Table 3.

Emerging therapies for HFrEF that have shown promise in experimental models

Mechanistic approach	Drug class	Model studied
Epigenetic modifiers	Histone deacetylase inhibitors	Genetic deletion, ischemia-reperfusion, pressure overload, mice
Epigenetic modifiers	Bromodomain and extraterminal bromodomain (BET) inhibitors	Presure overload and ischemic cardiomyopathy, mice; induced pluripotent stem cell cardiomyocytes, human
Epigenetic modifiers	Long noncoding RNAs	Pressure overload and ischemic cardiomyopathy, mice; embryonic stem cell-derived cardiomyocytes, human
Epigenetic modifiers	microRNAs
Calcium-calmodulin kinase II inhibitors	Calcium-calmodulin kinase II inhibitors	Ischemic cardiomyopathy, chronic catecholamine infusion, mice
G-protein receptor kinase inhibitors	G-protein receptor kinase 2 and 5 inhibitors	Chronic catecholamine infusion, mice; ischemic cardiomyopathy, mice, rabbits, and pigs
Mitochondrial ROS scavengers	MitoTEMPO	Combined pressure overload and chronic catecholamine infusion, guinea pig
Mitochondrial ROS scavengers	Apoptosis stress kinase-1 inhibitors to augment thioredoxin-2 signaling	Spontaneous cardiomyopathy in cardiac-specific thioredoxin-2 genetic deletion, mice
Antioxidants	Tetrahydrobiopterin to enhance eNOS-generation of NO, suppress inflammation	Pressure overload, mice
Intracellular calcium modulation	S100A1	Ischemic cardiomyopathy, pigs

HFrEF, Heart failure with reduced ejection fraction; ROS, reactive oxygen species; eNOS, endothelial nitric oxide synthase; NO, nitric oxide