Incomplete Recovery of Myocyte Contractile Function Despite Improvement of Myocardial Architecture With Left Ventricular Assist Device Support

Sustained recovery of the failing left ventricle (LV) during pressure-volume unloading with an LV assist device (LVAD) is rare and may be related to incomplete recovery of sarcomeric contractility. In this study, the authors evaluated contractility and biochemistry at the most fundamental contractile level of the heart: the sarcomere. Force development in muscle is the result of actin and myosin interactions and cross-bridge cycling, processes regulated by modifications of the sarcomeric contractile proteins. Sarcomeric contractility was assessed by measuring isometric forces on skinned LV myocytes from patients with nonischemic cardiomyopathy before and after LVAD placement. The authors found that contractile dysfunction at the level of the sarcomere was present in failing hearts and paralleled organ-level contractile dysfunction as assessed by ejection fraction. Furthermore, there were improvements in LV and myocyte size with partial recovery of sarcomeric force after LVAD placement, but LVAD-supported myocyte forces were still half of that seen in nonfailing hearts. The persistence of sarcomeric contractile dysfunction may be one of the reasons most LVADs cannot be explanted in clinical practice. In assessing for biochemical alterations of sarcomeric proteins after LVAD implantation, there were changes in troponin-I phosphorylation, which may account for some of the improvement in sarcomeric force, but the other sarcomeric contractile proteins revealed minimal biochemical changes, suggesting that other interventions (in addition to mechanical unloading with an LVAD) may be needed to optimize troponin-I phosphorylation, modify other sarcomeric protein biochemistry, or both to further enhance sarcomeric and organ-level recovery.