Novelties in the pharmacological approaches for chronic heart failure: new drugs and cardiovascular targets

Abstract

Despite recent advances in chronic heart failure (HF) management, the prognosis of HF patients is poor. This highlights the need for researching new drugs targeting, beyond neurohumoral and hemodynamic modulation approach, such as cardiomyocyte metabolism, myocardial interstitium, intracellular regulation and NO-sGC pathway. In this review we report main novelties on new possible pharmacological targets for HF therapy, mainly on new drugs acting on cardiac metabolism, GCs-cGMP pathway, mitochondrial function and intracellular calcium dysregulation.

Keywords: CGMP pathway; cardiac metabolism; heart failure; mitochondrial function; new drugs; therapy targets.

Figure 1

Chronologic development of drugs in HF with the shift from neurohormonal antagonism to specific cardiac targeting. Taken from Ghionzoli et al. (5). ACE, angiotensin-converting enzyme; ARBs, angiotensin receptor blockers; ARNI, angiotensin receptor neprilysin inhibitor; MRAs, mineralocorticoid receptor antagonists; sGC, soluble guanylate cyclase; SGLT2, sodium-glucose cotransporter 2.

Figure 2

Pathophysiological mechanisms and innovative potential cardiac targets in the failing heart. Taken from Weldy et al. (6). LV, left ventricular; RYR2, ryanodine receptor 2; SERCA2, sarcoplasmic–endoplasmic reticulum Ca²⁺ ATPase 2; SR, sarcoplasmic reticulum; TCA, tricarboxylic acid.

Figure 3

Summary figure (list of potential new drugs). FA, fatty acid; sGC, soluble guanylate cyclase; SGLT2i, sodium-glucose cotransporter 2 inhibitor; NHE-1, Na H⁺ exchanger; PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1 α; Ndufs1 NADH, ubiquinone oxidoreductase core subunit S1; mtCU, Ca²⁺ uniporter; SERCA2, sarcoplasmic–endoplasmic reticulum Ca²⁺ ATPase 2; mPTP, mitochondrial permeability transition pore; A1AR, adenosine A1 receptor; MitoQ, mitoquinone.

Figure 4

Figure summarizing the mechanism of actions of different drugs. FA, fatty acid; sGC, soluble guanylate cyclase; SGLT2i, sodium-glucose cotransporter 2 inhibitor; RyR, Ryanod receptor; NHE-1, Na H⁺ exchanger; PGC-1α, peroxisome proliferator-activated receptor γ coactivator 1 α; Nrf2, nuclear erythroid 2-related factor 2; Ndufs1 NADH, ubiquinone oxidoreductase core subunit S1; mtCU, Ca²⁺ uniporter; CPT1, carnitine palmitoyl-transferase; SERCA2, sarcoplasmic–endoplasmic reticulum Ca²⁺ ATPase 2; SR, sarcoplasmic reticulum; A1AR, adenosine A1 receptor; mPTP, mitochondrial permeability transition pore; PLN, phospholamban; ROS, reactive oxygen species; MitoQ, mitoquinone.