Cardiac Encephalopathy

Louis R. Caplan, MD
Address
Department of Neurology, Beth Israel Deaconess Medical Center,
330 Brookline Avenue, Boston, MA 02215, USA.
E-mail: lcaplan@caregroup.harvard.edu
Current Treatment Options in Cardiovascular Medicine 2004, 6:217–222
Current Science Inc. ISSN 1092-8464
Copyright © 2004 by Current Science Inc.

Opinion statement
Many patients develop confusion, lethargy, and cognitive and behavioral abnormali-
ties during or after cardiac decompensation. Congestive heart failure and the accom-
panying elevation in systemic venous pressure and decrease in cardiac output can lead
to changes within the cranial cavity that cause an encephalopathy. At times, excess
cerebrospinal fluid accumulates within the cranium causing an apathetic state identi-
cal to that seen in patients with other causes of hydrocephalus. Awareness of the syn-
drome of cardiac encephalopathy and optimal management of congestive heart failure
and body fluids can reverse the neurologic dysfunction. In some patients with excess
cerebrospinal fluid, lumbar puncture with removal of cerebrospinal fluid can reverse
the apathetic state.

Introduction
Patients with heart disease, especially those who have put, consumes about 65% of the glucose used by the
congestive heart failure, often develop confusion, body, and uses about 20% of the body’s oxygen supply
decreased alertness, diminished intellectual function- [3•]. Cerebral cortical gray matter nerve cells metabo-
ing, and focal neurologic signs [1••,2]. Often, these lize about 75% of the oxygen used by the brain,
neurologic abnormalities are explained by brain embo- although gray matter accounts for only 20% of brain
lism arising from the heart, aorta, and occlusive lesions mass [3•]. The brain has enormous needs and demands
within the cervicocranial arteries [2]. Occasionally, epi- for nutritional substrates and blood flow, explaining the
sodes of hypotension and systemic hypoperfusion are vulnerability of this very complex and precise organ to
responsible for the brain dysfunction. Sometimes the metabolic perturbations.
neurologic abnormalities are side effects of medicines
used to treat the cardiovascular disease. PRIOR STUDIES OF PATIENTS
The neurologic symptoms and signs in many WITH SEVERE CARDIAC DISEASE
other patients are caused by various physiologic and Cardiac encephalopathies are not well recognized by
biochemical perturbations that develop in patients cardiologists. I could find no mention of this condition
who have cardiac disease and congestive heart failure. in any cardiology text (except my chapters in Hurst’s The
Brain function depends importantly on its biochemi- Heart concerning neurologic disorders in cardiac
cal milieu. Just as a fresh water fish cannot swim, or patients [2]). Some reports of patients with severe heart
even survive, in ocean waters, the brain is quite sensi- disease, syncope, and congestive heart failure have
tive to any alteration in its chemical or physical envi- shown a high frequency of cognitive abnormalities,
ronment. Most biochemical perturbations affect the although none have defined the pathogenesis of the
brain globally, often first affecting the most complex loss of intellectual function. Zuccala et al. [4] studied 57
intellectual functions that are most vulnerable. Dif- consecutive patients (average age 76.7 years) with
fuse brain dysfunction related to potentially revers- chronic congestive heart failure. More than half (53%)
ible biochemical and physiologic changes is usually had low scores on a battery of cognitive function tests;
referred to as an encephalopathy. the presence of low scores was highly correlated with
Although the brain accounts for only about 2% of left ventricular ejection fractions of less than 30% [4].
body mass, it is a disproportionate consumer of Rosenberg et al. performed detailed neuropsychological
resources. The brain receives about 20% of cardiac out- testing on seven patients with recurrent cardiogenic syn-
218 Cerebrovascular Disease and Stroke

