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Pediatrics and Neonatology (2017) 58, 303e312

Available online at www.sciencedirect.com

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journal homepage: http://www.pediatr-neonatol.com

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 1 February 2017

Key Words Pediatric heart failure represents an important cause of morbidity and mortality in childhood.
cardiomyopathies; Currently, there are well-established guidelines for the management of heart failure in the
congenital heart adult population, but an equivalent consensus in children is lacking. In the clinical setting,
diseases; ensuring an accurate diagnosis and defining etiology is essential to optimal treatment. Di-
pediatric cardiac uretics and angiotensin-converting enzyme inhibition are the first-line therapies, whereas
transplantation; beta-blockers and devices for electric therapy are less used in children than in adults. In
pediatric heart the end-stage disease, heart transplantation is the best choice of treatment, while a left ven-
failure tricular 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 pa-
tients 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 (http://creativecommons.org/licenses/
by-nc-nd/4.0/).

1. Introduction the first mainly relates to ischemia (60e70% of cases), the


latter as a consequence of congenital heart diseases (CHDs)
Pediatric heart failure (PHF) represents an important cause or cardiomyopathies in most of the cases.2 Hence, man-
of morbidity and mortality in childhood.1 Etiology and aging PHF requires specific knowledge and skills.3 Pres-
pathogenesis are different between adults and children: ently, there are well-established guidelines for the
management of heart failure (HF) in the adult population,4
* Corresponding author. Cardiologia SUN e Heart Failure Unit,
but the equivalent consensus for PHF is lacking. This article
Department of Cardiothoracic Sciences, Second University of offers an overview on the etiology, diagnosis, and therapy
Naples, Via Leonardo Bianchi n 1, Naples 80100, Italy. of PHF, with a specific focus on practical issues required for
E-mail address: danielemasarone@libero.it (D. Masarone). management.

http://dx.doi.org/10.1016/j.pedneo.2017.01.001
1875-9572/Copyright ª 2017, Taiwan Pediatric Association. Published by Elsevier Taiwan LLC. This is an open access article under the
CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
304 D. Masarone et al

2. Definition 3. Etiology

In the 1950s, HF was described as a clinical syndrome In children, cardiac failure is most often due to CHDs and
caused by low cardiac output.5 In recent years, knowledge cardiomyopathies. The cardiac and noncardiac causes of PHF
of the pathophysiology has been expanded and neurohor- are summarized in Table 1. At birth, HF is caused by fetal
monal and molecular pathways that modulate cardiac cardiomyopathies or extracardiac conditions (such as sepsis,
performance in failing hearts have been discovered.6 The hypoglycaemia, and hypocalcaemia). In the 1st week after
contemporary vision describes HF as a clinical syndrome birth, CHDs with ductus-dependent systemic circulation (such
characterized by typical symptoms and signs associated as severe aortic stenosis/aortic coarctation and hypoplastic
with specific circulatory, neurohormonal, and molecular left heart syndrome), in which the closure of the ductus
abnormalities.7 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
Valvular regurgitation (volume overload) Mitral regurgitation
Aortic regurgitation
Outflow tract obstruction (pressure Aortic stenosis
overload)
Tunnel type subaortic stenosis
Supravalvular aortic stenosis
Pulmonary stenosis
Pulmonary vein stenosis
Coronary insufficiency (decreased O2 supply Coronary artery anomalies
to cardiomyocyte)
Cardiomyopathies Systolic dysfunction (low cardiac output) Dilated cardiomyopathy
(inherited or acquired) Diastolic dysfunction (elevated pulmonary
capillary pressure) - 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
Pediatric Heart Failure 305

