Appendix: analytical report of level of evidence, related primary studies, strength of recommendation within each guideline and provisional GRADE based recommendation made by the working group

Question 1. When do you choose rate control or rhythm control strategy?

Question 1a. In haemodynamically unstable patients affected by acute-onset non-valvular atrial fibrillation is rhythm control preferable to a rate-control strategy?CCS 2010 AHA 2014 ESC 2010-2012 Agreementelectrical cardioversion electrical cardioversion electrical cardioversion electrical cardioversion

Page: 40References: No referencesGRADE : Strong Recommendation,Low-Quality Evidence

Page: 52References: No referencesCOR/LOE: IB/IC

Page: 2395 eur heart j 2010: References: No referencesCOR/LOE: IC

GRADE : Strong Recommendation,

Low-Quality EvidenceOutcome: survival

GRADE : Strong Recommendation,Low-Quality Evidence

GRADE : Strong Recommendation,Low-Quality Evidence

GRADE : Strong Recommendation,Low-Quality Evidence

Question 1b. In haemodynamically stable patients affected by acute-onset (less than 48 hours) non-valvular atrial fibrillation for which patients rhythm control is preferable to a rate-control strategy? CCS 2010 AHA 2014 ESC 2010-2012 AgreementNo recommendation, left to patients and physicians preferences

Persistent symptoms associated with AF remain the most compelling indication for a rhythm-control strategy. Other factors that may favor attempts at rhythm control include difficulty in achieving adequate rate control, younger patient age, tachycardia-mediated cardiomyopathy, first episode of AF, AF that is precipitated by an acute illness, and patient preference.

Rate control should be the initial approach in elderly patients with AF and minor symptoms (EHRA score 1)1 Rhythm control is recommended inpatients with symptomatic (EHRA score >2) AF despite adequate rate control.2 Rhythm control in patients with AF and AF-related heart failure should be considered for improvement of symptoms.3 Rhythm control as an initial approach should be considered in young symptomatic patients in whom catheter ablation treatment has not been ruled out.4 Rhythm control should be considered in patients with AF secondary to a trigger or substrate that has been corrected (e.g. ischaemia, hyperthyroidism).

No agreementNo evidence

Outcomes: survival, hospitalization, stroke reduction, incidence of heart

failure and quality of lifeDisparity in evidence of

recommendation (ESC IB)

Page: 39 (Management of AF in ED 2010)

Page: 51References: -95. Olshansky B,

Page: 1398References: -86 AFFIRM

References: Not ApplicableCOR/LOE: Not Applicable

Rosenfeld LE, Warner AL, et al. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation. J Am Coll Cardiol. 2004;43:1201-8. -306 Van Gelder IC, Hagens VE, Bosker HA, et al. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med. 2002;347:1834-40.-129. Singh BN, Singh SN, Reda DJ, et al. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med. 2005;352:1861-72.COR/LOE: IC

Investigators. A comparison of rate control and rhythm control in patients with atrial fibrillation. N Engl J Med 2002;347:1825–1833.-87. Van Gelder IC,. A comparison of rate control and rhythm control in patients with recurrent persistent atrial fibrillation. N Engl J Med 2002;347:1834–1840.-90 Roy D, Rhythm control versus rate control for atrial fibrillation and heart failure. N Engl J Med 2008;358:2667–2677COR/LOE: IAPage: 23981 References: -3 Kirchhof P. Outcome parameters for trials in atrial fibrillation: executive summary. Recommendations from a consensus conference organized by the German Atrial Fibrillation Competence NETwork (AFNET) and the European Heart Rhythm Association (EHRA). Eur Heart J 2007;28:2803–2817.-46 Singh BN, Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005;352:1861–1872.-93 Hsu LF . Catheter ablation for atrial fibrillation in congestive heart failure. N Engl J Med 2004;351:2373–2383.-94 Khan MN . Pulmonary-vein isolation for atrial fibrillation in patients with heart failure. N Engl J Med 2008;359:1778–1785.96 Wilber DJ. Comparison of antiarrhythmic drug

therapy and radiofrequency catheter ablation in patients with paroxysmal atrial fibrillation: a randomized controlled trial. JAMA 2010;303:333–340.COR/LOE: IB2 References: -97 Talajic M. Maintenance of sinus rhythm and survival in patients with heart failure and atrial fibrillation. J Am Coll Cardiol 2010;55: 1796–1802.3 COR/LOE: IIaBReferences:Not ApplicableCOR/LOE: IIaC4 References: Not applicableCOR/LOE: IIaC

GRADE : Not applicable

GRADE: strong recommendation, low quality of evidence

GRADE :strong recommendation, moderate quality of evidence

Question 1c. In haemodynamically unstable patients affected by acute-onset non-valvular atrial fibrillation and WPW syndrome is rhythm control preferable to a rate-control strategy?CCS 2010 AHA 2014 ESC 2010-2012 AgreementRhythm Control Strategy (Urgent electrical cardioversion

Rhythm Control Strategy (Urgent electrical cardioversion)

Not covered by the guidelines

Urgent electrical cardioversion(ESC not covered)

Outcomes: Survival

Page: 43References: No referencesGRADE: Strong Recommendation,Low-Quality Evidence

Page: 52, 76References: No referencesCOR/LOE: IC

Page: References: Not applicableCOR/LOE: Not applicable

GRADE : Strong Recommendation, Low-Quality Evidence

GRADE : Strong Recommendation, Low-Quality Evidence

GRADE : Strong Recommendation, Low-Quality Evidence

GRADE : Not applicable

Question 1d. In haemodynamically stable patients affected by acute-onset non-valvular atrial fibrillation and WPW syndrome is rhythm control preferable to a rate-control strategy? CCS 2010 AHA 2014 ESC 2010-2012 AgreementRhythm Control Strategy (Pharmacological cardioversion with Ibutilide or Procainamide)

Rhythm Control Strategy (Pharmacological cardioversion with Ibutilide or Procainamide)

