pediatric heart failure a practical guide to diagnosis and management

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Pediatrics and Neonatology (2017) xx, 1e10

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REVIEW ARTICLE

Pediatric Heart Failure: A Practical Guide to
Diagnosis and Management
Daniele Masarone*, Fabio Valente, Marta Rubino,
Rossella Vastarella, Rita Gravino, Alessandra Rea,
Maria Giovanna Russo, Giuseppe Pacileo, Giuseppe Limongelli
Cardiologia SUN e Heart Failure Unit, Department of Cardiothoracic Sciences, Second University of
Naples, Naples, Italy
Received Jun 24, 2016; received in revised form Jan 4, 2017; accepted Jan 9, 2017

Available online - - -

Key Words
cardiomyopathies;
congenital heart
diseases;
pediatric cardiac
transplantation;
pediatric heart

failure

Pediatric heart failure represents an important cause of morbidity and mortality in childhood.
Currently, there are well-established guidelines for the management of heart failure in the
adult population, but an equivalent consensus in children is lacking. In the clinical setting,
ensuring an accurate diagnosis and defining etiology is essential to optimal treatment. Diuretics and angiotensin-converting enzyme inhibition are the first-line therapies, whereas
beta-blockers and devices for electric therapy are less used in children than in adults. In
the end-stage disease, heart transplantation is the best choice of treatment, while a left ventricular assist device can be used as a bridge to transplantation (due to the difficulties in
finding organ donors), recovery (in the case of myocarditis), or destination therapy (for patients with systemic disease).
Copyright ª 2017, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an
open access article under the CC BY-NC-ND license ( />by-nc-nd/4.0/).

1. Introduction
Pediatric heart failure (PHF) represents an important cause
of morbidity and mortality in childhood.1 Etiology and
pathogenesis are different between adults and children:
* Corresponding author. Cardiologia SUN e Heart Failure Unit,
Department of Cardiothoracic Sciences, Second University of
Naples, Via Leonardo Bianchi n 1, Naples 80100, Italy.
E-mail address: (D. Masarone).

the first mainly relates to ischemia (60e70% of cases), the
latter as a consequence of congenital heart diseases (CHDs)
or cardiomyopathies in most of the cases.2 Hence, managing PHF requires specific knowledge and skills.3 Presently, there are well-established guidelines for the
management of heart failure (HF) in the adult population,4
but the equivalent consensus for PHF is lacking. This article
offers an overview on the etiology, diagnosis, and therapy
of PHF, with a specific focus on practical issues required for
management.

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D. Masarone et al

2. Definition

3. Etiology

In the 1950s, HF was described as a clinical syndrome
caused by low cardiac output.5 In recent years, knowledge
of the pathophysiology has been expanded and neurohormonal and molecular pathways that modulate cardiac
performance in failing hearts have been discovered.6 The
contemporary vision describes HF as a clinical syndrome
characterized by typical symptoms and signs associated
with specific circulatory, neurohormonal, and molecular
abnormalities.7

In children, cardiac failure is most often due to CHDs and
cardiomyopathies. The cardiac and noncardiac causes of PHF
are summarized in Table 1. At birth, HF is caused by fetal
cardiomyopathies or extracardiac conditions (such as sepsis,
hypoglycaemia, and hypocalcaemia). In the 1st week after

birth, CHDs with ductus-dependent systemic circulation (such
as severe aortic stenosis/aortic coarctation and hypoplastic
left heart syndrome), in which the closure of the ductus
arteriosus causes severe reduction of end-organ perfusion,8

Table 1

Etiology of pediatric heart failure.

Type of diseases

Pathophisiology

Examples

Congenital heart diseases

Left to right shunt (volume overload)

Ventricular septal defects
Complete atrioventricular canal defects
Patent ductus arteriosus
Aortoepulmonary windows
Mitral regurgitation
Aortic regurgitation
Aortic stenosis

Valvular regurgitation (volume overload)
Outflow tract obstruction (pressure
overload)

Cardiomyopathies
(inherited or acquired)

Coronary insufficiency (decreased O2 supply
to cardiomyocyte)
Systolic dysfunction (low cardiac output)
Diastolic dysfunction (elevated pulmonary
capillary pressure)

