Signs and symptoms

Exertional dyspnea and/or dyspnea at

rest

Orthopnea

The common pathophysiologic state that

perpetuates the progression of heart failure
is extremely complex, regardless of the
precipitating
event.
Compensatory
mechanisms exist on every level of
organization, from subcellular all the way
through organ-to-organ interactions. Only
when this network of adaptations becomes
overwhelmed does heart failure ensue.

Acute pulmonary edema

Adaptations

Chest pain/pressure and palpitations

Most important among the adaptations are

the following:

Tachycardia

Fatigue and weakness

Nocturia and oliguria

Anorexia, weight loss, nausea

Exophthalmos
pulsation of eyes

Distention of neck veins

Weak, rapid, and thready pulse

Signs and symptoms of heart failure include

the following:

and/or

visible

Rales, wheezing

S3 gallop and/or pulsus alternans

Increased intensity of P2 heart sound

Hepatojugular reflux

Ascites,
anasarca

Central or peripheral cyanosis, pallor

Pathophysiology

hepatomegaly,

and/or

The Frank-Starling mechanism, in

which an increased preload helps to
sustain cardiac performance

Alterations in myocyte regeneration

and death

Myocardial hypertrophy with or

without cardiac chamber dilatation,
in which the mass of contractile
tissue is augmented

Activation of neurohumoral systems

The release of norepinephrine by adrenergic

cardiac nerves augments myocardial
contractility and includes activation of the
renin-angiotensin-aldosterone
system
[RAAS], the sympathetic nervous system
[SNS], and other neurohumoral adjustments
that act to maintain arterial pressure and
perfusion of vital organs.
In acute heart failure, the finite adaptive
mechanisms that may be adequate to
maintain the overall contractile performance
of the heart at relatively normal levels
become maladaptive when trying to sustain
adequate cardiac performance.

The primary myocardial response to chronic

increased
wall
stress
is
myocyte
hypertrophy,
death/apoptosis,
and
regeneration.This process eventually leads
to remodeling, usually the eccentric type.
Eccentric remodeling further worsens the
loading conditions on the remaining
myocytes and perpetuates the deleterious
cycle. The idea of lowering wall stress to
slow the process of remodeling has long
been exploited in treating heart failure
patients.
The reduction of cardiac output following
myocardial injury sets into motion a cascade
of hemodynamic and neurohormonal
derangements that provoke activation of
neuroendocrine systems, most notably the
above-mentioned adrenergic systems and
RAAS.
The
release
of
epinephrine
and
norepinephrine, along with the vasoactive
substances
endothelin-1
(ET-1)
and
vasopressin, causes vasoconstriction, which
increases calcium afterload and, via an
increase in cyclic adenosine monophosphate
(cAMP), causes an increase in cytosolic
calcium entry. The increased calcium entry
into the myocytes augments myocardial
contractility and impairs myocardial
relaxation (lusitropy).
The calcium overload may induce
arrhythmias and lead to sudden death. The
increase in afterload and myocardial
contractility (known as inotropy) and the
impairment in myocardial lusitropy lead to
an increase in myocardial energy
expenditure and a further decrease in cardiac
output. The increase in myocardial energy
expenditure leads to myocardial cell
death/apoptosis, which results in heart
failure and further reduction in cardiac
output, perpetuating a cycle of further
increased neurohumoral stimulation and

further
adverse
hemodynamic
myocardial responses.

and

In addition, the activation of the RAAS

leads to salt and water retention, resulting in
increased preload and further increases in
myocardial energy expenditure. Increases in
renin, mediated by decreased stretch of the
glomerular afferent arteriole, reduce
delivery of chloride to the macula densa and
increase beta1-adrenergic activity as a
response to decreased cardiac output. This
results in an increase in angiotensin II (Ang
II) levels and, in turn, aldosterone levels,
causing stimulation of the release of
aldosterone. Ang II, along with ET-1, is
crucial in maintaining effective intravascular
homeostasis mediated by vasoconstriction
and aldosterone-induced salt and water
retention.
The concept of the heart as a self-renewing
organ is a relatively recent development.
This new paradigm for myocyte biology has
created an entire field of research aimed
directly
at
augmenting
myocardial
regeneration. The rate of myocyte turnover
has been shown to increase during times of
pathologic stress. In heart failure, this
mechanism for replacement becomes
overwhelmed by an even faster increase in
the rate of myocyte loss. This imbalance of
hypertrophy and death over regeneration is
the final common pathway at the cellular
level for the progression of remodeling and
heart failure.
Ang II
Research indicates that local cardiac Ang II
production (which decreases lusitropy,
increases inotropy, and increases afterload)
leads to increased myocardial energy
expenditure. Ang II has also been shown in
vitro and in vivo to increase the rate of
myocyte apoptosis. In this fashion, Ang II

