Cardiology embryology, congenital heart disease

• Truncus arteriosus (TA): Ascending aorta and pulmonary trunk
• Bulbus cordis: Smooth parts (outflow tracts) of left and right ventricles
• Primitive ventricle: Trabeculated left and right ventricles
• Primitive atria: Trabeculated left and right atria
• Left horn of sinus venosus (SV): Coronary sinus
• Right horn of SV: Smooth part of right atrium
• Right common cardinal vein and right anterior cardinal vein: SVC

Neural crest migration → truncal and bulbar ridges that spiral and fuse to form the aorticopulmonary (AP) septum → ascending aorta and pulmonary turnk

• Pathology:
• -transposition of great vessels (failure to spiral)
• -tetralogy of Fallot (skewed AP septum development)
• -Persistent TA (partial AP septum development)

• Step 1:
• Muscular ventricular septum forms
• Opening is called interventricular foramen

• Step 2:
• AP septum rotates and fuses with muscular ventricular septum to form membranous interventricular septum, closing interventricular foramen

• Step 3:
• Growth of endocardial cushions separtes atria from ventricles and contributes to both atrial separation and membranous portion of the interventricular septum

• Improper neural crest migration into the TA can result in transposition of the great arteries or a persistent TA
• Membranous septal defect: initial left-to-right shunt, which later resverses due to the onset of pulmonary hypertension (Eisenmenger's syndrome)

Foramen primum narrows as septum prinum grows toward endocardial cushions

Perforations in septum primum form foramen secundum (foramen primum disappears)

Foramen secundum maintains right-to-left shunt as septum secundum begins to grow

Septum secundum contains a permanent opening (foramen ovale)

Foramen secundum enlarges and upper part of septum primum degenerates

Remaining portion of septum primum forms valve of foramen ovale

• Septum secundum and septum primum fuse to form the atrial septum
• Foramen ovale usually closes soon after birth because of ↑LA pressure

• Patent foramen ovale
• - failure of septum primum and septum secundum to fuse after birth

• Fetal erythropoeisis occurs in:
• -Yolk sac (3-10 wk)
• -Liver (6wk-birth
• -Spleen (15-30 wk)
• -Bone marrow (22wk to adult)

• Young Liver Synthesizes Blood
• 

• Fetal hemoglobin: α₂γ₂
• Adult hemoglobin: α₂β₂

• 1. BLood entering the fetus through umbilical vein is conducted via the ductus venosus into the IVC
• -Bypass the hepatic circulation

2. Most oxygenated blood reaching the heart via the IVC is diverted through the foramen ovale and pumped out the aorta to the head and body

3. Deoxygenated blood entering the RA from the SVC enters RV, expelled into pulmonary artery, then passes through the ductus arteriosus into the descending aorta

• 1. Ductus venosus
• 2. Foramen ovale
• 3. Ductus arteriosus

• Blood in umbilical vein has PO₂ 30mmHg, 80% saturated with O₂
• Umbilical arteries have low O₂ sat

• Infant takes a breath:
• ↓ pulmonary vascular resistance → ↑ LA pressure (compared to RA)
• Foramen ovale closes (now called fossa ovalis)
• ↑O₂ leads to ↓ prostaglandins, causing closure of ductus arteriosus
• Indomethacin helps close PDA
• Prostaglandins E₁ and E₂ keep PDA open

• 1st: maxillary artery (1st arch is maximal!)
• 2nd: Stapedial artery and hyoid artery (Second = Stapedial)
• 3rd: Common Carotid artery and proximal part of internal Carotid
• 4th: Left - aortic arch; Right - proximal part of right sublcavian
• 6th: proximal part of pulmonary arteries (ductus arteriosus on left, only)

• Umbilical vein: Ligamentum teres hepatis (Contained in falciform ligament)
• UmbiLical arteries: MediaL umbilical ligaments
• Ductus arteriosus: Ligamentum arteriosum
• Ductus venosus: Ligamentum venosum
• Foramen ovale: Fossa ovalis
• AllaNtois: Urachus-mediaN umbilical ligament (Urachus is the part of the allantoic duct between the bladder and the umbilicus)
• -Urachal cyst or sinus is a remnant
• Notochord: Neculeus pulposus of intervertebral disc

• Ascending aorta and pulmonary trunk: Truncus arteriosus
• Coronary sinus: Left horn of sinus venosus
• SVC: Right common cardinal vein, right anterior cardinal vein
• Smooth parts of the left and right ventricle: Bulbus cordis
• Smooth part of the right atrium: Right horn of sinus venosus
• Trabeculated left and right atrium: primitive atria
• Trabeculated parts of the left and right ventricles: primitive ventricle

• Spiral septum, aka aorticopulmonary septum
• Neural Crest cells

Young Liver Synthesizes Blood

• Yolk sac
• Liver
• Spleen
• Bone marrow

• Vertebrae
• Sternum
• Pelvis
• Ribs
• Cranial bones
• Tibia - up to age 25
• Femur - up to age 25

Umbilical vein → ductus venosus → IVC → RA

• 3rd: common carotid artery and proximal part of internal carotid artery
• 4th: Aortic arch and proximal part of right subclavian
• 6th: proximal part of pulmonary arteries and ductus arteriosus

