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U N I V E R S I T Y O F M I N N E S O T A A m p l at z C H I L D R E N ’ S H O S P I T A L
Heart Failure in Children
Rebecca Ameduri, M.D.
Elizabeth Braunlin, M.D.
Background
Heart failure is the final, common pathway of a complex
interplay of structural, functional, and biologic factors that
lead to cardiac pump and circulatory system dysfunction. Such
factors result in an inability of the heart to keep up with the
metabolic demands of the body. In contrast to adults in whom
ischemic heart disease is the most common etiology of heart
failure, in children, a range of defects, including congenital heart
defects, systemic metabolic disorders that affect the myocardium,
tachyarrhythmias, and acquired heart disease can cause heart
failure to develop.
Recent advances in the medical and surgical management of
heart failure have improved the morbidity and mortality of
heart failure in the pediatric population. Additionally, recent
advances in heart failure management have improved survival
rates for patients who develop end stage heart failure that requires
cardiac transplantation. This article will serve as an overview
of the physiology, etiologies, clinical presentation, diagnosis and
management of heart failure in children.
Pathophysiology
The symptoms, known as heart failure (HF), are the final
pathways that occur when the hemodynamic demands on the
heart exceed the pressure- or flow-generating capacity of the
systemic pump. Such might be secondary to either inadequate
inflow or inadequate outflow. Limited inflow (diastolic
capacity) is prevalent in disorders such as pericardial disease,
restrictive cardiomyopathy, mitral stenosis or pulmonaryvenous obstruction. Limited outflow (systolic capacity) has
characteristics of disorders that include dilated cardiomyopathy,
prolonged tachyarrhythmias and systemic-outflow obstruction.
HF might occur when normal hemodynamic demands are
imposed on myocardium with decreased systolic or diastolic
function, when an excess load is imposed on normal myocardium,
or when a combination of the two occurs. To determine
appropriate management, the practitioner must identify the
presence or absence of congenital heart defects and of myocardial
dysfunction. For most types of congenital heart disease, repair or
palliation of the underlying structural defect provides the most
definitive improvement; whereas medical management of the HF
symptoms might not be adequate. If the HF is secondary to nonmyocardial factors, such as hematologic, metabolic, endocrine or
renal disease, therapy is rarely successful unless the underlying
etiology also is treated.
At the basic biologic level, there is a complex interplay of
neurohormonal factors that occur in response to heart failure, to
meet the hemodynamic demands of the body. At the tissue level,
when regional flow is inadequate, there is a rise in metabolite
concentrations such as ADP, which stimulate local vasodilation.
Such allows flow to increase and metabolites to be removed. The
vasodilation produces a decrease in peripheral vascular resistance
and systemic blood pressure, which results in improved cardiac
output.
There are baroreceptors within the vasculature that respond
to the fall in pressure by stimulating reflex mechanisms,
including the sympathetic nervous system (SNS) and the reninangiotensisn-aldosterone system (RAAS). The SNS provides
the rapid response to the failing heart: tachycardia, stimulation
of myocardial contractility, and regional vasoconstriction. The
RAAS pathway provides longer term response by stimulating
renal fluid retention to expand vascular volume, thus improving
cardiac filling and restoring cardiac output. Under normal
conditions, these mechanisms work to maintain normal blood
pressure, cardiac output and volume. When the fall in cardiac
output and blood pressure are due to diminished cardiac
contractility, these same mechanisms might prove detrimental to
the failing myocardium. Chronic activation of the SNS causes
persistent tachycardia, which shortens diastole, thus decreases
coronary blood flow while vasoconstriction increases the cardiac
workload by increasing afterload. Volume expansion caused by
chronic activation of the RAAS system might cause pulmonary
edema or hepatic congestion in the presence of systolic or diastolic
cardiac dysfunction. In addition to the activation of the SNS
and RAAS systems, increased release of vasopressin, endothelin,
and inflammatory cytokines also occur during congestive
heart failure. The long term consequences of these maladaptive
mechanisms are still being studied but are thought to play a role
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in the adverse remodeling of the myocardium and vasculature that
occurs in chronic heart failure. The overall net effect is an increased
systemic vascular resistance and increased myocardial fiber length
classically described by Starling.