Not covered by the guidelines

Rhythm Control Strategy (Pharmacological cardioversion with Ibutilide or Procainamide) (ESC not

covered)Outcomes: survival, hospitalization, stroke reduction, incidence of heart

failure and quality of life

Page: 43References: No referencesGRADE: Strong Recommendation,Low-Quality Evidence

Page: 52, 76References: 64COR/LOE: IC

-64 Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias--executive summary. a report of the American college of cardiology/American heart association task force on practice guidelines and the European society of cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society. J Am Coll Cardiol. 2003;42:1493-531

Page: References: Not applicableCOR/LOE: Not applicable

GRADE : strong recommendation, low quality of evidence

GRADE : strong recommendation, low quality of evidence

GRADE : strong recommendation, low quality of evidence

GRADE : Not applicable

Question 2. When do you choose electrical or pharmacological cardioversion?

Question 2a. In haemodynamically unstable patients affected by acute-onset non-valvular atrial fibrillation is electrical cardioversion preferable to pharmacological cardioversion?CCS 2010 AHA 2014 ESC 2010 AgreementElectrical cardioversion Electrical cardioversion

when no prompt reaction to pharmacologic therapies

Electrical cardioversion when no prompt reaction to pharmacologic therapies

Electrical cardioversionOutcomes: Survival

Page: 40References: No referencesGRADE: Strong recommendation, Low-quality evidence

Page: 52References: No referencesCOR/LOE: IC

Page: 2395References: No referencesCOR/LOE: IC

GRADE : strong recommendation, low

quality of evidence

GRADE: Strong recommendation, Low-quality evidence

GRADE: Strong recommendation, Low-quality evidence

GRADE: Strong recommendation, Low-quality evidence

Question 2b. In haemodynamically unstable patients affected by acute-onset non-valvular atrial fibrillation and WPW is electrical cardioversion preferable to pharmacological cardioversion??CCS 2010 AHA 2014 ESC 2010 AgreementElectrical cardioversion. Electrical cardioversion. Electrical cardioversion. Electrical cardioversion

Outcomes: SurvivalPage: 43References: No referencesGRADE: Strong Recommendation, Low-Quality Evidence

Page: 52, 76References: No referencesCOR/LOE IC

Page: 2395References: 82-82 Gulamhusein S, Ko P, Carruthers SG, Klein GJ. Acceleration of the ventricular response during atrial fibrillation in the Wolff–Parkinson–White syndrome after verapamil. Circulation 1982;65:348–354.COR/LOE: IB

GRADE : strong recommendation, low

quality of evidence

GRADE: Strong Recommendation, Low-Quality Evidence

GRADE: Strong Recommendation, Low-Quality Evidence

GRADE: Strong Recommendation, Low-Quality Evidence

Question 2c. In haemodynamically stable patients affected by acute-onset (less than 48 hours) non-valvular atrial fibrillation is electrical cardioversion preferable to pharmacological cardioversion?CCS 2010 AHA 2014 ESC 2010 AgreementSynchronized electrical cardioversion or pharmacologic cardioversion may be used when a decision is made to cardiovert patients in the emergency department. Individual considerations

1. DCC is recommended for AF or atrial flutter to restore sinus rhythm. If unsuccessful, repeat cardioversion attempts may be made.2. Electrical cardioversion is recommended for AF with rapid ventricular

Elective DCC should be considered in order to initiate a long-term rhythm control management strategy for patients with AF.

No agreement

of the patient and treating physician are recognized in making specific decisions about method of cardioversion.

response that does not respond to pharmacological therapies.

Page: 41Ref: No references GRADE: Strong Recommendation, Low Quality Evidence

1. Page: 53Ref: -320 Oral H, Souza JJ, Michaud GF, Knight BP, Goyal R, Strickberger SA, Morady F. Facilitating transthoracic cardioversion of atrial fibrillation with ibutilide pretreatment. N Engl J Med 1999;340:1849-1854.COR/LOE: IB

2. Page: 53Ref: no references COR/LOE: IC

Page: 2395Ref: -46 Singh BN, Singh SN, Reda DJ, Tang XC, Lopez B, Harris CL, Fletcher RD, Sharma SC, Atwood JE, Jacobson AK, Lewis HD Jr, Raisch DW, Ezekowitz MD. Amiodarone versus sotalol for atrial fibrillation. N Engl J Med 2005;352:1861-1872.-78 Kirchhof P, Eckardt L, Loh P, Weber K, Fischer RJ, Seidl KH, Böcker D, Breithardt G, Haverkamp W, Borggrefe M. Anterior-posterior versus anterior-lateral electrode positions for external cardioversion of atrial fibrillation: a randomised trial. Lancet 2002;360:1275-1279.-83 Fetsch T, Bauer P, Engberding R, Koch HP, Lukl J, Meinertz T, Oeff M, Seipel L, Trappe HJ, Treese N, Breithardt G. Prevention of atrial fibrillation after cardioversion: results of the PAFAC trial. Eur Heart J 2004;25:1385-1394.COR/LOE: IIa B

GRADE: Strong Recommendation, Low Quality Evidence

GRADE: Strong Recommendation, Low Quality Evidence

GRADE: Strong Recommendation, Low Quality Evidence

Question 2d. In haemodynamically stable patients affected by acute-onset non-valvular atrial fibrillation and WPW syndrome is electrical cardioversion preferable to pharmacological cardioversion?CCS 2010 AHA 2014 ESC 2010 AgreementPharmacologic Cardioversion (Procainamide or Ibutilide)

Amiodarone should be used with caution in the case of preexcited AF as

Pharmacologic Cardioversion (Procainamide or Ibutilide)Intravenous procainamide or ibutilide to restore sinus rhythm or slow the ventricular

Not Covered Pharmacologic Cardioversion

Outcome: Survival

several case reports have described the occurrence of VF after intravenous administration.

rate is recommended for patients with pre-excited AF and rapid ventricular response.

