Double Outlet Right Ventricle With Transposition Clinical Presentation
- Author: M Silvana Horenstein, MD; Chief Editor: P Syamasundar Rao, MD more...
History of fetal bradycardia heart block during the first trimester of pregnancy has been associated with double outlet right ventricle (DORV), as opposed to autoimmune causes of fetal heart block, which occur after the second and third trimesters. Fetal heart block can be diagnosed ultrasonographically depending on the subtype of DORV (eg, with or without transposition of the great arteries); clinical history differs. In patients with DORV and transposition of the great arteries, the clinical presentation depends on the location of the ventricular septal defect (VSD) and the presence of pulmonary valve stenosis (PS), the degree of PS, or both.
If the VSD is subpulmonic, the physiology resembles that of transposition of the great arteries with VSD. Patients with this anatomy usually present in the newborn period or within the first few weeks of life with cyanosis and signs of pulmonary overcirculation.
If the VSD is subaortic, the patient may be only mildly cyanotic and may present primarily with pulmonary overcirculation at 3-6 weeks of life when pulmonary vascular resistance drops. If PS is present, which is often the case in DORV with subaortic VSD, the degree of PS greatly affects clinical presentation.
If PS is mild or moderate, the patient may present with mild cyanosis and little or no pulmonary overcirculation. If PS is severe, clinical presentation resembles that of tetralogy of Fallot (TOF). Cyanosis from diminished pulmonary blood flow (PBF) is likely to be the major clinical feature.
In patients with DORV and transposition of the great arteries (both uncommon lesions), the VSD may be doubly committed or remote from the great arteries. If the VSD is doubly committed, the conus septum is deficient and the VSD usually lies above the crista supraventricularis, closely related to both semilunar valves. Clinical presentation is often that of DORV with a subpulmonic VSD, although the patient may have slightly higher systemic oxygen saturation.
In DORV with transposition of the great arteries and remote VSD, many variables determine clinical presentation. If the VSD is remote from both semilunar valves, it is often part of an AV canal-type defect, in which case many other anomalies are likely.
Alternatively, multiple muscular VSDs may be remote from the semilunar valves. Clinical presentation depends on factors such as the location of the VSDs, the presence or absence of PS (right ventricular outflow tract obstruction), and the direction of streaming of blood flow through VSDs.
Physical findings vary, depending on the location of the VSD and the presence or absence of PS.
With a subaortic VSD and no PS, cyanosis is mild or absent. PBF is increased, thereby producing congestive heart failure (CHF). The precordium is hyperactive with a loud second heart sound, which may appear to be single. Harsh regurgitant systolic murmur is heard as pulmonary vascular resistance decreases. Clinically, these patients resemble those with a large VSD.
In DORV with subaortic VSD and PS, physical findings depend on the degree of PS. If PS is mild, little cyanosis and only mild CHF may be present. These patients present with a murmur from PS (systolic ejection murmur), from the VSD (regurgitant murmur), or both. If PS is moderate or severe, cyanosis is prominent because of decreased PBF (resembling TOF). If uncorrected, cyanosis leads to late findings such as polycythemia and digital clubbing.
In those patients with subpulmonic VSD (PS is rare in these patients), PBF increases as vascular resistance falls. These patients present similarly to those with transposition of the great arteries and VSD. Cyanosis is prominent early, and pulmonary overcirculation develops. Failure to thrive is likely to develop if treatment is not instituted. The second heart sound is loud and possibly single, and a regurgitant systolic murmur develops. If increased pulmonary vascular resistance occurs, signs of CHF diminish and the murmur decreases. An ejection click may appear along with a diastolic murmur of pulmonary valve insufficiency (late findings).
Patients with doubly committed VSD also present similarly to those with transposition of the great arteries and VSD. Cyanosis may be mild. Signs of CHF, including tachypnea, tachycardia, and hepatomegaly, lead to failure to thrive.
DORV is thought to be the result of a malformation in the outlet portion of the embryonic ventricular loop at 3-4 weeks' gestation. Although mostly sporadic, familial cases have been reported.
Fluorescence in situ hybridization (FISH) analysis has shown deletions in the 22q11.2 region in certain individuals with TOF, DORV, transposition of the great arteries, and VSD associated with other congenital heart disease (CHD).[3, 4, 5] As a matter of fact, DORV may be part of complex CHD in patients with DiGeorge syndrome, velocardiofacial syndrome, and conotruncal anomaly–face syndrome.
DORV has also been associated with trisomies 13 and 18 and tetrasomy 8p.
DORV has also been reported in patients with mutations in human cardiac transcription factor NKX2.5.
DORV, truncus arteriosus (TA), atrial septal defect (ASD), atrioventricular septal defect (AVSD), ventricular septal defect (VSD), transposition of the great arteries (TGA), and tetralogy of Fallot (TOF) occur with a higher incidence in the offspring of mothers with pregestational diabetes mellitus than in the general population. Teratogenic mechanisms involved are thought to be related to increased reactive oxygen species production, impaired cell proliferation, and altered Gata-4, Gata-5, and vascular endothelial growth factor (VEGF)–α expression. According to research studies in pregnant diabetic rats, antioxidant supplementation with vitamin E reduced the severity of malformations in their offspring and supplementation of their drinking water with N -acetylcysteine eliminated the incidence of AVSD, TOF, and TGA and decreased the incidence of ASD and VSD.
DORV has been reported to occur in mouse embryos homozygous for the JMJ mutation, which affects the nuclear protein jmj coded by chamber-specific genes.
Studies using animal models described a transcription factor that plays a critical role in directing cardiac asymmetric morphogenesis, known as Pitx2. Specifically, ectopic Pitx2c expression in the developing myocardium was found to correlate with the development of DORV. Whereas loss of function of the Pitx2 caused atrial isomerism, double inlet left ventricle, transposition of the great arteries, persistent truncus arteriosus, and abnormal aortic arch remodeling.
Most recently, hearts with persistent truncus arteriosus, DORV, and transposition of the great arteries, have been postulated to have rotation of the myocardial wall of the outflow tract that is arrested or fails to initiate. This is supported by the discovery that mutations in the NPHP4 gene involved in the formation of motile cilia in the Kupffer vesicle, which produce asymmetrical fluid flow necessary for normal left-to-right asymmetry, cause laterality defects such as dextrocardia, transposition of great arteries, DORV, and caval vein abnormalities.
In synthesis, the pathogenesis of DORV is currently believed to include impairment of neural crest–derivative migration and impairment of normal cardiac situs and looping.
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