cope, six of whom had documented arrhythmias [5]. to have only slight improvements [7]. Bornstein et al.
They found abnormalities on tests of memory function [8] studied 62 patients (mean age 44.7 years) who
not found in age- and education-matched control sub- were evaluated for cardiac transplantation. A total of
jects. Garcia et al. [6] tested 100 consecutive cardiac 45% of the patients had dilated cardiomyopathies and
patients admitted to a rehabilitation hospital. They 40% had ischemic cardiomyopathies. The patients
found that four out of 24 (16.7%) patients with were impaired on 50% of the neuropsychological mea-
ischemic heart disease but no known strokes had signif- sures and 58% of patients met criteria for overall intel-
icant cognitive impairment. lectual impairment. The highest rates of impairment
The most detailed information about cognitive and were on tests of memory, speed of motor activity, mea-
intellectual functions in patients with severe heart dis- sures of attention, reasoning, and concept formation.
ease comes from studies of patients considered for car- Impaired intellectual functioning correlated with ele-
diac transplantation [7,8]. Neuropsychological tests vated right atrial pressure. Better performance corre-
are often included as part of the routine battery of test- lated with higher stroke volume, stroke volume index,
ing before transplantation, and these tests are occa- and cardiac index. Pulmonary capillary wedge pres-
sionally repeated after transplantation. Schall et al. [7] sures and left ventricular ejection fractions did not cor-
studied 54 patients, among whom 20 had idiopathic relate with results of neuropsychological testing in this
myocardiopathies and 25 had ischemic cardiomyopa- series. Only 11 of these patients were retested (seven
thies. The mean left ventricular ejection fraction of who had transplantation and four who did not) a
these patients was 20% and the mean cardiac index mean of 36 months after the initial testing. The trans-
was 2.6 L/min/m 2 . The major impairments were in plant p atients showed improvement and tho se
tests of memory and visual and tactile perception; patients who did not have transplantation usually per-
56% of patients were moderately impaired on logical formed worse than they had before [10]. The authors
memory tests and this increased to 61% when 30- considered that elevated right atrial pressure was prob-
minute delays were introduced into the testing [7]. ably a marker for biventricular failure and low cardiac
Among the 54 patients, 20 were retested (mean of 7.7 output and that the cognitive deficits related to chron-
months after cardiac transplantation), and were found ically reduced brain blood flow [10].

Treatment
• Cardiac encephalopathy has not been recognized by cardiologists and there
are no trials of treatment. The family of patients often report intellectual
and behavioral changes that should alert clinicians to the early presence of
an encephalopathy. Measurements of hepatic and renal function and elec-
trolytes are important in the differential diagnosis, as is a review of medica-
tions and their use. Optimal management of congestive heart failure is
important. Blood pressures and fluid volume require close attention. In
patients with intracranial fluid effusions, lumbar puncture can dramatically
improve attention and behavior.

Recognition of the presence of an encephalopathy

• The six most common features found in patients with encephalopathies
are listed in Table 1. Brain functions are reduced, explaining the depressed
state of alertness, limb hypotonia, and decreased respirations that develop
in patients with encephalopathies. Some encephalopathies cause height-
ened excitability of neural structures, explaining hallucinations, seizures,
and increased muscle contractions [3•]. Decreased alertness is an invari-
able finding in encephalopathic patients. The earliest stage of altered alert-
ness is drowsiness. Patients may need prodding or stimulation to remain
fully awake and alert and they often sleep when not stimulated. Loss of
consciousness and restlessness with agitation and sometimes delirium fol-
low if the encephalopathy worsens. Patients may be unable to remain still,
move restlessly in bed, and become unable to hold and continue coherent
conversations. They flit from one topic to another and cannot concentrate
 Cardiac Encephalopathy Caplan 219

Table 1. Clinical findings in patients with encephalopathies

Altered state of alertness and consciousness
Global decrease in all intellectual functions
Variability from minute to minute and from hour to hour in the neurologic findings
Asterixis, a metabolic "flap"
Diffuse slowing of rhythms on electroencephalograms
Reversibility after correction of the biochemical and physiologic abnormalities

