Heart failure in children: Etiology, clinical

manifestations, and diagnosis

Authors: Rakesh K Singh, MD, MS, TP Singh, MD, MSc
Section Editor: John K Triedman, MD
Deputy Editor: Carrie Armsby, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Jan 2024. | This topic last updated: Nov 23, 2022.

INTRODUCTION

Heart failure (HF) results from structural or functional cardiac disorders that impair
the ability of the ventricle(s) to fill with and/or eject blood. The presentation of
pediatric HF is diverse because of the numerous underlying cardiac etiologies
( table 1) and varying clinical settings.

The etiology, clinical manifestations, and diagnostic evaluation of HF in children are

reviewed here. The management of HF in children is discussed separately. (See "Heart
failure in children: Management".)

EPIDEMIOLOGY

In the United States, HF is estimated to affect 12,000 to 35,000 children below the age
of 19 years in the United States each year [1,2]. HF-related hospitalizations account
for approximately 11,000 to 14,000 hospitalizations in children per year in the United
States [2]. Pediatric HF-related hospitalizations are associated with a higher length of
stay, readmission rate, hospital charges, and mortality rate compared with non HF-
related admissions [2-5].

ETIOLOGY AND PATHOPHYSIOLOGY

The causes of pediatric HF can be divided into pathophysiologic categories ( table 1).
This categorization helps in the understanding of the underlying physiology and
clinical manifestations of the different causes of pediatric HF and guides the approach
to management. It is important to recognize, however, that these categories may
overlap in some patients (eg, volume overload and pressure overload can be
associated with ventricular dysfunction).

Ventricular dysfunction — The cardiac causes of ventricular dysfunction can be

separated into children with structurally normal hearts and those born with
congenital heart disease (CHD) ( table 1).

Structurally normal heart — Ventricular dysfunction leads to impaired ejection of

blood from the ventricle. Unless specified, ventricular dysfunction implies systolic
dysfunction (reduced ventricular contractility). Ventricular diastolic dysfunction
implies impaired ventricular filling and noncompliance with abnormally steep
pressure-volume relationship, resulting in high ventricular filling pressures.
Ventricular dysfunction (systolic or diastolic) can occur in children with CHD and in
those with structurally normal hearts. Children with CHD may have ventricular
dysfunction at presentation but more commonly develop dysfunction and HF several
years (or even decades) following surgical repair of their cardiac defect (ie, "burnt-out"
CHD).

Causes of ventricular dysfunction in children with structurally normal hearts include:

● Cardiomyopathy – The most common cause of HF in children with a structurally
normal heart is cardiomyopathy. Based on data from large registry studies, the
estimated incidence of pediatric cardiomyopathy is approximately 1 case per
100,000 children per year [6,7]. Dilated cardiomyopathy accounts for 50 to 60
percent of cases, hypertrophic cardiomyopathy (HCM) accounts for 25 to 40
percent, left ventricular (LV) noncompaction accounts for 9 percent, and
restrictive or other types of cardiomyopathy accounts for approximately 3
percent. (See "Definition and classification of the cardiomyopathies".)

Although the primary physiologic abnormality in dilated cardiomyopathy is LV

systolic dysfunction, diastolic dysfunction can occur in more severe cases. In
contrast, LV systolic function is usually preserved in children with HCM and
 restrictive cardiomyopathy; when HF occurs in these settings, it is usually due to
diastolic dysfunction. HF is rare in children with HCM as most patients have
preserved ventricular function. Patients with HCM who present in infancy with HF
symptoms are at high risk of mortality. (See "Hypertrophic cardiomyopathy in
children: Clinical manifestations and diagnosis".)
● Myocarditis – Inflammation of the myocardium (myocarditis) is usually due to a
viral infection; less commonly, it may be caused by nonviral pathogens or
noninfectious causes ( table 2). Myocarditis often results in ventricular
dysfunction and HF [8]. Acute myocarditis may be followed by either a complete
recovery of LV function or a secondary dilated cardiomyopathy with chronic HF.
Myocarditis is discussed in greater detail separately. (See "Clinical manifestations
and diagnosis of myocarditis in children".)
● Myocardial ischemia/infarction – In children, HF as a result of myocardial
ischemia/infarction is uncommon:

• Infants born with anomalous left coronary artery arising from the pulmonary
artery (ALCAPA) usually present with symptoms and signs of myocardial
ischemia/infarction and are often in HF. (See "Congenital and pediatric
coronary artery abnormalities", section on 'Variations of coronary artery origin
from the pulmonary artery'.)

• Coronary vasculitis associated with Kawasaki disease may rarely present with
myocardial ischemia and LV dysfunction. (See "Cardiovascular sequelae of
Kawasaki disease: Clinical features and evaluation".)

• Myocardial ischemia/infarction due to premature atherosclerotic coronary

artery disease is very rare in childhood but can occur in homozygous familial
hypercholesterolemia. (See "Familial hypercholesterolemia in children".)
● Arrhythmias – The following arrhythmias may lead to ventricular dysfunction
and pediatric HF:

• Complete heart block – Complete heart block may lead to HF if the junctional
escape rhythm is not fast enough for the body's needs. Complete heart block is
discussed in greater detail separately. (See "Congenital third-degree (complete)
atrioventricular block" and "Third-degree (complete) atrioventricular block".)
 • Supraventricular and ventricular arrhythmias – Supraventricular
arrhythmias (eg, supraventricular tachycardia, atrial flutter, atrial fibrillation,
ectopic atrial tachycardia, or paroxysmal junctional reciprocating tachycardia),
if incessant and not recognized for hours/days after onset, may result in
ventricular dysfunction and HF. Similarly, junctional or ventricular tachycardia
may also lead to progressive HF. It may be difficult to ascertain in a child
presenting with ventricular dysfunction and a concurrent tachyarrhythmia
whether the arrhythmia is the primary diagnosis (with secondary ventricular
dysfunction) or is secondary to an underlying cardiomyopathy/ventricular
dysfunction. Control of arrhythmia with medications or ablative methods
usually leads to improved ventricular function. (See "Irregular heart rhythm
(arrhythmias) in children" and "Clinical features and diagnosis of
supraventricular tachycardia (SVT) in children" and "Management and
evaluation of wide QRS complex tachycardia in children", section on
'Monitoring'.)
● Drug/toxins – Pediatric cancer patients who have been treated with
chemotherapy agents, especially anthracyclines, carry a lifelong risk of
developing ventricular dysfunction and HF [9]. (See "Clinical manifestations,
diagnosis, and treatment of anthracycline-induced cardiotoxicity" and "Risk and
prevention of anthracycline cardiotoxicity".)
● Noncardiac causes – Noncardiac causes of HF due to ventricular dysfunction
include:

