Heart failure

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.
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
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.
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.
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 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 2dimensional 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 antiinflammatory drugs [NSAIDs], calcium channel blockers [CCBs], and most antiarrhythmic
drugs). (See the Medication Section for more information.)
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 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 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.[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.[21, 22]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 down-regulation of beta1-adrenergic
receptors, uncoupling of beta2-adrenergic receptors, and increased activity of inhibitory Gprotein. Changes in beta1-adrenergic receptors result in overexpression and promote
myocardial hypertrophy.
ANP and BNP
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).[23] 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.[24]
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.[25]
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 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 longstanding 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 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
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 of heart failure:

Profound anemia
Thyrotoxicosis
Myxedema
Paget disease of bone
Albright syndrome
Multiple myeloma
Glomerulonephritis
Cor pulmonale
Polycythemia vera
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.[26, 27] 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.[28]
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.[29]

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.[29] The recommended
screening consists of an electrocardiogram and an echocardiogram. If the patient has an
asymptomatic left ventricular dysfunction, it should be treated.[29]
Epidemiology
United States statistics
According to the American Heart Association, heart failure affects nearly 5.7 million
Americans of all ages[30] 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.[31, 32, 33, 34]
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 released by the Centers for
Disease Control and Prevention (CDC) in December 2015.[35, 36] 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.[35] 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[37] ; 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.[37]
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 [30]
Approximately 670,000 new cases of heart failure are diagnosed each year[30]
About 277,000 deaths are caused by heart failure each year [30]
Heart failure is the most frequent cause of hospitalization in patients older than 65 years,
with an annual incidence of 10 per 1,000 [30]
Rehospitalization rates during the 6 months following discharge are as much as 50% [38]
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, [39] 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.
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.[40]
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.[41, 42] 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.[30, 43, 44, 45, 46, 47] Each rehospitalization increases mortality by about 20-22%.[30]
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).
Heart failure related to systolic dysfunction has an associated mortality of 50% after 5
years.[21]
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.[48]
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.[49]
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.[50]
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 hazard ratio: 1.15).[51]
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.[52] A
randomized controlled trial of 605 patients with heart failure reported that the incidence of allcause 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.[53]