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.

The Impact of Pharmacotherapy for Heart Failure on Oxidative Stress—Role of New Drugs, Flozins

“…In the mitochondrial matrix, fatty acyl-CoA undergoes β-oxidation, generating acetyl-CoA, which enters the tricarboxylic acid (TCA) cycle. In this cycle, nicotinamide adenine dinucleotide (NADH) and flavin adenine dinucleotide (FADH2) are produced, which are substrates for oxidative phosphorylation (OXPHOS) and ATP production [ 17 , 18 ]. Another important fuel in the heart is glucose, mainly taken up by cardiomyocyte GLUT4, followed by GLUT1.…”

“…Cardiac dysfunction during chronic stress seems to be related to mitochondrial calcium content [ 20 , 69 ]. The dysfunction of systems preserving mitochondrial anatomy (number, size, and shape) through fission/fusion and mitophagy breaks up cellular bioenergetics and produces increased oxidative stress, leading to cardiomyocyte death [ 17 , 70 ].…”