Fibrillazione atriale e scompenso: come interrompere il circolo vizioso.

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Alessandria, September 23 th 2017 Fibrillazione atriale e scompenso: come interrompere il circolo vizioso. Professor Fiorenzo Gaita Chief of the Cardiovascular Department Città della Salute e della Scienza Hospital University of Turin, Italy

Patients with atrial fibrillation (%) Prevalence of AF in HF Trials 60 50 30% NYHA III-IV NYHA IV 40 NYHA II-III 30 20 NYHA I-II 10 0

AF in pts with HF increases the risk of death In the VEST study, AF caused an increase of 2.3 times the risk of death in patients with heart failure. (Konety, AHA 1998) In the AMIOVIRT study, AF resulted an independent risk factor for mortality (RR 4) in pts with CHF. (Strickberger, J Am Coll Cardiol 2004) In the SOLVD study, AF was an independent risk factor for mortality (RR 1.34) and progression of CHF (RR 1.42). (Vermes, Circulation 2003)

Heart failure and atrial fibrillation Triggered activity Heterogeneous conduction Atrial fibrosis Atrial stretch Pressure and volume overload Atrial fibrillation Heart failure Fast ventricular rate Irregular cycles Loss of atrial contraction Mitral and tricuspid regurgitation

Heart failure and atrial fibrillation Triggered activity Heterogeneous conduction Atrial fibrosis Atrial stretch Pressure and volume overload Atrial fibrillation Heart failure Fast ventricular rate Irregular cycles Loss of atrial contraction Mitral and tricuspid regurgitation

Heart Failure therapy: aims Symptoms relief and exercise tolerance Reduction of HF-related major morbidity Reduction mortality

RHYTHM CONTROL 2006 AF GUIDELINES HEART FAILURE AMIODARONE DOFETILIDE TC ABLATION ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation

Survival (%) Prospective, multi-center, randomized, double blind Placebo vs Amiodarone 667 pts with CHF NYHA II/IV EF 40% CHF-STAT Sub-study 564 (85%) in SR 103 (15%) with AF 33 (6%) New onset of AF at 1 year: 15 51 pts in Amiodarone 100 52 pts in Placebo 10 5 0 8% 4% Amiodarone Placebo 11/268 (4%) 22/296 (8%) 80 60 40 p = 0.04 20 Converted pts n = 16 n = 35 Non converted pts The 0 maintenance of sinus rhythm was associated to a better prognosis. 10 20 30 40 50 (wks) Circulation 1998; 98: 2574

Dedicated invasive atrial fibrillation options in patients with heart failure AV node ablation + RV pacing AV node ablation + CRT Direct AF ablation

MILOS study 1285 consecutive patients 243 with permanent AF (19%) LVEF < 35%, QRS > 120 ms, NYHA > II Follow-up 34 months (10-40) BVP 85% at 2 months AVJ ablation 1042 pts in SR 1285 pts 118 AV ablation (50% ICD) 243 (19%) pts in AF 125 pharmacological therapy Gasparini et al. Eur Heart J 2008

MILOS study Gasparini et al. Eur Heart J 2008

Transcatheter Atrial Fibrillation Ablation in patients with Heart Failure 58 patients Parox AF 9% Pers AF 91% 12 months f-up Ablation protocol 100% PVI 91% PVI+LLs 78% remained in sinus rhythm in 50% of the cases at least 1 redo procedure Hsu, L.-F. et al. N Engl J Med 2004;351:2373

Improvement of NYHA class and LV function after AF Ablation in Patients with Congestive Heart Failure NYHA Class PRE-ABLATION POST-ABLATION 2.3 ± 0.5 1.4 ± 0.5 LV Ejection fraction EF increase 21 13% Hsu, L.-F. et al. N Engl J Med 2004;351:2373

Khan M et al; NEJM 2008 41 pts PVI ablation 81 pts 40 pts PABA CHF AV node ablation and Biv pacing

PVI improved functional capacity (6-minute walk test) and QOL Distance increase 71 m Improvement by 26% QOL Distance increase 16 m Improvement by 6% NEJM 2008; 359 (17): 1778-1785

PVs ISOLATION EF improved in 76% of patients Improvement in EF by 8±8% AV-node ablation+biv Decrease in EF by 1±4% EF improved in only 25% of pts Khan M et al; NEJM 2008

RHYTHM CONTROL 2006 AF GUIDELINES 2012 AF GUIDELINES HEART FAILURE Yes HEART FAILURE No Due to AF AMIODARONE DOFETILIDE Yes No AMIODARONE Dronedarone /Sotalol TC ABLATION Patient choice TC ABLATION ACC/AHA/ESC 2006 Guidelines for the Management of Patients With Atrial Fibrillation ESC 2012 Guidelines for the Management of Patients With Atrial Fibrillation

# of AF ablation studies from 2004 to 2014 # of AF ablation and HF 4000 3500 3000 2500 2000 1500 1000 500 0 AF ablation AF ablation and HF # of studies (Pubmed search)

