Heart Failure-Medscpe

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emedicine.medscape.com
Heart Failure
Updated: May 07, 2018
Author: Ioana Dumitru, MD; Chief Editor: Gyanendra K Sharma, MD, FACC, FASE
Overview
Practice Essentials
Heart failure develops when the heart, via an abnormality of cardiac function (detectable or not), fails to pump blood at a rate
commensurate with the requirements of the metabolizing tissues or is able to do so only with an elevated diastolic filling
pressure. See the image below.
This chest radiograph shows an enlarged cardiac silhouette and edema at the lung bases, signs of acute heart failure.
Signs and symptoms

Signs and symptoms of heart failure include the following:
Exertional dyspnea and/or dyspnea at rest

Orthopnea
Acute pulmonary edema
Chest pain/pressure and palpitations
Tachycardia
Fatigue and weakness
Nocturia and oliguria
Anorexia, weight loss, nausea
Exophthalmos and/or visible pulsation of eyes
Distention of neck veins
Weak, rapid, and thready pulse
Rales, wheezing
S 3 gallop and/or pulsus alternans
Increased intensity of P 2 heart sound
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Hepatojugular reflux
Ascites, hepatomegaly, and/or anasarca
Central or peripheral cyanosis, pallor
See Presentation for more detail.
Diagnosis
Heart failure criteria, classification, and staging
The Framingham criteria for the diagnosis of heart failure consists of the concurrent presence of either two major criteria or one
major and two minor criteria.[1]
Major criteria comprise the following:
Paroxysmal nocturnal dyspnea

Weight loss of 4.5 kg in 5 days in response to treatment
Neck vein distention
Rales
S 3 gallop
Central venous pressure greater than 16 cm water
Circulation time of 25 seconds or longer
Radiographic cardiomegaly
Pulmonary edema, visceral congestion, or cardiomegaly at autopsy
Minor criteria (accepted only if they cannot be attributed to another medical condition) are as follows:
Nocturnal cough
Dyspnea on ordinary exertion
A decrease in vital capacity by one third the maximal value recorded
Pleural effusion
Tachycardia (rate of 120 bpm)
Hepatomegaly
Bilateral ankle edema
The New York Heart Association (NYHA) classification system categorizes heart failure on a scale of I to IV,[2] as follows:
Class I: No limitation of physical activity

Class II: Slight limitation of physical activity
Class III: Marked limitation of physical activity
Class IV: Symptoms occur even at rest; discomfort with any physical activity
The American College of Cardiology/American Heart Association (ACC/AHA) staging system is defined by the following four
stages[3] :
Stage A: High risk of heart failure but no structural heart disease or symptoms of heart failure
Stage B: Structural heart disease but no symptoms of heart failure
Stage C: Structural heart disease and symptoms of heart failure
Stage D: Refractory heart failure requiring specialized interventions
Testing
The following tests may be useful in the initial evaluation for suspected heart failure[3, 4, 5] :
Complete blood count (CBC)

Iron studies
Urinalysis
Electrolyte levels
Renal and liver function studies
Fasting blood glucose levels
Lipid profile
Thyroid stimulating hormone (TSH) levels
B-type natriuretic peptide levels
N-terminal pro-B-type natriuretic peptide levels
Electrocardiography
Chest radiography
Two-dimensional (2-D) echocardiography
Nuclear imaging [6]
Maximal exercise testing
Pulse oximetry or arterial blood gas
See Workup for more detail.
Management
Treatment includes the following:
Nonpharmacologic therapy: Oxygen and noninvasive positive pressure ventilation, dietary sodium and fluid restriction,
physical activity as appropriate, and attention to weight gain
Pharmacotherapy: Diuretics, vasodilators, inotropic agents, anticoagulants, beta blockers, and digoxin
Surgical options
Surgical treatment options include the following:
Electrophysiologic intervention
Revascularization procedures
Valve replacement/repair
Ventricular restoration
Extracorporeal membrane oxygenation
Ventricular assist devices
Heart transplantation
Total artificial heart
See Treatment and Medication for more detail.
Background
Heart failure is the pathophysiologic state in which the heart, via an abnormality of cardiac function (detectable or not), fails to
pump blood at a rate commensurate with the requirements of the metabolizing tissues or is able to do so only with an elevated
diastolic filling pressure.
Heart failure (see the images below) may be caused by myocardial failure but may also occur in the presence of near-normal
cardiac function under conditions of high demand. Heart failure always causes circulatory failure, but the converse is not
necessarily the case, because various noncardiac conditions (eg, hypovolemic shock, septic shock) can produce circulatory
failure in the presence of normal, modestly impaired, or even supranormal cardiac function. To maintain the pumping function of
the heart, compensatory mechanisms increase blood volume, cardiac filling pressure, heart rate, and cardiac muscle mass.
However, despite these mechanisms, there is a progressive decline in the ability of the heart to contract and relax, resulting in
worsening heart failure.
A 28-year-old woman presented with acute heart failure secondary to chronic hypertension. The enlarged cardiac silhouette
on this anteroposterior (AP) radiograph is caused by acute heart failure due to the effects of chronic high blood pressure on
the left ventricle. The heart then becomes enlarged, and fluid accumulates in the lungs (ie, pulmonary congestion).
Signs and symptoms of heart failure include tachycardia and manifestations of venous congestion (eg, edema) and low cardiac
output (eg, fatigue). Breathlessness is a cardinal symptom of left ventricular (LV) failure that may manifest with progressively
increasing severity.
Heart failure can be classified according to a variety of factors (see Heart Failure Criteria, Classification, and Staging). The New
York Heart Association (NYHA) classification for heart failure comprises four classes, based on the relationship between
symptoms and the amount of effort required to provoke them, as follows[2] :
Class I patients have no limitation of physical activity

Class II patients have slight limitation of physical activity
Class III patients have marked limitation of physical activity
Class IV patients have symptoms even at rest and are unable to carry on any physical activity without discomfort
The American College of Cardiology/American Heart Association (ACC/AHA) heart failure guidelines complement the NYHA
classification to reflect the progression of disease and are divided into four stages, as follows[3] :
Stage A patients are at high risk for heart failure but have no structural heart disease or symptoms of heart failure
Stage B patients have structural heart disease but have no symptoms of heart failure
Stage C patients have structural heart disease and have symptoms of heart failure
Stage D patients have refractory heart failure requiring specialized interventions
Laboratory studies for heart failure should include a complete blood count (CBC), electrolyte levels, and hepatorenal function
studies. Imaging studies such as chest radiography and two-dimensional echocardiography are recommended in the initial
evaluation of patients with known or suspected heart failure. B-type natriuretic peptide (BNP) and N-terminal pro-B-type
natriuretic peptide (NT-proBNP) levels can be useful in differentiating cardiac and noncardiac causes of dyspnea. (See
Workup for more information.)
In acute heart failure, patient care consists of stabilizing the patient's clinical condition; establishing the diagnosis, etiology, and
precipitating factors; and initiating therapies to provide rapid symptom relief and survival benefit. Surgical options for heart
failure include revascularization procedures, electrophysiologic intervention, cardiac resynchronization therapy (CRT),
implantable cardioverter-defibrillators (ICDs), valve replacement or repair, ventricular restoration, heart transplantation, and
ventricular assist devices (VADs). (See Treatment for more information.)
The goals of pharmacotherapy are to increase survival and to prevent complications. Along with oxygen, medications assisting
with symptom relief include diuretics, digoxin, inotropes, and morphine. Drugs that can exacerbate heart failure should be
avoided (nonsteroidal anti-inflammatory drugs [NSAIDs], calcium channel blockers [CCBs], and most antiarrhythmic drugs).
(See Medication for more information.)
For further information, see the Medscape Drugs & Diseases articles Pediatric Congestive Heart Failure, Congestive Heart
Failure Imaging, Heart Transplantation, Pediatric Heart Transplantation, Coronary Artery Bypass Grafting, and Implantable
Cardioverter-Defibrillators.
Pathophysiology
The common pathophysiologic state that perpetuates the progression of heart failure is extremely complex, regardless of the
precipitating event. Compensatory mechanisms exist on every level of organization, from the subcellular all the way through to
organ-to-organ interactions. Only when this network of adaptations becomes overwhelmed does heart failure ensue.[7, 8, 9, 10,
11]
Adaptations
Most important among the adaptations are the following[12] :
The Frank-Starling mechanism, in which an increased preload helps to sustain cardiac performance
Alterations in myocyte regeneration and death
Myocardial hypertrophy with or without cardiac chamber dilatation, in which the mass of contractile tissue is augmented
Activation of neurohumoral systems
The release of norepinephrine by adrenergic cardiac nerves augments myocardial contractility and includes activation of the
renin-angiotensin-aldosterone system [RAAS], the sympathetic nervous system [SNS], and other neurohumoral adjustments
that act to maintain arterial pressure and perfusion of vital organs.
In acute heart failure, the finite adaptive mechanisms that may be adequate to maintain the overall contractile performance of
the heart at relatively normal levels become maladaptive when trying to sustain adequate cardiac performance.[13]
The primary myocardial response to chronic increased wall stress is myocyte hypertrophy, death/apoptosis, and regeneration.
[14] This process eventually leads to remodeling, usually the eccentric type. Eccentric remodeling further worsens the loading
conditions on the remaining myocytes and perpetuates the deleterious cycle. The idea of lowering wall stress to slow the
process of remodeling has long been exploited in treating heart failure patients.[15]
The reduction of cardiac output following myocardial injury sets into motion a cascade of hemodynamic and neurohormonal
derangements that provoke activation of neuroendocrine systems, most notably the above-mentioned adrenergic systems and
RAAS.[16]
The release of epinephrine and norepinephrine, along with the vasoactive substances endothelin-1 (ET-1) and vasopressin,
causes vasoconstriction, which increases calcium afterload and, via an increase in cyclic adenosine monophosphate (cAMP),
causes an increase in cytosolic calcium entry. The increased calcium entry into the myocytes augments myocardial contractility
and impairs myocardial relaxation (lusitropy).
The calcium overload may induce arrhythmias and lead to sudden death. The increase in afterload and myocardial contractility
(known as inotropy) and the impairment in myocardial lusitropy lead to an increase in myocardial energy expenditure and a
further decrease in cardiac output. The increase in myocardial energy expenditure leads to myocardial cell death/apoptosis,
which results in heart failure and further reduction in cardiac output, perpetuating a cycle of further increased neurohumoral
stimulation and further adverse hemodynamic and myocardial responses.
In addition, the activation of the RAAS leads to salt and water retention, resulting in increased preload and further increases in
myocardial energy expenditure. Increases in renin, mediated by a decreased stretch of the glomerular afferent arteriole, reduce
delivery of chloride to the macula densa and increase beta1-adrenergic activity as a response to decreased cardiac output. This
results in an increase in angiotensin II (Ang II) levels and, in turn, aldosterone levels, causing stimulation of the release of
aldosterone. Ang II, along with ET-1, is crucial in maintaining effective intravascular homeostasis as mediated by
vasoconstriction and aldosterone-induced salt and water retention.
The concept of the heart as a self-renewing organ is a relatively recent development.[17] This paradigm for myocyte biology
created an entire field of research aimed directly at augmenting myocardial regeneration. The rate of myocyte turnover has been
shown to increase during times of pathologic stress.[14] In heart failure, this mechanism for replacement becomes overwhelmed
by an even faster increase in the rate of myocyte loss. This imbalance of hypertrophy and death over regeneration is the final
common pathway at the cellular level for the progression of remodeling and heart failure.
Angiotensin II
Research indicates that local cardiac Ang II production (which decreases lusitropy, increases inotropy, and increases afterload)
leads to increased myocardial energy expenditure. Ang II has also been shown in vitro and in vivo to increase the rate of
myocyte apoptosis.[18] In this fashion, Ang II has similar actions to norepinephrine in heart failure.
Ang II also mediates myocardial cellular hypertrophy and may promote progressive loss of myocardial function. The
neurohumoral factors above lead to myocyte hypertrophy and interstitial fibrosis, resulting in increased myocardial volume and
increased myocardial mass, as well as myocyte loss. As a result, the cardiac architecture changes which, in turn, leads to
further increase in myocardial volume and mass.
Myocytes and myocardial remodeling
In the failing heart, increased myocardial volume is characterized by larger myocytes approaching the end of their life cycle.[19]
As more myocytes drop out, an increased load is placed on the remaining myocardium, and this unfavorable environment is
transmitted to the progenitor cells responsible for replacing lost myocytes.
Progenitor cells become progressively less effective as the underlying pathologic process worsens and myocardial failure
accelerates. These features—namely, the increased myocardial volume and mass, along with a net loss of myocytes—are the
hallmark of myocardial remodeling. This remodeling process leads to early adaptive mechanisms, such as augmentation of
stroke volume (Frank-Starling mechanism) and decreased wall stress (Laplace law) and, later, to maladaptive mechanisms such
as increased myocardial oxygen demand, myocardial ischemia, impaired contractility, and arrhythmogenesis.
As heart failure advances, there is a relative decline in the counterregulatory effects of endogenous vasodilators, including nitric
oxide (NO), prostaglandins (PGs), bradykinin (BK), atrial natriuretic peptide (ANP), and B-type natriuretic peptide (BNP). This
decline occurs simultaneously with the increase in vasoconstrictor substances from the RAAS and the adrenergic system, which
fosters further increases in vasoconstriction and thus preload and afterload. This results in cellular proliferation, adverse
myocardial remodeling, and antinatriuresis, with total body fluid excess and worsening of heart failure symptoms.
Systolic and diastolic failure
Systolic and diastolic heart failure each result in a decrease in stroke volume.[20, 21] This leads to activation of peripheral and
central baroreflexes and chemoreflexes that are capable of eliciting marked increases in sympathetic nerve traffic.
Although there are commonalities in the neurohormonal responses to decreased stroke volume, the neurohormone-mediated
events that follow have been most clearly elucidated for individuals with systolic heart failure. The ensuing elevation in plasma
norepinephrine directly correlates with the degree of cardiac dysfunction and has significant prognostic implications.
Norepinephrine, while directly toxic to cardiac myocytes, is also responsible for a variety of signal-transduction abnormalities,
such as downregulation of beta1-adrenergic receptors, uncoupling of beta2-adrenergic receptors, and increased activity of
inhibitory G-protein. Changes in beta1-adrenergic receptors result in overexpression and promote myocardial hypertrophy.
Atrial natriuretic peptide and B-type natriuretic peptide
ANP and BNP are endogenously generated peptides activated in response to atrial and ventricular volume/pressure expansion.
ANP and BNP are released from the atria and ventricles, respectively, and both promote vasodilation and natriuresis. Their
hemodynamic effects are mediated by decreases in ventricular filling pressures, owing to reductions in cardiac preload and
afterload. BNP, in particular, produces selective afferent arteriolar vasodilation and inhibits sodium reabsorption in the proximal
convoluted tubule. It also inhibits renin and aldosterone release and, therefore, adrenergic activation. ANP and BNP are
elevated in chronic heart failure. BNP especially has potentially important diagnostic, therapeutic, and prognostic implications.
For more information, see the Medscape Drugs & Diseases article Natriuretic Peptides in Congestive Heart Failure.
Other vasoactive systems
Other vasoactive systems that play a role in the pathogenesis of heart failure include the ET receptor system, the adenosine
receptor system, vasopressin, and tumor necrosis factor-alpha (TNF-alpha).[22] ET, a substance produced by the vascular
endothelium, may contribute to the regulation of myocardial function, vascular tone, and peripheral resistance in heart failure.
Elevated levels of ET-1 closely correlate with the severity of heart failure. ET-1 is a potent vasoconstrictor and has exaggerated
vasoconstrictor effects in the renal vasculature, reducing renal plasma blood flow, glomerular filtration rate (GFR), and sodium
excretion.
TNF-alpha has been implicated in response to various infectious and inflammatory conditions. Elevations in TNF-alpha levels
have been consistently observed in heart failure and seem to correlate with the degree of myocardial dysfunction. Some studies
suggest that local production of TNF-alpha may have toxic effects on the myocardium, thus worsening myocardial systolic and
diastolic function.
In individuals with systolic dysfunction, therefore, the neurohormonal responses to decreased stroke volume result in temporary
improvement in systolic blood pressure and tissue perfusion. However, in all circumstances, the existing data support the notion
that these neurohormonal responses contribute to the progression of myocardial dysfunction in the long term.
Heart failure with preserved ejection fraction
In diastolic heart failure (heart failure with preserved ejection fraction [HFpEF]), the same pathophysiologic processes occur that
lead to decreased cardiac output in systolic heart failure, but they do so in response to a different set of hemodynamic and
circulatory environmental factors that depress cardiac output.[23]
In HFpEF, altered relaxation and increased stiffness of the ventricle (due to delayed calcium uptake by the myocyte
sarcoplasmic reticulum and delayed calcium efflux from the myocyte) occur in response to an increase in ventricular afterload
(pressure overload). The impaired relaxation of the ventricle then leads to impaired diastolic filling of the left ventricle (LV).
Morris et al found that right venticular (RV) subendocardial systolic dysfunction and diastolic dysfunction, as detected by
echocardiographic strain rate imaging, are common in patients with HFpEF. This dysfunction is potentially associated with the
same fibrotic processes that affect the subendocardial layer of the LV and, to a lesser extent, with RV pressure overload. It may
play a role in the symptomatology of patients with HFpEF.[24]
LV chamber stiffness
An increase in LV chamber stiffness occurs secondary to any one, or any combination, of the following three mechanisms:
Rise in filling pressure

Shift to a steeper ventricular pressure-volume curve
Decrease in ventricular distensibility
A rise in filling pressure is the movement of the ventricle up along its pressure-volume curve to a steeper portion, as may occur
in conditions such as volume overload secondary to acute valvular regurgitation or acute LV failure due to myocarditis.
A shift to a steeper ventricular pressure-volume curve results, most commonly, not only from increased ventricular mass and
wall thickness (as observed in aortic stenosis and long-standing hypertension) but also from infiltrative disorders (eg,
amyloidosis), endomyocardial fibrosis, and myocardial ischemia.
Parallel upward displacement of the diastolic pressure-volume curve is generally referred to as a decrease in ventricular
distensibility. This is usually caused by extrinsic compression of the ventricles.
Concentric LV hypertrophy
Pressure overload that leads to concentric LV hypertrophy (LVH), as occurs in aortic stenosis, hypertension, and hypertrophic
cardiomyopathy, shifts the diastolic pressure-volume curve to the left along its volume axis. As a result, ventricular diastolic
pressure is abnormally elevated, although chamber stiffness may or may not be altered.
Increases in diastolic pressure lead to an increased myocardial energy expenditure, remodeling of the ventricle, increased
myocardial oxygen demand, myocardial ischemia, and eventual progression of the maladaptive mechanisms of the heart that
lead to decompensated heart failure.
Arrhythmias
Although life-threatening rhythms are more common in ischemic cardiomyopathy, arrhythmia imparts a significant burden in all
forms of heart failure. In fact, some arrhythmias even perpetuate heart failure. The most significant of all rhythms associated
with heart failure are the life-threatening ventricular arrhythmias. Structural substrates for ventricular arrhythmias that are
common in heart failure, regardless of the underlying cause, include ventricular dilatatation, myocardial hypertrophy, and
myocardial fibrosis.
At the cellular level, myocytes may be exposed to increased stretch, wall tension, catecholamines, ischemia, and electrolyte
imbalance. The combination of these factors contributes to an increased incidence of arrhythmogenic sudden cardiac death in
patients with heart failure.
Etiology
Most patients who present with significant heart failure do so because of an inability to provide adequate cardiac output in that
scenario. This is often a combination of the causes listed below in the setting of an abnormal myocardium. The list of causes
responsible for presentation of a patient with heart failure exacerbation is very long, and searching for the proximate cause to
optimize therapeutic interventions is important.
From a clinical standpoint, classifying the causes of heart failure into the following four broad categories is useful:
Underlying causes: Underlying causes of heart failure include structural abnormalities (congenital or acquired) that affect
the peripheral and coronary arterial circulation, pericardium, myocardium, or cardiac valves, thus leading to increased
hemodynamic burden or myocardial or coronary insufficiency
Fundamental causes: Fundamental causes include biochemical and physiologic mechanisms, through which either an
increased hemodynamic burden or a reduction in oxygen delivery to the myocardium results in impairment of myocardial
contraction
Precipitating causes: Overt heart failure may be precipitated by progression of the underlying heart disease (eg, further
narrowing of a stenotic aortic valve or mitral valve) or various conditions (fever, anemia, infection) or medications
(chemotherapy, nonsteroidal anti-inflammatory drugs [NSAIDs]) that alter the homeostasis of heart failure patients
Genetics of cardiomyopathy: Dilated, arrhythmic right ventricular and restrictive cardiomyopathies are known genetic
causes of heart failure
Underlying causes
Specific underlying factors cause various forms of heart failure, such as systolic heart failure (most commonly, left vetricular [LV]
systolic dysfunction), heart failure with preserved LV ejection fraction (LVEF), acute heart failure, high-output heart failure, and
right heart failure.
Underlying causes of systolic heart failure include the following:
Coronary artery disease

Diabetes mellitus
Hypertension
Valvular heart disease (stenosis or regurgitant lesions)
Arrhythmia (supraventricular or ventricular)
Infections and inflammation (myocarditis)
Peripartum cardiomyopathy
Congenital heart disease
Drugs (either recreational, such as alcohol and cocaine, or therapeutic drugs with cardiac side effects, such as
doxorubicin)
Idiopathic cardiomyopathy
Rare conditions (endocrine abnormalities, rheumatologic disease, neuromuscular conditions)
Underlying causes of diastolic heart failure include the following:

Diabetes mellitus
Hypertension
Valvular heart disease (aortic stenosis)
Hypertrophic cardiomyopathy
Restrictive cardiomyopathy (amyloidosis, sarcoidosis)
Constrictive pericarditis
Underlying causes of acute heart failure include the following:
Acute valvular (mitral or aortic) regurgitation

Myocardial infarction (MI)
Myocarditis
Arrhythmia
Drugs (eg, cocaine, calcium channel blockers, or beta-blocker overdose)
Sepsis
Underlying causes of high-output heart failure include the following:
Anemia
Systemic arteriovenous fistulas
Hyperthyroidism
Beriberi heart disease
Paget disease of bone
Albright syndrome (fibrous dysplasia)
Multiple myeloma
Pregnancy
Glomerulonephritis
Polycythemia vera
Carcinoid syndrome
Underlying causes of right heart failure include the following:
LV failure
Coronary artery disease (ischemia)
Pulmonary hypertension
Pulmonary valve stenosis
Pulmonary embolism
Chronic pulmonary disease
Neuromuscular disease
Precipitating causes of heart failure

