atrial fibrillation: guidelines through clinical cases and

Atrial Fibrillation: Guidelines through clinical cases and

2010 updates Samy Claude ELAYICardiac Clinical Pacing and

Electrophysiology

AF: PUBLIC HEALTH PERSPECTIVE

Feinberg WM: Arch Intern Med 1995/ Murgatroyd F and Camm AJ: Lancet 1993

World incidence720, 000 new cases / year

World prevalence5.5 million

AF prevalence increasing

with aging of population

When talking about atrial fibrillation treatment, two separate issues:

1/ Prevent thrombo-embolic stroke

Coumadin/ASA/plavix/none/Dabigatran

2/ Manage the AF rhythm

Rate control/rhythm contol

Clinical case 1

65 yo male

PMH: HTN

Meds: metoprolol 50 mg BID

Comes for regular f/u visit, no symptoms

with a normal daily activity.

Clinically: irregular heart beat.

You discussed with the patient the potential

risk of stroke. What medication would you

consider daily regarding this risk?

No medication

Start Aspirin 81 mg

Start Aspirin 325 mg

Start Plavix

Start Coumadin

_______________________________________________________________________Moderate-Risk Factors High-Risk Factors_________

Heart failure Previous stroke, TIA or embolism

Hypertension Mitral stenosis

Age greater than or equal to 75 y

LV ejection fraction 35% or less

Diabetes mellitus_________________________________________________________________________________________________________________

Risk Category Recommended Therapy_

No risk factors Aspirin 81 to 325mg/day or none*

One moderate-risk factor Aspirin 81 to 325 mg daily, or warfarin (INR2.0 to 3.0, target 2.5)

Any high risk factor or >1 moderate risk factor warfarin (INR 2.0 to 3.0, target 2.5)

* Age less than 60 y, no heart disease (lone AF)

STROKE RISK/ ANTITHROMBOTIC THERAPY AND AF

2006 guidelines for the management of patients with AF

Stroke risk and CHADS2 scoreFor non valvular AFn Congestive Heart Failure +1n Hypertension +1n Age > 75 yo +1n Diabetes +1n Prior Stroke/TIA +2

Then classification as:

Low-risk = 0 High-risk >2

Heart failure Previous stroke, TIA or embolism

Age greater than or equal to 75 y

You discussed with the patient the potential

risk of stroke. What would you do next regarding

this risk?

Not start anything

Start Aspirin 81 mg

Start Aspirin 325 mg

Start Plavix

Start Coumadin

You decided to start Aspirin 325 mg and determine during the f/u that your patient is always in AF (=persistent AF).

AF CLASSIFICATION

PAROXYSMAL

PERSISTENT

PERMANENT

Terminates

spontaneously

Yes No No

AF can be converted to SR

(shock or drug)

N/A Yes No

Gallagher MM, Camm AJ. Classification of atrial fibrillation. PACE. 1992;20:1603-1605

What would you do next for this patient with HTN and asymptomatic persistent AF?

Restore sinus rhythm with cardioversion (RHYTHM CONTROL)

Keep the patient in AF but adjust the metoprolol dose to prevent fast ventricular heart rate to avoid potential tachycardia induced cardiomyopathy with heart failure (RATE CONTROL)

Send the patient for an ablation

Rate control Rhythm control

Keep the patient in atrial fibrillation but adjust the metoprolol dose to prevent fast ventricular heart rate to avoid potential tachycardia induced cardiomyopathy and heart failure (RATE CONTROL)

Design in the mid 1990 to help manage AF

Potential benefit of maintaining SR:

better survival

lower risk of stroke

better quality of life

Hypothesis: maintenance of SR with AAdrugswould improve mortality compared to rate control of AF with AV nodal blockers

AFFIRM NEJM 2002;347:1825-33

Rate vs. Rhythm control

The AFFIRM Trial

Inclusion criteria

One or more recent episodes of AF of > 6 hours (excluded permanent AF). Patients with at least one clinical risk factor for stroke:

age> 65HTNDMCHFLVEF < 40% prior stroke

AFFIRM NEJM 2002;347:1825-33

The AFFIRM Trial

Patients with frequent or severe symptoms were largely excluded

Although this subgroup would benefit the most from SR

Constitutes >1/3 of all AF patients

AFFIRM limitation

4060 patients were randomized to:

1. Rhythm control (maintain SR as much as possible using cardioversions and AAdrugs).

2. Rate control (with AV nodal blockers).

AFFIRM NEJM 2002;347:1825-33

The AFFIRM Trial

Primary endpoint: overall mortality

“Management of AF with the rhythm-control strategy offers no survival advantage over the rate-control strategy”-------> Current guidelines

It does not mean SR=AF in term of mortality.

