Heart Failure

Heart Failure: Practice Essentials, Background, Pathophysiology
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http://emedicine.medscape.com/article/163062-overview
Heart Failure
Author: Ioana Dumitru, MD; Chief Editor: Henry H Ooi, MD, MRCPI more...
Updated: Jul 13, 2015
Practice Essentials
Heart failure develops when the heart, via an abnormality of cardiac function
(detectable or not), fails to pump blood at a rate commensurate with the
requirements of the metabolizing tissues or is able to do so only with an elevated
diastolic filling pressure. See the image below.
This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases,
signs of acute heart failure.
Signs and symptoms
Signs and symptoms of heart failure include the following:

Exertional dyspnea and/or dyspnea at rest
Orthopnea
Acute pulmonary edema
Chest pain/pressure and palpitations
Tachycardia
Fatigue and weakness
Nocturia and oliguria
Anorexia, weight loss, nausea
Exophthalmos and/or visible pulsation of eyes
Distention of neck veins
Weak, rapid, and thready pulse
Rales, wheezing
S 3 gallop and/or pulsus alternans
Increased intensity of P 2 heart sound
Hepatojugular reflux
Ascites, hepatomegaly, and/or anasarca
Central or peripheral cyanosis, pallor
See Clinical Presentation for more detail.
Diagnosis
Heart failure criteria, classification, and staging
The Framingham criteria for the diagnosis of heart failure consists of the concurrent
presence of either 2 major criteria or 1 major and 2 minor criteria.[1]
Major criteria include the following:
Paroxysmal nocturnal dyspnea

Weight loss of 4.5 kg in 5 days in response to treatment
Neck vein distention
Rales
Acute pulmonary edema
Hepatojugular reflux
S 3 gallop
Central venous pressure greater than 16 cm water
Circulation time of 25 seconds
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Radiographic cardiomegaly
Pulmonary edema, visceral congestion, or cardiomegaly at autopsy
Minor criteria are as follows:
Nocturnal cough
Dyspnea on ordinary exertion
A decrease in vital capacity by one third the maximal value recorded
Pleural effusion
Tachycardia (rate of 120 bpm)
Bilateral ankle edema
The New York Heart Association (NYHA) classification system categorizes heart
failure on a scale of I to IV,[2] as follows:
Class I: No limitation of physical activity

Class II: Slight limitation of physical activity
Class III: Marked limitation of physical activity
Class IV: Symptoms occur even at rest; discomfort with any physical activity
The American College of Cardiology/American Heart Association (ACC/AHA)

staging system is defined by the following 4 stages[3, 4] :
Stage A: High risk of heart failure but no structural heart disease or
symptoms of heart failure
Stage B: Structural heart disease but no symptoms of heart failure
Stage C: Structural heart disease and symptoms of heart failure
Stage D: Refractory heart failure requiring specialized interventions
Testing
The following tests may be useful in the initial evaluation for suspected heart
failure[3, 5, 6] :
Complete blood count (CBC)
Urinalysis
Electrolyte levels
Renal and liver function studies
Fasting blood glucose levels
Lipid profile
Thyroid stimulating hormone (TSH) levels
B-type natriuretic peptide levels
N-terminal pro-B-type natriuretic peptide
Electrocardiography
Chest radiography
2-dimensional (2-D) echocardiography
Nuclear imaging [7]
Maximal exercise testing
Pulse oximetry or arterial blood gas
See Workup for more detail.
Management
Treatment includes the following:
Nonpharmacologic therapy: Oxygen and noninvasive positive pressure

ventilation, dietary sodium and fluid restriction, physical activity as
appropriate, and attention to weight gain
Pharmacotherapy: Diuretics, vasodilators, inotropic agents, anticoagulants,
beta blockers, and digoxin
Surgical options
Surgical treatment options include the following:

