Académique Documents
Professionnel Documents
Culture Documents
ORIGINAL ARTICLE
a,b,*
, Hossein Shenasa
a,b
, Mona Soleimanieh
KEYWORDS
Atrial brillation;
Catheter ablation;
Heart failure;
Hypertension;
Obstructive sleep apnea;
Stroke
Abstract Atrial brillation (AF) is the most common sustained arrhythmia encountered in clinical
practices with signicant morbidity, mortality and socioeconomic burden. Its prevalence and incidence are on the rise due to an increase in population age. AF has complex electrophysiological
mechanisms, etiology and natural history and thus management is a challenge. More than 80%
of cases in AF are related to an underlying structural heart disease. Stroke and congestive heart failure remain the most signicant complications of AF. Depending on the patients symptoms, duration and type of AF, structural heart disease and non-cardiac comorbidities, several management
options are currently available. Asymptomatic AF carries similar risks as symptomatic AF. Rate
control approach in majority of cases especially elderly patients is reasonable. Novel anticoagulation agents have shifted the paradigm in stroke prevention and management in patients with AF.
Catheter ablation of paroxysmal AF in patients with no to minimal structural heart disease who
have failed at least one antiarrhythmic agent appears reasonable.
2014 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology.
1. Introduction
Atrial brillation (AF) is the most common sustained arrhythmia worldwide with a current prevalence of 2.76.1 million in
the United States and Europe with an estimated increase of
15.9 million in 2050.1 We rst discuss selected topics on
etiologies followed by current management options and future
directions.
1110-2608 2014 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology.
http://dx.doi.org/10.1016/j.ehj.2014.03.004
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
M. Shenasa et al.
(1) First detected or diagnosed AF independent of its duration, and presence or absence of any symptoms.
(2) Paroxysmal AF: Episodes lasting less than 2448 h that
terminate spontaneously but may also last up to
7 days. After this period the rate of spontaneous termination is low and anticoagulation is warranted. Episodes that are longer than 30 seconds are considered
as recurrences. This duration is considered in trials
for drug efcacy.
(3) Persistent AF: Episodes lasting longer than 7 days that
require termination by either direct electrical cardioversion or pharmacological intervention.
(4) Long-lasting persistent AF: Episodes lasting longer than
one year. This denition is created for cases where a
rhythm control strategy is recommended mostly to consider catheter ablation of AF.
(5) Permanent AF: Episodes when patients and their physician accept to maintain AF, or when restoring sinus
rhythm is not attempted or failed and rate control is
the chosen strategy over rhythm control.
(6) Lone AF: Dened as AF in patients below age 60 with
no clinically detectable structural cardiovascular disease,
which could be paroxysmal, persistent, or permanent.
(7) AF Burden: Dened as the proportion of time patients
are in AF.
AF maybe associated with other arrhythmias, the most
common ones being atrial utter, atrial tachycardia. Less frequently AV nodal reentrant tachycardia (AVNRT) and accessory pathway tachycardia are associated with AF. These
arrhythmias may coexist with AF as seen in Fig. 2AD (same
patient).
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
Figure 2 (AD) Panel A: AF with rapid ventricular response. Panel B: Atrial utter with 2:1 AV conduction. Panel C: Sustained
AVNRT with conversion to sinus rhythm and reinitiation of AF in panel D.
Figure 3 Illustrates the different etiologies of AF. Many of them maybe interconnected. Modied from Shenasa et al. Individualized
therapy in patients with atrial brillation: new look at atrial brillation, Europace 2012.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
M. Shenasa et al.
Table 1 Risk factors and markers for AF. Modied from Shenasa et al. Atrial brillation in different clinical substrates. In Shenasa M,
Camm JA, editors. Management of atrial brillation: a practical approach. Oxford University Press, in publication.
Traditional risk factors
Electrolyte imbalance
Markers
Pulmonary disease
electrical
C a++-influx
contractility
size of reentry
number of reentries
AF
stretch
contractile
structural
dilatation
RAS activation
conduction
dis order
c omplianc e
fibrosis
loss of a-wave
ECG
LA pressure a
normal
dilated
V
Courtesy of Kb S,
Figure 4
Interplay between the electrical, mechanical and structural remodeling pathways in AF. Courtesy of Stephan Kaab.
silent have been documented by interrogation of implantable pacemakers, implantable cardioverter debrillators or
loop recorders. Importantly the stroke risk of asymptomatic
AF remains the same or even higher than symptomatic ones
(see section on Stroke and AF).8 The varieties of AF monitoring and detection devices that are currently available include
event recorders, smart phones, etc.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
Figure 5 Illustrates the interplay of different pathophysiological processes in AF. (MI : myocardial infarction, LV: left ventricular, AF:
atrial brillation) Courtesy of Ali Sovari MD.
processes and oxidative stress leading to brosis and subsequently AF is depicted in Fig. 5.6
Briey, AF is clearly associated with increased levels of inammatory markers and atrial biopsies in patients with AF have also
conrmed the presence of inammation. There is evidence supporting a link between inammation and AF, and some of the
drug therapies, such as the angiotensin-converting-enzyme
(ACE) inhibitors, angiotensin receptor blockers (ARBs), steroids, sh oils, and vitamin C, that might be efcacious in the prevention of AF by modulating inammatory pathways. However,
randomized trial and longitudinal studies are needed to conrm
the direct relationship between AF and inammation.
The left atrial (LA) anatomy, structure, function and electrophysiology is different than the right atrial (RA). Fibroblasts migrate selectively to the LA secreting collagen,
pectin and are not excitable. Fibroblasts produce atrial brosis and inhomogeneity, which are a good substrate for
arrhythmias.