• Sepsis (see "Sepsis in children: Definitions, epidemiology, clinical

manifestations, and diagnosis")

• Chronic kidney disease (see "Chronic kidney disease in children:

Complications", section on 'Risk for cardiovascular disease' and "Cardiorenal
syndrome: Definition, prevalence, diagnosis, and pathophysiology")

• Respiratory disorders (eg, obstructive sleep apnea, bronchopulmonary

dysplasia, cystic fibrosis, interstitial lung disease), which can cause pulmonary
hypertension and right HF (see "Pulmonary hypertension in children:
Classification, evaluation, and diagnosis", section on 'Lung disease')
 • HIV infection (see "Pediatric HIV infection: Classification, clinical
manifestations, and outcome", section on 'Long-term morbidities' and "Cardiac
and vascular disease in patients with HIV")

• Systemic lupus erythematous (see "Childhood-onset systemic lupus

erythematosus (SLE): Clinical manifestations and diagnosis", section on
'Cardiac')

Congenital heart disease — Ventricular dysfunction may develop in children born

with complex CHD who undergo surgical repair or palliation in early childhood.
Although impaired ventricular function is most frequently detected by the onset of
symptoms during adolescence and young adulthood, it may be detected earlier in the
first decade of life on routine echocardiographic imaging in asymptomatic patients.
The progression of ventricular dysfunction is variable depending on the underlying
pathophysiology of the corrected cardiac defect. As long-term survival following
complex CHD repair continues to improve, these patients with "burnt-out" CHD are
expected to represent a growing proportion of patients with chronic HF in the general
population [10]. (See "Management of complications in patients with Fontan
circulation", section on 'Heart failure'.)

Volume overload with preserved ventricular contractility — Volume overload may

be due to cardiac or noncardiac causes:
● Cardiac causes – Volume overload occurs due to a moderate or large
communication (shunt) between systemic and pulmonary circulations and may
occur with the following cardiac lesions ( table 1):

• Ventricular septal defect (see "Isolated ventricular septal defects (VSDs) in

infants and children: Anatomy, clinical features, and diagnosis")

• Patent ductus arteriosus (see "Clinical manifestations and diagnosis of patent

ductus arteriosus (PDA) in term infants, children, and adults")

• Atrial septal defect, rarely (see "Isolated atrial septal defects (ASDs) in children:
Classification, clinical features, and diagnosis")

• Aortopulmonary window
• Atrioventricular septal defect
 • Single ventricle physiology with unobstructed pulmonary blood flow
In the early neonatal period, infants with these defects generally do not have
clinically significant left-to-right shunting, due to high pulmonary vascular
resistance (PVR). During the first six to eight weeks after birth, the physiologic
decline in PVR leads to a progressive increase in shunting with increase in
pulmonary blood flow, pulmonary venous return, and left (systemic) ventricular
preload, resulting in symptoms and signs of HF. (See "Pathophysiology of left-to-
right shunts".)

Volume overload may also occur with valvular insufficiency from:

• Aortic regurgitation, seen in some children with bicuspid aortic valves and
following catheter-based intervention in patients with valvar aortic stenosis (ie,
balloon aortic valvuloplasty). (See "Aortic regurgitation in children" and
"Subvalvar aortic stenosis (subaortic stenosis)".)

• Mitral regurgitation. (See "Clinical manifestations and diagnosis of chronic

mitral regurgitation".)

• Pulmonary regurgitation, seen in some children as a long-term complication

following tetralogy of Fallot repair. (See "Tetralogy of Fallot (TOF): Long-term
complications and follow-up after repair", section on 'Chronic pulmonary
regurgitation'.)
● Noncardiac causes – Noncardiac causes of HF due to volume overload with
preserved ventricular pump function include:

• Arteriovenous malformation (extracardiac shunting)

• Fluid overload (eg, oliguric renal failure)
Pressure overload with preserved ventricular contractility — Pressure overload
may be caused by CHD with severe ventricular outflow obstruction that impedes
ejection of blood from the heart, resulting in inadequate cardiac output and/or high
filling pressures. Mild outflow obstruction is asymptomatic; however, severe
obstruction often presents acutely with HF (low cardiac output) in early infancy.
Moderate/severe outflow obstruction may also lead to HF from chronically elevated
filling pressures. Depending on severity and chronicity, pressure overload may result
in either systolic or diastolic dysfunction.

The obstructive lesions associated with HF include ( table 1):

● Aortic stenosis (see "Valvar aortic stenosis in children", section on 'Critical aortic
stenosis')
● Coarctation of the aorta (see "Clinical manifestations and diagnosis of coarctation
of the aorta", section on 'Manifestations according to age')
● Pulmonary stenosis (see "Clinical manifestations and diagnosis of pulmonic
stenosis in adults")

In addition, systemic hypertension can result in pressure overload of the heart. The
ventricular function is usually preserved, but dysfunction may occur with severe
hypertension. Similarly, pulmonary hypertension results in pressure overload on the
right ventricle (RV) and may result in right HF. (See "Evaluation of hypertension in
children and adolescents" and "Pulmonary hypertension in children: Classification,
evaluation, and diagnosis".)

CLINICAL MANIFESTATIONS

Symptoms and physical findings in children with HF reflect the patient's inability to
adequately increase cardiac output (eg, exercise intolerance and easy fatigue) and/or
pulmonary or systemic fluid overload (eg, shortness of breath at rest or with effort
due to pulmonary interstitial edema or hepatomegaly).

Symptoms — Symptoms of HF vary with the age of the patient as follows:

● Infants – The most common symptoms are tachypnea and diaphoresis during
feeds, easy fatigability, irritability, decreased volume of feeds, and poor weight
gain. Undernutrition may result in delayed motor milestones.
● Young children – In young children, symptoms may include gastrointestinal
symptoms (abdominal pain, nausea, vomiting, and poor appetite), poor weight
gain, easy fatigability, and recurrent or chronic cough with wheezing. These
 symptoms be mistaken for common childhood illnesses such as gastroenteritis,
reflux, asthma, or even behavioral issues.
● Older children – Older children may present with exercise intolerance, anorexia,
abdominal pain, wheezing, dyspnea, edema, palpitations, chest pain, or syncope
[11].

