MD Consult: Books: Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular ...

Page 1 of 9

Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular Medicine, 8th ed.

Copyright © 2007 Saunders, An Imprint of Elsevier

CHAPTER 37 – Hypotension and Syncope

Hugh Calkins Douglas P. Zipes

CHAPTER OUTLINE
Definition, 975
Classification, 975
Vascular Causes of Syncope, 975
Cardiac Causes of Syncope, 978
Neurological Causes of Apparent Syncope, 978
Metabolic Causes of Apparent Syncope, 978
Relationship Between Prognosis and Cause of Syncope,
978
Evaluation, 978
History and Physical Examination, 978
Diagnostic Tests, 979
Approach to the Evaluation of Patients with Syncope, 981
Management, 982
Neurally Mediated Syncope, 983
References, 983
DEFINITION
Syncope is a sudden transient loss of consciousness and postural tone with spontaneous
recovery. Loss of consciousness results from a reduction of blood flow to the reticular activating
system located in the brain stem and does not require electrical or chemical therapy for reversal.
The metabolism of the brain, in contrast to that of many other organs, is exquisitely dependent on
perfusion. Consequently, cessation of cerebral blood flow leads to loss of consciousness within
approximately 10 seconds. Restoration of appropriate behavior and orientation after a syncopal
episode is usually immediate. Retrograde amnesia is uncommon. Syncope is an important clinical
problem because it is common, costly, often disabling, may cause injury, and may be the only
warning sign before sudden cardiac death (see Chap. 36) . [1] Patients with syncope account for 1
percent of hospital admissions and 3 percent of emergency department visits. Elderly persons
have a 6 percent annual incidence of syncope (see Chap. 75) . Surveys of young adults have
revealed that up to 50 percent report a prior episode of loss of consciousness; most of these
episodes are isolated events that never come to medical attention. The Framingham Study, in
which biennial examinations were performed on 7814 individuals, reported the incidence of a first
report of syncope to be 6.2/1000 person-years follow-up. [2] Patients who experience syncope also
report a markedly reduced quality of life. The prognosis of patients with syncope varies greatly with
the diagnosis. In the Framingham Study, for example, participants with syncope, including those
with syncope of unknown origin, had increased mortality compared with participants without
syncope. The highest mortality was observed among those with a cardiac cause of syncope. In

mk:@MSITStore:I:\Cardiology\Braunwald's%20Heart%20Disease%20A%20Textbook%... 12/18/2008
MD Consult: Books: Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular ... Page 2 of 9

contrast, the subgroup of participants with neurally mediated syncope (including orthostatic
hypotension and medication-related syncope) did not experience increased mortality. [2]

Classification

The causes of apparent syncopal episodes can be separated initially into two groups—true
syncope, in which the transient loss of consciousness results from cerebral hypoperfusion, and
nonsyncopal conditions, with real or apparent loss of consciousness from other causes. [1] Table
37-1 shows the differential diagnosis of syncope and nonsyncopal conditions, which are indicated
by an asterisk. Vascular causes of syncope are most common, followed by cardiac causes. Among
cardiac causes of syncope, arrhythmias are most common. The importance of considering
nonsyncopal conditions when evaluating a patient with apparent loss of consciousness cannot be
underestimated. These nonsyncopal conditions include conditions in which consciousness is lost
as a result of metabolic disorders, epilepsy, or alcohol, as well as conditions in which
consciousness is only apparently lost (i.e., conversion reaction). These psychogenic causes of
syncope are now being recognized with increased frequency.

TABLE 37-1 -- Causes of Syncope

Vascular
Anatomical
Vascular steal
syndromes

Orthostatic
Autonomic insufficiency
Idiopathic
Volume depletion
Drug- and alcohol-
induced

Reflex-mediated
Carotid sinus hypersensitivity
Neurally mediated syncope
Glossopharyngeal syncope
Situational (cough, sneeze, swallow, micturition,
postprandial)

Cardiac
Anatomical
Obstructive cardiac valvular disease
Aortic dissection
Atrial myxoma
Pericardial disease, tamponade
Hypertrophic obstructive

mk:@MSITStore:I:\Cardiology\Braunwald's%20Heart%20Disease%20A%20Textbook%... 12/18/2008
MD Consult: Books: Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular ... Page 3 of 9

cardiomyopathy
Myocardial ischemia, infarction
Pulmonary embolus
Pulmonary hypertension

