October 2014

1. CCS Atrial Fibrillation Guidelines: Management Of AF In 2014: Putting The New Guidelines Into Practice October 2014

2. About this Slide Set This slide set is a quick-reference tool that features essential diagnostic and treatment recommendations based on the 2010 CCS Atrial Fibrillation Guidelines, the 2012 CCS Atrial Fibrillation Guidelines Update and the 2014 Focused Update of the CCS guidelines for the management of AF. These recommendations are aimed to provide a reasonable and practical approach to care for specialists and allied health professionals obliged with the duty of bestowing optimal care to patients and families, and can be subject to change as scientific knowledge and technology advance and as practice patterns evolve. The guideline is not intended to be a substitute for physicians using their individual judgment in managing clinical care in consultation with the patient, with appropriate regard to all the individual circumstances of the patient, diagnostic and treatment options available and available resources. Adherence to these recommendations will not necessarily produce successful outcomes in every case. For the complete CCS Atrial Fibrillation Guidelines, or for additional resources, please visit our guidelines website at www.ccs.ca.

3. The 2014 Focused Update of the Canadian Cardiovascular Society Guidelines for the Management of Atrial Fibrillation Co-chairs and Authors Jeff S. Healey and Atul Verma Authors John A. Cairns, Stuart Connolly, Jafna L. Cox, Paul Dorian, David Gladstone, Gordon J. Gubitz, Noah Ivers, Kori Leblanc, Laurent Macle, Michael Sean McMurtry, L. Brent Mitchell, Stanley Nattel, Pierre Pagé, Ratika Parkash, P. Timothy Pollak, Allan C. Skanes, Ian G. Stiell, Mario Talajic, Teresa S. M. Tsang and Carl Van Walraven. Publication date: October 2014

4. Faculty Jeff Healey, MD, FRCPC McMaster University Atul Verma, MD FRCPC FHRS Director of Electrophysiology Research & Labs Southlake Regional Health Centre Assistant Professor, University of Toronto Adjunct Professor, McGill University John A Cairns, MD, FRCPC, FACC Professor of Medicine Division of CardiologyUniversity of British Columbia Paul Dorian, MD, FRCPC Department Director, Division of Cardiology University of Toronto Staff Cardiac Electrophysiologist St. Michael's Hospital Professor of Medicine Division of Cardiology and Clinical Pharmacology University of Toronto Staff Scientist at the Li Ka Shing Knowledge Institute. Allan C. Skanes, MD FRCPC Associate Professor, Department of Medicine, Division of Cardiology 
Cardiologist, London Health Sciences Centre 
Director, Electrophysiology Lab London Health Sciences Centre L. Brent Mitchell, MD, FRCPC Professor of Medicine and Cardiac Sciences Libin Cardiovascular Institute of Alberta Alberta Health Services and University of Calgary

5. Overview of the 2014 Update • 2014 publication ismeant as an update to prior update in 2012 and original major guideline re-write in 2010 • Includes an executivesummary of ALL guidelines from 2010 onwards (updated) whichcanbedownloaded online at the CJC website

6. Overview of the 2014 Update Key new elements of the 2014 Update: • New, simplified stroke risk stratification scheme: “The CCS Algorithm” • Detection of AF in patients with stroke • Investigation and management of subclinical AF • Commentary on left atrial appendage closure • Re-write on cardioversion guidelines in ED • New section on peri-procedural management of oral anticoagulation • New rate/rhythm control algorithm

7. New CCS Algorithm

8. Detection of AF in Stroke Patients

9. Management of SCAF

10. Perioperative Management of OAC What constitutes low, intermediate and high risk procedures for perioperative bleeding When interruption of OAC is required and when it is not How to stop new direct oral anticoagulants around the time of surgery When and how to bridge for cessation of warfarin therapy When to restart OAC after surgery

