Myocyte Recovery After Mechanical Circulatory Support in Humans With End-Stage Heart Failure

Abstract

Background —The failing myocardium is characterized by decreased force production, slowed relaxation, and depressed responses to β-adrenergic stimulation. In some heart failure patients, heart function is so poor that a left ventricular assist device (LVAD) is inserted as a bridge to transplantation. In the present research, we investigated whether circulatory support with an LVAD influenced the functional properties of myocytes from the failing heart. Methods and Results —Myocytes were isolated from human explanted failing hearts (HF-myocytes) and failing hearts with antecedent LVAD support (HF-LVAD-myocytes). Studies of myocyte function indicated that the magnitude of contraction was greater (9.6±0.7% versus 6.9±0.5% shortening), the time to peak contraction was significantly abbreviated (0.37±0.01 versus 0.75±0.04 seconds), and the time to 50% relaxation was reduced (0.55±0.02 versus 1.45±0.11 seconds) in the HF-LVAD-myocytes compared with the HF-myocytes ( P <0.05). The HF-LVAD-myocytes had larger contractions than the HF-myocytes at all frequencies of stimulation tested. The negative force-frequency relationship of the HF-myocytes was improved in HF-LVAD-myocytes but was not reversed. Responses to β-adrenergic stimulation (by isoproterenol) were greater in HF-LVAD-myocytes versus HF-myocytes. Conclusions —The results of the study strongly support the idea that circulatory support with an LVAD improves myocyte contractile properties and increases β-adrenergic responsiveness.