Giornate Mediche Fiorentine

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1 Giornate Mediche Fiorentine Firenze 16 Novembre 2012 Dr Paolo Pieragnoli Università degli Studi di Firenze

2 Incidenza (n 10 3 /2 anni) Epidemiologia Incidenza e prevalenza della fibrillazione atriale (FA) aumentano con l aumentare dell età Framingham study Uomini Donne Età (anni) Benjamin EJ, et al. JAMA 1994

3 Prevalenza (%) Prevalenza di fibrillazione atriale per età e sesso nello Studio ATRIA ,974 soggetti con FA (0.95%) in una popolazione USA (California) di 1.89 milioni di persone Rif Donne Uomini 5 5 7,3 7,2 10,3 9,1 11, , ,1 0,2 0,9 0,4 1 1,7 1,7 < >85 Gruppi di età (anni) Go AS et al, JAMA 2001

4 Stima dei soggetti con FA (N, milioni) 16 Stima NON conservativa Continuo aumento di incidenza Stima conservativa Nessun ulteriore aumento di incidenza Anno Miyasaka Y. Circulation, 2006

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7 Risk factor-based approach expressed as a point based scoring system, with the acronym CHA2DS2-VASc European Heart Journal (2010) 31,

8 Etiology of Stroke 15% Vessel rupture 85% Artery occlusion % Atherothrombotic % Cardioembolic 15-20% % Lacunar 5-10 % Infrequent % Cryptogenic

9 Detection of Atrial Fibrillation After Stroke and the Risk of Recurrent Stroke Kamel et al. Journal of Stroke and Cerebrovascular Diseases, 2011

10 Atrial Fibrillation and Risk of Dementia: A Prospective Cohort Study Risk of Incident Dementia and Alzheimer s Disease (AD) Associated with Atrial Fibrillation Dublin et al. J Am Geriatric Soc 59: , 2011

11 Plots of mean rates of arrhythmia events Page et al. Circulation 1994; 89: Clin Med Cardiol FI

12 GISSI-AF Trial Disertori et al. Am Heart J 2011; 162:382-9

13 GISSI-AF Trial Disertori et al. Am Heart J 2011; 162:382-9

14 GISSI-AF Trial CHADS2 Score > 2 OAC Asymptomatic 77% Symptomatic 50% CHADS2 Score = 0 OAC Asymptomatic 73,3% Symptomatic 44,8% Disertori et al. Am Heart J 2011; 162:382-9

15 Practice-Level Variation in Warfarin Use Among Outpatients With Atrial Fibrillation (from the NCDR PINNACLE Program) Chan et al. Variation in treatment rates with warfarin across practices showed a median practice treatment rate with warfarin of 61%. Am J Cardiol 2011

16 Impact of the type of centre on management of AF patients: Surprising evidence for differences in antithrombotic therapy decisions Use of oral anticoagulation in the AFNET registry split by type of enrolling centre. A) Percentage of adequately anticoagulated patients according to the 2001 ESC/AHA/ACC guidelines. B) Percentage of adequately anticoagulated patients according to the CHADS2 score. C) Percentage of adequately anticoagulated patients according to the CHA2DS2-VASc score. Kirchhof et al. Thromb Haemost 2011; 105:

17 Stroke risk stratification schema tested Risk scheme Low risk Intermediate risk High risk AFI Investigators (1994) Age <65y and no risk factors Age >65y and no other risk factors CHADS 2 (2001) -classical Score 0 Score 1-2 Score 3-6 CHADS 2 (2001) -revised Score 0 Score 1 Score 2 NICE guidelines (2006) ACC/AHA/ESC guidelines (2006) Age <65y with no moderate/high risk factors No risk factors Age 65y with no high risk factors Age <75y with hypertension, diabetes or vascular disease* Age 75y, or hypertension, or heart failure, or LVEF 35%, or diabetes 8 th ACCP guidelines (2008) No risk factors Age >75y, or hypertension, or moderately or severely impaired LVEF and/or heart failure, or diabetes CHA 2 DS 2 -VASc (2009) No risk factors One combination risk factor: (heart failure / LVEF 40, hypertension, diabetes, vascular disease*, female gender, age 65-74) Prior stroke/tia, hypertension, diabetes Previous stroke/tia or thromboembolic event Age 75y with hypertension, diabetes or vascular disease Clinical evidence of valve disease or heart failure, or impaired left ventricular function Previous stroke, TIA or embolism, or 2 moderate risk factors of (age 75y, hypertension, heart failure, LVEF 35%, diabetes) Previous stroke, TIA or embolism, or 2 moderate risk factors of (age 75y, hypertension, moderately or severely impaired LVEF and/or heart failure, diabetes) Previous stroke, TIA or embolism, or age 75y, or 2 combination risk factors (heart failure / LVEF 40, hypertension, diabetes, vascular disease*, female gender, age 65-74) Poli et al, J Cardiovasc Electrophysiol 2010

18 Univariate and Multivariate predictive power of risk factors for thromboembolic events on anticoagulant therapy Risk factor (RF) rate rate pvalue OR(95%CI) p value with RF without RF Univariate Multivariate Age> ( ) 0.9 Female ( ) 0.29 Stroke/TIA/TE < ( ) <0.001 Hypertension ( ) 0.7 Diabetes mellitus ( ) 0.35 Heart failure (08.3.8) 0.34 LVEF<40% ( ) 0.89 Vascular Disease (*) ( ) 0.19 (*) Coronary artery disease, peripheral vascular disease, previous sistemic embolism Poli et al, J Cardiovasc Electrophysiol 2010

19 Proportions categorized as high, intermediate, and low-risk based on stroke risk stratification schema for atrial fibrillation Poli et al, J Cardiovasc Electrophysiol 2010

20 The proportion of patients assigned to individual risk categories varied widely across the schema, with those categorised as moderate-risk ranging from 5.3% (CHA 2 DS 2 - VASc) to 49.2% (CHADS 2 -classical). Patients classified as low-risk by all risk schemas were truly low risk, with no TE events recorded.

21 In this cohort of consecutive elderly AF patients attending an anticoagulation clinic, current published risk schemas have modest predictive ability, with c-statistics ranging from 0.54 (AFI) to 0.72 (CHA 2 DS 2 -VASc). CHADS 2 and CHA 2 DS 2 -VASc schemas show the best predictive value for thromboembolism.

22 Risk Stratification CHADS 2 Score, PAF Duration and Stroke Risk 568 pts. with MDT AT500 continuously monitored for 1 year CHADS 2 score No AF at FU (AT/AF < 5 min in 1 day) 58 Pts 80 Pts 24 Pts 4 Pts 5 min < AT/AF Episodes < 24 h 54 Pts 76 Pts 42 Pts 7 Pts AT/AF Episodes > 24 h 59 Pts 113 Pts 45 Pts 6 Pts (3 out of 351 Pts) 0.8 % vs 5 % (11 out of 217 Pts) Botto, Padeletti et al. J Cardiovasc El 2009 P = 0.035

23 Patients with a dual-chamber pacemaker (Medtronic AT-500) and history of paroxysmal atrial tachyarrhythmias were included into this study. A day by day trend of AF burden (= time spent in AF during each day) was available for each patient during 1-year follow-up. Patients were divided into 3 groups: (i) maximum AF burden <5min per day [AFfree]; (ii) maximum AF burden >5min but <24h per day [AF-5min]; and (iii) AF burden of 24h or higher (episodes longer than 24h) [AF-24h]. Stroke 2011, 42(6):

24 Results 1: Sensitivity & Specificity of CHADS 2 score Sensitivity Specificity 0 Sensitivity Specificity CHADS 2 score: CHADS 2 score: Case 1:Treating all Pts with score 1 Case 2: Treating all Pts with score 2 Stroke 2011, 42(6):

25 Results 2: Sensitivity & Specificity of CHADS 2 score + AF burden Sensitivity Specificity CHADS 2 score: Only those with AF>24h Only those with any AF + + All 3 Stroke 2011, 42(6):

