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.

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 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.)

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 G-protein.
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 long-standing
hypertension) but also from infiltrative disorders (eg, amyloidosis), endomyocardial fibrosis, and
myocardial ischemia.

Parallel upward displacement of the diastolic pressure-volume curve is generally referred to as a

decrease in ventricular distensibility. This is usually caused by extrinsic compression of the
ventricles.

Concentric LV hypertrophy

Pressure overload that leads to concentric LV hypertrophy (LVH), as occurs in aortic stenosis,
hypertension, and hypertrophic cardiomyopathy, shifts the diastolic pressure-volume curve to the
left along its volume axis. As a result, ventricular diastolic pressure is abnormally elevated,
although chamber stiffness may or may not be altered.
Increases in diastolic pressure lead to increased myocardial energy expenditure, remodeling of
the ventricle, increased myocardial oxygen demand, myocardial ischemia, and eventual
progression of the maladaptive mechanisms of the heart that lead to decompensated heart failure.

Arrhythmias

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

imparts a significant burden in all forms of heart failure. In fact, some arrhythmias even
perpetuate heart failure. The most significant of all rhythms associated with heart failure are the
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
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.[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.

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).

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 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.

History
In evaluating heart failure patients, the clinician should ask about the following comorbidities
and/or risk factors[3] :

Myopathy
Previous MI
Valvular heart disease, familial heart disease
Alcohol use
Hypertension
Diabetes
Dyslipidemia
Coronary/peripheral vascular disease
Sleep-disordered breathing
Collagen vascular disease, rheumatic fever
Pheochromocytoma
Thyroid disease
Substance abuse history
History of chemotherapy/radiation to the chest

The Heart Failure Society of America (HFSA) also has the following recommendations for
genetic evaluation of cardiomyopathy[54] :

For all patients with cardiomyopathy, take a detailed family history for at least 3 generations
(hypertrophic cardiomyopathy [HCM], dilated cardiomyopathy [DCM], arrhythmic right
ventricular dysplasia [ARVD], left ventricular noncompaction [LVNC], restrictive cardiomyopathy
[RCM], and cardiomyopathies associated with extra-cardiac manifestations)
Carefully assess the patient's medical history as well as that of asymptomatic first-degree
relatives, with special focus on heart failure symptoms, arrhythmias, presyncope, and syncope
Screen asymptomatic first-degree relatives for cardiomyopathy (HCM, DCM, ARVD, LVNC, RCM,
and cardiomyopathies associated with extra-cardiac manifestations)
Screen for cardiomyopathy at intervals in asymptomatic at-risk relatives who are known to carry
the disease-causing mutation(s) (for details, see Recommendations 17.2e and 17.2f in HFSA
Guideline Approach to Medical Evidence for Genetic Evaluation of Cardiomyopathy)
Screen for cardiomyopathy in asymptomatic at-risk first-degree relatives who have not
undergone genetic testing or in whom a disease-causing mutation has not been identified
Note: Due to the complexity of genetic evaluation, testing, and counseling of patients with
cardiomyopathy, it is recommended that patients be referred to centers with expertise in these
matters and in family-based management.[54]

The New York Heart Association (NYHA) classification of heart failure is widely used in
practice and in clinical studies to quantify clinical assessment of heart failure (see Heart Failure
Criteria and Classification). Breathlessness, a cardinal symptom of LV failure, may manifest
with progressively increasing severity as the following:

Exertional dyspnea
Orthopnea
Paroxysmal nocturnal dyspnea
Dyspnea at rest
Acute pulmonary edema

Other cardiac symptoms of heart failure include chest pain/pressure and palpitations. Common
noncardiac signs and symptoms of heart failure include anorexia, nausea, weight loss, bloating,
fatigue, weakness, oliguria, nocturia, and cerebral symptoms of varying severity, ranging from
anxiety to memory impairment and confusion. Findings from the Framingham Heart Study
suggest that subclinical cardiac dysfunction and noncardiac comorbidities are associated with
increased incidence of heart failure, supporting the idea that heart failure is a progressive
syndrome and that noncardiac factors are extremely important.[26, 27, 55]

Exertional dyspnea

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

Orthopnea

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

Cough, particularly during recumbency, may be an "orthopnea equivalent." This nonproductive

cough may be caused by pulmonary congestion and is relieved by the treatment of heart failure.

