Cardiomyopathy in Children And
Adolescents: What Begins in
Childhood…
James W. Wiggins, Jr. MD FAAP, FACC
St. Vincent Healthcare Pediatric Cardiology, Billings, MT
Clinical Professor of Pediatrics
University of Colorado School of Medicine
Cardiomyopathy in Children and
Adolescents
 Goals
– Incidence of cardiomyopathy in children
– Understand with wide spectrum of etiologies of
cardiomyopathy in children and adolescents
– Diagnostic modalities
– Genetics of cardiomyopathy and impact on the
family
– Current management of myocardial diseases
Incidence of cardiomyopathy in
children
 Incidence 1.13-1.24/100,000
 40% of children ultimately die of their disease (unaltered
over decades)
 Highest incidence is in the first year of life, (greater than 8
to 12 times that at any other time in life)
 Second peak occurs in adolescence
 Higher incidences in Black and Hispanic children. (Greater
in indigenous versus non-indigenous Australian
populations)
 Incidence greater in males than females secondary to
muscular dystrophies.
 9 to 20 percent of cardiomyopathies are familial
 4% presenting symptom was sudden death
Classification of Cardiomyopathy
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Dilated Cardiomyopathy
Hypertrophic Cardiomyopathy
Restrictive Cardiomyopathy
Right Ventricular Cardiomyopathy
Non-compaction of the Ventricular Myocardium
Some forms may change from one type to another
with time (i.e., hypertrophic to dilated)
Dilated Cardiomyopathy
 Etiologies
– Infective myocarditis
– Endocardial fibroelastosis
– Dystrophinopathies
– X-linked dilated cardiomyopathy
– Doxorubicin cardiomyopathy
– HIV associated cardiac disease
– Iron overload cardiomyopathy
– Thalassemia
– Inborn errors of metabolism
Hypertrophic Cardiomyopathy
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Familial
Sarcomeric
Maternally inherited
Beckwith-Wiedemann syndrome
Cranio-facial-cutaneous syndrome
Costello syndrome
Friedreich's ataxia
Lentiginosis (LEOPARD syndrome)
Noonan syndrome
Hypertrophic Cardiomyopathy
Secondary forms
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Anabolic steroid therapy and abuse
Infant of a diabetic mother
Pre and postnatal steroid therapy
Metabolic disorders
Carnatine deficiency
Fucosidosis type 1
Glycogenoses (types 2, 3 and 9: Pompe disease, Forbes disease, phosphoylase kinase
deficiency)
Glycolipid lipidosis (Fabry disease)
Glycosylation disorders
I-cell disease
Lipodystrophy, total
Lysosomal disorders
Mannosidosis
Mitchondrial disorders (multiple forms)
Mucopolysaccharidoses (types 1, 2 and 5; Hurler syndrome, Hunter Syndrome, Scheie
syndrome)
Selenium deficiency
Restrictive cardiomyopathy
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Primary restrictive cardiomyopathy
Endocardial fibrosis
Hypereosinophilic syndrome
Familial
Idiopathic
Interstitial
Amyloidosis
Anthracycline cardiomyopathy
Radiation toxicity
Scleroderma
Storage diseases
Fabry disease
Gaucher disease
Glycogenosis
Hemochromatosis
Hurler disease
Noninfiltrative
Carcinoid heart disease
Noncompaction of the myocardium
Pseudoxanthoma elasticum
Right Ventricular Cardiomyopathies
 Uhl anomaly
 Arrhythmogenic right ventricular dysplasia
Uhl Anomaly
Figure 1. Noninvasive investigations. A, ECG
showing type I atrioventricular block and complete
right bundle-branch block. B, Echocardiography
(4-chamber apical view) showing leftward
curveted IVS with normal systolic
thickening. Its right side is nontrabeculated, in
contrast to the trabeculated LV apex. Segmental
and global LV systolic functions were preserved.
C, Biventricular radionuclide angiography
at equilibrium in a left anterior oblique
projection (3-dimensional apical view). Note the
bean-like shape of the LV with otherwise normal
kinetics. ED indicates end diastole; ES, end
systole.
He´bert et al Fortuitous Discovery of Partial Uhl Anomaly e427
Downloaded from Circulation
Imaging ARVD
Figure. A, ECG with typical signs for ARVC; negative T waves and Epsilon waves in the precordial leads (arrow). B, Chest x-ray after
ICD implantation. Both the atrial and ventricular leads are visible. C through E, Signal attenuation in RV septum on MDCT (C), increased
signal intensity on delayed enhancement images (D), and decreased signal intensity on steady-state free precession images (E).
Noncompaction of the ventricular
myocardium
 Seen both with and without associated
congenital heart defects.
