Cardiomyopathy in Children And Cardiomyopathy in Children And Adolescents: What Begins in Adolescents: What Begins in

Childhood…Childhood…

James W. Wiggins, Jr. MD FAAP, FACCJames W. Wiggins, Jr. MD FAAP, FACCSt. Vincent Healthcare Pediatric Cardiology, Billings, MTSt. Vincent Healthcare Pediatric Cardiology, Billings, MT

Clinical Professor of PediatricsClinical Professor of PediatricsUniversity of Colorado School of MedicineUniversity of Colorado School of Medicine

Cardiomyopathy in Children and Cardiomyopathy in Children and AdolescentsAdolescents

GoalsGoals– Incidence of cardiomyopathy in childrenIncidence of cardiomyopathy in children– Understand with wide spectrum of etiologies of Understand with wide spectrum of etiologies of

cardiomyopathy in children and adolescentscardiomyopathy in children and adolescents– Diagnostic modalitiesDiagnostic modalities– Genetics of cardiomyopathy and impact on the Genetics of cardiomyopathy and impact on the

familyfamily– Current management of myocardial diseasesCurrent management of myocardial diseases

Incidence of cardiomyopathy in Incidence of cardiomyopathy in childrenchildren

Incidence 1.13-1.24/100,000Incidence 1.13-1.24/100,000 40% of children ultimately die of their disease (unaltered 40% of children ultimately die of their disease (unaltered

over decades)over decades) Highest incidence is in the first year of life, (greater than 8 Highest incidence is in the first year of life, (greater than 8

to 12 times that at any other time in life)to 12 times that at any other time in life) Second peak occurs in adolescenceSecond peak occurs in adolescence Higher incidences in Black and Hispanic children. (Greater Higher incidences in Black and Hispanic children. (Greater

in indigenous versus non-indigenous Australian in indigenous versus non-indigenous Australian populations)populations)

Incidence greater in males than females secondary to Incidence greater in males than females secondary to muscular dystrophies.muscular dystrophies.

9 to 20 percent of cardiomyopathies are familial9 to 20 percent of cardiomyopathies are familial 4% presenting symptom was sudden death4% presenting symptom was sudden death

Classification of CardiomyopathyClassification of Cardiomyopathy

Dilated CardiomyopathyDilated Cardiomyopathy Hypertrophic CardiomyopathyHypertrophic Cardiomyopathy Restrictive CardiomyopathyRestrictive Cardiomyopathy Right Ventricular CardiomyopathyRight Ventricular Cardiomyopathy Non-compaction of the Ventricular MyocardiumNon-compaction of the Ventricular Myocardium Some forms may change from one type to another Some forms may change from one type to another

with time (i.e., hypertrophic to dilated)with time (i.e., hypertrophic to dilated)

Dilated CardiomyopathyDilated Cardiomyopathy EtiologiesEtiologies

– Infective myocarditisInfective myocarditis– Endocardial fibroelastosisEndocardial fibroelastosis– DystrophinopathiesDystrophinopathies– X-linked dilated cardiomyopathyX-linked dilated cardiomyopathy– Doxorubicin cardiomyopathyDoxorubicin cardiomyopathy– HIV associated cardiac diseaseHIV associated cardiac disease– Iron overload cardiomyopathyIron overload cardiomyopathy– ThalassemiaThalassemia– Inborn errors of metabolismInborn errors of metabolism

Hypertrophic CardiomyopathyHypertrophic Cardiomyopathy Familial Familial Sarcomeric Sarcomeric Maternally inheritedMaternally inherited Beckwith-Wiedemann syndromeBeckwith-Wiedemann syndrome Cranio-facial-cutaneous syndromeCranio-facial-cutaneous syndrome Costello syndromeCostello syndrome Friedreich's ataxiaFriedreich's ataxia Lentiginosis (LEOPARD syndrome)Lentiginosis (LEOPARD syndrome) Noonan syndromeNoonan syndrome

Hypertrophic CardiomyopathyHypertrophic CardiomyopathySecondary formsSecondary forms

