For each patient with AF, the two principal goals of therapy are symptom control and the prevention of thromboembolism. Rate- and rhythm-control strategies improve symptoms, but neither has been conclusively shown to improve survival compared to the other. 

1. Atrial Fibrillation
Rate versus Rhythm Control
Samir Morcos Rafla, FACC, FESC, FHRS
Emeritus professor of cardiology
Alexandria University
smrafla@yahoo.com
Shorta Conference-Tolip Hotel-April 2019

2. Definitions
Paroxysmal AF is defined as recurrent AF ( 2
episodes) that terminates spontaneously within
seven days. Also lasting less than seven days
but necessitating pharmacologic or electrical
cardioversion.
Persistent AF is defined as AF which is
sustained beyond seven days. Included within
the category of persistent AF is ‘‘longstanding
persistent AF’’ which is defined as continuous
AF of greater than one year duration. The term
permanent AF is defined as AF in which
cardioversion has either failed or not been
attempted.

3. Atrial fibrillation (AF) is the most common
sustained arrhythmia. It may cause
significant symptoms and impair both
functional status and quality of life. Without
therapeutic intervention, affected patients are
at increased risk for mortality (1.5- to 1.9-fold
in the Framingham Heart Study) and
morbidity (thromboembolic events and
limiting symptoms).
3

4. In AF, the loss of the regular and organized
contraction of the left atrium as well as the
subsequent increase in ventricular rate, lead
to both immediate and long-term adverse
consequences: deterioration in
hemodynamics secondary to increased heart
rate and loss of atrioventricular (AV)
synchrony, an increased risk for stroke and
other embolic events from left atrial thrombi,
and progressive dysfunction of the left atrium
and left ventricle
4

5. 5
Patterns of atrial
fibrillation

6. Cardiovascular and other conditions
independently associated with atrial fibrillation
6

7. 7

10. Rhythm Control Versus Rate Control and Clinical
Outcomes in Patients With Atrial Fibrillation
Results From the ORBIT-AF Registry
JACC: Clinical Electrophysiology Volume 2, Issue 2, April 2016
Results The overall study population (N = 6,988) had
a median of 74 (65 to 81) years of age, 56% were
males, 77% had first detected or paroxysmal AF, and
68% had CHADS2 score ≥2. In unadjusted analyses,
rhythm control was associated with lower all-cause
death, cardiovascular death, first stroke/non–central
nervous system systemic embolization/transient
ischemic attack, or first major bleeding event (all p <
0.05); no difference in new onset heart failure
(p = 0.28); and more frequent cardiovascular
hospitalizations (p = 0.0006). 11

11. There was no difference in the incidence of
pacemaker, defibrillator, or cardiac resynchronization
device implantations (p = 0.99). In adjusted analyses,
there were no statistical differences in clinical
outcomes between rhythm control and rate control
treated patients (all p > 0.05); however, rhythm control
was associated with more cardiovascular
hospitalizations (hazard ratio: 1.24; 95% confidence
interval: 1.10 to 1.39; p = 0.0003).
Conclusions Among patients with AF, rhythm control
was not superior to rate control strategy for outcomes
of stroke, heart failure, or mortality, but was
associated with more cardiovascular hospitalizations.
12

12. Is rate more important than rhythm in
treating atrial fibrillation?
In addition to making the patient feel better, the
restoration of sinus rhythm may reduce the risk
of emergency hospital admission and stroke,
improve the ejection fraction, reduce atrial
remodelling, improve exercise capacity, and
improve outcome.
13

13. 14
STAF trial
Rhythm control by cardioversion and class I antiarrhythmic
agents or sotalol in the absence of coronary heart disease
and in patients with a normal left ventricular function versus
rate control using beta-blockers, digitalis, calcium channel
blockers or atrioventricular node ablation/modification.
Population:
Patients 18 years or older with one or more of following: AF
for >4 weeks; left atrial size >45 mm; congestive heart
failure, NYHA class II or greater; left ventricular ejection
fraction <45%; or ≥1 prior cardioversion with arrhythmia
recurrence.
Outcome
Death
Cardiopulmonary resuscitation
Cerebrovascular event; Systemic embolism

14. 15
PIAF trial
Rhythm control by amiodarone 600 mg for 3
weeks and then cardioversion if necessary.
Maintenance of sinus rhythm was attempted
by administration of amiodarone 200 mg/day
versus rate control diltiazem 90 mg two or
three times a day.
Patients 18–75 years presenting with
symptomatic persistent AF of between 7
days and 360 days duration.