AFFIRM study did not compare SR vs AF, but:

an ineffective and toxic tool to maintain SR (AAdrugs)

versus

maintaining AF with rate control drugs.

AFFIRM study can not be extrapolated to “Sinus rhythm and AF are equivalent in term of mortality”.

SR is better than AF mortality wise.

Sinus Rhythm vs. AF

Clinical impact of AF on mortality

AF has a 1.5- to 1.9-fold increased risk of mortality in the general population * compared to sinus rhythm

4.2-fold increased risk for CV mortality in lone AF;

2.5-fold increased risk for mortality in HF;

4.5-fold increased risk for mortality in acute coronary syndromes.

•Benjamin et al Circulation 1998;98:946-52

AFFIRM conclusion:

Trying to maintain sinus rhythm with an aggressive strategy using currently available drugs (relatively ineffective to maintain SR or with major side effects) is not better in term of mortality than keeping AF rate controlled in patients with moderately, minimally or not symptomatic AF.

The impact of maintaining SR on mortality with ablation or potential new drugs (less toxic, more effective to maintain SR) is unknown.

65 yo male HTN metoprolol asymptomatic persistent AF

You decided to cardiovert the patient and this restored normal sinus rhythm. However, 4 months latter, he is back in AF and still asymptomatic.

What would you do next?

Start cardioversion again

rate control the AF

65 yo male HTN metoprolol asymptomatic recurrent persistent AF

You decided to cardiovert the patient and this restored normal sinus rhythm. However, 4 months latter, he is back in AF and still asymptomatic.

Start cardioversion again

Rate control the AF

Clinical case 2 61 year old male

PMH: HTN treated with amlodipine (Norvasc)

Complaining of episodes of palpitations for the last year: several episodes/month, from few minutes to 1 hour spontaneous termination. Feels dizzy, SOB and exhausted.

He went to the local ED 6 weeks ago and was told he has "A-fib." Had heart echo (EF 65%)/TSH normal. Was started on ASA and metoprolol 150 mg BID and asked to f/u with his PCP.

Clinical exam: unremarkable with regular heart beat

The patient still has frequent palpitations despite 150 mg BID of metoprolol. His heart rate is around 50 bpm. What would you do next?

Consider increasing metoprolol

Consider starting antiarrhythmic drugs

Consider sending the patient for an AF ablation

Consider sending the patient for a pacemaker and AV node junction ablation

The patient still have frequent arrhythmia symptoms despite 300 mg of metoprolol. What would you do next?

Consider increasing metoprolol

Consider starting antiarrhythmic drugs

Consider sending the patient for a pacemaker and AV node junction ablation

Drugs used in 2010 for AF

FOR RHYTHM CONTROL (maintain SR)

Class IC

Flecainide (Tambocor*)

Propafenone (Rythmol*)

Class III

Amiodarone (Cordarone*;Pacerone*)

Sotalol (Betapace*)

Dofetilide (Tikosyn*)

Dronedarone (Multaq*)

FOR RATE CONTROL (control AF)

Betablockers/ calcium blockers (diltiazem/verapamil)/ digoxin

61 yo male HTN normal heart echo no CAD nor heart failure very symptomatic AF failed rate control.

Which antiarrhythmic could be started?

61 yo male HTN normal heart echo no CAD nor heart failure very symptomatic AF failed rate control.

Which antiarrhythmic could be started?

Depends on the heart condition

The patient was started on flecainide (IC) 50 mg BID, well tolerated. At his 2 months f/u, he reports a few episodes of AF<5 min still symptomatic. What would you consider?

Continue same medications and f/u

Increase the dose of flecainide to the standard dose of 100 mg BID

Change antiarrhythmic drug

The patient was started on flecainide 50 mg BID, well tolerated. At his 2 months f/u, he reports a few episodes of AF<5 min still symptomatic. What would you consider?

Continue same medications and f/u

Increase the dose of flecainide to the standard dose of 100 mg BID

Change antiarrhythmic drug

You increased the flecainide to 100 mg BID. The patient did well and did not came back to see you for seven months.

One day, he calls and wants to been seen quickly because he is short of breath and has bilateral pedal edema for the last few days.

Clinically, he is tachycardic around 160 bpm irregular and is in congestive heart failure with bilateral crackles and a systolic BP of 90 mmHG.

You send him to the ER where he was admitted.

His left ventricular EF is now 30% on echo. What do you expect them to do?

Keep the patient on aspirin

Initiate coumadin

Cardiovert the patient to sinus rhythm after TEE

Initiate long term amiodarone

Initiate immediately dronedarone (Multaq*)

Age greater than or equal to 75 y Previous stroke, TIA or embolism

Heart failure

His left ventricular EF is 30% on echo. What do you expect them to do?