are the main cause. In the 1st month of life, frequent causes of Infant and young children: The typical presentation is
PHF are CHDs with left to right shunt (such as ventricular characterized by difficulty in feeding (from prolonged
septal defects, patent ductus arteriosus, and aorto- feeding time intake to frank intolerance). Cyanosis,
pulmonary windows), in which pulmonary blood flow pro- tachypnea, sinus tachycardia, and diaphoresis can be
gressively increases with the fall of pulmonary resistance.9 present.
Finally, HF in adolescence is rarely secondary to CHDs, but is Older children and adolescence: Fatigue, shortness of
more often related to cardiomyopathies or myocarditis.10 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
4. Pathophysiology of PHF staged according to the Ross modified classification15 that
recognizes four functional classes with increasing severity
An “index event,” regardless of the cause, produces an initial of clinical features from I to IV (Table 2).
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” 6. Diagnostic approach
(Figure 1). The first of these mechanisms is the activation of
the sympathetic nervous system, resulting in increased The first step in diagnostic approach in patients with PHF is
release and decreased uptake of norepinephrine, with pe- based on noninvasive clinical investigations.
ripheral vasoconstriction to maintain (by increasing systemic
vascular resistance) mean arterial pressure and organ
perfusion. Enhanced catecholamine levels, however, lead to 6.1. Electrocardiogram
further cardiomyocyte injury, dysfunctional intracellular
signaling, and ultimately cardiomyocyte death.11 The second Sinus tachycardia is common in acute HF. In chronic HF, an
important “compensatory” mechanism is the stimulation of abnormal electrocardiogram increases the likelihood of
the rennineangiotensin aldosterone system, consisting of decompensated HF.16
increased circulating levels of renin, angiotensin II, and
aldosterone. Renin is responsible of cleaving angiotensi-
nogen in angiotensin I, which is converted into angiotensin II
by the angiotensin-converting enzyme (ACE). Angiotensin II
Table 2 Modified Ross classification for pediatric heart
is a potent vasoconstrictor that preserves end-organ perfu-
failure.
sion. Aldosterone causes salt and water retention, resulting
in increased preload and then cardiac output according to Class I Asymptomatic
the FrankeStarling mechanism. However, the elevation of Class II Mild tachypnea or diaphoresis with feeding in
both aldosterone and angiotensin II promotes cardiac fibrosis infants
and apoptosis.12 These mechanisms may temporarily Dyspnea on exertion in older children
contribute to circulatory stability, but over time become Class III Marked tachypnea or diaphoresis with feeding
maladaptive and promote the progression of HF.13 in infants. Prolonged feeding times with growth
failure
Marked dyspnea on exertion in older children
5. Clinical presentation Class IV 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.
306 D. Masarone et al

6.2. Chest radiography 6.5. Cardiac magnetic resonance

Chest radiography is indicated in all children with sus- Cardiac magnetic resonance is indicated to study complex
pected HF to assess heart size and to check for other signs CHDs or for tissue characterization and therefore for diag-
of HF such as pulmonary edema, septal lines (or Kerley B nosis, risk-stratification, and ongoing management of pa-
lines), and pleural effusions.17 tients with specific forms of cardiomyopathies.19

6.6. Cardiac catheterization


6.3. Echocardiography
Despite advances in noninvasive diagnostic techniques,
The echocardiogram is the most useful, widely available, cardiac catheterization is presently indicated for20:
and low-cost test for patients with PHF. Echocardiography
provides immediate data on cardiac morphology and - accurate evaluation of pressure gradients in patients
structure, chamber volumes/diameters, wall thickness, with complex valve diseases
ventricular systolic/diastolic function, and pulmonary - evaluation of hemodynamic parameters (pulmonary and
pressure. These data are crucial to make the correct systemic vascular resistance, cardiac output, and car-
diagnosis and to guide appropriate treatment.18 diac 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 summa- Endomyocardial biopsy is an invasive procedure with sig-
rized in Table 3. nificant 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.
Electrolytes 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.
Renal function tests Elevated BUN and BUN/creatinine ratio are seen in decompensated heart failure.
Liver function tests 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 Natriuretic peptides levels correlate closely with the NYHA/Ross classification of
(NT-proBNP/BNP) heart failure and with ventricular filling pressures.
CPK-MB, troponin I and T Useful if the clinical scenario is suggestive of an ischemic process or myocarditis
Lactate 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.
Thyroid function tests Both severe hyper or hypothyroidism can cause heart failure.
Arterial blood gas 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.
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.
Pediatric Heart Failure 307

clinical diagnosis of myocarditis and to choose the appro- 9.2. Medical therapy
priate therapeutic management21 (such as giant cell
myocarditis). Medical therapy for HF (Table 4) focuses on three main
goals25:
7. Therapeutic approach - decrease of pulmonary wedge pressure
- increase of cardiac output and the improvement of end-
Treatment of PHF aims to: organ perfusion
- delay of disease progression.
- eliminate the causes of PHF
- control the symptoms and disease progression.
9.3. Diuretics

