Abstract
Unloading a failing heart with a left ventricular assist device (LVAD) can improve ejection fraction (EF) and LV size; however, recovery with LVAD explantation is rare. We hypothesized that evaluation of myocyte contractility and biochemistry at the sarcomere level before and after LVAD may explain organ-level changes. Paired LV tissue samples were frozen from 8 patients with nonischemic cardiomyopathy at LVAD implantation (before LVAD) and before cardiac transplantation (after LVAD). These were compared with 8 nonfailing hearts. Isolated skinned myocytes were purified and attached to a force transducer, and dimensions, maximum calcium-saturated force, calcium sensitivity, and myofilament cooperativity were assessed. Relative isoform abundance and phosphorylation levels of sarcomeric contractile proteins were measured. With LVAD support, the unloaded EF improved (10.0±1.0% to 25.6±11.0%, P=0.007), LV size decreased (LV internal dimension at end diastole, 7.6±1.2 to 4.9±1.4 cm; P<0.001), and myocyte dimensions decreased (cross-sectional area, 1247±346 to 638±254 μm(2); P=0.001). Maximum calcium-saturated force improved after LVAD (3.6±0.9 to 7.3±1.8 mN/mm(2), P<0.001) implantation but was still lower than in nonfailing hearts (7.3±1.8 versus 17.6±1.8 mN/mm(2), P<0.001). An increase in troponin I (TnI) phosphorylation after LVAD implantation was noted, but protein kinase C phosphorylation of TnI decreased. Biochemical changes of other sarcomeric proteins were not observed after LVAD. There is significant improvement in LV and myocyte size with LVAD, but there is only partial recovery of EF and myocyte contractility. LVAD support was associated only with biochemical changes in TnI, suggesting that alternate mechanisms might contribute to contractile changes after LVAD and that additional interventions may be needed to alter biochemical remodeling of the sarcomere to further enhance myofilament and organ-level recovery.
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