Heart Failure

Heart Failure
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http://emedicine.medscape.com/article/163062-overview
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Author: Ioana Dumitru, MD; Chief Editor: Henry H Ooi, MB, MRCPI more...
Updated: Apr 5, 2013
Practice Essentials
Heart failure is 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.
Essential update: FDA approves imaging agent for cardiac risk evaluation in heart failure patients
In March 2013, the FDA approved the scintigraphic imaging agent iobenguane I 123 injection (AdreView) for the
evaluation of myocardial sympathetic innervation in patients with NYHA class 23 heart failure with an LVEF 35%. The
radionuclide tracer, which functions molecularly as a norepinephrine analog, can show relative levels of norepinephrine
uptake in the cardiac sympathetic nervous system and contribute to risk stratification in heart failure patients. Improved
reuptake of norepinephrine is associated with a better prognosis.[1]
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
S3 gallop and/or pulsus alternans
Increased intensity of P2 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
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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.[2]
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
S3 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,[3] 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 [4, 5] :
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 basic tests may be useful in the initial evaluation for suspected heart failure [4, 6, 7] :
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
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
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restriction, physical activity as appropriate, and attention to weight gain

Pharmacotherapy: Diuretics, vasodilators, inotropic agents, anticoagulants, beta blockers, and digoxin
Surgical options
Surgical treatment options include the following:
Electrophysiologic intervention
Revascularization procedures
Valve replacement/repair
Ventricular restoration
Extracorporeal membrane oxygenation
Ventricular assist devices
Heart transplantation
Total artificial heart
See Treatment and Medication for more detail.
Image library
This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases, signs of acute heart failure.
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.
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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).
This magnetic resonance image shows a scar in the anterior cardiac wall, which may be indicative of a previous myocardial infarction
(MI). MIs can precipitate heart failure.
Signs and symptoms of heart failure include tachycardia and manifestations of venous congestion (eg, edema) and
low cardiac output (eg, fatigue). Breathlessness is a cardinal symptom of left ventricular (LV) failure that may manifest
with progressively increasing severity.
Heart failure can be classified according to a variety of factors (see Heart Failure Criteria and Classification). The New
York Heart Association (NYHA) classification for heart failure comprises 4 classes, based on the relationship between
symptoms and the amount of effort required to provoke them, as follows[3] :
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 [4, 5] :
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.)
For further information, see the Medscape Reference articles Pediatric Congestive Heart Failure, Congestive Heart
Failure Imaging, Heart Transplantation, Coronary Artery Bypass Grafting, and Implantable Cardioverter-Defibrillators.
Pathophysiology
The common pathophysiologic state that perpetuates the progression of heart failure is extremely complex,
regardless of the precipitating event. Compensatory mechanisms exist on every level of organization, from subcellular
all the way through organ-to-organ interactions. Only when this network of adaptations becomes overwhelmed does
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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
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In the failing heart, increased myocardial volume is characterized by larger myocytes approaching the end of their life
cycle.[20] As more myocytes drop out, an increased load is placed on the remaining myocardium, and this unfavorable
environment is transmitted to the progenitor cells responsible for replacing lost myocytes.
Progenitor cells become progressively less effective as the underlying pathologic process worsens and myocardial
failure accelerates. These featuresnamely, the increased myocardial volume and mass, along with a net loss of
myocytesare the hallmark of myocardial remodeling. This remodeling process leads to early adaptive mechanisms,
such as augmentation of stroke volume (Frank-Starling mechanism) and decreased wall stress (Laplace's law), and,
later, to maladaptive mechanisms such as increased myocardial oxygen demand, myocardial ischemia, impaired
contractility, and arrhythmogenesis.
As heart failure advances, there is a relative decline in the counterregulatory effects of endogenous vasodilators,
including nitric oxide (NO), prostaglandins (PGs), bradykinin (BK), atrial natriuretic peptide (ANP), and B-type natriuretic
peptide (BNP). This decline occurs simultaneously with the increase in vasoconstrictor substances from the RAAS
and the adrenergic system, which fosters further increases in vasoconstriction and thus preload and afterload. This
results in cellular proliferation, adverse myocardial remodeling, and antinatriuresis, with total body fluid excess and
worsening of heart failure symptoms.
Systolic and diastolic failure

Systolic and diastolic heart failure each result in a decrease in stroke volume. This leads to activation of peripheral and
central baroreflexes and chemoreflexes that are capable of eliciting marked increases in sympathetic nerve traffic.
While there are commonalities in the neurohormonal responses to decreased stroke volume, the 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 beta2adrenergic 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).[21] ET, a substance produced
by the vascular endothelium, may contribute to the regulation of myocardial function, vascular tone, and peripheral
resistance in heart failure. Elevated levels of ET-1 closely correlate with the severity of heart failure. ET-1 is a potent
vasoconstrictor and has exaggerated vasoconstrictor effects in the renal vasculature, reducing renal plasma blood
flow, glomerular filtration rate (GFR), and sodium excretion.
TNF-alpha has been implicated in response to various infectious and inflammatory conditions. Elevations in TNF-alpha
levels have been consistently observed in heart failure and seem to correlate with the degree of myocardial
dysfunction. Some studies suggest that local production of TNF-alpha may have toxic effects on the myocardium, thus
worsening myocardial systolic and diastolic function.
In individuals with systolic dysfunction, therefore, the neurohormonal responses to decreased stroke volume result in
temporary improvement in systolic blood pressure and tissue perfusion. However, in all circumstances, the existing
data support the notion that these neurohormonal responses contribute to the progression of myocardial dysfunction in
the long term.
Heart failure with normal ejection fraction

In diastolic heart failure (heart failure with normal ejection fraction [HFNEF]), the same pathophysiologic processes
occur that lead to decreased cardiac output in systolic heart failure, but they do so in response to a different set of
hemodynamic and circulatory environmental factors that depress cardiac output.[22]
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In HFNEF, altered relaxation and increased stiffness of the ventricle (due to delayed calcium uptake by the myocyte
sarcoplasmic reticulum and delayed calcium efflux from the myocyte) occur in response to an increase in ventricular
afterload (pressure overload). The impaired relaxation of the ventricle then leads to impaired diastolic filling of the left
ventricle (LV).
Morris et al found that RV subendocardial systolic dysfunction and diastolic dysfunction, as detected by
echocardiographic strain rate imaging, are common in patients with HFNEF. This dysfunction is potentially associated
with the same fibrotic processes that affect the subendocardial layer of the LV and, to a lesser extent, with RV
pressure overload. This may play a role in the symptomatology of patients with HFNEF.[23]
LV chamber stiffness
An increase in LV chamber stiffness occurs secondary to any one of, or any combination of, the following 3
mechanisms:
Rise in filling pressure
Shift to a steeper ventricular pressure-volume curve
Decrease in ventricular distensibility
A rise in filling pressure is the movement of the ventricle up along its 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
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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
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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.[24, 25] Another analysis of over 36,000 patients undergoing outpatient echocardiography
reported that moderate or severe diastolic dysfunction, but not mild diastolic dysfunction, is an independent predictor
of mortality.[26]
Genetics of cardiomyopathy
Autosomal dominant inheritance has been demonstrated in dilated cardiomyopathy and in arrhythmic right ventricular
cardiomyopathy. Restrictive cardiomyopathies are usually sporadic and associated with the gene for cardiac troponin I.
Genetic tests are available at major genetic centers for cardiomyopathies.[27]
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In families with a first-degree relative who has been diagnosed with a cardiomyopathy leading to heart failure, the
at-risk patient should be screened and followed.[27] The recommended screening consists of an electrocardiogram
and an echocardiogram. If the patient has an asymptomatic left ventricular dysfunction, it should be treated.[27]
Epidemiology
United States statistics
According to the American Heart Association, heart failure affects nearly 5.7 million Americans of all ages[28] and is
responsible for more hospitalizations than all forms of cancer combined. It is the number 1 cause of hospitalization for
Medicare patients. With improved survival of patients with acute myocardial infarction and with a population that
continues to age, heart failure will continue to increase in prominence as a major health problem in the United
States.[29, 30, 31, 32]
Analysis of national and regional trends in hospitalization and mortality among Medicare beneficiaries from 1998-2008
showed a relative decline of 29.5% in heart failure hospitalizations[33] ; however, wide variations are noted between
states and races, with black men having the slowest rate of decline. A relative decline of 6.6% in mortality was also
observed, although the rate was uneven across states. The length of stay decreased from 6.8 days to 6.4 days,
despite an overall increase in the comorbid conditions.[33]
Heart failure statistics for the United States are as follows:
Heart failure is the fastest-growing clinical cardiac disease entity in the United States, affecting 2% of the
population
Heart failure accounts for 34% of cardiovascular-related deaths[28]
Approximately 670,000 new cases of heart failure are diagnosed each year[28]
About 277,000 deaths are caused by heart failure each year[28]
Heart failure is the most frequent cause of hospitalization in patients older than 65 years, with an annual
incidence of 10 per 1,000[28]
Rehospitalization rates during the 6 months following discharge are as much as 50%[34]
Nearly 2% of all hospital admissions in the United States are for decompensated heart failure, and the average
duration of hospitalization is about 6 days
In 2010, the estimated total cost of heart failure in the United States was $39.2 billion,[35] representing 1-2% of
all health care expenditures
The incidence and prevalence of heart failure are higher in blacks, Hispanics, Native Americans, and recent immigrants
from developing nations, Russia, and the former Soviet republics. The higher prevalence of heart failure in blacks,
Hispanics, and Native Americans is directly related to the higher incidence and prevalence of hypertension and
diabetes. This problem is particularly exacerbated by a lack of access to health care and by substandard preventive
health care available to the most indigent of individuals in these and other groups; in addition, many persons in these
groups do not have adequate health insurance.
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
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affluent, eating a more processed diet and leading a more sedentary lifestyle have resulted in an increased rate of
heart failure, along with increased rates of diabetes and hypertension. This change was illustrated in a population study
in Soweto, South Africa, where the community transformed into a more urban and westernized city, followed by an
increase in diabetes, hypertension, and heart failure.[36]
In terms of treatment, one study showed few important differences in uptake of key therapies in European countries
with widely differing cultures and varying economic status for patients with heart failure. In contrast, studies of
sub-Saharan Africa, where health care resources are more limited, have shown poor outcomes in specific
populations.[37, 38] For example, in some countries, hypertensive heart failure carries a 25% 1-year mortality rate, and
human immunodeficiency virus (HIV)associated cardiomyopathy generally progresses to death within 100 days of
diagnosis in patients who are not treated with antiretroviral drugs.
While data regarding developing nations are not as robust as studies of Western society, the following trends in
developing nations are apparent:
Causes tend to be largely nonischemic
Patients tend to present at a younger age
Outcomes are largely worse where health care resources are limited
Isolated right heart failure tends to be more prominent, with a variety of causes having been postulated, ranging
from tuberculous pericardial disease to lung disease and pollution
Prognosis
In general, the mortality following hospitalization for patients with heart failure is 10.4% at 30 days, 22% at 1 year, and
42.3% at 5 years, despite marked improvement in medical and device therapy.[28, 39, 40, 41, 42, 43] Each rehospitalization
increases mortality by about 20-22%.[28]
Mortality is greater than 50% for patients with NYHA class IV, ACC/AHA stage D heart failure. Heart failure associated
with acute MI has an inpatient mortality of 20-40%; mortality approaches 80% in patients who are also hypotensive (eg,
cardiogenic shock). (See Heart Failure Criteria and Classification).
Numerous demographic, clinical and biochemical variables have been reported to provide important prognostic value
in patients with heart failure, and several predictive models have been developed.[44]
A study by van Diepen et al suggests that patients with heart failure or atrial fibrillation have a significantly higher risk of
noncardiac postoperative mortality than patients with coronary artery disease; this risk should be considered even if a
minor procedure is planned.[45]
A study by Bursi et al found that among community patients with heart failure, pulmonary artery systolic pressure
(PASP), assessed by Doppler echocardiography, can strongly predict death and can provide incremental and clinically
significant prognostic information independent of known outcome predictors.[46]
Higher concentrations of galectin-3, a marker of cardiac fibrosis, were associated with an increased risk for incident
heart failure (hazard ratio: 1.28 per 1 SD increase in log galectin-3) in the Framingham Offspring Cohort. Galectin-3
was also associated with an increased risk for all-cause mortality (multivariable-adjusted hazard ratio: 1.15).[47]
Patient Education
To help prevent recurrence of heart failure in patients in whom heart failure was caused by dietary factors or
medication noncompliance, counsel and educate such patients about the importance of proper diet and the necessity
of medication compliance. Dunlay et al examined medication use and adherence among community-dwelling patients
with heart failure and found that medication adherence was suboptimal in many patients, often because of cost.[48] A
randomized controlled trial of 605 patients with heart failure reported that the incidence of all-cause hospitalization or
death was not reduced in patients receiving multi-session self-care training compared to those receiving a single
session intervention. The optimum method for patient education remains to be established. It appears that more
intensive interventions are not necessarily better.[49]
For patient education information, see the Heart Health Center, Cholesterol Center, and Diabetes Center, as well as
Congestive Heart Failure, High Cholesterol, Chest Pain, Heart Rhythm Disorders, Coronary Heart Disease, and Heart
Attack.
Contributor Information and Disclosures

