Congenital heart defects in the context of heterotaxy are severe, with a complex anatomy. These defects are described using the binary concept of clinical loop (D-Loop or L-Loop), which implies that ventricle position is determined during heart looping. Recent work in the mouse has shown unexpected plasticity of ventricle position after heart looping. Based on a analysis of Nodal mutants with heterotaxy and right bronchus isomerism, 27% of D-Loop mutants at birth underwent leftward embryonic heart looping. These mice with a revertant loop, all display abnormal ventricle position.

Analysis of 3D ventricle position in human patients with heterotaxy and right bronchus isomerism, using the strategy developed in the mouse based on the 3D orientation of the interventricular septum.

Constitution of an heterotaxy cohort from the Necker database. Controls were selected as patients with transposition of the great arteries who had a systematic CT scan at 6 years. Three dimensions reconstructions of CT scans and quantitative analyses were performed using the Imaris software.

Control patients had their right ventricle-left ventricle axis in the expected anteroposterior and left-right orientation. We collected 506 patients with heterotaxy syndrome, 186 of whom had CT scan. Forty patients had right bronchial isomerism. Among them, we found 29 (72%) patients who had an orientation of the interventricular septal axis similar to control, 7 (18%) patients with abnormal supero-inferior ventricles and 4 (10%) patients with abnormal left-right ventricles (Fig. 1). In total, 32% of patients in D-Loop have a malpositioned interventricular septum whereas 0 of patients in L-Loop.

There is a high proportion of malpositioned ventricles in patients with D-Loop (32%), similar to what is observed in Nodal mouse mutants. This result supports conserved mechanisms in the mouse and human, including plasticity of ventricle position after heart looping.