Vernakalant Versus Amiodarone for Post-operative Atrial Fibrillation in Cardiac Surgery Patients
Vernakalant Versus Amiodarone for Post-operative Atrial Fibrillation in Cardiac Surgery Patients
Post-operative atrial fibrillation is a common problem post cardiac surgery with rates
 exceeding 30%. Atrial fibrillation has multiple adverse effects on cardiac hemodynamics and
 can lead to hypotension, diminished end organ perfusion and lengthen the stay in ICU.
 Amiodarone is the medication of choice used for pharmacological cardioversion and can be used
 with vasoactive medications. Intravenous amiodarone is associated with hypotension and end
 organ perfusion requiring escalation in vasoactive support. Vernakalant is novel
 anti-arrhythmic agent approved in Canada for cardioversion of atrial fibrillation that
 primarily works on atrial channels and has no effect on contractility or vasodilation.
 Clinical trials have proved good efficacy of Vernakalant in conversion of paroxysmal atrial
 fibrillation however there is no comparison of Amiodarone to Vernakalant in post-operative
 cardiac surgery. We plan to perform a clinical trial comparing Vernakalant to amiodarone in
 post-cardiac surgery patients with a primary outcome of cardioversion at 90 minutes.
 Secondary outcomes will follow duration of vasoactive medications, days in ICU and economics.
1. Background - Atrial fibrillation (AF) is the most common cardiac arrhythmia post cardiac
 surgery. Estimates suggest that rates of patients experiencing post-operative atrial
 fibrillation (POAF) after cardiac surgery exceeds 30%. Atrial fibrillation has multiple
 effects on the cardiopulmonary hemodynamics. Rapid irregular ventricular rate results in
 decreased coronary flow diminishing the ability to preserve myocardial oxygen demand
 leading to ischemia. Atrial contraction provides 15-20% of LV filling in normal cardiac
 physiology and loss of synchronized atrial contraction in addition to decreased
 diastolic filling time may lead to decreased cardiac. This may lead to hypotension and
 diminished end organ perfusion requiring additional vasoactive support. Currently
 amiodarone is utilized as the pharmacological agent of choice for POAF in cardiac
 surgery, typical rate control agents are contraindicated due to need of vasoactive
 requirements. However direct effects of IV amiodarone include vasodilation and
 hypotension typically requiring escalating doses of vasoactive medications, which
 subsequently prolong stay in the CVICU (cardiovascular Intensive Care Unit), increase
 exposure to vasopressors and potentially mechanical ventilation. Vernakalant is a Von
 Williams Class III novel anti-arrhythmic agent with primary activity on atrial tissue
 with limited activity on ventricular myocardium. Primary mechanism of action is blocking
 early activating K+ atrial channels and frequency-dependent atrial Na+ channels which
 prolongs atrial refractory periods and decreasing atrial conduction without promoting
 ventricular arrhythmia. There have been many trials that proven efficacy in converting
 AF in patients with atrial fibrillation and in the post cardiac surgery patients,
 however this has never been compared to standard of care Amiodarone.

 2. Research Questions and objectives: We hypothesize administration of vernakalant compared
 to amiodarone will have a higher rate of cardioversion to sinus rhythm at 90 min in
 post-operative sustained atrial fibrillation. This will reduce duration of vasoactive
 medications, days in ICU and mortality.

 3. Methods: Patients will be recruited from the CVICU 24 hours after admission to CIVCU
 based on inclusion and exclusion criteria. Patients identified with new presentation
 atrial fibrillation with a sustained duration of greater than 30 minutes will be
 considered for the study. Patients will be randomized to Amiodarone versus Vernakalant
 using a computerized process. Patients randomized to an amiodarone arm will receive
 150mg IV bolus and an amiodarone infusion of 1mg/hr x 6 hours followed by 0.5mg/hr x 12
 hours. Patients randomized to Vernakalant will receive a bolus of 3mg/kg over 10 minutes
 and an observation period of 15 minutes, if the patient is still in AF, they will
 receive an additional 2.0mg/kg bolus of Vernakalant. Infusions will be discontinued if
 QT interval becomes >550ms, heart rate less than 45 bpm lasting >30 seconds with
 symptoms or <40bpm lasting >30 seconds with or without symptoms, ventricular tachycardia
 or development of heart block. At 90 minutes rate of conversion to sinus rhythm will be
 documented. Secondary outcomes including time to AF conversion, recurrence of atrial
 fibrillation will be documented along with safety events over 48h. Duration of
 vasoactive medications, days in ICU, time to initiation of beta blockers, mortality,
 Left Ventricular (LV) function and economics of ICU still will be followed. Patients
 will be excluded if they return to the OR.
Inclusion Criteria:

 1. Age >/=18 years

 2. Undergone heart surgery for coronary artery bypass surgery (on-pump or off-pump CABG)
 and/or valve repair or replacement (excluding mechanical valves), including
 re-operations.

 3. Hemodynamically stable with/without vasopressor support

 Exclusion Criteria:

 1. LVAD insertion or heart transplantation

 2. MAZE procedure

 3. Transcatheter aortic valve replacement (TAVR)

 4. History of or planned mechanical valve replacement

 5. Rheumatic heart disease

 6. Congenital cardiac defect (excluding bicuspid aortic valve or patent foramen ovale)

 7. History of prior atrial fibrillation or flutter

 8. History of ablation for atrial fibrillation

 9. Contraindication to amiodarone

 -  PR >240ms

 -  Heart block (2nd or 3rd degree)

 -  QTC >480ms

 -  Untreated thyroid disorder

 -  AST or ALT >2x upper limit of normal

 -  Hepatic cirrhosis

 -  Interstitial lung disease

 10. Received amiodarone within 6 weeks

 11. Contraindications to Vernakalant

 -  Known hypersensitivity to Vernakalant

 -  Prolonged QT

 -  Heart block (2nd or 3rd degree)

 -  Use of anti-arrhythmic medication in the past 4 weeks.

 12. Return to OR during CVICU stay or readmission to CIVCU from Cardiac Surgery ward.