is not found
do not need further studies, but those in which the mutation is present
must undergo a periodic follow-up including an ECG, an echocardiogra-
phy and a Holter.
Cases in which no mutation is found in the index patient should undergo
a periodic follow-up, despite the phenotypical initial appearance.
Prognosis
Most patients remain asymptomatic or have mild symptoms. How-
ever, there are other possible courses for the disease which provide
a poor prognosis, such as heart failure (usually diastolic), left ven-
tricle outflow tract obstruction, the development of atrial fibrilla-
tion (associated with a significant increase of thromboembolic com-
plications), and the presence of ventricular arrhythmias, which can
regrettably make the disease result in sudden death. In fact, in all
likelihood, hypertrophic cardiomiopathy is the most frequent sud-
den death cause of cardiac origin in young people and competition
athletes.
Annual mortality is approximately 1-2%. The most frequent cause is
sudden death, resulting from ventricular arrhythmias, usually poly-
morphic, with a higher risk among children (up to 6% annually) who
also present major hemodynamic mechanisms in addition to arrhyth-
mia.
Treatment
Treatment general goals are to control symptoms and to prevent sud-
den death with the implant of an ICD in selected patients. The diagnosis
of this entity contraindicates intense exercise and competition sports.
Treatment in patients
with left ventricle outflow tract obstruction
Treatment of symptomatic patients is summarized in Figure 47.
Symptomatic obstructive
hypertrophic cardiomyopathy
ß-blockers
Verapamil-
Disopyramide
Positive inotropic
diltiazem agents are
contraindicated
(digoxin)
If still Surgical Alcohol
symptomatic myectomy septal ablation
Of choice If high surgical risk
Figure 47. Symptomatic obstructive hypertrophic cardiomyopathy
treatment algorithm
Beta blockers are the treatment of choice due to their capability to
decrease contractility and cause bradycardia (then lengthening dias-
tole). However, it is not proven that β-blockers lower the risk of sud-
den death, thus their use has not proven benefit in asymptomatic
patients.
Card i o l ogy 1
Effective alternatives (in case of contraindications or inefficacy) are di-
sopyramide, verapamil or diltiazem. In refractory cases they may even
be combined.
Diuretics should be used with caution to avoid excessive preload de-
crease which would worsen the obstructive gradient; they are useful for
relieving pulmonary congestion.
If despite optimal medical treatment, a severe obstruction gradient
persists (> 50 mmHg at rest) together with disabling symptoms (usually
NYHA III-IV class), an intervention may be considered to decrease or
alleviate gradient:
• Septal myectomy (resection of part of the hypertrophied septum),
with or without intervention on the associated mitral valve if ap-
plicable, has been shown to improve symptoms and mitral insuf-
ficiency in the long term.
• Alcohol septal ablation. It is a therapeutic alternative, which causes
a nonsurgical septum reduction by means of cardiac catheterization
and causing a controlled septal infarction, by infusing ethanol to the
septal coronary branch. It requires favorable septal branch anatomy
and extensive experience. A significant ratio of patients suffer com-
plete AV block after the procedure.
• Dual chamber pacemaker (DDD). Implanting a DDD changes the
ventricular depolarization sequence, triggering gradient decrease
and hemodynamic and symptomatic improvement in some patients
(especially elderly patients). It is recommended.
Sudden Death Prevention
and Arrhythmia Management
One of the most important assessments to make in these patients is
the risk of having a sudden death, and whether it is indicated or not
to implant an ICD (only treatment proven to reduce the risk of sudden
death). There is a series of factors which enable to identify patients at
risk (Table 20). Classically, the presence of one or various of these fac-
tors were enough indication to implant an ICD. Currently, scores like
HCM-SCD score must be performed. This score takes into consideration
the classical factors, but including others like left atrium size, outflow
tract gradient, age, myocardial thickness, etc. It is considered to be at
high risk patients with a score > 6%, thus ICD implant might be consid-
ered in patients with a lower score.
Patients that present recurrent ventricular arrhythmias or ICD shocks,
ß-blockers or amiodarone might be an option to reduce its frequency.
HIGH RISK FACTORS POTENTIAL RISK MODIFIERS
· Aborted sudden death · Obstructive gradient
· Spontaneous sustained · Unfavorable genotypes
monomorphic VT (SMVT) · Delayed enhancement
· Premature sudden death event in gadolinium areas
first degree relatives in myocardium as a result
· Recent syncope of unknown origin of fibrosis
· Septal thickness > 30 mm · Left ventricle apical aneurism
· Nonsustained Holter VT
(especially among young people)
· HBP during ergometry
Table 20. Factors related to sudden death risk in hypertrophic
cardiomyopathy
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 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)
5.2. Dilated Cardiomyopathy
Concept and Etiology
The prevalence of this disease is about 1/2,500 individuals. It is defined
by evidence of left ventricular dilation and dysfunction without hemo-
dinamical overload or coronary artery disease, sufficient to cause the
observed overall systolic worsening. Right ventricle deterioration is not
necessary for diagnosis, although this is common in late stages and is
associated with worse prognosis.
When etiology is not detected by means of meticulous investigation the
case involves an idiopathic dilated cardiomyopathy, which occurs in al-
most half the cases. There are some hints which suggest that the origin
of these diseases is a previous asymptomatic viral miocarditis.
Apparently, the phenotype of dilated cardiomyopathy may be secondary to
genetic disorders (25%) or may as well be the final expression of myocardial
damage produced by a large amount of circumstances that converge in left
ventricular dysfunction and dilation; excessive alcohol consumption is the
most frequent cause of secondary dilated cardiomyopathy.
Some cardiomyopathies may be reversed by correcting triggering factors
such as alcoholism, tachycardiomyopathy, nutritional deficiency or hypo-
thyroidism. It has been described that mechanical spontaneous asynchro-
ny (in left bundle branch block) or the one produced by the pacemaker
chronic stimulation of RV might produce progressive systolic failure. This
can be prevented or reversed with cardiac resynchronization therapy.
Clinical History and Diagnosis
This primarily affects young individuals, especially males and African-
American people (who also seem to be more severely affected). This
disease is the paradigm of heart failure with systolic dysfunction, with
all the signs and symptoms of that situation.
Complementary tests reveal cavity growth and systolic dysfunction (Figure
48). It is mandatory to perform a diagnostic coronary angiography to dis-
miss the presence of myocardial ischemia as the cause of the ventricular
disfunction (coronary CT scan might be an alternative in selected patients).
Figure 48. Apical Four Chamber Echocardiogram view of left ventricle
dilation and loss of normal ventricular geometry in patient with dilated
cardiomyopathy
32
Cardiac magnetic resonance reveals a pattern of predominantly subepi-
cardial fibrosis, unlike infarct, which usually dominates the subendocar-
dium (Figure 49).
Figure 49. Four chamber cardiac magnetic resonance imaging in
diastole, revealing dilation of the left ventricle (A) and image obtained
with correct sequence that shows the absence of delayed myocardial
enhancement areas (B). Taken from G. Fernandez, G. Robles, Lopez
Zamorano. Manual de Imagen Cardíaca. CTO Editorial, 2010
Prognosis
and Treatment
Mortality seems to be lower compared to systolic disfunction of
ischemic origin, but it is increased in patients with high NYHA class
(even 50% in 5 years) and particularly into the first year after a hos-
pital admission. Half of the deaths are sudden, mainly due to ven-
tricular arrhythmias. Rest of the patients die because of progressive
systolic dysfunction. It is crucial to assess the treatable causes, if
present.
Treatment for this condition is the same as that of heart failure with
depressed systolic function (Chapter 4).
Peripartum cardiomyopathy and Chagas disease may manifest with
clinical evidence of dilated cardiomyopathy. Anthracyclines (adriamy-
cin, doxorubicin, etc.) may also cause dilated cardiomyopathy, thus it is
important to reevaluate the systolic function with an echocardiography
or a radionuclide ventriculography before, during and after chemother-
apy cycles.
5.3. Restrictive
Cardiomyopathy
Epidemiology
Much less frequent than dilated and hypertrophic cardiomyopathy,
restrictive cardiomyopathy is characterized by the presence of a
restrictive physiology for ventricular filling (with small increases in
volume there are large increases in intraventricular pressure, due to
increased rigidity of ventricular walls) in the absence of significant
dilation or abnormal parietal thickening of the ventricles. Therefore,

it is a disease which affects predominantly the dyastolic heart func-
tion, and only in late stages of the disease sistolic function is com-
promised.
In this condition, just as in constrictive pericarditis (with which it is
necessary to conduct a differential diagnosis, since it may benefit from
surgical treatment), the initial part of diastole is not compromised, dras-
tically reducing ventricular distensibility when it reaches its relaxation
capability limit. On the other hand, in cardiac tamponade all the dias-
tole is involved.
Clinical History
It is similar to constrictive pericarditis, with exertion dyspnea, fatigue,
and predominant systemic venous congestion (hepatomegaly, ascites).
Atrial fibrillation is very frequent, and up to one-third of patients suffer
stroke episodes.
Diagnosis
Furthermore, physical examination is similar to what may be seen in
constrictive pericarditis, with increased venous pressure, Kussmaul
sign, decreased sound intensity and third or fourth extra sounds. A deep
and quick y descent wave predominates in the jugular venous pulse, an
increased a wave, of similar width to v, and an x descent wave that can
also be quick, adopting a “W” morphology. Apical impulse is easily felt
in restrictive cardiomyopathy even if it is decreased, which does not oc-
cur in constrictive pericarditis.
Echocardiography is key for diagnosis; it helps on assessing the diastolic
function and its compromise. Sometimes, a slight symmetrical ventricu-
lar wall thickening can be seen. Systolic function is usually normal. Bi-
auricular dilation is really specific, due to the ventricular filling impair-
ment.
Cardiac biopsy, CT and MRI are really useful techniques for the differen-
tial diagnosis with constrictive pericarditis, and also permit the detailed
analysis of the pericardium and tissue characterization.
Treatment
Treatment is basically symptomatic.
Diuretics may alleviate congestive symptoms, but must be used care-
fully.
Beta blockers and calcium antagonists may improve diastolic function
by diminishing heart rate, although their negative inotrope effect may
worsen the condition in some cases.
Loeffler Eosinophilic
Endomyocardial Disease
Significant (over 1,500 eosinophils/mm3), persistent (hypereosinophilic
syndrome) eosinophilia may affect multiple organs (lungs, bone mar-
row, brain) and especially the heart, where Loeffler’s eosinophilic endo-
carditis with endomyocardial fibrosis may appear, key to determine the
disease’s prognosis.
Card i o l ogy 1
Treatment is for diastolic heart failure and anticoagulation, corticoste-
roids and hydroxyurea or interferon may be added. Surgery may obtain
good results in certain cases with established fibrosis.
Endomyocardial Fibrosis
or Davies Disease
There is endomyocardial fibrosis, mainly in both ventricular outflow
tracts and in the right ventricular apex, leading to obliteration of cavi-
ties and, frequently, affecting valves. It manifests mostly in children and
young adults living in tropical and subtropical areas in Africa.
When medical treatment of heart failure is unsatisfactory, and in ad-
vanced cases, surgical resection of fibrous endocardium replacing af-
fected valves is the alternative of choice.
Amyloidosis
It is rare for secondary amyloidosis (systemic amyloidosis [AA]) to af-
fect the myocardium, while cardiomyopathy is the most frequent cause
of death in primary amyloidosis. Here (primary amyloidosis [AL]), the
heart is involved in up to 90% of cases. Organs other than the heart are
frequently affected. Transthyretin-related (TTR) amyloidosis may cause
familiar cases of heart amyloidosis.
Amyloidosis may cause restrictive cardiomyopathy (most frequently),
dilated cardiomyopathy in advanced stages, in some cases ventricular
hypertrophy (infrequent in other etiologies of restrictive cardiomy-
opathy), atrial or ventricular arrhythmias, conduction disorders or or-
thostatic hypotension. Sudden death is not exceptional. This disorder
shows a preference for right cavities, at least in early stages. Pericardial
effusion is very frequent.
A characteristic echocardiographic feature is a shiny “speckled” appear-
ance of the myocardium with thickening of intraventricular septum.
Treatment for plasma cell dyscrasias may be effective on patients
during initial stages of the disease, although the general prognosis is
bleak.
Hemochromatosis
This disorder should be suspected in patients with signs of heart fail-
ure associated with alterations of liver function, diabetes and increased
skin pigmentation. Cardiac damage may also occur in the nongenetic
secondary forms because of increased iron supply (e.g., from multiple
transfusions).
5.4. Other Cardiomyopathies
Right Ventricular Arrhythmogenic
Cardiomyopathy (ARVC)
It is a rare genetic disorder, consisting on a gradual replacement of the
normal myocardial tissue with fibrofatty tissue, predominantly in the
33
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

region known as “triangle of dysplasia” (i.e., right ventricular outflow version and/or anti-arrthymic drugs if they are well tolerated or
tract, apex, and inflow tract), although it may extend to the rest of the recurrent. Beta blockers, sotalol and amiodarone are effective for
right ventricle and even to the left ventricle (50% of the cases). prevention.

The clinical effect is the formation of intramyocardial reentrant cir-
cuits in the fibrofatty replacement area which facilitates the devel-
opment of sustained monomorphic ventricular tachycardia, typically
during exertion, even before developing morphologic abnormalities
that may be detected.
This makes cardiomyopathy the main cause of sudden death in
sportspersons of certain European regions. In advanced stages, right
ventricle impairment progress towards severe right-sided heart fail-
ure; when both ventricles are affected it may mimic a dilated cardio-
myopathy.
Tachycardia reentrant circuit catheter ablation involves a limitation,
since the potential circuits are multiple and progressive, and therefore
recurrence avoidance cannot be guaranteed. ICD is prescribed for sud-
den death survivors and high risk individuals (such as those showing
impaired left ventricle and those with ventricular tachycardia, especially
if it is recurrent in spite of anti-arrhythmic drug therapy and/or catheter
ablation).
Treatment of right-sided heart failure (diuretics, water deprivation) is
applied in advanced cases.

Its prevalence is 1:5,000. Recessive autosomal patterns have been re-

ported (Naxos and Carvajal diseases are caused by mutations in plako-
globin and desmoplakin coding genes, respectively), but most cases are
caused by dominant autosomal inheritance due to mutations to pla-
kophilin-2 genes and other desmosomal proteins.

Diagnosis is made based on the presence of a number of higher and

lower criteria in several categories: structural/functional alterations of
the right ventricle, tissue characterization of the same, ECG conduction
or repolarization alterations, arrhythmias, family background). Such cri-
terion provides the basis for a conclusive diagnosis, besides detecting
borderline or potential cases.

Incipient cases frequently pose a challenge, even more when its clinical
debut is an episode of sudden death.
• Magnetic resonance is the most sensitive imaging study to de-
tect structural abnormalities (aneurysms, dyskinetic and akinetic
segments in the right ventricle wall and cavity dilation) and intra-
myocardial fibrosis (with late gadolinium-enhanced technique).
Echocardiography and ventriculography with contrast are also
useful.
• Endomyocardial biopsy, which is not usually necessary, confirms fi-
brofatty degeneration. However, the segmented nature of the dis-
ease may result in false negatives.
• An ECG is very useful even though it may be normal or near normal
during initial stages.
The most frequent anomaly is the presence of inverted T-waves in
right precordial leads (V1-V3) in people over 14 years of age (prior
to this, they may be normal) in the absence of right bundle branch
block.
The most specific abnormality is the presence of epsilon waves in
V1-V3 (signs of low voltage in the final part of QRS, which is usua-
lly slightly widened, a reflection of late activity of involved regions)
(Figure 50). Figure 50. 12-derivation ECG of a patient with right ventricle dysplasia,
• A documented ventricular tachycardia episode with left bundle where ε waves (epsilon) (arrows) and inverted t waves may be noted in
branch block morfology (since it starts in the right ventricle) and right precordials V1-V4
upper axis strongly supports its diagnosis.
• First-degree family confirmed history of disease, verified presence
of one of the mutations responsible or even a sudden death family Spongiform Cardiomyopathy
event attributable to this disease also strongly support this diag-
nosis.
(noncompacted myocardial)
Treatment is basically symptomatic. Sustained monomorphic ven- There is a developmental defect in the growth of left ventricle myocar-
tricular tachycardia episodes are treated with electrical cardio- dial wall sinusoids, which is therefore highly trabeculated and with large

34
 Card i o l ogy 1

Coronary Artery
intertrabecular recesses, resulting in a ventricular wall with spongy ap-
pearance. Patients may progress towards dilated forms, and the first
episodes may be strokes or arrhythmia.
Chapter 06
Disease
Tako-tsubo Cardiomyopathy
(dyskinesia or transient apical 6.1. Concepts
“ballooning”)
Myocardial blood supply comes from two coronary arteries which
come from the aorta (Figure 52 shows a diagram of the coronary
Initially reported in Japan, it usually affects postmenopausal women fol- anatomy).
lowing an emotionally or physical stressful situation (death of a relative,
medical procedures), and causes chest pain and electrical changes (ST-
segment transient elevation followed by deep, diffuse T-wave inversion)
similar to an acute myocardial infarction but in the absence of coronary
disease, together with mid-ventricular systolic and/or apical dysfunc-
Aorta Left main coronary
tion, disproportionate to the slightly increased cardiac enzymes reflect- artery
ing myocardial injury and over a surface greater than a single blood ves- Circumflex artery
sel (Figure 51). Right coronary
artery
Although its origin is unknown, it has been related to surges in sympa- Left anterior
thetic activity (stress cardiomyopathy) and usually returns to normality descending
artery
within the first two months. Treatment is empiric and customized, usu-
ally administering the treatment for an acute coronary syndrome with
ventricular dysfunction (beta blockers, ACE inhibitors). Prognosis is usu-
ally favorable and recurrences are rare.

Anterior wall, septum Posterior,

Inferior wall and lateral wall
of the right lateral
ventricle and inferior
wall
His bundle

Sinoatrial node
55% 45%
AV Node
90% 10%

Figure 52. Cardiac revascularization

The concept of ischemic heart disease encompasses all myocardial al-

terations happening as a result of an imbalance between the supplies
and the demand of oxygen, with impaired cardiac function. It can be
manifested in different ways, as shown in Table 21.

ISCHEMIC HEART DISEASE

Chronic coronary syndromes · Chronic stable angina

· Microvascular angina (X syndrome)
· Silent ischemia

Acute coronary syndromes · With a persistent elevation of the

ST: transmural acute myocardial
infarction
· Without a persistent elevation
of the ST: non ST elevation acute
myocardial infarction, unstable
Figure 51. Contrast ventriculography revealing dilation and dyskinesia angina, Prinzmetal’s angina
(“ballooning”) of left ventricular apical region in a female patient with
tako-tsubo cardiomyopathy Table 21. Clinical forms of ischemic heart disease