Tunnel type subaortic stenosis
Supravalvular aortic stenosis
Pulmonary stenosis
Pulmonary vein stenosis
Coronary artery anomalies
Dilated cardiomyopathy
-

Myocarditis
Barth syndrome
Carnitine deficency
Familial dilated cardiomyopathy
Neuromuscular disorder (i.e., Becker dystrophy/
Duchenne dystrophy)

Hypertrophic cardiomyopathy
-

Pompe diseases
Noonan syndrome

Maternal diabetes
Mitochondrial diseases
Familial hypertrophic cardiomyopathy

Idiopathic restrictive cardiomyopathy
Arrhythmias

Systolic dysfunction (low cardiac output)

Tachycardia induced cardiomyopathy
- Atrioeventricular node reentry tachycardia
- Atrioeventricular reentry tachycardia
- Ectopic atrial tachycardia

Congenital third degree atrioeventricular block
Infection

Systolic dysfunction

Sepsis induced myocardial dysfunction

High output state

Volume overload

Thyrotoxicosis
Systemic arteriovenous fistula
Severe anemia

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Pediatric Heart Failure
are the main cause. In the 1st month of life, frequent causes of
PHF are CHDs with left to right shunt (such as ventricular
septal defects, patent ductus arteriosus, and aortopulmonary windows), in which pulmonary blood flow progressively increases with the fall of pulmonary resistance.9
Finally, HF in adolescence is rarely secondary to CHDs, but is
more often related to cardiomyopathies or myocarditis.10

4. Pathophysiology of PHF
An “index event,” regardless of the cause, produces an initial
reduction of cardiomyocyte contractility in HF. The initial
injury results in a reduction in cardiac output that is, in turn,
countered by two major “compensatory mechanisms”
(Figure 1). The first of these mechanisms is the activation of
the sympathetic nervous system, resulting in increased
release and decreased uptake of norepinephrine, with peripheral vasoconstriction to maintain (by increasing systemic
vascular resistance) mean arterial pressure and organ
perfusion. Enhanced catecholamine levels, however, lead to
further cardiomyocyte injury, dysfunctional intracellular
signaling, and ultimately cardiomyocyte death.11 The second
important “compensatory” mechanism is the stimulation of
the rennineangiotensin aldosterone system, consisting of
increased circulating levels of renin, angiotensin II, and
aldosterone. Renin is responsible of cleaving angiotensinogen in angiotensin I, which is converted into angiotensin II
by the angiotensin-converting enzyme (ACE). Angiotensin II

is a potent vasoconstrictor that preserves end-organ perfusion. Aldosterone causes salt and water retention, resulting
in increased preload and then cardiac output according to
the FrankeStarling mechanism. However, the elevation of
both aldosterone and angiotensin II promotes cardiac fibrosis
and apoptosis.12 These mechanisms may temporarily
contribute to circulatory stability, but over time become
maladaptive and promote the progression of HF.13

5. Clinical presentation

3
Infant and young children: The typical presentation is
characterized by difficulty in feeding (from prolonged
feeding time intake to frank intolerance). Cyanosis,
tachypnea, sinus tachycardia, and diaphoresis can be
present.
Older children and adolescence: Fatigue, shortness of
breath, tachypnea, and exercise intolerance are the main
symptoms. Abdominal pain, oliguria, and leg pitting edema
may also be present. The severity of HF in children must be
staged according to the Ross modified classification15 that
recognizes four functional classes with increasing severity
of clinical features from I to IV (Table 2).

6. Diagnostic approach
The first step in diagnostic approach in patients with PHF is
based on noninvasive clinical investigations.

6.1. Electrocardiogram
Sinus tachycardia is common in acute HF. In chronic HF, an

abnormal electrocardiogram increases the likelihood of
decompensated HF.16

Table 2
failure.
Class I
Class II

Class III

Class IV

Modified Ross classification for pediatric heart
Asymptomatic
Mild tachypnea or diaphoresis with feeding in
infants
Dyspnea on exertion in older children
Marked tachypnea or diaphoresis with feeding
in infants. Prolonged feeding times with growth
failure
Marked dyspnea on exertion in older children
Symptoms such as tachypnea, retractions,
grunting, or diaphoresis at rest

The clinical picture of PHF is strictly related to age.14

Figure 1

Pathophysiology of heart failure. RAAS Z renin-angiotensin-aldosterone system; SNS Z sympathetic nervous system.

