CARDIOMYOPATHY & THE NEWBORN

1. CARDIOMYOPATHY&THE NEWBORN N. Felicia Ochei, M.D. Pediatrics-PL 2 November 2002

2. Introduction Topics • Peripartum Cardiomyopathy: Implications to the fetal well-being • Review of Cardiomyopathy in the Neonatal period • Fetal Cardiomyopathy: A Journal article Review

3. Peripartum Cardiomyopathy Definition Dilated cardiomyopathy of uncertain origin characterized by: • Cardiac failure in the last month of pregnancy or within 5 months after delivery • Absence of demonstrable cause for the cardiac failure • Absence of demonstrable heart disease before the last month of pregnancy • Documented systolic dysfunction*

4. Peripartum Cardiomyopathy Incidence • U.S. 1:1300 to 15,000 live births • Japan 1:6000 live births • South Africa 1:1000 • Nigeria High incidence: ? related to tradition of ingestion dried lake salt Age • Wide range probably more common > 30 years*

5. Medical Rx Inotropics Digioxin Dobutamine when indicated Loop diuretics Beta blockers Anticoagulation Heparin(unfractionated, LMWH) Warfarin (post partum) After load reduction Hydralazine Nitrates Obstetric mgt Spontaneous vaginal delivery at term is reasonable unless mother is decompensating Painless and effortless labor/delivery Inhaled analgesia preferred (epidural/spinal contraindicated for 24hrs after use of LMWH) Forceps/vacuum assisted delivery is the rule Vaginal delivery preferred as C/S carries a higher risk of PE and and endometritis (75%) Peripartum Cardiomyopathy

6. Peripartum Cardiomyopathy Fetal Implications • Fetal distress from maternal hypoxia • Placental hypo-perfusion • Poor cardiac output • Excessive use of diuretics • Hypotension from afterload reducers • Complications of instrumental delivery • Complications of intra partum anesthesia (choice & quantity) • Risks of Preterm delivery • Severe maternal decompensation • Adverse effects of medications (e.g. Digoxin, Beta blockers, LMWH) • Safety for use in pregnancy not established • Psychosocial issues • Infant maternal bonding

7. Peripartum Cardiomyopathy The pediatrician’s Role • Liaison with OB • Careful maternal history • Anticipate problems from • Preterm delivery • Maternal Medications • Fetal distress • Instrumental delivery

8. Neonatal Cardiomyopathy

9. Neonatal Cardiomyopathy Definitions • Neonate: Birth to 28 days of life • Neonatal Cardiomyopathy: Disease of the neonate in which the myocardium is affected without primary abnormalities of the valves, great vesselsor septum Epidemiology • Difficult to define: Few studies, rare disease entities • Estimates: 1: 10,000 live births (Nelson) • Constitutes about 1% of childhood cardiac disease • 10% of all pediatric cardiac deaths

10. WHO (1980) Guidance for therapy and prognosis Dilated Cardiomyopathy Insult to the myocardium tissue necrosis/interstitial fibrosis impaired systolic contractility/diastolic compliance ventricular dilation to maintain function Left +/- right sides Hypertrophic Cardiomyopathy Myocyte hypertrophy & disarray Increased mass & thickness Increased mass/volume ratio Poor diastolic chamber compliance Left ventricle High systolic pressure gradient Restrictive Cardiomyopathy Rare, very small L ventricular cavity Impaired diastolic function initially Unclassified cardiomyopathy Neonatal Cardiomyopathy:Pathophysiologic Classification

11. DILATED Perinatal insult/ maladjustment Asphyxia Persistent fetal circulation Congenital anomalies Anomalous origin of Left coronary Inborn errors of metabolism Glycogen storage dses (Pompe’s dse) Mucopolysaccharidosis Disorders of fatty acid metabolism (Carnitine deficiency) Amino & organic acidiurias Maternal connective Tissue dse SLE HYPERTROPHIC Familial Idiopathic Hypertrophic Maternal disease Diabetes Myocarditis Infectious endotoxins, exotoxicins Drugs /Iatrogenic Dexamathasone (BPD)( case report) ECMO (case report) Adriamycin Chloramphenicol Malformation syndromes Beckwith wiedemann Noonan Leopard Downs (case report) Neonatal Cardiomyopathy: Etiologic classification