In children without underlying heart disease, the nonspecific nature of HF symptoms

can present a diagnostic challenge since noncardiac causes of many of these
symptoms are far more common in children than are cardiac etiologies. This was
highlighted in a study of 191 children with new-onset HF presenting in the primary
care or emergency department setting, of whom nearly one-half initially received a
diagnosis other than HF [12]. The most common initial diagnoses included bacterial
infections (pneumonia, sinusitis, otitis media), viral illnesses, gastroenteritis, and
asthma. Compared with patients who were correctly diagnosed at the initial visit,
patients with an initial incorrect diagnoses were older at presentation (median age 4
years versus 10 months); had a longer duration of symptoms (median seven versus
three days); and more commonly presented with gastrointestinal symptoms such as
abdominal pain, loss of appetite, nausea, and vomiting. A high index of suspicion is
needed to distinguish HF from other far more common pediatric illnesses. (See
'Differential diagnosis' below.)

A family history of congenital heart disease (CHD) or cardiomyopathy in a sibling or

parent may suggest a similar diagnosis in the child being evaluated.

Physical examination — Physical findings vary depending on the cardiac output,

degree of volume overload and pulmonary congestion, and/or systemic venous
congestion.
● Tachycardia – Tachycardia is defined as the presence of a heart rate value
greater than expected for age ( table 3). In patients with depressed myocardial
contractility, tachycardia is a response to decreased stroke volume in attempt to
maintain cardiac output.
● Poor perfusion – Poor perfusion as a result of diminished cardiac output is
manifested by cool and mottled extremities, decreased capillary refill, decreased
peripheral pulses, and lowered systemic blood pressure.
● Gallop rhythm – A third heart sound (S3) gallop may be present in children with
diminished cardiac output or volume overload. (See "Approach to the infant or
child with a cardiac murmur", section on 'Third and fourth heart sounds'.)
● Pulmonary findings – Pulmonary congestion is manifested primarily with
changes in respiratory status:

• Tachypnea is the most common finding of pulmonary congestion. Normal

respiratory rate varies with age ( table 3).

• Other signs of respiratory distress seen in patients with HF include retractions,

use of accessory respiratory muscles, and grunting with nasal flaring (in
infants).

• Auscultatory findings, including wheezing and rales, are more commonly seen
in older children as compared with infants.
● Systemic congestion – Systemic congestion may be manifested by the following
findings:

• Hepatomegaly (the most common finding)

• Peripheral edema
• Ascites and splenomegaly (may be present in severe right HF)
• Jugular venous distension (not generally observed in infants and young
children)
● Other findings – Other findings may suggest an underlying etiology for HF, as
demonstrated by the following examples:

• High blood pressure limited to upper extremities and/or weak pulses in lower
extremities are suggestive of aortic coarctation. (See "Clinical manifestations
and diagnosis of coarctation of the aorta", section on 'Blood pressure and
pulses'.)

• The presence of a systolic murmur may be seen in patients with outflow

obstruction in hypertrophic cardiomyopathy or aortic stenosis, congenital
heart defects with left-to-right shunting (eg, ventricular septal defects), or
mitral regurgitation. (See "Approach to the infant or child with a cardiac
murmur", section on 'Heart murmurs'.)
 • Precordial examination may reveal a "thrill" in patients with shunt lesions,
whereas those with a longstanding cardiomyopathy may have a "heave" with a
laterally displaced point of maximal impulse. (See "Approach to the infant or
child with a cardiac murmur", section on 'Palpation of the chest'.)

DIAGNOSTIC EVALUATION

Goals — The diagnosis of HF in children is based on a combination of clinical,

echocardiographic, and laboratory findings. Characteristic signs and physical findings
of impaired cardiac output include exercise and/or feeding intolerance, tachycardia,
respiratory distress (eg, tachypnea and dyspnea), poor perfusion, and poor growth
[13,14]. (See 'Clinical manifestations' above.)

Noninvasive imaging studies and laboratory tests are initially obtained to confirm the
diagnosis, ascertain the severity of HF, and determine the underlying cause if unclear
from the history. Evaluation should only proceed if the patient is clinically stable.

Unstable patients — In patients who have severe cardiorespiratory compromise (ie,

shock or impending cardiac arrest), prompt initiation of treatment to restore
adequate perfusion should be provided prior to undergoing a detailed evaluation to
determine the underlying cause of HF. The initial management of shock in neonates
( algorithm 1) and in infants and children ( algorithm 2) is summarized in the
algorithms and discussed in detail separately. (See "Neonatal shock: Management"
and "Shock in children in resource-abundant settings: Initial management".)

Neonates presenting with unexplained shock should be started on prostaglandin

infusion, which should be continued until a ductal-dependent cardiac defect is
excluded using echocardiography. (See "Diagnosis and initial management of cyanotic
heart disease in the newborn", section on 'Prostaglandin E1'.)

Initial evaluation — The initial evaluation generally includes chest radiography,

electrocardiogram (ECG), echocardiography, and laboratory tests (including brain
natriuretic peptide [BNP] or N-terminal pro-BNP [NT-proBNP], troponin, complete
blood count, and serum chemistries).
 Chest radiography — Chest radiography is helpful to assess for cardiomegaly and
pulmonary congestion and to monitor the effectiveness of HF treatment. Pulmonary
interstitial edema and pleural effusion are common findings in newly diagnosed HF
( image 1).

Cardiomegaly may be seen in a number of cardiac diseases, including:

● Left-to-right shunting defects – In this setting, cardiomegaly reflects the presence
of a moderate to large shunt with volume overload and subsequent atrial and
ventricular dilatation ( image 2)
● Dilated cardiomyopathy – Cardiomegaly reflects the dilatation of left ventricle (LV)
( image 3)
● Myocarditis – Ventricular dilation may not be severe in this setting, or ventricular
size may be normal ( image 4 and image 5) (see "Clinical manifestations and
diagnosis of myocarditis in children", section on 'Chest radiograph')
● Arrhythmogenic right ventricular (RV) cardiomyopathy – RV dilation may
sometimes be seen (see "Arrhythmogenic right ventricular cardiomyopathy:
Diagnostic evaluation and diagnosis")
● Restrictive cardiomyopathy – Biatrial enlargement may be seen
● Pericardial effusion

In a prospective cohort of 95 children referred to a pediatric cardiology clinic,

cardiomegaly on chest radiograph had a specificity of 92.3 percent and a negative
predictive value of 91.1 percent in predicting ventricular dilation on echocardiogram
[15].