Clinical Presentation
Four cardinal signs of heart failure in children
• Tachypnea
• Tachycardia
• Cardiomegaly
• Hepatomegaly
The signs and symptoms of heart failure vary depending on the age
at presentation and the underlying etiology. The clinical findings
are different in infants versus older children and adolescents.
Infants with heart failure typically present with feeding difficulties
as this is one of their most demanding physical activities. They
might take more time to feed and have associated tachypnea,
tachycardia and diaphoresis. Growth failure is a classic feature in
infants with congestive heart failure. Alternatively, infants who
have chronic cough that are unresponsive to typical respiratory
therapies might be exhibiting signs of heart failure.
Physical examination of infants with heart failure will reveal resting
tachycardia and tachypnea. As HF symptoms progress, they might
develop signs of respiratory insufficiency including nasal flaring,
retractions, and grunting. The cardiac exam is variable, depending
on the etiology of heart failure. Murmurs might be present. Infants
with cardiomyopathy might have a mitral regurgitation murmur
and a third heart sound. The third heart sound, however, may be
difficult to appreciate with the rapid heart rate. Infants with HF
will have hepatomegaly associated with increased systemic venous
pressure and/or volume. Peripheral edema is rare in infants.
With severe heart failure and low cardiac output, infants might
have cool extremities, weak pulses, low blood pressure, mottling
of the skin and delayed capillary refill. A chest X-ray will typically
show cardiomegaly. Most infants with HF have some degree of
pulmonary venous congestion, which appears as a diffuse haziness
on the chest X-ray. Infants with large systemic to pulmonary
shunts show increased pulmonary vascular markings. Although
an electrocardiogram might be abnormal and provide clues to
the diagnosis, such as the presence of Wolff-Parkinson-White
syndrome, it does not usually help in defining heart failure severity.
Cardiac ultrasound provides the most useful information in the
evaluation of infants with heart failure. The imaging defines the
underlying cardiac anatomy. The imaging also allows practitioners
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to evaluate atrial and ventricular size, pulmonary artery pressure
and cardiac function.
Older infants and children with heart failure have signs and
symptoms similar to those of adults. Children might have
shortness of breath with dyspnea that is exaggerated by exercise.
A chronic cough secondary to pulmonary congestion might be
present. Symptoms of congestive heart failure in children might
be subtle but often an intercurrent illness will be enough to
exacerbate the underlying hemodynamic abnormalities and allow
congestive heart failure to become apparent.
Fatigue and weakness are late findings. On physical examination,
children with mild to moderate heart failure might not appear
in distress; however, children with more severe heart failure
might demonstrate dyspnea and tachypnea at rest. A child or
adolescent, who cannot speak in full sentences, is on the verge of
cardiorespiratory failure.
Children with chronic heart failure sometimes appear
malnourished and pale. Distention of the neck veins can be
difficult to appreciate but reveals increased systemic venous
pressure. Hepatomegaly is typically present and if the heart
failure is acute in nature, associated flank pain might occur as
a result of stretching of the liver capsule. Once an increase in
body weight oocurs - approximately 10 percent - the child might
develop peripheral edema in dependent parts of the body. In
more severe cases, children might develop ascites, pleural and
pericardial effusions. Occasionally, presacral edema is seen in
young as well as elderly recumbent persons in heart failure.
Cardiac exam is variable depending on the etiology and presence
of congenital heart disease. A murmur might be audible from a
large systemic to pulmonary shunt or from atrioventricular valve
regurgitation. A gallop heart sound with a third and possibly a
fourth heart sound might be heard. Palpation of the chest can
reveal a laterally displaced or diffuse apical impulse, and a right
ventricular heave.
The diagnosis of heart failure is sometimes made serendipitously
by ordering a chest X-ray for other reasons. The chest X-ray
in congestive heart failure typically shows cardiomegaly and
interstitial pulmonary edema, which, in more severe cases, causes
diffusely hazy lung fields. Cardiac ultrasound is the primary
modality for defining the cardiac anatomy and for assessing
ventricular function in children with heart failure. Although
initial diagnosis of congenital heart disease in an older child
is rare, some children who have undergone previous palliative
surgeries for congenital heart disease may later develop heart
failure several years after the palliation.
H eart F ai l ure in C hi l dren
Etiologies
There is a wide spectrum of etiologies that can lead to heart
failure in children. Tables 1 and 2 summarize the more common
etiologies of heart failure in pediatrics, organized by the presence
of a structurally normal heart (Table 1) or the presence of
congenital heart disease (Table 2).
