Gut Microbiome and Ventricular Arrhythmias
Gut Microbiome and Ventricular Arrhythmias
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.

 We propose to study the relation and interaction between gut microbiome and ventricular
 arrhythmogenesis.
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, we 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, we 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.
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