Paroxysmal nocturnal dyspnea

Paroxysmal nocturnal dyspnea usually occurs at night and is defined as the sudden awakening of
the patient, after a couple of hours of sleep, with a feeling of severe anxiety, breathlessness, and
suffocation. The patient may bolt upright in bed and gasp for breath. Bronchospasm increases
ventilatory difficulty and the work of breathing and is a common complicating factor of
paroxysmal nocturnal dyspnea. On chest auscultation, the bronchospasm associated with a heart
failure exacerbation can be difficult to distinguish from an acute asthma exacerbation, although
other clues from the cardiovascular examination should lead the examiner to the correct
diagnosis. Both types of bronchospasm can be present in a single individual.

In contrast to orthopnea, which may be relieved by immediately sitting up in bed, paroxysmal

nocturnal dyspnea may require 30 minutes or longer in this position for relief. Episodes may be
so frightening that the patient may be afraid to resume sleeping, even after the symptoms have
subsided.

Dyspnea at rest

Dyspnea at rest in heart failure is the result of the following mechanisms:

Decreased pulmonary function secondary to decreased compliance and increased airway

resistance
Increased ventilatory drive secondary to hypoxemia due to increased pulmonary capillary wedge
pressure (PCWP); ventilation/perfusion (V/Q) mismatching due to increased PCWP and low
cardiac output; and increased carbon dioxide production
Respiratory muscle dysfunction, with decreased respiratory muscle strength, decreased
endurance, and ischemia

Pulmonary edema

Acute pulmonary edema is defined as the sudden increase in PCWP (usually more than 25 mm
Hg) as a result of acute and fulminant left ventricular failure. It is a medical emergency and has a
very dramatic clinical presentation. The patient appears extremely ill, poorly perfused, restless,
sweaty, tachypneic, tachycardic, hypoxic, and coughing, with an increased work of breathing and
using respiratory accessory muscles and with frothy sputum that on occasion is blood tinged.
Chest pain/pressure and palpitations

Chest pain/pressure may occur as a result of either primary myocardial ischemia from coronary
disease or secondary myocardial ischemia from increased filling pressure, poor cardiac output
(and therefore poor coronary diastolic filling), or hypotension and hypoxemia.[56]

Palpitations are the sensation a patient has when the heart is racing. It can be secondary to sinus
tachycardia due to decompensated heart failure, or more commonly, it is due to atrial or
ventricular tachyarrhythmias.

Fatigue and weakness

Fatigue and weakness are often accompanied by a feeling of heaviness in the limbs and are
generally related to poor perfusion of the skeletal muscles in patients with a lowered cardiac
output. Although they are generally a constant feature of advanced heart failure, episodic fatigue
and weakness are also common in earlier stages.

Nocturia and oliguria

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

Cerebral symptoms

The following may occur in elderly patients with advanced heart failure, particularly in those
with cerebrovascular atherosclerosis:

Confusion
Memory impairment
Anxiety
Headaches
Insomnia
Bad dreams or nightmares
Rarely, psychosis with disorientation, delirium, or hallucinations

Physical Examination
Patients with mild heart failure appear to be in no distress after a few minutes of rest, but they
may be obviously dyspneic during and immediately after moderate activity. Patients with LV
failure may be dyspneic when lying flat without elevation of the head for more than a few
minutes. Those with severe heart failure appear anxious and may exhibit signs of air hunger in
this position.
Patients with recent onset of heart failure are generally well nourished, but those with chronic
severe heart failure are often malnourished and sometimes even cachectic. Chronic marked
elevation of systemic venous pressure may produce exophthalmos and severe tricuspid
regurgitation and may lead to visible pulsation of the eyes and of the neck veins. Central
cyanosis, icterus, and malar flush may be evident in patients with severe heart failure.