Among the more common causes of congestive heart failure likely
to present to the primary-care physician are myocarditis and
idiopathic dilated cardiomyopathy. Additionally, patients who
have had prior repair or palliation of congenital heart disease
Figure 1. Echocardiogram pictures of normal heart versus
patient with dilated cardiomyopathy. Four chamber view of a
normal heart (A) and a patient with dilated cardiomyopathy (B)
Short axis and m-mode demonstrating normal contractility (C)
versus dilation and decreased function (D).
Figure 2.
Cardiomyopathy Evaluation
Chest X-ray, EKG,
Echocardiogram
YES
Suspect Myocarditis
Viral Studies
Cardiac MRI
Endomyocardial Biopsy
Dilated cardiomyopathy:
Consider karyotype,
familial dilated cardiomyopathy
gene chip, mitochondrial DNA
sequencing, skeletal and/or
endomyocardial biopsy
NO
Family History
Initial blood/urine to evaluate
for metabolic and mitochondrial
diseases Genetics and
Neuromuscular consults
Hypertrophic cardiomyopathy:
Consider karyotype,
familial hypertrophic
cardiomyopathy
gene chip, mitochondrial
DNA sequencing, screening
for Noonan syndrome,
skeletal and/or
endomyocardial biopsy
might present in adolescence or adulthood with signs of heart
failure. See below for more detail.
Patients with myocarditis might present with a febrile illness and
have generalized viral symptoms, including upper respiratory
symptoms, vomiting and diarrhea. Myocarditis might be present
if a child has tachypnea and/or tachycardia that are out of
proportion to the severity of illness, or have key physical findings
such as hepatomegaly, a third heart sound, new onset of murmur
of mitral regurgitation, pericardial friction rub or distant heart
sounds. In this setting, a chest X-ray is useful to evaluate cardiac
size and presence of pulmonary edema. Patients should receive a
referral for an urgent evaluation by a pediatric cardiologist. The
immediate evaluation is necessary because the patient might have
rapidly progressive deterioration in status over the course of a few
hours.
In patients who have severe myocarditis, approximately onethird of them will have recovery of normal cardiac function,
one-third will continue to have compromised function but will
remain stable over time, and one-third will have a progressive
decline resulting in either death, need for mechanical circulatory
support or transplantation. However, the advent of ventricularassist devices for pediatric use have introduced a new, natural
history for myocarditis in which some patients who would
have previously died are able to receive support long enough to
recovery myocardial function.
Patients with idiopathic dilated cardiomyopathy can be
relatively asymptomatic until cardiac function becomes severely
compromised and signs of HF develop. On careful history, the
patient will typically report a decreased exercise tolerance and
increasing fatigue before the overt appearance of HF symptoms.
Additionally, such patients can be well compensated despite their
decreased function until an additional stress, such as a viral or
bacterial infection, imposes on them. Figure 1 demonstrates an
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echocardiogram from a patient with dilated cardiomyopathy, in
comparison to a normal echocardiogram. Most patients will not
develop symptoms until their function is severely diminished,
with ejection fractions of 25 to 30 percent (with normal being
>55 percent). In the acutely decompensated state, such patients
might require inotropic or mechanical support. Many of them,
however, will remain stable for a prolonged period with oral
medication treatments, before later progressing to require cardiac
transplantation.
Cardiac ultrasound, 12-lead electrocardiogram, and chest X-ray
are standard for the initial workup. Cardiac ultrasound is the
most useful tool for evaluation of congenital heart disease and
ventricular function. Standard laboratory evaluation includes
thyroid-function testing, hemoglobin and carnitine levels.
Additionally, patients typically undergo laboratory assessment of
the severity of heart failure by measurement of brain-anatriuretic
peptide (BNP), troponin, and by evaluation for markers of renal
and hepatic end-organ dysfunction.
Another increasingly important category of patients who have
heart failure are adolescents or adults with congenital heart
disease. Almost any patient who had repair or palliation of
congenital heart disease can later develop cardiac dysfunction
and HF. This might relate to poor myocardial preservation
during earlier surgeries, ventricular dysfunction from multiple
bypass runs, arrhythmias, residual defects or progressive valvular
dysfunction despite repair. Patients with two specific congenital
anomalies are particularly prone to the late development of
congestive heart failure. One is single ventricle after Fontan
procedure, the other is d-transposition of the great vessels
palliated with an atrial baffle procedure. Adolescents or adults
with repaired or palliated congenital heart disease and heart
failure often benefit from a referral to a pediatric cardiologist who
is familiar with the natural history of these repaired anomalies.