has similar actions to norepinephrine in

heart failure.
Ang II also mediates myocardial cellular
hypertrophy and may promote progressive
loss
of myocardial
function. The
neurohumoral factors above lead to myocyte
hypertrophy and interstitial fibrosis,
resulting in increased myocardial volume
and increased myocardial mass, as well as
myocyte loss. As a result, the cardiac
architecture changes, which, in turn, leads to
further increase in myocardial volume and
mass.
Myocytes and myocardial remodeling
In the failing heart, increased myocardial
volume is characterized by larger myocytes
approaching the end of their life cycle. As
more myocytes drop out, an increased load
is placed on the remaining myocardium, and
this unfavorable environment is transmitted
to the progenitor cells responsible for
replacing lost myocytes.
Progenitor cells become progressively less
effective as the underlying pathologic
process worsens and myocardial failure
accelerates. These featuresnamely, the
increased myocardial volume and mass,
along with a net loss of myocytesare the
hallmark of myocardial remodeling. This
remodeling process leads to early adaptive
mechanisms, such as augmentation of stroke
volume (Frank-Starling mechanism) and
decreased wall stress (Laplace's law), and,
later, to maladaptive mechanisms such as
increased myocardial oxygen demand,
myocardial ischemia, impaired contractility,
and arrhythmogenesis.

bradykinin (BK), atrial natriuretic peptide

(ANP), and B-type natriuretic peptide
(BNP). This decline occurs simultaneously
with the increase in vasoconstrictor
substances from the RAAS and the
adrenergic system, which fosters further
increases in vasoconstriction and thus
preload and afterload. This results in cellular
proliferation,
adverse
myocardial
remodeling, and antinatriuresis, with total
body fluid excess and worsening of heart
failure symptoms.
Systolic and diastolic failure
Systolic and diastolic heart failure each
result in a decrease in stroke volume. This
leads to activation of peripheral and central
baroreflexes and chemoreflexes that are
capable of eliciting marked increases in
sympathetic nerve traffic.
While there are commonalities in the
neurohormonal responses to decreased
stroke volume, the neurohormone-mediated
events that follow have been most clearly
elucidated for individuals with systolic heart
failure. The ensuing elevation in plasma
norepinephrine directly correlates with the
degree of cardiac dysfunction and has
significant
prognostic
implications.
Norepinephrine, while directly toxic to
cardiac myocytes, is also responsible for a
variety of signal-transduction abnormalities,
such as down-regulation of beta1-adrenergic
receptors, uncoupling of beta2-adrenergic
receptors, and increased activity of
inhibitory G-protein. Changes in beta1adrenergic receptors result in overexpression
and promote myocardial hypertrophy.
ANP and BNP

As heart failure advances, there is a relative

decline in the counterregulatory effects of
endogenous vasodilators, including nitric
oxide
(NO),
prostaglandins
(PGs),

ANP and BNP are endogenously generated

peptides activated in response to atrial and
ventricular volume/pressure expansion. ANP

and BNP are released from the atria and

ventricles, respectively, and both promote
vasodilation
and
natriuresis.
Their
hemodynamic effects are mediated by
decreases in ventricular filling pressures,
owing to reductions in cardiac preload and
afterload. BNP, in particular, produces
selective afferent arteriolar vasodilation and
inhibits sodium reabsorption in the proximal
convoluted tubule. It also inhibits renin and
aldosterone
release
and,
therefore,
adrenergic activation. ANP and BNP are
elevated in chronic heart failure. BNP, in
particular, has potentially important
diagnostic, therapeutic, and prognostic
implications.
Other vasoactive systems
Other vasoactive systems that play a role in
the pathogenesis of heart failure include the
ET receptor system, the adenosine receptor
system, vasopressin, and tumor necrosis
factor-alpha (TNF-alpha). ET, a substance
produced by the vascular endothelium, may
contribute to the regulation of myocardial
function, vascular tone, and peripheral
resistance in heart failure. Elevated levels of
ET-1 closely correlate with the severity of
heart
failure.
ET-1
is
a
potent
vasoconstrictor and has exaggerated
vasoconstrictor effects in the renal
vasculature, reducing renal plasma blood
flow, glomerular filtration rate (GFR), and
sodium excretion.
TNF-alpha has been implicated in response
to various infectious and inflammatory
conditions. Elevations in TNF-alpha levels
have been consistently observed in heart
failure and seem to correlate with the degree
of myocardial dysfunction. Some studies
suggest that local production of TNF-alpha
may have toxic effects on the myocardium,
thus worsening myocardial systolic and
diastolic function.

