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276 L. Stern et al.
blockade and Interleukin-6 antagonism, may
allow for further CNI minimization in the
future that may mitigate renal dysfunction.
Standardized schedules for assessment of symptoms and laboratory findings guide diagnosis
and prompt treatment for complications postHTx. Additionally, close collaboration with
multidisciplinary teams, including the primary
care physician, is critical for the health of the
post-transplant patient.
References
1. Velleca A, Shullo MA, Dhital K, Azeka E, Colvin
M, DePasquale E, et al. The International Society
for Heart and Lung Transplantation (ISHLT) guidelines for the care of heart transplant recipients. J
Heart Lung Transplant. 2023;42(5):e1–141.
2. Youn J-C, Kim D, Kim KA, Kim J-J, Kim I-C, Lee
HS, et al. Characteristics and outcomes of heart
transplant recipients with a pretransplant history of
malignancy. Am J Transplant. 2022;22(12):2942–50.
3. Buell JF, Trofe J, Hanaway MJ, Lo A, Rosengard
B, Rilo H, et al. Transmission of donor cancer
into cardiothoracic transplant recipients. Surgery.
2001;130(4):660–6; discussion 6–8.
4. Engels EA, Pfeiffer RM, Fraumeni JF Jr, Kasiske
BL, Israni AK, Snyder JJ, et al. Spectrum of cancer risk among US solid organ transplant recipients.
JAMA. 2011;306(17):1891–901.
5. Youn J-C, Stehlik J, Wilk AR, Cherikh W, Kim I-C,
Park G-H, et al. Temporal trends of de novo malignancy development after heart transplantation. J Am
Coll Cardiol. 2018;71(1):40–9.
6. Maluccio M, Sharma V, Lagman M, Vyas S, Yang
H, Li B, et al. Tacrolimus enhances transforming
growth factor-beta1 expression and promotes tumor
progression. Transplantation. 2003;76(3):597–602.
7. Kim I-C, Kim SH, Youn J-C, Kim D, Lee S, Kim
H, et al. Temporal trends, risk factors, and clinical outcomes of de novo lymphoproliferative disorders after heart transplantation. Heart Failure.
2024;12(2):395–405.
8. Mucha K, Foroncewicz B, Ziarkiewicz-Wróblewska B,
Krawczyk M, Lerut J, Paczek L. Post-transplant lymphoproliferative disorder in view of the new WHO
classification: a more rational approach to a protean
disease? Nephrol Dial Transplant. 2010;25(7):2089–98.
9. Williams K, Mansh M, Chin-Hong P, Singer J,
Arron ST. Voriconazole-associated cutaneous malignancy: a literature review on photocarcinogenesis in organ transplant recipients. Clin Infect Dis.
2014;58(7):997–1002.
10. Gensler HL, Williams T, Huang AC, Jacobson EL.
Oral Niacin Prevents Photocarcinogenesis and
Photoimmunosuppression in Mice. Nutr Cancer.
1999;34(1):36–41.
11. Chen AC, Martin AJ, Choy B, FernándezPeñas P, Dalziell RA, McKenzie CA, et al. A
Phase 3 Randomized Trial of Nicotinamide for
Skin-Cancer Chemoprevention. N Engl J Med.
2015;373(17):1618–26.
12. Allen NC, Martin AJ, Snaidr VA, Eggins R, Chong
AH, Fernandéz-Peñas P, et al. Nicotinamide for
Skin-Cancer Chemoprevention in Transplant
Recipients. N Engl J Med. 2023;388(9):804–12.
13. Rivinius R, Helmschrott M, Ruhparwar A, Schmack
B, Klein B, Erbel C, et al. Analysis of malignancies
in patients after heart transplantation with subsequent immunosuppressive therapy. Drug Des Devel
Ther. 2015;9:93–102.
14. Barten MJ, Hirt SW, Garbade J, Bara C, Doesch
AO, Knosalla C, et al. Comparing everolimus-based
immunosuppression with reduction or withdrawal of
calcineurin inhibitor reduction from 6 months after
heart transplantation: The randomized MANDELA
study. Am J Transplant. 2019;19(11):3006–17.