Page: 43Ref: No referencesGRADE: Strong Recommendation, Low-Quality Evidence

Page: 76-77Ref: -64 Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, Alpert JS et al.. ACC/AHA/ESC guidelines for the management of patients with supraventricular arrhythmias—executive summary. A report of the American College of Cardiology/American Heart Association task force on practice guidelines and the European Society of Cardiology committee for practice guidelines (writing committee to develop guidelines for the management of patients with supraventricular arrhythmias). J Am Coll Cardiol 2003;42:1493-1531.COR/LOE: IC

Page: Not ApplicableRef: Not ApplicableCOR/LOE: Not Applicable

GRADE Strong Recommendation, Low-

Quality Evidence

GRADE: Strong Recommendation, Low-Quality Evidence

GRADE: Strong Recommendation, Low-Quality Evidence

GRADE: Not applicable

Question 3: In case of pharmacological cardioversion which drug would you use?

Question 3a. In haemodinamically stable patients affected by acute-onset (less than 48 hours) non-valvular atrial fibrillation and no structural heart disease which drug preferable for pharmacological cardioversion?CCS 2010 AHA 2014 ESC 2010-2012 AgreementFlecainide, procainamide, propafenone, ibutilide

Flecainide, propafenone, dofetilide, and ibutilide

Propafenone, flecainide, ibutilide

Flecainide and propafenone.Less consensus regarding ibutilide Outcome: restoring sinus rhythm

Page: 41References: -13. Page RL. Newly diagnosed atrial fibrillation. N Engl J Med 2004;351:2408-16.-15. Taylor DM, Aggarwall A, Carter M, Garewal D, Hunt D. Management of new onset atrial fibrillation in previously well patients less than 60 years of age. Emerg Med Austral 2005;17:4-10.-16. Raghavan AV, Decker WW, Meloy TD. Management of atrial fibrillation in the emergency department. Emerg Med Clin N Am 2005;23:1127-39.-36. ACLS Guidelines: Part 7.3: Management of symptomatic bradycardia and tachycardia. Circulation 2005;112:IV-67-IV-77.-37. Nichol G, McAlister FA, Pham B, et al. Meta-analysis of randomized controlled trials of the effectiveness of antiarrhythmic agents at promoting sinus rhythm in patients with atrial fibrillation. Heart 2002;87:535-43.GRADE: Strong recommendation, high quality of evidence

Page: 53References:-321. Alboni P, Botto GL, Baldi N, et al. Outpatient treatment of recent-onset atrial fibrillation with the “pill-in-the-pocket” approach. N Engl J Med 2004;351:2384–91.-322. Ellenbogen KA, Clemo HF, Stambler BS, et al. Efficacy of ibutilide for termination of atrial fibrillation and flutter. Am J Cardiol 1996;78:42–5.-323. Khan IA. Single oral loading dose of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation. J Am Coll Cardiol 2001;37:542–7.-324. Patsilinakos S, Christou A, Kafkas N, et al. Effect of high doses of magnesium on converting ibutilide to a safe and more effective agent. Am J Cardiol 2010;106:673–6.-325. Singh S, Zoble RG, Yellen L, et al. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the Symptomatic Atrial Fibrillation Investigative Research on Dofetilide (SAFIRE-D) study. Circulation 2000;102:2385–90.

Page: 2394References: 71-73-71. Reisinger J, Gatterer E, LangW, Vanicek T, Eisserer G, Bachleitner T, Niemeth C, Aicher F, Grander W, Heinze G, Kuhn P, Siostrzonek P. Flecainide versus ibutilide for immediate cardioversion of atrial fibrillation of recent onset. Eur Heart J 2004;25:1318–1324.-72. Khan IA. Single oral loading dose of propafenone for pharmacological cardioversion of recent-onset atrial fibrillation. J Am Coll Cardiol 2001;37:542–547.-73. Martinez-Marcos FJ, Garcia-Garmendia JL, Ortega-Carpio A, Fernandez-Gomez JM, Santos JM, Camacho C. Comparison of intravenous flecainide, propafenone, and amiodarone for conversion of acute atrial fibrillation to sinus rhythm. Am J Cardiol 2000;86:950–953.COR/LOE: I/A (propafenone and fleicanide)IIb/A (ibutilide)

GRADE: weak recommendation, low quality of evidence

-326. Stambler BS, Wood MA, Ellenbogen KA, et al. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation. Ibutilide Repeat Dose Study Investigators. Circulation 1996;94:1613–21.COR/LOE: I/A

GRADE :weak recommendation, low quality of evidence

GRADE : weak recommendation, low quality of evidence

GRADE : weak recommendation, low quality of evidence

Question 3b. In haemodinamically stable patients affected by acute-onset (less than 48 hours) non-valvular atrial fibrillation and structural heart disease which drug is preferable for pharmacological cardioversion?CCS 2010 AHA 2014 ESC 2010-2012 AgreementIbutilide, Procainamide Ibutilide, Dofetilide,

AmiodaroneAmiodarone No agreement

Page: 41References: -13. Page RL. Newly diagnosed atrial fibrillation. N Engl J Med 2004;351:2408-16.-15. Taylor DM, Aggarwall A, Carter M, Garewal D, Hunt D. Management of new onset atrial fibrillation in previously well patients less than 60 years of age. Emerg Med Austral 2005;17:4-10.-16. Raghavan AV, Decker WW, Meloy TD. Management of atrial fibrillation in the emergency department. Emerg Med Clin N Am 2005;23:1127-39.-36. ACLS Guidelines: Part 7.3: Management of symptomatic bradycardia and tachycardia. Circulation 2005;112:IV-67-IV-77.-37. Nichol G, McAlister FA, Pham B, et al. Meta-analysis of randomized controlled trials of the effectiveness of antiarrhythmic agents

Page: 53References: -322. Ellenbogen KA, Clemo HF, Stambler BS, et al. Efficacy of ibutilide for termination of atrial fibrillation and flutter. Am J Cardiol 1996;78:42–5.-324. Patsilinakos S, Christou A, Kafkas N, et al. Effect of high doses of magnesium on converting ibutilide to a safe and more effective agent. Am J Cardiol 2010;106:673–6.-325. Singh S, Zoble RG, Yellen L, et al. Efficacy and safety of oral dofetilide in converting to and maintaining sinus rhythm in patients with chronic atrial fibrillation or atrial flutter: the Symptomatic Atrial Fibrillation Investigative Research on Dofetilide (SAFIRE-D) study. Circulation 2000;102:2385–90.-326. Stambler BS, Wood MA, Ellenbogen KA, et al. Efficacy and safety of repeated intravenous doses of ibutilide for rapid conversion of atrial flutter or fibrillation.