Electrocardiogram — The ECG is an important diagnostic tool in the evaluation of a

child with HF. Sinus tachycardia is the most common ECG finding and is nonspecific. It
represents a physiologic compensation for reduced stroke volume.

In some cases, the ECG may point toward an underlying cause. Examples include:
● ST segment and T wave abnormalities are common in all forms of
cardiomyopathy and myocarditis ( waveform 1).
 ● Increased QRS voltage that meets criteria for ventricular hypertrophy may be
seen in hypertrophic or dilated cardiomyopathy ( waveform 2).
● Decreased QRS voltage may suggest myocardial edema or pericardial effusion
and may be present in children with myocarditis ( waveform 3).
● Biatrial enlargement may be present in restrictive cardiomyopathy.
● A deep q wave in inferior and lateral leads (I, aVL, and V5-V6) with ST segment
and T wave changes is suggestive of a myocardial infarct and is a classic finding
in infants with anomalous left coronary arising from the pulmonary artery
(ALCAPA) ( waveform 4).
● Varying degrees of heart block may sometimes be observed in patients with
rheumatic or Lyme carditis or in patients with neonatal lupus.
● Atrial, junctional, or ventricular tachycardia or frequent atrial or ventricular
ectopy may suggest arrhythmia as an underlying cause of ventricular dysfunction
or may represent a complication.

Echocardiography — Echocardiography is the primary imaging modality to assess

ventricular size and function in children with signs and symptoms of HF. It also
establishes whether the child has a structurally normal heart or underlying structural
congenital heart disease (CHD).

Important aspects of the echocardiogram evaluation include [13]:

● Cardiac anatomy
● Arterial and venous connections
● Origin of coronary arteries
● Presence and amount of shunting
● Presence and amount of valvular stenosis and regurgitation
● Atrial and ventricular sizes (including chamber size, wall thickness, and
trabeculations)
● LV and RV global and regional systolic function
● LV diastolic function
● Estimation of RV and pulmonary artery pressures
● Atrial or ventricular thrombi
 ● Pericardial effusion

Measurements of ventricular size, mass, and volume are compared with normalized
pediatric values to account for variations by age and body size [14].

Echocardiographic findings in children with HF vary depending on the mechanism:

● Ventricular dysfunction – Findings that suggest ventricular dysfunction include:

• Impaired ventricular systolic function (eg, ejection fraction <56 percent or

fractional shortening <29 percent [16,17])
• Enlarged or dilated ventricle(s) assessed as Z-scores of ventricular volume
compared with healthy age-matched children [17,18]

Left atrial and ventricular size may be helpful in determining chronicity. LV

dilation, a spherical appearance, and eccentric hypertrophy (increased mass with
normal wall thickness), often described as components of remodeling, usually
suggest longstanding dilated cardiomyopathy rather than an acute process (eg,
myocarditis).
● Volume overload – Findings that suggest volume overload include:

• Atrial and/or ventricular enlargement

• Sizable septal defects with a large amount of shunting
• Severe valvar regurgitation
● Pressure overload – Findings that suggest pressure overload include:

• Ventricular hypertrophy (eg, increased LV wall thickness)

• Severe outflow tract obstruction (eg, valvar, subvalvar, or supravalvar aortic or
pulmonic stenosis)

Echocardiographic findings in specific causes of HF are discussed in detail separately:

● Dilated cardiomyopathy (see "Causes of dilated cardiomyopathy", section on
'Definition')
● Hypertrophic cardiomyopathy (HCM) (see "Hypertrophic cardiomyopathy: Clinical
manifestations, diagnosis, and evaluation", section on 'Echocardiography')
● Restrictive cardiomyopathy (see "Restrictive cardiomyopathies", section on
'Echocardiography')
 ● Arrhythmogenic RV cardiomyopathy (see "Arrhythmogenic right ventricular
cardiomyopathy: Diagnostic evaluation and diagnosis", section on
'Echocardiography')
● LV noncompaction (see "Isolated left ventricular noncompaction in adults: Clinical
manifestations and diagnosis", section on 'Echocardiography')
● Myocarditis (see "Clinical manifestations and diagnosis of myocarditis in
children", section on 'Echocardiogram')
● ALCAPA (see "Congenital and pediatric coronary artery abnormalities", section on
'Noninvasive imaging')
● Pulmonary hypertension (see "Pulmonary hypertension in children: Classification,
evaluation, and diagnosis", section on 'Echocardiography')
● CHD (eg, ventricular septal defect, patent ductus arteriosus, atrial septal defect)
(see "Echocardiographic evaluation of ventricular septal defects" and "Clinical
manifestations and diagnosis of patent ductus arteriosus (PDA) in term infants,
children, and adults", section on 'Echocardiography' and "Isolated atrial septal
defects (ASDs) in children: Classification, clinical features, and diagnosis", section
on 'Echocardiography')

Laboratory tests — For most children who present with new onset of HF symptoms,
initial laboratory tests include the following:
● BNP – BNP measurements are used to assess the severity of HF and monitor
response to therapy [19].

BNP and the inactive N-terminal fragment (NT-proBNP) levels have been
extensively studied in adults and are used to assist in the diagnosis and
monitoring of HF and as prognostic markers. (See "Natriuretic peptide
measurement in heart failure".)

BNP and NT-proBNP appear to be effective markers of structural and functional

heart disease in children and are useful in the integrated evaluation of children
with HF [14,19-22]. The role of these markers in pediatric patients is less well
established than in adults due to differences in ventricular impairment and
morphology between adult and pediatric cardiac diseases and the lack of
 normative pediatric standards (because of variation of levels due to assay
methods and age). BNP and NT-proBNP levels are higher at birth and decrease
rapidly during the first days of life [23].

BNP levels can help discriminate between cardiac disease and noncardiac causes
of HF symptoms (eg, pulmonary disease) [24-27]. BNP testing has been used in a
wide range of pediatric cardiac diseases, including CHD [22,28,29], myocarditis,
cardiomyopathy, pulmonary hypertension, and anthracycline-induced cardiac
toxicity [30-32].