12. History Non specific Pallor, irritability Tachypnea Diaphoresis Fatigue esp with feeds Poor wt gain PE Signs of CCF: Tachypnea, tachycardia, narrow pulse p Decreased peripheral pulse, hepatomegaly, wheezing +/- cyanosis Murmur of mitral insufficiency +/- left ventricular outflow obstruction(hypertrophic) Features of underlying etiology EKG Flat T wave ST depression Generalized low voltages Characteristic findings for the underlying abnormality CXR Cardiomegaly May be normal in fulminant cases Pulmonary edema Pericardial effusion may be present (Water-bottle configuration) ECHO Diagnostic Ventricular dilatation/dyskinesia Ventricular outflow obstruction Neonatal Cardiomyopathy:Clinical Features

13. Neonatal Cardiomyopathy:Asphyxia induced • Hypoxia leads to myocardial ischemia/dilation • Term infant with delivery complicated by hypoxic stress • Apgars usually <3 @ 1 • Metabolic acidosis/ multi system ischemia • Severe cases: Hypotension/shock • Murmur of mitral/tricuspid regurg may be present • EKG: Diffuse ST -T changes, R atrial hypertrophy • Prognosis: Good without cardiogenic shock

14. Neonatal Cardiomyopathy:From Maternal Diabetes • Asymmetric hypertrophic cardiomyopathy • Mechanism not clearly understood ? Hyperinsulinemia • Prevalence unrelated to diabetic control of mother • Puffy, Plethoric infant, with signs and symptoms of CCF • SEM common and related to degree of outflow obstruction • RX:Usually symptomatic • Prognosis: Usually good, resolves in months • Digitalis and other inotropics agents are contraindicated except in very severe depression of myocardial contractility

15. Neonatal Cardiomyopathy:Carnitine deficiency • Autosomal recessive inheritance • Plasma memb carnitine transport defect: Impairs fatty acid oxidation • Metabolic acidosis, intractable hypoglycemia, severe non-immune hydrops, +/-muscle weakness • EKG: Giant T waves(pathognomonic) • Subnormal carnitine level 1-2 %, heterozygous parents have 50 % levels • Symptomatic Rx for the cardiac failure gives minimal benefits • Definitive Rx: Oral carnitine supplements • Prognosis: Usually good with early diagnosis and Rx • Risk of growth and mental retardation

16. Neonatal Cardiomyopathy:Myocarditis • Any infectious agent, commonly Coxsackie B, ECHO viruses, herpes, HIV, Rubella • Bacterial/fungal infections • Vertical/horizontal spread • Pathology: multicellular infiltrates • Usually first 10 days of life • Features of acute infective process • Involvement of other organs like CNS esp Coxsackie B • Gamma globulins beneficial • Rx underlying infection: Interferon, Ribavirin

17. Neonatal Cardiomyopathy:Pompe’s Disease • Generalized form of glycogen storage dse (type II) • Lysosomal alpha- glucosidase deficiency • Autosomal recessive • Infiltrative cardiomyopathy • Skeletal muscular hypotonia: Protruding tongue, feeble cry, poor feeding • Hyporeflexia • Diagnosis: Measurement of enzyme activity or DNA analysis • EKG: (characteristic) • Short PR interval • prominent P waves • massive QRS voltage • Uniformly fatal

18. Neonatal Cardiomyopathy:1diopathic Familial • Multi gene disorder • Autosomal with variable penetrance • Ventricular dysrhthmias/ Sudden death • Normal Echo @ birth does not rule out disease in later life • Avoid diuretics & inotropics • Ventricular septal myomectomy • Cardiac transplantation • Those presenting @ birth have worse prognosis

19. Neonatal Cardiomyopathy:Endocardial Fibroelastosis • No established cause • Also called elastic tissue hyperplasia • Pathology: White opaque fibroblastic thickening of the endocardium • 1:6000 (1960); 1:70,000 (1980) • Infants < 6 months usually • Severe CCF/ rhythm disturbances • Failure to thrive • CXR : Massive cardiomegaly • EKG: Low voltage as in severe myocarditis • ECHO: Bright -appearing endocardial surface

20. Neonatal Cardiomyopathy:Anomalous origin of the left coronary artery • From the pulmonary artery • Should be ruled out in all cases of cardiomyopathy • EKG: anterolateral infarct • Surgical correction usually successful

