Abstract Body (Do not enter title and authors here): Introduction: Hypoplastic left heart syndrome (HLHS) is a severe congenital defect characterized by underdevelopment of the left ventricle (LV), requiring complex surgical palliation soon after birth. Chronic fetal lamb models using LV inflow obstruction have shown that reduced LV filling impairs growth, supporting the “no flow, no grow” theory. In the fetal circulation, the LV and right ventricle (RV) function in parallel due to shunting, and therefore the RV can sustain systemic output when LV function is absent. As a result, the functionally univentricular RV is viable prenatally but is lethal after birth without extensive surgical intervention. However, function and performance in the fetal RV in the absence of LV output is poorly understood.
Hypothesis: We hypothesized that acute mitral inflow occlusion in the fetal lamb reduces LV output and induces a shift in cardiac pressure and blood flow toward the right heart.
Methods: Fetal lambs at 120 gestational days (n=13) had an inflatable vascular balloon implanted in the left atrium to induce mitral inflow obstruction. Pressures in the LV and RV were measured using intravascular catheters. Aortic and pulmonary flows were recorded with perivascular flow probes. Transesophageal echocardiographic (TEE) and pressure-volume (PV) loop assessments were performed in a subset of animals. All parameters were compared statistically before and after balloon inflation.
Results: Inflation of the 3 mL balloon resulted in complete loss of antegrade aortic flow (324 ± 172 vs. –65 ± 49 mL/min, p=0.0020). Pulmonary artery flow tended to increase but this was not statistically significant (686 ± 140 vs. 789 ± 189 mL/min, p=0.1289). Heart rate significantly increased after balloon inflation (176 ± 22 vs. 184 ± 20 bpm, p=0.0490). In the LV, balloon inflation significantly reduced pressure, volume, and ejection fraction (EF), while these parameters were unchanged in the RV. PV loop analysis demonstrated a leftward shift in the LV and a rightward shift in the RV following mitral inflow obstruction (Figure).
Conclusions: Acute mitral inflow occlusion in fetal lambs significantly reduced LV pressure, volume, and EF, with minimal changes in RV parameters. These findings suggest that LV unloading reduces hemodynamic signals known to drive ventricular growth, thereby suppressing LV development without a concomitant change in RV function.