Regarding the clinical implication of our finding, the association between higher baseline concentration of leukocyte EVs and progression of systolic dysfunction in HFmrEF patients might provide a rationale for the initiation of HF pharmacotherapy (beta-blockers, angiotensin-converting-enzyme inhibitors or angiotensin receptor-neprilysin inhibitors, mineralocorticoid receptor antagonists and SGLT2-inhibitors) at an earlier stage to prevent progression to HFrEF. Here, NR3C2 is linked to hydrops fetalis.