15. Hot Café trial
Rhythm control by cardioversion prior to drug
treatment with propafenone, disopyramide,
or sotalol. Beta blockers were given if
clinically indicated versus rate control using
beta-blockers, digitalis, calcium channel
blockers or a combination of these drugs.
Cardioversion and atrioventricular ablation
with pacemaker placement were alternative
non-pharmacologic strategies.
16

16. CTAF trial:
Aggressive rhythm control: amiodarone and either sotalol
or dofetilide if required; electric cardioversion within 6
weeks after randomization in patients who did not have
conversion to SR after antiarrhythmic drug therapy; if
necessary a second cardioversion was recommended
within 3 months after enrolment; additional cardio-versions
were recommended for subsequent recurrences of AF;
installation of a permanent pacemaker was recommended
if bradycardia prevented the use of antiarrhythmic drugs
versus adjusted doses of beta blockers with digitalis to
achieve the targeted heart rate of less than 80 beats per
minute at rest and less than 110 beats per minute during a
6 minute walk test. AV nodal ablation and pacemaker
therapy were recommended for patients who did not meet
rate-control target with drug therapy. 17

17. AFFIRM trial:
Original Date of Publication: December 5, 2002
Rhythm control: Drugs chosen by the treating
physician and may include cardioversion.
Drugs could include amiodarone, disopyramide,
dofetilide, flecainide, procainamide, propafenone,
quinidine, sotalol and combinations of these drugs
versus rate control using beta-blockers, digoxin,
calcium channel blockers or a combination of these
drugs. Heart rate control during AF was assessed both
at rest and during activity, usually during a 6 minute
walk.
18

18. AFFIRM trial conclusions
1. Rate-control, along with anticoagulation,
should be the main approach to managing
patients with atrial fibrillation.
2. Compared to rhythm-control, rate-control
resulted in a lower incidence of adverse events
and no significant difference in mortality.
19

19. RACE trial
Rhythm control consisted of serial electrical
cardioversion with institution of antiarrhythmic
drugs (sotalol, class IC drugs including
flecainide or propafenone or amiodarone)
versus rate control was achieved using
negative chronotropic drugs including digitalis,
beta blocker and nondihydro-pyridine calcium
channel blocker.
20

20. 21
Economic evidence
Three studies compared the cost effectiveness of rhythm
control versus rate control in patients with AF.
Economic: Two cost–effectiveness analyses and one cost
utility analysis found that rate control was dominant (more
effective and less costly) when compared to rhythm control.
These analyses were assessed as partially applicable with
minor to potentially serious limitations.
Evidence statements: AF Clinical
Moderate quality evidence showed no difference between
rate and rhythm control in:
mortality (7 studies, N=6977)
bleeding (9 studies, N=12591)
Low quality evidence from six studies (N=7186) showed that
there may be no difference between rhythm and rate control
in: stroke; thromboembolic complications

21. Rate and rhythm control
When to offer rate or rhythm control
Offer rate control as the first-line strategy to people
with atrial fibrillation, except in people:
whose atrial fibrillation has a reversible cause
who have heart failure thought to be primarily caused
by atrial fibrillation
with new-onset atrial fibrillation
with atrial flutter whose condition is considered
suitable for an ablation strategy to restore sinus
rhythm
for whom a rhythm control strategy would be more
suitable based on clinical judgement.
22

22. Rate control: Offer either a standard beta-blocker (that
is, a beta-blocker other than sotalol) or a rate-limiting
calcium-channel blocker as initial monotherapy to
people with atrial fibrillation who need drug treatment as
part of a rate control strategy. Base the choice of drug
on the person's symptoms, heart rate, comorbidities
and preferences when considering drug treatment.
Consider digoxin monotherapy for people with
non-paroxysmal AF only if they are sedentary.
If monotherapy does not control symptoms, consider
combination therapy with any 2 of the following:
a beta-blocker; diltiazem; digoxin.
Do not offer amiodarone for long-term rate control.
23

23. Rhythm control: Consider pharmacological and/or
electrical rhythm control for people with AF whose
symptoms continue after heart rate has been
controlled or for whom a rate-control strategy has not
been successful.
Cardioversion: For people having cardioversion for
atrial fibrillation that has persisted for longer than
48 hours, offer electrical (rather than pharmacological)
cardioversion. Consider amiodarone therapy starting
4 weeks before and continuing for up to 12 months
after electrical cardioversion to maintain sinus rhythm,
and discuss the benefits and risks of amiodarone with
the person.
24