A previously stable, compensated patient may develop heart failure that is clinically apparent for the first time when the intrinsic
process has advanced to a critical point, such as with further narrowing of a stenotic aortic valve or mitral valve. Alternatively,
decompensation may occur as a result of the failure or exhaustion of the compensatory mechanisms but without any change in
the load on the heart in patients with persistent, severe pressure or volume overload. In particular, consider whether the patient
has underlying coronary artery disease or valvular heart disease.
The most common cause of decompensation in a previously compensated patient with heart failure is inappropriate reduction in
the intensity of treatment, such as dietary sodium restriction, physical activity reduction, or drug regimen reduction. Uncontrolled
hypertension is the second most common cause of decompensation, followed closely by cardiac arrhythmias (most commonly,
atrial fibrillation). Arrhythmias, particularly ventricular arrhythmias, can be life threatening. Also, patients with one form of
underlying heart disease that may be well compensated can develop heart failure when a second form of heart disease ensues.
For example, a patient with chronic hypertension and asymptomatic LV hypertrophy (LVH) may be asymptomatic until an MI
develops and precipitates heart failure.
Systemic infection or the development of unrelated illness can also lead to heart failure. Systemic infection precipitates heart
failure by increasing total metabolism as a consequence of fever, discomfort, and cough, increasing the hemodynamic burden
on the heart. Septic shock, in particular, can precipitate heart failure by the release of endotoxin-induced factors that can
depress myocardial contractility.
Cardiac infection and inflammation can also endanger the heart. Myocarditis or infective endocarditis may directly impair
myocardial function and exacerbate existing heart disease. The anemia, fever, and tachycardia that frequently accompany these
processes are also deleterious. In the case of infective endocarditis, the additional valvular damage that ensues may precipitate
cardiac decompensation.
Patients with heart failure, particularly when confined to bed, are at high risk of developing pulmonary emboli, which can
increase the hemodynamic burden on the right ventricle (RV) by further elevating RV systolic pressure, possibly causing fever,
tachypnea, and tachycardia.
Intense, prolonged physical exertion or severe fatigue, such as may result from prolonged travel or emotional crisis, is a
relatively common precipitant of cardiac decompensation. The same is true of exposure to severe climate change (ie, the
individual comes in contact with a hot, humid environment or a bitterly cold one).
Excessive intake of water and/or salt and the administration of cardiac depressants or drugs that cause salt retention are other
factors that can lead to heart failure. At the European Society of Cardiology 2017 Congress, investigators presented a study
comprising more than 4630 people that indicated high daily salt intake (>13.7 g) is associated with a substantial increased risk
of developing heart failure, independent of other risk factors.[25, 26]
Because of increased myocardial oxygen consumption and demand beyond a critical level, the following high-output states can
precipitate the clinical presentation of heart failure:
Profound anemia
Thyrotoxicosis
Myxedema
Paget disease of bone
Albright syndrome
Multiple myeloma
Glomerulonephritis
Cor pulmonale
Polycythemia vera
Obesity
Carcinoid syndrome
Pregnancy
Nutritional deficiencies (eg, thiamine deficiency, beriberi)
Longitudinal data from the Framingham Heart Study has suggested that antecedent subclinical LV systolic or diastolic
dysfunction is associated with an increased incidence of heart failure, supporting the notion that heart failure is a progressive
syndrome.[27, 28] Another analysis of over 36,000 patients undergoing outpatient echocardiography reported that moderate or
severe diastolic dysfunction, but not mild diastolic dysfunction, is an independent predictor of mortality.[29]
Genetics of cardiomyopathy
Autosomal dominant inheritance has been demonstrated in dilated cardiomyopathy and in arrhythmic right ventricular
cardiomyopathy. Restrictive cardiomyopathies are usually sporadic and associated with the gene for cardiac troponin I. Genetic
tests are available at major genetic centers for cardiomyopathies.[30]
In families with a first-degree relative who has been diagnosed with a cardiomyopathy leading to heart failure, the at-risk patient
should be screened and followed.[30] The recommended screening consists of an electrocardiogram and an echocardiogram. If
the patient has an asymptomatic LV dysfunction, it should be documented and treated.[30]
Epidemiology
United States statistics
According to 2017 American Heart Association (AHA) data, heart failure affects an estimated 6.5 million Americans aged 20
years and older.[31] With improved survival of patients with acute myocardial infarction and with a population that continues to
age, heart failure will continue to increase in prominence as a major health problem in the United States. The AHA projects a
46% increase of heart failure prevalence from year 2012 to year 2030, resulting in 8 million or more Americans aged 18 years or
older with heart failure.[31]
Despite a more than decade-long decrease (2000-2012) in the the incidence of heart failure–related deaths in the United States,
such deaths are on the rise again, particularly among men and non-Hispanic black populations, according to 2000-2014 data
(the most recent data available) released by the Centers for Disease Control and Prevention (CDC) in December 2015.[32, 33]
The crude rate for heart failure-related deaths decreased from 103.1 deaths per 100,000 population in 2000 to 89.5 in 2009; it
then increased to 96.9 in 2014. The age-adjusted rate for heart failure-related deaths decreased from 105.4 deaths per 100,000
standard population in 2000 to 81.4 in 2012; it then increased to 83.4 in 2013 and to 84.0 in 2014.[32] The trend appears to
represent a shift from coronary heart disease as the underlying cause of heart failure deaths toward other cardiovascular and
noncardiovascular causes, including malignancies, diabetes, chronic lower respiratory diseases, and renal disease.
Analysis of national and regional trends in hospitalization and mortality among Medicare beneficiaries from 1998-2008 showed a
relative decline of 29.5% in heart failure hospitalizations[31, 34] ; however, wide variations were noted between states and
races, with black men having the slowest rate of decline. A relative decline of 6.6% in mortality was also observed, although the
rate was uneven across states. The length of stay decreased from 6.8 days to 6.4 days, despite an overall increase in the
comorbid conditions.[34]
Heart failure statistics for the United States are as follows[31] :
Heart failure is the primary cause of hospitalization in the elderly. [35, 36]
An estimated one in eight deaths is from heart failure (about 309,000 deaths caused by heart failure each year)
Heart failure accounts for 8.5% of cardiovascular-related deaths
Approximately 960,000 new cases of heart failure are diagnosed each year
The annual incidence of heart failure in patients older than 65 years is 21 per 1,000 population
Rehospitalization rates during the 6 months following discharge are as much as 50% [37]
In 2012, the estimated total cost of heart failure in the United States was $30.7 billion (68% of which were direct medical
costs); by 2030, the total cost is projected to rise to $69.7 billion, a nearly 127% increase.
The incidence and prevalence of heart failure are higher in black persons, Hispanics, Native Americans, and recent immigrants
from developing nations, Russia, and the former Soviet republics. The higher prevalence of heart failure in blacks, Hispanics,
and Native Americans is directly related to the higher incidence and prevalence of hypertension and diabetes. This problem is
particularly exacerbated by a lack of access to health care and by substandard preventive health care available to the most
indigent of individuals in these and other groups; in addition, many persons in these groups do not have adequate health
insurance.
The higher incidence and prevalence of heart failure in recent immigrants from developing nations are largely due to a lack of
prior preventive health care, a lack of treatment, or substandard treatment for common conditions, such as hypertension,
diabetes, rheumatic fever, and ischemic heart disease.
Men and women have a similar incidence and prevalence of heart failure. However, many differences remain between men and
women with heart failure, such as the following:
Whereas the incidence of heart failure in men approximately doubles with each 10-year age increase between 65 and 85
years, it triples for women between ages 65 to 74 years and 75 to 85 years [31]
Women tend to develop heart failure later in life than men do
Women are more likely than men to have preserved systolic function
Women develop depression more commonly than men do
Women have signs and symptoms of heart failure similar to those of men, but they are more pronounced in women
Women survive longer with heart failure than men do
The prevalence of heart failure increases with age.[36] The prevalence is 1-2% of the population younger than 55 years and
increases to a rate of 10% for persons older than 75 years. Nonetheless, heart failure can occur at any age, depending on the
cause.
International statistics
Heart failure is a worldwide problem. The most common cause of heart failure in industrialized countries is ischemic
cardiomyopathy, with other causes, including Chagas disease and valvular cardiomyopathy, assuming a more important role in
developing countries. However, in developing nations that have become more urbanized and more affluent, eating a more
processed diet and leading a more sedentary lifestyle have resulted in an increased rate of heart failure, along with increased
rates of diabetes and hypertension. This change was illustrated in a population study in Soweto, South Africa, where the
community transformed into a more urban and westernized city, followed by an increase in diabetes, hypertension, and heart
failure.[38]
In terms of treatment, one study showed few important differences in uptake of key therapies in European countries with widely
differing cultures and varying economic status for patients with heart failure. In contrast, studies of sub-Saharan Africa, where
healthcare resources are more limited, have shown poor outcomes in specific populations.[39, 40] For example, in some
countries, hypertensive heart failure carries a 25% 1-year mortality, and human immunodeficiency virus (HIV)–associated
cardiomyopathy generally progresses to death within 100 days of diagnosis in patients who are not treated with antiretroviral
drugs.
Although data regarding developing nations are not as robust as studies of Western society, the following trends in developing
nations are apparent:
Causes tend to be largely nonischemic
Patients tend to present at a younger age
Outcomes are largely worse where healthcare resources are limited
Isolated right heart failure tends to be more prominent, with a variety of causes having been postulated, ranging from
tuberculous pericardial disease to lung disease and pollution
Prognosis
In general, the mortality following hospitalization for patients with heart failure is 10.4% at 30 days, 22% at 1 year, and 42.3% at
5 years, despite marked improvement in medical and device therapy.[31, 41, 42, 43, 44, 45]
Mortality is greater than 50% for patients with New York Heart Association (NYHA) class IV, American College of
Cardiology/American Heart Association (ACC/AHA) stage D heart failure. Heart failure associated with acute myocardial
infarction (MI) has an inpatient mortality of 20-40%; mortality approaches 80% in patients who are also hypotensive (eg,
cardiogenic shock). (See Heart Failure Criteria, Classification, and Staging).
Heart failure related to systolic dysfunction has an associated mortality of 50% after 5 years.[20]
Numerous demographic, clinical and biochemical variables have been reported to provide important prognostic value in patients
with heart failure, and several predictive models have been developed.[46]
A study by van Diepen et al suggested that patients with heart failure or atrial fibrillation have a significantly higher risk of
noncardiac postoperative mortality than patients with coronary artery disease; this risk should be considered even if a minor
procedure is planned.[47]
Bursi et al found that among community patients with heart failure, pulmonary artery systolic pressure (PASP), as assessed by
Doppler echocardiography, can strongly predict death and can provide incremental and clinically significant prognostic
information independent of known outcome predictors.[48]
In the Framingham Offspring Cohort, higher concentrations of galectin-3, a marker of cardiac fibrosis, were associated with an
increased risk for incident heart failure (hazard ratio: 1.28 per 1 standard deviation increase in log galectin-3). Galectin-3 was
also associated with an increased risk for all-cause mortality (multivariable-adjusted hazard ratio: 1.15).[49]
A more recent, retrospective study that evaluated data from the 2010 Nebraska Hospital Discharge files for 4319
hospitalizations of 3521 heart failure patients admitted to 79 in-state hospitals reported that risk factors for in-hospital mortality in
these patients were increasing age, the presence of comordities, and length of hospital day.[271]
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.[50] A randomized controlled trial of 605 patients
with heart failure reported that the incidence of all-cause hospitalization or death was not reduced in patients receiving
multisession self-care training compared to those receiving a single-session intervention.[51] The optimum method for patient
education remains to be established. It appears that more intensive interventions are not necessarily better.[51]
For patient education information, see the Heart Health Center, Cholesterol Center, and Diabetes Center, as well as Congestive
Heart Failure Symptoms, Causes, and Life Expectancy, High Cholesterol, Chest Pain, Arrhythmias (Heart Rhythm Disorders),
Heart Disease (Coronary Heart Disease), and Heart Attack.
Presentation
History
In evaluating patients with heart failure, the clinician should ask about the following comorbidities and/or risk factors:
Myopathy
Previous myocardial infarction
Valvular heart disease, familial heart disease
Alcohol use
Hypertension
Diabetes
Dyslipidemia
Coronary/peripheral vascular disease
Sleep-disordered breathing
Collagen vascular disease, rheumatic fever
Pheochromocytoma
Thyroid disease
Substance abuse (previous/current history)
History of chemotherapy/radiation to the chest
The New York Heart Association (NYHA) classification of heart failure is widely used in practice and in clinical studies to quantify
clinical assessment of heart failure (see Heart Failure Criteria, Classification, and Staging). Breathlessness, a cardinal symptom
of left ventricular (LV) failure, may manifest with progressively increasing severity as the following:
Exertional dyspnea
Orthopnea
Dyspnea at rest
Other cardiac symptoms of heart failure include chest pain/pressure and palpitations. Common noncardiac signs and symptoms
of heart failure include anorexia, nausea, weight loss, bloating, fatigue, weakness, oliguria, nocturia, and cerebral symptoms of
varying severity, ranging from anxiety to memory impairment and confusion. Findings from the Framingham Heart Study
suggested that subclinical cardiac dysfunction and noncardiac comorbidities are associated with increased incidence of heart
failure, supporting the idea that heart failure is a progressive syndrome and that noncardiac factors are extremely important.[27,
28, 52]
Older patients with heart failure frequently have preserved ejection fraction and an atypical and/or delayed presentation.[53]
Exertional dyspnea
The principal difference between exertional dyspnea in patients who are healthy and exertional dyspnea in patients with heart
failure is the degree of activity necessary to induce the symptom. As heart failure first develops, exertional dyspnea may simply
appear to be an aggravation of the breathlessness that occurs in healthy persons during activity, but as LV failure advances, the
intensity of exercise resulting in breathlessness progressively declines; however, subjective exercise capacity and objective
measures of LV performance at rest in patients with heart failure are not closely correlated. Exertional dyspnea, in fact, may be
absent in sedentary patients.
Orthopnea
Orthopnea is an early symptom of heart failure and may be defined as dyspnea that develops in the recumbent position and is
relieved with elevation of the head with pillows. As in the case of exertional dyspnea, the change in the number of pillows
required is important. In the recumbent position, decreased pooling of blood in the lower extremities and abdomen occurs. Blood
is displaced from the extrathoracic compartment to the thoracic compartment. The failing LV, operating on the flat portion of the
Frank-Starling curve, cannot accept and pump out the extra volume of blood delivered to it without dilating. As a result,
pulmonary venous and capillary pressures rise further, causing interstitial pulmonary edema, reduced pulmonary compliance,
increased airway resistance, and dyspnea.
Orthopnea occurs rapidly, often within a minute or two of recumbency, and develops when the patient is awake. Orthopnea may
occur in any condition in which the vital capacity is low. Marked ascites, regardless of its etiology, is an important cause of
orthopnea. In advanced LV failure, orthopnea may be so severe that the patient cannot lie down and must sleep sitting up in a
chair or slumped over a table.
Cough, particularly during recumbency, may be an "orthopnea equivalent." This nonproductive cough may be caused by
pulmonary congestion and is relieved by the treatment of heart failure.
Paroxysmal nocturnal dyspnea usually occurs at night and is defined as the sudden awakening of the patient, after a couple of
hours of sleep, with a feeling of severe anxiety, breathlessness, and suffocation. The patient may bolt upright in bed and gasp
for breath. Bronchospasm increases ventilatory difficulty and the work of breathing and is a common complicating factor of
paroxysmal nocturnal dyspnea. On chest auscultation, the bronchospasm associated with a heart failure exacerbation can be
difficult to distinguish from an acute asthma exacerbation, although other clues from the cardiovascular examination should lead
the examiner to the correct diagnosis. Both types of bronchospasm can be present in a single individual.
In contrast to orthopnea, which may be relieved by immediately sitting up in bed, paroxysmal nocturnal dyspnea may require 30
minutes or longer in this position for relief. Episodes may be so frightening that the patient may be afraid to resume sleeping,
even after the symptoms have subsided.
Dyspnea at rest
Dyspnea at rest in heart failure is the result of the following mechanisms:
Decreased pulmonary function secondary to decreased compliance and increased airway resistance
Increased ventilatory drive secondary to hypoxemia due to increased pulmonary capillary wedge pressure (PCWP);
ventilation/perfusion (V/Q) mismatching due to increased PCWP and low cardiac output; and increased carbon dioxide
production
Respiratory muscle dysfunction, with decreased respiratory muscle strength, decreased endurance, and ischemia
Pulmonary edema
Acute pulmonary edema is defined as the sudden increase in PCWP (usually >25 mm Hg) as a result of acute and fulminant LV
failure. It is a medical emergency and has a very dramatic clinical presentation. The patient appears extremely ill, poorly
perfused, restless, sweaty, tachypneic, tachycardic, hypoxic, and coughing, with an increased work of breathing and using
respiratory accessory muscles and with frothy sputum that on occasion is blood tinged.
Chest pain/pressure and palpitations
Chest pain/pressure may occur as a result of either primary myocardial ischemia from coronary disease or secondary
myocardial ischemia from increased filling pressure, poor cardiac output (and, therefore, poor coronary diastolic filling), or
hypotension and hypoxemia.
Palpitations are the sensation a patient has when the heart is racing. It can be secondary to sinus tachycardia due to
decompensated heart failure, or more commonly, it is due to atrial or ventricular tachyarrhythmias.
Fatigue and weakness
Fatigue and weakness are often accompanied by a feeling of heaviness in the limbs and are generally related to poor perfusion
of the skeletal muscles in patients with a lowered cardiac output. Although they are generally a constant feature of advanced
heart failure, episodic fatigue and weakness are also common in earlier stages.
Nocturia and oliguria
Nocturia may occur relatively early in the course of heart failure. Recumbency reduces the deficit in cardiac output in relation to
oxygen demand, renal vasoconstriction diminishes, and urine formation increases. Nocturia may be troublesome for patients
with heart failure because it may prevent them from obtaining much-needed rest. Oliguria is a late finding in heart failure, and it
is found in patients with markedly reduced cardiac output from severely reduced LV function.
Cerebral symptoms
The following may occur in elderly patients with advanced heart failure, particularly in those with cerebrovascular
atherosclerosis:
Confusion
Memory impairment
Anxiety
Headaches
Insomnia
Bad dreams or nightmares
Rarely, psychosis with disorientation, delirium, or hallucinations
Physical Examination
Patients with mild heart failure appear to be in no distress after a few minutes of rest, but they may be obviously dyspneic during
and immediately after moderate activity. Patients with left ventricular (LV) failure may be dyspneic when lying flat without
elevation of the head for more than a few minutes. Those with severe heart failure appear anxious and may exhibit signs of air
hunger in this position.
Patients with a recent onset of heart failure are generally well nourished, but those with chronic severe heart failure are often
malnourished and sometimes even cachectic. Chronic marked elevation of the systemic venous pressure may produce
exophthalmos and severe tricuspid regurgitation, and it may lead to visible pulsation of the eyes and of the neck veins. Central
cyanosis, icterus, and malar flush may be evident in patients with severe heart failure.
In mild or moderate heart failure, stroke volume is normal at rest; in severe heart failure, it is reduced, as reflected by a
diminished pulse pressure and a dusky discoloration of the skin. With very severe heart failure, particularly if cardiac output has
declined acutely, systolic arterial pressure may be reduced. The pulse may be weak, rapid, and thready; the proportional pulse
pressure (pulse pressure/systolic pressure) may be markedly reduced. The proportional pulse pressure correlates reasonably
well with cardiac output. In one study, when pulse pressure was less than 25%, it usually reflected a cardiac index of less than
2.2 L/min/m2.[54]
Ascites occurs in patients with increased pressure in the hepatic veins and in the veins draining into the peritoneum; it usually
reflects long-standing systemic venous hypertension. Fever may be present in severe decompensated heart failure because of
cutaneous vasoconstriction and impairment of heat loss.
Increased adrenergic activity is manifested by tachycardia, diaphoresis, pallor, peripheral cyanosis with pallor and coldness of
the extremities, and obvious distention of the peripheral veins secondary to venoconstriction. Diastolic arterial pressure may be
slightly elevated.
Rales heard over the lung bases are characteristic of heart failure that is of at least moderate severity. With acute pulmonary
edema, rales are frequently accompanied by wheezing and expectoration of frothy, blood-tinged sputum. The absence of rales
does not exclude elevation of pulmonary capillary pressure due to LV failure.
Systemic venous hypertension is manifested by jugular venous distention. Normally, jugular venous pressure declines with
respiration; however, it increases in patients with heart failure, a finding known as the Kussmaul sign (also found in constrictive
pericarditis). This reflects an increase in right atrial pressure and, therefore, right-sided heart failure. In general, elevated jugular
venous pressure is the most reliable indicator of fluid volume overload in older patients, and thorough evaluation is needed.[53]
The hepatojugular reflux is the distention of the jugular vein induced by applying manual pressure over the liver; the patient's
torso should be positioned at a 45° angle. The hepatojugular reflux occurs in patients with elevated left-sided filling pressures
and reflects elevated capillary wedge pressure and left-sided heart failure.
Although edema is a cardinal manifestation of heart failure, it does not correlate well with the level of systemic venous pressure.
In patients with chronic LV failure and low cardiac output, extracellular fluid volume may be sufficiently expanded to cause
edema in the presence of only slight elevations in systemic venous pressure. Usually, a substantial gain of extracellular fluid
volume (ie, a minimum of 5 L in adults) must occur before peripheral edema develops. Edema in the absence of dyspnea or
other signs of LV or right ventricular (RV) failure is not solely indicative of heart failure and can be observed in many other
conditions, including chronic venous insufficiency, nephrotic syndrome, or other syndromes of hypoproteinemia or osmotic
imbalance.
Hepatomegaly is prominent in patients with chronic right-sided heart failure, but it may occur rapidly in acute heart failure. When
hepatomegaly occurs acutely, the liver is usually tender. In patients with considerable tricuspid regurgitation, a prominent
systolic pulsation of the liver, attributable to an enlarged right atrial V wave, is often noted. A presystolic pulsation of the liver,
attributable to an enlarged right atrial A wave, can occur in tricuspid stenosis, constrictive pericarditis, restrictive cardiomyopathy
involving the right ventricle, and pulmonary hypertension (primary or secondary).
Hydrothorax is most commonly observed in patients with hypertension involving both the systemic and pulmonary circulation. It
is usually bilateral, although when unilateral, it is usually confined to the right side of the chest. When hydrothorax develops,
dyspnea usually intensifies because of further reductions in vital capacity.
Cardiac findings
Protodiastolic (S3) gallop is the earliest cardiac physical finding in decompensated heart failure in the absence of severe mitral
or tricuspid regurgitation or left-to-right shunts. The presence of an S3 gallop in adults is important, pathologic, and often the
most apparent finding on cardiac auscultation in patients with significant heart failure.
Cardiomegaly is a nonspecific finding that nonetheless occurs in most patients with chronic heart failure. Notable exceptions
include heart failure from acute myocardial infarction, constrictive pericarditis, restrictive cardiomyopathy, valve or chordae
tendineae rupture, or heart failure due to tachyarrhythmias or bradyarrhythmias.
Pulsus alternans (during pulse palpation, this is the alternation of one strong and one weak beat without a change in the cycle
length) occurs most commonly in heart failure due to increased resistance to LV ejection, as occurs in hypertension, aortic
stenosis, coronary atherosclerosis, and dilated cardiomyopathy. Pulsus alternans is usually associated with an S3 gallop,
signifies advanced myocardial disease, and often disappears with treatment of heart failure.
Accentuation of the P2 heart sound is a cardinal sign of increased pulmonary artery pressure; it disappears or improves after
treatment of heart failure. Mitral and tricuspid regurgitation murmurs are often present in patients with decompensated heart
failure because of ventricular dilatatation. These murmurs often disappear or diminish when compensation is restored. Note that
the correlation is poor between the intensity of the murmur of mitral regurgitation and its significance in patients with heart
failure. Severe mitral regurgitation may be accompanied by an unimpressively soft murmur.
Cardiac cachexia is found in long-standing heart failure, particularly of the RV, because of anorexia from hepatic and intestinal
congestion and sometimes because of digitalis toxicity. Occasionally, impaired intestinal absorption of fat occurs and, rarely,
protein-losing enteropathy occurs. Patients with heart failure may also exhibit increased total metabolism secondary to
augmentation of myocardial oxygen consumption, excessive work of breathing, low-grade fever, and elevated levels of
circulating tumor necrosis factor (TNF).
Predominant Right-Sided Heart Failure

Ascites, congestive hepatomegaly, and anasarca due to elevated right-sided heart pressures transmitted backward into the
portal vein circulation may result in increased abdominal girth and epigastric and right upper quadrant (RUQ) abdominal pain.
Other gastrointestinal symptoms, caused by congestion of the hepatic and gastrointestinal venous circulation, include anorexia,
bloating, nausea, and constipation. In preterminal heart failure, inadequate bowel perfusion can cause abdominal pain,
distention, and bloody stools. Distinguishing right-sided heart failure from hepatic failure is often clinically difficult.
Dyspnea, prominent in left ventricular failure, becomes less prominent in isolated right-sided heart failure because of the
absence of pulmonary congestion. However, when cardiac output becomes markedly reduced in patients with terminal right-
sided heart failure (as may occur in isolated right ventricular infarction and in the late stages of primary pulmonary hypertension
and pulmonary thromboembolic disease), severe dyspnea may occur as a consequence of the reduced cardiac output, poor
perfusion of respiratory muscles, hypoxemia, and metabolic acidosis.
Heart Failure in Children

In children, manifestations of heart failure vary with age.[55] Signs of pulmonary venous congestion in an infant generally
include tachypnea, respiratory distress (retractions), grunting, and difficulty with feeding. Often, children with heart failure have
diaphoresis during feedings, which is possibly related to a catecholamine surge that occurs when they are challenged with
eating while in respiratory distress.
Right-sided venous congestion is characterized by hepatosplenomegaly and, less frequently, with edema or ascites. Jugular
venous distention is not a reliable indicator of systemic venous congestion in infants, because the jugular veins are difficult to
observe. Also, the distance from the right atrium to the angle of the jaw may be no more than 8-10 cm, even when the infant is
sitting upright. Uncompensated heart failure in an infant primarily manifests as a failure to thrive. In severe cases, failure to
thrive may be followed by signs of renal and hepatic failure.
In older children, left-sided venous congestion causes tachypnea, respiratory distress, and wheezing (cardiac asthma). Right-
sided congestion may result in hepatosplenomegaly, jugular venous distention, edema, ascites, and/or pleural effusions.
Uncompensated heart failure in older children may cause fatigue or lower-than-usual energy levels. Patients may complain of
cool extremities, exercise intolerance, dizziness, or syncope.
For more information, see the Medscape Drugs & Diseases article Pediatric Congestive Heart Failure.
Heart Failure Criteria, Classification, and Staging

Framingham system for diagnosis of heart failure
In the Framingham system, the diagnosis of heart failure requires that either two major criteria or one major and two minor
criteria be present concurrently, as shown in Table 1 below.[1] Minor criteria are accepted only if they cannot be attributed to
another medical condition.
Table 1. Framingham Diagnostic Criteria for Heart Failure (Open Table in a new window)
Major Criteria Minor Criteria
Paroxysmal nocturnal dyspnea Nocturnal cough
Weight loss of 4.5 kg in 5 days in response to treatment Dyspnea on ordinary exertion
A decrease in vital capacity by one third the maximal value

recorded
Rales Pleural effusion
Acute pulmonary edema Tachycardia (rate of 120 bpm)
Hepatojugular reflux Hepatomegaly
S3 gallop Bilateral ankle edema
Central venous pressure >16 cm water
Circulation time of ≥25 seconds
Pulmonary edema, visceral congestion, or cardiomegaly at
autopsy
Source: Ho KK, Pinsky JL, Kannel WB, Levy D. The epidemiology of heart failure: the Framingham Study. J Am Coll
Cardiol. 1993 Oct;22(4 suppl A):6A-13A.[1]
NYHA classification of functional heart failure
The New York Heart Association (NYHA) functional classification of heart failure is based on the patient's symptom severity and
the amount of exertion that is needed to provoke their symptoms. See Table 2 below.
Table 2. NYHA Functional Classification of Heart Failure (Open Table in a new window)
Class Functional Capacity
I Patients without limitation of physical activity
Patients with slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation,
II
dyspnea, or anginal pain; they are comfortable at rest
Patients with marked limitation of physical activity, in which less than ordinary activity results in fatigue,
III
palpitation, dyspnea, or anginal pain; they are comfortable at rest
Patients who are not only unable to carry on any physical activity without discomfort but who also have symptoms
IV of heart failure or the anginal syndrome even at rest; the patient's discomfort increases if any physical activity is
undertaken
Source: American Heart Association. Classes of heart failure. Available at:

http://www.heart.org/HEARTORG/Conditions/HeartFailure/AboutHeartFailure/Classes-of-Heart-
Failure_UCM_306328_Article.jsp#.WUcGf-vyuHs. Accessed: June 18, 2017.[2]
ACC/AHA stages of heart failure
The American College of Cardiology/American Heart Association (ACC/AHA) developed a classification that described the
development and progression of heart failure and that "recognizes that there are established risk factors and structural
prerequisites for the development of [heart failure] and that therapeutic interventions introduced even before the appearance of
[left ventricular] dysfunction or symptoms can reduce the population morbidity and mortality of [heart failure]."[3] Table 3, below,
summarizes the development of heart failure.
Table 3. ACC/AHA Stages of Heart Failure Development (Open Table in a new window)
Level Description Examples Notes
A At high risk for Patients with coronary artery Patients with predisposing risk factors for
heart failure but disease, hypertension, or developing heart failure
without structural diabetes mellitus without
heart disease or impaired LV function, LVH, or Corresponds with patients with NYHA class I
symptoms of heart geometric chamber distortion heart failure
failure
Structural heart
Patients who are asymptomatic
disease but without
B but who have LVH and/or
signs/symptoms of
impaired LV function
heart failure
Structural heart The majority of patients with heart failure are

Patients with known structural
disease with in this stage
heart disease and shortness of
C current or past
breath and fatigue, reduced
symptoms of heart Corresponds with patients with NYHA class I-
exercise tolerance
failure IV heart failure
Patients in this stage may be eligible to

receive mechanical circulatory support,
Refractory heart receive continuous inotropic infusions,
Patients who have marked undergo procedures to facilitate fluid removal,
failure requiring
D symptoms at rest despite or undergo heart transplantation or other
specialized
maximal medical therapy procedures
interventions
Corresponds with patients with NYHA class IV
heart failure
LV = left ventricle; LVH = LV hypertrophy; NYHA = New York Heart Association.
Source: Yancy CW, Jessup M, Bozkurt B, et al, for the American College of Cardiology Foundation/American Heart
Association Task Force on Practice Guidelines. 2013 ACCF/AHA guideline for the management of heart failure: a report of
the American College of Cardiology Foundation/American Heart Association Task Force on Practice Guidelines.
Circulation. 2013 Oct 15;128(16):e240-327.[3]
ACC/AHA Staging
Stage A
American College of Cardiology/American Heart Association (ACC/AHA) stage A patients are at high risk for heart failure but do
not have structural heart disease or symptoms of heart failure. Thus, management in these cases focuses on prevention,
through reduction of risk factors. Measures include the following[3] :
Treat hypertension (optimal blood pressure: < 130/80 mm Hg [56] )

Encourage smoking cessation
Treat lipid disorders
Encourage regular exercise
Discourage alcohol intake and illicit drug use
Patients who have a family history of dilated cardiomyopathy should be screened with a comprehensive history and physical
examination together with echocardiography and transthoracic echocardiography every 2-5 years.[4]
Stage B
ACC/AHA stage B patients are asymptomatic, with left ventricular (LV) dysfunction from previous myocardial infarction (MI), LV
remodeling from LV hypertrophy (LVH), and asymptomatic valvular dysfunction, which includes patients with New York Heart
Association (NYHA) class I heart failure (see Heart Failure Criteria, Classification, and Staging for a description of NYHA
classes).[3] In addition to the heart failure education and aggressive risk factor modification used for stage A, treatment with an
angiotensin-converting enzyme inhibitor/angiotensin-receptor blocker (ACEI/ARB) and/or beta-blockade is indicated.
Evaluation for coronary revascularization either percutaneously or surgically, as well as correction of valvular abnormalities, may
be indicated.[3] Treatment with an implantable cardioverter-defibrillator (ICD) for primary prevention of sudden death in patients
with an LV ejection fraction (LVEF) below 30% that is more than 40 days post-MI is reasonable if the expected survival is more
than 1 year.
There is less evidence for implantation of an ICD in patients with nonischemic cardiomyopathy, an LVEF less than 30%, and no
heart failure symptoms. There is no evidence for use of digoxin in these populations.[57] Aldosterone receptor blockade with
eplerenone is indicated for post-MI LV dysfunction.
Stage C
ACC/AHA stage C patients have structural heart disease and current or previous symptoms of heart failure; ACC/AHA stage C
corresponds with NYHA class I-IV heart failure. The preventive measures used for stage A disease are indicated, as is dietary
sodium restriction.
Drugs routinely used in these patients include ACEI/ARBs, beta-blockers, or angiotensin receptor–neprilysin inhibitors (ARNIs),
in conjunction with evidence-based beta-blockers, and loop diuretics for fluid retention.[3, 56, 58] For selected patients,
therapeutic measures include aldosterone receptor blockers, hydralazine and nitrates in combination, and cardiac
resynchronization with or without an ICD (see Electrophysiologic Intervention).[3, 56, 58]
A meta-analysis performed by Badve et al suggested that the survival benefit of treatment with beta-blockers extends to patients
with chronic kidney disease and systolic heart failure (risk ratio 0.72).[59]
The 2016 and 2017 ACC/AHA focused updates to the 2013 guidelines added a class IIa recommendation for ivabradine, a
sinoatrial node modulator, in patients with stage C heart failure.[56, 58] They indicate that ivabradine may reduce hospitalization
for patients with symptomatic (NYHA class II-III) stable chronic heart failure with reduced ejection fraction (LVEF ≤35%) who are
receiving recommended therapy, including a beta blocker at the maximum tolerated dose, and who are in sinus rhythm with a
heart rate of 70 bpm or greater at rest.[56, 58]
Stage D
ACC/AHA stage D patients have refractory heart failure (NYHA class IV) that requires specialized interventions. Therapy
includes all the measures used in stages A, B, and C. Treatment considerations include heart transplantation or placement of an
LV assist device in eligible patients; pulmonary catheterization; and options for end-of-life care.[3] For palliation of symptoms,
continuous intravenous infusion of a positive inotrope may be considered.
DDx
Diagnostic Considerations
Many classes of disorders can result in increased cardiac demand or impaired cardiac function. Cardiac causes include
arrhythmias (tachycardia or bradycardia), structural heart disease, and myocardial dysfunction (systolic or diastolic). Noncardiac
causes include processes that increase the preload (volume overload), increase the afterload (hypertension), reduce the
oxygen-carrying capacity of the blood (anemia), or increase demand (sepsis). For example, renal failure can result in heart
failure due to fluid retention and anemia. Lymphatic obstruction and venous obstruction syndromes can also cause edema-
forming states, and obesity-hypoventilation syndrome (OHS) can lead to right-sided heart failure with right ventricular
hypertrophy.
Diastolic heart failure may be the most common form of heart failure in the US population.[21] Alterations in ventricular-arterial
coupling appear to have a key role in impaired hemodynamic response to exercise, but the diagnosis of diastolic heart failure
cannot be excluded even in the presence of normal diastolic function at rest.[21]
Cardiogenic and noncardiogenic pulmonary edema

Heart failure should also be differentiated from the pulmonary edema that is associated with injury to the alveolar-capillary
membrane caused by diverse etiologies (ie, noncardiogenic pulmonary edema, adult respiratory distress syndrome [ARDS]).
Increased capillary permeability is observed in trauma, hemorrhagic shock, sepsis, respiratory infections, administration of
various drugs, and ingestion of toxins (eg, heroin, cocaine, toxic gases). With the advent of natriuretic peptide testing,
differentiating cardiac from noncardiac causes of pulmonary edema has improved.[60, 61]
Several features may differentiate cardiogenic from noncardiogenic pulmonary edema. In heart failure, a history of an acute
cardiac event or of progressive symptoms of heart failure is usually present. The physical examination may yield clues to acute
heart failure. Findings such as an S3 gallop and elevated jugular venous pulsation are highly specific for acute heart failure, but
their low sensitivity makes them less-than-ideal screening tools.[54, 62]
Patients with noncardiogenic pulmonary edema may have clinical features similar to those with cardiogenic pulmonary edema
but will often lack an S3 gallop and jugular venous distention. The differentiation is often made based on pulmonary capillary
wedge pressure (PCWP) measurements from invasive hemodynamic monitoring. Left ventricular filling pressures measured by
PCWP are the single most reliable hemodynamic measure that predicts a fatal outcome in patients with acute heart failure.
PCWP is generally more than 18 mm Hg in heart failure and less than 18 mm Hg in noncardiogenic pulmonary edema, but
superimposition of chronic pulmonary vascular disease can make this distinction more difficult to discern.
Atypical presentations
Heart failure, in particular right-sided heart failure, can present as an abdominal syndrome with nausea, vomiting, right-sided
abdominal pain (as a sign of liver congestion), bloating, anorexia, and significant weight loss. In advanced cases, patients can
appear jaundiced because of cardiac cirrhosis. Constipation is a common complaint among patients with heart failure, and it can
be a manifestation of decreased intestinal transit secondary to poor perfusion. In very severe cases of cardiogenic shock, an
individual can present with severe abdominal pain mimicking bowel obstruction, perforation, acute abdomen, and peritonitis as a
manifestation of severe intestinal ischemia and possible infarction.
In elderly patients, fatigue and confusion can sometimes be the first symptoms of heart failure, which is related to a decrease in
cardiac output. The mnemonic DEFEAT-HF consists of five steps that may be helpful in the diagnosis and management of heart
failure in the older population: diagnosis, etiology, fluid volume, ejection fraction, and therapy.[53]
Differential Diagnoses
Acute Kidney Injury
Acute Respiratory Distress Syndrome (ARDS)
Bacterial Pneumonia
Cardiogenic Pulmonary Edema
Chronic Obstructive Pulmonary Disease (COPD)
Cirrhosis
Community-Acquired Pneumonia (CAP)
Emphysema
Goodpasture Syndrome
Idiopathic Pulmonary Fibrosis (IPF)
Interstitial (Nonidiopathic) Pulmonary Fibrosis
Myocardial Infarction
Nephrotic Syndrome
Neurogenic Pulmonary Edema
Pneumothorax Imaging
Pulmonary Embolism (PE)
Respiratory Failure
Venous Insufficiency
Viral Pneumonia
Workup
Workup
Approach Considerations
Careful evaluation of the patient's history and physical examination (including signs of congestion, such as jugular venous
distention) can provide important information about the underlying cardiac abnormality in heart failure.[3] However, other studies
and/or tests may be necessary to identify structural abnormalities or conditions that can lead to or exacerbate heart failure.[3]
Endomyocardial biopsy is indicated only when a specific diagnosis is suspected that would influence therapy in patients
presenting with heart failure (see the image below).
Transesophageal echocardiogram with continuous wave Doppler interrogation across the mitral valve demonstrating an
increased mean gradient of 16 mm Hg consistent with severe mitral stenosis.
Routine Laboratory Tests

Laboratory studies should include a complete blood cell (CBC) count, serum electrolyte levels (including calcium and
magnesium), and renal and liver function studies. Other tests may be indicated in specific patients. The CBC aids in the
assessment of severe anemia, which may cause or aggravate heart failure.[107, 267] Leukocytosis may signal underlying
infection. Otherwise, CBCs are usually of little diagnostic help.
An assessment for iron deficiency should be considered; about one third of heart failure patients are also iron deficient, which is
associated with poor cardiac function and can worsen outcomes in these individuals.[268, 269, 270] Iron deficiency appears to
impair contractility of human cardiomyocytes by impairing mitochondrial respiration and reducing contractility and relaxation;
these effects can be reversed by restoring intracellular iron levels.[269]
In a study that sought to define biomarker-based iron deficiency in heart failure based on bone marrow iron staining as the gold
standard, as well as evaluate the prognostic value of the optimized definition, investigators found that a transferrin saturation
(TSAT) up to 19.8% or a serum iron level up to 13 μmol/L had the best results in selecting patients with iron deficiency as well
as identifying heart patients with the greatest mortality risk.[267] These TSAT and serum iron values not only achieved a 94%
sensitivity, and a respective 84% and 88% specificity (ie, specificity of 84% for TSAT ≤19.8% and 88% for serum
iron ≤13 μmol/L), but both measures were also independent prognostic factors for mortality.[267]
Serum electrolyte values are generally within reference ranges in patients with mild to moderate heart failure before treatment.
In cases of severe heart failure, however, prolonged, rigid sodium restriction, coupled with intensive diuretic therapy and the
inability to excrete water, may lead to dilutional hyponatremia, which occurs because of a substantial expansion of extracellular
and intravascular fluid volume and a normal or increased level of total body sodium.
Potassium levels are usually within reference ranges, although the prolonged administration of diuretics may result in
hypokalemia. Hyperkalemia may occur in patients with severe heart failure who show marked reductions in glomerular filtration
rate (GFR) and inadequate delivery of sodium to the distal tubular sodium-potassium exchange sites of the kidney, particularly if
they are receiving potassium-sparing diuretics and/or angiotensin-converting enzyme inhibitors (ACEIs).
Pulmonary function testing is generally not helpful in the diagnosis of heart failure. However, such testing may demonstrate or
exclude respiratory causes of dyspnea and help in the assessment of any pulmonary causes of dyspnea.
Renal function tests
Blood urea nitrogen (BUN) and creatinine levels can be within reference ranges in patients with mild to moderate heart failure
and normal renal function, although BUN levels and BUN/creatinine ratios may be elevated.
Patients with severe heart failure, particularly those on large doses of diuretics for long periods, may have elevated BUN and
creatinine levels indicative of renal insufficiency owing to chronic reductions of renal blood flow from reduced cardiac output.
Diuresing this group of patients is complex. In some individuals, diuretics will improve renal congestion and renal function,
whereas in others, overaggressive diuresis may aggravate renal insufficiency due to volume depletion.
Liver function tests
Congestive hepatomegaly and cardiac cirrhosis are often associated with impaired hepatic function, which is characterized by
abnormal values of aspartate aminotransferase (AST), alanine aminotransferase (ALT), lactic dehydrogenase (LDH), and other
liver enzymes. Hyperbilirubinemia secondary to an increase in the directly and indirectly reacting bilirubin is common. In severe
cases of acute right ventricular (RV) or left ventricular (LV) failure, frank jaundice may occur.
Acute hepatic venous congestion can result in severe jaundice, with a bilirubin level as high as 15-20 mg/dL, elevation of AST to
more than 10 times the upper reference range limit, elevation of the serum alkaline phosphatase level, and prolongation of the
prothrombin time. The clinical and laboratory pictures may resemble viral hepatitis, but the impairment of hepatic function is
rapidly resolved by successful treatment of heart failure. In patients with long-standing heart failure, albumin synthesis may be
impaired, leading to hypoalbuminemia and intensifying the accumulation of fluid. Fulminant hepatic failure is an uncommon, late,
and sometimes terminal complication of cardiac cirrhosis.
Natriuretic Peptides
Clinical findings and routine diagnostic tests are not always sufficient to diagnose heart failure. In such ambiguous cases, rapid
measurement of B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) levels can aid clinicians in differentiating
between cardiac and noncardiac causes of dyspnea.[3, 4, 5, 60, 61, 63, 64] That is, BNP is mostly limited to the differentiation of
heart failure versus other causes of dyspnea in patients with an atypical presentation.
BNP is a 32-amino-acid polypeptide containing a 17-amino-acid ring structure common to all natriuretic peptides. The major
source of plasma BNP is the cardiac ventricles, and the release of BNP appears to be in direct proportion to ventricular volume
and pressure overload. BNP is an independent predictor of high LV end-diastolic pressure, and it is more useful than atrial
natriuretic peptide (ANP) or norepinephrine levels for assessing mortality risk in patients with heart failure.[65, 66, 67, 68]
Although BNP has been determined to be the strongest predictor of systolic versus nonsystolic heart failure (followed by oxygen
saturation, history of myocardial infarction, and heart rate), BNP does not reliably differentiate between heart failure with
preserved ejection fraction and heart failure with reduced ejection fraction.[63] Increased NT-proBNP was found to be the
strongest independent predictor of a final diagnosis of acute heart failure.[69, 70, 71]
Measurement of BNP and its precursor NT-proBNP in the urgent care setting can be used to establish the diagnosis of heart
failure when the clinical presentation is ambiguous or when confounding comorbidities are present.[3, 4, 5] BNP and NT-proBNP
assays have different cutoff values for ruling in and ruling out heart failure.[56, 58, 72, 73, 74]
BNP levels correlate closely with the New York Heart Association (NYHA) classification of heart failure.[75, 76] BNP levels
greater than 100 pg/mL have a specificity greater than 95% and a sensitivity greater than 98% when comparing patients without
heart failure to all patients with heart failure.[77] Even BNP levels greater than 80 pg/mL have a specificity greater than 95% and
a sensitivity greater than 98% in the diagnosis of heart failure.[72]
Table of cutoff values
Table 4, below, summarizes the evidence-based cutoff values of BNP and NT-proBNP for ruling in and ruling out the diagnosis
of heart failure in the dyspneic patient presenting to the emergency department.
Table 4. Evidence-Based BNP and NT-proBNP Cutoff Values for Diagnosing HF (Open Table in a new window)
BNP, pg/mL NT-proBNP, pg/mL
Criterion
HF Unlikely (LR- HF Likely (LR- HF Unlikely (LR- HF Likely (LR-
Negative) Positive) Negative) Positive)
>17 < 100 (0.13)* >500 (8.1)* - -
>21 - - < 300 (0.02)† -
Age, y 21-50 - - - >450 (14)†
50-75 - - - >900 (5.0)†
>75 - - - >1800 (3.1)†
Estimated GFR, < 60