35
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)
Etiology
The etiology of ischemic heart disease is usually atherosclerosis of the
epicardial arteries. Other causes may include:
• Alterations of the coronary microcirculation (microvascular angina
or syndrome X), endothelial dysfunction, etc.
• Coronary spasm (variant, vasospastic or Prinzmetal’s angina) gener-
ally occurs in areas close to small atheroma plaques, but can also be
triggered by cocaine, ergotamine or other vasoconstrictors.
• Coronary embolisms, ascending aortic aneurysms, when aorta is
proximally dissected, or congenital abnormalities of the coronary
anatomy.
• Metabolic demand increase because of myocardial hypertrophy:
hypertensive heart disease, aortic stenosis, hypertrophic cardiomy-
opathy, or tachycardia.
• Reduction of oxygen contribution because of anemia, increased car-
boxyhemoglobinemia or other conditions.
Risk Factors
Cardiovascular disease prevention is based in the adequate control of the
risk factors which influx in the onset of atherosclerotic disease. A global
cardiovascular evaluation should be performed to every person with an
increased risk: any major cardiovascular risk factor (hypertension, smok-
er, diabetes or dyslipidemia) or family history of cardiovascular events. It
should also be performed to postmenopausal woman or over 50 years
old or male over 40, even without cardiovascular risk factors.
To assess the total cardiovascular risk, it is recommended to use scores
or risk scales (validated in every country). According to the risk factors
every patient has, we can obtain a global risk estimation based on the
probability of cardiovascular death in the following 10 years, stratified as:
• Low risk: <1%
• Moderate risk: 1-5%
• High risk: 5-10%
• Very high risk: >10%
Treatment must be prescribed according to the individual risk of every pa-
tient, being tighter in patients with higher risk and in secondary prevention.
Table 22 summarizes the general recommendations for cardiovascular
disease prevention.
CARDIOVASCULAR DISEASE PREVENTION
· Low fat diet. Increase fruit, vegetable and fish consumption
· Physical activity: moderate periodic aerobic exercise
· Quit smoking
· Weight: BMI 20-25 kg/m2. Abdominal circumference <94cm in male
or <80cm in female
· BP:
- General goal: <140/90 mmHg
- High risk patients goal (specially diabetic patients): <130/80 mmHg
- Elder and fragile patients: <150/90 mmHg (avoiding hypotension
risk)
· Lipids:
- Very high risk or secondary prevention: LDL <55 mg/dl
(<1,4 mmol/l)
- High risk: LDL < 70 mg/dl (<1,8 mmol/l)
- Moderate risk: LDL <110 mg/dl (<2,6 mmol/l)
- Low risk: LDL <116 mg/dl (<3 mmol/l)
· Diabetes: glycated hemoglobin <7%
Table 22. Recommendations in cardiovascular prevention
36
Risk factors:
• Age and male sex. These are risk markers, therefore non-modifi-
able. The main marker for cardiovascular diseases is age, thus life
expectancy increase is one of the elements which has influenced
the most on the increase of the incidence and prevalence of isch-
emic cardiomyopathy.
• Smoking. This is the most important modifiable risk factor, due to
its prevalence and because, when it is reduced or quitted, clearly
reduces the risk of developing atherosclerosis. Smoking prevalence
is decreasing, but it is still high and is increasing among woman,
teenagers and lower classes. Tobacco is responsible of more than
20% of ischemic cardiomyopathy deaths. There is a 3-4 times higher
risk of developing ischemic cardiomyopathy in a patient smoking 1
cigarette pack a day compared to a non-smoker. Passive smoking
also increases the risk. After quitting smoke, the risk decreases pro-
gressively, nearly reaching non-smokers after 10-15 years (but never
matching the same risk).
• Dyslipidemia. Lipidic profile alterations have a crucial role in the
atherosclerotic onset:
ͳ LDL-cholesterol: main atherosclerotic risk determinant. In-
creased blood levels cause atherosclerotic disease, with a linear
association: the higher the LDL level, the higher the risk. Reduc-
ing LDL-c levels is associated with a decreased risk of develop-
ing atherosclerotic disease, without having found a level below
which there is no benefit: the lower the LDL, the lower the risk.
LDL-c levels management includes lifestyle recommendations
(low fat diet, increasing monounsaturated fatty acids and exer-
cise) and drugs: statins as treatment of choice, ezetimibe as a
coadjutant (if the goal levels are not reached or intolerance to
statins), and anti-PCSK9 which confers a remarkable decrease in
LDL levels and recommended in patients with very high risk or
with familiar hypercholesterolemia.
ͳ HDL-cholesterol. It is inversely associated with the develop-
ment of atherosclerotic disease. HDL-c levels are increased with
physical exercise, hypolipemic diet, female sexual hormones and
monounsaturated and polyunsaturated fatty acids. Their levels
are increased with obesity, sedentarism and smoking. Low HDL-c
levels increase cardiovascular risk.
ͳ Triglycerides. They increase cardiovascular risk, but its associa-
tion is weaker. Levels over 150 mg/dl are considered a risk mark-
er. Their control is based in dietary measures (including alcohol
abstinence) and some drugs as fibrates and niacin.
• Diabetes. Ischemic cardiomyopathy risk increases both in insulin-de-
pendent diabetic patients and in non-insulin-dependent diabetic ones.
Besides, ischemic cardiomyopathy mortality is higher among diabetic
patients when other risk factors concur, compared to non-diabetic. Dia-
betic patients with target organ damage, are classified as high or very
high risk or if they associate another major cardiovascular risk factor.
Therefore, risk factors control must be strict among these patients.
• Other risk factors:
ͳ Hypertension. This topic will be developed in the correspon-
dent Chapter.
ͳ Cardiovascular disease family antecedent. First line family
members, in males <55 years old or females <65 years old.
ͳ Lifestyle. Dietary habits, sedentarism, stress…
ͳ Obesity. BMI >25 kg/m2 and abdominal circumference > 94/102 cm
in male and >80/88 cm in female. It increases independently cardio-
vascular risk, besides its association with other risk factors (hyper-
cholesterolemia, hypertriglyceridemia, diabetes and hypertension).
 Card i o l ogy 1
ͳ Comorbidities. Certain diseases presence is associated with an
increased cardiovascular disease risk: chronic kidney injury, auto-
immune diseases, cancer (treated with chemotherapy or radio- LDL Endothelium
Oxidized LDL
therapy), OSAHS, periodontal diseases and erectile disfunction.
Macrophage
ͳ Metabolic syndrome. It is defined as an association of central Monocyte
obesity and two of these:
ͧ Triglycerides >150 mg/dl. Foam
cells
ͧ HDL <1 mmol/l in male or < 1.3 mmol/l in female.
ͧ SBP >130 mmHg or DBP >85 mmHg.
ͧ Blood glucose >100 mg/dl or previously diagnosed type 2 diabetes.
Smooth muscle
ͳ Peripheral arterial disease. Cytokines proliferation
ͳ Hypercoagulability syndromes (hyperfibrinogenemia, hyper-
homocysteinemia…).
ͳ Estrogens. Medium layer Migration of smooth
ͳ Alcohol. Alcohol intake has a “J” effect. Reduced consumption muscle cells

is presumed to have a protector effect, whereas elevated con-

sumption increases cardiovascular mortality risk and dilated car- Figure 53. Development of atherosclerosis
diomyopathy risk.
ͳ Inflammation. Increased C-reactive protein levels are associ-
ated with an increased risk of cardiovascular events, and their
reduction might dereased this risk.

Stages of Coronary Atherosclerosis

Atherothrombosis is a chronic inflammatory disease which commenc-
es with an endothelial dysfunction facilitating the flow of LDL choles-
terol towards the subendothelial space, which is then oxidized and
esterified, and seeks to be phagocytized by macrophages obtained
from the bloodstream, but these are unable to fully digest such cho-
lesterol and turn it into foam cells which finally commence their own
apoptosis.

The release of cytokines attracts other inflammatory cells (mono-

cytes-macrophages and lymphocytes), which multiply the release
of cytokines and, among other phenomena, increase even more
the endothelial permeability and dysfunction. Smooth muscle cells
migrate towards the subendothelial space and synthesize collagen,
which attempts to stabilize the increasing atheroma plaque with
a higher or lower efficiency, since the inflammatory cells produce
enzymes that degrade the matrix (metalloproteinase) and tend to
destabilize it. Figure 54. Pathophysiology of acute coronary syndromes

This generates the atheroma plaque, with a lipid core -formed by LDL
cholesterol esters- which is sometimes even crystalized, surrounded
by inflammatory cells, smooth muscle and collagen in different pro-
portions, with the presence of vulnerable plaques (high contents of
lipids and inflammatory cells) and stable plaques (high fiber contents;
Figure 53).
Ruptures in the vulnerable plaques exposes subendotelial material
to bloodstream and activates platelets, which attach and aggregate
themselves, and set in motion the coagulation cascade, thus pro-
ducing thrombosis of the atheroma plaque which triggers the acute
coronary syndromes (ACS), so that, if the occlusion is complete, it pro-
duces an ACS with a persistent ST segment elevation in the ECG (which
causes a transmural infarction), and if the occlusion is subocclusive, it
originates an ACS without ST segment elevation (with different vari-
ables ranging from the subendocardial infarction to the unstable an-
gina; Figure 54).
Generally, the risk of a plaque presenting a complication increases in
proportion to the size of the plaque, even though possible complica-
tions also depend on other factors.
Nevertheless, given that the number of small plaques is much greater
than the number of large plaques, the small but vulnerable plaques are
the ones that generally cause, in absolute terms, acute coronary syn-
dromes (Figure 55).
As an approximation, when a plaque occludes 70% of the arterial lu-
men, it produces an ischemia triggered by physical exertion, cold or
emotional stress, but not at rest. When the stenosis exceeds a value
of 80% to 90% (serious or “severe”), it can produce an ischemia at
rest. Generally, a stenosis is considered angiographically significant
whether it occludes >70% of the arterial lumen (>50% in the left
main coronary artery).

37
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Myocardial tissue degenerates into scar tissue, thinned, without

contractile function and non-reversible.
• Viable myocardium. Ischemia produces a contractility altera-
tion (akinesia or hypokinesia) but maintaining myocardial tis-
sue alive (viable). Vessel reperfusion will allow the myocardial
contractile capacity recovery. This might happen in two differ-
ent situations:
ͳ Hibernated myocardium. It occurs in patients with chronic se-
vere coronary artery stenosis. Myocardium depending on that
artery’s flow stops contracting in order to consume the mini-
mum oxygen possible.
ͳ Stunned myocardium. It is produced when the coronary artery
is acutely obstructed and, after some time, flow is restored. Af-
ter a few days or weeks stunned myocardium recovers its nor-
mal centrality function.

6.2. Angina Pectoris

Figure 55. Plaque complication risks depending on the luminal stenosis
caused by plaque growth
Myocardial Function Alteration
First, the diastolic function of the heart is involved as it is more sen-
sible to ischemia; later on, heart contractility is affected (systolic func-
tion). If ischemia affects the papillary muscles, mitral regurgitation
might occur.
The effects of ischemia in the myocardial tissue are summarized in Figure
56, and depend on the duration and intensity of the ischemia, among
other factors (collateral circulation presence, etc.).
Perfusion
(with profusion) Nonrecoverable
Clinical History
Angina is the clinical translation of a transitory myocardial ischemia,
most frequently caused by coronary atherosclerosis. The typical patient
is a male over 50 years old, with cardiovascular risk factors present-
ing, following physical exertion of a given intensity or an episode of
emotional stress, a retrosternal oppression which commences gradu-
ally and disappears progressively with rest or sublingual nitroglycerine.
Episodes generally last less than 10 minutes. When only two of these
three characteristics are present, the event is said to be an (probable)
atypical angina.
This oppression or heavy feeling can be irradiated to other zones (upper
limbs up to the fingers, precordium, jaws or teeth, torso, etc.) and be
accompanied by other symptoms such as dyspnea or a persistent veg-
etative state (cold sweats, anxiety, nausea, asthenia, imminent death
sensation, etc.).

Table 23 lists the characteristics of the different causes of thoracic pain.

The most characteristic element of the stable angina is that its clinical
signs always appear, in all patients, after a similarly intense effort. The
Healthy Stunned Hibernating
myocardium myocardium myocardium Necrosis classification created by the Canadian Cardiovascular Society (CCS) is
Exercise used to establish such effort levels (Table 24).
(dobutamine,
Acute ischemia Chronic ischemia
dipyridamole)
Sometimes, the angina follows a circadian pattern in which the effort
SPECT threshold is lower in the mornings, the postprandial period or with cold.
Gammagraphy
(Tc, TI) No defects Reversible defects Irreversible defects Women are more likely to present atypical symptoms.
Stress echo

Rest When a patient with stable angina shows symptoms at rest or for pro-
longed periods of time (up to 20 minutes), or more intense symptoms
with progressively lower efforts throughout a four-week period, the
angina is said to have “destabilized” and is known as an “unstable an-
Figure 56. Effects of myocardial ischemia gina”.

They are classified into: An angina which, having commenced recently (two months after the
• Non-viable myocardium. Necrosis. It is produced by a complete initial event) imposes a marked limitation on the patient’s habitual ac-
occlusion of enough duration and without collateral circulation flow. tivities is also deemed unstable (Table 25).

38

The pain is sudden, persistent and
especially intense (transfixing, tear) from
the very beginning. It migrates to the
AORTIC DISSECTION zones to which the dissection expands.
Asymmetric reduction of arterial beats.
Aortic regurgitation murmur. Mediastinal
widening in chest x-rays
The nature and location of the pain may be
similar to that of the coronary, but this one
is prolonged, usually pleuritic, and changes
with the patients’ posture (it is alleviated by
ACUTE PERICARDITIS
flexing the trunk). Pericardial rub. Concave
and diffuse elevation of the ST segment. It
can be alleviated with anti-inflammatories
and not with nitroglycerin
Exercise angina. Exercise syncope.
AORTIC STENOSIS Dyspnea. Aortic systolic murmur
irradiated to carotid
Usually atypical pain, with variable duration
and no clear triggering factors, which cannot
MITRAL PROLAPSE
be alleviated with nitroglycerin. Auscultation of
a mid-systolic or end-systolic click
It is originated by a right ventricular
ischemia. It may be very similar to
PULMONARY
an angina and is connected to acute
HYPERTENSION
pulmonary embolism or chronic
pulmonary hypertension events
Epigastric and retrosternal pain. Usually
connected with the intake of food, especially
ESOPHAGEAL SPASM when these are very hot or very cold. Like
angina, it can be alleviated with nitroglycerin.
It can cause dysphagia
Burning epigastric and retrosternal pain
GASTROESOPHAGEAL especially when lying down after meals.
REFLUX Presence of acidity in the mouth. Quickly
alleviated with alkaline substances
Epigastric pain. It is worsened by fasting and
PEPTIC ULCER alleviated by ingesting foods and taking
antacids
It is localized to the right hypochondrium,
although it can be irradiated to the
right hemithorax and epigastrium. It is a
BILIARY DISEASE
prolonged pain with colic characteristics
(it “comes and goes”), and responds to
analgesics-antispasmodic medication
Intense epigastric pain irradiated towards the
PANCREATITIS back as a belt. It decreases when the patient
bends forward
Pain in the surface of the thoracic wall
OSTEOMUSCULAR
PAIN
reproduced with mechanical palpation and
exacerbated when moving or coughing
Dull and persistent precordial pain with
acute pain crisis lasting a couple of
seconds. It is triggered by anxiety and
family, economic and self-esteem troubles.
It is in no way connected to physical
PSYCHOGENIC PAIN exertion. It usually causes dyspnea,
hyperventilation, palpitations, sighs,
paresthesia, and general weakness. It can
be alleviated by very different means:
rest, exercise, tranquilizers, analgesics or
placebo
Table 23. Differential diagnosis of chest pain
Card i o l ogy 1
Angina only ocurring during strenuous efforts. Does not limit
I
ordinary lifestyle
Slight limitation of physical activity. Angina appears when
walking fast or climbing stairs or steep roads.
II
Patients can walk more than one or two blocks or climb one
flight of stairs
Strong limitation of physical activity. Angina appears after
III
walking one or two blocks or climbing one flight of stairs
Inability to perform any activity without angina. This
IV
symptom can appear while at rest
Table 24. Angina clinical severity. Classification by the Canadian
Cardiovascular Society
Angina starting at rest. It usually persists for a
ANGINA AT REST
prolonged period of time (> 20 minutes)
ANGINA OF Recently commenced angina ( > 2 months)
RECENT ONSET reaching at least Class III on the CCS classification
In the previous four weeks, increase in the
ACCELERATED number, intensity, duration or reduction of the
ANGINA threshold of onset in a patient suffering from
stable stress angina
POST-INFARCTION Angina manifesting itself in the first few days
ANGINA following a myocardial infarction
Table 25. Classification of unstable angina
The general treatment of a patient with stable angina is shown in
Figure 57.
Diagnosis
The diagnosis of chest angina is based on the patient’s medical history,
with its logic and limited sensitivity, and is complemented with addi-
tional tests, such as a baseline ECG and an ergometry.
With current treatment, the prognosis of patients with stable angina is
usually favorable. The historic annual mortality rate has been estimated
to be 2% to 3%, even though recent studies show it to be lower (not
exceeding an annual 1%).
There are two ways to detect ischemia; exercise stress testing (assessing
repolarization alterations during physical exercise) and imaging tech-
niques (stress echocardiography or nuclear cardiology).
Stress testing
It is the most accessible and widely used coronary ischemia detection
test. It produces myocardial ischemia, increasing oxygen demand (due
to exercise), testing clinical (symptoms onset), blood pressure and ECG
changes.
Ergometries are deemed electrocardiographically positive when the ST
segment displaces at least 1 mm measured at 80 ms from the “J” point
(end of the QRS complex). Extension, magnitude and duration of ECG
changes are related with prognosis (Figure 58).
39
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Suspected angina

Anamnesis
Physical exploration
ECG at rest
Unstable angina Alternative diagnosis
Lab tests
Chest XR, if applicable
ACS management Confirm and treat

Risk stratification:
· Echocardiography: LVEF,
segmental contractility
· Ischemia detection tests: ergometry,
imaging ischemia detection

Low Medium High

Medical • General measures (lyfestile and risk factor control measures)

treatment • ASA or clopidogrel
• Statin (goal LDL < 70 mg/dl or < 55 in high risk patients)
• ACE inhibitor (if hypertension, diabetes, ventricular disfunction, HF or previous AMI)
• β-blockers (treatment of choice for angina pain relief )
• Other angina treatments: calcium antagonists, prolonged action nitrates, ivabradine, others
nicorandil, trimetazidine, ranolazine)

Assessment Consider coronary

Coronary angiography
of clinical response angiography

Good Poor Coronary angiography Revascularization, when possible

Figure 57. General treatment of patients with stable angina

The test it is considered to be diagnostic when the patient attains 85%

of the maximum predicted heart rate. The global sensitivity of the test is
75%, which justifies the existence of false positives (especially in wom-
en) and negatives. There is a series of criteria to identify patients with
the worst prognosis after an ergometry (Table 26).

PARAMETERS ASSOCIATED WITH ADVERSE PROGNOSIS

Inability to complete stage II of the Bruce protocol

Ischemic depression of the ST segment ≥ 2 mm before completion

of the second stage of the Bruce protocol or at a frequency of < 130 bpm

Early positivity in the first stage or prolonged duration (more than five
to six minutes) of ST segment depression upon exercise completion

Diffuse ST segment depression in five or more leads of the ECG

Elevation of the ST segment in leads without a Q wave

Figure 58. Positive exercise stress testing with consistent alterations in
ST-depression in II, III, aVF, V4-V6, and ST-elevation in Avr
Patients with abnormal baseline ECGs (LBBB, pacemaker stimulation,
preexcitation, hypertrophy, digital ST segment depression) are not suit-
able for ECG stress testing. These patients should undergo an imaging
stress testing.
Depression or flat response in systolic blood pressure after increasing
the stress level
Maximum heart rate achieved with limiting symptoms lower than
120 bpm in the absence of a treatment with β-blockers
Table 26. Parameters associated with adverse prognosis

40

Imaging
Imaging techniques to detect ischemia are indicated in these situa-
tions:
• Baseline ECG alterations which contraindicate stress test.
• Non conclusive stress test
• Need to further assess location, myocardial viability…
Ischemia induction can be performed both with physical exertion and
with drugs. The most physiological way and the one providing the most
information is physical exertion. If the patient cannot make enough ef-
fort, pharmacological stress test might be performed with either dobu-
tamine, dipyridamole or adenosine.
After ischemia induction, stress echocardiography, nuclear imaging
techniques or MRI can be used to detect it. These tests are more sensi-
tive and specific than conventional exercise stress testing.
Coronary angiography
The objective of this test is to assess coronary arteries anatomy by in-
troducing contrast through them. It is the gold standard when estimat-
ing anatomical severity degree in coronary artery disease, allowing to
take therapeutic decisions.
Although being an invasive procedure, complications’ risk is low. In-
dications are listed in Table 27 (briefly, every patient with limiting
symptoms despite optimal medical therapy and patients with un-
favorable prognosis). A lesion is considered to be angiographically
significant when the stenosis is >70% (or >50% in the left main coro-
nary artery).
CORONARY ANGIOGRAPHY
1. Stable angina with low exercise workload despite medical treatment
or poor prognosis data in diagnostic tests
2. In the non ST-segment elevation ACS in medium or high risk cases,
and, where positive results are obtained, in ischemia detection tests
in low risk cases
3. In the context of AMI
- Primary PTCA
- Failed thrombolysis
- Successful thrombolysis (first 24h)
Card i o l ogy 1
Treatment
Medical treatment
Angina medical treatment includes (Table 28):
• Antiaggregant therapy. Aspirin, in 75-150mg daily doses has prov-
en to reduce the incidence of acute events in patients with stable
angina. Clopidogrel should be used in patients with aspirin intoler-
ance.
• Statins. Reduce infarct risk and mortality, even in patients with nor-
mal cholesterol blood levels, therefore statins should be prescribed
to every patient at a high dose.
• ACE inhibitors. Should be prescribed in patient with stable an-
gina who also present diabetes, hypertension, HF, LVEF asymp-
tomatic disfunction or in patients with family history of AMI.
Although not accomplishing all these statements some authors
recommend its use in all patients with confirmed coronary artery
disease.
• ß-blockers. Have shown to increase survival rate in patients with
angina and history of AMI or HF. In the absence on these two,
they do not improve prognosis but prevent angina episodes, thus
although contraindicated beta blockers are the antianginals of
choice.
• Calcium channel blockers. Verapamil and diltiazem mainly have a
cardioinhibitory effect, so their use with betablockers should be re-
stricted. On the other hand, dihydropyridines produce vasodilation
with nearly no effect on cardiac contractibility, and therefore can be
used combined with betablockers. Calcium channel blockers are the
treatment of choice in Prinzmetal’s angina.
• Nitrates. These should be used only in the case of beta-blockers in-
efficiency or associated to them to alleviate angina symptoms.
• Ivabradine. It has been approved for the symptomatic treatment
of stable angina in patients in sinus rhythm >70bpm, especially if HF
or LVEF disfunction or in patients with beta-blockers intolerance or
contraindications. Despite beta-blockers and calcium channel block-
ers, ivabradine does not modify heart contractility or blood pres-
sure.
• Ranolazine. Sodium channel blockers. Based on its antianginal
effect and increasement in cardiac functional capacity, rano-
lazine is indicated as symptomatic treatment of stable angina
when first line treatment fails or in patients with beta-blockers
intolerance.

PROVEN PROGNOSIS SYMPTOMATIC

4. Sudden death survivors, unless a definite diagnosis has been
reached other than ischemic heart disease (long QT, Brugada IMPROVEMENT IMPROVEMENT
syndrome, and so forth)
· ASA (or clopidogrel) · β-blockers
5. Valvular heart disease preoperative period: when there is a risk of · Statins · Calcium antagonists
coronary artery disease. Consider CT angiography as an alternative · ACE inhibitors where there is · Nitrates
to an invasive angiography a confirmed cardiovascular · Ivabradine
disease · Coronary
6. Assessment of the dilated cardiomyopathy to discard ischemic · β-blockers where there is a revascularization
causes. Consider CT angiography as an alternative to an invasive history of AMI or ventricular · Nicorandil
angiography dysfunction · Ranolazine
· Coronary revascularization if · Trimetazidine
7. Patients with chest pain requiring a certain diagnosis (professional indicated · Molsidomine
pilots, drivers). Consider CT angiography as an alternative to an · Allopurinol?
invasive angiography · Pain therapy

Table 27. General guidelines for a coronarography Table 28. Treatment of stable angina

41
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Coronary reperfusion • Coronary surgical revascularization. Surgical revascularization

using aortocoronary bypass is performed with arterial grafts (left
Optimal medical therapy is the treatment of choice in patients with internal mammary artery) or venous grafts (mainly saphenous
stable angina. There are to main cases in which coronary reperfusion vein) (Figure 60). When technically possible, mammary artery
should be considered: grafts are preferred because long-term permeability rates are
• High risk parameters in non-invasive techniques and in coronary an- higher compared to saphenous vein. Surgery has shown to in-
giography. crease survival compared to medical treatment alone in patients
• Progressive symptoms worsening despite optimal medical therapy. with left main coronary artery disease, three-vessel disease or in
a two-vessel disease, where one of them is the proximal anterior
There are two coronary reperfusion methods: descending artery.
• Percutaneous coronary intervention (PCI). Using a peripheric artery
(radial or femoral) a catheter is directed towards coronary arteries.
When the obstruction is reached, a balloon is inflated, and the ath-
eroma plaques become dilated. Once the obstruction is reduced, coils
(stents) are placed (Figure 59). Stents may be antiproliferative drug-
eluting, being the ones preferred at the moment. After PCI, double anti-
platelet therapy must be prescribed (aspirin and clopidogrel) for at least
6 months and afterwards, aspirin should be prescribed indefinitely.
Complication rates are low, comparable to those of surgery. Main
complications are:
ͳ Restenosis appears gradually in 3-6 months after the procedure
and consists of reappearance of the angina and ischemia symp-
toms. It is more frequent in diabetic patients and stent thrombosis.
ͳ Thrombosis has a sudden onset. It develops as an acute cor-
onary syndrome in a patient who has previously undergone
a PCI.