15. Lund LH, Edwards LB, Kucheryavaya AY, Benden
C, Christie JD, Dipchand AI, et al. The registry
of the International Society for Heart and Lung
Transplantation: thirty-first official adult heart transplant report–2014; focus theme: retransplantation. J
Heart Lung Transplant. 2014;33(10):996–1008.
16. Hoorn EJ, Walsh SB, McCormick JA, Zietse R, Unwin
RJ, Ellison DH. Pathogenesis of calcineurin inhibitorinduced hypertension. J Nephrol. 2012;25(3):269–75.
17. Erinc K, Yamani MH, Starling RC, Crowe T, Hobbs
R, Bott-Silverman C, et al. The effect of combined
Angiotensin-converting enzyme inhibition and calcium antagonism on allograft coronary vasculopathy
validated by intravascular ultrasound. J Heart Lung
Transplant. 2005;24(8):1033–8.
18. Yabuno J, Patel J, Kittleson M, Luu M, Liou F,
Siddiqui S, et al. Abstract 13688: Patients With
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for Heart Transplantation. Circulation.
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19. Shane E, Mancini D, Aaronson K, Silverberg SJ,
Seibel MJ, Addesso V, et al. Bone mass, vitamin D
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20. Leidig-Bruckner G, Hosch S, Dodidou P, Ritschel
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liver transplantation: a follow-up study. Lancet.
2001;357(9253):342–7.
21. Shane E, Rivas M, Staron RB, Silverberg SJ, Seibel
MJ, Kuiper J, et al. Fracture after cardiac transplantation: a prospective longitudinal study. J Clin
Endocrinol Metab. 1996;81(5):1740–6.
22. Shane E, Addesso V, Namerow PB, McMahon DJ,
Lo SH, Staron RB, et al. Alendronate versus calcitriol for the prevention of bone loss after cardiac
transplantation. N Engl J Med. 2004;350(8):767–76.
Part V
Special Considerations
Pediatric Cardiomyopathies
Juan C. Alejos and Majid Husain
23
Abstract
Pediatric cardiomyopathies are a rare but
serious group of diseases. This chapter will
explore dilated, hypertrophic, and restrictive
cardiomyopathies with a focus on epidemiology, genetic factors, clinical features, diagnostic imaging modalities, and management
strategies. Additionally, oncological cardiomyopathies will be discussed.
Keywords
Dilated cardiomyopathy · Hypertrophic
cardiomyopathy · Restricted
cardiomyopathy · Oncologic
cardiomyopathies
Clinical Pearls
• Dilated cardiomyopathy (DCM) is the
most common cardiomyopathy in children and is also the most frequent indication for heart transplantation in children. An
J. C. Alejos (*) · M. Husain
UCLA Mattel Children’s Hospital, Los Angeles, CA,
USA
e-mail: jalejos@mednet.ucla.edu
M. Husain
e-mail: Majidhusain@mednet.ucla.edu
endomyocardial biopsy (EMB) can be important to determine the underlying pathologies
of DCM.
•
Outcome prediction in children with DCM
include age at presentation, clinical symptoms, ventricular size/mass, severity of dysfunction, the presence of arrhythmias, high
end-diastolic pressure, and endocardial
fibroelastosis.
• Hypertrophic cardiomyopathy (HCM) is
the second most common cardiomyopathy
seen in children and is often found to be the
underlying pathology in children and young
adults who suffer from sudden cardiac death.
Patient-centered shared decision-making for
an implantable cardioverter defibrillator for
the prevention of sudden cardiac death is
warranted.
Heart transplantation is not a first-line ther-
•
apy for HCM and is only considered when
there are ventricular arrhythmias refractory
to treatment or when features of DCM or
restrictive cardiomyopathy develop.
• Restrictive cardiomyopathy (RCM) is the
least common cardiomyopathy seen in children and carries a poor prognosis related to a
higher incidence of pulmonary hypertension,
thromboembolic events, and sudden death.
• Chemotherapy-induced cardiomyopathy
remains the most common cause of death
among pediatric cancer survivors for which
heart transplantation may be an option.
