This document discusses various treatment options for atrial fibrillation (AF) including rate control, rhythm control, and anticoagulation. It summarizes the findings of the RACE II trial which showed that lenient rate control (resting heart rate up to 110 bpm) is not inferior to strict rate control (resting rate up to 80 bpm) for patients with permanent AF. It also reviews different pharmacological agents for rate control including beta-blockers, calcium channel blockers, and digoxin. Finally, it discusses rhythm control strategies such as antiarrhythmic drugs and catheter ablation for restoring and maintaining sinus rhythm.

1. Niraj Sharma, MD

2. ATRIAL FIBRILLATION
RATE/AAD/ABLATION
Niraj Sharma MD
4rd Atrial Fibrillation Summit
May 30, 2015

3. 48 year old with symptomatic pAF, occurring 2-3 times
a month. Average duration 3 hours. No other medical
problems. To maintain normal rhythm, you would now:
1. Refer to Cardiology
2. If you are Cardiology refer to EP
3. Start Flecanide
4. Start Flecanide & Metoprolol
5. Recommend ablation
6. Evaluate clinically as well as by EKG/Echo ±
TTM for structural heart disease prior to
initiation of AAD
7. Start amiodarone

4. Priorities in the Management of A FIB
The Patient Care Pathway
Rhythm Control
Prevention of
Thromboembolism
Rate Control

5. Pillars of AF management
 Rate control:
AVN blockers
AVN ablation & Pacing
 Anti-coagulation:
0
ASA, ASA+Clopidogrel
Warfarin
New agents
 Rhythm Maintenance:
AAD
Ablation

6. Rate control
 Why?
 What rate?
 Bipolar afib (tachy-brady)

7. Rate control
 Unchecked HR (≥120bpm) leads to TCMP
 Poor exercise tolerence
 Affirm adequate control was defined as an average heart rate of up to 80
bpm at rest and either an average rate of up to 100 bpm over at least 18 hours of
ambulatory Holter monitoring with no rate greater than 100% of the maximum age
adjusted predicted exercise heart rate or a maximum heart rate of 110 bpm during
a 6-minute walk test
 Race II The potential benefits of strict (resting heart rate 80 bpm,
heart rate 110 bpm during moderate exercise) versus lenient (resting heart rate
110 bpm) rate control

8. RACE II
(Rate Control Efficacy in Permanent Atrial
Fibrillation)
 614 patients with permanent AF
 treated with a variety of atrioventricular (AV) nodal blocking agents to
control heart rate.
 Primary endpoints were death from cardiovascular causes, hospitalization
for heart failure, stroke, systemic embolism, bleeding, and life-threatening
arrhythmias.
 The 3-year estimated cumulative incidence of the primary outcome was
12.9% in the lenient-control group and 14.9% in the strict-control group,
with an absolute difference between lenient control and strict control of 2.0
percentage points, HR of 0.84 (90% CI, 0.58 to 1.21; P0.001.
 Symptoms were also similar in both groups.
 All patients included in the study were ambulatory and relatively young
(mean age, 68 years), predominantly male, and may have been healthier
and less symptomatic than many patients encountered in clinical practice
 The RACE II study shows that lenient-rate control 110 bpm is not inferior to
strict-rate control 80 bpm

9. RACE II TRIAL: LENIENT RATE CONTROL
IS NOT INFERIOR TO STRICT RATE
CONTROL

10. Rate control: Rate
 2011ACC/AHA/HRS Focused Update Recommendation:
 Class III–No Benefit
 Treatment to achieve strict rate control of heart rate (80
bpm at rest or 110 bpm during a 6-minute walk) is not
beneficial
compared to achieving a resting heart rate 110 bpm in
patients with persistent AF who have stable ventricular
function (left ventricular ejection fraction 0.40) and
no or acceptable symptoms related to the
arrhythmia, though uncontrolled tachycardia may over
time be associated with a reversible decline in
ventricular performance.

