A trial that will include patients with heart failure with preserved (HFpEF) or mid-range (HFmrEF) ejection fraction; i.e. fulfilling all of the following criteria: (a) LVEF ≥50 or 40–49%, respectively, (b) the presence of at least one typical symptom and one specific sign of heart failure as defined by the 2016 ESC Guidelines [5], (c) elevated levels of natriuretic peptides (BNP >35 pg/ml and/or NT-proBNP >125 pg/ml), (d) objective evidence of other cardiac functional and structural alterations underlying heart failure. This evidence concerns the gene NPPB and heart failure.