Syncope

Syncope
David G. Benditt, MD, J. Gert Van Dijk, MD, PhD,

Richard Sutton, DscMed, Wouter Wieling, MD, PhD,
Joseph C. Lin, MD, Scott Sakaguchi, MD, and
Fei Lu, MD, PhD
Abstract: Syncope is a syndrome consisting of a rela-

tively short period of temporary and self-limited loss of
consciousness caused by transient diminution of blood
flow to the brain (most often the result of systemic
hypotension). Syncope comprises part of a subset of
clinical conditions in which loss of consciousness is
transient. Other conditions in this group, which are not
syncope and should be clearly distinguished from syn-
cope, include, for example, seizure disorders, posttrau-
matic loss of consciousness, and cataplexy. Recent
surveys indicate that syncope accounts for approxi-
mately 1% of emergency department visits in Europe,
although older reports from the United States placed
this number closer to 3%. The reported prevalence of
syncope in the population varies: 15% of children
before the age of 18 years; 25% of a military popula-
tion aged 17 to 26 years; 16% and 19%, respectively, in
men and women aged 40 to 59 years; and up to 23% in
a nursing home population older than 70 years. The
highest frequency of syncope occurs in patients with
cardiovascular comorbidity and older patients in insti-
tutional care settings. The causes of syncope are nu-
merous and, not infrequently, multiple factors may
contribute. The diagnostic evaluation is benefited by
availability of a detailed medical history and reports of
eyewitnesses. In this context, the physician must con-
sider the classification of the causes of syncope, and
Dr Benditt is a shareholder and consultant for Medtronic Inc and St. Jude Medical, and is a shareholder in
Cardionet Inc. Dr Sutton is a consultant to Medtronic Inc. Drs van Dijk, Wieling, Lin, Sakaguchi, and Lu have
no conflicts of interest to disclose.
0146-2806/$ – see front matter
doi:10.1016/j.cpcardiol.2003.12.002
152 Curr Probl Cardiol, April 2004

address the most likely causes first. The principal
groups of causes may be summarized as: (1) neurally
mediated reflex syncope (eg, vasovagal faint, carotid
sinus syndrome); (2) orthostatic (postural) syncope; (3)
cardiac arrhythmias; (4) structural cardiac and pulmo-
nary causes; and (5) cerebrovascular disorders (rare).
In addition, conditions that may mimic syncope but are
not true syncope (eg, psychogenic pseudosyncope) must
be considered. Only after a definitive cause is estab-
lished can appropriate treatment be initiated. In this
regard, the syncope evaluation is facilitated by main-
taining an organized diagnostic approach. The practi-
tioner should avoid wasteful use of short-term ambu-
latory electrocardigraphic recordings (eg, Holter
monitors) and rarely positive neurologic tests (eg,
electroencephelography, head magnetic resonance im-
aging/computed tomography) in the absence of head
trauma or evident neurologic signs. In many medical
centers the evaluation of patients with syncope is
haphazard, and may be substantially enhanced by
establishment of a multidisciplinary syncope evalua-
tion unit or team. (Curr Probl Cardiol 2004;29:
145-229.)
yncope is a syndrome consisting of a relatively short period of

S temporary and self-limited loss of consciousness caused by
transient diminution of blood flow to the brain (most often the
result of systemic hypotension).1,2 Synonyms for syncope include “faint-
ing,” “blacking out,” and “passing out.” In some cases individuals will
report symptoms that suggest a near faint, but complete loss of conscious-
ness does not occur. Often these events are termed “gray outs,” “near
syncope,” or “presyncope.” On the other hand, many patients have less
specific symptoms such as dizziness or lightheadedness. More often than
not, these latter symptoms are not related to syncope either clinically or
pathophysiologically. Table 1 provides a diagnostic classification of the
most important causes of syncope.
Syncope falls within a larger category of clinical conditions that cause loss
of consciousness. Further, syncope comprises part of a subset in which the
loss of consciousness is transient (TLOC) (Fig 1).1 In some cases these
conditions reverse themselves spontaneously, whereas others require medical
Curr Probl Cardiol, April 2004 153

TABLE 1. Syncope classification
Neurally mediated reflex syncopal syndromes
• Vasovagal faint (common faint)
• Carotid sinus syncope
• Situational faint
-Acute hemorrhage
-Cough, sneeze
-Gastrointestinal stimulation (swallow, defecation, visceral pain)
-Micturition (postmicturition)
-Postexercise
-Other (eg1 brass instrument playing, weightlifting, postprandial)
• Glossopharyngeal and trigeminal neuralgia
Orthostatic
• Primary autonomic failure syndromes (eg, pure autonomic failure, multiple system
atrophy, Parkinson’s disease with autonomic failure)
• Secondary autonomic failure syndromes (eg, diabetic neuropathy, amyloid neuropathy,
drugs and alcohol)
• Volume depletion
-Hemorrhage, diarrhea, Addison’s disease
Cardiac arrhythmias as primary cause
• Sinus node dysfunction (including bradycardia/tachycardia syndrome)
• Atrioventricular conduction system disease
• Paroxysmal supraventricular and ventricular tachycardias
• Inherited syndromes (eg, long QT syndrome, Brugada syndrome)
• Implanted device (pacemaker, implantable cardiac defibrillator) malfunction drug-induced
proarrhythmias
Structural cardiac or cardiopulmonary disease
• Cardiac valvular disease
• Acute myocardial infarction/ischemia
• Obstructive cardiomyopathy
• Atrial myxoma
• Acute aortic dissection
• Pericardial disease/tamponade
• Pulmonary embolus/pulmonary hypertension
Cerebrovascular
• Vascular steal syndromes
intervention. Absent spontaneous reversal of symptoms, the condition is not

syncope. Similarly, if cerebral dysfunction is not a result of insufficient
cerebral nutrient flow, the loss of consciousness, or apparent loss of
consciousness (eg, seizure disorder) should not be termed “syncope.”
Furthermore, neurologic disturbances not causing loss of consciousness
should not be included in the differential diagnosis of syncope. By way of
example, it is a common misconception that a transient ischemic attack (TIA)
is a cause of syncope (Table 2). This is important, as many diagnostic tests
(eg, head computed tomography [CT] or magnetic resonance imaging [MRI]
scan, carotid Doppler) may be ordered inappropriately in an attempt to rule
out TIA as the presumed origin for loss of consciousness. By way of another

FIG 1. Schematic illustrating distinction between syncope and other conditions in which transient loss
of consciousness (TLOC) occurs or seems to occur. TIA, Transient ischemic attack.
TABLE 2. Causes of conditions commonly misdiagnosed as syncope

Disorders with impairment or loss of consciousness
• Metabolic disorders including hypoglycemia, hypoxia, hyperventilation with hypocapnia
• Epilepsy
• Intoxication (drugs, alcohol)
• Vertebrobasilar transient ischemic attack
Disorders resembling syncope without loss of consciousness
• Cataplexy
• Drop attacks
• Psychogenic pseudosyncope
• Transient ischemic attacks of carotid artery origin
example, Table 3 summarizes the main differences between syncope and

epilepsy. Perhaps the aspect of greatest importance in this regard is abnormal
motor activity. In syncope, it is not uncommon for patients to exhibit jerky
movements of the arms and legs for a brief period of time. Not infrequently,
nonexpert bystanders misinterpret these movements as being indicative of a
seizure. However, the jerky movements during a faint differ from those
accompanying a grand mal epileptic seizure. They are briefer, they occur
after the loss of consciousness has set in, and they are less coarse and do not
have the tonic-clonic features of a true grand mal epileptic seizure.

TABLE 3. Clinical features distinguishing syncope from seizures
Clinical findings
that suggest the Seizure likely Syncope likely
diagnosis
Findings during loss Tonic-clonic movements are Jerky movements are always of short
of consciousness usually prolonged and duration (⬍15 seconds and they
(as observed by their onset coincides with start after the loss of
an eyewitness) loss of consciousness consciousness
Hemilateral clonic
movement
Clear automatisms such as
chewing, lip smacking, or
frothing at the mouth
Tongue biting
Symptoms before Blue face Nausea, vomiting, abdominal
the event Aura (such as funny smell) discomfort, feeling of cold, sweating
(neurally mediated)
Symptoms after the Prolonged confusion Usually short duration nausea,
event Aching muscles vomiting, pallor (neurally mediated)
Other clinical findings of
less value for suspecting
seizure (low specificity):
Family history
Timing of the event (night)
Lightheadedness before the
event
Pins-and-needle’s sensation
before the event
Incontinence after the event
Injury after the event
Headache after the event
Sleepy after the event
B. J. Gersh: Among a large group of patients undergoing tilt table testing,

neurologic events including seizures, dysarthria or aphasia, and temporal
lobe epilepsy occurred in 8%. This was more frequent in patients with
asystole and a lower blood pressure (Passman R, Horvath G, Kruse TJ, et al.
Clinical spectrum and prevalence of neurologic events provoked by tilt table
testing. Arch Intern Med 2003;163:1945-8) (Dey AB, Kenny RA. Drop attacks
in the elderly revisited. Q J Med 1997;90:1-3).
M. M. Scheinman: The authors raise an important issue with regard to the

confusion between syncope and true seizures. In prior studies (Aminoff MJ,
Scheinman MM, Griffin JC, Herre JM. Electrocerebral accompaniments of
syncope associated with malignant ventricular arrhythmias. Ann Intern Med
1988;108:791-6), patients with induced VT or VF during electrophysiologic
testing underwent continuing EEG as well as video monitoring. Patients who

developed cerebral panhypoperfusion (due to ventricular arrhythmias) devel-
oped tonic contraction of the axial skeletal muscles accompanied by gross
motor activity of the extremeties (arm flailing). The gross motor activity is very
different from the very regular tonic-clonic contractions associated with true
seizure activity. Bystanders and even medical personnel may not clearly
appreciate these differences, leading to inappropriate treatment of these
patients for epilepsy. The authors do well to emphasize this important point.
The goals of this review are to summarize the principal causes of

syncope, and provide recommendations regarding optimal diagnostic
evaluation and treatment strategies. In addition, we have attempted to
focus attention on the clinical importance of distinguishing syncope from
other forms of TLOC.
Epidemiology
Recent surveys indicate that syncope accounts for approximately 1% of
emergency department visits in Europe,3,4 although older reports from the
United States placed this number closer to 3%.5 The reported prevalence
of syncope in the population varies5-14: 15% of children before the age of
18 years; 25% of a military population aged 17 to 26 years; 16% and 19%,
respectively, in men and women aged 40 to 59 years; and up to 23% in
a nursing home population older than 70 years. The highest frequency of
syncope occurs in patients with cardiovascular comorbidity and older
patients in institutional care settings.9 In regard to the latter group, it
should be noted that the quoted syncope prevalence figures for older
people are probably an underestimate because up to 20% of these patients
have amnesia for loss of consciousness.
The 1-year mortality of patients with cardiac syncope is consistently
higher (18%-33%) than patients with noncardiac cause (0%-12%) or
unexplained syncope (6%). One-year incidence of sudden death is 24%
for patients with a cardiac cause compared with 3% in the other 2 groups.
Although patients with cardiac syncope had higher mortality compared
with those of noncardiac or unknown causes, patients with cardiac causes
do not appear to exhibit a higher mortality when compared with matched
control subjects who have similar degrees of heart disease. The presence
and severity of structural heart disease are the most important predictors
of mortality. It may reasonably be expected that patients with syncope and
multiple comorbidities, and thereby multiple potential causes for syncope,
will have an even higher mortality. By contrast, certain subgroups of
patients with syncope have an excellent prognosis. These include young
healthy individuals without heart disease and normal electrocardiogram

(ECG) findings, neurally mediated syndromes, orthostatic hypotension
(the mortality of patients with orthostatic hypotension depends on the
causes of this disorder), and syncope of unknown cause (5% first-year
mortality in patients with unexplained syncope).3,8,12,14
B. J. Gersh: Although the mortality of neurocardiogenic and idiopathic

syncope in the absence of structural heart disease may not be increased, the
morbidity is considerable and affects multiple areas of daily life including
driving, employment, interpersonal relationships, anxiety, and depression.
Moreover, orthopedic injuries are quite common (Linzer M, Pontinen M, Gold
DT. Impairment of physical and psychosocial function in recurrent syncope.
J Clin Epidemiol 1991;44:1037-43). Among patients entered into a random-
ized trial of pacing or recurrent syncope, 12% had suffered a motor vehicle
accident, 40% driving restrictions, 10% bone fractures, and 37% had missed
15 days or more of work during the preceding year (Connolly SJ, Sheldon R,
Thorpe KE, Roberts RS, Ellenbogen KA, Wilkoff BL, et al. Pacemaker therapy
for prevention of syncope in patients with recurrent severe vasovagal
syncope: second vasovagal pacemaker study (VVS II): a randomized trial.
JAMA 2003;289;2224-9).
One-third of patients with syncope have symptom recurrences by 3

years of follow-up.1,8,14 The majority of these recurrences occur within
the first 2 years. Predictors of recurrence include having had recurrent
syncope at the time of presentation, age younger than 45 years, or a
psychiatric diagnosis. After positive tilt-table testing, patients with more
than 6 syncopal spells have a risk of recurrence of more than 50% over
2 years.
Patients with syncope are often admitted to the hospital and undergo
expensive investigations, many of which do not provide a definite
diagnosis.1,4,15,16 Despite the advent of newer diagnostic tests (eg, tilt
testing, wider use of electrophysiologic study [EPS], loop ECG monitor-
ing) the management of syncope remains disparate and unstructured in
most centers (see later section, “The Syncope Evaluation Unit or Team”).
Causes of Syncope: Classiﬁcation

Table 1 provides a classification of the principal causes of syncope.1
However, because patients often present multiple comorbidities, it is not
infrequent that several causes within this classification interact within a
given individual.2 The physician must not readily accept an observed
abnormality as the certain cause without careful consideration of alter-
native diagnoses or interactions among various conditions.

TABLE 4. Principal neurally mediated reflex syncopal syndromes
• Common or vasovagal faint
• Postexercise variant
• Carotid sinus syncope
• Postmicturition syncope
• Cough, sneeze syncope
• Defecation syncope
• Swallow syncope
• Glossopyharyngeal neuralgia
• Raised intrathoracic pressure, (airway stimulation) brass wind instrument playing
B. J. Gersh: In a large series of patients from Switzerland, a suspected cause

of syncope was found in 69%; arrhythmias and other cardiac diseases were
the cause in approximately only 10% of the patients, 36% had neurocardio-
genic syncope, and 24% had orthostatic hypotension. This is very similar to
our experience at the Mayo Clinic, in which cardiac syncope occurred in only
21% of patients, but with vasodepressor syncope, undetermined syncope,
and carotid sinus hypersensitivity responsible for 57% (Shen W-K, personal
communication) (Sarasin FP, Louis Simonet N, Carballo D, et al. Prospective
evaluation of patients with syncope: a population-based study. Am J Med
2001;111:177-84).
Neurally mediated reflex faints comprise a number of related clinical

conditions (Tables 1 and 4), the best known of which is the common or
vasovagal faint. Other reflex faints include carotid sinus syndrome (CSS)
and faints triggered by micturition or defecation. Swallowing or emptying
the bladder may also trigger a reflex faint. Coughing may also trigger
reflex hypotension, but the possibility that mechanical factors may
contribute to the decrease in blood pressure (BP) remains a possibility.
Orthostatic (postural) faints are also common, and are most often
associated with movement from lying or sitting to a standing position (Fig
2). Many healthy individuals experience a minor form of this faint when
they need to support themselves momentarily just after standing up.
However, orthostatic faints often occur a few moments after arising,
especially if the affected individual has walked a short distance. The most
dramatic postural faints occur in individuals who are older and frail, those
who have underlying medical problems causing autonomic failure (eg,
diabetes, certain nervous system diseases), or persons who are dehydrated
(eg, hot environments, inadequate fluid intake). Certain commonly
prescribed medications such as diuretics, ␤-adrenergic blockers, antihy-
pertensives, or vasodilators (eg, nitroglycerin) inhibit the autonomic
nervous system and may thereby predispose to postural faints.

FIG 2. Schematic illustrating impact of change of posture on displacement of blood from thorax to
lower extremities. Absent adequate lower-extremity vasoconstriction, excessive decrease in systemic
pressure may lead to orthostatic hypotension leading to greater susceptibility to posturally induced
syncope.
Cardiac arrhythmias may cause faints if the heart rate is excessively

slow or excessively fast to permit maintenance of an adequate systemic
arterial pressure. Bradycardia, such as in the case of sinus pauses or
high-grade atrioventricular (AV) block, or at the termination of an atrial
tachyarrhythmia, are the most common causes of syncope in this context.
Occasionally, however, such faints occur also at the onset of an episode
of paroxysmal supraventricular tachycardia (PSVT) or atrial fibrillation
(AF). For the most part, individuals with underlying heart disease (eg,
previous myocardial infarction, valvular heart disease) or vascular dis-
ease, or disturbances of autonomic nervous system responsiveness, are at
greatest risk for arrhythmia-related faints. However, arrhythmias can
induce faints for patients with normal hearts. The most common example
of the latter is symptomatic hypotension accompanying onset of an
episode of PSVT.
Structural cardiopulmonary diseases are relatively infrequent causes of
faints. The most common cause in this category is fainting associated with
an acute myocardial infarction or ischemia, or in association with
pulmonary embolism. The faint in these cases may be a result of the direct
hemodynamic impact of the acute disease, but in most cases it is thought
to be primarily caused by an abnormal nervous system reaction similar to
the reflex faints. In general, faints caused by structural disease of the heart
or blood vessels are particularly important to recognize as they are
warning of potentially life-threatening conditions.

