up to date atrial fibrillation.pdf

The Egyptian Heart Journal (2014) xxx, xxx–xxx

Egyptian Society of Cardiology

The Egyptian Heart Journal

www.elsevier.com/locate/ehjwww.sciencedirect.com

ORIGINAL ARTICLE

Update on atrial fibrillation

* Corresponding author at: Heart & RhythmMedical Group, 105 N.

Bascom Ave Suite 204, San Jose, CA, USA. Tel.: +1 (408) 918 9400;

fax: +1 (408) 286 2922.

E-mail address: [email protected] (M. Shenasa).

Peer review under responsibility of Egyptian Society of Cardiology.

Production and hosting by Elsevier

1110-2608 ª 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 fibrillation, The Egypt Heart J (2014), http://dx.doi.org/1j.ehj.2014.03.004

Mohammad Shenasa a,b,*, Hossein Shenasa a,b, Mona Soleimanieh a

a Heart & Rhythm Medical Group, San Jose, CA, USAb Department of Cardiovascular Services, O’Connor Hospital, San Jose, CA, USA

Received 12 March 2014; accepted 23 March 2014

KEYWORDS

Atrial fibrillation;

Catheter ablation;

Heart failure;

Hypertension;

Obstructive sleep apnea;

Stroke

Abstract Atrial fibrillation (AF) is the most common sustained arrhythmia encountered in clinical

practices with significant morbidity, mortality and socioeconomic burden. Its prevalence and inci-

dence 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 fail-

ure remain the most significant complications of AF. Depending on the patient’s symptoms, dura-

tion 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 anticoagula-

tion 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.ª 2014 Production and hosting by Elsevier B.V. on behalf of Egyptian Society of Cardiology.

1. Introduction

Atrial fibrillation (AF) is the most common sustained arrhyth-mia worldwide with a current prevalence of 2.7–6.1 million inthe United States and Europe with an estimated increase of

15.9 million in 2050.1 We first discuss selected topics onetiologies followed by current management options and futuredirections.

2. Clinical presentation of atrial fibrillation

AF is generally diagnosed by an electrocardiogram and ischaracterized by absence of P-wave, with fibrillatory wavesusually <200 ms with absolutely irregularly irregular heart

rate. Symptoms of AF depend mainly on the rate, irregular-ity, and underlying structural heart disease, such as heartfailure (HF) and coronary artery disease (CAD) and valvu-

lar heart disease. AF may present as rapid palpitations,chest pain, and shortness of breath, dizziness, light-headed-ness and rarely syncope where rapid ventricular response is

present. Diminished exercise capacity (malaise and fatigue)and symptoms of transient ischemic attack and stroke areamong other symptoms. AF impacts exercise capacity in

patients with HF either with preserved or reduced systolicfunction.2

On the other hand many episodes of AF remain unnoticed‘‘silent’’ and are often detected during routine physical exami-

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2 M. Shenasa et al.

nation or upon admissions to the hospital for other causessuch as HF and stroke.

3. Classification of atrial fibrillation

AF is classified into four categories based on its duration asshown in Fig. 1 below.

(1) First detected or diagnosed AF independent of its dura-tion, and presence or absence of any symptoms.

(2) Paroxysmal AF: Episodes lasting less than 24–48 h thatterminate spontaneously but may also last up to7 days. After this period the rate of spontaneous termi-

nation is low and anticoagulation is warranted. Epi-sodes that are longer than 30 seconds are consideredas recurrences. This duration is considered in trials

for drug efficacy.(3) Persistent AF: Episodes lasting longer than 7 days that

require termination by either direct electrical cardiover-sion or pharmacological intervention.

(4) Long-lasting persistent AF: Episodes lasting longer thanone year. This definition is created for cases where arhythm control strategy is recommended mostly to con-

sider catheter ablation of AF.(5) Permanent AF: Episodes when patients and their physi-

cian accept to maintain AF, or when restoring sinus

rhythm is not attempted or failed and rate control isthe chosen strategy over rhythm control.

