Management of Atrial Fibrillation

Dr.Ajmal Khan TMO Cardiology HMC

The Consequences of AFThromboembolism· Stroke: 4.5 increased risk· Microemboli: reduced cognitive

function· Prothrombotic state

Mortality· 2 increased risk independent

of comorbid CV disease· Sudden death in HF and HCM

Hospitalizations· Most common arrhythmia

requiring hospitalization· 2-3 increased risk for

hospitalization

Impaired Hemodynamics· Loss of atrial kick· Irregular ventricular contractions· HF· Tachycardia-induced

cardiomyopathy

Reduced QoL· Palpitations, dyspnea, fatigue,

reduced exercise tolerance• AF is an enormous contributor to the growing cost of medical care

Definition AF is a supraventricular tachyarrhythmia

characterized by uncoordinated atrial activation with consequent deterioration of mechanical function.

ECG shows, rapid oscillations, or fibrillatory waves that vary in amplitude, shape, and timing, replace consistent P waves, and there is an irregular ventricular response.

Classification

• Recurrent AF :(1) paroxysmal AF (2) persistent AF (3) permanent AF

Paroxysmal(Self-terminating)

First Detected

Permanent

Classification of Atrial FibrillationACC/AHA/ESC Guidelines

Persistent(Not self-terminating)

Epidemiology of Atrial Fibrillation• Most common sustained cardiac arrhythmia.

• 0.4% to 1% in the general population.• 8% in those older than 80 y.• Currently affects > 2.3 million Americans, or 1% of

population.

• Preferentially affects men and the elderly .• Prevalence expected to increase by ≥ 2.5-fold

by 2050 .• Lifetime risk of developing AF: 1 in 4 for men and

women ≥ 40 years of age .

Prevalence of Diagnosed AF

Go AS, et al. JAMA. 2001;285:2370-2375.

Prev

alen

ce (%

)

0

2

4

6

8

10

12

< 55 55–59 60–64 65–69 70–74 75–79 80–84 ≥ 85

Women

Age (years)

11.1

9.110.3

7.27.3

5.05.0

3.43.0

1.71.71.00.9

0.40.20.1

1.89 million adults in study population; N = 17,974 with AF

Men

Projected Number of Patients with AF by 2050

ATRIA = Anticoagulation and Risk Factors in Atrial Fibrillation.Naccarelli GV, et al. Am J Cardiol. 2009;104(11):1534-1539.

Year

2.08 2.44

5.1

5.1

0

2

4

6

8

12

14

16

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

Patie

nts

with

AF

(mill

ions

)

3.03

7.56

5.42

11.7

15.2

4.34

9.4

11.7

3.33

7.5

8.9

2.94

6.8

7.78.4

10.2

3.804.78

10.3

13.1

5.16

11.1

14.3

5.61

12.1

15.9

5.6

5.9

2.66

6.1

6.7

MarketScan and Thomson Reuters Medicare Databases, 2009Olmsted County Data, 2006(assuming a continued increase in AF incidence)

ATRIA Study Data, 2000

Olmsted County Data, 2006(assuming no further increase in AF incidence)

Etiologies and factors predisposing patients to AF

Electrophysiological abnormalities

Enhanced automaticity (focal AF) Conduction abnormality (reentry) Atrial pressure elevation

Mitral or tricuspid valve disease Myocardial disease (primary or secondary, leading to systolic or diastolic dysfunction) Semilunar valvular abnormalities (causing ventricular hypertrophy) Systemic or pulmonary hypertension (pulmonary embolism) Intracardiac tumors or thrombi Atrial ischemia

Coronary artery disease 

Etiologies and factors predisposing patients to AF

Inflammatory or infiltrative atrial disease

Pericarditis Amyloidosis Myocarditis Age-induced atrial fibrotic changes Drugs

Alcohol Caffeine Endocrine disorders

Hyperthyroidism Pheochromocytoma 

Etiologies and factors predisposing patients to AF

Changes in autonomic tone

Increased parasympathetic activity Increased sympathetic activity Primary or metastatic disease in or adjacent to the atrial wall

Postoperative

Cardiac, pulmonary, or esophageal Congenital heart disease

Neurogenic

Subarachnoid hemorrhage Nonhemorrhagic, major stroke Idiopathic (lone AF)

Familial AF

Diagnosis

CLINICAL FINDINGS

History • Mild symptoms : palpitations ,sweating ,fatigue.• Severe symptoms :hypotension ,myocardial

ischemia ,myocardial dysfunctions ,stroke ,mesenteric ischemia ,lower limb ischemia

• Presentations of precipitating factors • Asymptomatic

Examination

• Irregularly irregular pulse • Pulse deficit• Also look for

Hypertension ,Thyrotoxicosis ,CCF ,MS, Pulmonary diseases ,Other causative factors.