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2025
J. Kobashigawa (ed.), Clinical Guide to Heart Transplantation, https://doi.org/10.1007/978-3-031-88290-6_23
279
280 J. C. Alejos and M. Husain
Dilated Cardiomyopathy
Dilated cardiomyopathy (DCM) is the most
common cardiomyopathy in children, accounting for more than half of the total cases. The
overall incidence of DCM in the pediatric population is 0.57 per 100,000 per year, with boys
being slightly more susceptible than girls [1].
DCM is also one of the leading causes of heart
failure and the most frequent indication for heart
transplantation (HTx) in children. Notably, in
infants < 1 year of age, recipients with DCM
have nearly doubled from 21% in 1988–2003 to
38% in the modern era [2]. In recipients > 1 year
of age, DCM has remained the most common
diagnosis for transplantation for the past few
decades, accounting for 44–50% of pediatric HTx. Within the Pediatric Heart Transplant
Study Group (PHTSG), patients affected by
DCM represent 75% of the group of patients
with cardiomyopathy receiving a HTx [3]. DCM
is characterized by left ventricular or biventricular dilation with impaired systolic function in
the absence of any coronary artery pathology. It
can be congenital or acquired. Familial causes
were previously thought to be rare, but it is now
known that a majority of cases involve patients
with an underlying genetic abnormality [4]. The
causative genes encode proteins found in the
cytoskeleton, sarcomere, desmosomes, sarcoplasmic reticulum, nuclear envelope, nucleus,
ion channels, mitochondria, and the extracellular matrix. Novel candidate genes in various
other loci are being actively discovered. Viruses,
in particular, adenoviruses, Coxsackie A and B,
cytomegalovirus, and Epstein-Barr, are a significant etiology. Of note is that DCM is secondary
to anthracyclines, given that malignancy can be
a contraindication to transplantation. DCM can
also be related to neuromuscular diseases such
as dystrophinopathies (including Duchenne and
Becker muscular dystrophy), Friedreich’s ataxia,
and myotonic dystrophy. On rare occasions,
metabolic and endocrine conditions, as well as
infiltrative and autoimmune diseases, have been
implicated in the development of DCM.
It is important to differentiate DCM from
conditions with phenotypic overlap, including
but not limited to ischemic cardiomyopathy, advanced hypertrophic cardiomyopathy,
arrhythmogenic right ventricular cardiomyopathy (ARVC), noncompaction, and the welldefined Athlete’s heart.
In DCM, the dilated ventricle increases
the stress exerted on the chamber wall.
Consequently, there is contractile impairment,
functional mitral regurgitation, and arrhythmias
due to enlargement of the cardiac chambers.
Children may develop heart failure and present
with anorexia and weight loss. Clinical signs
include tachycardia, jugular venous distention,
hepatomegaly, and a systolic murmur consistent with mitral regurgitation. The echocardiogram findings, as mentioned above, include left
ventricular dilation with a decreased ejection
fraction and fractional shortening, mitral regurgitation, and/or pericardial effusion. The electrocardiograph (ECG) may show sinus tachycardia,
pathological Q waves, bundle-branch block,
heightened QRS complexes, atrial fibrillation,
or ventricular arrhythmias. Notably, the presence
of persistent tachycardia should raise suspicion
for tachycardia-induced cardiomyopathy, especially if there is recovery of ventricular function
with rhythm control over a period of time. Left
ventricular non-compaction (LVNC), a disease
of increased and prominent endomyocardial
trabeculations, can also present as DCM. The
biomarker brain natriuretic peptide (BNP) or
NT-proBNP can be useful when trying to distinguish lung disease from heart failure or for monitoring disease progression. An endomyocardial
biopsy (EMB) may be performed to determine
the etiology of DCM. This is especially necessary for identifying reversible underlying
pathologies or requiring different management
plans, such as sarcoidosis or glycogen storage
diseases. The biopsy sample can additionally
confirm or exclude viral myocarditis as the etiology by isolating viral genetic material via PCR
testing since serologies are generally unhelpful
because of high background seropositivity rates
in the population [4]. Several studies have suggested a greater than 50% chance of resolution
of myocarditis-related DCM within two years
of presentation, with fulminant myocarditis
28123 Pediatric Cardiomyopathies
having the highest likelihood of resolution [5].