In individuals with systolic dysfunction,

therefore, the neurohormonal responses to
decreased stroke volume result in temporary
improvement in systolic blood pressure and
tissue
perfusion.
However, in
all
circumstances, the existing data support the
notion that these neurohormonal responses
contribute to the progression of myocardial
dysfunction in the long term.
Heart failure
fraction

with

normal

ejection

In diastolic heart failure (heart failure with

normal ejection fraction [HFNEF]), the
same pathophysiologic processes occur that
lead to decreased cardiac output in systolic
heart failure, but they do so in response to a
different set of hemodynamic and
circulatory environmental factors that
depress cardiac output.
In HFNEF, altered relaxation and increased
stiffness of the ventricle (due to delayed
calcium uptake by the myocyte sarcoplasmic
reticulum and delayed calcium efflux from
the myocyte) occur in response to an
increase in ventricular afterload (pressure
overload). The impaired relaxation of the
ventricle then leads to impaired diastolic
filling of the left ventricle (LV).
Morris et al found that RV subendocardial
systolic
dysfunction
and
diastolic
dysfunction,
as
detected
by
echocardiographic strain rate imaging, are
common in patients with HFNEF. This
dysfunction is potentially associated with
the same fibrotic processes that affect the
subendocardial layer of the LV and, to a
lesser extent, with RV pressure overload.
This may play a role in the symptomatology
of patients with HFNEF.
LV chamber stiffness

An increase in LV chamber stiffness occurs

secondary to any one of, or any combination
of, the following 3 mechanisms:

Rise in filling pressure

Shift to a steeper
pressure-volume curve

ventricular

Decrease in ventricular distensibility

A rise in filling pressure is the movement of

the ventricle up along its pressure-volume
curve to a steeper portion, as may occur in
conditions such as volume overload
secondary to acute valvular regurgitation or
acute LV failure due to myocarditis.
A shift to a steeper ventricular pressurevolume curve results, most commonly, not
only from increased ventricular mass and
wall thickness (as observed in aortic stenosis
and long-standing hypertension) but also
from infiltrative disorders (eg, amyloidosis),
endomyocardial fibrosis, and myocardial
ischemia.
Parallel upward displacement of the
diastolic pressure-volume curve is generally
referred to as a decrease in ventricular
distensibility. This is usually caused by
extrinsic compression of the ventricles.
Concentric LV hypertrophy
Pressure overload that leads to concentric
LV hypertrophy (LVH), as occurs in aortic
stenosis, hypertension, and hypertrophic
cardiomyopathy, shifts
the
diastolic
pressure-volume curve to the left along its
volume axis. As a result, ventricular
diastolic pressure is abnormally elevated,
although chamber stiffness may or may not
be altered.

Increases in diastolic pressure lead to

increased myocardial energy expenditure,
remodeling of the ventricle, increased
myocardial oxygen demand, myocardial
ischemia, and eventual progression of the
maladaptive mechanisms of the heart that
lead to decompensated heart failure.
Arrhythmias
While life-threatening rhythms are more
common in ischemic cardiomyopathy,
arrhythmia imparts a significant burden in
all forms of heart failure. In fact, some
arrhythmias even perpetuate heart failure.
The most significant of all rhythms
associated with heart failure are the lifethreatening
ventricular
arrhythmias.
Structural
substrates
for
ventricular
arrhythmias that are common in heart
failure, regardless of the underlying cause,
include ventricular dilatation, myocardial
hypertrophy, and myocardial fibrosis.
At the cellular level, myocytes may be
exposed to increased stretch, wall tension,
catecholamines, ischemia, and electrolyte
imbalance. The combination of these factors
contributes to an increased incidence of
arrhythmogenic sudden cardiac death in
patients with heart failure.
Etiology
Most patients who present with significant
heart failure do so because of an inability to
provide adequate cardiac output in that
setting. This is often a combination of the
causes listed below in the setting of an
abnormal myocardium. The list of causes
responsible for presentation of a patient with
heart failure exacerbation is very long, and
searching for the proximate cause to
optimize therapeutic interventions is
important.