Page: 2394References: 74-76-74. Chevalier P, Durand-Dubief A, Burri H, Cucherat M, Kirkorian G, Touboul P. Amiodarone versus placebo and class Ic drugs for cardioversion of recent-onset atrial fibrillation: a meta-analysis. J Am Coll Cardiol 2003;41:255–262.-75. Vardas PE, Kochiadakis GE, Igoumenidis NE, Tsatsakis AM, Simantirakis EN, Chlouverakis GI. Amiodarone as a first-choice drug for restoring sinus rhythm in patients with atrial fibrillation: a randomized, controlled study. Chest 2000;117:1538–1545.-76. Bianconi L, Castro A, Dinelli M, Alboni P, Pappalardo A, Richiardi E, Santini M. Comparison of intravenously administered dofetilide versus amiodarone in the acute termination of atrial fibrillation and flutter. A multicentre, randomized, double-blind, placebo-controlled

at promoting sinus rhythm in patients with atrial fibrillation. Heart 2002;87:535-43.GRADE: strong recommendation, high quality of evidence

Ibutilide Repeat Dose Study Investigators. Circulation 1996;94:1613–21.-328. Letelier LM, Udol K, Ena J, et al. Effectiveness of amiodarone for conversion of atrial fibrillation to sinus rhythm: a meta-analysis. Arch Intern Med 2003;163:777–85.-329. Pedersen OD, Bagger H, Keller N, et al. Efficacy of dofetilide in the treatment of atrial fibrillation-flutter in patients with reduced left ventricular function: a Danish Investigations of Arrhythmia and Mortality on Dofetilide (DIAMOND) Substudy. Circulation 2001;104:292–6.COR/LOE: I/A (dofetilide, ibutilide) IIa/A (amiodarone)

study. Eur Heart J 2000;21:1265–1273COR/LOE: I/A

GRADE: weak recommendation, low quality of evidence

GRADE: weak recommendation, low quality of evidence

GRADE: weak recommendation, low quality of evidence

Question 3c. In haemodinamically stable patients affected by paroxysmal non-valvular atrial fibrillation and no structural heart disease would you recommend the pill in the pocket approach with flecainide or propafenone?CCS 2010 AHA 2014 ESC 2010-2012 Agreement

Pill-in-the-pocket Pill-in-the-pocket Pill-in-the-pocket

Pill-in-the-pocket approach is a feasible, safe and effective strategy Outcome: emergency room visits,

hospitalization, quality of lifePage: 55References: 59GRADE: Weak recommendation, low quality of evidence

Page: 53References: -321. Alboni P, Botto GL, Baldi N, et al. Outpatient treatment of recent-onset atrial fibrillation with the “pill-in-the-pocket” approach. N Engl J Med 2004;351:2384–91.COR/LOE: IIA/B

Page: 2394-2395References: -67. Alboni P, Botto GL, Baldi N, Luzi M, Russo V, Gianfranchi L, Marchi P, Calzolari M, Solano A, Baroffio R, Gaggioli G. Outpatient treatment of recent-onset atrial fibrillation with the ‘pill-in-the-pocket’ approach. N Engl J Med 2004;351:2384–2391COR/LOE: IIA/B

GRADE: Weak recommendation, low quality of evidence

GRADE: Weak recommendation, low quality of evidence

GRADE: Weak recommendation, low quality of evidence

GRADE: Weak recommendation, low quality of evidence

Question 4: In case of rate control strategy which drug would you use?

Question 4a. In patients affected by acute-onset non-valvular atrial fibrillation and no hypotension or heart failure which therapy would you recommend in order to obtain rate control?CCS 2010 AHA 2014 ESC 2010-2012 AgreementBeta blockers or non-

dihydropyridine calcium channel

antagonists

Beta blockers or non-dihydropyridine calcium

channel antagonists

Beta blockers or non-dihydropyridine calcium

channel antagonists

Beta blockers or non-dihydropyridine calcium channel

antagonistsOutcomes: rate control, quality of

lifePage: 49-50References: -13. Rawles JM. What is meant by a controlled ventricular rate in atrial fibrillation?Br Heart J 1990;63:157-61.-14. Dorian P, Connors P. Pharmacological and non pharmacological methods for rate control. Can J Cardiol 2005;21(suppl B):11B-14B.-15. Van Gelder IC, Groenveld HF, Crijns HJ, et al. Lenient vs strict rate control in patients with atrial fibrillation. N Engl J Med 2010;362:1363-73.-16. Nikolaidou T, Channer KS. Chronic atrial fibrillation: a systematic reviewof medical heart rate control management. Postgrad Med J 2009;85:303-12.-17. Bjerregaard P, Bailey WB, Robinson SE. Rate control in patients with chronic atrial fibrillation. Am J Cardiol 2004;93:329-32.-18. Segal JB, McNamara RL, Miller MR, et al. The evidence regarding the drugs used for ventricular rate control. J Fam