(6) Lone AF: Defined as AF in patients below age 60 withno clinically detectable structural cardiovascular disease,

which could be paroxysmal, persistent, or permanent.(7) AF Burden: Defined as the proportion of time patients

are in AF.

AF maybe associated with other arrhythmias, the mostcommon ones being atrial flutter, atrial tachycardia. Less fre-

quently AV nodal reentrant tachycardia (AVNRT) and acces-sory pathway tachycardia are associated with AF. Thesearrhythmias may coexist with AF as seen in Fig. 2A–D (same

patient).

Figure 1 Different types of AF according to its duration. ( CV:

Cardioversion) Camm J, Kirchhof P, Lip GYH, et al. Guidelines

for management of atrial fibrillation. Eur Heart J 2010;31:2369–

2429.

Please cite this article in press as: Shenasa M et al. Update on atriaj.ehj.2014.03.004

Furthermore, ventricular tachycardia and AF may be seenin the same patients especially those with advanced HF.

3.1. Atrial fibrillation and quality of life

It is shown that patients with AF have poorer quality of lifecompared to healthy individuals.3

3.2. Recent epidemiological observations of atrial fibrillation

The lifetime risk of developing AF after age 40 is one in four andwill increase with advanced age.1 Essentially, AF is an age-developed disease, occurring in 10% of patients at the age of

90. AF is more common in Caucasians thanAfrican–Americansand Hispanics.4 Subclinical silent or asymptomatic AF hasbecome more recognizable and recent observations suggest it

carries the same risk of stroke as symptomatic AF. AF is oneof the most common arrhythmias for emergency room visitsand hospitalizations and accounts for most of AF related costs.

Health outcomes: Incident of AF increases the risk of allcauses as well as cardiovascular mortality by 1.5–2 fold andthe risk is even higher in women (5-fold).1 AF has a diverse eti-ology as shown in Fig. 3

3.3. Etiologies of atrial fibrillation

AF has a very diverse and often multiple etiologies, such as

hypertension, coronary disease, HF, thyrotoxicosis, acutemyocardial infarction as shown in Fig. 3. Some recently recog-nized etiologies and risk factors such as obesity; obstructive

sleep apnea and impaired renal function are also related to AF.Hypertension is the most common cause of AF is followed

by HF, valvular heart disease, left ventricular hypertrophy

(LVH), left atrial enlargement, CAD and diabetes. Less com-mon etiologies are hyperthyroid state and alcohol use.Recently, novel etiologies such as obesity, obstructive sleepapnea (OSA), impaired renal function and smoking have

emerged. A variety of traditional and novel risk factors andmarkers are shown below in Table 1.

3.4. Pathophysiology and mechanisms of atrial fibrillation

Since the initial description by Gordon Moe.5 that multiplereentrant wavelets are present during computer simulations

and experimental models of AF, multiple mechanisms someof which maybe present simultaneously have been proposedand can be classified as follows:6

(A) Single source:a. Automatic focus from either pulmonary veins (PVs)

or atrial tissues.

b. Mother wave.c. Fixed rotor.d. Moving rotor.

(B) Multiple sources:

l fibril

1) Multiple foci.

2) Unstable circuits.3) Multiple wavelengths.4) Focus + multiple wave lengths.

lation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/



Figure 3 Illustrates the different etiologies of AF. Many of them maybe interconnected. Modified from Shenasa et al. Individualized

therapy in patients with atrial fibrillation: new look at atrial fibrillation, Europace 2012.

