Serelaxin: A Novel Therapy for Acute Heart Failure with a Range of Hemodynamic and Non-Hemodynamic Actions

Abstract

Acute heart failure (AHF) is characterized by high morbidity and mortality and high costs. Although the treatment of AHF has not changed substantially in recent decades, it is becoming clear that treatment strategies for AHF need to address both the immediate hemodynamic abnormalities giving rise to congestion as well as prevent organ damage that can influence long-term prognosis. Serelaxin, the recombinant form of human relaxin-2, a naturally occurring peptide hormone, has been found to significantly improve symptoms and signs of AHF, prevent in-hospital worsening heart failure, as well as significantly improve 180-day cardiovascular and all-cause mortality after a 48-h infusion commenced within 16 h of presentation (RELAX-AHF study). Available data suggest that the clinical benefits may be attributable to a potential combination of multiple actions of serelaxin, including improving systemic, cardiac, and renal hemodynamics, and protecting cells and organs from damage via anti-inflammatory, anti-cell death, anti-fibrotic, anti-hypertrophic, and pro-angiogenic effects. This manuscript describes the short- and long-term effects of serelaxin in AHF patients, analyzing how these effects can be explained by taking into account the range of hemodynamic and non-hemodynamic actions of serelaxin. In addition, this paper also addresses several aspects related to the role of serelaxin in the therapy of AHF that remain to be clarified and warrant further investigation.

Serelaxin in clinical development: past, present and future

“…The reduction in mortality observed following short‐term serelaxin treatment during hospitalization in Pre‐RELAX‐AHF and RELAX‐AHF‐1 has led to the hypothesis that serelaxin may be interrupting pathophysiological cascades of events that, if unmodified, lead to cumulative organ damage and subsequent adverse outcomes (Metra et al, ; Diez, ; Dschietzig, ; Du et al, ). This hypothesis could be envisioned as encompassing a beneficial effect of short‐term serelaxin infusion on the attenuation of myocardial fibrosis characteristic of HFpEF patients, as well.…”

Serelaxin improves cardiac and renal function in DOCA-salt hypertensive rats

“…Inflammatory activation can also contribute to organ injury, vascular dysfunction and fluid overload 47 , 48 . In current study, the DOCA-salt rat exhibited a marked increase in renal inflammation as determined by increased expression of proinflammatory cytokines, increased expression of the macrophage marker CD68 and increased abundance of the proinflammatory transcription factor NF-κB.…”

Serelaksyna i jej ochronne działanie narządowe w ostrej niewydolności serca

“…Podaż serelaksyny wiązała się ze zmniejszeniem wartości AST i ALT oraz z ograniczeniem wyżej wymienionych procesów, co skutkowało ochronnym działaniem na wątrobę i w rezultacie przekładało się na zmniejszenie śmiertelności w AHF. W badaniach wykazano także hepatoprotekcyjne działanie serelaksyny poprzez hamowanie procesów włóknienia wątroby [19]. Proces ten polegał na hamowaniu syntezy kolagenu oraz ekspresji receptorów RXFP1, których zwiększoną ekspresję obserwuje się we włókniejącym narządzie.…”