Anabolic steroid therapy and abuseAnabolic steroid therapy and abuse Infant of a diabetic motherInfant of a diabetic mother Pre and postnatal steroid therapyPre and postnatal steroid therapy Metabolic disordersMetabolic disorders Carnatine deficiencyCarnatine deficiency Fucosidosis type 1Fucosidosis type 1 Glycogenoses (types 2, 3 and 9: Pompe disease, Forbes disease, phosphoylase kinase Glycogenoses (types 2, 3 and 9: Pompe disease, Forbes disease, phosphoylase kinase

deficiency)deficiency) Glycolipid lipidosis (Fabry disease)Glycolipid lipidosis (Fabry disease) Glycosylation disordersGlycosylation disorders I-cell diseaseI-cell disease Lipodystrophy, totalLipodystrophy, total Lysosomal disordersLysosomal disorders MannosidosisMannosidosis Mitchondrial disorders (multiple forms)Mitchondrial disorders (multiple forms) Mucopolysaccharidoses (types 1, 2 and 5; Hurler syndrome, Hunter Syndrome, Scheie Mucopolysaccharidoses (types 1, 2 and 5; Hurler syndrome, Hunter Syndrome, Scheie

syndrome)syndrome) Selenium deficiencySelenium deficiency

Restrictive cardiomyopathyRestrictive cardiomyopathy Primary restrictive cardiomyopathyPrimary restrictive cardiomyopathy Endocardial fibrosisEndocardial fibrosis Hypereosinophilic syndromeHypereosinophilic syndrome FamilialFamilial IdiopathicIdiopathic InterstitialInterstitial AmyloidosisAmyloidosis Anthracycline cardiomyopathyAnthracycline cardiomyopathy Radiation toxicityRadiation toxicity SclerodermaScleroderma Storage diseasesStorage diseases Fabry diseaseFabry disease Gaucher diseaseGaucher disease GlycogenosisGlycogenosis HemochromatosisHemochromatosis Hurler diseaseHurler disease NoninfiltrativeNoninfiltrative Carcinoid heart diseaseCarcinoid heart disease Noncompaction of the myocardiumNoncompaction of the myocardium Pseudoxanthoma elasticumPseudoxanthoma elasticum

Right Ventricular CardiomyopathiesRight Ventricular Cardiomyopathies

Uhl anomalyUhl anomaly Arrhythmogenic right ventricular dysplasiaArrhythmogenic right ventricular dysplasia

Uhl AnomalyUhl Anomaly

Figure 1. Noninvasive investigations. A, ECGshowing type I atrioventricular block and completeright bundle-branch block. B, Echocardiography(4-chamber apical view) showing leftwardcurveted IVS with normal systolicthickening. Its right side is nontrabeculated, incontrast to the trabeculated LV apex. Segmentaland global LV systolic functions were preserved.C, Biventricular radionuclide angiographyat equilibrium in a left anterior obliqueprojection (3-dimensional apical view). Note thebean-like shape of the LV with otherwise normalkinetics. ED indicates end diastole; ES, endsystole.He´bert et al Fortuitous Discovery of Partial Uhl Anomaly e427Downloaded from Circulation

Imaging ARVDImaging ARVD

Figure. A, ECG with typical signs for ARVC; negative T waves and Epsilon waves in the precordial leads (arrow). B, Chest x-ray afterICD implantation. Both the atrial and ventricular leads are visible. C through E, Signal attenuation in RV septum on MDCT (C), increasedsignal intensity on delayed enhancement images (D), and decreased signal intensity on steady-state free precession images (E).

Noncompaction of the ventricular Noncompaction of the ventricular myocardiummyocardium

Seen both with and without associated Seen both with and without associated congenital heart defects.congenital heart defects.

Also described in conjunction withAlso described in conjunction with– Fabry disease Fabry disease – Barth syndromeBarth syndrome– Neuromuscular disordersNeuromuscular disorders– Mitochondrial disordersMitochondrial disorders– Trisomy 13Trisomy 13

Non-compaction of the left ventricular myocardiumNon-compaction of the left ventricular myocardium

Non-genetic causes of Non-genetic causes of cardiomyopathycardiomyopathy

Atherosclerotic heart diseaseAtherosclerotic heart disease Kawasaki diseaseKawasaki disease HypertensionHypertension DysrhythmiaDysrhythmia Congenital heart defectsCongenital heart defects Chronic alteration of circulatory volumeChronic alteration of circulatory volume Major cardiac surgeryMajor cardiac surgery ObesityObesity Pulmonary parenchyma; or vascular diseasePulmonary parenchyma; or vascular disease Toxin or drugToxin or drug RadiationRadiation Connective tissue diseasesConnective tissue diseases Endocrine diseaseEndocrine disease Nutritional deficiencyNutritional deficiency Granulomatous diseaseGranulomatous disease MalignancyMalignancy

DiagnosisDiagnosis HistoryHistory

– Family history of cardiomyopathyFamily history of cardiomyopathy– Presentation with congestive heart failurePresentation with congestive heart failure– Sudden cardiac arrestSudden cardiac arrest– Syncope with exerciseSyncope with exercise– Neuromuscular diseaseNeuromuscular disease– Congenital malformationsCongenital malformations– Metabolic disorderMetabolic disorder