Recent reports by Marrouche et al., demonstrated that the
magnitude of atrial brosis correlates with increased risk of
AF as well as progression from paroxysmal to persistent and
permanent. Furthermore, the presence of increased brosis will
lower the success rate of catheter ablation as well as an
increase in the risk of recurrence of AF. Marrouche et al., categorized the magnitude of atrial brosis to Utah 14. Utah 1
has 05% brosis, Utah II >520%, Utah III >2035%
and IV >35% (Ref. 8). Kottkamp recently proposed brotic
atrial cardiomyopathy as the substrate for AF.10 Fig. 6 shows
the relationship between magnitude of atrial brosis and types
of AF as detected by delayed-enhanced MRI.
3.7. Atrial brillation progression
In majority of cases AF may initially present as paroxysmal
form and may progress to persistent and eventually become
permanent. The rate of progression is variable and depends
on many factors including magnitude of atrial remodeling,
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
M. Shenasa et al.
Figure 6 Relationship between magnitude of atrial brosis and types of AF as detected by delayed-enhanced MRI. Courtesy of Nassir
Marrouche. (MRI: Magnetic resonance imaging, AF: Atrial brilation)
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
5.1. Atrial brillation and type II diabetes
Type II diabetes is an independent risk factor for developing
AF. Diabetes has been found in 20% of patients with AF
and patients with diabetes have approximately 40% greater
risk of developing AF. The exact mechanism and relationship
between diabetes type II and AF are not fully understood
however it is postulated to be due to atrial patchy amyloid
in the atrium leading to atrial remodeling and brosis which
promotes AF.
5.2. Atrial brillation and hypertrophic cardiomyopathy
Hypertrophic Cardiomyopathy (HCM) is an independent risk
factor for AF and is the most common arrhythmia in patients
with HCM with a prevalence of 22%. As such patients with
HCM carry a 46 fold higher risk of developing AF compared
to the general population.17 AF poses an adverse outcome
effect in patients with AF and once AF occurs in patients with
HCM the prognosis is poor. Most patients with HCM have
signicant hypertrophy, diastolic dysfunction and left atrial
enlargement all of which promote occurrence of AF. Management of AF in patients with HCM is a challenge.
5.3. Atrial brillation and stroke
AF is found in about 25% of patients admitted with ischemic
stroke and it increases the risk of stroke by 36 fold. Stroke is
the most devastating complication of AF and causes death,
neurological decits, longer hospitalization and disability.
Multiple studies have demonstrated the relationship between
AF and stroke. The Stroke Prevention in Atrial Fibrillation
Study (SPAF III) data showed that up to 45% of the patients
enrolled had ECG documentation of AF.18 Stroke can occur
as the rst manifestation of AF. A recent study by Healy
et al.,19 demonstrated that the patient with asymptomatic
silent AF and atrial tachyarrhythmias detected during interrogation of permanent pacemakers and ICDs revealed higher
incidence (50%) of stroke than those without silent AF.
Fig. 8 illustrates an example of asymptomatic atrial tachycardia. Another similar study (TRENDS) provided similar data
and conclusions.20 Based on the STROKESTOP trial it is
7
Table 2
CHADS2
C
H
A
D
S2
Congestive HF
Hypertension
Age P75 yrs
Diabetes
Stroke
1
1
1
1
2
point
point
point
point
points
CHADS2-VASc
C
H
A
D
S2
V
A
Sc
Congestive HF
Hypertension
Age P75 yrs
Diabetes
Stroke
Vascular disease
Age P65 yrs
Sex category, female
1
1
2
1
2
1
1
1
point
point
points
point
points
points
points
points
Figure 8 Example of atrial tachycardia from interrogation of an implantable device in a patient who was recurrent episodes of
asymptomatic (silent) AF.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
8
coronary artery bypass graft (CABG) and up to 6070% of
patients with combined CABG and valve surgery. Almost,
60% of episodes of AF happen in day 23 of post op and more
than 50% of patients experience one episode of post-op AF.
The majority of post-op AF converts to sinus rhythm spontaneously in the rst 2448 h, however if it takes longer than
48 hours it increases the risk of stroke and prolongs hospitalization and its related costs. Risk factors and predictors for
post-op AF include older age, male gender, pervious history
of AF, history of previous cardiac surgery, concomitant valve
surgery, LV dysfunction and impaired renal function. In the
postoperative period volume overload, hyper/hypotension,
inammation, post pericardiotomy syndrome are among the
common risk factors for AF.
Post-operative AF affects both early and late mortality
after isolated CABG. Most of the complications are related
to stroke therefore post-operative surveillance and long-term
management with antiarrhythmic agents and antithrombotic
management is warranted.
Preoperative treatments with beta-blockers have been
shown to effectively reduce the risk of AF since inammation
plays a signicant role in the genesis of post op AF. Colchicine
as well as statins is effective in prevention of this
arrhythmia.23,24.
5.5. Atrial brillation in athletes and during endurance exercise
AF is the most common arrhythmia seen in athletes. The incidence of AF in this population depending on the type of sport
ranges from 5 to 10% and is most common in marathon runners, cyclists and cross country skiers. The mechanism(s) of
endurance exercised AF is not fully understood but maybe
related to left atrial enlargement, inammation, remodeling
and brosis. As well as left ventricular hypertrophy, enhanced
vagal tone and sinus bradycardia, which is a physiological
response to exercise. Aside from restriction of endurance exercise management of AF in athletes remains the same as others,
however current guidelines recommend to rule out the presence of associated conditions such as WolffParkinsonWhite
syndrome, HCM and ARVD/C.25 History, physical examination, ECG and treadmill test should be part of the workup.26
5.6. Genetics of atrial brillation
Lone AF and those occurring in patients 60 years or younger
have a genetic background and it is important to screen
families with a history of AF in young population. Familial
AF is now a known entity and is often associated with
other inherited channelopathies such as Brugada syndrome,
Long and Short QT syndrome and other sodium-channel
mutations.