Furthermore, cardiovascular magnetic resonance imaging (CMR) is increasingly becoming a widely used noninvasive modality for the
diagnosis and evaluation of DCM as well as
other cardiomyopathies. It can detect myocardial edema and late gadolinium enhancement
(LGE), a maker of fibrosis due to prior myocardial injury that may be present in ischemic cardiomyopathy, muscular dystrophy, or previous
myocarditis. Notably, CMR is the current gold
standard for comprehensive biventricular assessment. Lastly, predictors of outcome in children
with DCM are highly variable. The factors
described in the literature range from ventricular size, mass, and severity of dysfunction to
the presence of arrhythmias, high end-diastolic
pressure, and endocardial fibroelastosis. Age at
presentation and constellation of symptoms have
similarly been implicated. However, none of the
above predictors have been definitively shown
to have better or worse outcomes. Nonetheless,
for those with evidence of progressive or refractory heart failure, the use of ventricular assist
devices or extracorporeal membrane oxygenation remains an option as a bridge to recovery or
transplantation.
Hypertrophic Cardiomyopathy
Hypertrophic cardiomyopathy (HCM) is the
second most common cardiomyopathy seen
in children, accounting for 30–50% of cases
(6). The overall incidence of HCM in the pediatric Population is 0.24–0.47 per 100,000 per
year [7]. HCM is the most common form of
Mendelian inherited heart disease, and it is often
found to be the underlying pathology in children and young adults who suffer from sudden
cardiac death (SCD) [8]. Several gene mutations
have been described, with most encoding for
proteins found in the sarcomere. Unlike DCM
and restrictive cardiomyopathy, no acquired
forms of this disease have been found. Despite
its incidence, HCM less often leads to transplantation, with only 5% of patients carrying
the diagnosis pre-operatively [3, 6]. Pediatric
HCM comprises a heterogeneous group of diseases with variable genotypes and phenotypic
expression. As stated above, genetic mutations in the sarcomeric proteins lead to primary
HCM. Pathogenic genes include MYH7, MYL2,
MYL3, MYBPC3, TNNT2, TNNI3, TPM1,
ACTC1, ACTN2, CSRP3 and PLN [9]. Like
DCM, novel candidate genes are being actively
discovered. Unlike DCM, the molecular mechanisms that lead to the variable HCM phenotype
remain uncertain. Causes of secondary HCM
include disease of glycogen storage (Pompe,
Danon, Cori, or Forbes disease), lysosomal
storage disorders (Mucopolysaccharidoses,
Anderson-Fabry disease), syndromic pathology (Noonan, Costello, or Beckwith-Widemann
syndrome), fatty acid oxidation disorders, mitochondrial diseases (Friedreich ataxia) and various endocrine disorders [10, 11]. There is also a
coexistence of HCM with congenital heart disease, specifically in patients with Noonan syndrome who have valvular pulmonary stenosis.
By echocardiography, HCM is character-
ized by the presence of a hypertrophied and
nondilated left ventricle in the absence of a
hemodynamically significant physiologic or
pathologic etiology. The hypertrophy is asymmetric and predominantly isolated to the interventricular septum. Primary diagnostic criteria
for pediatric HCM require adjusting the maximum diastolic septal thickness for body surface area. According to the American College
of Cardiology/American Heart Association
guidelines on pediatric HCM published in
2020, a Z-score > 2.5 for the maximal enddiastolic wall thickness has been suggested
to identify early HCM in asymptomatic children with no significant family history, and a
Z-score of > 2 may be sufficient for a diagnosis
of HCM in children with a positive family history or a positive genetic test [12]. Ventricular
function is generally normal, although early
diastolic dysfunction has been reported. There
may be associated structural anomalies, including mitral valve abnormalities, myocardial
crypts, or the presence of noncompaction.
