1. Indications on cardiac pacing and cardiac resynchronization therapy Michele Brignole Centro Aritmologico, Ospedali del Tigullio, Lavagna, Italy

2. Michele Brignole (Italy) Angelo Auricchio (Switzerland) Gonzalo Baron-Esquivias (Spain) Pierre Bordachar (France) Giuseppe Boriani (Italy) Ole-A Breithardt (Germany) John Cleland (UK) Jean-Claude Deharo (France) Victoria Delgado (Nertherlands) Perry M. Elliott (UK) Bulent Gorenek (Turkey) Carsten W. Israel (Germany) Christophe Leclercq (France) Cecilia Linde (Sweden) Lluís Mont (Spain) Luigi Padeletti (Italy) Richard Sutton (UK) Panos E. Vardas (Greece) Task Force members European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

3. Chair invitation letter14 March 2011 1° plenary meeting13-14 June 2011Table of contents & assignments 2° plenary meeting21-22 November 2011Mastercopy 3° plenary meeting2-3 March 2012Version 2 4° plenary meeting27 August 2012Revision round 1 5° plenary meeting28 November 2012Revision round 2 CPG comments28 February 2013CPG revision Ready for publication9 April 2013Sent to Eur Heart J and Euroapce Timelines European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

4. 70 Contributors 18 Task Force Members 26 CPG Members 26 Reviewers Contributors 690 comments (98 pages) European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

5. www.escardio.org/guidelines General structure of the document 1.Pacing for bradycardia –Indications –mode of pacing 2.Cardiac resynchronization therapy –Indications –mode of pacing 3.Complication of pacing and CRT 4.Management considerations European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

6. www.escardio.org/guidelines Classification of bradyarrhythmias based on the patient’s clinical presentation AV block: Sinus rhythm Atrial fibrillation AV block: Sinus rhythm Atrial fibrillation Sinus node disease Patients considered for antibradycardia PM therapy Parox AVB SSS (brady- tachy) Parox AVB SSS (brady- tachy) ECG- documented Intrinsic Extrinsic (functional) Extrinsic (functional) Vagal Idiopathic AVB Vagal Idiopathic AVB BBB Reflex syncope Unexplained syncope Carotid sinus Tilt-induced Carotid sinus Tilt-induced Suspected (ECG-undocumented) Suspected (ECG-undocumented) Intermittent bradycardia Persistent bradycardia European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

7. www.escardio.org/guidelines New classification of bradyarrhythmias: ECG instead of etiology Look for bradycardia Obtain an ECG documentation Obtain an ECG documentation No ECG documentation (bradycardia suspected) No ECG documentation (bradycardia suspected) ECG documentation (bradycardia established) ECG documentation (bradycardia established) Consider PM European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

8. www.escardio.org/guidelines Indication for pacing in patients with persistent bradycardia European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

9. www.escardio.org/guidelines Indication for pacing in intermittent documented bradycardia European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

10. www.escardio.org/guidelines Indication for cardiac pacing in patients with undocumented bradycardia (reflex syncope) European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

11. CSS: Syncope recurrence rate % Years Blanc 84 Brignole 92 (a) Brignole 92 (b) Claesson 07 Menozzi 93 Sugrue 86 Walter 78 Claesson 07 Brignole 92 (a) Brignole 92 (b) Morley 82 Blanc 84 Stryjer 86 Sugrue 86 Crilley 97 Lopes 11 Pacemaker No therapy

12. Clinical perspectives New Clinical perspectives The decision to implant a pacemaker should be made in the context of a relatively benign condition ………. ……. carotid sinus syndrome does not affect survival,……. …….. syncopal recurrences are still expected to occur in up to 20% of paced patients within 5 years…… Clinical perspectives The decision to implant a pacemaker should be made in the context of a relatively benign condition ………. ……. carotid sinus syndrome does not affect survival,……. …….. syncopal recurrences are still expected to occur in up to 20% of paced patients within 5 years……

13. www.escardio.org/guidelines Indication for cardiac pacing in patients with undocumented bradycardia (BBB) European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

14. www.escardio.org/guidelines Algorithm for patients with unexplained syncope and BBB BBB and unexplained syncope Reduced EF (<35%) Consider CSM/EPS Preserved EF (>35%) Consider ICD/CRT-D (if negative) Consider ILR (if negative) Consider ILR Appropriate therapy (if negative) Clinical follow-up (if negative) Clinical follow-up European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

15. www.escardio.org/guidelines Dual-chamber versus ventricular pacing European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

16. www.escardio.org/guidelines Choice of pacing mode Sinus node disease AV block Persistent 1° choice DDDR + AVM 2° choice AAIR 1° choice DDDR + AVM 2° choice AAIR 1° choice DDD + AVM 2° choice AAI 1° choice DDD + AVM 2° choice AAI Intermittent 1° choice DDDR + AVM 2° choice DDDR, no AVM 3° choice AAIR 1° choice DDDR + AVM 2° choice DDDR, no AVM 3° choice AAIR Persistent SND No SND AF 1° choice DDDR 2° choice DDD 3° choice VVIR 1° choice DDDR 2° choice DDD 3° choice VVIR 1° choice DDD 2° choice VDD 3° choice VVIR 1° choice DDD 2° choice VDD 3° choice VVIR VVIR Intermittent DDD + AVM (VVI if AF) Consider CRT if low EF/HF European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