< 200 (0.13)‡ >500 (9.3)‡ - -
mL/min
BNP = B-type natriuretic peptide; GRF = glomerular filtration rate; HF = heart failure; LR = likelihood ratio; NPV = negative
predictive value; NT-pro-BNP = N-terminal proBNP; PPV = positive predictive value; – = not specifically defined.
* Derived from Breathing Not Properly data (1586 emergency department [ED] patients, prevalence of HF = 47%).[60]
† Derived from PRIDE data (1256 ED patients, prevalence of HF = 57%).[61, 64]
‡ Derived from subset of Breathing Not Properly data (452 ED patients, prevalence of HF = 49%).[63]
BNP and NT-proBNP levels are higher in older patients,[78] women,[78] and patients with renal dysfunction[79] or sepsis. Atrial
fibrillation has also been associated with increased BNP levels in the absence of acute heart failure. However, BNP levels may
be disproportionately lower in patients who are obese due to fat metabolism or who have hypothyroidism or advanced end-stage
heart failure (the latter due to increased fibrosis). NT-proBNP plasma levels are also lower in obese heart failure patients relative
to nonobese patients with heart failure, regardless of whether the etiology is ischemic or nonischaemic.[80]
However, NT-proBNP may be elevated in severely obese patients (BMI >40 kg/m2) owing to an increased cardiac burden in
these individuals.[81] NT-pro-BNP may be a better marker for detecting cardiac dysfunction than BNP, because its chemical
stability is better in circulating blood than that of BNP, and it is a sensitive marker of cardiac function even in early cardiac
decompensation.[82]
BNP measurement not indicated with nesiritide therapy
Nesiritide is a synthetic BNP analogue; therefore, the measurement of BNP is not indicated in patients who are receiving
nesiritide. If BNP is used as a diagnostic marker to rule in heart failure, the level must be determined before nesiritide therapy is
started.[83, 84, 85, 86]
In a study by Miller et al, levels of NT-proBNP and BNP decreased in patients with advanced heart failure after therapy with
nesiritide, but the majority of the patients did not have biochemically significant decreases in these markers even with a clinical
response.[87] The investigators were unable to give a definitive reason for their results, and they indicated that nesiritide therapy
should not be guided by the use of levels of both markers.[87] Fitzgerald et al also found decreased levels of both natriuretic
peptides following nesiritide therapy in patients with decompensated heart failure.[88]
For more information, see the Medscape Drugs & Diseases article Natriuretic Peptides in Congestive Heart Failure.
Genetic Testing
Cardiomyopathy phenotypes that have known genetic cause(s) include hypertrophic (HCM), dilated (DCM), restrictive (RCM),
arrhythmogenic right ventricular dysplasia/cardiomyopathy (ARVD/C), and left ventricular noncompaction (LVNC). Because most
cases of cardiomyopathy are treatable—which is not the case in many genetic diseases—and screening for genetic risk of
cardiomyopathy before the onset of disease can guide the recommendations for early detection of disease and therapy (see
Presentation, History),[5, 30] it is recommended that consideration be given for patients with cardiomyopathy to be referred to
centers with expertise in these matters and in family-based management.[5] These specialized centers will have a better
understanding of the complexities involved in genetic evaluation, testing, and counseling of patients with cardiomyopathy.
To establish specific gene testing and laboratories offering tests, please see www.genetests.org for further information and
larger reviews.
Genetic testing has the highest yield in three types of cardiomyopathy: DCM, HCM, and autosomal dominant ARVD/C. The
diagnosis must be established using the specific criteria for each type of cardiomyopathy, as the genetic testing is different for
each type.
Dilated cardiomyopathy
It is thought that approximately 20-50% of idiopathic dilated cardiomyopathy (IDC) may have a genetic basis. Screening first-
degree relatives of a proband with IDC by echocardiography and electrocardiography (ECG) reveals that 20-48% of probands
have affected relatives, consistent with a diagnosis of familial dilated cardiomyopathy (FDC).[89, 90, 91]
Molecular genetic testing of the proband for an LMNA mutation is probably indicated, particularly if significant conduction system
disease is present in the family. It should be noted that although the analytical sensitivity for detecting LMNA gene mutations is
quite high, the clinical sensitivity (likelihood of identifying a mutation in a person with the disorder) is approximately 8% for FDC.
Because molecular genetic testing for MYH7 has comparable clinical sensitivity, testing for mutations in MHY7 may also be
considered.
Hypertrophic cardiomyopathy
HCM, caused by mutation in one of the genes currently known to encode different components of the sarcomere, is
characterized by left ventricular (LV) hypertrophy (LVH) in the absence of predisposing cardiac conditions (eg, aortic stenosis) or
cardiovascular conditions (eg, long-standing hypertension). Most often, the LVH of HCM becomes apparent during adolescence
or young adulthood, although it may also develop late in life, in infancy, or in childhood.
Molecular genetic testing of any of the 14 genes currently known to encode different components of the sarcomere is clinically
available. A detailed 3- to 4-generation family history should be obtained from relatives to assess the possibility of familial HCM.
Attention should be directed to a history of any of the following in relatives: heart failure, HCM, cardiac transplantation,
unexplained sudden death, unexplained cardiac conduction system disease and/or arrhythmia, or unexplained stroke or other
thromboembolic disease.
Autosomal dominant arrhythmogenic right ventricular dysplasia/cardiomyopathy
ARVD/C is characterized by progressive fibrofatty replacement of the myocardium that predisposes to ventricular tachycardia
and sudden death in young individuals and athletes. It primarily affects the RV; with time, it may also involve the LV. The
presentation of disease is highly variable even within families, and affected individuals may not meet the established clinical
criteria. The mean age at diagnosis is 31 years (±13 y; range, 4-64 y).
Genetic testing should be considered in individuals who have a clinical diagnosis of ARVD based on the diagnostic criteria. A
case can be made to offer genetic testing to all with a clinical diagnosis of ARVD with a negative family history based on the
high rate of reduced penetrance thus far identified with the ARVD genes. Molecular genetic testing is available on a clinical
basis for TGFB3, RYR2, TMEM43, DSP, PKP2, DSG2, DSC2, and JUP.[92]
For more information regarding genetic testing and cardiomyopathy, please see HFSA Guideline Approach to Medical Evidence
for Genetic Evaluation of Cardiomyopathy, as well as 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.[30]
Assessment of Hypoxemia
Arterial and venous blood gases
Although arterial blood gas (ABG) measurement is more accurate than pulse oximetry for measuring oxygen saturation, it is
unclear if ABG results add any clinical utility to pulse oximetry. In the setting of acute heart failure, ABG measurement is rarely
performed. Indications include severe respiratory distress, documented hypoxemia by pulse oximetry not responsive to
supplemental oxygen, and evidence of acidosis by serum chemistry findings or elevated lactate levels.
In general, heart failure patients who do not have comorbid lung disease do not manifest hypoxemia except in severe acute
decompensation. Patients with severe heart failure may have signs and symptoms ranging from severe hypoxemia, or even
hypoxia, along with hypercapnia, to decreased vital capacity and poor ventilation.
ABG measurement helps assess the presence of hypercapnia, a potential early marker for impending respiratory failure.
Hypoxemia and hypocapnia occur in stages 1 and 2 of pulmonary edema because of a ventilation/perfusion (V/Q) mismatch. In
stage 3 of pulmonary edema, right-to-left intrapulmonary shunt develops secondary to alveolar flooding and further contributes
to hypoxemia. In more severe cases, hypercapnia and respiratory acidosis are usually observed. The decision regarding
intubation and the use of mechanical ventilation is frequently based on many clinical parameters, including oxygenation,
ventilation, and mental status. ABG values in isolation are rarely useful, but they may add to the entire clinical picture.
Mixed venous oxygen saturation (obtained from the main pulmonary artery in the absence of an intracardiac shunt) is a good
marker of the blood circulation time and thus of the cardiac output and cardiac performance. Patients who have advanced heart
failure have low cardiac output and slower circulation time, which translate into an increased oxygen extraction by the tissues
and therefore lower oxygen (< 60% saturation).
Pulse oximetry
Pulse oximetry is highly accurate at assessing the presence of hypoxemia and, therefore, the severity of acute heart failure
presentations. Patients with mild to moderate acute heart failure may show modest reductions in oxygen saturation, whereas
patients with severe heart failure may have severe oxygen desaturation, even at rest. Pulse oximetry is also useful for
monitoring the patient's response to supplemental oxygen and other therapies.
Patients with mild to moderate heart failure may have normal oxygen saturations at rest, but they may exhibit marked reductions
in oxygen saturations during physical exertion or recumbency. In general, arterial desaturation during exercise is not expected in
heart failure and suggests the presence of comorbid lung disease. The use of continuous oxygen may be needed until
compensation returns oxygen saturation to normal during exertion and recumbency or on a permanent basis if oxygen
desaturation during exertion and/or recumbency exists during compensated severe chronic heart failure.
Electrocardiography
A screening electrocardiogram (ECG) is reasonable in patients with symptoms suggestive of heart failure. The presence of left
atrial enlargement and left ventricular (LV) hypertrophy (LVH) is sensitive (although nonspecific) for chronic LV dysfunction. It is
unlikely that an ECG would be completely normal in the presence of heart failure; therefore, an alternative diagnosis should be
sought in such cases.[4, 5]
Electrocardiography may suggest an acute tachyarrhythmia or bradyarrhythmia as the cause of heart failure. It may also aid in
the diagnosis of acute myocardial ischemia or infarction as the cause of heart failure, or it may suggest the likelihood of a prior
myocardial infarction or the presence of coronary artery disease as the cause of heart failure.[3, 5]
Heart failure can have multiple and diverse presentations on ECGs (see the images below).
This electrocardiogram (ECG) is from a 32-year-old female with recent-onset congestive heart failure and syncope. The ECG
demonstrates a tachycardia with a 1:1 atrial:ventricular relationship. It is not clear from this tracing whether the atria are
driving the ventricles (sinus tachycardia) or the ventricles are driving the atria (ventricular tachycardia).At first glance, sinus
tachycardia in this ECG might be considered with severe conduction disease manifesting as marked first-degree
atrioventricular block with left bundle branch block. Looking more closely, electrocardiographic morphology gives clues to the
actual diagnosis of VT. These clues include the absence of RS complexes in the precordial leads, a QS pattern in V6, and an
R wave in aVR. The patient proved to have an incessant VT associated with dilated cardiomyopathy.
Electrocardiogram depicting ventricular fibrillation in a patient with a left ventricular assist device (LVAD). Ventricular fibrillation
is often due to ischemic heart disease and can lead to myocardial infarction and/or sudden death.
This electrocardiogram (ECG) shows evidence of severe left ventricular hypertrophy (LVH) with prominent precordial voltage,
left atrial abnormality, lateral ST-T abnormalities, and a somewhat leftward QRS axis (–15º). The patient had malignant
hypertension with acute heart failure, accounting also for the sinus tachycardia (blood pressure initially 280/180 mmHg). The
ST-T changes seen here are nonspecific and could be due to, for example, LVH alone or coronary artery disease. However,
the ECG is not consistent with extensive inferolateral myocardial infarction. Image courtesy of http://ecg.bidmc.harvard.edu .
This electrocardiogram shows an extensive acute/evolving anterolateral myocardial infarction pattern, with ST-T changes
most apparent in leads V2-V6, I, and aVL. Slow R wave progression is also present in leads V1-V3. The rhythm is borderline
sinus tachycardia with a single premature atrial complex (PAC) (4th beat). Note also the low limb lead voltage and probable
left atrial abnormality. Left ventriculography showed diffuse hypokinesis as well as akinesis of the anterolateral and apical
walls, with an ejection fraction estimated at 33%. Image courtesy of http://ecg.bidmc.harvard.edu.
This electrocardiogram shows a patient is having an evolving anteroseptal myocardial infarction secondary to cocaine. There
are Q waves in leads V2-V3 with ST segment elevation in leads V2-V5 associated with T-wave inversion. Also noted are
biphasic T-waves in the inferior leads. These multiple abnormalities suggest occlusion of a large left anterior descending
artery that wraps around the apex of the heart (or multivessel coronary artery disease). Image courtesy of
http://ecg.bidmc.harvard.edu .
Electrocardiography is of limited help when an acute valvular abnormality or LV systolic dysfunction is considered to be the
cause of heart failure; however, the presence of left bundle branch block (LBBB) on an ECG is a strong marker for diminished
LV systolic function.
Chest Radiography
Chest radiographs (see the images below) are used in cases of heart failure to assess heart size, pulmonary congestion,
pulmonary or thoracic causes of dyspnea, and the proper positioning of any implanted cardiac devices.[3, 4, 5] Posterior-
anterior and lateral views are recommended.[5]
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).
Although up to 50% of patients with heart failure and documented elevation of pulmonary capillary wedge pressure (PCWP) do
not manifest typical radiographic findings of pulmonary congestion, two principal features of chest radiographs are useful in the
evaluation of patients with heart failure: (1) the size and shape of the cardiac silhouette and (2) edema at the lung bases.
Echocardiography
Two-dimensional (2-D) echocardiography is recommended in the initial evaluation of patients with known or suspected heart
failure.[3, 4, 5] Ventricular function may be evaluated, and primary and secondary valvular abnormalities may be accurately
assessed.[93, 94, 95, 96, 97, 98]
Doppler echocardiography, along with 2-D echocardiography, may play a valuable role in determining diastolic function and in
establishing the diagnosis of diastolic heart failure. Approximately 30-40% of patients presenting with heart failure have normal
systolic function but abnormal diastolic relaxation. The primary finding to differentiate diastolic heart failure is the presence of a
normal ejection fraction; however, note that findings of diastolic dysfunction are common in the elderly and may not be
associated with clinical heart failure. Because the therapy for this condition is distinctly different from that for systolic
dysfunction, establishing the appropriate etiology and diagnosis is essential.
Doppler and 2-D echocardiography may also be used to determine both systolic and diastolic left ventricular (LV) performance,
cardiac output (ejection fraction), and pulmonary artery and ventricular filling pressures. In addition, echocardiography may be
used to identify clinically important valvular disease (see the images below).
Cervicocephalic fibromuscular dysplasia (FMD) can lead to complications such as hypertension and chronic kidney failure,
which can lead to heart failure. In this color Doppler and spectral Doppler ultrasonographic examination of the left internal
carotid artery (ICA) in a patient with cervicocephalic FMD, stenoses of about 70% is seen in the ICA.
Cervicocephalic fibromuscular dysplasia (FMD) can lead to complications such as hypertension and chronic kidney failure,
which, in turn, can lead to heart failure. Nodularity in an artery is known as the string-of-beads sign, and it can be seen this
color Doppler ultrasonographic image from a 51-year-old patient with low-grade stenosing FMD of the internal carotid artery
(ICA).
Echocardiogram of a patient with severe pulmonic stenosis. This image shows a parasternal short axis view of the thickened
pulmonary valve. Pulmonic stenosis can lead to pulmonary hypertension, which can result in hepatic congestion and in right-
sided heart failure.
This video is an echocardiogram of a patient with severe pulmonic stenosis. The first segment shows the parasternal short
axis view of the thickened pulmonary valve. The second segment shows the presence of moderate pulmonary insufficiency
(orange color flow). AV = aortic valve, PV = pulmonary valve, PA = pulmonary artery, PI = pulmonary insufficiency.
The following video is from a patient with arrhythmogenic right ventricular dysplasia (ARVD), a congenital cardiomyopathy that
can lead to heart failure.
Apical 4-chamber echocardiogram in a 37-year-old man with arrhythmogenic right ventricular dysplasia (ARVD), a congenital
cardiomyopathy. Note the prominent trabeculae and abnormal wall motion of the dilated right ventricle.ARVD can result in
ventricular and supraventricular arrhythmias. The most significant of all rhythms associated with heart failure are the life-
threatening ventricular arrhythmias.
Transesophageal echocardiography
Transesophageal echocardiography (TEE) is particularly useful in patients who are on mechanical ventilation or are morbidly
obese and in patients whose transthoracic echocardiogram is suboptimal in its imaging.[4, 99] It is an easy and safe alternative
to conventional transthoracic echocardiography (TTE) and provides better imaging quality (see the following video).
Transesophageal echocardiography also has the potential to be a noninvasive alternative to pulmonary artery catherization
(Swan-Gantz catheterization) for hemodynamic monitoring, as it also allows the measurement of central venous, pulmonary
arterial, and pulmonary capillary wedge pressures, as well as pulmonary and systemic vascular resistance, and stroke volume
and cardiac output.[99]
Transthoracic echocardiogram demonstrating severe mitral regurgitation with heavily calcified mitral valve and prolapse of the
posterior leaflet into the left atrium.
Stress echocardiography
Stress echocardiography, also known as dobutamine or exercise echocardiography, has several uses; however, in heart failure,
this technique is used mainly to assess coronary artery disease. This imaging modality may be used to detect ventricular
dysfunction caused by ischemia, evaluate myocardial viability in the presence of marked hypokinesis or akinesis, identify
myocardial stunning and hibernation, and relate heart failure symptoms to valvular abnormalities.[4] However, stress
echocardiography may have a lower sensitivity and specificity in heart failure patients because of LV dilatation or because of the
presence of bundle branch block.
CT Scanning and MRI

Computed tomography (CT) scanning or magnetic resonance imaging (MRI) may be useful in evaluating cardiac chamber size
and ventricular mass, cardiac function, and wall motion; delineating congenital and valvular abnormalities; and demonstrating
the presence of pericardial disease.[3] However, cardiac CT scanning is usually not required in the routine diagnosis and
management of heart failure, and echocardiography and MRI may provide similar information without exposing the patient to
ionizing radiation.
The benefits of cardiac MRI (cMRI) include the ability to obtain a great deal of information with a noninvasive test. This modality
provides detailed functional and morphologic information; can be used to assess ischemic versus nonischemic disease,
infiltrative disease, and hypertrophic disease; and can be employed to determine viability. It is used principally for the delineation
of congenital cardiac abnormalities and for the assessment of valvular heart disease, and it is the gold standard for evaluating
right ventricular (RV) function (see the video below).
Cardiac magnetic resonance image (CMRI), short axis view. This image shows right ventricular dilatation, trabucular
derangement, aneurysm formation and dyskinetic free wall in a patient with arrhythmogenic right ventricular dysplasia.
MRI has become particularly useful for evaluating abnormalities in wall motion and viable myocardium, and MRI findings can
help predict the success of revascularization in patients with low ejection fractions.[100] However, the detailed information
obtained by MRI must be balanced by its high costs and the fact that this imaging modality cannot be performed in patients with
implantable defibrillators.
Nuclear Imaging
Radionuclide multiple-gated acquisition scanning
Radionuclide multiple-gated acquisition (MUGA) scan is a reliable imaging technique for the evaluation of left ventricular (LV)
and right ventricular (RV) function and wall motion abnormalities. Because of its reliability, LV ejection fraction (LVEF), as
determined by MUGA scanning, is often used for serial assessment of postchemotherapy LV function.[101]
Electrocardiogram-gated myocardial perfusion imaging
The high photon flux of compounds labeled with technetium-99m (99mTc) makes it feasible to acquire myocardial perfusion
images in an electrocardiogram (ECG)-gated mode. ECG-gated single-photon emission computed tomography (SPECT)
images allow for the assessment of the global LVEF, regional wall motion, and regional wall thickening at rest in patients with
documented stress-induced wall motion and perfusion abnormalities.
In general, LVEF from gated SPECT scanning agrees well with resting LVEF determined by other modalities. Quality assurance
is important, however, because determinations of LVEF with gated SPECT scanning may be less accurate, even invalidated, in
the presence of an irregular heart rate, low count density, intense extracardiac radiotracer uptake adjacent to the LV, or a small
LV.
Combined interpretation of perfusion and function on ECG-gated images substantially increases the confidence of the
interpretation. Taillefer and associates reported that the interpretation of stress and rest end-diastolic section, rather than
summed ungated sections, may enhance the overall sensitivity for the detection of mild coronary artery disease.[102]
ECG-gated images are also useful for recognizing artifactual defects caused by attenuation (breast and diaphragm) and thus
are useful in the quality control of SPECT imaging. ECG-gated SPECT imaging is considered state of the art of radionuclide
myocardial perfusion imaging.
Three important practical issues need to be addressed in the evaluation of patients with presumed ischemic dysfunction, as
follows:
Assessment of the relative regional myocardial uptake of thallium-201 ( 201Tl; often after rest reinjection), 99mTc-
sestamibi, or 99m Tc-tetrofosmin (often after rest administration of nitroglycerin); when the resting uptake of radiotracer is
greater than 50% of normal, expect recovery of function after revascularization
Assessment of the presence of demonstrable ischemia (eg, partially reversible defect) in a myocardial segment with
decreased uptake, even if the resting uptake is less than 50%
Data reported in 2011 from a STICH viability substudy failed to demonstrate a significant impact on survival based on the
extent of the viable myocardium in patients with coronary artery disease and LV dysfunction treated surgically or
medically [103]
Equilibrium radionuclide angiocardiography
Equilibrium radionuclide angiocardiography (ERNA) uses ECG events to define the temporal relationship between the
acquisition of nuclear data and the volumetric components of the cardiac cycle. Sampling is performed repetitively over several
hundred heartbeats, with physiologic segregation of the nuclear data in accordance with their occurrence within the cardiac
cycle.
Data are quantified and displayed in an endless-loop, cinegraphic format for additional qualitative visual interpretation and
analysis. Equilibrium blood-pool labeling is achieved by use of 99mTc. Data are analyzed by use of a computer, generally with
some operator interaction.
Analysis may be obtained in either the frame or list mode. Radionuclide data are collected and segregated temporally. The
process generally requires 3-10 minutes for completion of each view. Following data acquisition, data from the several hundred
individual beats are summed, processed, and displayed as a single representative cardiac cycle.
Data from the left anterior oblique (LAO) view are also used for qualitative analysis of global LV function. On this view, overlap of
the two ventricles is minimal. In a count-based approach, LVEF and other indices of filling and ejection are calculated from the
LV radioactivity preset at various points throughout the cardiac cycle.
Right ventricular (RV) function is best evaluated by first-pass techniques. The LAO view provides qualitative information
concerning contraction of the septal, inferoapical, and lateral walls. The anterior view provides data concerning the regional
motion of the anterior and apical segments. The left lateral or left posterior oblique view provides optimal qualitative information
concerning contraction of the inferior wall and posterobasal segment.
ERNA may easily be combined with additional physiologic stress testing or provocation, which may be in the form of either
physiologic stress, such as exercise; pharmacologic stress, with the use of positive inotropic agents, such as dobutamine or
isoproterenol; or psychological stress. The degree of confidence with ERNA is moderately high. False-positive and false-
negative findings are infrequent.
Radionuclide ventriculography
Radionuclide ventriculography is most often performed as part of a myocardial perfusion scan to obtain accurate measurements
of LV function and RV ejection fraction (RVEF),[3, 4] but it is unable to directly assess valvular abnormalities or cardiac
hypertrophy and has limited value for assessing volumes or more subtle indices of systolic or diastolic function.
Iobenguane scanning for cardiac risk evaluation

The scintigraphic imaging agent iobenguane I 123 injection (AdreView) is used for the evaluation of myocardial sympathetic
innervation in patients with New York Heart Association (NYHA) class 2-3 heart failure with an LVEF of 35% or less.[6] This
radionuclide tracer, which functions molecularly as a norepinephrine analogue, 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.[6]
Catheterization and Angiography

In patients with a nonischemic cardiomyopathy, perfusion deficits and segmental wall-motion abnormalities suggestive of
coronary artery disease are commonly present on noninvasive imaging.[3] Only coronary angiography, however, can reliably
demonstrate or exclude the presence of obstructed coronary vessels (see the following image).[3]
A color-enhanced angiogram of the heart left shows a plaque-induced obstruction (top center) in a major artery, which can
lead to myocardial infarction (MI). MIs can precipitate heart failure.
The procedures are frequently indicated when systolic dysfunction of unexplained cause is present on noninvasive testing or
when normal systolic function with episodic heart failure suggests ischemically mediated left ventricular (LV) dysfunction.
However, although coronary angiography may be indicated in young patients to exclude the presence of congenital coronary
anomalies, this procedure may not be as useful in older patients, because revascularization has not been shown to improve
clinical outcomes in patients without angina.[3] Despite this, because revascularization may improve LV function, some experts
suggest that coronary artery disease should be excluded whenever possible, especially in patients with diabetes mellitus or
other states associated with silent myocardial ischemia.[3] The degree of confidence is moderately high.
Right-sided heart catheterization
Right heart catheterization is useful in providing important hemodynamic information about filling pressures, vascular resistance,
and cardiac output when there is doubt about the patient's fluid status; in heart failure refractory to initial therapy; in the
presence of significant hypotension (systolic blood pressure typically < 90 mm Hg or symptomatic low systolic blood pressure)
and/or worsening renal function during initial treatment; and when heart transplantation or placement of a mechanical circulatory
support device is being considered.[3] However, it plays a limited role in the diagnosis of heart failure, as studies evaluating right
heart catheterization and overall improved outcomes have been essentially neutral.[104]
Normal right-sided hemodynamics include a right atrial pressure less than 7 mm Hg, right ventricular (RV) pressure below 30/7
mm Hg, pulmonary pressure less than 30/18 mm Hg, pulmonary capillary wedge pressure (PCWP) below 18 mm Hg, and
cardiac index (CI) above 2.2 L/min/m2.
PCWP can be measured by using a pulmonary arterial catheter (Swan-Ganz catheter). This helps to differentiate cardiogenic
causes of decompensated heart failure from noncardiogenic causes, such as acute respiratory distress syndrome (ARDS),
which occurs secondary to injury to the alveolar-capillary membrane rather than to alteration in Starling forces. A PCWP
exceeding 18 mm Hg in a patient not known to have chronically elevated left atrial pressure is indicative of cardiogenic
decompensated heart failure. In patients with chronic pulmonary capillary hypertension, capillary wedge pressures exceeding 25
mm Hg are generally required to overcome the pumping capacity of the lymphatics and produce pulmonary edema.
Large V waves may be observed in the PCWP tracing in patients with significant mitral regurgitation because large volumes of
blood regurgitate into a poorly compliant left atrium. This raises the pulmonary venous pressure and may cause pulmonary
edema.
Left-sided heart catheterization
Left-sided heart catheterization and coronary angiography should be undertaken when the etiology of heart failure cannot be
determined by clinical or noninvasive imaging methods or when the etiology is likely to be due to acute myocardial ischemia or
infarction. Coronary angiography is particularly helpful in patients with LV systolic dysfunction and known or suspected coronary
artery disease in whom myocardial ischemia is thought to play a dominant role in the reduction of LV systolic function and the
worsening of heart failure.
Assessment of Functional Capacity

Cardiopulmonary stress testing (maximal exercise stress testing with measurement of respiratory gas exchange) can help in the
assessment of a patient’s chance of survival within the next year, as well as determine the need for referral for either cardiac
transplantation or implantation of mechanical circulatory support. A 6-minute walk test evaluates the distance walked, dyspnea
index on a Borg scale from 0 to 10, oxygen saturation, and heart rate response to exercise. A normal value is walking more than
1500 feet. Patients who walk less than 600 feet have severe cardiac dysfunction and a worse short- and long-term prognosis.[4]
Treatment
Approach Considerations
Medical care for heart failure includes a number of nonpharmacologic, pharmacologic, and invasive strategies to limit and
reverse its manifestations.[3, 4, 105] Depending on the severity of the illness, nonpharmacologic therapies include dietary
sodium and fluid restriction; physical activity as appropriate; and attention to weight gain. Pharmacologic therapies include the
use of diuretics, vasodilators, inotropic agents, anticoagulants, beta-blockers, and digoxin.
Invasive therapies for heart failure include electrophysiologic intervention such as cardiac resynchronization therapy (CRT),
pacemakers, and implantable cardioverter-defibrillators (ICDs); revascularization procedures such as coronary artery bypass
grafting (CABG) and percutaneous coronary intervention (PCI); valve replacement or repair; and ventricular restoration.[3, 4, 56,
58, 105]
Heart transplantation has been the criterion standard for therapy when progressive end-stage heart failure occurs despite
maximal medical therapy, when the prognosis is poor, and when there is no viable therapeutic alternative.[3, 4, 5] However,
mechanical circulatory devices such as ventricular assist devices (VADs) and total artificial hearts (TAHs) can bridge the patient
to transplantation; in addition, VADs are increasingly being used as permanent therapy.[4]
Comorbidities to consider
Patients with heart failure should be evaluated for coronary artery disease, which can lead to heart failure (see Etiology). Not
only may this condition be the underlying cause in up to two thirds of heart failure patients with low ejection fraction, but
coronary artery disease may also play a role in the progression of heart failure through mechanisms such as endothelial
dysfunction, ischemia, and infarction, among others.[3]
Patients with coronary artery disease with modestly reduced ejection fraction and angina have demonstrated symptomatic and
survival improvement with coronary artery bypass grafting (CABG) in studies; however, the trials did not include individuals with
heart failure or those with severely reduced ejection fractions.[3] In patients with angina and ventricular dysfunction, evaluation
with coronary angiography should not be delayed (see Catheterization and Angiography). Noninvasive cardiac testing is not
recommended in patients with significant ischemic chest pain, as revascularization is advised in these patients independent of
their degree of ischemia/viability.[3]
Although there are no reports of controlled trials evaluating heart failure without angina and their outcomes with coronary
revascularization, surgical revascularization is recommended in those with significant left main stenosis and in those with
extensive noninfarcted but hypoperfused and hypocontractile myocardium on noninvasive testing.[3] In patients with heart
failure and reduced left ventricular (LV) ejection fraction but without angina, it has not yet been determined whether routine
evaluation of possible myocardial ischemia/viability and coronary artery disease should be performed.[3]
For patients with heart failure from LV dysfunction without chest pain and without a history of coronary artery disease, coronary
angiography may be useful in young patients to exclude congenital coronary anomalies. However, because clinical outcomes
have not been shown to improve in patients without angina, coronary angiography may not be as useful in older patients for
evaluating the presence of coronary artery disease.[3] Some experts nonetheless suggest excluding coronary artery disease
whenever possible, particularly in the presence of diabetes or other conditions associated with silent myocardial ischemia,
because LV function may show improvement with revascularization.[3]
In general, if coronary artery disease has already been excluded as the cause of abnormalities in LV function, it is not necessary
to perform repeated evaluations for ischemia (invasive or noninvasive) provided the patient’s clinical status has not changed to
suggest the development of ischemic disease.[3]
For more information, see the Medscape Drugs & Diseases articles Primary and Secondary Prevention of Coronary Artery
Disease, Risk Factors for Coronary Artery Disease, and Coronary Artery Atherosclerosis.
Valvular heart disease
Valvular heart disease may be the underlying etiology or an important aggravating factor in heart failure.[3, 4, 5]
Sleep apnea
Sleep apnea has an increased prevalence in patients with heart failure and is associated with increased mortality[4] due to
further neurohormonal activation, although randomized, controlled data are lacking. Patients with heart failure and suspected
sleep-disordered breathing or excessive daytime sleepiness should undergo a formal sleep assessment.[56] [105]
Sleep apnea should be treated aggressively in heart failure patients. Guidelines recommend providing oxygen supplementation
and continuous positive airway pressure (CPAP).[4, 56, 105] However, the recommendations differ on the use of adaptive
servo-ventilation (ASV): The 2017 focused update guideline of the 2013 American College of Cardiology/American Heart
Association/Heart Failure Society of America (ACC/AHA/HFSA) guidelines indicates ASV causes harm in patients with New
York Heart Association (NYHA) class II-IV heart failure with reduced ejection fraction (HFpEF) and central sleep apnea,[56]
whereas the 2016 European Society of Cardiology (ESC) indicates that ASV may be considered for treating noctural
hypoxemia in those with heart failure and sleep apnea.[4]
A long-term study involving 283 heart failure patients who had an implanted cardiac resynchronization device with cardioverter-
defibrillator concluded that obstructive sleep apnea (OSA) and/or central sleep apnea (CSA) are independently associated with
an increased risk for ventricular arrhythmias requiring cardioverter-defibrillator therapies.[106]
Anemia
Anemia is also common in chronic heart failure. Whether anemia is a reflection of the severity of the heart failure or contributes
to worsening heart failure is not clear. Potential etiologies of anemia in heart failure involve poor nutrition, angiotensin-converting
enzyme inhibitors (ACEIs), the renin-angiotensin-aldosterone system (RAAS), inflammatory cytokines, hemodilution, and renal
dysfunction. Anemia in heart failure is associated with increased mortality.[107]
The 2010 HFSA,[5] 2013 ACC Foundation (ACCF)/AHA,[3] 2016 ACC/AHA/HFSA,[58] and 2016 ESC guidelines[4] made no
recommendations regarding the administration of iron to patients with heart failure, although the ACC/AHA noted that several
small studies suggested a benefit in mild anemia and heart failure,[3] and the ESC observed that intravenous (IV) ferric
carboxymaltose may potentially lead to sustainable improvements in function, symptoms, and quality of life.[4] However, the
ACC/AHA's 2017 focused update to the 2013 guidelines has a class IIb recommendation for IV iron replacement for patients
with NYHA class II and III heart failure and iron deficiency (ferritin < 100 ng/mL or 100-300 ng/mL if transferrin saturation <
20%).[56] In addition, their class III recommendation is to avoid using erythropoietin-stimulating agents in patients with heart
failure and anemia to improve morbidity and mortality owing to a lack of benefit.[56]
Cardiorenal syndrome
Cardiorenal syndrome reflects advanced cardiorenal dysregulation manifested by acute heart failure, worsening renal function,
and diuretic resistance. It is equally prevalent in patients with HFpEF and those with LV systolic dysfunction. Worsening renal
function is one of the three predictors of increased mortality in hospitalized patients with heart failure regardless of the LVEF.
Cardiorenal syndrome can be classified into the following five types[108] :
CR1: Rapid worsening of cardiac function leading to acute kidney injury (HFpEF, acute heart failure, cardiogenic shock,
and right ventricular [RV] failure)
CR2: Worsening renal function due to progression of chronic heart failure
CR3: Abrupt and primary worsening of kidney function leading to acute cardiac dysfunction (heart failure, arrhythmia,
ischemia)
CR4: Chronic kidney disease leading to progressive cardiac dysfunction, LV hypertrophy (LVH), and diastolic dysfunction
CR5: Combination of cardiac and renal dysfunction due to acute and chronic systemic conditions
The pathophysiology of CR1 and CR2 is complex and multifactorial, involving neurohormonal activation (RAAS, sympathetic
nervous system, arginine vasopressin, natriuretic peptides, adenosine receptor activation), low arterial pressure, and high
central venous pressure, leading to lower transglomerular perfusion pressure and decreased availability of diuretics to the
proximal nephron. This results in an increased reabsorption of sodium and water and poor diuretic response—hence, diuretic
resistance despite escalating doses of oral or IV diuretics.
Treatment of cardiorenal syndrome in patients with heart failure is largely empirical, but it typically involves the use of
combination diuretics, vasodilators, and inotropes as indicated.[109] Ultrafiltration is recommended for symptomatic relief by the
ACC/AHA guidelines for patients with heart failure that is refractory to diuretic therapy.[3, 56] The 2017 ACC/AHA focused
update noted the following five criteria may be indications for renal replacement therapy in these patients[56] :
Oliguria unresponsive to fluid resuscitation measures

