In fact, despite the previous use of angiotensin converting enzyme inhibitors (ACEi) or angiotensin receptor blockers (ARB), which was the most difficult criterion to be met when applying PARADIGM to real world, it was not necessary to be enrolled in PARAGON-HF; 69.6% of patients in our real-world HFpEF cohort had been treated with ACEi/ARB, but still most of them did not meet the trial criteria. This evidence concerns the gene ACE and hydrops fetalis.