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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
_______________________________________________________________________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
A
D
H
C S2
2006 guidelines for the management of patients with AF
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
AF
PERSISTENT
AF
PERMANENT
AF
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
2006 guidelines for the management of patients with AF
Rate control Rhythm control
2006 guidelines for the management of patients with AF
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 atrial fibrillation but adjust the metoprolol dose to prevent fast ventricular heart rate to avoid potential tachycardia induced cardiomyopathy and heart failure (RATE CONTROL)
Send the patient for an ablation
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
Rate vs. Rhythm control
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
Rate vs. Rhythm control
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
2006 guidelines for the management of patients with 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.
What would you do next?
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
2006 guidelines for the management of patients with AF
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 an AF ablation
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
2006 guidelines for the management of patients with AF
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
Consider sending the patient for an AF ablation
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
Consider sending the patient for an AF ablation
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*)
_______________________________________________________________________Moderate-Risk Factors High-Risk Factors_________
Age greater than or equal to 75 y Previous stroke, TIA or embolism
Hypertension Mitral stenosis
Heart failure
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
You send him to the ER where he was admitted.
His left ventricular EF is 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*)
Amiodarone the most effective but side
effects +++:
-life threatening pulmonary fibrosis
-thyroid (hyper or hypo)
-QT prolongation (ventricular arrhythmias)
-ocular, neurologic, dermatologic, liver…
You send him to the ER where he was admitted.
His left ventricular EF is 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*)
Wei Sun et al Circ 1999;100:2276-2281
Class III K blockers
Available in the US since august 2009
Dronedarone (Multaq*)
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%)
-cost
Dronedarone
Dronedarone
Dronedarone
Dronedarone?
2006 guidelines for the management of patients with AF
You send him to the ER where he was admitted.
His left ventricular EF is 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*)
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.
What would you do next?
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.
What would you do next?
Stop the tikosyn and start sotalol
Send the patient for AF ablation
I
II
IIIaVr
aVl
aVf
V1
V2
V3
V4
V5
V6
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
Left
atrium
Left
atrium
Veno-atrial
junction
Veno-atrial
junction
Lung
hilum
Lung
hilum
Myocardial sleeveMyocardial sleeve
LA
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
2006 guidelines for the management of patients with AF
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)
2006 guidelines for the management of patients with AF
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:
-oral
-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
*RA
RVLV
LA
*
1
PAC
.
.
1
.
.
1
.
.
1
.
.
1
AF wavelets 400 to 600 bpm
AV node filters
the atrial
activity and
determines
the ventricular
rate
*
1
RHYTHM CONTROL
(antiarrhythmic drugs,
Ablation)
.
.
1
.
.
1
.
.
1
*
1
RATE CONTROL
(AV nodal blockers filter AF waves)
.
.
1
.
.
1
.
.
1
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 atrial fibrillation but adjust the metoprolol dose to prevent fast ventricular heart rate to avoid potential tachycardia induced cardiomyopathy and heart failure (RATE CONTROL)
Send the patient for an ablation
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
What would you do next?
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
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
Hemodynamics Symptoms
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.
Hemodynamics Symptoms
(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
bpm)
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