atrial fibrillation- management

Management of Atrial Fibrillation

03.01.2014

Presenter - Dr. Amish Bhutani Moderator - Dr. Barun Kumar

Atrial Fibrillation• Introduction• Causes, Consequences,

Classification & Epidemiology of AF• Presentation• AF: Acute Management• Rhythm Control• Rate Control• Rate Vs Rhythm• Prevention of Thromboembolism:

Anticoagulation• Newer OACs• Summary

Atrial Fibrillation

- Atrial fibrillation (AF) is a supraventricular arrhythmia characterized electrocardiographically by low-amplitude baseline oscillations (fibrillatory or f waves) and an irregularly irregular ventricular rhythm

- Uncoordinated atrial activation

- The f waves have a rate of 300 to 600 beats/min and are variable in amplitude, shape, and timing.

• Hypertension (usually with left ventricular hypertrophy)• Ischemic heart disease,• Dilated cardiomyopathy• Restrictive cardiomyopathies such as amyloidosis, constrictive

pericarditis • Cardiac tumors• Severe pulmonary hypertension • Obesity and obstructive sleep • Excessive alcohol intake (holiday heart),• Open heart or thoracic surgery,• Myocarditis • Pulmonary embolism.• Hyperthyroidism • Tachycardia induced. Patients with tachycardia-induced AF most

often have AV nodal reentrant tachycardia or a tachycardia related to the Wolff-Parkinson-White syndrome that degenerates into AF

Causes of AF

Reversible causes of AF• Alcohol intake (‘holiday heart syndrome’),• Surgery, • Electrocution,• MI, pericarditis, myocarditis, • Pulmonary embolism or other pulmonary

diseases, • Hyperthyroidism, Pheochromocytoma and other

metabolic disorders.• Drugs , Caffeine• Subarachnoid hemorrhage, Nonhemorrhagic,

major stroke

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

HCM=hypertrophic cardiomyopathy; QoL=quality-of-life.Van Gelder IC, et al. Europace. 2006;8:943-949; Narayan SM, et al. Lancet. 1997;350:943-950; Wattigney WA, et al. Circulation. 2003;108:711-716; Wyse DG, et al. Circulation. 2004;109:3089-3095; Favale S, et al. PACE. 2003;26:637-639.

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

Classification of AF Paroxysmal AF - that terminates spontaneously within 7

days

Persistent AF - present continuously for more than 7 days

Longstanding AF - persistent for more than 1 year

Permanent AF - longstanding AF refractory to cardioversion is termed permanent.

Lone AF - AF in patients younger than 60 years who do not have hypertension or any evidence of structural heart disease

• First episode - Symptomatic or asymptomatic Self limited or persistent

• Recurrent AF - 2 or more episodes lasting > 30 seconds

Guideline-BasedAF Treatment Options

CCB = calcium channel blocker; SR = sinus rhythm; ACE-I = angiotensin-converting enzyme inhibitor; ARB = angiotensin II receptor blocker; LA = left atrial.Fuster V, et al. J Am Coll Cardiol. 2006;48(4):854-906.

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

Atrial Fibrillation: Epidemiology• Prevalence - 3.8% ≥ 60 Yrs - 9% >80 Yrs ( JAMA 2001;285:2370)• Stroke Rate in AF- 5-9.6% (JACC 2004, 43: 929-35) (JAMA 2001,285, 2864-70)

(Stroke rate is similar in Paroxysmal and persistent AF)

• Relative risk of death 1.3- 2 times

1.Lloyd-Jones DM, et al. Circulation 2004;110:1042–10462. Go et al. JAMA 2001;285:2370-5

Prevalence of Atrial Fibrillation

Atrial Fibrillation: Presentation• Dyspnoea• Palpitation• Syncope• Dizziness• Myocardial Ischemia• Asymptomatic

AF: Acute Mx & Rhythm Control

Atrial Fibrillation: Ac Mx• Assess the hemodynamic Status • If unstable: DC Shock• If stable:

Assess risk factor Start Anticoagulation Rate controlling drugs Decide Rate vs Rhythm Control Pharmacological vs DC cardioversion

Anticoagulation and Cardioversion

• Afib < 48 hours: – Cardioversion (CV)– No anticoagulation

indicated

• Afib > 48 hours: – Anticoagulate for 3-4

weeks before CV– OR get TEE

– Anticoagulate for 1 month after CV

Atrial Fibrillation: DC Cardioversion

• Advantage- More effective• Disadvantage- Risk of Thrombo-embolism Requires conscious sedation Arrhythmia