Severe hyperkalaemia (potassium level >6.5 mmol/L)
Severe acidemia (pH < 7.2)
Serum urea level above 25 mmol/L (150 mg/dL)
Serum creatinine over 300 µmol/L (>3.4 mg/dL)
A sudden increase in creatinine levels can be seen after the initiation of diuretic therapy, and it is often mistakenly considered
evidence of overdiuresis or intravascular depletion (even in the presence of fluid overload). A common error in this situation is to
decrease the dose of ACEIs, angiotensin-receptor blockers (ARBs), and/or diuretics, or to even withdraw one of these agents. In
fact, when diuresis or ultrafiltration is continued, patients demonstrate improved renal function, decreased total body fluid, and
increased response to diuretics, as central venous pressure falls.
Low-dose dopamine has been used in combination with diuretic therapy, on the supposition that it can increase kidney
perfusion. Data have been contradictory, however. In a randomized controlled study, Giamouzis et al found that the combination
of low-dose furosemide and low-dose dopamine was equally as effective as high-dose furosemide for kidney function in patients
with acute decompensated heart failure.[110] In addition, patients who received dopamine and furosemide were less likely to
have worsened renal function or hypokalemia at 24 hours.[110]
Use of nesiritide, a synthetic natriuretic peptide, to increase diuresis in these cases has not been studied. A meta-analysis of
several trials using nesiritide suggested the potential of worsening renal function, although this has not been demonstrated in
prospective trials. Results of the Acute Study of Clinical Effectiveness of Nesiritide in Decompensated Heart Failure (ASCEND-
HF) trial suggested that, although nesiritide is safe, it does not provide additional efficacy when added to standard therapy.[111]
In another large study comprising 7141 patients with decompensated heart failure, the use of nesiritide did not have an effect
on renal function, rehospitalization, and mortality, albeit there was a small but nonsignificant impact on dyspnea when used in
conjunction with other therapies.[112]
The Efficacy of Vasopressin Antagonism in Heart Failure Outcome Study with Tolvaptan (EVEREST) trial showed that the
addition of the vasopressin antagonist tolvaptan to diuretic therapy facilitates diuresis in acute heart failure. However, tolvaptan
had no impact on mortality or hospitalizations in this setting.[113]
Adenosine receptor antagonists have been proposed for protecting renal function in acute heart failure. However, in a double-
blind, placebo-controlled trial, the adenosine A1−receptor antagonist rolofylline demonstrated no benefit for patients hospitalized
for acute heart failure with impaired renal function.[114]
A meta-analysis performed by Badve et al suggested that treatment with beta-blockers reduced all-cause mortality in patients
with chronic kidney disease and systolic heart failure (risk ratio, 0.72).[115]
Atrial fibrillation
Many patients with heart failure also have atrial fibrillation, and the two conditions can adversely affect each other. However, in
the AFFIRM (Atrial Fibrillation Follow-up Investigation of Rhythm Management) trial, there was no difference in stroke, heart
failure exacerbation, or cardiovascular mortality in patients treated with rhythm control (amiodarone) and patients treated with
rate control.[116] All of these patients require anticoagulation for stroke prevention, which can be achieved by using warfarin or
a direct thrombin inhibitor (no need to follow protime).
A meta-analysis found that patients with LV systolic dysfunction who underwent catheter ablation for atrial fibrillation
demonstrated significant improvements in LVEF, and their risk for recurrent atrial fibrillation or atrial tachycardia after catheter
ablation was similar to that in patients with normal LV function after ablation.[117] However, patients with LV systolic dysfunction
were more likely to require repeat procedures.
In contrast, MacDonald et al reported that in patients with advanced heart failure and severe LV systolic dysfunction,
radiofrequency ablation for persistent atrial fibrillation resulted in long-term restoration of sinus rhythm in only 50% of cases.[118]
Radiofrequency ablation also failed to improve such secondary outcomes as walking distance or quality of life, and the rate of
related serious complications was 15%.
Nonpharmacologic Therapy
Patients with heart failure can benefit from attention to exercise, diet, and nutrition.[3, 5] Restriction of activity promotes physical
deconditioning, so physical activity should be encouraged. However, limitation of activity is appropriate during acute heart failure
exacerbations and in patients with suspected myocarditis. Most patients should not participate in heavy labor or exhaustive
sports.
A 2012 meta-analysis showed that aerobic exercise training, particularly over the long term, can reverse left ventricular
remodelling in clinically stable heart failure patients, whereas strength training had no effect on remodelling.[119]
Because nonadherence to diet and medication can have rapid and profound adverse effects on patients’ clinical status, close
observation and follow-up are important aspects of care.[3, 4] Patient education and close supervision, including surveillance by
the patient and family, can improve adherence. These measures also facilitate early detection of weight gain or slightly
worsened symptoms, which often occur several days before major clinical episodes that require emergency care or
hospitalization. Patients can then alert their clinicians, who may be able to prevent such episodes through prompt intervention.
Dietary sodium restriction to 2-3 g/day is recommended. Fluid restriction to 2 L/day is recommended for patients with evidence
of hyponatremia (Na < 130 mEq/dL) and for those whose fluid status is difficult to control despite sodium restriction and the use
of high-dose diuretics. Caloric supplementation is recommended for patients with evidence of cardiac cachexia.
An analysis of concentrations of plasma eicosapentaenoic acid (EPA), a long-chain omega-3 fatty acid, in the Cardiovascular
Health Study identified plasma phospholipid EPA concentration as being inversely related to incident congestive heart failure.
[120] These results support additional studies on the potential benefits of omega-3 fatty acids for primary prevention of heart
failure.
The GISSI-HF (Gruppo Italiano per lo Studio della Sopravvivenza nell'Infarto Miocardico) trial, which included nearly 7000
patients with systolic heart failure (any LV ejection fraction) who received either 1 g of omega-3 polyunsaturated fatty acids
(PUFAs) or placebo daily, demonstrated that the PUFA regimen had a small but significant reduction in both all-cause mortality
and all-cause mortality/hospitalization for cardiovascular causes.[121]
Pharmacologic Therapy
Pharmacologic therapy includes[3, 4, 5, 58] :
Diuretics (to reduce edema by reduction of blood volume and venous pressures) and salt restriction (to reduce fluid
retention) in patients with current or previous heart failure symptoms and reduced left ventricular (LV) ejection fraction
(EF) for symptomatic relief
Angiotensin-converting enzyme inhibitors (ACEIs) for neurohormonal modification, vasodilatation, improvement in LVEF,
and survival benefit
Angiotensin receptor blockers (ARBs) for neurohormonal modification, vasodilatation, improvement in LVEF, and survival
benefit
Hydralazine and nitrates to improve symptoms, ventricular function, exercise capacity, and survival in patients who
cannot tolerate an ACEI/ARB or as an add-on therapy to ACEI/ARB and beta-blockers in the black population for survival
benefit
Beta-adrenergic blockers for neurohormonal modification, improvement in symptoms and LVEF, survival benefit,
arrhythmia prevention, and control of ventricular rate
Aldosterone antagonists, as an adjunct to other drugs for additive diuresis, heart failure symptom control, improved heart
rate variability, decreased ventricular arrhythmias, reduction in cardiac workload, improved LVEF, and increase in survival
Digoxin, which can lead to a small increase in cardiac output, improvement in heart failure symptoms, and decreased
rate of heart failure hospitalizations
Anticoagulants to decrease the risk of thromboembolism
Inotropic agents to restore organ perfusion and reduce congestion
The I(f) "funny current" inhibitor, ivabradine (Corlanor) received FDA approval in 2015 to reduce the risk of hospitalization for
worsening heart failure in patients with stable, symptomatic chronic heart failure with an LVEF of 35% or lower, who are in sinus
rhythm with a resting heart rate of 70 bpm or higher, and who are either on maximally tolerated doses of beta-blockers or have a
contraindication to beta-blocker use.[122, 123] This drug blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN)
channel responsible for the cardiac pacemaker I(f) "funny" current, which regulates heart rate without any effect on ventricular
repolarization or myocardial contractility.
Approval for ivabradine was based on the international, placebo-controlled SHIFT trial published in 2010, which randomized
more than 6500 patients with New York Heart Association (NYHA) class II-IV heart failure and an LVEF of 35% or lower.[122,
123] The trial saw a highly significant 18% drop in risk for cardiovascular death or hospitalization for worsening heart failure over
an average of 23 months in patients treated with ivabradine.
The FDA approved the combination tablet sacubitril/valsartan (Entresto) in 2015 to reduce the risk of cardiovascular death and
hospitalization for heart failure in patients with NYHA class II-IV heart failure and reduced ejection fraction.[124] The
combination drug is the first approved agent in the angiotensin receptor-neprilysin inhibitor (ARNI) class and consists of the ARB
valsartan affixed to the neprilysin inhibitor sacubitril. The cardiovascular and renal effects of sacubitril’s active metabolite
(LBQ657) in heart failure are attributed to the increased levels of peptides that are degraded by neprilysin (eg, natriuretic
peptide). Administration results in increased natriuresis, increased urine cGMP (cyclic guanosine monophosphate), and
decreased plasma mid-regional proatrial natriuretic peptide (MR-proANP) and N-terminal pro-brain natriuretic peptide (NT-
proBNP).
The approval was based on the Prospective Comparison of ARNI with ACE-I to Determine Impact on Global Mortality and
Morbidity in Heart Failure (PARADIGM-HF) trial.[125] PARADIGM-HF studied 8442 patients with chronic heart failure treated
with either valsartan/sacubitril or enalapril. The combination significantly reduced cardiovascular death or heart-failure
hospitalizations (the study's primary end point) by 20% compared with treatment with enalapril alone. All-cause mortality, a
secondary end point, was also significantly reduced with the ARNI when compared with enalapril.[125]
The Prospective Comparison of ARNI with ARB on Management of Heart Failure with Preserved Ejection Fraction
(PARAMOUNT) trial compared reduction of NP-proBNP levels with sacubitril plus valsartan and valsartan alone over 12 weeks
in 149 patients with LVEF of 45% or greater. Sacubitril/valsartan reduced NT-proBNP levels to a significantly greater extent (783
pg/mL at baseline and 605 pg/mL at 12 weeks) compared with valsartan alone (862 pg/mL at baseline and 835 pg/mL at 12
weeks).[126]
Patients with heart failure and depressed LVEF are thought to have an increased risk of thrombus formation due to low cardiac
output.[3, 4] ref6} Anticoagulation with an international normalized ratio (INR) goal of 2-3 is indicated in the presence of LV
thrombus, thromboembolic event with or without evidence of an LV thrombus, and paroxysmal or chronic atrial arrhythmias.[5]
Routine anticoagulation with warfarin in patients with normal sinus rhythm, heart failure, and LV dysfunction has not proven to be
superior to aspirin alone in decreasing death, myocardial infarction (MI), and stroke, and it was associated with an increased risk
of bleeding in the warfarin arm of the WATCH (warfarin and antiplatelet therapy in chronic heart failure) trial.[127]
The use of regularly scheduled intermittent intravenous infusions of positive inotropic drugs in a supervised outpatient setting
has been proposed, but the 2013 American College of Cardiology/American Heart Association/Heart Failure Society of America
(ACCF/AHA/HFSA) guidelines advise against this, given the lack of evidence to support efficacy and concerns about toxicity
with an increase in mortality rate. Rather, the guidelines recommend infusion of a positive inotrope only as palliation in patients
with end-stage disease who cannot be stabilized with standard medical treatment.[3]
Nonsteroidal anti-inflammatory drugs (NSAIDs), calcium channel blockers, and most antiarrhythmic agents may exacerbate
heart failure and should be avoided in most patients.[3, 4] NSAIDs can cause sodium retention and peripheral vasoconstriction
and can attenuate the efficacy and enhance the toxicity of diuretics and ACEIs.
Antiarrhythmic agents can have cardiodepressant effects and may promote arrhythmia; only amiodarone and dofetilide have
been shown not to adversely affect survival. Calcium channel blockers can worsen heart failure and may increase the risk of
cardiovascular events; only the vasoselective calcium channel blockers have been shown not to adversely affect survival.[3, 4]
In a community-based cohort study of 2891 digoxin-naive adults with newly diagnosed systolic heart failure, 18% of whom
initiated treatment with digoxin, incident digoxin use was associated with significantly higher rates of death (14.2 vs 11.3 per 100
person-years) during a median of 2.5 years of follow-up.[128] Digoxin use was not associated with a significant difference in the
risk of hospitalization for heart failure. Results were similar when the analyses were stratified by sex and use of beta-blockers.
Digoxin currently occupies places in both US and European guidelines as no more than a second-line agent for systolic heart
failure.
In a review of the safety and efficacy of digoxin in heart failure patients with a reduced EF, Konstantinou et al suggest that
digoxin may still have a role in the setting of severe heart failure with evidence of congestion in patients unable to tolerate high
doses of disease-modifying agents because of borderline blood pressure/renal function.[129] The investigators indicate the goal
of digoxin use should be a reduction in hospital readmissions, and that clinicians should closely monitor levels of serum digoxin,
creatinine, and potassium.[129]
Acute Heart Failure Treatment

Most patients who present with acute heart failure have exacerbation of chronic heart failure, with only 15-20% having acute de
novo heart failure. Approximately 50% of patients with acute heart failure have a preserved left ventricular (LV) ejection fraction
(EF) (>40%).[130, 131] Less than 5% of patients presenting with acute heart failure are hypotensive and require inotropic
therapy.[132] Pulmonary edema is a medical emergency, but it is only one of the many presentations of acute heart failure.
A systematic and expeditious approach to management of acute heart failure is required, starting in the outpatient setting (eg,
emergency department, urgent care center, office), continuing during hospitalization, and extending after discharge to the
outpatient setting. The clinician’s agenda in these cases is three-fold:
Stabilize the patient's clinical condition

Establish the diagnosis, etiology, and precipitating factors
Initiate therapies to rapidly provide symptomatic relief
Administration of oxygen, if oxygen saturation is less than 90%, and noninvasive positive pressure ventilation (NIPPV) provides
patients with respiratory support to avoid intubation. NIPPV has been shown to decrease the rate of intubation, hospital morality,
and mechanical ventilation.[133, 134, 135, 136, 137] No difference has been noted between continuous positive airway pressure
(CPAP) and bilevel positive airway pressure (BiPAP). A prospective randomized trial that compared the use of noninvasive
ventilation (NIV) and standard therapy with the use of standard therapy alone suggested that although NIV may improve
dyspnea and respiratory acidosis, it does not appear to improve mortality.[138]
Medical therapy for heart failure patients, the majority who present with normal perfusion and evidence of congestion, focuses
on the following goals:
Preload and afterload reduction for symptomatic relief using vasodilators (nitrates, hydralazine, nipride, nesiritide,
angiotensin-converting enzyme inhibitors/angiotensin receptor blockers [ACEI/ARB]) and diuretics
Inhibition of deleterious neurohormonal activation (renin-angiotensin-aldosterone system [RAAS] and sympathetic
nervous system) using ACEIs/ARBs, beta-blockers, and aldosterone antagonists resulting in long-term survival benefit
Preload reduction results in decreased pulmonary capillary hydrostatic pressure and reduction of fluid transudation into the
pulmonary interstitium and alveoli. Preload and afterload reduction provide symptomatic relief. Inhibition of the RAAS and
sympathetic nervous system produces vasodilation, thereby increasing cardiac output and decreasing myocardial oxygen
demand. While reducing symptoms, inhibition of the RAAS and neurohumoral factors also results in significant reductions in
morbidity and mortality.[139, 140, 141] Diuretics are effective in preload reduction by increasing urinary sodium excretion and
decreasing fluid retention, with improvement in cardiac function, symptoms, and exercise tolerance.[3, 4]
Once congestion is minimized, a combination of three types of drugs (a diuretic, an ACEI or an ARB, and a beta-blocker) is
recommended in the routine management of most patients with heart failure.[3, 4] This combination can accomplish all of the
above goals. ACEIs/ARBs and beta-blockers are generally used together. Beta-blockers are started in the hospital once
euvolemic status has been achieved.
If there is evidence of organ hypoperfusion, use of inotropic therapies and/or mechanical circulatory support (eg, intra-aortic
balloon pump, extracorporeal membrane oxygenator [ECMO], left ventricular assist device [LVAD]) and continuous
hemodynamic monitoring are indicated.[3, 4, 142] If arrhythmia is present and if uncontrolled ventricular response is thought to
contribute to the clinical scenario of acute heart failure, either pharmacologic rate control or emergent cardioversion with
restoration of sinus rhythm is recommended.
A study of 85 patients with confirmed hypertensive acute heart failure found that the intravenous (IV) calcium channel blocker
clevidipine (Cleviprex) was safe and more effective than standard IV drugs for rapidly reducing blood pressure and improving
dyspnea.[143, 144] In the 32 study patients who received clevidipine, dyspnea resolved completely in 3 hours, compared with
12 hours in the 53 patients who received usual care (mainly IV nitroglycerin or nicardipine). Target blood pressure range was
achieved more often (71% vs 37% for standard care; P =.002) and reached sooner (P =.0006) in patients receiving clevidipine .
[143, 144]
Diuretics
Diuretics remain the cornerstone of standard therapy for acute heart failure. In such patients, IV administration of a loop diuretic
(ie, furosemide, bumetanide, torsemide) is preferred initially because of potentially poor absorption of the oral form in the
presence of bowel edema. In patients with hypertensive heart failure who have mild fluid retention, thiazide diuretics may be
preferred because of their more persistent antihypertensive effects.[3, 4]
Diuretics can be given by bolus or continuous infusion and in high or low doses. In a study of patients with acute
decompensated heart failure, however, Felker et al found that there were no significant differences in effect on symptoms or
renal function changes with furosemide given either by bolus or by continuous infusion; additionally, no differences were found
with high versus low doses.[145] The dose and frequency of administration depend on the diuretic response 2-4 hours after the
first dose is given. If the response is inadequate, then increasing the dose and/or increasing the frequency can help enhance
diuresis.
Diuretic resistance is diagnosed if there is persistent pulmonary edema despite the following[146] :
Repeated doses of 80 mg of furosemide or

Greater than 240 mg of furosemide per day (including continuous furosemide infusion) or
Combined diuretic therapy (including loop diuretics with thiazide or an aldosterone antagonist)
Volume status, sodium levels, water intake, and hemodynamic status (for signs of poor perfusion) need to be reevaluated in
case of diuretic resistance. Diuretic resistance is a known effect of long-term use of these agents. Some approaches to
managing resistance to diuretics include increasing the dose and/or frequency of the drug, restricting sodium or water intake,
administering the drug as an IV bolus or IV infusion, and combining diuretics.[3, 147] In addition, diuretic resistance is an
independent predictor of mortality in patients with chronic heart failure.[148] Eventually, alternative strategies, such as
hemodialysis or ultrafiltration,[149] may be used to overcome it. Other agents, such as vasopressin antagonists and adenosine
receptor blockers, can be used to assist diuretics.
Transition to oral diuretic therapy is made when the patient reaches a near-euvolemic state. The oral diuretic dose is usually
equal to the IV dose. In most cases, 40 mg/day of furosemide is equivalent to 20 mg of torsemide and 1 mg of bumetanide.
Weight, signs and symptoms, fluid balance, electrolyte levels, and renal function must be monitored carefully on a daily basis.
Vasodilators
Vasodilators (eg, nitroprusside, nitroglycerin, or nesiritide) may be considered as an addition to diuretics for patients with acute
heart failure for relief of symptoms. Vasodilators decrease preload and/or afterload.
Nitrates are potent venodilators. These agents decrease preload and therefore decrease LV filling pressure and relieve
dyspnea. They also selectively produce epicardial coronary artery vasodilatation and help with myocardial ischemia. Although
nitrates can be used in different forms (sublingual, oral, transdermal, IV), the most common route of administration in acute heart
failure is IV. However, their use is limited by tachyphylaxis and headache.
Sodium nitroprusside is a potent, primarily arterial, vasodilator that causes a very efficient afterload reduction and decrease of
intracardiac filling pressures. This agent is particularly helpful for patients who present with severe pulmonary congestion in the
presence of hypertension and severe mitral regurgitation. Sodium nitroprusside requires not only careful hemodynamic
monitoring, often necessitating indwelling catheters, but also monitoring for cyanide toxicity, especially in the presence of renal
dysfunction. Sodium nitroprusside should be titrated to off rather than abruptly stopped because of the potential for rebound
hypertension.
Nesiritide (human brain natriuretic peptide [BNP] analogue) is a vasodilator that was initially thought to alleviate dyspnea faster
than nitroglycerin when used in combination with diuretics.[150, 151] This agent reduces pulmonary capillary wedge pressure
(PCWP), right atrial pressure, and systemic vascular resistance but has no effect on heart contractility.
Ultrafiltration and refractory heart failure
In ultrafiltration, blood is removed from the body and run through a device that applies hydrostatic pressure across a
semipermeable membrane to separate isotonic plasma water. Solutes cross the semipermeable membrane freely, so fluid can
be removed without causing significant changes in the concentration of electrolytes and other solutes in serum.[152]
Ultrafiltration was shown to be an effective alternative to IV diuretics in the Ultrafiltration Versus Intravenous Diuretics for
Patients Hospitalized for Acute Decompensated Heart Failure (UNLOAD) trial.[153]
Indications for hospitalization
A patient whose condition is refractory to standard therapy will often require hospitalization to receive IV diuretics, vasodilators,
and inotropic agents. Hospitalization is indicated for acute heart failure in the presence of the following[5] :
Severe acute decompensated heart failure (low blood pressure, worsening renal dysfunction, altered mentation)
Dyspnea at rest
Hemodynamically significant arrhythmia
Acute coronary syndrome
Hospitalization should also be considered in the presence of the following[5] :
Worsening congestion with or without dyspnea

Worsening signs and symptoms of systemic or pulmonary congestion, even in the absence of weight gain
Major electrolyte abnormalities
Associated comorbid conditions (eg, pneumonia, pulmonary embolism, diabetic ketoacidosis, stroke/strokelike
symptoms)
Repeated implantable cardioverter-defibrillator (ICD) firings
New diagnosis of heart failure with signs of active systemic/pulmonary congestion
Most patients requiring hospitalization should be admitted to a telemetry bed or intensive care unit; a small percentage can be
admitted to the floor or observation unit. The goal is to continue the diagnostic and therapeutic processes started in the office or
emergency department. Treatment includes the following:
Optimization of volume and hemodynamic status using careful clinical monitoring, and optimization of the heart failure
medical regimen
Consideration of surgical intervention with a ventricular device
Provision of heart failure education, behavior modification, and exercise and diet recommendations
Enrollment in heart failure disease management programs for patients with advanced and difficult-to-control heart failure
Invasive hemodynamic monitoring
Invasive hemodynamic monitoring is not indicated for stable patients with heart failure who respond appropriately to medical
therapy.[3, 5, 104] The Evaluation Study of Congestive Heart Failure and Pulmonary Artery Catheterization Effectiveness
[ESCAPE] trial showed no mortality or hospitalization benefit in such cases.[104] In patients with acute decompensated heart
failure, the following are indications for invasive hemodynamic monitoring[3, 5, 154] :
Respiratory distress
Signs of impaired perfusion
Inability to determine intracardiac pressures on the basis of clinical examination
No improvement in clinical status despite maximal heart failure therapy
Clinical situations in which invasive hemodynamic monitoring is recommended to guide therapy include the following[3, 5] :
Persistent symptomatic hypotension despite initial therapy

Worsening renal function despite initial therapy or despite adjustment of recommended therapies
Need for parenteral vasoactive agents after initial clinical improvement
Presumed cardiogenic shock requiring escalating inotrope and/or pressor therapy and consideration of mechanical
support
When advanced device therapy or cardiac transplantation is under consideration
Physicians have implemented different monitoring methods in an attempt to reduce hospitalization for heart failure. The results
have been equivocal, regardless of the severity of heart failure. No differences in death or hospitalization for heart failure have
been found with either standard outpatient monitoring or intense telemonitoring for heart failure.[155, 156]
The FDA approved the first permanently implantable wireless hemodynamic monitoring system (CardioMEMS HF System) in
2014 for patients with New York Heart Association (NYHA) class III heart failure with a history of hospitalization for heart failure
within the past year.[157, 158] The device measures pulmonary artery (PA) pressures (eg, systolic, diastolic, and mean) as well
as heart rate, and consists of a sensor/monitor implanted permanently in the PA, a transvenous catheter to deploy the sensor
within the distal PA, and an electronics system that acquires and processes the signal from the sensor/monitor and transfers PA
measurements to a secure database.[157, 158] This device also permits ambulatory monitoring and is designed to detect early-
stage elevations in PA pressure, so that appropriate medical intervention can be provided before worsening elevation leads to
congestion.[159]
Approval for the device was based on results from 550 patients from the open-label CHAMPION study (CardioMEMS Heart
Sensor Allows Monitoring of Pressure to Improve Outcomes in NYHA Class III Heart Failure Patients), in which the device
reduced hospitalizations by 30% compared with standard care.[158, 159]
Discharge
The patient must be on a stable oral regimen for at least 24 hours before discharge. Patients are ready for discharge when they
meet the following criteria:
Exacerbating factors have been addressed

Volume status has been optimized
Diuretic therapy has been successfully transitioned to oral medication, with discontinuation of IV vasodilator and inotropic
therapy for at least 24 hours
Oral chronic heart failure therapy has been achieved with stable clinical status
Before discharge, patient and family education should be completed, and extensive postdischarge instructions and follow-up in
3-7 days should be arranged. Refractory end-stage heart failure (American College of Cardiology/American Heart Association
[ACC/AHA] stage D, NYHA class IV) is often difficult to manage on an outpatient basis. Therefore, these patients may be
referred to a heart failure program with expertise in management of refractory heart failure.[3]
To ensure compliance and understanding of a complex medical regimen, a follow-up phone call can be made 3 days after
discharge by a nurse with training in heart failure. Ideally, the patient should be seen in clinic 7-10 days after discharge.
Treatment of Heart Failure with Preserved LVEF

Treatment of heart failure with preserved left ventricular ejection fraction (HFpEF) is directed toward alleviating symptoms and
addressing the underlying condition triggering HFpEF.[3] Evaluation of cardiac ischemia or sleep apnea as potential precipitating
factors should also be considered.
The 2017 American College of Cardiology/American Heart Association/Heart Failure Society of American (ACC/AHA/HFSA)
focused update guideline has a class IIa recommendation for the use of aldosterone antagonists in appropriate patients with
stage C HFpEF (ejection fraction [EF] ≥45%, elevated brain natriuretic peptide [BNP] level or hospitalization for heart failure
within 1 year, estimated glomerular filtration rate [eGFR] >30 and creatinine level < 2.5 mg/dL, potassium level < 5.0 mEq/L).[56]
The guideline indicates no benefit for the routine use of nitrates or phosphodiesterase-5 inhibitors to increase activity or quality
of life as well as for the routine use of nutritional supplements in HFpEF.[56]
There is a paucity of randomized, controlled studies addressing HFpEF. Control of blood pressure, volume, or other risk factors
is the mainstay of therapy.[3, 5] Lifestyle modification is important and may include the following:
Low-sodium diet
Restricted fluid intake
Daily measurement of weight
Exercise
Weight loss
Diuretic therapy is recommended to reduce fluid retention. However, patients must be monitored carefully to avoid hypotension.
Angiotensin-converting enzyme inhibitors/angiotensin receptor blockers (ACEIs/ARBs) are used as indicated for patients with
atherosclerotic disease, prior myocardial infarction (MI), diabetes mellitus, or hypertension. Use of candesartan, irbesartan, or
perindopril has not been shown to decrease mortality but has produced a trend toward improved morbidity and decreased
hospitalizations.[160] Some evidence shows that losartan and valsartan may promote left ventricular (LV) reverse remodeling,
with improvement in diastolic function and regression of LV hypertrophy (LVH).
Beta-blockers are indicated for patients with prior MI or hypertension and for control of ventricular rate in those with atrial
fibrillation. In the Acute Decompensated Heart Failure National Registry (ADHERE), the subset of patients with HFpEF not
treated with a beta-blocker had a higher mortality, potentially because of the higher incidence of coronary artery disease (CAD)
in this population.[161]
Aldosterone receptor blockers are indicated for hypertension and to reduce myocardial fibrosis, although no randomized,
controlled studies have been performed to evaluate their role in HFpEF. Calcium channel blockers may improve exercise
tolerance via their vasodilatory properties, and nondihydropyridine calcium channel blockers are also used for ventricular rate
control in patients with atrial fibrillation. Amlodipine has antianginal properties and is also indicated in hypertension.
Restoration of sinus rhythm should be considered if the patient remains symptomatic despite the above efforts. Use of digitalis
or inotropes in patients with HFpEF is not indicated.
Treatment of Right Ventricular Heart Failure

Management of right ventricular (RV) failure includes treatment of the underlying cause; optimization of preload, afterload, and
RV contractility; maintenance of sinus rhythm; and atrioventricular synchrony. Hypotension should be avoided, as it can
potentially lead to further RV ischemia.
General measures should be applied, as follows:
Sodium and fluid restriction

Moderate physical activity, with avoidance of isometric exercises
Avoidance of pregnancy
Compliance with medications
Avoidance, or rapid treatment of, precipitating factors
Precipitating factors include the following:

Sleep apnea
Pulmonary embolism
Sepsis
Arrhythmia
Ischemia
High altitude
Anemia
Hypoxemia
Use of an angiotensin-converting enzyme inhibitor/angiotensin receptor blocker (ACEI/ARB) is beneficial if RV failure is