Hypoglycemia, metabolic acidosis, hyperammonemiaHypoglycemia, metabolic acidosis, hyperammonemia HypotoniaHypotonia MucopolysaccharidosisMucopolysaccharidosis

Inborn Errors of MetabolismInborn Errors of Metabolism

Infiltrative (storage disease)Infiltrative (storage disease)Disorders of glycogen metabolismDisorders of glycogen metabolismDisorders of mucopolysaccharide degradationDisorders of mucopolysaccharide degradation

Disorders of glycosphingolipid degradationDisorders of glycosphingolipid degradation Disorders of glycoceramide degradationDisorders of glycoceramide degradation Disorders of phytanic acid oxidationDisorders of phytanic acid oxidation Combined degradations disordersCombined degradations disorders Disorders of glycoprotein metabolismDisorders of glycoprotein metabolism Disorder of oxalic acid metabolismDisorder of oxalic acid metabolism

Inborn errors of metabolismInborn errors of metabolism Disorders of energy productionDisorders of energy production

– Disorders of pyruvate metabolismDisorders of pyruvate metabolism– Disorders of oxidative phosphorylationDisorders of oxidative phosphorylation– Combined respiratory chain deficienciesCombined respiratory chain deficiencies

Mitochondrial disordersMitochondrial disorders Mitochondrial DNA deletions and deficienciesMitochondrial DNA deletions and deficiencies Barth syndromeBarth syndrome Sengers syndromeSengers syndrome

– Disorders of fatty acid metabolismDisorders of fatty acid metabolism Carnitine deficiency (primary, systemic, muscle)Carnitine deficiency (primary, systemic, muscle) Etc.Etc.

Toxic intermediary metabolitesToxic intermediary metabolites– Proprionic acidemiaProprionic acidemia– Methylmalonic acidemiaMethylmalonic acidemia– Malonic acidemiaMalonic acidemia– Beta-ketothiolase deficiencyBeta-ketothiolase deficiency– Mevalonic acidemiaMevalonic acidemia– TyrosinemiaTyrosinemia

Genetics and CardiomyopathyGenetics and Cardiomyopathy

Malformation SyndromesMalformation Syndromes Neuromuscular disordersNeuromuscular disorders Isolated CardiomyopathyIsolated Cardiomyopathy Autosomal Dominant inheritanceAutosomal Dominant inheritance X-linked inheritanceX-linked inheritance Autosomal recessive inheritanceAutosomal recessive inheritance Maternal mitochondrial inheritanceMaternal mitochondrial inheritance

Case ReportCase Report 16 year old male has sudden cardiac arrest while playing soccer. 16 year old male has sudden cardiac arrest while playing soccer.

Resuscitation results in return of circulation but sustains neurologic Resuscitation results in return of circulation but sustains neurologic sequelae. Diagnosis ARVD, receives AICD.sequelae. Diagnosis ARVD, receives AICD.

Echocardiography of immediate family members detects ARVD in the Echocardiography of immediate family members detects ARVD in the patient’s father and one brother. Younger brother with ARVD, refuses patient’s father and one brother. Younger brother with ARVD, refuses AICD later arrests while playing soccer with friends. Resuscitation AICD later arrests while playing soccer with friends. Resuscitation successfully, gets AICD.successfully, gets AICD.

Family history of uncle with AICD for Arrhythmia 4 years previously. No Family history of uncle with AICD for Arrhythmia 4 years previously. No attempts made at family history or screening.attempts made at family history or screening.

Genetic testing becomes available 2 years ago and 2 younger siblings Genetic testing becomes available 2 years ago and 2 younger siblings with negative echoes screened. One positive with no evidence of with negative echoes screened. One positive with no evidence of cardiomyopathy at this time.cardiomyopathy at this time.

Genetics and CardiomyopathyGenetics and Cardiomyopathy

Many cardiomyopathies have well known patterns Many cardiomyopathies have well known patterns of inheritance and now have genetic testing of inheritance and now have genetic testing available to identify family members both with and available to identify family members both with and without risk of potentially life threatening disease.without risk of potentially life threatening disease.

Adults presenting with cardiomyopathy for the first Adults presenting with cardiomyopathy for the first time should have detailed family history and time should have detailed family history and possible genetic testing.possible genetic testing.

In the absence of genetic testing other family In the absence of genetic testing other family members should be screened.members should be screened.

