Despite advances in therapy, patients with heart failure (HF) continue to 
experience unacceptably high rates of hospitalization and death, as well as poor 
quality of life. As a consequence, there is an urgent need for new treatments 
that can improve the clinical course of the growing worldwide population of HF 
patients. Serelaxin and ularatide, both based on naturally occurring peptides, 
have potent vasodilatory as well as other effects on the heart and kidneys. For 
both agents, phase 3 studies that are designed to determine whether they improve 
outcomes in patients with acute HF have completed enrollment. TRV027, a biased 
ligand for the type 1 angiotensin receptor with effects that extend beyond 
traditional angiotensin-receptor blockers is also being studied in the acute HF 
population. Omecamtiv mecarbil, an inotropic agent that improves myocardial 
contractility by a novel mechanism, and vericiguat, a drug that stimulates 
soluble guanylate cyclase, are both being developed to treat patients with 
chronic HF. Finally, despite the negative results of the CUPID study, gene 
transfer therapy continues to be explored as a means of improving the function 
of the failing heart. The basis for the use of these drugs and their current 
status in clinical trials are discussed. (Circ J 2016; 80: 1882-1891).