secondary to left ventricular (LV) failure; the efficacy of these agents in isolated RV failure is not known. The same
recommendation applies for use of beta-blockers. The role of nesiritide in RV failure is not well defined. Use of digoxin in RV
failure associated with chronic obstructive pulmonary disease (COPD) not associated with LV dysfunction does not appear to
improve exercise tolerance or RV ejection fraction (EF). Treatment of pulmonary-induced RV failure is to address the correction
of a primary pulmonary etiology and a decrease in RV afterload via specific pulmonary artery vasodilatory therapies (see
Primary Pulmonary Hypertension for treatment).
In patients with severe, hemodynamically compromising RV failure, inotropic therapy is administered, using dobutamine (2-5
mcg/kg/min), dobutamine and inhaled nitric oxide, or dopamine alone. Milrinone is preferred if the patient is tachycardic or on
beta-blockers.
Anticoagulation indications are standard for evidence of an intracardiac thrombus, thromboembolic events, pulmonary arterial
hypertension, paroxysmal or persistent atrial fibrillation/flutter, and mechanical right-sided valves. Hypoxemia should be
corrected, and positive pressure should be avoided when mechanical ventilation is needed.
Atrial septostomy can be considered as a palliative measure in patients with severe symptoms in whom standard therapy has
failed. RV mechanical assist device is indicated only for RV failure secondary to LV failure or post–cardiac transplantation.
The prognosis in patients with RV failure depends on the etiology. Volume overload, pulmonary stenosis, and Eisenmenger
syndrome are associated with a better prognosis. Decreased exercise tolerance predicts poor survival.
Electrophysiologic Intervention
Devices for electrophysiologic intervention in heart failure include pacemakers, cardiac resynchronization therapy (CRT)
devices, and implantable cardioverter-defibrillators (ICDs). CRT should be considered in patients with NYHA class II-IV, an LVEF
of 35% or less, normal sinus rhythm and a QRS duration of 150 ms or longer, with a left bundle branch pattern.[3, 56]
In April 2014, the FDA approved 10 Medtronic biventricular pacemakers, some with defibrillators and some without, for use in
patients with less severe systolic heart failure and atrioventricular (AV) block.[162, 163] Approval was based on a study of 691
patients with first-, second-, or third-degree AV block, New York Heart Association (NYHA) class I-III heart failure, and left
ventricular ejection fraction (LVEF) below 50%, in which biventricular pacing over 3 years reduced all-cause mortality by 26%,
reduced heart failure-related urgent care, and increased LV end-systolic volume index by more than 15%.[162, 163]
Pacemakers
Maintaining a normal chronotropic response and AV synchrony may be particularly significant for patients with heart failure.[4]
Because right ventricular (RV) pacing may worsen heart failure due to an increase in ventricular dysynchrony, placement of a
dual-chamber pacemaker in heart failure patients in the absence of symptomatic bradycardia or high-degree AV block is not
recommended.
Implantable cardioverter-defibrillators
The role of implantable cardioverter-defibrillators (ICDs) has rapidly expanded. Sudden death is 5-10 times more common in
patients with heart failure than in the general population. ICD placement results in remarkable reductions in sudden death from
ischemic and nonischemic sustained ventricular tachyarrhythmias in heart failure patients. (See also the Medscape Reference
articles Implantable Cardioverter-Defibrillators and Pacemakers and Implantable Cardioverter Defibrillators.)
In moderately symptomatic heart failure patients with an LVEF of 35% or less, primary prevention with an ICD provides no
benefit in some cases but substantial benefit in others. A model based on routinely collected clinical variables can be used to
predict the benefit of ICD treatment, according to a study by Levy et al.[164] Using data from the placebo arm of the Sudden
Cardiac Death in Heart Failure Trial (SCD-HeFT) with their risk prediction model, Levy et al showed that patients could be
classified into five groups on the basis of predicted 4-year mortality. In the treatment arm, ICD implantation decreased the
relative risk of sudden cardiac death by 88% in patients with the lowest baseline mortality risk but only by 24% in the highest-risk
group. ICD treatment decreased relative risk of total mortality by 54% in the lowest-risk group but only by 2% in the highest-risk
group.[164]
It is important to note that use of the SCD-HeFT model has not been prospectively validated for risk stratification in the decision
for ICD implantation. More trials are needed.
Cardiac resynchronization therapy/biventricular pacing
Patients with heart failure and interventricular conduction abnormalities (roughly defined as those with a QRS interval >120 ms)
are potential candidates for cardiac resynchronization therapy (CRT) by means of an inserted biventricular pacemaker. CRT
aims to improve cardiac performance by restoring the heart’s interventricular septal electrical and mechanical synchrony.[5, 165]
Thus, it reduces presystolic mitral regurgitation and optimizes diastolic function by reducing the mismatch between cardiac
contractility and energy expenditure.[166]
The combination of biventricular pacing with ICD implantation (CRT-ICD) may be beneficial for patients with NYHA class II heart
failure, an LVEF of 30% or less, and a QRS duration longer than 150 ms. The Multicenter Automatic Defibrillator Implantation
Trial with Cardiac Resynchronization Therapy (MADIT-CRT) and Resynchronization/Defibrillation for Ambulatory Heart Failure
Trial (RAFT) investigators reported significant improvement in mortality and morbidity with CRT-ICD treatment versus ICD alone
in this group of patients.[167]
Patients with unfavorable coronary sinus anatomy often cannot have a CRT properly placed adjacent to the posterolateral wall
of the LV. A study by Giraldi et al suggests that in such patients, a mini-thoracotomy allows for proper lead placement.[168]
These patients, when compared to those who had typical transvenous placement (thus not allowing for the preferred
posterolateral wall lead placement), had improved outcomes in terms of improved EF and decreased end-systolic volume.[168]
Regarding technique, three cardiac leads are placed transvenously: an atrial lead, an RV lead, and an LV lead (which is
threaded through the coronary sinus and out one of its lateral wall tributaries). Surgeons have assisted difficult transvenous LV
placements by epicardially inserting LV leads using a number of techniques (eg, mini-thoracotomy, thoracoscopy, robotically
assisted methods).
Clinical trials of cardiac resynchronization therapy
Several prospective, randomized trials have been performed to evaluate the effectiveness of CRT. The Multicenter InSync
Randomized Clinical Evaluation (MIRACLE) study group demonstrated an improvement in NYHA functional class, quality of life,
and LVEF.[169]
As noted above, the MADIT-CRT demonstrated reduction in the risk of heart failure events in patients treated with CRT plus an
ICD over that of individuals treated with ICD alone. This randomized trial included 1820 patients with an EF of 30% or less, a
QRS duration of 130 ms or more, and NYHA class I or II symptoms.[170] During an average follow-up of 2.4 years, death from
any cause or a nonfatal heart failure event occurred in 17.2% of patients in the CRT-ICD group versus 25.3% of patients in the
ICD-only group. In particular, there was a 41% reduction in the risk of heart failure events in patients in the CRT group, which
was evident primarily in patients with a QRS duration of 150 ms or more. CRT was associated with a significant reduction in LV
volume and improvement in the EF. No significant difference occurred between the two groups in the overall risk of death.[170]
In a follow-up to MADIT-CRT, women seemed to achieve a better response result from resynchronization therapy than men, with
a significant 69% reduction in death or heart failure and a 70% reduction in heart failure alone. Those benefits were associated
with consistently greater echocardiographic evidence of reverse cardiac remodeling.[171]
Additional findings from MADIT-CRT concerned the relative effects of metoprolol and carvedilol in heart failure patients with
devices in place.[172] The key variables were (a) rate of hospitalization for heart failure or death and (b) incidence of ventricular
arrhythmia.
Treatment with carvedilol yielded a significantly lower rate of hospitalization for heart failure or death than treatment with
metoprolol (23% vs 30%), a reduction that was especially pronounced in patients undergoing CRT with implantable cardioverter-
defibrillator (CRT-D), including those with left bundle-branch block (LBBB).[172] The incidence of ventricular arrhythmia was
26% with metoprolol and 22% with carvedilol. There was a clear dose-dependent relation for carvedilol, which was not seen for
metoprolol.
In addition to augmenting functional capacity, CRT also appears to favorably affect mortality. The Cardiac Resynchronization-
Heart Failure (CARE-HF) trial, which studied CRT placement in patients with NYHA class III or IV heart failure due to LV systolic
dysfunction and cardiac dyssynchrony, showed a 36% reduction in death with biventricular pacing.[173]
In the Comparison of Medical Therapy, Pacing, and Defibrillation in Heart Failure (COMPANION) trial, biventricular pacing
reduced the rate of death from any cause or hospitalization for any cause by approximately 20%. The COMPANION trial was
conducted in patients with NYHA class III or IV heart failure due to ischemic or nonischemic cardiomyopathies and a QRS
interval of at least 120 ms. The addition of a defibrillator to biventricular pacing incrementally increased the survival benefit,
resulting in a substantial 36% reduction in the risk of death compared with optimal pharmacologic therapy.[174]
In both the CARE-HF and the COMPANION studies, mortality was largely due to sudden death.[173, 174]
Noting that high percentages of RV apical pacing could promote LV systolic dysfunction, the investigators from Biventricular
versus Right Ventricular Pacing in Heart Failure Patients with Atrioventricular Block (BLOCK-HF) trial found that biventricular
pacing improved outcomes in patients with AV block and NYHA class I-III heart failure over that of RV pacing.[175] A total of
691 volunteers received a pacemaker or ICD with leads in both ventricles (the LV lead was kept inactive in about half of
participants). At follow-up (average, 37 months), 55.6% of the patients in the RV pacing group had died or had worsening heart
failure, compared with 45.8% in the biventricular pacing group. The rate of adverse events was comparable in the two groups,
and most problems occurred during the first month.[175]
Revascularization Procedures
Coronary artery bypass grafting (CABG) and percutaneous coronary intervention (PCI) are revascularization procedures that
should be considered in selected patients with heart failure and coronary artery disease (CAD). The choice between CABG and
PCI depends on the following factors:
Patient comorbidities
Procedural risk
Coronary anatomy
Likely extent of viable myocardium in the area to be revascularized
Ischemic symptoms
Left ventricular (LV) function
Presence of hemodynamically significant valvular disease
In patients who are at low risk for CAD, findings from noninvasive tests such as exercise electrocardiography (ECG), stress
echocardiography, and stress nuclear perfusion imaging should determine whether subsequent angiography is indicated.[3, 4, 5]
Studies of medical versus surgical therapy for CAD have historically focused on patients with normal LV function. However, a
significantly increased survival rate after CABG in a subset of patients with an LV ejection fraction (EF) below 50%, in
comparison with the survival rate in patients who were randomly selected to receive medical therapy, was demonstrated in the
Veterans Affairs Cooperative Study of Surgery. This survival benefit was particularly evident at the 11-year follow-up point (50%
CABG vs 38% medical therapy).[176] However, at 18-year follow-up, overall survival rates were 30% for the CABG group and
33% for the medical therapy group; the investigators noted that CABG appeared to be effective for reducing mortality solely in
those with a poor natural history and did not reduce the myocardial infarction incidence or combined incidence infarction or
death.[177] Patients with low risk and a good prognosis with medical therapy received no survival benefit with CABG at any
point during the follow-up period.
Surgical revascularization prolonged survival to a greater degree than did medical therapy in most clinical and angiographic
subgroups in the Coronary Artery Surgery Study (CASS) of patients with left main equivalent disease.[178] Of importance, this
study demonstrated that surgical therapy markedly improved the 5-year cumulative survival rate in patients with an EF of less
than 50% (80% vs 47%).[176]
These early randomized trials were limited by their inclusion of patients who had what is currently considered a good EF. That is,
many patients referred for coronary revascularization live with EFs below 35%.
According to a number of studies, surgical revascularization can benefit patients who have ischemic heart failure and substantial
areas of viable myocardium in the following ways:
Reduced mortality rates

Improved New York Heart Association (NYHA) classification
Favorable alteration of LV geometry
Increased LVEFs
For example, surgical revascularization confers a dramatic survival benefit in patients with a substantial amount of hibernating
myocardium (ie, regions of the heart that are dysfunctional under ischemic conditions but that can regain normal function after
blood flow is restored).[179, 180] For patients with at least 5 of 12 segments showing myocardial viability, revascularization has
been found to result in a cardiac mortality of 3%, versus 31% for medically treated patients with viable myocardium.
Coronary artery bypass grafting
The role of CABG in patients with CAD and heart failure has been unclear. Clinical trials from the 1970s that established the
benefit of CABG for patients with CAD excluded patients with an EF below 35%. In addition, major advances in medical therapy
and cardiac surgery have taken place since these trials.[181]
Investigators from Yale University and the University of Virginia, among many others, published their results of CABG in patients
with extremely poor LV function who were on the transplant waiting list. Elefteriades et al reported that in patients with EFs
below 30% who underwent CABG, the survival rate was 80% at 4.5 years.[182] This figure approaches that of cardiac
transplantation. Kron et al reported a similar 3-year survival rate (83%) in patients who underwent coronary artery bypass with
an EF below 20%.[183]
STICH trial
The Surgical Treatment for Congestive Heart Failure (STICH) study found no significant difference between medical therapy
alone and medical therapy plus CABG with respect to death from any cause (the primary study outcome).[181, 184, 185] STICH
included 1212 patients with an EF of 35% or less and CAD amenable to CABG. Patients were randomized to either CABG with
intensive medical therapy or medical therapy alone and followed up for a median of 56 months.
There was no difference between the treatment groups for all-cause mortality.[181] Owing to the lack of significant difference in
the primary endpoint, the secondary endpoints should be viewed cautiously. Except for 30-day mortality, secondary study results
favored CABG; compared with study patients assigned to medical therapy alone, patients assigned to CABG had lower rates of
death from cardiovascular causes and of death from any cause or hospitalization for cardiovascular causes.[181] Surprisingly,
the presence of viable, hibernating myocardium was not predictive of improved outcomes from CABG.[103]
Taken together, these findings suggest that in the absence of severe angina or left main disease, medical therapy alone remains
a reasonable option for patients with an EF of 35% or less and CAD. Furthermore, current methods of assessing myocardial
viability/hibernating myocardium may not accurately predict benefit from revascularization, although cardiac magnetic resonance
imaging offers a promise of accuracy in identifying viable myocardium and predicting the success of revascularization in patients
with low EFs.[100]
Results from the STICH Extension Study (STICHES), which evaluated the long-term, 10-year outcomes of CABG in 1212
patients with ischemic cardiomyopathy and an ejection fraction of 35% or less, concluded that the rates of death from any
cause, death from cardiovascular causes, and death from any cause or hospitalization for cardiovascular causes were
significantly lower in patients who underwent CABG and received medical therapy than among those who received medical
therapy alone.[143]
The adoption of techniques on and off cardiopulmonary bypass, as well as beating-heart techniques for revascularization,
highlight the aim of treating high-risk patients.[186] The surgery in the STICH trial was performed with these modern surgical
advantages. Preventive strategies include the increased use of bilateral mammary and arterial grafting.[187]
Valvular Surgery
Valvular heart disease may be the underlying etiology or an important aggravating factor in heart failure.[3, 4, 5]
Aortic valve replacement
Diseases of the aortic valve can frequently lead to the onset and progression of heart failure. Although the natural histories of
aortic stenosis and aortic regurgitation are well known, patients are often followed up conservatively after they present with
clinically significant heart failure.
Heart failure is a common indication for aortic valve replacement (AVR), but one must be cautious in patients with a low left
ventricular ejection fraction (LVEF) and possible aortic stenosis. Assessment of contractile reserve with dobutamine has been
demonstrated as a reliable method to determine which patients with low EF and aortic stenosis may benefit from AVR.[188]
If no contractile reserve is present (a finding that suggests some ventricular reserve), the outcome with standard AVR is poor. In
this situation, transplantation might be the only option, although the use of percutaneous valves, an apical aortic conduit, or a
left ventricular assist device (LVAD) may offer an intermediate solution.
Indications
Decision making regarding valve surgery should not be delayed by medical treatment. Be cautious in using vasodilators
(angiotensin-converting enzyme inhibitors [ACEIs], angiotensin-receptor blockers [ARBs], and nitrates) in patients with severe
aortic stenosis, as these agents may cause significant hypotension.[3, 4, 5, 56]
Surgery is recommended in selected patients with symptomatic heart failure and severe aortic stenosis or severe aortic
regurgitation, as well as in asymptomatic patients with severe aortic stenosis or severe aortic regurgitation and impaired LVEF
(< 50%). This intervention may be considered in patients with a severely reduced valve area and LV dysfunction.
Patient survival
Of the three classic symptoms of aortic stenosis—syncope, angina, and dyspnea—dyspnea is the most robust risk factor for
death. Only 50% of patients with dyspnea in this setting are still alive within 2 years.[189] Angina is associated with a mortality
risk of 50% within 5 years, whereas syncope confers a 50% mortality risk in 3 years.
In contrast, the age-corrected survival rate for patients undergoing AVR for aortic stenosis is similar to that for the normal
population.[190] Once patients develop severe LV dysfunction, however, the results of AVR are somewhat guarded.[191]
Because of poor LV function, these patients are unable to develop significant transvalvular gradients (ie, low-output, low-
gradient aortic stenosis).
A critical aspect of the decision for or against AVR is whether the ventricular dysfunction is truly valvular or reflects other forms
of cardiomyopathy, such as ischemia or restrictive processes. Valvular dysfunction improves with AVR; other forms do not.
Precise measurement of the area of the aortic valve is difficult, because the calculated area is directly proportional to cardiac
output. Also, the Gorlin constant varies at lower outputs. Therefore, in this situation, valvular areas might be considered critically
small when at surgery the valve is found to be only moderately diseased.
Preoperative evaluation with dobutamine testing to increase contractile reserve or with vasodilator-induced stress
echocardiography by using the continuity equation rather than the Gorlin formula can be helpful in making this distinction. The
results can guide the physician or surgeon in determining whether the patient is a candidate for the relatively high-risk
procedure.[192] Nevertheless, because of the possibility of ventricular recovery and lengthened patient survival, most patients
with heart failure and aortic stenosis are offered valve replacement.[193]
Surgical timing
Timing of surgical intervention for aortic insufficiency is more challenging in patients just described than in patients with aortic
stenosis. However, as before, once symptoms occur and once evidence of LV structural changes become apparent, morbidity
and mortality due to aortic insufficiency increase.[194]
As with aortic stenosis, early intervention before the onset of severe LV dysfunction is crucial to improving the survival of
patients with aortic insufficiency, as was shown in a retrospective review from the Mayo Clinic.[195, 196] In this study, in which
450 patients who underwent AVR for aortic insufficiency were compared according to ranges of EF (< 35%, 35-50%, >50%),
although the group with severe dysfunction had an operative mortality of 14%, the EF improved, and the group's 10-year
survival rate was 41%.[195, 196]
Mitral valve repair
Mitral valve regurgitation can either cause or result from chronic heart failure. Its presence is an independent risk factor for
cardiovascular morbidity and mortality.[197] In addition to frank rupture of the papillary muscle in association with acute
myocardial infarction (MI), chronic ischemic cardiomyopathies result in migration of the papillary muscle as the ventricle dilates.
This dilation causes tenting of the mitral leaflets, restricting their coaptation.
Dilated cardiomyopathies can have similar issues, as well as annular dilatation. In addition to mitral regurgitation, the alteration
in LV geometry contributes to volume overload, increases LV wall tension, and leaves patients susceptible to exacerbations of
heart failure.[198]
Mitral valve surgery in patients with heart failure has gained favor because it abolishes the regurgitant lesion and decreases
symptoms. The pathophysiologic rationales for repair or replacement are to reverse the cycle of excessive ventricular volume, to
allow for ventricular unloading, and to promote myocardial remodeling.
Among other researchers, a group from Michigan advocated mitral repair in the population with heart failure. Bolling and
colleagues demonstrated that mitral valve repair increased the EF, improved NYHA classes from 3.9 to 2.0, and decreased the
number of hospitalizations, although the results were reproducible by other centers.[199] Additional effects with repair in these
patients were an increase in coronary blood flow reserve afforded by the reduction in LV volume.[200]
Despite the potential benefits of mitral reconstruction surgery, a retrospective review showed no reduction in long-term mortality
among patients with severe mitral regurgitation and significant LV dysfunction who underwent mitral valve repair.[201] Mitral
valve annuloplasty was not predictive of clinical outcomes and did not improve mortality. Factors associated with lower mortality
were ACEI use, beta blockade, normal mean arterial pressures, and normal serum sodium concentrations.[201] The results of
this analysis were not overly surprising. For example, in most patients in this situation, heart failure is not due to flail leaflets but
is secondary to ventricular dysfunction.
In evaluating studies of heart failure with mitral regurgitation, it is important to separate the etiology (eg, ischemic vs dilated) as
well as the surgical approaches. Future trials must be designed to distinguish differences between various surgical strategies,
such as annuloplasty, resuspension of the papillary muscle, secondary chordal transection, ventricular reconstruction, passive
restraints, and chordal-sparing valve replacement. A paramount goal with these procedures is for the patient to have little or no
residual mitral regurgitation.[202]
Indications
Consider mitral valve surgery in patients with heart failure and severe mitral valve regurgitation whenever coronary
revascularization is an option.[4] Candidates would include the following[4] :
Patients with severe mitral regurgitation due to an organic structural abnormality or damage to the mitral valve in whom
symptoms of heart failure develop
Patients with an LVEF greater than 30%
Patients with severe ischemic mitral regurgitation and an LVEF greater than 30% when coronary artery bypass grafting
(CABG) is planned
Cardiac resynchronization therapy (CRT) should be considered in eligible patients with functional mitral regurgitation, as it may
improve LV geometry and papillary muscle dyssynchrony as well as potentially reduce mitral regurgitation.[4]
Annuloplasty
Treatment of cardiomyopathy-associated mitral regurgitation most commonly involves the insertion of either a complete or a
partial band attached to the annulus of the mitral valve. Thus, mitral repair deals with only one aspect of the patient's overall
pathophysiologic condition. That is, annuloplasty rings may assist with tenting of the leaflet, but they do not address
displacement of the papillary muscle with ventricular scarring.[203] In many patients, the underlying problem (ie, primary
myopathy) continues unabated.
In general, ischemic mitral regurgitation is a ventricular problem. Many operations allow for coaptation and no mitral
regurgitation when the patient leaves the operating room. However, as the LV continues to dilate, mitral regurgitation often
recurs. Therefore, it is overambitious to say that annuloplasty cures this condition. As a result, many other approaches have
been attempted (eg, chordal cutting, use of restraint devices, papillary relocation). However, results have been mixed.
Mitral valve replacement
If repair is deemed improbable, mitral replacement should be performed. Traditional mitral valve replacement includes complete
resection of the leaflets and the chordal attachments. This destruction of the subvalvular apparatus results in ventricular
dysfunction. In patients with mitral regurgitation and heart failure, preservation of the chordal attachments to the ventricle with
valve replacement might provide results similar to, or even better than, those of annuloplasty.[204, 205]
Although the benefits in terms of quality of life (decreased heart failure) might not portend increased survival in these high-risk
patients,[206, 207] they likely keep low-EF mitral valve interventions in the armamentarium of surgeons who manage heart
failure.
A relatively recent approach to functional and degenerative mitral valve regurgitation is percutaneous mitral valve repair,[208,
209] using devices such as the MitraClip system. The EVEREST (Endovascular Valve Edge-to-Edge Repair Study II)
randomized trial reported low rates of morbidity and mortality and reduction of acute mitral regurgitation to less than 2+ in the
majority of patients, with sustained freedom from death, surgery, or recurrent mitral regurgitation in a substantial proportion of
patients.[210]
A systematic review and meta-analysis of data from 2615 patients over nine studies found that percutaneous edge-to-edge
mitral valve repair with the MitraClip is likely to be a safe and effective option in patients with both functional and degenerative
mitral regurgitation.[211] Similarly, data from the German Transcatheter Mitral Valve Interventions (TRAMI) Registry found
comparable MitraClip results for procedural safety of percutaneous mitral valve repair, efficacy, and clinical improvement after 1
year between patients with severely impaired LVEF (EF < 30%) and those with preserved LV function (EF >50%).[212] Over two
thirds (69.5%) of those with an EF below 30% improved by one or more NYHA functional class, a significantly higher proportion
than the 56.8% of patients with preserved LV function whose NYHA class improved (P< 0.05).
Ventricular Restoration
After a transmural myocardial infarction (MI) occurs, the ventricle pathologically remodels from its normal elliptical shape to a
spherical shape. This change in geometry is in part responsible for the constellation of symptoms associated with heart failure
and decreased survival.[213, 214]
Several ventricular restoration techniques exist. All aim to correct the above-described pathologic alteration in geometry. Most
approaches involve incising and excluding nonviable myocardium with either patch or primary reconstruction to decrease
ventricular volume.
The Batista procedure (reduction left ventriculoplasty) was designed with the intent of providing ventricular restoration, but it was
associated with high failure rates. Although the initial enthusiasm for ventricular resection to treat nonischemic dilated
cardiomyopathies has faded, a long-established finding is that resection of dyskinetic segments associated with left ventricle
(LV) aneurysms can increase patients' functional status and prolong life.[215, 216]
The success of early lytic and percutaneous therapy for acute MI has decreased the incidence of true LV aneurysms. As such,
ventricular restoration now focuses on excluding relatively subtle regions of akinetic myocardium.
Benefits from ventricular restoration using the technique described by Dor were reported in by the International Reconstructive
Endoventricular Surgery Returning Torsion Original Radius Elliptical Shape to the Left Ventricle (RESTORE) group.[217] The
investigators reported that among the patients studied, ejection fractions (EFs) increased from 29.6% to 39.5%, the end-systolic
volume index decreased, and New York Heart Association (NYHA) functional classes improved from 67% class III/IV patients
before surgery to 85% class I/II patients after surgery.[217]
The major study of ventricular reconstruction has been the STICH trial.[218] Investigators randomly assigned 1000 patients with
an EF below 35%, coronary artery disease that was amenable to coronary artery bypass grafting (CABG), and dominant
anterior LV dysfunction that was amenable to surgical ventricular reconstruction to undergo either CABG alone or CABG with
surgical ventricular reconstruction (SVR) and found that SVR reduced the end-systolic volume index by 19%, as compared with
a reduction of 6% with CABG alone. The median follow-up was 48 months. Cardiac symptoms and exercise tolerance improved
to a similar degree in both groups. However, no significant difference was observed in death from any cause and hospitalization
for cardiac causes.[218] On the basis of these results, SVR cannot be recommended for routine use in patients with ischemic
cardiomyopathy and dominant anterior left ventricular dysfunction.
Extracorporeal Membrane Oxygenation

In some cases of extreme cardiopulmonary failure (ie, American College of Cardiology/American Heart Association [ACC/AHA]
stage D), the only recourse is complete support with extracorporeal membrane oxygenation (ECMO). ECMO provides both
oxygenation and circulation of blood, allowing the lungs and heart time to recover.[142] Unlike cardiopulmonary bypass, whose
duration of use is measured in hours, ECMO can be used for 3-10 days.
For ECMO, one cannula is placed percutaneously via the right jugular vein or femoral vein into the right atrium, or it is placed
surgically into the right atrial appendage, and another cannula is placed arterially either in the femoral artery or in the aortic arch.
The drained venous blood is pumped through the ECMO device, where it is oxygenated, warmed, and anticoagulated. It is then
returned to the arterial circulation.
ECMO devices can be used for short-term circulatory support in patients who are expected to recover from a major cardiac
insult. Despite encouraging results with ECMO for the management of cardiogenic shock, most patients requiring circulatory
assistance can be helped with ventricular support alone.
Ventricular Assist Devices

Ventricular assist devices (VADs) are invaluable tools in the treatment of heart failure, particularly in those with advanced heart
failure.[272] A number of these devices are available to support the acutely or chronically decompensated heart (ie, American
College of Cardiology/American Heart Association [ACC/AHA] stage D). Depending on the particular device used, the right
ventricle (RV) and left ventricle (LV) can be assisted with a LV assist device (LVAD), a RVAD, or a biventricular assist device
(BiVAD). An alternative term for a VAD is a ventricular assist system (VAS).[219, 220]
In concept, LVADs, RVADs, and BiVADs are similar. Blood is removed from the failing ventricle and diverted into a pump that
delivers blood to either the aorta (in the case of an LVAD) or the pulmonary artery (in the case of an RVAD). An exception is the
Impella device, which is inserted percutaneously into the LV; it draws blood from the LV and expels it into the ascending aorta.
LVADs can often be placed temporarily. In patients with acute, severe myocarditis or those who have undergone cardiotomy, this
approach can serve as a bridge to recovery, unloading the dysfunctional heart and perhaps allowing reverse remodeling; in
patients with end-stage heart failure, it can serve as a bridge to heart transplantation,[3, 4, 5, 105] allowing them to undergo
rehabilitation and possibly go home before transplantation.
Long-term use (ie, destination therapy rather than bridge therapy) may be a consideration when no definitive procedure is
planned.[4] Patients with severe heart failure who are not transplant candidates and who otherwise would die without treatment
are candidates for lifetime use of VADs. Destination therapy with LVADs is superior to medical therapy in terms of quantity and
quality of life, according to the Randomized Evaluation of Mechanical Assistance for the Treatment of Congestive Heart Failure
(REMATCH) trial and several later studies.[221, 222]
In the United States, several Food and Drug Administration (FDA)–approved options are available for bridging the patient to
recovery and transplantation. These options continue to change and evolve. Some examples include the following:
Abiomed AB5000 Ventricle

AB Portable Driver
Thoratec CentriMag Blood Pump
Thoratec PVAD (Paracorporeal Ventricular Assist Device)
Thoratec IVAD (Implantable Ventricular Assist Device)
HeartMate XVE LVAD (also known as HeartMate I)
HeartMate II LVAS
TandemHeart Percutaneous LVAD
HeartAssist 5 Pediatric VAD
The HeartMate LV and HeartWare HVAD[223] assist systems are the only LVADs that are approved by the US Food and Drug
Administration (FDA) for destination therapy. Other devices are also under study in the United States for use as destination
therapy (eg, Jarvik 2000 VAS[224] ).
The HeartMate XVE LVAD does not require warfarin anticoagulation, unlike another well-known first-generation pulsatile pump,
the Novacor LVAD. The newer axial-flow pumps (eg, HeartMate II LVAS, Jarvik 2000, HeartAssist 5 Pediatric VAD) are relatively
small and easy to insert, and they reduce morbidity; however, these devices do require anticoagulation.
Potential complications of VADs include mechanical breakdown, infection, bleeding, and thromboembolic events. Despite these
potential drawbacks, however, the survival rate for patients receiving VADs is roughly 70%. This rate is impressive given the
severity of illness in this cohort of patients. Furthermore, the evolving technology raises a host of clinical and physiologic
questions that, when studied and answered, continue to advance the field.
Selected trials
In the REMATCH study, survival rates of medically treated and LVAD-treated patients were, respectively, 25% and 52% at 1 year
and 8% and 23% at 2 years.[225] This study offered the first prospective, randomized data of very ill, non–transplant-eligible
patients with heart failure receiving optimal medical therapy versus an early-generation HeartMate LVAD. In addition to survival
advantage, LVAD recipients had improvements in several measures of quality of life.
Modifications in technique and perioperative care have reduced the rates of LVAD-related morbidity and mortality observed in
the REMATCH trial.[226] Although REMATCH was a single study in very high risk patients, the data serve as proof of concept
for the future development of VAD technologies.
Despite the need for an external energy source, most patients can use mechanical circulatory devices in the outpatient setting.
Many patients have lived productive lives for longer than 4-6 years with their original device (depending on the device).
Starling et al used INTERMACS (Interagency Registry for Mechanically Assisted Circulatory Support) data to determine that
following postmarket approval by the FDA, the HeartMate II LVAS, a continuous-flow LVAD, continues to have excellent results
as a bridge to heart transplantation relative to other types of LVADs in the following measures[227] :
The 30-day operative mortality was 4% for the group receiving the HeartMate II compared with 11% for other LVADs
Ninety-one percent of the group receiving the HeartMate II reached transplantation, cardiac recovery, or ongoing LVAD
support by 6 months, compared with 80% for the group receiving other LVADs
Renal function test measurements such as creatinine and blood urea nitrogen levels were lower in the HeartMate II
group
For all adverse events, the rates were similar or lower for the group that received the HeartMate II, with bleeding being
the most frequent adverse event for both groups
Survival for patients remaining on support at 1 year was 85% for the HeartMate II group, versus 70% for the group with
other LVADs
Relative to baseline, both groups had significant improvement of quality of life at 3 months of support, which was
sustained through 12 months
In another study, Ventura et al used a large national data registry to compare posttransplant outcomes between pulsatile-flow
(HeartMate XVE [HeartMate I]) and continuous-flow (HeartMate II) LVADs as bridges to transplantation and found similar 1- and
3-year survival rates but less risk of early allograft rejection and sepsis with the HeartMate II device.[228]
Patients with class IV stage D heart failure who are symptomatic despite optimal medical heart failure therapy for 45 of 60 days
or who require inotropic support for 14 days or intra-aortic balloon pump (IABP) support for 7 days and have no contraindication
for anticoagulation are eligible for implantation on LVAD HM II as destination therapy if they are not eligible for or do not desire
cardiac transplantation. The INTERMACS registry has established a patient profile (1-7) that determines urgency to implantation
and assesses risk and survival at 90 days.
Recommendations for clinical management of continuous-flow LVAD assist providers with standardized care for this patient
population.[229] Bleeding, infection, and stroke are postimplantation complications, and death may occur due to right heart
failure, sepsis, or stroke. A multidisciplinary approach to LVAD implantation is needed, as destination therapy identifies patients
at high risk for complications and the need to optimize these patients medically before surgery. In a report from INTERMACS, 1-
year survival for destination-therapy patients was 61% for pulsatile devices and 74% for continuous-flow devices.[230]
Heart Transplantation
Selected patients with severe heart failure, debilitating refractory angina, ventricular arrhythmia, or congenital heart disease that
cannot be controlled despite pharmacologic, medical device, or alternative surgical therapy should be evaluated for heart
transplantation.[5] The patient must be well informed, motivated, and emotionally stable; have a good social support network;
and be capable of complying with intensive medical treatment.[4]
Since Christiaan Barnard performed the first orthotopic heart transplantation in 1967, the world has seen tremendous
advancement in the field of cardiac transplantation. For patients with progressive end-stage heart failure despite maximal
medical therapy who have a poor prognosis and no viable alternative form of treatment,[4] heart transplantation has become the
criterion standard for therapy.[3]
Compared to patients who receive only medical therapy, transplant recipients have fewer rehospitalizations; marked functional
improvements; enhanced quality of life; more gainful employment; and longer survival, with 50% surviving 10 years
postoperatively.[231] Heart transplantation is associated with a 1-year survival rate of 83%; subsequently, survival decreases in
a linear manner by approximately 3.4% per year.
Careful selection of donors and recipients is critical for ensuring good outcomes. In addition, transplant teams must strive to
minimize potential perioperative dangers, including ischemic times, pulmonary hypertension, mechanical support, and
cardiogenic shock.
For more information, see the Medscape Drugs and Diseases article Heart Transplantation.
Indications
Absolute indications for heart transplantation include hemodynamic compromise following heart failure, such as in the following
scenarios[3] :
Refractory cardiogenic shock

Dependence on intravenous (IV) inotropic support for adequacy of organ perfusion
Peak oxygen consumption per unit time (VO 2) below 10 mL/kg/min
Severe ischemic symptoms with consistent limitations of routine activity that are not amenable to revascularization
procedures (coronary artery bypass grafting [CABG], percutaneous coronary intervention [PCI])
Recurrent symptomatic ventricular arrhythmias despite all therapeutic interventions
Relative indications for heart transplantation include the following[3] :
Peak VO 2 between 11 and 14 mL/kg/min (or 55% of predicted) with major limitation of routine activities
Recurrent unstable ischemia that is not amenable to other treatment
Recurrent instability of fluid balance/renal function despite patient compliance with medical therapy
In the absence of other indications, however, the following are not sufficient indications for heart transplantation[3] :
Low left ventricular ejection fraction (LVEF)

History of New York Heart Association (NYHA) class III/IV heart failure symptoms
Peak VO 2 above 15 mL/kg/min (and >55% predicted)
Contraindications
Heart transplantation is contraindicated in patients with the following conditions[4] :
Active infection
Severe peripheral arterial or cerebrovascular disease
Irreversible pulmonary hypertension
Active malignancy
Significant renal failure (creatinine clearance < 30 mL/min)
Systematic disease with multiorgan involvement
Other serious comorbidity with a poor prognosis
Body mass index (BMI) avove 35 kg/m 2
Current alcohol or drug use
Insufficient social supports to achieve compliant care
Note that the Heart Failure Society of America (HFSA) indicates that cardiomyoplasty and partial left ventriculectomy (Batista
operation) is not recommended to treat heart failure, nor should it be used as an alternative to heart transplantation.[5]
Coronary graft atherosclerosis
The Achilles heel of the long-term success of heart transplantation is the development of coronary graft atherosclerosis, the
cardiac version of chronic rejection. Coronary graft atherosclerosis is uniquely different from typical coronary artery disease in
that it is diffuse and is usually not amenable to revascularization.
Shortage of donor hearts
In the United States, fewer than 2500 heart transplantation procedures are performed annually[232, 233] ; between January
1988 and September 2017, an average of 2350 people received heart transplants per year.[233] Each year, an estimated 10-
20% of patients die while awaiting a heart transplant. Of the 5 million people with heart failure, approximately 30,000 to 100,000
have such advanced disease that they would benefit from transplantation or mechanical circulatory support.[234] This disparity
between the number of patients needing transplants and the availability of heart donors has refocused efforts to find other ways
to support severely failing hearts.
Total Artificial Heart

The creation of a suitable total artificial heart (TAH) for orthotopic implantation has been the subject of intense investigation for
decades.[235] In 1969, Dr Denton Cooley implanted the Liotta TAH (which is no longer made) into a high-risk patient after failing
to wean the patient off cardiopulmonary bypass after left ventricular (LV) aneurysm repair. The patient was sustained until a
donor heart became available after 3 days, but the patient subsequently died of pneumonia and multiple organ failure.[236]
Compared with LV assist devices (LVADs), the TAH has several potential advantages, including the ability to assist patients with
severe biventricular failure; a lack of device pocket and thus a lessened risk of infection; and the opportunity to treat patients
with systemic diseases (eg, amyloidosis, malignancy) who are not otherwise candidates for transplantation.[237, 238, 239, 240,
241]
Two TAHs have received the most attention:
SynCardia (formerly CardioWest) TAH

