Inhibition of CaMKII Attenuates Progressing Disruption of Ca2+ Homeostasis Upon Left Ventricular Assist Device Implantation in Human Heart Failure

In heart failure, left ventricular assist device (LVAD) implantation is performed to ensure sufficient cardiac output. Whereas some patients are subsequently weaned from LVAD support, other patients still need heart transplantation. To elucidate underlying mechanisms, we assessed the arrhythmogenic SR‐Ca2+ leak at the time of LVAD implantation (HF‐Im) and heart transplantation (HF‐Tx) and evaluated the effects of CaMKII‐inhibition. Human left‐ventricular cardiomyocytes were isolated, paced at 1 Hz for 10 beats to ensure SR‐Ca2+ loading and scanned for diastolic Ca2+ sparks (confocal microscopy). In HF‐Im, the high diastolic spark frequency (CaSpF) of 0.76 ± 0.12 × 100 μm−1 × s−1 could be reduced to 0.48 ± 0.10 × 100 μm−1 × s−1 by CaMKII inhibition (AIP, 1 μM). The amplitude of Ca2+ sparks, width, and length was not significantly altered. In sum, CaMKII inhibition yielded a clear tendency toward a reduction of the SR‐Ca2+ leak (n cells/patients = 76/6 vs. 108/6, P = 0.08). In HF‐Tx, we detected an even higher CaSpF of 1.00 ± 0.10 100 μm−1 × s−1 and a higher SR‐Ca2+ leak compared with HF‐Im (increase by 81 ± 33%, n cells/patients = 156/7 vs. 130/7, P