RAFF4 Trial: Vernakalant vs. Procainamide for Acute Atrial Fibrillation in the Emergency Department

Inclusion Criteria:

The investigators will include stable (see below) patients presenting with an episode of acute non-valvular AF of at least 3 hours duration and no greater than 7 days, where symptoms require urgent management and where immediate cardioversion is a reasonable option because:

1. The patient has been adequately anticoagulated for a minimum of 3 weeks (warfarinand INR > 2.0 or novel oral anticoagulants [dabigatran, rivaroxaban, edoxaban, andapixaban]), or

2. The patient is not adequately anticoagulated for > 3 weeks, has no history of strokeor TIA, and does not have valvular heart disease, AND:

i) onset < 12 hours ago, or ii) if onset 12 - 48 hours ago and there are <2 of these CHADS-65 criteria (age ≥ 65, diabetes, hypertension, heart failure), or iii) negative for thrombus on transesophageal echocardiography. Of note, we will not exclude patients with prior episodes of acute AF. Patients will only be enrolled if the attending physician is confident about time of onset, based upon the patient's symptoms. Physicians are well aware of the importance of this determination and will not attempt to cardiovert patients otherwise.

Exclusion Criteria: The investigators will exclude patients who have any of the reasons listed below.

1. Appropriateness:

2. unable to understand the study and integrated consent due to language barrierand/or cognitive impairment;

3. have permanent (chronic) AF;

4. have valvular heart disease (mitral stenosis, rheumatic or mechanical);

5. increased risk of stroke because onset not clearly <48 hours and notanticoagulated (or abnormal TEE); or do not meet the inclusion criteria a or b;

6. deemed unstable and require immediate cardioversion: i) systolic blood pressure <100 mmHg; ii) rapid ventricular preexcitation (Wolff-Parkinson-Whitesyndrome); iii) acute coronary syndrome - chest pain and acute ischemic changeson ECG; or iv) pulmonary edema - severe dyspnea requiring immediate IVdiuretic, nitrates, or BIPAP;

7. primary presentation was for another condition; examples include pneumonia,pulmonary embolism, and sepsis;

8. convert spontaneously to sinus rhythm prior to randomization;

9. were previously enrolled in the study; or

10. have atrial flutter.

11. Safety

12. has heart failure Class NYHA III or NYHA IV; left ventricular ejection fraction <30%; or has clinical or radiological evidence of acute HF;

13. has presented with an acute coronary syndrome or acute decompensated heartfailure, in the last 30 days; or has had a recent myocardial infarction (< 3months);

14. has severe aortic stenosis;

15. has a systolic blood pressure < 100 mmHg;

16. has a significantly prolonged QT interval at baseline e.g. uncorrected > 440msec, congenital or acquired long QT syndrome; or a family history of Long QTsyndrome; or ECG shows QTc >460ms (when heart rate >100 measured by theFridericia formula);

17. has severe bradycardia (heart rate < 55 bpm), sinus node dysfunction, or secondor third degree atrioventricular heart block, in the absence of an in situproperly functioning pacemaker; or, has Brugada syndrome (genetic disease withincreased risk of sudden cardiac death);

18. has received an intravenous antiarrhythmic drug Class I, e.g. procainamide, orClass Ill, e.g. amiodarone or ibutilide, within the prior 4 hours; or currentlytakes oral class I or III antiarrhythmic drugs other than amiodarone (last dose < 5 half-lives before enrollment);

19. has received an IV beta-blocker within the 2 hours prior

20. has hypersensitivity to the active substance or to any of the ingredients ofeither drug;

21. has advanced or end-stage liver disease; or

22. is breast feeding or pregnant (safety not established).