Page: 44References: -260. Farshi R, Kistner D, Sarma JS, et al. Ventricular rate control in chronic atrial fibrillation during daily activity and programmed exercise: a crossover open-label study of five drug regimens. J Am Coll Cardiol 1999;33:304–10.-261. Steinberg JS, Katz RJ, Bren GB, et al. Efficacy of oral diltiazem to control ventricular response in chronic atrial fibrillation at rest and during exercise. J Am Coll Cardiol 1987;9:405–11.-262. Olshansky B, Rosenfeld LE, Warner AL, et al. The Atrial Fibrillation Follow-up Investigation of Rhythm Management (AFFIRM) study: approaches to control rate in atrial fibrillation. J Am Coll Cardiol 2004;43:1201–8.-263. Abrams J, Allen J, Allin D, et al. Efficacy and safety of esmolol vs propranolol in the treatment of supraventricular tachyarrhythmias: a multicenter doubleblind clinical trial. Am Heart J 1985;110:913–22.-264. Ellenbogen KA, Dias VC, Plumb VJ, et al. A placebo-controlled

Page: 2398-2399, 2401References: -100. Segal JB, McNamara RL, Miller MR, Kim N, Goodman SN, Powe NR, Robinson K, Yu D, Bass EB. The evidence regarding the drugs used for ventricular rate control. J Fam Pract 2000;49:47–59.100COR/LOE: IA

GRADE : Strong recommendation, low quality of evidence

Pract 2000;49:47-59.-19. Boriani G, Biffi M, Diemberger I, Martignani C, Branzi A. Rate control in atrial fibrillation: choice of treatment and assessment of efficacy. Drugs 2003;63:1489-509.GRADE: Strong Recommendation, Moderate-Quality Evidence

trial of continuous intravenous diltiazem infusion for 24-hour heart rate control during atrial fibrillation and atrial flutter: a multicenter study. J Am Coll Cardiol 1991;18:891–7.-265. Siu CW, Lau CP, Lee WL, et al. Intravenous diltiazem is superior to intravenous amiodarone or digoxin for achieving ventricular rate control in patients with acute uncomplicated atrial fibrillation. Crit Care Med 2009;37:2174–9.-266. Platia EV, Michelson EL, Porterfield JK, et al. Esmolol versus verapamil in the acute treatment of atrial fibrillation or atrial flutter. Am J Cardiol 1989;63:925–9.COR/LOE: IB

GRADE: Strong recommendation, moderate quality of evidence

GRADE: Strong recommendation, low quality of evidence

GRADE: Strong recommendation, low quality of evidence

Question 4b. In patients affected by acute-onset non-valvular atrial fibrillation with hypotension or heart failure which drug would you recommend?CCS 2010 AHA 2014 ESC 2010-2012 AgreementDigitalis Digitalis or amiodarone Digitalis or amiodarone Digitalis

Outcomes: Rate control, worsening of heart failure

Page: 50References: no referencesGRADE: Conditional recommendation, moderate quality of evidence

Page: 78References: -268. Delle KG, Geppert A, Neunteufl T, et al. Amiodarone versus diltiazem for rate control in critically ill patients with atrial tachyarrhythmias. Crit Care Med 2001;29:1149–53.-269. Hou ZY, Chang MS, Chen CY, et al. Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone: a randomized, digoxin-

Page: 2398-2399, 2401References: -101. Hou ZY, Chang MS, Chen CY, Tu MS, Lin SL, Chiang HT, Woosley RL. Acute treatment of recent-onset atrial fibrillation and flutter with a tailored dosing regimen of intravenous amiodarone. A randomized, digoxin-controlled study. Eur Heart J 1995;16:521–528COR/LOE:I B

GRADE: Strong recommendation, low quality of evidence

controlled study. Eur Heart J-270. Clemo HF, Wood MA, Gilligan DM, et al. Intravenous amiodarone for acute heart rate control in thecritically ill patient with atrial tachyarrhythmias. Am J Cardiol 1998;81:594–8.-497. Tamariz LJ, Bass EB. Pharmacological rate control of atrial fibrillation. Cardiol Clin 2004;22:35–45.1995;16:521–8.-500. Roberts SA, Diaz C, Nolan PE, et al. Effectiveness and costs of digoxin treatment for atrial fibrillation and flutter. Am J Cardiol 1993;72:567–73.-501. Segal JB, McNamara RL, Miller MR, et al. The evidence regarding the drugs used for ventricular rate control. J Fam Pract 2000;49:47–59.COR/LOE: IB

GRADE : Strong recommendation, low quality of evidence

GRADE : Strong recommendation, low quality of evidence

GRADE : Strong recommendation, low quality of evidence

Question 4c In haemodinamically stable patients affected by acute-onset non-valvular atrial fibrillation with WPW which drug would you recommend?CCS 2010 AHA 2014 ESC 2010-2012 AgreementIntravenous antiarrhythmic agents procainamide or ibutilide in stable patients. AV nodal blocking agents (digoxin, calcium channel blockers, beta-blockers, adenosine) are contraindicated

Intravenous procainamide or ibutilide to restore sinus rhythm or slow the ventricular rate is recommended for patients with pre-excited AF and rapid ventricular response who are not hemodynamically compromised. intravenous amiodarone, adenosine, digoxin (oral or intravenous), or nondihydropyridine calcium channel antagonists (oral or intravenous) is potentially harmful because these drugs

In pre-excitation, preferred drugs are class I antiarrhythmic drugs or amiodarone.When pre-excited AF is present, b-blockers, non-dihydropyridine calcium channel antagonists, digoxin, and adenosine are contraindicated.