8. Eliminate the causes of HF Diuretics therapy plays a crucial role in the treatment of
pediatric patients with HF. The benefits of diuretic therapy
When possible, the causes of HF must be corrected through include reduction of systemic, pulmonary, and venous
different approaches: congestion.26
Spironolactone may exert additional beneficial effects by
- corrective treatment should be performed in CHDs22 attenuating the development of aldosterone-induced
- systemic diseases (such as sepsis) or electrolytic imbal- myocardial fibrosis27 and catecholamine release. Potential
ance (such as hypocalcemia) must be carefully complications of diuretic therapy include electrolyte ab-
researched and treated. normalities (hyponatremia, hypo- or hyperkaliemia, and
hypochloremia) and metabolic alkalosis. Electrolyte balance
should be carefully monitored, especially during aggressive
9. Control of symptoms and disease
progression
Table 4 Drugs used in pediatric heart failure.
9.1. General measures Drugs Routes of Doses
administration
In infants, nutritional support must ensure a caloric intake Furosemide Oral 1e2 mg/kg q6e12h
about of 150 kcal/kg/d. This is achieved using dietary Furosemide Intermittent 0.5e2 mg/kg q6e12h
supplements, preferring small and frequent meals that are bolus
better tolerated.23 Furosemide Continuous 0.1e0.4 mg/kg/h
In children and adolescents, current recommendations infusion
suggest that 25e30 kcal/kg/d is a reasonable target for Captopril Oral 0.3e2 mg/kg q8h
most patients. Enalapril Oral 0.05e0.25 mg/kg q12h
Carbohydrates should not exceed 6 g/kg/d and lipids Losartan Oral 0.5e1.5 mg/kg/d
should not exceed 2.5 g/kg/d. The provision of essential Carvedilol Oral 0.05 mg/kg/d q12h
amino acids is necessary in the critically ill. Evidence sug- Metoprolol Oral 0.25 mg/kg/d q12h
gests that 1.2e1.5 g/kg/d of protein is needed. Spironolactone Oral 0.5e1.5 mg/kg q12h
Nutritional supplementation is required in HF secondary Nitroglycerin Continuous 0.5e10 mg/kg/min
to metabolic and mitochondrial diseases (such as carnitine infusion
and ubiquinone). Nitroprusside Continuous 0.5e4 mg/kg/min
In acyanotic CHD patients or in patients with cardiomy- infusion
opathies, ventilatory support with oxygen must be initiated Hydralazine Intermittent 0.1e0.2 mg/kg every 4e6 h
when SaO2 < 90%. bolus
On the contrary, in patients with cyanotic CHD, oxygen Hydralazine Oral 0.3e1 mg/kg/d in q8e12h
has little effect in raising SaO2 and is not indicated. Digoxin Oral 5e10 mg/kg/d
However, in some cases with chronic left to right Dobutamine Continuous 2.5e10 mg/kg/min
shunting, irreversible pulmonary vascular disease can Infusion
develop and cause right to left shunting (Eisenmenger Epinephrine Continuous 0.01e0.1 mg/kg/min
syndrome). In the early stages, the resulting pulmonary Infusion
hypertension may be responsive to oxygen; hence, this is Epinephrine Intermittent 0.01 mg/kg
indicated while the child is waiting for cardiac trans- bolus
plantation or for palliation surgery.24 Reduction of salt Milrinone Continuous 0.5e1 mg/kg/min
intake is recommended in all patients with edemas and Infusion
fluid retention. Restriction of fluids is indicated in patients Levosimendan Continuous 0.05e0.2 mg/kg/min
with edemas unresponsive to diuretic therapy or Infusion
hyponatremia.
308 D. Masarone et al