Cerebrovascular disease is almost never the cause of a true faint,
meaning loss of consciousness due to cerebral hypoperfusion without
focal neurologic deficit.1,2 In fact, TIAs are the opposite: focal deficit
without loss of consciousness. This definitely holds for carotid TIAs;
vertebrobasilar TIAs might cause TLOC, but even then associated focal
neurologic deficits are very likely. Perhaps subclavian steal is the best
example in this class, but it is uncommon. It should be considered when
syncope occurs during exercise of 1 arm, and when BP differs between
the 2 arms. As a rule, this category should be considered only after other
causes have been eliminated.
Conditions that mimic faints are included here primarily because they
are commonly confused with true faints (Table 2). As a consequence of
this confusion, often compounded by imprecision in the medical litera-
ture, the process needed to arrive at the correct diagnosis is impeded. The
most common conditions in this category include: seizures; sleep distur-
bances; accidental falls; and some psychiatric conditions (eg, anxiety
attacks, cataplexy, and hysteric reactions).
B. J. Gersh: Drop attacks have traditionally been considered a symptom of

vertebral basilar insufficiency. In contrast, a recent study of elderly patients
with drop attacks identified a higher proportion with cardiovascular syncope,
the majority due to carotid hypersensitivity. In many of these patients, the
absence of a history may have been due to amnesia for the event (Dey AB,
Stout NR, Kenny RA. Cardiovascular syncope is the most common cause of
drop attacks in the elderly. Pacing Clin Electrophysiol 1997;20:818-9).
Pathophysiology and Clinical Presentation

The common thread underlying the mechanism of all forms of syncope
is transient global cerebral hypoperfusion.1,16-21 Absent this, a real or
apparent episode of loss of consciousness is not syncope. In the vast
majority of cases, diminished cerebral perfusion is a result of a transient
decrease in systemic BP such as might occur at the onset of a tachyar-
rhythmia or in conjunction with a prolonged bradycardic pause in the
cardiac rhythm. Loss of postural tone is an inevitable consequence of loss
of consciousness. Thus, if affected individuals are not restrained they will
slump to a gravitationally neutral position (eg, fall to the ground).
Furthermore, on occasion, nonskeletal muscles may be affected, resulting
in loss of bladder (common) or bowel (rare) control.
In healthy young persons, cerebral blood flow is in the range of 50 to 60

FIG 3. Graph illustrating manner in which cerebral blood flow is autoregulated over wide range of
systemic pressures under normal conditions. Cerebral blood flow (ordinate) remains relatively
constant during arterial pressure range (abscissa) at 60 to 140 mm Hg. Only at lower or higher
pressures is flow pressure-dependent.
mL/100 g of brain tissue/minute, representing about 12% to 15% of

resting cardiac output.22-24 A flow of this magnitude easily meets the
minimum oxygen requirement to sustain consciousness (approximately
3.0-3.5 mL oxygen/100 g tissue/min). However, the safety factor for
oxygen delivery may be markedly impaired in older individuals or in
those with diseases like diabetes mellitus or hypertension.23 A sudden
cessation of cerebral blood flow for only 6 to 10 seconds has been shown
to be sufficient to cause complete loss of consciousness. Further,
experience with tilt-table testing has indicated that a decrease in systolic
BP to 60 mm Hg or less invariably leads to syncope.
Cerebral blood flow is normally autoregulated between a range of
systemic BPs (Fig 3). Consequently, the integrity of cerebral nutrient flow
is dependent on mechanisms that maintain systemic pressure.17,25-27 The
most important of these are:
• arterial baroreceptor-induced adjustments of systemic vascular resis-
tance, cardiac contractility, and heart rate.
• intravascular volume regulation, incorporating renal and hormonal
influences to maintain central blood volume.
• autonomic control over systemic BP.
• cerebrovascular autoregulation, which permits cerebral blood flow to
be maintained over a relatively wide range of perfusion pressures.

Transient failure of protective mechanisms, perhaps accentuated by the
superimposed adverse impact of other factors such as vasodilator drugs,
diuretics, dehydration, or hemorrhage, any of which may reduce systemic
BP below the autoregulatory range, could induce a syncopal episode. Risk
of failure of normal protective compensatory mechanisms is greatest in
patients who are older or ill and those with various forms of autonomic
failure.17
Orthostatic BP Adjustment
On moving from the supine to the erect posture there is a large
gravitational shift of blood away from the chest to the venous capacitance
system below the diaphragm (Fig 2).25-28 This shift is estimated to total
500 to 1000 mL of blood, and largely occurs in the first 10 seconds of
standing. In addition, with prolonged standing, the high capillary trans-
mural pressure in dependent parts of the body causes a filtration of
protein-free fluid into the interstitial spaces. It is estimated that this latter
effect results in a further decrease of about 15% to 20% (700 mL) in
plasma volume within 10 minutes in healthy human beings. As a
consequence of this gravitationally induced blood pooling and the
superimposed decline in plasma volume, the return of venous blood to the
heart is reduced. The result is rapid diminution of cardiac filling pressure
and decrease in stroke volume.
Despite the decreased cardiac output associated with movement to the
upright posture (ie, orthostatic stress), a decrease in mean arterial pressure
is prevented both by compensatory vasoconstriction (splanchnic, muscu-
locutaneous, and renal vascular beds) and an increase in heart rate.
However, it is the vasoconstriction of systemic blood vessels, mediated
exclusively by neural pathways of the autonomic nervous system, that is
the key factor.25,27,28 After longer periods of upright posture, additional
adjustments are mediated by the humoral limb of the neuroendocrine
system; specifically, these include the renin-angiotensin-aldosterone sys-
tem and vasopressin release. Heart rate increase on its own is insufficient
to maintain cardiac output.
The main sensory receptors involved in initiating orthostatic neural
reflex adjustments to postural change are the arterial mechanoreceptors
(baroreceptors) located in the aortic arch and carotid sinuses.25,27,28
Mechanoreceptors located in the heart and lungs (cardiopulmonary
receptors) are thought to play a minor role. Reflex activation of central
sympathetic outflow to the systemic blood vessels can be reinforced by
local mechanisms such as the venoarteriolar reflex and a myogenic
response of the smooth muscle of resistance vessels in the dependent

parts. The skeletal muscle pump and the respiratory pump play an
important adjunctive role in the maintenance of arterial pressure in the
upright posture by promoting venous return.27 In fact, enhancement of
respiratory pump activity appears to be a promising means for reducing
susceptibility to excessive orthostatic hypotension.
Factors That May Undermine Orthostatic Compensatory
Responses
Cerebral perfusion is autoregulated over a wide range of systemic arterial
pressures in most individuals.24 Therefore, as long as systemic pressure
remains within this range, cerebral blood flow will likely be unimpaired.
However, systemic pressure is itself dependent on cardiac output and
systemic vascular resistance. Thus, anything that decreases either or both of
these latter factors will diminish systemic arterial pressure and cerebral
perfusion pressure, and may thereby predispose to syncope.
Low peripheral resistance. An inappropriately low systemic peripheral
resistance often plays a critical role in decreasing arterial pressure and
thereby diminishing cerebral blood flow.19-21 This may occur as the result
of untimely vasodilation, or an inadequate degree of vasoconstriction (eg,
autonomic dysfunction). Excessive vasodilatation is the main cause of
fainting in the neural reflex syncopal disorders.19,20 These disorders refer
to conditions in which neural reflexes, which are normally useful in
controlling the circulation (ie, maintaining BP), respond paradoxically
and inappropriately. The result is a decrease of systemic BP as a result of
vasodilatation and/or bradycardia (so-called vasovagal reaction). Im-
paired capacity to increase vascular resistance during standing is the
principal cause of orthostatic hypotension and syncope for patients using
vasoactive drugs, and for patients with various primary and secondary
autonomic neuropathies. High environmental temperature causing cuta-
neous vasodilation is another important contributing factor in many cases.
Low cardiac output. Maintenance of an adequate cardiac output is
critically dependent on the adequacy of venous filling of the heart.
Venous return may be insufficient when there is improper distribution of
circulating volume such as when blood becomes pooled in lower parts of
the body during movement to the upright posture. Alternatively, inade-
quate venous return may occur when there is diminished overall circu-
lating volume, or when the heart itself performs inadequately as a result
of bradyarrhythmias, tachyarrhythmias, myocardial dysfunction, or val-
vular heart disease.
With regard to arrhythmias, supraventricular tachycardia (SVT) rarely
causes syncope except when rates are very high (usually ⬎200 bpm), or in

case of concomitant significant intrinsic structural cardiac disease (eg,
coronary artery disease, valvular stenosis). Ventricular tachycardia (VT), by
contrast, is a frequent cause of syncope or near syncope. However, in this
instance it is the close association between VT with underlying heart disease
(especially left ventricular [LV] dysfunction) that is responsible. Absent
structural heart disease, even relatively rapid VTs may not cause syncope. As
far as bradycardia is concerned, the rate will have to decrease to well below
50 bpm (and more often below 30 bpm) for it to have a significant effect on
cardiac output (absent concomitant significant structural heart disease).
Increased resistance to cerebral blood flow. Cerebral hypoperfusion
may result from an abnormally high cerebral vascular resistance and
(although believed to be rare) syncope may occur as a result. Vasocon-
striction, induced by low carbon-dioxide tension as a result of hyperven-
tilation, has been proposed as the most common manifestation of this
pathophysiology, but it is in fact unknown whether or not this can cause
unconsciousness. In this regard, it has been suggested that in some
patients vasospasm may contribute to neurally mediated faints, but this
concept is also very controversial.29
In summary, the most important mechanism underlying all forms of
syncope is a transient pronounced decrease in systemic BP with conse-
quent cerebral hypoperfusion. The most frequent source of the hypoten-
sion is the vasodilation component associated with one or the other of the
neural reflex syncope disorders (eg, the vasovagal faint). Orthostatic
decreases in systemic pressure may be equally frequent, and are often, in
part, iatrogenic. Less commonly, other factors contribute to a reduced
cardiac output with systemic hypotension (eg, tachyarrhythmias or
bradyarrhythmias).
B. J. Gersh: My own clinical impression is that syncope in the elderly is often

multifactorial and associated with preload reduction due to cardioactive
medications and a failure of orthostatic compensation leading to a form of
neurocardiogenic syncope.
Strategy for the Syncope Evaluation

Development of effective strategies for evaluating patients with syn-
cope has become of increased interest lately, given substantial evidence
that current practice is erratic and largely cost-ineffective. In this regard
the reader is referred to recently published guidelines and recommenda-
tions. These offer more detail than can be provided in this article.1,30-33

As noted earlier, many conditions may present as TLOC, but only
certain of these fall within the diagnostic category of syncope (Fig 1).
Consequently, it is crucial to ascertain whether the loss of consciousness
episode reported by a patient was in fact true syncope. Thereafter,
assuming syncope is indeed suggested, it is essential to determine the
basis of syncope in each case. In this regard, the Task Force on Syncope
of the European Society of Cardiology (ESC) has provided in the form of
a practice guideline the most current and comprehensive approach to the
evaluation of such patients.1
The Initial Evaluation

The initial evaluation of patients with TLOC begins with a detailed
medical history and careful physical examination.1,15,31-39 Carotid sinus
massage (CSM) is a recommended diagnostic step during the physical
examination, especially in older (⬎60 years) individuals with syncope.
Other procedures, such as ECG, echocardiogram, chest radiograph, and
blood count may be reasonably incorporated as well when they appear to
be warranted by the history.1
Taking the Medical History in Patients with Syncope

Obtaining a detailed medical history is the first step in determining whether
apparent TLOC episodes are true syncope. If the history taking is careful and
thorough, the story provided by the patient (and witnesses) will often reveal
the most likely cause of the faint, and will provide a means of guiding an
efficient and cost-effective subsequent evaluation to confirm the clinical
suspicion.33,37-39 Three key questions to be considered at this stage are:
• Is loss of consciousness attributable to syncope or not?

• Is heart disease present or absent?
• Are there important clinical features in the history that suggest the
diagnosis?
In this section we highlight certain of the most important clinical features

often associated with various causes of syncope. To take advantage of this
information, the details surrounding syncope events must be documented
in considerable detail by the careful history taker. However, history
taking is very user experience– dependent, and even in the best circum-
stances the sensitivity of the process is not established. Consequently,
confirmatory testing (albeit focused by virtue of having considered the
historic findings) is often essential to establish a confident diagnosis.

B. J. Gersh: The history is the single most important diagnostic aid, and Dr
Benditt and his colleagues provide a superb treatise on how to take a medical
history.
Important Components of the Medical History in

Syncope
Before beginning the history taking it is important to determine whether
the patient can give an accurate account of events. This limitation
particularly applies to the very young patient, the elderly individual, and
patients who are uncomfortable (eg, pain) or generally infirm. In this
regard, it has been estimated that cognitive impairment is present in 5%
of those aged 65 year and 20% of those aged 80 years.1 In such cases, and
often even in the case of seemingly good historians, it is crucial that one
try to secure additional information from eyewitnesses.1,31,38,40
General features. To characterize the symptom events, it is helpful to
have the patient focus on the most recent episode. After a thorough
description is obtained (including events before and after symptoms),
turn the patient’s attention to the next most recent episode and
document details. Witnesses can be very valuable in filling in items
that the patient may not recall. Obtain details on as many events as
needed to assess the symptoms. In some patients multiple causes may
be responsible for symptoms. These may be identified or at least
suggested by the medical history. Comorbidities need to be identified
as they may act synergistically (eg, diabetic neuropathy and drug-
induced orthostasis) or independently, thereby resulting in more than
one cause for the faint.
Among the historic factors of importance are: (1) number and
frequency of episodes experienced by the patient; (2) period of time
during which episodes have occurred; (3) nature of associated pre-
monitory symptoms; (4) character of any falls or unexplained acci-
dents that the patient may have experienced; and (5) nature of any
resulting physical injuries. Is there any common thread with regard to
time or circumstances of onset?
Characterize situations in which syncope tends to occur. Establish
position (supine, sitting, standing), activity (at rest, supine, upright), and
change in posture. Do symptoms seem to occur during or after exercise;
during or immediately after voiding; during or after defecation, cough, or
swallowing? Do they tend to occur more often in crowded or warm
places; during prolonged standing; or during the postprandial period? Are

symptoms associated with fear, intense pain, or being emotionally upset?
Do they occur in conjunction with abrupt neck movements?
Characterize prodromal symptoms. Are symptoms associated with
nausea, vomiting, feeling of cold, sweating, visual aura, pain in neck or
shoulders, blurred vision, or palpitations?
Document eyewitness observations. Describe the manner in which the
fall occurred (eg, abrupt fall with possibility of injury, purposeful
avoidance of injury), skin color changes associated with the faint,
duration of loss of consciousness, breathing pattern, physical movements
(eg, tonic-clonic or myoclonic movements), incontinence, and tongue
biting.
B. J. Gersh: The importance of obtaining observations from eye witnesses is

emphasized in a recent case report in Lancet entitled, “A Fainting Mechanic.”
The report deals with a diagnosis of vasovagal syncope in a young man who
ultimately turned out to have epilepsy, and emphasizes that if there is no
witness available at the time you see the patient, you should persist in getting
in contact with all potential witnesses (Sandercock P. A Fainting Mechanic.
Lancet 2002;360:305).
Symptoms noticed after the event. Note confusion, palpitations, dura-

tion of symptoms, headache, nausea, vomiting, sweating, feeling of cold,
muscle aches, skin color, injury, or chest pain. Inability to stand up
without triggering another episode may suggest neurally mediated reflex
syncope.
Characterizing patient risk for syncope recurrence and/or life-threat-
ening consequences.
Family history.
Is there a family history of sudden death, or known genetically
transmitted arrhythmogenic states (eg, long QT syndrome, Brugada
syndrome, arrhythmogenic ventricular dysplasia)? Is there a familial
predisposition to episodic loss of consciousness, or a history of migraine
in the patient or family?
Fainter’s medical history.
Is there any history of structural cardiac disease (eg, myocardial
infarction, valvular heart disease, congenital conditions, cardiac opera-
tion), neurologic conditions (eg, Parkinson’s disease, epilepsy, migraine),
metabolic/intoxication disorders (eg, diabetes, alcoholism), or drug abuse
(eg, cocaine, diuretics)?

Prescribed medication predisposing to syncope. Is the patient taking
drugs known to predispose to syncope such as antihypertensives, antian-
ginal drugs, antidepressant agents, antiarrhythmics, diuretics, or QT-
prolonging agents? Has there been any recent dosing change? Have any
new drugs been added that might produce an undesirable effect or drug
interaction?
Additional Elements of the Initial Evaluation

Physical findings that may help to establish a basis for syncope include
orthostatic BP changes, cardiovascular abnormalities, and (less fre-
quently) neurologic signs. Important cardiovascular findings include
differences in BP in each arm, pathologic cardiac and vascular murmurs,
signs of pulmonary embolism, aortic stenosis, hypertrophic obstructive
cardiomyopathy (HOCM), myxomas, or aortic dissection. Signs of focal
neurologic lesions, such as hemiparesis, dysarthria, diplopia, and vertigo
or signs of Parkinsonism are suggestive of, but not diagnostic of, a
neurologic cause of impairment of consciousness. Such patients warrant
a neurologic evaluation. In general, however, neurologic disease is a very
rare cause of syncope,15 but may be responsible for other forms of TLOC
such as epilepsy.
The 12-lead ECG only rarely identifies a specific (arrhythmic) cause of
TLOC or syncope. However, from time to time ECG findings such as a
Q wave, LV hypertrophy, a prolonged QT interval, or ventricular
pre-excitation may indicate the presence of organic heart disease and
thereby provide a basis for proceeding with further testing. Similarly,
although the echocardiogram rarely pinpoints the cause, it is often
considered a useful element of the initial evaluation in these patients. Its
particular use is in assessing the severity of suggested underlying
structural heart disease, and in some cases identifying previously un-
known abnormalities. In any case, because the recognition of underlying
heart disease is a crucial aspect of the initial evaluation, echocardio-
graphic assessment is warranted at an early stage of the syncope
evaluation if there is any uncertainty regarding the presence of structural
cardiac disease.
Outcomes of the Initial Evaluation
The initial evaluation of the patient may result in 1 of several possible
outcomes: a certain basis for symptoms; a suggested basis for symptoms;
or an unknown or unexplained cause.1 The strategy for dealing with each
has been delineated in detail by the Task Force on Syncope of the ESC,1
and each will be addressed in turn below.