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6.2. Chest radiography

6.5. Cardiac magnetic resonance

Chest radiography is indicated in all children with suspected HF to assess heart size and to check for other signs
of HF such as pulmonary edema, septal lines (or Kerley B
lines), and pleural effusions.17

Cardiac magnetic resonance is indicated to study complex
CHDs or for tissue characterization and therefore for diagnosis, risk-stratification, and ongoing management of patients with specific forms of cardiomyopathies.19

6.6. Cardiac catheterization
6.3. Echocardiography
The echocardiogram is the most useful, widely available,
and low-cost test for patients with PHF. Echocardiography
provides immediate data on cardiac morphology and
structure, chamber volumes/diameters, wall thickness,
ventricular systolic/diastolic function, and pulmonary
pressure. These data are crucial to make the correct

diagnosis and to guide appropriate treatment.18

Despite advances in noninvasive diagnostic techniques,
cardiac catheterization is presently indicated for20:
- accurate evaluation of pressure gradients in patients
with complex valve diseases
- evaluation of hemodynamic parameters (pulmonary and
systemic vascular resistance, cardiac output, and cardiac index) in Fontan patients or during pre-transplant
screening

6.4. Laboratory investigations

6.7. Endomyocardial biopsy

The role of laboratory tests in HF management is summarized in Table 3.

Endomyocardial biopsy is an invasive procedure with significant risk and should be performed only to confirm the

Table 3

Laboratory test in heart failure.

Test

Rationale

Complete blood count

Useful to assess anemia, which may cause or aggravate heart failure.
Leukocytosis may result from stress or signal an underlying infection.

Hyponatremia reflects an expansion of extracellular fluid volume in the setting of
a normal total body sodium.
Hypokalemia and hypochloremia can be the result of prolonged administration of
diuretics.
Hyperkalemia can be the result of impaired renal perfusion and marked
reductions in glomerular filtration rate or from intracellular potassium release due
to impaired tissue perfusion.
Elevated BUN and BUN/creatinine ratio are seen in decompensated heart failure.
Congestive hepatomegaly is often associated with impaired hepatic function,
which is characterized by elevation of AST, ALT, LDH, and other liver enzymes.
Hyperbilirubinemia (both direct and indirect) is related to acute hepatic venous
congestion and is common with severe right heart failure.
Elevated ALP, and prolongation of the PTT time can be seen.
In children with long-standing heart failure and poor nutritional status,
hypoalbuminemia results from hepatic synthesis impairment.
Natriuretic peptides levels correlate closely with the NYHA/Ross classification of
heart failure and with ventricular filling pressures.
Useful if the clinical scenario is suggestive of an ischemic process or myocarditis
Elevated lactate is seen in patients with decompensated heart failure as a result
of decreased tissue perfusion and/or decreased metabolism due to secondary
liver dysfunction and can be a useful serologic marker for monitoring response to
therapeutic interventions.
Both severe hyper or hypothyroidism can cause heart failure.
Usually reveal mild hypoxemia in patients who have mild-to-moderate heart
failure.
Severe heart failure often leads to severe hypoxemia, or even hypoxia.
Hypocapnia occurs in the early stages of pulmonary edema because of V/Q
mismatch, progressing to hypercapnia and respiratory acidosis, related to
decreased vital capacity and poor ventilation.

Electrolytes

Renal function tests
Liver function tests

Natriuretic peptides
(NT-proBNP/BNP)
CPK-MB, troponin I and T
Lactate

Thyroid function tests
Arterial blood gas

ALT Z alanine aminotransferase; AST Z aspartate aminotransferase; BNP Z B-type natriuretic peptide; BUN Z blood urea
nitrogen; CPK-MB Z creatine phosphokinase; LDH Z lactic dehydrogenase; NT-proBNP Z N-terminal proBNP; PTT Z prothrombin time;
V/Q Z ventilation/perfusion.

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clinical diagnosis of myocarditis and to choose the appropriate therapeutic management21 (such as giant cell
myocarditis).

7. Therapeutic approach
Treatment of PHF aims to:

- eliminate the causes of PHF
- control the symptoms and disease progression.