These two groups of patients represent a large proportion
of adults with congenital heart disease who are referred for
consideration for cardiac transplantation.
In the absence of structural cardiac disease, evidence for
myocarditis is sought by viral culture and polymerase chain
reaction (PCR) analysis. Genomic testing of the more common
forms of familial dilated cardiomyopathy is indicated if a firstdegree relative has a cardiomyopathy. Urine organic acids and
serum amino acids are tested to rule out the possibility of
metabolic disorders. Skeletal muscle biopsy can be obtained if
there is suspicion of systemic mitochondrial or metabolic disease,
or if cardiac muscle biopsy is considered to be high risk.. After
stabilization of the child, completion of cardiac catheterization
with endomyocardial biopsy often helps to determine
hemodynamics and establish a diagnosis. Figure 2 provides a
paradigm for the stepwise approach to this diagnostic workup.
Diagnosis
The diagnostic approach for patients with heart failure
depends on:
• Age of patient
• Presence or absence of congenital heart disease
• Presence of systemic disorders
• Severity of heart failure
Patients who have signs and symptoms of congestive heart failure
should have an evaluation by a pediatric cardiologist. Depending
on the child’s presentation, the evaluation might take place on an
outpatient basis during the course of a few days. Patients also can
have an inpatient evaluation — sometimes on an intensive care
unit — over the course of a few hours.
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Management
Therapy for heart failure depends on the age of the patient,
specific cardiac diagnosis, time course of the symptoms (acute
versus chronic), and existence of other underlying conditions.
Practitioners should customize treatment plans based on these
factors.
Just as heart failure is a continuum — with symptoms ranging
from mild to life-threatening, so is the management. Therapies
range from outpatient administration of oral medications
to listing for cardiac transplantation and implantation of
left ventricular-assist devices. The goal in managing acutely
decompensated heart failure is to restore pump function to
improve hemodynamic instability, improve symptoms and
minimize end-organ damage.
First-line therapy for mild to moderate congestive heart failure
includes diuretics such as furosemide (Lasix) or bumetanide
(Bumex) with angiotensin-converting enzyme inhibitor (ACE) or
angiotensin-recptor blocker (ARB) medications such as enalapril
and losartan and beta-blocker therapy such as carvedilol. See table
H eart F ai l ure in C hi l dren
3 for a description of the mechanism of action and the physiologic
action of these medications. While there are many large, national
treatment protocols for evaluation of HF management in adults,
no such protocols exist for children or infants.
For children with more severe presentation of heart failure,
intravenous administration of inotropic drugs, such as milrinone
and dopamine, can be given acutely or chronically. The most
severe types of heart failure will require the urgent use of
extracorporeal membrane oxygenator (ECMO) or placement
of left ventricular-assist devices, and listing for cardiac
transplantation. Before 2000, the only type of circulatory support
available for infants and small children with cardiogenic shock
was ECMO. Children have a limited survival time of six to eight
weeks on ECMO before significant ECMO-related complications
usually ensue. Such difficulties include stroke, hemorrhage or
infection. Significant developments in ventricular-assist devices
(VAD) for pediatric use have occurred within the past 10 years.
The advantage of using a VAD is longer periods of use than
ECMO. The expanded use time allows a bridge to transplantation
or potentially as a bridge to recovery by giving the myocardium
a longer period of time to heal. Additionally, patients can be
extubated, awake, active, and participate in rehabilitation while
awaiting transplant.
The initial VAD use in pediatrics was limited to larger-size
children and adolescents who could receive support with devices
designed for adults, e.g., Thoratec and Heart Mate II. The initial
experience with these devices was encouraging, with 68 percent of
patients surviving to transplantation or device removal.
Figure 3.
