Abstract 292: Maternal Transfer of Anti-Cardiac Myosin Antibody Induces Dilated Cardiomyopathy and Underdevelopment of Aortic Arch in Newborn Rats

Introduction: Anti-cardiac myosin (CM) antibodies are induced following certain infectious diseases. We evaluated for the first time the effect of maternally-transferred anti-CM antibody on the newborn heart in a rat model. Methods: Female Lewis rats were immunized with 1 µg of emulsified CM and boosters (0.5 µg) were administered every 2 weeks, followed by mating; control rats (n=3) were injected with saline. After birth, pups were continually housed with dams. Echocardiography was performed on pups on day 20. Pups were sacrificed on day 21 and hearts were fixed, sectioned, and analyzed for morphological changes. Trichrome staining was performed to detect fibrotic changes. Results: All the pups in CM group (n=22) showed anti-CM antibody titers of more than 12800. Echocardiographic study revealed that 45.4% (10/22) of pups in the CM group had evidence of decreased left ventricular systolic function. The affected pups had both thinner anterior and inferior left ventricle walls compared with pups in control group (3.43±0.33 vs. 3.82±0.24, p=0.017 and 3.71±0.32 vs. 4.18±0.31, p=0.009 respectively). There were also evidence of underdevelopment of thoracic aorta and aortic arch (3.1±0.16 vs. 3.3±0.16 for ascending aorta diameter, p=0.002 and 2.6±0.14 vs. 2.8±0.25 for descending aorta diameter, p=0.008). Morphological changes consistent with dilated cardiomyopathy (image) and fibrosis were detected. Conclusion: Maternal anti-CM antibodies can cross the placenta and affect the development of the newborn heart; the resulting phenotype is one of dilated cardiomyopathy with associated hypoplasia of vascular structures perhaps secondary to reduced flow.