8. Eliminate the causes of HF
When possible, the causes of HF must be corrected through
different approaches:
- corrective treatment should be performed in CHDs22
- systemic diseases (such as sepsis) or electrolytic imbalance (such as hypocalcemia) must be carefully
researched and treated.

9. Control of symptoms and disease
progression

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9.2. Medical therapy
Medical therapy for HF (Table 4) focuses on three main
goals25:
- decrease of pulmonary wedge pressure
- increase of cardiac output and the improvement of endorgan perfusion
- delay of disease progression.

9.3. Diuretics
Diuretics therapy plays a crucial role in the treatment of
pediatric patients with HF. The benefits of diuretic therapy
include reduction of systemic, pulmonary, and venous
congestion.26
Spironolactone may exert additional beneficial effects by
attenuating the development of aldosterone-induced
myocardial fibrosis27 and catecholamine release. Potential

complications of diuretic therapy include electrolyte abnormalities (hyponatremia, hypo- or hyperkaliemia, and
hypochloremia) and metabolic alkalosis. Electrolyte balance
should be carefully monitored, especially during aggressive

Table 4

Drugs used in pediatric heart failure.

9.1. General measures

Drugs

In infants, nutritional support must ensure a caloric intake
about of 150 kcal/kg/d. This is achieved using dietary
supplements, preferring small and frequent meals that are
better tolerated.23
In children and adolescents, current recommendations
suggest that 25e30 kcal/kg/d is a reasonable target for
most patients.
Carbohydrates should not exceed 6 g/kg/d and lipids
should not exceed 2.5 g/kg/d. The provision of essential
amino acids is necessary in the critically ill. Evidence suggests that 1.2e1.5 g/kg/d of protein is needed.
Nutritional supplementation is required in HF secondary
to metabolic and mitochondrial diseases (such as carnitine
and ubiquinone).
In acyanotic CHD patients or in patients with cardiomyopathies, ventilatory support with oxygen must be initiated
when SaO2 < 90%.
On the contrary, in patients with cyanotic CHD, oxygen
has little effect in raising SaO2 and is not indicated.
However, in some cases with chronic left to right

shunting, irreversible pulmonary vascular disease can
develop and cause right to left shunting (Eisenmenger
syndrome). In the early stages, the resulting pulmonary
hypertension may be responsive to oxygen; hence, this is
indicated while the child is waiting for cardiac transplantation or for palliation surgery.24 Reduction of salt
intake is recommended in all patients with edemas and
fluid retention. Restriction of fluids is indicated in patients
with edemas unresponsive to diuretic therapy or
hyponatremia.

Furosemide
Furosemide

Routes of
Doses
administration

Oral
Intermittent
bolus
Furosemide
Continuous
infusion
Captopril
Oral
Enalapril
Oral
Losartan
Oral
Carvedilol

Oral
Metoprolol
Oral
Spironolactone Oral
Nitroglycerin Continuous
infusion
Nitroprusside Continuous
infusion
Hydralazine
Intermittent
bolus
Hydralazine
Oral
Digoxin
Oral
Dobutamine
Continuous
Infusion
Epinephrine
Continuous
Infusion
Epinephrine
Intermittent
bolus
Milrinone
Continuous
Infusion
Levosimendan Continuous
Infusion

1e2 mg/kg q6e12h
0.5e2 mg/kg q6e12h
0.1e0.4 mg/kg/h
0.3e2 mg/kg q8h
0.05e0.25 mg/kg q12h
0.5e1.5 mg/kg/d
0.05 mg/kg/d q12h
0.25 mg/kg/d q12h
0.5e1.5 mg/kg q12h
0.5e10 mg/kg/min
0.5e4 mg/kg/min
0.1e0.2 mg/kg every 4e6 h
0.3e1 mg/kg/d in q8e12h
5e10 mg/kg/d
2.5e10 mg/kg/min
0.01e0.1 mg/kg/min
0.01 mg/kg
0.5e1 mg/kg/min
0.05e0.2 mg/kg/min

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diuretic therapy, as the failing myocardium is more sensitive
to arrhythmias induced by electrolyte imbalance.