The most common type of genetic AF is linked to chromosome 4q25.27 In addition, several other genes identied have
been to be linked to AF such as KCNQ1, KCNE2, SCN5A
and others.
Giustetto et al.28 recently reported on the prevalence of AF
in large patient population with Brugada syndrome. The
results revealed that the prevalence with AF and Flutter is
higher than the general population of the same age. Patients
who developed AF and utter after the diagnosis of Brugada
ECG are younger, have a greater prevalence of spontaneous
M. Shenasa et al.
type 1 Brugada ECG and more often experience cardiac arrest.
The prognosis is worse in this patient population compared to
those with Brugada Syndrome without AF and Flutter. At
present genetic testing is not recommended.
5.7. Novel risk factors in atrial brillation
Several novel risk factors have emerged in relation to AF as
seen in Table 1.
5.8. Atrial brillation and obesity
Obesity carries a high risk of developing AF, as it shares multiple etiologies with other comorbidities such as hypertension,
diastolic dysfunction, diabetes type 2, sleep apnea and metabolic syndrome. Obesity adversely affects the response of AF
to antiarrhythmic agents and catheter ablation. Therefore
aggressive lifestyle modications should be discussed with the
patient to potentially reduce the risk of AF.29
5.9. Atrial brillation and obstructive sleep apnea
Obstructive sleep apnea (OSA) is a recognized independent
risk factor for AF. In particular nocturnal AF of either paroxysmal or persistent type is often detected in patients with OSA.
Thus patients with signicant OSA should be screened for the
risk of AF and likewise patients with nocturnal AF should be
screened for possible sleep apnea. Appropriate management of
OSA will decrease the incidence of AF. OSA signicantly
decreases the efcacy of antiarrhythmic agents as well as radiofrequency ablation of AF.30
6. Atrial brillation and kidney disease
Impaired renal function is now recognized among novel risk
factors for incident AF and progression of this arrhythmia.
Chronic kidney disease may be found in about 35% of patients
with AF.31 Patients with end stage renal disease and on kidney
dialysis are at highest risk for developing AF. On the other
hand newly diagnosed AF doubles the mortality in patients
with end stage renal disease and those on dialysis. Furthermore, chronic kidney disease is now emerging as an independent risk factor for occurrence of AF and stroke.32,33
With increasing use of novel oral anticoagulant (NOAC)
agents, caution should be practiced to the use of these agents
as some of them have signicant renal clearance such as
Dabigatran.
7. Management of atrial brillation
The goals of AF management are:
1. Prevention of recurrences and maintenance of sinus
rhythm.
2. Prevention of AF complications: most importantly stroke
prevention including risk stratication for stroke.
3. Prevention of HF.
4. Improving quality of life.
5. Improving survival.
6. Anticoagulation in AF.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
7.1. Acute management of atrial brillation
A majority of patients with acute AF present to hospitals
(emergency rooms). Acute management of AF depends on
the severity of symptoms, which often present as rapid palpitations, increasing shortness of breath, chest pain, light headedness, and rarely syncope. If the patient is hemodynamically
compromised, direct current cardioversion is the safest. If
patients are stable enough pharmacological cardioversion is
done with intravenous Procainamide, Flecainide, Ibutilide,
Vernakalant or Amiodarone depending on the availability of
these drugs34 Fig. 9.
7.2. Drug therapy for atrial brillation
Long-term management of AF should be individualized and
evidence based. Selection should be based according to the
underlying structural heart disease. Although most trials on antiarrhythmic drugs for AF remain unsatisfactory, antiarrhythmic
therapy remains the mainstay of AF management. Two strategies
of rate control versus rhythm control have been discussed in
length elsewhere. 35 Current evidence suggests that rate control
even lenient rate control is not inferior to rhythm control.
7.3. Pharmacologic therapy for rhythm control
In patients with paroxysmal AF with no structural heart disease and normal LV function, Class I C agents may be used
safely. In patients with congestive HF, Amiodarone is more
effective than Sotalol, but has more non-cardiac side effects.36
9
Dofetilide can be used in patients with reduced LV ejection
fraction37 (Fig. 10).
8. Pharmacological therapy for rate control
The selection of pharmacological agents is dictated by a
patients type of AF, underlying structural heart disease most
importantly degree and left ventricular dysfunction and coronary artery disease34 Fig. 11.
8.1. Rate versus rhythm control strategies
The rate control strategies became popular after the large scale
AFFIRM Trial: Atrial brillation follow up investigation of
rhythm management3840 was published. The AFFIRM study
included 4060 patients, 65 years and older with AF and were
randomized into rate or rhythm control strategies. Follow up
included stroke, heart failure, hospitalization and death. The
study found slightly higher trends toward increased mortality
in patients with rhythm control compared to rate control
(p = 0.08). This may have been due to adverse effect of antiarrhythmic therapy that has offset the benet of sinus rhythm. In
a similar trial of rate control versus electrical cardioversion
(RACE Trial), there was no signicant difference between rate
versus rhythm control strategy.41
From these controlled randomized trials it can be concluded
that in older and less active individuals who make the majority
cases of AF, a rate control strategy with appropriate stroke risk
stratication and anticoagulation therapy is acceptable.
Figure 9 Indications for electrical and pharmacological cardioversion, and choice of antiarrhythmic drugs for pharmacological
cardioversion in patients with recent-onset AF. Adopted from Camm JA, Lip GYH, De Caterina R, et al. 2012 Focused update of the ESC
Guidelines for the management of atrial brillation. Eur Heart J 2012;33:27102747.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
10
M. Shenasa et al.
Figure 10 A and B demonstrates a simplied approach with antiarrhythmic therapy for rhythm control in patients with normal LV
systolic function (Panel A) and reduced LV systolic function (Panel B).
