Abstract 13151: Left Ventricular Hypovolemia Secondary to in Utero Mitral Valve Inflow Obstruction in a Late-Gestation Fetal Lamb Model

Abstract

Introduction: Hypoplastic left heart syndrome (HLHS) is a congenital heart defect of an underdeveloped left ventricle (LV), necessitating palliative interventions after birth to survive. HLHS often occurs alongside mitral or aortic valve stenosis, lending to the hypothesis that reduced blood flow into and out of the LV in utero could retard LV growth. We have developed a late-gestation fetal lamb model to investigate if in utero mitral inflow obstruction could cause LV hypovolemia. Methods: Twelve pregnant ewes with twin fetuses at 82% gestation were used. In the experimental fetuses (EXPT), mitral inflow obstruction was achieved with an inflatable balloon catheter implanted into the left atrium (LA) in a beating heart. Other implants included a flow probe on the ascending aorta to measure cardiac output, and carotid artery and jugular vein catheters to monitor fetal health. After recovery from surgery, progressive LA balloon inflation began at ~86% gestation, and was left inflated for 8 days (92% gestation). Transesophageal fetal ultrasound was performed at baseline and at termination to measure cardiac chamber volumes and function. Hearts were explanted, weighed and prepared for histology. Results: Fetal body weights were similar (EXPT: 4.6±0.9kg vs CTRL: 4.5±0.6kg, p=0.8597). Total heart weight was higher in EXPT (31.4±5.6g) than CTRL (26.4±2.4g, p=0.0471), but LV weight was similar (EXPT: 7.4± 1.8g vs. CTRL: 7.9± 1.1g, p=0.5652). LV end-diastolic volume was 2.3± 0.7ml in EXPT vs. 7.1± 0.8ml in CTRL (p<0.0001), and end-systolic volume was 1.01ml (0.95 to 1.95ml) in EXPT vs. 3.38ml (3.28 to 3.57ml) in CTRL (p=0.0025). LV/RV weight ratio was 0.83±0.17 in EXPT and 1.08±0.19 in CTRL (p=0.0209), whereas LV/RV chamber area ratio was 0.21±0.06 in EXPT and 0.56±0.05 in CTRL (p=0.0005). Conclusions: In this fetal sheep model, obstructing mitral inflow retarded LV growth, demonstrating a potential mechanistic link between blood inflow and in utero LV volumetric growth.