HF

Grand Rounds May 2, 2025: Fluid REStriction in Heart failure versus liberal fluid UPtake: The FRESH-UP Study (Roland RJ van Kimmenade, MD, PhD)

Posted on by Sophia Ramirez

Speaker

Roland RJ van Kimmenade, MD, PhD
Cardiologist, Radboud University Medical Center
Nijmegen, the Netherlands

Keywords

Heart Failure; Fluids; Cardiology

Key Points

  • We are facing a pandemic of heart failure (HF), with an incidence of 1 – 20 cases of heart failure per 1,000 people. The incidence of HF is stable – if not declining – but mortality remains high, at about 15 – 30% after one year. Attributable health care costs are up, and the prevalence of HF in the general population is increasing.
  • Orthopnea and edema are symptoms of heart failure caused by congestion, or “fluid retention.” This has led to an intuitive assumption that patients should monitor their fluid intake to 1.5 – 2L per day (including beverages, ice cream, soup, and some fruit). Patients are advised to do things like chew gum or suck on frozen grapes to relieve dry mouth and thirst.
  • The literature supporting fluid restriction is limited; as of 2018, the studies supporting it had small sample sizes and heterogeneous populations. They found no differences in mortality and hospitalization. Sets of clinical practice guidelines from 2021 and 2022 also noted that more evidence was needed for fluid restriction, and that existing evidence was low quality.
  • To address this gap in the evidence, the research team used crowdfunding to conduct the Fluid REStriction in Heart failure versus liberal fluid Uptake (FRESH-UP) Study. The randomized, open-label, multicenter clinical trial study took place between May 17, 2021 and June 13, 2024.
  • The primary outcome was health status at 3 months, as assessed by the Kansas City Cardiomyopathy Questionnaire – Overall Summary Score (KCCQ-OSS). The key secondary outcome was thirst distress at 3 months, as assessed by the Thirst Distress Scale for patients with HF (TDS-HF).
  • Participants were randomized to one of two arms: liberal fluid intake (no restriction) or fluid restriction, with a maximum of 1500 mL of fluid per day.
  • After three months, the research team found that the difference in KCCQ-OSS (adjusted for baseline scores) was 2.17, with a p value of 0.06. These findings favor liberal fluid intake, but the primary outcome was not met.
  • Thirst distress was higher in the fluid restriction group. No differences were observed for safety events between groups.
  • The FRESH-UP study questions the benefit of fluid restriction in chronic HF.

Discussion Themes

Patient-centered research is key in pragmatic trials; this trial came about because a patient voiced their discomfort and questioned the validity of fluid restriction. The researchers took this as a cue to question a key assumption in their field.

The Dutch Heart Foundation facilitated the crowdfunding, from the legal requirements to the website. The money raised from crowdfunding got them far enough to apply for a second grant.

As in clinical practice, the pragmatic nature of the trial made it difficult to guarantee participant fidelity throughout the entire experiment (though they did monitor intake at week six). The research team conducted a survey of participants afterwards to assess adherence. 93% of the patients reported that they adhered well to their regimes.

“Gaps in Evidence” in clinical guidelines is not a summary of failure, but a source of inspiration!