21. Step 1: Initial Evaluation EKG CXR ECHO Step 2: Screening Evaluation CBC CMP Enzymes:LDH, SGOT, SGPT, CPK, aldolase ABG Fractionated serum carnitine Urine organic & amino acids Urine muco/oligosacharides Skeletal survey Viral studies: Stool, NPW, urine, blood Step 3: Specific Testing Cardiac catheterization Myocardial biopsy Holter monitoring Carnitine levels (skeletal, cardiac tissue, urine) Serum ketone bodies, ammonia, pyruvate, lactate Fibroblast studies Chromosomes Neonatal Cardiomyopathy;Diagnostic Evaluation

22. Supportive Therapy Non specific therapy for heart failure, to improve survival & alleviate symptoms ACE inhibitors (captopril, enalpril) Reduce afterload Improve cardiac ejection Reduce catecholamine drive prolonging cardiac survival Careful titration necessary B blockers (metoprolol, carvedilol) Digoxin Diuretics Specific Therapy Depends on the underlying disease condition Most have no effective Rx Carnitine supplements Surgery Correction of aberrant vessels Implanable defibrillators Partial left venticulectomy Cardiac transplant Neonatal Cardiomyopathy:Management

23. Neonatal Cardiomyopathy:Prognosis • Not well described in infants • Generally poor for infants • Depends on underlying condition • Some carry 100% mortality rate e.g. Pompe,s disease • Annual mortality 6% -8% in children • One year survival rate: 63% • 5 year survival rate • Clinical adage 1/3rd die; 1/3rd significant damage; 1/3rd recover (infective myocarditis)

24. FETAL CARDIOMYOPATHY

25. Fetal Cardiomyopathy:A Journal Article Review Schmidt KG, Einat B, Silverman NH, Scagneli SA. Echocardiographic Evaluation of Dilated Cardiomyopathy in the Human Fetus The American Journal of Cardiology 1989; 63:599-605

26. Fetal Cardiomyopathy:A Journal Article Review Study Objectives • To explore the possibility of detecting dilated cardiomyopathy in the prenatal period • To follow the the development of the disease during gestation • To determine the effects of prenatal presentation on the postnatal course of the disease

27. Fetal Cardiomyopathy:A Journal Article Review Study Methodology • 625 women had fetal echocardiography at the Univ. of California in San Francisco from 1980 to 1987 • Criteria for inclusion in the study: • Family history of congenital heart defects • Abnormal findings in obstetrics sonogram • No history of antecedent maternal illness • The echo was performed from 20 to 26 weeks gestation for family Hx and @ time of presentation for the others

28. Fetal Cardiomyopathy:A Journal Article Review Study Findings • 6 of the 625 had dilated cardiomyopathy but had structurally normal hearts • 2 fetuses referred for family Hx had normal findings initially but later developed cardiomyopathy on serial ECHOs • Abnormal findings included: • Reduced systolic myocardial performance(5) • AV valve regurgitation (3) • Abnormal chamber dimensions (3) • 4 deaths (1 fetus, 3 neonates) 1 survivor required cardiac transplant in infancy

29. Fetal Cardiomyopathy:A Journal Article Review Study conclusions • Dilated cardiomyopathy may develop during fetal life • Diagnosis can be achieved by serial echocardiogram • Normal findings in mid-trimester do not always rule out the subsequent development of cardiomyopathy • Reduced systolic performance; most sensitive finding and preceded the presence of progressive dilation • Fetal onset cardiomyopathy carried poor prognosis (Conflicts with other studies that suggested better outcomes for early childhood onset) • There were no predictive factors for outcome of the disease (Similar to findings in studies of dilated cardiomyopathy in childhood)

30. Fetal Cardiomyopathy:A Journal Article Review Study Limitations • Technical limitations: Unable to calculate ventricular volumes ejection fraction earlier in the study • Difficulty comparing chamber enlargements and performance with normal values • As was with all previous studies • No defined normal values

31. Fetal Cardiomyopathy:A Journal Article Review Discussion • The value of fetal echocardiogram in cardiomyopathy • Research and further development • Fetal echo usually done not solely for cardiomyopathy but for cardiac anomalies in general • Intervention ? • Prenatal period • Immediate postnatal period • Cost effectiveness • Prognostic value?

32. DR SCHUSTER THANK YOU