11. Heart Rate Control
What’s new?

12. Rate control: AVN blockers
Which ones?
 Beta-blockers-which one
 CCB-when/which one
 Digoxin
 ?Amiodarone

13. Mechanism of Action: β-
blockers
Gs Protein
cAMP
β1
Stimulation
(Cardiac Sarcolemma)
ProteinKinase A
SR release of Ca
Phosphorylates Trop I
Increase If in SN/AVN

14. Beta-Blocker Generations

15. Differences in BB properties

16. Beta-blockers

18. CCB better for Rate control than BB
The RATAF trial (in Select Populations)

19. Summary Rate control
 Acute Rate Control
 In the acute setting in the absence of pre-excitation, intravenous administration of beta blockers or non-dihydropyridine calcium channel antagonists is
recommended to slow the ventricular response to AF, exercising caution in patients with hypotension or heart failure.
 In the acute setting, intravenous administration of digoxin or amiodarone is recommended to control the heart rate in patients with AF and concomitant
heart failure, or in the setting of hypotension.
 In pre-excitation, preferred drugs are class I antiarrhythmic drugs or amiodarone.
 When pre-excited AF is present, beta blockers, non-dihydropyridine calcium channel antagonists, digoxin, and adenosine are contraindicated. Use
Amiodarone or Procainamide.
 Long-term Rate Control
 Rate control using pharmacological agents (β-blockers, nondihydropyridine. Calcium channel antagonists, digitalis, or a combination thereof) is
recommended in patients with paroxysmal, persistent, or permanent AF.
 The choice of medication should be individualized and the dose modulated to avoid bradycardia.
 In patients who experience symptoms related to AF during activity, the adequacy of rate control should be assessed during exercise, and therapy
should be adjusted to achieve a physiological chronotropic response and to avoid bradycardia.
 It is reasonable to initiate treatment with a lenient rate control protocol aimed at a resting heart rate <110 bpm.
 It is reasonable to adopt a stricter rate control strategy when symptoms persist or tachycardiomyopathy occurs, despite lenient rate control: resting
heart rate <80 bpm and heart rate during moderate exercise <110 bpm.
 After achieving the strict heart rate target, a 24 h Holter monitor is recommended to assess safety.
 Digoxin is indicated in patients with heart failure and LV dysfunction, and in sedentary (inactive) patients. It is not effective for rate control during
exercise.
 Rate control may be achieved by administration of oral amiodarone when other measures are unsuccessful or contraindicated. Note can convert to
SR….MUST be adequately ACed
 Digoxin should not be used as the sole agent to control the rate of ventricular response in patients with AF.

20. Rate control: Ablate (AVN) &
Pace
 Symptomatic (SOB, DOE, Palpitation, dizzy..)
 Permanent AF or persistent failed AAD/AB
 Hypotensive with poor rate control

21. Rhythm Maintenance
 The AFFIRM, RACE, and AF-CHF trials have shown no mortality benefit
to a rhythm control strategy compared to a rate control strategy. Therefore,
a rate control strategy, without attempts at restoration or maintenance of
sinus rhythm (SR), is reasonable in some patients with AF, especially those
who are elderly and asymptomatic.
 If rate control offers inadequate symptomatic relief, restoration of sinus
rhythm becomes a clear long-term goal. Restoration and maintenance of
sinus rhythm continues to be a reasonable treatment approach in many
patients with AF
 Keep in mind rhythm maintenance may not be chronic. Can be used “as
needed” for infrequent episodes (once a year) as “pill in pocket”

22. Affirm
Total Mortality in AFFIRM Trial

23. Asymptomatic or not?
 Check with spouse
 6 min walk test-300m-NYHA class I
 Treadmill
 DCCV to SR & note if any improvement in
symptoms

24. Rhythm Maintenance: 1) AAD

25. Issues with these Guidelines
 These guidelines are based NOT on efficacy
but by limiting side effects/proarrhythmia
 E.G. sotalol/propafenone/flecanide above
amiodarone and ablation