Agreement on class I drugs. Agreement against calcium channel

blockers, beta blockers, digitalis and adenosine

No agreement on amiodarone (suggested by ESC, advice against by AHA, use with caution by Canadian)Outcomes: mortality (risk of major

adverse events)

accelerate the ventricular rate

Page: 42References:-45. Tijunelis MA, Herbert ME. Myth: intravenous amiodarone is safe in patients with atrial fibrillation and Wolff-Parkinson-White syndrome in the emergency department. Can J Emerg Med 2005;7:262-5.GRADE: Strong Recommendation, Low-Quality Evidence

Page: 76, 77References:-64. Blomstrom-Lundqvist C, Scheinman MM, Aliot EM, et al. ACC/AHA/ESC guidelines for the managementnof patients with supraventricular arrhythmias: executive summary: a report of the American College of Cardiology/American Heart Association Task Force on Practice Guidelines and the European Society of Cardiology Committee for Practice Guidelines (Writing Committee to Develop Guidelines for the Management of Patients With Supraventricular Arrhythmias) developed in collaboration with NASPE-Heart Rhythm Society. J Am Coll Cardiol 2003;42:1493–531.-487. Boriani G, Biffi M, Frabetti L, et al. Ventricular fibrillation after intravenous amiodarone in Wolff-Parkinson-White syndrome with atrial fibrillation. Am Heart J 1996;131:1214–6.-488. Kim RJ, Gerling BR, Kono AT, et al. Precipitation of ventricular fibrillation by intravenous diltiazem and metoprolol in a young patient with occult Wolff-Parkinson-White syndrome. Pacing Clin Electrophysiol 2008;31:776–9. -489. Simonian SM, Lotfipour S, Wall C, et al. Challenging the superiority of amiodarone for rate control in Wolff-Parkinson-White and

Page:2398References: no references.COR/LOE: IC

GRADE: Strong recommendation, low quality of evidence

atrial fibrillation. Intern Emerg Med 2010;5:421–6.COR/LOE:IC-IB

GRADE: Strong recommendation, low

quality of evidence

GRADE: Strong recommendation, low

quality of evidence

GRADE: Strong recommendation, low

quality of evidence

Question 5. Considering the setting of atrial fibrillation cardioversion in patients without indication for long-term anticoagulation, how would you manage anticoagulation therapy?

Question 5a-1. In haemodinamically unstable patients affected by acute-onset non-valvular atrial fibrillation undergoing to a rhythm control strategy, before the cardioversion would you recommend for anticoagulation instead of no anticoagulation for the prevention of thromboembolic complications (outcomes: survival, stroke reduction)?

Canadian 2010 AHA 2014 ESC 2010-2012Generally, unstable patients need not be given an anticoagulant either before cardioversion if the duration of AF/AFL is known to have occurred <48 hours. However, if the duration of AF/AFL is ≥48 hours or unknown or the patient is at particularly high risk of stroke(eg, mechanical valve, rheumatic valve disease, recent stroke, or transient ischemic attack), we suggest administering the patient intravenous unfractionated heparin or low-molecular-weight heparin before cardioversion if possible or immediately thereafter

Initiation of anticoagulation should not delay interventions to stabilize the patient. It is reasonable to administer heparin (intravenous bolus of UFH followed by infusion, or LMWH) or newer anticoagulant before cardioversion.

Before immediate/emergency cardioversion heparin (i.v. UFH bolus followed by infusion, or weight-adjusted therapeutic dose LMWH) is recommended.

There is no agreement on anticoagulation therapy prior

cardioversion.

Page: 40References: NoGRADE: Strong Recommendation, Low-Quality Evidence

Page: 51, 53, 55References: NoCOR/LOE: I/C

Page: 2391References: NoCOR/LOE: I/C

GRADE: Strong Recommendation, Low-Quality Evidence

GRADE: Strong Recommendation, Low-Quality evidence.

GRADE: Strong Recommendation, Low- Quality evidence

Question 5a-2. In haemodinamically unstable patients affected by acute-onset non-valvular atrial fibrillation undergoing to a rhythm control strategy, after the cardioversion would you recommend for anticoagulation instead of no anticoagulation for the prevention of thromboembolic complications (outcomes: survival, stroke reduction) ? Canadian 2010 AHA 2014 ESC 2010-2012In unstable patients need not be given an anticoagulant following cardioversion if the duration of AF/AFL is known to have occurred <48 hours. However, if AF/AFL persists or recurs or if AF/AFL has been recurrent,antithrombotic therapy as appropriate (CHADS2 score) should be initiated and continued indefinitely . Aspirin is sufficient for those with a CHADS2 score of 0, whereas oral anticoagulants are

Following cardioversion for AF of any duration, the decision regarding long-term anticoagulation therapy should be based on the thromboembolic risk profile (OAC if CHA2DS2-VASc ≥2)

After immediate/emergency cardioversion in patients with AF of 48 h duration or longer, or when the duration ofAF is unknown, OAC therapy is recommended for at least 4 weeks, similar to patients undergoing elective cardioversion; duration of OAC therapy (4 weeks or lifelong) will depend on the presenceof risk factors for stroke.

Post cardioversion guidelines agree on immediate need of the

thromboembolic risk profile assessment and

continuing/starting of antithrombotic therapy based on

this profile.Outcomes: stroke incidence

GRADE: Strong recommendation, low quality of evidence

Question 5b-1. In haemodinamically stable patients affected by acute-onset (< 48 hours) non-valvular atrial fibrillation undergoing to a rhythm control strategy, before the cardioversion would you recommend for anticoagulation instead of no anticoagulation for the prevention of thromboembolic complications (outcomes: survival, stroke reduction)?

Canadian 2010 AHA 2014 ESC 2010-2012 AgreementNo anticoagulation prior cardioversion. However, if the patient is at particularly high risk of stroke (eg, mechanical valve, rheumatic heart disease, recent stroke, or transient ischemic attack), cardioversion should be delayed and the patient should receiveOAC for 3 weeks before postcardioversion.

For patients with AF or atrial flutter of less than 48-hour duration who are at low thromboembolic risk, anticoagulation (intravenous heparin, LMWH, or a new oral anticoagulant)or no antithrombotic therapy may be considered for cardioversion. In patients with high risk of stroke, intravenous heparin or LMWH, or administration of a factor Xa or direct thrombin inhibitor, is recommended for cardioversion.

