Although the RELAX trial, a large clinical trial of PDE5 inhibition in heart failure with preserved ejection fraction (HFpEF), failed to show robust beneficial effects (Redfield et al., 2013), single-center trials in patients with heart failure with reduced ejection fraction (HFrEF) reported improved exercise capacity and quality of life (Lewis et al., 2007). This evidence concerns the gene PDE5A and heart failure.