1. Transposition of the Great Arteries
Eric Osborn
January 27, 2010

2. Outline Definitions Embryology Epidemiology
Complete transposition (D-TGA)
Congenitally corrected transposition (L-TGA)
Echocardiography
Types of repairs and outcomes

3. Definitions
The key anatomic characteristic of transposition complexes is ventriculoarterial discordance.
The aorta arises from the morphological RV
The PA arises from the morphological LV

4. Definitions Complete transposition (D-TGA)
Atrioventricular concordance
D=dextro
RV is on the right and anterior = systemic ventricle
Aorta is to the right and anterior
Great arteries are parallel rather than crossing
TV = systemic AV valve because always associated with the morphological RV

5. Definitions Congenitally corrected transposition (L-TGA)
Atrioventricular discordance
L = levo
RV is to the left and posterior = systemic ventricle
Aorta is on the left and anterior
Great arteries may be side-by-side
TV = systemic AV valve because always associated with the morphological RV

6. Embryology 22 days gestation …
the primitive straight cardiac tube is formed
Composed of 5 chambers with patterning regulated by homeobox genes
Truncus = aorta and pulmonary artery
Bulbis = outflow tracts and ventricle

7. Embryology
23 days gestation … the straight cardiac tube elongates and bends forming the cardiac loop.
Cephalic portion bends ventrally, caudally, and right-ward.
Caudal portion moves dorsally, cranially, and left-ward.
The rotational motion folding over of the bulboventricular portion bringing the future ventricles side-by-side.
Fig 11.6 Langmans
This process is completed by 28 days.
Normal rightward rotation of the tube results in the normal D configuration with the RV anterior and to the right – AV concordance
Left-handed looping of the heart tube leaves the morphologic RV posterior and to the left – AV discordance

8. Embryology
4th-7th weeks gestation … the heart divides into 4 chambers via formation of swellings (cushions) of tissue that exhibit differential growth.
Endocardial cushions divide the AV canal forming the mitral and tricuspid valves.
Conotruncal cushions form the outflow tracts, aortic and pulmonary roots.

9. Embryology 5th week gestation … the conotruncal cushions.
Right superior truncal cushion grows distally and left-ward.
Left inferior truncal cushion grows distally and right-ward.
The net effect is a twisting motion.
The truncal cushions fuse to form the truncal septum.
Additional cushions develop in the conus which grow down and towards each other until they fuse with the truncal septum to form the RVOT and LVOT.
RVOT (anterolateral) and LVOT (posteromedial)
The subpulmonic conus elongates and the subaortic conus resorbs, allowing the aorta to move posteriorly and connect with the left ventricule

10. Embryology Mechanism of great artery transposition
Conotruncal cushion defect
Leads to failure of the conotruncal septum to spiral and instead extends straight downward
Aorta fuses with the RV and PA with the LV
Fig Langmans
Conotruncal cushion defect of neural crest cells
Truncus = aorta and pulmonary trunks
Conus = aortic and pulmonary outflow tracts
Resorption of the subpulmonic instead of the subaortic conus may be central to TGA

11. Epidemiology
~0.8% of live births are complicated by a cardiovascular malformation*.
>750,000 adult patients with congenital heart disease.
Transposition of the great arteries occurs in approximately 1 per 5,000 live births.
More common in males
Diagnosis possible in utero with fetal echocardiography
Transvaginal ultrasound at weeks (limited views)
Transabdominal ultrasound at 16 weeks
Antenatal detection rates between 20-70%.
*not including bicuspid aortic valve and mitral valve prolapse

12. Complete transposition (D-TGA)
Pulmonary and systemic circulations are in parallel
Lethal, if no mixing (ASD, PDA, VSD)
¾ are simple with no major associated abnormalities
¼ are complex
VSD (16%)
Pulmonary/subpulmonary stenosis (9%)
Coarctation of the aorta (4%)
Fig in Braunwalds shows parallel configuration (path/echo) of PA and Ao
Nearly all have an intraatrial connection, 2/3 with PDA, and 1/3 with VSD
The amount of mixing determines the systemic oxygen saturation and thus the clinical course
Small PFO or PDA with intact septum are most severely hypoxemic and cyanotic; similarly LVOT obstruction
Large PDA or VSD may result in minimal cyanosis, but they develop heart failure in the first few weeks of life