Clinical evaluation in patients with AF

Electrocardiogram, to identify• Rhythm (verify AF) • LV hypertrophy • P-wave duration and morphology or fibrillatory waves • Preexcitation • Bundle-branch block • Prior MI • Other atrial arrhythmias • To measure and follow the R-R, QRS, and QT intervals in

conjunction with antiarrhythmic drug therapy 

Clinical evaluation in patients with AF

Transthoracic echocardiogram, to identify• Valvular heart disease • LA and RA size • LV size and function • Peak RV pressure (pulmonary hypertension) • LV hypertrophy • LA thrombus (low sensitivity) • Pericardial disease  Blood tests of thyroid, renal, and hepatic function• For a first episode of AF, when the ventricular rate is difficult to

control 

Clinical evaluation in patients with AF• Additional testing• One or several tests may be necessary.  Exercise testing• If the adequacy of rate control is in question (permanent

AF) • To reproduce exercise-induced AF • To exclude ischemia before treatment of selected patients

with a type IC antiarrhythmic drug Holter monitoring or event recording• If diagnosis of the type of arrhythmia is in question • As a means of evaluating rate control  Transesophageal echocardiography• To identify LA thrombus (in the LA appendage) 

Management

Preventionofthrombo-embolism

ReductionofAF burden* QoL Symptoms

Reduction inthe risk ofCV eventsandhospitalizationsandcosts

Reductioninmortality

Goals of AF Management

AFib Management Treatment Options

VENTRICULARRATE CONTROL

PharmacologicNonpharmacologic

ACHIEVEMENT AND MAINTENANCE OF SINUS

RHYTHM

PharmacologicNonpharmacologic

ANTITHROMBOTIC THERAPY

Guideline-BasedAF Treatment Options

Maintenance of SR

Pharmacologic

Class IA Class ICClass III-blockers

Nonpharmacologic

Catheter ablationPacingSurgery Implantable

devices

Stroke prevention

Pharmacologic• Warfarin• Aspirin +/- clopidogrel• Dabigatran• Factor Xa inhibitorsNonpharmacologic• Removal/isolation

LA appendage

Rate control

Preventremodeling

CCBsACE-Is, ARBsStatinsFish oil

Pharmacologic• CCBs• -blockers• Digitalis• Amiodarone• DronedaroneNonpharmacologic• Ablate and pace

Rate and Rhythm ControlDefinitions

• Rate control– Rest and exertion control of ventricular response– No commitment to maintaining SR

• Rhythm control– Attempts restoration and maintenance of SR– Rate control required as needed

• Can switch from rhythm control to rate control• Difficult to switch from rate to rhythm control as

duration of AF becomes longer• ANTICOAGULATION NEEDED for either strategy

Fuster V, et al. J Am Coll Cardiol. 2006;48:854-906.

Major Trials Comparing Rhythm Strategy and Rate Strategy

• Major trials include–AFFIRM–RACE–PIAF, STAF, HOT CAFE–AF-CHF

Trial Reference Patients (n)

AF duration

Follow-up (y)

Age (mean y ±SD)

Clinical events (n)

Stroke/embolism Death

Rate Rhythm Rate Rhythm

AFFIRM (2002) 128 4060 b/NR 3.5 70±9 88/2027 93/2033 310/2027 356/2033

RACE (2002) 124 522 1 to 399 d 2.3 68±9 7/256 16/266 18/256 18/266

PIAF (2000) 130 252 7 to 360 d 1 61±10 0/125 2/127 2/125 2/127

Trials comparing rate control and rhythm control strategies in patients with AF

AFFIRM: All-Cause Mortality

Rate N:

Rhythm N:

2027

2033

1925

1932

1825

1807

1328

1316

774

780

236

255

0

5

10

15

20

25

30

0 1 2 3 4 5

Mor

talit

y, %

RateRhythm

p=0.078 unadjusted

Time (years)

p=0.068 adjusted

The AFFIRM Investigators. N Engl J Med. 2002;347:1825-1833.