9.4. ACE inhibitors
ACE inhibitors prevent, attenuate, or possibly reverse the
pathophysiological myocardial remodeling. In addition,
they decrease afterload by antagonizing the rennineangiotensin aldosterone system.28 According to recent
guidelines of The International Society of Heart and Lung
Transplantation on the management of pediatric HF, ACE
inhibitors are recommended in all patients with HF and left
ventricular systolic dysfunction.29 Therapy with ACE inhibitors should be started at low doses with a subsequent
up-titration to the target dose with careful monitoring of
blood pressure, renal function, and serum potassium.

9.5. b blockers
b blockers are now an accepted therapy in the pediatric
population. b blockers antagonize the deleterious effects of
chronic sympathetic myocardial activation and can reverse
left ventricular remodeling and improve systolic function.
Recent reports seem to show that the addition of b blockers
to the standard therapy may be useful in patients with left
ventricular systolic dysfunction.30 In addition, a recent
Cochrane Database of Systematic Reviews on b blockers for
children with congestive HF was published. Seven studies
with a total of 420 children were included in the review and
the authors conclude that the current available data suggest
that children with HF might benefit from b-blocker treatment.31 Low-dose therapy should be started in stable patients with a progressive up-titration to the target dose.

D. Masarone et al

9.8. Phosphodiesterase type III inhibitors
This class of drugs incorporates amrinone, enoximone,

milrinone, and olprinone, of which milrinone, the strongest
and shortest acting with the best control, is the most
commonly used in pediatric intensive care.
Phosphodiesterase type III inhibitors have vasodilatory
and inotropic actions and improve diastolic ventricular
relaxation.34 Despite the pro-arrhythmic effects of milrinone, it represents the first choice of therapy in patients
with moderate/severe ventricular dysfunction with hypoperfusion symptoms.

9.9. Calcium sensitizer
Levosimendan exerts strong inotropic and vasodilating effects, possibly stronger than dobutamine, with less potential for myocardial ischemia. The absence of proarrhythmic effects35 and the ability to reverse the effects
of b blockade make levosimendan a potential drug of
choice in the context of postoperative low-cardiac output
syndrome rather than in acute HF in children.36

9.10. Vasodilators
Vasodilators administered intravenously (nitroglycerin and
nitroprusside) or orally (hydralazine and nifedipine) are
indicated only in cases of37:
- hypertensive acute HF refractory to treatment (b
blockers and ACE inhibitors)
- severe valve regurgitations in patients intolerant to ACE
inhibitors.

9.6. Inotropes

9.11. Promising new therapies

Digoxin is the main oral inotropic drug used in PHF and is
indicated in symptomatic patients with left and/or right
ventricular systolic dysfunction.32 The use of intravenous

inotropes should be reserved for patients with a severe
reduction of cardiac output resulting in compromised vital
organ perfusion (hypotensive acute/decompensated HF).
Although increased inotropy results in improved cardiac
output and blood pressure, the final result is increased
myocardial oxygen consumption and demand.
The failing myocardium has a limited contractile reserve
and hemodynamic collapse can occur with high-dose
inotropic support in this setting.

There are several promising medications for PHF. An
elevated baseline heart rate is a risk factor for mortality in
adults with HF. Ivabradine, an If current inhibitor in the
sinoatrial node, has an indication in patients with chronic HF.
The use of ivabradine was associated with fewer HF hospitalizations and deaths from HF.38 More recently, the combination of a neprilysin inhibitor and valsartan was compared
with enalapril in a large, prospective, randomized trial.
Neprilysin is a neutral endopeptidase involved with
degradation of natriuretic peptides, bradykinin, and adrenomedullin. Inhibition of neprilysin can result in decreased
vasoconstriction, sodium retention, and remodeling. The
trial was stopped early because of significantly improved
mortality, risk of hospitalization, and improved symptoms
among patients receiving the neprilysin inhibitor valsartan
combination.39 Further study with these drugs will be
warranted in children with HF.

9.7. Sympathomimetic amines
Dopamine and dobutamine have been shown to be effective
inotropes and vasopressors in neonates, infants, and children with circulatory failure. These drugs increase cardiac
output and decrease systemic and pulmonary vascular
resistance; however, they can induce tachycardia/tachyarrhythmia with a mismatch between myocardial oxygen

delivery and the requirement.33 Therefore, we reserve the
use of these drugs only for patients with low cardiac output
despite other therapies.