Author
Ioana Dumitru, MD Associate Professor of Medicine, Division of Cardiology, Founder and Medical Director, Heart
Failure and Cardiac Transplant Program, University of Nebraska Medical Center; Associate Professor of Medicine,
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Division of Cardiology, Veterans Affairs Medical Center

Ioana Dumitru, MD is a member of the following medical societies: American College of Cardiology, Heart Failure
Society of America, and International Society for Heart and Lung Transplantation
Disclosure: Nothing to disclose.
Coauthor(s)
Mathue M Baker, MD Cardiologist, BryanLGH Heart Institute and Saint Elizabeth Regional Medical Center
Mathue M Baker, MD is a member of the following medical societies: American College of Cardiology
Chief Editor
Henry H Ooi, MB, MRCPI Director, Advanced Heart Failure and Cardiac Transplant Program, Nashville Veterans
Affairs Medical Center; Assistant Professor of Medicine, Vanderbilt University School of Medicine
Additional Contributors
Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program
Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University
School of Medicine
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American
Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency
Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas
Medical Society, New York Academy of Medicine, New York AcademyofSciences,and Society for Academic
Emergency Medicine
David FM Brown, MD Associate Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair,
Department of Emergency Medicine, Massachusetts General Hospital
David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians
and Society for Academic Emergency Medicine
William K Chiang, MD Associate Professor, Department of Emergency Medicine, New York University School of
Medicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center
William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology,
American College of Medical Toxicology, and Society for Academic Emergency Medicine
Joseph Cornelius Cleveland Jr, MD Associate Professor, Division of Cardiothoracic Surgery, University of
Colorado Health Sciences Center
Joseph Cornelius Cleveland Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American
Association for the Advancement of Science, American College of Cardiology, American College of Chest
Physicians, American College of Surgeons, American Geriatrics Society, American Physiological Society, American
Society of Transplant Surgeons, Association for Academic Surgery, Heart Failure Society of America, International
Society for Heart and Lung Transplantation, Phi Beta Kappa, Society of Critical Care Medicine, Society of Thoracic
Surgeons, and Western Thoracic Surgical Association
Disclosure: Thoratec Heartmate II Pivotal Tria; Grant/research funds Principal Investigator - Colorado; Abbott
Vascular E-Valve E-clip Honoraria Consulting; Baxter Healthcare Corp Consulting fee Board membership;
Heartware Advance BTT Trial Grant/research funds Principal Investigator- Colorado; Heartware Endurance DT trial
Grant/research funds Principal Investigator-Colorado
Shamai Grossman, MD, MS Assistant Professor, Department of Emergency Medicine, Harvard Medical School;
Director, The Clinical Decision Unit and Cardiac Emergency Center, Beth Israel Deaconess Medical Center
Shamai Grossman, MD, MS is a member of the following medical societies: American College of Emergency
Physicians
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John D Newell Jr, MD Professor of Radiology, Head, Division of Radiology, National Jewish Health; Professor,
Department of Radiology, University of Colorado School of Medicine
John D Newell Jr, MD is a member of the following medical societies: American College of Chest Physicians,
American College of Radiology, American Roentgen Ray Society, American Thoracic Society, Association of
University Radiologists, Radiological Society of North America, and Society of Thoracic Radiology
Disclosure: Siemens Medical Grant/research funds Consulting; Vida Corporation Ownership interest Board
membership; TeraRecon Grant/research funds Consulting; Medscape Reference Honoraria Consulting; Humana
Press Honoraria Other
Craig H Selzman, MD, FACS Associate Professor of Surgery, Surgical Director, Cardiac Mechanical Support and
Heart Transplant, Division of Cardiothoracic Surgery, University of Utah School of Medicine
Craig H Selzman, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American
Association for Thoracic Surgery, American College of Surgeons, American Physiological Society, Association for
Academic Surgery, International Society for Heart and Lung Transplantation, Society of Thoracic Surgeons,
Southern Thoracic Surgical Association, and Western Thoracic Surgical Association
Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division
of Emergency Medicine, Harvard Medical School
Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians,
National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management
position; ProceduresConsult.com Royalty Other
Brett C Sheridan, MD, FACS Associate Professor of Surgery, University of North Carolina at Chapel Hill School of
Medicine
George A Stouffer III, MD Henry A Foscue Distinguished Professor of Medicine and Cardiology, Director of
Interventional Cardiology, Cardiac Catheterization Laboratory, Chief of Clinical Cardiology, Division of Cardiology,
University of North Carolina Medical Center
George A Stouffer III, MD is a member of the following medical societies: Alpha Omega Alpha, American College
of Cardiology, American College of Physicians, American Heart Association, Phi Beta Kappa, and Society for
Cardiac Angiography and Interventions
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
Additional Contributors
Barry E Brenner, MD, PhD, FACEP Professor of Emergency Medicine, Professor of Internal Medicine, Program
Director, Emergency Medicine, Case Medical Center, University Hospitals, Case Western Reserve University
School of Medicine
Barry E Brenner, MD, PhD, FACEP is a member of the following medical societies: Alpha Omega Alpha, American
Academy of Emergency Medicine, American College of Chest Physicians, American College of Emergency
Physicians, American College of Physicians, American Heart Association, American Thoracic Society, Arkansas
Medical Society, New York Academy of Medicine, New York AcademyofSciences,and Society for Academic
Emergency Medicine
David FM Brown, MD Associate Professor, Division of Emergency Medicine, Harvard Medical School; Vice Chair,
Department of Emergency Medicine, Massachusetts General Hospital
David FM Brown, MD is a member of the following medical societies: American College of Emergency Physicians
and Society for Academic Emergency Medicine
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14 of 27

