Our findings may partially be explained by the mechanism by which hypoperfusion accompanied by LV dysfunction in HFrEF could induce skeletal myopathy, which subsequently yields increased activation of the sympathetic nervous system as well as the renin–angiotensin–aldosterone system and consequently leads to endothelial dysfunction, vasoconstriction and myocardial injury [3, 15–17]. Here, REN is linked to endothelial dysfunction.