For at high risk of stroke (CHADS2 score ≥ 2), i.v. heparin or weight-adjusted therapeutic dose LMWH isrecommended peri-cardioversion. For patients with no thrombo-embolic risk factors, i.v. heparin or weight adjustedtherapeutic dose LMWH may be considered peri-cardioversion.

No agreement before cardioversion

Outcomes: stroke

Page: 41,43-44References: -30 Lown B. Electrical reversion of cardiac arrhythmias. Br Heart J 1967;29: 469-89-31 Goldman MJ. The management of chronic atrial fibrillation: indications and method of conversion to sinus rhythm. Prog Cardiovasc Dis 1959;2:465-79.GRADE: Strong Recommendation, Low-Quality Evidence

Page: 51, 52-55References: -315. Jaber WA, Prior DL, Thamilarasan M, et al. Efficacy of anticoagulation in resolving left atrial and left atrial appendage thrombi: A transesophageal echocardiographic study. Am Heart J. 2000;140:150-6.-316. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e531S-e575S.-319 von Besser K, Mills AM. Is discharge to home after emergency department cardioversion safe for the treatment of recent-onset atrial fibrillation? Ann Emerg Med. 2011;58:517-20.-334 Berger M, Schweitzer P. Timing of thromboembolic events after electrical cardioversion of atrial fibrillation or flutter: a retrospective analysis. Am J Cardiol. 1998;82:1545-7-335 Juhani Airaksinen K, Gronberg T, Nuotio I, et al. Thromboembolic Complications After Cardioversion of Acute

Page: 2391References: -47 Hughes M, Lip GY. Stroke and thromboembolism in atrial fibrillation: a systematic review of stroke risk factors, risk stratification schema and cost effectiveness data. Thromb Haemost 2008;99:295–304.-54 Hart RG, Pearce LA, Aguilar MI. Meta-analysis: antithrombotic therapy to prevent stroke in patients who have nonvalvular atrial fibrillation. Ann Intern Med 2007;146:857–867.-63 Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, Lip GY, Manning WJ. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:546S–592S. High risk of stroke:COR/LOE: I B

Low risk of stroke:COR/LOE: IIb C

Question 5c-1. In haemodinamically stable patients affected by acute-onset (> 48 hours) non-valvular atrial fibrillation undergoing to a rhythm control strategy, before the cardioversion would you recommend for anticoagulation instead of no anticoagulation for the prevention of thromboembolic complications (outcomes: survival, stroke reduction)?Canadian 2010 AHA 2014 ESC 2010-2012 AgreementOral anticoagulants (OAC) therapy (warfarin or dabigatran) for 3 weeks before cardioversion.

With AF or atrial flutter for ≥48 h, or unknown duration, anticoagulatewith warfarin for at least 3 weeks prior to and 4 weeks after cardioversion regardless of the CHA2DS2-VASc score and the method(electrical or pharmacological) used to restore sinus rhythm.

For patients with AF of 48 h duration or longer, or when the duration of AF is unknown, OAC therapy (INR 2.0–3.0) isrecommended for at least 3 weeks prior cardioversion, regardless of the method (electricalor oral/i.v. pharmacological).

Agreement on oral anticoagulants (OAC) therapy

for 3 weeks before cardioversion.

Outcomes stroke incidence

GRADE: Strong recommendation, moderate

quality of evidence

Page: 43References: -1 Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the management of patients with atrial fibrillation. J Am Coll Card 2006;48:149-246.-32 Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, Lip GY, Manning WJ. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:546S–592S.

GRADE: Strong Recommendation,Moderate-Quality Evidence

Page: 53,References: -313 Moreyra E, Finkelhor RS, Cebul RD. Limitations of transesophageal echocardiography in the risk assessment of patients before nonanticoagulated cardioversion from atrial fibrillation and flutter: an analysis of pooled trials. Am Heart J. 1995;129:71-5.-314. Gallagher MM, Hennessy BJ, Edvardsson N, et al. Embolic complications of direct current cardioversion of atrial arrhythmias: association with low intensity of anticoagulation at the time of cardioversion. J Am Coll Cardiol. 2002;40:926-33.-315. Jaber WA, Prior DL, Thamilarasan M, et al. Efficacy of anticoagulation in resolving left atrial and left atrial appendage thrombi: A transesophageal

Page: 2391References: -63 Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, Lip GY, Manning WJ. Antithrombotic therapy in atrial fibrillation: American College ofChest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition).Chest 2008;133:546S–592S.

COR/LOE: I B

echocardiographic study. Am Heart J. 2000;140:150-6.-316. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e531S-e575S.

COR/LOE: I B GRADE: Strong Recommendation, Moderate-Quality Evidence

GRADE: Strong Recommendation, Moderate-Quality Evidence

GRADE: Strong Recommendation, Moderate-Quality Evidence

Question5c-2. In haemodinamically stable patients affected by acute-onset (> 48 hours) non-valvular atrial fibrillation undergoing to a rhythm control strategy, after the cardioversion would you recommend for anticoagulation instead of no anticoagulation for the prevention of thromboembolic complications (outcomes: survival, stroke reduction)? Canadian 2010 AHA 2014 ESC 2010-2012 AgreementOral anticoagulants (OAC) therapy (warfarin or dabigatran) for at least 4 weeks postcardioversion.Following attempted cardioversion: If AF/AFL persists or recurs or if symptoms suggest thatthe pre senting AF/AFL has been recurrent, the patient should have antithrombotic therapy continued indefinitely (using OAC if CHADS2≥1or aspirin if CHADS2=0). If sinus rhythm is achieved and sustained for 4 weeks, the need for ongoing antithrombotic therapy should be determined based on the risk of stroke, and in selected cases, expert consultation may be required

With AF or atrial flutter for ≥48 h, or unknown duration, anticoagulation for at least 4 weeks postcardioversion; the decision regarding long-term anticoagulation therapy should be based on the thromboembolic risk profile (OAC if CHA2DS2-VASc ≥2)

For patients with AF of 48 h duration or longer, or when the duration of AF is unknown, OAC therapy (INR 2.0–3.0) is recommended for at least 4 weeks after cardioversion, regardless of the method (electrical or oral/i.v. pharmacological). In patients with risk factors for stroke or AF recurrence, OAC therapy should be continued lifelong irrespective of the apparent maintenance of sinus rhythm following cardioversion.