Certain diagnosis. On occasion, the initial evaluation may lead to a
relatively certain diagnosis of the cause of loss of consciousness. In such
cases, further diagnostic evaluation may not be needed. This in fact
occurs quite frequently, especially in the case of classic vasovagal
syncope. Thus, examples of situations in which the physician may believe
that the diagnosis of the basis of syncope is certain on the basis of initial
evaluation include:
• classic vasovagal syncope in which precipitating events such as fear,
severe pain, or emotional distress are associated with typical prodro-
mal symptoms.
• situational faints that occur during or immediately after certain
circumstances, such as emptying the bladder, coughing, or swallowing.
• postural (orthostatic) syncope in which there is documentation of
orthostatic hypotension associated with syncope or presyncope. Ortho-
static BP measurements are recommended after 5 minutes of lying
supine, followed by each minute, or more often, after standing for at
least 3 minutes.
Arrhythmia-related syncope is only rarely diagnosed by the 12-lead ECG
during the initial evaluation. More often, a long-term ambulatory ECG
(AECG) recording is needed. However, the 12-lead ECG may provide
sufficient evidence when there is:
• sustained sinus bradycardia less than 40 bpm (other than during sleep)
or repetitive asystolic pauses (ie, sinoatrial block, sinus pauses) more
than 3 seconds in duration.
• Mobitz II second-degree AV block.
• Third-degree (complete or high-grade) AV block.
• rapid PSVT or VT recorded.
• pacemaker malfunction with cardiac pauses.
Suspected diagnosis. Even when inconclusive, the initial evaluation is
often useful because it may reveal abnormalities that suggest the possible
cause of syncope, thus, guiding the subsequent evaluation strategy.
Certain clinical and ECG findings that may not be conclusive but provide
clues to specific diagnoses are listed in Tables 3 and 4, respectively.
For patients with a suggested diagnosis after the initial evaluation,
specific confirmatory testing is often warranted to solidify or rule out the
suggested diagnosis. Such testing may also aid in the planning of
treatment. Tilt-table testing is an example of a confirmatory test, which is
often used when the diagnosis of a vasovagal faint is suggested, but the
presentation is not classic. In this regard, only about 40% of the presumed

FIG 4. Ambulatory electrocardiographic recording obtained during spontaneous vasovagal faint in
17-year-old healthy boy. Patient had finished exercising and sat down on ground because of feeling
unwell. Event was marked by gradual sinus slowing followed by several prolonged asystolic episodes.
Patient recovered spontaneously.
vasovagal faints are typical. The majority are only suggested by the
experienced physician after other causes have been essentially eliminated.
Tilt testing is most valuable in individuals without evident structural heart
disease.
Unexplained diagnosis. When the results of the initial evaluation are
completely nondiagnostic, the patient may be considered to have either
TLOC or, when syncope is more likely than other causes of TLOC,
unexplained syncope. In these cases, the strategy for subsequent assess-
ment varies according to the severity and frequency of the episodes and
the presence or absence of heart disease.40
No evidence of structural heart disease.
The majority of patients with single or rare episodes in this category
probably have neurally mediated syncope. Apart from education and
advice regarding recognition of episodes and preventing triggers, and
perhaps discussion of physical maneuvers to interrupt attacks, more
aggressive treatment measures are generally not recommended in this
group of patients. Close follow-up without immediate further evalua-
tion is recommended.
For patients with recurrent unexplained faints in the absence of
structural heart disease, and who have a normal ECG finding, neurally
mediated reflex syncope remains the most probable diagnosis (Fig 4).
At this stage, tilt-table testing and CSM (if not already done) should
be undertaken. CSM undertaken with the patient in the upright posture
may yield useful findings not observed in the supine posture. An
additional consideration for patients without structural heart disease,

with a normal ECG finding, and with many faints is psychiatric illness.
Psychiatric assessment is especially recommended for patients with
frequent syncope (actually pseudosyncope) recurrences in conjunction
with multiple other somatic symptoms and medical concern for stress,
anxiety, and possibly other psychiatric disorders. For patients with
signs of autonomic failure or neurologic disease, a specific neurologic
diagnosis should be made and will require appropriate consultation. In
all cases, long-term AECG monitoring and an implantable loop
recorder (ILR) may be helpful in an attempt to determine conclusively
(often for patient reassurance) whether an arrhythmia is associated
with symptoms. Similarly, although less cost-effective, EPS may be
needed in selected individuals in this group.
B. J. Gersh: I strongly agree with the approach suggested by the authors.

When there is no evidence of structural heart disease in patients with
recurrent syncope, but a diagnosis has not been made, it is a good
indication for tilt table testing or the use of the implantable loop recorder.
In my own practice, the latter has been extremely helpful in patients who
have recurrent, relatively brief events. Often, the value of the ILR may
relate to the fact that an event has occurred without a documented rhythm
disturbance, in which case, the test is useful from a negative standpoint.
Obviously, in other patients in whom a bradycardia or an arrhythmia is
documented, the test is equally useful and will dictate therapy (Sivaku-
maran S, Krahn AD, Klein GJ, et al. A prospective randomized comparison
of loop recorders versus Holter monitors in patients with syncope or
presyncope. Am J Med 2003;115:1-5). In certain patients, the ILR may be
cost-effective (Krahn AD, Klein GJ, Yee R., et al. Cost implications of
testing strategy in patients with syncope: randomized assessment of
syncope trial. J Am Coll Cardiol 2003;42:495-501).
Structural heart disease.

In patients with structural heart disease or who have an abnormal
ECG finding, cardiac evaluation consisting of echocardiography (if
not already done), stress testing, and tests for arrhythmia detection
such as prolonged AECG monitoring (including use of ILRs) or EPS
are recommended. In some cases, long-term monitoring with an
external recorder offering Internet downloading of signals and a global
positioning system (GPS) locator in the event that assistance is needed
may prove useful, but currently is only available in a limited number
of locales in the United States (Fig 5). The appropriate prioritization
of these diagnostic procedures will vary depending on specific clinical

FIG 5. Photograph illustrating ambulatory electrocardiography (ECG) monitor (Cardionet, San Diego,
Calif) capable of transmitting ambulatory ECG recordings by wireless Internet to central receiving
station for analysis and subsequent medical overview.
circumstances. However, the ESC Syncope Task Force publication

offers valuable guidance.1
Apart from the prognostic importance of the presence of heart disease,
its absence excludes a cardiac cause of syncope with few exceptions. In
a recent study, heart disease was an independent predictor of cardiac
cause of syncope, with a sensitivity of 95% and a specificity of 45%; by
contrast, the absence of heart disease allowed exclusion of a cardiac cause
of syncope in 97% of patients. If cardiac evaluation does not show
evidence of arrhythmia as a cause of syncope, evaluation for neurally
mediated reflex syndromes is recommended in those with recurrent or
severe syncope.
For patients with palpitations associated with syncope, AECG
monitoring (including ILRs in many cases) is especially valuable. ILR
monitoring should be used for patients with relatively infrequent but
recurrent unexplained syncope whose symptoms are suggestive of
arrhythmic syncope. ILRs are particularly valuable in patients who are

older or infirm, who may not be able to manage external devices. In
patients with chest pain suggestive of ischemia before or after loss of
consciousness or patients with syncope during or after effort, stress
testing is recommended.
Speciﬁc Causes of Syncope: Evaluation and

Treatment Strategies
Neurally Mediated Reflex Syncope
Neurally mediated reflex syncope encompasses a group of disorders, the
best known and most frequently occurring forms of which are the
vasovagal (or common) faint and CSS (Table 1).1,2,30 Postmicturition
syncope, defecation syncope, and cough syncope are the next most
commonly encountered forms of reflex faints. These latter conditions are
often also characterized as situational faints, because they are associated
with specific scenarios (eg, micturition, straining at stool, coughing,
respectively).
Evaluation.
Medical history.
The strategy for establishing a diagnosis of 1 of the neurally mediated
reflex syncopes relies heavily on obtaining a detailed medical history,
along with eyewitness accounts.
The vasovagal (or common) faint may be triggered by any of a variety
of factors including unpleasant sights, pain, extreme emotion, and
prolonged standing. Consequently, circumstances surrounding a faint
may lead to suggestion of vasovagal syncope as the cause. For instance,
autonomic activation (eg, tachycardia, palpitation, sweating) in the
premonitory phase suggests a vasovagal origin. However, most informed
practitioners have come to realize that the so-called classic features of
vasovagal are more often than not either absent or not recollected.
Therefore, even a detailed medical history undertaken by an experienced
individual may not provide a definitive diagnosis. In such cases additional
testing is prudent. Tilt-table testing is the most important readily available
supportive test.41-57 Furthermore, symptoms such as erratic muscle
movements occurring after the patient has become unconscious, and
urinary (or more rarely bowel) incontinence, may occur in the setting of
a vasovagal faint. These may result in confusion with seizure disorders
and necessitate a neurologic consultation.
Spontaneous CSS may be defined as syncope that seems to occur in
close relationship with accidental mechanical manipulation of the neck

(and presumably the carotid sinuses), and can be reproduced by CSM.
Conventional experience suggests that spontaneous CSS is relatively rare,
reportedly accounting for only about 1% of all causes of syncope. Induced
CSS is more broadly defined and is diagnosed when patients are found to
have an abnormal response to CSM and an otherwise negative workup for
syncope. Thus, diagnosis of the induced form does not require the classic
history. Regarded in this way, CSS is much more frequent, having been
reported in the Newcastle experience to be 26% to 60% of patients
affected by unexplained syncope.58-60 In other centers the percentages are
lower, but not trivial. The occurrence of syncope or unexplained falls,
especially in older persons, should lead to consideration of CSS.
Situational faints (eg, postmicturition syncope, cough syncope) are
diagnosed primarily by a careful history taking. The trigger events
surrounding the faints must be carefully sought out during the history
taking and documented. Thus, the triggering of faints by voiding
(postmicturition), coughing, laughing, bowel movements, or using wind
instruments reasonably results in the diagnosis of one or another form of
situational neurally mediated reflex faint.
B. J. Gersh: The location in which syncope occurs may be helpful.

Syncope in an aircraft is often neurocardiogenic, related to volume
depletion, alcohol, and perhaps emotions engendered by the fear of flying
or in relationship to meetings and departures. Similarly, syncope in the
setting of a church service, particularly in hot weather, suggests to me that
it is neurocardiogenic.
Laboratory studies: Basic autonomic assessment.

Head-up tilt test. The head-up tilt-table test is the only available
diagnostic tool to have been scrutinized with regard to its effectiveness in
the diagnosis of vasovagal syncope (Figs 6 and 7).41-54 In this regard,
head-up tilt-table testing, especially when undertaken in the absence of
drugs, appears to discriminate well between patients who are symptom-
atic and control subjects who are asymptomatic. There is strong evidence
to suggest that tilt-table testing at angles of 60 to 70 degrees, in the
absence of pharmacologic provocation, exhibits a specificity of approxi-
mately 90%. In the presence of pharmacologic provocation, test speci-
ficity may be reduced, but nonetheless remains in a range that permits the
test to be clinically useful.42,49 Test sensitivity is more difficult to
estimate, but is likely increased with use of pharmacologic provocation.

FIG 6. Schematic illustration of head-up tilt-table procedure.
FIG 7. Electrocardiography (V1) and blood pressure recording (femoral artery [FA]) obtained during
final phase of head-up tilt-table study in otherwise healthy patient with history of multiple faints.
Findings illustrate evolution of hypotension and bradycardia. Ultimately, prolonged asystolic pause
developed. After patient was returned to supine position (movement artifact on tracing), spontaneous
recovery was prompt. Also see Fig 4.

Detailed discussion of tilt-table testing protocols, test reproducibility,
and estimated specificity and sensitivity are best found in the American
College of Cardiology (ACC) Expert Consensus Report30 and the recent
guideline document from the ESC.1 As a rule, the first step is passive
head-up tilt at 60 to 70 degrees, during which the patient is supported by
a footplate and gently applied body straps, for a period not less than 20
minutes and perhaps as long as 45 minutes. Tilt angles less than 60
degrees and more than 80 degrees lead to loss of sensitivity and
specificity. Subsequently, if needed, tilt testing in conjunction with a drug
challenge (eg, isoproterenol, edrophonium, nitroglycerin) may be under-
taken either immediately or as a separate procedure. This is particularly
pertinent if a short passive phase is used (ie, 20-30 minutes). Until
recently, the most frequently used provocative drug was isoproterenol
usually given in escalating doses from 1 to 3 ␮g/min.42,46,51 However,
nitroglycerin intravenously or sublingually has gained favor, in part
because it expedites the procedure without adversely affecting diagnostic
use.49,52,54 The so-called Italian protocol in which a 20-minute passive tilt
is followed, if necessary, by sublingual nitroglycerine (0.4-mg spray) has
become the most popular protocol as a result of its relatively short
duration with well-preserved specificity and sensitivity.
An additional advantage of the head-up tilt test is that it provides the
opportunity to precipitate a typical vasovagal attack in the presence of the
physician. As a result, it helps the patient by giving confidence that the
physician has witnessed the problem, and it also provides the patient
valuable experience that may help recognition of impending faints and
thereby avert future events. Nonetheless, tilt-table testing is imperfect.
The false positive rate is approximately 10%. Acute (ie, same day or
within a few days) test reproducibility, in terms of whether syncope is
induced or not, is approximately 80% to 90%. Longer-term reproducibil-
ity (ie, more than 1 year) is around 60%. Because there is no gold standard
for diagnosis of neurally mediated syncope, the sensitivity of tilt testing
cannot be estimated with confidence.
It has been known for some time that tilt testing does not always result
in the same hemodynamic picture when repeated in the same patient.
Thus, cardioinhibition (ie, bradycardia) may predominate on one occasion
whereas vasodilation with hypotension may occur at another time. Thus,
tilt testing may not be optimal for directing treatment strategy. In this
regard, the recently published International Study of Syncope of Un-
known Etiology (ISSUE) study indicates that even when tilt testing
indicated a prominent vasodilatory component to the faint, the subsequent
recording of spontaneous faints by means of an ILR often revealed

bradycardic events.55-57 Further study of this phenomenon with devices
that can monitor BP (or a surrogate of BP) and heart rate is needed.
In brief, for patients without severe structural heart disease, a positive
tilt-table test (especially if it reproduces the patient’s spontaneous
symptoms) can be considered diagnostic. In that circumstance, no further
tests need to be performed. By contrast, for patients with significant
structural heart disease, arrhythmias should be excluded as a cause before
relying on a positive tilt-test result.
Carotid Sinus Massage. CSS can be assessed in the clinical laboratory,
although the specificity and sensitivity of the CSM procedure has not
been rigorously studied.58-62 Nevertheless, on the basis of consensus
opinion, CSS may be diagnosed when CSM reproduces symptoms in
conjunction with a period of asystole, paroxysmal AV block, a marked
decrease (usually a drop in BP ⬎50 mm Hg systolic) in systemic arterial
pressure, or a combination of these.1,58 In many instances, the most
convincing results from CSM are obtained when massage is undertaken
with the patient in the upright position.57 In that scenario, the impact of
gravity on systemic pressure during induced bradycardia or vasodilation
can be assessed. Continuous arterial pressure and ECG recordings should
be obtained throughout. For the former measurement, a noninvasive BP
measurement device may be suitable but satisfactory recordings are often
difficult to obtain. A conventional sphygomanometer is not adequate.
It has long been known that pressure at the site where common carotid
artery bifurcates produces a reflex slowing in heart rate and decrease in
BP (Fig 8). This observation is the basis of the technique of CSM. In
some patients with syncope, an exaggerated response to CSM can be
observed. In the absence of a history of spontaneous syncope, the
exaggerated response is defined as carotid sinus hypersensitivity, and
must be distinguished from CSS.
Two approaches to the diagnostic use of CSM have been advocated.1
The first method is probably the most widely used. CSM is performed
with the patient supine. Pressure is applied for no more than 5 seconds. A
positive response is defined as a ventricular pause longer than 3 seconds,
a decrease of systolic BP more than 50 mm Hg, or both. Pooled data from
4 studies performed in elderly patients with syncope show a positive rate
of 35% (235 of 663 patients). Abnormal responses can also be frequently
observed in subjects without syncope. The diagnosis may be missed in
about one-third of cases if only supine massage is performed. The second
method requires reproduction of spontaneous symptoms during CSM.
Eliciting symptoms requires a longer period of massage (10 seconds) and
performance in both supine and upright positions. A positive response

FIG 8. Electrocardiographic (leads II and V1), intracardiac recordings from the His bundle (His) and
right atrium (RA), and blood pressure (femoral artery [FA]) recordings obtained during evaluation of
72-year-old man with history of 2 abrupt loss-of-consciousness spells. Right-sided carotid sinus
massage (RCM) in supine position reproducibly resulted in asystolic pauses of 6 to 8 seconds
duration. In addition, hypotension persisted for more than 40 seconds despite supine posture. Had
patient been in upright posture, it is easy to conceive that syncopal symptoms may have occurred.
was observed in 49% of 100 patients with syncope of uncertain origin and
in 60% of elderly patients with syncope and sinus bradycardia, but only
in 4% of 101 control subjects without syncope pooled from 3 studies. The
eliciting of symptoms is probably the more useful end point for CSS
evaluation, and consequently seems to be the more desirable method.
The main complications of CSM are neurologic.61,62 In 1 study, 7
neurologic complications were reported among 5000 CSMs, with an
incidence of 0.14%. In another study, 16 neurologic complications were
reported in 16,000 massages (0.01%). These complication rates apply to
5 seconds of CSM in supine, upright, or both positions.
It is generally agreed that CSM should not be performed in patients who
have experienced TIAs or strokes within the past 3 months or in patients
with carotid bruits (unless carotid Doppler studies convincingly exclude
significant carotid artery narrowing).1 On rare occasion CSM may elicit
self-limited AF of little clinical significance. Finally, findings recorded in
the period after an acute myocardial infarction may not be representative,
and should not be used to make a CSS diagnosis.
Adenosine triphosphate test. The value of bolus administration of
adenosine triphosphate (ATP) remains a controversial topic.63-66 The

