Clinical Recovery From End-Stage Heart Failure Using Left-Ventricular Assist Device and Pharmacological Therapy Correlates With Increased Sarcoplasmic Reticulum Calcium Content but Not With Regression of Cellular Hypertrophy

Abstract

Background— Left ventricular assist device (LVAD) treatment is known to lead to structural and functional cellular modifications in the heart. The relevance of these changes for clinical recovery is unknown. Methods and Results— We compared properties of cardiomyocytes obtained from tissue taken at explantation of the LVAD in patients with clinical recovery with those obtained from hearts of patients who did not show clinical recovery, thus requiring transplantation. Compared with myocytes taken at implantation, both the recovery and nonrecovery groups showed ≈50% reduction in cell capacitance, an index of cell size. However, action potential duration shortened, L-type Ca 2+ current fast inactivation was more rapid, and sarcoplasmic reticulum Ca 2+ content was increased in the recovery compared with the nonrecovery group. Conclusions— These results show that specific changes in excitation-contraction coupling, and not regression of cellular hypertrophy, are specifically associated with clinical recovery after LVAD and further identify sarcoplasmic reticulum Ca 2+ handling as a key functional determinant in patients with heart failure.