Initiate coumadin

Amiodarone the most effective but side

effects +++:

-life threatening pulmonary fibrosis

-thyroid (hyper or hypo)

-QT prolongation (ventricular arrhythmias)

-ocular, neurologic, dermatologic, liver…

Initiate coumadin

Wei Sun et al Circ 1999;100:2276-2281

Class III K blockers

Available in the US since august 2009

Dronedarone (Multaq*)

Advantages-no lung or thyroid toxicity (with a half life <24h)

-reduces hospitalization for AF (ATHENA trial NEJM 2009)

-no hospital admission for initiation/ no special certification

Limits-Contra-indication in unstable heart failure (IV) or class II

III< 1 month

-efficacy less than amiodarone (-12%)

Dronedarone

Dronedarone?

Initiate coumadin

The patient has been cardioverted. Patient has been discharged on coumadin and Tikosyn 500 mcg BID (maximal dose).

He comes at his 2 months f/u after repeating a new heart echo: EF 70% (arrhythmia induced cardiomyopathy).

He still reports palpitations and dizziness which are impairing his quality of life.

So 61 yo male HTN very symptomatic AF

failed two AADS at maximal doses.

Stop the tikosyn and start sotalol

Send the patient for AF ablation

So 61 yo male HTN very symptomatic AF

failed two AADS at maximal doses.

Stop the tikosyn and start sotalol

Send the patient for AF ablation

IIIaVr

Posterior Basal View –Left Atrium

R. superior pulmonary vein

R. inferior pulmonary vein

Coronary sinus

L. inferior pulmonary vein

L. atrium

L. superior pulmonary vein

L. auricle

L. pulmonary artery

R. pulmonary artery

Netter F. Atlas of Human Anatomy. 1989;Plate 202.

LSPVLSPVLSPV

atrium

Veno-atrial

junction

Veno-atrial

junction

Myocardial sleeveMyocardial sleeve

Atrial Fibrillation: Catheter ablation of PV focus

The fluoroscopy images

show the ablation catheter

(ABL) in the left anterior

oblique (LAO) and right

anterior oblique (RAO)

projections.

Straight mapping catheter

Intracardiac echo probe

Circular mapping catheter

Esophagus temperature monitoring probe

Ablation catheter

LA CT to define the anatomy more precisely

Mapping system during ablation

Complex procedure

Paroxysmal AF

Targets mainly the trigger by disconnecting the pulmonary veins from the rest of the left atrium

Ablation in paroxysmal AF

Elayi et al. Heart rhythm 2006

Persistent AF

May need to target

-the trigger (isolation of the pulmonary veins)

-the rest of the left atrium and sometimes right atrium (to modify the atrial substrate capable of sustaining persistent AF)

Ablation in persistent AF

Elayi et al. Heart rhythm 2008

Main complications of AF ablation

Stroke (0.5 to 1%)+++ like left heart cath

Pericardial effusion/tamponnade

Others:

hematomas; PV stenosis; fistula with esophagus, phrenic nerve paralysis…

Ablation versus Drugs

Advantages-Relative efficacy with a success rate around 70-90% inparoxysmal AF and 50-75% in persistent AF (less successfulin enlarged atrium).-Potential cure (no life long treatment) -Potentially stop coumadin

Disadvantages-Immediate procedure risk-Operator dependant (long learning curve)-Lack on very long term data

Maintenance of sinus rhythmCatheter ablation is a reasonable alternative to pharmacological therapy to prevent recurrent AF in symptomatic patients with little or no LA enlargement (Class IIA; level of

evidence C)

AF Ablation summary

GOAL=Alleviate AF symptoms

Relatively effective procedure especially in paroxysmal patients

For symptomatic AF

After failure of at least one antiarrhythmic drug

With potential significant complications

long term survival and data unknown (>10 years)

Dabigatran

Oral direct thrombin inhibitor

Advantages over coumadin/enoxaparin:

-no routine anticoagutation checks (INR)

-few drugs interaction

Disavantages:

-BID with short half life (compliance)

-Liver toxicity

RE-LY trial NEJM 2009

Dabigatran

Was compared to coumadin at two doses (RE-LY trial):

-110 mg BID: same embolic stroke rate but less hemorrhagic stroke than coumadin.