17. www.escardio.org/guidelines All LBBBn=1283 Womenn=396 Menn=887 Class In=145 Class IIn=1138 QRS <150n=302 QRS ≥150n=981 USn=871 OUSn=412 All Non-LBBBn=537 Womenn=59 Menn=478 Class In=121 Class IIn=416 QRS <150n=343 QRS ≥150n=194 USn=398 OUSn=139 Challenging indications for CRT: the “Entry criterium” LBBB Non LBBB 0.10.20.512510 Hazard ratio Font: MADIT CRT Favors CRT-DFavors ICD European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

18. www.escardio.org/guidelines Magnitude of benefit from CRT Indications for CRT in patients in sinus rhythm European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118 Highest (responders) Lowest (non-responders) Wider QRS, LBBB, females, non-ischemic cardiomyopathy Males, ischemic cardiomyopathy Narrower QRS, non-LBBB

19. www.escardio.org/guidelines Indications for CRT in patients in sinus rhythm European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

20. www.escardio.org/guidelines Indication for CRT in patients with permanent AF European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

21. www.escardio.org/guidelines Indications for AVJ ablation (± CRT) in permanent AF AVJ ablation Heart failure, NYHA class III-IV and EF <35% Heart failure, NYHA class III-IV and EF <35% Reduced EF and uncontrollable HR, any QRS Reduced EF and uncontrollable HR, any QRS Incomplete BiV pacing Incomplete BiV pacing No AVJ ablation No AVJ abl No CRT* No AVJ abl No CRT* Adequate rate control Adequate rate control Inadequate rate control Inadequate rate control AVJ abl & CRT * Consider ICD according guidelines AVJ abl & CRT Complete BiV pacing Complete BiV pacing QRS <120 ms CRT * QRS ≥120 ms European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

22. www.escardio.org/guidelines Upgraded or de novo CRT in patients with conventional pacemaker indications and HF European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118 Clinical perspectives A strategy of initially conventional antibrady pacing with late upgrade in case of worsening symptoms seems reasonable In the decision process physicians should take into account the excess complication rate related to the more complex biventricular system, the shorter longevity of CRT devices and the excess of costs. Clinical perspectives A strategy of initially conventional antibrady pacing with late upgrade in case of worsening symptoms seems reasonable In the decision process physicians should take into account the excess complication rate related to the more complex biventricular system, the shorter longevity of CRT devices and the excess of costs.

23. www.escardio.org/guidelines Time to death of any cause in the European CRT Survey 1,00 0,98 0,96 0,94 0,92 0,90 0,88 0,86 0,84 0,82 0,80 050100150200250300350400450500 Days after implantation Proportion of patients surviving De-novo implantations Upgrades p=0.85 European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

24. Backup ICD in patients indicated for CRT Factors favouring CRT-DFactors favouring CRT-P Life expectancy >1 yearAdvanced heart failure Stable heart failure, NYHA IISevere renal insufficiency or dialysis Ischemic heart disease (low and intermediate MADIT risk score) Other major co-morbidities Lack of comorbiditiesFrailty Cachexia CRT-DCRT-P Mortality reduction Similar level of evidence but CRT-D slightly better Similar level of evidence but CRT-P slightly worse ComplicationsHigherLower CostsHigherLower Comparative results of CRT-D versus CRT-P in primary prevention Clinical guidance to the choice of CRT-P or CRT-D in primary prevention European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118 New

25. www.escardio.org/guidelines Clinical perspectives The usual (standard) modality of CRT pacing consists of simultaneous biventricular pacing (RV and LV) with a fixed 100-120 ms AV delay with LV lead located in a posterolateral vein, if possible. Clinical perspectives The usual (standard) modality of CRT pacing consists of simultaneous biventricular pacing (RV and LV) with a fixed 100-120 ms AV delay with LV lead located in a posterolateral vein, if possible. Choice of pacing mode (and CRT optimization) European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118 New

26. www.escardio.org/guidelines Indication for prevention and termination of atrial tachyarrhythmias European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118 New

27. www.escardio.org/guidelines Optimal pacing mode in children Sinus node dysfunction Prevent dyssynchrony Atrial pacing only Prevent dyssynchrony Atrial pacing only (Complete) AV block (Complete) AV block Prevent dyssynchrony (Left) ventricular pacing only Prevent dyssynchrony (Left) ventricular pacing only Intrinsic LBBB Treat dyssynchrony Single-site LV (or BIV) pacing Treat dyssynchrony Single-site LV (or BIV) pacing RV pacing induced dyssynchrony Treat dyssynchrony Single-site LV (or BIV) pacing Treat dyssynchrony Single-site LV (or BIV) pacing Bradycardia Dyssynchrony associated HF European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118 New Clinical perspectives LV pacing alone… seems to be non-inferior to biventricular pacing for improving soft end-points (quality of life, exercise capacity and LV reverse remodelling) …. LV pacing alone seems particularly appealing in children and young adults. Clinical perspectives LV pacing alone… seems to be non-inferior to biventricular pacing for improving soft end-points (quality of life, exercise capacity and LV reverse remodelling) …. LV pacing alone seems particularly appealing in children and young adults.

28. www.escardio.org/guidelines MRI in patients with implanted cardiac devices European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118 New

29. www.escardio.org/guidelines European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118

30. www.escardio.org/guidelines Remote management of arrhythmias and device European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118 New

31. Clinically oriented, simple, ready for use Short and simple articulation of recommendations Description of benefit and harm Rating of quality of evidence Acknowledgment of differences of opinion Style innovation European Heart Journal 2013; 34: 2281–2329 Europace 2013; 15: 1070-1118