The Need for F ib e r A ddition in S ymp t omatic H eart F ailure (FEAST-HF): A Randomized Controlled Pilot Trial

Abstract

Background: Preclinical and observational studies suggest that the gut microbiome plays a role in the pathogenesis of heart failure (HF); the gut microbiome may be modified by fermentable dietary fibre (FDF). The Need for Fiber Addition in Symptomatic Heart Failure (FEAST-HF) trial evaluated feasibility of recruitment and supplementation with FDF in HF and whether FDF (acacia), compared to control, reduced the level of N-terminal pro-b-type natriuretic peptide (NT-proBNP) and growth stimulation expressed gene 2 (ST2), and produced changes in the gut microbiome.

Methods: Participants were randomly allocated 1:1:1 to either of the intervention arms (5 g/d or 10 g/d acacia) or to the control arm (10 g/d microcrystalline cellulose (MCC; nonfermentable active control). Adherence and tolerance were assessed, and clinical events were monitored for safety. All outcomes (NT-proBNP, ST2, New York Heart Association class, Kansas City Cardiomyopathy Questionnaire scores, 6-minute walk test score, gut microbiome) were measured at baseline, and at 6 and 12 weeks.

Results: Between September 13, 2018 and December 16, 2021, 51 patients were randomly allocated to either MCC (n = 18), acacia 5 g daily (n = 13), or acacia 10 g daily (n = 18). No differences occurred between either dose of acacia and MCC in NT-proBNP level, ST2, New York Heart Association class, or questionnaire scores over 12 weeks. Dietary treatment arms had a negligible impact on microbial communities. No safety, tolerability, or adherence issues were observed.

Conclusions: Dietary supplementation with acacia gum was both safe and well tolerated in ambulatory patients with HF; however, it did not change NT-proBNP level, ST2, or the composition of the gut microbiome.ClinicalTrials.gov: NCT03409926.

Graphical abstract

Figure 1

Primary and secondary outcomes. Relative changes at 12 weeks (baseline adjusted ratio [± standard error {SE}]) by treatment arm for (A) N-terminal pro–b-type natriuretic peptide (NT-proBNP) and (B) growth stimulation expressed gene 2 (ST2). The table at the top is for comparison of the relative changes in each intervention arm to that in the microcrystalline cellulose (MCC) arm. CI, confidence interval.

Figure 2

Kansas City Cardiomyopathy Questionnaire (KCCQ) quality-of-life outcomes. (A) Overall summary score (OSS); (B) clinical summary score (CSS); (C) physical limitation score (PLS). Means are adjusted for the respective score at baseline. MCC, microcrystalline cellulose; SE, standard error.

Figure 3

Baseline microbial community analysis between 10-mg group, microcrystalline cellulose (MCC) group, and 5-mg group. (A) Principal coordinate analysis (PCoA) plots of unweighted and weighted UniFrac distance indices for beta-diversity comparison. (B) Boxplot of inverse Simpson, Shannon, and Chao1 alpha-diversity metrics. (C) Plot of significant asymptotic variances (ASVs; unadjusted P < 0.05) from DEseq2 analyses between the 3 treatment groups. Bolded ASVs signifying the significant adjusted P-value < 0.10, < 0.05 (∗), < 0.01 (∗∗), and < 0.001 (∗∗∗). PC1, principal component 1; PC2, principal component 2.

Figure 4

Microbial community analysis of GroupA, GroupB, and GroupC after 12 weeks of treatment. (A) Principal coordinate analysis (PcoA) plots of unweighted and weighted UniFrac distance indices for beta-diversity comparison. (B) Boxplot of inverse Simpson, Shannon, and Chao1 alpha-diversity metrics. (C) Plot of significant asymptotic variances (ASVs; unadjusted P < 0.05) from DEseq2 analyses between the 3 treatment groups. Bolded ASVs signifying the significant adjusted P-value < 0.10, < 0.05 (∗), < 0.01 (∗∗), and < 0.001 (∗∗∗). MCC, microcrystalline cellulose; PC2, principal component 2.