Favors Rate Control Favors Rhythm Control

Persistent AF Paroxysmal AF

Newly Detected AF

Less Symptomatic More Symptomatic

>65 years of age < 65 years of age

Hypertension No Hypertension

No History of Congestive Heart Failure Congestive Heart Failure clearly

exacerbated by AF

Previous Antiarrhythmic Drug Failure No Previous Antiarrhythmic Drug Failure

Canadian Cardiovascular Society Recommendations 2011

Cardioversion of AFib

• Pharmacological– Early onset AFib– Long-standing AFib

• Electrical

Pharmacological Cardioversion

Our Goal

Pharmacological Cardioversion• More effective in recent-onset AFib

– Class IA-IC-III drugs administered IV– Class IC favoured in non-cardiopathic patients – Class III favoured in cardiopathic patients or those

with delays in conduction• Oral loading can be performed with class IC drugs

– Flecainide (200-300 mg) – Propafenone (450-600 mg)

Treatment Out-of-Hospital with Class IC Drugs

• Symptomatic, rare episodes of AFib• Recent onset AFib• No structural heart disease• Prior hospital experience• Good physician-patient relationship• Resting conditions for at least 4 hours

Pill-in-the-Pocket

• In a selected (no or mild HD), risk-stratified patient population with recurrent AFib not currently taking AADs

– 79% developed ≥ 1 episodes of recurrent AFib during 15 ± 5m follow-up

– Acute oral flecainide or propafenone successfully terminated 94% of episodes within 113 ± 84 min, with side effects in 7% of patients

Alboni P, et al. N Engl J Med (2004) 351: 2384

Amiodarone for Cardioversion of Recent-Onset AFib: Meta-analysis

• Amiodarone IV (3-7 mg/kg ± infusion 0.9-3.0 g/day)

• Amiodarone oral (25-30 mg/kg)

• Time to conversion > 6-8 h

• Amiodarone > 1.5 g/day IV > placebo

• Amiodarone 25-30 mg/kg oral > placebo

• Amiodarone not > other AADs

• Safe in patients with structural cardiopathies and low LVEF

100

80

60

40

20

Con

vers

ion

(%

)

Bolus onlyBolus+infusion

2-4 h 8 h0

34

55

69

95

Electrical Cardioversion

Indications

• Failure of pharmacological measures for patients with AF with ongoing myocardial ischemia, symptomatic hypotension, angina, or HF.

• Immediate direct-current cardioversion is recommended for patients with AF involving preexcitation when very rapid tachycardia or hemodynamic instability occurs.

• AF of <48hr ---cardioversion without prior anticoagulation.• For high risk patients---IV UFH or LMWH before

cardioversion.• AF of > 48 hr or uncertain duration follow the protocol of

anticoagulation.

A Safety-Driven Approach

2011 ACC/AHA/HRS Guidelines:Antiarrhythmic Approaches to Maintain SR in Patients with Recurrent PAF

or Persistent AF*

HF

AmiodaroneDofetilide

Maintenance of SR

AmiodaroneDofetilide

Catheterablation

DronedaroneFlecainidePropafenoneSotalol

No (or minimal)heart disease

DronedaroneFlecainidePropafenoneSotalol

Amiodarone

No Yes

AmiodaroneDofetilide

Catheterablation

Catheterablation

HTN

Substantial LVH

CAD

Catheterablation

Amiodarone Catheterablation

DofetilideDronedroneSotalol

Efficacy of AADs in AF Trials

DronedaroneSotalol

Amiodarone

Class ICPlacebo

100

80

60

40

20

0

Patie

nts

in S

R at

1 Y

ear (

%)

CTAF SAFE-T AFFIRM DAFNE* EURIDIS* ADONISEURIDIS/ADONIS Pooled

DIONYSOS†

Treatment Options for AFib

Drugs to Control Ventricular Rate

Permanent AFib and Ventricular Rate Control

Indications for control of ventricular rate:

• Failure of antiarrhythmic therapy for preventing recurrence

• Alternative treatment to maintain sinus rhythm

Favors Rate Control Favors Rhythm Control

Persistent AF Paroxysmal AF

Newly Detected AF

Less Symptomatic More Symptomatic

>65 years of age < 65 years of age

Hypertension No Hypertension

No History of Congestive Heart Failure Congestive Heart Failure clearly

exacerbated by AF

Previous Antiarrhythmic Drug Failure No Previous Antiarrhythmic Drug Failure

Canadian Cardiovascular Society Recommendations 2011

Anticoagulation and Antiplatelet Therapy

Intermittent AFPermanent AF

Annual Stroke Rate (%)

AF and Stroke• AF increases stroke risk 4- to 5-fold

• Stroke is the most common and devastating complication of AF

– Incidence of all-cause stroke in patients with AF is 5%

• AF is an independent risk factor for stroke.