In mild or moderate heart failure, stroke volume is normal at rest; in severe heart failure, it is
reduced, as reflected by a diminished pulse pressure and a dusky discoloration of the skin. With
very severe heart failure, particularly if cardiac output has declined acutely, systolic arterial
pressure may be reduced. The pulse may be weak, rapid, and thready; the proportional pulse
pressure (pulse pressure/systolic pressure) may be markedly reduced. The proportional pulse
pressure correlates reasonably well with cardiac output. In one study, when pulse pressure was
less than 25%, it usually reflected a cardiac index of less than 2.2 L/min/m2.

Ascites occurs in patients with increased pressure in the hepatic veins and in the veins draining
into the peritoneum and usually reflects long-standing systemic venous hypertension. Fever may
be present in severe decompensated heart failure because of cutaneous vasoconstriction and
impairment of heat loss.

Increased adrenergic activity is manifested by tachycardia, diaphoresis, pallor, peripheral

cyanosis with pallor and coldness of the extremities, and obvious distention of the peripheral
veins secondary to venoconstriction. Diastolic arterial pressure may be slightly elevated.

Rales heard over the lung bases are characteristic of heart failure of at least moderate severity.
With acute pulmonary edema, rales are frequently accompanied by wheezing and expectoration
of frothy, blood-tinged sputum. The absence of rales certainly does not exclude elevation of
pulmonary capillary pressure due to LV failure.

Systemic venous hypertension is manifested by jugular venous distention. Normally, jugular

venous pressure declines with respiration; however, it increases in patients with heart failure, a
finding known as the Kussmaul sign (also found in constrictive pericarditis). This reflects an
increase in right atrial pressure and therefore right-sided heart failure.

Hepatojugular reflux is the distention of the jugular vein induced by applying manual pressure
over the liver; the patient's torso should be positioned at a 45 angle. Hepatojugular reflux occurs
in patients with elevated left-sided filling pressures and reflects elevated capillary wedge
pressure and left-sided heart failure.

Although edema is a cardinal manifestation of heart failure, it does not correlate well with the
level of systemic venous pressure. In patients with chronic LV failure and low cardiac output,
extracellular fluid volume may be sufficiently expanded to cause edema in the presence of only
slight elevations in systemic venous pressure. Usually, a substantial gain of extracellular fluid
volume (ie, a minimum of 5 L in adults) must occur before peripheral edema develops. Edema in
the absence of dyspnea or other signs of LV or RV failure is not solely indicative of heart failure
and can be observed in many other conditions, including chronic venous insufficiency, nephrotic
syndrome, or other syndromes of hypoproteinemia or osmotic imbalance.
Hepatomegaly is prominent in patients with chronic right-sided heart failure, but it may occur
rapidly in acute heart failure. When hepatomegaly occurs acutely, the liver is usually tender. In
patients with considerable tricuspid regurgitation, a prominent systolic pulsation of the liver,
attributable to an enlarged right atrial V wave, is often noted. A presystolic pulsation of the liver,
attributable to an enlarged right atrial A wave, can occur in tricuspid stenosis, constrictive
pericarditis, restrictive cardiomyopathy involving the right ventricle, and pulmonary
hypertension (primary or secondary).

Hydrothorax is most commonly observed in patients with hypertension involving both the
systemic and pulmonary circulation. It is usually bilateral, although when unilateral, it is usually
confined to the right side of the chest. When hydrothorax develops, dyspnea usually intensifies
because of further reductions in vital capacity.

Cardiac findings

Protodiastolic (S3) gallop is the earliest cardiac physical finding in decompensated heart failure
in the absence of severe mitral or tricuspid regurgitation or left-to-right shunts. The presence of
an S3 gallop in adults is important, pathologic, and often the most apparent finding on cardiac
auscultation in patients with significant heart failure.

Cardiomegaly is a nonspecific finding that nonetheless occurs in most patients with chronic heart
failure. Notable exceptions include heart failure from acute MI, constrictive pericarditis,
restrictive cardiomyopathy, valve or chordae tendineae rupture, or heart failure due to
tachyarrhythmias or bradyarrhythmias.