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
11
Figure 11 Illustrates the ESC guidelines for rate control approach in patients with AF. Camm JA, Lip GYH, De Caterina R, et al. 2012
Focused update of the ESC guidelines for the management of atrial brillation. Eur Heart J 2012;33:27102747.
Electrical activity arises from pulmonary veins (PVs) that triggers AF and ablation of these triggers eliminates recurrences of
AF. Many reports have conrmed these observations and PV
isolation (PVI) is now the corner stone of catheter ablation of
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
12
M. Shenasa et al.
Table 3 Comparison of warfarin to novel oral anticoagulants. Adopted and modied from Cairn JA. Canadian Journal of
Cardiology 2013;29:11651172.
Feature
Warfarin
Dabigatran
Rivaroxaban
Apixaban
Mechanism
Prodrug
Dose regiment
Administration
AF dose (mg)
Food eect
Food interaction
Bioavailability (%)
tmax (h)
T (h)
Substrate CYP
Substrate P-gp
Renal clearance
Protein binding (%)
Monitoring
AF trial complete
Direct Xa inhibitor
No
Oral
OD
20, 15
Delays absorption
No
80100
24
513
3A4, 2J2
Yes
33
9095
No
Phase III (2010)
Dirext Xa inhibitor
No
Oral
BID
5, 25
No
No
50
34
513
3A4
Yes
27
8793
No
Phase III (2011)
Today catheter ablation of paroxysmal AF is commonly preformed generally after a failure of at least one antiarrhythmic
agent. In 2012 about 50,000 procedures were performed in the
United States. On average the short-term success rate in high
volume experienced centers is about 60% for the rst procedure and 71% after multiple procedures. 1535% of patients
undergo a redo procedure.47
PVI remains the cornerstone of AF ablation, which is often
effective in 5060% of patients with paroxysmal AF
(Figs. 14A and 14B).
Substrate modication, i.e., left atrial and other sources are
often necessary in cases of persistent and long-lasting persistent AF. In more complex cases extensive substrate modication including rooine, posterior left atrial wall ablation;
ablation around the left atrial appendage may be needed.
Fig. 15AC is from our laboratory illustrates a case of AF
as detected in intracardiac electrograms from His bundle and
coronary sinus electrodes. Occasionally after termination of
AF, atrial utter emerges may necessitate ablation at the
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
13
Figure 13
A histogram of published articles between 2000 and 2013 in the English language.
Figure 14A Electroanatomical mapping of the left atrium in a posterioranterior projection illustrates left atrium and pulmonary veins.
Each red dot denotes one ablation lesion for isolation of PVs. CS, coronary sinus; LIPV, left inferior pulmonary vein; LSPV, left superior
pulmonary vein; Posterior LA, Posterior left atrium; RIPV, right inferior pulmonary vein; RSPV, right superior pulmonary vein.
carvo-tricuspid isthmus as shown in Fig. 16. Extensive ablation to the left atrium in some cases produces left atrial tachycardia/utter at the mitral isthmus that also may require
ablation of that region.
Several randomized trials have compared catheter ablation
with antiarrhythmic agents in a randomized fashion. All the
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
14
M. Shenasa et al.
Figure 14B Electroanatomical mapping (EMA) and computerized tomography (CT) of the left pulmonary veins. LAA, left atrial
appendage. Abbreviations same as Fig. 14A above.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
15
Figure 15 (AC) From our laboratory illustrates a case of AF as detected in intracardiac electrograms from HIS bundle and coronary
sinus electrodes.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
16
M. Shenasa et al.
Figure 16 Ablation at the carvo-tricuspid isthmus that abolishes atrial utter in the same patient as Figs. 14A and 14B. The red dots
denote the site of RF ablation.
Figure 17B 2014 AHA/ACC/HRS Guideline for the Management of Patients with AF: Executive Summary. January CT,
Wann S, Alpert JA, et al. J Am College Cardiol 2014.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
procedures without antiarrhythmic agents is at best 71% (65
77%) and multiple procedures with antiarrhythmic agents are
77% (7381%).47 The immediate 3 months are considered a
blanking period as many asymptomatic recurrences have been
detected. Weerasooriya et al.55 reported on the long-term
results after multiple catheter ablation procedures of AF having shown that the sinus rhythm maintained at 1, 2, and
5 years was 87%, 81% and 63%. However after a single procedure 40%, 37% and 29% at 1, 2 and 5 years were reported.55
The associated comorbidities such as hypertension, diastolic
dysfunction, heart failure, obstructive sleep apnea, obesity
and impaired renal function have shown to lower the success
rate of catheter ablation of AF and increase recurrences.
11.1. Outcomes of catheter ablation of atrial brillation
Catheter ablation of AF is taken with much enthusiasm and
the ablationists promoting that the long term outcomes of
AF ablation are superior to antiarrhythmic therapy. However,
there are no large randomized trials to show that the catheter
ablation is superior to medical management in terms of reduction of mortality, stroke, hospitalization, and improvement in
heart failure. Only the MANTRA trial demonstrates that after
2 years the quality of life was better compared to antiarrhythmic therapy. A very recent trial comparing antiarrhythmic
therapy to radiofrequency ablation of AF as rst line therapy
just published showed a lower rate of recurrent paroxysmal
AF in patients who underwent catheter ablation of AF.56,57.
It is hoped that with early intervention and maintenance of
sinus rhythm, atrial remodeling is minimized and improves
the burden of AF. At present no data has demonstrated that
maintaining sinus rhythm with catheter ablation will reduce
the death rate related to AF. Recently Mont et al.58 reported
on catheter ablation vs. antiarrhythmic drug treatment of persistent AF: a multicenter, randomized, controlled trial (SARA
study). The results revealed that catheter ablation was superior
to medical therapy in maintaining sinus rhythm in patients
with persistent AF during a 12-month follow up. The shortcoming of this trial was that the trial was terminated prematurely due to low patient recruitment and the primary
endpoint of the study was only recurrences of AF 24 h after
ablation.