26. William Vaughn Classification

27. Class Ic: Flecanide &
Propafenone
 Can be started in an out patient setting as long as
sinus node and AV conduction normal
 Avoid in conduction blocks, SHD: ischemia, significant
LVH (1.4cm)
 Ideal for pill in pocket: flecanide 300mg or
propafenone 600mg x 1 dose with verapamil 80mg
(unless already on an AV blocking agent)
 Can also be used to “top off” if chronically on Ic agent
(as long max daily dose not reached 400/900)
 Effective in converting to SR 70-80% (within 4hours)
in maintaining SR in~40% (exception RAFT trial-70%)

28. Class III:
Sotalol/Amiodarone/Dofetilide/Dron
edarone
 Can be initiated as an out patient if: not bradycardic,
baseline borderline QTc, hypokalemia,
hypomagnesemia, female gender
 Efficacy 40%
 Main issue prolonged QTc and TdP, especially if QTc
>500ms+bradycardia+ K or Mg
 Risk of TdP was <1% in trials
 Renal excreated not used if GFR <40ml/min
 Beta blocking effects plateau at a lower dose (≤240/day)
than class III effects
 Not effective for pharmacological conversion

29. Class III:
Sotalol/Amiodarone/Dofetilide/D
ronedarone
 Most effective, efficacy of 50-60%
 2nd line in structurally normal hearts 1st in
patients with CHF
 Maintenance dose in AF should be no more
than 200mg/day: even at this dose 15% may
have thyroid abnormalities (usually hypo), 2%
pulmonary toxicity annually
 Monitor 2 x a year lft, tsh and eye exam, x-ray
once a year

30. Class III:
Sotalol/Amiodarone/Dofetilide/D
ronedarone
 Efficacy 40% better with paroxysmal 60%
 High risk of TdP, requires initiation
hospitalization
 Renal elimination
 Can be used in CHF
 Well tolerated

31. Class III:
Sotalol/Amiodarone/Dofetilide/D
ronedarone
 Like amiodarone but no iodine
 Less effective
 Only drug shown to reduce cv mortality and
hospitalization

32. Dronedarone
Dronedarone does not
contain iodine, and has
the addition of a
methane-sulfonyl group
that reduces
lipophilicity to decrease
accumulation in tissue.dronedarone
amiodarone

33. New developments in
AAD therapy---Dronedarone
 The Good—Athena
 The Bad---Andromeda---Black Box
---Dionysos
 The Ugly—Pallas—Black Box

38. Dronedarone current state
 Avoid in Permanent AF
 Avoid in Class III/IV heart failure
 Monitor LFT’s at least in 6 weeks and then as
needed
 Consider dronedarone to avoid toxicities such
as thyroid dysfunction or pulmonary toxicities
 Caution with Dabigatran
 Keep cost and formulary issues in mind

39. Dronedarone….JAMA Feb17th 2014
 5 trials measured mortality: 13 more deaths
per 1000 treated than placebo
 3 trials measured adverse effects: 46 more
1000 treated
 1 trial vs amio: 214 more AF recurrences per
1000
 Athena trial: only “positive” trial driven by
hospital admissions
 Guidelines: faulty management of COI,
inadequate composition of writing group, lack
of systematic reviews etc.

40. AAD

41. W/u needed prior to initiation of
AAD
 H & P: CAD, PCTA, CABG, severe
uncontrolled HTN, valve disorders
 EKG:(2/3 deg block, LBBB, RBBB+hb,
QRS/QT)
 Echo: EF, valve, wall motion/thickness
 ± Ischemic evaluation: at initiation and at
regular intervals or if symptoms develop

42. Rhythm Maintenance: 2) Ablation
Class IIa

43. Rate control plus
anticoagulation preferred
Rhythm control
preferred
• No or lesser AF
symptoms
• Longer AF Hx
• More SHD
• Toxicity Risk
• Elderly
• Greater risk of
proarrhythmia
• Greater AF symptoms
• Symptoms despite rate control
• Younger age
• No or lesser SHD
In anticoagulation candidates, continue anticoagulation indefinitely
APPROACH TO AFIB THERAPY

44. Digoxin 2015 update

45. VA physician guidelines..

46. Thank you

47. ANY QUESTIONS?