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.
View Media Gallery
Signs and symptoms
Signs and symptoms of heart failure include the following:
 Exertional dyspnea and/or dyspnea at rest
 Orthopnea
 Acute pulmonary edema
 Chest pain/pressure and palpitations
 Tachycardia
 Fatigue and weakness
 Nocturia and oliguria
 Anorexia, weight loss, nausea
 Exophthalmos and/or visible pulsation of eyes
 Distention of neck veins
 Weak, rapid, and thready pulse
 Rales, wheezing
 S 3 gallop and/or pulsus alternans
 Increased intensity of P 2 heart sound
 Hepatojugular reflux
 Ascites, hepatomegaly, and/or anasarca
  Central or peripheral cyanosis, pallor
See 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
 Acute pulmonary edema
 Hepatojugular reflux
 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
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.

This chest radiograph shows

an enlarged cardiac silhouette and edema at the lung bases, signs of acute
heart failure.
View Media Gallery
 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).
View Media Gallery
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:
 Coronary artery disease
 Diabetes mellitus
 Hypertension
 Valvular heart disease (aortic stenosis)
 Hypertrophic cardiomyopathy
 Restrictive cardiomyopathy (amyloidosis, sarcoidosis)
 Constrictive pericarditis
Underlying causes of acute heart failure include the following:
 Acute valvular (mitral or aortic) regurgitation
 Myocardial infarction (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]
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
 Paroxysmal nocturnal dyspnea
 Dyspnea at rest
 Acute pulmonary edema
Other cardiac symptoms of heart failure include chest pain/pressure and
palpitations. Common noncardiac signs and symptoms of heart failure include
anorexia, nausea, weight loss, bloating, fatigue, weakness, oliguria, nocturia,
and cerebral symptoms of varying severity, ranging from anxiety to memory
impairment and confusion. Findings from the Framingham Heart Study
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
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).