Case ReportCase Report Follow a 9 year-old female patient since fetal life Follow a 9 year-old female patient since fetal life

diagnosed with dextrocardia, fetal hydrops VSD, diagnosed with dextrocardia, fetal hydrops VSD, coarctation of the aorta, left ventricular coarctation of the aorta, left ventricular diverticulum (resolves by birth). Has had VSD, diverticulum (resolves by birth). Has had VSD, coarctation repair complicated by complete heart coarctation repair complicated by complete heart block.block.

Mother diagnosed with hypertrophic Mother diagnosed with hypertrophic cardiomyopathy 1 year ago.cardiomyopathy 1 year ago.

Screened brother: asymptomatic hypertrophic Screened brother: asymptomatic hypertrophic cardiomyopathy.cardiomyopathy.

Premortem EvaluationPremortem Evaluation

Diagnosis in a moribund patient obtain studies to Diagnosis in a moribund patient obtain studies to determine etiology and/or genetic or metabolic determine etiology and/or genetic or metabolic cause of the disease.cause of the disease.

Includes:Includes: BloodBlood

– Blood-Glucose, electrolytes, bicarbonate, ABG, BUN, Blood-Glucose, electrolytes, bicarbonate, ABG, BUN, Creatinine, Lactate and pyruvate, CBC with WBC, Creatinine, Lactate and pyruvate, CBC with WBC, Creatine kinase, Cholesterol and Triglycerides, Alkaline Creatine kinase, Cholesterol and Triglycerides, Alkaline aminotransferase, aspartate aminotransferase, bilirubin, aminotransferase, aspartate aminotransferase, bilirubin, PT/PTT, albumin, uric acidPT/PTT, albumin, uric acid

Diagnostic StudiesDiagnostic Studies HistoryHistory ECGECG EchocardiographyEchocardiography Cardiac CatheterizationCardiac Catheterization

– HemodynamicsHemodynamics– Coronary angiographyCoronary angiography– Endomyocardial biopsyEndomyocardial biopsy– Skeletal muscle biopsySkeletal muscle biopsy

Metabolic studiesMetabolic studies Genetic testingGenetic testing

Premortem LaboratoryPremortem Laboratory

Urine (or vitreous)Urine (or vitreous)– Urinalysis, organic acids, quantitative amino Urinalysis, organic acids, quantitative amino

acids, acylglycines, mucopolysaccarides and acids, acylglycines, mucopolysaccarides and oligosaccarides by thin layer chromatographyoligosaccarides by thin layer chromatography

Additional studiesAdditional studies– ECG, Chest X-ray, EchocardiographyECG, Chest X-ray, Echocardiography– Ophthalmologic examOphthalmologic exam– Skeletal x-ray surveySkeletal x-ray survey– PhotographsPhotographs

Additional StudiesAdditional Studies

TissueTissue– HeartHeart– Skeletal muscleSkeletal muscle– LiverLiver– Kidney BrainKidney Brain– SkinSkin(Flash frozen before or soon after death)(Flash frozen before or soon after death)

Medical ManagementMedical Management Depending on etiology and type of cardiomyopathyDepending on etiology and type of cardiomyopathy Hypertrophic obstructive cardiomyopathyHypertrophic obstructive cardiomyopathy

– SymptomaticSymptomatic Calcium channel blockersCalcium channel blockers Asynchronous ventricular pacingAsynchronous ventricular pacing Surgical myectomySurgical myectomy Septal ablationSeptal ablation AntiarrhythmicsAntiarrhythmics AICDAICD TransplantationTransplantation

Hypertrophic cardiomyopathy (non-obstructive)Hypertrophic cardiomyopathy (non-obstructive)– Beta blockersBeta blockers– AICDAICD– TransplantationTransplantation

Metabolic myopathyMetabolic myopathy– Depends on etiology and any available treatment Depends on etiology and any available treatment – L-Carnitine for carnitine deficiencyL-Carnitine for carnitine deficiency

ConclusionConclusion The diagnosis of cardiomyopathy in childhood involves an The diagnosis of cardiomyopathy in childhood involves an

extensive evaluation for possible etiology.extensive evaluation for possible etiology. Familial disease is common and even asymptomatic family Familial disease is common and even asymptomatic family

members should be screened.members should be screened. Genetic evaluation should be pursued where there is the Genetic evaluation should be pursued where there is the

possibility of inheritable disease and availability of genetic possibility of inheritable disease and availability of genetic testing.testing.

Consider metabolic disease in the infant with Consider metabolic disease in the infant with cardiomyopathy.cardiomyopathy.

With better understanding of the molecular causes of With better understanding of the molecular causes of cardiomyopathy, future medical management may allow for cardiomyopathy, future medical management may allow for greater longevity and quality of life in this population.greater longevity and quality of life in this population.