Electrophysiologic intervention
Revascularization procedures
Valve replacement/repair
Ventricular restoration
Extracorporeal membrane oxygenation
Ventricular assist devices
Heart transplantation
Total artificial heart
See Treatment and Medication for more detail.
Background
Heart failure is the pathophysiologic state in which the heart, via an abnormality of
cardiac function (detectable or not), fails to pump blood at a rate commensurate with
the requirements of the metabolizing tissues or is able to do so only with an elevated
diastolic filling pressure.
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Heart failure (see the images below) may be caused by myocardial failure but may
also occur in the presence of near-normal cardiac function under conditions of high
demand. Heart failure always causes circulatory failure, but the converse is not
necessarily the case, because various noncardiac conditions (eg, hypovolemic
shock, septic shock) can produce circulatory failure in the presence of normal,
modestly impaired, or even supranormal cardiac function. To maintain the pumping
function of the heart, compensatory mechanisms increase blood volume, cardiac
filling pressure, heart rate, and cardiac muscle mass. However, despite these
mechanisms, there is progressive decline in the ability of the heart to contract and
relax, resulting in worsening heart failure.
This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases,
signs of acute heart failure.
A 28-year-old woman presented with acute heart failure secondary to chronic hypertension.
The enlarged cardiac silhouette on this anteroposterior (AP) radiograph is caused by acute
heart failure due to the effects of chronic high blood pressure on the left ventricle. The heart
then becomes enlarged, and fluid accumulates in the lungs (ie, pulmonary congestion).
Signs and symptoms of heart failure include tachycardia and manifestations of

venous congestion (eg, edema) and low cardiac output (eg, fatigue). Breathlessness
is a cardinal symptom of left ventricular (LV) failure that may manifest with
progressively increasing severity.
Heart failure can be classified according to a variety of factors (see Heart Failure
Criteria and Classification). The New York Heart Association (NYHA) classification
for heart failure comprises 4 classes, based on the relationship between symptoms
and the amount of effort required to provoke them, as follows[2] :
Class I patients have no limitation of physical activity

Class II patients have slight limitation of physical activity
Class III patients have marked limitation of physical activity
Class IV patients have symptoms even at rest and are unable to carry on any
physical activity without discomfort
The American College of Cardiology/American Heart Association (ACC/AHA) heart

failure guidelines complement the NYHA classification to reflect the progression of
disease and are divided into 4 stages, as follows[3, 4] :
Stage A patients are at high risk for heart failure but have no structural heart
disease or symptoms of heart failure
Stage B patients have structural heart disease but have no symptoms of
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heart failure
Stage C patients have structural heart disease and have symptoms of heart
failure
Stage D patients have refractory heart failure requiring specialized
interventions
Laboratory studies for heart failure should include a complete blood count (CBC),
electrolytes, and renal function studies. Imaging studies such as chest radiography
and 2-dimensional echocardiography are recommended in the initial evaluation of
patients with known or suspected heart failure. B-type natriuretic peptide (BNP) and
N-terminal pro-B-type natriuretic peptide (NT-proBNP) levels can be useful in
differentiating cardiac and noncardiac causes of dyspnea. (See the Workup Section
for more information.)
In acute heart failure, patient care consists of stabilizing the patient's clinical
condition; establishing the diagnosis, etiology, and precipitating factors; and initiating
therapies to provide rapid symptom relief and survival benefit. Surgical options for
heart failure include revascularization procedures, electrophysiologic intervention,
cardiac resynchronization therapy (CRT), implantable cardioverter-defibrillators
(ICDs), valve replacement or repair, ventricular restoration, heart transplantation,
and ventricular assist devices (VADs). (See the Treatment Section for more
information.)
The goals of pharmacotherapy are to increase survival and to prevent complications.

Along with oxygen, medications assisting with symptom relief include diuretics,
digoxin, inotropes, and morphine. Drugs that can exacerbate heart failure should be
avoided (nonsteroidal anti-inflammatory drugs [NSAIDs], calcium channel blockers
[CCBs], and most antiarrhythmic drugs). (See the Medication Section for more
information.)
For further information, see the Medscape Reference articles Pediatric Congestive
Heart Failure, Congestive Heart Failure Imaging, Heart Transplantation, Coronary
Artery Bypass Grafting, and Implantable Cardioverter-Defibrillators.
Pathophysiology
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.[8, 9, 10, 11, 12]
Adaptations
Most important among the adaptations are the following[13] :
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.[14]
The primary myocardial response to chronic increased wall stress is myocyte

hypertrophy, death/apoptosis, and regeneration.[15] 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.[16]
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.[17]
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
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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 and
myocardial responses.
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 beta1adrenergic 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.[18] 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.[15]
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.[19] 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.[20] 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.
As heart failure advances, there is a relative decline in the counterregulatory effects
of endogenous vasodilators, including nitric oxide (NO), prostaglandins (PGs),
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
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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.
For more information, see the Medscape Reference article Natriuretic Peptides in
Congestive Heart Failure.
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).[21] 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 with normal ejection fraction
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.[22]
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.[23]
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 ventricular pressure-volume curve
Decrease in ventricular distensibility
A rise in filling pressure is the movement of the ventricle up along its pressurevolume 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 pressure-volume 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
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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 life-threatening 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.
Underlying causes
Specific underlying factors cause various forms of heart failure, such as systolic
heart failure (most commonly, left ventricular systolic dysfunction), heart failure with
preserved LVEF, acute heart failure, high-output 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 (supraventricular or ventricular)
Infections and inflammation (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)
Underlying causes of diastolic heart failure include the following:

Coronary artery disease
Diabetes mellitus
Hypertension
Valvular heart disease (aortic stenosis)
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy (amyloidosis, sarcoidosis)
Constrictive pericarditis
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Underlying causes of acute heart failure include the following:
Acute valvular (mitral or aortic) regurgitation

Myocardial infarction
Myocarditis
Arrhythmia
Drugs (eg, cocaine, calcium channel blockers, or beta-blocker overdose)
Sepsis
Underlying causes of high-output heart failure include the following:

Anemia
Systemic arteriovenous fistulas
Hyperthyroidism
Beriberi heart disease
Paget disease of bone
Albright syndrome (fibrous dysplasia)
Multiple myeloma
Pregnancy
Glomerulonephritis
Polycythemia vera
Carcinoid syndrome
Underlying causes of right heart failure include the following:

Left ventricular failure
Coronary artery disease (ischemia)
Pulmonary hypertension
Pulmonary valve stenosis
Pulmonary embolism
Chronic pulmonary disease
Neuromuscular disease
Precipitating causes of heart failure

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
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of heart failure:
Profound anemia
Thyrotoxicosis
Myxedema
Paget disease of bone
Albright syndrome
Multiple myeloma
Glomerulonephritis
Cor pulmonale
Polycythemia vera
Obesity
Carcinoid syndrome
Pregnancy
Nutritional deficiencies (eg, thiamine deficiency, beriberi)
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.[24, 25] 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.[26]
Genetics of cardiomyopathy
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.[27]
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.[27] The recommended screening consists of an electrocardiogram and an
echocardiogram. If the patient has an asymptomatic left ventricular dysfunction, it
should be treated.[27]
Epidemiology
United States statistics

According to the American Heart Association, heart failure affects nearly 5.7 million
Americans of all ages[28] and is responsible for more hospitalizations than all forms
of cancer combined. It is the number 1 cause of hospitalization for Medicare
patients. With improved survival of patients with acute myocardial infarction and with
a population that continues to age, heart failure will continue to increase in
prominence as a major health problem in the United States.[29, 30, 31, 32]
Analysis of national and regional trends in hospitalization and mortality among
Medicare beneficiaries from 1998-2008 showed a relative decline of 29.5% in heart
failure hospitalizations[33] ; however, wide variations are noted between states and
races, with black men having the slowest rate of decline. A relative decline of 6.6%
in mortality was also observed, although the rate was uneven across states. The
length of stay decreased from 6.8 days to 6.4 days, despite an overall increase in
the comorbid conditions.[33]
Heart failure statistics for the United States are as follows:
Heart failure is the fastest-growing clinical cardiac disease entity in the United
States, affecting 2% of the population
Heart failure accounts for 34% of cardiovascular-related deaths [28]
Approximately 670,000 new cases of heart failure are diagnosed each year
[28]
About 277,000 deaths are caused by heart failure each year [28]
Heart failure is the most frequent cause of hospitalization in patients older
than 65 years, with an annual incidence of 10 per 1,000 [28]
Rehospitalization rates during the 6 months following discharge are as much
as 50% [34]
Nearly 2% of all hospital admissions in the United States are for
decompensated heart failure, and the average duration of hospitalization is
about 6 days
In 2010, the estimated total cost of heart failure in the United States was
$39.2 billion, [35] representing 1-2% of all health care expenditures
The incidence and prevalence of heart failure are higher in blacks, Hispanics, Native
Americans, and recent immigrants from developing nations, Russia, and the former
Soviet republics. The higher prevalence of heart failure in blacks, Hispanics, and
Native Americans is directly related to the higher incidence and prevalence of
hypertension and diabetes. This problem is particularly exacerbated by a lack of
access to health care and by substandard preventive health care available to the
most indigent of individuals in these and other groups; in addition, many persons in
these groups do not have adequate health insurance.
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The higher incidence and prevalence of heart failure in recent immigrants from
developing nations are largely due to a lack of prior preventive health care, a lack of
treatment, or substandard treatment for common conditions, such as hypertension,
diabetes, rheumatic fever, and ischemic heart disease.
Men and women have the same incidence and the same prevalence of heart failure.
However, there are still many differences between men and women with heart
failure, such as the following:
Women tend to develop heart failure later in life than men do