Electrocardiographically, there is LVH by welldefined voltage criteria, abnormal Q-waves, and
282 J. C. Alejos and M. Husain
repolarization abnormalities in patients with
pathogenic genetic mutations. Consequently,
children with HCM are prone to life-threatening
malignant arrhythmias requiring screening, surveillance, and appropriate risk stratification with
patient-centered shared decision-making for an
implantable cardioverter defibrillator (ICD) for
the prevention of SCD. On a microscopic level,
cardiac myocytes are in disarray. Functionally,
the collective anatomical changes may result
in left ventricular outflow obstruction, termed
hypertrophic obstructive cardiomyopathy
(HOCM).
Like the diverse genetic origins of HCM,
its clinical presentation is also highly variable. Most patients are asymptomatic, with
some experiencing chest pain and dyspnea.
Palpitations and pre-syncopal episodes can
occur. Syncope is rare but is a prominent risk
factor for SCD. Children under the age of 1
often present with congestive heart failure.
HCM is infamous for its insidiousness and its
tendency to present with SCD in young athletes.
Therefore, it is imperative to screen and survey
this population closely using electrocardiography, echocardiography, and CMR. Additionally,
Holter monitoring is useful for identifying
occult and pathologic arrhythmias, which carry
an increased risk of SCD. Given the autosomal
dominance of HCM, screening of parents, siblings, and 1st-degree relatives is advisable.
Treatment depends on the severity of symptoms and the presence of risk factors for SCD.
Patients with chest pain and dyspnea are treated
medically with beta-blockers and calcium channel antagonists. The detection of ventricular
arrhythmias warrants the placement of an ICD.
Patients with severe left ventricular outflow
obstruction may undergo septal myectomy,
although this is only for symptom relief and
does not slow disease progression, nor does it
prevent potentially fatal arrhythmias.
HTx is not a first-line therapy for HCM and
is only considered when there are ventricular
arrhythmias refractory to treatment or when
features of DCM or restrictive cardiomyopathy
develop. Risk factors for death or transplantation
include age < 1 year, low presenting shortening
fraction, and increased LV posterior wall thickness [6]. The 5-year survival rate for children
with HCM ranges from 42% in children with an
Associated inborn error of metabolism (IEM)
to 94% in children with noninfantile idiopathic
disease presenting after one year of age; the
overall survival at 9 years across various other
disease processes, including infantile presentation < 1 year of age, but excluding IEM is
approximately 80% [7].
Recently, the EXPLORER-HCM [13] clinical
trial showed that Mavacamten, a cardiac myosin
inhibitor, was superior to placebo in improving the functional status and health status of
patients with HOCM. Specifically, it was associated with a significant reduction in post-exercise
left ventricular outflow tract gradient compared
with placebo at 30 weeks, which was sustained
to 48 weeks. CMR found that Mavacamten was
also associated with favorable remodeling compared with placebo. Additionally, Mavacamten
improved various measures of cardiopulmonary exercise testing, including peak VE/VCO2,
METs, and peak circulatory power. Lastly, it
was shown to be well tolerated with no significant long-term adverse events. The increasing
use of pharmacologic therapy to treat HCM
may slow the progression of the disease and further delay or potentially eliminate the need for
transplantation.
Restrictive Cardiomyopathy
Restrictive cardiomyopathy (RCM) is the least
common cardiomyopathy seen in children and
represents only 3% of pediatric cases [14].
The overall incidence of RCM in the pediatric
population is unclear. Compared to other cardiomyopathies, pediatric RCM carries a poor
prognosis related to a higher incidence of pulmonary hypertension, thromboembolic events,
and sudden death. Despite being the rarest cardiomyopathy in children, sudden death occurs in
approximately 25% of pediatric RCM patients,
with an annual mortality of 7%. Medical and
surgical treatment options are limited and not
well supported by clinical studies in this patient
28323 Pediatric Cardiomyopathies
population. Freedom from death was 68% at
5 years, with a transplant-free survival of 22%
[15]. Due to these high mortality rates, transplantation is often the only therapeutic option.
Not surprisingly, despite being the least common cardiomyopathy, patients affected by RCM
represent 12% of transplant recipients within
PHTSG [3].
