Chronically increased afterload alters left ventricular growth patterns in fetal sheep

  • Mr Andrew Hattam, Heart Research Group, Murdoch Children's Research Institute, Australia
  • Dr Paul Brooks, Heart Research Group, Murdoch Children’s Research Institute, Australia
  • Prof Daniel Penny, The Royal Children's Hopsital, Melbourne, Australia
  • A/Prof Joseph Smolich, Heart Research Group, Murdoch Children’s Research Institute, Australia
  • Objective: Although the mid-gestation fetus with aortic stenosis and normal left ventricular (LV) chamber geometry frequently evolves into hypoplastic left heart syndrome in late-gestation, little is known about the effects of a chronic increase in LV afterload on fetal LV growth patterns. We addressed this question in fetal lambs with chronically increased LV afterload induced by aortic banding at mid-gestation.

    Methods: Surgery was performed in 17 anaesthetised twin-pregnancy ewes (gestation=92±3 days; term=147 days), with one fetus undergoing non-constrictive ascending aortic banding, and the second serving as the un-operated control. Serial fetal echocardiography studies were performed under maternal sedation at fortnightly intervals until near-term (140±1days) to measure LV wall and chamber dimensions. Changes in LV growth patterns were assessed by comparing the slopes of the relationship between echocardiography parameters and gestation in banded and control fetuses.

    Results: With aortic banding, peak ascending aortic pressure gradient rose from 8±4 mmHg at mid-gestation to 26±13 mmHg near-term, with no evidence of cardiac failure. This elevated LV afterload was accompanied by an increase in the slope of the LV posterior-wall thickness relationship (p<0.01), a decrease in the slope of the LV diastolic short-axis chamber diameter relationship (p<0.001), and an unchanged LV long-axis relationship. Furthermore, the slope of the LV short-to-long axis ratio relationship was decreased in banded fetuses (p<0.05).

    Conclusion: Chronically elevated LV afterload in fetal sheep results in substantial changes in LV growth patterns, manifest not only via alterations in LV wall thickness and cavity dimensions, but also in LV chamber geometry.