Arrhythmias
Bradyarrhythmias
Sinus node dysfunction, bradycardia
Atrioventricular block
Tachyarrhythmias
Supraventricular arrhythmias
Ventricular arrhythmias (including long-QT and Brugada
syndromes)

Implanted pacemaker or implantable cardioverter-defibrillator malfunction

Neurological and cerebrovascular [*]

Arnold-Chiari malformation
Migraine
Seizure (partial complex, temporal lobe)
Vertebrobasilar insufficiency/transient ischemic
attack

Metabolic [*]
Drugs, alcohol
Hyperventilation
(hypocapnia)
Hypoglycemia
Hypoxemia

Psychogenic syncope [*]

Anxiety, panic
disorder
Somatization
disorders

Syncope of unknown origin

* Disorders resembling syncope.

Although knowledge of the common conditions that can cause syncope is essential and allows the
clinician to arrive at a probable cause of syncope in most patients, it is equally important to be
aware of several of the less common but potentially lethal causes of syncope, such as the long-QT

mk:@MSITStore:I:\Cardiology\Braunwald's%20Heart%20Disease%20A%20Textbook%... 12/18/2008
MD Consult: Books: Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular ... Page 4 of 9

syndrome, arrhythmogenic right ventricular cardiomyopathy, Brugada syndrome, idiopathic

ventricular fibrillation, catecholaminergic polymorphic ventricular tachycardia, short-QT syndrome
(see Chap. 9) , hypertrophic cardiomyopathy (see Chap. 65) , and pulmonary emboli (see Chap.
72) . [3] [4] [5] [6] [7] [8] [9] [10] It is also important to recognize that distribution of the causes of syncope
varies with age.

In young individuals, neurally mediated syncope is the most common, but is an unusual type of
syncope in elderly persons. [11] Common causes of syncope in elderly persons include orthostatic
hypotension, postprandial hypotension, medication, aortic stenosis (see Chap. 62) , carotid sinus
hypersensitivity, and bradyarrhythmias (e.g., sick sinus syndrome, heart block; see Chap. 35 ).

Vascular Causes of Syncope

Vascular causes of syncope, particularly reflex-mediated syncope and orthostatic hypotension, are
the most common causes, accounting for at least one third of all syncopal episodes. [1] [2] [11] In
contrast, vascular steal syndromes are exceedingly uncommon causes of syncope.

Orthostatic Hypotension

When a person stands, 500 to 800 ml of blood is displaced to the abdomen and lower extremities,
resulting in an abrupt drop in venous return to the heart. This drop leads to a decrease in cardiac
output and stimulation of aortic, carotid, and cardiopulmonary baroreceptors, which trigger a reflex
increase in sympathetic outflow. As a result, heart rate, cardiac contractility, and vascular
resistance increase to maintain a stable systemic blood pressure on standing. Orthostatic
hypotension, which is defined as a 20-mmHg drop in systolic blood pressure or a 10-mmHg drop in
diastolic blood pressure within 3 minutes of standing, results from a defect in any portion of this
blood pressure control system. Orthostatic hypotension can be asymptomatic or associated with
symptoms such as lightheadedness, dizziness, blurred vision, weakness, palpitations,
tremulousness, and syncope. These symptoms are often worse immediately on arising in the
morning or after meals or exercise. Syncope that occurs after meals, particularly in elderly people,
can result from a redistribution of blood to the gut. A decline in systolic blood pressure of about 20
mmHg approximately 1 hour after eating has been reported in up to one third of elderly nursing
home residents. Although usually asymptomatic, it can result in lightheadedness or syncope.