diuretic therapy, as the failing myocardium is more sensitive 9.8. Phosphodiesterase type III inhibitors
to arrhythmias induced by electrolyte imbalance.
This class of drugs incorporates amrinone, enoximone,
9.4. ACE inhibitors milrinone, and olprinone, of which milrinone, the strongest
and shortest acting with the best control, is the most
ACE inhibitors prevent, attenuate, or possibly reverse the commonly used in pediatric intensive care.
pathophysiological myocardial remodeling. In addition, Phosphodiesterase type III inhibitors have vasodilatory
they decrease afterload by antagonizing the ren- and inotropic actions and improve diastolic ventricular
nineangiotensin aldosterone system.28 According to recent relaxation.34 Despite the pro-arrhythmic effects of milri-
guidelines of The International Society of Heart and Lung none, it represents the first choice of therapy in patients
Transplantation on the management of pediatric HF, ACE with moderate/severe ventricular dysfunction with hypo-
inhibitors are recommended in all patients with HF and left perfusion symptoms.
ventricular systolic dysfunction.29 Therapy with ACE in-
hibitors should be started at low doses with a subsequent 9.9. Calcium sensitizer
up-titration to the target dose with careful monitoring of
blood pressure, renal function, and serum potassium. Levosimendan exerts strong inotropic and vasodilating ef-
fects, possibly stronger than dobutamine, with less poten-
9.5. b blockers tial for myocardial ischemia. The absence of pro-
arrhythmic effects35 and the ability to reverse the effects
b blockers are now an accepted therapy in the pediatric of b blockade make levosimendan a potential drug of
population. b blockers antagonize the deleterious effects of choice in the context of postoperative low-cardiac output
chronic sympathetic myocardial activation and can reverse syndrome rather than in acute HF in children.36
left ventricular remodeling and improve systolic function.
Recent reports seem to show that the addition of b blockers 9.10. Vasodilators
to the standard therapy may be useful in patients with left
ventricular systolic dysfunction.30 In addition, a recent Vasodilators administered intravenously (nitroglycerin and
Cochrane Database of Systematic Reviews on b blockers for nitroprusside) or orally (hydralazine and nifedipine) are
children with congestive HF was published. Seven studies indicated only in cases of37:
with a total of 420 children were included in the review and
the authors conclude that the current available data suggest - hypertensive acute HF refractory to treatment (b
that children with HF might benefit from b-blocker treat- blockers and ACE inhibitors)
ment.31 Low-dose therapy should be started in stable pa- - severe valve regurgitations in patients intolerant to ACE
tients with a progressive up-titration to the target dose. inhibitors.

9.6. Inotropes 9.11. Promising new therapies

Digoxin is the main oral inotropic drug used in PHF and is There are several promising medications for PHF. An
indicated in symptomatic patients with left and/or right elevated baseline heart rate is a risk factor for mortality in
ventricular systolic dysfunction.32 The use of intravenous adults with HF. Ivabradine, an If current inhibitor in the
inotropes should be reserved for patients with a severe sinoatrial node, has an indication in patients with chronic HF.
reduction of cardiac output resulting in compromised vital The use of ivabradine was associated with fewer HF hospi-
organ perfusion (hypotensive acute/decompensated HF). talizations and deaths from HF.38 More recently, the combi-
Although increased inotropy results in improved cardiac nation of a neprilysin inhibitor and valsartan was compared
output and blood pressure, the final result is increased with enalapril in a large, prospective, randomized trial.
myocardial oxygen consumption and demand. Neprilysin is a neutral endopeptidase involved with
The failing myocardium has a limited contractile reserve degradation of natriuretic peptides, bradykinin, and adre-
and hemodynamic collapse can occur with high-dose nomedullin. Inhibition of neprilysin can result in decreased
inotropic support in this setting. vasoconstriction, sodium retention, and remodeling. The
trial was stopped early because of significantly improved
mortality, risk of hospitalization, and improved symptoms
9.7. Sympathomimetic amines
among patients receiving the neprilysin inhibitor valsartan
combination.39 Further study with these drugs will be
Dopamine and dobutamine have been shown to be effective warranted in children with HF.
inotropes and vasopressors in neonates, infants, and chil-
dren with circulatory failure. These drugs increase cardiac
output and decrease systemic and pulmonary vascular 10. Device therapy
resistance; however, they can induce tachycardia/tachy-
arrhythmia with a mismatch between myocardial oxygen Medical therapy has improved the survival and quality of
delivery and the requirement.33 Therefore, we reserve the life of children with HF; however, there is still a significant
use of these drugs only for patients with low cardiac output proportion of patients with poor prognosis due to the pro-
despite other therapies. gression of the disease or sudden cardiac death. These
Pediatric Heart Failure 309