Pre-PTCA
coronarography
Figure 60. Myocardial revascularization with internal mammary artery
graft and aortocoronary saphenous vein graft

Indications on whether to use PCI or coronary surgical revascularization

are summarized in Table 29.

Plaque
CORONARY ANATOMY PREFERRED TECHNIQUE
1 or 2 vessel disease non affecting PCI
Balloon catheter proximal LAD
2 vessel disease affecting proximal LAD PCI or surgery
Left main disease Surgery (or PCI*)
Diabetes with multivessel disease Surgery (or PCI*)
Guide
3 vessel disease Surgery (or PCI*)
Inflated
balloom Bypass stenosis PCI
* Selected patients

Table 29. Preferred revascularization technique based

on clinical profile and coronary anatomy

Stent
Prinzmetal Angina
and Cardiac Syndrome X
Post-PTCA
coronarography The pathophysiology of Prinzmetal -or variant angina is coronary
spasm. The episodes usually occur at rest and preferably at night, and
cause elevation of the ST segment. The recommended treatment is the
Figure 59. Percutaneous transluminal coronary angioplasty use of calcium antagonists and nitrates. The intracoronary infusion of

42

acetylcholine or ergonovine enables physicians to induce spasms and
confirm the diagnosis.
Cardiac syndrome X (demonstrable angina and ischemia in detect on tests
with normal epicardial coronary arteries) is usually the result of a dysfunct
on of the microvascular endothelium in patients with multiple cardiovascu-
lar risk factors.
Card i o l ogy 1
The incidence of NSTE-ACS is somewhat greater than that of the
STE-ACS. The hospital mortality rates of this second case are higher
(7%) than those of NSTEACS (5%), but after a few months mortality
rates become equal for both cases (around 12% after six months)
and even seem to be higher in the case of NSTE-ACS in the long term,
probably because this condition usually affects older patients with
higher comorbidity levels (diabetes, renal failure, among others) and
a longer history of coronary disease. Therefore, recurrent reinfarc-
tion and ischemia rates are higher in patients suffering NSTE-ACS.
The general steps in case of an NEST-ACS are shown in Figure 62.

Acute Coronary Current recommendations suggest that the risk should be assessed
(hospital and long-term mortality) using one of the available scales

Syndrome
Chapter 07 (GRACE, TIMI, PURSUIT, etc.), which collect clinical variables with
prognosis implications (age, heart rate, blood pressure, Killip class,
diabetes, and coronary history), electrocardiographic, biochemi-
cal and imaging findings (mentioned above). The prognosis fac-
tors shown in cases of stable angina are also useful in this con-
7.1. Acute Coronary Syndrome text. These enable the patient to be placed in the low, medium
or high risk groups, and the treatment to be adjusted accordingly
Without ST Segment Elevation (Table 30).

Most ACS presents a common pathophysiology, a rupture or erosion · At-rest or prolonged angina
phenomenon followed by thrombosis in an atheroma plaque, together · Hemodynamic alterations (heart
failure, mitral insufficiency, peripheral
with coronary spasms and distal embolization of thrombus fragments. CLINICAL
hypoperfusion)
· Old age (> 75 years)
The degree of occlusion of the vessel lumen determines whether · Diabetes mellitus
there will be an acute coronary syndrome with a persistent rise/el-
evation (> 20 min) of the ST segment (STE-ACS, usually a complete Changes in the ST segment or profound T
ELECTROCARDIOGRAPHIC
occlusion and evolving towards a transmural infarction) or an acute wave inversion in all precordial leads
coronary syndrome without a persistent rise/elevation of the ST seg- · Ventricular dysfunction
ECHOCARDIOGRAPHY
ment (NSTE-ACS, usually subtotal or intermittent total occlusion be- · Extended contraction abnormalities
cause of distal embolization of thrombus fragments rich in plaques,
· Assessment of markers:
including unstable angina). The distal embolization of small thrombus
- Necrosis (T or I troponins, CPK-MB)
fragments is suspected to determine the presence of isolated sites of - Inflammation (C-reactive protein)
necrosis surrounded by myocardial inflammation zones causing the LAB TESTS - Neurohumoral activation (NT-pro-
increase in troponins (Figure 61). BNP, BNP)
· Renal impaired renal function
· Previous bypass surgery
OTHERS · PTCA over the last months
· Post-infarction angina
Table 30. High-risk criteria in patients with unstable angina

7.2. Acute Coronary Syndrome

with ST Segment Elevation

At present, acute myocardial infarction (AMI) is considered upon the

Figure 61. Unstable plaques in atherosclerosis
existence of myocardial necrosis on an ischemia clinic episode; that
is, elevation and posterior fall of necrosis markers levels (preferably
troponins with values above the 99.th percentile, which is the normal
baseline) with at least one of the following factors (remember that in
patients with characteristic symptoms with some of the other criteria,
treatment must be commenced despite the fact that markers valuation
may not be still available):

43
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Suspected NSTE-ACS

· Anamnesis
· Physical exploration
STE-ACS Alternative diagnosis
· ECG at rest (< 10 min) include V3R, V4R, V7-V9
· Lab test: troponin, CPK-MB, hemoglobin, leukocytes, creatinine

Specific management Appropriate tests and treatment

Confirmed NSTE-ACS

· Rest, O2 if PaO2 < 90 mmHg

· ECG/ST monitoring
· Repeat ECG after 6 and 24 h
· Repeat troponin after 6-12 h or after 3 h in ultrasensitive ones
· Echocardiography at rest
· Estimate hemorrhagic risk
· Estimate risk and commence medical treatment

Low risk Medium-high risk Extrem risk (10%)

If:
· ASA + clopidogrel or ticagrelor if moderate-high risk · Refractory angina
· Anticoagulation · Recurrent angina with generalized ST or T wave changes
· Statin (precocious) · Heart failure
· Antianginals: -blockers (of choice) + nitroglycerine, others · Hemodynamic instability
· ACE inhibitor/ARA (in most cases) · Serious arrhythmias
Medical treatment and...

· No recurrence
· No heart failure Coronarography Urgent
· No changes in the ECG < 24-48 h coronarography
· No increased troponins

Ischemia detection test Revascularization

Upon discharge:
_ · Changes in lifestyle
+
· Medical treatment
· CVRF control

Medical Elective coronarography

management

Figure 62. General steps in case of NSTE-ACS

• Symptoms compatible with ischemia.
• Changes in ECG compatible with acute ischemia (changes in ST or T
wave or new-onset left bundle branch block).
• Development of new pathologic Q waves
• Onset of new anomalies in segmental contractility or loss of viable
tissue in imaging.
• Sudden cardiac death, commonly preceded by symptoms compat-
ible with infarction, associated with changes in ECG or thrombus
image of coronarography or autopsy.
• Elevation of necrosis markers in relation to reperfusion therapy/re-
vascularization:
ͳ Increase in troponins above five times the normal 99th percentile
after PTCA.
ͳ Troponins elevation above ten times the normal 99th percentile
during the myocardial revascularization surgery associated with
Q waves, left bundle branch block, and occlusion of grafts or
new loss of viable tissue.
Evidence of prior myocardial infarction is considered upon:
• Development of pathologic Q waves.
• Segmental thinning and hypocontractility image in ventricular wall
with no further possible causes present.
• Findings in pathologic anatomy compatible with cardiac necro-
sis.
Operatively, initial classification of acute coronary syndromes, accord-
ing to initial ECG in ACS, with or without persistent ST segment eleva-
tion (20 min) (STE-ACS towards NSTE-ASC), is useful because it modifies
the initial therapeutic attitude. So, most STE-ACSs are to develop a clas-
sic AMI, whereas NSTE-ACS may develop a subendocardial AMI, a mi-
croinfarction episode (low myocardial damage) or an unstable angina,
according to ischemia intensity.
The most frequent cause of AMI is epicardial coronary thrombosis oc-
curring generally by rupture of the atheromatous plaque, which pro-
duces mild or moderate lumen obstruction in 75% of cases, but has high
lipid and inflammatory content (vulnerable plaque). A period of many
days between the initial rupture and the coronary thrombotic occlusion
causing the STE-ACS is frequent. After 15 minutes from the complete
coronary occlusion, myocardial necrosis begins.
Angina pain, oppressive and retrosternal with characteristic radiation
(or equivalent), usually lasts over 20 minutes. It does not completely
respond to rest or nitroglycerine, and is more intense than angina.

44

Sometimes, this pain is not present or is atypical (patients with diabe-
tes, the elderly or women). It is frequently accompanied by vegetative
symptoms (cold sweating, nausea, vomiting, anxiety and a feeling of
imminent death). It also appears at rest (sometimes, during or after ex-
ercising); it is more frequent early in the morning (due to sympathetic
activation and changes in circadian coagulation and platelet activity).
Prior angina frequently occurs.
Card i o l ogy 1
tricle AMI (V3R and V4R) or posterior wall (V7, V8 and V9), mainly in
patients with inferior AMI associated with those two subtypes.
Changes may affect the following:
• T wave (myocardial ischemic image):
ͳ Positive-peaked or isoelectric T: subendocardial ischemia.
ͳ Negative T: subendocardial or transmural ischemia.

Other forms include dyspnea, weakness, arrhythmias, systemic em- • ST segment (myocardial injury current; Figure 64).
bolism, hypotension, or any of the AMI complications when the initial ͳ Descended ST: subendocardial injury.
episode has gone undetected. It must be mentioned that the highest ͳ Elevated ST: subendocardial injury.
myocardial infarction mortality occurs during the first two hours after
appearance of symptoms, and ventricular fibrillation is the most com-
mon etiology.

No physical sign is pathognomonic of myocardial infarction; however, ST ST

sympathetic or parasympathetic activity, signs of ventricular dysfunc-
tion, apical systolic murmur related to ischemic mitral insufficiency, and V5
pericardial rub by meta-infarction pericarditis may appear. If jugular V5
vein pressure increases (with Kussmaul sign and/or paradoxic pulse), ST
right ventricle infarction (febricula may exist during the first week) or A ST A
cardiac rupture with tamponade must be suspected.

Killip classification (Table 31) on arrival refers to the degree of hemo- Subendocardial ischemia Transmural ischemia
dynamic compromise of a clinically defined patient. The Forrester clas-
sification (Figure 63) is related to invasive hemodynamic measures, Figure 64. Injury current in ECG
which require rectification actions (shown in the figure). Both classifica-
tions have a prognostic influence. • QRS complex. Pathologic Q waves indicate transmural myocardial
necrosis. There are infarctions with Q waves (which are generally
transmural, consequence of STE-ACS) and infarctions without Q
I No cardiac failure waves (generally limited to subendocardial or nontransmural, con-
sequence of NSTE-ACS). The new-onset left bundle branch block in
II Mild cardiac failure (crackling, S3, pulmonary congestion) the setting of an AMI usually indicates extensive involvement of the
conduction system, and is associated with bigger-sized infarctions
III Acute pulmonary edema and of worse-prognosis.
IV Cardiogenic shock
ECG progression of an AMI because of complete occlusion of an epicar-
Table 31. Killip classification dial coronary artery shows evolutionary alterations that follow a spe-
cific pattern (Figure 65).

Ischemia
1.º
To increase cardiac Diuretics
output with amines,
vasodilators and IABP IV Peaked T
(typical:
Reduce preload cardiogenic Symmetric negative T
with diuretics shock)
and vasolidators 2.º
Infarction or necrosis

III
Decrease O2 Convex ST
(typical consumption elevation
Increase preload of RV AMI) with β-blockers Q wave
with fluids

Injury 3.º
2,2 L/min/m2 Cardiac index

Q wave
and negative T
Figure 63. Basic treatment according to the degree ST elevation
in Forrester classification

ECG is not usually normal even during the first minutes of the AMI. It Figure 65. Electrocardiographic progress in MI and localization
is recommended to register additional leads to evaluate the right ven- of electric alterations

45
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

• While necrosis is completed, ST segment tends to return to the iso- Traditionally, the markers used in the diagnosis of AMI have been cre-
electric line. Simultaneously, Q waves (and loss of R wave) develop atine phosphokinase (CPK), its CPK-MB fraction, and GOT and LDH en-
in the leads in which ST segment occurs. zymes (these two are no longer recommended). At present, the first
• Inversion of T wave usually persists or normalizes after several choice marker is cardiac specific troponin T or I. The time pattern of the
weeks or months. Persistence of ST elevation in leads in which ne- markers has major diagnostic value (Figure 68).
crosis waves have developed may indicate ventricular aneurysm
or segments with dyskinetic movements (paradoxic). However, in
some exceptional cases, a complete ECG normalization may occur.
• T wave alterations generally take up more leads than ST’s, which, in turn, Enzymes
CPK GOT LDH
take up more leads than Q waves (the ischemia area is greater than the Myoglobin
injury current area, and this is greater than the electric necrosis area).
• In regions opposite to where AMI is localized, electrocardiographic
alterations reciprocal (opposite) to those appearing in the leads lo-
calizing the AMI are appreciated, although these changes may also Troponin
correspond to concomitant ischemia, in other regions, because of
other compromised coronary bundle branch (Figures 66 and 67).

4-8 h 24 h 48 h 3-5 días 7-10 días 10-14 días

Figure 68. Enzymatic evolution in AMI

Remember the possible causes of cardiac specific troponin elevation

shown in Table 32.

MYOCARDIAL NECROSIS CAUSED BY

· Ischemia
· Severe, acute or chronic cardiac insufficiency
· Myocarditis or myopericarditis, complicates endocarditis
· Myocardial damage by contusion, catheter ablation, endomyocardial
biopsy or electric cardioversion
· Myocardial infarction in aortic dissection, aortic valvulopathy, severe
arrhythmias, hypertension episodes or pulmonary hypertension,
(pulmonary embolism, idiopathic, etc.)
· Cardiomyopathy such as hypertrophic, tako-tsubo or infiltrating
· Severe episode of sepsis or shock
· Cardiotoxic chemotherapy (5-fluorouracil, anthracycline, herceptin)

OTHER CIRCUMSTANCES
Figure 66. Anterolateral MI in acute phase
· Renal function impairement (acute or chronic)
· Hypothyroidism
I · Ischemic or hemorrhagic acute stroke
· Large burns or rhabdomyolysis
· Some poisoning
II
Table 32. Causes of cardiac specific troponin elevation

III
The initial action recommended in STE-ACS is shown in Figure 69.

The aim of reperfusion therapy is recanalization of the obstructive

artery and avoidance of reocclusion. The benefit of reperfusion exists
aVR
in the short and long run, and it also minimizes complications and re-
lieves the pain. Myocardial necrosis is limited when repermeabilizes,
aVL reducing final ventricular dysfunction. This treatment is highly useful
in the first hours after pain has begun. As a general rule, it is indicated
in the first 12 hours of clinical course.
aVF
There are two methods of emergency reperfusion: the administration
of intravenous thrombolytic drugs (fibrinolytic medication) or perform-
ing emergency coronarography or angioplasty (PTCA or primary PCI).
Figure 67. Inferior Wall MI in acute phase
46
 Card i o l ogy 1
RELATIVE
ABSOLUTE CONTRAINDICATIONS
CONTRAINDICATIONS
STE-ACS suspicion
· Active hemorrhage (menstruation · Transitory ischemic
• Anamnesis excluded) accident in the previous
V3R, V4R, V7-V9 values
• Exploration
· History of intracranial bleeding six months
• ECG (< 10 min)
· Ischemic ictus during the six previous · Oral anticoagulation
months · Active peptic ulcer
Alternative · Known brain injury (e.g., neoplasia · Pregnancy or immediate
SCASEST Consider ECG diagnosis and traumatism) puerperium (one week)
and serial necrosis markers
· Severe trauma, major surgery or head · Refractory arterial
Relevant • Tests injury in the three previous weeks hypertension (> 180/110
actions Persistent ST elevation, • Treatment · Gastrointestinal bleeding in the last mmHg)
left bundle branch block month · Severe hepatopathology
· Noncompressible punctures (lumbar, · Infective endocarditis
• ECG monitoring hepatic biopsy, etc.) · Prolonged or traumatic
• Rest · Aortic dissection resuscitation
• Oxygen · Hemorrhagic abnormality
• Anti-emetic opiates
• Watch AP and peripheral perfusion Table 33. Contraindications for thrombosis treatment
• ASA (prasugrel or ticagrelor or clopidogrel
should be added to ASA)
• Reperfusion therapy Rescue PTCA is indicated in the first 12 hours of progression of symp-
toms after thrombolysis has failed, and if an increase in ST over 50% is
observed in the leads with the maximum recorded elevation (generally
Yes Primary PTCA possible in less than two hours? No with persistent pain and with no reperfusion arrhythmias). Immediate
coronarography with PTCA is also appropriate upon evidence of recur-
Primary Contraindications?
rent ischemia (post infarction angina) or arterial reocclusion after an
Yes initially efficient fibrinolysis.
PTCA Thrombolysis

After the acute phase, medical treatment after a STE-ACS is shown in

No Table 34.

Consider Fibrinolysis LONG TERM TREATMENT IN AMI

coronarography Effective (In-hospital
3-24 h or out-of-hospital) · Changes in lifestyle
· Diabetes control (HbA1c < 7%) and hypertension (AP < 140/90 mmHg)
· Acetylsalicylic acid (ASA)
Ineffective
· Prasugrel/ticagrelor or clopidogrel for 12 months
· Anticoagulation if indicated for any other reason
Rescue · β-blocker
PTCA · ACE inhibitors and ARAs
· Statins
· Eplerenone if LVEF < 40% or cardiac insufficiency
· Consider ICD and TRS implants
Figure 69. Initial performance in STE-ACS
· Revascularization if indicated

At present, PTCA is considered the first-choice treatment as long as it is
performed immediately (within two hours after consultation) by a spe-
cialized team. It has been demonstrated that PTCA provides better clinical
results than in-hospital thrombolysis (less reinfarctions, artery reclusions,
and less residual ventricular dysfunction), and that it may even improve
by using stent, since the risk of the vessel reintervention is reduced.
Door-to-balloon time (the period from hospital arrival to angioplasty)
must not exceed 90 minutes; otherwise, it loses its advantage over fibri-
nolysis. If the patient presents cardiogenic shock or if fibrinolysis is con-
traindicated, PTCA is the treatment of choice, regardless of the delay.
Nowadays, in the acute phase, it is recommended to only act over the
artery responsible for the infarction and to consider complete revascu-
larization, when indicated, by PTCA or surgery in a differed way, after
the patient has stabilized.
There follow some contraindications of thrombolytic medication (Table
33) to be checked before their administration to patients.
Table 34. Long term treatment for MI
Apart from the medical treatment, smoking cessation, a cardiac healthy
diet and weight loss are recommended if BMI is greater than 30 and
waist circumference is over 102 cm in men and over 88 cm in women. A
strict control of risk factors, aerobic physical exercising at least five days
a week (including participation in cardiac rehabilitation programs), and
evaluation of arrhythmic risk are also recommended.
An implanted cardiac defibrillator is indicated after 40 days, to prevent
arrhythmic sudden death, if the patient remains with LVEF < 30%. Opti-
mal medical treatment and revascularization must always be granted, if
indicated, before the implant. The main risk determinants are LV ejec-
tion fraction and functional class, as well as nonsustained ventricular
tachycardia and inducement of sustained ventricular tachycardia in the
electrophysiologic study. It is convenient to wait for the resolution of
stunned myocardium in order to estimate residual ejection fraction.
Table 35 shows current indications to implant a defibrillator after a
myocardial infarction.

