Abstract 19453: Mechanical Unloading with a Micro LVAD after Acute Myocardial Infarction Reduces Adverse Cardiac Remodeling and Left Ventricular Systolic Asynchrony

Abstract

Introduction: Mechanical stress plays a critical role during cardiac remodeling post-MI. LVADs can provide circulatory support and profound mechanical unloading both to the preload and afterload of the left ventricle. To demonstrate that short-term cardiac unloading with a left ventricular assist device (LVAD) after an acute myocardial infarction (MI) can prevent cardiac remodeling and improve heart function. Methods: Adult ovine hearts were unloaded with an axial-flow LVAD (Impella LD) during the first 2 weeks after an acute MI and were analyzed for 10 more weeks (n=8, MI+LVAD group). Eight sheep with a MI only and 4 sham sheep were used as controls. Regional diastolic and contractile strain in the left ventricle was measured by sonomicrometry. Apoptosis, hypertrophy, and the related ultrastructures were studied regionally in the remote zone and the non-ischemic adjacent zone. Left ventricular systolic asynchrony was analyzed by sonomicrometry. Results: The regional myocardial strain (stretch) was minimized during the unloading period and even attenuated at 12 weeks compared to the MI only group. LV dilation and cardiac dysfunction were alleviated in the unloaded animal at 12 weeks (EDV: 81.9±5.4 ml vs. 105.9±9.5 ml; EF value: 39.3±4.2% vs. 46.4±1.8%, p<0.05). Infarct size was smaller in the unloaded animal at 12 weeks although the initial infarct size had no statistical difference in the two groups. Regional apoptosis, hypertrophy, and ultrastructural changes in the adjacent zone were prevented by the short-term LVAD unloading and the Calcineurin/BAD apoptotic pathway and the Raf/MEK/ERK hypertrophic pathway were involved. Left ventricular systolic asynchrony was evident among the remote zone, adjacent zone, and infarcted zone in the MI group, but reduced in the unloaded group. Conclusion: Short-term LVAD unloading can reduce apoptosis, hypertrophy, prevent left ventricular systolic asynchrony, and improve heart function during the post-infarct period. This translational study supports the application LVAD at the early stage post MI to prevent cardiac remodeling rather to “reverse” remodeling at the end-stage of heart failure.