AF ablation studies in patients with HF Author, Year (Ref) N. pts F-U Success Redo Success months single (%) (%) final (%) LVEF (%) Chen 2004 94 14 52 22 73 36 41 Hsu 2004 58 12 28 50 78 35 56 Tondo 2006 40 14 55 33 87 33 47 Gentlesk 2007 67 6 55 31 86 42 56 Nademanee 2008 129 27-21 79 30 37 Lutomsky 2008 18 6 50 - - 41 52 De Potter 2010 36 16 50 31 69 41 58 Cha Total: 2011 111 12 - - 76% 35 56 Anselmino 2013 196 46 45 30 62 40 50 Calvo 2013 36 6 70 31 83 41 48 Nedios 2014 69 28 40 46 65 33 48 Bunch 2015 267 60 39 - - 27 42 Khan 2008 41 6 71 20 88 27 35 MacDonald 2010 22 10-30 50 36 41 Jones 2013 26 10 69 19 88 21 32 Hunter 2014 26 6 38 54 81 32 40 1236 34 46%

Long-term sinus rhythm 196 patients 78% pers AF 3 years follow-up 62% patients free from AF 29% redos Ablation protocol 100% PVI 85% PVI+LLs+CFAEs J Cardiovasc Electrophysiol 2013

Impact of AF ablation on NYHA class and LVEF NYHA Class 100 80 60 40 20 0 Baseline NYHA class F-up I II III o IV p<0,001 LV Ejection fraction PRE-ABLATION POST-ABLATION 40.4 ± 7.2 50.3 ± 9.5

Multicenter meta-analysis - 25 studies, 1,838 patients from 9 countries and 3 continents - direct contact whit each center will published long-term data

Baseline characteristics AF ablation in patients with HF n=1,838 Mean value Age, years 59 Paroxysmal AF, % 45 Persistent AF, % 50 Long-standing persistent, % 5 Time since first AF diagnosis (M) 42 Time since first HF diagnosis (M) 27 Basal pro-bnp (pg/ml) 11,187 Cardiomiopathy - Ischemic, % 41 - Hypertensive, % 10 - Valvular heart disease, % 10 - Idiopathic, % 39 LV ejection fraction, % 40 Anselmino et al. Circ Arrhythm Electrophysiol 2014

Periprocedural efficacy and complications Mean follow-up: 23 (18-40) months 40% (33-50) 60% (54-67) after redos in 32% (25-38) No death (out of 1838 patients) 21 thromboembolic events TIA/stroke (1.14%) 12 pericardial tamponade (0.65%)

Impact on Symptoms (NYHA class) Baseline 20 80 Follow up after ablation after ablation 37 63

Impact on Left Ventricular Function Baseline Baseline Study end Study end Anselmino et al. Circ Arrhythm Electrophysiol 2014

Patients with LVEF<35% with indication for ICD in primary prevention Baseline Baseline 459 Study end Study end 183 459 at baseline reduced to 183 after ablation Avoid ICD implantation with RRR 60%

AF ablation protocol in patients with HF PVI only Author, Year PVI (%) LLs (%) CFAE (%) Chen 2004 100 0 0 Hsu 2004 100 91 0 Tondo 2006 100 85 0 Gentlesk 2007 100 - - Nademanee 2008 0 0 100 Atrial Linear Lines CFAEs De Potter 2010 Cha 2011 100 100 0 100 69 - Anselmino 2013 100 85 16 Nedios 2014 100 64 0 Khan 2008 100 - - MacDonald 2010 100 100 100 Jones 2013 100 100 100 Hunter 2014 100-100

AF ablation in HF our Institution s approach Parox AF Pers >6m or long-standing AF LA volume <100 ml YES Antral PVI NO Antral PVI + Linear lines and CFAEs

Pts in SR without drugs Surgical ablation in pts with structural heart disease long-standing AF, and enlarged left atrium U 7 PV PV 105 pts (3 groups of 35 pts) Gaita et al, Circulation 2005

What are the results at more than 10-year follow-up? 73% of pts in sinus rhythm 81% of patients with complete 43% with incomplete scheme Gaita et al, Ann Thorac Surg 2013

Persistent AF, ICD or CRT, NYHA II to III, EF <40% Catheter ablation for AF (group 1, n=102) Amiodarone (group 2, n=101). 71% 34% Catheter ablation of AF is superior to Amiodarone in achieving freedom from AF at long-term follow-up and reducing unplanned hospitalization and mortality in patients with heart failure and persistent AF. Di Biase et al Circulation 2016;133:1637-1644

Rhythm control in heart failure 2012 ESC Guidelines 2016 ESC Guidelines Heart failure AMIODARONE (I B) DOFETILIDE (I B) Catheter Ablation (IIb B) Jones JACC 2013; Anselmino Circ AE 2014; Ganesan Heart Lung Circ 2015; Khan NEJM 2008; Al Halabi JACC CE 2015; Di Biase Circ 2016; Hunter Circ AE 2014; MacDonald Heart 2011

Conclusion Rhythm control by AF ablation is under recommended despite it achieves an arrhythmia freedom of about 76-60 % Rhythm control by AF ablation has shown to improve quality of life, LVEF and reduces ICD indications (stroke and mortality) To achieve the best results AF ablation should be recommended soon ( early stage) In pts with increased LA volume end/or persistent AF ablation protocol needs to be more extensive than PVI alone

Thank you for your attention!