10. Device therapy
Medical therapy has improved the survival and quality of
life of children with HF; however, there is still a significant
proportion of patients with poor prognosis due to the progression of the disease or sudden cardiac death. These

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patients are candidates for device therapy. The two main
devices used in patients with heart failure are the
implantable cardioverter defibrillator (ICD) and cardiac
resynchronization therapy (CRT). In HF patients, ICD has a
key role in preventing sudden cardiac death due to ventricular arrhythmias. Based on data from observational
studies, accepted indications for ICD implantation in PHF
are40,41:
- secondary prevention of sudden cardiac death in patients with aborted cardiac arrest or in patients with a
previous episode of ventricular tachycardia determining
hemodynamic instability
- unexplained syncope in patients with surgically repaired
CHDs
- patients with severe left systolic ventricular dysfunction

(left ventricular ejection fraction < 35%).
Approximately 30% of adults with HF exhibit a left
bundle branch block (LBBB) with mechanical dyssynchrony.
In contrast to the adult HF population, only 9% of pediatric
HF patients present with LBBB and a QRS duration > 120
milliseconds, which likely reflects the variable causes of HF
in the pediatric population.42
The rationale behind left ventricular dyssynchrony is
that in failing hearts, left ventricular function is affected
not only by a depressed contractile status of the myocardium, abnormal loading conditions, or both, but also by a
disturbed synchronicity of the myocardial walls.43 Late
activation of some segments leads to a slower rise in systolic pressure and delayed left ventricular ejection and also
to slower relaxation and delayed left ventricular filling.44
This pathophysiological condition is the assumption that
CRT, through biventricular pacing, improves the pattern of
contraction of the left ventricle.45 Despite the lack of
randomized clinical trials, retrospective studies demonstrated the utility of CRT in pediatric patients with46:
- dilated cardiomyopathy, complete LBBB, and severe
reduction of left ventricular systolic function (left ventricular ejection fraction < 35%)
- third-degree atrioventricular block requiring the implantation of a pacemaker in DDD modality in patients
with mild/moderate systolic dysfunction (left ventricular ejection fraction < 55%)
- CHDs with double-ventricle physiology with systemic left
ventricle with severe reduction of systolic function.
In patients with single ventricle physiology, evidence
supporting CRT is limited to a few studies.47,48 These series
demonstrated improved cardiac index, systolic blood
pressure, and indexes of asynchrony after CRT, but in the
heterogeneous patient population, technical limitations
imposed by patient body size and unique forms of ventricular dyssynchrony have made it difficult to draw strong
conclusions or to rationalize widespread use.

There are controversial results about the efficacy of CRT
in patients with isolated right ventricle dysfunction. Some
studies have shown that CRT can improve right ventricle
ejection fraction and New York Heart Association/Ross class
and reduce QRS duration. However, this response was

7
significantly less pronounced than the response seen in
patients with left ventricle dysfunction.42
Mechanical circulatory support systems can be used in
patients with PHF who cannot be stabilized with medical
therapy to unload the failing ventricle and maintain endorgan perfusion.49,50 Patients with cardiogenic shock/acute
HF with underperfusion not responsive to medical therapy
must be initially treated with short-term assistance using
extracorporeal nondurable life support systems including
extracorporeal life support51 and extracorporeal membrane
oxygenation.52
In patients with chronic refractory HF despite medical
therapy, a permanent implantable left ventricular assist
device53 must be used as a bridge to transplantation or as a
bridge to recovery and rarely as destination therapy.

