RYR2 and hydrops fetalis: In summary, these results indicate that nanoscale reorganization of RyRs in HF promotes non-spark-mediated SR Ca2+ leak by two mechanisms: (1) by creating smaller CRUs which produce Ca2+ release events below the detection limit, and (2) by creating more distributed CRU configurations in which multiple RyR clusters are less likely to co-operatively generate sparks.