Dagres et al.,59 reported on a meta-analysis of randomized
trial that there were no mortality benets of catheter ablation
over drug therapy. Similarly two Canadian trials of AF-CHF60
Figure 18
17
and the RAAFT study (rst line radiofrequency ablation versus antiarrhythmic drugs for atrial brillation treatment) did
not show mortality benet of catheter ablation.
12. Imaging before and during AF ablation
(1) Preprocedure imaging includes transthoracic echocardiogram, cardiac computerized tomography (CT) to
evaluate left atria and PVs geometry and its branch as
seen in Fig. 19.
(2) Intraprocedural imaging includes magnetic resonance
imaging (MRI) to evaluate the degree of brosis, intracardiac echocardiography (ICE), electroanatomical
mapping, magnetic resonance imaging and direct visualization of ablation lesion (currently under investigation).
(A) Depicts circular mapping and ablation catheter. (B) Cryoballoon ablation catheter. Image courtesy of Medtronic, Inc.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
18
M. Shenasa et al.
Figure 19
CT angio and Fly Thru of the LA and Pulmonary Veins. (LA : left Atrium).
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
blanking period which may be due to the signicant amount
of tissue damage and edema that promotes AF.
14.6. Procedural end points
At present there is no uniform agreement on what is accepted
as end points of catheter ablation. These uncertainties are due
in part to the following issues: (1) AF types, i.e., paroxysmal,
persistent and long lasting persistent. (2) Ablation protocols,
i.e., PVI only or additional ablation. (3) Ablation techniques
i.e. radiofrequency, cyroablation, laser, etc. (4) Immediate post
ablation protocol, i.e., burst pacing, isoproterenol infusion,
adenosinetriphosphate administration etc. (5) Duration and
methods of rhythm monitoring.
14.7. Cost of catheter ablation of atrial brillation
Catheter ablation is an expensive procedure with the initial
cost and 5 year follow up totaling a sum of $30,00035,000
per patient in the United States.55,79 McKenna et al.76 report
the cost of catheter ablation in United Kingdom to be
7700 - 7900 pound while Canada having a cost of $16,278.7577
15. Future directions in catheter ablation of atrial brillation
Due to relatively high recurrence rates even after the blanking
period and the need for repeated procedure, newer ablation
technologies are sought. Endoscopic navigation and visualization of the target tissue and ablation effect on the atria are
under investigation. Preliminary reports have examined the
feasibility of this method in experimental animal and the rst
200 patients.78
(1) Recent reports revealed that case done in community
hospitals with low volume procedures had higher complication rates of about 6.2%. Whereas procedures that
are performed in high volume centers with experienced
operators had lower complication rates (3.9%).6164
(2) Direct vision during catheter ablation to better identify
the target tissue and its effect on the atrial tissue.78,79
(3) Since radiation during the procedure is an important
issue to the patient, operator and cath lab staff, newer
technologies are emerging to use ionized radiation free
techniques such as magnetic resonance guided EP study
and ablation. Preliminary results are favorable however;
no long-term results are available.
15.1. Concepts to consider in the future management of AF
Selective ion channel blockers.
Multi-channel blockade (like Amiodarone, Dronedarone
and Ranolazine).
Atrial channel selective (usually relative).
Substrate based mapping and ablation.
Gap junction conduction.
Fibrosis.
Inammation.
Future AF management should focus on personalized risk
factors that better predict the best approach (pharmacological
or nonpharmacological), identify risk and biomarkers as well
19
as better understanding of genetic, environmental interaction
with such complex arrhythmias. At the same time improvement in AF detection tools and imaging techniques of both
the heart and brain to better understand the pathophysiology
of AF, i.e., system biology. Furthermore, the burden of
brosis should be on the future agenda.
16. Future opportunities
(1) Noninvasive characterization of AF and its types maybe
useful in the identication of patient proles.
(2) At present there are no uniform protocols for catheter
ablation of AF and it remains empirical. Hopefully the
future trials will provide insights to design uniform protocols. This inconsistency maybe imparted due to the
complexity of substrate and presence of evolving underlying heart disease such as HF, hypertension. As such
there remain many unanswered questions like endpoints,
follow-ups and denition of success, etc.
(3) Atrial selective antiarrhythmic and upstream therapy
will continue to expand.
(4) Results and technology of catheter ablation of AF will
expand.
(5) The design of future trials should attempt to answer
some of the following questions::
1. What is the best method and duration of rhythm
monitoring post ablation?
2. Comparative effectiveness of various ablation
approaches in paroxysmal and persistent AF, i.e.,
PVI only versus PVI and substrate modication
and neuraplexi ablation, rotor ablation, etc.
3. Can anticoagulation be discontinued in some
patients if they maintain sinus rhythm?
4. Best outcome measures, AF recurrences, hospitalization, stroke, death and quality of life.
5. Cost-effectiveness of catheter ablation.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
20
M. Shenasa et al.
Figure 20 Opportunities and challenges for future AF. AF, atrial brillation; AA, antiarrhythmic therapy; SHD, structural heart
disease; HF, heart failure; CRT, cardiac resynchronization therapy; NOAC, novel oral anticoagulants; LAA, left atrial appendage; CHF,
chronic heart failure; NOAC, novel oral anticoagulants; Echo, echocardiography; CT, computerized tomography; MRI, magnetic
resonance imaging.
Figure 21
Final common pathways of diverse etiologies of inammation, brosis and remodeling lead to AF.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
arrhythmia management according to the guidelines and patient
underlying structural heart disease, and (4) treatment of the
underlying causes.