47

PRIMARY PREVENTION
(always, at least, 40 days
following the AMI)
· LVEF < 40%, VT
nonsustained and VT
sustained inducible in
electrophysiologic study
· LVEF < 35% and II-III
functional class of NYHA
· LVEF < 30% and I-III
functional class of NYHA
(indication IIa*)
* Indication shows that the benefit appears greater than the implantation risk, so it is
advisable
Table 35. Indications for automatic defibrillator implant after an AMI
7.3. Complications
of myocardial infarction
Arrhythmias
Tachyarrhythmias
Mechanisms producing ventricular arrhythmias in the acute phase of
an infarction (primary arrhythmias) differ from those appearing in the
chronic phase of the disease (in which there is an anatomic substrate
for the onset of anatomica re-entries in the scar). The main arrhythmias
are shown in Table 36.
ARRHYTHMIA
VF in the first 24-48h
VF or SMVT badly
tolerated beyond 48h
SMVT well tolerated
with normal or quasi
normal LVEF
Symptomatic NSVT
Asymptomatic
NSVT or ventricular
extrasystole
Torsades de Pointes
AIVR
48
A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)
SECONDARY PREVENTION
Supraventricular Tachycardia
Sinus tachycardia generally indicates a major infarction with ventricular
· VF-produced sudden death
dysfunction and cardiac insufficiency associated. It must not be treated
recovered outside the acute
phase as such.
· Sustained VT with poor
hemodynamic tolerance and Sinus bradycardia is common in the acute phase of inferior infarction
depressed LVEF due to vagal hypertonicity, or secondary to opiates, and it appears in
· Sustained VT well tolerated with
25% of cases.
normal LVEF (or almost normal)
(indication IIa*)
Atrial fibrillation occurs in 10% to 20% and is associated with major
infarctions with important ventricular dysfunction mainly in the elderly.
Anticoagulation is indicated due to the embolic risk involved.
Conduction disturbances
Almost 10% of STE-ACSs are found with AV block, and are more related
to mortality (due to the myocardial extension producing the block than
the block itself, since the block associated with the inferior infarction
has a good prognosis; Table 37).
AV BLOCKS POST AMI SUPRA-HISIAN INFRA-HISIAN
Heart rate 40-60 bpm (narrow) < 40 bpm (wide)
AMI Location Inferior Anterior
Atropine response Responds No response
Prognosis Good Poor
Table 37. Atrial ventricular blocks in AMI
TREATMENT SECONDARY PREVENTION PRIMARY PREVENTION
Defibrillation · Reperfusion · Reperfusion
· β-blockers · β-blockers
· Amiodarone 24-48h
Defibrillation/cardioversion · Revascularization if indicated · Reperfusion
· ICD implant · β-blockers
· Treatment of heart failure · Treatment of heart failure
· Amiodarone or ablation in special · ICD implant :
cases - LVEF < 40%, SMVT and
inducible NSVT
- CF II-III and LVEF < 35%
- CF I and LVEF < 30%
· Cardioversion · β-blockers · Reperfusion
· Anti-arrhythmics · VT ablation · β-blockers
(procainamide or amiodarone) · Consider ICD · Treatment of heart failure
· Amiodarone in special cases
· β-blockers · β-blockers · Reperfusion
· Amiodarone in refractory cases · Amiodarone in special cases · β-blockers
· Valuate the indication of ICD implant · Treatment of heart failure
as primary prevention
· β-blockers · β-blockers · Reperfusion
· Avoid anti-arrhythmics of Ic group · Treatment of heart failure · β-blockers
· Valuate the indication of ICD implant · Treatment of heart failure
as primary prevention
Defibrillation if sustained · Reperfusion · Reperfusion
· Magnesium · Correct electrolytes
· Shorten QT (pacemaker, isoproterenol)
· Correct electrolytes
· No (indicates reperfusion) No No
· Atropine if symptomatic
Table 36. Treatment of ventricular arrhythmias in STE-ACS
 Card i o l ogy 1
Almost 20% of infarctions develop transitory bundle branch block, Mechanical Complications
which persists in 5% of cases. New-onset bundle branch block, mainly
left-sided, is related to extensive infarctions with severe systolic dys- These are included in Table 38, and in Figures 71, 72, 73, 74 and 75.
function and a poor prognosis.

Acute Heart Failure because

of LV Systolic Disfunction
It may be mild or turn into cardiogenic shock, and may increase mortal-
ity in the short and long term. Symptoms, signs, diagnosis and treat-
ment are similar to other heart failure-related clinical situations. Killip
and Forrester classifications are used to categorize the clinical situation.

The main causes of arterial hypotension in inferior wall STE-ACS are

shown in Figure 70.

Inferior AMI
with hypotension Cardiac rupture

RV infarction Cardiac rupture Bradycardia Pump failure

· Liquids · Fluids · Atropin · Rare: diuretics
· Inotropes · Pericardiocentesis · Inotropes
· Reperfusion · Surgery · Contrapulsation
· Reperfusion
Correction with pericardiac patch

Figure 70. Causes and treatment of inferior infarction with arterial Figure 71. Free wall rupture
hypotension

TYPICAL LOCALIZATION AND

COMPLICATIONS
Free wall rupture
Ventricular septal
rupture
Mitral regurgitation
Ventricular aneurysm
Pseudo aneurysm
Right ventricular
infarction
SYMPTOMS AND DIAGNOSIS TREATMENT
PREDISPOSING FACTORS
Anterolateral · Electromechanical dissociation · Cardiopulmonary resuscitation
· Old woman · High vein pressure · Immediate surgery
· Hypertension · Echocardiography
· First infarction
· Reperfusion and β-blocker reduce
the risk
Anterior septum (anterior infarction) · Shock and acute pulmonary edema · Immediate surgery
· Similar to rupture · Parasternal murmur · IABP
· Oximetry gap in RV · Diuretics
· Echocardiography · Vasodilators
Inferoposterior (posterior papillary · If rupture, shock and acute · Reperfusion
muscle) pulmonary edema. Unilateral edema · In mild or moderate cases,
sometimes. surgery is to be delayed
· Murmur in apex (absent or mild in · IABP
severe cases) · Diuretics
· Giant V wave in PCW · Vasodilators
· Echocardiography · Severe cases: immediate surgery
Apical (anterior infarction) · Double apical impulse Anticoagulation if intraventricular
· First infarction · Persistent ST elevation thrombus or stroke
· Reperfusion ACE inhibitors and ARAII · Associated with heart failure,
reduce the risk embolism or arrhythmias
· No risk of rupture · ECG
Anterolateral · Chest pain Immediate surgery
· Thrombus-contained rupture · ECG
Inferoposterior · Hypotension · Reperfusion
· High vein pressure and absence · Intravenous fluids
of rales · No diuretics, no vasodilators
· Increased ST in V4R · Inotropes
· ECG
Table 38. Mechanical complications of infarction

49
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Apical IVC

Mural thrombus

Infarcted
segment

RV LV

Infarct area True aneurysm

Correction with patch

Transmural infarction
Figure 72. Repair of ventricular septal rupture because with rupture
of septum rupture in AMI
Pericardium

Thrombus

RV LV

Pseudoaneurysm

Figure 75. Differences between aneurysm and pseudoaneurysm

Others
Figure 73. Mitral regurgitation correction by papillary muscle rupture Postinfarction ischemia requires immediate intervention and an early
coronarography.

Thrombosis (apart from those related to supraventricular arrhythmias)

is commonly related to the formation of intracavitary thrombus present
Conventional in almost 5% of infarctions, mainly anterior infarctions.
suture
Meta infarction acute pericarditis (epistenocardiac) produces ST el-
evation and pericardial pain, requiring only if the pain is not con-
trolled under conventional analgesia NSAIDs or colchicine for the
Suture treatment.
in inverted “T”
Dressler syndrome is defined by fever, pneumonitis and polyserositis
(pleuropericarditis) probably immune-mediated. It is equivalent to
the post pericardiotomy syndrome appearing, in some occasions, af-
ter cardiac surgery. It generally occurs between the first and second
Pericardial week after infarction, though it may be delayed. Treatment is similar
patch
to that of pericarditis. Recurrence is frequent (especially in patients
who have been administered glucocorticoids, which are very effi-
cient in relieving symptoms). Colchicine may be useful to prevent
Figure 74. Repair of ventricular aneurysm (aneurysmectomy) recurrence.

50
 Card i o l ogy 1

Dyslipidemia
Statins are classified according to the expected reduction of LDL-
cholesterol levels in high-, moderate- or low-intensity therapy (Table
40).
Chapter 08
HIGH-INTENSITY MODERATE-INTENSITY LOW-INTENSITY
STATIN THERAPY STATIN THERAPY STATIN THERAPY
Although a comprehensive study of dyslipidemia is included in the En-
docrinology chapter, some considerations must be mentioned. Daily dose lowers Daily dose lowers LDL- Daily dose lowers
LDL-cholesterol cholesterol on average, LDL-cholesterol
on average, by by approximately on average, by
LDL elevation is related to a greater risk of coronary heart disease, and
approximately > 50% 30% to 49% < 30%
it is similarly related to VLDL. Levels of HDL are inversely related to de-
velopment of premature arteriosclerosis. Factors leading to a rise in
· Atorvastatin · Atorvastatin 10-(20) mg · Simvastatin 10 mg
HDL levels are physical exercise, lipid-lowering diet and female sexual (40)-80 mg · Rosuvastatin (5)-10 mg · Pravastatin 10-
hormones, whereas factors lowering HDL levels are obesity, sedentary · Rosuvastatin · Simvastatin 20-40 mg 20 mg
and smoking. 20-(40) mg · Pravastatin 40-(80) mg · Lovastatin 20 mg
· Lovastatin 40 mg · Fluvastatin 20-
· Fluvastatin 40 mg bid 40 mg
Saturated fatty acids (common in animal fat) cause an increase LDL
· Pitavastatin 2-4 mg · Pitavastatin 1 mg
cholesterol, whereas monounsaturated and polyunsaturated acids
cause an increase HDL. There are many drugs to decrease LDL, such Table 40. High, moderate and Low-Statin Therapy.
as statins. Others are ezetimibe or resins, such as cholestyramine, ( ) indicates less evidence
though these are hardly used nowadays due to the adverse events
produced.
The use of other lipid-lowering agents such as niacin or ezetimib has not
There is a close relationship between abdominal obesity (abdominal been shown to reduce the risk of atherosclerotic cardiovascular disease
waist diameter over 102 cm in men and over 88 in women) and isch- (Table 41).
aemic heart disease; hypercholesterolemia, hypertriglyceridemia and
hypertension are also associated.
CALORIES RELEASED
ACTIVE CONTRIBUTION TO DIET (%)
Metabolic syndrome is defined as a group of cardiovascular risk factors ap- IN COMPLETE
SUBSTANCE OVER TOTAL CALORIES
OXIDATION
pearing more frequently than usual. Metabolic syndrome components are
hypertension, abdominal obesity, hypertriglyceridemia, lower HDL levels Carbohydrates 4.1 kcal/g 50% to 65%%
and altered baseline glycemia. The metabolic syndrome pathophysiologic
basis seems to be related to insulin-resistance due to abdominal obesity. Fat 9.3 kcal/g Saturated: < 10%
Nowadays, there is a debate over whether metabolic syndrome adds an- Polyunsaturated: < 10%
other risk to the existing cardiovascular risks, although preliminary data Monounsaturated: 10% to 15%
suggests so, at least, in some cases. Treatment includes adequate diet
and regular physical exercise. Cholesterol - < 300 mg/day

The lastest guidelines for the treatment of blood colesterol to reduce Proteins 4.3 kcal/g 10% to 20%
atherosclerotic cardiovascular disease recommends:
Table 41. Active substances proportion in normal diet

AGE CRITERIA TREATMENT Hypercholesterolemia reduction is followed by a reduction in arterio-

All ages LDL≥ 190 mg/dL High-intensity statin sclerosis progression. The initial treatment of hyperlipidemia is a low-
or atherosclerotic fat diet (< 30% to 35% of total caloric intake). Likewise, cholesterol in
cardiovascular disease saturated fatty acids and polyunsaturated acids must be poor. It is nec-
(ASCVD)
essary that most fat be ingested by way of monounsaturated fatty acids
20-39 years Familiar history and Consider statin since they increase HDL levels (Table 40).
LDL ≥ 160 mg/dL
40-75 years LDL 70-189 mg/dL · 7.5% 10-year risk: high- Physical exercise prevents elevation of cholesterolemia and keeps
without ASCVD or intensity statin HDL levels high. In order to carry out a selective detection of hyper-
diabetes · 5-7.5% 10-year risk: lipidemia, a cholesterol blood test is recommended for all adults,
moderate-intensity statin especially for young individuals with a family history of premature
· ≤ 5% 10-year risk: no statin
ischemic cardiopathology. Cholesterol determination is recom-
40-75 years LDL 70-189 mg/dL · ≥ 7.5% 10-year risk: high- mended at least in men under 35 years of age and in women under
with diabetes intensity statin 45 years of age. From that age on, an analytic determination ev-
· ≤ 7.5% 10-year risk: ery five or six years is recommended. In the last years, inhbitors of
moderate-intensity statin PCSK9 (evolocumab and alirocumab) have emerged as an additional
Table 39. American College of Cardiology/American Heart Association alternative for patients with insuffiecient control of LDL despite
Treatment Guidelines statin therapy.

51
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Hypertension
Chapter 09
9.1. Essential Hypertension
High blood pressure or hypertension is highly prevalent (30% to 45%
in the general population) and has a steady incidence. Almost half
the people with hypertension are unaware of the condition and, in
spite of new therapeutic advances, optimum control is achieved in
less than half of patients; it is therefore a first-order public health
issue.
Systolic isolated HTN, common among the elderly, is characterized
by values over 140 mmHg of systolic and below 90 mmHg of dia-
stolic pressure and is also correlated with morbidity and mortality.
However, systolic isolated HTN among young people has not been
revealed to improve prognosis with treatment, data also suggests
that this entity does not progress to systolic/diastolic HTN in every
case.
Malignant HTN is a hypertensive emergency with ischemic organic
damage (retina, kidney, heart or brain), especially papilledema on oph-
talmoscopy. Although the most frequent cause is untreated essential
hypertension, secondary causes of HTN must be thoroughly analyzed.
Prognosis without treatment is 50% mortality in the first year. For treat-
ment, intravenous drugs such as labetalol, nitrates, nitroprusside or ni-
cardipine are used.

Elevations in systolic and diastolic blood pressure are related to this
cardiovascular disease –systolic blood pressure (SBP) being a stron-
ger sign of potential complications than diastolic blood pressure
(DBP) after 50 years of age-, and pulse pressure (difference between
systolic and diastolic pressure) in elderly patients also adds predic-
tive value.
The most frequent form of HBP is essential (usually starting between
30 and 50 years of age, although starting to appear in younger people,
even teenagers). Among younger people, secondary causes such as
aortic coarctation should be ruled out, and among elderly patients, it
is convenient to rule out other etiologies such as renal artery athero-
sclerosis.
By consensus, adult high blood pressure (HBP) is defined as the pres-
ence of SBP over 140 mmHg (systolic HTN) and/or DBP over 90 mmHg
(diastolic HTN). However, these limits are arbitrary since there is a con-
nection with cardiovascular risks at lower values, especially in patients
with high cardiovascular risk. Complete patient risk level should be de-
termined, not only the BP level, to apply the correct therapeutic action
(this is carried out using calculation tables of cardiovascular risk, such as
Framingham’s risk score or Euroscore).
The most common classification of BP values is shown in Table 42. How-
ever, the lastest guidelines defines HTN by BP > 130/80 mmHg.
Accelerated hypertension refers to patients who do not have papillede-
ma but who have other severe vascular damage signs, such as hemor-
rhages or retinal exudates.
Hypertensive crisis are SBP elevations > 180 mmHg and/or DBP > 120
mmHg. There are two types: hypertensive emergency and hypertensive
urgency.
Hypertensive emergency describes an elevation in blood pressure ac-
companied by severe acute damage to target organs threatening the
patient’s life (encephalopathy, acute coronary syndrome, acute heart
failure, aortic dissection, ischemic or hemorrhagic stroke, pheochro-
mocytoma crisis, drugs such as cocaine, amphetamines or MDMA,
eclampsia or perioperative hypertension). The magnitude and speed
for correction of pressure values will depend on the involvement of
the organ at issue. For instance, for a stroke, correction will be small
and slow, whereas in a case of acute pulmonary edema or aortic dis-
section, the correction must be major and quick. However, in most
cases it is sufficient with a 25% correction of the BP values during the
first hours and slowly thereafter, since a sudden and intense BP drop
could cause greater organic and ischemic damage. The i.v. drugs used
are similar to the ones used for malignant HTN. When a major BP el-
evation is not accompanied by severe, acute organic damage, there
is hypertensive emergency. It is usually managed by restoring or in-
creasing antihypertensive therapy (in many cases it is the result of a
break in use).

TYPE SBP (mmHg) DBP (mmHg) Resistant or refractory hypertension occurs when values cannot be
lowered to desired levels in spite of lifestyle changes and after at least
Optimum < 120 and < 80
three drugs (including a diuretic). It may comprise up to 15% of patients
Normal 120-129 and/or 80-84 and the main causes are inadequate compliance with nonpharmaco-
logic instructions, use of hypertensive substances (liquorice, NSAIDs,
Normal-high 130-139 and/or 85-89
corticosteroids, cocaine, etc.), sleep apnea, unsuspected secondary
HTN level 1 140-159 and/or 90-99 cause, irreversible injury to target organs or volume overload (sodium
ingestion, insufficient doses of diuretic, progressive kidney failure or
HTN level 2 160-179 and/or 100-109
hyperaldosteronism). In these cases it is convenient to rule out “white
HTN level 3 ≥ 180 and/or ≥ 110 coat” hypertension, pseudo hypertension or the use of a cuff of inad-
equate size.
Systolic isolated HTN ≥ 140 and ≤ 90

Table 42. Classification of BP values
In pediatrics, there is hypertension with BP values over 95% percent,
adjusted to age and sex; values ranging between 90% and 95% are con-
sidered prehypertension.
“White coat” HTN or isolated clinical hypertension defines patients
with normal BP values outside of medical consultation -determined
by ambulatory blood pressure measurement (ABPM), see below- and,
however, with consistently high values during consultation. It affects
15% of the population. It involves lower risk of damage to target organs

52

than the real hypertension, but apparently greater than people with
normal BP, therefore requiring close follow up and even consideration
of application of treatment if vascular risk is high or there are signs of
damage to target organs.
Masked HTN or isolated ambulatory HTN is the contrary phenomenon
(normal values during consultation, but higher elsewhere). It is just as
prevalent as clinical isolated HTN and is frequently associated with dam-
age to some target organ, therefore requiring similar management as
HTN.
Exertion HTN is characterized by normal BP at rest, but with excessive
increase during exertion (there is no consensus, but most define it as
SBP > 210 mmHg among men and > 190 mmHg among women). Its
usefulness for diagnosis and prognosis of patients with HTN is contro-
versial. In the event of abnormal results, ABPM is advisable.
Measurement
of Blood Pressure
A correct measurement of blood pressure is based on the auscultatory
method of Korotkoff sounds. Pseudo hypertension appearing with ath-
erosclerosis may be suspected by palpating the radial artery with the
inflated cuff (Osler’s sign).
Diagnosis of HTN requires several elevated values over several days, ex-
cept in extreme cases.
Measurement of ambulatory blood pressure (ABPM) -with automatic
devices- which takes multiple measurements throughout the day, ap-
pears to have greater correlation with some organic damage mark-
ers and morbimortality. ABPM can be useful with certain patients, for
instance, to assess the degree of control over BP values during “val-
ley” periods of drug effect, for the diagnosis of “white coat HTN” or
“masked HTN”, or for detecting nondipper patients whose BP during
sleep does not fall and who appear to have higher risk. However, it
should be noted that mean BP values obtained with this method are
lower than those obtained during office visits; therefore HTN diag-
nosis will not be defined with values over 140/90 mmHg, but over
130/80 mmHg, 135/85 mmHg during the day and 120/70 mmHg at
night.
Self-measurement of blood pressure at home (SMBP) with auto-
matic devices that are correctly calibrated is more closely related
the organic damage caused by HTN than with measurement at office
visits, as well as with a better estimate of cardiovascular (CV) mor-
bimortality (similar to ABPM’s). In addition, it is useful with certain
patients, since it has the benefit of avoiding the “white coat” ef-
fect and shows the variation in BP values after, for instance, altering
drug therapy. In this context, normal BP values are lower than those
determined at office visits, thus values over 135/85 mmHg are con-
sidered HTN.
Basic complementary studies to be performed on every hypertensive
patient include blood and urine analysis, and ECG (Table 43). Other
tests such as echocardiography, chest X-ray, ankle-brachial index, ca-
rotid ultrasound or ophthalmoscopy, are advisable for many patients,
as well as other specific studies to determine suspected secondary
causes.
Card i o l ogy 1
ADVISABLE FOR ALL PATIENTS
· Blood analysis: fasting glycemia, cholesterol and its fractions,
fasting triglycerides, potassium, uric acid, creatinine, hemoglobin
and hematocrit. Assessment of creatinine clearance or glomerular
filtration rate using appropriate formulas
· Urine analysis: microscopic analysis and microalbumin test (reagent strip)
· ECG: to assess the presence of arrhythmia and signs of left-sided
ventricular hypertrophy
ADVISABLE FOR MANY PATIENTS
· Echocardiograph (size of ventricular hypertrophy)
· Carotid ultrasound (intima media thickness)
· Chest X-ray
· Ankle-brachial index
· Ophthalmoscopy
· Quantitation of proteinuria if reagent strip was positive for microalbumin
· Glucose tolerance test if glycemia is over 100 mg/dL
· ABPM and/or SMBP
· Pulse wave velocity calculation
Table 43. Complementary examination of hypertensive patients
The main “target” organs with damage caused by hypertension are the cen-
tral nervous system (typically strokes), heart (hypertrophy, myocardial isch-
emia or arrhythmia) see Figure 76. Also, kidneys (renal failure because of
nephroangiosclerosis) and the retina (hypertensive retinopathy), Table 44.
Figure 76. 12-lead ECG of hypertensive patient with left-sided ventricular
hypertrophy and secondary repolarization alterations
GRADE I Arteriolar constriction and sclerosis
GRADE II Arteriovenous nicking
GRADE III Exudates and hemorrhages
GRADE IV Papilledema
Table 44. Hypertensive retinopathy. Keith-Wagener-Barker classification
Hypertensive heart disease usually shows ventricular hypertrophy and
predominantly diastolic failure, although in advanced stages of severe
hypertension it can cause dilation and systolic ventricular dysfunction,
mimicking a dilated cardiomyopathy.
Atrial fibrillation is the arrhythmia most closely related to hypertension,
due to retrograde elevation of left-sided pressures. Further, hyperten-
sion is a stroke risk factor in atrial fibrillation.
Treatment
Hypertensive patients must comply with lifestyle and dietary in-
structions (low salt content, avoid overweight, perform exercise,
53
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

avoid anti-inflammatories) and monitor other cardiovascular risk with a combination of two drugs and later adjustment of doses or addi-
factors. tion of a third drug.