11. Heart transplantation
Heart transplantation is an accepted treatment for patients
with refractory HF. Although controlled trials have never
been conducted, there is a consensus that cardiac transplantation significantly increases survival, functional capacity, and quality of life. The indications and
contraindications54 for pediatric heart transplantation are
summarized in Table 5. In recent years, the outcome of
pediatric transplantation has continued to improve. The
most recent data from the The International Society of

Heart and Lung Transplantation demonstrate that the median survival is 19.7 years for infants, 16.8 years for children ages 1e5 years, 14.5 years for children ages 6e10
years, and 12.4 years for children 11e17 years of age at the
time of transplantation.55
The major post-transplantation complications are:
Rejection: Rejection is one of the main post-transplant
complications limiting long-term graft survival. Data from
the Paediatric Heart Transplant Study demonstrate that
64% of patients were free of rejection in the 1st year (36% of
patients experiencing rejection) and 5-year freedom from
rejection was 52%.56
Infection: Immunosuppression renders the host potentially susceptible to opportunistic infections that account
for approximately 12% of deaths during the first year
following transplantation.57
Cardiac allograft vasculopathy: Cardiac allograft vasculopathy remains one of the leading causes of mortality
following pediatric transplantation affecting 34% of patients by 10 years’ post-transplantation.58
Malignancy: Tumors, particularly lymphoproliferative
disease, remain a relatively uncommon post-transplant
complication.
The incidence of malignancy in the ISHTL registry at 5
years and 10 years following transplantation is 5% and 9.5%,
respectively.59

12. Proposed approach to PHF
A simplified approach to PHF is summarized in Figure 2. In
the emergency setting, at the first stage, acute HF should
be considered as a unique syndrome independent from the
underlying causes. One exception is for patients with de

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Table 5

Pediatric heart transplantation: indication and contraindication.

Patients to consider

Contraindications

End-stage HF associated with systemic ventricular dysfunction in patients with cardiomyopathies or
previously repaired/palliated CHDs.
Advanced HF associated with severe limitation of exercise and activity. If measurable, such patients
would have a peak maximum oxygen consumption <50% predicted for age and sex.
Advanced HF with associated life-threatening arrhythmias untreatable with pharmacological/device
therapy.
Advanced HF in patients with restrictive cardiomyopathy associated with reactive pulmonary
hypertension.
Advanced HF associated with reactive pulmonary hypertension and a potential risk of developing
fixed, irreversible elevation of pulmonary vascular resistance that could preclude orthotopic heart
transplantation in the future.
Recent or recurrent malignancy.
Serious active or recurrent infection.
Significant systemic diseases.

Genetic or metabolic diseases with poor long term prognosis.
Renal or hepatic dysfunction not explained by the underlying heart failure and deemed irreversible.
Pharmacologically irreversible pulmonary hypertension (pulmonary vascular resistance > 6 mm2).

CHD Z congenital heart diseases; HF Z heart failure.

Figure 2 Practical approach to acute and chronic heart failure. CHDs Z congenital heart diseases; HF Z heart failure;
PGE1 Z prostaglandin E1; Tx Z transplantation; VAD Z ventricular assist device.

novo acute HF due to CHD with ductus-dependent circulation or to extracardiac causes in which prostaglandin E1 or
tailored treatment must be started as soon as possible. In
the remaining patients, management is balanced according
to the presence of volume overload and hypoperfusion.
Volume overload is almost universally present, and therefore, the early use of intravenous loop diuretics is effective
in virtually all patients with acute/decompensated HF.
However, considering the adverse effects of diuretic use,
including sodium and potassium depletion, ototoxicity, and
of course renal insufficiency, diuretic use should not be
indiscriminate or excessive. In cases of underperfusion, the
use of low-moderate dose of inotropes is indicated. After
stabilization, accurate research of the etiology must be
conducted.
In cases of cardiomyopathies and in patients with moderate/severe left ventricular systolic dysfunction, ACE inhibitors and b blockers represent the mainstay of medical
therapy.

In patients with CHD, a corrective/palliative intervention must be planned and medical therapy is used only if
left ventricular systolic dysfunction is present. Finally, in
end-stage patients, ventricular assist device implantation/
cardiac transplantation should be considered and discussed
case by case for timing and indications.

13. Conclusion
HF in children is a complex syndrome with heterogeneous
etiology and presentation. Unlike adults, PHF is commonly
due to structural heart disease and reversible conditions,
thus lending it amenable to definitive therapy or short-term
aggressive therapy.
While the general principles of management are similar
to those in adults, there is a lack of randomized clinical
trials and international guidelines for PHF.
A judicious balance between extrapolation from adult
HF guidelines and the development of child-specific data on

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Pediatric Heart Failure
treatment represent a wise approach to optimize management in this challenging field.

Conflicts of interest
The authors have no conflicts of interest relevant to this
article.

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