Atrial Fibrillation: DC Cardioversion• Method –• Synchronized DC shock- External - Internal (COPD, obese)• Biphasic preferred ( high success- 79-84%)

[ Mittal et al, Circ 2000, 101:1282] [ Page et al , JACC 2002,39:1956]

• Monophasic- 100 J- 14% success 200 J- 39% success 360 J- 95% success• Initial 200 J is recommended with monophasic 100 J with biphasic

[ Jogler et al, AJC 2000, 86: 348]


• Complication• Thromboembolism- 1-7% ↓sed by prior anticoagulation

[ Arnold et al, JACC 1992;19:851]• Arrhythmia- Sinus Arrest , Bradycardia - VF, VT

(Risk factor- Hypokalemia, Dig intoxication, improper synchronization)


Recurrence• Complete shock failure and immediate

recurrence – 25%• Subacute recurrence in 2 wk – 25%• 70% in NSR at 24 hour after cardioversion• High chance of recurrences- old age, long

duration of AF [ van Gelder et al, AJC 1991;68: 41]

Pharmacological Cardioversion of AFAMIODARONE [ IIa]• Efficacy - 18-80% • IV – 3-7 mg/kg bolus – 1.2 -1.8 gm/day 300 mg iv in 1 hr f/b 20 mg/ kg infusion in 24 hr

with • Tab Amiodarone 200 mg TDS x 1 wk 200 mg BD x 3 wk• Efficacy – 48.5% at 30 days vs placebo 0% - 82% if LA size < 45 mm - 76 % if AF duration < 1 month

[ Kochiadakis et al AJC 1999, 83: 58]

Pharmacological Cardioversion

Amiodarone side effects- • Hypotension ( 5-15%)-

t/t- iv fluid• Phlebitis (10-33%)• TDP ( 0-5%)• QT prolongation• Pulmonary toxicity

Phlebitis, ↑QT

Hypotension

other

TDP

Pharmacological Cardioversion of AF

IBUTILIDE [CORVERT]• Efficacy- 45-60%• If f/b DC Cardioversion – 100%• Only IV 1 mg bolus [ 0.01 mg/kg]• Risk- TDP [1.7-4%]

DOFETILIDE [TIKOSYN]• Efficacy- 30%• Only oral 500 microgm BD• Risk- TDP


FLECAINIDE [ TOMBOCOR]• Efficacy- 75-91% for recent onset AF• Should be avoided in patients with

underlying organic heart disease with LV dysfunction

• Dose – 200-300 mg PO - 1.5 -3 mg/kg over 10-20 min• Side effects- TDP, Reduce LV contractility,

exacerbation of sinus node dysfunction


PROPAFENONE [ RYTHMOL]• Useful for recent onset AF• Efficacy- 56-83% • Dose- 600 mg PO - 1.5 – 2 mg/kg over 10-20 min• Should be used cautiously or not at all in

patients with HF or severe COPD.• Side effects- Atrial Flutter, VT, Hypotesion,

Bradycardia, Intraventricular conduction defects.

Pharmacological Cardioversion: “PILL IN THE POCKET APPROACH”

• A single oral bolus dose of propafenone or flecainide(‘pill-in-the-pocket’) –terminate persistent AF outside the

hospital if treatment was safe in hospital previously. For selected patients without• Sinus or AV node dysfunction,• Bundle-branch block, • QT interval prolongation, the Brugada syndrome, or structural

heart disease.

Before antiarrhythmic medication is initiated, • A beta blocker or ccb should be given to prevent rapid AV

conduction in the event atrial flutter occurs.

Pharmacological Cardioversion: “PILL IN THE POCKET APPROACH”

Intermittent antiarrhythmic drug therapy ("pill in pocket") in symptomatic patients with infrequent, longer-lasting episodes of AF or AFL as an alternative to daily antiarrhythmic therapy.

– Single dose flecainide (200-300 mg) or propafenone (450-600 mg) as an oral dose.

– Often prescribed with a short-acting beta-blocker at the same time (metoprolol 50-100 mg).

Rhythm control of AF

• PHARMACOLOGICAL Established - AMIODARONE - FLECAINIDE/PROPAFENONE - SOTALOL New - DRONEDARONE - VERNAKALANT• ELECTRICAL - CATHETER ABLATION (More successful in Paroxysmal AF)

Rhythm control

EfficacyAntiarrhythmic drugs for AF

Placebo

Class IA* , IC* , Sotalol

Amiodarone

25%

40-60%

60-70%

Sinus rhythm after 1 year

*Concurrent use of AV nodal blocking drug

FDA = US Food and Drug Administration; AFL = atrial flutter.Multaq [package insert]. Bridgewater, NJ: sanofi-aventis U.S. LLC; 2009.

