What embryologic defect causes double outlet right ventricle and what are its resulting anatomic and physiologic consequences?

Embryologic Pathophysiology of Double Outlet Right Ventricle

Embryologic Defect

DORV results from failure of the embryonic conotruncus to properly incorporate into the left ventricle, causing both great arteries to arise predominantly or entirely from the morphologically right ventricle. 1

The fundamental embryologic abnormality occurs during weeks 5-8 of development when the conotruncal region undergoes septation and alignment. 1 Specifically:

• The secondary heart field, which normally contributes to the right ventricle and outflow tract, fails to properly align with the left ventricle 1
• The aorticopulmonary septum must fuse with the endocardial cushions and muscular interventricular septum to form the membranous septum—this process is disrupted in DORV 1
• Experimental models demonstrate that preventing incorporation of the posteromedial conus into the left ventricle during stages 17-22 of embryonic development consistently produces DORV 2

Three Distinct Embryologic Mechanisms

The pathogenesis varies based on which embryologic structure fails:

• Conotruncal type: Abnormal development of the outflow tract derivatives (great arteries and subpulmonary ventricular septum) 3
• Conoventricular type: Malformation of the conoventricular flange (crista prima) 3
• Atrioventricular type: Abnormal orientation of the tricuspid orifice axis, causing the muscular ventricular septum to connect abnormally to the left portion of the conus septum rather than the right 3

Anatomic Consequences

Ventriculoarterial Connection Abnormality

• Both the aorta and pulmonary artery arise from the morphologically right ventricle, with loss of normal fibrous continuity between the mitral valve and semilunar valves 4, 5
• The relationship between the ventricular septal defect (VSD) and great arteries determines the specific anatomic subtype 4, 5
• A double conus (bilateral infundibulum) is typically present, separating both semilunar valves from the atrioventricular valves 6

VSD Position Variants

The VSD location creates distinct anatomic subtypes with different surgical implications:

• Subaortic VSD: The defect is positioned beneath the aortic valve, allowing potential for intraventricular tunnel repair 4
• Subpulmonary VSD: The defect is beneath the pulmonary valve (Taussig-Bing variant) 7
• Doubly committed VSD: The defect relates to both great arteries 4
• Noncommitted (remote) VSD: The defect is distant from both arterial valves by more than one aortic diameter, representing the most primitive form where the entire conotruncus remains with the right ventricle 6

Septal Malalignment

• The subarterial portion of the ventricular septum may be oriented in a frontal plane anterior to both great arteries rather than the normal oblique plane between them 8
• This creates separation of the right ventricular infundibulum from both great vessels and lack of continuity between the malpositioned septum and the semilunar valve level 8
• The septation of the conotruncus involves at least two different septa—one dividing the conus and another dividing the truncus arteriosus 8

Physiologic Consequences

Hemodynamic Derangements

• Obligatory mixing of systemic and pulmonary venous return occurs at the ventricular level through the VSD, resulting in variable degrees of cyanosis depending on pulmonary blood flow 4, 5
• The physiologic presentation depends critically on the presence and severity of right ventricular outflow tract obstruction 4

RVOT Obstruction Present

• Reduced pulmonary blood flow leads to significant cyanosis 4
• Physiology resembles tetralogy of Fallot with right-to-left shunting predominating 4

RVOT Obstruction Absent

• Excessive pulmonary blood flow occurs with left-to-right shunting 4
• Congestive heart failure symptoms develop in infancy 4
• Progressive pulmonary vascular disease may develop if untreated, requiring periodic screening with transthoracic echocardiography 5

Left Ventricular Outflow Considerations

• DORV patients carry substantially higher risk of residual left ventricular outflow tract obstruction compared to standard tetralogy of Fallot, even after surgical repair 4, 5
• This occurs because the intraventricular tunnel created during repair may cause subaortic obstruction, particularly when the VSD is distant from the aorta 6

Right Ventricular Volume and Pressure Overload

• The right ventricle must handle the entire cardiac output from both ventricles 1
• Chronic volume overload from the VSD shunt leads to RV dilation 1
• If RVOT obstruction exists, pressure overload compounds the hemodynamic burden 4

Pulmonary Vascular Disease Risk

• Patients with unrestricted pulmonary blood flow develop elevated pulmonary vascular resistance, with collaborative assessment required when PVR ≥2.5 Wood units 4, 5
• Cardiac catheterization is indicated when clinical symptoms, signs, or echocardiographic findings suggest pulmonary hypertension 5

Common Pitfalls

• Failing to recognize that DORV is fundamentally an infundibular malformation rather than simply abnormal great artery position 2
• Underestimating the risk of subaortic obstruction after intraventricular tunnel repair, which exceeds that seen in standard tetralogy of Fallot 4, 5
• Not appreciating that the crista supraventricularis in the normal heart and the infundibular septum in DORV are anatomically and embryologically distinct structures 2