-150 mg BID: less embolic stroke but same hemorrhagic stroke than coumadin

FDA approval last week

RE-LY trial NEJM 2009

Conclusion In AF, first evaluate thrombo-embolic risk and

decide aspirin versus coumadin Several Rx options are available for the rhythm

Asymptomatic patients: -Make sure patient really asymptomatic-Rate control is an acceptable option (try cardioversion once reasonable)

Symptomatic patients:-AADrugs are always the first option-Failure of AADrugs : ablation

Thank you very much

If further questions:

Email:samy-claude.elayi@uky.edu

Phone:(859)-3236036

AF wavelets 400 to 600 bpm

AV node filters

the atrial

activity and

determines

the ventricular

RHYTHM CONTROL

(antiarrhythmic drugs,

Ablation)

RATE CONTROL

(AV nodal blockers filter AF waves)

Keep the patient in atrial fibrillation but adjust the metoprolol dose to prevent fast ventricular heart rate to avoid potential tachycardia induced cardiomyopathy and heart failure (RATE CONTROL)

Clinical case 3

87 yo female

PMH: HTN DM several surgeries COPD

AF: permanent with several hospitalizations over the last 2 years for CHF and ventricular heart rate in the 160-170 despite digoxin and metoprolol which alternates with episodes of heart rate in the 30’s very tired and dizzy

Clinically systolic BP in the 90’s

Add another AV nodal blockers (diltiazem)

Send the patient for a pacemaker

Send the patient for a pacemaker and AV node ablation

AVN ABLATION AND PACEMAKER

Rationale:

AVN ablation prevent the fast atria rate (500 bpm) to conduct rapidly and irregularly to the ventricle by disconnecting atria and ventricles

The ventricle can be paced regularly.

AV Node Ablation

AVN ablation and pacing

Only for selected patients with:

symptomatic AF

failed AADs (rhythm or rate control)

not good candidate for ablation

Clinical case 4

64 yo male

h/o GERD Comes to see you in regular f/u visit. used to be very active but now cannot do any significant effort because of fatigue so limit his activity and doing OK

Clinically irregular heart beat 85 bpm

You do a general workup (CBC…) than is

negative. What would you do next?

f/u in a few months

Do a 24 hours holter to make sure he is correctly rate controlled

Try to cardiovert him

Assess symptoms is critical

because it is going to guide your

treatment

Hemodynamics Symptoms

Reduced cardiac output

-Hypotension

-Pulmonary and/or systemic CHF

Fast/slow/irregular ventricular rate is symptomatic for many patients, resulting in:

Palpitations

Dyspnea

Dizziness

Post conversion pauses/ syncope

Inappropriate increases in heart rate with exercise may cause

-exercise intolerance +++

-fatigue +++

If chronic cardiomyopathy with low EF

Increase myocardial oxygen demand may precipitate coronary ischemia.

(ACC/AHA/ESC 2006 guidelines for the management

of patients with atrial fibrillation)

CONCLUSION

Several AF treatment options available

AADs always 1st option to rhythm control before ablation

Rate control is an acceptable primary therapy:

-if reach target (80 bpm at rest and 110 bpm exercise)

-consider DCV for the 1st documented AF, even if not symptomatic

-no data to compare mortality with ablation and rate control

Patient stays symptomatic despite rate/rhythm control

consider ablation

AVN ablation+ pacemaker last resort

Atrial fibrillation conducting quickly to the ventricles can lead to tachycardia induced dilated cardiomyopathy with low ventricle ejection fraction.

If rate control strategy is chosen, rate control should be efficient.

Symptoms and AF (2)

Dronedarone jeff email

Multaq is contraindicated in patients with NYHA Class IV heart failure, or NYHA Class II-III heart failure with a recent decompensation requiring hospitalization or referral to a specialized heart failure clinic. The Athena trial characterized recent decompensation as occurring in the previous 4 weeks. No criteria were used for ejection fraction however Athena had 1165 patients with Class 1 or 2 CHF and 200 patients with Class 3. There were 179 patients with a LVEF <35% and 4365 patients with LVEF >35%.

If a patient has CHF Class 1, 2, or 3, has a normal EF, and is Clinically stable. Multaq may be used just as it was in Athena. If they are becoming unstable they should not be started or the medication should be stopped.

dronedarone

Pros:-no hospital admission/ drug certification-no renal excretion-should replace IC drugs-multi channel, also AV nodal blocade (per rep, dim HR in AF by 10-15

Cons:-longer study f/u 1.5 year-efficacy -12% compared to amiodarone (dionysos)QT-indicated in parox AF-CI in class IV and class 2 to 3 recent within one month= unstable CHF

His main concern is the risk of stroke (father had a massive stroke). What would you do regarding his treatment:

Keep on ASA

Stop ASA and start clopidogrel (Plavix)

Stop ASA and start coumadin

ACC/AHA/ESC guidelines 2006

Rx options for recurrent AF

Rhythm control [keep the patient in SR]

with antiarrhythmics drugs (AADs)

with ablation- Catheter ablation - Surgery (Maze)

With hybrid approach: combining AADs and/or ablation and/or pacemakers

Rate control [keep patient in AF but control ventricular rate]

with AV nodal blockers

with AV nodal ablation and pacemaker

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