Pediatric RCM is characterized by diastolic
dysfunction due to restrictive filling with a normal ventricle wall thickness, chamber size, and
ejection fraction. Like DCM and HCM, it represents a heterogeneous group of diseases with
variable genotypes and phenotypic expression. The etiology of RCM includes inherited
and acquired causes. Inherited causes involve
defects in sarcomeric, cytoskeleton, and nuclear
envelope genes. Among the aforementioned,
mutations in the sarcomeric genes, including MYBPC3, MYH7, TTN, TNNI3, TNNT2,
and ACTC, are the most commonly identified
[16]. Other inherited etiologies include storage
diseases (namely, Anderson Fabry and Danon
disease), as well as infiltrative processes, such
as cardiac amyloidosis and sarcoidosis. Iron
overload cardiomyopathies related to betathalassemia, sickle-cell anemia, and hereditary
hemochromatosis have also been implicated
in the familial causes of RCM. Acquired RCM
includes chemotherapy or radiotherapy-related
cardiomyopathies.
Clinically, RCM often lacks symptoms early
on and can present with decreased exercise tolerance, exertional chest pain, and syncope.
Children with RCM may report a history of frequent respiratory infections. It can also present
with acute right and/or left heart failure with
pulmonary hypertension. Physical exam findings include jugular venous distension (possibly
with Kussmaul sign), hepatomegaly, a prominent S
heart sound, a gallop rhythm, periph-
2
eral edema, and ascites in the setting of heart
failure. Echocardiography shows markedly
dilated atria with normal-sized ventricles and
generally preserved ejection fraction. There are
abnormal mitral inflow and tissue Doppler variables consistent with diastolic dysfunction. With
disease progression, the estimated pulmonary
artery pressure will be elevated. Notably, echocardiography is helpful in distinguishing RCM
from constrictive pericarditis, which can present in a similar manner but carries a different
outcome and is treated differently. The electrocardiogram is abnormal and most commonly
shows right and/or left atrial enlargement. ST-T
segments are elevated and notched, or biphasic
T-waves are frequently present. ST-T segment
depressions, prolonged PR, and wide QRS complex have also been reported and implicated as
risk factors for SCD in this patient population
[17, 18]. Holter evaluation is useful for detecting atrial or ventricular arrhythmias, WPW with
SVT, or AV block. Cardiac catheterization is
useful for confirming elevated pulmonary pressures seen on the echocardiogram, determining
the severity of pulmonary vascular resistance,
testing pulmonary vascular reactivity, and evaluating cardiac index. Hemodynamic assessment
can further help distinguish restrictive and constrictive physiology beyond echocardiographic
assessment. An endomyocardial biopsy (EMB)
is only done to exclude etiologies such as amyloidosis or sarcoidosis, which more commonly
cause RCM in adults. Lastly, CMR can be used
to obtain detailed structural, functional, and tissue characteristics of the myocardium to aid in
clarifying the etiology of RCM. Once the diagnosis is established, first-degree relatives should
be screened.
Pharmacological treatments for RCM are
principally for palliative symptom relief.
Diuretics are used to reduce venous congestion.
Caution should be exercised, however, to ensure
cardiac output is not compromised. Angiotensinconverting enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARBs) may be used
if there is associated systemic hypertension.
Although beta-blockers and calcium channel blockers may theoretically provide relief
to patients by prolonging the diastolic interval,
allowing for better filling, these medications are
generally not recommended in pediatric RCM
since cardiac output is dependent on heart rate
due to the compromised stroke volume in the
setting of significant diastolic dysfunction.
Similarly, digoxin, intravenous inotropes, and
284 J. C. Alejos and M. Husain
pulmonary vasodilators are not recommended
unless they are being used to treat secondary
complications of the disease. Given the risk of
atrial fibrillation and the presence of abnormal
hemodynamics, anticoagulants are sometimes
used prophylactically to prevent the formation
and embolization of mural thrombi. Due to the
lack of studies and consensus on the efficacy
and use of antiplatelet agents versus vitamin K
antagonists versus low molecular weight heparin
[19], the type and choice of antithrombotic or
anticoagulation therapy varies by institution and
professional experience.
