How to detect andtreatATRIALFIBRILLATION

Dr Dadang Hendrawan SpJP(K)

Bagian Kardiologi & Kedokteran VaskulerFK. Unibraw RSU Dr. Saiful Anwar

M A L A N G

Atrial Fibrillation

AF is a supraventricular tachyarrhythmiacharacterized by uncoordinated atrial activationwith consequent deterioration of atrialmechanical function ( ACC / AHA / ESC Guideline 2006 )

Characteristics of an ECG recordingfor a patient with AF

2

Normal sinus rhythm

Atrial fibrillationTP

R

An ECG of a patient with AF is characterized by disorganized electricalactivity:

1. Consistent P waves are replaced by rapid irregular waves2. Irregular RR intervals

12

Fuster et al, Circulation 2011; Camm et al, Eur Heart J 2010

SQ

P

Background

Atrial fibrillation is the most commonsustained arrhythmia

Affects 2 million Americans 6% over the age of 65 experience it Responsible for 15% strokes

Benjamin E: Epidemiology of Atrial Fibrillation. In Falk RH, Podrida PJ, eds:Atrial Fibrillation: Mechanisms and Management.2nd Ed, Lippincott-Raven Press, New York 1997, pp.1-22.

Atrial fibrillation is the most commonsustained arrhythmia

Affects 2 million Americans 6% over the age of 65 experience it Responsible for 15% strokes

Benjamin E: Epidemiology of Atrial Fibrillation. In Falk RH, Podrida PJ, eds:Atrial Fibrillation: Mechanisms and Management.2nd Ed, Lippincott-Raven Press, New York 1997, pp.1-22.

Atrial Fibrillation Demographics by Age

U.S. population

Population withatrial fibrillation

U.S. populationx 1000

Population with AFx 1000

30,000

20,000

10,000

0

500

400

300

200

100

0

Adapted from Feinberg WM. Arch Intern Med. 1995;155:469-473.Age, yr

95

30,000

20,000

10,000

0

500

400

300

200

100

0

Atrial fibrillation accountsfor 1/3 of all patient

dischargeswith arrhythmia as

principal diagnosis.

18%Unspecified

6%PSVT

6%PVCs4%

AtrialFlutter

Atrial fibrillation accountsfor 1/3 of all patient

dischargeswith arrhythmia as

principal diagnosis.

2%VF

Data source: Baily D. J Am Coll Cardiol. 1992;19(3):41A.

34%Atrial

Fibrillation

9%SSS

8%Conduction

Disease

3% SCD

10% VT

Classification After 2 or more episodes, AF is considered recurrent AF. If the arrhythmia terminates spontaneously, recurrent AF is

designated paroxysmal AF When sustained beyond 7 d, it is termed persistent AF. The category of persistent AF also includes cases of long-

standing AF (e.g., longer than 1 y), usually leading topermanent AF

Lone AF applies to individuals younger than 60 y withoutclinical or echocardiographic evidence of cardiopulmonarydisease, including hypertension.

After 2 or more episodes, AF is considered recurrent AF. If the arrhythmia terminates spontaneously, recurrent AF is

designated paroxysmal AF When sustained beyond 7 d, it is termed persistent AF. The category of persistent AF also includes cases of long-

standing AF (e.g., longer than 1 y), usually leading topermanent AF

Lone AF applies to individuals younger than 60 y withoutclinical or echocardiographic evidence of cardiopulmonarydisease, including hypertension.

AF can be symptomaticand asymptomatic

Typical symptoms of AF include palpitations, fatigue, chest pain, lightheadedness, dyspnoea, syncope1

However, AF may be asymptomatic2 Patients (n=110) with history of AF underwent ECG monitoring with implantable

pacemakerfor 1911 months2

50 patients had AF episodes lasting >48 hours 19 (38%) of these were asymptomatic, with no AF detected by serial ECG

recordingsCumulative incidence of asymptomatic AF recurrence >48 hours not detected by serialECG recordings during follow-up (FU)

Typical symptoms of AF include palpitations, fatigue, chest pain, lightheadedness, dyspnoea, syncope1

However, AF may be asymptomatic2 Patients (n=110) with history of AF underwent ECG monitoring with implantable

pacemakerfor 1911 months2

50 patients had AF episodes lasting >48 hours 19 (38%) of these were asymptomatic, with no AF detected by serial ECG

recordings

1. Fuster et al, Circulation 2011; 2. Israel et al, J Am Coll Cardiol 2004

Baseline FU1 FU2 FU3 FU4 FU5 FU6 FU7 FU8 FU9 FU10 FU11 FU12 FU13

No

of p

atie

nts

110

20

15

10

5

Cumulative incidence of asymptomatic AF recurrence >48 hours not detected by serialECG recordings during follow-up (FU)

Prognosis

AF is associated with an increased long-term riskof stroke and HF

The mortality rate of patients with AF is aboutdouble that of patients in normal sinus rhythm andis linked to the severity of underlying heartdisease

One of every 6 strokes occurs in a patient withAF.

