Temporary Autonomic Blockade to Prevent Atrial Fibrillation After Cardiac Surgery
Condition: Atrial Fibrillation
MeSH terms: Atrial Fibrillation
Study type: Interventional
Phase: Phase 1/Phase 2

Summary: 
      In this study, the investigators aim to determine whether injecting botulinum toxin into
      epicardial fat pads is efficacious and safe for decreasing postoperative atrial fibrillation
      (POAF) after cardiac surgery. The investigators will test the hypothesis that botulinum toxin
      injected into the epicardial fat pads reduces POAF and length of stay (LOS) without
      increasing adverse events. This will be a prospective randomized trial of 130 patients
      undergoing coronary artery bypass graft (CABG), valve surgery or CABG + valve surgery with
      cardiopulmonary bypass. Patients will be randomized to receive either botulinum toxin (50
      units per fat pad, n=65) or normal saline/placebo (1 mL per fat pad, n=65) injected into
      epicardial fat pads. All patients will receive standardized anesthetic, surgical, and
      post-surgical care. The primary outcome in this study will be time to occurrence of
      in-hospital POAF. Based on previous work and a pilot trial showing a pronounced reduction
      (relative risk reduction 77%) in POAF after injecting botulinum into the epicardial fat pads,
      the investigators anticipate a significant reduction in the risk for POAF with epicardial
      botulinum in this cohort, which includes valve surgery patients.
    

Detailed description: 
      Purpose of the study: A pilot study to determine whether injecting botulinum toxin into
      epicardial fat pads is efficacious and safe for decreasing postoperative atrial fibrillation
      (POAF) after cardiac surgery

      Hypothesis to be tested: Botulinum toxin injected into the epicardial fat pads reduces POAF.

      Design and Procedures: This will be a prospective randomized pilot trial of 130 patients
      undergoing coronary artery bypass graft (CABG), valve surgery or CABG + valve surgery via
      median sternotomy with cardiopulmonary bypass. Patients <50 years of age, with chronic atrial
      fibrillation, prior cardiac surgery, EF<25%, preoperative inotropic support, hepatic or renal
      failure, known sensitivity to botulinum toxin, debilitating neuromuscular disease, or those
      with a history of atrioventricular block will be excluded from the study. Prior to surgery,
      all patients will have baseline Mini-Mental State Examination (MMSE) and blood sampling from
      an indwelling arterial line or venipuncture for measurement of inflammatory and genomic
      markers. Half of the patients will be randomized to receive injection of epicardial botulinum
      toxin in addition to standard of care, as described below. The other half will receive
      epicardial injection of normal saline.

      Institution of cardiopulmonary bypass will be performed according to the routine surgical
      protocol. After instituting CPB, botulinum toxin (or normal saline) injections will be
      performed by the surgeon. This dose was selected given the prior report of its effectiveness
      in preventing POAF after cardiac surgery in a small pilot study.(Pokushalov et al., 2014)
      After completion of surgery and separation from CPB, patients will proceed along the
      institutional Cardiac Surgical Caremap. All patients will be monitored with continuous ECG
      (telemetry) until hospital discharge. POAF will be diagnosed by telemetry or 12-lead ECG, and
      will be defined as new-onset if it occurs postoperatively at any time before hospital
      discharge. POAF, if it occurs, will be treated as per routine of care. POAF will be defined
      as any detectable atrial fibrillation before discharge that lasts >30 seconds. On
      postoperative day (POD) 4, a member of the study team will visit each patient to administer
      the MMSE and capture a 5-minute ECG with a Holter monitor. In addition, patients will be
      contacted monthly for 4 months and at one year after surgery for follow up, and medical
      records will be reviewed for evidence of readmissions, arrhythmias, or other adverse events.
    

Intervention name(s): Botulinum Toxin Type A; Placebo
Intervention type(s): Drug; Drug
Intervention description(s): The botulinum toxin will be injected into epicardial fat pads shortly after cardiopulmonary bypass is initiated.
Other intervention name(s): Botox; Onabotulinumtoxin A; normal saline
Intervention MeSH terms: Botulinum Toxins; Botulinum Toxins, Type A; abobotulinumtoxinA
Allocation: Randomized
Intervention model: Parallel Assignment
Masking: Quadruple (Participant, Care Provider, Investigator, Outcomes Assessor)
Primary purpose: Prevention
Keywords: Cardiac Surgery; Postoperative Complications; Autonomic Nerve Block