AbioCor TAH
The SynCardia TAH is a structural cousin of the original Jarvik-7 TAH that was implanted into patient Barney Clark with great
publicity in 1982. In 2004, investigators reported data that allowed this device to receive FDA approval for use as a bridge to
transplantation.
The AbioCor TAH involves a novel method of transcutaneous transmission of energy, freeing the patient from external
drivelines. The patient exchanges the external battery packs, which can last as long as 4 hours. This TAH is unique in that it is
the first TAH to use coils to transmit power across the skin; therefore, no transcutaneous conduits are needed. This feature
allows for the advantages of a closed system, which potentially reduces sources of infection, a known complication of earlier
devices.
The first clinical implantation of the AbioCor TAH was performed in July 2001. Before the end of 2004, 14 patients had received
this device as part of a trial in patients whose expected survival was less than 30 days. Although all subsequently died, 4
patients were ambulatory after surgery, and 2 were discharged from the hospital to a transitional-care setting. One of the
discharged patients was discharged on postoperative day 209. A limitation of the AbioCor TAH is its large size, which permits its
implantation in only 50% of men and 20% of women. In 2006, the FDA approved the Abiocor TAH as a permanent TAH for
humanitarian uses.
The SynCardia and AbioCor TAHs require recipient cardiectomy before implantation. The devices are similar in that they are
sewn to atrial cuffs and to the great vessels after the native heart is explanted.
A European study involving the CARMAT TAH is evaluating survival on this device of patients with advance heart failure at 180
days postimplant or survival to cardiac transplantion if occurring before 180 days postimplant.[242]
Despite several decades of effort, the clinical application of artificial-heart technology remains immature. However, with the
approval of the SynCardia and AbioCor devices as well as with new efforts to create small pumps, TAHs will ultimately be
routine components of heart failure surgery for very sick patients with heart failure and biventricular failure.
Guidelines
Guidelines Summary
Heart Failure Criteria, Classification, and Staging
Guideline contributor: Henry H Ooi, MD, MRCPI, Director, Advanced Heart Failure and Cardiac Transplant Program, Nashville
Veterans Affairs Medical Center; Assistant Professor of Medicine, Vanderbilt University School of Medicine.
Heart failure criteria, classification, and staging
In the Framingham classification, the diagnosis of heart failure is based on the concurrent presence of either two major
criteria or one major and two minor criteria.[1]
Major criteria comprise the following:

Weight loss of 4.5 kg or more in 5 days in response to treatment
Rales
S 3 gallop
Central venous pressure greater than 16 cm water
Circulation time of 25 seconds or longer
Pulmonary edema, visceral congestion, or cardiomegaly at autopsy
Minor criteria (accepted only if they cannot be attributed to another medical condition) are as follows:
Nocturnal cough
Dyspnea on ordinary exertion
A decrease in vital capacity by one third the maximal value recorded
Pleural effusion
Tachycardia (rate of ≥120 bpm)
Hepatomegaly
Bilateral ankle edema
The New York Heart Association (NYHA) functional classification of heart failure is widely used in practice and in clinical studies.
It is based on symptom severity and the amount of exertion needed to provoke symptoms. NYHA heart failure classes are as
follows[2] :
Class I: No limitation of physical activity

Class II: Slight limitation of physical activity, in which ordinary physical activity leads to fatigue, palpitation, or dyspnea;
the person is comfortable at rest
Class III: Marked limitation of physical activity, in which less-than-ordinary activity results in fatigue, palpitation, or
dyspnea; the person is comfortable at rest
Class IV: Inability to carry on any physical activity without discomfort but also symptoms of heart failure at rest, with
increased discomfort if any physical activity is undertaken
The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) staging system complements the
NYHA classification to reflect the progression of disease and comprises four stages, as shown in Table 1. below.[3]
Table 5. American College of Cardiology Foundation/American Heart Association (ACCF/AHA) heart failure staging system
(Open Table in a new window)
Level Description Examples Notes
At high risk for

Patients with coronary artery disease, Patients with predisposing risk factors for
heart failure but
hypertension, or diabetes mellitus developing heart failure
without structural
A without impaired left ventricular (LV)
heart disease or
function, LV hypertrophy (LVH), or No corresponding New York Heart Association
symptoms of heart
geometric chamber distortion (NYHA) functional classification
failure
Structural heart
disease but Patients who are asymptomatic but
B without who have LVH and/or impaired LV Corresponds with patients with NYHA class I
signs/symptoms function
of heart failure
Structural heart
Patients with known structural heart The majority of patients with heart failure are in
disease with
disease and shortness of breath and this stage
C current or past
fatigue, as well as reduced exercise
symptoms of heart
tolerance Corresponds with NYHA classes I, II, III and IV
failure
Patients in this stage may be eligible to receive

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

Heart Rhythm Society (HRS) and the European Heart Rhythm Association (EHRA) select
recommendations for genetic testing for channelopathies and cardiomyopathies
Long QT syndrome (LQTS)[249]
Comprehensive or LQT1-3 (KCNQ1, KCNH2, and SCN5A)–targeted LQTS genetic testing is recommended for the following:
Individuals with a strong clinical index of suspicion for LQTS based on the patient's clinical history, family history, and
expressed electrocardiographic (ECG) (resting 12-lead ECGs and/or provocative stress testing with exercise or
catecholamine infusion) phenotype
Asymptomatic individuals with idiopathic QT prolongation on serial 12-lead ECGs defined as QTc over 480 ms
(prepuberty) or longer than 500 ms (adults); may also be considered in asymptomatic individuals with idiopathic QT
prolongation on serial 12-lead ECGs for QTc values over 460 ms (prepuberty) or longer than 480 ms (adults)
Mutation-specific genetic testing is recommended for family members following identification of the LQTS mutation in an index
case.
Catecholaminergic polymorphic ventricular tachycardia (CPVT)[249]
Comprehensive or CPVT1 and CVPT2 ( RYR2 and CASQ2)–targeted CPVT genetic testing is recommended for any
individual with a clinical index of suspicion for CPVT based on the patient's clinical history, family history, and expressed
ECG phenotype during provocative stress testing with cycle, treadmill, or catecholamine infusion.
Mutation-specific genetic testing is recommended for family members following identification of the CPVT mutation in an
index case.
Brugada syndrome (BrS)[249]
Consider comprehensive or BrS1 ( SCN5A)–targeted BrS genetic testing for individuals with a clinical index of suspicion
for BrS based on the patient's clinical history, family history, and expressed ECG (resting 12-lead ECGs and/or
provocative drug challenge testing) phenotype.
Mutation-specific genetic testing is recommended for family members following identification of the BrS mutation in an
index case.
Genetic testing is not indicated in individuals with an isolated type 2 or type 3 Brugada ECG pattern.
Cardiac conduction disease (CCD)[249]
Consider genetic testing as part of the diagnostic evaluation for individuals with either isolated CCD or CCD with
concomitant congenital heart disease, particularly in cases of a documented positive family history of CCD.
Mutation-specific genetic testing is recommended for family members following identification of the CCD mutation in an
index case.
Short QT syndrome (SQTS)[249]
Consider comprehensive or SQT1-3 ( KCNH2, KCNQ1, and KCNJ2)–targeted SQTS genetic testing for individuals with a
clinical index of suspicion for SQTS based on the patient's clinical history, family history, and ECG phenotype.
Mutation-specific genetic testing is recommended for family members following identification of the SQTS mutation in an
index case.
Hypertrophic cardiomyopathy (HCM)[249]
Comprehensive or targeted ( MYBPC3, MYH7, TNNI3, TNNT2, TPM1) HCM genetic testing is recommended for
individuals with a clinical diagnosis of HCM based on the patient's clinical history, family history, and
ECG/echocardiographic phenotype.
Mutation-specific genetic testing is recommended for family members following identification of the HCM mutation in an
index case.
Arrhythmogenic cardiomyopathy (ACM) / arrhythmogenic right ventricular cardiomyopathy (ARVC)[249]
Comprehensive or targeted ( DSC2, DSG2, DSP, JUP, PKP2, and TMEM43) ACM/ARVC genetic testing can be
useful for individuals who fulfill the task force diagnostic criteria for ACM/ARVC.
Consider genetic testing for patients with possible ACM/ARVC (1 major or 2 minor criteria) based on the 2010 task force
criteria. [243]
Mutation-specific genetic testing is recommended for family members following identification of the ACM/ARVC mutation
in an index case.
Genetic testing is not recommended for patients with only a single minor criterion according to the 2010 task force
criteria. [243]
Dilated cardiomyopathy (DCM)[249]
Comprehensive or targeted ( LMNA and SCN5A) DCM genetic testing is recommended for individuals with
DCM and significant cardiac conduction disease (ie, first-, second-, or third-degree heart block) and/or a family history of
premature unexpected sudden death.
Mutation-specific genetic testing is recommended for family members following identification of the DCM mutation in an
index case.
Genetic testing can be useful for individuals with familial DCM to confirm the diagnosis, identify those at highest risk of
arrhythmia/syndromic features, facilitate cascade screening among family members, and aid in family planning.
Left ventricular noncompaction (LVNC)[249]
Genetic testing may be useful for individuals with a clinical diagnosis of LVNC based on the patient's clinical history,
family history, and ECG/echocardiographic phenotype
Mutation-specific genetic testing is recommended for family members following identification of the LVNC mutation in an
index case.
Restrictive cardiomyopathy (RCM)[249]
Consider genetic testing for individuals with a suspected clinical diagnosis of RCM based on the patient's clinical history,
family history, and ECG/echocardiographic phenotype.
Mutation-specific genetic testing is recommended for family members following identification of the RCM mutation in an
index case.
2013 ACCF/AHA guidelines for screening and genetic testing for DCM
Familial DCM (DCM with 2 close relatives who meet the criteria for idiopathic DCM)[3]
First-degree relatives not known to be affected should undergo periodic, serial echocardiographic screening with
assessment of LV function and size.
Although the screening frequency is uncertain, every 3-5 years is reasonable.
Consider genetic testing in conjunction with genetic counseling.
Idiopathic DCM[3]
Inform first-degree relatives of index diagnosis.

Relatives should discuss with their clinicians whether they should undergo echocardiographic screening.
Although the value of genetic testing is unclear in this setting, it is potentially valuable in patients with significant cardiac
conduction disease and/or a family history of premature sudden cardiac death.
Heart Failure Society of America (HFSA) recommendations for genetic evaluation of cardiomyopathy
Note the following[5] :
For all patients with cardiomyopathy, obtain a detailed family history for at least 3 generations (HCM, DCM, arrhythmic
right ventricular dysplasia [ARVD], LVNC, RCM, and cardiomyopathies associated with extracardiac manifestations)
Carefully assess the patient's medical history as well as that of asymptomatic first-degree relatives, with special focus on
heart failure symptoms, arrhythmias, presyncope, and syncope.
Screen asymptomatic first-degree relatives for cardiomyopathy (HCM, DCM, ARVD, LVNC, RCM, and cardiomyopathies
associated with extracardiac manifestations)
Screen for cardiomyopathy at intervals in asymptomatic at-risk relatives who are known to carry the disease-causing
mutation(s) (For details, see Recommendations 17.2e and 17.2f in HFSA Guideline Approach to Medical Evidence for
Genetic Evaluation of Cardiomyopathy [5] )
Screen for cardiomyopathy in asymptomatic at-risk first-degree relatives who have not undergone genetic testing or in
whom a disease-causing mutation has not been identified.
Note: Due to the complexity of genetic evaluation, testing, and counseling of patients with cardiomyopathy, it is recommended
that patients be referred to centers with expertise in these matters and in family-based management.[5]
Diagnostic Procedures
Guidelines for the diagnosis and management of heart failure have been issued by the following organizations:
American College of Cardiology Foundation/American Heart Association (ACCF/AHA) [3]

Heart Failure Society of America (HFSA) [5]
European Society of Caridiology (ESC) [4]
The 2013 ACCF/AHA guidelines and its 2017 ACC/AHA/HFSA focused update,[3, 56] 2010 HFSA guidelines,[5] and 2016
ESC guidelines [4] all recommend the following basic laboratory tests and studies in the initial evaluation of patients with
suspected heart failure:
Complete blood count (CBC), which may indicate anemia or infection as potential causes of heart failure
Urinalysis (UA), which may reveal proteinuria, which is associated with cardiovascular disease
Serum electrolyte levels, which may be abnormal owing to causes such as fluid retention or renal dysfunction
Blood urea nitrogen (BUN) and creatinine levels, which may indicate decreased renal blood flow
Fasting blood glucose levels, because elevated levels indicate a significantly increased risk for heart failure (diabetic and
nondiabetic patients
Liver function tests (LFTs), which may show elevated liver enzyme levels and indicate liver dysfunction due to heart
failure
Electrocardiography (ECG) (12-lead), which may reveal arrhythmias, ischemia/infarction, and coronary artery disease as
possible causes of heart failure
In addition, these guidelines recommend measuring B-type natriuretic peptide (BNP) and N-terminal pro-B-type (NT-proBNP)
natriuretic peptide levels, which are increased in heart failure.[3, 4, 5, 56] Baseline measurements correlate closely with the New
York Heart Association (NYHA) heart failure functional classification and can be useful for prognosis in acutely decompensated
patients.[56] The ACCF/AHA, HFSA, and ESC also indicate obtaining BNP or NT-proBNP levels in the workup of heart failure
particularly when the diagnosis is unclear.[3, 4, 5] The HFSA recommends this test in all cases of suspected heart failure,
particularly in ambiguous cases.[5]
The ACC/AHA recommendations also include obtaining a lipid profile and thyroid stimulating hormone (TSH) level.[3] These
tests reveal potential cardiovascular or thyroid disease as causes of heart failure. If the clinical presentation also suggests an
acute coronary syndrome, the ESC recommends obtaining levels of troponin I or T[4] ; increased troponin levels indicate injury
to the myocytes and the severity of heart failure.
The ACC/AHA, HFSA, and ESC also recommend the following imaging studies and procedures[3, 4, 5] :
Chest radiography (posterior-anterior, lateral), which may show pulmonary congestion, an enlarged cardiac silhouette, or
other potential causes of the patient's symptoms
Two-dimesional echocardiographic and Doppler flow ultrasonographic studies, which may reveal ventricular dysfunction
and/or valvular abnormalities
Coronary arteriography in patients with a history of exertional angina or suspected ischemic left ventricular (LV)
dysfunction, which may reveal coronary artery disease (CAD)
Maximal exercise testing with/without respiratory gas exchange and/or blood oxygen saturation, which assesses cardiac
and pulmonary function with activity, the inability to walk more than short distances, and a decreased peak oxygen
consumption reflect more severe disease
Other studies may be indicated in selected patients,[3] such as the following:
Screening for hemochromatosis, in which iron overload affects cardiac function

Screening for sleep-disturbed breathing, which affects neurohormonal activation
Screening for human immunodeficiency virus (HIV), which may result in heart failure from possible direct infectious
effects, from disease treatment effects causing CAD, or from other causes
Testing for rheumatologic diseases, amyloidosis, or pheochromocytoma, all of which may cause cardiomyopathy
Serum and urine electrophoresis for light-chain disease
Genetic testing for at-risk patients with a first-degree relative who has been diagnosed with a cardiomyopathy leading to
heart failure, which may aid in detecting early disease onset and guide treatment [30]
Holter monitoring, which may reveal arrhythmias or abnormal electrical activity (eg, in patients with heart failure and a
history of myocardial infarction (MI) who are being considered for electrophysiologic study to document ventricular
tachycardia [VT] inducibility) [4, 5]
Catheterization and angiography
According to the ACCF/AHA, HFSA, and ESC cardiac catheterization and coronary angiography should be considered for
patients with heart failure in the following situations[3, 4, 5] :
When symptoms worsen without a clear cause in patients with heart failure, no angina, and known coronary artery
disease
In heart failure caused by systolic dysfunction in association with angina or regional wall-motion abnormalities and/or
scintigraphic evidence of reversible myocardial ischemia when revascularization is being considered
When the pretest probability of the underlying ischemic cardiomyopathy is high and surgical coronary procedures are
being considered
Before cardiac transplantation or LV assist device placement
In cases of heart failure secondary to postinfarction ventricular aneurysm or other mechanical complications of MI
Endomyocardial biopsy
According to the ACCF/AHA guidelines, routine endomyocardial biopsy (EMB) is not recommended in all cases of HF given the
risk of complications. However, it may be considered in the following situations[3] :
In rapidly progressive heart failure or worsening ventricular dysfunction that persists despite appropriate medical therapy
In suspected cases of acute cardiac rejection status after heart transplantation or myocardial infiltrative processes
In rapidly progressive and unexplained cardiomyopathy for which active myocarditis, especially giant cell myocarditis, is
being considered
When a specific diagnosis is suspected and EMB would influence therapy
The 2016 ESC guidelines recommend considering EMB in rapidly progressive HF despite appropriate medical therapy when
there is a probability of a specific diagnosis that can be confirmed only in mycardial samples and there is an effective specfic
therapy available.[4]
The HFSA suggests that EMB be considered in patients with rapidly progressive clinical heart failure or ventricular dysfunction,
despite appropriate medical therapy, as well as in patients suspected of having myocardial infiltrative processes (eg,
sarcoidosis, amyloidosis) or in patients with malignant arrhythmias out of proportion to their LV dysfunction (eg, sarcoidosis,
giant cell myocarditis).[5]
Assessment of functional capacity
The ACCF/AHA indicates the 6-minute walk test may be indicated in patients with heart failure whose adequacy of rate control
is in question[3] ; the HFSA indicates it is a good indicator of functional status and prognosis in patients with heart failure.[5]
The ACCF/AHA and HFSA do not recommend routine maximal exercise stress testing.[3, 5] HFSA guidelines indicate it may be
useful in situations such as the following with measurement of gas exchange[5] :
To assess the disparity between symptomatic limitation and objective indicators of disease severity
To distinguish non HF-related causes of functional limitation, specifically cardiac versus pulmonary
To consider whether patients are candidates for cardiac transplantation or mechanical circulatory support
To determine the prescription for cardiac rehabilitation
ACCF/AHA and ESC guidelines note that values of peak oxygen consumption of less than 50% of predicted or less than 14
mL/kg/min reflect poor cardiac performance and a likelihood of 1-year survival less than 50%, facilitating referral for cardiac
transplantation or mechanical circulatory device placement.[3, 4]
Nonpharmacologic Therapy
By definition, stage A patients are at high risk for heart failure but do not have structural heart disease or symptoms of heart
failure. For these individuals, guidelines from the American College of Cardiology Foundation/American Heart Association
(ACCF/AHA), Heart Failure Society of America (HFSA), European Society of Cardiology recommend nonpharmacologic
management focused on prevention through reduction of risk factors. Measures include the following[3, 4, 5] :
Treat hypertension and lipid disorders

Encourage smoking cessation
Discourage heavy alcohol intake and illicit drug use
Control and/or prevent diabetes mellitus
Encourage physical activity
Encourage weight reduction if obese or overweight
For patients with chronic heart failure, the ACCF/AHA, HFSA, and ESC recommend regular aerobic exercise to improve
functional capacity and symptoms.[3, 4, 5] However, ACCF/AHA cautions that limitation of activity is appropriate during acute
heart failure exacerbations and in patients with suspected myocarditis. Most patients should not participate in heavy labor or
exhaustive sports.[3]
The ACCF/AHA and ESC recommend specific patient education to facilitate self-care and close observation and follow-up are
important aspects of care. Close supervision, including surveillance by the patient and family, home-based visits, telephone
support, or remote monitoring should be provided to improve adherence.[3, 5]
Dietary sodium should be restricted to 2-3 g/day according the ACCF/AHA and HFSA,[3, 5] although the ACCF/AHA notes that
evidence to support this recommendation is inconclusive.[3]
Fluid restriction to 2 L/day is recommended for patients with evidence of hyponatremia (Na < 130 mEq/dL) and for those whose
fluid status is difficult to control despite sodium restriction and the use of high-dose diuretics.[3, 4, 5]
The ACCF/AHA, HFSA, and ESC guidelines recommend caloric supplementation for patients with evidence of cardiac cachexia.
[3, 4, 5] The HFSA recommends against the use of anabolic steroids for these patients.[5]
The HFSA recommends against naturoceutical use for relief of symptomatic heart failure or for the secondary prevention of
cardiovascular events.[5] Avoid natural or synthetic products containing ephedra (ma huang), ephedrine, or its metabolites, as
well as products that have significant drug interactions with digoxin, vasodilators, beta blockers, antiarrhythmic drugs, and
anticoagulants.[5]
Pharmacologic Therapy
In 2016, the American College of Cardiology, American Heart Association, and Heart Failure Society of America
(ACC/AHA/HFSA) published a focused update on new pharmacologicaly therapy for heart failure[58] which were developed in
collaboration with the International Society for Heart and Lung Transplantation (ISHLT). The recommendations are aligned with
those of the 2016 ESC guidelines[4] and the 2017 ACC/AHA focused updates to the 2013 guidelines,[56] and are summarized
below.
Class I
Reduction of morbidity and mortality
In patients with chronic heart failure with reduced ejection fraction (HFrEF), one of the following agents should be administered
in conjunction with evidence-based beta blockers:
Angiotensin-converting enzyme inhibitors (ACEIs) (Level of evidence: A)

Angiotensin receptor blockers (ARBs) (Level of evidence: A)
Angiotensin receptor–neprilysin inhibitor (ARNI) (Level of evidence: B-R)
In patients with prior or current symptoms of chronic HFrEF, ACEIs are beneficial. (Level of evidence: A)
In patients with prior or current symptoms of chronic HFrEF who are intolerant to ACEIs because of cough or angioedema,
ARBs are recommended. (Level of evidence: A)
In patients with chronic symptomatic HFrEF New York Heart Association (NYHA) class II or III, replace an ACEI or ARB with an
ARNI. (Level of evidence: B-R)
Class IIa
Ivabradine can reduce heart failure hospitalization for patients receiving guideline-directed evaluation and management who
have symptomatic (NYHA class II-III) stable chronic HFrEF (left ventricular ejection fraction of ≤35%) and who are in sinus
rhythm with a heart rate of at least 70 bpm at rest.(Level of evidence: B-R)
Class III
ARNI should not be given in the following situations:
Concomitantly with or within 36 hours of the last dose of an ACEI

Patients with a history of angioedema
Electrophysiologic Intervention
The 2010 Heart Failure Society of America (HFSA) guidelines indicate that device therapy is an integral part of the treatment of
heart failure and that considerations such as the nature and severity of the condition and any patient comorbidities are essential
in optimizing the use of this therapy.[5] The Committee for Practice Guidelines (CPG) of the European Society of Cardiology
(ESC) as well as the American College of Cardiology, American Heart Association, and Heart Rhythm Society (ACC/AHA/HRS)
emphasized the importance of medical devices in heart failure in their respective 2010 and 2012 focused updates on these
interventions.[105, 244]
Pacemakers
Because right ventricular (RV) pacing may worsen heart failure due to an increase in ventricular dysynchrony, the 2010 HFSA
Practice Guidelines recommend against placement of a dual-chamber pacemaker in heart failure patients in the absence of
symptomatic bradycardia or high-degree atrioventricular (AV) block.[5]
The ACC/AHA heart failure guidelines recommend consideration of cardiac resynchronization therapy (CRT) for patients with
heart failure who have indications for permanent pacing (eg, first implant, upgrading of a conventional pacemaker) and New
York Heart Association (NYHA) class III-IV symptoms or those who have an left ventricular ejection fraction (LVEF) below 35%
despite being on optimal heart failure therapy and who may have a dependence on RV pacing.[3, 244] These recommendations
also include patients with NYHA class II symptoms and the presence of left bundle-branch block (LBBB) with a QRS duration
that is at least 150 ms. The ESC guidelines have similar recommendations.[4]
Implantable cardioverter-defibrillators
ACC Foundation (ACCF)/AHA guidelines recommend placing an implantable cardioverter-defibrillator (ICD) in virtually all
patients with an LVEF below 35%. The ACCF/AHA and ESC recommend ICD placement for the following categories of heart
failure patients[3, 4, 245] :
Patients with LV dysfunction (LVEF ≤35%) from a previous myocardial infarction (MI) who are at least 40 days post-Ml
Patients with nonischemic cardiomyopathy; with an LVEF of 35% or less; in NYHA class II or III; receiving optimal
medical therapy; and expected to survive longer than 1 year with good functional status
Patients with ischemic cardiomyopathy who are at least 40 days post-MI; have an LVEF of 30% or less; are in NYHA
functional class I; are on chronic optimal medical therapy; and are expected to survive longer than 1 year with good
functional status
Patients who have had ventricular fibrillation (VF)
Patients with documented hemodynamically unstable ventricular tachycardia (VT) and/or VT with syncope; with an LVEF
below 40%; on optimal medical therapy; and expected to survive longer than 1 year with good functional status
Cardiac resynchronization therapy/biventricular pacing
The ACCF/AHA guidelines recommend cardiac resynchronization therapy (CRT) for patients in sinus rhythm or atrial fibrillation
with a QRS duration of 120 ms or longer (the greatest benefit is in patients with a QRS >150 ms) and an LVEF of 35% or less
with persistent, moderate-to-severe heart failure (NYHA class III and functional NYHA class IV) despite optimal medical therapy.
[3] A 2012 update of ACC/AHA/HRS guidelines on CRT expanded class I indications to patients with NYHA class II symptoms
and LBBB duration of 150 ms or longer.[244] Additional CRT recommendations include[3, 244] :
Patients with a reduced LVEF and a QRS of 150 ms or longer who have NYHA I or II symptoms
Patients with a reduced LVEF who require chronic pacing and in whom frequent ventricular pacing is expected
CRT is not recommended for patients with NYHA class I or II symptoms and non-LBBB pattern with a QRS duration
shorter than 150 ms
CRT is not indicated in patients who are not expected to survive for more than 1 year due to their comorbidities or frailty
The ESC guidelines gives class I recommendations for the use of CRT in the following groups[4] :
Symptomatic patients in sinus rhythm with a QRS duration of 150 ms or longer, LBBB QRS morphology and an LVEF of
35% or less despite optimal medical therapy. (Level of evidence: A)
Symptomatic patients in sinus rhythm with a QRS duration of 130-149 ms or longer, LBBB QRS morphology and an
LVEF of 35% or less despite optimal medical therapy. (Level of evidence: B)
CRT rather than RV pacing for patients with heart failure with reduced ejection fraction (HFrEF) regardless of NYHA
class, including patients with atrial fibrillation who have an indication for ventricular pacing and a high degree AV block.
(Level of evidence: A)
CRT should be considered for the following groups[4] :
Symptomatic patients in sinus rhythm with a QRS duration of 150 ms or longer, non-LBBB QRS morphology and an
LVEF of 35% or less despite optimal medical therapy. (Class IIa; level of evidence: B)
Patients with LVEF of 35% or less in NYHA Class III-IV despite optimal medical therapy, if they are in atrial fibrillation and
have a QRS duration of 130 ms or longer provided a strategy to ensure biventricular capture is in place or the patient is
expected to return to sinus rhythm. (Class IIa; level of evidence: B)
CRT may be considered for the following groups[4] :
Symptomatic patients in sinus rhythm with a QRS duration of 130-149 ms, non-LBBB QRS morphology and with an
LVEF of 35% or less despite optimal medical therapy. (Class IIb; level of evidence: B)
Patients with HFrEF who have received a conventional pacemaker or an ICD and subsequently develop worsening heart
failure despite optimal medical therapy and who have a high proportion of RV pacing. (Class IIb; level of evidence: B)
CRT is contraindicated in patients with a QRS duration below 130 ms. (Class III; level of evidence: A)
Revascularization Procedures
The American College of Cardiology Foundation/American Heart Association (ACCF/AHA), Heart Failure Society of America
(HFSA), and European Society of Cardiology (ESC) guidelines recommend coronary artery bypass graft (CABG) and
percutaneous coronary intervention (PCI) revascularization procedures in selected patients with heart failure and coronary
artery disease (CAD) to improve symptoms and survival.[3, 4, 5] In patients who are at low risk for CAD, findings from
noninvasive tests such as exercise electrocardiography (ECG), stress echocardiography, and stress nuclear perfusion imaging
should determine whether subsequent angiography is indicated.
The ACCF/AHA guidelines recommend revascularization procedures for the following heart failure patients[3] :
CABG or PCI for those on medical therapy with angina and suitable coronary anatomy, especially significant left main
stenosis (>50%) or left main equivalent
CABG to improve survival in patients with mild to moderate left ventricular (LV) systolic dysfunction (ejection fraction [EF]
OF 35%-50%) and significant (≥70% stenosis) multivessel CAD or proximal left anterior descending (LAD) artery
stenosis in the presence of viable myocardium
CABG to improve morbidity and survival for patients with an LVEF of 35% or less, heart failure, and significant
multivessel CAD
CABG may also be considered in patients with ischemic heart disease, severe LV systolic dysfunction (EF < 35%), and
operable coronary anatomy, regardless of whether or not viable myocardium is present
The ESC guidelines are in general agreement with those of ACCF/AHA, with the choice between CABG and PCI individualized
for each patient.[4] In addition, the ESC points out that the benefit-risk balance of revascularization in patients without angina
and without viable myocardium remains uncertain.
Valvular Surgery
The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) recommends aortic valve
replacement for patients with critical aortic stenosis and predicted surgical mortality of 10% or less, as well as transcatheter
aortic valve replacement for selected patients who are considered to be inoperable.[3] The benefit of transcatheter mitral valve
repair or mitral valve surgery for functional mitral insufficiency is unclear and should only be considered after careful candidate
selection.
The Heart Failure Society of America (HFSA) indicates that isolated mitral valve repair or replacement for severe mitral
regurgitation secondary to ventricular dilatation in the presence of severe left ventricular (LV) systolic dysfunction is not generally
recommended.[5]
Although the European Society of Cardiology (ESC) recommends optimized medical treatment for aortic stenosis, it also
cautions that vasodilators may cause hypotension and should be used with caution. Surgical decision making should not be
delayed. For patients unfit for surgery, transcatheter aortic valve replacement should be considered. Additional valvular surgery
recommendations include[4] :
Aortic valve repair or replacement in all symptomatic patients with severe aortic regurgitation as well as asymptomatic
patients with an LV ejection fraction (EF) of 50% or less who are fit for surgery.
Consider a combination valve and coronary surgery for secondary mitral regurgitation in symptomatic patients with an
LVEF below 30% with suitable arteries for revascularization. Surgery is also recommended for those with severe mitral
regurgitation with an LVEF over 30% undergoing coronary artery bypass grafting.
Isolated mitral valve surgery in patients with severe functional mitral regurgitation and severe LV systolic dysfunction
(LVEF < 30%) who cannot be revascularized or have non-ischemic cardiomyopathy is questionable; conventional
medical and device therapy are preferred. In selected cases, consider repair to avoid or postpone transplantation.
Mechanical Circulatory Support Devices

The following organizations have released guidelines for the utilization of mechanical circulatory support (MCS):
Society for Cardiovascular Angiography and Interventions, American College of Cardiology, Heart Failure Society of
America, and Society for Thoracic Surgeons (SCAI/ACC/HFSA/STS)
International Society of Heart and Lung Transplantation (ISHLT)
American Heart Association (AHA)
Historically, the intra-aortic balloon bump (IABP) and extracorporeal membrane oxygenation (ECMO) devices had been the only
MCS devices available to clinicians, but axial flow pumps (eg, Impella) and left atrial to femoral artery bypass pumps (eg,
TandemHeart) have more recently entered clinical practice.[246]
The 2015 SCAI/ACC/HFSA/STS clinical expert consensus-based recommendations include the following[246] :
Percutaneous circulatory assist devices provide superior hemodynamic support (reduce left ventricular [LV] pressures, LV
volumes, LV stroke volume) compared with pharmacologic therapy; this is particularly apparent for the Impella and
TandemHeart devices.
In those with cardiogenic shock who fail to stabilize or show signs of improvement after initial interventions, consider
early placement of an appropriate MCS.
For profound cardiogenic shock, IABP is less likely to provide benefit than continuous flow pumps (including the Impella
CP and TandemHeart). ECMO may also be beneficial, particularly for patients with impaired respiratory gas exchange.
Consider MCS for isolated acute right ventricular (RV) failure complicated by cardiogenic shock.
MCS can be beneficial in high-risk percutaneous coronary intervention (PCI) (eg, multivessel, left main, or last patent
conduit interventions), particularly if the patient is inoperable or has severely reduced ejection fraction or elevated cardiac
filling pressures
MCS can be utilized when patients fail to wean off of cardiopulmonary bypass.
Early MCS may benefit patients with acute decompensated heart failure when they continue to deteriorate despite initial
interventions.
MCS can be used in severe biventricular failure via both right- and left-sided percutaneous devices or venoarterial
ECMO.
However, there was insufficient evidence to support or refute routine use of MCS as an adjunct to primary revascularization in
the setting of large acute MI (myocardial infarction) to reduce reperfusion injury or infarct size.[246]
In its 2013 guidelines for mechanical circulatory support, the ISHLT recommended long-term MCS for the following patients in
acute cardiogenic shock (class IIa)[247] :
Those whose ventricular function is considered unrecoverable or unlikely to recover without long-term device support
(level of evidence: C)
Those considered too ill to maintain normal hemodynamics and vital organ function with temporary MCS, or who cannot
be weaned from temporary MCS or inotropic support (level of evidence: C)
Those with the capacity for meaningful recovery of end-organ function and quality of life (level of evidence: C)
Those without irreversible end-organ damage (level of evidence: C)
Those who are dependent on inotropic agents (level of evidence: B)
Those with end-stage systolic heart failure who do not fall into one of the recommendations: Routine risk stratification at
regular intervals to determine the need for and optimal timing of MCS (level of evidence: C)
Additional recommendations for heart failure therapy include[247] :
Diuretic agents for the management of volume overload during MCS (class I; level of evidence: C)
An angiotensin-converting enzyme inhibitor (ACEI) or an angiotensin receptor blocker (ARB) for managing hypertension
or for risk reduction in patients with vascular disease and diabetes (class I; level of evidence: C.)
Beta-blockers for hypertension or for rate control in patients with tachyarrhythmias (class I; level of evidence: C.)
Mineralocorticoid receptor antagonists to limit the need for potassium repletion in patients with adequate renal function
and for potential beneficial antifibrotic effects on the myocardium (class I; level of evidence: C.)
Digoxin, potentially, for treating atrial fibrillation with rapid ventricular response (class II; level of evidence: C.)
The 2012 AHA guidelines on heart device strategies, patient selection, and postoperative care focuses on risk stratification and
early referral of high-risk patients with heart failure to centers that can implant MCS.[248] The specific recommendations for
MCS include[248] :
Consider MCS as a bridge to transplantation (BTT) for eligible patients with end-stage heart failure who are failing
optimal medical, surgical, and or device therapies and are at high risk for dying before receiving heart transplantation.
Early referral for MCS before development of advanced heart failure is preferred.
Durable, implantable MCS devices is beneficial as permanent or destination therapy for patients with advanced heart
failure, high 1-year mortality resulting from HF, and the absence of other life-limiting organ dysfunction; who are failing
medical, surgical, and/or device therapies; and who are not heart transplant candidates.
Consider patients who are ineligible for heart transplantation because of pulmonary hypertension related to heart failure
alone for bridge to potential transplant eligibility with durable, long-term MCS.
Consider urgent nondurable MCS in hemodynamically compromised patients with heart failure and end-organ
dysfunction and/or relative contraindications to heart transplantation/durable MCS that are expected to improve with
restoration of an improved hemodynamic profile.
Long-term MCS is not recommended in patients with advanced kidney disease in whom renal function is unlikely to
recover despite improved hemodynamics.
Consider long-term MCS as a bridge to heart-kidney transplantation on the basis of the availability of outpatient
hemodialysis.
Heart Transplantation
According to the American College of Cardiology Foundation/American Heart Association (ACCF/AHA) and Heart Failure
Society of America (HFSA) guidelines, selected patients with refractory end-stage heart failure, debilitating refractory angina,
ventricular arrhythmia, or congenital heart disease that cannot be controlled despite pharmacologic, medical device, or
alternative surgical therapy should be evaluated for heart transplantation.[3, 5]
The European Society of Cardiology (ESC) guidelines recommend heart transplantation be considered for patients with
progressive end-stage heart failure despite maximal medical therapy who have a poor prognosis and no viable alternative form
of treatment; these patients must be well informed, motivated, and emotionally stable, and they must be capable of complying
with intensive medical treatment.[4]
The ESC considers the following conditions as contraindications for heart transplantation[4] :
Active infection
Severe peripheral arterial or cerebrovascular disease
Current alcohol and/or drug abuse
Malignancy (collaborate with oncologists for risk stratification of tumor recurrence)
Irreversible renal dysfunction (creatinine clearance < 30 mL/min)
Pharmacologically irreversible pulmonary hypertension (consider placing a left ventricular assist device and then
reevaluating eligibility)
Multiorgan systemic disease
Other serious comorbidity with a poor prognosis
Pretransplant body mass index above 35 kg/m 2
insufficient social support in the outpatient setting to achieve compliant care
Note that the HFSA does not recommend partial left ventriculectomy (Batista operation) to treat nonischemic cardiomyopathy.[5]
Management of Acute Decompensated Heart Failure (ADHF)