William K Chiang, MD Associate Professor, Department of Emergency Medicine, New York University School of
Medicine; Chief of Service, Department of Emergency Medicine, Bellevue Hospital Center
William K Chiang, MD is a member of the following medical societies: American Academy of Clinical Toxicology,
American College of Medical Toxicology, and Society for Academic Emergency Medicine
Joseph Cornelius Cleveland Jr, MD Associate Professor, Division of Cardiothoracic Surgery, University of
Colorado Health Sciences Center
Joseph Cornelius Cleveland Jr, MD is a member of the following medical societies: Alpha Omega Alpha, American
Association for the Advancement of Science, American College of Cardiology, American College of Chest
Physicians, American College of Surgeons, American Geriatrics Society, American Physiological Society, American
Society of Transplant Surgeons, Association for Academic Surgery, Heart Failure Society of America, International
Society for Heart and Lung Transplantation, Phi Beta Kappa, Society of Critical Care Medicine, Society of Thoracic
Surgeons, and Western Thoracic Surgical Association
Disclosure: Thoratec Heartmate II Pivotal Tria; Grant/research funds Principal Investigator - Colorado; Abbott
Vascular E-Valve E-clip Honoraria Consulting; Baxter Healthcare Corp Consulting fee Board membership;
Heartware Advance BTT Trial Grant/research funds Principal Investigator- Colorado; Heartware Endurance DT trial
Grant/research funds Principal Investigator-Colorado
Shamai Grossman, MD, MS Assistant Professor, Department of Emergency Medicine, Harvard Medical School;
Director, The Clinical Decision Unit and Cardiac Emergency Center, Beth Israel Deaconess Medical Center
Shamai Grossman, MD, MS is a member of the following medical societies: American College of Emergency
Physicians
John D Newell Jr, MD Professor of Radiology, Head, Division of Radiology, National Jewish Health; Professor,
Department of Radiology, University of Colorado School of Medicine
John D Newell Jr, MD is a member of the following medical societies: American College of Chest Physicians,
American College of Radiology, American Roentgen Ray Society, American Thoracic Society, Association of
University Radiologists, Radiological Society of North America, and Society of Thoracic Radiology
Disclosure: Siemens Medical Grant/research funds Consulting; Vida Corporation Ownership interest Board
membership; TeraRecon Grant/research funds Consulting; Medscape Reference Honoraria Consulting; Humana
Press Honoraria Other
Craig H Selzman, MD, FACS Associate Professor of Surgery, Surgical Director, Cardiac Mechanical Support and
Heart Transplant, Division of Cardiothoracic Surgery, University of Utah School of Medicine
Craig H Selzman, MD, FACS is a member of the following medical societies: Alpha Omega Alpha, American
Association for Thoracic Surgery, American College of Surgeons, American Physiological Society, Association for
Academic Surgery, International Society for Heart and Lung Transplantation, Society of Thoracic Surgeons,
Southern Thoracic Surgical Association, and Western Thoracic Surgical Association
Gary Setnik, MD Chair, Department of Emergency Medicine, Mount Auburn Hospital; Assistant Professor, Division
of Emergency Medicine, Harvard Medical School
Gary Setnik, MD is a member of the following medical societies: American College of Emergency Physicians,
National Association of EMS Physicians, and Society for Academic Emergency Medicine
Disclosure: SironaHealth Salary Management position; South Middlesex EMS Consortium Salary Management
position; ProceduresConsult.com Royalty Other
Brett C Sheridan, MD, FACS Associate Professor of Surgery, University of North Carolina at Chapel Hill School of
Medicine
George A Stouffer III, MD Henry A Foscue Distinguished Professor of Medicine and Cardiology, Director of
Interventional Cardiology, Cardiac Catheterization Laboratory, Chief of Clinical Cardiology, Division of Cardiology,
University of North Carolina Medical Center
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15 of 27
George A Stouffer III, MD is a member of the following medical societies: Alpha Omega Alpha, American College
of Cardiology, American College of Physicians, American Heart Association, Phi Beta Kappa, and Society for
Cardiac Angiography and Interventions
Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College
of Pharmacy; Editor-in-Chief, Medscape Drug Reference
Disclosure: Medscape Salary Employment
References
1. Stiles S. FDA Approves Heart Sympathetic Activity Imaging Agent for HF Evaluation. Available at
http://www.medscape.com/viewarticle/781309. Accessed April 5, 2013.
2. Framingham Classification: Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the
Framingham Study. J Am Coll Cardiol. Oct 1993;22(4 Suppl A):6A-13A. [Medline].
3. 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.
4. [Guideline] Hunt SA, Abraham WT, Chin MH, et al, and the American College of Cardiology Foundation;
American Heart Association. 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.
[Medline].
5. [Guideline] Hunt SA, for the 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. Sep 20
2005;46(6):e1-82. [Medline].
6. [Guideline] Dickstein K, Cohen-Solal A, Filippatos G, et al. for the Task Force for the Diagnosis and
Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. ESC Guidelines
for the diagnosis and treatment of acute and chronic heart failure 2008: the Task Force for the Diagnosis and
Treatment of Acute and Chronic Heart Failure 2008 of the European Society of Cardiology. Developed in
collaboration with the Heart Failure Association of the ESC (HFA) and endorsed by the European Society of
Intensive Care Medicine (ESICM). Eur Heart J. Oct 2008;29(19):2388-442. [Medline].
7. [Guideline] Lindenfeld J, Albert NM, Boehmer JP, et al, for the Heart Failure Society of America. Executive
summary: HFSA 2010 comprehensive heart failure practice guideline. J Card Fail. Jun 2010;16(6):e1-194.
[Medline].
8. Braunwald E. The pathogenesis of heart failure: Then and now. Medicine. 1991;70:68.
9. Braunwald E, Ross J Jr, Sonnenblick EH. 2 ed. Mechanisms of Contraction of the Normal and Failing
Heart. Boston: Little Brown & Co; 1976:417.
10. Clifford R Greyson, MD. Pathophysiology of right ventricular failure. Crit Care Med. 2008;36(suppl):S57-65.
11. Haddad F, Doyle R, Murphy DJ, Hunt SA. Right ventricular function in cardiovascular disease, part II:
pathophysiology, clinical importance, and management of right ventricular failure. Circulation. Apr 1
2008;117(13):1717-31. [Medline].
12. Onwuanyi A, Taylor M. Acute decompensated heart failure: pathophysiology and treatment. Am J Cardiol. Mar
26 2007;99(6B):25D-30D. [Medline].
13. Ross J Jr, Braunwald E. Studies on Starling's law of the heart. The effects of impeding venous return on
performance of the normal and failing human left ventricle. Circulation. 1954;30:719.
14. Gheorghiade M, Pang PS. Acute heart failure syndromes. J Am Coll Cardiol. Feb 17 2009;53(7):557-73.
[Medline].
15. Kajstura J, Leri A, Finato N, Di Loreto C, Beltrami CA, Anversa P. Myocyte proliferation in end-stage cardiac
failure in humans. Proc Natl Acad Sci U S A. Jul 21 1998;95(15):8801-5. [Medline]. [Full Text].
14/04/2013 15:17
Heart Failure
16 of 27
16. Cohn JN. Structural basis for heart failure. Ventricular remodeling and its pharmacological inhibition.
Circulation. May 15 1995;91(10):2504-7. [Medline].
17. Cody RJ. Hormonal alterations in heart failure. In: Hosenpud JB, Greenberg BH, eds. Congestive Heart
Failure: Pathophysiology, Diagnosis and Comprehensive Approach to Management. Philadelphia:
Lippincott Williams & Wilkins; 2000:199-212.
18. Anversa P, Nadal-Ginard B. Myocyte renewal and ventricular remodelling. Nature. Jan 10
2002;415(6868):240-3. [Medline].
19. Leri A, Claudio PP, Li Q, Wang X, Reiss K, Wang S, et al. Stretch-mediated release of angiotensin II induces
myocyte apoptosis by activating p53 that enhances the local renin-angiotensin system and decreases the
Bcl-2-to-Bax protein ratio in the cell. J Clin Invest. Apr 1 1998;101(7):1326-42. [Medline]. [Full Text].
20. Kajstura J, Leri A, Castaldo C, Nadal-Ginard B, Anversa P. Myocyte growth in the failing heart. Surg Clin North
Am. Feb 2004;84(1):161-77. [Medline].
21. Feldman AM, Combes A, Wagner D, Kadakomi T, Kubota T, Li YY, et al. The role of tumor necrosis factor in
the pathophysiology of heart failure. J Am Coll Cardiol. Mar 1 2000;35(3):537-44. [Medline].
22. Rebecca Gary, RN, PhD, Leslie Davis, MSN, RN, et al. Diastolic heart failure. Heart & Lung.
2007;37(6):405-16.
23. Morris DA, Gailani M, Vaz Perez A, et al. Right ventricular myocardial systolic and diastolic dysfunction in heart
failure with normal left ventricular ejection fraction. J Am Soc Echocardiogr. Aug 2011;24(8):886-97.
[Medline].
24. Lam CS, Lyass A, Kraigher-Krainer E, et al. Cardiac dysfunction and noncardiac dysfunction as precursors of
heart failure with reduced and preserved ejection fraction in the community. Circulation. Jul 5
2011;124(1):24-30. [Medline].
25. Ho KK, Anderson KM, Kannel WB, Grossman W, Levy D. Survival after the onset of congestive heart failure
in Framingham Heart Study subjects. Circulation. Jul 1993;88(1):107-15. [Medline].
26. Halley CM, Houghtaling PL, Khalil MK, Thomas JD, Jaber WA. Mortality rate in patients with diastolic
dysfunction and normal systolic function. Arch Intern Med. Jun 27 2011;171(12):1082-7. [Medline].
27. Murphy RT, Starling RC. Genetics and cardiomyopathy: where are we now?. Cleve Clin J Med. Jun
2005;72(6):465-6, 469-70, 472-3 passim. [Medline].
28. Roger VL, Go AS, Lloyd-Jones DM, et al, for the American Heart Association Statistics Committee and
Stroke Statistics Subcommittee. Heart disease and stroke statistics--2011 update: a report from the American
Heart Association. Circulation. Feb 1 2011;123(4):e18-e209. [Medline].
29. Fonarow GC. Epidemiology and risk stratification in acute heart failure. Am Heart J. Feb 2008;155(2):200-7.
[Medline].
30. Gottlieb SS, Khatta M, Friedmann E, Einbinder L, Katzen S, Baker B, et al. The influence of age, gender, and
race on the prevalence of depression in heart failure patients. J Am Coll Cardiol. May 5 2004;43(9):1542-9.
