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vs. 78/8, P 0.05 each). Myocardial contractility of human ventricular trabeculae was not acutely affected by Sac treatment as the developed force remained unchanged over a time course of 30 min (n trabeculae/hearts = 3/3 vs. 4/3). This study demonstrates that neprilysin inhibitor Sac directly improves Ca homeostasis in human end-stage HF by reducing pro-arrhythmogenic SR Ca leak without acutely affecting systolic Ca release and inotropy. These effects might contribute to the mortality benefits observed in the PARADIGM-HF trial. This s