26 Results 3: Sensitivity & Specificity of CHA 2 DS 2 -VASc score Sensitivity Specificity CHA 2 DS 2 -VASc score: Sensitivity Specificity CHA 2 DS 2 -VASc score: Case 1: Treating all Pts with score 1 Case 2. Treating all Pts with score 2 Stroke 2011, 42(6):

27 Results 4: Sensitivity & Specificity of CHA 2 DS 2 -VASc score + AF burden Sensitivity Specificity CHA 2 DS 2 -VASc score: Only those Pts with AF>24h + all > 3 Stroke 2011, 42(6):

28 Risk stratification for stroke can be improved by combining either CHADS 2 or CHA 2 DS 2 -VASc score with AF parameters. CHA 2 DS 2 -VASc scheme has the highest sensitivity to predict TE: its integration with continuous AF burden improves specificity and the discriminating ability for TE. Thus, data on AF burden may refine risk stratification for stroke and this is evident even when OAC is more commonly prescribed, as expected, in patients with the highest AF burden.

29 European Heart Journal (2010) 31,

30 Risks of Thromboembolism and Bleeding with Thromboprophylaxis in patients with Atrial Fibrillation: A net clinical benefit analysis using a real world nationwide cohort study Olesen et al. What does this paper add? Regardless of HAS-BLED score, there is negative net clinical benefit of oral anticoagulation if patients are truly low risk (i.e. CHA2DS2-VASc score = 0) and, a neutral or positive net clinical benefit of oral anticoagulation for patients with CHADS2 score 0 or CHA2DS2-VASc score 1. Acetylsalicylic acid should not be used for thromboprophylaxis in any patient with atrial fibrillation. Thromb Haemost 2011

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36 Eur Heart J 2010

37 Choice between ablation and antiarrhythmic drug therapy for patients with and without structural heart disease European Heart Journal (2010) 31,

38 Treatment of AF With Antiarrhythmic Drugs Calkins et al. Circ Arrhythmia Electrophysiol. 2009;2:

39 M. Gulizia et al Diagnosi e terapia del Flutter e della Fibrillazione atriale 2009 Efficacy of antiarrhythmic drugs Low efficacy

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44 Registry on Cardiac Rhythm Disorders Assessing the Control of Atrial Fibrillation (RecordAF) Rhythm control Atrial fibrillation and Structural Heart Disease. Atrial fibrillation and Congestive Heart Failure. Lone Atrial Fibrillation Kowey PR et al. Clin. Cardiol. 33, 3, (2010)

45 Registry on Cardiac Rhythm Disorders Assessing the Control of Atrial Fibrillation (RecordAF) Rate control Atrial fibrillation and Structural Heart Disease. Atrial fibrillation and Congestive Heart Failure. Lone Atrial Fibrillation Kowey PR et al. Clin. Cardiol. 33, 3, (2010)

46 UK General Practice Research Database (GPRD) Rhythm control agents and Adverse Events Relative risk of adverse effects of Amiodarone, Flecainide or Sotalol in cases compared with controls. Taylor et al. Int J Clin Pract 2010

47 Canadian Registry of Atrial Fibrillation (CARAF) Patients at baseline with paroxysmal AF (n = 723) with contraindications (C), warnings (W) and/or precautions (P), including concomitant drug use, for use of antiarrhythmic drugs Patients taking antiarrhythmic therapy at 3-month follow-up despite presence of contraindications and/or warnings, including concomitant drug use (n = 465) Humphries K.H et al. CMAJ SEPT. 28, 2004; 171 (7)

48 Amiodarone and Dronedarone: not innocent drugs! Dronedarone in patients with congestive heart failure: insights from ATHENA Stefan H. Hohnloser et al. Conclusion. Dronedarone should be controindicated in patients with NYHA class IV or unstable classes II and III CHF. Tung R et al. J Am Coll Cardiol 2008;52: European Heart Journal April 30, 2010

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54 Conclusion: High dose oral ranolazine shows utility as a possible safe agent to convert new or paroxysmal AF (13 on 18)