[Medline].
31. He J, Ogden LG, Bazzano LA, Vupputuri S, Loria C, Whelton PK. Risk factors for congestive heart failure in
US men and women: NHANES I epidemiologic follow-up study. Arch Intern Med. Apr 9
2001;161(7):996-1002. [Medline].
32. Masoudi FA, Havranek EP, Smith G, Fish RH, Steiner JF, Ordin DL, et al. Gender, age, and heart failure with
preserved left ventricular systolic function. J Am Coll Cardiol. Jan 15 2003;41(2):217-23. [Medline].
33. Chen J, Normand SL, Wang Y, Krumholz HM. National and regional trends in heart failure hospitalization and
mortality rates for Medicare beneficiaries, 1998-2008. JAMA. Oct 19 2011;306(15):1669-78. [Medline].
34. Jencks SF, Williams MV, Coleman EA. Rehospitalizations among patients in the Medicare fee-for-service
program. N Engl J Med. Apr 2 2009;360(14):1418-28. [Medline].
35. Lloyd-Jones D, Adams RJ, Brown TM, Carnethon M, Dai S, De Simone G, et al. Executive summary: heart
disease and stroke statistics--2010 update: a report from the American Heart Association. Circulation. Feb
23 2010;121(7):948-54. [Medline].
36. Stewart S, Wilkinson D, Hansen C, Vaghela V, Mvungi R, McMurray J, et al. Predominance of heart failure in
the Heart of Soweto Study cohort: emerging challenges for urban African communities. Circulation. Dec 2
14/04/2013 15:17
Heart Failure
17 of 27
2008;118(23):2360-7. [Medline].
37. Damasceno A, Cotter G, Dzudie A, Sliwa K, Mayosi BM. Heart failure in sub-saharan Africa: time for action. J
Am Coll Cardiol. Oct 23 2007;50(17):1688-93. [Medline].
38. Cardiovascular Diseases. Dean T. Jamison, Richard G. Feachem, Eduard R. Bos, Malegapuru W. Makgoba,
Florence K. Baingana, Karen J. Hofman, Kahma O. Rogo. Disease and mortality in Sub-Saharan Africa. 2.
Washington D.C: World Bank Publications; 2006:21.
39. Dries DL, Exner DV, Domanski MJ, Greenberg B, Stevenson LW. The prognostic implications of renal
insufficiency in asymptomatic and symptomatic patients with left ventricular systolic dysfunction. J Am Coll
Cardiol. Mar 1 2000;35(3):681-9. [Medline].
40. Fonarow GC, Adams KF Jr, Abraham WT, Yancy CW, Boscardin WJ. Risk stratification for in-hospital
mortality in acutely decompensated heart failure: classification and regression tree analysis. JAMA. Feb 2
2005;293(5):572-80. [Medline].
41. Levy D, Kenchaiah S, Larson MG, Benjamin EJ, Kupka MJ, Ho KK, et al. Long-term trends in the incidence of
and survival with heart failure. N Engl J Med. Oct 31 2002;347(18):1397-402. [Medline].
42. Lucas C, Johnson W, Hamilton MA, Fonarow GC, Woo MA, Flavell CM, et al. Freedom from congestion
predicts good survival despite previous class IV symptoms of heart failure. Am Heart J. Dec
2000;140(6):840-7. [Medline].
43. MacIntyre K, Capewell S, Stewart S, Chalmers JW, Boyd J, Finlayson A, et al. Evidence of improving
prognosis in heart failure: trends in case fatality in 66 547 patients hospitalized between 1986 and 1995.
Circulation. Sep 5 2000;102(10):1126-31. [Medline].
44. Ketchum ES, Levy WC. Establishing prognosis in heart failure: a multimarker approach. Prog Cardiovasc
Dis. Sep-Oct 2011;54(2):86-96. [Medline].
45. van Diepen S, Bakal JA, McAlister FA, Ezekowitz JA. Mortality and readmission of patients with heart failure,
atrial fibrillation, or coronary artery disease undergoing noncardiac surgery: an analysis of 38 047 patients.
Circulation. Jul 19 2011;124(3):289-96. [Medline].
46. Bursi F, McNallan SM, Redfield MM, et al. Pulmonary pressures and death in heart failure a community study.
J Am Coll Cardiol. Jan 17 2012;59(3):222-31. [Medline]. [Full Text].
47. Ho JE, Liu C, Lyass A, Courchesne P, Pencina MJ, Vasan RS, et al. Galectin-3, a marker of cardiac fibrosis,
predicts incident heart failure in the community. J Am Coll Cardiol. Oct 2 2012;60(14):1249-56. [Medline].
48. Dunlay SM, Eveleth JM, Shah ND, McNallan SM, Roger VL. Medication adherence among communitydwelling patients with heart failure. Mayo Clin Proc. Apr 2011;86(4):273-81. [Medline]. [Full Text].
49. Dewalt DA, Schillinger D, Ruo B, Bibbins-Domingo K, Baker DW, Holmes GM, et al. A Multisite Randomized
Trial of a Single- versus Multi-Session Literacy Sensitive Self-Care Intervention for Patients with Heart Failure.
Circulation. May 9 2012;[Medline].
50. Lindenfeld J, Albert NM, Boehmer JP, Collins SP, Ezekowitz JA, Givertz MM, et al. HFSA 2010
Comprehensive Heart Failure Practice Guideline. J Card Fail. Jun 2010;16(6):e1-194. [Medline].
51. Lainscak M, Cleland JG, Lenzen MJ, Follath F, Komajda M, Swedberg K. International variations in the
treatment and co-morbidity of left ventricular systolic dysfunction: data from the EuroHeart Failure Survey. Eur
J Heart Fail. Mar 2007;9(3):292-9. [Medline].
52. [Guideline] Peacock WF, Fonarow GC, Ander DS, Maisel A, Hollander JE, Januzzi JL Jr, et al. Society of
Chest Pain Centers Recommendations for the evaluation and management of the observation stay acute
heart failure patient: a report from the Society of Chest Pain Centers Acute Heart Failure Committee. Crit
Pathw Cardiol. Jun 2008;7(2):83-6. [Medline].
53. [Best Evidence] Steinhart B, Thorpe KE, Bayoumi AM, Moe G, Januzzi JL Jr, Mazer CD. Improving the
diagnosis of acute heart failure using a validated prediction model. J Am Coll Cardiol. Oct 13
2009;54(16):1515-21. [Medline].
54. Jessup M, Abraham WT, Casey DE, Feldman AM, Francis GS, Ganiats TG, et al. 2009 focused update:
ACCF/AHA 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. Circulation. Apr 14
2009;119(14):1977-2016. [Medline].
14/04/2013 15:17
Heart Failure
18 of 27
55. Rich MW, McSherry F, Williford WO, Yusuf S. Effect of age on mortality, hospitalizations and response to
digoxin in patients with heart failure: the DIG study. J Am Coll Cardiol. Sep 2001;38(3):806-13. [Medline].
56. Badve SV, Roberts MA, Hawley CM, et al. Effects of Beta-adrenergic antagonists in patients with chronic
kidney disease a systematic review and meta-analysis. J Am Coll Cardiol. Sep 6 2011;58(11):1152-61.
[Medline].
57. Maisel AS, Krishnaswamy P, Nowak RM, et al. Rapid measurement of B-type natriuretic peptide in the
emergency diagnosis of heart failure. N Engl J Med. Jul 18 2002;347(3):161-7. [Medline].
58. Januzzi JL Jr, Camargo CA, Anwaruddin S, et al. The N-terminal Pro-BNP investigation of dyspnea in the
emergency department (PRIDE) study. Am J Cardiol. Apr 15 2005;95(8):948-54. [Medline].
59. Wang CS, FitzGerald JM, Schulzer M, Mak E, Ayas NT. Does this dyspneic patient in the emergency
department have congestive heart failure?. JAMA. Oct 19 2005;294(15):1944-56. [Medline].
60. Stevenson LW, Perloff JK. The limited reliability of physical signs for estimating hemodynamics in chronic
heart failure. JAMA. Feb 10 1989;261(6):884-8. [Medline].
61. Pinamonti B, Di Lenarda A, Sinagra G, Camerini F. Restrictive left ventricular filling pattern in dilated
cardiomyopathy assessed by Doppler echocardiography: clinical, echocardiographic and hemodynamic
correlations and prognostic implications. Heart Muscle Disease Study Group. J Am Coll Cardiol. Sep
1993;22(3):808-15. [Medline].
62. Temporelli PL, Scapellato F, Eleuteri E, Imparato A, Giannuzzi P. Doppler echocardiography in advanced
systolic heart failure: a noninvasive alternative to Swan-Ganz catheter. Circ Heart Fail. May 2010;3(3):387-94.
[Medline].
63. Maisel AS, McCord J, Nowak RM, et al. Bedside B-Type natriuretic peptide in the emergency diagnosis of
heart failure with reduced or preserved ejection fraction. Results from the Breathing Not Properly Multinational
Study. J Am Coll Cardiol. Jun 4 2003;41(11):2010-7. [Medline].
64. [Best Evidence] Januzzi JL, van Kimmenade R, Lainchbury J, et al. NT-proBNP testing for diagnosis and
short-term prognosis in acute destabilized heart failure: an international pooled analysis of 1256 patients: the
International Collaborative of NT-proBNP Study. Eur Heart J. Feb 2006;27(3):330-7. [Medline].
65. Maeda K, Tsutamoto T, Wada A, Hisanaga T, Kinoshita M. Plasma brain natriuretic peptide as a biochemical
marker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction.
Am Heart J. May 1998;135(5 Pt 1):825-32. [Medline].
66. Fisher C, Berry C, Blue L, Morton JJ, McMurray J. N-terminal pro B type natriuretic peptide, but not the new
putative cardiac hormone relaxin, predicts prognosis in patients with chronic heart failure. Heart. Aug
2003;89(8):879-81. [Medline]. [Full Text].
67. Hall C, Rouleau JL, Moye L, et al. N-terminal proatrial natriuretic factor. An independent predictor of long-term
prognosis after myocardial infarction. Circulation. May 1994;89(5):1934-42. [Medline].
68. Andersson B, Hall C. N-terminal proatrial natriuretic peptide and prognosis in patients with heart failure and
preserved systolic function. J Card Fail. Sep 2000;6(3):208-13. [Medline].
69. Chen HH, Burnett JC. Natriuretic peptides in the pathophysiology of congestive heart failure. Curr Cardiol
Rep. May 2000;2(3):198-205. [Medline].
70. Cheng V, Kazanagra R, Garcia A, Lenert L, Krishnaswamy P, Gardetto N, et al. A rapid bedside test for B-type
peptide predicts treatment outcomes in patients admitted for decompensated heart failure: a pilot study. J
Am Coll Cardiol. Feb 2001;37(2):386-91. [Medline].
71. Cowie MR, Struthers AD, Wood DA, Coats AJ, Thompson SG, Poole-Wilson PA, et al. Value of natriuretic
peptides in assessment of patients with possible new heart failure in primary care. Lancet. Nov 8
1997;350(9088):1349-53. [Medline].
72. Dao Q, Krishnaswamy P, Kazanegra R, Harrison A, Amirnovin R, Lenert L, et al. Utility of B-type natriuretic
peptide in the diagnosis of congestive heart failure in an urgent-care setting. J Am Coll Cardiol. Feb
2001;37(2):379-85. [Medline].
73. Maeda K, Tsutamoto T, Wada A, Hisanaga T, Kinoshita M. Plasma brain natriuretic peptide as a biochemical
marker of high left ventricular end-diastolic pressure in patients with symptomatic left ventricular dysfunction.
Am Heart J. May 1998;135(5 Pt 1):825-32. [Medline].
74. Maisel AS, Koon J, Hope J, et al. A rapid bedside test for brain natriuretic peptide accurately predicts cardiac
14/04/2013 15:17
Heart Failure
19 of 27
function in patients referred for echocardiography. Am Heart J. 2001;141:374-9.