Our current biomarkers for AF are nonspecic, however a
multimarker approach may improve their sensitivity.
Improved detection methods of AF especially after antiarrhythmic therapy and ablative procedures are important.
Overall, trials to date have failed to show that rhythm control
approach is superior to rate control approach in all-composite
measures, although some trials have shown that patients who
maintained sinus rhythm reported improved quality of life.
According to the recent evidence based and guidelines catheter ablation of AF seems reasonable in patients with paroxysmal AF with no to minimal structural heart disease who have
failed at least one antiarrhythmic agent. Aggressive risk modication of comorbidities such as obesity sleep apnea, impaired
renal function. is necessary and should be an integral part of
AF management. Finally, Berti et al. proposed a multidisciplinary nurse-coordinated AF program to improve detection
management and outcome of patients with AF. This approach
will begin with comprehensive risk assessment, patient education, patient centered medical care and evaluation of management outcome.86
As AF is an evolving disease we will witness a signicant
paradigm shift in understanding the pathophysiology and
management of AF. Fig. 20 demonstrates the opportunities
and challenges for future AF.
Finally, all AF patients are not the same and AF is not a
disease it is a symptom like fever, syncope, etc. Management
should be etiology based rather than mechanism based. Prevention should be the rst line of therapy. As inammation,
brosis and remodeling are the nal common pathway of
diverse etiologies, innovative therapies should focus on brosis
and inammation as shown in Fig. 21.
Conict of Interest
None.
References
1. Lloyd-Jones DM, Wang TJ, Leip EP, et al. Lifetime risk for
development of atrial brillation: the Framingham Heart Study.
Circulation 2004;110:10426.
2. Zakeri R, Borlaug BA, McNulty ST, et al. Impact of atrial
brillation on exercise capacity in heart failure with preserved
ejection fraction. A RELAX trial ancillary study. Circ Heart Fail
2014;7:12330.
3. Dorian P, Guerra PG, Kerr CR, et al. Validation of a new simple
scale to measure symptoms in atrial brillation: the Canadian
cardiovascular society severity in atrial brillation scale. Circ
Arrhythm Electrophysiol 2009;2:21824.
4. Dewland TA, Olgin JE, Vittinghoff E. Incident atrial brillation
among Asians, Hispanics, Blacks, and Whites. Circulation
2013;128:24707.
5. Moe GK, Rheinbolt WC, Abildskov JA. A computer model of
atrial brillation. Am Heart J 1964;67:20020.
6. Guo Y, Lip GYH, Apostolakis S. Inammation in atrial brillation. J Am Coll Cardiol 2012;60:226370.
7. Haissaguerre M, Jais P, Shah DC, et al. Spontaneous initiation of
atrial brillation by ectopic beats originating in the pulmonary
veins. N Engl J Med 1998;339:65966.
21
8. Mittal S, Movsowski C, Steinberg JS. Ambulatory external
electrocardiographic monitoring: focus on atrial brillation. J
Am Coll Cardiol 2011;58:17419.
9. Akoum N, Daccarett M, McGann C, et al. Atria brosis helps
select the appropriate patient and strategy in catheter ablation of
atrial brillation: a DE-MRI guided approach. J Cardiovasc
Electrophysiol 2011;22(1):1622.
10. Kottkamp H. Human atrial brillation substrate: towards a
specic brotic atrial cardiomyopathy. Eur Heart J 2013;34:
27318.
11. de Vos CB, Pister R, Nieuwlaat R, et al. Progression from
paroxysmal to persistent atrial brillation. J Am Coll Cardiol
2010;55:72531.
12. Tedrow UB, Conen D, Ridker PM, et al. The long-and short-term
impact of elevated body mass index on the risk of new atrial
brillation: the WHS (Womens Health Study). J Am Coll Cardiol
2010;55:231927.
13. Manolis AJ, Rosel EA, Coca A, et al. Hypertension and atrial
brillation: diagnostic approach, prevention and treatment. J
Hypertens 2012;30:23952.
14. Braunwald E. Shattuck lecturecardiovascular medicine at the
turn of the millennium: triumphs, concerns, and opportunities. N
Engl J Med 1997;337(19):13609.
15. Connolly SJ, Camm JA, Halperin JL, et al. Dronedarone in highrisk permanent atrial brillation. N Engl J Med 2011;365:226876.
16. Rosenberg MA, Manning WJ. Diastolic dysfunction and risk of
atrial brillation: a mechanistic appraisal. Circulation 2012;126:
235362.
17. Olivotto I, Cecchi F, Casey SA, Dolara A, Traverse JH, Maron
BJ, et al. Impact of atrial brillation on the clinical course of
hypertrophic cardiomyopathy. Circulation 2001;104:251724.
18. The SPAF III Writing Committee for the Stroke Prevention in
Atrial Fibrillation Investigators. Patients with noninvasive atrial
brillation at low risk of stroke during treatment with aspirin:
stroke prevention in atrial brillation study. J Am Med Assoc
1998;279:12737.
19. Healey JS, Connolly SJ, Gold MR, et al. Subclinical atrial
brillation and the risk of stroke. N Engl J Med 2012;366:
1209.
20. Daoud EG, Glotzer TV, Wyse DG, et al. Temporal relationship
of atrial tachyarrhythmias, cerebrovascular events, and systemic
emboli based on stored device data: a subgroup analysis of
TRENDS. Heart Rhythm 2011;8:141623.
21. Friberg L, Engdahl J, Frykman V, et al. Population screening of
75-and 76-year-old men and women for silent atrial brillation
(STROKESTOP). Europace 2013;15:13540.
22. Mason PK, Lake DE, DiMarco JP, et al. Impact of the CHA2DS2
score on anticoagulation recommendations for atrial brillation.
Am J Med 2012;125(6):603e16.