11. New Rate/Rhythm Algorithm

12. Case 1 : Dr. YDAF in Emergency Departmentby John A. Cairns, MD FRCPC FACC October 2014

13. Disclosures • DSMBs Chair: AVERROES (apixaban), SHIELD-2 (azimilide), ARTESIA (apixaban) Member: ACTIVE Trials (aspirin, clopidogrel, warfarin), PALLAS (dronedarone), COMPASS (rivaroxaban), • Advisory Boards BoehringerIngelheim Canada (Since Nov 2010), St Jude Medical (since Jan 2012), Bayer (intermittent), BMS (intermittent) • Research trial funding Medtronic, Sanofi Aventis, Astrazeneca, Bayer, Boston Scientific • Speaker honoraria BoehringerIngelheim Canada, Lilly, Pfizer/BMS, Bayer

14. Dr. YD, Age 42, Family Practitioner • Last evening he was out celebrating the marriage of his receptionist and consumed about 12 ounces of Johnny Walker Black label. • He went home by taxi, slept poorly and realized this morning about 6:00 am that his heart rate was rapid and pulse irregular. • He has a mild bitemporal headache and is driven to the ED by his wife. • He has been well, no known hypertension, DM, heart disease, TIA/stroke and no known arrhythmias although he does have mild palpitations from time to time. No COPD or asthma. • In ED: no chest pain, mild SOB, slightly sweaty. HR 140, irregularly irregular, BP 140/90, JVD 4 cm, Chest clear. ECG shows AF, rate 140.

15. Overview of AF Management AF Detected Management of Arrhythmia Assessment of Thromboembolic Risk (CHADS2) ASA OAC Rate Control Rhythm Control No antithrombotic therapy may be appropriate in selected young patients with no stroke risk factors

16. Dr. YD, Age 42, Family Practitioner How will you manage his rhythm? • Electrical cardioversion (150-200 j) in ED as soon as it can be done. • IV metoprolol 5 mg, repeated Q 5 min up to 3 times if rate remains above 110. Home on pometoprolol 50-100 mg bid if AF persists. • IV metoprolol 5 mg, repeated Q 5 min up to 3 times if rate remains above 110. Addpropofenone 450 mg po about 10-15 minutes after first dose of metoprolol if AF persists. • IV metoprolol 5 mg, repeated Q 5 min up to 3 times if rate remains above 110. Electrical cardioversion if AF persists. • Digoxin 0.25 mg IV, repeat at 1 hour intervals up to 4 doses if AF persists.

17. Dr. YD, Age 42, Family Practitioner How will you manage his rhythm? • Electrical cardioversion (150-200 j) in ED as soon as it can be done. • IV metoprolol 5 mg, repeated Q 5 min up to 3 times if rate remains above 110. Home on po metoprolol 50-100 mg bid if AF persists. • IV metoprolol 5 mg, repeated Q 5 min up to 3 times if rate remains above 110. Add propofenone 450 mg po about 10-15 minutes after first dose of metoprolol if AF persists. • IV metoprolol 5 mg, repeated Q 5 min up to 3 times if rate remains above 110. Electrical cardioversion if AF persists. Best answer! * • Digoxin 0.25 mg IV, repeat at 1 hour intervals up to 4 doses if AF persists. *This is a young man with no stroke risk factors. His AF has been present for only a few hours. It is likely the AF was precipitated by his alcohol indiscretion and he is likely to return to NSR with cardioversion and likely to remain in sinus rhythm. Accordingly, electrical cardioversion is a good option. It makes sense to give IV metoprolol to slow his rate before cardioversion. The cardioversion may be done without prior anticoagulation. He requires no ongoing OAC or ASA. Hence, the best answer is #4. #3 would be acceptable if there is some reason not to do electrical cardioversion, or if there is any expectation that he may have recurrent episodes of AF and might be suitable for a pill in the pocket regimen, but this does not appear indicted in this first presentation of AF. #2 is OK, but in a young person with acute onset, electrical (or pharmacological) cardioversion has a high likelihood of resolving the AF. #1 is not advised since there is no rush to cardiovert him and giving metoprolol will be likely to decrease symptoms prior to cardioversion. #5 would not be a good choice.