Dronedarone Indication• ATHENA: Landmark Trial

• Approved by the FDA in July 2009 to – Reduce the risk of CV hospitalization in patients with paroxysmal or

persistent AF or AFL, with a recent episode of AF/AFL, and 1 or more associated CV risk factors

• Age >70

• HTN

• Diabetes

• Prior CVA

• LA diameter ≥50 mm or LVEF <40%

• Contraindicated in class IV HF or lesser HF with recentdecompensation

J. Am. Coll. Cardiol. 2011;57;223-242

A Safety-Driven Approach

*Within each box, drugs are listed alphabetically and not in order of suggested use. HTN = hypertension; CAD = coronary artery disease; HF = heart failure; CHF = congestive heart failure.Wann LS, et al. Circulation. Published online Dec 20, 2010. Camm AJ, et al. Eur Heart J. Published online August 29, 2010.

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

or Persistent AF*

HF

AmiodaroneDofetilide

Maintenance of SR


Catheterablation

DronedaroneFlecainidePropafenoneSotalol

No (or minimal)heart disease

DronedaroneFlecainidePropafenoneSotalol

Amiodarone

No Yes


Catheterablation

Catheterablation

HTN

Substantial LVH

CAD

Catheterablation

Amiodarone Catheterablation

DofetilideDronedroneSotalol

2010 ESC Guidelines – Dronedarone recommended for patients with LVH and stable NYHA I/II CHF

AF: Rate Control

Rate Control in AF

WHY [Adverse consequences of high rate]

• ↓ time for ventricular filling • Hypotension- dizziness• CHF- worsening hemodynamics• Rate related ischemia• Tachycardiomyopathy

Rate control: How much is ADEQUATE?

• No strict definition of rate control• Rest – 60-80/min• Holter – Mean 80 - 100/min• Moderate exercise – 90-115/min• Peak exercise – 20-30% reduction of age

predicted heart rate

2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Updating the 2006 Guideline) J. Am. Coll. Cardiol. 2011;57;223-242;

Rate Control in AF: HOW?Pt WITHOUT CHF, Hypotension,

Accessory pathway1. Esmolol2. Metoprolol3. Propanolol4. Diltiazem5. Verapamil6. Dig + B- blocker7. AV ablation when drug

ineffective

I level B

II a

Rate Control in AF: HOW?In patients WITH CHF , Without Accessory

Pathway-• IV Digoxin Class I [ Level B]• 0.25 mg/kg iv every 2 hour up to 1.5 mg

– Onset : 60 min or more• IV Amiodarone [ Class IIa level C]

– 150 mg iv over 10 min f/b 0.5 – 1 mg/min infusion

Rate Control in AFEsmolol [ I level C]• 500 μg/ kg iv bolus over 1 min f/b • 60-200 μg/ kg/min infusion• Onset – 2-5 min• Adv- short acting [half life – 9 min]• Found to be effective in converting AF to

NSR vs Verapamil and Diltiazem

Rate Control in AFMetoprolol [ I level C]• 2.5-5 mg iv bolus over 2 min, upto 3 doses• Onset 5 min• Maintainence dose 25- 100 mg PO bdPropanolol [ I level C]• 0.15 mg/kg iv over 2 min• Onset- 5 min• s/p Asthma, CHF, hypotension• Maintainence dose 80-240 mg PO divided dose

Rate Control in AFDiltiazem [ I level B]• 0.25 mg/kg iv over 2 min f/b• 0.1- 0.3 mg/kg/hr• Onset 2-7 min• Oral 120-360 mg/dayVerapamil [ I level C]• 0.075-0.15 mg/kg iv over 2 min• Onset 3-5 min• Oral 120-360 mg/day

Rate control – Choice of therapy

• No structural heart disease1. Diltiazem/Verapamil2. Beta-blockers

• CAD; EF >40%1. Beta-blockers2. Diltiazem/Verapamil

• LV dysfunction EF<40% + CHF1. Digoxin2. + Beta blockers

• Refractory cases1. Amiodarone2. AVN ablation

Rate Control: Dosages of Drugs

Atrial Fibrillation with Accessory Pathway

• Class I– Dc cardioversion

• Class II a– IV Procainamide– IV Ibutilide

Rate Vs Rhythm

Rate vs Rhythm Control

All cause mortality

Arch Intern Med, 2005

Rhythm Control of AF

• Strategy of rhythm control has never been shown to reduce mortality compared to rate control (AFFIRM, RACE, PIAF trials, AF CHF)

