Congenital Heart Disease Flashcards
What is the mechanism of the issue that VSD causes?
- shunt from LV –> RV b/c of opening (L side of heart is higher pressure than R side of heart, so w/ an opening, blood will flow from LV to RV) (oxygenated blood to travel to the lungs again)
- increased blood volume in R ventricle –> pulmonary hypertension (higher pressure on R side of heart)
- If RV reaches higher pressure than LV, the shunt will change to R –> L and deoxygenated blood is now getting to the LV and the aorta.
- leads to cyanosis: bluish skin around lips and fingertips
- surgical closure of VSD may be needed
Do not need to know cyanotic part of this defect, we know it for this class as a non-cyanotic heart defect
In the absence of pulmonary hypertension, a ventricular septal defect leads to a (right to left/left to right) shunt.
In the absence of pulmonary hypertension, a ventricular septal defect leads to a (right to left/left to right) left to right shunt.
What genetic testing should be considered for congenital heart defects and what is an example of what you would be looking for?
- CMA (eg:22q11 del, aneuploidies)
- multigene cong. heart panel (eg:NKX2.5 CHARGE)
- karyotype (eg: Turner)
What genes are important in formation of the primitive heart tube?
A number of growth factors are involved in the formation of the primitive heart
tube. Bmp/Fgf8 secreted by the pharyngeal foregut antagonized the inhibitory
effects of Wnt and Chordin/noggin, thereby promoting the expression of Nkx2.5,
Gata4 which drives the lengthening of the heart tube.
TGFBeta family
What are the 5 major steps of caridac development?
- formation of primitive heart tube
- looping of the primitive heart tube
- septation of the heart tube in to 4 chambers and formation of AV valves
- conotruncal septation
- development of the vascular system (arterial and venous)
Direction of blood flow in primitive heart tube when it initiates contractile activity
caudal flow direction
heart cells come from anterior portion of primitive streak
What is the first functional organ in development?
heart
When does the primitive hart begin beating?
5 1/2 weeks gestation
What structure brings in nutrients to the developing fetus from the yolk sac during development?
Vitelline vein
What structure supplies oxygen to the fetus?
umbilical vein
What genetic findings are associated with conotruncal defects?
- 22q11.2 Deletion Syndrome (DiGeorge, velocardiofacial, CATCT22)
- CHARGE (coloboma, heart defects, atresia of the choanae (nasal passage), restriction of growth, genital, ears) gene = CDH7
Cardiac looping is dependent on laterality inducing genes such as ? and ?
Cardiac looping is dependent on laterality inducing genes such as NODAL and LEFTY2
Other gene inovlved in cardiac looping: PITX2, HAND1, HAND2
Heart is mostly formed by 10/12 weeks?
Umbilical vein provides…
- nutrients
- oxygen
Umbilical arteries take care of…
- carbon dioxide
- waste
What parts of the heart close after birth?
- septum secundum
- foramen ovale
- ductus arteriosus
Congenital heart disease classifications
- location
- embryonic origin
- cyanotic vs non-cyanotic (oxygen desaturation or not)
If a congenital heart disease starts with the letter T it is likely…
cyanotic heart disease
There are 8 cyanotic heart diseases, 5 of them begins with the letter T.
What are the 8 cyanotic heart disease?
- Tetralogy of Fallot
- (Persistant) Truncus Arteriosis
- Tricuspid Atresia
- Total Anomalous Pulmonary Venous Return
- Transposition of the Great Vessels
- Pulmonary Valvular Stenosis
- Hypoplastic Left Heart
- Ebstein’s Anomaly
5 begin with letter T
What is the primary problem in Tetralogy of Fallot?
narrowing of outflow tract
Tetrology of Fallot is a ? defect
conotruncal
Describe Tetralogy of Fallot
- stenosis of puonary infundibulum leading to narrowing of the right ventricular outflow tract (harder for deoxygenated blood to get to the lungs)
- RV myocardium hypertrophies to push past stenosis
- Ventricular septal defect, b/c of higher pressure on R side due to stenosis, blood shunts from R –> L leading to circulation of deoxygenated blood and cyanosis
- over-riding aorta
cyanotic heart defect. Tetra = 4 components of defect
What is the most common congenital cyanotic heart defect?
Tetralogy of Fallot
(50-70%)
Which genetic condition is associated with Tetralogy of Fallot?
22q11 del & DiGeorge
(Persistant) Truncus Arteriosus ia a ? defect
conotruncal
Describe (Persistant) Truncus Arteriosus
- truncus arteriosus is a structure that is present during fetal development and divides to become the aorta and pulmonary artery
- in this condition, they don’t divide completly and there is a VSD and blood mixing before traveling down the aorta or pulmonary artery
- leads to cyanosis and heart failure
cyanotic heart diease, conotruncal defect
Describe Tricuspid Atresia
congenital heart defect where tricuspid valve between the RA and RV did not form well and leads to cyanosis
Describe Total Anomalous Pulmonary Venous Return
Total anomalous pulmonary venous return (TAPVR) is a rare congenital (present at birth) defect. With TAPVR, all four pulmonary veins do not connect normally to the left atrium. Instead, the four pulmonary veins drain abnormally to the right atrium (right upper chamber) through an abnormal (anomalous) connection.
