Gut Microbiome and Ventricular Arrhythmias

Recruiting

• Conditions: Ventricular Tachycardia; Gut Microbiome; Ventricular Fibrillation
• Interventions: Diagnostic Test: Stool test for microbial analysis

• Registration Number: NCT04466072
• Lead Sponsor: North Florida Foundation for Research and Education

Brief Summary

Ventricular tachycardia and ventricular fibrillation (VT/VF) are the most common causes of sudden cardiac death in patients with diseased hearts. The factors contributing to these deadly arrhythmias are not well understood.

The presence of a wide variety of microbial flora in the human GI tract, particularly colon has been well recognized for a long time. There are also emerging links showing the effect of an intact gut microbiome having effects on left ventricular remodeling after myocardial infarction and hypertension. Gut microbiota has also been associated with outcomes in atrial fibrillation.

There is little available in current literature showing a relationship between gut microbiome characteristics and ventricular arrhythmia burden. The gut microbiome has particularly strong interactions with neuroendocrine and immunologic mediators and has effects on the modulation of the autonomic nervous system. These systems are also hypothesized to influence ventricular arrhythmias. The investigators propose to study the relation and interaction between gut microbiome and ventricular arrhythmogenesis.

Detailed Description

Specific Aims:

Aim 1: To identify specific gut microbiome characteristics of patients who are prone to clinically significant or high burden of ventricular arrhythmias compared with patients with similar conventional risk factors and low burden of ventricular arrhythmias.

Aim 2: To examine changes that occur in the gut microbiome composition after treatment of ventricular arrhythmias.

Research Plan:

This study will enroll 30 subjects recruited from the electrophysiology device clinic at the VA medical center, who are individuals with underlying cardiomyopathy and prone to ventricular arrhythmias.

Out of this cohort, the investigators will identify 2 groups who have different ventricular arrhythmia burden despite similar conventional clinical factors.

This information regarding ventricular arrhythmia burden will be obtained from device interrogation at the time of recruitment. Our proposal is study and compare the fecal microbial composition of these groups to analyze association with ventricular arrhythmia burden. Patients will provide a fecal sample for analysis at the time of enrollment.

After clinically indicated treatment in the high ventricular arrhythmia group, the investigators will retest fecal samples to assess for changes in characteristics after treatment. This will be done to study changes in the gut microbiome with ventricular arrhythmia in the same individual.

After initial testing of the high burden group, they will undergo treatment aimed at decreasing their burden of arrhythmia, with some combination of anti-arrhythmic drugs, sympathetic blockade, or ventricular tachycardia ablation. After demonstrating a period of 3 months without sustained VT/VF on device interrogation, their fecal samples will be re-analyzed. If a patient continues to have VT/VF requiring intermittent device therapies despite a 6 month period of intensification of therapy, their fecal sample will be re-analyzed after that 6 month timeframe.

Study Timeline

• Study First Submitted: 2020-07-07
• Study First Submitted QC: 2020-07-07
• Study First Posted: 2020-07-10
• Study Start: 2020-11-30
• Status Verified: 2022-04
• Last Update Submitted: 2022-04-11
• Last Update Posted: 2022-04-18
• Primary Completion: 2024-12-31
• Study Completion: 2024-12-31

Recruitment & Eligibility

• Status: RECRUITING
• Sex: All
• Target Recruitment: 30

Inclusion Criteria

• Inclusion criteria for all groups:

  • age >18 years-old
  • competent and willing to provide consent
  • presence of implantable cardioverter-defibrillator
  • diagnosis of cardiomyopathy
  • left ventricular ejection fraction of 35% or less as assessed by echocardiogram within 1 year prior to enrollment

• Inclusion criteria for control group:

  • no VT/VF on device interrogation for a period of at least 3 months preceding study enrollment

• Inclusion criteria for high ventricular arrhythmia burden group:

  • at least one episode of sustained VT/VF or VT/VF requiring ICD therapies within the preceding 3 months as assessed on device interrogation at the time of study enrollment

Exclusion Criteria

• currently pregnant or have been pregnant in the last 6 months
• antibiotic treatment within 5 months of study enrollment (i.e. antibiotic therapy in the two months prior to the 3-month period of analysis for VT/VF)
• chronic use of medications/supplements that can potentially affect gut microbiota (i.e. probiotics, anti-inflammatory agents, glucocorticoids, other immune modulating medications, antacids or proton pump inhibitors)
• history of intestinal surgery, inflammatory bowel disease, celiac disease, lactose intolerance, chronic pancreatitis, or other malabsorption disorder

Study & Design

• Study Type: OBSERVATIONAL
• Study Design: Not specified

Arm && Interventions

Group	Intervention	Description
High Ventricular Arrhythmia burden group	Stool test for microbial analysis	Inclusion criteria for all groups: * age \>18 years-old * competent and willing to provide consent * presence of implantable cardioverter-defibrillator * diagnosis of cardiomyopathy * left ventricular ejection fraction of 35% or less as assessed by echocardiogram within 1 year prior to enrollment Inclusion criteria for high ventricular arrhythmia burden group: • at least one episode of sustained VT/VF or VT/VF requiring ICD therapies within the preceding 3 months as assessed on device interrogation at the time of study enrollment Both groups will have stool sample collected for microbial analysis. This is anticipated twice for the high ventricular arrhythmia (VA) burden group. Once at the time of diagnosis of VA and later after the clinically indicated treatment for the VA.
Control group	Stool test for microbial analysis	Inclusion criteria for all groups: * age \>18 years-old * competent and willing to provide consent * presence of implantable cardioverter-defibrillator * diagnosis of cardiomyopathy * left ventricular ejection fraction of 35% or less as assessed by echocardiogram within 1 year prior to enrollment Inclusion criteria for control group: • no VT/VF on device interrogation for a period of at least 3 months preceding study enrollment Both groups will have stool sample collected for microbial analysis. This is anticipated only once for the control group.

Primary Outcome Measures

Name	Time	Method
Difference in microbial composition of gut microbiome in study and control groups	1 year	Microbial components identified through genetics will be compared between groups.

Secondary Outcome Measures

Name	Time	Method
Change in microbial composition of gut microbiome after successful VT therapy	1 year	Microbial components identified through genetics will be compared before and after VT therapy in the high VT burden group.

Trial Locations

Locations (1)

Malcolm Randall VA medical center; 🇺🇸 Gainesville, Florida, United States