18. Dr. YD, Age 42, Family Practitioner How will you reduce his risk of strokeif you decide to cardiovert him? • IV LMWH or a NOACpo about 1 hour prior to any cardioversion attempt. • IV LMWH or a NOACpo about 1 hour prior to electrical cardioversion, but not required for pharmacologic cardioversion. • No anticoagulant required pre cardioversion attempt. • Start dabigatran 150 mg bid and have him return for cardioversion after 3 weeks of dabigatran.

19. Dr. YD, Age 42, Family Practitioner How will you reduce his risk of strokeif you decide to cardiovert him? • IV LMWH or a NOACpo about 1 hour prior to any cardioversion attempt. • IV LMWH or a NOACpo about 1 hour prior to electrical cardioversion, but not required for pharmacologic cardioversion. • No anticoagulant required pre cardioversion attempt. Best answer! He isyoung, has no riskfactors for stroke, and the duration of AF has been short. The risk of a stroke withcardioversion and no anticoagulation isverylow. He requires no anticoagulation precardioversion. • Start dabigatran 150 mg bid and have him return for cardioversion after 3 weeks of dabigatran.

20. Management of AF in the ED – Recommendations Is Patient Stable? YES NO Immediate Risk for Stroke? High Risk** No therapeutic OAC ≥ 3 weeksand one of: 1. Onset >48 hours or unknown, or 2. Stroke/TIA <6 months or 3. Mechanical or rheumatic valve disease. Low Risk 1. Clear onset <48 hours, or 2. Therapeutic OAC ≥ 3 wks Unstable – AF causing: 1. Hypotension, or 2. Cardiac ischemia, or 3. Pulmonary edema Pharmacological or electrical CV at 150-200 J (Immediate anticoagulation in ED before CV not required) * Rate-control Consider urgent electrical CV if rate control not effective Therapeutic OAC for 3 weeks before outpatient CV Trans-esophageal echocardiography (TEE) guided CV • Antithrombotic therapy • Initiate OAC upon discharge from ED (or continue current OAC) if age ≥ 65 or CHADS2 ≥ 1 • Otherwise, initiate ASA if CAD or vascular disease • Early follow-up to review long-term OAC Antithrombotic therapy - Continue OAC for ≥4 weeks after CV - Early follow-up to review long-term OAC • Antithrombotic therapy • Initiate immediate OAC* in ED and continue for≥4 weeks if any ‘high risk’ ** features present • - Early follow-up to review long-term OAC Antithrombotic therapy - Initiate immediate OAC* in ED and continue for ≥4 weeks - Early follow-up to review long-term OAC * Immediate OAC = a dose of OAC should be given just prior to cardioversion - either a novel direct oral anticoagulant (NOAC) or a dose of heparin or low molecular weight heparin with bridging to warfarin if a NOAC is contraindicated.

21. Supporting Data • Post CV TE 0.8% vs 5.3% with oralanticoagulation. Prospective cohort study (Bjerkelund et al 1969). • 90% of TE occur within 10 d of CV. Meta-analysis (Berger 1998) • TE < 1% for CV < 48 hrs with no OAC (case series 1997, 2002) • CV > 48 hrs, TE occurs following CV even with OAC (< 1% by 30 days). Rate with NOACs similar to with VKA (NOAC RCTs 2012-14)

22. Supporting Data • Finnish Study 2014 (Nuotio I et al. JAMA 2014;312:647) Rates of TE with duration of AF: <12 hrs: 0.3%; 12-24 hrs: 1.1%; 24-48 hrs: 1.1% Multivariable Analysis of Risk Factors for TE (n= 5116) OR(95% CI) P Value Time:12-24 vs <12 4.0 (1.7-9.1) .001 24-48 vs <12 3.3 (1.3-8.9) .02 Age, y (continuous) 1.06 (1.03-1.09) <.001 Female sex 2.1 (1.1-4.3) .04 Heart failure 3.5 (1.4-8.6) <.001 Diabetes 2.7 (1.3-5.8) .01