Given that RCM is refractory to other therapies, patients are more likely to be considered for
transplantation. In the United States, many centers advocate immediate listing for transplantation
because of the rapid development of pulmonary
hypertension, the high risk of thromboembolism,
and a mean survival of approximately 2 years
[20]. The use of mechanical circulatory support
as a bridge to transplantation remains an option
since many children with RCM would otherwise
die on the waitlist due to the progression of their
heart failure, resulting in multi-organ failure.
Oncological Cardiomyopathy
at the lowest doses. There can be a delay of up
to 20 years after the completion of chemotherapy before cardiomyopathy becomes clinically
apparent [24]. Radiotherapy can similarly result
in radiation-induced restrictive cardiomyopathy as a result of biventricular fibrosis reducing
myocardial compliance. An initial echocardiogram should be obtained prior to initiation of
chemotherapy to delineate structural anatomy
and establish baseline ventricular function.
Follow-up studies should be performed routinely
post-therapy to monitor ventricular function and
survey for early signs, development, and progression of cardiomyopathy. A baseline ECG
should also be obtained. ECG changes related
to anthracycline therapy are non-specific and
include sinus tachycardia, a flattened T wave, or
a prolonged QT interval. Treatment options for
this drug-induced cardiomyopathy are limited. It
is refractory to usual regimens. Symptom relief
can be provided by pharmacologic therapies
highlighted in the RCM subsection, but there
is no improvement in mortality. HTx remains
the only therapeutic option if the malignancy
is well-controlled or in remission. The decision
to evaluate for transplant candidacy is made in
concert with the patient’s oncology team.
Despite progress in cancer therapeutics over
the past few decades in improving survival
across most childhood malignancies, cardiacrelated disease remains the most common nononcologic cause of death among survivors [21].
Anthracycline chemotherapy agents such as
doxorubicin, daunorubicin, and epirubicin,
which are typically used for hematologic cancers and solid tumors, are cardiotoxic. One of
the most detrimental side- effects of this class of
drugs is the development of drug-induced cardiomyopathy, specifically DCM, with a restrictive physiology. The mechanism of action is
thought to be free radical-induced oxidative
damage to cardiac myocytes [22]. There is a
dose-dependent relationship between the cumulative anthracycline dose and cardiotoxicity. At
very high doses, cardiomyopathy develops in
36% of patients [23]. This number is negligible
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Pediatric Heart Transplantation
Juan C. Alejos and Majid Husain
24
Abstract
Pediatric heart transplantation (HTx) is the
ultimate option in the treatment of end-stage
heart disease refractory to maximum medical therapy or surgical management. This
chapter comprehensively overviews pediatric
HTx indications, pre-transplant evaluation,
donor selection, waitlist management, posttransplant management and surveillance, and
long-term complications. In addition, the survival and outcomes of pediatric HTx were
discussed.
Keywords
Pediatric heart
transplantation · Infants · ABO-incompatible
heart transplantation · Congenital heart
disease
Clinical Pearls
• Waitlist mortality in children is higher than in
the adult population for heart transplantation
due to donor shortages and the limited availability of VADs.
• Children can be transplanted safely with a
pre-operative pulmonary vascular resistance
index of up to 9 Woods units/m2
• Contrary to the adult population, ABO-
incompatible heart transplantation is possible
in infants and younger children with comparable outcomes.
• Pediatric patients with congenital heart dis-
ease and with palliative procedures have led
to a higher risk of pre-transplant sensitization.
• Steroid-avoidance immunosuppressive regi-
mens show good outcomes in children who
are not sensitized.
Children of minority race or ethnicity have
•
been shown to have worse outcomes.
• Post-transplant survival in the pediatric popu-
lation continues to improve with enhanced
immunosuppression regimens, and advancement in invasive and non-invasive techniques
for monitoring rejection
J. C. Alejos (*) · M. Husain
UCLA Mattel Children’s Hospital, Los Angeles,
CA, USA
e-mail: jalejos@mednet.ucla.edu
M. Husain
e-mail: Majidhusain@mednet.ucla.edu
© The Author(s), under exclusive license to Springer Nature Switzerland AG 2025
J. Kobashigawa (ed.), Clinical Guide to Heart Transplantation, https://doi.org/10.1007/978-3-031-88290-6_24
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