Congenital Heart Disease

1. Congenital Heart Disease

2. CHD CHD = Abnormalities of the heart or great vessels present from birth Most – faulty embryogenesis during the 3rd-8th week when the CVS form and begin functioning Worst ones don’t survive to term Those who do usually have only discrete regions of the heart affected e.g. septal defect or valvular defect

3. CHD Dx Some when change from fetal to postnatal circulation 50% diagnosed by one year of life Mild forms - adulthood

4. CHD Incidence 1% of all live births CV defects among most common malformations and are the most common cause of heart disease in children Higher in premies and stillborns Table 12-2 VSD most common Tetralogy of Fallot most common cyanotic Many survive into adulthood - repairs arrhythmias additional surgery ventricular dysfunction use of prosthetics risk of childbearing

5. CHD Cardiac Development – figure 12-3 First heart field TFs: TBX5, Hand1 Mainly LV Second heart field TF: Hand2, FGF=10 Outflow tract, RV, most of atria Cardiac neural crest Septation of outflow tract, aortic arches

6. CHD ECM – swellings – endocardial cushions Future valve development Day 50 – 4 chambered heart Signaling pathways regulating TFs Wnt VEgf bone morphogenetic factor TGF-beta FGF Notch Heart – mechanical organ – exposed to flowing blood from earliest stages – hemodynamic forces play a role Specific micro RNAs – critical role- patterns and levels of TF expression

7. CHD AD mutations – partial loss of function in one or more required factors, TFs usually “The main known cause of CHD consist of sporadic genetic abnormalities.” single gene mutations small chromosome deletions additions or deletions of whole chromosomes Table 12-3

8. CHD Heterozygotes = 50% reduction in activity = deranged cardiac development Factors work together- large protein complexes – different single gene mutations produce similar defects Signaling pathways or structural roles NOTCH1 – bicuspid AV NOTCH2, JAGGED1 – TOF Fibrillin – Marfan’s

9. CHD DiGeorge Syndrome Small deletion of 22q11.2 in 50% 4th branchial arch and 3rd and 4th pharyngeal pouches Thymus, parathyroids, heart TBX1 Chromosomal aneuploidies Turner Syndrome Trisomies 13,18, 21 21- most common genetic cause of CHD endocardial cushion defects

10. CHD First-degree relatives of affected patients are at increased of CHD – subtle forms of genetic variation Environmental factors? +/- genetic factors congenital rubella infection gestational diabetes exposure to teratogens nutritional factors? transient environmental stresses during 1st trimester?

11. CHD Clinical features Left-to-right shunts Right-to-left shunts Obstructive lesions Shunt= abnormal communication between chambers or vessels Obstruction = narrowing (if complete- atresia)

12. CHD R to L Hypoxemia Cyanosis Emboli bypass lungs – brain infarction, abscess ( paradoxical embolism) Clubbing (hypertrophic osteoarthropathy) Polycythemia

13. CHD L to R Normally low-pressure, low-resistance pulmonary circulation now sees high flow volumes and pressures RVH Atherosclerosis of pulmonary vessels medial hypertrophy vasoconstriction irreversible obstructive intimal lesions Pulm pressures reach systemic levels R to L shunt Eisenmenger Syndrome Altered hemodynamics of CHD Dilation, hypetrophy or both Decreased volume and muscle mass – hypoplasia – before birth, atrophy – postnatally

14. CHD L to R ASD VSD PDA AV septal defects

15. CHD ASD abnormal, fixed opening in the atrial septum usually asymptomatic until adulthood 3 types Secundum (90%) – center of the septum Primum (5%) –adjacent to the AV valves Sinus venosus ( 5%) – SVC, associated with APVR Clinical L to R Pulmonary blood flow -2-4 times normal murmur from increased pulmonic valve blood flow Surgical or catheter correction – low mortality, normal long-term survival PVO –oval fossa, 80% closed permanently, 20% potential opening that can become clinically important r-to-l

16. CHD VSD Most common congenital anomaly 20-30% isolated finding Most are associated with other cardiac anomalies Classified by size and location 90% membranous Rest are infundibular ( below the PV) or muscular Muscular can be multiple ( “Swiss-cheese”) Clinical Large – problems from birth, RVH, pulmonary hypertension, correct before irreversible changes Smaller – well-tolerated

17. CHD PDA DA stays open, allowing L to R shunt from aorta to pulmonary artery 90% isolated anomaly “machinery-like” murmur close as soon as possible to prevent irreversible PH Some congenital lesions are ductus dependent and there by need to keep the DA open- e.g. aortic atresia, use prostaglandin E)

18. CHD AV septal defect Complete atrioventricular canal defect Partial – primum ASD with mitral insufficiency Complete – large combined AV septal defect and a common AV valve – all 4 chambers communicate, all have hypertrophy 1/3 have Down syndrome Surgically correctible

19. CHD R to L Tetralogy of Fallot Transposition of the Great Arteries Truncus arteriosus Tricupsid Atresia Total Anomalous Venous Connection

20. CHD Tetralogy of Fallot 4 cardinal features VSD Obstruction of the right ventricular outflow tract (subpulmonary stenosis) An aorta that overrides the VSD RVH Embryoloigcally – anterosuperior displacement of the infundibular septum “Boot-shaped” heart – marked apical RVH Sometimes PVS, PV atresia Sometines AV insufficiency, ASD 25% right aortic arch Clinical – Classic TOF – r-to-l shunt Pink TOF – l to r shunt because of mild subpulmonary stenosis As child grows obstuction becomes worse Stenosis protects pulmnary arteries from overload and RV failure rare because RV decompressed by the VSD

21. CHD TGA Ventriuloarterial discord Aorta from RV PA from LV Separation of the systemic and pulmonary circulations – incompatible with life unless a shunt exists VSD or PFO or PDA or artificial shunt –balloon atrial septostomy Surgical repair

22. CHD TA Failure of separation into the aorta and PA a single vessel giving rise to the systemic, pulmonary and coronary circulation Associated VSD

23. CHD TAPC Pulmonary veins fail to join the left atrium PFO or ASD Aplastic Left atrium LV normal size

24. CHD Obstructive Congenital Anomalies Coartation of the aorta PS and atresia AS and atresia

25. CHD Coarctation of the Aorta Males 2x females Associated with Turner syndrome 2 classic types “infantile” – hypoplasia of the arch proximal to a PDA, symptomatic in early childhood, cyanosis over lower half of body, surgical correction needed early “adult” – discrete ridgelike infolding of the aorta, just opposite a closed DA (ligamentum arteriosus) distal to the arch vessels, hypertension in upper extremities, signs of arterial insufficiency in lower, notching of the ribs due to collateral circulation Clinical – murmur with thrill LVH

26. CHD PS and atresia Obstruction of the PV Isolated or part of a more complex anomaly RVH Poststenotic dilation of PA Complete obstruction- need shunt to survive Mild – asymptomatic Symptomatic – surgical correction

27. CHD AS and atresia Vavular-hypoplastic, dysplastic, decreased number Subvalular-dense fibrous tissue below the cusps Supravavular- aortic dysplasia, thickened and constricted, deletion on chromosome 7, elastin gene, Williams-Beuren syndrome, hypercalcemia, cognitive abnormalities, facial anomalies Hypoplastic left heart syndrome – severe stenosis of atresia – underdevelopment of LV and aorta – endocardial fibroelastosis Clinical – systolic murmur, thrill, LVH, antibiotic prophylaxis for SBE, avoid strenuous activity, sudden death