To decide when to start drug therapy for hypertension, systolic and dia- Table 46 shows the main cases for or against the use of each drug
stolic pressure values alone are not enough in every case. It is advis- group.
able to assess the presence of established clinical or subclinical damage
of target organs and determine the overall cardiovascular risk (which
includes analyzing the presence and state of other cardiovascular risk DRUG ADVISABLE NOT ADVISABLE
factors). First line drugs

The latest recommendations for hypertension treatment published Thiazides · Heart failure · Gout
by the Joint National Committee of United States are included in the · Elderly · Diabetes risk
· African American · Metabolic
table below; there are slight differences with other available guidelines
syndrome
(Table 45).
ACE inhibitors · Heart failure · Pregnancy
or angiotensin II · Systolic dysfunction · Renal artery
RECOMENDATIONS FOR HTN TREATMENT · Diabetes bilateral stenosis
· Proteinuria · Hyperkalemia
· Drug therapy is advised for adults over 60 years of age if · Chronic kidney failure
their systolic blood pressure (SBP) > 150 mmHg or diastolic · Renovascular HTN
(DBP) > 90 mmHg. If SBP values obtained are < 140 mmHg · Metabolic syndrome
and there are no adverse effects, treatment does not need · Ventricular hypertrophy
to be adjusted
Calcium · Angina · Dihydropyridine
· In patients under 60 years of age, drug therapy is advised to reduce antagonists · Elderly in monotherapy
DBP < 90 mmHg. With lower levels of scientific evidence, it is · African american for myocardial
advisable to start treatment to lower SBP < 140 mmHg · Intermittent claudication ischemia
· In patients with chronic nephropathy or diabetes over 18 years · Metabolic syndrome · Constipation
of age, drug therapy aims for blood pressure < 140/90 mmHg · Ventricular hypertrophy
· For the general population (including diabetic patients) treatment · Pregnancy (second line)
may start with thiazides, calcium antagonists, ACE inhibitors
or angiotensin II. For African American patients (including diabetics), Second line drugs
thiazides or calcium antagonists are advisable to commence α-blockers · Benign prostatic · Heart failure
therapy. In case of chronic nephropathy, ACE inhibitors or hypertrophy · Orthostatic
angiotensin II are recommended to start therapy · Pheochromocytoma hypotension
· If targets are not attained within a month, it is recommended to
β-blockers · Coronary disease · Asthma
increase doses of the drug of choice or add a new drug (assess this
· Tachyarrhythmia · Bradyarrhythmia
to start with if BP > 160/100 mmHg). If targets are not met with
· Heart failure · Severe claudication
three drugs referring the patient to a unit specialized
· Hyperthyroidism · Diabetes risk
in hypertension is recommended · Pregnancy (second line) · Metabolic
Table 45. Recommendations for HTN treatment of the JNC-8 (2014) syndrome
Table 46. Situations that encourage or discourage the use of various
The therapeutic objective of hypertension treatment is to lower morbi- drugs for hypertension
mortality of the patient; for this purpose an operational goal is followed
aimed at lowering blood pressure to values below 140/90 mmHg in
general, being lower in diabetic patients, and with more leniency with ACE inhibitors are the drugs of choice in the presence of diabetes mel-
regard to SBP in elderly patients. litus, renovascular hypertension, and diabetic nephropathy -or from
another source-, ventricular systolic dysfunction or severe heart valve
The benefit of treatment is more closely related to lowering BP itself than failure, myocardial infarction history or high risk of developing diabetes.
with a specific drug. For this reason, it is considered that all antihyper- In case of cough or angioedema caused by ACE inhibitors, the alterna-
tensive drugs are first line and all combinations are accepted, except for tive is angiotensin II, which is useful when there is major ventricular
ACE inhibitors with angiotensin II. However, the only drugs, compared hypertrophy.
against placebos, which have been statistically shown to decrease mor-
bimortality, are diuretics and beta blockers. Newer drugs have not rep- Beta blockers are preferred in coronary patients, with atrial fibril-
licated this since it is unethical to design new studies against placebo. lation or other tachyarrhythmias, hyperthyroidism, heart failure,
sometimes migraine or if there is essential tremor. They are not the
For patients with mild blood pressure elevation and low-moderate car- best option in case of high risk of developing diabetes (metabolic
diovascular risk, treatment usually starts with a single drug in mono- syndrome).
therapy and doses are subsequently adjusted or other drugs are com-
bined to keep blood pressure values under control. However, patients Calcium antagonists are preferred in cases of isolated systolic HTN in
with markedly elevated blood pressure and high-very high cardiovascu- the elderly, African Americans, angina with contraindication for beta
lar risk usually require starting with antihypertensive therapy directly, blockers, atrial fibrillation or, sometimes, for patients with migraine.

54

In resistant HTN cases, the application of potassium-sparing diuretics
such as spironolactone/eplerenone and amiloride or alpha blockers
such as doxazosin should be considered. In case medical treatment fails,
invasive procedures, such as renal denervation and carotid barorecep-
tor stimulation may be considered.
9.2. Secondary Hypertension
The most frequent cause of secondary hypertension is renal (renovas-
cular or renal parenchymaytous).
Kidneys are both involved as victims (they develop nephroangiosclerosis)
and executioners (pathogenesis involvement) in essential hypertension.
Many drugs (vasoconstrictors, hydrosaline retention facilitators such
as anti-inflammatories, and so forth) and endocrine and metabolic
disorders (hyperaldosteronism, hyperthyroidism, Cushing’s syndrome,
among others) cause hypertension.
Figure 77 lists the main causes of secondary HTN.
Neurogenic
alterations
Drugs
Hyperthyroidism
Aortic coarctation
Atherosclerosis Aortic regurgitation
Arteriovenous
fistules Suprarenal
alterations
Pregnancy
Kidney alterations
Figure 77. Main causes of secondary hypertension
When HTN is secondary to an identifiable etiology, a treatment
should be conducted, if possible, according to the cause of the dis-
ease. For instance, in case of renovascular hypertension, an angio-
plasty of the artery involved, or its surgical repair may be prescribed.
However, medial fibromuscular dysplasia (a nonatherosclerotic, non-
inflammatory vascular disease that causes abnormal growth within
the wall of the renal artery), HTN tends to remain stable and does
not require mechanical treatment if blood pressure is controlled by
means of drug treatment. When subadventitial fibrodysplasia is in-
Card i o l ogy 1
volved, this tends to be progressive and more frequently requires
angioplasty or surgery.
9.3. Special Cases
In African American patients, diuretics and calcium antagonists appear
to offer more protection than other drug groups.
For isolated systolic hypertension in advanced age, the drugs of choice
are calcium antagonists or thiazides. Nevertheless, other first-line
drugs may be used, avoiding abrupt BP falls and monitoring orthostat-
ic hypotension with more lenient goals than with other hypertensive
patients.
In left-sided ventricular hypertrophy and in metabolic syndrome, the
drugs of choice are ACE inhibitors, ARB or calcium antagonists.
Alpha blockers (alpha-adrenergic-antagonists) are advisable for pheo-
chromocytoma.
For benign prostatic hypertrophy, alpha blockers are advisable (al-
though they may be less safe than other antihypertensives in mono-
therapy).
Patients with previous stoke may, in general, use any drugs. However,
treatment should be avoided during the first week after a stroke, unless
there is very high blood pressure.
Hospital admission is not required for hypertensive emergencies; ini-
tial treatment is applied with oral drugs such as captopril, furosemide
or amlodipine. Fast acting nifedipine should not be considered, since it
may cause hypotension and trigger myocardial ischemia.
Hypertensive emergencies require immediate treatment with intra-
venous drugs in an intensive care unit, being careful not to cause an
abrupt decline in BP to prevent hypoperfusion of vital organs. Nitro-
prusside, nitroglycerine, furosemide, urapidil and labetalol are highly
suitable drugs in this context.
With regard to pregnancy, it should be noted that during the second
trimester BP values drop approximately 10-15 mmHg, returning to
baseline levels in the third trimester. For HTN diagnosis during pregnan-
cy, the limit is defined for values over 140/90 mmHg, although ABPM
may be more accurate. Hygiene and dietary steps are recommended,
including strict supervision and limitation of physical exercise (sodium
restriction, weight loss or dietary supplements are not advised during
pregnancy). In the presence of gestational hypertension with or without
proteinuria, the use of drugs is recommended for values over 140/90
mmHg. Drugs of choice are methyldopa, labetalol or, less frequently,
calcium antagonists (they may delay birth) or beta blockers (especially
metoprolol, with low risk of intrauterine growth retardation). ACE in-
hibitors and angiotensin II are contraindicated due to their potential
teratogenic effects. Values over 170/110 mmHg require emergency
admission, with the use of intravenous nitroprusside or labetalol, oral
methyldope or nifedipine. Hydralazine use in this situation has been
discontinued because of higher perinatal risks than with other drugs. In
case of pulmonary edema, nitroglycerine is the drug of choice.
55
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

leans forward. It is important to distinguish retrosternal pain from the

Pericardial Disease
pain generated by other conditions, especially by acute myocardial in-
farction (Table 48).

Chapter 10
ACUTE MYOCARDIAL
ACUTE PERICARDITIS
INFARCTION

ECG

10.1. Acute Pericarditis

ST Diffuse ST segment Localized ST segment
Pericarditis is inflammation of the pericardium. It is called acute pericar- elevation (concave) elevation (usually with
ditis when signs and/or symptoms of pericardial inflammation exist for reciprocal changes)
one or two weeks (less than six weeks).
PR Sometimes depression Rare elevation
More than 80% of cases are idiopathic and a viral etiology is supposed Changes T waves become inverted T waves can become
in most cases. However, there are many disorders that could be associ- in evolution after the ST segment inverted when
ated with pericarditis (Table 47). becomes isoelectric the ST segment is still
elevated,
Q waves evolve
CAUSES Pain Pleuritic, sharp, stabbing, Oppressive, often
Idiopathic (over 80%) positional changes, postural associated with vegetative
changes, radiating to symptoms, radiates to the
Infectious the back, to one or both left arm, jaw and other
· Virus: Coxsackie A and B, echovirus, adenovirus, infectious trapezius ridges areas
mononucleosis, chickenpox,
B hepatitis and HIV infection Fever It often appears on the days If it appears, it is usually a
· Bacterial: tuberculosis, pneumococcus, Hemophilus, staphylococcus, before or simultaneously few days after the AMI
streptococcus, gram-negative, Borrella and mycobacteria Table 48. Differential diagnosis of acute pericarditis and AMI
· Fungi: Histoplasma, Coccidioides and Candida
· Others: amebiasis and toxoplasmosis
Radiation of the pain towards one or both trapezius ridges is charac-
Transmural acute myocardial infarction teristic of pericarditis, but it is very rare in cases of acute myocardial
Chronic kidney disease infarction. However, the pain may be absent when the etiology is tuber-
culosis, neoplastic, radiation or uremia.
Malignancy
· Metastatic neoplasms: lung cancer, breast cancer, lymphomas,
A pericardial friction rub is very specific, resembling the sound of
leukemia and melanoma
· Primary neoplasms: mesothelioma and lipoma squeaky leather, often reported as grating, scratching, or rasping. It is
· Post-radiotherapy syndrome usually best heard at the left sternal border when the patient leans for-
ward and during expiration, preferably in systole (sometimes it can also
Autoimmune diseases: acute rheumatic fever, systemic lupus be heard during early diastolic filling or during atrial contraction). It is
erythematosus, rheumatoid arthritis, scleroderma, polyarteritis not constant, it may be intermittent according to chest position or other
nodosa, Wegener’s disease, Dressler’s syndrome
factors. There may be fever often appearing simultaneously with the
and postpericardiotomy pericarditis
pain. Tachycardia and malaise are common.
Inflammatory processes: sarcoidosis, amyloidosis and inflammatory
bowel disease The ECG is the most useful diagnostic test. It can reveal:
Trauma: cardiac trauma, cardiopulmonary resuscitation, iatrogenic • Concave ST segment elevation, diffuse in almost all leads. As days
hemopericardium (implanted pacemakers or defibrillators, go by, the ST segment returns to normal and the T waves become
angioplasty, endomyocardial biopsy, catheter ablation, etc.) negative (they may remain like that for weeks or months). Clinical
course over time is very characteristic, although the full sequence
Drugs: hydralazine, procainamide, diphenylhydantoin, isoniazid, can be observed in less than half of patients.
phenylbutazone, dantrolene, doxorubicin, methysergide, penicillin,
• There may be a decrease in QRS complex voltage and electrical al-
cromolyn and minoxidil among others
ternans (variation in the amplitude of the QRS complex) when there
Other: myxedema, chylopericardium and aortic dissection is a large pericardial effusion associated.
Table 47. Causes of pericardial disease • There may be a PR segment depression, a sign of atrial involvement.
This sign shows high specificity but low sensitivity for the disease.
Atrial arrhythmias can also be observed.
The main symptom is retrosternal pain originating in the parietal peri-
cardium with pleuritic characteristics. Pain severity increases by deep Chest x-ray and echocardiography may be normal, unless there is a se-
inspiration, coughing and exercise, and decreases when the patient vere pericardial effusion (Figure 78).

56

A B
PE
P
LV
RV
PE
LA
RA
PE
Figure 78. Echocardiography image of severe pericardial effusion (PE) in apical (A) and subcostal (B) four-chamber view
Specific forms
of pericarditis
Idiopathic pericarditis
Idiopathic pericarditis is the most common cause of acute pericarditis and
is usually caused by certain viruses, although no systematic tests for their
detection are performed. There are usually signs and symptoms of infec-
tion of the gastrointestinal or upper respiratory tract during the previous
days or simultaneous to the disease. It is characteristic of young adults
and is sometimes associated with pleuritis and/or pneumonitis. It does
not usually evolve into pericardial effusion with cardiac tamponade or
constrictive pericarditis.
For treatment, NSAID (ibuprofen, ASA in high doses and indomethacin)
are prescribed for several weeks with a gradual dose reduction. Nowa-
days, colchicine is recommended as first line treatment of acute pericar-
ditis. On the other hand, glucocorticoids should be avoided, due to the
increased risk of recurrence by reducing dose, except for some specific
cases. Anticoagulants should be avoided because of the risk of hemor-
rhagic transformation. It usually heals without sequelae.
The major problem in this condition is the tendency to relapse (25% of
cases). Colchicine is the preferred drug for preventing relapse, admin-
istered during the acute phase and several weeks later, in association
with a NSAID, or alone. When recurrences are frequent, pericardiec-
tomy could be evaluated.
Dressler’s Syndrome
and Postpericardiotomy
The former usually occurs the first few weeks after myocardial infarc-
tion and the second after cardiac surgery or trauma. Both seem to have
an autoimmune etiology and are characterized by fever, pericarditis,
pleuritis, pneumonitis and, sometimes, arthralgia. Anticardiomyocyte
antibodies are frequently detected. Treatment is similar to idiopathic
pericarditis. Recurrence is also very common, especially if glucocorti-
Card i o l ogy 1
PE
RV
RA LV
LA PE
coids have been administered. A transmural infarction or cardiac trau-
ma can also lead to pericarditis with no autoimmune etiology, such as
epistenocardiac pericarditis, during the early days of the condition.
Other Etiologies
• Connective tissue diseases especially systemic lupus erythemato-
sus and rheumatoid arthritis, are frequently associated with asymp-
tomatic pericardial effusion, although they may manifest as acute
pericarditis.
• Acute rheumatic fever associated with pericarditis is often a mani-
festation of severe pancarditis.
• Pyogenic pericarditis may occur after cardiothoracic surgery, in immu-
nocompromised patients, esophageal rupture into the pericardium,
by extension of foci of pyogenic infection of mediastinal or pulmonary
origin, or within sepsis (sometimes sepsis is associated with aseptic in-
flammatory pericarditis). Since pyogenic pericarditis has a high mortal-
ity rate, early treatment with intravenous antibiotics is required.
• Tuberculous pericarditis manifests with pain (which is not usually
as intense as in idiopathic pericarditis), pericardial rub and fever.
There may be other signs of systemic tuberculosis infection (anorex-
ia, weight loss, among others). Sometimes there is asymptomatic
chronic pericardial effusion, subacute or chronic pericarditis prone to
constriction. In addition to the tuberculosis treatment, NSAIDs and,
sometimes, corticosteroids are administered to prevent obstruction.
• Uremic pericarditis is very common, appearing in about one-third
of patients with advanced kidney failure, especially in those under-
going dialysis. It is usually subacute and is frequently painless, al-
though pericardial rub is often present. Fluid may be fibrinous or
hematic. Treatment includes anti-inflammatory drugs and hemodi-
alysis. If there is cardiac tamponade, pericardiocentesis should be
performed. When pericarditis is recurrent or persistent, pericardi-
ectomy may be indicated.
Chronic Constrictive Pericarditis
Chronic constrictive pericarditis (CCP) is caused by chronic inflammation
of the pericardium. Granulation tissue, fibrosis and calcification may de-
velop (the fibrous process may extend to the adjacent myocardium),
57
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)
with subsequent loss of normal elasticity of the pericardial tissue and
impairing diastolic function. In the early phase of diastole, ventricular
filling is normal, but it is abruptly disrupted when the maximum elastic-
ity of the pericardium is attained. Stroke volume decreases while there
is equalization of diastolic pressure in all four heart chambers.
CCP can potentially occur as a result of any pericardial disease, but it
rarely occurs after acute pericarditis. In most cases, the origin is un-
known, but among the most common known causes are cardiac sur-
gery, mediastinal radiotherapy, tuberculous pericarditis, connective
tissue diseases, and recurrent uremic pericarditis.
Systemic congestion signs such as increased jugular venous pressure,
hepatosplenomegaly and edema are predominant. Hepatosplenomegaly
is often accompanied by ascites and liver dysfunction, so it can easily be
confused with cirrhosis. Dyspnea is uncommon, although there may be
weakness and signs of malnutrition (systemic congestion may produce
protein-losing enteropathy). Other signs that can be detected include de-
creased apical impulse and intensity of heart sounds. Sometimes a sound
appears immediately after the second sound, which corresponds to a
pericardial knock and should not be confused with a third sound. The
Kussmaul sign (raised jugular vein pressure on inspiration) is very com-
mon. A rapid “y” descent (prominent diastolic collapse of JVP) is usually
noted followed by a rapid rise and subsequent plateau, with a greater “a”
wave and, sometimes, a prominent “x” descent.
The ECG may reveal decreased QRS complex voltage, flattening and in-
version of T waves, and atrial fibrillation in about one-third of patients.
In about 50% of the patients, chest x-ray shows calcification of the peri-
cardium, although this does not always causes constriction. An echocar-
diography generally shows thickening of the pericardium but, in case it
is normal, this diagnosis should not be ruled out.
Cardiac MRI and CT scans are more reliable for detection of pericar-
dial thickening than echocardiography. However, pericardial thickening
does not necessarily indicate constriction (Figure 79).
Figure 79. CT scan from a patient with constrictive pericarditis showing
intense pericardial calcification
58
Catheterization is usually unnecessary although, in some cases, it is
performed to distinguish it from restrictive cardiomyopathy. The x and
y descents are prominent and a wave is usually increased, resulting in
an “M” shape. In jugular vein pressure, y descent is the most prominent
wave, interrupted by a rapid rise in pressure (called h wave).
In the ventricle, diastolic pressure acquires a square root or dip-plateau
shape, since pressure increases rapidly when the limit of pericardium
distensibility is reached and it remains on a plateau.
This pressure pattern is very similar to the one in restrictive cardiomy-
opathy and, on rare occasions, endomyocardial biopsy may be required
to differentiate them. Left filling pressure is higher than right filling pres-
sure by more than 5 mmHg in restrictive cardiomyopathy (in constrictive
pericarditis they are usually almost equal); this difference is magnified
by volume overload or Valsalva maneuver in restrictive cardiomyopathy.
BNP elevation may support the diagnosis of restrictive cardiomyopathy.
Pericardiectomy (pericardial stripping) is the only definitive treatment
for constrictive pericarditis. This procedure consists of performing a
longitudinal incision on the pericardium, finding a dissection plane and
removing it carefully to prevent myocardial tears or lesions of the coro-
nary vessels. If there is serious calcareous infiltration of the epicardium,
it is better to leave some portions than run the risk of a complete re-
moval.
The success of the intervention depends on the clinical course of the
condition since, in very advanced cases, pericardial stripping is very
complex and the improvement obtained is limited. Therefore, surgery
should be carried out at a relatively early stage.
Operative mortality is about 5% to 10%. Benefits obtained from com-
plete cardiac decortication are progressive, it is only after several
months that complete improvement can be observed and that jugular
venous pressure returns to normal. Long term benefits are often very
satisfactory.
Medical therapy consists of sodium restriction, diuretics, digoxin and, in
some cases, repeated pericardiocentesis. Due to the fact a large number of
cases of constrictive pericarditis are of tuberculous origin, this must be treat-
ed before surgery if suspected or this etiology cannot be ruled out. In case of
atrial fibrillation, anti-coagulation is indicated.
10.2. Cardiac Tamponade
This is caused by accumulation of fluid in the pericardial cavity that
compromises the filling of the ventricles by extrinsic compression.
The presence of fluid in the pericardium gradually increases the pres-
sure, thus becoming the main pathophysiologic factor (Figure 80).
The increase in pericardial pressure compresses cardiac chambers (first
the right atrium and the right ventricle during diastole, the moment of
lowest pressure) and produces collapse. This complicates the filling of
the right cavities and results in an increase in the pressure of the sys-
temic venous territory (this is why in chronic pericardial effusion there
is systemic congestion) and a fall in cardiac output that may cause hypo-
tension and signs of antegrade low output.
 Card i o l ogy 1
Pathophysiology
of cardiac tamponade

Pericardial effusion Normal heart

(the pericardium facilitates
ventricular distention)
↑ Pressure
in pericardial cavity

Restrictive filling
of the right cavities

Arterial pulse
↑ Pressure in heart chambers ↓ Cardiac output

Decompensation Expiration - Inspiration - Expiration

Compensation

Peripheral congestion Hypotension - low output

Cardiac tamponade
Sympathetic activation (pericardial fluid prevents
Renin-angiotensin-aldosterone system ventricular relaxation; it exerts
pressure on the septum)

