Giornate Mediche Fiorentine - ASIAM - congressi … Paolo Pieragnoli Università degli Studi di...

Dr Paolo Pieragnoli Università degli Studi di Firenze

Giornate Mediche Fiorentine

Firenze 16 Novembre 2012

• Incidenza e prevalenza della fibrillazione atriale (FA) aumentano con l’aumentare dell’età

Epidemiologia

Inc

ide

nza

(n

• 1

03/2

an

ni)

Benjamin EJ, et al. JAMA 1994

Uomini

Donne

Età (anni)

0

20

40

80

60

55-64 75-84 65-74 85-94

Framingham study

Prevalenza di fibrillazione atriale per età e sesso nello Studio ATRIA

0,10,4

1

1,7

3,4

5

7,2

9,1

0,2

0,9

1,7

3

5

11,1

10,3

7,3

<55 55-64 60-64 70-74 65-69 80-84 75-79 >85

Gruppi di età (anni)

Pre

vale

nza (

%)

0

2

4

6

8

10

12

Uomini

Donne

Go AS et al, JAMA 2001

17,974 soggetti con FA (0.95%) in

una popolazione USA (California)

di 1.89 milioni di persone

Rif. 1.7.1996-31.12.1997

Sti

ma d

ei so

gg

ett

i co

n F

A

(N, m

ilio

ni)

0

4

8

12

16

2000 2010 2020 2030

Anno

2040

Stima conservativa – Nessun

ulteriore aumento di incidenza

Miyasaka Y. Circulation, 2006

2050

Stima NON conservativa –

Continuo aumento di incidenza

Risk factor-based approach expressed as a point based

scoring system, with the acronym CHA2DS2-VASc

European Heart Journal (2010) 31, 2369–2429

25 % Cardioembolic

Atherothrombotic

5-20 % Lacunar

5-10 % Infrequent

20 % Cryptogenic

25-30 %

20 %

15-20%

5-10 %

25-30 %

Artery

occlusion Vessel

rupture

15% 85%

Etiology of Stroke

Detection of Atrial Fibrillation After Stroke

and the Risk of Recurrent Stroke

Kamel et al. Journal of Stroke and Cerebrovascular Diseases, 2011

Atrial Fibrillation and Risk of Dementia:

A Prospective Cohort Study

Dublin et al. J Am Geriatric Soc 59:1369-1375, 2011

Risk of Incident Dementia and Alzheimer’s Disease (AD) Associated with Atrial Fibrillation

Clin Med Cardiol FI

Page et al. Circulation 1994; 89: 224-227

Plots of mean rates of arrhythmia events

Disertori et al. Am Heart J 2011; 162:382-9

GISSI-AF Trial

Disertori et al. Am Heart J 2011; 162:382-9

GISSI-AF Trial

CHADS2 Score > 2

OAC

Asymptomatic 77%

Symptomatic 50%

CHADS2 Score = 0

OAC

Asymptomatic 73,3%

Symptomatic 44,8%

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

Kirchhof et al. Thromb Haemost 2011; 105: 1010–1023

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 .

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

Prior stroke/TIA, hypertension, diabetes

CHADS2 (2001) -classical Score 0 Score 1-2 Score 3-6

CHADS2 (2001) -revised Score 0 Score 1 Score ≥2

NICE guidelines (2006) Age <65y with

no

moderate/high

risk factors

Age ≥65y with no high risk

factors

Age <75y with

hypertension, diabetes or

vascular disease*

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

ACC/AHA/ESC guidelines

(2006)

No risk factors Age ≥75y, or hypertension,

or heart failure, or LVEF

≤35%, or diabetes

Previous stroke, TIA or embolism, or ≥2

moderate risk factors of (age ≥75y,

hypertension, heart failure, LVEF

≤35%, diabetes)

8th ACCP guidelines (2008) No risk factors Age >75y, or hypertension,

or moderately or severely

impaired LVEF and/or

heart failure, or 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)

CHA2DS2-VASc (2009) No risk factors One ‘combination’ risk

factor: (heart failure /

LVEF ≤40, hypertension,

diabetes, vascular disease*,

female gender, age 65-74)

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

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

Age>75 5.8 6.0 0.9 0.97(0.5-1.9) 0.9

Female 8.3 4.5 0.045 1.9(1.01-3.7) 0.29

Stroke/TIA/TE 12.5 2.5 <0.001 5.6 (2.7-11.4) <0.001

Hypertension 7.2 3.7 0.07 2.0 (0.9-4.3) 0.7

Diabetes mellitus 7.6 3.8 0.37 1.4 (0.7-2.9) 0.35

Heart failure 8.0 5.3 0.12 1.8 (08.3.8) 0.34

LVEF<40% 6.1 5.5 0.8 1.1 (0.5-2.6) 0.89

Vascular Disease (*) 7.6 5.1 0.2 1.5 (0.8-3.0) 0.19

(*) Coronary artery disease, peripheral vascular disease, previous sistemic embolism

with RF without RF Univariate Multivariate

Proportions categorized as high, intermediate, and low-risk

based on stroke risk stratification schema for

atrial fibrillation


5.3

49.2

23.6

27.6

20.4

23.7

9.8

The proportion of patients assigned to

individual risk categories varied widely across

the schema, with those categorised as

‘moderate-risk’ ranging from 5.3% (CHA2DS2-

VASc) to 49.2% (CHADS2-classical). Patients

classified as ‘low-risk’ by all risk schemas were

truly low risk, with no TE events recorded.

