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Heart Failure
Updated: Mar 02, 2021
Author: Ioana Dumitru, MD; Chief Editor: Gyanendra K Sharma, MD, FACC, FASE  more...

OVERVIEW

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.

Heart Failure. 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 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 two major criteria or one major and two minor criteria.
[1]

Major criteria comprise 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 or longer
Radiographic cardiomegaly
Pulmonary edema, visceral congestion, or cardiomegaly at autopsy

Minor criteria (accepted only if they cannot be attributed to another medical condition) 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)
Hepatomegaly
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 four stages
[3] :

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, 4, 5] :

Complete blood count (CBC)

Iron studies
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 levels
Electrocardiography
Chest radiography
Two-dimensional (2-D) echocardiography
Nuclear imaging
[6]
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,
ACE inhibitors, ARBs, CCBs, digoxin, nitrates, B-type natriuretic peptids, I(f) inhibitors,
ARNIs, and soluble guanylate cyclase stimulators

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.

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 a
progressive decline in the ability of the heart to contract and relax, resulting in worsening heart
failure.

Heart Failure. This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases, signs of acute
heart failure.

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,
Classification, and Staging). The New York Heart Association (NYHA) classification for heart failure
comprises four 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 four stages, as follows
[3] :

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 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), electrolyte levels,
and hepatorenal function studies. Imaging studies such as chest radiography and two-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
Workup 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 Treatment 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 Medication for more information.)

For further information, see the Medscape Drugs & Diseases articles Pediatric Congestive Heart
Failure, Congestive Heart Failure Imaging, Heart Transplantation, Pediatric 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 the subcellular all the way through to organ-to-organ interactions. Only when
this network of adaptations becomes overwhelmed does heart failure ensue.
[7, 8, 9, 10, 11]

Adaptations

Most important among the adaptations are the following

[12] :
 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.
[13]

The primary myocardial response to chronic increased wall stress is myocyte hypertrophy,
death/apoptosis, and regeneration.
[14] 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.
[15]

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.
[16]

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 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 a
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 as 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.

[17] This
paradigm for myocyte biology 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.
[14] 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.

Angiotensin 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.
[18] 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.
[19] 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 features—namely, the increased myocardial volume and
mass, along with a net loss of myocytes—are 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 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.
[20, 21] This leads to
activation of peripheral and central baroreflexes and chemoreflexes that are capable of eliciting
marked increases in sympathetic nerve traffic.

Although 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 downregulation of beta1-adrenergic receptors, uncoupling of beta2-
adrenergic receptors, and increased activity of inhibitory G-protein. Changes in beta1-adrenergic
receptors result in overexpression and promote myocardial hypertrophy.

Atrial natriuretic peptide and B-type natriuretic peptide

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
especially has potentially important diagnostic, therapeutic, and prognostic implications.

For more information, see the Medscape Drugs & Diseases 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).
[22] 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 preserved ejection fraction

In diastolic heart failure (heart failure with preserved ejection fraction [HFpEF]), 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.
[23]

In HFpEF, 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 right venticular (RV) subendocardial systolic dysfunction and diastolic
dysfunction, as detected by echocardiographic strain rate imaging, are common in patients with
HFpEF. 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. It may play a
role in the symptomatology of patients with HFpEF.
[24]

LV chamber stiffness
An increase in LV chamber stiffness occurs secondary to any one, or any combination, of the
following three 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 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 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 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 an 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

Although 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 dilatatation,
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 scenario. 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 four 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 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, nonsteroidal anti-
inflammatory drugs [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 vetricular [LV] systolic dysfunction), heart failure with preserved LV ejection fraction
(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

Underlying causes of acute heart failure include the following:

Acute valvular (mitral or aortic) regurgitation

Myocardial infarction (MI)
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:

LV 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 the 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 LV hypertrophy (LVH) may be asymptomatic until an 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 (RV) by
further elevating 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 salt and the administration of cardiac depressants or drugs that
cause salt retention are other factors that can lead to heart failure. At the European Society of
Cardiology 2017 Congress, investigators presented a study comprising more than 4630 people
that indicated high daily salt intake (>13.7 g) is associated with a substantial increased risk of
developing heart failure, independent of other risk factors.
[25, 26]

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
Nutritional deficiencies (eg, thiamine deficiency, beriberi)

Longitudinal data from the Framingham Heart Study has suggested that antecedent subclinical LV
systolic or diastolic dysfunction is associated with an increased incidence of heart failure,
supporting the notion that heart failure is a progressive syndrome.
[27, 28] 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.
[29]

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.
[30]

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.
[30] The recommended screening
consists of an electrocardiogram and an echocardiogram. If the patient has an asymptomatic LV
dysfunction, it should be documented and treated.
[30]