patients are candidates for device therapy. The two main significantly less pronounced than the response seen in
devices used in patients with heart failure are the patients with left ventricle dysfunction.42
implantable cardioverter defibrillator (ICD) and cardiac Mechanical circulatory support systems can be used in
resynchronization therapy (CRT). In HF patients, ICD has a patients with PHF who cannot be stabilized with medical
key role in preventing sudden cardiac death due to ven- therapy to unload the failing ventricle and maintain end-
tricular arrhythmias. Based on data from observational organ perfusion.49,50 Patients with cardiogenic shock/acute
studies, accepted indications for ICD implantation in PHF HF with underperfusion not responsive to medical therapy
are40,41: must be initially treated with short-term assistance using
extracorporeal nondurable life support systems including
- secondary prevention of sudden cardiac death in pa- extracorporeal life support51 and extracorporeal membrane
tients with aborted cardiac arrest or in patients with a oxygenation.52
previous episode of ventricular tachycardia determining In patients with chronic refractory HF despite medical
hemodynamic instability therapy, a permanent implantable left ventricular assist
- unexplained syncope in patients with surgically repaired device53 must be used as a bridge to transplantation or as a
CHDs bridge to recovery and rarely as destination therapy.
- patients with severe left systolic ventricular dysfunction
(left ventricular ejection fraction < 35%). 11. Heart transplantation
Approximately 30% of adults with HF exhibit a left
Heart transplantation is an accepted treatment for patients
bundle branch block (LBBB) with mechanical dyssynchrony.
with refractory HF. Although controlled trials have never
In contrast to the adult HF population, only 9% of pediatric
been conducted, there is a consensus that cardiac trans-
HF patients present with LBBB and a QRS duration > 120
plantation significantly increases survival, functional ca-
milliseconds, which likely reflects the variable causes of HF
pacity, and quality of life. The indications and
in the pediatric population.42
contraindications54 for pediatric heart transplantation are
The rationale behind left ventricular dyssynchrony is
summarized in Table 5. In recent years, the outcome of
that in failing hearts, left ventricular function is affected
pediatric transplantation has continued to improve. The
not only by a depressed contractile status of the myocar-
most recent data from the The International Society of
dium, abnormal loading conditions, or both, but also by a
Heart and Lung Transplantation demonstrate that the me-
disturbed synchronicity of the myocardial walls.43 Late
dian survival is 19.7 years for infants, 16.8 years for chil-
activation of some segments leads to a slower rise in sys-
dren ages 1e5 years, 14.5 years for children ages 6e10
tolic pressure and delayed left ventricular ejection and also
years, and 12.4 years for children 11e17 years of age at the
to slower relaxation and delayed left ventricular filling.44
time of transplantation.55
This pathophysiological condition is the assumption that
The major post-transplantation complications are:
CRT, through biventricular pacing, improves the pattern of
Rejection: Rejection is one of the main post-transplant
contraction of the left ventricle.45 Despite the lack of
complications limiting long-term graft survival. Data from
randomized clinical trials, retrospective studies demon-
the Paediatric Heart Transplant Study demonstrate that
strated the utility of CRT in pediatric patients with46:
64% of patients were free of rejection in the 1st year (36% of
patients experiencing rejection) and 5-year freedom from
- dilated cardiomyopathy, complete LBBB, and severe
rejection was 52%.56
reduction of left ventricular systolic function (left ven-
Infection: Immunosuppression renders the host poten-
tricular ejection fraction < 35%)
tially susceptible to opportunistic infections that account
- third-degree atrioventricular block requiring the im-
for approximately 12% of deaths during the first year
plantation of a pacemaker in DDD modality in patients
following transplantation.57
with mild/moderate systolic dysfunction (left ventricu-
Cardiac allograft vasculopathy: Cardiac allograft vas-
lar ejection fraction < 55%)
culopathy remains one of the leading causes of mortality
- CHDs with double-ventricle physiology with systemic left
following pediatric transplantation affecting 34% of pa-
ventricle with severe reduction of systolic function.
tients by 10 years’ post-transplantation.58
Malignancy: Tumors, particularly lymphoproliferative
In patients with single ventricle physiology, evidence
disease, remain a relatively uncommon post-transplant
supporting CRT is limited to a few studies.47,48 These series
complication.
demonstrated improved cardiac index, systolic blood
The incidence of malignancy in the ISHTL registry at 5
pressure, and indexes of asynchrony after CRT, but in the
years and 10 years following transplantation is 5% and 9.5%,
heterogeneous patient population, technical limitations
respectively.59
imposed by patient body size and unique forms of ventric-
ular dyssynchrony have made it difficult to draw strong
conclusions or to rationalize widespread use. 12. Proposed approach to PHF
There are controversial results about the efficacy of CRT
in patients with isolated right ventricle dysfunction. Some A simplified approach to PHF is summarized in Figure 2. In
studies have shown that CRT can improve right ventricle the emergency setting, at the first stage, acute HF should
ejection fraction and New York Heart Association/Ross class be considered as a unique syndrome independent from the
and reduce QRS duration. However, this response was underlying causes. One exception is for patients with de
310 D. Masarone et al