23. Dr. YD, Age 42, Family Practitioner How will you reduce his risk of strokeif you decide to cardiovert him? • IV LMWH or a NOACpo about 1 hour prior to any cardioversion attempt. • IV LMWH or a NOACpo about 1 hour prior to electrical cardioversion, but not required for pharmacologic cardioversion. • No anticoagulant required pre cardioversion attempt. • Start dabigatran 150 mg bid and have him return for cardioversion after 3 weeks of dabigatran.

24. Dr. YD, Age 42, Family Practitioner How will you reduce his risk of strokeif you decide to cardiovert him? • IV LMWH or a NOACpo about 1 hour prior to any cardioversion attempt. • IV LMWH or a NOACpo about 1 hour prior to electrical cardioversion, but not required for pharmacologic cardioversion. • No anticoagulant required pre cardioversion attempt. Best answer! He isyoung, has no riskfactors for stroke, and the duration of AF has been short. The risk of a stroke withcardioversion and no anticoagulation isverylow. He requires no anticoagulation precardioversion. • Start dabigatran 150 mg bid and have him return for cardioversion after 3 weeks of dabigatran.

25. Dr. YD, Age 42, Family Practitioner How will you reduce his risk of strokepost dischargefrom Ed? • If AF persists, he requires maintenance ASA 81 mg daily at least until follow-up at 1 month. • Whether AF persists or resolves, he requires maintenance ASA 81 mg at least until follow-up at 1 month. • If AF persists, he requires maintenance OAC at least until follow-up at 1 month. • Whether AF persists or resolves, he requires maintenance OAC at least until follow-up at 1 month. • Whether AF persists or resolves, he requires no maintenance antithrombotic therapy.

26. Dr. YD, Age 42, Family Practitioner How will you reduce his risk of strokepost dischargefrom Ed? • If AF persists, he requires maintenance ASA 81 mg daily at least until follow-up at 1 month. • Whether AF persists or resolves, he requires maintenance ASA 81 mg at least until follow-up at 1 month. • If AF persists, he requires maintenance OAC at least until follow-up at 1 month. • Whether AF persists or resolves, he requires maintenance OAC at least until follow-up at 1 month. • Best Answer! Whether AF persists or resolves, he requires no maintenance antithrombotic therapy. - He isyoung, has no riskfactors for stroke. He fits the CCS algorithm of no antithrombotictherapy for AF.

27. Dr. YD, Age 42, Family Practitioner Within the group of patients with CHADS2 = 0 (annual stroke risk 1.9%): • Data from Danish epidemiological studies indicate the following annual risks of stroke: Age 65-74: 2.13% Vascular disease: 1.40% Age < 65, no vascular disease:0.7%

28. The “CCS Algorithm” for OAC Therapy in AF YES YES NO NO NO OAC* Age ³ 65 Consider and modify (if possible) all factors influencing risk of bleeding on OAC (hypertension, antiplatelet drugs, NSAIDs, excessive alcohol, labile INRs) and specifically bleeding risks for NOACs (low eGFR, age ≥ 75, low body weight)** **may require lower dosing Prior Stroke/SE/TIA or Hypertension or Heart failure or Diabetes Mellitus (CHADS2 risk factors) OAC* CAD or Arterial vascular disease (coronary, aortic, peripheral) ASA YES No Antithrombotic * We suggest that a NOAC be used in preference to warfarin for non-valvular AF.

29. Dr. YD, Age 42, Family Practitioner How will you reduce his risk of stroke post discharge from ED? • If AF persists, he requires maintenance ASA 81 mgdaily at least until follow-up at 1 month. • Whether AF persists or resolves, he requires maintenance ASA 81 mg at least until follow-up at 1 month. • If AF persists, he requires maintenance OAC at least until follow-up at 1 month. • Whether AF persists or resolves, he requires maintenance OAC at least until follow-up at 1 month. • Whether AF persists or resolves, he requires no maintenance antithrombotic therapy.