Drugs that cause volume depletion or result in vasodilation are the most common cause of
orthostatic hypotension ( Table 37-2 ). Elderly patients are particularly susceptible to the
hypotensive effects of drugs because of reduced baroreceptor sensitivity, decreased cerebral
blood flow, renal sodium wasting, and an impaired thirst mechanism that develops with aging.
Orthostatic hypotension can also result from neurogenic causes, which can be subclassified into
primary and secondary autonomic failure. [12] Primary causes are generally idiopathic, whereas
secondary causes are associated with a known biochemical or structural anomaly or are seen as
part of a particular disease or syndrome. There are three types of primary autonomic failure (see
Chap. 89) . Pure autonomic failure (Bradbury-Eggleston syndrome) is an idiopathic sporadic
disorder characterized by orthostatic hypotension, usually in conjunction with evidence of more
widespread autonomic failure, such as disturbances in bowel, bladder, thermoregulatory, and
sexual function. Patients with pure autonomic failure have reduced supine plasma norepinephrine
levels. Multiple system atrophy (Shy-Drager syndrome) is a sporadic, progressive, adult-onset
disorder characterized by autonomic dysfunction, parkinsonism, and ataxia in any combination.
The third type of primary autonomic failure is Parkinson disease with autonomic failure. A small
subset of patients with Parkinson disease may also experience autonomic failure, including
orthostatic hypotension. In addition to these forms of chronic autonomic failure is a rare acute
panautonomic neuropathy. This neuropathy generally occurs in young people and results in
widespread severe sympathetic and parasympathetic failure, with orthostatic hypotension, loss of

mk:@MSITStore:I:\Cardiology\Braunwald's%20Heart%20Disease%20A%20Textbook%... 12/18/2008
MD Consult: Books: Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular ... Page 5 of 9

sweating, disruption of bladder and bowel function, fixed heart rate, and fixed dilated pupils.

TABLE 37-2 -- Causes of Orthostatic Hypotension

Drugs
Diuretics
Alpha-adrenergic blocking drugs—terazosin (Hytrin), labetalol
Adrenergic neuron blocking drugs—guanethidine
Angiotensin-converting enzyme inhibitors
Antidepressants
Monoamine oxidase inhibitors
Alcohol
Diuretics
Ganglion-blocking drugs—hexamethonium, mecamylamine
Tranquilizers—phenothiazines, barbiturates
Vasodilators—prazosin, hydralazine, calcium channel
blockers
Centrally acting hypotensive drugs—methyldopa, clonidine

Primary Disorders of Autonomic Failures

Pure autonomic failure (Bradbury-Eggleston
syndrome)
Multisystem atrophy (Shy-Drager syndrome)
Parkinson disease with autonomic failure

Secondary Neurogenic Causes

Aging
Autoimmune disease
Guillain-Barré syndrome, mixed connective tissue disease, rheumatoid
arthritis
Eaton-Lambert syndrome, systemic lupus erythematosus

Carcinomatosis autonomic neuropathy

Central brain lesions
Multiple sclerosis, Wernicke encephalopathy
Vascular lesions or tumors involving the hypothalamus and
midbrain

Dopamine β-hydroxylase deficiency

Familial hyperbradykininism
General medical disorders—diabetes, amyloidosis, alcoholism, renal failure

mk:@MSITStore:I:\Cardiology\Braunwald's%20Heart%20Disease%20A%20Textbook%... 12/18/2008
MD Consult: Books: Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular ... Page 6 of 9

Hereditary sensory neuropathies, dominant or recessive

Infections of the nervous system—human immunodeficiency virus infection, Chagas' disease,
botulism, syphilis
Metabolic disease—vitamin B12 deficiency, porphyria, Fabry disease, Tangier disease
Spinal cord lesions
Adapted from Bannister SR (ed): Autonomic Failure, 2nd ed. Oxford, Oxford University Press, 1988, p
8.

Postural orthostatic tachycardia syndrome (POTS) is a milder form of chronic autonomic failure
and orthostatic intolerance characterized by the presence of symptoms of orthostatic intolerance,
an increase of 28 beats/min or more in heart rate, and absence of a significant change in blood
pressure within 5 minutes of standing or upright tilt. [13] POTS appears to result from a failure of the
peripheral vasculature to vasoconstrict appropriately under orthostatic stress. POTS can also be
associated with syncope related to neurally mediated hypotension (see later).

Reflex-mediated Syncope

There are many reflex-mediated syncopal syndromes ( Table 37-3 ). In each case, the reflex is
composed of a trigger (the afferent limb) and a response (the efferent limb). This group of reflex-
mediated syncopal syndromes has in common the response limb of the reflex, which consists of
increased vagal tone and a withdrawal of peripheral sympathetic tone and leads to bradycardia,
vasodilation and, ultimately, hypotension, presyncope, or syncope. What distinguishes these
causes of syncope are the specific triggers. For example, micturition syncope results from
activation of mechanoreceptors in the bladder, defecation syncope results from neural inputs from
gut wall tension receptors, and swallowing syncope results from afferent neural impulses arising
from the upper gastrointestinal tract. The two most common types of reflex-mediated syncope,
carotid sinus hypersensitivity and neurally mediated hypotension, are discussed later.

