Pathology Of Congential Heart Disease And Sudden Death Flashcards
Congenital heart diseases broad facts
Account for 20-30% of all birth defects
- some are incomparable with survival intrauterine or after birth
- nearly affect 1% of all newborns
- higher incidence in premature infants and stillborns
What 10 congenital heart diseases account for 85% of all diseases
Ranked in most common to least common
1) ventricular septal defect
2) atrial septal defect
3) pulmonic stenosis
4) patent ductus arteriosis
5) tetralogy of Fallot
6) atrioventricular septal defect
7) aortic stenosis
8) transposition of great vessels
9) truncus arteriosus
10) tricuspid atresia
What gestation weeks does congenital heart disease most commonly form?
3-8 weeks
Possible Pathogenesis of congenital heart diseases
Idiopathic = 90% of the time
Known causes include 1) environmental exposure of teratogens Examples: - rubella infection - maternal diabetes
2) chromosomal abnormalities (trisomy 13/15/18 or 21) (and Turner syndrome)
* trisomy 21 especially has high rates of cardiac issues*
Key steps of cardiac morphogenesis
always includes multiple genes working together
1) commitment of progenitor cells -> myocytes
2) formation and looping of the heart tube
3) segmentation and growth of the cardiac chambers
4) cardiac valve formation
5) movement and connection of the great vessels
What signal molecules work together to coordinate heart formation?
WNT
VEGF
BMP
TGF-B
NOTCH
also the flow of pulsation blood to the cells is required in proper looping of the vessels
What is the inheritance pattern of most congenital heart diseases?
Usually autosomal dominant
- can be gain-o-function or loss-o-function
Mutations in what bio markers are the most common causes for congenital diseases?
Transcription factors
MicroRNAs
Intracellular signaling cascades
Digeorge syndrome reminder
Deletion of chromosome 22q11.2
- causes the 4th branchial arch and the derivatives of the 3rd and 4th pharyngeal arches to (thymus and parathyroids) form abnormally
- TBX1 transcription factor gene is the most common chromosome segment deleted
- CATCH-22 is the acronym for digeorge*
- Cardiac abnormality
- Abnormal facies
- Thymic aplasia
- Cleft palate
- Hypocalcemia
Genes associated with ASD and VSD
NKX 2.5 and GATA4 genes
The most common genetic cause of congenital heart disease is what?
Down syndrome (trisomy 21)
- usually results in AV septal defects-
- 40% of Down syndrome patients have one or more heart defects
Three major groups of structural abnormalities in Congenital heart disease
1) malformation causes right-left shunting
- tetralogy of Fallot
- transposition of the great vessels
2) malformations causes left-right shunting
- ASD/VSD
- patent ductus arteriosus
3) malformations causes obstruction of blood flow
- coarctation of the aorta
Right-to-left shunting clinical features
A dusky blue cyanosis
- caused by pulmonary circulation being bypassed and poorly oxygenated blood
This is seen in tetralogy of Fallot and transposition of the great vessels
Left-to-right shunting clinical features
- Increased lung vascular resistance (pulmonary HTN)
- RVH and RHF
will show late-onset cyanosis since the increased pulmonary HTN will eventually get so bad that the pressure gradient moves right -> left shunting
(Called eisenmenger syndrome and once this stage is hit it is irreversible)
3 cardiac disorders associated with left-> right shunts
ASDs
VSDs
Patent ductus arteriosus
Patent foramen ovale
Unsealed atrial septa which causes right -> left blood flow during valsalva maneuvers or sneezing.
- caused by the Ostium primum and secundum not forming together properly.
- can present w/ paradoxical embolisms that enter the systemic arterial circulation
20% of births show this/ 80% are normal
What is the exact pathogensis of the majority of ASDs?