AF is associated with an increased long-term riskof stroke and HF

The mortality rate of patients with AF is aboutdouble that of patients in normal sinus rhythm andis linked to the severity of underlying heartdisease

One of every 6 strokes occurs in a patient withAF.

Pathophysiology Focal triggering mechanism involving automaticity Multiple reentrant wavelets These mechanisms are not mutually exclusive and may coexist

Presentation

History Physical Examination ECG

Etiologies and Factors PredisposingPatients to AF

Electrophysiological abnormalities Atrial pressure elevation Atrial ischemia Inflammatory or infiltrative atrial

disease Drugs

Electrophysiological abnormalities Atrial pressure elevation Atrial ischemia Inflammatory or infiltrative atrial

disease Drugs

Endocrine disordes Changes in autonomic tone Primary or metastatic disease in or adjacent to

the atrial wall Postoperative Congenital heart disease Neurogenic Idiopathic (lone AF) Familial AF

Etiologies and Factors PredisposingPatients to AF

Endocrine disordes Changes in autonomic tone Primary or metastatic disease in or adjacent to

the atrial wall Postoperative Congenital heart disease Neurogenic Idiopathic (lone AF) Familial AF

Minimun evaluation

1. History and physical examination. to define2. Electrocardiogram. to identify3. Transthoracic echocardiogram. to identify4. Blood test of thyroid, renal and hepatic

function

1. History and physical examination. to define2. Electrocardiogram. to identify3. Transthoracic echocardiogram. to identify4. Blood test of thyroid, renal and hepatic

function

Additional Testing

One or several tests may be necessary :1. Six-minute walk test2. Exercise testing3. Holter monitoring or event recording4. Transesophageal echocardiograpy5. Electrophysiological study6. Chest radiograph. to evaluate

One or several tests may be necessary :1. Six-minute walk test2. Exercise testing3. Holter monitoring or event recording4. Transesophageal echocardiograpy5. Electrophysiological study6. Chest radiograph. to evaluate

MANAGEMENTMANAGEMENT

Objectives

Rate Control Prevention of thromboembolism Restoration or maintenance sinus

rhythm

Rate Control Prevention of thromboembolism Restoration or maintenance sinus

rhythm

Rate control VS Rhythm control

Two landmark studies published (AFFIRM) and (RACE)trials, found that treating atrial fibrillation (AF) with a rhythmcontrol strategy offers no survival or clinical advantagesover simpler rate control therapy using medications

Two landmark studies published (AFFIRM) and (RACE)trials, found that treating atrial fibrillation (AF) with a rhythmcontrol strategy offers no survival or clinical advantagesover simpler rate control therapy using medications

Rate Control

Rate control may be reasonable initial therapy in olderpatients with persistent AF who have hypertension orheart disease

The definition of adequate rate control has beenbased primarily on short-term hemodynamic benefitsand not well studied with respect to regularity orirregularity of the ventricular response to AF, quality oflife, symptoms,or development of cardiomyopathy.

Rate control may be reasonable initial therapy in olderpatients with persistent AF who have hypertension orheart disease

The definition of adequate rate control has beenbased primarily on short-term hemodynamic benefitsand not well studied with respect to regularity orirregularity of the ventricular response to AF, quality oflife, symptoms,or development of cardiomyopathy.

Criteria for rate control vary with patient age butusually ventricular rates 60 - 80 beats/m at rest between 90 and 115 beats/m during moderate exercise

Criteria for rate control vary with patient age butusually ventricular rates 60 - 80 beats/m at rest between 90 and 115 beats/m during moderate exercise

Rate Control Prevention of thromboembolism Restoration or maintenance sinus

rhythm

Rate Control Prevention of thromboembolism Restoration or maintenance sinus

rhythm

20

15

10

5

0

RiskFactor Points

Congestive 1Heart failure

Hypertension 1

Age > 75 1

Diabetes 1

Prior stroke/TIA 2

Key Risk Factors: CHADS2 Score HelpsPredict Stroke Risk in Patients With AF

20

15

10

5

00 1 2 3 4 5

6CHADS2 score

RiskFactor Points

Congestive 1Heart failure

Hypertension 1

Age > 75 1

Diabetes 1

Prior stroke/TIA 2

ACC / AHA / ESC Guideline 2006

ACCF/AHA/HRS 2011 and ACCP2008 guidelines: based on CHADS2

CHADS2 scoring1

CHF +1 Hypertension +1 Age 75 years +1 Diabetes mellitus +1 Prior Stroke or TIA +2

CHADS2 scoring1

CHF +1 Hypertension +1 Age 75 years +1 Diabetes mellitus +1 Prior Stroke or TIA +2