23. Omae T, Kanmura Y. Management of postoperative atrial
brillation. J Anesth 2012;26(3):42937.
24. Deftereos S, Giannopoulos G, Papoutsidakis N, et al. Colchicine
and the heart: pushing the envelope. J Am Coll Cardiol 2013;
62(20):181725.
25. Calvo N, Brugada J, Sitges M, Mont L. Atrial brillation and
atrial utter in athletes. Br J Sports Med 2012;46:i3743.
26. La Gerche A et al. Atrial Fibrillation in athletes and the interplay
between exercise and health. Eur Heart J 2013;34:3599602.
27. Lubitz SA, Ozcan C, Magnani JW, Kaab S, Benjamin EJ, Ellinor
PT. Genetics of atrial brillation: implications for future research
directions and personalized medicine. Circ Arrhythm Electrophysiol 2010;3:2919.
28. Giustetto C, Cerrato N, Gribaudo E, et al. Atrial Fibrillation in a
large population with Brugada electrocardiographic pattern:
prevalence; management, and correlation with prognosis. Heart
Rhythm 2014;11:25965.
29. Abed HS, Wittert GA. Obesity and atrial brillation. Obes Rev
2013;13(11):92938.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
22
30. Chilukuri K, Dalal D, Gadrey S. A prospective study evaluating
the role of obesity and obstructive sleep apnea for outcomes after
catheter ablation of atrial brillation. J Cardiovasc Electrophysiol
2010;21:5215.
31. Angiolillo DJ, Capodanno A. Antithrombotic therapy in patients
with chronic kidney disease. Circulation 2012;125:264961.
32. Piccini JP, Stevens SR, Chang Y, Singer DE, Lokhnygina Y, Go
AS, et al. Renal dysfunction as a predictor of stroke and systemic
embolism in patients with nonvalvular atrial brillation: validation of the R2CHADS2 index in the ROCKET AF (Rivaroxaban
vitamin K antagonism for prevention of stroke and embolism trial
in atrial brillation) and the ATRIA (Anticoagulation and risk
factors in atrial brillation) study cohorts. Circulation 2013;127:
22432.
33. Camm J, Kirchhof P, Lip GYH, et al. The ESC textbook of
cardiovascular medicine. 2nd ed. Atrial Fibrillation; 2008.
34. Camm JA, Lip GYH, De Caterina R, et al. 2012 Focused update
of the ESC Guidelines for the management of atrial brillation.
Eur Heart J 2012;33:271047.
35. Falk RH. Is rate control or rhythm control preferable in patients
with atrial brillation? Circulation 2005;111:314157.
36. Singh BN, Singh SN, Reda DJ, et al. Amiodarone versus sotalol
for atrial brillation. N Engl J Med 2005;352:186172.
37. Torp-Pedersen C, Moller M, Bloch-Thomsen PE, et al. Dofetilide
in patients with congestive heart failure and left ventricular
dysfunction. NEJM 1999;341(12):85865.
38. Wyse DG, Waldo AL, DiMarco JP, et al. A comparison of rate
control and rhythm control in patients with atrial brillation. New
Engl J Med 2008;358:266777.
39. Afrm Investigators. A comparison of rate control and rhythm
control in patients with atrial brillation. NEJM 2002;347:
182533.
40. Corley SD, Epstein AE, DiMarco JP, et al. Relationships between
sinus rhythm, treatment, and survival in the atrial brillation
follow-up investigation of rhythm management (AFFIRM) study.
Circulation 2004;109:150913.
41. Van Gelder IC, Hagens VE, Bosker HA. A comparison of rate
control and rhythm control in patients with recurrent persistent
atrial brillation. NEJM 2002;347:183440.
42. Zimetbaum P. An argument for maintenance of sinus rhythm in
patients with atrial brillation. Circulation 2005;111:314150.
43. Cairns JA. Which oral anticoagulant for which atrial brillation
patient: recent clinical trials and evidence-based choices. Can J
Cardiol 2013;29:116572.
44. Jais P, Haissaguerre M, Shah DC, et al. A focal source of atrial
brillation treated by discrete radiofrequency ablation. Circulation
1997;95:5726.
45. Dixit S, Lin D, Frankel DS, et al. Is the elimination of triggers
sufcient? Current controversies in catheter ablation of persistent
atrial brillation. Catheter ablation of persistent atrial brillation:
antral pulmonary vein isolation and elimination of nonpulmonary
vein triggers are sufcient. Circ Arrhyhm Electrophysiol 2012;5:
121623.
46. Hocini M, Ho SY, Kawara T, et al. Electrical conduction in
canine pulmonary veins: electrophysiology and anatomic correlation. Circulation 2002;105:24428.
47. Calkins H. Catheter ablation to maintain sinus rhythm. Circulation 2012;125:143945.
48. Po SS, Nakagawa H, Jackman WM. Localization of left atrial
ganglionated plexi in patients with atrial brillation. J Cardiovasc
Electrophysiol 2009;20:11869.
49. Santangeli P, Di Biase L, Burkhart JD, et al. Catheter ablation of
atrial brillation under therapeutic warfarin should be adopted
worldwide. J Cardiovasc Electrophysiol 2013;24(5):5168.
50. Nademanee K, Amnueypol M. Recent observations in mapping of
complex fractionated atrial electrograms in atrial brillation
(CFAE). In: Shenasa et al., editor. Cardiac mapping. 4th ed.
Wiley-Blackwell, 2013; 351.
M. Shenasa et al.
51. Dinov B, Arya A, Hindricks G. Stepwise approach to management of atrial antiarrhythmias after catheter ablation of atrial
brillation. In: Shenasa et al., editor. Cardiac Mapping, 4th ed.
Wiley-Blackwell, 2013; 351.