ATP test may prove to be a useful way of identifying a form of syncope
associated with presumably neurally mediated paroxysmal AV block in
certain older individuals in whom other causes have been excluded. This
suggests that ATP bolus administration might actually unmask occult AV
nodal disease in susceptible individuals, and guide a decision to initiate
permanent pacing. The diagnostic and predictive value of the test remains
to be confirmed by prospective studies. In the absence of sufficient hard
data, the test may be indicated at the end of the diagnostic workup.
The protocol proposed by Flammang et al63 consists of the injection
in a brachial vein of a bolus (⬍2 seconds) of 20 mg of ATP followed
by a 20-mL flush of dextrose solution or dissolved in 10 mL of saline
solution. During injection, patients remain supine with continuous
ECG recordings just before and 2 minutes after drug administration.
BP is monitored noninvasively. As a result of possible bronchospastic
reactions, ATP test is contraindicated for patients with known asthma.
Interpretation of the result of the test is on the basis of the duration of
the cardiac pause induced by ATP infusion. Pauses longer than 10
seconds, even if interrupted by escape beats, is defined as abnormal.
Some reports suggest that a pause longer than 6 seconds is sufficient
to declare the test abnormal.65 For patients with abnormal responses,
reproducibility was approximately 80% both in the short- and long-
term period.
Miscellaneous autonomic system tests. Several studies are occasionally
used for syncope evaluations in the autonomic function testing laborato-
ry,17,67 but their clinical value is as yet unclear.
1. Valsalva Maneuver. The use of the Valsalva maneuver is in assess-

ment of the integrity of the arterial baroreceptor reflex arc. In this
sense it provides an estimate of autonomic nervous system integrity
and may, as such, indicate the presence of autonomic failure that can
cause syncope through orthostatic hypotension. In itself, however, the
Valsalva maneuver does not directly implicate a mechanism for
syncope.
2. Active standing test. This procedure, as its name implies, assesses
patient response to active movement from supine to upright posture.
Normally, active muscle movement is expected to propel more blood
toward the central circulation, thereby aiding the needed increase in
cardiac output. However, active use of lower limb muscles may play
a role in aggravating peripheral vascular dilation and, as a result,
induce greater hypotension. The balance between these physiologic
effects of active muscle movement determines the net effect with

regard to systemic pressure. A 5-minute active standing test is useful
to assess initial orthostatic hypotension (first 30 seconds of upright
posture). The initial hypotension occurs on active standing, but not on
tilting. To detect the pressure decrease, beat-to-beat pressure monitor-
ing (usually noninvasive) is essential (eg, Finapres). A 5-minute
standing up test may also demonstrate later diminution of BP indica-
tive of classic orthostatic hypotension. In regard to the latter, there are
no data that prove that 5-minute standing is a stronger test than
5-minute tilting.
3. Cold pressor test. Like the Valsalva maneuver, this test provides
insight into autonomic reflex integrity. It has not been used as a means
of identifying a specific diagnosis.
4. Eyeball compression test. This test, previously used to induce a vagal
reflex, should be abandoned. Its use is low, and its clinical diagnostic
benefit is marginal compared with potential risks.
5. Cough test. The use of induced cough to assess susceptibility to cough
(tussive) syncope has been discussed, but few data are available (Fig
9). Like CSM, it may be best undertaken with the patient in the upright
posture.
The situational faints are not readily assessed in the laboratory. Cough
syncope may be an exception, but diagnostic criteria for hemodynamic
response to induced cough have yet to be determined.
Neurologic studies. Head MRI or CT scans and electroencephelog-
raphy (EEG) are often ordered by physicians confronted with a
syncope evaluation. Nevertheless, their value is at best negligible, and
this practice is to be strongly discouraged. In 1990, Kapoor15
demonstrated the futility of such a strategy, and this view has been
endorsed by the Task Force on Syncope of the ESC.1 However, this is
only true if 2 important caveats are considered. First, syncope must be
certain, because otherwise all categories of TLOC should be consid-
ered, which include epilepsy, the analysis of which may well call for
an EEG and MRI or CT scans. Second, orthostatic syncope may be a
result of autonomic failure, itself a result of a large variety of diseases
of the central or peripheral nervous system. In both cases the choice of
additional tests is best left to a neurologist.
Treatment options. In general, initial treatment of all forms of
neurally mediated reflex syncope comprises education regarding
avoidance of triggering events (eg, hot crowded environments, volume
depletion, effects of cough, tight collars), recognition of warning
symptoms, and maneuvers to abort the episode (eg, supine posture, leg

FIG 9. Electrocardiographic and blood pressure (BP) recordings illustrating initiation of hypotensive
response by cough in laboratory. Maximum decrease in systolic BP was approximately 60 mm Hg
and was maintained for about 17 seconds before normal pressure was restored. Patient was supine
and remained asymptomatic. As with carotid sinus massage in carotid sinus syndrome, symptoms for
patients with cough syncope are usually only reproduced if coughing is sustained and patient is
upright. Normal responses to cough test are not yet fully established.
crossing, arm tugging). In addition, if possible, strategies should

address trigger factors directly (eg, suppressing the cause of cough in
cough syncope).
B. J. Gersh: An essential aspect of the treatment of vasovagal syncope is to

reassure the patient and to inject a dose of “common sense.” I occasionally
see younger patients who have had one or two episodes of syncope and yet
have been started on therapy such as beta blockers. Reassurance and
patient education are the key for the majority, and Dr Benditt and colleagues
have listed in detail the recommendations that should be made. A recent
study in Germany is somewhat disappointing in that it emphasized the large
gap between recommendations and clinical reality with regard to driving
recommendations in patients with syncope. Even among patients who had
experienced injuries during syncope and had had syncope while driving,
almost all continued driving despite having received advice to the contrary
(Maas R, Ventura R, Kretzschmar C, et al. Syncope, driving recommenda-
tions, and clinical reality: a survey of patients. BMJ 2003;326:21).

Vasovagal syncope.
In the vast majority of cases, patients who seek medical advice after
having experienced a vasovagal faint require, principally, reassurance and
education regarding the nature of the condition. Patients should be
informed that vasovagal syncope is common in human beings, and that in
most people its occurrence is infrequent with only 1 or 2 events in a
lifetime. However, certain individuals have greater susceptibility, and
multiple random recurrences are not uncommon in such cases. Initial
advice should include review of the types of environments in which faints
are more common (eg, hot, crowded, emotionally upsetting) and provide
insight into the typical warning symptoms (eg, hot/cold feeling, sweaty,
clammy, nauseated), which may permit many individuals to recognize an
impending episode and thereby avert the faint. Thus, avoiding venipunc-
ture may be desirable when possible (eg, not volunteering for blood
donation), but psychologic deconditioning may be necessary. Additional
common-sense measures such as keeping well hydrated and avoiding
prolonged exposure to upright posture, hot and confining environments,
or both should also be discussed. In regard to these latter treatment
concepts, formal randomized studies are not available.
When a further step in the treatment strategy is needed, volume
expanders (eg, increased dietary salt/electrolyte intake with fluids [eg,
sports drinks, salt tablets]) or moderate exercise training appear to be
among the safest initial approaches.1,68 In addition, in highly motivated
patients with recurrent vasovagal symptoms, the prescription of progres-
sively lengthening periods of enforced upright posture (so-called tilt
training) may reduce syncope recurrence.69,70 Finally, recent reports have
identified physical maneuvers that can be initiated on onset of premoni-
tory symptoms, which may abort or ameliorate the attack.71 Thus, there
is good reason to instruct patients regarding leg-crossing and arm-tugging
maneuvers. The first of these is the most robust hemodynamically, but
leaves the standing patient in a somewhat awkward position, and one that
may itself result in a fall. The arm-tugging maneuver is less effective,
perhaps a result of incorporation of a smaller muscle mass (ie, upper
extremities). However, it may be safer in older or very frail individuals.
Finally, the use of a respiratory impedance valve that forces patients to
breathe with a greater intrathoracic negative pressure may help increase
venous return to the heart and reduce orthostatic pressure decreases
(Advanced Circulatory Systems, Inc, Eden Prairie, Minn).
Many drugs have been used in the treatment of vasovagal syncope (eg,
␤-blockers, disopyramide, scopolamine, clonidine, theophylline, fludro-
cortisone, ephedrine, etilephrine, midodrine, clonidine, serotonin inhibi-

tors).72-87 Although the results have often been satisfactory in uncon-
trolled trials, placebo-controlled prospective trials have been unable to
show a benefit for most of these drugs. The principal exception is
midodrine, a vasoconstrictor agent.82,83
B. J. Gersh: It is sobering to realize how relatively few patients have

undergone randomized trials of therapy for vasovagal syncope. There have
been 5 randomized drug trials involving 271 patients, 4 trials of pacing
involving 289 patients (only one of which was blinded), and orthostatic
training, which appears to be highly successful, but has been subjected to
only one randomized trial of 47 patients. Of the drug trials, the 2 that were
positive (using paroxetine and midodrine) involved a total of 84 patients,
whereas trials of disopyramide, etilefrine, and atenotol, which demonstrated
no benefit, totaled 187 patients. Our own experience with syncope in a
retrospective study was that recurrent syncope was slightly more common in
patients receiving beta blockers as opposed to standard conservative
medical management (Alegria JR, Gersh BJ, Scott CG, et al. Comparison of
frequency of recurrent syncope after beta-blocker therapy versus conserva-
tive management of patients with vasovagal syncope. Am J Cardiol
2003;92:82-4).
Because failure of appropriate vasoconstriction of peripheral blood

vessels is common to all of the neurally mediated reflex faints, vasocon-
strictors may be used. The ␣-stimulating agents etilephrine and midodrine
have both been studied in a placebo-controlled fashion.80,81 Etilephrine
was studied as a segment of the randomized placebo-controlled Vasova-
gal Syncope International Study (VASIS) trial, and proved to be ineffec-
tive.86 By contrast, studies from the United Kingdom and United States
on short-term outcomes with midodrine in vasovagal syncope have shown
a beneficial effect.79,82,83
Head-up tilt laboratory findings have generally reported that cardiac
pacing is not very effective for preventing posturally induced vasovagal
syncope, although it may prolong the premonitory warning phase.
Nevertheless, unlike most other treatment avenues in this condition,
pacing has been the subject of a number of both small single- and
multiple-center studies and major multicenter randomized controlled
trials demonstrating effectiveness in select highly symptomatic patient
populations.84-88 In this regard, the strongest supportive evidence comes
from 3 randomized controlled trials: the North American vasovagal
pacemaker study (VPS)1; the European VASIS trial86; and the Syncope
Diagnosis and Treatment Study (SYDIT) report.85-87 For example, in the
case of the North American trial, the actuarial 1-year rate of recurrent

syncope was 18% for patients with a pacemaker and 60% for control
subjects. The results of the pacing arm of the VASIS trial were similar;
5% of patients in the pacemaker arm experienced recurrence of syncope
compared with 61% in the no-pacemaker arm during a mean follow-up of
3.7 years. However, these studies failed to account for the potential
placebo effect of pacemaker implantation because patients without pacing
did not have devices implanted. In this regard, the recently reported VPS2
trial suggests that when both groups (paced and not paced) undergo
pacemaker implantation, the pacing benefit appears to be reduced in the
first 6 months of follow-up.88 The as yet unreported syncope pacemaker
(SYNPACE) study from Europe appears to be heading in the same
direction as VPS2.88 Consequently, the ultimate role to be played by
pacing in this setting remains uncertain at this time. One might argue that
only older patients with documented severe bradycardia during sponta-
neous faints (such as can be documented by an ILR) should be considered
for pacing therapy.
Carotid Sinus Syndrome.
Treatment of CSS is, in part, guided by the results of the CSM (ie,
relative importance of cardioinhibitory vs vasodepressor responses).
Cardiac pacing appears to be beneficial in CSS and is acknowledged to be
the treatment of choice when bradycardia has been documented.89-91 For
the most part, dual-chamber cardiac pacing is preferred. Medical therapy
for CSS has largely been abandoned, but may be needed in conjunction
with pacing. The latter would be particularly the case for patients in
whom the vasodepressor aspect of the reflex is prominent. In such cases,
judicious use of vasoconstrictors (eg, midodrine) may be needed.
Situational faints.
Treatment of most forms of neurally mediated situational syncope relies
primarily on avoiding or ameliorating the trigger event. However, this
may be difficult. For example, the cough trigger in cough syncope (eg,
chronic obstructive pulmonary disease or asthma) is readily recognized,
but suppressing it (the ideal treatment) is not easily accomplished. In
other cases, avoidance of the trigger may have economic or avocation
implications (eg, syncope associated with blowing a wind instrument). In
yet other cases, it is impossible to avoid exposure to the trigger situation
(eg, unpredictable emotional upset or painful stimuli, bowel movement
[defecation syncope], bladder emptying [postmicturition syncope]).
In conditions where trigger avoidance is not entirely feasible, certain
general treatment strategies may be advocated. These include: mainte-
nance of central volume; protected posture (eg, sitting during micturition
rather than standing); slower changes of posture (eg, waiting after a bowel

movement before arising); and recognition of increased risk when getting
out of a warm bed. In specific conditions, certain additional advice may
be helpful. Thus, use of stool softeners may help patients with defecation
syncope. Avoidance of excessive fluid intake (especially alcohol) just
before bedtime may reduce risk in postmicturition syncope. Elimination
of excessively cold drinks or large boluses of food may help for patients
with swallow syncope.
M. M. Scheinman: Treatment rationale as described rests on a number of

triggers. Tilt table testing is a potent trigger because tilting, as described,
results in decreased venous return, which in turn triggers an adrenergic
response. This response is countered by a strong parasympathetic overre-
action producing both bradycardia and hypotensions, and, ultimately, syn-
cope (Linzer M, Yang E, Estes NA 3rd, et al. Diagnosing syncope. Part I: value
of history, clinical examination and electrocardiography. Clinical efficacy
assessment project of The American College of Physicians [review]. Ann
Intern Med 1997;126:989-96). This explains the rationale for the use of
beta-blockers (to counter the initial adrenergic response and alpha adrener-
gic agents) to prevent the ensuing hypotension (Linzer et al).
Clearly, acute hypovolemia alone is not the sole trigger, because neuro-
cardiogenic syncope may be initiated by emotionally traumatic events (ie,
pain, fear, and anxiety), as well as by stimuli from visceral organs. This might
explain the possible benefits of psychotropic agents (ie, serotonin uptake
antagonists) for some of these patients.
Orthostatic (Postural) Syncope

Orthostatic or posturally induced faints are those associated with
movement from a more gravitationally neutral position (eg, supine
position) to one (eg, upright posture) in which the effects of gravity may
not be adequately balanced by adjustments of peripheral vascular tone
(Fig 2).25,27,28 Consequently, systemic pressure may decrease exces-
sively. If the decrease in systemic pressure is sufficiently severe the
outcome is an insufficient blood supply to the retina and cerebrum (Fig 3).
Resulting symptoms include visual disturbances (gray out or black out),
lightheadedness, dizziness, or even loss of consciousness (ie, orthostatic
syncope). Symptoms resulting from impaired perfusion of muscle tissue
causing symptoms such as pain in the neck and shoulder region
(coat-hanger distribution), lumbar pain, and angina pectoris may also
occur. Typically symptoms resolve on lying down.
The orthostatic faint is most readily identified by a careful medical
history in which the association with postural change is documented (ie,
syncope occurring shortly after moving from a lying or sitting to a

standing position). Healthy individuals often experience a tendency to
orthostatic hypotensive symptoms when they stand up (eg, transient gray
out or black out). However, the individuals most susceptible to frank
syncope associated with postural change tend to be individuals who are
older and frail, and patients with other underlying medical problems
leading to autonomic failure (eg, diabetes, alcoholic neuropathy). In
addition, persons who are dehydrated as a result of illness, hot environ-
ments, prolonged exertion, diuretics, or inadequate fluid intake, and
individuals taking certain commonly prescribed medications such as
diuretics, antidepressants and antipsychotics, antihypertensives, ␤-adren-
ergic blockers, and vasodilators like nitroglycerin and ␣-adrenergic
blockers are also at increased risk.
In patients who are elderly and nonvolume-depleted, in whom central or
peripheral autonomic nervous system diseases have been excluded,
orthostatic hypotension has been reported to be present in about 10%
older than 80 years and about 12% older than 85 years. It is a significant
independent predictor of all-cause mortality.
Diagnosis. Orthostatic syncope can be diagnosed when there is docu-
mentation of orthostatic hypotension associated with syncope or presyn-
cope. For the diagnosis of orthostatic hypotension, arterial BP must be
measured when the patient adopts the standing position after 5 minutes of
lying supine. Abrupt-onset orthostatic hypotension is almost impossible
to assess with conventional measurement of BP with cuff and stetho-
scope, as the BP changes occur very rapidly. Continuous noninvasive BP
measurement on standing is needed to document this abnormality.
For practical diagnostic purposes, orthostatic hypotension is often
defined as a decline in systolic BP of at least 20 mm Hg, a decrease in
diastolic pressure more than 10 mm Hg, or both within 3 minutes of
assuming a standing posture, regardless of whether or not symptoms
occur. If the patient does not tolerate standing for this period, the lowest
systolic BP during the upright position should be recorded. Measurements
should be continued after 3 minutes of standing if BP is still decreasing,
as long as there is no immediate risk of the patient falling.
There are some patients with syncope in whom there is a history
suggestive of impaired orthostatic BP control but in whom measurements
in upright position may be normal. In these patients additional tests after
major provocative stimuli as food ingestion and exercise may be needed
to unmask orthostatic hypotension. Use of a device capable of recording
extended periods of ambulatory BP under daily living circumstances may
be useful, but currently the technology is not optimal.