13. Complete transposition (D-TGA) Clinical Presentation and Outcomes
Larger size and weight at birth
Dyspnea and cyanosis
Progressive hypoxemia
Congestive heart failure
Without treatment, the outlook is dismal
30% mortality within the 1st week
90% mortality within the 1st year

14. Complete transposition (D-TGA) Management
Prostaglandin E1 to maintain the PDA
Atrial septostomy (balloon or surgical)
Palliative prior to corrective surgery
Repair within the first days to weeks of life
2-4% mortality with 90% 1 year survival
Atrial switch
Mustard or Senning
Arterial switch
Rastelli procedure
PGE1 does not enhance mixing at the PDA, but maintains its patency and dilates the pulmonary bed increasing pulm blood flow/LA pressure to enhance transatrial mixing.
Septostomy can palliate for >1 year in some cases prior to requiring surgical correction.

15. Complete transposition (D-TGA) Atrial switch (Mustard/Senning)
Developed in the 1950s
Baffle directs venous return to contralateral ventricle
Fig from Braunwald or Fig 1 Love
Estimated to be ~9000 atrial switch adult patients currently alive in the US
Blood is redirected via baffles made of atrial flaps (Senning) or Dacron or pericardium (Mustard)
Described in one paper as complicated ‘origami-style’ cutting and folding of tissues.
Systemic venous return is directed to the lungs and oxygenated pulmonary venous return to the periphery.
The RV functions as the systemic ventricle; the LV pumps blood to the lungs.
Both Senning and Mustard tried to switch the great arteries but were unsuccessful primarily due to transposing the coronaries.

16. Complete transposition (D-TGA) Atrial switch (Mustard/Senning)
Disadvantages
RV functions as the systemic ventricle
Several significant long term complications
Congestive heart failure
Arrhythmias
Baffle leaks and obstruction
Pulmonary hypertension
Paradoxial embolus
Endocarditis
Overall survival 75% at 25 years
Senning may be better than Mustard [Moons et al, Heart 2004]
340 patients (~⅔ Senning) compared
Less obstruction (1 vs. 15%) and better functional class with Senning
No significant mortality benefit
Excellent midterm results, but multiple longterm complications
Fig 4 from Love et al, Nature

17. Complete transposition (D-TGA) Atrial switch (Mustard/Senning) Arrhythmias
Palpitations, presyncope, and syncope are not uncommon
Both brady and tachyarrythmias frequently seen
50% develop sinus node dysfunction
Physical damage during surgery and baffle construction
Disruption of blood supply leading to ischemia
20% develop atrial flutter
Sensitive to nodal agents due to conduction system disease
11% required pacemakers at 20 years [Gelatt et al, J Am Coll Cardiol 1997]
Pacemakers are difficult to place due to distorted anatomy
Should be avoided if residual intracardiac communications due to risk of paradoxical embolus and stroke
Predominately atrial conduction disorders until more develop ventricular failure
Scar lines across the atrium are substrate

18. Complete transposition (D-TGA) Atrial switch (Mustard/Senning) Congestive heart failure
Most adult patients develop congestive heart failure
By 20 years most are NYHA Class I or II
RV filling compromised due to defects in baffle construction
Baffle leaks (Mustard>Senning)
Left-to-right shunts with pulmonary hypertension (7%)
Risk of paradoxical embolus and stroke
Indications for intervention include >1.5:1 left-to-right shunt or any right-to-left shunt
Baffle obstruction (5-15%, Mustard>Senning)
SVC>IVC manifesting as SVC syndrome or hepatic congestion/cirrhosis
Often undetected due to collateral venous drainage (e.g. azygous vein)
40% develop right ventricular dysfunction
10-40% develop 2+ or greater tricuspid (systemic AV valve) regurgitation
Annular dilatation from RV failure
Damage from surgery or endocarditis
?RV ischemia plays role in dysfunction