30. Recommendation For patients with no high-risk factors for stroke(recent stroke or TIA within 6 months; rheumatic heart disease; mechanical valve) and clear AF onset within 48 hours or therapeutic OAC therapy for 3 weeks, we recommend that they may undergo cardioversion in the ED without immediate initiation of anticoagulation. After attempted or successful cardioversion, antithrombotic therapy should be initiated as per the CCS algorithm. (Strong Recommendation, Moderate-Quality Evidence) AF Management in the ED

31. Recommendation For patients at high risk of strokewith cardioversion (not receiving therapeutic OAC therapy for 3 weeks with any of the following: AF episode duration not clearly < 48 hours, stroke or TIA within 6 months, rheumatic heart disease, mechanical valve), we recommend optimized rate control and therapeutic OAC for 3 weeks before and at least 4 weeks after cardioversion. (Strong Recommendation, Moderate-Quality Evidence) AF Management in the ED

32. Recommendation We suggest that patients at high risk of stroke(not receiving therapeutic OAC therapy for 3 weeks with any of the following: AF episode duration not clearly < 48 hours, stroke or TIA within 6 months, rheumatic heart disease, mechanical valve) may undergo cardioversion guided bytransesophagealechocardiographywith immediate initiation of intravenous heparin or low molecular weight heparin (LMWH) before cardioversion followed by therapeutic OAC for at least 4 weeks after cardioversion. (Conditional Recommendation, Moderate-Quality Evidence) AF Management in the ED

33. Recommendation For patients whose recent-onset AF/AFL is the direct cause of instabilitywith hypotension, acute coronary syndrome, or florid pulmonary edema, we recommend that immediate electrical cardioversionbe considered with immediate initiation of intravenous or LMWH before cardioversion followed by therapeutic OAC for 4 weeks afterward (unless AF onset was clearly within 48 hours or the patient has received therapeutic OAC for 3 weeks) followed by therapeutic OAC for at least 4 weeks after cardioversion (Strong Recommendation, Low-Quality Evidence) AF Management in the ED

35. Case 2 : Mrs. BBRate and Rhythm Control by Paul Dorian, MD FRCPC October 2014

36. Disclosures • Paul Dorian has received grant support and honoraria from Bayer, Boehringer-Ingleheim, BMS, Pfizer, Sanofi

37. A guidelines based approach to AF management Mrs. BB, a 77 year old lady has hypertension, otherwise well Lives alone, has a dog On Ramipril 10 mg and bisoprolol 5 mg a day for hypertension 5 ft 5 in, 190lbs. Comes to the office for routine BP follow-up

38. Pulse rate 85/min, irregular BP 145/95 , repeated X 3 No murmurs , no signs CHF Says she feels well On closer questioning, she walks the dog around the block; she used to walk to the park, 2-3 kms away, but “no longer feels like it” EKG shows AF, otherwise normal, rate 88/min

39. What next? Why does she have AF? • Thyroid • Hypertension • Sleep apnea • Ethanol

40. What next? What are the risks and benefits of rhythm control?

42. Establish AF SeverityUse to Guide Therapeutic Approach Dorian et al Can J Cardiol 2006;22:383-386

43. SAF class 2-3 on detailed discussion • Choices: • increase beta blocker • attempt to restore sinus rhythm • CHADS = 2 (CHADSVaSC 4) • OAC for 3-4 weeks • Electrical Cardioversion