Identification of the underlying cardiovascular, neurologic, or pharma-
cologic origin is of particular importance for patients with orthostatic
hypotension. At the onset, it is important to identify nonneurogenic
reversible causes of orthostatic hypotension such as volume depletion,
adrenal insufficiency (not common), and the effect of medications
(common). The most frequent drugs associated with orthostatic syncope
are vasodilators and diuretics. Alcohol can also be associated with
orthostatic syncope, not only causing orthostatic intolerance but also
because it can induce autonomic and somatic neuropathy. Elimination of
the responsible drug or offending agent usually is enough to improve
symptoms. Reversible causes often coexist with neurogenic mechanisms
and must be appreciated for optimal treatment, because they may
substantially worsen orthostatic hypotension. Details of the diagnosis of
primary and secondary autonomic disorders will not be discussed further
here, but it is important to remember that secondary autonomic failure
(eg, diabetes, alcohol) is very common.
Treatment. The most extensive experience in treatment of orthostatic
hypotension has been gained for patients with chronic primary autonomic
failure.17,27,28,92,93 Typically, these individuals have structural disorders
with consistent failure of circulatory control and severe symptomatic
orthostatic hypotension. Treatment strategies developed for patients with
autonomic failure have been important for other patients with impairment
of orthostatic BP control.
The initial treatment for patients with orthostatic syncope includes
education regarding factors that can aggravate or provoke hypotension on
assuming the upright posture. These include avoiding sudden head-up
postural change, especially in the morning after being in bed all night;
standing still for a prolonged period of time; or straining during
micturition and defecation. Other less common yet important consider-
ations are high environmental temperature (including hot baths, showers,
and saunas leading to dehydration with vasodilation), large meals
(especially with refined carbohydrates), and severe exertion.
Iatrogenic factors play a role in aggravating symptoms in many patients
with orthostatic syncope. These are often older individuals who are being
treated for a number of commonly occurring comorbidities such as
hypertension, coronary artery disease, and benign prostatic hyperplasia.
Patients are prescribed drugs such as diuretics, vasodilators, and ␤-ad-
renergic and ␣-adrenergic blockers. Each of these can aggravate any
predisposition to hypotension on standing, and in some instances (eg,
excessive diuresis) may induce orthostatic symptoms.

Patients with orthostatic hypotension should be encouraged to have a
high dietary salt intake if there are no contraindications (eg, concomitant
hypertension, heart failure). This is best achieved by the liberal use of salt
at mealtimes, by eating foods with a high salt content, or even with the
use of salt tablets. A target of 8 g of salt per day has been advocated.
Patients are also advised to drink 2 to 2.5 L of fluids every day. The use
of electrolyte-containing beverages (eg, sports drinks) may be more
effective than free water. Elderly patients may have a decreased sense of
thirst and many tend to avoid fluids to prevent urinary frequency or
incontinence. It is particularly important that they be encouraged to
increase fluid intake.94,95
Some patients with autonomic failure exhibit postprandial hypotension.
In these patients, symptoms typically begin about 30 minutes after food
ingestion and can last, even while supine, for up to 3 hours. Carbohy-
drates appear to play a major role in causing hypotension. Alcohol can
exert an additional effect by causing splanchnic vasodilatation. Conse-
quently, these patients may improve by eating frequent smaller meals
with reduced carbohydrate content and avoiding alcohol.
B. J. Gersh: Postprandial hypotension is an extremely common and clinically

unrecognized entity in the elderly. Just think about the elderly patients who
get up in the morning and are prone to orthostatic hypotension. Many are on
cardioactive vasodilator medications which result in a reduction in preload,
and the drugs are often taken with a meal. Thereafter, they may be sedentary
for awhile, and then the telephone rings and they jump up suddenly. Profound
changes in blood pressure may take place leading to syncope, and the
consequences can be minimized by judicious advice and changes in their
schedules in medication (Jansen RW, Lipsitz LA. Postprandial hypotension:
epidemiology, pathophysiology, and clinical management. Ann Intern Med
1995;122:286-95). Dr Lipsitz’s work in this area is of profound clinical
importance; this is summarized in this review, which is well worth reading.
Head-up sleeping at night.

For patients with autonomic failure, head-up sleeping increases the
extracellular fluid volume and improves orthostatic tolerance, with
improvement of symptoms.96 Some have suggested that head-up tilt
reduces renal arterial pressures and promotes renin release with conse-
quent angiotensin II formation and aldosterone release that increases
extracellular fluid and circulating blood. Others have suggested that by
sleeping with the upper part of the body and head tilted upward (head-up
sleeping) there is an increase of the content of extracellular fluid volume

in the lower extremities that leads to an increase in tissue pressure that
prevents venous pooling. In any case, effective head-up sleeping can be
achieved by elevating the head of the bed by 20 to 25 cm.
Physical counter maneuvers.
In most patients with orthostatic intolerance, immobility can worsen
symptoms whereas bending forward, sitting, or moving around can
improve them. On the basis of these observations, several physical
maneuvers that reduce venous pooling have been described. Patients can
be educated to apply one or another of these maneuvers as soon as
symptoms begin.92,93,97 However, for patients with cognitive difficulty,
or who have motor or balance problems, these maneuvers may prove
impracticable.
Leg crossing. Crossing one leg over the other at thigh level while
standing or sitting is an effective and easy maneuver that increases
BP.71,97 The physiologic benefit has been attributed to mechanical
compression of the venous vascular beds in the legs, buttocks, and
abdomen. Leg crossing can be performed casually in public without
drawing attention to the patient’s problem. Muscle tensing during leg
crossing further increases the beneficial effect.
Squatting. Squatting increases venous return rapidly, and produces an
important increase in systolic and diastolic arterial BP.97 It can be used as
an emergency maneuver to prevent loss of consciousness when presyn-
copal symptoms develop rapidly. Bending over as to tie one’s shoes has
similar effects, as does sitting in the knee-chest position, or placing one
foot on a chair while standing. When arising from the squatting position
muscle tensing is advised to prevent triggering hypotension as venous
return decreases.
Bending forward. Lowering the head between the knees is a commonly
known maneuver to fend off a faint. Similarly, lowering the head to heart
level is also a rapid way to enhance cerebral perfusion by decreasing the
hydrostatic column between the heart and brain. Compression of the
abdomen by this or alternative maneuvers98 may also enhance venous
return to the heart, thereby providing an additional benefit.
Arm tugging. Recently, it has been shown that if the hands are clasped
and the arms tugged against each other, an increase in systemic pressure
sufficient to abort a faint may be achieved. This effect appears to be most
effective in younger individuals with greater muscle mass compared with
persons who are older or more frail.
Other measures.
Other measures that decrease dependent pooling that can be used in
patients with orthostatic hypotension include use of various types of

pressure garments.98 In addition, ingestion of a substantial amount of
water or electrolyte-containing beverages is likely to be helpful. After
rapid drinking of about .50 L of water, an increase in BP is apparent
within several minutes. The maximum effect (an increase of 20-30 mm
Hg on seated and standing systolic BP) is reached after approximately
30 minutes and the effects are sustained for about 1 hour. For patients
with autonomic failure the intervention is also effective to combat
postprandial hypotension. Finally, the role of the impedance threshold
valve, a breathing device, remains investigational.
Pharmacologic treatment. When physical maneuvers alone are not
sufficiently effective, pharmacologic interventions may be warranted. The
most important of these are considered here.
Fludrocortisone is a synthetic mineralocorticoid with minimal glucocor-
ticoid effect. It has several pharmacologic effects that can act to improve
orthostatic BP control for patients with autonomic failure.99,100 The most
important effect is an expansion of intravascular and extravascular body
fluid. Other possible effects are a sensitization of vascular receptors to
pressor amines and an increase in fluid content of vessel walls that
increases their resistance to stretching. The starting dose is usually 0.1 mg
once a day, increased by 0.1 mg at 1- to 2-week intervals up to 0.3 mg
daily, if needed. The pressor action is not immediate and takes some days
to be manifest, and the full effect requires a high dietary salt intake. A
weight gain of 2 to 3 kg is reasonably good clue for adequate volume
expansion. Mild dependent edema can be expected. Hypokalemia may
develop within 2 weeks for patients on fludrocortisone, and potassium
supplements are advised.
Midodrine is an agent that is converted to its active metabolite
desglymidodrine after absorption. It acts on ␣-adrenoreceptors to cause
constriction of both arterial resistance and venous capacitance vessels. It
has little in the way of undesirable central nervous system stimulant
effects. Midodrine is administered in doses of 2.5 to 10 mg 3 times daily.
Supine hypertension is a potential side effect, but is rarely severe.
Midodrine is of particular value for patients with severe postural
hypotension and those with autonomic failure.101-104
In selected difficult-to-treat instances, a number of infrequently used
agents have been advocated; however, little is known of their true
effectiveness. Thus, desmopressin may be of value for patients with
nocturnal polyuria, octeoride in those with postprandial hypotension, and
erythropoietin in those with anemia. Such patients need to be referred to
a specialized unit experienced in the use of these interventions.

Cardiac Arrhythmias as the Primary Cause of Syncope:
The Role of EPS Testing
Although cardiac arrhythmias are an important cause of syncope, the real
arrhythmic problem is frequently secondary to other conditions such as in the
case of bradyarrhythmias associated with the various forms of neurally
mediated reflex syncope (eg, vasovagal syncope). Circumstances in which
cardiac arrhythmias are the primary cause of syncope tend to be less frequent,
and are for the most part (but not exclusively) restricted to individuals with
structural heart disease. This section details the most common arrhythmias to
keep in mind when considering arrhythmia as the potential primary cause of
syncope, and reviews the role of the invasive EPS.
Bradyarrhythmias.
Sinus node dysfunction.
Sinus node dysfunction is characterized by any of several types of
rhythm disturbances, including sinus/junctional bradycardia, sinus
pauses, and episodes of supraventricular tachyarrhythmia (most com-
monly paroxysmal AF). Syncope can be caused by severe bradycardia
(eg, sinus pauses or sinus arrest) or may be associated with tachycar-
dia.105,106 In regard to tachycardias, the faint may occur at the beginning
of the episode before blood vessels have had a chance to constrict
adequately, or later as a result of a long asystolic pause occurring after
termination of the tachyarrhythmia (before the sinus pacemaker has an
opportunity to recover) (Fig 10).
For patients with syncope of unknown origin, sinus node dysfunction can
be suggested in the presence of severe sinus bradycardia (heart rates
persistently ⬍ 50 bpm), atrial tachycardias with slow ventricular rates (Fig
11), long asystolic pauses, or episodes of sinoatrial block. The role of EPS for
the diagnosis of sinus node dysfunction as a cause of syncope is limited.107
The tests used to evaluate the function of sinus node (sinus node recovery
time and sinoatrial conduction time) exhibit good specificity, but they are
relatively insensitive and may miss many affected individuals. Furthermore,
with the possible exception of the findings reported by Gann et al108 with
respect to the prognostic value of a very prolonged corrected sinus node
recovery time (CSNRT), they do not provide direction regarding the
appropriate treatment strategy for the patient.
B. J. Gersh: I would reinforce these comments. Tests of sinus node

dysfunction are not sensitive, and in many patients, the implantable loop
recorder may be extremely helpful.

FIG 10. Ambulatory monitor recording in elderly patient with recurrent syncope and falls. Findings
reveal termination of relatively slow supraventricular tachycardia. Subsequently there is long asystolic
pause (⬎6 seconds) indicative of underlying sinus node dysfunction. Patient was treated with both
drugs and pacemaker.
The diagnosis of sinus node dysfunction leading to syncope is best

established when a clear correlation of symptoms with arrhythmia
(usually bradycardia) is documented. Event recorders or ILRs have the
best chance of making the diagnosis by virtue of their long recording
periods. In absence of such correlation, severe sinus bradycardia lower
than 40 bpm, repetitive sinoatrial block, or sinus pauses longer than 3
seconds are highly suggestive of symptomatic sinus node disease.
For patients with sinus node dysfunction and syncope as a result of
bradyarrhythmia, implantation of a pacemaker has been shown to
improve symptoms. In these patients physiologic pacing (atrial or dual
chamber) has been definitively shown to be superior to single chamber
ventricular (VVI) pacing. As these patients usually also have an inappro-
priate sinus node chronotropic response, the use of rate adaptive pacing is
recommended.
For patients with paroxysmal atrial tachycardias associated with sinus
node dysfunction, antiarrhythmic drug therapy may be needed. In such
cases, however, aggravation of susceptibility to bradycardia may be
unmasked by drug treatment and cardiac pacing may become necessary.
AV conduction disorders.
Chronic or paroxysmal AV block can be the cause of syncopal epi-
sodes.109-112 Patients with congenital AV block can be severely symptomatic
early in life or may remain asymptomatic for a long period of time.
Previously, congenital AV block was considered a relatively benign condi-
tion. This is no longer the case. Careful follow-up has demonstrated that such
patients, especially if they have had syncope, have an increased mortality.
Consequently, it is now believed that they should be treated with pacemakers
from an earlier age than had previously been believed. Nonetheless, the
optimum age for pacemaker implantation must be individualized based on
symptom status and lifestyle issues.

FIG 11. A 78-year-old man with a history of atrial fibrillation presented to emergency department (ER)
with several episodes of syncope at home. He was taking ␤-adrenergic blocker for hypertension.
Twelve-lead electrocardiography in ER showed atrial flutter with approximately 9:1 atrioventricular
conduction and ventricular rate of 34 bpm. His atrial flutter was successfully ablated. Patient has
adequate sinus rate for his level of activity and has not yet required pacemaker therapy.
Bradycardia as a result of intermittent AV block is among the more

important causes of syncope. The presence of Mobitz II type second-
degree AV block, third-degree AV block (Fig 12), or alternating left
bundle branch block (LBBB) and right bundle branch block (RBBB) can
reasonably be considered as being diagnostic of the cause of syncope. In
absence of these observations, there are other findings (albeit inferential)
that can suggest that syncope may be a result of AV block. Such
observations include: presence of bifascicular block (LBBB or RBBB
associated with left anterior or left posterior fascicular block); other
intraventricular conduction abnormalities with a QRS duration longer
than 120 milliseconds; or documented Mobitz I second-degree AV block
in older individuals. In the presence of these abnormalities further
investigation should be performed to confirm the diagnosis, but the
suspicion of AV block as the cause is important in directing the
subsequent diagnostic plan.
In the evaluation of patients with suspected paroxysmal AV block, the
conventional 24-hour AECG monitoring has low diagnostic yield because the
chance of recording a symptomatic arrhythmic event during such a brief
recording period is low. An event recorder, and especially an ILR, markedly
extend the recording time and thereby improve the chance of detecting an
abnormality. In any case, AECG monitoring can be considered diagnostic

FIG 12. An 85-year-old woman presented to emergency department with syncope. Twelve-lead
electrocardiography showed complete atrioventricular block and slow escape rhythm. Cardiac
pacemaker therapy is indicated absent readily reversible cause such as severe drug toxicity.
when a correlation between syncope and AV block is obtained. In the

absence of such correlation, the presence of ventricular pauses longer than 3
seconds when the patient is awake, or periods of Mobitz II or third-degree
AV block can be considered diagnostic even in the absence of symptoms.
For patients with syncope of unknown origin and bifascicular block, or
intraventricular conduction defects, an EPS is usually indicated. EPS in these
patients should not only analyze the properties of the conduction system, but
also the inducibility of ventricular arrhythmias. The latter is particularly
important for patients with structural heart disease. The assessment of the
His-Purkinje system during EPS should include the measurement of baseline
HV interval, incremental atrial pacing, and, if baseline study is inconclusive,
pharmacologic provocation with ajmaline (not available in the USA),
procainamide, or disopyramide. An HV (ie, His’ bundle to ventricle conduc-
tion time) interval longer than 100 milliseconds, the presence of second- or
third-degree AV block with progressive atrial pacing, or high-degree AV
block after intravenous administration of ajmaline, disopyramide, or procain-
amide are considered sufficiently diagnostic findings. There remains a
long-standing difference of opinion regarding the significance of HV inter-
vals between 70 and 100 milliseconds in duration.113,114 In such cases, there
may be suggestion that AV conduction disease is the source of the problem
but it would be prudent to seek additional supportive information.1

The absence of abnormal EPS findings for patients with syncopal episodes
and bundle branch block does not exclude an arrhythmia as a possible cause
of syncope. In these patients an ILR may be justified. The ISSUE trial
results55-57 strongly suggest that with prolonged recording periods (often
5-10 months is needed) it is ultimately possible to detect correlation between
arrhythmia (often paroxysmal AV block) and syncope.
Tachyarrhythmias.
Supraventricular tachyarrhythmias.
Syncope is not often a result of SVT. However, lightheadedness (and
occasionally syncope) may occur at the onset of episodes of tachycardia,
before vascular compensation is possible (Fig 13). In others, symptoms occur
at the end of episodes, when an asystolic pause may occur before sinus
rhythm resumes. The recognition of SVT, and especially PSVT, as a cause of
syncope or near syncope has particular importance as most of these
arrhythmias can be successfully cured by transcatheter ablation techniques.
PSVT as a result of AV nodal re-entry or accessory pathway. Except in
those cases in which PSVT is documented in relation to a syncopal
episode, the recognition of an arrhythmic origin in these patients can be
difficult. Most of these patients have no structural heart disease and,
except in those patients with pre-excitation syndrome (eg, Wolff-Parkinson-
White syndrome), the baseline ECG is usually normal. Some patients may
recall experiencing palpitations immediately before loss of consciousness,
however, in many instances there is no recollection of unusual heart
action. In those patients in whom PSVT is suggested, EPS is indicated.
The induction of PSVT, especially if it provokes hypotension or repro-
duces clinical symptoms (this may not happen with the patient lying
supine in the laboratory), can be considered diagnostic. More often than
not, hypotension and symptom reproduction is only achieved if tachycar-
dia is induced with the patient in an upright posture such as on a tilt table.
In any case, if tachycardia with a rapid rate consistent with the potential
for hypotension is observed, transcatheter ablation is the treatment of
choice.
B. J. Gersh: It is my impression that profound hypotension and loss of

consciousness is more common in patients with AV nodal re-entry tachycar-
dia, as opposed to those utilizing an accessory pathway. This may relate to
the very short V-A interval in the former condition which, in turn, results in
atrial contraction against closed AV valve, and possibly the generation of a
vasodepressor reflex, such as occurs with the pacemaker syndrome. On the
other hand, a patient with an accessory pathway may have a much longer V-A
interval, thus preserving atrial contraction at a time when the AV valve is
open. Obviously, another factor determining hypotension is the rate of the