Figure 80. Pathophysiology of cardiac tamponade

Over
The increase in pericardial pressure compresses cardiac chambers (first 10 mmHg
the right atrium and the right ventricle during diastole, the moment of Arterial pulse
lowest pressure) and produces collapse. This complicates the filling of
the right cavities and results in an increase in the pressure of the sys- Expiration - Inspiration - Expiration
temic venous territory (this is why in chronic pericardial effusion there
is systemic congestion) and a fall in cardiac output that may cause hypo- Figure 81. Interdependence of the chambers
tension and signs of low anterograde cardiac output. in pericardial tamponade

Since all chambers are surrounded by the pericardial sac, the increase
in volume results in higher pressure compensated by interdependence
of the chambers (Figure 81).
During inspiration, the negative pressure in the chest allows more blood
to return to the right chambers. In order to hold a greater volume in
“compressed” cavities, there is distention of the right ventricle at the
expense of “compression” of the left ventricle by the septum, which can
lead to paradoxic pulse. As a result of the tamponade, the whole dias-
tole process is compromised (unlike cases of constrictive pericarditis, in
which the first stage is not affected).
The body adapts by activating compensation mechanisms analogous to
those of heart failure: activation of the sympathetic and renin-angioten-
sin-aldosterone system aims at increasing cardiac output and maintain
peripheral perfusion. In cases of acute tamponade (aortic dissection, car-
diac rupture, etc.), intrapericardial pressure rises so fast that the possibili-
ties of compensation are limited. In case of slow onset effusion, tempo-
rary compensation is possible, but additional minor pressure elevations
can trigger florid tamponade. The factors that determine the presence
or absence of signs of pericardial tamponade are directly related to the
magnitude and speed of the onset of the effusion and the stiffness of the
parietal pericardium, and inversely related to myocardial thickness.
Any pericarditis is a potential cause of cardiac tamponade. The most
frequent are tumors, idiopathic pericarditis (it rarely produces tampon-
ade, but since it is the most common cause of pericarditis, it has a high
incidence in global tamponades), and pericarditis with uremic and iatro-
genic etiology (in interventional procedures or cardiac surgery).
Clinical manifestations are related to the decrease in cardiac output and
systemic congestion: hypotension, tachycardia and oliguria, increased
central venous pressure, dyspnea with orthopnea, liver congestion,
among other conditions Physical examination reveals:
• Increased jugular venous pressure with a prominent X descent and
a reduced or almost absent Y descent. Dullness on percussion of the
anterior chest.
• There is often paradoxic pulse (inspiratory decline in systolic blood
pressure of more than 10 mmHg). This sign is not pathognomonic
and can be observed in constrictive pericarditis (one-third of cases),
restrictive cardiomyopathy, hypovolemic shock, asthma or severe
lung disease, and in other conditions of right ventricular diastolic
involvement.
• Kussmaul’s sign is characteristic of constrictive pericarditis, but it
can also be observed during cardiac tamponade, especially if there
is a component of pericardial constriction.
• Pericardial rub is rare and, if present, it suggests the possibility of
constrictive pericarditis.
Complementary Studies
• ECG. There is often reactive sinus tachycardia. Decreased amplitude
of the QRS complex can be observed, as well as electrical alternans
of the waves if the effusion is considerable.
• Chest x-ray. The cardiac silhouette may be normal or, if the effusion
is large, it may be increased in size or acquire a “water bottle” shape
most frequently, lung fields are “clear”, with minimal or no alveolar
infiltrate (Figure 82).

59
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Also, during inspiration, there may be an increase in right ventricu-

Decreased pulmonary vascularization lar diameter, a decrease of the left ventricular diameter and a sma-
ller opening of the mitral valve.
• Catheterization. This is not usually necessary for diagnosis, but it
shows increased right atrium pressure with a prominent X wave and a
smaller Y wave. Intrapericardial pressure is similar to right atrium pre-
ssure. Equivalent pressures: right atrium pressure, right ventricle
pressure, pulmonary artery pressure and pulmonary wedge pres-
sure are all very similar.

Enlarged cardiac silhouette with "tent shape"
Figure 82. X-ray of a pericardial effusion
• Echocardiography. Diastolic collapse of the right cavities and strik-
ing changes in ventricular filling flow with respiration are echocar-
diographic signs of tamponade (Figure 83).
Treatment
Expanding blood volume with serum or additional blood reduces col-
lapse of the cavities. Diuretics are contraindicated, since they reduce
blood flow volume and may increase collapse, which can induce shock.
Treatment consists of evacuating pericardial fluid and, as a result, in-
trapericardial pressure is reduced. In extreme cases, pericardiocentesis
should be performed as soon as possible. Drainage can be performed
using two techniques:
• Pericardiocentesis. Under local anesthesia, a long needle is inserted
between the xiphoid process and the left costal arch, guiding it to-
ward the left shoulder. The puncture can be guided by ECG, echocar-
diography or fluoroscopy (Figure 84).

A
PE
PE

LV
RV

RA LA
D
Pericardial effusion

Pericardiocentesis needle

Figure 84. Pericardiocentesis guided by fluoroscopy in patient with

cardiac tamponade

A pericardial catheter can be placed and left for several hours or

Expiration Expiration days, enabling continuous drainage. In some cases, it may also be
Inspiration Inspiration helpful for intrapericardial treatment. There is risk of puncture of
cardiac cavities, pleura or other structures.
• Pericardial window. This technique is indicated for patients who
need “something more” than a simple puncture. When there are
frequent relapses, septation, and purulent effusion or in cases of
uremic etiology, this is the preferred procedure. It is performed us-
ing a subxiphoid approach or left thoracotomy. This surgical drain-
age has the advantage that it is more complete and a biopsy of the
Figure 83. Echocardiographic image (apical four-chamber view) showing pericardium can be performed. Since it is performed under direct
severe pericardial effusion (PE) in a case of cardiac tamponade (A). vision, it is easier to remove adhesions and localized effusions. Risk
Doppler image of transmitral flow showing ample respiratory variations in is minimal and long-term outcome is better than that of performing
diastolic filling flow velocity (B)
a puncture.

60
 Card i o l ogy 1

Valvular Heart
According to the speed of onset, VHD may produce different clinical
events because of the different heart chambers, pulmonary vascular-
ization and compensation mechanisms. For left VHD:

Disease
Chapter 11 • Acute onset (acute myocardial infarction, endocarditis, aortic dis-
section, prosthetic valve thrombosis) is generally poorly tolerated,
leading to heart failure with low cardiac output and pulmonary
edema. Therapeutic action must be immediate (generally surgery).
• Progressive or chronic onset activates compensatory mechanisms,
11.1. Basic Concepts with little or no symptoms, even maintaining normal ventricular
function until advanced stages. For these reason is essential to
Cardiac valves may be affected by congenital heart disease or by ac- recognize them early, because the surgical treatment in advanced
quired heart disease (Figure 85). stages can be harmful.

Increased life expectancy and reduction of rheumatic fever incidence in
industrialized countries have altered the prevalence and the predomi-
nant etiology of valvular heart disease (VHD); calcific aortic stenosis is the
most common, nowadays. An important detail regarding the prevalence
and incidence is that studies usually refer to severe VHD requiring medi-
cal care, treatment or surgical intervention since mild VHD constitutes an
incidental finding in healthy individuals. For instance, up to one-third of
the population presents mild or low mitral or tricuspid regurgitation with
no risk of progressive deterioration. Likewise, rigid valves, slightly degen-
erated or sclerotic, are commonly detected in old patients, with mild or
no functional alteration, whose progression risk is hard to estimate.
Primary VHD (consequence of rheumatic fever, degenerative diseases)
frequently progress, and surgical intervention becomes necessary soon-
er or later. Functional (secondary) VHD (related to dilation or to valve
system failure because of another reason) may reduce after treating the
primary cause.
Semilunar valves stenosis (pulmonary and aortic valves) produces an el-
evated afterload compensated with concentric hypertrophy, maintaining a
good systolic function until advanced stages (hypertrophy stimulates the
onset of coronary diseases). As a general rule, symptoms appear before
ventricular systolic dysfunction, suggesting that surgery is to be performed.

Arterial cone
Anterior semilunar cusp
Pulmonary valve Right semilunar cusp Left fibrous trigone
Left semilunar cusp

Right (coronary)
semilunar cusp
Aortic Left (coronary)
valve semilunar cusp
Posterior (noncoronary)
semilunar cusp
Anterior cusp
Tricuspid
Septal cusp valve
Posterior cusp

Anterior cusp
Mitral valve
Posterior cusp Right fibrous ring
(of tricuspid valve)
Left fibrous ring
(of mitral valve) Right fibrous trigone
Heart in systole viewed from base with atria removed

Left atrium
Anterior valve
Posterior valve

Tendinous chords

Anterior papillary muscle

Anterior papillary muscle

Posterior papillary muscle

Mitral valve (left atrioventricular)

Figure 85. Fibrous skeleton of the heart and mitral valve

61
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Valve regurgitation produces volume overload with eccentric hyper-
trophy associated with progressive ventricular dilation, initially com-
pensatory, and then becoming degenerative. It is frequently prior to
symptoms, for which close monitoring is required for asymptomatic pa-
tients. Likewise, this volume overload increases ejection fraction, and
an apparently normal value may indicate incipient myocardial systolic
dysfunction.
In atrio-ventricular stenosis (mitral and tricuspid) symptoms are caused
by the increase in atrial pressure and retrograde congestion of the vein
system (pulmonary in mitral stenosis and systemic in tricuspid stenosis).
However, ventricles are not affected since they are protected against
such pressure or volume, so, ventricular diastole, rather than systole,
is compromised.
VHD symptoms may be anterograde (low cardiac output data such as
asthenia, tendency to tiredness) or retrograde. In left VHD, mitral or
aortic, high blood pressure flows back into the pulmonary veins (result-
ing in dyspnea and pulmonary edema). These vessels become more
resistant, which initially protects the lung from pulmonary edema,
but subsequently if the edema persists, it leads to irreversible organic
changes in the pulmonary arteriole with the pulmonary hypertension
and secondary right-side heart failure.
VHD may manifest by the onset of complications (emboli, endocardi-
tis, arrhythmias or sudden death). Sometimes, ergometry is useful to
determine “hidden” symptoms, especially in people with poor physical
activity level.
Upon clinical suspicion based on exploratory findings, the first-choice
diagnosis method for all VHD is the echocardiogram, and the VHD is
classified as mild, moderate or severe according to its hemodynamic
severity.
Apart from studying the hemodynamic degree of the valve, it is rec-
ommended to analyze its anatomy and subvalvular apparatus in an
attempt to establish the etiology and healing possibilities. A study on
the impact over myocardial function (volumes and ejection fraction),
on the pulmonary vessels (pulmonary hypertension data), on systemic
veins (size and flow of inferior vena cava), and on potentially altered
structures associated with VHD (e.g. aortic regurgitation associated
with ascending aortic dilation or coarctation) must also be performed.
Mild or moderate VHD does not itself significantly affect cardiac func-
tion and does not require surgical treatment, except for special cases.
However, severe left VHD frequently requires surgical intervention.
Although there are some peculiarities included in the relevant chapter,
surgery is indicated in two cases:
• Where symptoms exist.
• In asymptomatic cases, where significant impact over the cardiac
function exists. In mitral stenosis, impact data appear in the atrium
(atrial arrhythmias) and in the pulmonary artery (pulmonary hyper-
tension), since the left ventricle “only” suffers a chronic diastolic
deficit. Mitral regurgitation and aortic stenosis or regurgitation im-
plies chronic pressure overload (aortic stenosis) or volume overload
(regurgitation) of the left ventricle, which makes it fail (ejection frac-
tion decreases). Surgery is indicated.
Table 49 shows a summary including etiology, symptoms and treat-
ment of left valve heart diseases.
As a general rule, a presurgical coronary angiography or cardiac CT is
indicated when surgery is scheduled with the purpose of reducing peri-
operative morbimortality and assessing the need for myocardial revas-
cularization associated with the valve surgery, in patients with coronary
disease or risk of acquiring it (Table 50).

SUMMARY OF VHD
In MR and AR, if LVEF < 30%: transplantation
  MS MR AS AR
Rheumatic fever (RF) RF (MS + MR) < 30 years: unicuspid Valvular:
Mitral valve prolapse 30-70 years: bicuspid · Acute: endocarditis
ETIOLOGY MI isolated >70 years: degenerative · Chronic: RF
  Dilation of annulus:
· Acute: aorta dissection
· Chronic: Marfan syndrome
Dyspnea Dyspnea Angina Dyspnea
SYMPTOMS · Syncope
· Dyspnea (more frequent)
· Diuretics
· Digoxin
MEDICAL TREATMENT
Nonvasodilators ACE inhibitors Nonvasodilators ACE inhibitors/Dihydropyridine
calcium antagonists
Surgery upon symptoms
If PH although LVEF < 60% and/ · LVEF< 50% although LVEF < 50% or LVESD > 50 mm
asymptomatic or LVESD ≥ 40 mm asymptomatic or LVEDD > 65 mm although
although asymptomatic · Children: surgery always asymptomatic
SURGICAL TREATMENT Favorable anatomy: Repair attempt: if not PROSTHESIS PROSTHESIS
PMBC possible, prosthesis · Alternative: Ross procedure · Alternative: Ross procedure
Unfavorable anatomy: · Children: valvuloplasty · In some cases, repair
prosthesis · Upon high surgical risk,
consider TAVI
Table 49. VHD summary

62
 Card i o l ogy 1
PRESURGICAL CORONAROGRAPHY. INDICATIONS It is appropriate to know the differences (shown in Table 51) between
· Known coronary disease mechanical and biological prosthesis well, although the choice of one
· Suspected unstudied myocardial ischemia type of prosthesis over the other must be individualized.
· LV systolic dysfunction
· Existence of any coronary risk factor
· Men over 40 years of age or postmenopausal women
MECHANICAL PROSTHESIS BIOLOGICAL PROSTHESIS
· Suspicion of ischemic severe mitral regurgitation
Table 50. Indications of presurgical coronarography in VHD · No contraindications to chronic · Difficulties in or
anticoagulation contraindications for correct
Some concepts about valve prosthesis should be known. · Patients with coagulation chronic anticoagulation (high
indications for another reason hemorrhagic risk, lifestyle
Some prosthesis are made of biological material and others are purely or with high embolic risk or occupation, compliance
mechanical, Figure 86. (atrial fibrillation, mechanical problems)
prosthesis in another valve, · Resurgery because of prosthetic
severe left systolic dysfunction, thrombosis with proven poor
emboli family background, anticoagulation control
hypercoagulability conditions) · > 70 years of age
· High risk of valvular · Young woman with pregnancy
deterioration desire
(hyperparathyroidism) · Express desire of informed
· < 60 years of age patient
· Patients with high reintervention
risk (left ventricular dysfunction,
prior bypass surgery, multiple
prosthesis)

Table 51. Favorable factors to implementation of each type

Figure 86. Biological prosthesis (left) and mechanical prosthesis (right)
Biological prosthesis on the left side of the heart (mitral and aortic)
presents risk of deteriorating in the long run, thus requiring interven-
tion. When in the right side of the heart, the risk is lower.
The deterioration risk is higher in cases of renal insufficiency, hyper-
parathyroidism, people under 60-65 years of age, or hypercholesterol-
emia, Figure 87.
of prosthesis
The main complications of valve prosthesis are prosthetic endocarditis
(premature or late), thrombosis (requiring surgery or fibrinolysis), pros-
thetic dysfunction (requiring surgery when needed), emboli and hemo-
lysis (destruction of red blood cells because of collision of the elements
of the prosthesis, not common in current models unless a prosthetic dys-
function exists).
Mechanical prosthesis causes a normal metallic click when opening and
closing.

Almost all prosthesis are slightly restrictive and produce a murmur simi-
lar to mild stenosis of the relevant valve.

11.2. Mitral Stenosis

Mitral stenosis is considered severe when it becomes smaller than

1.5 cm2 (and very severe if ≤ 1 cm2). This usually corresponds to a trans-
mitral mean gradient of > 5 mmHg to 10 mm Hg at a normal heart rate.

The main cause of mitral stenosis is rheumatic fever, and mitral insuf-
ficiency is commonly associated (double mitral injury).

The main symptoms are secondary to the retrograde increase in pulmo-

Figure 87. Deteriorated biological prosthesis
Mechanical prosthesis requires chronic anti coagulation in order to at-
tain an INR between 2.5 and 3.5 in mitral prothesis or in the right side
prothesis and between 2.0 and 3.0 in aortic prothesis.
nary pressure causing dyspnea, overload of the right side of the heart
(including right valves regurgitation as a result of dilation of the annulus
and even right heart failure.
The pathophysiology is shown in Figure 88.

Biological prosthesis only requires anticoagulation (INR 2.5) in the first Atrial fibrillation associated with mitral stenosis is very common; this
three months until endothelialization of the prosthetic material. association represents an extreme embolic risk.

63
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Upon examination, malar flushing is observed and murmur auscultat-

ed in the apex with the chestpiece, in mid-diastole after the opening
snap with presystolic accentuation (as long as the patient is in sinus
rhythm).

↑ LA-LV Gradient
Mitral focus
better auscultated
in apex
↑ LA Pressure ↓ LV Filling
MT MT
AP ChA
Pulmonary Dilation
↓ Cardiac output
congestion of LA

Initial phase in sinus rhythm

Pulmonary Blood Atrial
hypertension: accumulates fibrilation
- Active
- Passive
Advanced phase in atrial fibrillation

RV Emboli Figure 89. Mitral stenosis auscultation

hypertrophy

Right HF
Figure 88. Mitral stenosis pathophysiology
The main exploratory findings are summarized in Figure 89. Remember
that the greater the severity, the more accelerated the opening snap
and the more delayed the closing. In the same way, the murmur presys-
tolic accentuation is lost upon atrial fibrillation.
In Figure 90, general guidelines for mitral stenosis are shown. Normally,
this disease progresses slowly over period of 10-20 years before pro-
ducing symptoms. However, when symptoms appear, they progress in a
few years, which constitute a significant increase in mortality if no mea-
sures are performed. This is why symptoms with ordinary activity are
the base of surgical indication. Likewise, in asymptomatic patients, per-
cutaneous mitral balloon commissurotomy (PMBC) can be performed
in cases of atrial fibrillation, PCWP > 25 mmHg with exercise or in very
severe stenosis.

Area > 1.5 cm2 Area > 1.5 cm2

PCWP >25 mmHg with exercise

PMBC Periodic monitoring

Atrial Fibrillation
or area <1 cm2

Favorable for PMBC

Favorable for PMBC

NYHA class III-IV

PMBC with high surgical risk
Yes
No

MVR

Figure 90. General Intervention in mitral stenosis

64

Medical treatment consists of bradycardia (upon an increased diastolic
time, a greater LV preload occurs), diuretics and antithrombotic treat-
ment, especially in case of atrial fibrillation.
PMBC (surgical commissurotomy is no longer used) can be performed
when the valvular anatomy is favorable and there are no contraindica-
tions (left atrial thrombus or moderate-to-severe MR). If unfavorable
(generally when one of these three criteria is met), replacement of the
prosthetic valve is indicated.
Card i o l ogy 1
From a pathophysiologic view, symptoms of retrograde congestion
(ejection of blood retrograde into the atria) and that of low anterograde
output (“lack of blood” flowing onwards since it flows back into the left
ventricle) are also included.
Chronic mitral regurgitation murmur is better auscultated in the apex
or armpit; it is systolic and generally larger when regurgitation becomes
more severe, Figure 91.

11.3. Mitral Regurgitation

Nowadays, mitral regurgitation is the second most common VHD after

aortic stenosis. There are three types: organic, ischemic and functional.
• Organic mitral regurgitation is produced by diseases affecting the
valve and/or the subvalvular apparatus, such as mitral valve pro-
lapse and rheumatic fever (the latter, frequently related to stenosis). Mitral focus
• Ischemic mitral regurgitation appears as a consequence of dysfunc- radiates armpit
MT
tion or rupture of a papillary muscle, or because of distortion of AP
S3 MT

ventricular geometry upon an infarction altering spatial position of

papillary muscles and subvalvular apparatus, complicating the clos-
ing of the valve.
Hyperflux murmur
• Functional mitral regurgitation is caused as a consequence of the
annular remodeling in any cardiomyopathy with significant ventric- Figure 91. Auscultation in mitral regurgitation
ular dilation.
Severe acute mitral regurgitation usually runs with acute pulmonary
Severe acute mitral regurgitation is usually due to infective endocardi- edema, cardiogenic shock, and S3 is common. Murmur may be short
tis, dysfunction/rupture of a papillary muscle during infarction, rupture or inaudible.
of tendinous cord in mitral prolapse or traumatisms, including iatrogen-
ic mitral regurgitation. In Figure 92, general measures of mitral regurgitation are shown.

Suspected mitral regurgitation

· Anamnesis
· Physical Mild
Follow-up
examination or moderate
· Echocardiogram

Define etiology

Primary MR Secondary MR

Coronary artery disease treatment,

Symptoms Asymptomatic heart failure treatment, consider CRT

Surgery
(attempt of repair Symptomatic severe Asymptomatic
if possible) EF 30% to ≤60% EF 30% to ≥ 60%
MR with persistent severe MR
or LVESD ≥40mm and LESD <40 mm
NYHA class III-IV or progressive MR
or new onset AF
symptoms
or PASP >50 mmHg

Periodic monitoring
Likelihood of succesful MV surgery
repair > 95% and expected (MV repair preferred)
mortality < 1%

MV repair Periodic monitoring

Figure 92. General Intervention in mitral regurgitation

65
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Medical treatment includes diuretics for congestion, digoxin (posi-

tive inotrope) and vasodilators (ACE inhibitors) reducing preload and S1
S2
afterload (in order to reduce regurgitation and to increase anterograde C
output).