– Risk for stroke increases with age

• Stroke risk persists even in asymptomatic AF

• Stroke risk persists in patients with a “high-risk” profile despite a strategy of rhythm control (AFFIRM study, RACE study)

Low

RiskModerateRisk

HighRisk

10

8

6

4

2

0

Approach to thromboprophylaxis in patients with AF

Stroke Risk Stratification in AFCHADS2 Risk criteria score

Risk Factor Score

Cardiac failure 1

HTN 1

Age ≥75 y 1

Diabetes 1

Stroke 2

Lip GY, Halperin JL. Am J Med. 2010;123(6):484-488.

CHAD2 score and stroke rate

Less validated or weaker risk factors Moderate-risk factors High-risk factors

Female gender Age greater than or equal to 75 y

Previous stroke, TIA or embolism

Age 65 to 74 y Hypertension Mitral stenosis

Coronary artery disease Heart failure Prosthetic heart valvea

Thyrotoxicosis LV ejection fraction 35% or less

Diabetes mellitus

Risk category Recommended therapy

No risk factors Aspirin, 81 to 325 mg daily

One moderate-risk factorAspirin, 81 to 325 mg daily, or warfarin (INR 2.0 to 3.0, target 2.5)

Any high-risk factor or more than 1 moderate-risk factor

Warfarin (INR 2.0 to 3.0, target 2.5)

Antithrombotic therapy for patients with atrial fibrillation

Warfarin vs Placebo inStroke Prevention in AF

100% 50% 0% -50% -100%

AFASAK-1

SPAFBAATAF

CAFA

SPINAF

EAFT

ALL Trials

Favors Warfarin Favors Placebo/Control

Hart R, et al. Ann Intern Med. 2007;146:857-867.

Warfarin reduces incidence of stroke by about 64%

ACTIVE = AF Clopidogrel Trial with Irbesartan for Prevention of Vascular Events.

Antiplatelet Therapy in AFACTIVE-W:6706 randomized patients;trial stopped

6

4

0

2

Out

com

e/Ye

ar (%

)

StrokeVascularEvent

MajorBleeding

5

3

1

P = .0003

P = .001 P = .53

WarfarinClopidogrel +ASA

Active = AF Clopidogrel Trial with Irbesartan for Prevention of Vascular Events. ACTIVE Investigators. N Engl J Med. 2009;360(20):2066-2078.

Antiplatelet Therapy in AFACTIVE-A:7554 randomized patients;median follow-up of 3.6 years8

6

4

0

2

Out

com

e/Ye

ar (%

)

StrokeVascularEvent

MajorBleeding

7

5

3

1

P = .01

P<.001

P<.001

ASAClopidogrel +ASA

NEW ANTICOAGULANTS

Characteristics of new oral anticoagulants

Sobieraj-Teague M, et al. Semin Thromb Hemost. 2009;35:515-524.

AgentMechanism of

ActionDosing Onset Half Life Reversibility

Clinical Development

Apixaban Direct factor Xa inhibitor

Oral2x daily

3 hr 12 hr NoPhase 3;

ARISTOTLE, AVERROES

RivaroxabanDirect factor Xa inhibitor

Oral1–2x daily

3 hr 9 hr NoPhase 3;

ROCKET AF

DU 176bDirect factor Xa inhibitor

Oral1–2x daily

1–2 hr 9–11 hr NoPhase 3;

ENGAGE-AF

BetrixabanDirect factor Xa inhibitor

Oral2x daily

Not reported

19 hr NoPhase 2;

EXPLORE Xa

YM 150Direct factor Xa inhibitor

Not reportedNot

reportedNot

reportedNo Phase 2

IdrabiotaparinuxIndirect factor Xa inhibitor

WeeklySC Injection

1–2 hr 80–130 hr Yes, IV avidinPhase 3;

BOREALIS–AF

Dabigatran etexilate

Direct thrombin inhibitor

Oral1–2x daily

1–2 hr 12–17 hr No Phase 3; RE–LY

AZD 0837Direct thrombin inhibitor

Oral1–2x daily

1 hr 9 hr No Phase 2

ATI-5923Tecarfarin

Vitamin K antagonistVariable

Oral 1x dailyNot

reported136 hr Yes, vitamin K

Phase 2/3; EMBRACE AC

Connolly S, et al. N Engl J Med. 2009;361:1139-1151.