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

Accentuation of P2 heart sound is a cardinal sign of increased pulmonary artery pressure; it

disappears or improves after treatment of heart failure. Mitral and tricuspid regurgitation
murmurs are often present in patients with decompensated heart failure because of ventricular
dilatation. These murmurs often disappear or diminish when compensation is restored. Note that
correlation between the intensity of the murmur of mitral regurgitation and its significance in
patients with heart failure is poor. Severe mitral regurgitation may be accompanied by an
unimpressively soft murmur.

Cardiac cachexia is found in long-standing heart failure, particularly of the right ventricle,
because of anorexia from hepatic and intestinal congestion and sometimes because of digitalis
toxicity. Occasionally, impaired intestinal absorption of fat occurs, and rarely, protein-losing
enteropathy occurs. Patients with heart failure may also exhibit increased total metabolism
secondary to augmentation of myocardial oxygen consumption, excessive work of breathing,
low-grade fever, and elevated levels of circulating tumor necrosis factor (TNF).
Predominant Right-Sided Heart Failure
Ascites, congestive hepatomegaly, and anasarca due to elevated right-sided heart pressures
transmitted backward into the portal vein circulation may result in increased abdominal girth and
epigastric and right upper quadrant (RUQ) abdominal pain. Other gastrointestinal symptoms,
caused by congestion of the hepatic and gastrointestinal venous circulation, include anorexia,
bloating, nausea, and constipation. In preterminal heart failure, inadequate bowel perfusion can
cause abdominal pain, distention, and bloody stools. Distinguishing right-sided heart failure from
hepatic failure is often clinically difficult.

Dyspnea, prominent in LV failure, becomes less prominent in isolated right-sided heart failure
because of the absence of pulmonary congestion. On the other hand, when cardiac output
becomes markedly reduced in patients with terminal right-sided heart failure (as may occur in
isolated RV infarction and in the late stages of primary pulmonary hypertension and pulmonary
thromboembolic disease), severe dyspnea may occur as a consequence of the reduced cardiac
output, poor perfusion of respiratory muscles, hypoxemia, and metabolic acidosis.

Heart Failure Criteria, Classification, and Staging

Framingham system for diagnosis of heart failure

In the Framingham system, the diagnosis of heart failure requires that either 2 major criteria or 1
major and 2 minor criteria be present concurrently, as shown in Table 1 below.[1] Minor criteria
are accepted only if they cannot be attributed to another medical condition.

Table 1. Framingham Diagnostic Criteria for Heart Failure (Open Table in a new window)

Major Criteria Minor Criteria

Paroxysmal nocturnal dyspnea Nocturnal cough

Weight loss of 4.5 kg in 5 days in response to

Dyspnea on ordinary exertion
treatment

A decrease in vital capacity by one third the

Neck vein distention
maximal value recorded

Rales Pleural effusion

Acute pulmonary edema Tachycardia (rate of 120 bpm)

Hepatojugular reflux Hepatomegaly

S3 gallop Bilateral ankle edema

Central venous pressure > 16 cm water

Circulation time of 25 sec

Radiographic cardiomegaly

Pulmonary edema, visceral congestion, or

cardiomegaly at autopsy

Source: Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study.
J Am Coll Cardiol. 1993 Oct;22(4 suppl A):6A-13A.[1]

NYHA classification of functional heart failure

The New York Heart Association (NYHA) functional classification of heart failure is based on
the patient's symptom severity and the amount of exertion that is needed to provoke their
symptoms. See Table 2 below.

