Chronic in utero mitral inflow obstruction unloads left ventricular volume in a novel late gestation fetal lamb model.

The in utero no flow/no grow hypothesis postulates that reduced inflow of blood into the left ventricle due to a stenotic mitral valve could lead to ventricular hypoplasia and hypoplastic left heart syndrome. This has been demonstrated in chick embryos, but less so in large animals. We investigated the impact of mitral obstruction on left and right ventricular growth in fetal lambs. Twelve pregnant ewes, most bearing twins, were instrumented at 119 ± 1 days gestational age. Carotid artery and jugular vein catheters, an ascending aorta flow probe, and a left atrial deflated balloon catheter were implanted into 1 fetus (left atrial balloon group), and the twin remained an uninstrumented control. The balloon was inflated gradually over 8 days until net antegrade aortic flow was eliminated. Fetal transesophageal echocardiography was performed at the time of surgery and just before termination in both groups. Terminal fetal body weights were comparable between groups. Terminal heart/body weight ratio was higher in left atrial balloon group fetuses (6.9 ± 0.8 g/kg) compared with controls (5.9 ± 0.6 g, In this late-gestation fetal lamb model, in utero obstruction of mitral inflow slowed left ventricular growth and caused right ventricular remodeling.

© 2023 The Author(s).

M.P. reports stock ownership, board directorship, and employment in Nyra Medical Inc; receives personal consulting fees from Heart Repair Technologies and research grants from Heart Reparit Technologies; received Single Ventricle Blue Sky grant from Additional Ventures; and led this work when he was at Emory University. D.O. received personal consulting fees from Nyra Medical Inc. All other authors reported no conflicts of interest. The Journal policy requires editors and reviewers to disclose conflicts of interest and to decline handling or reviewing manuscripts for which they may have a conflict of interest. The editors and reviewers of this article have no conflicts of interest.