Cyanotic Heart Defect
Describe Transposition of the Great Vessels
- aorta arises from RV and pulomary artery arises from LV (switched spots)
- spiraling during embryology did not happen
- ductus arteriosis provides some O2 and must be kept open after birth (connects pulmonary artery and aorta)
Cyanotic heart disease, conotruncal defect
What does the foramen ovale connect in a fetus?
LA & RA
What does the ductus arteriosus connect in a fetus?
pumonary artery and aorta
Is pulmonary valvular stenosis a cyanotic or non-cyanotic heart defect?
cyanotic
Hypoplastic Left Heart Syndrome: Which areas of the heart are most affected?
hypo = under, plastic = formation
LV and ascending aorta are under developed (very small ventricle)
Which other defect must be present for a baby to survive with hypoplastic left heart syndrome?
- Atrial septal defect
- since the ductus arteriosus remains present for a few weeks after birth, babies may be asymptomatic, but once this closes it is too difficult for the body to get oxygenated blood and babies become cyanotic
Is Ebstein’s anomy a cyanotic or non-cyanotic heart defect?
cyanotic
What is Ebstein’s anomaly?
- tricuspid valve (between the RA and RV) forms abnormally and is always open - so blood flows back and forth between RA and RV
cyanotic heart disease
In ~?% of patients with congenital heart disease, additional non-cardiac findings are seen. This often suggests the presence of a ? (?%) or a ? (?%).
In ~25% of patients with congenital heart disease, additional non-cardiac findings are seen. This often suggests the presence of a chromosomal abnormality (15%) or a genetic syndrome (10%).
75% of congenital heart disease is multifactorial. What is the recurrence rate for siblings? What is the higher end of recurrence for multiple first degree relatives?
This means recurrence of congenital heart disease
is generally ~2-3% among sibs. As part of the general property of multifactorial
inheritance, the number and severity or previous affected sibs strongly influences
the risk of recurrence, such that with multiple affected first-degree relatives, the
recurrence risk can be as high as 15-25%.
Genotype-phenotype correlation is not prsent in congenital heart disease, even for single genes. Generally, it is best to counsel on ? and suggest ? for precision of the anomaly.
Genotype-phenotype correlation is not prsent in congenital heart disease, even for single genes. Generally, it is best to counsel on “congenital heart disease” as a phenotype and suggest fetal echocardiogram for precision of the anomaly.
Which congenital heart diseases are associated with Down Syndrome?
- ASD (common in gen pop)
- VSD (common in gen pop)
- AV canal (otherwise rare in gen pop) (all 4 chambers can be connected)
Which congenital heart diseases are associated with Turner Syndrome?
- coarctation of the aorta
- bicuspid aortic valve (instead of tricuspid)
- valve abnormalities
Which congenital heart diseases are assocaited with 22q11.2 Deletion Synrdrome (DiGeorge, velocardiofacial, CATCT22, etc.)?
- conotruncal defects
conotruncal defects: Tetraology of Fallot, (Persistant) Truncus Arteriosus, Transposition of the Greast Vessels
Deletion of a critical region of 22q11.2 including which gene leads to congenital heart disease?
TUPLE1
Features of 22q11.2 deletion syndrome
Other Clinical Findings (abbreviated): cleft palate, pharyngeal insufficiency, growth
and developmental delay, dysmorphic features, T-cell deficiency, primary
hypoparathyroidism, psychiatric disorder)
Velocardiofacial syndrome is similar to what other genetic condition?
DiGeorge Syndrome
Holt Oran Syndrome
* gene & inheritance
* cardiac anomalies
* other clinical findings
- gene = TBX5 (AD inheritance)
- ASD, VSD predominates
- radial defects, most notably triphalangeal
thumb, but can have other variations
Ellis van Creveld Syndrome
* inheritance pattern
* genes
* cardiac anomalies
* other clinical findings
- Autosomal Recessive
- Cause: biallelic pathogenic variants in DYNC2H1, DYNC2LI1, EVC, EVC2, GLI, SMO, or WDR35 or heterozygous pathogenic variant in PRKACA or PRKACB
- ASD, VSD, single atrium, AV canal
- skeletal dysplasia with postaxial polydactly, proportionate short stature, dystrophic nails
- prenatal growth restriction
- cong. heart disease
- polydactyly
- neonatal teeth
- autosomal recessive
What are the conotruncal defects? (3)
- Transposition of the Great Vessels
- (Persistant) Truncus Arteriosus
- Tetraology of Fallot