75. Masson S, Vago T, Baldi G, et al. Comparative measurement of N-terminal pro-brain natriuretic peptide and
brain natriuretic peptide in ambulatory patients with heart failure. Clin Chem Lab Med. Aug 2002;40(8):761-3.
[Medline].
76. Song BG, Jeon ES, Kim YH, et al. Correlation between levels of N-terminal pro-B-type natriuretic peptide and
degrees of heart failure. Korean J Intern Med. Mar 2005;20(1):26-32. [Medline].
77. Hobbs FD, Davis RC, Roalfe AK, et al. Reliability of N-terminal pro-brain natriuretic peptide assay in diagnosis
of heart failure: cohort study in representative and high risk community populations. [abstract]. BMJ. Jun 22
2002;324(7352):1498.
78. Redfield MM, Rodeheffer RJ, Jacobsen SJ, Mahoney DW, Bailey KR, Burnett JC Jr. Plasma brain natriuretic
peptide concentration: impact of age and gender. J Am Coll Cardiol. Sep 4 2002;40(5):976-82. [Medline].
79. St Peter JV, Hartley GG, Murakami MM, Apple FS. B-type natriuretic peptide (BNP) and N-terminal pro-BNP in
obese patients without heart failure: relationship to body mass index and gastric bypass surgery. Clin Chem.
Apr 2006;52(4):680-5. [Medline].
80. Rivera M, Cortes R, Salvador A, ET AL. Obese subjects with heart failure have lower N-terminal pro-brain
natriuretic peptide plasma levels irrespective of aetiology. Eur J Heart Fail. Dec 2005;7(7):1168-70.
[Medline].
81. Hermann-Arnhof KM, Hanusch-Enserer U, Kaestenbauer T, et al. N-terminal pro-B-type natriuretic peptide as
an indicator of possible cardiovascular disease in severely obese individuals: comparison with patients in
different stages of heart failure. Clin Chem. Jan 2005;51(1):138-43. [Medline].
82. Seino Y, Ogawa A, Yamashita T, et al. Application of NT-proBNP and BNP measurements in cardiac care: a
more discerning marker for the detection and evaluation of heart failure. Eur J Heart Fail. Mar 15
2004;6(3):295-300. [Medline].
83. Colucci WS, Elkayam U, Horton DP, Abraham WT, Bourge RC, Johnson AD, et al. Intravenous nesiritide, a
natriuretic peptide, in the treatment of decompensated congestive heart failure. Nesiritide Study Group. N
Engl J Med. Jul 27 2000;343(4):246-53. [Medline].
84. Ezekowitz JA, Hernandez AF, Starling RC, Yancy CW, Massie B, Hill JA, et al. Standardizing care for acute
decompensated heart failure in a large megatrial: the approach for the Acute Studies of Clinical Effectiveness
of Nesiritide in Subjects with Decompensated Heart Failure (ASCEND-HF). Am Heart J. Feb
2009;157(2):219-28. [Medline].
85. Mills RM, LeJemtel TH, Horton DP, Liang C, Lang R, Silver MA, et al. Sustained hemodynamic effects of an
infusion of nesiritide (human b-type natriuretic peptide) in heart failure: a randomized, double-blind, placebocontrolled clinical trial. Natrecor Study Group. J Am Coll Cardiol. Jul 1999;34(1):155-62. [Medline].
86. Silver MA, Horton DP, Ghali JK, Elkayam U. Effect of nesiritide versus dobutamine on short-term outcomes in
the treatment of patients with acutely decompensated heart failure. J Am Coll Cardiol. Mar 6
2002;39(5):798-803. [Medline].
87. Miller WL, Hartman KA, Burritt MF, Borgeson DD, Burnett JC Jr, Jaffe AS. Biomarker responses during and
after treatment with nesiritide infusion in patients with decompensated chronic heart failure. Clin Chem. Mar
2005;51(3):569-77. [Medline].
88. Fitzgerald RL, Cremo R, Gardetto N, et al. Effect of nesiritide in combination with standard therapy on serum
concentrations of natriuretic peptides in patients admitted for decompensated congestive heart failure. Am
Heart J. Sep 2005;150(3):471-7. [Medline].
89. Michels VV, Moll PP, Miller FA, et al. The frequency of familial dilated cardiomyopathy in a series of patients
with idiopathic dilated cardiomyopathy. N Engl J Med. Jan 9 1992;326(2):77-82. [Medline].
90. Baig MK, Goldman JH, Caforio AL, Coonar AS, Keeling PJ, McKenna WJ. Familial dilated cardiomyopathy:
cardiac abnormalities are common in asymptomatic relatives and may represent early disease. J Am Coll
Cardiol. Jan 1998;31(1):195-201. [Medline].
91. Grunig E, Tasman JA, Kucherer H, Franz W, Kubler W, Katus HA. Frequency and phenotypes of familial
dilated cardiomyopathy. J Am Coll Cardiol. Jan 1998;31(1):186-94. [Medline].
92. McNally E, MacLeod H, Dellefave L. Arrhythmogenic right ventricular dysplasia/cardiomyopathy, autosomal
dominant. 2005;[Medline].
14/04/2013 15:17
Heart Failure
20 of 27
93. Cheitlin MD, Alpert JS, Armstrong WF, Aurigemma GP, Beller GA, Bierman FZ, et al. ACC/AHA Guidelines
for the Clinical Application of Echocardiography. A report of the American College of Cardiology/American
Heart Association Task Force on Practice Guidelines (Committee on Clinical Application of
Echocardiography). Developed in collaboration with the American Society of Echocardiography. Circulation.
Mar 18 1997;95(6):1686-744. [Medline].
94. Patel AR, Alsheikh-Ali AA, Mukherjee J, Evangelista A, Quraini D, Ordway LJ, et al. 3D Echocardiography to
Evaluate Right Atrial Pressure in Acutely Decompensated Heart Failure Correlation With Invasive
Hemodynamics. JACC Cardiovasc Imaging. Sep 2011;4(9):938-45. [Medline].
95. Prior D, Coller J. Echocardiography in heart failure - a guide for general practice. Aust Fam Physician. Dec
2010;39(12):904-9. [Medline].
96. Kirkpatrick JN, Wiegers SE, Lang RM. Left ventricular assist devices and other devices for end-stage heart
failure: utility of echocardiography. Curr Cardiol Rep. May 2010;12(3):257-64. [Medline].
97. Abraham J, Abraham TP. The role of echocardiography in hemodynamic assessment in heart failure. Heart
Fail Clin. Apr 2009;5(2):191-208. [Medline].
98. Kim RJ, Wu E, Rafael A, Chen EL, Parker MA, Simonetti O, et al. The use of contrast-enhanced magnetic
resonance imaging to identify reversible myocardial dysfunction. N Engl J Med. Nov 16
2000;343(20):1445-53. [Medline].
99. Ritchie JL, Bateman TM, Bonow RO, Crawford MH, Gibbons RJ, Hall RJ, et al. Guidelines for clinical use of
cardiac radionuclide imaging. Report of the American College of Cardiology/American Heart Association
Task Force on Assessment of Diagnostic and Therapeutic Cardiovascular Procedures (Committee on
Radionuclide Imaging), developed in collaboration with the American Society of Nuclear Cardiology. J Am
Coll Cardiol. Feb 1995;25(2):521-47. [Medline].
100. Taillefer R, DePuey EG, Udelson JE, Beller GA, Latour Y, Reeves F. Comparative diagnostic accuracy of
Tl-201 and Tc-99m sestamibi SPECT imaging (perfusion and ECG-gated SPECT) in detecting coronary
artery disease in women. J Am Coll Cardiol. Jan 1997;29(1):69-77. [Medline].
101. Bonow RO, Maurer G, Lee KL, et al. Myocardial Viability and Survival in Ischemic Left Ventricular Dysfunction.
N Engl J Med. Apr 4 2011;[Medline].
102. Binanay C, Califf RM, Hasselblad V, et al. Evaluation study of congestive heart failure and pulmonary artery
catheterization effectiveness: the ESCAPE trial. JAMA. Oct 5 2005;294(13):1625-33. [Medline].
103. Bitter T, Westerheide N, Prinz C, Hossain MS, Vogt J, Langer C, et al. Cheyne-Stokes respiration and
obstructive sleep apnoea are independent risk factors for malignant ventricular arrhythmias requiring
appropriate cardioverter-defibrillator therapies in patients with congestive heart failure. Eur Heart J. Jan
2011;32(1):61-74. [Medline].
104. Groenveld HF, Januzzi JL, Damman K, et al. Anemia and mortality in heart failure patients a systematic review
and meta-analysis. J Am Coll Cardiol. Sep 2 2008;52(10):818-27. [Medline].
105. Ronco C, Haapio M, House AA, Anavekar N, Bellomo R. Cardiorenal syndrome. J Am Coll Cardiol. Nov 4
2008;52(19):1527-39. [Medline].
106. House AA, Haapio M, Lassus J, Bellomo R, Ronco C. Therapeutic strategies for heart failure in cardiorenal
syndromes. Am J Kidney Dis. Oct 2010;56(4):759-73. [Medline].
107. Giamouzis G, Butler J, Starling RC, Karayannis G, Nastas J, Parisis C, et al. Impact of dopamine infusion on
renal function in hospitalized heart failure patients: results of the Dopamine in Acute Decompensated Heart
Failure (DAD-HF) Trial. J Card Fail. Dec 2010;16(12):922-30. [Medline].
108. Pleister AP, Baliga RR, Haas GJ. Acute study of clinical effectiveness of nesiritide in decompensated heart
failure: nesiritide redux. Curr Heart Fail Rep. Sep 2011;8(3):226-32. [Medline].
109. Konstam MA, Gheorghiade M, Burnett JC Jr, Grinfeld L, Maggioni AP, Swedberg K, et al. Effects of oral
tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. Mar 28
2007;297(12):1319-31. [Medline].
110. Massie BM, O'Connor CM, Metra M, Ponikowski P, Teerlink JR, Cotter G, et al. Rolofylline, an adenosine
A1-receptor antagonist, in acute heart failure. N Engl J Med. Oct 7 2010;363(15):1419-28. [Medline].
111. Badve SV, Roberts MA, Hawley CM, et al. Effects of Beta-adrenergic antagonists in patients with chronic
kidney disease a systematic review and meta-analysis. J Am Coll Cardiol. Sep 6 2011;58(11):1152-61.
14/04/2013 15:17
Heart Failure
21 of 27
[Medline].
112. Roy D, Talajic M, Nattel S, et al, for the Atrial Fibrillation and Congestive Heart Failure Investigators. Rhythm
control versus rate control for atrial fibrillation and heart failure. N Engl J Med. Jun 19 2008;358(25):2667-77.
[Medline].
113. Hsu LF, Jas P, Sanders P, Garrigue S, Hocini M, Sacher F, et al. Catheter ablation for atrial fibrillation in
congestive heart failure. N Engl J Med. Dec 2 2004;351(23):2373-83. [Medline].
114. Wilton SB, Fundytus A, Ghali WA, Veenhuyzen GD, Quinn FR, Mitchell LB, et al. Meta-analysis of the
effectiveness and safety of catheter ablation of atrial fibrillation in patients with versus without left ventricular
systolic dysfunction. Am J Cardiol. Nov 1 2010;106(9):1284-91. [Medline].
115. MacDonald MR, Connelly DT, Hawkins NM, Steedman T, Payne J, Shaw M, et al. Radiofrequency ablation for
persistent atrial fibrillation in patients with advanced heart failure and severe left ventricular systolic
dysfunction: a randomised controlled trial. Heart. May 2011;97(9):740-7. [Medline].
116. Chen YM, Li ZB, Zhu M, Cao YM. Effects of exercise training on left ventricular remodelling in heart failure
patients: an updated meta-analysis of randomised controlled trials. Int J Clin Pract. Aug 2012;66(8):782-791.
[Medline].
117. Mozaffarian D, Lemaitre RN, King IB, et al. Circulating Long-Chain {omega}-3 Fatty Acids and Incidence of
Congestive Heart Failure in Older Adults: The Cardiovascular Health Study: A Cohort Study. Ann Intern Med.
Aug 2 2011;155(3):160-70. [Medline].
118. Marchioli R, Levantesi G, Silletta MG, et al, for the GISSI-HF investigators. Effect of n-3 polyunsaturated fatty
acids and rosuvastatin in patients with heart failure: results of the GISSI-HF trial. Expert Rev Cardiovasc
Ther. Jul 2009;7(7):735-48. [Medline].
119. Massie BM, Collins JF, Ammon SE, Armstrong PW, Cleland JG, Ezekowitz M, et al. Randomized trial of
warfarin, aspirin, and clopidogrel in patients with chronic heart failure: the Warfarin and Antiplatelet Therapy in
Chronic Heart Failure (WATCH) trial. Circulation. Mar 31 2009;119(12):1616-24. [Medline].
120. Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM. Trends in prevalence and
outcome of heart failure with preserved ejection fraction. N Engl J Med. Jul 20 2006;355(3):251-9. [Medline].
121. Hogg K, Swedberg K, McMurray J. Heart failure with preserved left ventricular systolic function; epidemiology,
clinical characteristics, and prognosis. J Am Coll Cardiol. Feb 4 2004;43(3):317-27. [Medline].