“Ostium Secundum” (90%)
- failure of the septum secundum to fully fuse with the septum primum and generate the atrial septum
- usually do not present with other cardiac abnormalities unless severe
Severe can cause the following
- right atrial/ventricular dilation
- RVH
- common atrioventricular canals
- VSDs
- pulmonary hypotension
Note that ASDs are the most common cardiac defects to be first diagnosis disease in adults
Ostium primum ASDs
Account for 5% of ASDs
- occur at the lowest part of the atrial septum and is associated w/ mitral and tricuspid valve abnormalities
in serious cases, shows VSD in conjunction
Sinus venosus ASDs
Account for 5%
- are located at the highest point of the atrial septum and often are associated w/ pulmonary vein drainage into the right atrium or the SVC
ASDs treatment and signs/symptoms
Mostly are asymptomatic until adult hood especially if the defect is <1cm in diameter
- initially cause left-> right shunting but over time (once Pulmonary HTN occurs) can cause right -> left shunting
- overtime will generate pulmonary hypertension, in which case surgical intervention is required
Mortality rates are low But if they exist are caused by one of the following
- RHF
- paradoxical embolization
- irreversible pulmonary vascular disease
Ventricular septal defects (VSDs)
Allow left -> right shunting and
- 90% of these occur at the basal region of the septum
- most will close spontaneously in childhood
Size is variable, however if significant right-> left shunting is present, causes the following
- RVH or dilation
- pulmonary artery dilation (leads to pulmonary HTN)
Note: these are the most common cardiac anomalies to be first diagnosed in children
Difference between small and large VSDs
Small = asymptomatic and often resolve by themselves
Large = cause progressive pulmonary HTN and requires surgery before CHF occurs
Note: both VSDs and ASDs cause pulmonary HTN, however VSDs have this occur earlier and more frequently
ductus arteriosus
When first taking a breath out of the womb, this ductus arteriosus will begin to close and constrict
- due to increased arterial oxygenation
- decreased pulmonary vascular resistance
- declining local levels of prostaglandin E2
This is usually complete by 1-2 months leaving the ligamentum arteriosum
Patent ductus arteriosus (PDA)
In patients with PDA, the ductus arteriosis doesnt close or is delayed
- often due to hypoxia in infants
- account for 7% of congenital heart lesions and are generally isolated defects
Causes high pressure left-> right shunts which produce harsh “machine-like” murmurs
- eventually leads to eisenmenger syndrome and leaves patients w/ high chance of infective endocarditis
What is the distinguishing sign for right -> left shunting?
Very early cyanosis (usually at onset)
What are the two most important congenital heart diseases w/ right -> left shunting
Tetralogy of Fallot
- most common cause of cyanotic CHD and accounts for 5% of all cardiac malformations
Transposition of the great vessels
4 cardinal features of tetralogy of Fallot
Ventricular septal defects
Right ventricular outflow tract obstruction
Overriding of the VSD by the aorta
RVH
Morphology of tetralogy of Fallot
Boot-shaped enlarged heart (due to RVH) “looks like a foot”
Proximal aorta is dilated w/ hypoplastic pulmonary trunk
Subpulmonic stenosis
Obstruction of the right ventricular outflow due to the narrowing of the infundibulum
- seen in tetralogy of Fallot
What are the clinical features of tetralogy of Fallot?
Cyanotic heart disease
- will look blue
Hypertrophic osteoarthritis
Polycythemia (different shaped blood cells)
Clinical features of transposition great arteries
all are caused due to the aorta being tied to the right ventricle and the pulmonary trunk being tied to the left ventricle
Marked right ventricular hypertrophy
- due to right ventricle having to pump as the left ventricle now w/ high systemic resistance
Marked left ventricular hypoplastic
- due to left ventricle now acting as the right ventricle and pumping to low pulmonary resistance
may or may not show a patent foramen ovale or PDA
May or may not show VSDs (occurs in 1/3rd of cases)
Symptoms:
- max cyanosis with necrosis of tissue due to hypoxia
- requires immediate surgery*
Common examples of obstructive lesions that lead to malformations
Pulmonic valve stenosis
Aortic valve stenosis
Coarctation of the aorta
- more common in males and females w/ turners syndrome almost always get this
Two forms of aortic coarctation
Infantile preductal form
- features hypoplastic aortic arch proximal to the PDA
- dilated pulmonary trunk
- RVH
Adult postductal form
- features ridge like unfolding of the aorta adjacent to the ligamentum arteriosum
- LVH
- aortic dilation
What is the most common secondary pathology associated with aortic coarctation
Bicuspid aortic valve
note it can be solitary and is not always present w/ bicuspid aortic valves
Outcomes of both prenatal and adult forms of aortic coarctation
Prenatal:
- requires surgery or will die within 3 months of birth
Adult (postductal)
- usually asymptomatic (as long as PDA has shrunk)
- can show the following symptoms however:
1) upper-extremity HTN
2) lower-extremity hypotension
3) claudication of extremities
Imaging results of coarctation of the aorta
Notching of the ribs is present w/ markedly enlarged intercostals
Eisenmenger syndrome
Late-onset cyanosis caused by right-left shunting due to chronic left- right shunting
- overtime the pressure becomes so high on the right side that the shunting reverses itself
At this stage it is irreversible