1. Gage et al, JAMA 2001; 2. Singer et al, Chest 2008; 3. Fuster et al, Circulation 2011

Recommended therapyCHADS2

scoreACCP20082

ACCF/AHA/HRS20113

0 ASA75325 mg/day

ASA81325 mg/day

1 VKA (INR 23) orASA 75325 mg/day

VKA (INR 23) orASA 81325 mg/day

2 VKA (INR 23) VKA (INR 23)

ESC 2010 guidelines: based onCHADS2 and CHA2DS2-VASc

CHF/LV dysfunction +1 Hypertension +1 Age 75 years +2 Diabetes mellitus

+1 Prior Stroke/TIA/TE +2 Vascular disease +1 Age 6574 years

+1 Sex category (female) +1

Initial evaluation: CHADS2 If CHADS2 2 oral anticoagulation If CHADS2

VKA limitations

Significant inter- and intra-patient variability in doseresponse1 due to: Co-morbidities Genetic polymorphisms Interactions with food and concomitant drugs Unpredictable pharmacology

Narrow therapeutic window1 Regular coagulation monitoring and dose adjustments

required Increased risk of stroke or bleeding outside the INR range2

Significant inter- and intra-patient variability in doseresponse1 due to: Co-morbidities Genetic polymorphisms Interactions with food and concomitant drugs Unpredictable pharmacology

Narrow therapeutic window1 Regular coagulation monitoring and dose adjustments

required Increased risk of stroke or bleeding outside the INR range2

1. Ansell et al, Chest 2008; 2. Nieuwlaat et al, Am Heart J 2007

VKAs have a narrow therapeuticwindow

15

Ischaemicstroke Intracranialbleeding

20

Odd

s ra

tio fo

r eve

nt

Data on bleeding and stroke risk supportrecommendation for narrow INR targetrange

Adjusted odds ratios for ischaemic stroke andintracranial bleeding in relation to intensity of

anticoagulation

28Fuster et al, Circulation 2011

5.0 6.0 8.01.0 2.0 3.0 4.0 7.0

5

10Ischaemic

stroke Intracranialbleeding

1

Odd

s ra

tio fo

r eve

nt

International normalized ratio

Rationale for novel oralanticoagulants

Novel oral anticoagulants should fulfill the followingunmet needs: Predictable pharmacology

Target a single coagulation factor Fewer interactions with food or concomitant drugs Can be used at a fixed dose No requirement for routine coagulation monitoring

Improved benefitrisk profile compared with VKAs in patientswith suboptimal INR control

Novel oral anticoagulants should fulfill the followingunmet needs: Predictable pharmacology

Target a single coagulation factor Fewer interactions with food or concomitant drugs Can be used at a fixed dose No requirement for routine coagulation monitoring

Improved benefitrisk profile compared with VKAs in patientswith suboptimal INR control

Bauer, Rev Neurol Dis 2010; Turpie, Eur Heart J 2007; Weitz, Thromb Haemost 2010

Newer oral anticoagulants for strokeprevention in AF: clinical trialoverview

Oral anticoagulant Phase II studies Phase III studiesDirect thrombin inhibitorsDabigatran PETRO1 RE-LY2,3

RELY-ABLE4

Direct Factor Xa inhibitorsRivaroxaban ROCKET AF5

J-ROCKET AF6Rivaroxaban ROCKET AF5

J-ROCKET AF6

Apixaban Phase II safety (Japan)7 ARISTOTLE8

AVERROES9

AVERROES-LTOLE10

Edoxaban Phase II dose-finding11

Phase II safety (Asia)12ENGAGE AF-TIMI 4813

Studies in yellow are complete, the others are ongoing1. Ezekowitz et al, Am J Cardiol 2007; 2. Connolly et al, N Engl J Med 2009; 3. Connolly et al, N Engl J Med 2010;4. clinicaltrials.gov, NCT00808067; 5. Patel et al, N Engl J Med 2011; 6. Hori et al, J Thromb Haemost 2011;7. Ogawa et al, Circ J 2011; 8. Granger et al, N Engl J Med 2011; 9. Connolly et al, N Engl J Med 2011;10. clinicaltrials.gov, NCT00496769; 11. Weitz et al, Thromb Haemost 2010; 12. Chung et al, Thromb Haemost 2011;13. Ruff et al, Am Heart J 2010

Rivaroxaban20 mg once daily**

N=14,264

ROCKET AF: rivaroxaban vswarfarinRandomized, double-blind, double-dummy, non-inferiority,event-driven trial

Non-valvular AF

History of stroke,TIA or non-CNSSE

OR

2* of the following:

CHF or LVEF35%

Hypertension Age 75 years Diabetes

30-d

ay fo

llow

-up

End

of s

tudy

Warfarin target INR 2.5(23 inclusive)

*Enrolment of patients with

ROCKET AF: primary efficacyendpoint

Population/analysis*

No. ofpatients

Rivaroxaban(% per year)

Warfarin(% peryear)

Hazardratio

(95% CI)

p-valueNon-

inferiority SuperiorityPer-protocol,on-treatment

6958 1.7 2.2 0.79(0.660.96)

Summary

Control the rate Decide whether NOT to anticoagulate Consider referral for antiarrhythmic or non

pharmacological treatment