44. Recommendations • We recommend that an AV blocking agent should be used in patients with AF or AFL being treated with a class I antiarrhythmic drug (eg, propafenone or flecainide) in the absence of advanced AV node disease (Strong Recommendation, Low Quality Evidence). • We recommend electrical or pharmacologic cardioversion for restoration of sinus rhythm in patients with AF or AFL who are selected for rhythm-control therapy and are unlikely to convert spontaneously (Strong Recommendation, Low Quality Evidence). • We recommend pre-treatment with antiarrhythmic drugs prior to electrical cardioversion in patients who have had AF recurrence post cardioversion without antiarrhythmic drug pre-treatment (Strong Recommendation, Moderate Quality Evidence). Rhythm Management

45. Recommendations • We suggest that patients requiring pacing for the treatment of symptomatic bradycardia secondary to sinus node dysfunction, atrial or dual-chamber pacing be generally used for the prevention of AF (Conditional Recommendation, High Quality Evidence). • We suggest that, in patients with intact AV conduction, pacemakers be programmed to minimize ventricular pacing for prevention of AF (Conditional Recommendation, Moderate Quality Evidence). Rhythm Management

46. How likely is cardioversion to be successful? ( distinguish “success” with IRAF from “failure”) • If sinus rhythm restored , how likely is AF to recur? • What can be done to prevent recurrence? • HT control, ETOH reduction if excessive, sleep apnea treatment if appropriate

47. How do we tell if rhythm control is justified? Assess QOL without knowing the rhythm or doing an EKG eg QOL improves post CV, and worsens again with recurrence, vs No better, or better, but AF recurs without symptoms

48. Recommendations • We recommend that the goals of ventricular rate control should be to improve symptoms and clinical outcomes which are attributable to excessive ventricular rates. (Strong Recommendation, Low Quality Evidence) • We recommend that the goals of rhythm control therapy should be to improve patient symptoms and clinical outcomes, and that these do not necessarily imply the elimination of all AF. (Strong Recommendation, Moderate Quality Evidence) Major Goals of AF/AFL Arrhythmia Management • Identify and treat underlying structural heart disease and other predisposing conditions • Relieve symptoms • Improve functional capacity/quality of life • Reduce morbidity/mortality associated with AF/AFL • Prevent tachycardia-induced cardiomyopathy • Reduce/prevent emergency room visits or hospitalizations secondary to AF/AFL • Prevent stroke or systemic thromboembolism

49. Rate vs Rhythm Control for Patients with Symptomatic AF SYMPTOMATIC AF ATTEMPT RATE CONTROL Beta-blocker Calcium channel blocker Special circumstances in which to consider early rhythm control: Highly symptomatic Multiple recurrences Extreme impairment in QOL Arrhythmia-induced cardiomyopathy YES CONTINUE RATE CONTROL SYMPTOMS RESOLVE NO MODIFY RATE CONTROL - CONSIDER RHYTHM CONTROL Paroxysmal AF Persistent AF High burden recurrence Consider cardioversion Low burden recurrence Pill in pocket antiarrhythmic therapy Maintenance antiarrhythmic therapy Symptoms improve, but AF recurs Symptoms improve, and patient maintains sinus rhythm Symptoms don’t change in sinus rhythm and AF recurs Catheter ablation Observe. If AF recurs, determine if symptomatic

50. Overview of Rhythm Management Rhythm Control Choices Normal Systolic Function No Hx of CHF Rhythm Control Choices Hx of CHF or Left Ventricular Systolic Dysfunction EF > 35% EF ≤ 35% Dronedarone+ Flecainide* Propafenone* Sotalol# Catheter Ablation Amiodarone Sotalol** Amiodarone Amiodarone Catheter Ablation • Drugs are listed in alphabetical order • + Dronedarone should be used with caution in combination with digoxin • Class I agents should be AVOIDED in CAD and should be COMBINED with AV-nodal blocking agents • # Sotalol should be used with caution in those at risk for torsades de pointes VT (e.g. female, age > 65 yr, taking diuretics) ** Sotalol should be used with caution with EF 35-40% and those at risk for torsades de pointes VT (e.g. female, age > 65 yr, taking diuretics)