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. See the image below.

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

Signs and symptoms

Signs and symptoms of heart failure include the following:

Exertional dyspnea and/or dyspnea at rest

Orthopnea
Acute pulmonary edema
Chest pain/pressure and palpitations
Tachycardia
Fatigue and weakness
Nocturia and oliguria
Anorexia, weight loss, nausea
Exophthalmos and/or visible pulsation of eyes
Distention of neck veins
Weak, rapid, and thready pulse
Rales, wheezing
S 3 gallop and/or pulsus alternans
Increased intensity of P 2 heart sound
Hepatojugular reflux
Ascites, hepatomegaly, and/or anasarca
Central or peripheral cyanosis, pallor
See Clinical Presentation for more detail.

Diagnosis
Heart failure criteria, classification, and staging
The Framingham criteria for the diagnosis of heart failure consists of the concurrent presence of either 2 major criteria or 1
major and 2 minor criteria.[1]
Major criteria include the following:

Paroxysmal nocturnal dyspnea

Weight loss of 4.5 kg in 5 days in response to treatment

Neck vein distention

Rales
Acute pulmonary edema
Hepatojugular reflux
S 3 gallop
Central venous pressure greater than 16 cm water
Circulation time of 25 seconds
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

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 neurohormonemediated 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. [29]

http://emedicine.medscape.com/article/163062-overview#showall

Heart Failure