122. Gheorghiade M, Abraham WT, Albert NM, et al, for the OPTIMIZE-HF Investigators and Coordinators.
Systolic blood pressure at admission, clinical characteristics, and outcomes in patients hospitalized with acute
heart failure. JAMA. Nov 8 2006;296(18):2217-26. [Medline].
123. Masip J, Roque M, Sanchez B, Fernandez R, Subirana M, Exposito JA. Noninvasive ventilation in acute
cardiogenic pulmonary edema: systematic review and meta-analysis. JAMA. Dec 28 2005;294(24):3124-30.
[Medline].
124. Peter JV, Moran JL, Phillips-Hughes J, Graham P, Bersten AD. Effect of non-invasive positive pressure
ventilation (NIPPV) on mortality in patients with acute cardiogenic pulmonary oedema: a meta-analysis.
Lancet. Apr 8 2006;367(9517):1155-63. [Medline].
125. Winck JC, Azevedo LF, Costa-Pereira A, Antonelli M, Wyatt JC. Efficacy and safety of non-invasive ventilation
in the treatment of acute cardiogenic pulmonary edema--a systematic review and meta-analysis. Crit Care.
2006;10(2):R69. [Medline]. [Full Text].
126. Vital FM, Saconato H, Ladeira MT, et al. Non-invasive positive pressure ventilation (CPAP or bilevel NPPV) for
cardiogenic pulmonary edema. Cochrane Database Syst Rev. Jul 16 2008;CD005351. [Medline].
127. Maeder MT, Kaye DM. Heart failure with normal left ventricular ejection fraction. J Am Coll Cardiol. Mar 17
2009;53(11):905-18. [Medline].
128. Gray A, Goodacre S, Newby DE, Masson M, Sampson F, Nicholl J, et al. Noninvasive ventilation in acute
cardiogenic pulmonary edema. N Engl J Med. Jul 10 2008;359(2):142-51. [Medline].
129. The CONSENSUS Trial Study Group. Effects of enalapril on mortality in severe congestive heart failure.
Results of the Cooperative North Scandinavian Enalapril Survival Study (CONSENSUS). The CONSENSUS
Trial Study Group. N Engl J Med. Jun 4 1987;316(23):1429-35. [Medline].
130. The SOLVD Investigators. Effect of enalapril on survival in patients with reduced left ventricular ejection
fractions and congestive heart failure. N Engl J Med. Aug 1 1991;325(5):293-302. [Medline].
14/04/2013 15:17
Heart Failure
22 of 27
131. Zannad F, Alla F, Dousset B, Perez A, Pitt B. Limitation of excessive extracellular matrix turnover may
contribute to survival benefit of spironolactone therapy in patients with congestive heart failure: insights from
the randomized aldactone evaluation study (RALES). Rales Investigators. Circulation. Nov 28
2000;102(22):2700-6. [Medline].
132. Felker GM, Lee KL, Bull DA, Redfield MM, Stevenson LW, Goldsmith SR, et al. Diuretic strategies in patients
with acute decompensated heart failure. N Engl J Med. Mar 3 2011;364(9):797-805. [Medline].
133. Liu PP. Cardiorenal syndrome in heart failure: a cardiologist's perspective. Can J Cardiol. Jul 2008;24 suppl
B:25B-9B. [Medline]. [Full Text].
134. Kramer BK, Schweda F, Riegger GA. Diuretic treatment and diuretic resistance in heart failure. Am J Med.
Jan 1999;106(1):90-6. [Medline].
135. Nieminen MS, Bohm M, Cowie MR, et al for the ESC Committe for Practice Guideline (CPG). Executive
summary of the guidelines on the diagnosis and treatment of acute heart failure: the Task Force on Acute
Heart Failure of the European Society of Cardiology. Eur Heart J. Feb 2005;26(4):384-416. [Medline].
136. Neuberg GW, Miller AB, O'Connor CM, et al. Diuretic resistance predicts mortality in patients with advanced
heart failure. Am Heart J. Jul 2002;144(1):31-8. [Medline].
137. Costanzo MR, Saltzberg M, O'Sullivan J, Sobotka P. Early ultrafiltration in patients with decompensated heart
failure and diuretic resistance. J Am Coll Cardiol. Dec 6 2005;46(11):2047-51. [Medline].
138. Young JB, Abraham WT, Stevenson LW, et al. Results of the VMAC Trial: vasodilation in the management of
acute congestive heart failure. N Engl J Med. 2000;102:a2794.
139. Publication Committee for the VMAC Investigators (Vasodilatation in the Management of Acute CHF).
Intravenous nesiritide vs nitroglycerin for treatment of decompensated congestive heart failure: a randomized
controlled trial. JAMA. Mar 27 2002;287(12):1531-40. [Medline].
140. Costanzo MR, Jessup M. Treatment of congestion in heart failure with diuretics and extracorporeal therapies:
effects on symptoms, renal function, and prognosis. Heart Fail Rev. May 11 2011;[Medline].
141. Costanzo MR, Guglin ME, Saltzberg MT, Jessup ML, Bart BA, Teerlink JR, et al. Ultrafiltration versus
intravenous diuretics for patients hospitalized for acute decompensated heart failure. J Am Coll Cardiol. Feb
13 2007;49(6):675-83. [Medline].
142. CIBIS Investigators and Committees. A randomized trial of beta-blockade in heart failure. The Cardiac
Insufficiency Bisoprolol Study (CIBIS). Circulation. Oct 1994;90(4):1765-73. [Medline].
143. Chaudhry SI, Mattera JA, Curtis JP, Spertus JA, Herrin J, Lin Z, et al. Telemonitoring in patients with heart
failure. N Engl J Med. Dec 9 2010;363(24):2301-9. [Medline].
144. Koehler F, Winkler S, Schieber M, et al. Impact of Remote Telemedical Management on Mortality and
Hospitalizations in Ambulatory Patients With Chronic Heart Failure: The Telemedical Interventional Monitoring
in Heart Failure Study. Circulation. May 3 2011;123(17):1873-1880. [Medline].
145. Abraham WT, Adamson PB, Bourge RC, Aaron MF, Costanzo MR, Stevenson LW, et al. Wireless pulmonary
artery haemodynamic monitoring in chronic heart failure: a randomised controlled trial. Lancet. Feb 19
2011;377(9766):658-66. [Medline].
146. Eisen HJ, Kobashigawa J, Keogh A, Bourge R, Renlund D, Mentzer R, et al. Three-year results of a
randomized, double-blind, controlled trial of mycophenolate mofetil versus azathioprine in cardiac transplant
recipients. J Heart Lung Transplant. May 2005;24(5):517-25. [Medline].
147. Yancy CW, Lopatin M, Stevenson LW, De Marco T, Fonarow GC. Clinical presentation, management, and
in-hospital outcomes of patients admitted with acute decompensated heart failure with preserved systolic
function: a report from the Acute Decompensated Heart Failure National Registry (ADHERE) Database. J Am
Coll Cardiol. Jan 3 2006;47(1):76-84. [Medline].
148. Dickstein K, Vardas PE, Auricchio A, et al al for the Task Force on Acute Heart Failure of the European
Society of Cardiology. 2010 Focused Update of ESC Guidelines on device therapy in heart failure: an update
of the 2008 ESC Guidelines for the diagnosis and treatment of acute and chronic heart failure and the 2007
ESC guidelines for cardiac and resynchronization therapy. Developed with the special contribution of the
Heart Failure Association and the European Heart Rhythm Association. Eur Heart J. Nov
2010;31(21):2677-87. [Medline].
149. Tracy CM, Epstein AE, Darbar D, Dimarco JP, Dunbar SB, Estes NA 3rd, et al. 2012 ACCF/AHA/HRS
Focused Update of the 2008 Guidelines for Device-Based Therapy of Cardiac Rhythm Abnormalities: A
14/04/2013 15:17
Heart Failure
23 of 27
Report of the American College of Cardiology Foundation/American Heart Association Task Force on
Practice Guidelines. Circulation. Sep 10 2012;[Medline].
150. Miller R. AHA issues mechanical circulatory-support guidance for referring docs. Medscape Medical News.
November 1, 2012;Accessed November 13, 2012. Available at http://www.medscape.com/viewarticle
/773806.
151. Peura JL, Colvin-Adams M, Francis GS, et al, on behalf of the American Heart Association Heart Failure and
Transplantation Committee of the Council on Clinical Cardiology, Council on Cardiopulmonary, et al.
Recommendations for the Use of Mechanical Circulatory Support: Device Strategies and Patient Selection: A
Scientific Statement From the American Heart Association. Circulation. Oct 29 2012;[Medline].
152. [Best Evidence] Levy WC, Lee KL, Hellkamp AS, Poole JE, Mozaffarian D, Linker DT, et al. Maximizing
survival benefit with primary prevention implantable cardioverter-defibrillator therapy in a heart failure
population. Circulation. Sep 8 2009;120(10):835-42. [Medline].
153. Rosanio S, Schwarz ER, Ahmad M, Jammula P, Vitarelli A, Uretsky BF, et al. Benefits, unresolved questions,
and technical issues of cardiac resynchronization therapy for heart failure. Am J Cardiol. Sep 1
2005;96(5):710-7. [Medline].
154. Tang AS, Wells GA, Talajic M, Arnold MO, Sheldon R, Connolly S, et al. Cardiac-resynchronization therapy for
mild-to-moderate heart failure. N Engl J Med. Dec 16 2010;363(25):2385-95. [Medline].
155. Giraldi F, Cattadori G, Roberto M, et al. Long-term effectiveness of cardiac resynchronization therapy in heart
failure patients with unfavorable cardiac veins anatomy comparison of surgical versus hemodynamic
procedure. J Am Coll Cardiol. Jul 26 2011;58(5):483-90. [Medline].
156. Abraham WT, Fisher WG, Smith AL, Delurgio DB, Leon AR, Loh E, et al. Cardiac resynchronization in chronic
heart failure. N Engl J Med. Jun 13 2002;346(24):1845-53. [Medline].
157. Moss AJ, Hall WJ, Cannom DS, Klein H, Brown MW, Daubert JP, et al. Cardiac-resynchronization therapy for
the prevention of heart-failure events. N Engl J Med. Oct 1 2009;361(14):1329-38. [Medline].
158. Arshad A, Moss AJ, Foster E, Padeletti L, Barsheshet A, Goldenberg I, et al. Cardiac resynchronization
therapy is more effective in women than in men: the MADIT-CRT (Multicenter Automatic Defibrillator
Implantation Trial with Cardiac Resynchronization Therapy) trial. J Am Coll Cardiol. Feb 15
2011;57(7):813-20. [Medline].
159. Cleland JG, Daubert JC, Erdmann E, Freemantle N, Gras D, Kappenberger L, et al. The effect of cardiac
resynchronization on morbidity and mortality in heart failure. N Engl J Med. Apr 14 2005;352(15):1539-49.
[Medline].
160. Bristow MR, Saxon LA, Boehmer J, Krueger S, Kass DA, De Marco T, et al. Cardiac-resynchronization
therapy with or without an implantable defibrillator in advanced chronic heart failure. N Engl J Med. May 20
2004;350(21):2140-50. [Medline].
161. Caracciolo EA, Davis KB, Sopko G, Kaiser GC, Corley SD, Schaff H, et al. Comparison of surgical and
medical group survival in patients with left main equivalent coronary artery disease. Long-term CASS
experience. Circulation. May 1 1995;91(9):2335-44. [Medline].
162. Eleven-year survival in the Veterans Administration randomized trial of coronary bypass surgery for stable
angina. The Veterans Administration Coronary Artery Bypass Surgery Cooperative Study Group. N Engl J
Med. Nov 22 1984;311(21):1333-9. [Medline].
163. Robinson TN, Morrell TD, Pomerantz BJ, Heimbach JK, Cairns CB, Harken AH. Therapeutically accessible
clinical cardiac states. J Am Coll Surg. Oct 2000;191(4):452-63. [Medline].
164. Senior R, Lahiri A, Kaul S. Effect of revascularization on left ventricular remodeling in patients with heart
failure from severe chronic ischemic left ventricular dysfunction. Am J Cardiol. Sep 15 2001;88(6):624-9.
[Medline].
165. Velazquez EJ, Lee KL, Deja MA, Jain A, Sopko G, Marchenko A, et al. Coronary-Artery Bypass Surgery in
Patients with Left Ventricular Dysfunction. N Engl J Med. Apr 4 2011;[Medline]. [Full Text].
166. Elefteriades JA, Morales DL, Gradel C, Tollis G Jr, Levi E, Zaret BL. Results of coronary artery bypass
grafting by a single surgeon in patients with left ventricular ejection fractions < or = 30%. Am J Cardiol. Jun
15 1997;79(12):1573-8. [Medline].
167. Kron IL, Flanagan TL, Blackbourne LH, Schroeder RA, Nolan SP. Coronary revascularization rather than
cardiac transplantation for chronic ischemic cardiomyopathy. Ann Surg. Sep 1989;210(3):348-52; discussion
14/04/2013 15:17
Heart Failure
24 of 27
352-4. [Medline]. [Full Text].