The Heart Failure Society of America (HFSA) guidelines recommend the following treatment goals for patients with acute
decompensated heart failure (ADHF)[5] :
Symptomatic improvement (ie, congestion, low output)
Restoration of normal oxygenation
Optimization of volume status
Identification of the etiology and addressing precipitating factors
Optimization of long-term oral therapy
Minimization of side effects
Identification of patients in whom revascularization or device therapy may be beneficial
Risk stratification for venous thromboembolism and potential need for anticoagulation
Patient education regarding medications and self-management of heart failure
Initiation of a disease management program, where possible
HFSA indications for hospital admission in patients with ADHF are as follows[5] :
Evidence of severely decompensated heart failure, including hypotension, worsening renal function, and altered
mentation
Dyspnea at rest
Hemodynamically significant arrhythmia, including new onset of rapid atrial fibrillation
Acute coronary syndromes
The American College of Cardiology Foundation/American Heart Association (ACCF/AHA) comments regarding adjustment of
maintenance heart failure medications in patients admitted with ADHF are as follows:
Oral therapy should be continued, or even uptitrated, in most patients with reduced ejection fraction heart failure.
Most patients tolerate well the continuation of angiotensin-converting enzyme inhibitors (ACEIs) or angiotensin receptor
blockers (ARBs) and beta-blockers; this also results in better outcomes.
Only consider withholding or reducing beta-blockers in patients hospitalized after a recent beta-blocker initiation or
increase in beta-blocer therapy, or in those with marked volume overload or marginal/low cardiac output.
In patients with significant worsening of renal function, consider a reduction in, or temporary discontinuation of, ACEIs,
ARBs, and/or aldosterone antagonists until renal function improves.
Pharmacologic therapy
The ACCF/AHA, HFSA, and European Society of Cardiology (ESC) agree that diuretics remain the cornerstone of standard
therapy.[3, 4, 5] The aim of diuretic therapy is to achieve and maintain euvolaemia with the lowest achievable dose.[4]
Intravenous (IV) administration of a loop diuretic (eg, furosemide, bumetanide, torsemide) is preferred initially.[3, 4, 5] In
patients with hypertensive heart failure who have mild fluid retention, thiazide diuretics (eg, bendroflumethiazide,
hydrochlorothiazide, metolazone) may be preferred because of their more persistent antihypertensive effects.[4]
When diuresis is inadequate, the ACCF/AHA, HFSA and ESC guidelines recommend higher doses or the addition of a second
diuretic (eg, a thiazide).[3, 4, 5] Careful monitoring to avoid hypokalemia, renal dysfunction, and hypovolemia is required. The
ACC/AHA and ESC suggest the use of ultrafiltration for fluid reduction when diuretic therapies are unsuccessful.[3, 4]
Vasodilators (eg, nitroprusside, nitroglycerin, or nesiritide) are recommended as an adjuvant to diuretics for relief of symptoms.
[3, 4, 5] However, the ESC cautions against their use in patients with a systolic blood pressure below 90 mm Hg or those with
significant mitral or aortic stenosis.[4]
The ACCF/AHA, HFSA, ESC recommend that in hospitalized patients, beta-blocker therapy should be initiated after optimization
of volume status and successful discontinuation of IV diuretics, vasodilators, and inotropic agents.[3, 4, 5] Beta-blockers should
be started at a low dose and only in stable patients, and should be used cautiously in patients who have required inotropes
during their hospital course.[3, 4, 5]
Additional recommendations from the 2013 ACC/AHA and 2010 HSFA guidelines include the following[3, 5] :
If symptomatic hypotension is absent, consider IV nitroglycerin, nitroprusside, or nesiritide an adjuvant to diuretic therapy
for relief of dyspnea in hospitalized patients.
Administer venous thromboembolism prophylaxis with an anticoagulant medication for patients admitted to the hospital, if
the risk-benefit ratio is favorable.
Invasive hemodynamic monitoring
The 2013 ACCF/AHA and 2010 HSFA guidelines found no benefit found for the routine use of invasive hemodynamic monitoring
in normotensive patients with acute decompensated heart failure and congestion with symptomatic response to diuretics and
vasodilators.[3, 5] The HSFA guidelines include a recommendation for consideration of invasive hemodynamic monitoring for
patients with any of the following[5] :
Heart failure refractory to initial therapy
Unclear volume status and cardiac filling pressures
Clinically significant hypotension (systolic blood pressure < 80 mm Hg) or worsening renal function during therapy
Need for assessment of degree and reversibility of pulmonary hypertension, as part of the evaluation for possible cardiac
transplantation
Need for documentation of an adequate hemodynamic response to inotropic therapy, when considering long-term
outpatient infusion
Ventilation
The HFSA recommends routine administration of supplemental oxygen only in the presence of hypoxia; noninvasive positive
pressure ventilation (NIPPV) should be considered for severe dyspnea and clinical evidence of pulmonary edema.[5] The ESC
recommends noninvasive ventilation as an adjunctive therapy to improve outcomes in patients with acute respiratory failure due
to hypercapnic exacerbation of chronic obstructive pulmonary disease or heart failure in the setting of acute pulmonary edema.
[4]
Medication
Medication Summary
The goals of pharmacotherapy for heart failure are to reduce morbidity and to prevent complications. Along with oxygen,
medications assisting with symptom relief include: (1) diuretics, which reduce edema by reduction of blood volume and venous
pressures; (2) vasodilators, for preload and afterload reduction; (3) digoxin, which can cause a small increase in cardiac output;
(4) inotropic agents, which help to restore organ perfusion and reduce congestion; (5) anticoagulants, to decrease the risk of
thromboembolism; (6) beta-blockers, for neurohormonal modification, left ventricular ejection fraction (LVEF) improvement,
arrhythmia prevention, and ventricular rate control; (7) angiotensin-converting enzyme inhibitors (ACEIs), for neurohormonal
modification, vasodilatation, and LVEF improvement; (8) angiotensin II receptor blockers (ARBs), also for neurohormonal
modification, vasodilatation, and LVEF improvement; and (9) analgesics, for pain management.
Ivabradine, an I(f) inhibitor is available in the United States. It blocks the hyperpolarization-activated cyclic nucleotide-gated
(HCN) channel responsible for the cardiac pacemaker I(f) "funny" current, which regulates heart rate without any effect on
ventricular repolarization or myocardial contractility.
Sacubitril/valsartan (Entresto), an angiotensin receptor-neprilysin inhibitor (ARNI), was approved by the FDA in July 2015 to
reduce the risk of cardiovascular death and hospitalization for heart failure in patients with congestive heart failure (New York
Heart Association [NYHA] class II-IV) and reduced ejection fraction.
Drugs that can exacerbate heart failure should be avoided, such as nonsteroidal anti-inflammatory drugs (NSAIDs), calcium
channel blockers (CCBs), and most antiarrhythmic drugs (except class III). NSAIDs can cause sodium retention and peripheral
vasoconstriction, and they can attenuate the efficacy and enhance the toxicity of diuretics and ACEIs. Calcium channel blockers
(CCBs) can worsen heart failure and may increase the risk of cardiovascular events; only the vasoselective CCBs have been
shown not to adversely affect survival. Antiarrhythmic agents can have cardiodepressant effects and may promote arrhythmia;
only amiodarone and dofetilide have been shown not to adversely affect survival.
Beta-Blockers, Alpha Activity
Class Summary
Beta-blockers inhibit the sympathomimetic nervous system and block alpha1-adrenergic vasoconstrictor activity. These agents
have moderate afterload reduction properties and cause slight preload reduction. In addition to decreasing mortality rates, beta-
blockers also reduce hospitalizations and the risk of sudden death; improve LV function and exercise tolerance; and reduce
heart failure functional class. Although other beta-blockers with similar pharmacologic properties might hypothetically be
beneficial in heart failure, the target doses have not been identified in clinical trials.
Carvedilol (Coreg, Coreg CR)
Carvedilol is a nonselective beta- and alpha1-adrenergic blocker. It does not appear to have intrinsic sympathomimetic activity.
Carvedilol at the target dose of 25 mg twice daily has been shown to reduce mortality in clinical trials of heart failure patients
with reduced ejection fraction.
Beta-Blockers, Beta-1 Selective
Class Summary
Certain beta-1 blockers are selective in blocking beta-1 adrenoreceptors. These agents are used in heart failure to reduce heart
rate and blood pressure.
Metoprolol (Lopressor, Toprol XL)

Metoprolol is a selective beta1-adrenergic blocker at lower doses. It inhibits beta2-receptors at higher doses. It does not have
intrinsic sympathomimetic activity. The long-acting formulation (metoprolol succinate) at a target dose of 200 mg daily has been
shown to reduce mortality in a clinical trial of patients with heart failure and low ejection fraction.
Bisoprolol (Zebeta)
Bisoprolol is a highly selective beta1-adrenergic receptor blocker that decreases the automaticity of contractions. Bisoprolol at
the target dose of 10 mg daily has been shown to reduce mortality in a clinical trial of patients with heart failure and reduced
ejection fraction, but is not approved for heart failure use in the US.
ACE Inhibitors
Class Summary
Angiotensin-converting enzyme inhibitors (ACEIs) prevent conversion of angiotensin I to angiotensin II, which results in lower
aldosterone secretion. Use of ACEIs increases survival, improves symptoms, and decreases repeat hospitalizations.
Captopril
Captopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in lower aldosterone
secretion. Captopril at a target dose of 25 mg three times daily has been shown to improve survival in patients with low ejection
fraction after myocardial infarction.
Enalapril (Vasotec)
Enalapril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma
renin and a reduction in aldosterone secretion. It helps control blood pressure and proteinuria. Enalapril decreases the
pulmonary-to-systemic flow ratio in the catheterization laboratory and increases systemic blood flow in patients with relatively
low pulmonary vascular resistance. It has a favorable clinical effect when administered over a long period. It helps prevent
potassium loss in distal tubules. The body conserves potassium; thus, less oral potassium supplementation is needed. Enalapril
at a target dose of 10 mg twice daily has been shown to improve survival in patients with heart failure and reduced ejection
fraction.
Lisinopril (Prinivil, Zestril)

Lisinopril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma
renin and a reduction in aldosterone secretion. Lisinopril at a target dose of 10 mg daily has been shown to reduce mortality
after myocardial infarction.
Ramipril (Altace)
Ramipril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma
renin and a reduction in aldosterone secretion. Ramipril at a target dose of 5 mg twice daily has been shown to reduce mortality
in patients with heart failure after myocardial infarction.
Quinapril (Accupril)
Quinapril prevents conversion of angiotensin I to angiotensin II, a potent vasoconstrictor, resulting in increased levels of plasma
renin and a reduction in aldosterone secretion.
ARBs
Class Summary
Angiotensin receptor blockers (ARBs) are reasonable first-line therapy for patients with mild to moderate heart failure symptoms
and left ventricular (LV) dysfunction when patients are already taking these agents for other indications. ARBs block the renin-
angiotensin-aldosterone system (RAAS) by competitive inhibition of the AT1 receptor, thereby decreasing afterload and
preventing LV remodeling. The use of ARBs increases survival and decreases hospitalization rates, but these agents are not
superior to angiotensin-converting enzyme inhibitors (ACEIs). ARBs can also be used as add-on therapy for patients who have
refractory heart failure symptoms despite optimal heart failure therapy.
Losartan (Cozaar)
Losartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II at tissue receptor sites. It may induce
more complete inhibition of the renin-angiotensin system than ACE inhibitors, and it does not affect the response to bradykinin
(less likely to be associated with cough and angioedema). These agents are used in patients unable to tolerate ACE inhibitors.
Losartan has not been demonstrated to improve survival in heart failure.
Valsartan (Diovan)
Valsartan is a prodrug that produces direct antagonism of angiotensin II receptors. It displaces angiotensin II from the AT1
receptor and may lower blood pressure by antagonizing AT1-induced vasoconstriction, aldosterone release, catecholamine
release, arginine vasopressin release, water intake, and hypertrophic responses. It may induce more complete inhibition of the
renin-angiotensin system than ACE inhibitors, does not affect the response to bradykinin, and is less likely to be associated with
cough and angioedema. It is used in patients unable to tolerate ACE inhibitors. Valsartan at a target dose of 160 mg twice daily
has been shown to improve survival in patients with heart failure and reduced ejection fraction.
Candesartan (Atacand)
Candesartan blocks the vasoconstriction and aldosterone-secreting effects of angiotensin II. It may induce more complete
inhibition of the renin-angiotensin system than ACE inhibitors, does not affect the response to bradykinin, and is less likely to be
associated with cough and angioedema. Use candesartan in patients unable to tolerate ACE inhibitors. Candesartan at a target
dose of 32 mg daily has been shown to improve survival in patients with heart failure and reduced ejection fraction.
Irbesartan (Avapro)
Irbesartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II at tissue receptor sites. It may induce
(less likely to be associated with cough and angioedema). Irbesartan has not been shown to improve survival in heart failure.
Azilsartan (Edarbi)
Azilsartan blocks the vasoconstrictor and aldosterone-secreting effects of angiotensin II at tissue receptor sites. It may induce
(less likely to be associated with cough and angioedema).
Inotropic Agents
Class Summary
Inotropic agents such as milrinone, digoxin, dopamine, and dobutamine are used to increase the force of cardiac contractions.
Intravenous positive inotropic agents should only be used in inpatient settings — and then only in patients who manifest signs
and symptoms of low cardiac output syndrome (volume overload with evidence of organ hypoperfusion).
Milrinone
Milrinone is a type 3 phosphodiesterase inhibitor that increases inotropy, chronotropy, and lusitropy, acting via cyclic guanosine
monophosphate (cGMP) to increase the intramyocardial adenosine triphosphate (ATP). It is a potent vasodilator agent, being a
venous and arterial vasodilator, and it is used in patients with pulmonary hypertension. Milrinone can be used in the presence of
a beta-blocker. Milrinone is thought to create less tachycardia, because it does not directly stimulate beta-receptors.
Digoxin (Lanoxin)
Digoxin is a cardiac glycoside with direct inotropic effects, in addition to indirect effects, on the cardiovascular system. It acts
directly on cardiac muscle, increasing myocardial systolic contractions. Indirect actions result in increased carotid sinus nerve
activity and enhanced sympathetic withdrawal for any given increase in mean arterial pressure. It is used to improve symptoms
associated with HF by enhancing cardiac contractility. Although digoxin does not confer a survival benefit, it has reduced the
number of hospitalizations that occur as a result of worsening heart failure.
Dopamine
Dopamine is a naturally occurring catecholamine that acts as a precursor to norepinephrine. It stimulates both adrenergic and
dopaminergic receptors. The hemodynamic effect is dose dependent. Low-dose use is associated with dilation within renal and
splanchnic vasculature, resulting in enhanced diuresis. Moderate doses enhance cardiac contractility and the heart rate. Higher
doses cause increased afterload through peripheral vasoconstriction. Administer by continuous intravenous infusion. It is usually
used in severe heart failure and is reserved for patients with moderate hypotension (eg, systolic blood pressure 70-90 mm Hg).
Typically, moderate or higher doses are used.
Dobutamine
Dobutamine, a beta-receptor agonist, increases inotropy and chronotropy and decreases afterload, thereby improving end-
organ perfusion. It produces vasodilation and increases the inotropic state. At higher dosages, it may cause increased heart
rate, exacerbating myocardial ischemia. Careful hemodynamic and patient monitoring is required.
Vasodilators
Class Summary
In addition to diuretic therapy, vasodilators are recommended as first-line therapy for patients with acute heart failure in the
absence of hypotension, for relief of symptoms. Vasodilators decrease preload and/or afterload as well as reduce systemic
vascular resistance (SVR).
Nitroprusside sodium (Nitropress)

Nitroprusside sodium is a potent balanced arterial and venous vasodilator, resulting in a very efficient decrease of intracardiac
filling pressures. It requires careful hemodynamic monitoring using indwelling catheters and monitoring for cyanide toxicity,
especially in the presence of renal dysfunction. It is particularly helpful for patients who present with severe pulmonary
congestion in the presence of hypertension and severe mitral regurgitation. The drug should be titrated down to cessation rather
than abruptly stopped, owing to the rebound potential.
Hydralazine
Hydralazine decreases systemic resistance through direct vasodilation of arterioles. A hydralazine and nitrate combination
reduces preload and afterload. Combinations of hydralazine and nitrates are recommended to improve outcomes for African
Americans with moderate-to-severe symptoms of heart failure on optimal medical therapy with ACEIs/ARBs, beta-blockers, and
diuretics.
Nitrates
Class Summary
Nitrates improve hemodynamic effects in heart failure by decreasing left ventricular filling pressure and systemic vascular
resistance. These agents also result in a slight improvement on cardiac output.
Nitroglycerin (Nitrostat, Nitro-Dur, Nitrolingual, Nitro-Time, NitroMist, Minitran)

Nitroglycerin is first-line therapy for patients who are not hypotensive. It provides excellent and reliable preload reduction. Higher
doses provide mild afterload reduction. It has rapid onset and offset (both within minutes), allowing rapid clinical effects and
rapid discontinuation of effects in adverse clinical situations. It produces vasodilation and increases inotropic activity of the heart.
At higher dosages, it may exacerbate myocardial ischemia by increasing the heart rate.
Isosorbide dinitrate (Dilatrate-SR, Isordil Titradose)

Isosorbide dinitrate relaxes vascular smooth muscle by stimulating intracellular cyclic GMP. It decreases left ventricular pressure
(preload) and arterial resistance (afterload). By decreasing left ventricular pressure and dilating arteries, it reduces cardiac
oxygen demand. Chronic use of isosorbide dinitrate as a sole vasodilating agent is not recommended.
Isosorbide dinitrate and Hydralazine (BiDil)

This is a fixed-dose combination of isosorbide dinitrate (20 mg/tab), a vasodilator with effects on both arteries and veins, and
hydralazine (37.5 mg/tab), a predominantly arterial vasodilator. It is indicated for heart failure in black patients, based in part on
results from the African American Heart Failure Trial. Two previous trials in the general population of patients with severe heart
failure found no benefit but suggested a benefit in black patients. Black patients showed a 43% reduction in mortality rate, a
39% decrease in hospitalization rate, and a decrease in symptoms from heart failure.
Isosorbide mononitrate (Monoket)

Isosorbide mononitrate causes relaxation of vascular smooth muscle and consequent dilatation of peripheral arteries and veins.
Dilation of the veins promotes peripheral pooling of blood and decreases venous return to the heart, thereby reducing left
ventricular end-diastolic pressure and pulmonary capillary wedge pressure (preload). Arteriolar relaxation reduces systemic
vascular resistance, systolic arterial pressure, and mean arterial pressure (afterload).
B-type Natriuretic Peptides
Class Summary
Human B-type natriuretic peptides (hBNPs) such as nesiritide are used in patients with acutely decompensated heart failure.
These agents reduce pulmonary capillary wedge pressure and improve dyspnea.
Nesiritide (Natrecor)
Nesiritide is a recombinant DNA form of hBNP that dilates veins and arteries. hBNP binds to the particulate guanylate cyclase
receptor of vascular smooth muscle and endothelial cells. Binding to the receptor causes an increase in cGMP, which serves as
a second messenger to dilate veins and arteries. It reduces PCWP and improves dyspnea in patients with acutely
decompensated HF.
I(f) Inhibitors
Class Summary
The I(f) inhibitor ivabradine is used to lower heart rate and has been shown to reduce the risk for hospitalization.
Ivabradine (Corlanor)
Ivabradine blocks the hyperpolarization-activated cyclic nucleotide-gated (HCN) channel responsible for the cardiac pacemaker
I(f) ‘funny' current, which regulates heart rate without any effect on ventricular repolarization or myocardial contractility. It is
indicated to reduce the risk of hospitalization for worsening heart failure in patients with stable, symptomatic chronic heart failure
with LVEF ≤35%, who are in sinus rhythm with resting heart rate ≥70 bpm and either are on maximally tolerated doses of beta-
blockers or have a contraindication to beta-blocker use.
ARNIs
Class Summary
Angiotensin receptor-neprilysin inhibitor (ARNI) combinations have been shown to significantly reduce cardiovascular death and
hospitalization in patients with chronic heart failure.
Sacubitril/valsartan (Entresto)
An angiotensin receptor-neprilysin inhibitor (ARNI). The cardiovascular and renal effects of sacubitril’s active metabolite
(LBQ657) in heart failure are attributed to the increased levels of peptides that are degraded by neprilysin (eg, natriuretic
peptide). Administration results in increased natriuresis, increased urine cGMP, and decreased plasma MR-proANP (mid-
regional proatrial natriuretic peptide) and NT-proBNP (N-terminal pro B-type natriuretic peptide). It is indicated to reduce the risk
of cardiovascular death and hospitalization for heart failure in patients with CHF (NYHA class II-IV) and reduced ejection
fraction. The combo drug is also indicated for symptomatic HF with systemic left ventricular systolic dysfunction in children 1
year and older.
Diuretics, Loop
Class Summary
Diuretics remain the mainstay of therapy and the current standard of care for acute heart failure. First-line diuretic therapy is a
loop diuretic (furosemide, bumetanide, torsemide) in the lowest effective dose, either once or twice a day — although it can be
used up to 3-4 times a day — depending on the individual response and renal function. Response to diuretic therapy often
depends on bioavailability of the drug (better on an empty stomach) and nutritional level (loop diuretics are bound to proteins for
renal delivery).
Furosemide (Lasix)
Furosemide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits
sodium and chloride reabsorption in the ascending loop of Henle and distal renal tubule. The dose must be individualized to the
patient. Depending on the response, administer furosemide at small dose increments (20-200 mg) until desired diuresis occurs.
Torsemide (Demadex)
Torsemide acts from within the lumen of the thick ascending portion of the loop of Henle, where it inhibits the sodium,
potassium, and chloride carrier system. It increases urinary excretion of sodium, chloride, and water, but does not significantly
alter the glomerular filtration rate, renal plasma flow, or acid-base balance. Torsemide is roughly twice as potent as furosemide
on a milligram basis. Depending on the response, administer furosemide at small dose increments (10-100 mg) until desired
diuresis occurs.
Bumetanide
Bumetanide increases the excretion of water by interfering with the chloride-binding cotransport system, which, in turn, inhibits
sodium, potassium, and chloride reabsorption in the ascending loop of Henle. These effects increase urinary excretion of
sodium, chloride, and water, resulting in profound diuresis. Renal vasodilation occurs following administration, renal vascular
resistance decreases, and renal blood flow is enhanced. Bumetanide is roughly four times as potent as furosemide on a
milligram basis. Depending on the response, administer bumetanide at small dose increments (0.5-5 mg) until desired diuresis
occurs.
Diuretics, Thiazide
Class Summary
If patients with heart failure do not have a response to treatment with loop diuretics, a thiazide diuretic such as
hydrochlorothiazide or metolazone can be added 30 minutes before adminstration of the loop diuretic to enhance the response.
Thiazide diuretics inhibit reabsorption of sodium and chloride in the cortical thick ascending limb of the loop of Henle and the
distal tubules. They also increase potassium and bicarbonate excretion as well as decrease calcium excretion and uric acid
retention. Combination diuretic therapy should be monitored closely for development of hypovolemia, hypokalemia,
hypomagnesemia, and hyponatremia.
Hydrochlorothiazide (Microzide)
Hydrochlorothiazide inhibits reabsorption of sodium in the distal tubules, causing increased excretion of sodium, water,
potassium, and hydrogen ions.
Indapamide
Indapamide has a diuretic effect that is localized at the proximal segment of the distal tubule of the nephron. Similar to other
diuretics it may enhance sodium, chloride and water excretion.
Chlorthalidone (Thalitone)
Chlorthalidone inhibits the reabsorption of sodium in distal tubules, causing increased excretion of sodium and water, as well as
potassium and hydrogen ions.
Chlorothiazide (Diuril)
Chlorothiazide affects the distal renal tubular mechanism of electrolyte reabsorption. It increases excretion of sodium and
chloride in approximately equivalent amounts. Natriuresis may be accompanied by some loss of potassium and bicarbonate
Diuretics, Other
Class Summary
Metolazone is a diuretic of the quinazoline class and has thiazidelike properties. This agent interferes with the renal tubular
mechanism of electrolyte reabsorption.
Metolazone (Zaroxolyn)
Metolazone increases excretion of sodium, water, potassium, and hydrogen ions by inhibiting reabsorption of sodium in the
distal tubules. Metolazone may be more effective in patients with impaired renal function.
Diuretics, Potassium-Sparing
Class Summary
The potassium-sparing diuretics interfere with sodium reabsorption at the distal tubules, resulting in decreased potassium
secretion. These agents have a weak diuretic and antihypertensive effect when used alone. The potassium-sparing diuretics
spironolactone or triamterene are usually used in addition to the loop diuretics. Note that careful monitoring of renal function and
potassium is necessary for all diuretics.
Spironolactone (Aldactone)
Spironolactone is used for the management of edema resulting from excessive aldosterone excretion. It competes with
aldosterone for receptor sites in the distal renal tubules, increasing water excretion while retaining potassium and hydrogen
ions. Spironolactone at a target dose of 25 mg has been shown to improve survival in patients with heart failure and reduced
ejection fraction.
Amiloride (Midamor)
Amiloride is unrelated chemically to other known antikaliuretic or diuretic agents. It is a potassium-conserving (antikaliuretic)
drug that, compared with thiazide diuretics, possesses weak natriuretic, diuretic, and antihypertensive activity.
Triamterene (Dyrenium)
Triamterene is a potassium-sparing diuretic with relatively weak natriuretic properties. It exerts its diuretic effect on the distal
renal tubules by inhibiting the reabsorption of sodium in exchange for potassium and hydrogen. It increases sodium excretion
and reduces excessive loss of potassium and hydrogen associated with hydrochlorothiazide.
Aldosterone Antagonists, Selective
Class Summary
Aldosterone antagonists are weak diuretics that reduce mortality and the risk of sudden death by blocking the effects of
aldosterone, thereby decreasing myocardial and vascular inflammation and collagen production. This, in turn, prevents
apoptosis, decreases stimulation of the renin-angiotensin-aldosterone system (RAAS) and sympathetic nervous system (SNS),
and acts as a membrane stabilizer, thus preventing arrhythmia. Aldosterone antagonists are recommended for patients who
have moderately severe and severe heart failure and reduced left ventricular (LV) systolic function (Randomized Aldactone
Evaluation Study [RALES]) who can be carefully monitored for preserved renal function and normal potassium concentration.
Eplerenone (Inspra)
Eplerenone selectively blocks aldosterone at the mineralocorticoid receptors in epithelial (eg, kidney) and nonepithelial (eg,
heart, blood vessels, and brain) tissues; thus, it decreases blood pressure and sodium reabsorption. It is indicated to improve
survival for heart failure or left LV dysfunction following acute MI. Compared with placebo, a significant risk reduction (15%) has
been observed. The EMPHASIS-HF trial has shown that patients with systolic heart failure with mild symptoms treated with
eplerenone have a significant reduction in cardiovascular death or heart failure hospitalization when compared with placebo.
Alpha/Beta Adrenergic Agonists
Class Summary
In the presence of significant hypotension, adrenergic agonists are used to improve cardiac output and organ perfusion.
Epinephrine (Adrenaclick, Adrenalin, EpiPen, EpiPen Jr.)

Epinephrine is an alpha-agonist and its effects include increased peripheral vascular resistance, reversed peripheral
vasodilatation, systemic hypotension, and vascular permeability. Beta2-agonist effects include bronchodilatation, chronotropic
cardiac activity, and positive inotropic effects.
Norepinephrine (Levophed)
Norepinephrine is a naturally occurring catecholamine with potent alpha-receptor and mild beta-receptor activity. It stimulates
beta1- and alpha-adrenergic receptors, resulting in increased cardiac muscle contractility, heart rate, and vasoconstriction. It
increases blood pressure and afterload. Increased afterload may result in decreased cardiac output, increased myocardial
oxygen demand, and cardiac ischemia. It is generally reserved for use in patients with severe hypotension (eg, systolic blood
pressure < 70 mm Hg) or hypotension that is unresponsive to other medications.
Calcium Channel Blockers
Class Summary
Generally, calcium channel blockers (CCBs) should be avoided. CCBs do not play a direct role in the management of heart
failure; however, these agents may be used to treat other conditions, such as hypertension or angina in heart failure patients.
CCBs may be used in heart failure with normal left ventricular ejection fraction. These drugs may also improve exercise
tolerance via their vasodilatory properties.
Amlodipine (Norvasc)
Amlodipine has antianginal and antihypertensive effects. It blocks the post-excitation release of calcium ions into cardiac and
vascular smooth muscle, thereby inhibiting the activation of ATPase on myofibril contraction. The overall effect is reduced
intracellular calcium levels in cardiac and smooth muscle cells of the coronary and peripheral vasculature, resulting in dilatation
of the coronary and peripheral arteries. It also increases myocardial oxygen delivery in patients with vasospastic angina.
Nifedipine (Adalat CC, Afeditab CR, Nifediac CC, Nifedical XL, Procardia,
Procardia XL)
Nifedipine relaxes coronary smooth muscle and produces coronary vasodilation, which in turn, improves myocardial oxygen
delivery. Sublingual administration is generally safe, despite theoretical concerns.
Felodipine
Felodipine is a dihydropyridine calcium channel blocker. It inhibits the influx of extracellular calcium across the myocardial and
vascular smooth muscle cell membranes. The resultant decrease in intracellular calcium inhibits the contractile processes of the
smooth muscle cells, resulting in dilation of coronary and systemic arteries.
Anticoagulants, Cardiovascular
Class Summary
Patients with heart failure and depressed left ventricular (LV) ejection fraction are thought to have an increased risk of thrombus
formation due to low cardiac output. Hospitalized patients with heart failure are at a high risk for venous thromboembolism and
should receive prophylaxis. Anticoagulation with an international normalized ratio (INR) goal of 2-3 is indicated in the presence
of: (1) an LV thrombus, (2) a thromboembolic event with or without evidence of an LV thrombus, and (3) paroxysmal or chronic
atrial arrhythmias.
Warfarin (Coumadin, Jantoven)

Warfarin interferes with hepatic vitamin K–dependent carboxylation. It is used for the prophylaxis and treatment of
thromboembolic disorders.
Dabigatran (Pradaxa)
Competitive, direct thrombin inhibitor. Thrombin enables fibrinogen conversion to fibrin during the coagulation cascade, thereby
preventing thrombus development. Inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation.
Opioid Analgesics
Class Summary
Opioid analgesics such as morphine sulfate may help to relieve patients’ anxiety, distress, and dyspnea.
Morphine sulfate (Astramorph, Avinza, DepoDur, Duramorph, Infumorph 200,

Infumorph 500, Kadian, MS Contin, Oramorph SR, Roxanol)
Morphine is the drug of choice for narcotic analgesia because of its reliable and predictable effects, safety profile, and ease of
reversibility with naloxone. Morphine sulfate administered intravenously may be dosed in a number of ways and commonly is
titrated until the desired effect is obtained. Morphine sulfate also decreases preload in heart failure and relieves dyspnea.
Questions & Answers

