In PAH patients, while acute treatment with the phosphodiesterase (PDE)5 inhibitor Sildenafil improved RV diastolic function (55), recent trials in non-PAH heart failure patients with Sildenafil or the soluble guanylate cyclase (sGC) stimulator Riociguat failed to meet their primary clinical endpoints (56, 57). This evidence concerns the gene PDE5A and pulmonary arterial hypertension.