52. Lin YJ, Chang SL, Lo LW. Mapping of the atrial electrogram in
sinus rhythm and different atrial brillation substrates. In:
Shenasa et al., editor. Cardiac Mapping, 4th ed. Wiley-Blackwell,
2013; 328.
53. ONeill MD, Jais P, Hocini M, et al. Catheter ablation for atrial
brillation. Circulation 2007;116:151523.
54. Narayan SM, Krummen DE, Shivkumar K. Treatment of atrial
brillation by the ablation of localized sources: CONFIRM
(conventional ablation for atrial brillation with or without focal
impulse and rotor modulation) trial. J Am Coll Cardiol 2012;60:
62836.
55. Weerasooriya R, Khairy P, Litalien J, et al. Catheter ablation for
atrial brillation: are results maintained at 5 years of follow-up? J
Am Coll Cardiol 2011;57:1606.
56. Morillo CA, Verma A, Connolly SJ, et al. Radiofrequency
ablation vs. antiarrhythmic drugs as rst line treatment of
paroxysmal atrial brillation (RAFFT-2): a randomized trial.
JAMA 2014;311(7):692.
57. Calkins H, Reynold MR, Spector P, et al. Treatment of atrial
brillation with antiarrhythmic drugs or radiofrequency ablation:
two systematic literature reviews and meta-analyses. Circulation
2009;2:34961.
58. Mont L, Bisbal F, Hernandez-Madrid A, et al. Catheter ablation
vs. antiarrhythmic drug treatment of persistent atrial brillation: a
multicentre, randomized, controlled trial (SARA study). Eur
Heart J 2013.
59. Dagres N, Varounis C, Flevari P, et al. Mortality after catheter
ablation for atrial brillation compared with antiarrhythmic drug
therapy. A meta-analysis of randomized trials. Am Heart J 2009;
158(1):1520.
60. Roy D, Talajic M, Nattel S, et al. Rhythm control versus rate
control for atrial brillation and heart failure. N Engl J Med
2008;358:266777.
61. Cappato R, Calkins H, Chen SA, et al. Worldwide survey on the
methods, efcacy, and safety of catheter ablation for human atrial
brillation. Circulation 2005;111:11005.
62. Cappato R, Calkins H, Chen SA, et al. Updated worldwide
survey on the methods, efcacy, and safety of catheter ablation for
human atrial brillation. Circ Arrhythm Electrophysiol 2010;3:
328.
63. Gupta A, Perera T, Ganesan A, et al. Complications of catheter
ablation of atrial brillation: a systemic review. Circulation
2013;6:10828.
64. Deshmukh A, Patel NJ, Pant S, et al. In-hospital complications
associated with catheter ablation of atrial brillation in the United
States between 2000 and 2010; analysis of 93,801 procedures.
Circulation 2013;128:210412.
65. Calkins H. Breaking news! When it comes to complications of
catheter ablation of atrial brillation. Exp Matter Circulation
2013;128:2099100.
66. Lee G, Sparks PB, Morton JB, et al. Low risk of major
complications associated with pulmonary vein antral isolation
for atrial brillation: results of 500 consecutive ablation procedures in patients with low prevalence of structural heart disease
from a single center. J Cardiovasc Electrophysiol 2011;22:1638.
67. Queiroga A, Marshall HJ, Clune M, et al. Ablate and pace
revisited: long term survival and predictors of permanent atrial
brillation. Heart 2003;89(9):10358.
68. Ozcan C, Jahangir A, Friedman PA, et al. Long-term survival
after ablation of the atrioventricular node and implantation of a
permanent pacemaker in patients with atrial brillation. N Engl J
Med 2001;344:104351.
69. Brignole M, Botto G, Mont L, et al. Cardiac resynchronization
therapy in patients undergoing atrioventricular junction ablation
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004
atrial brillation
70.
71.
72.
73.
74.
75.
76.
77.
78.
23
79. Dukkipati SR, Neuzil P, Kautzner J, et al. The durability of
pulmonary vein isolation using the visually guided laser balloon
catheter: multicentre results of pulmonary vein remapping studies.
Heart Rhythm 2012;9:91925.
80. Catheter ablation vs. anti-arrhythmic Drug Therapy for Atrial
Fibrillation
(CABANA).
http://clinicaltrials.gov/ct2/show/
NCT00911508.
81. Kirchhof P, Breithardt G, Camm JA, et al. Improving outcomes
in patients with atrial brillation: Rationale and design of the
Early treatment of Atrial brillation for Stroke prevention(EAST)
Trial. Am Heart J 2013;156:4428.
82. University of Ottawa Heart Institute. Rate versus catheter
ablation rhythm control in patients with heart failure and highburden atrial brillation (RAFT-AF). Available at http://clinicaltrials.gov/ct2/show/NCT01420393.
83. Population Health Research Institute. First line radiofrequency
ablation versus antiarrhythmic drugs for atrial brillation treatment (The RAAFT Study). Available at http://http://clinicaltrials.gov/ct2/show/NCT00392054
84. Morillo CA, Verma A, Connolly SJ, et al. Radiofrequency
ablation vs. antiarrhythmic drugs as rst line treatment of
paroxysmal atrial brillation (RAFFT-2): A randomized trial.
JAMA 2014;311(7):692.
85. Marrouche NF, Wilber D, Hindricks G, et al. Association of
Atrial Tissue Fibrosis Identied by Delayed Enhancement MRI
and Atrial Fibrillation Catheter Ablation. The DECAAF Study.
JAMA 2014;311(5):498506.
86. Berti D, Hendricks JML, Brandes A, et al. A proposal for
interdisciplinary nurse-coordinated atrial brillation expert programmes as a way to structure daily practice. Eur Heart J
2013;34:272530.
Please cite this article in press as: Shenasa M et al. Update on atrial brillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/
j.ehj.2014.03.004