19. Complete transposition (D-TGA) Suggested Follow-up
Table 1 Love, Nature

20. Complete transposition (D-TGA) Arterial switch
Developed in the 1980s
Great arteries and coronaries are transected and re-anastamosed
Fig from Braunwald; first reported by Jatene (1976) now the procedure of choice for transposition repair
Arterial trunks are transected and reanastamosed to the proper root positions (aorta brought under the PA bifurcation).
VSDs are closed during the operation.
Coronary arteries are excised along with a button and transposed; this is the most challenging portion of the procedure and accounts for most mortality (<2% at most centers).
LV is the systemic pump; RV pumps to the lung; maintanance of sinus rhythm.

21. Complete transposition (D-TGA) Arterial switch
Advantages
LV is the systemic pump
No disruption of atrial conduction (sinus rhythm)
Fewer long term complications compared to atrial switch
Coronary ostial stenosis
Supravalvular pulmonary/aortic stenosis
Intervention indicated for RVOT gradient >50 mmHg
Neoaortic regurgitation
Arrhythmias
Follow up with normal LV function and good exercise capacity
Normal examination in uncomplicated patients
Outcomes for adults just starting to be realized but appear favorable
Less arrythmias than atrial switch procedure
Coronary patency and growth are not generally impacted

22. Complete transposition (D-TGA) Rastelli procedure
TGA with VSD and LVOT obstruction
Outcomes
RV-PA conduit obstruction
Exercise intolerance/angina
RV failure
Intervention for RV-PA
gradient >50 mmHg
LV-Ao patch obstruction
Dyspnea or syncope
Circ 2006 Fig 3
VSD is patched to allow LV outflow to the aorta
Pulmonary valve is oversown and a synthetic valved bypass graft is placed from the RV to the PA to bypass the pulmonary stenosis
LV is systemic ventricle but conduit replacement is inevitable, requiring re-operation

23. Complete transposition (D-TGA) RV Failure after Atrial Switch
Standard heart failure therapies are unproven
The two-stage arterial switch
Stage 1 – the PA is banded to ‘re-train’ the LV to handle systemic pressures
Stage 2 – the atrial baffles and pulmonary band are taken down and an arterial switch is performed
50% survival at 8 years in early results
Appears to be more successful in patients under 12
As more patients with atrial switch reach adulthood and develop severe RV failure +/- severe TR, additional interventions may be necessary
Medical management with standard heart failure therapies is unproven
Two-stage switch still experimental in adults
Pulmonary banding allows ‘retraining’ of the LV
Early results – 50% survival at 8 years

24. Congenitally corrected transposition (L-TGA)
A rare disorder that may present in adulthood.
Associated anomalies (95% of patients)
VSD (75%, commonly perimembranous)
Pulmonary stenosis (75%, commonly subvalvular)
Tricuspid valve anomalies (>75%)
Congenital complete heart block (5%)
Fig in Braunwalds
TV anomalies similar to Ebsteins with apical displacement but leflet structure often distinct
In the absence of associated anomalies (isolated L-TGA) patients live normal life span

25. Congenitally corrected transposition (L-TGA) Outcomes
Arrhythmias
Abnormal AV node and His positions
Dual AV nodes
2% per year incidence of complete heart block
Susceptible to fibrosis of conduction system
Median survival 40 years
Mortality from progressive RV failure or arrhythmias
Tricuspid regurgitation is major predictor
Coronary anatomy is concordant, and therefore the systemic RV is supplied by the single RCA.

26. Congenitally corrected transposition (L-TGA) Double Switch Procedure
Traditionally only fixed associated congenital defects leaving RV as systemic ventricle
Double switch procedure uses atrial and arterial switch to restore the LV as the systemic pump
As with the two-stage arterial switch, the PA must be banded to ‘re-train’ and hypertrophy the LV prior to surgery
Decreases the incidence of TR and RV failure which lead to death