Epidemiology
United States statistics

According to 2017 American Heart Association (AHA) data, heart failure affects an estimated 6.5
million Americans aged 20 years and older.
[31]  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. The AHA projects a 46%
increase of heart failure prevalence from year 2012 to year 2030, resulting in 8 million or more
Americans aged 18 years or older with heart failure.
[31]  

Despite a more than decade-long decrease (2000-2012) in the the incidence of heart failure–
related deaths in the United States, such deaths are on the rise again, particularly among men and
non-Hispanic black populations, according to 2000-2014 data (the most recent data available)
released by the Centers for Disease Control and Prevention (CDC) in December 2015.
[32, 33]  The
crude rate for heart failure-related deaths decreased from 103.1 deaths per 100,000 population in
2000 to 89.5 in 2009; it then increased to 96.9 in 2014. The age-adjusted rate for heart failure-
related deaths decreased from 105.4 deaths per 100,000 standard population in 2000 to 81.4 in
2012; it then increased to 83.4 in 2013 and to 84.0 in 2014.
[32]  The trend appears to represent a
shift from coronary heart disease as the underlying cause of heart failure deaths toward other
cardiovascular and noncardiovascular causes, including malignancies, diabetes, chronic lower
respiratory diseases, and renal disease.

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
[31, 34] ; however, wide variations were 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.
[34]

Heart failure statistics for the United States are as follows

[31] :

Heart failure is the primary cause of hospitalization in the elderly.

[35, 36]
An estimated one in eight deaths is from heart failure (about 309,000 deaths caused by heart
failure each year)
Heart failure accounts for 8.5% of cardiovascular-related deaths
Approximately 960,000 new cases of heart failure are diagnosed each year
The annual incidence of heart failure in patients older than 65 years is 21 per 1,000
population
Rehospitalization rates during the 6 months following discharge are as much as 50%
[37]
In 2012, the estimated total cost of heart failure in the United States was $30.7 billion (68% of
which were direct medical costs); by 2030, the total cost is projected to rise to $69.7 billion, a
nearly 127% increase.

The incidence and prevalence of heart failure are higher in black persons, 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.

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 a similar incidence and prevalence of heart failure. However, many
differences remain between men and women with heart failure, such as the following:

Whereas the incidence of heart failure in men approximately doubles with each 10-year age
increase between 65 and 85 years, it triples for women between ages 65 to 74 years and 75
to 85 years
[31]
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.

[36] 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.
[38]

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 healthcare resources are more
limited, have shown poor outcomes in specific populations.
[39, 40] For example, in some countries,
hypertensive heart failure carries a 25% 1-year mortality, 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.

Although 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 healthcare 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.
[31, 41, 42, 43, 44, 45]

Mortality is greater than 50% for patients with New York Heart Association (NYHA) class IV,
American College of Cardiology/American Heart Association (ACC/AHA) stage D heart failure.
Heart failure associated with acute myocardial infarction (MI) has an inpatient mortality of 20-40%;
mortality approaches 80% in patients who are also hypotensive (eg, cardiogenic shock). (See
Heart Failure Criteria, Classification, and Staging).

Heart failure related to systolic dysfunction has an associated mortality of 50% after 5 years.
[20]

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.
[46]

A study by van Diepen et al suggested 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.
[47]

Bursi et al found that among community patients with heart failure, pulmonary artery systolic
pressure (PASP), as assessed by Doppler echocardiography, can strongly predict death and can
provide incremental and clinically significant prognostic information independent of known outcome
predictors.
[48]

In the Framingham Offspring Cohort, 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
standard deviation increase in log galectin-3). Galectin-3 was also associated with an increased
risk for all-cause mortality (multivariable-adjusted hazard ratio: 1.15).
[49]

A more recent, retrospective study that evaluated data from the 2010 Nebraska Hospital Discharge
files for 4319 hospitalizations of 3521 heart failure patients admitted to 79 in-state hospitals
reported that risk factors for in-hospital mortality in these patients were increasing age, the
presence of comordities, and length of hospital day.
[50]

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.
[51] 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 multisession
self-care training compared to those receiving a single-session intervention.
[52] The optimum
method for patient education remains to be established. It appears that more intensive
interventions are not necessarily better.
[52]

For patient education information, see the Heart Health Center, Cholesterol Center, and Diabetes
Center, as well as Congestive Heart Failure Symptoms, Causes, and Life Expectancy, High
Cholesterol, Chest Pain, Arrhythmias (Heart Rhythm Disorders), Heart Disease (Coronary Heart
Disease), and Heart Attack.

Clinical Presentation
 
 

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