Dipartimento di Cardiologia Arcispedale S. Anna Azienda ... · Dipartimento di Cardiologia Arcispedale S. Anna ... Sincope Fatigue Others No symptoms ... Late Breaking Trial, ESC

Fibrillazione atriale persistente e Fibrillazione atriale asintomatica

Rischio di strokeClaudio Pratola Matteo BertiniU.O. Cardiologia

Dipartimento di CardiologiaArcispedale S. Anna

Azienda Ospedaliero-UniversitariaCona-Ferrara

AF

ELECTRICAL

MECHANICAL STRUCTURAL

Ca Channels

Intra-atrial circuits

Stretching

AP duration

Refractory period

Conduction velocity

Contractility

Compliance

Dilatation Connessin

Fybrosis

Anisotropy

AF physiopathology

remodeling

- Atrial refractory period shortening

- Contractility reduction

- Conduction velocity reduction

- Atrial chamber dilatation

- Fibrosis (point of no return.?.)

Paroxysmal atrial fibrillation..is it always the same?

Atrial fibrillation

• Similar patients with different presentations (3P)

• Different patients with the same presentation

• Variable symptoms

Types of Atrial Fibrillation

(19(19thth Ann Scientific Sessions NASPE, 1998)Ann Scientific Sessions NASPE, 1998)

100100

8080

6060

4040

2020

00SincopeSincope Effort Effort

intoleranceintolerance

Paz

ient

s (%

)P

azie

nts

(%)

AnginaAngina DizzinessDizziness Dyspnoea Dyspnoea

1414

29293333

4949

6868 6969

7878

FatigueFatigue PalpitationsPalpitations

Symptoms

(Levy S et al. Circulation 1999; 99. 3028(Levy S et al. Circulation 1999; 99. 3028 --35) 35)

SymptomsSymptoms in AF in AF patientspatients

PalpitationPalpitation

Thoracic painThoracic pain

DyspnoeaDyspnoea

SincopeSincope

FatigueFatigue

OthersOthers

No symptomsNo symptoms

ALFA ALFA studystudy

Total Total

populationpopulation

% (n=756)% (n=756)

54,154,1

10,110,1

44,444,4

10,410,4

14,314,3

0,90,9

11,411,4

Paroxysmal Paroxysmal

AFAF% (n=167)% (n=167)

79,079,0

13,213,2

22,822,8

17,417,4

12,612,6

00

5,45,4

ChronicChronic

AFAF% (n=389)% (n=389)

44,744,7

8,2 8,2

46,846,8

8,08,0

13,113,1

1,81,8

16,216,2

Recent onset Recent onset

AFAF

% (n=200)% (n=200)

51,5 51,5

11,011,0

58,058,0

9,59,5

18,018,0

00

7,07,0

SintomiSintomi

30% 30% -- 45%45%

12:112:1

AF as an occasional findingAF as an occasional finding

AF: asymptomatic/symptomatic episodesAF: asymptomatic/symptomatic episodes

(Page RL et al. Circulation 1994)(Page RL et al. Circulation 1994)

(Furberg CD et al. Am J Cardiol 1994; Blackshear JL et al. MPC 1(Furberg CD et al. Am J Cardiol 1994; Blackshear JL et al. MPC 1 996)996)

70% no sympotms70% no sympotms

AF: asymptomatic vs symptomatic relapsesAF: asymptomatic vs symptomatic relapses

(PAFAC TRIAL, Late Breaking Trial, ESC 2002)(PAFAC TRIAL, Late Breaking Trial, ESC 2002)

AFFIRM STUDY

0

10

20

30

40

50

60

70

80

1 2

rate control rhythm control

Pat

ient

s

34%

62%

Sinus rhythm after five years

Non-Valvular Atrial Fibrillation

• Affects 1-1.5% of population in developed world

• Lifetime risk in men & women >40 is 1 in 4

• Prevalence• 0.5% age 0-59

• 9.0% age >80

• Currently 2.5 million adults in U.S.

Savelieva: J Intern Med 250, 2001Savelieva: J Intern Med 250, 2001Go: JAMA 285, 2001Go: JAMA 285, 2001Miyasaka: Circ 114, 2006Miyasaka: Circ 114, 2006

Non-Valvular Atrial Fibrillation

An EPIDEMIC

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0

2

4

6

8

10

12

14

16

1990 1995 2000 2005 2010 2015 2020 2025 2030 2035 2040 2045 2050

Mayo Clinic data (assuming a Mayo Clinic data (assuming a continued increase in AF continued increase in AF incidence)incidence)Mayo Clinic data (assuming further Mayo Clinic data (assuming further increase in AF incidence)increase in AF incidence)ATRIA study data (50% >80 yo)ATRIA study data (50% >80 yo)

Patients Patients with atrial with atrial fibrillation fibrillation (millions)(millions)

YearYear

2.08 2.26 2.44 2.66 2.943.33

3.8 4.344.78 5.16 5.42 5.61

5.1 5.66.1

6.87.5

8.4

9.410.3

11.111.7 12.1

5.15.9

6.7

7.78.9

10.2

11.7

13.1

14.315.2

15.9

0

5

10

15

20

25

30

35

50-59 60-69 70-79 80-89

Non-Valvular Atrial Fibrillation

%%

Percent of Total StrokesPercent of Total StrokesAttributable to Atrial FibrillationAttributable to Atrial Fibrillation

Stroke 22(18), 1991Stroke 22(18), 1991

• 500,000 strokes/year in U.S.

