Novel Therapies for Right Ventricular Failure

Traditionally viewed as a passive player in circulation, the right ventricle (RV) has become a pivotal force in hemodynamics. RV failure (RVF) is a recognized complication of primary cardiac and pulmonary vascular disorders and is associated with a poor prognosis. Unlike treatments for left ventricular failure (LVF), strategies such as adrenoceptor signaling inhibition and renin-angiotensin system modulation have shown limited success in RVF. This review aims to reassure about the progress in RVF treatment by exploring the potential of contemporary therapies for heart failure, including angiotensin receptor and neprilysin inhibitors, sodium-glucose co-transporter 2 inhibitors, and soluble guanylate cyclase stimulators, which may be beneficial for treating RV failure, particularly when associated with left heart failure. Additionally, it examines novel therapies currently in the pipeline.

Over the past decade, a new wave of RVF therapies has emerged, both pharmacological and device-centered. Novel pharmacological interventions targeting metabolism, calcium homeostasis, oxidative stress, extracellular matrix remodeling, endothelial function, and inflammation have shown significant promise in preclinical studies. There is also a burgeoning interest in the potential of epigenetic modifications as therapeutic targets for RVF.

Undoubtedly, a deeper understanding of the mechanisms underlying RV failure, both with and without pulmonary hypertension, is urgently needed. This knowledge is not just a theoretical pursuit, but a crucial step that could lead to the development of pharmacological and cell-based therapeutic options that directly target the RV and pulmonary vasculature, aligning with the principles of precision medicine.