Table 2. NYHA Functional Classification of Heart Failure (Open Table in a new window)

Class Functional Capacity

I Patients without limitation of physical activity

Patients with slight limitation of physical activity, in which ordinary physical activity leads to
II
fatigue, palpitation, dyspnea, or anginal pain; they are comfortable at rest

Patients with marked limitation of physical activity, in which less than ordinary activity results in
III
fatigue, palpitation, dyspnea, or anginal pain; they are comfortable at rest

Patients who are not only unable to carry on any physical activity without discomfort but who also
IV have symptoms of heart failure or the anginal syndrome even at rest; the patient's discomfort
increases if any physical activity is undertaken

Source: American Heart Association. Classes of heart failure. Available at:

http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/Classes-of-Heart-
Failure_UCM_306328_Article.jsp. Accessed: September 6, 2011.[2]

ACC/AHA stages of heart failure

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

classification that described the development and progression of heart failure and that
"recognizes that there are established risk factors and structural prerequisites for the development
of HF and that therapeutic interventions introduced even before the appearance of LV
dysfunction or symptoms can reduce the population morbidity and mortality of HF."[3] Table 3,
below, summarizes the development of heart failure.

Table 3. ACC/AHA Stages of Heart Failure Development (Open Table in a new window)

level Description Examples Notes

Patients with coronary

At high risk for heart artery disease,
failure but without hypertension, or diabetes
A structural heart disease mellitus without impaired
or symptoms of heart LV function, hypertrophy, Patients with predisposing risk
failure or geometric chamber factors for developing heart failure
distortion Corresponds with patients with NYHA
class I heart failure
Structural heart disease Patients who are
but without asymptomatic but who
B
signs/symptoms of have LVH and/or impaired
heart failure LV function

Patients with known

Structural heart disease The majority of patients with heart
structural heart disease and
with current or past failure are in this stage
C shortness of breath and
symptoms of heart Corresponds with patients with NYHA
fatigue, reduced exercise class II and III heart failure
failure
tolerance

Patients in this stage may be eligible

to receive mechanical circulatory
support, receive continuous inotropic
Refractory heart failure Patients who have marked infusions, undergo procedures to
D requiring specialized symptoms at rest despite facilitate fluid removal, or undergo
interventions maximal medical therapy heart transplantation or other
procedures
Corresponds with patients with NYHA
class IV heart failure

Sources: (1) Hunt SA, American College of Cardiology, and the American Heart Association Task Force
on Practice Guidelines (Writing Committee to Update the 2001 Guidelines for the Evaluation and
Management of Heart Failure). ACC/AHA 2005 guideline update for the diagnosis and management of
chronic heart failure in the adult: a report of the American College of Cardiology/American Heart
Association Task Force on Practice Guidelines. J Am Coll Cardiol. 2005 Sep 20;46(6):e1-82.[4] ; and (2)
Hunt SA, Abraham WT, Chin MH, et al. 2009 Focused update incorporated into the ACC/AHA 2005
Guidelines for the Diagnosis and Management of Heart Failure in Adults A Report of the American
College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines
Developed in Collaboration With the International Society for Heart and Lung Transplantation. J Am Coll
Cardiol. Apr 14 2009;53(15):e1-e90

ACC/AHA Staging
Stage A

ACC/AHA stage A patients are at high risk for heart failure but do not have structural heart
disease or symptoms of heart failure. Thus, management in these cases focuses on prevention,
through reduction of risk factors. Measures include the following[58] :

Treat hypertension
Encourage smoking cessation
Treat lipid disorders
Encourage regular exercise
Discourage alcohol intake and illicit drug use

Patients who have a family history of dilated cardiomyopathy should be screened with a
comprehensive history and physical examination together with echocardiography and
transthoracic echocardiography every 2-5 years.[5]

Stage B

ACC/AHA stage B patients are asymptomatic, with LV dysfunction from previous MI, LV
remodeling from LV hypertrophy, and asymptomatic valvular dysfunction, which includes
patients with New York Heart Association (NYHA) class I heart failure (see Heart Failure
Criteria and Classification for a description of NYHA classes).[3] In addition to the heart failure
education and aggressive risk factor modification used for stage A, treatment with an ACEI/ARB
and/or beta-blockade is indicated.

Evaluation for coronary revascularization either percutaneously or surgically, as well as

correction of valvular abnormalities, may be indicated.[3] Treatment with an ICD for primary
prevention of sudden death in patients with an LVEF of less than 30% that is more than 40 days
post-MI is reasonable if expected survival is more than 1 year.