FIG 13. A 43-year-old woman with clinically normal heart presented to electrophysiology clinic for
evaluation of recurrent syncope. Because her syncope was occasionally preceded by nausea,
shortness of breath, mild chest pain, and dizziness, origin of her syncope had been considered
vasovagal. However, episode of supraventricular tachycardia at rate of approximately 220 bpm was
documented on event monitor immediately before one of her episodes of syncope (baseline recording
showed normal in sinus rhythm at top). Electrophysiologic study showed typical orthodromic
atrioventricular re-entry tachycardia using left posterior septal accessory pathway, which was
successfully ablated. She has remained syncope-free postablation.
tachycardia (Wood KA, Drew BJ, Scheinman MM. Frequency of disabling

symptoms and supraventricular tachycardia. Am J Cardiol 1997;79:145-9).
Patients with evidence of pre-excitation on baseline ECG have addi-

tional clinical risks that may contribute to syncope (or even sudden death
on rare occasion). In these patients, apart from paroxysmal AV re-entrant
tachycardias, episodes of AF with very fast ventricular response (as a
result of conduction over the accessory connection) can cause not only
syncopal episodes but may also induce ventricular fibrillation leading to
sudden death. In these patients, radiofrequency catheter ablation is clearly
the treatment of choice.
AF and atrial flutter. Syncopal episodes may also develop for patients
susceptible to paroxysmal AF. As noted earlier, syncope most often
occurs at the beginning of the episode. However, it may also occur at the
end of the episode (especially for patients with concomitant sinus node
dysfunction) when there may be a long asystolic pause before a regular
heart rhythm resumes.
Syncope with paroxysmal AF is most likely to occur in older patients
who often have an inadequate or delayed vasomotor response at the

beginning of the arrhythmia. However, it is important to keep in mind
certain special situations in which paroxysmal AF can cause acute
hemodynamic deterioration leading to syncope. These high-risk situations
include patients who are dehydrated or exposed to hot environments, and
individuals with LV outflow obstruction (eg, HOCM, severe aortic
stenosis).
Patients with atrial flutter have many of the same risks for syncope, as
do those with AF. However, during exertion, patients with atrial flutter are
at particularly high risk of very rapid ventricular rates developing (eg, 1:1
AV conduction), and hypotension may ensue. Further, it has been
reported that the use of class IC antiarrhythmic drugs in patients with
atrial flutter, and even with AF, can slow the cycle length of the atrial
tachyarrhythmia. Paradoxically, this slowing may reduce the degree of
physiologic block offered by the AV node. The result is 1:1 AV
conduction. Although the atrial rate may be slower than before drug, the
net ventricular rate is much faster as a result of 1:1 AV transmission. The
result may be a sufficiently fast ventricular rate to cause severe hemody-
namic compromise and syncope. Thus, when using antiarrhythmic drugs
for treatment of atrial flutter (or similar atrial ectopic tachycardias) it is
essential to try and avoid the risk of setting the stage for 1:1 AV
conduction by concomitant administration of drugs that slow AV con-
duction, such as ␤-blockers or calcium channel blockers. In the case of
many forms of atrial flutter and atrial ectopic tachycardias, transcatheter
ablation may be the preferred treatment strategy to eliminate susceptibil-
ity to the underlying arrhythmia.
Ventricular tachycardias.
VT most often occurs for patients with structural heart disease,
especially ischemic heart disease and dilated cardiomyopathies.1,112
However, approximately 10% to 15% of patients with VT have no overt
structural heart disease (Fig 14).
VT associated with ischemic heart disease or dilated cardiomyopathies.
Ventricular tachyarrhythmias have been reported to be responsible for
syncope in up to 20% of patients referred for EPS (Fig 15). Tachycardia
rate, status of LV function, and the efficiency of peripheral vascular
constriction determine whether the arrhythmia will induce syncopal
symptoms.
Nonsustained VT is a common finding during AECG monitoring,
especially for patients with ischemic heart disease and dilated cardiomy-
opathies. Consequently, such a finding during the assessment of a patient
with syncope has not in the past been considered very helpful in the
absence of documented concomitant symptoms. However, this view is

FIG 14. A 36-year-old man with clinically normal heart presented for evaluation of recurrent syncope.
Holter monitor showed frequent ventricular premature complexes (VPCs) and nonsustained ventricular
tachycardia (VT), which correlated well with his symptoms. Twelve-lead electrocardiography showed
VPCs and non-sustained VT, consistent with right ventricular outflow tract tachycardia origin. He
underwent electrophysiologic study and his ventricular arrhythmias were successfully ablated. He has
remained symptom-free thereafter.
changing, especially for patients with ischemic heart disease and severely
diminished LV function (ie, ejection fractions ⬍ 35%), given the
Multicenter Unsustained Tachycardia Trial (MUSTT) and Multicenter
Automatic Defibrillator Implantation Trial 2 (MADIT2) results. These
studies suggest that such patients have a high mortality, and that
implantable cardioverter defibrillator (ICD) therapy can be effective in
diminishing mortality risk. Therefore, in the absence of other causes of
syncope, the potential role of nonsustained VT raises concern. In fact, on
the basis of the combined findings of MUSTT, the Sudden Cardiac
Death–Heart Failure Trail (SCD-HEFT), and MADIT 2,115,116 it can be
argued that ICD therapy may be warranted without undertaking an EPS in
patients with heart disease and poor ejection fractions. Further, it would
seem reasonable to assume that such patients who present with syncope
are likely to be at even higher risk.117-122
The appropriate approach to be taken when syncope occurs for patients
with severe underlying LV dysfunction as a result of dilated cardiomy-
opathy has been less clear than is the case for ischemic disease.122
Consideration of prophylactic placement of an ICD is becoming increas-
ingly frequent in this setting, although the appropriateness of this strategy

FIG 15. A 52-year-old man with medical history of myocardial infarction and angina presented for
evaluation of recurrent syncope. Echocardiogram showed essentially normal left ventricular function.
Telemetry recordings in-hospital revealed multiple episodes of ventricular tachycardia associated with
syncope but without any symptoms of palpitations or other sense of abnormal heart action.
has until recently been uncertain. Completion of the SCD-HEFT study

supports this approach. The 2002 ACC/American Heart Association/
North American Society of Pacing Electrophysiology (NASPE) guideline
for pacemaker and antiarrhythmia device implantation provide a class IIB
indication for empiric ICD implantation in this setting irrespective of the
cause of the heart disease.123
Idiopathic VTs and syncope.
1. Right ventricular outflow tract tachycardia. Idiopathic right ventricu-
lar (RV) outflow tract tachycardia (RVOFT) is the most frequent type
of idiopathic VT (Fig 14).124,125 It represents approximately 80% of
all idiopathic VT, and about 10% of all patients who are evaluated for
VT. Syncope is not a common presentation, but can occur. Palpitations
as a result of transient or sustained arrhythmia are more common. By
definition, patients with RVOFT have no evident structural heart
disease, but some minor abnormalities in the RV outflow tract have
been described on the basis of MRI techniques. As the morphology of
this tachycardia can be similar to tachycardia observed for patients
with a more worrisome condition called arrhythmogenic RV dysplasia
(ARVD), it is important that the second of these 2 conditions be
excluded in each case.
RVOFT can be present at any age, but it is most frequently seen
between the second and fourth decade of life. Typically RVOFT
can be terminated by ATP administration, but this is only a
temporizing step. The arrhythmia will recur if a more permanent
solution is not provided, and in this regard transcatheter ablation
has proved highly effective. Baseline ECG findings in these
patients usually demonstrate a normal QRS. Some patients have
frequent premature ventricular beats with the same morphology of
tachycardia (ie, a QRS that appears to have a LBBB appearance but
relatively narrow, with a vertical or rightward frontal axis).

Tachycardia in these patients can manifest as episodes of nonsus-
tained VT, repetitive monomorphic VT interrupted by short periods
of in sinus rhythm, or episodes of paroxysmal sustained VT.
2. Idiopathic LV outflow tract tachycardia. Idiopathic LV outflow tract
tachycardia is less common than but analogous to RVOFT.124 It
exhibits subtle variations in QRS morphology during tachycardia,
consisting mainly of the presence of an R wave in V1 and V2 leads.
It has been shown, by intracavitary mapping techniques, that in
these patients tachycardia most often originates at LV outflow tract
(Fig 4). In patients with LV outflow tract tachycardia, as in patients
with RVOFT, syncope can be a clinical manifestation of the
arrhythmia but such a presentation is rare. Palpitations are a much
more likely initial presentation. Once again, transcatheter ablation
is the preferred treatment option.
M. M. Scheinman: As described by the authors, a wide variety of idiopathic

ventricular tachycardias have been described. These occur in patients
without evident cardiac disease. Patients with left ventricular outflow tract VT
(LVOT) may have the VT focus islolated to areas beneath the aortic valve or
in association with the inflow tract.
Most recent studies have emphasized localization of these foci to the aortic
valve cusps. Apparently, myocardial muscle fibers may extend into the base
of the aortic valve cusps and may serve as the nidus for LVOT (Kanagaratnam
L, Tomassoni G, Schweikert R, et al. Ventricular tachycardias arising from the
aortic sinus of valsalva: an under-recognized variant of left outflow tract
centricular tachycardia. J Am Coll Cardiol 2001;37:1408-14). Aortic cusp VT
is amenable to ablation, but care must be used to avoid damage to the
coronary artery ostia.
3. Idiopathic left posterior fascicular tachycardia. This is the most

frequent form of idiopathic LV tachycardia. Although it can be present
at any age, idiopathic LV fascicular tachycardia is most often seen for
patients between the second and fourth decade of life, and predomi-
nates in male patients. During EPS, the arrhythmia can be induced and
terminated by programmed ventricular stimulation. Usually it can also
be terminated by verapamil infusion (although long-term oral therapy
is not generally effective for prevention of recurrences).
The most frequent form of presentation is as paroxysmal VT, with a
QRS pattern of RBBB and left-axis deviation. Occasionally, similar
RBBB but with right-axis deviation can be seen, suggesting that
re-entry arises from left anterior fascicle. Clinically, these patients may
be asymptomatic, but when they have symptoms, usually they expe-

rience palpitations, dizziness, or syncope. Baseline ECG does not
show specific abnormalities. As in RVOFT, the prognosis in these
patients is generally benign, but syncope can occur. Consequently,
patients who are symptomatic should be treated. In most of these
patients, transcatheter ablation can be very effective.
4. Arrhythmogenic right ventricular dysplasia. ARVD is a hereditary
disease, in which RV myocardium is replaced by fatty infiltration of
varying degrees of severity. In some cases the LV is affected as
well.125-127 The clinical picture ranges from patients who are asymp-
tomatic, to symptoms secondary to ventricular arrhythmias (some-
times life-threatening) or RV failure. For patients with ARVD,
ventricular arrhythmias are usually triggered by adrenergic stimula-
tion. Syncope related to exercise should bring this diagnosis to mind.
ARVD must be considered in those patients with syncope of
unknown origin with family history of premature sudden death or
unexplained syncope, or when the baseline ECG shows certain
suggestive abnormalities. The most important of these abnormalities
include: ⑀ waves (a finding of a small late signal analogous to late
potentials in ischemic heart disease, found in the ST segment, most
often in V1 lead); low amplitude and localized prolongation of the
QRS complex in leads V1 to V3; or inverted T waves in right
precordial leads in the absence of RBBB. In addition, some of these
patients have frequent ventricular premature beats with a pattern of
LBBB suggesting a RV site of origin.
Once suggested, the diagnosis of ARVD can be confirmed by
imaging techniques, especially MRI. These images, especially if done
in a cine mode, can show dyskinetic areas, dilatation or depressed RV
function, and fatty replacement in the RV wall. On the downside,
moving image MRI (cine-MRI) is expensive, not universally available,
and perhaps overly sensitive. Consequently, especially in view of
concerns regarding overdiagnosis by MRI, recently developed criteria
for the ARVD registry have tended to focus on clinical and ECG
abnormalities, and de-emphasize MRI findings. It has also been
suggested that ARVD may also masquerade as a dilated cardiomyop-
athy.
An optimum treatment strategy for patients with ARVD and syncope
has not been fully established. In general, effectiveness of drug therapy
is not well proven, and long-term transcatheter ablation success is
limited by virtue of the potential for many regions of the heart to be
affected and thereby become arrhythmogenic sites. Consequently, in
those patients with syncope in which the presence of malignant

ventricular arrhythmias can be demonstrated (either during a sponta-
neous recording or induced at EPS) an ICD is the prudent treatment
approach currently.
5. Long QT syndromes (primary, secondary). Long QT syndromes may
be a primary disorder128-130 or secondary to other factors (most
commonly various drugs) (Table 5).131 Drug-induced long QT syn-
dromes are far more common than primary long QT, and new drugs
capable of inducing the problem are being identified each year. The
result is an increasing risk of iatrogenic syncope or even sudden death
secondary to polymorphous VT (torsades de pointes) (Fig 16). Given
the substantial public health hazard associated with drug-induced long
QT, physicians must be very attentive to the risk. Eliminating the
offending agent is the key to treatment.
The primary long QT syndromes comprise a group of disorders,
generally familial in nature, and characterized by a prolongation of
ventricular repolarization (ie, long QT interval). These conditions
predispose to life-threatening polymorphous VT (torsades de pointes).
Syncope is one of the most common clinical presentations, but
malignant ventricular arrhythmias can lead to sudden death.
Recently there has been considerable interest in the molecular
biology of long QT syndromes and related conditions (eg, Brugada
syndrome). Two main forms of clinical (phenotypic) presentation have
been described for long QT syndrome. The most common is the
so-called Romano-Ward syndrome, which has an autosomal dominant
pattern of transmission and the second one, Jervell and Lange-Neilsen
syndrome, is inherited in an autosomal recessive pattern. Multiple
gene mutations have been identified for the Romano-Ward syndrome
and it is likely that many more will be identified in coming years.
These mutations appear to correlate with different patterns of clinical
presentation.
Although the most characteristic alteration at baseline ECG is an
abnormal prolongation of QT interval, it has been recognized that
there are some patients who have normal baseline QT interval
duration. However, in many of these cases other abnormalities can be
observed, such as T-wave alternans or abnormalities in the morphol-
ogy of T wave. Polymorphous VTs develop in these patients in the
form of torsades de pointes that can degenerate to ventricular fibril-
lation.
Clinical manifestations may consist of syncopal episodes or sudden
death. Syncope tends to begin at an early age, usually between 5 and
15 years. In the most common form of long QT syndrome, syncopal

TABLE 5. Drugs commonly associated with prolongation of the QT interval*
Antiarrhythmic agents
Class IA
• Quinidine
• Procainamide
• Disopyramide
Class III
• Sotalol
• Ibutilide
• N-acetylprocainamide
• Dofetilide
• Amiodarone (relatively low risk)
Antianginal agents†
• Bepridil
Psychoactive/Antidepression agents
• Phenothiazines
• Thioridazine
• Amitriptyline
• Imipramine
Antibiotics
• Erythromycin
• Pentamidine
• Fluconazole
Nonsedating antihistamines
• Terfenadine†
• Astemizole
Miscellaneous
• Cisapride†
• Arsenic
• Droperidol
*Only the more commonly used agents are listed here.
†
Removed from market in the United States.
episodes are usually triggered by adrenergic stimulus, such as exercise

or stressful situations. However, other forms of long QT syndrome
may result in torsades being triggered by bradycardia.
For patients with syncope of unknown origin, the presence of long QT
syndrome must be considered when there are abnormalities of repolar-
ization, or family history of long QT syndrome, syncope, or sudden death.
There are several findings that, when present, seem to further enhance the
risk of sudden death. These are: the presence of previous cardiac arrest;
syncope at young age; family history of sudden death; a very prolonged
QTc interval (⬎600 milliseconds); and the presence of the recessive form
of long QT with hearing impairment (Jervell and Lange-Neilsen syn-
drome).
For patients with long QT syndrome, a first syncopal episode, and no
other risk factors, treatment with ␤-blockers is considered appropriate.