TABLE 37-3 -- Differentiating Syncope Caused by Neurally Mediated Hypotension,

Arrhythmias, and Seizures
Neurally Mediated
Parameter Hypotension Arrhythmia Seizure
Demographics, Female > male Male > female gender Younger age (<45 yr)
clinical setting gender
Younger age (<55 yr) Older age (>54 yr) Any setting
More episodes (more Fewer episodes (less than
than two) three)
Standing, warm room, During exertion, or supine
emotional upset
Family history of
sudden death
Premonitory Longer duration (>5 Shorter duration (<6 sec) Sudden onset or brief
symptoms sec) aura (déjà vu, olfactory,
gustatory, visual)

mk:@MSITStore:I:\Cardiology\Braunwald's%20Heart%20Disease%20A%20Textbook%... 12/18/2008
MD Consult: Books: Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular ... Page 7 of 9

Palpitations Palpitations less common

Blurred vision
Nausea
Warmth
Diaphoresis
Lightheadedness
Observations Pallor Blue, not pale Blue face, no pallor
during the event
Diaphoretic Incontinence can occur. Frothing at the mouth
Dilated pupils Brief clonic movements can Prolonged syncope
occur. (duration > 5 min)
Slow pulse, low blood Tongue biting
pressure
Incontinence—may Horizontal eye deviation
occur
Brief clonic Elevated pulse and blood
movements—may pressure
occur
Incontinence more likely
[*]

Tonic-clonic movements
if grand mal
Residual Residual symptoms Residual symptoms Residual symptoms
symptoms common uncommon (unless prolonged common
unconsciousness)
Prolonged fatigue Aching muscles
common (>90%)
Oriented Disoriented
Oriented Fatigue
Headache
Slow recovery
* May be observed with any of these causes of syncope but more common with
seizures.

NEURALLY MEDIATED HYPOTENSION OR SYNCOPE.

The term neurally mediated hypotension or syncope (also known as neurocardiogenic,

vasodepressor, and vasovagal syncope and as “fainting”) has been used to describe a common
abnormality of blood pressure regulation characterized by the abrupt onset of hypotension with or
without bradycardia. Triggers associated with the development of neurally mediated syncope are
those that reduce ventricular filling or increase catecholamine secretion. [1] [14] They include the
sight of blood, pain, prolonged standing, a warm environment or hot shower, and stressful
situations. In these types of situations, patients with this condition experience severe
lightheadedness, syncope, or both. It has been postulated that these clinical phenomena result

mk:@MSITStore:I:\Cardiology\Braunwald's%20Heart%20Disease%20A%20Textbook%... 12/18/2008
MD Consult: Books: Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular ... Page 8 of 9

from a paradoxical reflex that is initiated when ventricular preload is reduced by venous pooling.
This reduction leads to a reduction in cardiac output and blood pressure, which is sensed by
arterial baroreceptors. The resultant increased catecholamine levels, combined with reduced
venous filling, lead to a vigorously contracting volume-depleted ventricle. The heart itself is
involved in this reflex by virtue of the presence of mechanoreceptors, or C-fibers, consisting of
nonmyelinated fibers found in the atria, ventricles, and pulmonary artery. It has been proposed that
vigorous contraction of a volume-depleted ventricle leads to activation of these receptors in
susceptible individuals. These afferent C-fibers project centrally to the dorsal vagal nucleus of the
medulla, leading to a “paradoxical” withdrawal of peripheral sympathetic tone and an increase in
vagal tone, which, in turn, causes vasodilation and bradycardia. The ultimate clinical consequence
is syncope or presyncope.

Not all neurally mediated syncope results from the activation of mechanoreceptors. In humans, it is
well known that the sight of blood or extreme emotion can trigger syncope. These observations
suggest that higher neural centers can also participate in the pathophysiology of vasovagal
syncope. In addition, central mechanisms can contribute to the production of neurally mediated
syncope.

