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ESC Heart Fail. 2018 Oct;5(5):977-984. doi: 10.1002/ehf2.12332. Epub 2018 Aug 7.

Design of the GutHeart-targeting gut microbiota to treat heart failure-trial: a Phase II, randomized clinical trial.

Author information

1
Department of Cardiology, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
2
Research Institute of Internal Medicine, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
3
Institute of Clinical Medicine, Faculty of Medicine, University of Oslo, Oslo, Norway.
4
K.G. Jebsen Inflammation Research Centre, Institute of Clinical Medicine, University of Oslo, Oslo, Norway.
5
Center for Clinical Heart Research, Department of Cardiology, Oslo University Hospital, Ullevål, Oslo, Norway.
6
Department of Cardiology, Oslo University Hospital, Ullevål, Postboks 4956 Nydalen, 0424, Oslo, Norway.
7
Laboratory of Immunopharmacology, Oswaldo Cruz Institute, Rio de Janeiro, Brazil.
8
Division of Internal Medicine, Nordlandssykehuset, Bodø, Norway.
9
Institute of Clinical Medicine, University of Tromsø, Tromsø, Norway.
10
Norwegian PSC Research Center and Section of Gastroenterology, Department of Transplantation Medicine, Division of Surgery, Inflammation Medicine and Transplantation, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
11
Section of Clinical Immunology and Infectious Diseases, Oslo University Hospital, Rikshospitalet, Oslo, Norway.
12
Instituto Nacional de Cardiologia, Rio de Janeiro, Brazil.

Abstract

AIMS:

Heart failure (HF) is a multifactorial disease. Current treatments target only a fraction of the putative pathophysiological pathways. In patients with HF, reduced cardiac output and congestion cause increased gut wall permeability. It has been suggested that leakage of microbial products is detrimental to the heart, at least partly through activation of systemic inflammatory pathways, which again could promote gut leakage. Whether manipulating the gut microbiota can improve cardiac function in patients with HF remains unknown. We aim to evaluate the effect of drugs targeting the gut microbiota on left ventricular function, quality of life, and functional capacity, as well as on markers of gut leakage and inflammation, in stable patients with HF with reduced ejection fraction.

METHODS AND RESULTS:

GutHeart is a randomized, open-label, controlled trial. Four centres will randomize 150 patients with stable HF and a left ventricular ejection fraction <40% to receive the antibiotic rifaximin, the probiotic yeast Saccharomyces boulardii (ATCC 74012), or no treatment (control) in a 1:1:1 fashion. Treatment will last for 3 months. The primary endpoint is baseline-adjusted left ventricular ejection fraction as measured by echocardiography after 3 months. A further follow-up 6 months after randomization will be undertaken.

CONCLUSIONS:

This trial is likely to give new insights into important disease processes involving the gut microbiota in HF patients, hereby leading to new potential therapeutic strategies to prevent and down-regulate the inflammation seen in these patients.

KEYWORDS:

Gut microbiota; Heart failure; Microbial translocation; Randomized controlled trial; Remodelling; Study design

PMID:
30088346
PMCID:
PMC6165929
DOI:
10.1002/ehf2.12332
[Indexed for MEDLINE]
Free PMC Article

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