Table 5 Pediatric heart transplantation: indication and contraindication.


Patients to consider 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.
Contraindications 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 circula- In patients with CHD, a corrective/palliative interven-
tion or to extracardiac causes in which prostaglandin E1 or tion must be planned and medical therapy is used only if
tailored treatment must be started as soon as possible. In left ventricular systolic dysfunction is present. Finally, in
the remaining patients, management is balanced according end-stage patients, ventricular assist device implantation/
to the presence of volume overload and hypoperfusion. cardiac transplantation should be considered and discussed
Volume overload is almost universally present, and there- case by case for timing and indications.
fore, the early use of intravenous loop diuretics is effective
in virtually all patients with acute/decompensated HF. 13. Conclusion
However, considering the adverse effects of diuretic use,
including sodium and potassium depletion, ototoxicity, and HF in children is a complex syndrome with heterogeneous
of course renal insufficiency, diuretic use should not be etiology and presentation. Unlike adults, PHF is commonly
indiscriminate or excessive. In cases of underperfusion, the due to structural heart disease and reversible conditions,
use of low-moderate dose of inotropes is indicated. After thus lending it amenable to definitive therapy or short-term
stabilization, accurate research of the etiology must be aggressive therapy.
conducted. While the general principles of management are similar
In cases of cardiomyopathies and in patients with mod- to those in adults, there is a lack of randomized clinical
erate/severe left ventricular systolic dysfunction, ACE in- trials and international guidelines for PHF.
hibitors and b blockers represent the mainstay of medical A judicious balance between extrapolation from adult
therapy. HF guidelines and the development of child-specific data on
Pediatric Heart Failure 311

treatment represent a wise approach to optimize man- 20. Feltes TF, Bacha E, Beekman 3rd RH, Cheatham JP,
agement in this challenging field. Feinstein JA, Gomes AS, et al. Indications for cardiac cathe-
terization and intervention in pediatric cardiac disease: a sci-
entific statement from the American Heart Association.
Conflicts of interest Circulation 2011;123:2607e52.
21. Webber SA, Boyle GJ, Jaffe R, Pickering RM, Beerman LB,
The authors have no conflicts of interest relevant to this Fricker FJ. Role of right ventricular endomyocardial biopsy in
article. infants and children with suspected or possible myocarditis. Br
Heart J 1994;72:360e3.
22. Stout KK, Broberg CS, Book WM, Cecchin F, Chen JM,
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