Editor's Choice-Recent therapeutic trials on fluid removal and vasodilation in acute heart failure

Eur Heart J Acute Cardiovasc Care. 2016 Feb;5(1):86-95. doi: 10.1177/2048872614560504. Epub 2014 Nov 20.


Recent therapeutic trials regarding the management of acute heart failure (AHF) failed to demonstrate the efficacy of newer therapeutic modalities and agents. Low- versus high-dose and continuous administration of furosemide were shown not to matter. Ultrafiltration was not found to be more efficacious than sophisticated diuretic therapy including dose-adjusted intravenous furosemide and metolazone. Dopamine and nesiritide were not shown to be superior to current therapy. Tezosentan and tovalptan had no effect on mortality. The development of rolofylline was terminated due to adverse effect (seizures). Lastly, preliminary experience with serelaxin indicates a mortality improvement at six months that remains to be confirmed. The disappointing findings of these recent trials may reflect the lack of efficacy of newer therapeutic modalities and agents. Alternatively the disappointing findings of these recent trials may be in part due to methodological issues. The AHF syndrome is complex with many clinical phenotypes. Failure to match clinical phenotypes and therapeutic modalities is likely to be partly responsible for the disappointing findings of recent AHF trials.

Keywords: Acute heart failure; fluid removal; future directions; vasodilating agents.

Publication types

  • Review

MeSH terms

  • Diuretics / therapeutic use
  • Furosemide / therapeutic use
  • Heart Failure / physiopathology
  • Heart Failure / therapy*
  • Humans
  • Randomized Controlled Trials as Topic
  • Recombinant Proteins / therapeutic use
  • Relaxin / therapeutic use
  • Therapeutic Human Experimentation
  • Ultrafiltration / methods
  • Vasodilation / drug effects


  • Diuretics
  • Recombinant Proteins
  • serelaxin protein, human
  • Furosemide
  • Relaxin