From a clinical standpoint, classifying the

causes of heart failure into the following 4
broad categories is useful:

Underlying
causes:
Underlying
causes of heart failure include
structural abnormalities (congenital
or acquired) that affect the peripheral
and coronary arterial circulation,
pericardium, myocardium, or cardiac
valves, thus leading to increased
hemodynamic burden or myocardial
or coronary insufficiency
Fundamental causes: Fundamental
causes include the biochemical and
physiologic mechanisms, through
which
either
an
increased
hemodynamic burden or a reduction
in
oxygen
delivery to the
myocardium results in impairment of
myocardial contraction
Precipitating causes: Overt heart
failure may be precipitated by
progression of the underlying heart
disease (eg, further narrowing of a
stenotic aortic valve or mitral valve)
or various conditions (fever, anemia,
infection)
or
medications
(chemotherapy, NSAIDs) that alter
the homeostasis of heart failure
patients
Genetics
of
cardiomyopathy:
Dilated, arrhythmic right ventricular
and restrictive cardiomyopathies are
known genetic causes of heart
failure.

preserved LVEF, acute heart failure, highoutput heart failure, and right heart failure.
Underlying causes of systolic heart failure
include the following:

Coronary artery disease

Diabetes mellitus

Hypertension

Valvular heart disease (stenosis or

regurgitant lesions)

Arrhythmia
ventricular)

Infections
and
(myocarditis)

Peripartum cardiomyopathy

Congenital heart disease

Drugs (either recreational, such as

alcohol and cocaine, or therapeutic
drugs with cardiac side effects, such
as doxorubicin)

Idiopathic cardiomyopathy

Rare
conditions
(endocrine
abnormalities,
rheumatologic
disease, neuromuscular conditions)

(supraventricular

or

inflammation

Underlying causes of diastolic heart failure

include the following:

Underlying causes

Coronary artery disease

Specific underlying factors cause various

forms of heart failure, such as systolic heart
failure (most commonly, left ventricular
systolic dysfunction), heart failure with

Diabetes mellitus

Hypertension

Valvular
stenosis)

Hypertrophic cardiomyopathy

heart

disease

(aortic

Restrictive
cardiomyopathy
(amyloidosis, sarcoidosis)
Constrictive pericarditis

Acute valvular (mitral or aortic)

regurgitation

Myocardial infarction

Myocarditis

Arrhythmia

Drugs (eg, cocaine, calcium channel

blockers, or beta-blocker overdose)
Sepsis

Glomerulonephritis

Polycythemia vera

Carcinoid syndrome

Left ventricular failure

Coronary artery disease (ischemia)

Pulmonary hypertension

Pulmonary valve stenosis

Pulmonary embolism

Chronic pulmonary disease

Neuromuscular disease

Precipitating causes of heart failure

Underlying causes of high-output heart

failure include the following:

Anemia

Systemic arteriovenous fistulas

Hyperthyroidism

Beriberi heart disease

Paget disease of bone

Albright
dysplasia)

Pregnancy

Underlying causes of right heart failure

include the following:

Underlying causes of acute heart failure

include the following:

syndrome

Multiple myeloma

(fibrous

A previously stable, compensated patient

may develop heart failure that is clinically
apparent for the first time when the intrinsic
process has advanced to a critical point, such
as with further narrowing of a stenotic aortic
valve or mitral valve. Alternatively,
decompensation may occur as a result of
failure or exhaustion of the compensatory
mechanisms but without any change in the
load on the heart in patients with persistent,
severe pressure or volume overload. In
particular, consider whether the patient has
underlying coronary artery disease or
valvular heart disease.
The most common cause of decompensation
in a previously compensated patient with
heart failure is inappropriate reduction in the

intensity of treatment, such as dietary

sodium restriction, physical activity
reduction, or drug regimen reduction.
Uncontrolled hypertension is the second
most common cause of decompensation,
followed closely by cardiac arrhythmias
(most commonly, atrial fibrillation).
Arrhythmias,
particularly
ventricular
arrhythmias, can be life threatening. Also,
patients with one form of underlying heart
disease that may be well compensated can
develop heart failure when a second form of
heart disease ensues. For example, a patient
with chronic hypertension and asymptomatic
LVH may be asymptomatic until a
myocardial infarction (MI) develops and
precipitates heart failure.
Systemic infection or the development of
unrelated illness can also lead to heart
failure. Systemic infection precipitates heart
failure by increasing total metabolism as a
consequence of fever, discomfort, and
cough, increasing the hemodynamic burden
on the heart. Septic shock, in particular, can
precipitate heart failure by the release of
endotoxin-induced factors that can depress
myocardial contractility.
Cardiac infection and inflammation can also
endanger the heart. Myocarditis or infective
endocarditis may directly impair myocardial
function and exacerbate existing heart
disease. The anemia, fever, and tachycardia
that frequently accompany these processes
are also deleterious. In the case of infective
endocarditis, the additional valvular damage
that ensues may precipitate cardiac
decompensation.
Patients with heart failure, particularly when
confined to bed, are at high risk of
developing pulmonary emboli, which can
increase the hemodynamic burden on the
right ventricle by further elevating right

