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

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

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

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

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.
Hebert 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

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

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

Disorders of energy production

Disorders of pyruvate metabolism

Disorders of oxidative phosphorylation
Combined respiratory chain deficiencies

Mitochondrial disorders
Mitochondrial DNA deletions and deficiencies
Barth syndrome
Sengers syndrome

Disorders of fatty acid metabolism

Carnitine deficiency (primary, systemic, muscle)
Etc.

Toxic intermediary metabolites

Proprionic acidemia
Methylmalonic acidemia
Malonic acidemia
Beta-ketothiolase deficiency
Mevalonic acidemia
Tyrosinemia

Genetics and Cardiomyopathy

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
patients 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

History
ECG
Echocardiography
Cardiac Catheterization

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

Depending on etiology and type of cardiomyopathy

Hypertrophic obstructive cardiomyopathy
Symptomatic

Hypertrophic cardiomyopathy (non-obstructive)

Calcium channel blockers

Asynchronous ventricular pacing
Surgical myectomy
Septal ablation
Antiarrhythmics
AICD
Transplantation

Beta blockers
AICD
Transplantation

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.