27. Echocardiography Segmental approach to congenital heart disease
Position of the apex
Situs of the atria
Morphological atria based on anatomic appearance of their appendages
75% concordance with abdominal situs (aorta and IVC positions)
Atrioventricular relationship
Differentiate the morphological RV from LV:
Trabeculated apex
Moderator band
Septal attachment of the tricuspid valve
Lower (apical) insertion of the tricuspid valve
Ventriculoarterial relationship
Pulmonary artery is distinguished by its early branching pattern
Curved contour of the aortic arch with three major branches
Standard subcostal view with the probe 90° to spine
Solitus = aorta on left and IVC on right, inversus is opposite
Tricuspid valve is always attached to the morphological RV (similarly mitral valve with morphological LV); Pulmonary valve always with PA (similarly aortic valve with Ao)
Following segmental analysis, move to usual echo windows

28. Echocardiography Complete Transposition with Atrial Switch
Hallmark is parallel great arteries (parasternal long axis)
Aorta is anterior to PA

29. Echocardiography Complete Transposition with Atrial Switch
Systemic hypertrophied RV septum bows into LV
May impact TR and enhance subpulmonary stenosis
Fig 5 Love, short axis echo of patient with TGA following atrial switch – bowing of RV septum towards LV – can worsen TR and increase subpulmonary stenosis

30. Echocardiography Complete Transposition with Atrial Switch
Aortic and pulmonic valves lie in the same plane
Aorta is anterior and to the right (parasternal short axis)
Also cardiac apex points to the left

31. Echocardiography Congenitally Corrected Transposition
Hallmark is reversed offsetting of the AV valves
Aorta is anterior and to the left (parasternal short axis)
Close evaluation of ventricular morphology shows systemic ventricle with apically displaced AV valve
Great vessels are parallel as in D-TGA
Cardiac apex points to the right which may cause poor windows due to shadowing from the sternum

32. Echocardiography Special Considerations
Atrial switch
RV function
Tricuspid regurgitation
Subpulmonary obstruction
Baffle leak or obstruction (color Doppler)
Normal baffle flow is phasic with peak velocity <1 m/sec
Arterial switch
Neoaortic valve regurgitation
Supraneopulmonary valve stenosis
Wall motion abnormalities due to coronary artery ostial stenosis
Rastelli procedure
LV-Ao tunnel patch obstruction
RV-PA conduit degeneration (stenosis/regurgitation)
Normal baffle flow is phasic with respiratory variation, and peak velocity < 1m/sec

33. Echocardiography Special Techniques
Index of myocardial performance
dP/dT from tricuspid regurgitant velocity
Isovolumic myocardial acceleration
Tissue Doppler measurement of myocardial acceleration during isovolumic contraction
?sensitive assessment of RV contractility that is less load dependent
Normal baffle flow is phasic with respiratory variation, and peak velocity < 1m/sec

34. Endocarditis Prophylaxis
ACC/AHA 2008 Guidelines state that antibiotic prophylaxis is reasonable to consider for patients at the highest risk of adverse outcomes (Class IIa)
Prosthetic valves
Prior endocarditis
Congenital heart disease
Unrepaired cyanotic, including palliative shunts and conduits
Completely repaired with prosthetic material or device (6 months)
Repaired with defects at or near a prosthetic device
Post-cardiac transplant with valvular disease
There are no Class I indications
*endothelialization

35. Endocarditis Prophylaxis

36. References
Webb et al., Congenital Heart Disease in Braunwald’s Heart Disease, 8th ed., Chapter 61,
Sadler, Cardiovascular System in Langman’s Medical Embryology, 8th ed., Chapter 11,
Otto, The Adult with Congenital Heart Disease in Clinical Echocardiography, 4th ed., Chapter 17,
Warnes, Transposition of the Great Arteries, Circulation :
Love et al., Evaluation and Management of the Adult Patient with Transposition of the Great Arteries Follow Atrial-level (Senning or Mustard) Repair, Nature Clinical Practice Cardiovasc Med :
Verhuegt et al., Long-term Prognosis of Congenital Heart Defects: A Systematic Review, Int J Cardiol :25-32.
Skinner et al., Transposition of the Great Arteries: from Fetus to Adult, Heart :
ACC/AHA Guidelines for the Management of Adults with Congenital Heart Disease, J Am Coll Cardiol :e1-121.