Recent observations have focused attention on the PVs as a source of ectopic activity i determining i AF

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1 Atrial Fibrillation in 2010 Panos Vardas Professor of Cardiology President of EHRA Atrial Fibrillation

2 Pathophysiology of AF Triggers Recent observations have focused attention on the PVs as a source of ectopic activity i determining i AF Other anatomical structures that may also provide ectopic beats causing AF are: the superior vena cava the vein of Marshall the musculature of coronary sinus the posterior wall of LA Pathophysiology of AF Substrate-Fibrosis Fibrosis has an apparent, clear impact in facilitating AF by reducing the conduction velocity and possibly creating areas of conduction block The precise mechanisms and signaling pathways involved in the development of atrial fibrosis are unknown Currently three interrelated pathways appear to be involved: the renin angiotensin system growth factors (TGF-1) the oxidative stress pathways (CRP)

3 Pathophysiology of AF Substrate-Genetic factors It is now evident that lone AF may be caused by mutations of different genes controlling cardiac excitability the final effect is that of reduced action potential duration. Mutations in connexin 40 lead to an impaired electrical coupling between cells and decreased atrial conduction velocity Asymptomatic AF Facts AF is often present without any symptoms In chronic AF, the asymptomatic form is estimated up to 30% of the cases The impact of asymptomatic paroxysmal AF is higher In patients with symptomatic AF, asymptomatic AF occurs frequently in about 1 in 5 patients before symptomatic recurrence is detected The only accurate screening method -the gold standardis the ILRs

4 Goals of AF therapy Abolish precipitants / Reduce underlying structural heart disease Improve Quality of Life Reduce Symptoms Rate vs Rhythm control Reduce Complications Anticoagulation (central to all AF management strategies) Extend survival Minimize treatment-related adverse effects Anti-arrhythmic options in 2010 Antiarrhythmic drugs Drugs with no specific antiarrhythmic h i actions Non pharmacological agents Non pharmacological agents Catheter ablation Devices Antiarrhythmic surgery

5 Investigational & experimental AAD I. Savelieva and J. Camm. Europace 2008 AAD - SR maintenance The rate of efficacy in maintaining SR 6 months Amio

6 Amiodarone - SR maintenance Vardas et al, Am J Card 1998 Roy et al, N Engl J Med Side effects: Hypo-hyper thyroidism Skin discoloration Lung toxicity Visional so a problems obe Dronedarone - SR maintenance The ATHENA trial evaluated 4,628 pts >75 years with AF or years with AF and at least one additional cardiovascular risk factor randomized to dronedarone or placebo. Primary Endpoint: composite of all-cause mortality combined with cardiovascular hospitalization. tive Incidence (%) Cummulat HR=0.76 P=< Placebo Dronedarone Months Placebo Dronedarone Dronedarone decreased the risk of cardiovascular ascu a hospitalizations a o s or death from any cause by 24% (p<0.001). Hohnloser et al, Presented at Heart Rhythm 2008

7 Rate or Rhythm control? PIAF STAF AFFIRM RACE HOT CAFE Pts F-u (mo) Age AF Persistent Persistent Therapies Am-ECV Endpoint Symptoms Persistent/ Paroxysmal Persistent/ Recurrent after ECV Am-Prop-Fl- Am-Sot- Sot-Fl-Prop- ECV Prop-ECV Am-ECV Comp clinical events Death Comp clinical events Persistent Am-Sot-Prop Comp clinical events Results No differ No differ No differ No differ No differ None of these trials demonstrated the expected superiority of the rhythm control strategy Rate or Rhythm control? AF-CHF trial 1376 patients with a LVEF 35%, symptoms of CHF, and a history of AF were randomly assigned to a rhythm-control (amiodarone 82%) or rate-control (beta-blockers 88%) strategy and were followed for a mean of 37 months Primary endpoint: death from cardiovascular causes In patients with AF and CHF, a routine strategy of rhythm control does not reduce the rate of death from cardiovascular causes, as compared to arate-control t strategy t Roy D et al, N Engl J Med 2008;358:

8 Upstream therapies Experimental and clinical investigations that elucidate the molecular mechanisms of atrial remodeling have shown that: ACE inhibitors and ARBs Statins Low dose steroids N-3 polyunsaturated fatty acids (PUFAs) have a beneficial i effect to prevent AF. Upstream therapies The GISSI AF Trial Large, randomized, prospective, placebo-controlled, controlled, multicenter trial to test whether the ARB valsartan could reduce the recurrence of AF The 2 primary end points were time to first recurrence of AF and proportion of pts with more than one recurrence of AF in 1 year. At 1 year, no significant reduction in the incidence of recurrent AF was found The Gissi-AF investigators, N Engl J Med 2009;360:

9 AF ablation - Facts Catheter ablation of AF is one of the most complex interventional electrophysiologic procedures. Recurrences of AF or atrial tachycardia after an initial AF ablation procedure lead to a reablation in 20% to 40% of patients. The risk associated with AF ablation is higher than for ablation of most other cardiac arrhythmias. The world-wide survey of AF ablation reported that at least one major complication was seen in 6% of patients but with only four early deaths recorded in 8,745 patients. Cappato R et al. Worldwide survey on the methods, efficacy, and safety of catheter ablation for human AF. Circulation 2005

10 AF ablation - Guidelines New AF ablation techniques and technologies Irrigated-tip ablation catheters. Balloon cryo-ablation. Intracardiac-echo. Robotic navigation systems. stems Multi-slice CT or MRI image integration in electroanatomic maping.

11 Image integration Remote navigation systems

12 AF ablation SR maintenance At the end of the 9-month evaluation period, 66% of patients in the catheter ablation group remained free from protocoldefined treatment failure compared with 16% of patients treated with ADD. Wilber D et al. JAMA 2010 AF and stroke

13 Risk stratification & recommendations for antithrombotic therapy RELY STUDY Randomized Evaluation of Long-term anticoagulant therapy 0.05 Primary EP: Stroke or peripheral embolism hazard ra ates Warfarin Dabigatran etexilate 110 mg Dabigatran etexilate 150 mg RR 0.91 (95% CI: ) p<0.001 (NI) p=0.34 (Sup) RRR 34% Cum mulative RR 0.66 (95% CI: ) p< (NI) p<0.001 (Sup) Years Connolly SJ., et al. NEJM 2009.

14 AF in 2010 Conclusions There has been no marked progress in the pharmaceutical cure of AF. Dronedarone seems to be effective in AF patients with mild or no HF. Although the evolving techniques of ablation are maturing and seem to be promising, they are not yet recognized as a first line treatment. Could an early initiation of rhythm control therapy (drugs, ablation, and upstream therapy ) result in a slower progression of AF and can, in the long term, AF-related complications be prevented by such a therapy?