on queries or directions. Stupor may develop as the encephalopathy

becomes more severe. All intellectual functions are usually compromised.
The most complex and difficult functions (eg, mathematical computa-
tions, abstractions, and writing) are affected earliest and most severely.
Memory, language, planning, concentration, persistence in tasks, visual-
spatial abilities, and computational skills are all affected. Strokes and
other focal brain disorders such as tumors and abscesses, in contrast, affect
only isolated functions depending on their location within the brain. Per-
ceptual abilities are also effected and patients may have visual illusions
and frank hallucinations.
• Encephalopathic patients have difficulty maintaining concentration on
tasks. Although they may understand the nature of a request and can begin
to answer correctly, they are unable to persevere and finish tasks. For exam-
ple, ask the patient to name 10 colors, zoo animals, articles of clothing, and
so forth. If they can produce two or three correct names then they clearly
understand the directions and the nature of the task and have sufficient lan-
guage abilities to supply items within the category requested. The inability
to persevere and give further items usually means that they cannot sustain
attention long enough to finish the task. Alternative tests of concentration
and attention are counting backwards quickly from 20 to zero, and count-
ing backwards from 100 by threes or sevens.
• Asterixis, a metabolic flap, is an important sign in patients with encepha-
lopathy. Although asterixis was first described in patients with hepatic
encephalopathy, it is nonspecific and is present in patients with encepha-
lopathy of diverse causes. Asterixis is most often elicited by asking the
patient to hold the upper limbs outstretched in front of them with the
wrists and fingers held in full extension. After a short latency, side-to-side
and flexion or extension movements of the fingers at the metacarpopha-
langeal joints and at the wrist appear [9,10]. The flexion movements are
quick; the flexion phase is much more rapid than the extension movements
used to return the fingers and wrists to their former positions. Asterixis can
also be elicited in the lower limbs by having patients dorsiflex the feet with
the legs elevated and extended [9]. Alternatively, the examiner can use his
or her arms placed under the patient’s knees to gently lift the lower extrem-
ities off the bed while the patient’s thighs and legs are flexed. Flapping
movements of the legs and feet appear. Asterixis represents a failure to
maintain a sustained posture. Just as the patient cannot sustain concentra-
tion on mental tasks, they also cannot sustain attention to hold a fixed-
limb posture. Asterixis can usually be elicited when some degree of reduced
alertness develops. Some degree of attention and wakefulness is required.
When patients become frankly stuporous, asterixis may not be elicitable.
220 Cerebrovascular Disease and Stroke

Differential diagnosis of toxic-metabolic encephalopathy in cardiac patients

• Cardiac patients, especially those who are acutely ill with congestive heart
failure, have many potential explanations for encephalopathy. The most
common causes of encephalopathy in cardiac patients are the following: 1)
dysfunction of other systemic organs, especially the kidneys, lungs, and
liver; 2) effects of pharmacologic agents used to treat cardiovascular abnor-
malities or used for pain control or sedation and tranquilization; 3) hypo-
volemia; 4) electrolyte and acid-based abnormalities; and 5) lung and
urinary tract infections with fever.
• Pulmonary congestion, pulmonary edema, and pleural effusions are all
common in patients with cardiac decompensation. Patients with heart dis-
ease very often also have concurrent chronic bronchopulmonary disease,
especially if they smoke cigarettes. Hypoventilation can lead to hypoxia and
carbon dioxide retention. Morphine, sedatives, and psychotropic agents
that are often used to treat cardiac pain and anxiety can depress ventilatory
drive and further decrease ventilation. Pulmonary embolism, an important
complication of congestive heart failure, can further compromise ventila-
tion and perfusion within the lung. Liver congestion is another very fre-
quent accompaniment of congestive heart failure, especially in those
patients with right heart disease and tricuspid valve incompetence. Renal
dysfunction with elevation of blood urea nitrogen and creatinine levels
may also occur in patients with acute cardiac decompensation. Many
patients with hypertension and atherosclerotic coronary artery disease have
nephrosclerosis and chronic kidney disease due to concurrent involvement
of the small and large renal arteries. Changes in blood and serum volume
and acid-based components are common with congestive heart failure and
are often related to the use of diuretics and other pharmacologic agents.
Kidney congestion and reduced perfusion also occur. Renal failure is espe-
cially common in patients who have transient or persistent hypotension
during cardiac decompensation and its treatment. Renal and hepatic dys-
function affect the metabolism and excretion of drugs. Toxic effects of drugs
previously well tolerated may develop in the presence of renal failure, even
when the dose of the drugs is not changed. Patients with fever, infection,
and pain often develop confusion and an encephalopathic clinical picture
without any definite abnormality of metabolic parameters measured by
blood tests. Patients who are acutely ill because of congestive heart failure
frequently have more than one metabolic abnormality. For example, a
patient with congestive heart failure who has an encephalopathy may have
slight hypoxemia, slight hyponatremia, modest elevation of blood urea
nitrogen, and a low-grade fever. Each of these single problems may be
insufficient alone to explain the encephalopathy, but when added together
the combined effect of all the metabolic changes may be enough to cause
important brain dysfunction.