In patients with left-to-right shunting defects (eg, atrial or ventricular septal

defects, patent ductus arteriosus), BNP levels correlate with the degree of
shunting [22,33]; and in children with ventricular dysfunction, BNP levels
correlate negatively with ejection fraction [34-37]. BNP levels also correlate with
functional class of HF and with outcome [22,26,33-39]. Higher age-adjusted NT-
proBNP levels have been shown to be a predictor of major adverse cardiovascular
events in children with CHD [40].
● Troponin – Cardiac troponin I and troponin T are sensitive biomarkers for
myocyte injury. Troponin levels are elevated in myocarditis and myocardial
ischemia. Among children presenting with LV dysfunction, an elevated troponin
level may suggest acute myocarditis rather than dilated cardiomyopathy [41].
(See "Troponin testing: Clinical use".)
● Complete blood count and iron studies – Anemia may contribute to HF in a
predisposed patient (eg, one with a moderate to severe ventricular septal defect)
or exacerbate the severity of HF symptoms in a patient with preexisting HF. In a
single institutional study of children hospitalized for acute HF, the prevalence of
anemia at the time of admission was 18 percent and nearly 40 percent of patients
developed anemia at some time during the hospitalization [42].

In children with HF and anemia, the cause of anemia should be investigated. The
evaluation should include iron studies since iron deficiency is the most common
cause. Iron deficiency is particularly common in children with advanced HF and
may occur even in absence of anemia [43]. (See "Approach to the child with
anemia" and "Iron deficiency in infants and children <12 years: Screening,
 prevention, clinical manifestations, and diagnosis", section on 'Laboratory
testing'.)
● Serum chemistries – This includes electrolytes, blood urea nitrogen, creatinine,
and liver function tests.

• Hyponatremia may be seen in children with severe HF [44]

• Renal impairment may be a contributing factor for HF or may exacerbate
preexisting failure
• Baseline electrolytes are needed prior to initiating therapy with diuretics or
ACE inhibitors to avoid potential side effects of these drugs
• Liver function studies may be elevated due to hepatic congestion with right-
sided HF

Additional evaluation — Additional testing in children with HF may include cardiac

magnetic resonance imaging (MRI) and or cardiac catheterization if the information
from echocardiography is insufficient. Ambulatory ECG testing is performed in
children with symptoms suggestive of arrhythmia and in patients at risk for
arrhythmia. Exercise testing may be helpful in determining the patient's functional
class, particularly for children with cardiomyopathy. A three-generation pedigree is an
important part of the evaluation in children with a suspected familial cause of HF (eg,
cardiomyopathy). Tests to identify the underlying etiology may be warranted if the
cause is unclear from the initial evaluation.
● MRI – Occasionally, the information from echocardiography is insufficient
because of altered geometry, particularly in the assessment of RV and single
ventricular function in children with complex CHD [1] or in patients with
inflammation. In these settings, cardiac MRI can provide accurate and detailed
information regarding cardiac anatomy, ventricular function, myocardial
inflammation, and infiltration by fat and fibrous tissues [45]. The need for
sedation, particularly in young children, is an important limitation of cardiac MRI
in pediatric patients. In addition, cardiac MRI may not be available at all centers.

Clinical settings in which cardiac MRI may have utility in pediatric HF include (see
"Clinical utility of cardiovascular magnetic resonance imaging"):
 • Evaluation of anatomic details in complex CHD and for providing quantitative
assessment of shunts and RV function

• Distinguishing restrictive cardiomyopathy from constrictive pericarditis (see

"Differentiating constrictive pericarditis and restrictive cardiomyopathy")

• Noninvasive assessment of myocardial inflammation in patients with

suspected myocarditis (see "Clinical manifestations and diagnosis of
myocarditis in children", section on 'Cardiac magnetic resonance')

• Evaluation of RV function, dilation, and fatty infiltration in patients with

arrhythmogenic RV cardiomyopathy (see "Arrhythmogenic right ventricular
cardiomyopathy: Diagnostic evaluation and diagnosis")

• Assessing the extent of noncompacted myocardium in noncompaction

cardiomyopathy (see "Isolated left ventricular noncompaction in adults: Clinical
manifestations and diagnosis")

• Quantitative assessment of myocardial fibrosis by measuring late gadolinium

enhancement, an independent risk factor for ventricular arrhythmia and
sudden cardiac death (see "Hypertrophic cardiomyopathy in children: Clinical
manifestations and diagnosis", section on 'Additional testing' and
"Hypertrophic cardiomyopathy: Clinical manifestations, diagnosis, and
evaluation", section on 'Cardiovascular magnetic resonance')
● Cardiac catheterization – Cardiac catheterization can provide useful information
in the following settings:

• It may help in establishing the etiology of HF if the underlying cause remains

unclear after noninvasive testing with echocardiography and/or MRI.

• If the coronary anatomy is unclear or equivocal on echocardiography and there

is clinical concern for a coronary anomaly (eg, ALCAPA, Kawasaki disease),
coronary angiography can be helpful. (See "Congenital and pediatric coronary
artery abnormalities" and "Cardiovascular sequelae of Kawasaki disease:
Clinical features and evaluation", section on 'Coronary artery abnormalities'.)

• Cardiac catheterization with endomyocardial biopsy may be performed in the

evaluation of suspected myocarditis or to differentiate restrictive
 cardiomyopathy from constrictive pericarditis. These issues are discussed
separately. (See "Clinical manifestations and diagnosis of myocarditis in
children", section on 'Endomyocardial biopsy' and "Differentiating constrictive
pericarditis and restrictive cardiomyopathy", section on 'Cardiac
catheterization'.)

• Cardiac catheterization may be performed to evaluate pulmonary vascular

resistance (PVR) and vasodilator responsiveness in children with known or
suspected pulmonary hypertension. (See "Pulmonary hypertension in children:
Classification, evaluation, and diagnosis", section on 'Cardiac catheterization'.)

