Gut Microbiome and Ventricular Arrhythmias

Overview

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.

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.