ventricular (RV) systolic pressure, possibly

causing fever, tachypnea, and tachycardia.
Intense, prolonged physical exertion or
severe fatigue, such as may result from
prolonged travel or emotional crisis, is a
relatively common precipitant of cardiac
decompensation. The same is true of
exposure to severe climate change (ie, the
individual comes in contact with a hot,
humid environment or a bitterly cold one).
Excessive intake of water and/or sodium and
the administration of cardiac depressants or
drugs that cause salt retention are other
factors that can lead to heart failure.
Because of increased myocardial oxygen
consumption and demand beyond a critical
level, the following high-output states can
precipitate the clinical presentation of heart
failure:

Profound anemia

Thyrotoxicosis

Myxedema

Paget disease of bone

Albright syndrome

Multiple myeloma

Glomerulonephritis

Cor pulmonale

Polycythemia vera

Obesity

Carcinoid syndrome

Pregnancy

Previous MI

Nutritional deficiencies (eg, thiamine

deficiency, beriberi)

Valvular heart disease, familial heart

disease

Longitudinal data from the Framingham

Heart Study suggests that antecedent
subclinical left ventricular systolic or
diastolic dysfunction is associated with an
increased incidence of heart failure,
supporting the notion that heart failure is a
progressive syndrome. Another analysis of
over 36,000 patients undergoing outpatient
echocardiography reported that moderate or
severe diastolic dysfunction, but not mild
diastolic dysfunction, is an independent
predictor of mortality.

Alcohol use

Hypertension

Diabetes

Dyslipidemia

Coronary/peripheral vascular disease

Sleep-disordered breathing

Genetics of cardiomyopathy

Collagen vascular disease, rheumatic

fever

Pheochromocytoma

Thyroid disease

Substance abuse history

History of chemotherapy/radiation to
the chest

Autosomal dominant inheritance has been

demonstrated in dilated cardiomyopathy and
in
arrhythmic
right
ventricular
cardiomyopathy.
Restrictive
cardiomyopathies are usually sporadic and
associated with the gene for cardiac troponin
I. Genetic tests are available at major genetic
centers for cardiomyopathies.
In families with a first-degree relative who
has been diagnosed with a cardiomyopathy
leading to heart failure, the at-risk patient
should be screened and followed. The
recommended screening consists of an
electrocardiogram and an echocardiogram.
If the patient has an asymptomatic left
ventricular dysfunction, it should be treated.
History
In evaluating heart failure patients, the
clinician should ask about the following
comorbidities and/or risk factors:

Myopathy

Exertional dyspnea
The principal difference between exertional
dyspnea in patients who are healthy and
exertional dyspnea in patients with heart
failure is the degree of activity necessary to
induce the symptom. As heart failure first
develops, exertional dyspnea may simply
appear to be an aggravation of the
breathlessness that occurs in healthy persons
during activity, but as LV failure advances,
the intensity of exercise resulting in
breathlessness
progressively
declines;
however, subjective exercise capacity and
objective measures of LV performance at
rest in patients with heart failure are not

closely correlated. Exertional dyspnea, in

fact, may be absent in sedentary patients.
Orthopnea
Orthopnea is an early symptom of heart
failure and may be defined as dyspnea that
develops in the recumbent position and is
relieved with elevation of the head with
pillows. As in the case of exertional
dyspnea, the change in the number of
pillows required is important. In the
recumbent position, decreased pooling of
blood in the lower extremities and abdomen
occurs. Blood is displaced from the
extrathoracic compartment to the thoracic
compartment. The failing LV, operating on
the flat portion of the Frank-Starling curve,
cannot accept and pump out the extra
volume of blood delivered to it without
dilating. As a result, pulmonary venous and
capillary pressures rise further, causing
interstitial pulmonary edema, reduced
pulmonary compliance, increased airway
resistance, and dyspnea.
Orthopnea occurs rapidly, often within a
minute or two of recumbency, and develops
when the patient is awake. Orthopnea may
occur in any condition in which the vital
capacity is low. Marked ascites, regardless
of its etiology, is an important cause of
orthopnea. In advanced LV failure,
orthopnea may be so severe that the patient
cannot lie down and must sleep sitting up in
a chair or slumped over a table.
Cough, particularly during recumbency, may
be an "orthopnea equivalent." This
nonproductive cough may be caused by
pulmonary congestion and is relieved by the
treatment of heart failure.
Paroxysmal nocturnal dyspnea