• Cardiac catheterization is also used to guide the need and timing of cardiac
transplantation in children with HF by assessing their hemodynamic status
(intracardiac pressures, pulmonary artery pressure, PVR, and cardiac output).
● Ambulatory ECG monitoring – Ambulatory ECG monitoring (eg, 24-hour Holter
monitoring) should be performed in patients with symptoms suggestive of
arrhythmia (eg, palpitations, syncope). In addition, ambulatory ECG monitoring is
helpful in the assessment of children at risk for arrhythmia, including patients
with cardiomyopathy, heterotaxy syndromes, congenitally corrected transposition
of the great arteries, and patients who have undergone Fontan palliation or atrial
switch operation [13].
● Exercise testing – For children with known or suspected cardiomyopathy who
are able to perform exercise testing, this assessment can provide useful
information that can be used in determining the child's functional class and can
help with risk stratification (ie, risk of ventricular arrhythmia and sudden cardiac
death) [13]. (See "Exercise testing in children and adolescents: Principles and
clinical application".)
● Other studies – Additional testing may be warranted depending on the clinical
findings:

• For patients with clinical evidence of myocarditis, diagnostic evaluation is

performed to determine the underlying infectious etiology. (See "Clinical
manifestations and diagnosis of myocarditis in children", section on 'Etiologic
evaluation'.)
 • For patients with cardiomyopathy, studies to determine the etiology may
include thyroid function tests, metabolic screening, and genetic testing. For
children with newly diagnosed HF due to cardiomyopathy, referral to a clinical
geneticist may be warranted since many types of cardiomyopathy may have a
genetic origin, particularly HCM. (See "Genetics of dilated cardiomyopathy"
and "Hypertrophic cardiomyopathy in children: Clinical manifestations and
diagnosis", section on 'Genetic testing'.)

• For patients with clinical findings that suggest a rheumatologic disorder,

additional testing may include inflammatory markers (eg, C-reactive protein,
erythrocyte sedimentation rate), antistreptolysin titers (rheumatic heart
disease), and antinuclear antibody testing (collagen vascular diseases including
systemic lupus erythematous). (See "Acute rheumatic fever: Clinical
manifestations and diagnosis", section on 'Diagnosis' and "Childhood-onset
systemic lupus erythematosus (SLE): Clinical manifestations and diagnosis",
section on 'Laboratory findings'.)

STAGING AND SEVERITY

Categorization of the stage and severity of the patient's HF is important for

monitoring the disease progression and guiding management decisions [13]:
● Staging – The staging system of pediatric HF (stages A to D) is used to describe
the development and progression of disease following exposure to a risk factor
for HF ( table 4).
● Severity – The two main classification systems used for describing severity of
pediatric HF are the New York Heart Association (NYHA) and Ross classifications
( table 5):

• NYHA class – The NYHA classes (I to IV) are most commonly used to quantify
the degree of functional limitation imposed by HF in adults and may be used in
adolescents ( table 5) [46]. The NYHA classification relies on patient reporting
of symptom severity and thus has limitations in infants and young children.
 (See "Predictors of survival in heart failure with reduced ejection fraction",
section on 'NYHA functional class'.)

• Ross classification – The Ross HF Classification is an adaptation of the NYHA

system that is used to describe HF severity in infants and children based on a
history of feeding intolerance, growth problems, exercise intolerance, and
physical findings ( table 5) [47,48]. The Ross classification has been validated
in two prospective studies in infants in which the Ross class demonstrated
correlation with physiologic measures of HF severity (ie, plasma levels of
norepinephrine and peripheral lymphocytic beta-adrenergic receptor density)
[49,50].

DIFFERENTIAL DIAGNOSIS

Numerous noncardiac conditions can present with signs and symptoms that mimic
HF. Often, the initial symptoms of HF are nonspecific (respiratory distress, abdominal
pain, nausea, vomiting, poor appetite, poor weight gain), and a high index of
suspicion is needed to distinguish HF from other far more common pediatric illnesses
that present with these symptoms. Particular findings that should raise suspicion for
HF in this setting include a gallop rhythm, tachycardia out of proportion to other
symptoms, hepatomegaly, altered systemic perfusion, and/or ectopy or other
abnormalities on cardiac monitoring or electrocardiogram (ECG). Additional
evaluation including chest radiograph and laboratory tests (eg, brain natriuretic
peptide [BNP]) can help distinguish HF from noncardiac conditions. Serial assessment
of the vital signs and physical examination in response to treatment can also be
informative. For example, if the patient responds to intravenous fluid resuscitation
with clinical deterioration (eg, increased tachycardia, dyspnea, rales) rather than
improvement, HF should be considered. Ultimately, echocardiography is necessary to
confirm a cardiac etiology.
● Respiratory distress – Noncardiac causes of respiratory distress in neonates
include transient tachypnea of the newborn, respiratory distress syndrome,
meconium aspiration, congenital diaphragmatic hernia, pneumothorax,
pneumonia, and pulmonary hypoplasia. In older infants and children, common
 causes include pneumonia, bronchiolitis, and asthma. (See "Overview of neonatal
respiratory distress and disorders of transition" and "Causes of acute respiratory
distress in children".)
● Poor weight gain – Other causes of poor weight gain include gastrointestinal
disorders (eg, protein-milk allergy, cystic fibrosis, celiac disease), chronic
infections, hyperthyroidism, and metabolic disorders. (See "Poor weight gain in
children younger than two years in resource-abundant settings: Etiology and
evaluation", section on 'Causes'.)
● Edema – Peripheral edema may be caused by renal failure, venous thrombosis, or
adverse drug effects. (See "Pathophysiology and etiology of edema in children",
section on 'Etiology'.)
● Shock – Shock may be due to overwhelming sepsis or hypovolemia. (See "Initial
evaluation of shock in children", section on 'Pathophysiology'.)

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and

regions around the world are provided separately. (See "Society guideline links: Heart
failure in children".)

SUMMARY AND RECOMMENDATIONS

● Epidemiology – Heart failure (HF) results from structural or functional cardiac
disorders that impair the ability of the ventricle(s) to fill with and/or eject blood. It
is estimated to affect 12,000 to 35,000 children in the United States each year.
(See 'Introduction' above and 'Epidemiology' above.)
● Causes – The causes of pediatric HF can be divided into the following
pathophysiologic categories ( table 1). (See 'Etiology and pathophysiology'
above.)

• Ventricular dysfunction may occur in both patients with a structurally normal

heart (eg, cardiomyopathy, myocarditis, and complete heart block) and those
 with complex congenital heart disease (CHD). Although HF in patients with
CHD may be present at the time of diagnosis, it is more commonly a long-term
complication following surgical cardiac repair. (See 'Ventricular dysfunction'
above.)

• Volume overload with preserved ventricular contractility is most

commonly due to CHD with significant left-to-right shunting of blood from the
systemic to pulmonary circulation. (See 'Volume overload with preserved
ventricular contractility' above.)