Cardiac encephalopathies without apparent other causes

• Some patients with acute and chronic congestive heart failure have the clin-
ical findings of an encephalopathy without recognized liver, renal, pulmo-
nary, or definite biochemical or metabolic abnormality detected by blood
tests sufficient to explain the encephalopathy. These patients are often
sleepy, confused, inattentive, and unable to consistently sustain intelligent
conversations. There are two different clinical syndromes found in patients
with cardiac encephalopathy: one that resembles in every way the findings
 Cardiac Encephalopathy Caplan 221

Table 2. Clinical findings in cardiac patients

with intracranial fluid accumulations
Decreased spontaneity of behavior
Apathy and disinterest
Latency in responding to queries and directions
Short, terse responses
Difficulty persevering with tasks
Preserved memory, language, and visual-spatial functions
Preserved alertness

discussed in patients with systemic organ failures and metabolic perturba-

tions, and a different clinical syndrome that closely mimics that found in
patients with hydrocephalus.
• The mechanisms of brain dysfunction in patients with congestive heart fail-
ure are multifactorial. Systemic venous pressure is increased causing an
increase in pressure in the venous structures in the cranial cavity. Increased
intracranial venous pressure diminishes absorption of cerebrospinal fluid
(CSF) and so an increased amount of fluid accumulates in the cisterns
around the brain, in the subarachnoid spaces, and within the ventricles.
The CSF pressure may be elevated when measured by lumbar puncture.
Brain edema may result from the increased venous pressure and increased
amounts of CSF. In order to perfuse the brain and maintain an effective
arteriovenous pressure difference adequate for brain perfusion, arterial
pressure and cerebral blood flow must be maintained and even augmented
in patients with elevated intracranial venous pressures. Cardiac decompen-
sation can limit the ability of the heart and systemic circulation to augment
cerebral blood flow. Hypoxia related to pulmonary dysfunction and
hypoventilation reduces the oxygen content of the blood that does reach
neurons in the brain. Neurologic abnormalities occur when cardiac failure
is most severe and the clinical signs are indistinguishable from those found
in patients with renal failure and carbon dioxide narcosis.
• A different clinical picture, similar to that found in patients with hydroceph-
alus, can also be found in patients with congestive heart failure. This syndrome
can develop during treatment of congestive failure and may occur even after
cardiac compensation when the patient is recovering from heart failure. The
findings are listed in Table 2. The major feature of this syndrome is abulia.
Abulic patients have severely reduced spontaneous behavior. There are apa-
thetic and seem content to sit or lie about without doing much. They show lit-
tle or no interest in television, reading, listening to the radio, conversations, or
any other activity. The amount of spontaneous initiated speech is much
reduced. When asked questions or urged to perform tasks, abulic patients often
fail to respond or do so only after a relatively long interval. When questions or
directions are repeated, patients often say that they had heard you the first time
but just couldn’t get rolling to reply or act. Responses that are forthcoming are
generally short, laconic, and terse. Patients don’t persist with familiar tasks.
Intellectual functions including memory, language, and ability to draw and
copy are preserved, although these functions take longer than usual to perform
and require frequent prodding to complete. The patients remain alert despite
their inactivity and slowness, in contrast to all other encephalopathies, which
are invariably accompanied by drowsiness and later stupor. Friends and family
describe abulic patients as “bumps on a log” or “couch potatoes.”
• The abulic syndrome is most likely caused by retention of CSF within the
intracranial cavity. Pericardial, pleural, and peritoneal effusions are quite
common and well known in patients with congestive heart failure. Effu-
222 Cerebrovascular Disease and Stroke