168. Doenst T, Velazquez EJ, Beyersdorf F, Michler R, Menicanti L, Di Donato M, et al. To STICH or not to STICH:
we know the answer, but do we understand the question?. J Thorac Cardiovasc Surg. Feb
2005;129(2):246-9. [Medline].
169. Joyce D, Loebe M, Noon GP, McRee S, Southard R, Thompson L, et al. Revascularization and ventricular
restoration in patients with ischemic heart failure: the STICH trial. Curr Opin Cardiol. Nov 2003;18(6):454-7.
[Medline].
170. Sharoni E, Song HK, Peterson RJ, Guyton RA, Puskas JD. Off pump coronary artery bypass surgery for
significant left ventricular dysfunction: safety, feasibility, and trends in methodology over time--an early
experience. Heart. Apr 2006;92(4):499-502. [Medline]. [Full Text].
171. Calafiore AM, Di Giammarco G, Teodori G, Di Mauro M, Iac AL, Bivona A, et al. Late results of first
myocardial revascularization in multiple vessel disease: single versus bilateral internal mammary artery with or
without saphenous vein grafts. Eur J Cardiothorac Surg. Sep 2004;26(3):542-8. [Medline].
172. Nishimura RA, Grantham JA, Connolly HM, Schaff HV, Higano ST, Holmes DR Jr. Low-output, low-gradient
aortic stenosis in patients with depressed left ventricular systolic function: the clinical utility of the dobutamine
challenge in the catheterization laboratory. Circulation. Aug 13 2002;106(7):809-13. [Medline].
173. Carabello BA. Clinical practice. Aortic stenosis. N Engl J Med. Feb 28 2002;346(9):677-82. [Medline].
174. Lindblom D, Lindblom U, Qvist J, Lundstrm H. Long-term relative survival rates after heart valve
replacement. J Am Coll Cardiol. Mar 1 1990;15(3):566-73. [Medline].
175. Connolly HM, Oh JK, Schaff HV, Roger VL, Osborn SL, Hodge DO, et al. Severe aortic stenosis with low
transvalvular gradient and severe left ventricular dysfunction:result of aortic valve replacement in 52 patients.
Circulation. Apr 25 2000;101(16):1940-6. [Medline].
176. deFilippi CR, Willett DL, Brickner ME, Appleton CP, Yancy CW, Eichhorn EJ, et al. Usefulness of dobutamine
echocardiography in distinguishing severe from nonsevere valvular aortic stenosis in patients with depressed
left ventricular function and low transvalvular gradients. Am J Cardiol. Jan 15 1995;75(2):191-4. [Medline].
177. Vaquette B, Corbineau H, Laurent M, Lelong B, Langanay T, de Place C, et al. Valve replacement in patients
with critical aortic stenosis and depressed left ventricular function: predictors of operative risk, left ventricular
function recovery, and long term outcome. Heart. Oct 2005;91(10):1324-9. [Medline]. [Full Text].
178. Dujardin KS, Enriquez-Sarano M, Schaff HV, Bailey KR, Seward JB, Tajik AJ. Mortality and morbidity of aortic
regurgitation in clinical practice. A long-term follow-up study. Circulation. Apr 13 1999;99(14):1851-7.
[Medline].
179. Chaliki HP, Mohty D, Avierinos JF, Scott CG, Schaff HV, Tajik AJ, et al. Outcomes after aortic valve
replacement in patients with severe aortic regurgitation and markedly reduced left ventricular function.
Circulation. Nov 19 2002;106(21):2687-93. [Medline].
180. Enriquez-Sarano M, Tajik AJ. Clinical practice. Aortic regurgitation. N Engl J Med. Oct 7
2004;351(15):1539-46. [Medline].
181. Lancellotti P, Grard PL, Pirard LA. Long-term outcome of patients with heart failure and dynamic functional
mitral regurgitation. Eur Heart J. Aug 2005;26(15):1528-32. [Medline].
182. Patel JB, Borgeson DD, Barnes ME, Rihal CS, Daly RC, Redfield MM. Mitral regurgitation in patients with
advanced systolic heart failure. J Card Fail. Aug 2004;10(4):285-91. [Medline].
183. Bolling SF, Pagani FD, Deeb GM, Bach DS. Intermediate-term outcome of mitral reconstruction in
cardiomyopathy. J Thorac Cardiovasc Surg. Feb 1998;115(2):381-6; discussion 387-8. [Medline].
184. Akasaka T, Yoshida K, Hozumi T, Takagi T, Kaji S, Kawamoto T, et al. Restricted coronary flow reserve in
patients with mitral regurgitation improves after mitral reconstructive surgery. J Am Coll Cardiol. Dec
1998;32(7):1923-30. [Medline].
185. Wu AH, Aaronson KD, Bolling SF, Pagani FD, Welch K, Koelling TM. Impact of mitral valve annuloplasty on
mortality risk in patients with mitral regurgitation and left ventricular systolic dysfunction. J Am Coll Cardiol.
Feb 1 2005;45(3):381-7. [Medline].
186. McGee EC, Gillinov AM, Blackstone EH, Rajeswaran J, Cohen G, Najam F, et al. Recurrent mitral
regurgitation after annuloplasty for functional ischemic mitral regurgitation. J Thorac Cardiovasc Surg. Dec
2004;128(6):916-24. [Medline].
14/04/2013 15:17
Heart Failure
25 of 27
187. Srichai MB, Grimm RA, Stillman AE, Gillinov AM, Rodriguez LL, Lieber ML, et al. Ischemic mitral regurgitation:
impact of the left ventricle and mitral valve in patients with left ventricular systolic dysfunction. Ann Thorac
Surg. Jul 2005;80(1):170-8. [Medline].
188. Morishita A, Shimakura T, Nonoyama M, Takasaki T. Mitral valve replacement in ischemic mitral regurgitation.
Preservation of both anterior and posterior mitral leaflets. J Cardiovasc Surg (Torino). Apr
2002;43(2):147-52. [Medline].
189. Yun KL, Sintek CF, Miller DC, Pfeffer TA, Kochamba GS, Khonsari S, et al. Randomized trial comparing
partial versus complete chordal-sparing mitral valve replacement: effects on left ventricular volume and
function. J Thorac Cardiovasc Surg. Apr 2002;123(4):707-14. [Medline].
190. Gillinov AM, Wierup PN, Blackstone EH, Bishay ES, Cosgrove DM, White J, et al. Is repair preferable to
replacement for ischemic mitral regurgitation?. J Thorac Cardiovasc Surg. Dec 2001;122(6):1125-41.
[Medline].
191. Miller DC. Ischemic mitral regurgitation redux--to repair or to replace?. J Thorac Cardiovasc Surg. Dec
2001;122(6):1059-62. [Medline].
192. Feldman T, Kar S, Rinaldi M, Fail P, Hermiller J, Smalling R, et al. Percutaneous mitral repair with the MitraClip
system: safety and midterm durability in the initial EVEREST (Endovascular Valve Edge-to-Edge REpair
Study) cohort. J Am Coll Cardiol. Aug 18 2009;54(8):686-94. [Medline].
193. Buckberg GD. Ventricular restoration--a surgical approach to reverse ventricular remodeling. Heart Fail Rev.
Oct 2004;9(4):233-9; discussion 347-51. [Medline].
194. Yamaguchi A, Ino T, Adachi H, Murata S, Kamio H, Okada M, et al. Left ventricular volume predicts
postoperative course in patients with ischemic cardiomyopathy. Ann Thorac Surg. Feb 1998;65(2):434-8.
[Medline].
195. Mickleborough LL, Carson S, Ivanov J. Repair of dyskinetic or akinetic left ventricular aneurysm: results
obtained with a modified linear closure. J Thorac Cardiovasc Surg. Apr 2001;121(4):675-82. [Medline].
196. Ott DA, Parravacini R, Cooley DA, DePuey EG, Reul GJ, Duncan JM, et al. Improved cardiac function
following left ventricular aneurysm resection: pre- and postoperative performance studies in 150 patients. Tex
Heart Inst J. Sep 1982;9(3):267-73. [Medline]. [Full Text].
197. Athanasuleas CL, Buckberg GD, Stanley AW, Siler W, Dor V, Di Donato M, et al. Surgical ventricular
restoration in the treatment of congestive heart failure due to post-infarction ventricular dilation. J Am Coll
Cardiol. Oct 6 2004;44(7):1439-45. [Medline].
198. Jones RH, Velazquez EJ, Michler RE, et al. Coronary bypass surgery with or without surgical ventricular
reconstruction. N Engl J Med. Apr 23 2009;360(17):1705-17. [Medline]. [Full Text].
199. Timms D. A review of clinical ventricular assist devices. Med Eng Phys. Jun 10 2011;[Medline].
200. Pamboukian SV, Tallaj JA, Brown RN, Holman WL, Blood M, George JF, et al. Improvement in 2-year survival
for ventricular assist device patients after implementation of an intensive surveillance protocol. J Heart Lung
Transplant. Aug 2011;30(8):879-87. [Medline].
201. Lietz K, Long JW, Kfoury AG, Slaughter MS, Silver MA, Milano CA, et al. Outcomes of left ventricular assist