FIG 16. Electrocardiographic telemetry recordings from 70-year-old woman who had been treated
with quinidine and digoxin for paroxysmal atrial fibrillation. Patient presented with history of recurrent
falls during past month. Recordings reveal atrial fibrillation/flutter, relatively long QT interval (see first
QRS complex on upper trace), and polymorphous ventricular tachycardia compatible with diagnosis
of torsades de pointes. Quinidine was discontinued and rate control alone instituted. Patient has since
remained asymptomatic.
However, if bradycardia-triggered torsades are implicated, the additional

use of an implanted cardiac pacemaker is justified. In patients who, in
addition to syncope, have other risk factors, or those who have syncope
recurrences in spite of ␤-blockers, implantation of an ICD is indicated.
6. Brugada syndrome. In 1992, a syndrome was described in which the
initial cohort consisted of 8 patients who had experienced recurrent
episodes of aborted sudden death without any apparent structural heart
disease and in whom there was a distinct pattern on ECG that was
associated with life-threatening ventricular tachycardia.130,132,133 Fur-
ther observations have resulted in this entity being recognized as a
hereditary disease, characterized by an ECG pattern of RBBB and ST
elevation in V1 to V3. These individuals are at risk of episodes of
polymorphous VT developing. In addition it has been observed that
this characteristic pattern of ECG can change over time in the same
patient from a strictly normal ECG to the full characteristic pattern. In
those patients with suggested Brugada syndrome who have an appar-
ently normal ECG, intravenous administration of a class I antiarrhyth-
mic drug (eg, procainamide) can provoke the typical QRS-ST segment
changes, thereby confirming the diagnosis.
For patients with syncope of unknown origin, the diagnosis of
Brugada syndrome should be suggested when there is a family history
of established Brugada syndrome, sudden death or unexplained syn-
cope, or when baseline ECG shows the typical pattern. Although the
risk of sudden death for patients who are asymptomatic with Brugada

syndrome is not well known, it is generally accepted that those patients
who have had syncope or an aborted sudden death are at increase risk
of sudden death. Currently available antiarrhythmic drugs are not
useful in preventing arrhythmia recurrences in Brugada syndrome.
Patients who are symptomatic or those with a strong family history of
premature sudden death should be treated with an ICD.
7. Hyperthrophic obstructive cardiomyopathy. Syncope may occur and
be a presenting feature in conditions in which there is fixed or dynamic
obstruction to LV outflow such as valvular aortic stenosis or
HOCM.134 Symptoms are often provoked by physical exertion, but
may also develop if an otherwise benign arrhythmia should occur (eg,
AF). Furthermore, even relatively slow VTs may cause syncope in
such cases.
The basis for the faint is, in part, inadequate blood flow as a result
of the mechanical obstruction. However, especially in the case of
valvular aortic stenosis, ventricular mechanoreceptor-mediated brady-
cardia and vasodilatation is thought to be an important contributor. In
obstructive cardiomyopathy, neural reflex mechanisms may also play
a role, but occurrence of atrial tachyarrhythmias (particularly AF) or
VT (even at relatively modest rates) may trigger syncope.135
B. J. Gersh: Sudden cardiac death in patients with hypertrophic cardiomy-

opathy is a complex and multifactorial entity, but an event that often and
unfortunately occurs in young, previously relatively asymptomatic patients. A
hypotensive response to exercise, which may in part be due to vasodepres-
sor mechanisms, is an important risk factor, but in patients with hypertrophic
cardiomyopathy and syncope, irrespective of the exercise test results, there
has to be a definitive diagnosis if an implantable cardioverter/defibrillator is
not to be placed.
Syncope with exercise. Syncope may occur during or after exercise.

The former raises concern regarding underlying structural heart disease
(eg, myocardial ischemia, HOCM), whereas syncope after exertion is
often a result of a variant of the neurally mediated reflex faints. Exercise
testing is usually of limited use in the evaluation of syncope unless the
events are clearly exertionally related by history. Only in rare instances
does exercise testing uncover certain helpful findings (eg, rate-dependent
AV block, exertionally related tachyarrhythmias, severe degrees of
chronotropic incompetence, excessively rapid heart rate deceleration after
exercise) or the exercise-associated variant of neurally mediated syncope.

For the most part, obtaining ECG documentation during spontaneous
symptoms (if feasible at all) necessitates an extended period of cardiac
monitoring using Holter monitors or event recorders. The latter systems
can be used in a continuous-loop mode for patients whose symptoms
preclude responding appropriately when the episode begins. Recently, the
introduction of ILRs (Reveal, Medtronic Inc, Minneapolis, Minn) has
added a powerful new diagnostic tool. The ability of these devices to be
programmed for automatic storage of rhythm strips in which heart rates
fall outside a predetermined range is particularly advantageous.
Role of EPS in the syncope evaluation. The role of invasive EPS in the
evaluation of the patients with syncope is primarily to confirm a clinical
suggestion (derived from the initial evaluation) that a primary cardiac
rhythm abnormality or conduction disturbance is likely the cause of
syncope in a given individual.136-142 This is accomplished by demon-
strating that an arrhythmia substrate or clinically significant conduction
disturbance is present and, in the absence of other explanation, inferring
a relationship between the abnormality and syncope. However, absent
clinical suspicion, EPS is not a reliable screening tool.136 This is
particularly true for patients without structural heart disease.
One of the distinct advantages of EPS is the potential to identify and
cure certain arrhythmias during the same session. In this regard, trans-
catheter ablation using radiofrequency energy is now an integral part of
the capabilities of most EPS laboratories, and can be used to cure many
arrhythmias that may cause syncope (eg, various rapid heart rhythms
associated with Wolff-Parkinson-White syndrome or other forms of
ventricular pre-excitation, other accessory pathway mediated tachycar-
dias, PSVT as a result of AV node re-entry).
EPS in specific clinical conditions. This section is designed to provide
only a very brief overview of the role EPS may play in defining the basis
of syncope in certain patients. Further details and a more complete set of
references can be found in the ESC Syncope Guidelines,1 in a recent
monograph reviewing the evaluation and treatment of syncope,112 and in
the syncope literature.136-146
EPS assessment of sinus node function should include assessment of
sinus automaticity (heart rate, sinus node recovery time, intrinsic heart
rate). Other available but clinically less effective measures of sinus node
function include sinoatrial conduction time and sinus node refractoriness.
Sinus node recovery time is usually corrected for baseline heart rate
(CSNRT). Sinus node recovery time longer than 1500 to 1720 millisec-
onds or CSNRT longer than 525 milliseconds is considered abnormal,
with sensitivity of 50% to 80% and specificity of more than 95%,

respectively, for detecting sinus node dysfunction. The prognostic value
of a prolonged sinus node recovery time is not certain. However, patients
with a CSNRT of longer than 800 milliseconds have a risk 8 times higher
of syncope than patients with a CSNRT below this value. The ESC
Syncope Task Force panel advocated that, in the presence of a sinus node
recovery time longer than 2.0 seconds or CSNRT longer than 1 second,
sinus node dysfunction may be reasonably surmised to be the cause of
syncope if no other diagnostic candidates remain.
Transient high-degree AV block should be considered for patients with
syncope in the presence of bundle branch block. Extended AECG
monitoring is often needed to document transient high-degree AV
block.137-139 EPS is used mainly to evaluate intra-His and infra-His
conduction (ie, the portion of the conduction system below the AV node)
in these patients. A prolonged HV interval or a split His potential (rare)
is associated with a higher risk of AV block developing. The progression
rate to AV block is 2% to 4% for patients with normal (⬍55 milliseconds)
or slightly prolonged (55-60 milliseconds) HV intervals, and increases to
21% and 24% when the HV interval is 70 or more milliseconds and 100
or more milliseconds, respectively. Incremental atrial pacing and phar-
macologic provocation with antiarrhythmic drugs (eg, procainamide) are
often used to increase the diagnostic yield of EPS when HV interval is
borderline.
Development of intra-His or infra-His block during incremental atrial
pacing (ie, pacing the atria at progressively more rapid rates to stress the
adequacy of the AV conduction system) is highly predictive of impending
AV block. Progression to complete AV block occurs in 30% to 40% of
these patients during 2 to 4 years of follow-up.112-114 However, its
sensitivity is low (⬍10%). In patients with moderate prolongation of the
HV interval, pharmacologic stress testing of the His-Purkinje system may
be used to assess His-Purkinje system reserve by acute intravenous
administration of class IA agents (eg, procainamide [10 mg/kg]). A
significant increase of HV interval duration (ie, a resultant HV ⬎ 100
milliseconds or the precipitation of second- or third-degree intra-His or
infra-His block) after pharmacologic challenge with or without incremen-
tal atrial pacing is highly predictive of subsequent spontaneous AV block
during follow-up. Pooled data (n ⫽ 333) show that pharmacologic stress
was able to elicit susceptibility to high-degree AV block in 15% of
patients studied. Spontaneous AV block developed in approximately 68%
of these patients during follow-up for a period of 2 to 5 years.
The ESC Syncope Task Force panel offered the opinion that, for
patients with syncope and bifascicular block, EPS is highly sensitive in

identifying patients with intermittent or impending high-degree AV
block.1 This block is likely the cause of syncope in most cases, but not of
the high mortality. The latter seems to be mainly related to underlying
structural heart disease and ventricular tachyarrhythmias. Unfortunately,
EPS does not seem to be very effective for identifying patients at high
mortality risk. In this regard, the finding of inducible ventricular arrhyth-
mias should be interpreted with caution.136
PSVT should be suspected for patients with syncope and palpitations
(and in some instances even without palpitations) in the absence of
structural heart disease. EPS with and without pharmacologic challenge
(usually individually titrated doses of parenteral isoproterenol, atropine,
or both) may be used to both facilitate induction of PSVT and evaluate the
hemodynamic effects of tachycardia. In either case, it may be necessary
to position the patient in an upright posture (eg, using a tilt table) to
recognize the full hemodynamic impact of the arrhythmia.
VT may present as syncope with or without palpitations or other
accompanying symptoms. In cases in which spontaneous VT has been
documented, EPS may prove helpful as a guide to ablation therapy, or as
a means of assessing effectiveness of drug treatment, or as baseline
information for programming an ICD. In cases in which VT is suggested,
but a spontaneous arrhythmia has not been documented, there is reason-
able concern regarding EPS sensitivity and specificity in various clinical
settings and with differing stimulation protocols. Generally speaking,
programmed electrical stimulation is thought to be a sensitive tool
(90%-95%) in patients with chronic ischemic heart disease (previous
myocardial infarction) and susceptibility for spontaneous monomorphic
VT. Programmed electrical stimulation has a low predictive value for
patients with nonischemic dilated cardiomyopathy and most primary
electrical disturbances in the setting of a relatively normal heart structure
(eg, long QT syndrome).
B. J. Gersh: In many patients, the electrophysiologic study may be the final

“court of appeal,” but there is no perfect goal standard other than correlation
of symptoms with or without the documentation of an arrhythmia (Klein GJ,
Gersh BJ. Electrophysiological testing: the final court of appeal for the
diagnosis of syncope? Circulation 1995;92:1332-5).
The predictive value of EPS remains controversial for patients with

unexplained syncope and nonischemic dilated cardiomyopathy. In 14
patients with nonischemic dilated cardiomyopathy, unexplained syncope,

and negative EPS, the incidence of appropriate ICD therapy is approxi-
mately 50% at 2-year follow-up, similar to that for patients with a
documented cardiac arrest as a result of ventricular tachyarrhythmias
(42%). The relapse of syncope or presyncope in these patients is primarily
because of ventricular fibrillation. Finally, ICD therapy in these patients
has been shown to be associated with improved survival.
In summary, EPS is generally a helpful diagnostic test for patients with
unexplained syncope but who have coronary artery disease and markedly
decreased cardiac function. Its use is more questionable for patients with
nonischemic dilated cardiomyopathy or valvular heart dis-
ease.112,136,140,141 EPS is of little diagnostic value for patients with
normal hearts, absent a documented (or at least strongly suspected)
supraventricular or ventricular tachyarrhythmia.
Structural Cardiac and Pulmonary Causes of Syncope

Structural cardiac, vascular, or pulmonary diseases are not very often
the principal cause of syncope. More often, the relationship of structural
cardiopulmonary abnormalities to syncope events is indirect, by virtue of
increased susceptibility to tachy or bradyarrythmias, or hypotension of
other cause (eg, low cardiac output, acute myocardial infarction). In many
of these cases a neural reflex mechanism contributes to the faint, for
example, syncope associated with acute myocardial ischemia, severe
aortic stenosis, or pulmonary hypertension. In any case, syncope associ-
ated with severe structural heart disease is potentially serious, and
warrants immediate and thorough evaluation. Consideration needs to be
given to hospitalizing these patients on an ECG monitored cardiac station
for their diagnostic evaluation, and often for initiation of therapy. As a
rule, treatment is best directed at amelioration of the specific structural
lesion or its consequences.
Risk stratification. Many different forms of structural cardiac and
pulmonary disease may be associated with syncope. The most common
are ischemic heart disease, nonischemic cardiomyopathies, and pulmo-
nary hypertension.142 A clinical prediction rule for risk stratification of
patients with syncope has been developed and uses a composite outcome
of having cardiac arrhythmias as a cause of syncope or death (or cardiac
death) within 1 year of follow-up. Four variables were identified and
included age older than 45 years, history of congestive heart failure,
history of ventricular arrhythmias, and abnormal ECG (other than
nonspecific ST changes). Arrhythmias or death within 1 year occurred in
4% to 7% of patients without any of the risk factors and progressively

increased to 58% to 80% for patients with 3 or more factors. The critical
importance of identifying cardiac causes of syncope is that many of the
arrhythmias and other cardiac diseases are now treatable with drugs,
devices, or both.
Most important conditions. Excluding syncope as a result of arrhyth-
mias complicating structural heart disease, probably the most common
cause of syncope directly attributable to structural disease is that which
occurs in conjunction with acute myocardial ischemia or infarc-
tion.112,142,143 Other relatively common acute medical conditions associ-
ated with syncope include pulmonary embolism, acute aortic dissection,
and pericardial tamponade. The basis of syncope in these conditions is
multifactorial, including both the hemodynamic impact of the specific
lesion and neurally mediated reflex effects leading to inappropriate
bradycardia and peripheral vascular dilation. The latter is especially
important in the setting of acute ischemic events, exemplified by the
atropine-responsive bradycardia and hypotension often associated with
inferior wall myocardial infarction.
Syncope is of considerable concern when it is associated with condi-
tions with fixed or dynamic obstruction to LV outflow (eg, aortic stenosis,
HOCM, prosthetic valve malfunction).144 In such cases symptoms are
often provoked by physical exertion, but may also develop if an otherwise
benign arrhythmia should occur (eg, AF). The basis for the faint is, in
part, inadequate blood flow as a result of the mechanical obstruction.
However, especially in the case of valvular aortic stenosis, neural reflex
disturbance of vascular control is an important contributor to hypotension.
In HOCM, with or without LV severe outflow obstruction, neural reflex
mechanisms may also play a role. However, in HOCM, the occurrence of
atrial tachyarrhythmias (particularly AF) or VT (even at relatively modest
rates) are important causes of syncopal events.134,135
Much less frequent causes of syncope directly resulting from structural
cardiovascular disease include LV inflow obstruction for patients with
mitral stenosis or atrial myxoma, RV outflow obstruction, and right-to-
left shunting secondary to pulmonic stenosis or pulmonary hypertension.
The mechanism of the faint may once again be multifactorial, with
hemodynamic, arrhythmic, and neurally mediated origins in need of
evaluation.
Vascular steal syndromes are very rarely the basis for syncope.145
Subclavian steal syndrome,145 albeit very uncommon, is perhaps the most
important of these conditions and can reasonably be incorporated in the
context of cardiopulmonary disease. Subclavian steal may occur on a
congenital or acquired basis. Low pressure within the subclavian artery as

a result of a stenosis in its most proximal portion near the aorta causes
retrograde flow to occur in the ipsilateral vetebral artery (especially
during upper arm exercise). The result is a diminution of cerebral blood
flow. Syncope is typically associated with upper extremity exercise.
Direct corrective angioplasty or operation is usually feasible and effec-
tive. Other forms of vascular steal, particularly within the cranium, are
recognized as potential causes of syncope, but are virtually impossible to
diagnose.
Evaluation. Apart from identifying the nature and severity of any
underlying cardiopulmonary disease in a patient with syncope, the cause
of the faint needs special consideration. The same disease may induce
syncope by different mechanisms. For example, acute myocardial infarc-
tion may initiate VTs or ventricular asystole (particularly in the case of
inferior wall infarction). Similarly, faints during exertion in the setting of
severe valvular aortic stenosis can be a result of inadequate cardiac
output, or an inappropriate vascular response resulting in transient
systemic hypotension. The latter is thought to be the more important.
Syncope for patients with HOCM can also be the consequence of several
mechanisms. Hypotension may again be a result of direct obstruction to
LV ejection, but transient ventricular and atrial tachyarrhythmias and
neural reflex causes are probably more common. In essence, it is crucial
to consider whether structural cardiopulmonary disease is present in every
patient with syncope.
Treatment. The treatment of syncope in the setting of structural
cardiopulmonary disease is dependent on the nature and severity of the
underlying structural abnormalities, and the apparent mechanism (ie,
arrhythmia, hemodynamic abnormality) leading to syncope. In an emer-
gency situation the underlying structural disturbance must be treated first
(eg, acute myocardial infarction, severe aortic stenosis). Referral to a
facility experienced with and capable of dealing with the problem is
recommended. In nonemergent circumstances, treatment of the structural
disease should be considered if feasible (eg, aortic valve replacement in
case of severe aortic stenosis). However, in most cases it is reasonable to
turn attention to determining the cause of syncope (eg, VT in dilated
cardiomyopathy) and focusing on its treatment (eg, antiarrhythmic drugs,
ICD).
In syncope associated with acute myocardial ischemia, pharmacologic
therapy and/or revascularization is clearly the appropriate strategy in most
cases. Similarly, when syncope is closely associated with surgically
addressable lesions (eg, valvular aortic stenosis, atrial myxoma, congen-
ital cardiac anomaly), a direct corrective approach is often feasible. By