• Therefore, goals of rhythm control should focus on improving quality of life

• Rhythm control does not necessitate elimination of all AF


• All cause mortality – No difference• CV mortality - No difference• Non CV mortality – Higher with rhythm control• Stroke - No difference• Quality of life – No major difference• Cost – Rhythm control less cost-effective• Improved outcome with rhythm maintenance- STAF• On-treatment analysis favors rhythm control-AFFIRM

Favors Rate Control Favors Rhythm Control

Persistent AF Paroxysmal AF

Recurrent 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

Patient preference Patient preference

Canadian Cardiovascular Society AF Guidelines. 2011


Predictors of Atrial Fibrillation Recurrence

• Age > 70• AF duration > 3 months• Hypertension• Heart Failure• LA enlargement (>4 cm)• Rheumatic heart disease

Rheumatic AF

• Younger age• Higher risk of thromboembolism• Haemodynamic burden• Advanced atrial pathology• Valvular intervention is no guarantee for

prevention of AF• Rhythm control may be a superior strategy

Risk stratification for stroke and thrombo-embolism

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

– Approximately 15% of all strokes in the United States caused by AF

– 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)

RACE II = Rate Control Efficacy in Permanent Atrial Fibrillation.Fuster V, et al. J Am Coll Cardiol. 2006;48(4):e149-e246. Kannel WB, et al. Med Clin North Am. 2008;92(1):17-42. Page RL, et al. Circulation. 2003;107(8):1141-1145. Hart RG, et al. J Am Coll Cardiol. 2000; 35(1):183-187. Dulli DA, et al. Neuroepidemiology. 2003;22(2):118-123.

LowRisk

ModerateRisk

HighRisk

10

8

6

4

2

0

Stroke Risk Stratification in AFCHADS2

CHA2DS2-VASc

Risk Factor ScoreCardiac failure 1HTN 1Age ≥75 y 1Diabetes 1Stroke 2

Risk Factor ScoreCardiac failure 1HTN 1Age ≥75 y 2Diabetes 1Stroke 2Vasc dz (MI, PAD, aortic ath) 1Age 65-74 y 1Sex category (female) 1

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

Total Score Annual Risk of Stroke (%)

0 1.9 1 2.8 2 4.0

3 5.9 4 8.5 5 12.5 6 18.2

CHA2DS2-Vasc Score Annual Stroke Risk

0 ~0%

1 1.3%

2 2.2%

3 3.2%

4 4.0%

5 6.7%

6 9.8%

7 9.6%

8 6.7%

9 15.2%

CHADS2 Score Utilization

CHADS2 Score

Stroke Risk Consideration

0 Low No treatment(or aspirin 75-325 mg / day)

1 ModerateOral anticoagulationWarfarin with INR 2-3 or new oral anticoagulant(or aspirin 75-325 mg / day)

2 or higher

Moderate to High

Oral anticoagulationWarfarin with INR 2-3 or new oral anticoagulant

(Singer DE. Chest. 2008 Jun;133(6 Suppl):546S-592S)

Echocardiographic features of High Risk of Stroke in AF

• Mod to Sev LV Dysfunction• LA thrombus• Dense SEC• ↓ velocity of blood flow in LAA• Diameter of LA > 45 mm

Oral Drugs Used for Prevention of Thromboembolism

• Aspirin• Clopidogrel• Warfarin• Newer oral anticoagulants

Stroke Prevention in AFib

• Currently approved medications are oral anticoagulants (vitamin K antagonists such as warfarin) and aspirin1

• Vitamin K antagonists are effective in preventing stroke among AFib patients with a 68% relative reduction versus placebo

(SPAF Trial. Arch Intern Med 1994;154:1449-1457)

OAC Vs Clopidogrel plus ASA• Oral anticoagulation is superior to clopidogrel plus ASA for

prevention of vascular events• Rates of major hemorrhage are similar• For patients at centers not achieving good INR control,

oral anticoagulation may offer little benefit over clopidogrel plus ASA.

• aspirin plus clopidogrel therapy could perhaps be considered as an interim measure where VKA therapy is unsuitable, but not as an alternative to VKA in patients at high bleeding risk.

