Myocyte recovery after mechanical circulatory support in humans with end-stage heart failure

Background-The failing myocardium is characterized by decreased force production, slowed relaxation, and depressed responses to beta-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 (0.55t0.02 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 beta-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 beta-adrenergic responsiveness.