device implantation as destination therapy in the post-REMATCH era: implications for patient selection.
Circulation. Jul 31 2007;116(5):497-505. [Medline].
202. Daneshmand MA, Rajagopal K, Lima B, Khorram N, Blue LJ, Lodge AJ, et al. Left ventricular assist device
destination therapy versus extended criteria cardiac transplant. Ann Thorac Surg. Apr 2010;89(4):1205-9;
discussion 1210. [Medline].
203. Rose EA, Gelijns AC, Moskowitz AJ, Heitjan DF, Stevenson LW, Dembitsky W, et al. Long-term use of a left
ventricular assist device for end-stage heart failure. N Engl J Med. Nov 15 2001;345(20):1435-43. [Medline].
204. Park SJ, Tector A, Piccioni W, Raines E, Gelijns A, Moskowitz A, et al. Left ventricular assist devices as
destination therapy: a new look at survival. J Thorac Cardiovasc Surg. Jan 2005;129(1):9-17. [Medline].
205. Starling RC, Naka Y, Boyle AJ, Gonzalez-Stawinski G, John R, Jorde U, et al. Results of the post-U.S. Food
and Drug Administration-approval study with a continuous flow left ventricular assist device as a bridge to
heart transplantation: a prospective study using the INTERMACS (Interagency Registry for Mechanically
Assisted Circulatory Support). J Am Coll Cardiol. May 10 2011;57(19):1890-8. [Medline].
206. Ventura PA, Alharethi R, Budge D, Reid BB, Horne BD, Mason NO, et al. Differential impact on
14/04/2013 15:17
Heart Failure
26 of 27
post-transplant outcomes between pulsatile- and continuous-flow left ventricular assist devices. Clin
Transplant. Jul 2011;25(4):E390-5. [Medline].
207. Slaughter MS, Pagani FD, et al, for the HeartMate II Clinical Investigators. Clinical management of
continuous-flow left ventricular assist devices in advanced heart failure. J Heart Lung Transplant. Apr
2010;29(4 suppl):S1-39. [Medline].
208. Kirklin JK, Naftel DC, Kormos RL, et al. Third INTERMACS Annual Report: the evolution of destination
therapy in the United States. J Heart Lung Transplant. Feb 2011;30(2):115-23. [Medline].
209. Taylor DO, Edwards LB, Boucek MM, Trulock EP, Deng MC, Keck BM, et al. Registry of the International
Society for Heart and Lung Transplantation: twenty-second official adult heart transplant report--2005. J Heart
Lung Transplant. Aug 2005;24(8):945-55. [Medline].
210. Boucek MM, Edwards LB, Keck BM, Trulock EP, Taylor DO, Hertz MI. Registry of the International Society for
Heart and Lung Transplantation: eighth official pediatric report--2005. J Heart Lung Transplant. Aug
2005;24(8):968-82. [Medline].
211. Stevenson LW, Kormos RL, Bourge RC, Gelijns A, Griffith BP, Hershberger RE, et al. Mechanical cardiac
support 2000: current applications and future trial design. June 15-16, 2000 Bethesda, Maryland. J Am Coll
Cardiol. Jan 2001;37(1):340-70. [Medline].
212. Gray NA Jr, Selzman CH. Current status of the total artificial heart. Am Heart J. Jul 2006;152(1):4-10.
[Medline].
213. Cooley DA, Liotta D, Hallman GL, Bloodwell RD, Leachman RD, Milam JD. Orthotopic cardiac prosthesis for
two-staged cardiac replacement. Am J Cardiol. Nov 1969;24(5):723-30. [Medline].
214. Platis A, Larson DF. CardioWest temporary total artificial heart. Perfusion. Sep 2009;24(5):341-6. [Medline].
215. Roussel JC, Snage T, Baron O, Prigaud C, Habash O, Rigal JC, et al. CardioWest (Jarvik) total artificial
heart: a single-center experience with 42 patients. Ann Thorac Surg. Jan 2009;87(1):124-9; discussion 130.
[Medline].
216. Anderson E, Jaroszewski D, Pierce C, DeValeria P, Arabia F. Parallel application of extracorporeal membrane
oxygenation and the CardioWest total artificial heart as a bridge to transplant. Ann Thorac Surg. Nov
2009;88(5):1676-8. [Medline].
217. Morris RJ. Total artificial heart--concepts and clinical use. Semin Thorac Cardiovasc Surg. Fall
2008;20(3):247-54. [Medline].
218. Meyer A, Slaughter M. The total artificial heart. Panminerva Med. Sep 2011;53(3):141-54. [Medline].
219. Anand IS, Carson P, Galle E, Song R, Boehmer J, Ghali JK, et al. Cardiac resynchronization therapy reduces
the risk of hospitalizations in patients with advanced heart failure: results from the Comparison of Medical
Therapy, Pacing and Defibrillation in Heart Failure (COMPANION) trial. Circulation. Feb 24
2009;119(7):969-77. [Medline].
220. [Guideline] Bangalore S, Kumar S, Messerli FH. When conventional heart failure therapy is not enough:
angiotensin receptor blocker, direct renin inhibitor, or aldosterone antagonist?. Congest Heart Fail. Dec 12
2012;[Medline].
221. Libby, Bonow, Mann, Zipes. Braunwald's Heart Disease a Textbook of Cardiovascular Medicine. 8th edition.
2008:509-727.
222. Cleland JG, Teerlink JR, Senior R, Nifontov EM, Mc Murray JJ, Lang CC, et al. The effects of the cardiac
myosin activator, omecamtiv mecarbil, on cardiac function in systolic heart failure: a double-blind, placebocontrolled, crossover, dose-ranging phase 2 trial. Lancet. Aug 20 2011;378(9792):676-83. [Medline].
223. DeBakey ME. Development of mechanical heart devices. Ann Thorac Surg. Jun 2005;79(6):S2228-31.
[Medline].
224. [Guideline] DiDomenico RJ, Park HY, Southworth MR, Eyrich HM, Lewis RK, Finley JM, et al. Guidelines for
acute decompensated heart failure treatment. Ann Pharmacother. Apr 2004;38(4):649-60. [Medline].
225. Eklind-Cervenka M, Benson L, Dahlstrm U, Edner M, Rosenqvist M, Lund LH. Association of candesartan vs
losartan with all-cause mortality in patients with heart failure. JAMA. Jan 12 2011;305(2):175-82. [Medline].
226. [Guideline] Feldman D, Pamboukian SV, Teuteberg JJ, et al. The 2013 International Society for Heart and
Lung Transplantation Guidelines for Mechanical Circulatory Support: Executive Summary. J Heart Lung
14/04/2013 15:17
Heart Failure
27 of 27
Transplant. 2013;32:157-187.
227. Fumoto H, Horvath DJ, Rao S, Massiello AL, Horai T, Takaseya T, et al. In vivo acute performance of the
Cleveland Clinic self-regulating, continuous-flow total artificial heart. J Heart Lung Transplant. Jan
2010;29(1):21-6. [Medline]. [Full Text].
228. Jarcho JA. Biventricular pacing. N Engl J Med. Jul 20 2006;355(3):288-94. [Medline].
229. Jennings DL, Chambers RM, Schillig JM. The pharmacotherapy of the HeartMate II, a continuous flow left
ventricular assist device, in patients with advanced heart failure: integration of disease, device, and drug. Ann
Pharmacother. Oct 2010;44(10):1647-50. [Medline].
230. Stiles S. Doubling down on RAAS blockade in HF? Aldosterone antagonists, not ARBs, says meta-analysis.
Medscape [serial online]. Dec 26 2012;Accessed Jan 9 2013. Available at http://www.medscape.com
/viewarticle/776725.
231. Stiles S. A Walk Through Long-Term Mechanical Circulatory Support: New ISHLT Guidelines. Available at
http://www.medscape.com/viewarticle/777744. Accessed January 23, 2013.
232. Topilsky Y, Oh JK, Atchison FW, Shah DK, Bichara VM, Schirger JA, et al. Echocardiographic findings in
stable outpatients with properly functioning HeartMate II left ventricular assist devices. J Am Soc
Echocardiogr. Feb 2011;24(2):157-69. [Medline].
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Heart Failure

Signs and symptoms

restriction, physical activity as appropriate, and attention to weight gain

heart failure ensue.[8, 9, 10, 11, 12]

Myocytes and myocardial remodeling

Systolic and diastolic failure

ANP and BNP

Other vasoactive systems

Heart failure with normal ejection fraction

Precipitating causes of heart failure

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Division of Cardiology, Veterans Affairs Medical Center

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function in patients referred for echocardiography. Am Heart J. 2001;141:374-9.

352-4. [Medline]. [Full Text].

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