OAC Associated Bleeding Risk Factors

• Patient-related factors– Age– History of bleeding– Previous stroke– Anemia– Genetic factors– Sex– Uncontrolled hypertension– Renal insufficiency– Hepatic dysfunction– Malignancy

• OAC treatment-related factors*– Inception vs OAC experience– Adherence– Intensity of anticoagulation (INR)*– Time in therapeutic range*– Dietary intake of vitamin K*– Management of OAC (self-monitoring,– dedicated OAC clinic, usual care)*– Concomitant medications/alcohol– Antiplatelet drugs / NSAIDs– Other medications affecting OAC intensity– Excessive alcohol intake*Vitamin K antagonist therapy only

(Lane, Circulation. 2012;126:860-865)

Risk with Warfarin Anticoagulation

(Oden A. Thromb Res. 2006;117:493-9)

Item Score

Hypertension (SBP > 160 mm Hg) 1

Abnormal renal function 1

Abnormal liver function 1

Stroke 1

Bleeding predisposition 1

Labile INRs (if on warfarin) 1

Elderly (> 65 yrs) 1

Drug use 1

Alcohol use 1

Bleeding Risk – HAS BLED

HAS-BLED Score > 3 indicates caution is warranted

(Pisters R. Chest. 2010;138:1093-100)

Limitations of Vitamin K Antagonists

· Narrow therapeutic window · Wide variation in metabolism, with

numerous food and drug interactions · Need for regular coagulation monitoring

and dose adjustment · Slow onset/offset

New Antithrombotic Agents

Tissue Factor

Plasma ClottingCascade

Prothrombin

Thrombin

Fibrinogen Fibrin

Thrombus

Platelet Aggregation

Conformational Activation of GPIIb/IIIa

Collagen

Thromboxane A2

ADP

AT

Aspirin

ClopidogrelPrasugrelAZD6140

DabigatranXimelagatran

FactorXa

Idraparinux

ApixabanRivaroxaban

Characteristics of New Oral Anticoagulants1,2

Drug Dabigatran Rivaroxaban Apixaban

Mechanism of action Thrombin inhibitor FXa inhibitor FXa inhibitor

Half-life 14-17 h 5-9 h 12 h

Regimen BID QD, BID BID

Peak to trough ~7x 12x (QD) 3-5x

Renal excretion of absorbed drug

~80% 36-45% 25-30%

Potential for drug interactions

P-glycoprotein inhibitor

CYP3A4 substrate and P-glycoprotein inhibitor

CYP3A4 substrate and P-glycoprotein inhibitor

1. Usman MH, et al. Curr Treat Cardiovasc Med. 2008;10(5):388-397.2. Piccini JP, et al. Curr Opin Cardiol. 2010;25(4):312-320.

RE-LY® Trial• Dabigatran 110 mg b.i.d. was non-inferior to VKA for the prevention of

stroke and systemic embolism with lower rates of major bleeding.

• Dabigatran 150 mg b.i.d. was associated with lower rates of stroke and systemic embolism with similar rates of major haemorrhage, compared with VKA.

• The FDA approved dabigatran for prevention of stroke in patients with AF in October 2010.

• A dose of 150 mg twice daily was approved for patients with a creatinine clearance 30 mL/min, whereas in patients with severe renal insufficiency (creatinine clearance 15 to 30 mL/min) the approved dose is 75 mg twice daily.

2011 ACCF/AHA/HRS Focused Update on the Management of Patients With Atrial Fibrillation (Update on Dabigatran) J Am Coll Cardiol 2011;57:1330 –7.

Summary of ROCKET AF trial• Efficacy:

– Rivaroxaban was non-inferior to warfarin for prevention of stroke and non-CNS embolism.

– By intention-to-treat, rivaroxaban was non-inferior to warfarin but did not achieve superiority.

• Safety:

– Similar rates of bleeding and adverse events.– Less ICH and fatal bleeding with rivaroxaban.

• Conclusion:

– Rivaroxaban is a proven alternative to warfarin for moderate or high risk patients with AF.

RIVAROXABAN• FDA Approves XARELTO® (rivaroxaban) to

Reduce the Risk of Stroke and Systemic Embolism in Patients with Nonvalvular Atrial Fibrillation.

• At a dose of 20 mg once daily, or 15 mg once daily for patients with moderate to severe renal impairment, taken with the evening meal.

U.S FDA November 4, 2011

FDA NEWS RELEASEFor Immediate Release: Dec. 28, 2012

• FDA approves Eliquis to reduce the risk of stroke, blood clots in patients with non-valvular atrial fibrillation

• The U.S. Food and Drug Administration today approved the anti-clotting drug Eliquis (apixaban), an oral tablet used to reduce the risk of stroke and dangerous blood clots (systemic embolism) in patients with atrial fibrillation that is not caused by a heart valve problem.

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

atrial fibrillation- management

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