There is less evidence for implantation of an ICD in patients with nonischemic cardiomyopathy,
an LVEF less than 30%, and no heart failure symptoms. There is no evidence for use of digoxin
in these populations.[59] Aldosterone receptor blockade with eplerenone is indicated for post-MI
LV dysfunction.
Stage C

ACC/AHA stage C patients have structural heart disease and current or previous symptoms of
heart failure; ACC/AHA stage C corresponds with NYHA class II and III heart failure. The
preventive measures used for stage A disease are indicated, as is dietary sodium restriction.

Drugs routinely used in these patients include ACEI/ARBs, beta-blockers, and loop diuretics for
fluid retention. For selected patients, therapeutic measures include aldosterone receptor blockers,
hydralazine and nitrates in combination, and cardiac resynchronization with or without an ICD
(see Electrophysiologic Intervention).[58]

A meta-analysis performed by Badve et al suggested that the survival benefit of treatment with
beta-blockers extends to patients with chronic kidney disease and systolic heart failure (risk ratio
0.72).[60]

Stage D

ACC/AHA stage D patients have refractory heart failure (NYHA class IV) that requires
specialized interventions. Treatment includes all the measures used in stages A, B, and C.
Treatment considerations include heart transplantation or placement of an LV assist device in
eligible patients; pulmonary catheterization; and options for end-of-life care.[3] For palliation of
symptoms, continuous intravenous infusion of a positive inotrope may be considered.

Diagnostic ConsiderationsCardiogenic and noncardiogenic

pulmonary edemaAtypical presentations
Many classes of disorders can result in increased cardiac demand or impaired cardiac function.
Cardiac causes include arrhythmias (tachycardia or bradycardia), structural heart disease, and
myocardial dysfunction (systolic or diastolic). Noncardiac causes include processes that increase
the preload (volume overload), increase the afterload (hypertension), reduce the oxygen-carrying
capacity of the blood (anemia), or increase demand (sepsis). For example, renal failure can result
in heart failure due to fluid retention and anemia. Lymphatic obstruction and venous obstruction
syndromes can also cause edema-forming states, and obesity-hypoventilation syndrome (OHS)
can lead to right-sided heart failure with right ventricular hypertrophy.

Diastolic heart failure may be the most common form of heart failure in the US population.[22]
Alterations in ventricular-arterial coupling appear to have a key role in impaired hemodynamic
response to exercise, but the diagnosis of diastolic heart failure cannot be excluded even in the
presence of normal diastolic function at rest.[22]

Heart failure should also be differentiated from pulmonary edema associated with injury to the
alveolar-capillary membrane caused by diverse etiologies (ie, noncardiogenic pulmonary edema,
adult respiratory distress syndrome [ARDS]). Increased capillary permeability is observed in
trauma, hemorrhagic shock, sepsis, respiratory infections, administration of various drugs, and
ingestion of toxins (eg, heroin, cocaine, toxic gases). With the advent of natriuretic peptide
testing, differentiating cardiac from noncardiac causes of pulmonary edema has improved.[61, 62]

Several features may differentiate cardiogenic from noncardiogenic pulmonary edema. In heart
failure, a history of an acute cardiac event or of progressive symptoms of heart failure is usually
present. The physical examination may yield clues to acute heart failure. Findings such as an S3
gallop and elevated jugular venous pulsation are highly specific for acute heart failure, but their
low sensitivity makes them less than ideal screening tools.[63, 64]

Patients with noncardiogenic pulmonary edema may have clinical features similar to those with
cardiogenic pulmonary edema but will often lack an S3 gallop and jugular venous distention.
Differentiation is often made based on pulmonary capillary wedge pressure (PCWP)
measurements from invasive hemodynamic monitoring. Left ventricular filling pressures
measured by PCWP are the single most reliable hemodynamic measure that predicts a fatal
outcome in patients with acute heart failure. PCWP is generally more than 18 mm Hg in heart
failure and is less than 18 mm Hg in noncardiogenic pulmonary edema, but superimposition of
chronic pulmonary vascular disease can make this distinction more difficult to discern.