55 The present study compared amiodarone versus ranolazine for the prevention of AF after CABG The patients received either amiodarone (400 mg preoperative followed by 200 mg twice daily for 10 to 14 days) or ranolazine (1500 mg preoperative followed by 1000 mg twice daily for 10 to 14 days) Number of Patients: 393 Amiodarone (n=211 [53.7%]) Ranolazine (n=182 [46.3%]) Am J Cardiol 2011;108:

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60 Catheter ablation: pulmonary veins isolation

61 Catheter ablation: pulmonary veins isolation

62 Catheter ablation: pulmonary veins isolation

63 The left and right ipsilateral PVs were isolated by long encircling lesions (red ablation tags).in addition, a roof line connecting both circular linear lesions and an anterior line connecting the anterior mitral annulus with the left superior PV were deployed. PACE 2011; 34:

64 As the first ablation step, an ostial PV isolation was performed (ablations shown in dark brown). As the second step, CFAE (complex fractionated atrial electrograms) were ablated, shown with yellow ablation tags PACE 2011; 34:

65 Fluoroscopic anteroposterior view of the circular mapping catheter positioned at the ostium of the LAA and the ablation catheter during isolation of the LAA. 3-dimensional CT reconstruction registered into the CARTO mapping system showing the ablation sites required to complete the LAA isolation.

66 AF Ablation Have we done enough work on the left atrium to prevent atrial fibrillation? 85

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71 Long-term outcome after catheter ablation for atrial fibrillation: safety, efficacy and impact on prognosis Long-term freedom from AF or other atrial tachyarrhythmias for paroxysmal AF and persistent AF. The studies shown have the longest follow-up reported to date (2.5 e 4.7 years). Hunter RJ et al. Heart 2010;96:1259e1263

72 Catheter Ablation Is Established as a Treatment Option for Atrial Fibrillation Freedom from atrial fibrillation in Randomized Clinical Trials comparing the outcomes of catheter ablation and antiarrhythmic drugs Takahashi A. Circ J 2010; 74:

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74 Percentiles (70%, 80% and 90%) of the burden of atrial fibrillation in the two groups at baseline and during follow-up are shown. The same poercentiles are also shown for the cumulative burden of atrial fibrillation

75 Cost Comparison of Ablation Versus Antiarrhythmic Drugs as First-Line Therapy for Atrial Fibrillation: An Economic Evaluation of the RAAFT Pilot Study Khaykin Y et al. J Cardiovasc Electrophysiol, Vol. 20, pp. 7-12, January 2009

76 there are substantial data that clearly show ablation to be a reasonable alternative to antiarrhythmic drugs at least in patients with no or minimal heart disease who have paroxysmal AF, assuming that the electrophysiologist performing the study has substantial experience in ablation J Cardiovasc Electrophysiol, Vol. 21, pp , August 2010

77 Circulation 2010,122:

78 Circulation 2010,122:

79 LA transcatheter ablation for AF is associated with silent cerebral thromboembolism. Periprocedural symptomatic cerebral thromboembolism (transient ischemic attack) represents only a minimal part of the thromboembolic risk (0.4% symptomatic versus 14% asymptomatic; odds ratio40.53). The thromboembolic risk is independent from clinical parameters such as age, hypertension, and diabetes mellitus and from the type of AF, occurrence of previous cerebral thromboembolic events, preprocedural antithrombotic treatment, and the ablation strategy used. In univariate and multivariable analyses, the most important factor that correlated with cerebral embolism was electric or pharmacological conversion to sinus rhythm during the procedure,with a significantly increased odds ratio of Circulation 2010,122:

80 RF PVAC CRYO

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83 40% 37% 29%

84 87% 81% 63%

85 Statua romana di Atlante (sec II d.) Museo Archeologico Nazionale di Napoli

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87 Sept Dear Professor Einthoven, At present we are working at Fibrillation of the Auricles, but it is a very tough nut to crack. With kindest regards, Very sincerely, yours, Thomas Lewis.