Gut Microbiome Profiling in Patients With Chronic Heart Failure

Longitudinal Gut Microbiome and Host Multi-omic Profiling in Patients With Chronic Heart Failure

The goal of this observational study is to learn about the composition and function of the gut microbiome in adults with chronic heart failure with reduced ejection fraction. The main questions the study aims to answer are:

1. How does the gut microbiome and its interactions with the host change over time in adults with chronic heart failure?
2. How do these changes relate to heart failure disease severity and complications?

Study Overview

• Status: Enrolling by invitation
• Conditions: Heart Failure With Reduced Ejection Fraction; Nonischemic Cardiomyopathy

Detailed Description

During this study, investigators will recruit adults diagnosed with chronic heart failure with reduced ejection fraction caused by non-ischemic cardiomyopathy. These individuals will undergo longitudinal profiling. This will include detailed profiling of their (1) gut microbiome, (2) blood metabolic and immune markers, and (3) heart failure clinical status. Integrated results will lead to deeper understanding of how gut microbiome interacts with and affects the host in chronic heart failure.

• Study Type: Observational
• Enrollment (Estimated): 150

Contacts and Locations

Study Locations

• United States
  • California
    • Stanford, California, United States, 94305-5210
      • Stanford University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult; Older Adult
• Accepts Healthy Volunteers: No

• Sampling Method: Non-Probability Sample

Study Population

Adults diagnosed with heart failure with reduced ejection fraction due to non-ischemic cardiomyopathy will be recruited from outpatient cardiomyopathy/heart failure clinic.

Description

Inclusion Criteria:

• Heart failure with reduced ejection fraction (left ventricular ejection fraction less than 50%)
• Non-ischemic cardiomyopathy
• Body mass index (BMI) 18-40 kg/m2

Exclusion Criteria:

• Treated diabetes
• Advanced kidney disease
• Cirrhosis
• Significant gastrointestinal disease including any history of inflammatory bowel disease
• History of extensive bowel resection
• Active malignancy or systemic chemotherapy within the past 12 months
• Active infection
• Current or recent (within 4 weeks) use of systemic antibiotics, commercial probiotics, immunosuppressive or immunomodulatory medications
• Pregnancy/lactation

Study Plan

How is the study designed?

Number of groups / cohorts

1

Cohorts and Interventions

Group / Cohort
Heart failure; Adults with heart failure with reduced ejection fraction; no intervention

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Advanced heart failure-associated microbiome signatures	A map of gut microbiome compositional and functional features associated with a composite clinical outcome of advanced heart failure (composite of needing heart transplantation (including active listing), left ventricular assist device implantation, transition to hospice, or death) that occurs within 24 months of baseline visit. Fecal samples will be collected every 3 months over the first 12 month period. Microbiota composition will be determined by shotgun metagenomic sequencing, with taxonomic and metabolic pathway signatures generated using bioinformatic pipelines, respectively. Comprehensive microbiome signatures will encompass alpha and beta diversity, and differential abundance analysis.	24 months from baseline visit
Temporal changes in the gut microbiome community composition in chronic heart failure	Longitudinal changes in the gut microbiome composition and functionality in chronic heart failure will be determined. Microbiome signatures will be mapped from fecal samples collected every 3 months over a 12 month period, generated from shotgun metagenomic sequencing data and after processing through bioinformatic pipelines.	12 months from baseline visit

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Comprehensive longitudinal metabolome profile in chronic heart failure	Changes in the host (human) metabolome profile in chronic heart failure with reduced ejection fraction will be determined. Participants provide fasting blood samples every 3 months for 12 months, from which plasma samples are prepared. Plasma metabolites are run through liquid chromatography-mass spectrometry (LC-MS) columns. MetID (Metabolite Identification from a reference database) and our LC-MS data are used to identify hundreds of metabolites with confidence levels 1-2. Many of the identified metabolites are gut microbiome-derived.	12 months from baseline visit
Comprehensive longitudinal cytokine profile in chronic heart failure	Changes in the host (human) cytokines in chronic heart failure with reduced ejection fraction will be determined. Participants provide fasting blood samples every 3 months for 12 months, from which serum samples are prepared. Cytokines are profiled using a 76-cytokine Luminex profiling system at the Stanford Human Immune Monitoring Center. This involves attaching antibodies specific to cytokines to beads using a capture molecule. The fluorescent molecules are attached to the cytokines, and fluorescence is used as the measure of cytokine abundance.	12 months from baseline visit
Longitudinal change in New York Heart Association (NYHA) functional class	Participants' functional status (as measured by NYHA class, which ranges from 1 to 4, with 1 being no to minimal symptoms with activity, and 4 being symptoms at rest) will be assessed at each study visit for the first 12 months (every 3 months).	12 months from baseline visit
Longitudinal change in the self-reported functional status	Participant self-reported functional status will be assessed via Kansas City Cardiomyopathy Questionnaire-12, which participant will complete at each study visit (every 3 months for 12 months). Overall summary and clinical summary scores (each 0-100, with 0 corresponding to severe and 100 corresponding to no functional limitations) will be calculated and compared over visits.	12 months from baseline visit

Collaborators and Investigators

• Sponsor: Stanford University
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI); American Heart Association

Study record dates

Study Major Dates

• Study Start (Actual): August 1, 2018
• Primary Completion (Estimated): December 1, 2028
• Study Completion (Estimated): December 1, 2028

Study Registration Dates

• First Submitted: April 5, 2024
• First Submitted That Met QC Criteria: April 10, 2024
• First Posted (Actual): April 12, 2024

Study Record Updates

• Last Update Posted (Actual): May 16, 2025
• Last Update Submitted That Met QC Criteria: May 13, 2025
• Last Verified: May 1, 2025

More Information

Terms related to this study

• Keywords: Heart failure; Gut microbiota; Gut microbiome; Multiomics; Nonischemic Cardiomyopathy
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure; Cardiomyopathies
• Other Study ID Numbers: 44967; 5F32HL143916 (U.S. NIH Grant/Contract); 856341 (Other Grant/Funding Number: American Heart Association)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: YES
• IPD Plan Description: De-identified clinical data, gut microbiome (taxonomic and metabolic pathway) profiles, plasma metabolome and cytokines (see details below), in addition to analytical code
• IPD Sharing Time Frame: Immediately upon publication, without end date
• IPD Sharing Access Criteria: All nucleic acid raw read and processed data will be deposited in Sequence Read Archive (SRA) (metagenomics). Metabolomics and cytokine data will be deposited in Metabolomics Workbench and ImmPort (both of these are National Institutes of Health (NIH) data repositories), respectively. All genomic data sharing will be done in accordance with NIH policies, including the Genomic Data Sharing Policy, and the Institutional Review Board (IRB) approved consent types for each sample type. Detailed metadata will be associated with each dataset. To request access of the data, researchers will use the standard processes at the above repositories. The standard data access processes typically allow access for one year and are renewable. Once the data are submitted to the above repositories, those archive will control the long-term persistence of the data set.
• IPD Sharing Supporting Information Type: STUDY_PROTOCOL; ANALYTIC_CODE

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No