Surgery is indicated when symptoms appear (dyspnea, generally) or

upon the slightest evidence of deterioration of ventricle systolic func-
tion (ejection fraction < 60% or LV telesystolic diameter > 40 mm) since S1
it is irreversible once it occurs. S2
C

Mitral valve repair is preferred over mitral valve replacement when pos-
sible (more feasible in mitral valve prolapse and lesser in rheumatic mi-
tral regurgitation) (Figure 93).

S1
Concomitant mitral valve surgery (preferred repair) is reasonable in pa- S2
tients with chronic primary moderate MR when undergoing cardiac sur- C
gery for other indications or for patients with chronic severe secondary
MR who are undergoing coronary coronary artery bypass graft or aortic
valve replacement.

In the last years, percutaneous repair of the mitral valve (MitraClip®),

emerged as an alternative in those patients with high surgical risk. Figure 94. Variations of mitral valve prolapse murmur

Usual treatment of mitral regurgitation because of annulus dilation is In significant organic mitral regurgitation, mitral prolapse relat-
that of advanced heart failure. ed to the murmur involves a deterioration risk, especially in men
(Figure 95).

RV

Ao
LV

LA

Figure 95. Echocardiographic image in an apical four chamber

view showing a mitral valve prolapse (arrow)

11.4. Aortic Stenosis

Degenerative aortic stenosis in the elderly is the most common valvular

Figure 93. Mitral valve repair
Mitral valve prolapse (Barlow syndrome) usually produces a mid-
systolic click followed by a mitral-regurgitation-produced murmur
(click-murmur syndrome). When preload decreases (Valsalva, bi-
pedestation), the click comes earlier and murmur duration extends
(Figure 94).
heart disease in developed countries, frequently associated with ath-
erosclerosis.
Bicuspid valve usually predisposes to aortic stenosis at middle-age
(Figure 96), “as a result of early degeneration over the years”. In
children, it is the unicuspid aortic valve which predisposes to aortic
stenosis.

66

Figure 96. ECG of bicuspid aortic valve with evidence of deterioration in
both walls (parasternal short-axis plane)
Aortic stenosis is considered severe when the aortic valve area is < 1.0 cm2
(or indexed AVA ≤ 0.6 cm2/m2). If systolic function and cardiac output
are normal, aortic stenosis is severe as long as the mean systolic trans-
valvular gradient exceeds 40 mmHg.
Upon systolic dysfunction, the ventricle cannot open the valve com-
pletely. The aortic valve area may still be compatible with aortic steno-
sis. Dobutamine stress echo is used to determine the gradient growth
with poor increase of the valvular area in cases of true aortic stenosis.
Characteristic symptoms of severe aortic stenosis are triggered by ef-
fort (angina, syncope or dyspnea). Nowadays, the main predominat-
ing symptom is dyspnea. The risk of sudden death in aortic stenosis
increases exponentially when symptoms appear. The latter indicates
the need for aortic valve replacement.
Aortic stenosis murmur is auscultated in the aortic focus, radiating to
carotids and supraclavicular area (occasionally the apex: Gallavardin
phenomenon). It is systolic and rhomboidal after aortic opening (some-
times an opening click may be heard, mainly in bicuspid valves). As the
murmur lasts longer, its severity also increases (Figure 97).
Aortic focus
radiating to carotids
Clic AP
MT MT
Initial phase
S4
MT PA MT
Advanced phase
Figure 97. Aortic stenosis auscultation
Card i o l ogy 1
Aortic valve sclerosis without stenosis is common in elderly patients
with hypertension and produces a low intensity and short murmur. Se-
vere aortic stenosis is usually accompanied by a decrease in intensity
and inverted closure in S2. It is also common to indentify a parvus et
tardus pulse.
Figure 98 shows general measures for patients with aortic stenosis.
Medical treatment is of limited use in severe aortic stenosis. Surgery
is indicated in adults with severe aortic stenosis when symptoms or
ventricular dysfunction arise, in which surgery replacement of valvu-
lar prosthesis is performed (Ross surgery is occasionally conducted in
young people; in adults, the valvulopathy results are negative).
Mechanical prosthesis is indicated in children with severe congenital
aortic stenosis because they have a greater risk of sudden death and
progressive ventricular dysfunction. Results of balloon valvuloplasty in
children are positive, making it the first-choice treatment.
Transcatheter aortic valve replacement is recommended in patients
who meet an indication for aortic valve replacement, who have a
moderate or high risk for surgical replacement.
Aortic valvular sclerosis without stenosis is common in the elderly with
hypertension and produces a murmur with similar characteristics (albe-
it short and with low intensity). In order to differentiate them, remem-
ber that severe aortic stenosis is usually accompanied by a decrease in
intensity and inverted splitting in S2, and, at times, by parvus et tardus
pulse.
11.5. Aortic Regurgitation
The most common cause of aortic regurgitation in developed
countries is that associated with bicuspid aortic valve and primary
diseases causing dilation of the ascending aorta or the sinuses of
Valsalva.
Considering etiologies of aortic regurgitation as a result of direct in-
volvement of aortic leaflets, we must mention rheumatic heart disease
(chronic) and infective endocarditis (acute).
Considering etiologies of aortic regurgitation because of ascending aor-
ta dilatation, we must mention Marfan Syndrome (chronic) and acute
thoracic aortic dissection (acute). LV volume overload (because of blood
regurgitation) usually causes dilation, and, in the long-term, it may de-
teriorate systolic function (ejection fraction).
The characteristic pulse of aortic regurgitation is magnus, celer et altus,
and, at times, bisferiens (two systole peaks). The difference between
systolic and diastolic pressure is distinctive and produces characteristic
physical signs (Corrigan, Musset, Quincke).
The diastolic murmur of aortic regurgitation may be preferentially aus-
cultated in the Erb accessory aortic focus (third left parasternal intercos-
tal space) rather than in the aortic focus. If the regurgitation jet flows
to the anterior mitral cusp, it may obstruct opening of the valve and
produce mitral fluttering and, sometimes, mitral stenosis (Austin-Flint
murmur) (Figure 99).
67
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Abnormal Aortic Valve With

Reduced Systolic Opening

Severe AS
Vmax ≥4 m/s Vmax 3 m/s-3.9 m/s
∆Pmean ≥4 mmHg ∆Pmean 20-39 mmHg

Symptomatic Asymptomatic Asymptomatic

(stage D1) (stage C) Symptomatic
(stage B)

LVEF < 50%

LVEF < 50%
(stage C2)
YES NO
Other cardiac
Other cardiac surgery
surgery
DSE with
V max ≥ 5 m/s AVA ≤ 1cm2
AVA ≤ 1cm2
∆Pmean ≥ 60 mmHg and LVEF ≥ 50%
and Vmax ≥ 4m/s
Low surgical risk (stage D3*)
(stage D2)

Abdominal ETT

∆Vmax > 0.3 m/s/y

Low surgical risk

AVR AVR AVR AVR

Stages of Valvular Aortic Stenosis (AS):
- Stage A: at risk of AS.
- Stage B: Progressive AS.
- Stage C: Asymptomatic Severe AS.
- C1: Asymptomatic Severe AS.
- C2: Asymptomatic Severe AS with left ventricular dysfunction.
- Stage D: Symptomatic Severe AS.
- D1: Symptomatic Severe high-gradient AS.
- D2: Symptomatic Severe low-flow/low-gradient AS with reduced LVEF.
- D3: Symptomatic severe low gradient.

Figure 98. Indications for surgical treatment of aortic stenosis

Medical treatment includes diuretics for pulmonary congestion. Di-

goxin may be administered as a positive inotrope. Administration of
vasodilators (ACE inhibitors) is not effective to postpone surgery. Its
use is only recommended in case of ventricular dysfunction, arterial
hypertension, or when surgery is contraindicated. In patients with
Marfan syndrome, beta blockers and ACE inhibitors or ARBs must be
considered.
Erb focus
In general, surgery is indicated when symptoms appear, when sys-
(aortic accessory)
Radiates to left tolic function deteriorates (LVEF < 50%) or when LV dilates (Figure
sternal border 100).

The presence of ascending aorta dilation along with severe aortic regur-
gitation implies concomitant operative intervention to repair the aortic
MT AP MT
sinuses or replace the ascending aorta in patients with:
• Bicuspid aortic valve if the diameter of the aortic sinuses or ascend-
ing aorta is greater than 4.5 cm.
• Marfan Syndrome when the aorta reached 4.5 cm.
• Patients with ascending aorta or aortic sinus diameter 4.5 cm or
Hyperflux murmur Austin-Flint murmur greater.

Prosthesis replacement is the usual surgical treatment when only

Figure 99. Aortic regurgitation auscultation
Symptoms combine both the effects of low anterograde flow with ret-
rograde congestion.
Management of patients with AR is summarized in Figure 100.
the valve is affected. In some cases it may be possible to repair the
aortic valve. In case of dissection or major dilation of the aortic
root, either David Procedure (ascending aortic valve is kept and
reconnected, preserving the native aortic valve) or Benthal Proce-
dure (implant of a valvular tube with reimplantation of coronary
arteries when the native aortic valve is too damaged) may be per-
formed.

68
 Card i o l ogy 1
Aortic Regurgitation

Severe AR Progresive AR
(stages C and D) (stage B)
Vena contracta > 0.6 cm Vena contracta ≤ 0.6 cm
Holodiastolic aortic RVol < 60 mL/beat
flow reversal RF < 50%
RVol ≥ 50% ERO < 0.3 cm2
ERO ≥ 0.3 cm2
LV dilation
Other cardiac surgery
Symptomatic Asymptomatic YES NO
(stage D) (stage C)

LVEF < 50% Other cardiac LVEF ≥ 50% LVEF ≥ 50% LVEF ≥ 50%
(stage C2) surgery LVESD > 50 mm LVEDD > 65 mm LVESD ≤ 50 mm
(stage C2) Low surgical risk LVEDD ≤ 65 mm

AVR AVR AVR Periodic monitoring AVR

Stages of Chronic Aortic Regurgitation (AR):

- Stage A: at risk of AR. - Stage C: Asymptomatic Severe AR.
- Stage B: Progressive AR. - Stage D: Symptomatic Severe AR.

Figure 100. General performance procedure for severe aortic regurgitation

11.6. Right Valvular

Heart Diseases
Vascular
Chapter 12
Disease
Table 52 shows the main characteristics of tricuspid valve disease.

With regard to pulmonary valve disease, it should be noted that:
• Pulmonary stenosis is most frequently congenital.
• The most common cause of respiratory failure is pulmonary hyper-
tension, usually secondary to left heart diseases.
• Pulmonary valve disease murmurs are increased during inspiration
(Rivero-Carvallo’s sign).
• Graham-Steele’s murmur is the murmur of pulmonary regurgitation.
• Treatment for severe pulmonary stenosis is usually by means of per-
cutaneous catheter-balloon valvuloplasty.
• For severe respiratory failure, an annuloplasty is performed concur-
rently with surgery on the originating left heart valve disease.
12.1. Aortic Aneurysm
Infrarenal abdominal aortic aneurysm is the most common form, al-
though they may occur in almost any artery (Figure 101).
Infrarenal abdominal aortic aneurysm (IAAA) is most frequent among
males. The most frequent etiology is atherosclerosis. The aneurysm is
often identified by chance during another addominal test. The main risk
factors for IAAA rupture are diameter, hypertension, active smoking, fe-
male sex and presence of symptoms (expanding aneurysm).

STENOSIS REGURGITATION
Most frequent cause Rheumatic · Functional: pulmonary hypertension
· Organic: endocarditis
Symptoms · Of associated left-sided valve disease · Of originating disease
· Systemic congestion · Systemic congestion
Jugular pulse Increased A wave · Increased V wave
· Decreased (reversed) x sinus
Auscultation · Diastolic murmur · Systolic murmur
· Increase during inspiration · Increase during inspiration
Severity Severe: T 1/2 ≥ 190 ms or valve area ≤ 1.0 cm2 Reversed systolic flow in suprahepatic veins
Medical treatment Low sodium diet, diuretics Low sodium diet and diuretics
Surgery instructions · Severe tricusipd stenosis (TS) at the time of · Recommended for patients with severe tricuspid regurgitation (TR)
operation for left-sided valve disease undergoing left-sided valve surgery
· Isolated, symptomatic severe TS · Mild, moderate, or greater functional TR at the time of left-sided valve surgery
with either tricuspid annular dilation or prior evidence of right heart failure
· Symptoms because of severe primary TR unresponsive to medical therapy
Technique · Bioprosthesis · Prosthetic
· Commissurotomy · De Vega annuloplasty
· Percutaneous valvuloplasty in some cases · Bioprosthesis
Table 52. Main features of tricuspid valve disease

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 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Abdominal aortic aneurysm diagnosis is usually by means of abdominal Suspected abdominal

ultrasound. However, in case of suspected complex aneurism or in view aorta aneurysm

of surgical intervention, CT angiography or magnetic resonance angiog-

raphy with contrast are more useful techniques. Opaque contrast aor- Ultrasound screening
for detection.
tography may underestimate the aneurysm’s diameter in case of mural CT or MR angio
thrombus, but it is excellent for assessing adjacent arterial branches. for detailed
Currently, an aortography is not usually required for intervention, since characterization
· No smoking
· Treat risk factors
· Consider β-blockers

CT and magnetic resonance angiography may provide sufficient and ac-

curate preoperative information. Symptomatic Asymptomatic

CT Angio > 5.5 cm 5.0-5.5 cm < 5.0 cm

Berry aneurysm
Consider: Consider Follow-up every
· RM Angio intervention 6 to 12 months
· Aortography Low High if low surgical using ultrasound
surgical surgical risk or CT scan
risk risk

Growth
*Emergency Programmed If not Consider
feasible > 0.5 cm/year
surgery surgery graft stent
Takayasu *Preferrable
if there
disease
is no rupture
Syphilitic
aneurysm

Kawasaki Figure 102. Management of abdominal aortic aneurysms

Renal disease
artery Aneurysms involving the aortic arch or descending aorta usually have
aneurysm
Dissecting aneurysm atherosclerotic etiology (Figure 103).

Splenic
Mycotic aneurysm aneurysm 11,5 mm

Vasculitis 76,4 mm
Atherosclerotic with aneurysmal
aneurysm dilatation

20,3 mm
Figure 101. Types of vascular aneurysms

Examination of these patients is key for the associated coronary dis-
ease; the latter may affect the prognosis and surgical risk of the patient.
Current treatment for this kind of aneurysms is shown in Figure 102.
The presence of symptoms, growth velocity over 0.5 cm a year, or the
presence of aorta diameter over 5.5 cm (5 cm in patients with low surgi-
cal risk) is indicative for surgery.
Figure 103. Ascending aorta aneurysm
Ascending aorta thoracic aneurysm may appear because of cystic medi-
al necrosis (typical with Marfan, Ehler-Danlos syndromes or associated
with bicuspid aortic valve) or tertiary syphilis.
Treatment for thoracic aortic aneurysms is shown in Figure 104.

Surgical repair requires a midline transabdoiminal approach or an ex-
traperitoneal incision in the left flank to perform aneurysmectomy and
placement of a synthetic tubular graft with iliac extension (if the ter-
ritory is also affected). Endovascular repair clearly represents a major
advance in patients who have severe cardiopulmonary disease or other
risk factors.
A diameter of ascending aorta aneurysms ≥ 5.5 cm, the presence of
symptoms, or a growth velocity ≥ 0.5 cm a year are indications for sur-
gery. In case of association with bicuspid aortic valve, aortic dissection or
Marfan syndrome, the former criteria are applied with lower diameters
(> 45mm in Marfan and > 50 mm in bicuspid) according to the presence
of other associated rupture risk factors.

70
 Card i o l ogy 1
Thoracic aortic aneurysm
· Semi-annual size
follow-up
Symptomatic Asymptomatic · Treat risk factors
· Avoid intense exercise
· Beta blockers

Emergency surgery Ascending Arch Descending

With high surgical

High risk factors of rupture Surgery Surgery
risk, consider graft
or dissection: if > 5.5 cm if > 6 cm*
stent in descending
· Connective tissue disease: Marfan,
aorta
Ehler Danlos, Loeys-Dietz....
* With connective
· Bicuspid aorta, dissection, Turner,
tissue disease,
Noonan...
consider graft
· Family association
stent if > 5.5 cm

* If high surgical risk,

Yes No
consider graft stent
Consider surgery Surgery
if > 4-5 cm if > 5.5 cm
or growth
> 0.5 cm/year

Figure 104. Procedure for action in the event of thoracic aortic aneurysm

For patients undergoing aortic valve surgery coexisting with ascending
aorta dilation, aorta intervention is also recommended at lower diam-
eters (4.5 cm). Bentall procedure is used for ascending aorta aneurysms
with associated aortic failure; it consists of implanting an aortic valve
graft with reimplantation of coronary arteries.
Hypertensive treatment of choice in Marfan patients consists of beta
blockers and possibly ARB.
aspects of these three pictures are nearly the same. The main charac-
teristics of intramural hematoma and penetrating ulcer are shown in
Table 53.
Hypertension is the main condition associated with increased wall
stress and development of thoracic aortic dissection. The dissection
flap is commonly found in the ascending thoracic aortic, within its first
2-3 cm.

The most frequent type of peripheral aneurysm is popliteal. It is usually
bilateral and, if it becomes thrombotic, there is a high risk of losing the
limb involved. Therefore, treatment requires surgical repair based on
aneurysm exclusion and placement of femoral popliteal bypass.
Acute aortic dissection must be considered in all patients presenting
intense chest, back or abdominal pain, especially with migratory fea-
tures. Dissection may involve arterial branches and lead to ischemia
perfusion deficits in the area involved. Typical findings of aortic dis-
section are asymmetric decrease of upper limb pulses and a diastolic
murmur of aortic valve regurgitation.

12.2. Acute Aortic Syndrome
Traumatic aortic rupture usually occurs after car accidents or serious
falls and is often located distal to left subclavian artery. Acute aortic
syndrome comprises three entities: classic aortic dissection, intramural
aortic hematoma and penetrating aortic ulcer. Clinical and therapeutic
Stanford’s classification (Table 54 and Figure 105) divides acute
aortic syndromes (and aortic dissection) into type A or proximal:
if the ascending aorta is involved (the most frequent, prognosis is
poor, and requires surgical repair) and type B or distal: if they do
not involve the ascending aorta (less frequent, better prognosis,
treatment is medical and it should be managed medically unless life-
threatening complications develop).

INTRAMURAL AORTIC HEMATOMA PENETRATING ULCER

Etiopathogenesis · Adventitia bleeding towards the media · Intima disruption secondary to atherosclerotic damage
· More frequent in descending aorta · More frequent in descending aorta
Epidemiology Elderly patients with same risk factors as aortic dissection
Diagnosis CT angio, MR angio or TEE focus on thoracic aorta
Treatment Similar to aortic dissectionin the corresponding segment of the · Similar to type B dissection
aorta · Surgery if:
- Hemodynamically unstable
- Pseudo aneurysm
- Acute rupture
- Continuous pain
- Distal embolization
Table 53. Intramural hematoma and penetrating ulcer

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 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

DE BAKEY CLASSIFICATION Urgent and definitive imaging of the aorta using transesophageal echo-
I Ascending aorta rupture, extending to descending cardiogram, computed tomographic imaging, or magnetic resonance
aorta imaging is recommended to identify or exclude thoracic aortic dissec-
II Ascending aorta rupture (only) tion in patients at high risk for the disease. Figure 106 shows recom-
III Descending aorta rupture mendations for acute aortic syndrome management.
STANFORD CLASSIFICATION
A (proximal) Involving ascending aorta Blood pressure and heart rate should be controlled in all patients with
B (distal) Not involving ascending aorta acute aortic syndrome, usually with nitroprusside and intravenous beta
blockers or labetalol. Type A dissections require emergency surgical repair
Table 54. Aorta dissection classification
(Figure 107). Anticoagulants are formally contraindicated.