Heart failure, in particular right-sided heart failure, can present as abdominal syndrome with
nausea, vomiting, right-sided abdominal pain (as a sign of liver congestion), bloating, anorexia,
and significant weight loss. In advanced cases, patients can appear jaundiced because of cardiac
cirrhosis. Constipation is a common complaint among patients with heart failure, and it can be a
manifestation of decreased intestinal transit secondary to poor perfusion. In very severe cases of
cardiogenic shock, an individual can present with severe abdominal pain mimicking bowel
obstruction, perforation, acute abdomen, and peritonitis as a manifestation of severe intestinal
ischemia and possible infarction.

In elderly patients, fatigue and confusion can sometimes be the first symptoms of heart failure,
which is related to a decrease in cardiac output.

Differential Diagnoses
Acute Kidney Injury
Acute Respiratory Distress Syndrome
Bacterial Pneumonia
Cardiogenic Pulmonary Edema
Chronic Obstructive Pulmonary Disease (COPD)
Cirrhosis
Community-Acquired Pneumonia
Emphysema
Goodpasture Syndrome
Idiopathic Pulmonary Fibrosis
Interstitial (Nonidiopathic) Pulmonary Fibrosis
Myocardial Infarction
Nephrotic Syndrome
Neurogenic Pulmonary Edema
 Pneumothorax Imaging
Pulmonary Embolism
Respiratory Failure
Venous Insufficiency
Viral Pneumonia

Approach Considerations
Careful evaluation of the patient's history and physical examination (including signs of
congestion, such as jugular venous distention [JVD]) can provide important information about
the underlying cardiac abnormality in heart failure.[3] However, other studies and/or tests may be
necessary to identify structural abnormalities or conditions that can lead to or exacerbate heart
failure.[3]

The American College of Cardiology/American Heart Association (ACC/AHA),[3] Heart Failure

Society of America (HFSA),[6, 54] and European Society of Cardiology (ESC)[5] recommend the
following basic laboratory tests and studies in the initial evaluation of patients with suspected
heart failure:

Complete blood count (CBC), which may indicate anemia or infection as potential causes
of heart failure
Urinalysis (UA), which may reveal proteinuria, which is associated with cardiovascular
disease
Serum electrolyte levels, which may be abnormal owing to causes such as fluid retention
or renal dysfunction
Blood urea nitrogen (BUN) and creatinine levels, which may indicate decreased renal
blood flow
Fasting blood glucose levels, because elevated levels indicate a significantly increased
risk for heart failure (diabetic and nondiabetic patients)
Liver function tests (LFTs), which may show elevated liver enzyme levels and indicate
liver dysfunction due to heart failure
B-type natriuretic peptide (BNP) and N-terminal pro-B-type (NT-proBNP) natriuretic
peptide levels, which are increased in heart failure; these measurements are closely
correlated with the NYHA heart failure classification
Electrocardiogram (ECG) (12-lead), which may reveal arrhythmias, ischemia/infarction,
and coronary artery disease as possible causes of heart failure

The ACC/AHA recommendations also include obtaining a lipid profile and thyroid stimulating
hormone (TSH) level.[3] These tests reveal potential cardiovascular or thyroid disease as causes
of heart failure. If the clinical presentation also suggests an acute coronary syndrome, the ESC
recommends obtaining levels of troponin I or T[5] ; increased troponin levels indicate injury to the
myocytes and the severity of heart failure.

The ACC/AHA, HFSA, and ESC also recommend the following imaging studies and
procedures[3, 5, 6] :
 Chest radiography (posterior-anterior, lateral), which may show pulmonary congestion,
an enlarged cardiac silhouette, or other potential causes of the patient's symptoms
2-D echocardiographic and Doppler flow ultrasonographic studies, which may reveal
ventricular dysfunction and/or valvular abnormalities [65, 66]
Coronary arteriography in patients with a history of exertional angina or suspected
ischemic LV dysfunction, which may reveal coronary artery disease
Maximal exercise testing with/without respiratory gas exchange and/or blood oxygen
saturation, which assesses cardiac and pulmonary function with activity, the inability to
walk more than short distances, and a decreased peak oxygen consumption reflect more
severe disease