Women are more likely than men to have preserved systolic function
Women develop depression more commonly than men do
Women have signs and symptoms of heart failure similar to those of men, but
they are more pronounced in women
Women survive longer with heart failure than men do
The prevalence of heart failure increases with age. The prevalence is 1-2% of the
population younger than 55 years and increases to a rate of 10% for persons older
than 75 years. Nonetheless, heart failure can occur at any age, depending on the
cause.
International statistics
Heart failure is a worldwide problem. The most common cause of heart failure in
industrialized countries is ischemic cardiomyopathy, with other causes, including
Chagas disease and valvular cardiomyopathy, assuming a more important role in
developing countries. However, in developing nations that have become more
urbanized and more affluent, eating a more processed diet and leading a more
sedentary lifestyle have resulted in an increased rate of heart failure, along with
increased rates of diabetes and hypertension. This change was illustrated in a
population study in Soweto, South Africa, where the community transformed into a
more urban and westernized city, followed by an increase in diabetes, hypertension,
and heart failure.[36]
In terms of treatment, one study showed few important differences in uptake of key
therapies in European countries with widely differing cultures and varying economic
status for patients with heart failure. In contrast, studies of sub-Saharan Africa,
where health care resources are more limited, have shown poor outcomes in
specific populations.[37, 38] For example, in some countries, hypertensive heart
failure carries a 25% 1-year mortality rate, and human immunodeficiency virus
(HIV)associated cardiomyopathy generally progresses to death within 100 days of
diagnosis in patients who are not treated with antiretroviral drugs.
While data regarding developing nations are not as robust as studies of Western
society, the following trends in developing nations are apparent:
Causes tend to be largely nonischemic

Patients tend to present at a younger age
Outcomes are largely worse where health care resources are limited
Isolated right heart failure tends to be more prominent, with a variety of
causes having been postulated, ranging from tuberculous pericardial disease
to lung disease and pollution
Prognosis
In general, the mortality following hospitalization for patients with heart failure is
10.4% at 30 days, 22% at 1 year, and 42.3% at 5 years, despite marked
improvement in medical and device therapy.[28, 39, 40, 41, 42, 43] Each
rehospitalization increases mortality by about 20-22%.[28]
Mortality is greater than 50% for patients with NYHA class IV, ACC/AHA stage D
heart failure. Heart failure associated with acute MI has an inpatient mortality of
20-40%; mortality approaches 80% in patients who are also hypotensive (eg,
cardiogenic shock). (See Heart Failure Criteria and Classification).
Numerous demographic, clinical and biochemical variables have been reported to

provide important prognostic value in patients with heart failure, and several
predictive models have been developed.[44]
A study by van Diepen et al suggests that patients with heart failure or atrial
fibrillation have a significantly higher risk of noncardiac postoperative mortality than
patients with coronary artery disease; this risk should be considered even if a minor
procedure is planned.[45]
A study by Bursi et al found that among community patients with heart failure,
pulmonary artery systolic pressure (PASP), assessed by Doppler echocardiography,
can strongly predict death and can provide incremental and clinically significant
prognostic information independent of known outcome predictors.[46]
Higher concentrations of galectin-3, a marker of cardiac fibrosis, were associated
with an increased risk for incident heart failure (hazard ratio: 1.28 per 1 SD increase
in log galectin-3) in the Framingham Offspring Cohort. Galectin-3 was also
associated with an increased risk for all-cause mortality (multivariable-adjusted
14-Oct-15 11:14 AM
11 of 23
hazard ratio: 1.15).[47]
Patient Education
To help prevent recurrence of heart failure in patients in whom heart failure was
caused by dietary factors or medication noncompliance, counsel and educate such
patients about the importance of proper diet and the necessity of medication
compliance. Dunlay et al examined medication use and adherence among
community-dwelling patients with heart failure and found that medication adherence
was suboptimal in many patients, often because of cost.[48] A randomized controlled
trial of 605 patients with heart failure reported that the incidence of all-cause
hospitalization or death was not reduced in patients receiving multi-session self-care
training compared to those receiving a single session intervention. The optimum
method for patient education remains to be established. It appears that more
intensive interventions are not necessarily better.[49]
For patient education information, see the Heart Health Center, Cholesterol Center,
and Diabetes Center, as well as Congestive Heart Failure, High Cholesterol, Chest
Pain, Heart Rhythm Disorders, Coronary Heart Disease, and Heart Attack.
Clinical Presentation
Contributor Information and Disclosures
Author
Ioana Dumitru, MD Associate Professor of Medicine, Division of Cardiology, Founder and Medical Director, Heart
Failure and Cardiac Transplant Program, University of Nebraska Medical Center; Associate Professor of
Medicine, Division of Cardiology, Veterans Affairs Medical Center
Ioana Dumitru, MD is a member of the following medical societies: American College of Cardiology, International
Society for Heart and Lung Transplantation, Heart Failure Society of America
Disclosure: Nothing to disclose.
Coauthor(s)
Mathue M Baker, MD Cardiologist, BryanLGH Heart Institute and Saint Elizabeth Regional Medical Center
Mathue M Baker, MD is a member of the following medical societies: American College of Cardiology
Specialty Editor Board

Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of
Pharmacy; Editor-in-Chief, Medscape Drug Reference
Chief Editor
Henry H Ooi, MD, MRCPI Director, Advanced Heart Failure and Cardiac Transplant Program, Nashville Veterans
Affairs Medical Center; Assistant Professor of Medicine, Vanderbilt University School of Medicine
Acknowledgements
Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program
Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University
School of Medicine
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha,
American Academy of Emergency Medicine, American College of Chest Physicians, American College of
Emergency Physicians, American College of Physicians, American Heart Association, American Thoracic Society,
Arkansas Medical Society, New York Academy of Medicine, New York AcademyofSciences,and Society for
Academic Emergency Medicine
David FM Brown, MD Associate Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair,
Department of Emergency Medicine, Massachusetts General Hospital
David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians
and Society for Academic Emergency Medicine
14-Oct-15 11:14 AM
12 of 23
William K Chiang, MD Associate Professor, Department of Emergency Medicine, New York University School of
Medicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center
William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology,
American College of Medical Toxicology, and Society for Academic Emergency Medicine
Joseph Cornelius Cleveland Jr, MD Associate Professor, Division of Cardiothoracic Surgery, University of
Colorado Health Sciences Center
Joseph Cornelius Cleveland Jr, MD is a member of the following medical societies: Alpha Omega Alpha,
American Association for the Advancement of Science, American College of Cardiology, American College of
Chest Physicians, American College of Surgeons, American Geriatrics Society, American Physiological Society,
American Society of Transplant Surgeons, Association for Academic Surgery, Heart Failure Society of America,
International Society for Heart and Lung Transplantation, Phi Beta Kappa, Society of Critical Care Medicine,
Society of Thoracic Surgeons, and Western Thoracic Surgical Association
Disclosure: Thoratec Heartmate II Pivotal Tria; Grant/research funds Principal Investigator - Colorado; Abbott
Vascular E-Valve E-clip Honoraria Consulting; Baxter Healthcare Corp Consulting fee Board membership;
Heartware Advance BTT Trial Grant/research funds Principal Investigator- Colorado; Heartware Endurance DT
trial Grant/research funds Principal Investigator-Colorado
Shamai Grossman, MD, MS Assistant Professor, Department of Emergency Medicine, Harvard Medical School;
Director, The Clinical Decision Unit and Cardiac Emergency Center, Beth Israel Deaconess Medical Center
Shamai Grossman, MD, MS is a member of the following medical societies: American College of Emergency
Physicians
John D Newell Jr, MD Professor of Radiology, Head, Division of Radiology, National Jewish Health; Professor,
Department of Radiology, University of Colorado School of Medicine
John D Newell Jr, MD is a member of the following medical societies: American College of Chest Physicians,
American College of Radiology, American Roentgen Ray Society, American Thoracic Society, Association of
University Radiologists, Radiological Society of North America, and Society of Thoracic Radiology
Disclosure: Siemens Medical Grant/research funds Consulting; Vida Corporation Ownership interest Board
membership; TeraRecon Grant/research funds Consulting; Medscape Reference Honoraria Consulting; Humana
Press Honoraria Other
Craig H Selzman, MD, FACS Associate Professor of Surgery, Surgical Director, Cardiac Mechanical Support and
Heart Transplant, Division of Cardiothoracic Surgery, University of Utah School of Medicine
Craig H Selzman, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American
Association for Thoracic Surgery, American College of Surgeons, American Physiological Society, Association for
Academic Surgery, International Society for Heart and Lung Transplantation, Society of Thoracic Surgeons,
Southern Thoracic Surgical Association, and Western Thoracic Surgical Association
Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor,
Division of Emergency Medicine, Harvard Medical School
Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians,
National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management
position; ProceduresConsult.com Royalty Other
Brett C Sheridan, MD, FACS Associate Professor of Surgery, University of North Carolina at Chapel Hill School
of Medicine
George A Stouffer III, MD Henry A Foscue Distinguished Professor of Medicine and Cardiology, Director of
Interventional Cardiology, Cardiac Catheterization Laboratory, Chief of Clinical Cardiology, Division of Cardiology,
University of North Carolina Medical Center
George A Stouffer III, MD is a member of the following medical societies: Alpha Omega Alpha, American College
of Cardiology, American College of Physicians, American Heart Association, Phi Beta Kappa, and Society for
Cardiac Angiography and Interventions
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
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Heart Failure: Practice Essentials, Background, Pathophysiology