Paroxysmal nocturnal dyspnea usually

occurs at night and is defined as the sudden
awakening of the patient, after a couple of
hours of sleep, with a feeling of severe
anxiety, breathlessness, and suffocation. The
patient may bolt upright in bed and gasp for
breath. Bronchospasm increases ventilatory
difficulty and the work of breathing and is a
common complicating factor of paroxysmal
nocturnal dyspnea. On chest auscultation,
the bronchospasm associated with a heart
failure exacerbation can be difficult to
distinguish from an acute asthma
exacerbation, although other clues from the
cardiovascular examination should lead the
examiner to the correct diagnosis. Both
types of bronchospasm can be present in a
single individual.
In contrast to orthopnea, which may be
relieved by immediately sitting up in bed,
paroxysmal nocturnal dyspnea may require
30 minutes or longer in this position for
relief. Episodes may be so frightening that
the patient may be afraid to resume sleeping,
even after the symptoms have subsided.
Dyspnea at rest
Dyspnea at rest in heart failure is the result
of the following mechanisms:

Decreased
pulmonary
function
secondary to decreased compliance
and increased airway resistance

Increased
ventilatory
drive
secondary to hypoxemia due to
increased pulmonary capillary wedge
pressure
(PCWP);
ventilation/perfusion
(V/Q)
mismatching due to increased PCWP
and low cardiac output; and
increased carbon dioxide production

Respiratory muscle dysfunction, with

decreased
respiratory
muscle
strength, decreased endurance, and
ischemia

Pulmonary edema
Acute pulmonary edema is defined as the
sudden increase in PCWP (usually more
than 25 mm Hg) as a result of acute and
fulminant left ventricular failure. It is a
medical emergency and has a very dramatic
clinical presentation. The patient appears
extremely ill, poorly perfused, restless,
sweaty, tachypneic, tachycardic, hypoxic,
and coughing, with an increased work of
breathing and using respiratory accessory
muscles and with frothy sputum that on
occasion is blood tinged.
Chest pain/pressure and palpitations
Chest pain/pressure may occur as a result of
either primary myocardial ischemia from
coronary disease or secondary myocardial
ischemia from increased filling pressure,
poor cardiac output (and therefore poor
coronary diastolic filling), or hypotension
and hypoxemia.[54]
Palpitations are the sensation a patient has
when the heart is racing. It can be secondary
to sinus tachycardia due to decompensated
heart failure, or more commonly, it is due to
atrial or ventricular tachyarrhythmias.
Fatigue and weakness
Fatigue
and
weakness
are
often
accompanied by a feeling of heaviness in the
limbs and are generally related to poor
perfusion of the skeletal muscles in patients
with a lowered cardiac output. Although
they are generally a constant feature of
advanced heart failure, episodic fatigue and
weakness are also common in earlier stages.

Nocturia and oliguria

Nocturia may occur relatively early in the
course of heart failure. Recumbency reduces
the deficit in cardiac output in relation to
oxygen demand, renal vasoconstriction
diminishes, and urine formation increases.
Nocturia may be troublesome for patients
with heart failure because it may prevent
them from obtaining much-needed rest.
Oliguria is a late finding in heart failure and
is found in patients with markedly reduced
cardiac output from severely reduced LV
function.
Cerebral symptoms
The following may occur in elderly patients
with advanced heart failure, particularly in
those with cerebrovascular atherosclerosis:

Confusion

Memory impairment

Anxiety

Headaches

Insomnia

Bad dreams or nightmares

Rarely,
psychosis
disorientation,
delirium,
hallucinations

with
or

Physical Examination
Patients with mild heart failure appear to be
in no distress after a few minutes of rest, but
they may be obviously dyspneic during and
immediately after moderate activity. Patients
with LV failure may be dyspneic when lying
flat without elevation of the head for more