Other studies may be indicated in selected patients,[3] such as the following:

Screening for hemochromatosis, in which iron overload affects cardiac function

Screening for sleep-disturbed breathing, which affects neurohormonal activation
Screening for human immunodeficiency virus (HIV), which may result in heart failure
from possible direct infectious effects, from disease treatment effects causing CAD, or
from other causes
Testing for rheumatologic diseases, amyloidosis, or pheochromocytoma, all of which
may cause cardiomyopathy
Serum and urine electrophoresis for light-chain disease
Genetic testing for at-risk patients with a first-degree relative who has been diagnosed
with a cardiomyopathy leading to heart failure, which may aid in detecting early disease
onset and guide treatment [29, 54]
Holter monitoring, which may reveal arrhythmias or abnormal electrical activity (eg, in
patients with heart failure and a history of MI who are being considered for
electrophysiologic study to document ventricular tachycardia [VT] inducibility) [5, 6]

The ESC indicates that pulmonary function testing is generally not helpful in the diagnosis of
heart failure. However, it may demonstrate or exclude respiratory causes of dyspnea and help
assess any pulmonary causes of dyspnea.

Routine Laboratory Tests

Laboratory studies should include a complete blood count (CBC), serum electrolytes (including
calcium and magnesium), and renal and liver function studies. Other tests may be indicated in
specific patients. The CBC aids in the assessment of severe anemia, which may cause or
aggravate heart failure. Leukocytosis may signal underlying infection. Otherwise, CBCs are
usually of little diagnostic help.

Serum electrolyte values are generally within reference ranges in patients with mild to moderate
heart failure before treatment. In cases of severe heart failure, however, prolonged, rigid sodium
restriction, coupled with intensive diuretic therapy and the inability to excrete water, may lead to
dilutional hyponatremia, which occurs because of a substantial expansion of extracellular and
intravascular fluid volume and a normal or increased level of total body sodium.
Potassium levels are usually within reference ranges, although the prolonged administration of
diuretics may result in hypokalemia. Hyperkalemia may occur in patients with severe heart
failure who show marked reductions in glomerular filtration rate (GFR) and inadequate delivery
of sodium to the distal tubular sodium-potassium exchange sites of the kidney, particularly if
they are receiving potassium-sparing diuretics and/or angiotensin-converting enzyme inhibitors
(ACEIs).

Renal function tests

Blood urea nitrogen (BUN) and creatinine levels can be within reference ranges in patients with
mild to moderate heart failure and normal renal function, although BUN levels and
BUN/creatinine ratios may be elevated.

Patients with severe heart failure, particularly those on large doses of diuretics for long periods,
may have elevated BUN and creatinine levels indicative of renal insufficiency because of
chronic reductions of renal blood flow from reduced cardiac output. Diuresing this group of
patients is complex. In some individuals, diuretics will improve renal congestion and renal
function, whereas in others, overaggressive diuresis may aggravate renal insufficiency due to
volume depletion.

Liver function tests

Congestive hepatomegaly and cardiac cirrhosis are often associated with impaired hepatic
function, which is characterized by abnormal values of aspartate aminotransferase (AST),
alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and other liver enzymes.
Hyperbilirubinemia secondary to an increase in the directly and indirectly reacting bilirubin is
common. In severe cases of acute RV or LV failure, frank jaundice may occur.

Acute hepatic venous congestion can result in severe jaundice, with a bilirubin level as high as
15-20 mg/dL, elevation of AST to more than 10 times the upper reference range limit, elevation
of the serum alkaline phosphatase level, and prolongation of the prothrombin time. The clinical
and laboratory pictures may resemble viral hepatitis, but the impairment of hepatic function is
rapidly resolved by successful treatment of heart failure. In patients with long-standing heart
failure, albumin synthesis may be impaired, leading to hypoalbuminemia and intensifying the
accumulation of fluid. Fulminant hepatic failure is an uncommon, late, and sometimes terminal
complication of cardiac cirrhosis.