• Pressure overload with preserved ventricular contractility is most

commonly due to CHD with ventricular outflow obstruction. (See 'Pressure
overload with preserved ventricular contractility' above.)
● Clinical manifestations – Symptoms and physical findings reflect a limited ability
to adequately increase cardiac output (eg, exercise intolerance, easy fatigue, or
gastrointestinal symptoms) and/or pulmonary or systemic fluid overload (eg,
shortness of breath, tachypnea, hepatomegaly, edema). Clinical features vary
with age at presentation. (See 'Clinical manifestations' above.)
● Diagnostic evaluation – The diagnosis of HF in children is based on a
combination of clinical, echocardiographic, and laboratory findings. Noninvasive
imaging studies and laboratory tests are initially obtained to confirm the
diagnosis, ascertain the severity of HF, and determine the underlying cause if
unclear from the history. (See 'Diagnostic evaluation' above.)

The initial evaluation generally includes (see 'Initial evaluation' above):

• Chest radiography (see 'Chest radiography' above)

• Electrocardiogram (ECG) (see 'Electrocardiogram' above)
• Echocardiography (see 'Echocardiography' above)
• Laboratory tests (brain natriuretic peptide [BNP] or N-terminal pro-BNP [NT-
proBNP], troponin, complete blood count, and serum chemistries) (see
'Laboratory tests' above)

Evaluation should only proceed if the patient is clinically stable. In patients who
have severe cardiorespiratory compromise (ie, shock or impending cardiac
arrest), prompt initiation of treatment to restore adequate perfusion should be
 provided prior to undergoing a detailed evaluation to determine the underlying
cause of HF ( algorithm 2 and algorithm 1). (See "Shock in children in
resource-abundant settings: Initial management" and "Neonatal shock:
Management".)
● Staging and severity – Categorization of the stage and severity of the patient's
HF is important for monitoring the disease progression and guiding
management decisions. The staging system of pediatric HF (stages A to D) is used
to describe the development and progression of disease following exposure to a
risk factor for HF ( table 4). The New York Heart Association (NYHA) class is most
commonly used to quantify the degree of functional limitation imposed by HF in
adults and may be used in adolescents ( table 5). The Ross HF classification is an
adaptation of the NYHA system that is used to describe HF severity in infants and
children ( table 5). (See 'Staging and severity' above.)
● Differential diagnosis – Numerous noncardiac conditions can present with signs
and symptoms that mimic HF. The clinical history and physical examination can
distinguish HF from many of these disorders, though echocardiography and
other testing (eg, ECG, chest radiograph, BNP) may ultimately be necessary to
confirm the diagnosis. (See 'Differential diagnosis' above.)
REFERENCES