Overview
What is heart failure?
What are the signs and symptoms of heart failure?
What are the Framingham diagnostic criteria for heart failure?
What are the Framingham major diagnostic criteria for heart failure?
What are the Framingham minor diagnostic criteria for heart failure?
How does the New York Heart Association (NYHA) classification system categorize heart failure?
What is the American College of Cardiology/American Heart Association (ACC/AHA) staging system?
Which tests may be performed in the initial evaluation for suspected heart failure?
What are the nonsurgical treatment options for heart failure?
What are the surgical treatment options for heart failure?
What is heart failure?
What causes heart failure?
What are the signs and symptoms of heart failure?
How is heart failure classified?
What are the stages of heart failure defined by the American College of Cardiology/American Heart Association (ACC/AHA)
staging system?
What is the role of lab studies in the diagnosis of heart failure?
What is included in patient care for acute heart failure?
What are the goals of drug treatment for heart failure?
How is heart failure progression pathophysiologically perpetuated?
Which pathophysiological adaptations prevent heart failure?
What is the role of norepinephrine in the pathogenesis of heart failure?
What is the pathophysiology of acute heart failure?
What is the role of chronic increased wall stress in the pathogenesis of heart failure?
What can trigger hemodynamic and neurohormonal derangements in the pathogenesis of heart failure?
What is the role of epinephrine in the pathogenesis of heart failure?
What is the role of calcium overload in the pathophysiology of heart failure?
What is the role of the renin-angiotensin-aldosterone system (RAAS) in the pathophysiology of heart failure?
What is the paradigm of myocyte biology and heart failure?
What is the role of angiotensin II in the pathogenesis of heart failure?
What is the role of myocardial volume in the pathogenesis of heart failure?
What are the features of myocardial remodeling in the pathogenesis of heart failure?
What is the pathophysiology of advanced heart failure?
What is the pathophysiology of systolic and diastolic heart failure?
What is the role of neuro-hormone mediated events in the pathogenesis of heart failure?
What is the role of atrial natriuretic peptide (ANP) and B-type natriuretic peptide (BNP) in the pathophysiology of heart failure?
Which vasoactive systems have a role in the pathogenesis of heart failure?
What is the role of tumor necrosis factor (TNF)-alpha in the pathogenesis of heart failure?
What is systolic heart failure?
What is diastolic heart failure?
What is the pathophysiology of heart failure with preserved ejection fraction (HFpEF)?
What causes increase in left ventricle (LV) chamber stiffness in the pathophysiology of heart failure?
How does the rise in filling pressure affect the pathogenesis of heart failure?
What is the role of ventricular pressure-volume curve in the pathophysiology of heart failure?
What is parallel upward displacement in the pathogenesis of heart failure?
What is the role of increased diastolic pressure in the pathogenesis of heart failure?
What is the role of arrhythmias in the pathogenesis of heart failure?
What causes heart failure?
What are the categories used to classify causes of heart failure?
Which underlying factors cause heart failure?
What are the underlying causes of systolic heart failure?
What are the underlying causes of diastolic heart failure?
What are the underlying causes of acute heart failure?
What are the underlying causes of high-output heart failure?
What are the underlying causes of right heart failure?
How does decompensation result in heart failure?
What is the most common cause of decompensation in heart failure?
How does systemic infection cause heart failure?
How does cardiac infection and inflammation cause heart failure?
What causes fever, tachypnea, and tachycardia due to heart failure?
What are common precipitants of cardiac decomposition causing heart failure?
How does salt retention cause heart failure?
What are the high-output states that can precipitate heart failure?
What does longitudinal data from the Framingham Heart Study reveal about the etiology of heart failure?
What is the role of genetics in the etiology of heart failure?
Which patients at high-risk of heart failure should be screened and followed?
What is the prevalence of heart failure in the US?
What is the incidence of heart failure in the US?
What is the mortality rate for heart failure?
What are the AHA statistics for heart failure in the US?
What are the racial predilections of heart failure in the US?
What has caused an increase in incidence of heart failure in the US among recent immigrants from developing countries?
How does the presentation of heart failure in the US vary by sex?
How does the prevalence of heart failure vary by age in the US?
What are the common causes for the increased prevalence of heart failure in industrialized countries?
How does the mortality rate for heart failure vary between industrialized and developing countries?
What are the trends for heart failure in developing nations?
What is the mortality rate for heart failure?
What is the mortality rate for systolic heart failure?
What variables are used as prognostic factors in heart failure?
How does the prognosis of heart failure compare to that of coronary artery disease?
How does pulmonary artery systolic pressure (PASP) affect the prognosis of heart failure?
Which factors worsen the prognosis of heart failure?
How can recurrence of heart failure be prevented?
What information about heart failure should patients receive?
Presentation
What should be the focus of clinical history during the evaluation of heart failure?
What are common cardiac signs and symptoms of heart failure?
What are non-cardiac symptoms of heart failure?
What is a common presentation of heart failure in the elderly?
How is exertional dyspnea characterized in patients with heart failure?
How is orthopnea characterized in patients with heart failure?
How is paroxysmal nocturnal dyspnea characterized in patients with heart failure?
What causes dyspnea at rest in heart failure?
How is acute pulmonary edema characterized in heart failure?
What causes chest pain or chest pressure in heart failure?
What causes palpitations in heart failure?
How are fatigue and weakness characterized in heart failure?
What causes nocturia and oliguria in heart failure?
Which symptoms of heart failure in the elderly are caused by cerebrovascular atherosclerosis?
How do the presentations of mild and severe heart failure differ?
What are the clinical presentations of recently onset heart failure?
What are the clinical presentations of mild or moderate heart failure?
What causes ascites in patients with heart failure?
What are the signs and symptoms of increased adrenergic activity in patients with heart failure?
What is the significance of rales in patients with heart failure?
How is systemic venous hypertension manifested during heart failure?
What causes hepatojugular reflux in heart failure?
What is the significance of edema in heart failure?
What causes hepatomegaly in heart failure?
What causes hydrothorax in heart failure?
What is protodiastolic gallop in heart failure?
What is the significance of cardiomegaly in heart failure?
What is the significance of pulsus alternans in heart failure?
What are the common heart sounds in patients with heart failure?
What is the significance of cardiac cachexia in heart failure?
What are the clinical manifestations of predominant right-sided heart failure?
What are the clinical manifestations of heart failure in children?
What are the characteristics of right-sided venous congestion in heart failure?
What are the characteristics of left-sided venous congestion in heart failure?
What is required for the diagnosis of heart failure using the Framingham system?
What is the basis for the New York Heart Association (NYHA) functional classification of heart failure?
How does the American College of Cardiology/American Heart Association (ACC/AHA) classify heart failure?
What are the prevention measures for ACC/AHA stage A heart failure?
What screening should patients with a family history of dilated cardiomyopathy receive?
What are the clinical characteristics of ACC/AHA stage B heart failure?
What are the clinical characteristics of ACC/AHA stage C heart failure?
What are the clinical characteristics of ACC/AHA stage D heart failure?
DDX
What are the cardiac and noncardiac causes of heart failure?
What is the most common form of heart failure in the US?
How is heart failure differentiated from pulmonary edema?
Which features may differentiate cardiogenic from noncardiogenic pulmonary edema in heart failure?
What are the clinical features of noncardiogenic pulmonary edema in heart failure?
How is right-sided heart failure presented?
How is heart failure diagnosed in elderly patients?
What are the differential diagnoses for Heart Failure?
Workup
What is included in a careful workup of suspected heart failure?
When is endomyocardial biopsy indicated in the workup of suspected heart failure?
Which lab studies are performed in the diagnosis of heart failure?
Should iron levels be measured in the workup of heart failure?
What is the role of serum electrolyte values in the diagnosis of heart failure?
What is the role of potassium levels in the diagnosis of heart failure?
What is the role of pulmonary function testing (PFT) in the diagnosis of heart failure?
What is the role of renal function tests in the diagnosis of heart failure?
What is the role of liver function tests in the diagnosis of heart failure?
How is acute hepatic venous congestion identified in heart failure?
What is the role of rapid measurement of B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) in the diagnosis of
heart failure?
What are the limitations of B-type natriuretic peptide (BNP) measurements for the diagnosis of heart failure?
When is measurement of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) indicated for the diagnosis of
heart failure?
What is the specificity and sensitivity of B-type natriuretic peptide (BNP) testing for diagnosis of heart failure?
What are the cutoff values of B-type natriuretic peptide (BNP) or N-terminal proBNP (NT-proBNP) for the diagnosis of heart
failure?
In which patient groups do BNP and NT-proBNP levels vary from the norm for the diagnosis of heart failure?
When is the measurement of B-type natriuretic peptide (BNP) contraindicated in the diagnosis of heart failure?
What are the levels of B-type natriuretic peptide (BNP) and N-terminal proBNP (NT-proBNP) in patients with advanced heart
failure?
What is the role of genetic testing in the diagnosis of heart failure?
Where can one go for specific genetic testing information related to the diagnosis of heart failure?
Which types of cardiomyopathy have the highest yield of genetic testing for heart failure?
How is genetic testing used to diagnose dilated cardiomyopathy and heart failure?
How is genetic testing used to diagnose hypertrophic cardiomyopathy and heart failure?
How is autosomal dominant arrhythmogenic right ventricular dysplasia/cardiomyopathy diagnosed in heart failure?
When should genetic testing be considered for the diagnosis of heart failure?
When is the measurement of arterial blood gas (ABG) indicated for the diagnosis of heart failure?
What is the significance of a finding of hypoxemia in the evaluation of heart failure?
What is assessed with arterial blood gas (ABG) measurement in the evaluation of heart failure?
What is the role of mixed venous oxygen saturation in the diagnosis of heart failure?
How is pulse oximetry used for the diagnosis of heart failure?
What is the significance of oxygen saturation in the diagnosis of heart failure?
When is a screening electrocardiogram (ECG) indicated in the evaluation of heart failure?
What are the possible presentations of heart failure on electrocardiography?
What is the role of chest radiographs in the diagnosis of heart failure?
How is transesophageal echocardiography (TEE) used for the diagnosis of heart failure?
How is stress echocardiography used for the diagnosis of heart failure?
What is the role of two-dimensional (2-D) echocardiography in the diagnosis of heart failure?
What is the role of Doppler echocardiography in the diagnosis of heart failure?
What is the appearance of arrhythmogenic right ventricular dysplasia (ARVD) on echocardiogram for the diagnosis of heart
failure?
How are CT scanning and MRI used in the diagnosis of heart failure?
What are the benefits of MRI in the diagnosis of heart failure?
How is radionuclide multiple-gated acquisition (MUGA) scan used for the diagnosis of heart failure?
What is the role of ECG-gated SPECT imaging in the diagnosis of heart failure?
What is the benefit of combining interpretations of perfusion and function on electrocardiogram (ECG)-gated SPECT images for
the diagnosis of heart failure?
Why is ECG-gated SPECT considered state of the art for radionuclide myocardial perfusion imaging in heart failure?
Which issues need to be addressed in the evaluation of presumed ischemic dysfunction in heart failure?
How is equilibrium radionuclide angiocardiography (ERNA) used for the diagnosis of heart failure?
How is the analysis from radionuclide angiocardiography (ERNA) obtained for the diagnosis of heart failure?
How is radionuclide ventriculography used for the diagnosis of heart failure?
How is the scintigraphic imaging agent iobenguane I 123 injection (AdreView) used in the diagnosis of heart failure?
What is the role of coronary angiography in the diagnosis of heart failure?
When is angiography indicated in the evaluation of heart failure?
What is the role of right heart catheterization in the diagnosis of heart failure?
What are normal right-sided hemodynamics in the evaluation of heart failure?
How is pulmonary capillary wedge pressure (PCWP) measured for the diagnosis of heart failure?
When are left-sided heart catheterization and coronary angiography indicated for the diagnosis of heart failure?
How is cardiopulmonary stress testing used in the evaluation of heart failure?
Treatment
What is the prognostic relationship between sleep apnea and heart failure?
What is the relationship between anemia and heart failure?
What is included in the medical care of heart failure?
Which invasive therapies are used in the treatment of heart failure?
What is the role of heart transplantation in the treatment of heart failure?
Why is it important to evaluate patients with heart failure for coronary artery disease?
What is the benefit of coronary artery bypass grafting (CABG) in patients with heart failure?
When is surgical revascularization recommended for the treatment of heart failure?
When is coronary angiography useful in the management of heart failure?
When are repeated evaluations for ischemia indicated in the management of heart failure?
What is the relationship between valvular heart disease and heart failure?
What are the treatment approaches to sleep apnea in patients with heart failure?
What risks are increased in patients with comorbid sleep apnea and heart failure?
What are the treatment approaches for anemia in patients with heart failure?
What is the relationship between cardiorenal syndrome and heart failure?
What are the classifications of cardiorenal syndrome in patients with heart failure?
What is the pathophysiology of CR1 and CR2 of cardiorenal syndrome in heart failure?
What are the indications for renal replacement therapy in heart failure?
What is the significance of an increase in creatine levels in heart failure?
How is dopamine used in the treatment of heart failure?
What is the role of nesiritide in the treatment of heart failure?
What is the role of tolvaptan in the treatment of heart failure?
What is the role of adenosine receptor antagonists in the treatment of heart failure?
What is the role of beta-blockers in the treatment of heart failure?
What is the relationship between atrial fibrillation and heart failure?
What is the role of catheter ablation in the treatment of heart failure?
What is the role of radiofrequency ablation in the treatment of heart failure?
What are the nonpharmacologic therapy options for heart failure?
What are the benefits of aerobic exercise in the treatment of heart failure?
Which measures improve treatment adherence in heart failure?
What are the dietary restrictions for patients with heart failure?
What is the significance of plasma eicosapentaenoic acid (EPA) concentrations in the prognosis of heart failure?
What is the benefit of polyunsaturated fatty acids (PUFA) in the treatment of heart failure?
Which pharmacologic therapies are used in the treatment of heart failure?
What is the role of ivabradine (Corlanor) in the treatment of heart failure?
What is the role of combination therapies for the treatment of heart failure?
What is the role of anticoagulation therapy in the treatment of heart failure?
When is infusion of positive inotropic drugs indicated in the treatment of heart failure?
Which drugs should be avoided during the treatment of heart failure?
What is the role of digoxin in the treatment of heart failure?
What are the clinical characteristics of acute heart failure?
How is acute heart failure managed?
What are the treatment options to increase ventilation in patients with acute heart failure?
What are the goals of medical therapy for acute heart failure?
How is preload reduction achieved in the treatment of acute heart failure?
Which 3 drugs are used in combination to manage acute heart failure following preload reduction?
How is hypoperfusion treated in acute heart failure?
What is the role of calcium channel blockers in the treatment of acute heart failure?
What is the role of diuretics in the treatment of acute heart failure?
How are diuretics administered for the treatment of heart failure?
How is diuretic resistance diagnosed in acute heart failure?
How is diuretic resistance managed in the treatment of acute heart failure?
When is the transition to oral diuretic therapy made in the treatment of acute heart failure?
What is the role of vasodilators in the treatment of acute heart failure?
What is the role of nitrates in the treatment of acute heart failure?
What is the role of sodium nitroprusside in the treatment of acute heart failure?
What is the role of nesiritide in the treatment of acute heart failure?
What is the role of ultrafiltration in the treatment of acute heart failure?
When is inpatient treatment required for acute heart failure?
When should hospitalization be considered for the treatment of acute heart failure?
What is included in inpatient treatment of acute heart failure?
What is the role of invasive hemodynamic monitoring in the treatment of acute heart failure?
When is invasive hemodynamic monitoring used to guide therapy for acute heart failure?
What is the role of monitoring in the management of acute heart failure?
Which implantable wireless hemodynamic monitoring system are FDA approved for acute heart failure?
What are the discharge criteria following treatment of acute heart failure?
What are the predischarge requirements for patients with acute heart failure?
What further care is required following treatment for acute heart failure?
What are the goals of treatment for heart failure with preserved left ventricular ejection fraction (HFpEF)?
What are the ACC/AHA/HFSA treatment guidelines for stage C of left ventricular ejection fraction (HFpEF) heart failure?
What are lifestyle modifications for the treatment of left ventricular ejection fraction (HFpEF) heart failure?
What is the role of diuretic therapy in the treatment of left ventricular ejection fraction (HFpEF) heart failure?
What is the role of ACEIs and ARBs in the treatment of left ventricular ejection fraction (HFpEF) heart failure?
When are beta-blockers indicated for the treatment of left ventricular ejection fraction (HFpEF) heart failure?
When are aldosterone receptor and calcium channel blockers indicated for the treatment of left ventricular ejection fraction
(HFpEF) heart failure?
When should restoration of sinus rhythm be considered for the treatment of left ventricular ejection fraction (HFpEF) heart
failure?
What is the treatment approach for right ventricular (RV) heart failure?
What are the general measures for the management of right ventricular (RV) heart failure?
What are the precipitating factors for right ventricular (RV) heart failure?
What is the role of ACEI/ARB therapy in the treatment of right ventricular (RV) heart failure?
What is the role of inotropic therapy in the treatment of right ventricular (RV) heart failure?
When are anticoagulants indicated for the treatment of right ventricular (RV) heart failure?
When is atrial septostomy considered for the treatment of right ventricular (RV) heart failure?
What is the prognosis of right ventricular (RV) heart failure?
What are the electrophysiological interventions used to treat heart failure?
What is the role of biventricular pacemakers in the treatment of heart failure?
When are dual chamber pacemakers contraindicated in the management of heart failure?
What is the role of implantable cardioverter-defibrillators (ICDs) in the treatment of heart failure?
What are the benefits of using implantable cardioverter-defibrillators (ICDs) for the primary prevention of heart failure?
How is cardiac resynchronization therapy (CRT) used in the treatment of heart failure?
What are the benefits of combined CRT-ICD for the treatment of heart failure?
When is cardiac resynchronization therapy (CRT) contraindicated in the treatment of heart failure?
What is the CRT techniques used in the treatment of heart failure?
What improvements have been seen following cardiac resynchronization therapy (CRT) for the treatment of heart failure?
What is the efficacy of combined CRT-ICD treatment for heart failure?
What is the difference in outcomes between men and women treated with combined CRT-ICD for heart failure?
Which medications were evaluated in the Multicenter Automatic Defibrillator Implantation Trial with Cardiac Resynchronization
Therapy (MADIT-CRT) for the treatment of heart failure?
What is the role of carvedilol in the treatment of heart failure?
How does CRT affect mortality in patients with heart failure?
What decrease in mortality was seen from biventricular pacing in the treatment of heart failure?
What is a common cause of mortality in patients with heart failure?
What is the efficacy of biventricular pacing for the treatment of heart failure?
What factors are used to determine choice of revascularization procedure in the treatment of heart failure?
How is the need for angiography determined in patients with heart failure at low risk for coronary artery disease (CAD)?
What are the prognostic comparisons between medical and surgical therapy for coronary artery disease (CAD) in heart failure?
What is the efficacy of surgical revascularization for the treatment of heart failure?
What are the benefits of surgical revascularization in ischemic heart failure?
What is the role of coronary artery bypass grafting (CABG) in the treatment of coronary artery disease (CAD) and heart failure?
What is the prognosis of coronary artery diseases (CAD) and heart failure following coronary artery bypass grafting (CABG)?
What is the efficacy of combined medical therapy and CABG for the treatment of heart failure?
In which patient groups is medical therapy alone effective for the treatment of heart failure?
How do mortality rates compare between combined CABG with medical therapy and medical therapy alone for the treatment of
heart failure?
Which surgical techniques and preventive strategies are used in the treatment of high-risk patients with heart failure?
What is the relationship between valvular heart disease and heart failure?
What is the relationship between diseases of the aortic valve and heart failure?
When is aortic valve replacement indicated in the treatment of heart failure?
What precautions should be taken when treating heart failure in patients with aortic valve disease?
In which patient group is valvular surgery recommended for the treatment of heart failure?
Which common symptom of aortic stenosis is a strong indicator of mortality from heart failure?
What is the age-corrected survival rate for heart failure following aortic valve replacement (AVR)?
How does the etiology of ventricular dysfunction affect the efficacy of aortic valve replacement (AVR) for treatment of heart
failure?
Why is precise measurement of the aortic valve difficult in patients with heart failure?
What is the role of dobutamine testing in the preoperative evaluation of patients with heart failure?
How does surgical timing affect the survival in heart failure?
What the relationship between mitral valve regurgitation and heart failure?
What are the goals of mitral valve surgery in patients with heart failure?
What are the benefits of mitral valve repair for the treatment of heart failure?
What are the limitations of mitral valve repair in patients with heart failure?
What is the role of mitral regurgitation etiology in treatment selection for heart failure?
In which patients should mitral valve surgery be considered for the treatment of heart failure?
What is the role of cardiac resynchronization therapy (CRT) in the treatment of heart failure with mitral valve regurgitation?
What is the role of annuloplasty in the treatment of heart failure?
What are the limitations of annuloplasty in the treatment of heart failure?
How is mitral valve replacement performed in the treatment of heart failure?
What is the role of percutaneous mitral valve repair in the treatment of heart failure?
What is the efficacy of percutaneous mitral valve repair in the treatment of heart failure?
What is the ventricular response to heart failure?
What is the goal of ventricular restoration following heart failure?
What is the role of the Batista procedure in the treatment of heart failure?
What is the focus of ventricular restoration following heart failure?
What are the benefits from ventricular restoration in the treatment of heart failure?
What is the efficacy of ventricular restoration in the treatment of heart failure?
What is the role of extracorporeal membrane oxygenation (ECMO) in the treatment of heart failure?
What are the indications for extracorporeal membrane oxygenation (ECMO) in the treatment of heart failure?
What is the role of ventricular assist devices in the treatment of heart failure?
How are ventricular assistive devices used in the treatment of heart failure?
What are the options for bridging patient with heart failure to recovery and transplantation?
Which left ventricular assist devices (LVADs) are FDA approved for heart failure destination therapy?
What are the potential complications of left ventricular assist devices (LVADs) for the treatment of heart failure?
What is efficacy of left ventricular assist devices (LVADs) in the treatment of heart failure?
What modifications have reduced the mortality rates of left ventricular assist devices (LVADs) for the treatment of heart failure?
Which types of ventricular assist devices (VADs) can be used by outpatients with heart failure?
What is the postmarket approval efficacy of left ventricular assist devices (LVADs) for the treatment of heart failure?
What are the advantages of continuous-flow left ventricular (LV) assist devices (LVADs) in the bridge treatment of heart failure?
How is class IV stage D heart failure treated?
What are the possible complications of continuous-flow left ventricular assist devices (LVADs) in severe heart failure?
What is the role of heart transplantation in the treatment of heart failure?
In which patient groups is heart transplantation the criterion standard for therapy for heart failure?
What are the benefits of heart transplantation for heart failure?
Which factors are critical for a good outcome following heart transplantation for heart failure?
What are the absolute indications for heart transplantation for treatment of heart failure?
What are the relative indications for heart transplantation for treatment of heart failure?
Which indications in isolation are not sufficient for heart transplantation to treat heart failure?
When is heart transplantation contraindicated for the treatment of heart failure?
Which treatments are not recommended by the HFSA for the treatment of heart failure?
How does coronary graft atherosclerosis affect the outcome of heart transplantation for heart failure?
How often is heart transplantation performed in the US?
What is the role of the total artificial heart (TAH) in the treatment of heart failure?
What are the advantages of the total artificial heart (TAH) in the treatment of heart failure?
Which artificial hearts (TAHs) are commercially available for the treatment of heart failure?
What is the SynCardia TAH for the treatment of heart failure?
What is the AbioCor TAH for the treatment of heart failure?
What are the limitations of the AbioCor TAH for the treatment of heart failure?
What surgery is required prior to implementation of TAHs for the treatment of heart failure?
How is the CARMAT TAH used in the treatment of heart failure?
What are the clinical applications of artificial-heart technology in the treatment of heart failure?
Guidelines
Who is the contributor for heart failure guidelines?
What is the Framingham classification of heart failure?
What are the major diagnostic criteria for heart failure?
What are the minor diagnostic criteria for heart failure?
What are the New York Heart Association (NYHA) functional classifications of heart failure?
What is the ACCF/AHA staging system for heart failure?
What are the HRS-EHRA guidelines for targeted LQTS genetic testing in individuals at high risk for heart failure?
What are the HRS-EHRA guidelines for LQTS mutation specific genetic testing in individuals at high risk for heart failure?
What are the HRS-EHRA guidelines for targeted CPVT genetic testing in individuals at high risk for heart failure?
What are the HRS-EHRA guidelines for targeted BrS genetic testing in individuals at high risk for heart failure?
What are the HRS-EHRA guidelines for genetic testing for cardiac conduction disease (CCD) in individuals at high risk for heart
failure?
What are the HRS-EHRA guidelines for targeted SQTS genetic testing in individuals at high risk for heart failure?
What are the HRS-EHRA guidelines for targeted HCM genetic testing in individuals at high risk for heart failure?
What are the HRS-EHRA guidelines for targeted ACM/ARVC genetic testing in individuals at high risk for heart failure?
What are the HRS-EHRA guidelines for targeted DCM genetic testing in individuals at high risk for heart failure?
What are the HRS-EHRA guidelines for genetic testing for left ventricular noncompaction (LVNC) in individuals at high risk for
heart failure?
What are the HRS-EHRA guidelines for genetic testing for restrictive cardiomyopathy (RCM) in individuals at high risk for heart
failure?
What are the HRS-EHRA guidelines for genetic testing for familial DCM in individuals at high risk for heart failure?
What are the HRS-EHRA guidelines for genetic testing for idiopathic DCM in individuals at high risk for heart failure?
What are HFSA recommendations for genetic evaluation of cardiomyopathy in individuals at high risk for heart failure?
Which organizations have issued guidelines for the diagnosis and management of heart failure?
Which basic lab tests are recommended for the initial evaluation of suspected heart failure?
What are the guidelines for measurement of BNP and NT-proBNP levels in the evaluation of suspected heart failure?
What are the guidelines for use of imaging studies in evaluation of suspected heart failure?
According to guidelines, which studies may be indicated in selected patients with heart failure?
What are the guidelines for use of cardiac catheterization and coronary angiography in the evaluation of suspected heart
failure?
According to the ACCF/AHA guidelines, when is routine endomyocardial biopsy (EMB) indicated to diagnose heart failure?
When does the ESC recommend considering endomyocardial biopsy (EMB) in the diagnosis of heart failure?
When does the ACCF/AHA recommend a 6-minute walk test in the diagnosis of heart failure?
In which situations does HFSA guidelines suggest routine maximal exercise stress testing in the diagnosis of heart failure?
Which values of peak oxygen consumption reflect poor cardiac performance in the evaluation of heart failure?
What are the guidelines for nonpharmacologic therapy of heart failure?
What are the treatment guidelines for chronic heart failure?
What is the purpose of patient education in the management of heart failure?
What are the dietary treatment guidelines for heart failure?
Which agents should be avoided by patients with heart failure?
When are angiotensin receptor blockers (ARBs) recommended in patients with chronic heart failure?
Which organizations have aligned their guidelines for pharmacologic therapy of heart failure?
What are the class I recommendations for pharmacologic therapy of chronic heart failure with reduced ejection fraction
(HFrEF)?
When are ACE inhibitors recommended in patients with chronic heart failure?
When are angiotensin receptor–neprilysin inhibitors (ARNIs) recommended in patients with chronic heart failure?
When is ivabradine recommended in the treatment of chronic heart failure?
When should angiotensin receptor–neprilysin inhibitors (ARNIs) contraindicated in the treatment of chronic heart failure?
What is the role of device therapy for heart failure?
What are the HFSA recommendations for the use of pacemakers in patients with heart failure?
What are the ACC/AHA guidelines for consideration of cardiac resynchronization therapy (CRT) to treat heart failure?
What are the ACCF/AHA and ESC guidelines for implantable cardioverter-defibrillator (ICD) placement in patients with heart
failure?
What are the ACCF/AHA guidelines for patient selection for cardiac resynchronization therapy (CRT) in heart failure?
What are European Society of Cardiology (ESC) guidelines class I recommendations for the use of cardiac resynchronization
therapy (CRT) in patients with heart failure?
For which groups should cardiac resynchronization therapy (CRT) be considered for the treatment of heart failure?
For which groups should cardiac resynchronization therapy (CRT) be considered for the treatment of heart failure?
When is cardiac resynchronization therapy (CRT) contraindicated in the treatment of heart failure?
What are the guidelines for use of coronary artery bypass graft (CABG) and percutaneous coronary intervention (PCI)
revascularization procedures in patients with heart failure?
For which patients with heart failure is revascularization recommended?
In which patients with heart failure is the benefit-risk balance of revascularization uncertain?
When is aortic valve replacement (AVR) recommended by the ACCF/AHA for the treatment of heart failure?
What is the HFSA guideline for mitral valve repair or replacement in patients with heart failure?
What are the ESC recommendations for valvular surgery in heart failure?
Which organizations have release guidelines for the use of mechanical circulatory support (MCS) in patients with heart failure?
Which mechanical circulatory support (MCS) devices are available for the treatment of heart failure?
What are the SCAI/ACC/HFSA/STS recommendation for the use of mechanical circulatory support (MCS) devices in heart
failure?
What is the recommendation for routine use of mechanical circulatory support (MCS) devices for heart failure?
What are the ISHLT guidelines for mechanical circulatory support (MCS) devices in the treatment of patients in acute
cardiogenic shock?
What are the ISHLT guidelines for heart failure therapy via mechanical circulatory support (MCS) devices?
What are the AHA guidelines for mechanical circulatory support (MCS) in the treatment of heart failure?
What are the ACCF/AHA and HFSA guidelines for consideration of heart transplantation in the treatment of heart failure?
What are the ESC guidelines for consideration of heart transplantation in the treatment of heart failure?
What do the ESC guidelines consider contraindications for heart transplantation in patients with heart failure?
What are the HFSA recommended treatment goals for acute decompensated heart failure (ADHF)?
What are the HFSA guidelines indications for hospital admission in acute decompensated heart failure (ADHF)?
What are the ACCF/AHA guidelines for adjustment of maintenance medications in acute decompensated heart failure (ADHF)?
What is the aim of diuretic therapy for heart failure?
What are the recommended doses of diuretics for the treatment of heart failure?
When is beta-blocker therapy initiated in hospitalized patients with heart failure?
What are the recommendations for adjuvant treatment in heart failure?
What are the HFSA guidelines for invasive hemodynamic monitoring in patients with heart failure?
What are the HFSA recommendations for routine administration of supplemental oxygen in the treatment of heart failure?
Medications
What are the goals of drug treatment for the treatment of heart failure?
What is the role of ivabradine (Corlanor) in the treatment of heart failure?
What is the role of combination sacubitril/valsartan (Entresto) therapy for the treatment of heart failure?
Which drugs should be avoided by patients with heart failure?
Which medications in the drug class Opioid Analgesics are used in the treatment of Heart Failure?
Which medications in the drug class Anticoagulants, Cardiovascular are used in the treatment of Heart Failure?
Which medications in the drug class Calcium Channel Blockers are used in the treatment of Heart Failure?
Which medications in the drug class Alpha/Beta Adrenergic Agonists are used in the treatment of Heart Failure?
Which medications in the drug class Aldosterone Antagonists, Selective are used in the treatment of Heart Failure?
Which medications in the drug class Diuretics, Potassium-Sparing are used in the treatment of Heart Failure?
Which medications in the drug class Diuretics, Other are used in the treatment of Heart Failure?
Which medications in the drug class Diuretics, Thiazide are used in the treatment of Heart Failure?
Which medications in the drug class Diuretics, Loop are used in the treatment of Heart Failure?
Which medications in the drug class ARNIs are used in the treatment of Heart Failure?
Which medications in the drug class I(f) Inhibitors are used in the treatment of Heart Failure?
Which medications in the drug class B-type Natriuretic Peptides are used in the treatment of Heart Failure?
Which medications in the drug class Nitrates are used in the treatment of Heart Failure?
Which medications in the drug class Vasodilators are used in the treatment of Heart Failure?
Which medications in the drug class Inotropic Agents are used in the treatment of Heart Failure?
Which medications in the drug class ARBs are used in the treatment of Heart Failure?
Which medications in the drug class ACE Inhibitors are used in the treatment of Heart Failure?
Which medications in the drug class Beta-Blockers, Beta-1 Selective are used in the treatment of Heart Failure?
Which medications in the drug class Beta-Blockers, Alpha Activity are used in the treatment of Heart Failure?
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, Division of Cardiology,
Veterans Affairs Medical Center
Ioana Dumitru, MD is a member of the following medical societies: American College of Cardiology, International Society for
Heart and Lung Transplantation, Heart Failure Society of America
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
Specialty Editor Board
Mary L Windle, PharmD Adjunct Associate Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-
Chief, Medscape Drug Reference
Yasmine S Ali, MD, FACC, FACP, MSCI Assistant Clinical Professor of Medicine, Vanderbilt University School of Medicine;
President, LastSky Writing, LLC
Yasmine S Ali, MD, FACC, FACP, MSCI is a member of the following medical societies: American College of Cardiology,
American College of Physicians, American Heart Association, American Medical Association, American Medical Writers
Association, National Lipid Association, Tennessee Medical Association
Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: MCG Health, LLC; LastSky
Writing, LLC; Philips Healthcare; Cardiac Profiles, Inc.; Corvidane; M Health; GE Healthcare; Athena Health; PeerView Institute;
Verywell Health; HealthCentral.
Chief Editor
Gyanendra K Sharma, MD, FACC, FASE Professor of Medicine and Radiology, Director, Adult Echocardiography Laboratory,
Section of Cardiology, Medical College of Georgia at Augusta University
Gyanendra K Sharma, MD, FACC, FASE is a member of the following medical societies: American Association of Cardiologists
of Indian Origin, American Association of Physicians of Indian Origin, American College of Cardiology, American Society of
Echocardiography, Society for Cardiovascular Magnetic Resonance, Society of Cardiovascular Computed Tomography
Additional Contributors
Henry H Ooi, MD, MRCPI Director, Advanced Heart Failure and Cardiac Transplant Program, Nashville Veterans Affairs
Medical Center; Assistant Professor of Medicine, Vanderbilt University School of Medicine
Mariclaire Cloutier Freelance editor, Medscape Drugs & Diseases
Acknowledgements
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
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
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1/3/2021 https://emedicine.medscape.

Signs and symptoms

Exertional dyspnea and/or dyspnea at rest

See Presentation for more detail.

Heart failure criteria, classification, and staging

Major criteria comprise the following:

Paroxysmal nocturnal dyspnea

Class I: No limitation of physical activity

Complete blood count (CBC)

See Workup for more detail.

Treatment includes the following:

Surgical treatment options include the following:

See Treatment and Medication for more detail.

Class I patients have no limitation of physical activity

Most important among the adaptations are the following[12] :

Myocytes and myocardial remodeling

Systolic and diastolic failure

Atrial natriuretic peptide and B-type natriuretic peptide

Other vasoactive systems

Heart failure with preserved ejection fraction

Rise in filling pressure

Underlying causes of systolic heart failure include the following:

Coronary artery disease

Underlying causes of diastolic heart failure include the following:

Coronary artery disease

Underlying causes of acute heart failure include the following:

Acute valvular (mitral or aortic) regurgitation

Underlying causes of high-output heart failure include the following:

Underlying causes of right heart failure include the following:

Precipitating causes of heart failure

Heart failure statistics for the United States are as follows[31] :

Paroxysmal nocturnal dyspnea

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

Chest pain/pressure and palpitations

Fatigue and weakness

Nocturia and oliguria

Predominant Right-Sided Heart Failure

Heart Failure in Children

Heart Failure Criteria, Classification, and Staging

Major Criteria Minor Criteria

Paroxysmal nocturnal dyspnea Nocturnal cough

Weight loss of 4.5 kg in 5 days in response to treatment Dyspnea on ordinary exertion

A decrease in vital capacity by one third the maximal value

Rales Pleural effusion

Acute pulmonary edema Tachycardia (rate of 120 bpm)

Hepatojugular reflux Hepatomegaly

S3 gallop Bilateral ankle edema

Central venous pressure >16 cm water

Circulation time of ≥25 seconds

NYHA classification of functional heart failure

Class Functional Capacity

I Patients without limitation of physical activity

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

ACC/AHA stages of heart failure

Level Description Examples Notes

Structural heart The majority of patients with heart failure are

Patients in this stage may be eligible to

LV = left ventricle; LVH = LV hypertrophy; NYHA = New York Heart Association.

Treat hypertension (optimal blood pressure: < 130/80 mm Hg [56] )

Cardiogenic and noncardiogenic pulmonary edema

Acute Respiratory Distress Syndrome (ARDS)

Cardiogenic Pulmonary Edema

Chronic Obstructive Pulmonary Disease (COPD)