• Up to 20% of ischemic strokes occur in patients with atrial fibrillation

Conditions predisposing to, or encouraging progression of AF

Risk factors for stroke andthrombo -embolism in non -valvular AF

AF= atrial fibrillation; EF = ejection fraction (as documented by echocardiography, radionuclide ventriculography, cardiaccatheterization, cardiac magnetic resonance imaging, etc.); LV = left ventricular; TIA = transient ischaemic attack.

Risk factor-based point-based scoring system - CHA 2DS2-VASc

*Prior myocardial infarction, peripheral artery disease, aortic plaque. Actual rates of stroke in contemporary cohorts may vary from these estimates.

Adjusted stroke rate according to CHA 2DS2-VASc score

The management cascade for patients with AF

ACEI = angiotensin-converting enzyme inhibitor; AF = atrial fibrillation; ARB = angiotensin receptor blocker;PUFA = polyunsaturated fatty acid; TE = thrombo-embolism.

Approach to thromboprophylaxis in AF

AF = atrial fibrillation; CHA2DS2-VASc = cardiac failure, hypertension, age ≥ 75 (doubled), diabetes, stroke (doubled)-vascular disease, age 65–74 and sex category (female); INR = international normalized ratio; OAC = oral anticoagulation, such as a vitamin K antagonist (VKA) adjusted to an intensity range of INR 2.0–3.0 (target 2.5).

The HAS-BLED bleeding risk score

*Hypertension is defined as systolic blood pressure > 160 mmHg.

INR = international normalized ratio.

Use of oral anticoagulation forstroke prevention in AF

AF = atrial fibrillation; OAC = oral anticoagulant; TIA = transient ischaemic attack.

Prevention of thromboembolism in AF

Prevention of thromboembolism in AF

Cardioversion, TOE and anticoagulation

AF = atrial fibrillation; DCC = direct current cardioversion; LA = left atrium; LAA = left atrial appendage; OAC = oral anticoagulant;SR= sinus rhythm; TOE= transoesophageal echocardiography.AF = atrial fibrillation; DCC = direct current cardioversion; LA = left atrium; LAA = left atrial appendage; OAC = oral anticoagulant;SR= sinus rhythm; TOE= transoesophageal echocardiography.

Monitoring

CONFIRM™ REVEAL®

Volume 7cc 9cc

Mass 15g 15g

Length 56.3mm 62mm

Width 18.4mm 19mm

Thickness 7.5mm 8mm

Non-Valvular Atrial Fibrillation Stroke Prevention

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Cooper: Arch Int Med 166, 2006Cooper: Arch Int Med 166, 2006Lip: Thromb Res 118, 2006Lip: Thromb Res 118, 2006

• Warfarin cornerstone of therapy• Assuming 51 ischemic strokes/1000 pt-yr

– Adjusted standard dose warfarin prevents 28 strokes at expense of 11 fatal bleeds

– Aspirin prevents 16 strokes at expense of 6 fatal bleeds

• Warfarin– 60-70% risk reduction vs no treatment– 30-40% risk reduction vs aspirin

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Non-Valvular Atrial Fibrillation Stroke Prevention

Warfarin Problematic

• Narrow therapeutic window– Multiple drug-drug/drug-food interactions– Genetic variability

• Long half-life

• PCI issues – triple therapy

• Compliance

• Contraindications

• Bleeding risks

010203040506070

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

Non-Valvular Atrial Fibrillation Warfarin Use in AF Patients by Age

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%%

Ann Int Med 131(12), 1999Ann Int Med 131(12), 1999

≥≥≥≥• Only 55% of AF patients with no contraindications have

evidence of warfarin use in previous 3 months

• Other studies cite warfarin use in AF patients from 17-50%

• Elderly patients with increased absolute risk least likely to betaking warfarin

• Contraindications 30-40%

0 20 40 60 80 100

Non-Valvular Atrial Fibrillation Adequacy of Anticoagulation in Clinic

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%%

Bungard: Pharmacotherapy 20:1060, 2001Bungard: Pharmacotherapy 20:1060, 2001

Low INR <1.6Low INR <1.6

TherapeuticTherapeuticINR 2INR 2--33

High INR >3.2High INR >3.2

Efficacy Efficacy ↓↓↓↓↓↓↓↓ 44--foldfold

Non-Valvular Atrial FibrillationStroke Pathology

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Brass. Stroke 28(12), 1997Brass. Stroke 28(12), 1997VanWalraven: JAMA 288, 2002VanWalraven: JAMA 288, 2002

• Major fatal bleed with age >75 = 3%/year (30% over 10 years)

• Intracranial hemorrhage– 0.3-0.5%/100 patient-years

– 3% in INR >4.0– 10% if INR >4.5

Costo efficacia dei nuovi anticoagulanti

• Giornate lavorative• Spesa del Sistema Sanitario in termini

di controlli • Cardioversione• Preparazione a procedura ablativa• Ripresa della terapia anticoagulante e

dimissione