The Role of Gut Microbiota in Heart Failure and Pre-Heart Failure With Preserved Ejection Fraction

Characterize the Gut Microbiota in Subjects With Heart Failure and Pre-heart Failure With Preserved Ejection Fraction

Gut microbiota play an important role in normal cardiovascular function and pathophysiology of cardiovascular diseases. Patients with heart failure (HF) have substantial hemodynamic changes which lead to intestinal hypoperfusion and congestion and eventually change gut morphology, permeability, function and composition of gut microbiota and cause translocation of microbial and endotoxins into the blood stream. Additionally, metabolites derived from gut microbiota modulate the pathophysiology of HF. Patients with HF have intestinal overgrowth of pathogenic bacteria and increased gut permeability. Accumulating evidence demonstrates that antibiotic treatment benefits patients with acute coronary syndromes and reduces the incidence of ischemic cardiovascular events. Taking the strong association of gut microbiota with HF into account, it is reasonable to speculate that gut microbiota could contribute to the progression of pre-HF with preserved ejection fraction (pre-HFpEF) to HF with preserved ejection fraction (HFpEF). Pre-HFpEF remains poorly understood, yet has high prevalence and a significantly high risk for death in comparison to patient without pre-HFpEF. We hypothesize that altered gut microbiota is involved in the initiation and establishment of HF and pre-HFpEF.

Study Overview

• Status: Withdrawn
• Conditions: Heart Failure
• Intervention / Treatment: Other: Blood Sample; Other: Stool Sample

Detailed Description

The research study will initially enroll 50 subjects without HF as normal controls,120 subjects with history of HF and 50 subjects with pre-HFpEF to characterize gut microbiota. The subjects will provide blood samples and a stool sample.

• Study Type: Observational

Contacts and Locations

Study Locations

• United States
  • Florida
    • Gainesville, Florida, United States, 32610
      • Cardiovascular Clinic at UF Health

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years and older (Adult, Older Adult)
• Accepts Healthy Volunteers: Yes

• Sampling Method: Non-Probability Sample

Study Population

Consenting participants who have normal, diastolic dysfunction or heart failure

Description

Inclusion Criteria:

• Competent and willing to provide consent
• Control subjects with normal heart function
• Subjects with history of HF
• Subjects with impaired ventricular relaxation and/or elevated left ventricular end diastolic pressure measured by echocardiography and/or catheterization, yet has not had HF clinical presentations

Exclusion Criteria:

• intestinal surgery,
• inflammatory bowel disease,
• celiac disease,
• lactose intolerance,
• chronic pancreatitis or
• other malabsorption disorder

Study Plan

How is the study designed?

Design Details

• Observational Models: Cohort
• Time Perspectives: Prospective

Number of groups / cohorts

3

Cohorts and Interventions

Group / Cohort	Intervention / Treatment
Normal control; The subjects in the normal heart function group will provide a blood sample and stool sample.	Other: Blood Sample; One tablespoon of blood will be drawn once during the study.; Other: Stool Sample; One stool sample will be collected.
heart failure; The subjects in history of heart failure group will provide a blood sample and stool sample.	Other: Blood Sample; One tablespoon of blood will be drawn once during the study.; Other: Stool Sample; One stool sample will be collected.
pre-HFpEF; The subjects in history of diastolic dysfunction but not had heart failure clinical presentations group will provide a blood sample and stool sample.	Other: Blood Sample; One tablespoon of blood will be drawn once during the study.; Other: Stool Sample; One stool sample will be collected.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Stool sample for fecal microbiota between the groups	Stool samples will be collected to compare the fecal microbiota of subjects with normal, diastolic heart dysfunction before heart failure developed and heart failure.	Day 1

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Blood samples for inflammatory cytokines between the groups	Blood samples will be used to compare difference in inflammatory cytokines including Interleukin-1 (IL-1), 6, 17 between groups using ELISA kits.	Day 1
Blood samples for SAA between the groups	Blood samples will be used to compare difference in serum amyloid (SAA) a between groups using ELISA kits.	Day 1
Blood samples for inflammatory cells between the groups	Blood samples will be used for difference in progenitor/inflammatory cells between the groups.	Day 1

Collaborators and Investigators

• Sponsor: University of Florida
• Collaborators: National Heart, Lung, and Blood Institute (NHLBI)
• Investigators: Principal Investigator: Carl J Pepine, MD, University of Florida

Study record dates

Study Major Dates

• Study Start (Actual): October 1, 2016
• Primary Completion (Estimated): June 8, 2025
• Study Completion (Estimated): June 8, 2025

Study Registration Dates

• First Submitted: March 30, 2016
• First Submitted That Met QC Criteria: March 30, 2016
• First Posted (Estimated): April 5, 2016

Study Record Updates

• Last Update Posted (Actual): April 10, 2025
• Last Update Submitted That Met QC Criteria: April 7, 2025
• Last Verified: April 1, 2025

More Information

Terms related to this study

• Keywords: pre-clinical diastolic dysfunction (pre-HFpEF)
• Additional Relevant MeSH Terms: Cardiovascular Diseases; Heart Diseases; Heart Failure
• Other Study ID Numbers: IRB201600380 - N; 5R01HL132448 (U.S. NIH Grant/Contract)

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: UNDECIDED