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

Study Overview
=================
Brief Summary
-----------------
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.

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.

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

Conditions
-----------------
Heart Failure

Intervention / Treatment
-----------------
* Other: Blood Sample
* Other: Stool Sample


Participation Criteria
=================
Eligibility Criteria
-----------------
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

Ages Eligible for Study
-----------------
Minimum Age: 18 Years

Sexes Eligible for Study
-----------------
All

Accepts Healthy Volunteers
-----------------
Accepts Healthy Volunteers

Study Plan
=================
How is the study designed?
-----------------

Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| Normal control<br>The subjects in the normal heart function group will provide a blood sample and stool sample. | Other: Blood Sample<br>* One tablespoon of blood will be drawn once during the study.<br>Other: Stool Sample<br>* One stool sample will be collected.<br>|
| heart failure<br>The subjects in history of heart failure group will provide a blood sample and stool sample. | Other: Blood Sample<br>* One tablespoon of blood will be drawn once during the study.<br>Other: Stool Sample<br>* One stool sample will be collected.<br>|
| pre-HFpEF<br>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<br>* One tablespoon of blood will be drawn once during the study.<br>Other: Stool Sample<br>* One stool sample will be collected.<br>|

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 | 

 Terms related to the study
=================
Keywords Provided by Centre Hospitalier Valida
-----------------
pre-clinical diastolic dysfunction (pre-HFpEF)