1. Hsu DT, Pearson GD. Heart failure in children: part I: history, etiology, and
pathophysiology. Circ Heart Fail 2009; 2:63.
2. Rossano JW, Kim JJ, Decker JA, et al. Prevalence, morbidity, and mortality of heart
failure-related hospitalizations in children in the United States: a population-based
study. J Card Fail 2012; 18:459.
3. Mejia EJ, O'Connor MJ, Lin KY, et al. Characteristics and Outcomes of Pediatric
Heart Failure-Related Emergency Department Visits in the United States: A
Population-Based Study. J Pediatr 2018; 193:114.
4. Amdani S, Marino BS, Rossano J, et al. Burden of Pediatric Heart Failure in the
United States. J Am Coll Cardiol 2022; 79:1917.
 5. Lasa JJ, Gaies M, Bush L, et al. Epidemiology and Outcomes of Acute
Decompensated Heart Failure in Children. Circ Heart Fail 2020; 13:e006101.
6. Lipshultz SE, Sleeper LA, Towbin JA, et al. The incidence of pediatric
cardiomyopathy in two regions of the United States. N Engl J Med 2003; 348:1647.
7. Nugent AW, Daubeney PE, Chondros P, et al. The epidemiology of childhood
cardiomyopathy in Australia. N Engl J Med 2003; 348:1639.
8. Canter CE, Simpson KE. Diagnosis and treatment of myocarditis in children in the
current era. Circulation 2014; 129:115.
9. Raj S, Franco VI, Lipshultz SE. Anthracycline-induced cardiotoxicity: a review of
pathophysiology, diagnosis, and treatment. Curr Treat Options Cardiovasc Med
2014; 16:315.
10. Book WM. Heart failure in the adult patient with congenital heart disease. J Card
Fail 2005; 11:306.
11. Hollander SA, Addonizio LJ, Chin C, et al. Abdominal complaints as a common first
presentation of heart failure in adolescents with dilated cardiomyopathy. Am J
Emerg Med 2013; 31:684.
12. Puri K, Singh H, Denfield SW, et al. Missed Diagnosis of New-Onset Systolic Heart
Failure at First Presentation in Children with No Known Heart Disease. J Pediatr
2019; 208:258.
13. Kirk R, Dipchand AI, Rosenthal DN, et al. The International Society for Heart and
Lung Transplantation Guidelines for the management of pediatric heart failure:
Executive summary. [Corrected]. J Heart Lung Transplant 2014; 33:888.
14. Hsu DT, Pearson GD. Heart failure in children: part II: diagnosis, treatment, and
future directions. Circ Heart Fail 2009; 2:490.
15. Satou GM, Lacro RV, Chung T, et al. Heart size on chest x-ray as a predictor of
cardiac enlargement by echocardiography in children. Pediatr Cardiol 2001;
22:218.
16. Lang RM, Bierig M, Devereux RB, et al. Recommendations for chamber
quantification: a report from the American Society of Echocardiography's
Guidelines and Standards Committee and the Chamber Quantification Writing
 Group, developed in conjunction with the European Association of
Echocardiography, a branch of the European Society of Cardiology. J Am Soc
Echocardiogr 2005; 18:1440.
17. Sluysmans T, Colan SD. Theoretical and empirical derivation of cardiovascular
allometric relationships in children. J Appl Physiol (1985) 2005; 99:445.
18. Boston Children's Hospital Z-score calculator. The Boston Children’s Hospital z-sco
re system is based on data gathered over 12 years on normal children. Available a
t: http://zscore.chboston.org/.
19. Favilli S, Frenos S, Lasagni D, et al. The use of B-type natriuretic peptide in
paediatric patients: a review of literature. J Cardiovasc Med (Hagerstown) 2009;
10:298.
20. Neves AL, Henriques-Coelho T, Leite-Moreira A, Areias JC. The Utility of Brain
Natriuretic Peptide in Pediatric Cardiology: A Review. Pediatr Crit Care Med 2016;
17:e529.
21. Cantinotti M, Law Y, Vittorini S, et al. The potential and limitations of plasma BNP
measurement in the diagnosis, prognosis, and management of children with
heart failure due to congenital cardiac disease: an update. Heart Fail Rev 2014;
19:727.
22. Eindhoven JA, van den Bosch AE, Boersma E, Roos-Hesselink JW. The usefulness of
brain natriuretic peptide in simple congenital heart disease - a systematic review.
Cardiol Young 2013; 23:315.
23. Mir TS, Marohn S, Läer S, et al. Plasma concentrations of N-terminal pro-brain
natriuretic peptide in control children from the neonatal to adolescent period and
in children with congestive heart failure. Pediatrics 2002; 110:e76.
24. Ko HK, Lee JH, Choi BM, et al. Utility of the rapid B-type natriuretic peptide assay
for detection of cardiovascular problems in newborn infants with respiratory
difficulties. Neonatology 2008; 94:16.
25. Koulouri S, Acherman RJ, Wong PC, et al. Utility of B-type natriuretic peptide in
differentiating congestive heart failure from lung disease in pediatric patients
with respiratory distress. Pediatr Cardiol 2004; 25:341.
26. Law YM, Hoyer AW, Reller MD, Silberbach M. Accuracy of plasma B-type natriuretic
peptide to diagnose significant cardiovascular disease in children: the Better Not
Pout Children! Study. J Am Coll Cardiol 2009; 54:1467.
27. Maher KO, Reed H, Cuadrado A, et al. B-type natriuretic peptide in the emergency
diagnosis of critical heart disease in children. Pediatrics 2008; 121:e1484.
28. Law YM, Ettedgui J, Beerman L, et al. Comparison of plasma B-type natriuretic
peptide levels in single ventricle patients with systemic ventricle heart failure
versus isolated cavopulmonary failure. Am J Cardiol 2006; 98:520.
29. Lowenthal A, Camacho BV, Lowenthal S, et al. Usefulness of B-type natriuretic
peptide and N-terminal pro-B-type natriuretic peptide as biomarkers for heart
failure in young children with single ventricle congenital heart disease. Am J
Cardiol 2012; 109:866.
30. Hayakawa H, Komada Y, Hirayama M, et al. Plasma levels of natriuretic peptides in
relation to doxorubicin-induced cardiotoxicity and cardiac function in children with
cancer. Med Pediatr Oncol 2001; 37:4.
31. Pinarli FG, Oğuz A, Tunaoğlu FS, et al. Late cardiac evaluation of children with solid
tumors after anthracycline chemotherapy. Pediatr Blood Cancer 2005; 44:370.
32. Aggarwal S, Pettersen MD, Bhambhani K, et al. B-type natriuretic peptide as a
marker for cardiac dysfunction in anthracycline-treated children. Pediatr Blood
Cancer 2007; 49:812.
33. Holmström H, Hall C, Thaulow E. Plasma levels of natriuretic peptides and
hemodynamic assessment of patent ductus arteriosus in preterm infants. Acta
Paediatr 2001; 90:184.
34. Sugimoto M, Manabe H, Nakau K, et al. The role of N-terminal pro-B-type
natriuretic peptide in the diagnosis of congestive heart failure in children. -
Correlation with the heart failure score and comparison with B-type natriuretic
peptide -. Circ J 2010; 74:998.
35. Mangat J, Carter C, Riley G, et al. The clinical utility of brain natriuretic peptide in
paediatric left ventricular failure. Eur J Heart Fail 2009; 11:48.
36. Price JF, Thomas AK, Grenier M, et al. B-type natriuretic peptide predicts adverse
cardiovascular events in pediatric outpatients with chronic left ventricular systolic
dysfunction. Circulation 2006; 114:1063.
37. Nasser N, Perles Z, Rein AJJT, Nir A. NT-proBNP as a marker for persistent cardiac
disease in children with history of dilated cardiomyopathy and myocarditis.
Pediatr Cardiol 2006; 27:87.
38. Auerbach SR, Richmond ME, Lamour JM, et al. BNP levels predict outcome in
pediatric heart failure patients: post hoc analysis of the Pediatric Carvedilol Trial.
Circ Heart Fail 2010; 3:606.
39. Sachdeva S, Song X, Dham N, et al. Analysis of clinical parameters and cardiac
magnetic resonance imaging as predictors of outcome in pediatric myocarditis.
Am J Cardiol 2015; 115:499.
40. Palm J, Holdenrieder S, Hoffmann G, et al. Predicting Major Adverse
Cardiovascular Events in Children With Age-Adjusted NT-proBNP. J Am Coll Cardiol
2021; 78:1890.
41. Soongswang J, Durongpisitkul K, Nana A, et al. Cardiac troponin T: a marker in the
diagnosis of acute myocarditis in children. Pediatr Cardiol 2005; 26:45.
42. Goldberg JF, Shah MD, Kantor PF, et al. Prevalence and Severity of Anemia in
Children Hospitalized with Acute Heart Failure. Congenit Heart Dis 2016; 11:622.
43. Puri K, Price JF, Spinner JA, et al. Iron Deficiency Is Associated with Adverse
Outcomes in Pediatric Heart Failure. J Pediatr 2020; 216:58.
44. Price JF, Kantor PF, Shaddy RE, et al. Incidence, Severity, and Association With
Adverse Outcome of Hyponatremia in Children Hospitalized With Heart Failure.
Am J Cardiol 2016; 118:1006.
45. Attili AK, Parish V, Valverde I, et al. Cardiovascular MRI in childhood. Arch Dis Child
2011; 96:1147.
46. Criteria Committee of the New York Heart Association. Nomenclature and Criteria
for Diagnosis of Diseases of the Heart and Great Vessels, 9th ed, Little, Brown & C
o., Boston 1994.
47. Ross RD, Bollinger RO, Pinsky WW. Grading the severity of congestive heart failure
in infants. Pediatr Cardiol 1992; 13:72.
48. Ross RD. The Ross classification for heart failure in children after 25 years: a
review and an age-stratified revision. Pediatr Cardiol 2012; 33:1295.
49. Ross RD, Daniels SR, Schwartz DC, et al. Plasma norepinephrine levels in infants
and children with congestive heart failure. Am J Cardiol 1987; 59:911.
50. Wu JR, Chang HR, Huang TY, et al. Reduction in lymphocyte beta-adrenergic
receptor density in infants and children with heart failure secondary to congenital
heart disease. Am J Cardiol 1996; 77:170.

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