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