Abstract 16914: Structural and Functional Investigation of Myocardial Fiber Architecture in Genetic Mouse Models of Heterodoxy and Situs Inverses Totalis

Introduction: Heterotaxy (HTX) patients with congenital heart disease have higher risk of post-surgical complications and increased morbidity and mortality. Given HTX involves disruption of left-right patterning, this suggests laterality disturbance may drive the poor outcome in CHD patients with HTX. To investigate this, we used mouse models with laterality defects. Although HTX mutant mice invariably die prenatally/neonatlly from complex CHD, many mutations causing HTX also giive rise to mice that are adult viable with situs inversus totalis (SIT), or situs solitus (SS) without CHD. Hence, our goal is to delineate myocardial fiber architecture in the SIT and SS mutant mice to gain insights into possible functional deficits associated with HTX. Hypothesis: Disturbance in specification of laterality results in abnormal myocardial fiber architecture that can cause cardiac dysfunction and make the heart more vulnerable to stress. Methods: Diffusion tensor imaging (DTI) was used to delineate the myocardial fiber organization in SIT and SS mutant mice, and wild-type (WT) control mice. Cardiac MRI and echocardiography were used to evaluate cardiac function with or without dobutamine stress. Results: Echocardiography showed no significant differences in global systolic function in the SIT and SS mutant hearts, but they displayed compromised strain rates under dobutamine stress. SIT and SS hearts also exhibited reduced rotation and torsion, suggesting altered myocardial fiber organization. Myocardial tractography by DTI (Fig.A-D) showed less coherent myocardial fiber organization (Fig. G-I) and more diverse helix angles (Fig. K&M) in SIT mutant hearts. Overall, our data showed the mutant SS and SIT hearts have disrupted myocardial fiber architecture resulting in abnormal torsion, rotation, and strain when stressed. Conclusions: These findings suggest abnormal myocardial architecture may contribute to the poor clinical outcome in HTX patients with CHD.