contrast, when syncope is caused by certain difficult-to-treat conditions
such as primary pulmonary hypertension or restrictive cardiomyopathy, it
is often impossible to ameliorate the underlying problem adequately.
It should be emphasized that for patients with structural cardiopulmo-
nary disease, additional factors could participate in the triggering of a
syncope event. For instance, electrolyte disturbances, increasing heart
failure, or worsening oxygenation may all facilitate arrhythmia initiation
leading to syncope. Hypokalemia occurring as a side effect of diuretic
therapy is one of the most common scenarios to keep in mind. It is, of
course, of crucial importance to recognize these triggering factors as their
reversal can eliminate the symptoms.
Cerebrovascular Disorders, Neurologic Disease, and
Syncope
Cerebrovascular conditions and neurologic disease are only rarely the
cause of true syncope, although they may cause periods of transient
impairment of consciousness that can be mistaken for syncope (eg,
epilepsy). Consequently, although neurologic testing is rarely indicated in
the diagnostic evaluation of the cause of syncope, if neurologic signs are
present a neurologist should be consulted and may be the appropriate
person to carry on the investigation. For example, patients with Parkin-
sonism, suspected seizures, or those patients thought to have primary
autonomic failure or epilepsy should be referred to a neurologist.146-148
Similarly, if there is concern that a neurologic issue may have triggered
a fall that mimicked a syncopal event, speciality consultation is recom-
mended.149
Transient ischemic attacks. TIAs are too often considered to be part of
the differential diagnosis of the causes of syncope. With very rare
exception, TIAs do not cause loss of consciousness.1 Carotid artery
distribution TIAs are characterized by transient focal neurologic deficits
without loss of consciousness. In carotid TIAs, neurologic deficits such as
hemiparesis or aphasia predominate whereas consciousness is normal.
Only TIAs causing ischemia to a very large proportion of the cortex can
impair consciousness, and even these do not usually result in complete
loss of consciousness. Vertebrobasilar TIAs are more likely to cause
unconsciousness. However, once again, they may be distinguished from
true syncope by the usual concomitant presence of other focal neurologic
deficits such as hemianopsia or ataxia.
Subclavian steal. Syncope provoked by physical exercise of the arms
points to a steal phenomenon (often termed “subclavian steal syndrome”).
Apart from measuring BP in both arms, ultrasound studies are indicated

to search for a steal syndrome. As a cause of syncope, subclavian steal is
quite rare. However, it is a reversible lesion, and consequently one worth
bearing in mind.
Migraine. In individuals who experience migraines, syncope of an
orthostatic or vasovagal nature occurs statistically more often than in
persons who do not have migraines. These attacks do not occur at the
same time as the migraine attacks, however, and so they can usually be
distinguished without additional diagnostic confusion. A rather rare type
of vertebrobasilar migraine may cause impaired consciousness, but
usually these events last longer than does a true syncope.
Autonomic failure. Patients who have suggestions of autonomic failure
can benefit from ancillary neurologic testing.147 In such patients, the faint
may occur through an orthostatic hypotension mechanism and through
postexercise hypotension. In autonomic failure the neurologic dysfunc-
tion is often not restricted to BP regulation, so history taking should
include sexual function (impotence), sweating (dry skin, sometimes with
patches of compensatory hyperhidrosis), bladder function (both inconti-
nence and retention), gastointestinal function (delayed stomach emptying,
diarrhea), and pupillary function (blurred vision).
History taking is also important to distinguish among the 3 groups of
autonomic failure: primary autonomic failure encompasses degenerative
diseases such as multiple system atrophy, pure autonomic failure, and
autonomic failure in the context of Parkinson’s disease147; secondary
autonomic failure concerns damage to the autonomic nervous system in
the context of other diseases such as diabetes, kidney, and liver failure,
and alcoholism; autonomic failure occurs as a side effect of medication–
likely culprits are antidepressants, antihypertensives, vasodilators, and
␤-adrenergic receptor blocking drugs. In this drug-induced group, auto-
nomic failure may be restricted to orthostatic hypotension.
The differential diagnosis of autonomic failure is complex. When the
more obvious causes, such as diabetes and drug effects, have been
excluded, an expert opinion should be sought.
Hyperventilation syndrome. This name was (and sometimes still is)
used for attacks of anxiety together with a variety of somatic symptoms,
such as shortness of breath, a tight sensation in the chest, and tingling
fingers. It was built on the theory that hyperventilation induced hypocap-
nia, which induced cerebral vasoconstriction, leading to cerebral hypoxia
and the symptoms. However, subsequent studies have showed that the
attacks also occurred in the absence of hypocapnia. Thus, the presumed
pathophysiologic theory has been proved to be incorrect. This also means
that the hyperventilation provocation test aiming for symptom recognition

is dubious. Attacks of a similar nature fall under the term panic attacks in
the psychiatric nomenclature.
Epilepsy. Epilepsy is a result of aberrant functioning of neural net-
works. Because epilepsy is a disorder of the cerebral cortex, it is logical
that generalized forms of epilepsy, affecting the cortex bilaterally, can
cause unconsciousness (Table 3). However, in some forms of epilepsy,
consciousness is altered but not lost. The best-known examples of this
latter type are complex partial seizures in adults and absence epilepsy in
children.
As discussed earlier, although epilepsy may cause TLOC it is not part
of the differential diagnosis of the causes of syncope. Thus, for patients
with syncope, EEGs (and other neurologic tests, for that matter) are not
indicated.
Conditions that Mimic Syncope

Certain medical conditions may cause a real or apparent loss of
consciousness that might appear to be syncope, but which is in fact not a
true syncope (Table 2). To sort these out, it is essential to recall that
syncope is defined as a self-limited TLOC caused by global cerebral
hypoperfusion. That final element of the definition is crucial to under-
standing why many conditions that may affect consciousness are not
categorized as syncope.
Conditions in Which There is an Apparent TLOC
Whether conditions listed below actually mimic syncope depends
largely on the quality of the account of the events obtained by the
physician. This section deals with conditions, in which loss of conscious-
ness is not present but may appear to be so. These include cataplexy,
psychiatric causes, TIAs, and drop attacks.
Cataplexy. Cataplexy occurs for all practical purposes only in the
context of the disease narcolepsy. Cataplexy refers to loss of muscle tone
as a result of emotions, particularly laughter. In contrast to vasovagal
syncope, triggers such as pain, fear, and anxiety are not important. Startle
may provoke cataplexy, but over a series of attacks it is never the only
trigger. According to most textbooks, patients suddenly slump to the
ground with complete paralysis. Partial attacks are, however, more
common. These can be restricted to dropping of the jaw and sagging or
nodding of the head. Attacks may develop slowly enough to allow the
patient to stagger and break the fall before he comes to the floor.
Complete attacks look like syncope in that the victim is unable to respond
at all, although he or she is completely conscious and aware of what is

going on. The presence of consciousness can in fact only be assessed later
through the absence of amnesia. Although narcolepsy may start with
cataplexy, this is rare. Faced with laughter-related attacks, physicians
should ask for the presence of excessive daytime sleepiness, narcolepsy’s
main symptom.
Psychiatry and syncope. Although the term “psychogenic syncope”
may be found in the literature, a better term is “psychogenic pseudosyn-
cope.”1 In any event, the diagnosis of a psychiatric origin for an apparent
(not true syncope) loss of consciousness episode relies on careful
exclusion of other causes rather than on a positive set of diagnostic
criteria. In this regard, if it is possible to witness and record an episode,
a psychogenic pseudosyncope state will be unassociated with changes in
BP or heart rate.149-153 Further, these conditions are often characterized
by a frequency (eg, many episodes per day) far in excess of what might
be expected for a true fainter.
Hyperventilation. Hyperventilation simply refers to breathing more
than metabolic needs warrant. This leads to a series of physiologic events,
including hypocapnia, constriction of cerebral vessels, and reduced
cerebral blood flow. As such, the act of hyperventilation could certainly
contribute to syncope. Lightheadedness and tingling fingers or toes may,
with good reason, be seen as physiologic manifestations of breathing too
much, and do not necessarily indicate psychologic factors.
Within the term “hyperventilation syndrome” is the assumption that
hyperventilation is evoked by stress, and that the resulting overbreathing
and hypocapnia cause the symptoms. However, this concept has been
called into question by experiments in which hyperventilating subjects
were supplied with extra carbon dioxide to make them normocapnic. The
findings suggested that many symptoms were in fact not linked to
hypocapnia.
Syncope in patients with psychiatric conditions. Nonpsychiatrists may
tend to label symptoms of patients with a psychiatric history as psycho-
genic. The 3 psychiatric disorders resembling syncope are conversion
reactions, factitious disorders, and malingering. However, other patients
with major psychiatric conditions such as bipolar disorder, depression,
and schizophrenia take medications that can cause autonomic failure
leading to syncope, or other syncope-prone conditions such as long QT
syndrome. The main culprits are phenothiazines, tricyclic antidepressives,
and monoamine oxidase inhibitors.
Drop attacks. The term “drop attack” refers to a phenomenon in which
there is a very short-lasting attack in which a patient suddenly falls
without any warning. These attacks tend to occur in middle-aged people,

and more often in women. The attacks are too brief for patients to be
certain whether there was any loss of consciousness, but most likely there
was none. Commonly, the victim remembers hitting the ground often
experiencing some degree of minor physical injury. As a result of this
recollection, any loss of consciousness would have to have been ex-
tremely short, if it had occurred at all.
In-Hospital Versus Out-of-Hospital Evaluation and

Treatment and the Syncope Evaluation Unit or
Team
In-Hospital Versus Out-of-Hospital Evaluation
Loss of consciousness inevitably incorporates risk of personal injury,
and depending on the circumstance, potential risks to others (eg, if a
noncompliant fainter resumes driving a commercial vehicle or piloting an
aircraft before treatment is proven effective). However, the key factor
determining need for in-hospital evaluation is most often uncertainty
regarding the fainter’s immediate mortality risk (which is largely deter-
mined by the severity of underlying heart disease).1 To some extent,
particularly when antiarrhythmic drugs are involved, the issue of whether
initiation of certain treatments require hospital monitoring also plays a
role.
Hospitalization Strongly Recommended
Several prognostic markers may assist in identifying patients with
syncope who should be considered for in-hospital evaluation. The
presence of underlying structural heart disease and abnormalities of the
baseline ECG are important indicators suggesting cardiac syncope. A less
frequent, but crucial, prognostic marker is a family history of sudden
death because certain malignant ventricular arrhythmias can have a
genetic basis (eg, long QT syndrome, Brugada syndrome, familial
cardiomyopathies).
Hospitalization Desirable on Case-by-Case Basis
These situations generally involve patients in whom the risk of death is
thought to be low, and there is low likelihood of a near-term recurrence
precipitating injury or harm to the public health.
Hospitalization not Necessary
For patients with isolated or rare syncopal episodes, who have no
evidence of structural heart disease and a normal baseline ECG, the

probability is high that the event was of a neurally mediated origin. These
patients have a low mortality risk (although recurrences and physical
injury are possible), and generally their evaluation can be completed
entirely on an out-patient basis. However, in those cases in which
in-hospital evaluation is not deemed necessary, cautionary advice regard-
ing avoidance of unnecessary driving, risky occupational and/or avoca-
tional exposure should be provided.
The Syncope Evaluation Unit or Team

Currently, strategies for assessment for syncope vary widely among
physicians and among hospitals and clinics.154-156 More often than not,
the evaluation and treatment of syncope is not organized in an effective
manner. The result is considerable center-to-center (and even within a
given center) variability in the frequency with which various diagnostic
tests are applied, the distribution of apparent attributable causes of
syncope arrived at by attending clinicians, and the proportion of patients
with syncope in which the diagnosis remains unexplained.4 Assuming the
status quo of the syncope evaluation is left as is, diagnostic and treatment
effectiveness is unlikely to improve substantially. Even implementation
of the published syncope management guidelines is likely to be diverse,
uneven in application, and of uncertain benefit. However, with the
development of increasingly more organized approaches to syncope
evaluation, overall outcomes in terms of diagnostic precision and cost-
effectiveness of diagnosis and treatment will improve.155,156
In Newcastle, United Kingdom, a multidisciplinary approach to refer-
rals with syncope or unexplained falls has been developed, and serves as
a useful model for development of syncope evaluation units or teams
elsewhere.154 All patients attend the same facility (with access to
cardiovascular equipment, investigations, and trained staff) but are
evaluated by a geriatrician, cardiovascular physician, or neurologist as
deemed appropriate on the basis of the individual’s presentation (eg,
TLOC vs fall). The availability of various specialists on a regular basis
each week permits problems to be evaluated from several perspectives.
The opportunity to make a correct diagnosis in a timely manner is much
better in such a circumstance than can be expected by the conventional
unorganized approach. Recently, this group showed that activity at the
acute hospital at which the day case syncope evaluation facility was based
experienced a marked reduction of hospital bed-days for the International
Classification of Diseases code categories comprising syncope and
collapse compared with peer teaching hospitals.
Syncope evaluation units or teams will differ from hospital to hospital,

and the unit’s administration might similarly differ depending on which
individuals are most interested in the problem (eg, neurologist, cardiol-
ogist, internist). However, individuals comprising the unit should bring, at
a minimum, skills in cardiology, circulatory physiology, cardiac electro-
physiology, neurology, and geriatric medicine. In addition, access to other
specialists such as psychiatry, physiotherapy, occupational therapy, ENT,
and clinical psychology is recommended. Core equipment for the syncope
evaluation facility should include surface ECG recording, phasic BP
monitoring, tilt-table testing equipment, external and ILR event recorder
systems, 24-hour ambulatory BP, 24-hour AECG, and autonomic func-
tion testing. The facility should also have access to intracardiac EPS,
stress testing, cardiac imaging, CT MRI/head scans, and EEG. Current
experience suggests that careful audit of the syncope unit activity and
performance will quickly justify the initial resource allocation, both in
terms of more efficient patient care and a magnet for additional referrals.
Conclusion
This article has attempted to provide an overview of the causes,
evaluation, and treatment of syncope. Only by establishing an accurate
diagnosis can the patient’s prognosis be established and effective treat-
ment begun.
The principal lesson is to develop an organized approach to the
classification of the causes of syncope, and bear in mind which of these
is the most likely in a given clinical setting. In this regard, neurally
mediated reflex syncope, orthostatic syncope, and cardiac arrhythmias
account for approximately 60% to 70% of the recognized causes of
syncope. Further, in many cases there may be multiple possible causes,
and distinguishing among them in an effort to find a sole cause may be
both impossible and incorrect.
The initial patient evaluation (particularly the medical history) is the
key to finding the most likely diagnosis for patients with syncope. A
strategy for the initial evaluation, and especially for taking and
assessing the history, has been detailed. On the basis of findings in this
initial step, subsequent carefully selected diagnostic tests can be
chosen. Syncope is very common. Consequently, random screening
tests, apart from not being very effective, can result in a huge medical
expense for the patient and society. A key goal of this review has been
to develop an evaluation and treatment pathway that minimizes waste
of resources and focuses attention on the most efficient means for
making an accurate diagnosis.

B. J. Gersh: This is a very comprehensive monograph by Dr Benditt and his
colleagues, which deals with the frequent and often frustrating clinical
dilemma of recurrent syncope. The evaluation of syncope reinforces the need
for basic clinical skills, because the history, plus the physical examination to
exclude structural heart disease, provide the highest diagnostic yield. The
implantable loop recorder is an important adjunct to our diagnostic arma-
mentarium. The majority of patients with syncope have a neurocardiogenic or
related cause, and although recurrences are common, much can be done
with patient education and commonsense practical advice. Drugs and
pacemakers may be effective, but only after other measures have been tried.
In patients with structural heart disease and syncope, this was an ominous
symptom and the implantable cardioverter/defibrillator is often lifesaving; but
this remains an area where the pacemaker, antiarrhythmic drugs, and
nonpharmacologic ablative techniques play an important role in addition to
correction, if possible, of the underlying cardiac structural disease.
M. M. Scheinman: This renowned group of authors has put together an

exemplary review of current evaluation and treatment for patients with
syncope. There is an excellent focus on the use of clinical criteria for
diagnoses. The review is authoritative, very complete, and rigorously honest
in the evaluation of current treatment options. They do not ride favorite
hobbyhorses. The bibliography is complete and the work constitutes an
important reference chapter for those interested in syncope. I have already
made fruitful use of this most important work.
Acknowledgment: The authors wish to thank the many members of the

ESC Syncope Task Force (Chairman Michele Brignole, MD, Lavagna, Italy),
who, through multiple conversations, have inevitably contributed importantly
to ideas presented here. We also thank Barry L. S. Detloff, BA, and Wendy
Markuson, for assistance in preparing the manuscript.
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David G. Benditt, MD, J. Gert Van Dijk, MD, PhD,

Abstract: Syncope is a syndrome consisting of a rela-

152 Curr Probl Cardiol, April 2004

yncope is a syndrome consisting of a relatively short period of

Curr Probl Cardiol, April 2004 153

intervention. Absent spontaneous reversal of symptoms, the condition is not

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TABLE 2. Causes of conditions commonly misdiagnosed as syncope

example, Table 3 summarizes the main differences between syncope and

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B. J. Gersh: Among a large group of patients undergoing tilt table testing,

M. M. Scheinman: The authors raise an important issue with regard to the

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The goals of this review are to summarize the principal causes of

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B. J. Gersh: Although the mortality of neurocardiogenic and idiopathic

One-third of patients with syncope have symptom recurrences by 3

Causes of Syncope: Classiﬁcation

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B. J. Gersh: In a large series of patients from Switzerland, a suspected cause

Neurally mediated reflex faints comprise a number of related clinical

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Cardiac arrhythmias may cause faints if the heart rate is excessively

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B. J. Gersh: Drop attacks have traditionally been considered a symptom of

Pathophysiology and Clinical Presentation

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mL/100 g of brain tissue/minute, representing about 12% to 15% of

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B. J. Gersh: My own clinical impression is that syncope in the elderly is often

Strategy for the Syncope Evaluation

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The Initial Evaluation

Taking the Medical History in Patients with Syncope

• Is loss of consciousness attributable to syncope or not?

In this section we highlight certain of the most important clinical features

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Important Components of the Medical History in

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B. J. Gersh: The importance of obtaining observations from eye witnesses is

Symptoms noticed after the event. Note confusion, palpitations, dura-

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Additional Elements of the Initial Evaluation

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B. J. Gersh: I strongly agree with the approach suggested by the authors.

Structural heart disease.

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circumstances. However, the ESC Syncope Task Force publication

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Speciﬁc Causes of Syncope: Evaluation and

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B. J. Gersh: The location in which syncope occurs may be helpful.

Laboratory studies: Basic autonomic assessment.

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