Antiarrhythmic drug therapy in Heart Failure and Atrial Fibrillation, what is reasonable? Presented in the 8th International conference of the Egyptian Cardiac Arrhythmia Association (ECRA) on 23 October 2013

1. Antiarrhythmic drug therapy
in HF with AF, what is
reasonable
Prof. Samir Rafla, FACC, FESC
Alexandria Univ.
smrafla@hotmail.com
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4. Recommendations for Use of
Dronedarone (Multaq) in Atrial
Fibrillation
Class IIa
1.Dronedarone is reasonable to decrease
the need for hospitalization for
cardiovascular events in patients with
paroxysmal AF or after conversion of
persistent AF. Dronedarone can be
initiated during outpatient therapy.
(Level of Evidence: B
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5. Recommendations for Use of
Dronedarone in Atrial Fibrillation
Class III–Harm
1. Dronedarone should not be
administered to patients with class IV
heart failure or patients who have had an
episode of decompensated heart failure
in the past 4 weeks, especially if they
have depressed LV function (EF<35%).
(Level of Evidence: B)
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6. - The major adverse cardiac effects of
dronedarone are bradycardia and QT
prolongation. Torsades de pointes has
been reported.
- Like amiodarone, dronedarone inhibits
renal tubular secretion of creatinine,
which can increase plasma creatinine
levels. However, there is no reduction in
GFR.
- Dronedarone increases digoxin levels
1.7- to 2.5-fold.
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7. - Dronedarone is predominantly
metabolized by the liver (CYP3A4). It can
be administered with verapamil or
diltiazem, but low doses of these agents
should be used initially .
- Dronedarone does not alter the INR
when used with warfarin.
- The recommended oral dose of
dronedarone is 400 mg twice a day with
meals.
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8. Dronedarone - Adverse Events
VARIABLE
DRONEDARONE
N=828
PLACEBO
N=409
P value
Stroke
4 (0.5)
3 (0.7)
0.69
Cough
Dyspnea
19 (2.3)
7(1.7)
0.67
Hyperthyroidism
Hypothyroidism
67/801 (8.4)
44/801 (5.5
56/396 (14.1)
14/396 (3.5)
0.002
0.15
Abnormal LFTs
100/822 (12.2)
55/404(13.6)
0.52
Elev of Serum
Creatinine
20 (2.4)
1 (0.2)
0.004
Bradycardia
Heart Failure
22 (2.7)
20 (2.4)
8 (2.2)
4 (1.0)
0.56
0.12

9. Dronedarone - ATHENA: Summary
Dronedarone significantly prolongs time to first CV
hospitalization or death in moderate- to high-risk AF
patients
All-cause mortality was not increased in patients
receiving dronedarone
CV mortality was lower in the dronedarone compared
to the placebo group
The reduction in CV hospitalization was mainly due to
fewer admissions for AF and acute coronary
syndromes
The application of Dronedarone may be useful in low
risk patients (only in NYHA Class I and II)
Hohnloser SH. Heart Rhythm Society 2008 Scientific Sessions;
May 15, 2008; San Francisco, CA.

10. Atrial Fibrillation and Acute Decompensated
Heart Failure
Although the optimal resting HR during AF is
between 60 and 100 bpm, rates below 100 bpm
may not be achievable during AHDF until volume
overload and hypoxia have been corrected. A
more realistic target is to achieve a HR < 120
bpm during the first hours of treatment. Digoxin
should be the first rate-control agent considered.
If the patient has already been taking digoxin, add
doses only if serum digoxin concentration is <0.5
ng/mL.
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11. Atrial Fibrillation and Acute Decompensated
Heart Failure
Cautious addition of small doses of an IV B blocker,
usually metoprolol in 2.5- to 5-mg increments or, if
systolic function is preserved, diltiazem will often be
required.
If rate control along with relief of volume overload
and dyspnea can be achieved, patients will
frequently revert back to SR if the AF episode is of
recent onset. If the patient does not improve with
these measures, meets anticoagulation criteria for
conversion, and if not already on an antiarrhythmic
drug, a trial of IV amiodarone may be helpful.
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12. Amiodarone can be reloaded in patients already
on chronic, moderate doses (<200 mg daily) but
should not be added if the patient has been
taking another antiarrhythmic drug that prolongs
the QT interval, such as sotalol or dofetilide.
If this approach fails and heart rates during AF
remain elevated, cardioversion after a period of
loading with an antiarrhythmic drug, usually
amiodarone, is the next step.
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13. Pharmacological Cardioversion of AF of up to 7 Days
Duration
Vernakalant
IV or oral
I
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19. Torsade de Pointes
Occurs in 1% of patients taking Amiodarone
Predisposing conditions
– LVH, congestive heart failure
– Bradycardia
– Hypokalemia
– Hypomagnesemia
– Digitalis therapy
– Baseline QT prolongation
– High drug concentration (except quinidine)

20. Patient Who Was Treated with Amiodarone
for Atrial Fibrillation

21. Treatment of Torsade de Pointes
Remove offending
agent
Temporary ventricular
or atrial pacing
Isoproterenol
– Increases rate and
decreases QT
interval
Lidocaine
Mexiletine
Phenytoin
Magnesium

22. Porto-marina Beach - Egypt
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23. Flecainide (Tambocor) & propafenone
(Rythmol®) Toxicity and Cautions for Class
IC Drugs:
- They are proarrhythmic drugs causing
worsening of a preexisting arrhythmia or de
novo occurrence of life-threatening ventricular
tachycardia
- Notice: Class 1C drugs are particularly of
low safety and have shown even to increase
mortality when used chronically after MI.

24. With Sotalol (Betapace) and Dofetilide
(Tikosyn), the QT interval should be monitored
carefully during drug loading. Serum potassium
levels should also be watched carefully; in fact,
one should use torsades de pointes producing
agents with caution in patients requiring
potassium-wasting diuretics.
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25. Dofetilide (Tikosyn) had no effect on cardiac
output, cardiac index, or systemic vascular
resistance in patients with ventricular
tachycardia, mild to moderate congestive heart
failure .
Because increase in QT interval and the risk of
ventricular arrhythmias are directly related to
plasma concentrations of dofetilide, dosage
adjustment based on calculated creatinine
clearance is critically important
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26. Ras Sidr Beach. Saini. Egypt
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27. Atrial Specific AADs
Vernakalant is a sodium channel blocker (I
Na) and a potassium channel blocker.
In ACT study, adverse events were reported in
32% of placebo recipients and 38% of
Vernakalant recipients. No deaths or torsade
de points were reported.
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28. Vernakalant BRINAVESS is contraindicated
in patients with severe aortic stenosis, systolic
BP<100 mm Hg, and heart failure class III and
IV.
Vernakalant is contraindicated in patients with
prolonged QT at baseline (uncorrected >440
msec), severe bradycardia, sinus node
dysfunction, or second-degree or third-degree
heart block in the absence of a pacemaker.
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29. Vernakalant is also contraindictated in patients
who use IV rhythm control antiarrhythmics
(class I and class III) within 4 hours prior to
administration of Vernakalant and patients with
acute coronary syndrome (including myocardial
infarction) within the last 30 days.
Adverse reactions (>5%) seen in the first 24
hours after receiving Vernakalant were taste
disturbance (20.1%), sneezing (14.6%), and
paraesthesia (9.7%).
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34. Ain Sokhna – Stella di Mare Hotel and Beach - Egypt
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