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 (CHA2DS2-VASc).

CHADS2 and CHA2DS2-VASc schemas show the

best predictive value for thromboembolism.

CHADS2 Score, PAF Duration and Stroke Risk

• 568 pts. with MDT AT500 continuously monitored for 1 year

No AF at FU (AT/AF < 5 min in 1 day)

5 min < AT/AF Episodes < 24 h

AT/AF Episodes > 24 h

CHADS2 score 0 1 2 3

58 Pts 4 Pts 24 Pts

54 Pts 7 Pts 76 Pts 42 Pts

59 Pts 113 Pts 6 Pts 45 Pts

(3 out of 351 Pts) 0.8 % vs 5 % (11 out of 217 Pts)

P = 0.035 Botto, Padeletti et al. J Cardiovasc El 2009

Risk Stratification

80 Pts

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 [AF-

free]; (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):1768-70

Results 1:

Sensitivity & Specificity of CHADS2 score

0

20

40

60

80

100

Sensitivity Specificity

Case 1:Treating all Pts with score ≥ 1

CHADS2 score:

0 1 2 ≥3

0

20

40

60

80

100


Case 2: Treating all Pts with score ≥ 2

CHADS2 score:

0 1 2 ≥3

Stroke 2011, 42(6):1768-70

86

30 43

78

Results 2:

Sensitivity & Specificity of CHADS2 score + AF burden

0

20

40

60

80

100


Only those

with AF>24h

Only those

with any AF All ≥3

CHADS2 score:

0 1 2 ≥3

+ +

Stroke 2011, 42(6):1768-70

79

63

Results 3:

Sensitivity & Specificity of CHA2DS2-VASc score

Case 1: Treating all Pts with score ≥ 1

CHA2DS2-VASc score:

0 1 2 ≥3

Case 2. Treating all Pts with score ≥ 2

CHA2DS2-VASc score:

0 1 2 ≥3

0

20

40

60

80

100

Sensitivity Specificity0

20

40

60

80

100


Stroke 2011, 42(6):1768-70

100

7

100

24

Results 4:

Sensitivity & Specificity of CHA2DS2-VASc score + AF burden

0

20

40

60

80

100


CHA2DS2-VASc score:

0 1 2 ≥3

Only those Pts

with AF>24h all > 3 +

Stroke 2011, 42(6):1768-70

93

42

• Risk stratification for stroke can be improved by combining either CHADS2 or CHA2DS2-VASc score with AF parameters.

• CHA2DS2-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.

Thromb Haemost 2011

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.

Eur Heart J 2010


Choice between ablation and antiarrhythmic drug therapy for patients

with and without structural heart disease

Treatment of AF With Antiarrhythmic Drugs

Calkins et al. Circ Arrhythmia Electrophysiol. 2009;2:349-361

Efficacy of antiarrhythmic drugs

M. Gulizia et al “Diagnosi e terapia del Flutter e della Fibrillazione atriale” 2009

Low efficacy

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, 172–178 (2010)

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, 172–178 (2010)

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

Canadian Registry of Atrial Fibrillation (CARAF)

Humphries K.H et al. CMAJ SEPT. 28, 2004; 171 (7)

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)

Tung R et al. J Am Coll Cardiol 2008;52:1111–21

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.

European Heart Journal April 30, 2010

Conclusion: High

dose oral ranolazine

shows utility as a

possible safe agent to

convert new or

paroxysmal AF

(13 on 18)

Am J Cardiol 2011;108:673-676

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%])

Catheter ablation: pulmonary veins isolation

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; 34:939–948

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; 34:939–948

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.

Angioplasty in Acute MI

We were overzealous with the angiojet. Let

us fly her to Boston for

a body transplant

Have we done enough work

on the left atrium to prevent

atrial fibrillation?

AF Ablation

85

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

Catheter Ablation Is Established as a Treatment Option for Atrial Fibrillation

Takahashi A. Circ J 2010; 74: 1972 – 1977

Freedom from atrial fibrillation in Randomized Clinical Trials comparing the outcomes of

catheter ablation and antiarrhythmic drugs

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

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

…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. 946-958, August 2010

Circulation 2010,122:1667-1673

Circulation 2010,122:1667-1673

• 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 2.75.

RF PVAC CRYO

40% 37% 29%

87% 81% 63%

Statua romana di Atlante (sec II

d.) Museo Archeologico

Nazionale di Napoli

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.

Sept. 2 1919

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