[Fetal Heart Failure: Exploring Diagnosis and Treatment Strategies]

It is difficult to appropriately diagnose the severity of fetal heart failure using only ultrasonography. Biomarkers of fetal heart failure in the fetal blood, amniotic fluid, and maternal blood have not been established. Therefore, we investigated natriuretic peptides (NPs) such as Atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and N-terminal proBNP (NT-proBNP) in umbilical cord blood and amniotic fluid in cases of fetuses with congenital heart disease, and investigated whether maternal serum biomarkers could diagnose fetal heart failure. The features of NPs in the umbilical cord blood and amniotic fluid provide a strong basis for their use as biomarkers of fetal heart failure. Maternal serum concentrations of tumor necrosis factor (TNF-α), vascular endothelial growth factor-D (VEGF-D), and heparin-binding epidermal growth factor-like growth factor (HB-EGF) can be used to assess fetal heart failure severity. There are no established transplacental treatments for heart failure in utero, and no animal models or experimental systems of fetal heart failure have been established. We first used an ultra-high-frequency ultrasound imaging system in utero and demonstrated that Hrt2 knockout (KO) embryos had marked left ventricular (LV) dilatation as well as worsening fractional shortening (FS) as gestation progressed, indicating that the embryos can be used as a murine model of fetal heart failure. Subsequently, we evaluated the effect of tadalafil treatment on fetoplacental circulation in Hrt2 KO embryos. LV FS was significantly higher in the tadalafil group than in the control group. Maternal administration of tadalafil improved LV systolic function without altering LV morphological abnormalities in Hrt2 KO embryos. Our findings suggest that tadalafil may effectively treat impaired fetal ventricular systolic function.