than a few minutes. Those with severe heart

failure appear anxious and may exhibit signs
of air hunger in this position.
Patients with recent onset of heart failure are
generally well nourished, but those with
chronic severe heart failure are often
malnourished
and
sometimes
even
cachectic. Chronic marked elevation of
systemic venous pressure may produce
exophthalmos
and
severe
tricuspid
regurgitation and may lead to visible
pulsation of the eyes and of the neck veins.
Central cyanosis, icterus, and malar flush
may be evident in patients with severe heart
failure.
In mild or moderate heart failure, stroke
volume is normal at rest; in severe heart
failure, it is reduced, as reflected by a
diminished pulse pressure and a dusky
discoloration of the skin. With very severe
heart failure, particularly if cardiac output
has declined acutely, systolic arterial
pressure may be reduced. The pulse may be
weak, rapid, and thready; the proportional
pulse pressure (pulse pressure/systolic
pressure) may be markedly reduced. The
proportional pulse pressure correlates
reasonably well with cardiac output. In one
study, when pulse pressure was less than
25%, it usually reflected a cardiac index of
less than 2.2 L/min/m2.
Ascites occurs in patients with increased
pressure in the hepatic veins and in the veins
draining into the peritoneum and usually
reflects long-standing systemic venous
hypertension. Fever may be present in
severe decompensated heart failure because
of
cutaneous
vasoconstriction
and
impairment of heat loss.
Increased adrenergic activity is manifested
by
tachycardia,
diaphoresis,
pallor,
peripheral cyanosis with pallor and coldness

of the extremities, and obvious distention of

the peripheral veins secondary to
venoconstriction. Diastolic arterial pressure
may be slightly elevated.
Rales heard over the lung bases are
characteristic of heart failure of at least
moderate severity. With acute pulmonary
edema, rales are frequently accompanied by
wheezing and expectoration of frothy,
blood-tinged sputum. The absence of rales
certainly does not exclude elevation of
pulmonary capillary pressure due to LV
failure.
Systemic venous hypertension is manifested
by jugular venous distention. Normally,
jugular venous pressure declines with
respiration; however, it increases in patients
with heart failure, a finding known as the
Kussmaul sign (also found in constrictive
pericarditis). This reflects an increase in
right atrial pressure and therefore right-sided
heart failure.
Hepatojugular reflux is the distention of the
jugular vein induced by applying manual
pressure over the liver; the patient's torso
should be positioned at a 45 angle.
Hepatojugular reflux occurs in patients with
elevated left-sided filling pressures and
reflects elevated capillary wedge pressure
and left-sided heart failure.
Although edema is a cardinal manifestation
of heart failure, it does not correlate well
with the level of systemic venous pressure.
In patients with chronic LV failure and low
cardiac output, extracellular fluid volume
may be sufficiently expanded to cause
edema in the presence of only slight
elevations in systemic venous pressure.
Usually, a substantial gain of extracellular
fluid volume (ie, a minimum of 5 L in
adults) must occur before peripheral edema
develops. Edema in the absence of dyspnea

or other signs of LV or RV failure is not

solely indicative of heart failure and can be
observed in many other conditions,
including chronic venous insufficiency,
nephrotic syndrome, or other syndromes of
hypoproteinemia or osmotic imbalance.

chronic heart failure. Notable exceptions

include heart failure from acute MI,
constrictive
pericarditis,
restrictive
cardiomyopathy, valve or chordae tendineae
rupture, or heart failure due to
tachyarrhythmias or bradyarrhythmias.

Hepatomegaly is prominent in patients with

chronic right-sided heart failure, but it may
occur rapidly in acute heart failure. When
hepatomegaly occurs acutely, the liver is
usually tender. In patients with considerable
tricuspid regurgitation, a prominent systolic
pulsation of the liver, attributable to an
enlarged right atrial V wave, is often noted.
A presystolic pulsation of the liver,
attributable to an enlarged right atrial A
wave, can occur in tricuspid stenosis,
constrictive
pericarditis,
restrictive
cardiomyopathy
involving
the
right
ventricle, and pulmonary hypertension
(primary or secondary).

Pulsus alternans (during pulse palpation, this

is the alternation of 1 strong and 1 weak beat
without a change in the cycle length) occurs
most commonly in heart failure due to
increased resistance to LV ejection, as
occurs in hypertension, aortic stenosis,
coronary atherosclerosis, and dilated
cardiomyopathy. Pulsus alternans is usually
associated with an S3 gallop, signifies
advanced myocardial disease, and often
disappears with treatment of heart failure.