 Also described in conjunction with
– Fabry disease
– Barth syndrome
– Neuromuscular disorders
– Mitochondrial disorders
– Trisomy 13
Non-compaction of the left ventricular myocardium
Non-genetic causes of
cardiomyopathy
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Atherosclerotic heart disease
Kawasaki disease
Hypertension
Dysrhythmia
Congenital heart defects
Chronic alteration of circulatory volume
Major cardiac surgery
Obesity
Pulmonary parenchyma; or vascular disease
Toxin or drug
Radiation
Connective tissue diseases
Endocrine disease
Nutritional deficiency
Granulomatous disease
Malignancy
Diagnosis
 History
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Family history of cardiomyopathy
Presentation with congestive heart failure
Sudden cardiac arrest
Syncope with exercise
Neuromuscular disease
Congenital malformations
Metabolic disorder
 Hypoglycemia, metabolic acidosis, hyperammonemia
 Hypotonia
 Mucopolysaccharidosis
Inborn Errors of Metabolism
Infiltrative (storage disease)
Disorders of glycogen metabolism
Disorders of mucopolysaccharide degradation
 Disorders of glycosphingolipid degradation
 Disorders of glycoceramide degradation
 Disorders of phytanic acid oxidation
 Combined degradations disorders
 Disorders of glycoprotein metabolism
 Disorder of oxalic acid metabolism
Inborn errors of metabolism
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Disorders of energy production
– Disorders of pyruvate metabolism
– Disorders of oxidative phosphorylation
– Combined respiratory chain deficiencies
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Mitochondrial disorders
Mitochondrial DNA deletions and deficiencies
Barth syndrome
Sengers syndrome
– Disorders of fatty acid metabolism
 Carnitine deficiency (primary, systemic, muscle)
 Etc.
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Toxic intermediary metabolites
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Proprionic acidemia
Methylmalonic acidemia
Malonic acidemia
Beta-ketothiolase deficiency
Mevalonic acidemia
Tyrosinemia
Genetics and Cardiomyopathy
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Malformation Syndromes
Neuromuscular disorders
Isolated Cardiomyopathy
Autosomal Dominant inheritance
X-linked inheritance
Autosomal recessive inheritance
Maternal mitochondrial inheritance
Case Report
 16 year old male has sudden cardiac arrest while playing soccer.
Resuscitation results in return of circulation but sustains neurologic
sequelae. Diagnosis ARVD, receives AICD.
 Echocardiography of immediate family members detects ARVD in the
patient’s father and one brother. Younger brother with ARVD, refuses
AICD later arrests while playing soccer with friends. Resuscitation
successfully, gets AICD.
 Family history of uncle with AICD for Arrhythmia 4 years previously. No
attempts made at family history or screening.
 Genetic testing becomes available 2 years ago and 2 younger siblings
with negative echoes screened. One positive with no evidence of
cardiomyopathy at this time.
Genetics and Cardiomyopathy
 Many cardiomyopathies have well known patterns
of inheritance and now have genetic testing
available to identify family members both with and
without risk of potentially life threatening disease.
 Adults presenting with cardiomyopathy for the first
time should have detailed family history and
possible genetic testing.
 In the absence of genetic testing other family
members should be screened.
Case Report
 Follow a 9 year-old female patient since fetal life
diagnosed with dextrocardia, fetal hydrops VSD,
coarctation of the aorta, left ventricular
diverticulum (resolves by birth). Has had VSD,
coarctation repair complicated by complete heart
block.
 Mother diagnosed with hypertrophic
cardiomyopathy 1 year ago.
 Screened brother: asymptomatic hypertrophic
cardiomyopathy.
Premortem Evaluation
 Diagnosis in a moribund patient obtain studies to
determine etiology and/or genetic or metabolic
cause of the disease.
 Includes:
 Blood
– Blood-Glucose, electrolytes, bicarbonate, ABG, BUN,
Creatinine, Lactate and pyruvate, CBC with WBC,
Creatine kinase, Cholesterol and Triglycerides, Alkaline
aminotransferase, aspartate aminotransferase, bilirubin,
PT/PTT, albumin, uric acid
Diagnostic Studies
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History
ECG
Echocardiography
Cardiac Catheterization
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Hemodynamics
Coronary angiography
Endomyocardial biopsy
Skeletal muscle biopsy
 Metabolic studies
 Genetic testing
Premortem Laboratory
 Urine (or vitreous)
– Urinalysis, organic acids, quantitative amino
acids, acylglycines, mucopolysaccarides and
oligosaccarides by thin layer chromatography
 Additional studies
– ECG, Chest X-ray, Echocardiography
– Ophthalmologic exam
– Skeletal x-ray survey
– Photographs
Additional Studies
 Tissue
– Heart
– Skeletal muscle
– Liver
– Kidney Brain
– Skin
(Flash frozen before or soon after death)
Medical Management
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Depending on etiology and type of cardiomyopathy
Hypertrophic obstructive cardiomyopathy
– Symptomatic
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Calcium channel blockers
Asynchronous ventricular pacing
Surgical myectomy
Septal ablation
Antiarrhythmics
AICD
Transplantation
Hypertrophic cardiomyopathy (non-obstructive)
– Beta blockers
– AICD
– Transplantation
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Metabolic myopathy
– Depends on etiology and any available treatment
– L-Carnitine for carnitine deficiency
Conclusion
 The diagnosis of cardiomyopathy in childhood involves an
extensive evaluation for possible etiology.
 Familial disease is common and even asymptomatic family
members should be screened.
 Genetic evaluation should be pursued where there is the
possibility of inheritable disease and availability of genetic
testing.
 Consider metabolic disease in the infant with
cardiomyopathy.
 With better understanding of the molecular causes of
cardiomyopathy, future medical management may allow for
greater longevity and quality of life in this population.