Modulating energy metabolism to treat non-obstructive hypertrophic cardiomyopathy? Insights from IMPROVE-HCM

Heart Fail Rev. 2025 Jan;30(1):39-43. doi: 10.1007/s10741-024-10440-8. Epub 2024 Sep 23.

Abstract

Hypertrophic cardiomyopathy (HCM) is the most common genetic heart disease worldwide and may present with or without dynamic left ventricular outflow tract obstruction (LVOTO). Significant advances have been made in the management of obstructive HCM. On the other hand, despite their significant symptomatic burden, patients with non-obstructive HCM (nHCM) (i.e., without LVOTO) still do not have evidence-based therapeutical options. The recent IMPROVE-HCM study, a phase 2 randomized, double-blinded trial, aims to place a first step in filling this gap in knowledge. The study assessed the safety (primary endpoint) and efficacy (secondary endpoint) of ninerafaxstat, a novel cardiac mitotrope drug that increases adenosine triphosphate production. We highlighted the main findings of the trial, contextualizing these results within the larger landscape of completed and ongoing trials in nHCM.

Keywords: IMPROVE-HCM trial; Ninerafaxstat; Non-obstructive HCM.

Publication types

  • Review

MeSH terms

  • Benzylamines
  • Cardiomyopathy, Hypertrophic* / drug therapy
  • Cardiomyopathy, Hypertrophic* / metabolism
  • Energy Metabolism* / drug effects
  • Humans
  • Randomized Controlled Trials as Topic
  • Treatment Outcome
  • Uracil / analogs & derivatives
  • Ventricular Outflow Obstruction / drug therapy

Substances

  • MYK-461
  • Benzylamines
  • Uracil