Heart failure in children: Etiology, clinical manifestations, and diagnosis

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.)