• Right-to-left shunts: Blue babies
• The 5 T's:
• -Tetralogy of Fallot (most common cause of early cyanosis)
• -Transposition of great vessels
• -Persistent Truncus arteriosus - failure of truncus arteriosus to divide into pulmonary trunk and aorta; post patients have accompanying VSD
• -Tricuspid atresia: absence of tricuspid valve and hypoplastic RV; requires both ASD and VSD for viability
• -Total anomalous pulmonary venous return (TAPVR): pulmonary veins drain into right heart circulation (SVC, coronary sinus, etc.); associated with ASD and sometimes PDA to allow for right-to-left shunting to maintain CO

• Left-to-right shunts: Blue kids
• -VSD (most common congenital cardiac anomaly)
• -ASD (loud S1, wide, fixed split S2)
• -PDA (close with indomethacin)

Frequency: VSD > ASD > PDA

• Associated with maternal lithium use
• Tricuspid leaflets are displaced into right ventricle, hypoplastic right ventricle, tricuspid regurg or stenosis
• 80% have a patent foramen ovale with R → L shunt
• Dilated right atrium → increased risk of SVT and WPW
• PE: widely split S2, tricuspid regurg
• Rx: PGE, digoxin, diuresis, propranolol for SVT

• Uncorrected VSD, ASD, or PDA causes compensatory pulmonary vascular hypertrophy
• Pulmonary vascular hypertrophy → Pulmonary HTN → right ventricle hypertorphy
• ↑ Pulmonary resistance → reversal of shunt from left-to-right to right-to-left
• Causes late cyanosis, clubbing, polycythemia

• TOF is caused by anterosuperior displacement of the infundibular septum
• Larger aorta side, smaller pulmonary side

• PROVe:
• 1. Pulmonary infundibular stenosis (most important determinant for prognosis)
• 2. RVH
• 3. Overriding aorta (overrides the VSD)
• 4. VSD

• Early cyanosis ("tet spells") caused by a right-to-left shunt across VSD (isolated VSD usually flow left-to-right... acyanotic)
• - Pulmonary stenosis forces R-to-L shunt (cyanotic) and causes RVH

• Older patients learn to squat to relieve cyanotic symptoms
• -Squatting reduces blood flow to legs, ↑ peripheral vascular resistance → ↓ cyanotic R-to-L shunt across VSD

Tx: early surgical correction

• Aorta leaves RV (anterior)
• Pulmonary trunk leaves LV (posterior)
• →separation of systemic and pulmonary circulations
• **Not compatible with life, unless shunt is present to allow adequate mixing of blood (VSD, PDA, or patent foramen ovale)
• Due to failure of aorticopulmonary septum to spiral
• Lethal without surgery in first few months of life

Failure to divide spiral septum

• Absent tricuspid valve
• hypoplastic right ventricle
• **Requires both ASD and VSD for viability

Can result in aortic regurgitation

• Infantile type: aortic stenosis proximal to insertion of ductus arteriosus (preductal)
• -Associated with Turner syndrome
• **Infantile: in close to the heart
• -Check femoral pulses on physical exam

• Adult type: stenosis is distal to ligamentum arteriosum (postductal)
• -Associated with notching of the ribs (due to collateral circulation)
• -Most commonly associated with bicuspid aortic valve
• -Hypertension in upper extremities
• -Weak pulses in lower extremities
• **Adult: distal to ductus

• Fetal period: right-to-left shunt (normal in utero, should close after birth <24hrs)
• Neonatal: lung resistance ↓ and shunt becomes Left-to-right, which leads to RVH and/or LVH and failure (abnormal)
• -Associated with continuous, "machine-like" murmur
• -Patency is maintained by PGE synthesis and low O2 tension

Uncorrected: PDA eventually results in late cyanosis in the lower extremities (differential cyanosis)

• **Endomethacin (indomethacin) ends patency of PDA
• **PGE kEEps it open (may be necessary to sustain life in pts with transposition of great vessels)

• 22q11 syndromes (DiGeorge is one): Truncus arteriosus, tetralogy of Fallot
• Down syndrome: ASD, VSD, AV septal defect (endocardial cushion defect)
• Congenital rubella: Septal defects, PDA, pulmonary artery stenosis
• Turner syndrome: Coarcation of aorta (preductal)
• Marfan's syndrome: Aortic insufficiency and dissection (late complication)
• Infant of diabetic mother: Transposition of great vessels

• Adult coarctation of the Aorta 
• -notching of ribs
• -postductal

Ductus arteriosus (in utero) has different flow: Right to left (bypass pulmonary circulation)

• PDA: low pressure on the Right; so you get a Left-to-Right shunt
• -Aortic to pulmonic artery

• Chrom 22q11 deletions: Truncus arteriosus, ToF
• Down Syndrome: Endocardial cushion defect (ASD, VSD, AV septal defect)
• Congenital rubella: Septal defects, PDA, pulmonary artery stenosis
• Turner's syndrome: Coarcation of aorta (preductal)
• Marfan's syndrome: Aortic insufficiency

• Transposition of great vessels
• Hypoglycemia
• Large for gestagional age: clavical fractures, Erb-Duchenne palsy, Shoulder dystocia, failure to progress during labor