Transposition of the Great Arteries Eric Osborn January 27, 2010

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

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

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

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

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

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

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.

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

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 11.22 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

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 13-14 weeks (limited views) Transabdominal ultrasound at 16 weeks Antenatal detection rates between 20-70%. *not including bicuspid aortic valve and mitral valve prolapse

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 61-25 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

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

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.

Complete transposition (D-TGA) Atrial switch (Mustard/Senning) Developed in the 1950s Baffle directs venous return to contralateral ventricle Fig 61-23 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.

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

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

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

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

Complete transposition (D-TGA) Arterial switch Developed in the 1980s Great arteries and coronaries are transected and re-anastamosed Fig 61-24 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.

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

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

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

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 61-27 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

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.

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

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

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

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

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

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

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

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

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

Endocarditis Prophylaxis

References Webb et al., Congenital Heart Disease in Braunwald’s Heart Disease, 8th ed., Chapter 61, 1561-1624. Sadler, Cardiovascular System in Langman’s Medical Embryology, 8th ed., Chapter 11, 208-259. Otto, The Adult with Congenital Heart Disease in Clinical Echocardiography, 4th ed., Chapter 17, 418-447. Warnes, Transposition of the Great Arteries, Circulation 2006 114:2699-2709. 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 2008 5:454-67. Verhuegt et al., Long-term Prognosis of Congenital Heart Defects: A Systematic Review, Int J Cardiol 2008 131:25-32. Skinner et al., Transposition of the Great Arteries: from Fetus to Adult, Heart 2008 94:1227-35 ACC/AHA Guidelines for the Management of Adults with Congenital Heart Disease, J Am Coll Cardiol 2008 52:e1-121.