Type A dissection Left

(ascending aorta) subclavia artery

Intimal tear

Adventitia
True lumen

False
lumen Type B dissecton
(does not involve
ascending aorta)

Figure 105. Aortic dissection classification Figure 107. Surgical treatment of type-A dissection

Acute aortic syndrome treatment

· Pain and signs/symptoms typical of hypertensive patients

Suspected
· Mediastinal widening

CT Angio + TEE · Consider MR angio if stable

· Conduct TEE if there is aortic insufficiency or too unstable to transfer

· Opiates. Avoid anticoagulation

Medical · Beta blockers or calcium antagonists: target HR < 60 bpm
treatment · Vasodilators: ACE inhibitors or nitroprusside (if systolic BP > 120 mmHg)

Type A Type B

Urgent surgery High risk data:

· Hemodynamically unstable
· Consider after stabilization (24-72 hours) only with · Fast growth
- Stable retrograde thrombosis dissection · Peri-aortic hematoma
- Stable intramural hematoma with aorta · Ischemia in arterial branches
< 50 mm and hematoma < 10 mm
· Contraindicated with irreversible brain damage
· Consider medical management if:
- Chronic dissection Yes No
- Stable and limited to arch

Consider graft stent Close follow-up

* Fenestration in some cases

Figure 106. Management of acute aortic syndrome

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 Card i o l ogy 1
12.3. Deep Vein Thrombosis RISK OF DEEP VEIN THROMBOSIS

· Immobilization (paralysis, stroke-derived sequel, orthopedic

Deep vein thrombosis (deep vein thrombophlebitis) is the most fre-
quent cause of pulmonary embolism. Predisposing factors are blood
stasis, hypercoagulability and traumatism (Virchow’s triad).
Patients undergoing orthopedic-traumatologic treatment either surgi-
cal or leading to immobilization are at risk of suffering deep vein throm-
bosis. The main causes are shown in Table 55.
Diagnosis is usually confirmed by means of Doppler ultrasound. Treatment
consists of rest, elevation of involved limbs to avoid edema, and antico-
agulation to avoid progression and development of pulmonary embolism.
Anticoagulation therapy must be commenced and maintained for three
months. However, patients with recurrent episodes or nonreversible
causes must be considered for indefinite anticoagulation.
General management of this entity is shown in Figure 108.
Complete early ambulation, pneumatic compression stockings, and low
doses of anticoagulants are used for prophylaxis of deep vein thrombosis.
treatments, long flights: “economy-class” syndrome and others)
· Surgery: especially major orthopedic surgery of lower limbs (hip
surgery represents a major risk factor for DVT, which may appear
in up to 50% of cases) and abdomen
· Admission for medical reasons
· Previous history of DVT or pulmonary embolism
· Pregnancy, postpartum, hormone-based therapies
· Heart failure or myocardial infarction
· Obesity
· Congenital or acquired hypercoagulability: antithrombin III
deficiency, protein C and S deficiency, antiphospholipid syndrome,
nephrotic syndrome, activated protein C resistance (Factor V Leiden)
and dysfibrinogenemia
· Neoplasm: pancreas, ovary, lung, breast and others. Sometimes
they are associated with surface thrombosis or migrating
thrombophlebitis as paraneoplastic syndrome (e.g. Trousseau
syndrome)
· Intravascular (venous) devices or catheters, both transient
and permanent (pacemakers, defibrillators, central catheters
for chemotherapy or hemodialysis)
Table 55. Risk factors of deep vein thrombosis (DVT)

Risk factors
(bedridden patients, surgery, obesity, among others)

Prophylaxis

· Early ambulation
· Compression (elastic stockings Swelling
or intermittent pneumatic Pain
Clinical
compression) Cyanosis
· Nonfractionated heparin Edema
· Low molecular weight heparin
· Fondaparinux
· Antithrombotic or oral
anti-activated
Factor X drugs MR angio
Doppler ultrasound Plethysmography
Alternatives
D-dimer Venography
CT angio

No DVT DVT Anticoagulation

Search Contraindications
Pulmonary Resolution
for other diagnosis for anticoagulants
embolism recurrence
in spite of treatment

Chronic
Vena cava filter anticoagulation

Reversible cause · Nonreversible cause

three months · Recurrence

Indefinite
anticoagulation

Figure 108. Overall management of deep vein thrombosis (DVT)

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 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Other Venous Disorders
Chronic venous insufficiency is usually the consequence of deep vein
thrombosis, since the healing process may cause a dysfunction of the vein
valve system, which leads to blood reflux to the superficial venous system
through perforating veins (Figure 109).
Posthrombotic syndrome leading to chronic venous insufficiency can be
treated using elastic compression stockings, appropriate management
during the acute phase of deep vein thrombosis, phlebotonic drugs (dis-
crete efficacy) and avoiding prolonged standing.
Superficial venous thrombosis, unlike the deep form, does not cause
pulmonary embolism or chronic venous insufficiency. Its treatment con-
sists of relative rest, elastic compression stockings and anti-inflammato-
ry drugs. It does not require oral anticoagulation.

Varicose veins may be a consequence of chronic venous insufficiency af-

ter a deep vein thrombosis, weakness of the venous valve system, often
Normal with family history, may also cause varicose veins. When the problem
venous flow affects small areas, it only represents an esthetic issue, but when large
areas are affected, truncal varicose veins may require surgical interven-
tion (phlebectomy).
Competent closed valve

The most common cause for superior vena cava obstruction is tumors,
especially microcytic lung tumors, which are not resectable. It may
cause a typical edema on the face and upper limbs (Figure 111).

Incompetent open valve.

Retrograde flow

Normal vein Varicose vein

Figure 109. Venous valve system incompetence

Venous ulcers usually affect the internal malleolus and have a humid
base. They are less painful than arterial ulcers, Figure 110.

Low pain Painful

Chronic venous
Figure 111. Patient with edema on the face and upper limbs
insufficiency

Skin atrophy,
Edema no hair 12.4. Peripheral Artery Disease
Pallor
Erythema
or cyanosis
Peripheral artery disease, also known as chronic limb ischemia, is due
to atherosclerosis and mainly affects the lower limbs of elderly patients,
causing intermittent claudication symptoms.

The presence of chronic ischemia in lower limbs is detected by the pres-

Venous ulcer Ischemic ulcer ence of ankle-brachial index below 0.9.

The most frequent place for atherosclerotic obstruction in the lower

limbs is the adductor canal or Hunter’s canal, located in the thigh (it
Figure 110. Differential treatment between venous and ischemic ulcers thus causes femoral and popliteal claudication; Figure 112).

74
 Card i o l ogy 1
episodes) and, sometimes, drugs that improve walking distances until
claudication, especially cilostazol (or, less markedly, pentoxifylline).

Subclavia (7%) Arterial revascularization is recommended in patients with incapacitating

intermittent claudication, pain at rest or with ischemic ulcers... (stages IIb,
III and IV, respectively, of Fontaine classification; Table 56).

Humeral (15%)

Aortoiliac Cold, tingling, paresthesia, cramps, skin pallor,

STAGE I
(7%) appendages disorders (nails, hair)
Iliac (17%) Intermittent claudication:
· IIa: nonincapacitating intermittent claudication
STAGE II (for patient’s regular activity)
· IIb: incapacitating intermittent claudication
Femoral (43%) Popliteal (10%) (for patient’s regular activity)
STAGE III Pain or paresthesia at rest
STAGE IV Ischemic ulcers (ulcers, gangrene)
Table 56. Clinical Fontaine stages

Aortoiliac surgical treatment of choice is aorto-iliac anatomic bypass or

Figure 112. Atherosclerosis location
Depending on the location of the artery obstruction there are three
clinical forms: Leriche’s syndrome or aorto-iliac occlusive disease (clau-
dication in leg, buttocks and, in men, usually erectile dysfunction), pop-
liteal artery occlusive disease (the most common clinical type in which
pain of intermittent claudication is most often in the calf) and tibial and
peroneal occlusive disease (Figure 113).
unilateral or bilateral aortofemoral bypass. In cases with high surgical
risk, extra-anatomy axillary-femoral or femoro-femoral crossover by-
pass are the alternatives used.
For stenosis in the iliac artery with incomplete occlusion, percutaneous
treatment by means of angioplasty offers good results and is usually the
first option.
In the femoro-popliteal sector, stenosis is usually too long and there-
fore percutaneous procedures often have worse results, limited to
nonocclusive short stenosis of the superficial femoral.

Here, the treatment of choice is anatomic bypass, using autologous sa-

Location
Aortic occlusion
Iliac occlusion
Symptoms phenous vein grafting.
Lumbar claudication
of hip and thigh General treatment of this disease is shown in Figure 114.
Buttock claudication
of hip and thigh

Iliac stenosis Thrill and femoral murmur

Rate decrease

Bilateral hypogastric Sexual impotence

occlusion

Common and deep Claudication and atrophy

femoral occlusion of thigh muscles

Occlusion of superficial Sural claudication

femoral and popliteal

Tibial and peroneal Sural and pedal claudication

occlusion Pain at rest
Ischemic ulcers

Figure 113. Clinical forms of chronic arterial occlusion according

to location of lesion

Medical treatment consists of adopting hygienic and dietary steps

(most importantly, smoking cessation and doing adapted physical exer-
cise), chronic antiplatelet treatment (clopidogrel appears to be slightly
better than ASA in absolute terms), statins, ACE inhibitors (although Figure 114. Examples of extra-anatomy bypass in proximal area
they do not improve claudication, they lower the risk of cardiovascular of lower limbs

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 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

Long-term prognosis of the disease is shown in Figure 115. Acute peripheral occlusion

Acute

Intermittent claudication Peripheral embolism Suspected acute arterial thrombosis

· No vascular history History of claudication
· Normal contralateral pulse or vascular disease

Prognosis Aprox. Mortality

of involved limbs 20% to 30% in five years Embolic heart Nonembolic
Arteriography
disease heart disease

Advanced Need Coronary disease

Stable Amputation
claudication of surgery Cardiovascular
75% 5% Poorly-tolerated ischemia Well-tolerated ischemia
aprox. 15% aprox. 10% disease
(with motor and sensitive (with no motor
changes) or sensory changes)
Figure 115. Five-year prognosis with intermittent claudication

Other Artery Diseases Consider

Transcatheter Fibrinolysis
The most common etiology of acute arterial ischemia is an embolism due to thrombectomy Consider
atrial fibrillation and its treatment of choice is embolectomy (Figure 116). if high risk

Figure 117. Acute arterial occlusion protocol for treatment

Buerger’s disease or thromboangiitis obliterans is strongly connected with

smoking and causes ischemic intermittent claudication in distal areas, Rayn-
aud’s phenomenon and migrating thrombophlebitis. The main differences
with obliterating arterial atherosclerosis are shown in Table 58.

OBLITERATING OBLITERATING
ATHEROSCLEROSIS THROMBOANGIITIS
Age Usually, over Young, below
50 years of age 45 years of age
Blood pressure Usually, hypertension Often hypotension
Raynaud’s syndrome No Commonly present
and migrating
phlebitis
Cholesterolemia High Normal or low
ESR (erythrocyte Normal High
Figure 116. Anatomy of thoracic outlet of upper limb nerve bundle sedimentation rate)
X-rays, · Hard, calcified, · Straight and small-
arteriography deformed, tortuous, caliber arteries, with
Etiology should be differentiated since local thrombosis may cause the irregularly-sized no calcification
same symptoms. Table 57 shows data which enables making a differ- arteries · Nonatheromatous
ential diagnosis. · Atheromatous aorta aorta
Table 58. Differential diagnosis between atherosclerosis and obliterating
Acute arterial ischemia treatment is shown in Figure 117. thromboangiitis

ARTERIAL EMBOLISM ACUTE ARTERIAL THROMBOSIS

Anamnesis Embolic heart disease (AF)
Obliterating atherosclerosis risk factors Rare
Onset of symptoms Sudden/Acute
Predominant symptom Pain
Lower limb chronic ischemia findings Rare
Arteriographic findings · “STOP” image (cupola)
· Minimum atherosclerosis
· Scarce collateral circulation
Table 57. Differential diagnosis between stroke and thrombosis
Lower limb chronic ischemia history
(prior intermittent claudication)
Frequent
Sudden/progressive (acute/subacute)
Pain/Paresthesia (+++)
Frequent (decrease or absence of arterial pulse in contralateral limb)
· Irregular “STOP” image
· Segmented arterial atherosclerotic lesions
· Abundant collateral circulation

76
 Card i o l ogy 1
RAYNAUD’S DISEASE Idiopathic
Quitting tobacco usually stops the progression of the disease; there-
fore, it is the most important step. The appearance of new lesions is a · Scleroderma
sign that patient has not achieved cessation. · Systemic erythematosus lupus
CONNECTING TISSUE
· Rheumatoid arthritis
DISORDERS
· Diabetes mellitus
Administration of nicotine gum or patches may be sufficient to maintain
· Dermatomyositis
the disease active. In certain cases, deviation of large vessels and local
debridement of lesions may be performed. Anticoagulant therapy has Cryoglobulinemia, macroglobulinemia
BLOOD DYSCRASIA
not yielded the expected results and use of corticosteroids has not been of Waldenstrom, myeloproliferative disorders
useful either. In some cases, amputation is necessary, usually more lim- · Hammer syndrome
ited than with obliterating atherosclerosis. TRAUMA · Vibration lesions
· Electric shocks
In subclavian steal syndrome, the occlusion is in the subclavian artery · Ergotamine
before the exit of the vertebral artery and causes symptoms of verte- DRUGS · β-blockers
brobasilar insufficiency (Figure 118). · Bleomycin, vincristine, cisplatin
· Syringomyelia
Raynaud’s phenomenon consists of recurrent episodes of vasocon- NEUROLOGIC
· Carpal tunnel syndrome
ALTERATIONS
striction affecting fingers most commonly, caused by exposure to cold · Poliomyelitis
or intense emotions. It is important to differentiate Raynaud’s disease Table 59. Diseases where Raynaud’s phenomenon is involved
from Raynaud’s phenomenon. Raynaud’s disease is not the result of an
underlying associated medical condition (idiopathic); it comprises more
than half the cases, being predominant among young women and with
usually milder manifestations.
12.5. Lymphedema

Basilar artery The most common cause of lymphedema globally, and mostly in tropi-
External
carotid Internal carotid cal Africa, is filariasis, which causes lymphatic obstruction due to nema-
artery artery
todes and a corresponding inflammatory response, which leads to el-
Common
Vertebral artery ephantiasis.
carotid
artery
Frequent causes of lymphedema are tumors, both due to lymphatic
infiltration of malignant cells and treatment (surgery with lymph
node exeresis or fibrosis caused by radiation therapy to the lymph
Left subclavian
artery system).

The clinical aspects are very important for diagnosis of this disease,
since lymphography is rarely used. Lympho-gammagraphy may be used
Right subclavian Occlusion to detect the blocking point of lymphatic drainage, and it is a useful
artery technique in oncology to detect the “sentinel ganglion” where sick tis-
sue is drained and in order to plan the surgery.

Lymphedema, unlike edemas with different etiology, has an “orange

Aortic artery skin” appearance on the surface area involved, it has a hard feel
(woody) and shows little response to diuretics or rest. In secondary
lymphedema, ducts are usually dilated and it is possible to determine
the occlusion level. On the contrary, in the primary form, lymph vessels
Figure 118. Subclavian steal syndrome are absent or are hyperplastic or ecstatic.

On the contrary, Raynaud’s phenomenon may be secondary to an un-
derlying disorder (Table 59), often some process causing organic le-
sions of the arterial wall.
Most patients with mild and infrequent episodes do not require spe-
cial treatment. They should be instructed to avoid cold environmental
temperatures by using thick gloves and socks, and to avoid mechanic
microtrauma. Tobacco is contraindicated due to its potential vasocon-
stricting effect. In severe cases, vasodilator therapy with drugs may be
administered, calcium antagonists are advisable to this end, and if there
is no response, surgical sympathectomy may be considered, although
any benefits are usually temporary.
The main goals of lymphedema treatment are to control edema (super-
ficial lymphatic massage, soft, and applied from a distal to proximal di-
rection, physiotherapy and other techniques; any element compressing
the limbs, venous punctures, intense exercise or trauma of the involved
limb should be avoided, which should be as long as possible above the
heart level), maintain a healthy and clean skin, and prevent complica-
tions such as cellulitis or erysipelas and lymphangitis. It is advisable to
raise the feet while in bed, use compression stockings and bandages
after emptying the edema by means of manual drainage; or use se-
quential pneumatic compression boots during the day. Especially with
lymphedema after breast surgery, good results have been shown with
low-level laser therapy.

77
 A m e r i c a n Manua l o f Ex am i na ti o n i n Me di c ine (2CK)

The presence of redness, pain and edema usually involves cellulitis or
bacterial lymphangitis (it is known as linear swelling throughout the
length of the limb). Common etiologic organisms are positive-coagu-
lase staphylococcus or β-hemolytic streptococcus, which require strong
treatment, nearly always with intravenous antibiotics. Chronic lymph-
edemas may exceptionally progress to lymphangiosarcoma.
Surgery is used in severe cases which do not respond to medical treat-
ment and it consists of removing hypertrophied tissue and applying
lympho-venous anastomosis to rechannel the flow from an obstructed
lymphatic vessel to the venous system.
epilepsy, intoxication, and narcolepsy, loss of consciousness with en-
docrine and metabolic origin (hypoglycemia, hypoxia or hypocapnia
because of hyperventilation) or vertebrobasilar transient ischemic at-
tack are not syncope episodes either. In subclavian steal syndrome,
syncope is exceptional without other associated focal vertebrobasilar
symptoms, triggered by physical exercise of the ipsilateral arm with
obstruction.
True syncopes are classified into three groups, according to their patho-
physiology (Table 60).
Clinical history is the most profitable data for diagnosing the type of
syncope. It is essential to investigate the situation and triggering fac-
tors, symptoms before and after the episode, as well as the presence

Syncope
Chapter 13
Syncope is a symptom which consists of transient loss of consciousness
(usually just a few seconds, sometimes for some minutes), associated
with postural tone loss and falling, with spontaneous and complete re-
covery, because of transient global cerebral hypoperfusion. There may be
warning signs (weakness, dizziness, ear ringing, cold sweat). Presyncope
is the imminent feeling of syncope without actually losing consciousness.
of heart disease or neuropathy by means of thorough physical exami-
nation. Episodes during exertion, associated palpitations, episodes
while lying down, or family history of sudden death are risk data.
Among other complementary tests, electrocardiogram (ECG) (if normal,
it almost completely rules out cardiac origin of syncope), orthostatism
test or active standing (measurement of BP in supine position and af-
ter three minutes of standing, a drop of over 20 mmHg of systolic BP
or over 10 mmHg of symptomatic diastolic BP is considered positive),
carotid sinus massage (which is diagnostic if it reproduces the syncope
with a pause over three seconds or with a BP drop over 50 mmHg), basic
blood work and chest X-rays are key.
There are some ECG alterations that indicate a high risk in case of syn-
cope (Table 61).

13.1. Differential Diagnosis
Since there is no transient loss of consciousness, casual falling, cata-
plexy (loss of muscle tone associated with emotions or “fits of laugh-
ter”, frequently associated with narcolepsy), drop attacks (“blue
knees” disease in middle-aged women), psychogenic pseudosyncope
or transient ischemic attack, are not true syncope episodes. Even with
transient loss of consciousness, cases of cranio-encephalic trauma,
If this initial assessment is enough to reach a diagnosis, patient treat-
ment follows. If not, it is known as syncope of unknown origin, and
other tests are necessary that should be considered only with certain
suspected clinical origins, such as Holter, echocardiography, tilt test,
electrophysiology study, stress test, cardiac catheterization. Events loop
recorder or implantable Holter are useful with syncope of unknown ori-
gin with suspected arrhythmic origin, especially when the frequency of
syncope is very low (since in this context it is rare for the conventional
Holter to provide any data of interest).

· Vaso-vagal (neurocardiogenic) classic: induced by emotional stress, fear, blood-phobia, pain or orthostatic stress
REFLEX OR
· Situational syncope: tusigen, sneezing, gastrointestinal stimulation (deglutition, defecation, abdominal pain,
NEURALLY
glossopharyngeal neuralgia), postprandial, postexercise, playing wind instruments, laughter
MEDIATED
· Carotid sinus syncope
SYNCOPE
· Atypical forms
· Primary autonomic failure (Shy-Drager, Parkinson, Lewy bodies disease, etc.) or secondary (neuropathy, diabetes,
ORTHOSTATIC
amyloidosis, uremia, marrow damage, etc.)
HYPOTENSION
· Drugs (diuretics, vasodilators, neuroleptics, antidepressants) or alcohol
SYNCOPE
· Volume depletion (bleeding, Addison, dehydration, digestive loss)
· Of arrhythmic origin:
- Sinus diffusion
- AV blocks
- Pacemaker or defibrillator dysfunction
CARDIAC SYNCOPE - Supraventricular or ventricular tachyarrhythmia
- Pro-arrhythmic drugs
· Cardiopulmonary structural disease: heart valve disorders, myocardial ischemia, pulmonary embolism, hypertrophic
cardiomyopathy or other outflow tract obstructions, aortic dissection, pericardium tamponade, atrial myxoma, valve
prosthesis dysfunction, pulmonary hypertension
Table 60. Syncope pathophysiology types

78
 · 2.nd or 3.rd degree AV block Vaso-vagal syncope is the most common type. It is triggered by seeing
RHYTHM
· Sustained or nonsustained ventricular blood, prolonged standing, hot or tight environments, or even by emo-
ALTERATIONS
tachycardia tional stress. It appears to be caused by a reflex alteration which usually
· Pre-excitation begins with a decrease in venous return and secondary release of cate-
· Branch block cholamines which cause strong ventricular contractions, with a relatively
QRS ALTERATIONS · Left-sided ventricular hypertrophy criteria empty ventricle, with associated vagal discharge, hypotension and brady-
· Pathologic Q waves cardia. It has an excellent prognosis with almost null mortality.
· Epsilon wave
· Right precordial negative T waves A tilt test or tilt table test (not required for diagnosis in most cases) en-
REPOLARIZATION · Ischemic changes ables differentiating cardioinhibitory (with predominant bradycardia),
ALTERATIONS · Brugada pattern vasodepressor (with predominant hypotension) or mixed forms. Treat-
· Long QT interval ment consists of explaining the benign quality of the clinical picture in
Table 61. ECG Alterations involving high risk in patients with syncope spite of recurrence risk, advising the avoidance of triggering factors
and, in patients with prodrome symptoms, isometric counter-pressure
Figure 119 shows the general risk stratification of a patient with syn- maneuvers (cross legs while standing). It may be useful to increase hy-
cope. drosaline intake, avoiding diuretics and vasodilators. In refractory cases,
drugs may be used, drugs may be used and midodrine is the drug of
choice (adrenergic receptor stimulants), since serotonin reuptake in-
hibitors, other adrenergic stimulants (etilefrine), and mineralocorticoid
1. Confirmation of Suspected Syncope drugs (useful with orthostatic syncope), are not usually effective and
No show common side effects. Beta blockers are currently considered con-
Was there loss of consciousness? Fall, tonal crisis, cataplexy
traindicated.
Yes
No
Was recovery spontaneous? Metabolic alteration, In very special cases of vaso-vagal syncope recurrent in patients over
intoxication, RPC
Yes 40 years of age, with no response to usual treatment and with a cardio-
No
Is it due to global brain hypoperfusion? Concussion, epileptic crisis, inhibitory form, the use of a pacemaker may be prescribed, the same
pseudosyncope, as with cardioinhibitory carotid syncope, although this does not always
Yes
TIA/vertebrobasilar migraine
decrease syncope episodes since it does not mitigate the vasodepres-
sant effect.
2. Risk Classification of Syncope

Syncope during exertion? Yes

Cardiogenic profile syncope
Syncope while sitting?

No
Suspected neuromediated Yes
Benign Syncope
or orthostatic syncope?
No
Syncope with Unknown Profile

3. Patient Risk Classification

Family History:
• Sudden death
Yes High Risk
• Family heart disease

Structural Heart Disease

(history, PE, Chest X-ray +/- Echo) No Low Risk
Abnormal ECG

Figure 119. Clinical Approach to Patient with Potential Syncope