Signs and symptoms

Signs and symptoms of heart failure include the following:

See Clinical Presentation for more detail.

Heart failure criteria, classification, and staging

Paroxysmal nocturnal dyspnea

Heart Failure: Practice Essentials, Background, Pathophysiology

Minor criteria are as follows:

Class I: No limitation of physical activity

The American College of Cardiology/American Heart Association (ACC/AHA)

See Workup for more detail.

Treatment includes the following:

Nonpharmacologic therapy: Oxygen and noninvasive positive pressure

Surgical treatment options include the following:

See Treatment and Medication for more detail.

Heart Failure: Practice Essentials, Background, Pathophysiology

Signs and symptoms of heart failure include tachycardia and manifestations of

Class I patients have no limitation of physical activity

The American College of Cardiology/American Heart Association (ACC/AHA) heart

Heart Failure: Practice Essentials, Background, Pathophysiology

The goals of pharmacotherapy are to increase survival and to prevent complications.

Most important among the adaptations are the following[13] :

The Frank-Starling mechanism, in which an increased preload helps to

The release of norepinephrine by adrenergic cardiac nerves augments myocardial

The primary myocardial response to chronic increased wall stress is myocyte

Heart Failure: Practice Essentials, Background, Pathophysiology

impairment in myocardial lusitropy lead to an increase in myocardial energy

The concept of the heart as a self-renewing organ is a relatively recent

Myocytes and myocardial remodeling

In the failing heart, increased myocardial volume is characterized by larger myocytes

Systolic and diastolic failure

ANP and BNP

Heart Failure: Practice Essentials, Background, Pathophysiology

Other vasoactive systems

In individuals with systolic dysfunction, therefore, the neurohormonal responses to

Heart failure with normal ejection fraction

An increase in LV chamber stiffness occurs secondary to any one of, or any

A shift to a steeper ventricular pressure-volume curve results, most commonly, not

Pressure overload that leads to concentric LV hypertrophy (LVH), as occurs in aortic

Heart Failure: Practice Essentials, Background, Pathophysiology

Increases in diastolic pressure lead to increased myocardial energy expenditure,

While life-threatening rhythms are more common in ischemic cardiomyopathy,

Underlying causes: Underlying causes of heart failure include structural

Coronary artery disease

Underlying causes of diastolic heart failure include the following:

Heart Failure: Practice Essentials, Background, Pathophysiology

Underlying causes of acute heart failure include the following:

Acute valvular (mitral or aortic) regurgitation

Underlying causes of high-output heart failure include the following:

Underlying causes of right heart failure include the following:

Precipitating causes of heart failure

Because of increased myocardial oxygen consumption and demand beyond a

Heart Failure: Practice Essentials, Background, Pathophysiology

Autosomal dominant inheritance has been demonstrated in dilated cardiomyopathy

United States statistics

Heart Failure: Practice Essentials, Background, Pathophysiology

Women tend to develop heart failure later in life than men do

Causes tend to be largely nonischemic

Numerous demographic, clinical and biochemical variables have been reported to

Heart Failure: Practice Essentials, Background, Pathophysiology

hazard ratio: 1.15).[47]

Contributor Information and Disclosures

Specialty Editor Board

Heart Failure: Practice Essentials, Background, Pathophysiology