Stroke Prevention in Atrial FibrillationDabigatran etexilate vs warfarin (RE-LY)

0.00

0.50

1.00

1.50

2.00

2.50

3.00

3.50

4.00

Stroke/SystemicEmbolism

Major Bleed IntracranialHemorrhage

Perc

ent/

Year

Dabigatran 110 mgDabigatran 150 mgWarfarin INR 2.0–3.0

***

†

†† §

Dabigatran vs warfarin* P < 0.001 Non-inferiority**P < 0.001 Non-inferiority, superiority†P = 0.003††P < 0.001§ P < 0.001

AVERROES TrialASA(81-324 mg daily; up to 36 mo/end of study)

Apixaban(5 mg twice daily; 2.5 mg in selected patients up to 36 mo/end of study)

E

Unsuitable for warfarin therapyN= 5600

Double-blind

AVERROES, Apixaban Versus ASA to Reduce the Risk Of Stroke.

R

Cum

ulati

ve R

isk

0.0

0.01

0.03

0.05

0 3 6 9 12 18 21

ASA

Apixaban*

No. at RiskASAApix

2791 2720 2541 2124 1541 626 3292809 2761 2567 2127 1523 617 353

Months

RR=0.4595% CI, 0.32-0.62P<.001

AVERROES: Stroke or Systemic Embolic Event

Clinical Challenges With New Anticoagulants

• No validated tests to measure anticoagulation effect• No established therapeutic range• No antidote for most agents• Assessment of compliance more difficult than with

vitamin K antagonists• Potential for unknown long-term adverse events• Balancing cost against efficacy• Lack of head-to-head studies comparing new agents

Catheter AF Ablation

Indications:• Symptomatic AF refractory or intolerant to at

least 1 class I or III AAD.• Selected symptomatic patients with HF and/or

reduced ejection fraction• Presence of an LA thrombus is contraindication

to catheter ablation of AF• Discontinuation of anticoagulation is not an

indication for ablation

A. Circumferential ablation around left and right PV antra

B. and C. Additional linear lesion sets for the roof, mitral isthmus, carinae, SVC, and cavotricuspid isthmus

D. Targeting fractionated electrograms and/or ganglionic plexi

Common Lesions Performed in AF Ablation

A. B.

LSPV

LIPV

RSPV

IVC

RIPV

LSPV

LIPV

RSPV

IVC

RIPV

LSPV

LIPV

RSPV

IVC

RIPV

SVC

C. D.

LSPV

LIPV

RSPV

IVC

RIPV

SVC

SVCSVC

Treatment of atrial fibrillation in special population

Management of atrial fibrillation associated with the Wolff-Parkinson-White (WPW) preexcitation

syndrome

Immediate direct-current cardioversion is recommended in hemodynamically unstable patients.

Intravenous procainamide , ibutilide ,flecainide or amiodarone is recommended to restore sinus rhythm in hemodynamically stable patients.

Intravenous administration of AV nodal blocking drugs i.e. digitalis glycosides or nondihydropyridine calcium channel antagonists is not recommended.

Catheter ablation of the accessory pathway is recommended in symptomatic patients.

Hyperthyroidism

Administration of a beta blocker to control the rate of ventricular response .

Alternative is nondihydropyridine calcium channel antagonist (diltiazem or verapamil).

Oral anticoagulation (INR 2.0 to 3.0) is recommended in the presence of risk factors for stroke.

Management of atrial fibrillation during pregnancy

Digoxin, a beta blocker, or nondihydropyridine calcium channel to control the rate .

Flecainide , ibutilide , quinidine or procainamide to restore sinus rhythm in hemodynamically stable patient.

Direct-current cardioversion in hemodynamically unstable patient.

Anticoagulation in the presence of risk factor for stroke.

Management of atrial fibrillation in patients with pulmonary disease

Correction of hypoxemia and acidosis . A nondihydropyridine calcium channel antagonist

(diltiazem or verapamil) to control the ventricular rate.

Direct-current cardioversion in hemodynamically unstable patient.

IV flecainide may be used to restore sinus rhythm in hemodynenicall y stable patient.

Interruption of anticoagulation for diagnostic or therapeutic procedures

Anticoagulation may be interrupted for a period of up to 1 wk for surgical or diagnostic procedures.

In high-risk patients (particularly those with prior stroke, TIA, or systemic embolism), or when a series of procedures requires interruption of oral anticoagulant therapy for longer periods, unfractionated or low-molecular-weight heparin may be administered.

Summary AF is a common disease that is increasing in prevalence For any patient with AF, decisions need to be made

regarding antithrombotic therapy, rate control, and/or rhythm control

Guidelines provide recommendations for the management of patients with AF

Anticoagulation is essential in AF patients with risk markers, regardless of any restoration of SR

New agents and procedures may provide antiarrhythmic and antithrombotic options with improved outcomes for managing AF

Thank you for your attention!