CAROTID SINUS HYPERSENSITIVITY.

Syncope caused by carotid sinus hypersensitivity results from stimulation of carotid sinus
baroreceptors, located in the internal carotid artery above the bifurcation of the common carotid
artery. Carotid sinus hypersensitivity is diagnosed by applying gentle pressure over the carotid
pulsation just below the angle of the jaw, where the carotid bifurcation is located. Pressure should
be applied for 5 to 10 seconds. It is important to perform carotid sinus massage in both the supine
and upright positions. The main complications associated with performing carotid sinus massage
are neurological. Because of this, carotid sinus massage should be avoided in patients with prior
transient ischemic attacks, strokes within the past 3 months, and carotid bruits.

A normal response to carotid sinus massage is a transient decrease in the sinus rate, slowing of
atrioventricular (AV) conduction, or both. Carotid sinus hypersensitivity is defined as a sinus pause
longer than 3 seconds in duration and a fall in systolic blood pressure of 50 mmHg or more. The
response to carotid sinus massage can be classified as cardioinhibitory (asystole), vasodepressive
(fall in systolic blood pressure), or mixed. Carotid sinus hypersensitivity is detected in
approximately one third of elderly patients who present with syncope or after falls. [1] [15] It is
important to recognize, however, that carotid sinus hypersensitivity is also commonly observed in
asymptomatic elderly patients. [16] Thus, the diagnosis of carotid sinus hypersensitivity should be
approached cautiously after excluding alternative causes of syncope. Once diagnosed, dual-
chamber pacemaker implantation is recommended for patients with recur-rent syncope or falls
resulting from carotid sinus hypersensitivity. [17] [18]

Cardiac Causes of Syncope

Cardiac causes of syncope, particularly tachyarrhythmias and bradyarrhythmias, are the second
most common causes, accounting for 10 to 20 percent of syncopal episodes (see Chap. 35) .
Ventricular tachycardia (VT) is the most common tachyarrhythmia that can cause syncope.
Supraventricular tachycardia can also cause syncope, although the great majority of patients with
supraventricular arrhythmias present with less severe symptoms, such as palpitations, dyspnea,
and lightheadedness. Bradyarrhythmias that can result in syncope include sick sinus syndrome as
well as AV block. Anatomical causes of syncope include obstruction to blood flow, such as a
massive pulmonary embolus, an atrial myxoma, or aortic stenosis.

Neurological Causes of Apparent Syncope

mk:@MSITStore:I:\Cardiology\Braunwald's%20Heart%20Disease%20A%20Textbook%... 12/18/2008
MD Consult: Books: Libby: Braunwald's Heart Disease: A Textbook of Cardiovascular ... Page 9 of 9

Neurological causes of apparent syncope, including migraines, seizures, Arnold-Chiari

malformations, and transient ischemic attacks, are surprisingly uncommon, accounting for less
than 10 percent of all cases of syncope. Most patients with an apparent neurological cause of
syncope have seizures rather than true syncope.

Metabolic Causes of Apparent Syncope

Metabolic causes of syncope are rare, accounting for less than 5 percent of syncopal episodes.
The most common metabolic causes of syncope are hypoglycemia, hypoxia, and hyperventilation.
Establishing hypoglycemia as the cause of an apparent loss of consciousness requires
demonstration of hypoglycemia during the syncopal episode. Although hyperventilation-induced
syncope has been generally considered to be caused by a reduction in cerebral blood flow, this
remains an area of debate. Hyperventilation-induced syncope may also have a psychological
component. Psychiatric disorders may also cause syncope. Up to 25 percent of patients with
syncope of unknown origin may have psychiatric disorders for which apparent syncope is one of
the presenting symptoms. [1]

Relationship Between Prognosis and Cause of Syncope

The prognosis for patients with syncope varies greatly with the diagnosis. Syncope of unknown
origin or syncope with a noncardiac cause (including reflex-mediated syncope) is generally
associated with a benign prognosis. In contrast, syncope with a cardiac cause is associated with
up to 30 percent mortality at 1 year. [1] [2]

Copyright © 2007 Elsevier Inc. All rights reserved. - www.mdconsult.com

mk:@MSITStore:I:\Cardiology\Braunwald's%20Heart%20Disease%20A%20Textbook%... 12/18/2008