sions within the cranial cavity probably have the same explanation as pleu-
ral and peritoneal effusions. The meninges are connective tissue structures
very similar in structure and function to the pleura, pericardium, and peri-
toneum. Increased venous pressure leads to decreased absorption of CSF at
the same time that production of CSF continues unchanged. The amount
of CSF increases and fluid accumulates in the cisterns around the brain, in
the subarachnoid space, and in the ventricles. As is well known, compensa-
tion and correction of congestive heart failure does not necessarily result in
full reabsorption of pleural and pericardial effusions and ascites. The pres-
sure in the intracranial venous sinuses and neck and cranial veins that
drains the head may normalize sufficiently to prevent further CSF effusions
but not enough to allow absorption and clearing of the effusions already
present. Similarly, thoracentesis and abdominocentesis may be required to
remove persistent pleural fluid and ascites even after treatment with diuret-
ics and cardiac drugs. The same syndrome can develop in patients with ana-
sarca due to the nephrotic syndrome and liver failure.

Brain imaging abnormalities

• Computed tomography (CT) scans in patients with the hydrocephalic, abulic
syndrome are often read as showing “brain atrophy.” Radiologists see increased
CSF between cerebral and cerebellar gyri and interpret the widening of the sulci
as an indication of loss of brain tissue. Increased quantity of intracranial CSF
can expand the sulci and cause an increased amount of fluid outside the brain
as well as enlargement of the ventricular system. Lumbar puncture with removal
of 30 to 50 cm3 of CSF in patients with the abulic syndrome is often followed
by clinical improvement and normalization of the “brain atrophy” shown by
CT. Sulci become smaller and the gyri widen. CT scans may take time to normal-
ize after lumbar puncture and after treatment of congestive heart failure.

References and Recommended Reading

Papers of particular interest, published recently, have been highlighted as:
• Of importance
•• Of major importance
1.•• Caplan LR: Encephalopathies and neurological effects 5. Cardiogenic dementia [no authors listed]. Lancet
of drugs used in cardiac patients. In Clinical Neurocar- 1981, 2:1171.
diology. Edited by Caplan LR, et al. New York: Marcel 6. Garcia CA, Tweedy JR, Blass JP: Underdiagnosis of cog-
Dekker; 1999:186–225. nitive impairment in a rehabilitation setting. J Am
Discusses in detail neurologic and neuroradiologic findings in Geriatr Soc 1984, 32:339–342.
patients with various forms of encephalopathy. 7. Schall RR, Petrucci RJ, Brozena SC, et al.: Cognitive
2. Caplan LR: Cerebrovascular disease and neurological function in patients with symptomatic dilated cardi-
manifestations of heart disease. In Hurst’s The Heart, omyopathy before and after cardiac transplantation.
edn 9. Edited by Alexander RW, et al. New York: McGraw J Am Coll Cardiol 1989, 14:1666–1672.
Hill; 1998:2483–2504. 8. Bornstein RA, Starling RC, Myerowitz P, Haas GJ: Neu-
3.• Arieff AI, Griggs RC: General considerations in meta- ropsychological function in patients with end-stage
bolic encephalopathies and systemic disorders affect- heart failure before and after cardiac transplantation.
ing the nervous system. In Metabolic Brain Dysfunction Acta Neurol Scand 1995, 91:260–265.
in Systemic Disorders. Edited by Arieff AI, Griggs RC. Bos- 9. Raskin NH: Neurological complications of renal fail-
ton: Little Brown and Co.; 1992:1–20. ure in neurology and general medicine. In The Neuro-
General discussion of encephalopathy and its causes logical Aspects of Medical Disorders, edn 2. Edited by
and recognition. Aminoff M. New York: Churchill Livingstone;
4. Zuccala G, Cattel C, Manes-Gravina E, et al.: Left ven- 1995:303–316.
tricular dysfunction: a clue to cognitive impairment in 10. Leavitt S, Tyler HR: Studies in asterixis. I. Arch Neurol
older patients with heart failure. J Neurol Neurosurg Psy- 1964, 10:360–368.
chiatry 1997, 63:509–512.