Temporary Autonomic Blockade to Prevent Atrial Fibrillation After Cardiac Surgery

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.

Inclusion criteria

• Undergoing cardiac surgery with cardiopulmonary bypass via median sternotomy
• coronary artery bypass graft (CABG)
• valve surgery
• CABG + valve surgery

Exclusion criteria

• < 50years of age
• > 90years of age
• chronic AF or AF at the time of screening
• preoperative heart block (second degree or greater)
• LVEF < 25%
• renal failure
• hepatic failure
• known sensitivity to Botulinum toxin
• debilitating neuromuscular disease
• preoperative need for inotropes/vasopressors or intra-aortic balloon pump
• planned MAZE procedure
• history of catheter ablation for AF
• use of Vaughan-Williams class I or III drugs within 5 elimination half lives (or within 2 months for amiodarone)
• undergoing minimally-invasive cardiac surgery
• prior cardiac surgery