Agreement on oral anticoagulants (OAC) therapy

for at least 4 weeks postcardioversion. After the 4

weeks of anticoagulation with achievement of sinus rhythm there is a general agreement on considering

stroke risk to guide the decision on the need of a long

term anticoagulationOutcomes stroke incidence

GRADE: Strong recommendation, moderate

quality of evidence

Page: 43References: -1 Fuster V, Ryden LE, Cannom DS, et al. ACC/AHA/ESC 2006 guidelines for the

Page: 53,References: -313 Moreyra E, Finkelhor RS, Cebul RD. Limitations of transesophageal

Page: 2391References: -63 Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, Lip GY, Manning WJ.

management of patients with atrial fibrillation. J Am Coll Card 2006;48:149-246.-32 Singer DE, Albers GW, Dalen JE, Fang MC, Go AS, Halperin JL, Lip GY, Manning WJ. Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:546S–592S.-60 Cairns JA, Connolly S, McMurtry S, Stephenson M, Talajic M, CCS Atrial Fibrillation Guidelines Committee. Canadian Cardiovascular Society Atrial Fibrillation Guidelines 2010: prevention of stroke and systemic thromboembolism

GRADE: Strong Recommendation,Moderate-Quality Evidence

echocardiography in the risk assessment of patients before nonanticoagulated cardioversion from atrial fibrillation and flutter: an analysis of pooled trials. Am Heart J. 1995;129:71-5.-314. Gallagher MM, Hennessy BJ, Edvardsson N, et al. Embolic complications of direct current cardioversion of atrial arrhythmias: association with low intensity of anticoagulation at the time of cardioversion. J Am Coll Cardiol. 2002;40:926-33.-315. Jaber WA, Prior DL, Thamilarasan M, et al. Efficacy of anticoagulation in resolving left atrial and left atrial appendage thrombi: A transesophageal echocardiographic study. Am Heart J. 2000;140:150-6.-316. You JJ, Singer DE, Howard PA, et al. Antithrombotic therapy for atrial fibrillation: Antithrombotic Therapy and Prevention of Thrombosis, 9th ed: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines. Chest. 2012;141:e531S-e575S.

COR/LOE: I B

Antithrombotic therapy in atrial fibrillation: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest 2008;133:546S–592S.

COR/LOE: I B

GRADE:Strong Recommendation, Moderate-Quality Evidence

GRADE: Strong Recommendation, Moderate-Quality Evidence

GRADE: Strong Recommendation, Moderate-Quality Evidence

Question 5d. In patients affected by acute-onset non-valvular atrial fibrillation can transesophageal echocardiography undergoing modify antithrombotic strategy for the prevention of thromboembolic complications (outcomes: survival, stroke reduction)?Canadian 2010 AHA 2014 ESC 2010-2012 AgreementWhen the duration of an With AF or atrial flutter For patients undergoing Agreement on TOE-guided

episode of AF/AFL is uncertain, we suggest that patients may undergo cardioversion guided by transesophageal echocardiography, as an alternative to anticoagulation prior to cardioversion. However, anticoagulation needs to be simultaneously started and maintained for ≥4 weeks postcardioversion

for ≥48 h or unknown duration and no anticoagulation for preceding 3 wk, it is reasonable to perform a TEE prior to cardioversion, and then cardiovert if no LA thrombus is identified, provided anticoagulation is achieved before TEE and maintained after cardioversion for at least 4 weeks

TEE who have no identifiable thrombus, cardioversion is recommended immediately after anticoagulation with heparin, and heparin should be continued until OAC therapy has been established, which should be maintained for at least 4 weeks after cardioversion.

cardioversion as an alternative to anticoagulation prior to

cardioversionOutcomes: stroke incidence

GRADE: Strong recommendation, low quality

of evidence

Page: 44References: -63 Klein AL, Grimm RA, Murray RD, Apperson-Hansen C, Asinger RW, Black IW, Davidoff R, Erbel R, Halperin JL, Orsinelli DA, Porter TR, Stoddard MF. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001;344:1411–1420.-64 Manning WJ. Strategies for cardioversion of atrial fibrillation: time for a change? (Editorial). N Engl J Med 2001;344:1468-70.

COR/LOE: Conditional Recommendation,High-Quality Evidence

Page: 52, 53References: -157 Klein AL, Grimm RA, Murray RD, Apperson-Hansen C, Asinger RW, Black IW, Davidoff R, Erbel R, Halperin JL, Orsinelli DA, Porter TR, Stoddard MF. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001;344:1411–1420.

COR/LOE: IIa B

Page: 2391References: -42 Klein AL, Grimm RA, Murray RD, Apperson-Hansen C, Asinger RW, Black IW, Davidoff R, Erbel R, Halperin JL, Orsinelli DA, Porter TR, Stoddard MF. Use of transesophageal echocardiography to guide cardioversion in patients with atrial fibrillation. N Engl J Med 2001;344:1411–1420.

COR/LOE: I B,

GRADE: Conditional Recommendation,High-Quality Evidence

GRADE: Weak recommendation,Moderate-Quality Evidence

GRADE: Strong recommendation,Moderate-Quality Evidence

CCS: Canadian Cardiovascular Society; AHA: American Heart Association; ESC: European Society of Cardiology. COR: Classification of recommendation; LOE: Level of Evidence; AF = Atrial fibrillation, AFL = Atrial flutter, DCC: Direct-current cardioversion, ECG: Electrocardiogram, LOE: Level of Evidence, WPW: Wolff-Parkinson-White.