In the Prospective Comparison of ARNI (Angiotensin Receptor–Neprilysin Inhibitor) with ACEI (Angiotensin-Converting–Enzyme Inhibitor) to Determine Impact on Global Mortality and Morbidity in Heart Failure Trial (PARADIGM-HF) study [24], the control group, despite being on optimal treatment, had a significantly decreased Hr-QoL, indicating that Hr-QoL are to be expected to decrease in patient with HF in spite of continuous pharmacologic treatment. This evidence concerns the gene MME and hydrops fetalis.