24. (Cont.) For people with atrial fibrillation of greater than
48 hours' duration, in whom elective cardioversion is
indicated:
both transoesophageal echocardiography
(TOE)-guided cardioversion and conventional
cardioversion should be considered equally effective
a TOE-guided cardioversion strategy should be
considered: where experienced staff and appropriate
facilities are available and where a minimal period of
precardioversion anticoagulation is indicated due to
the person's choice or bleeding risks.
25

25. Recommendations for rhythm control therapy
26
ClassRecommendations
IRhythm control therapy is indicated for symptom
improvement in patients with AF.
IIaManagement of cardiovascular risk factors and
avoidance of AF triggers should be pursued in patients
on rhythm control therapy to facilitate maintenance of
sinus rhythm.
IIaWith the exception of AF associated with haemodynamic
instability, the choice between electrical and
pharmacological cardioversion should be guided by
patient and physician preferences.

26. Rate control therapy in atrial fibrillation
27

27. Recommendations for rate control
28
IBeta-blockers, digoxin, diltiazem,
or verapamil are recommended to
control heart rate in AF patients with
LVEF ≥40%.
IBeta-blockers and/or digoxin are
recommended to control heart rate
in AF patients with LVEF <40%.
IIaCombination therapy comprising
different rate controlling agents
should be considered if a single agent
does not achieve the necessary heart
rate target.

28. Recommendations for rate control (cont.)
29
In patients with haemodynamic instability or
severely depressed LVEF, amiodarone may be
considered for acute control of heart rate. Ilb
In patients with permanent AF (i.e. where no
attempt to restore sinus rhythm is planned),
antiarrhythmic drugs should not routinely be
used for rate control. III (harm)

29. Oral antiarrhythmic drugs used for maintaining
sinus rhythm after cardioversion
30
Main contra-indications and precautionsDoseDrug
Caution when using concomitant therapy with QT
prolonging drugs and in patients with SAN or AV
node and conduction disease. The dose of VKAs
and of digitalis should be reduced. Increased risk of
myopathy with statins. Caution in patients with pre-
existing liver disease.
600 mg in
divided doses for
4 weeks, 400 mg
for 4 weeks,
then 200 mg
once daily
Amiodarone
(Cordarone)
Contra-indicated in IHD or reduced LV ejection
fraction. Caution in the presence of SAN or AV
node and conduction disease, renal or liver
impairment, and asthma. Increases concentration
of digitalis and warfarin.
100–150 mg
twice daily
Propafenone
(Rytmonorm)
hypertrophy, systolic heart failure, asthma, pre-
existing QT Contra-indicated in the presence of
significant LV prolongation, hypokalaemia, CrCl<50
mg/mL Moderate renal dysfunction requires careful
adaptation of dose.
80–160 mg
twice daily
d,l sotalol
(Betacor)

30. 31

31. Indications for Catheter Ablation
- Presence of symptomatic AF refractory or
intolerant to at least one Class 1 or Class 3
antiarrhythmic medication.
- In rare clinical situations, it may be
appropriate to perform catheter ablation of AF
as first line therapy. Catheter ablation of AF is
also appropriate in selected symptomatic
patients with heart failure and/or reduced
ejection fraction.
- The presence of a left atrial thrombus is a
contraindication to catheter ablation of AF.

32. 33
Cryo-ablation
In recent years, Cryoballoon (CB) ablation has become
the most efficient alternative to RF catheter ablation
(RFCA) for the treatment of AF (Fig. 9B). The
Cryoballoon (CB) single shot ablation approach to AF
has been designed to shorten and simplify the
ablation procedure for achieving an effective PVI.
Preclinical and clinical studies have shown that CB is
effective in achieving PVI, offering a valid alternative
to RF’s point-by-point approach to PAF treatment.

33. Indications for surgical AF ablation:
(1) Symptomatic AF patients undergoing other
cardiac surgery;
(2) Selected asymptomatic AF patients
undergoing cardiac surgery in whom the ablation
can be performed with minimal risk;
(3) Stand-alone surgery for AF should be
considered for symptomatic AF patients who
prefer a surgical approach, have failed one or
more attempts at catheter ablation, or are not
candidates for catheter ablation.

34. 35

35. COMPLICATIONS OF CATHETER
ABLATION
Catheter ablation of AF is one of the most
complex interventional electro-physiological
procedures. It is therefore to be expected that
the risk associated with AF ablation is higher
than for ablation of most other cardiac
arrhythmias.
36

36. 37
Atrial Fibrillation
Rate versus Rhythm Control
For each patient with AF, the two principal goals of
therapy are symptom control and the prevention of
thromboembolism.
Rate- and rhythm-control strategies improve
symptoms, but neither has been conclusively shown
to improve survival compared to the other.