Hydrothorax is most commonly observed in

patients with hypertension involving both
the systemic and pulmonary circulation. It is
usually bilateral, although when unilateral, it
is usually confined to the right side of the
chest. When hydrothorax develops, dyspnea
usually intensifies because of further
reductions in vital capacity.
Cardiac findings
Protodiastolic (S3) gallop is the earliest
cardiac physical finding in decompensated
heart failure in the absence of severe mitral
or tricuspid regurgitation or left-to-right
shunts. The presence of an S3 gallop in
adults is important, pathologic, and often the
most apparent finding on cardiac
auscultation in patients with significant heart
failure.
Cardiomegaly is a nonspecific finding that
nonetheless occurs in most patients with

Accentuation of P2 heart sound is a cardinal

sign of increased pulmonary artery pressure;
it disappears or improves after treatment of
heart failure. Mitral and tricuspid
regurgitation murmurs are often present in
patients with decompensated heart failure
because of ventricular dilatation. These
murmurs often disappear or diminish when
compensation is restored. Note that
correlation between the intensity of the
murmur of mitral regurgitation and its
significance in patients with heart failure is
poor. Severe mitral regurgitation may be
accompanied by an unimpressively soft
murmur.
Cardiac cachexia is found in long-standing
heart failure, particularly of the right
ventricle, because of anorexia from hepatic
and intestinal congestion and sometimes
because of digitalis toxicity. Occasionally,
impaired intestinal absorption of fat occurs,
and rarely, protein-losing enteropathy
occurs. Patients with heart failure may also
exhibit
increased
total
metabolism
secondary to augmentation of myocardial
oxygen consumption, excessive work of

breathing, low-grade fever, and elevated

levels of circulating tumor necrosis factor
(TNF).
Predominant Right-Sided Heart Failure
Ascites, congestive hepatomegaly, and
anasarca due to elevated right-sided heart
pressures transmitted backward into the
portal vein circulation may result in
increased abdominal girth and epigastric and
right upper quadrant (RUQ) abdominal pain.
Other gastrointestinal symptoms, caused by
congestion
of
the
hepatic
and
gastrointestinal venous circulation, include
anorexia, bloating, nausea, and constipation.
In preterminal heart failure, inadequate
bowel perfusion can cause abdominal pain,
distention, and bloody stools. Distinguishing
right-sided heart failure from hepatic failure
is often clinically difficult.
Dyspnea, prominent in LV failure, becomes
less prominent in isolated right-sided heart
failure because of the absence of pulmonary
congestion. On the other hand, when cardiac
output becomes markedly reduced in
patients with terminal right-sided heart
failure (as may occur in isolated RV
infarction and in the late stages of primary
pulmonary hypertension and pulmonary
thromboembolic disease), severe dyspnea
may occur as a consequence of the reduced
cardiac output, poor perfusion of respiratory
muscles, hypoxemia, and metabolic
acidosis.
Nonpharmacologic Therapy
Patients with heart failure can benefit from
attention to exercise, diet, and nutrition.
Restriction of activity promotes physical
deconditioning, so physical activity should
be encouraged. However, limitation of
activity is appropriate during acute heart
failure exacerbations and in patients with

suspected myocarditis. Most patients should

not participate in heavy labor or exhaustive
sports.
A 2012 meta-analysis showed that aerobic
exercise training, particularly long-term, can
reverse left ventricular remodelling in
clinically stable heart failure patients, while
strength training had no effect on
remodelling.
Because nonadherence to diet and
medication can have rapid and profound
adverse effects on patients clinical status,
close observation and follow-up are
important aspects of care. Patient education
and close supervision, including surveillance
by the patient and family, can improve
adherence. These measures also facilitate
early detection of weight gain or slightly
worsened symptoms, which often occur
several days before major clinical episodes
that
require
emergency
care
or
hospitalization. Patients can then alert their
clinicians, who may be able to prevent such
episodes through prompt intervention.
Dietary sodium restriction to 2-3 g/day is
recommended. Fluid restriction to 2 L/day is
recommended for patients with evidence of
hyponatremia (Na < 130 mEq/dL) and for
those whose fluid status is difficult to
control despite sodium restriction and the
use of high-dose diuretics. Caloric
supplementation is recommended for
patients with evidence of cardiac cachexia.
An analysis of concentrations of plasma
eicosapentaenoic acid (EPA), a long-chain
omega-3 fatty acid, in the Cardiovascular
Health Study identified plasma phospholipid

EPA concentration as being inversely related

to incident congestive heart failure.] These
results support additional studies on the
potential benefits of omega-3 fatty acids for
primary prevention of heart failure.
The GISSI-HF (Gruppo Italiano per lo
Studio della Sopravvivenza nell'Infarto
Miocardico) trial included nearly 7000
patients with systolic heart failure (any LV
ejection fraction) who received either 1 g of
omega-3 polyunsaturated fatty acids
(PUFAs) or placebo daily and demonstrated
that the PUFA regimen had a small but
significant reduction in both all-cause
mortality
and
all-cause
mortality/hospitalization for cardiovascular
causes

sustaining tachycardia is established. If allowed to

progress, such a tachycardia may deteriorate into
fibrillation (e.g. ventricular fibrillation)