Outcomes of Berlin
Heart Recipients
8%
On Device
26%
Death
5.5%
Weaned
60.5%
Transplant
Once a patient develops end-stage heart failure, or are unlikely
to have recovery of myocardial function, they might need to be
listed for heart transplantation. The current indications for heart
transplantation in children include:
• Need for ongoing intravenous inotropic support
• Mechanical circulatory support
• Complex CHD not amenable to repair or palliation
The newest device available for pediatric use is the Berlin Heart
EXCOR. It is commercially available in Europe and is available
on a compassionate use or FDA study use in the United States.
The Berlin Heart is available in multiple pump sizes for various
patient sizes. To date, more than 500 patients worldwide have
received support on this device, and over 200 patients within
North America.
• Progressive deterioration of ventricular function or functional
status despite optimal medical care
Through 2008, the survival rates for the North American
experience are approaching 75 percent in the current era; the
most recent outcomes are shown in figure 3. The University of
Minnesota is one of 15 centers in the country that is an FDA
study site for the Berlin Heart. Since 2008, our program has
implanted devices in five children, and have outcomes similar to
the national data.
• Growth failure secondary to severe heart failure
• Malignant arrhythmia
• Survival after cardiac arrest unresponsive to medical
treatment, catheter ablation or AICD
• Progressive pulmonary hypertension that could preclude
transplantation at a later date
• Unacceptably poor quality of life secondary to heart failure
• Progressive deterioration in functional status and/or presence
of certain high-risk conditions following the Fontan
procedure
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Once it is determined that a child needs to be listed for heart
transplantation, the child is entered into the United Network
for Organ Sharing (UNOS) wait list. Each candidate awaiting
heart transplant is assigned a status code, which corresponds to
how medically urgent it is that the child receive a transplant.
The criteria for the different status levels for pediatric heart
transplant candidates are shown in table 4. Depending on the
severity of their illness, children awaiting transplantation might
be hospitalized requiring mechanical or ventilatory support,
intravenous inotropic medications, intravenous inotropic
medications at home, or oral medications at home.
A computerized match system, that UNOS operates, matches
donors and recipients based on blood type, age, size, listing status,
wait-list time and location.
The number of pediatric heart transplantations has been fairly
stable over the last 10 years, with approximately 350 to 400
transplants occurring worldwide each year. Approximately 25
percent of transplantations are on infants under the age of 1, with
the remaining number equally divided between children ages 1 to
10 years and adolescents ages 11 to 18.
The overall survival at one year after transplantation is 85
percent, with a five-year survival of 75 percent. Such survival
rates have increased in the recent era due to multiple factors
including improved surgical technique, better organ preservation,
better understanding of immunosuppression, and newer
immunosuppression medications with improved side-effect
profiles. Given these survival statistics, it is clear that heart
transplantation is not a cure and brings a host of new issues to
the forefront. However, a full discussion of the post-transplant
concerns is beyond the scope of this article. Our goal is to allow
a child to keep their own heart as long as possible. If a child has
recovery of function and practitioners are able to maintain the
child on oral medications with a good quality of life, they might
be de-listed for transplant and followed closely.
Conclusions
Heart failure in children is a complex disease process that has
widespread effects throughout the body. The clinical presentation
of heart failure in infants and children can be easily mistaken for
primary respiratory illness or other systemic disease processes,
making the diagnosis can be difficult.
Discovering the exact etiology of HF in children can be a difficult
challenge. In the acute setting, therapy is directed at restoring
hemodynamic stability and minimizing end organ damage. In
the patient with chronic heart failure, therapies are directed at
improving long-term outcomes by minimizing inflammatory and
fibrotic changes to the myocardium and systemic and pulmonary
vascular systems. Some patients might have progression of their
heart failure despite optimal medical therapy. New ventricularassist devices in development for pediatric patients offer another
therapeutic option with the hopes of decreasing wait-list mortality
for children who are awaiting heart transplantation. Heart
transplantation remains a viable option for patients with end-stage
heart failure, with improving survival outcomes in the most recent
decade. However, wait-list mortality due to limited donor organ
availability and long-term morbidity and mortality associated with
transplantation continue to be an issue.
References
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4. Jeffries, JL. Progress in Pediatric Cardiology 2007; 23: 61-66.
Novel medical therapies for pediatric heart failure.
5. Lipschultz, SE. Progress in Pediatric Cardiology 2000; 12:
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6. Gandhi, SK. Progress in Pediatric Cardiology 2009; 26:
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8. Swedberg K, et al. Circulation 1990; 82: 1730-6.
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