Figure 2 (A–D) Panel A: AF with rapid ventricular response. Panel B: Atrial flutter with 2:1 AV conduction. Panel C: Sustained

AVNRT with conversion to sinus rhythm and reinitiation of AF in panel D.

atrial fibrillation 3

It is now well established that AF begets AF and cellular
and ionic remodeling (electrical, mechanical and neuro hor-monal) plays a significant role in initiation and progression
of AF (Fig. 4).With the landmark report by Haisseguerre et al.7 rapid

depolarization from PVs that can initiate and perpetrate AF


has led investigators to better understand mechanism(s) ofAF and develop novel therapeutic approaches to AF. The

mechanism by which PV fires and triggers AF is poorly under-stood, but it may be related to genetic factors, stretch, neuro-hormonal and autonomic influences. Non-pulmonary thoracicveins such as coronary sinus, superior and inferior vena cava

l fibrillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/



action potential duration

stretch

compliance

contractile

electricalAPD

refractoryperiod

size of reentry

contractility

RAS activation

fibrosis

dilatationstructural

number of reentriesAF

loss of a-wave

ECGLA pressure a V

normal dilated

Ca++-influx

conductiondis order

Remodeling in Atrial Fibrillation

Courtesy of Kääb S,

Figure 4 Interplay between the electrical, mechanical and structural remodeling pathways in AF. Courtesy of Stephan Kaab.

Table 1 Risk factors and markers for AF. Modified from Shenasa et al. Atrial fibrillation in different clinical substrates. In Shenasa M,

Camm JA, editors. Management of atrial fibrillation: a practical approach. Oxford University Press, in publication.

Traditional risk factors Novel risk factors Markers

Age, male sex Reduced vascular compliance Increased arterial stiffness

Hypertension/diabetes mellitus Atherosclerosis Prolonged QRS duration

Alcohol consumption Insulin resistance P-wave dispersion

Clinical conditions Environmental factors (air pollution, etc.) Low birth weight

Left ventricular hypertrophy Excess vitamin D Inflammatory markers

Myocardial infarction/heart failure Atrial fibrosis Neurohormones

Valvular heart disease Antiarrhythmic agents Genetic variants

Thyroid disease Extreme exercise Pulse pressure

Prior cardiac surgery/post-cardiac surgery Inflammation Thyroid stimulation hormone, T3, T4

Congenital heart disease Obstructive sleep apnea ANP

Cardiomyopathies Obesity/metabolic syndrome Hs-CRP

Inherited channelopathies Smoking Interleukin-6

Autonomic imbalance Chronic kidney disease Angiotensin II

Markers for fibrosis

Electrolyte imbalance Echocardiographic predictors of AF: - LV fractional

shortening- Mitral annular calcification- Left atrial

enlargment- LVH ( LV wall thickness)

Pulmonary disease

4 M. Shenasa et al.

and vein of Marshall can but less often, be a source of

abnormal firing and triggers of AF. Autonomic innervationto the heart particularly in the atria as well as intrinsicneural pelxi in the atria, as well as direct sympathetic and para-sympathetic activity can play a significant role in the pathogen-

esis of AF.

3.5. Diagnosis and detection of atrial fibrillation

First step in diagnosis of AF is by rhythm documentation,either by electrocardiogram (ECG), rhythm strips or long-termelectrocardiography, such as Holter monitor or event record-

ers. Recently, many episodes of AF asymptomatic so-called


‘‘silent’’ have been documented by interrogation of implant-

able pacemakers, implantable cardioverter defibrillators orloop recorders. Importantly the stroke risk of asymptomaticAF remains the same or even higher than symptomatic ones(see section on Stroke and AF).8 The varieties of AF monitor-

ing and detection devices that are currently available includeevent recorders, smart phones, etc.

3.6. Inflammation, fibrosis and atrial fibrillation

Several studies have elaborated on the role of inflammationand subsequently fibrosis as an integral part of the

pathophysiology of AF.9 A complex cascade of inflammatory




Figure 5 Illustrates the interplay of different pathophysiological processes in AF. (MI : myocardial infarction, LV: left ventricular, AF:

atrial fibrillation) Courtesy of Ali Sovari MD.


processes and oxidative stress leading to fibrosis and subse-

quently AF is depicted in Fig. 5.6

Briefly,AF is clearly associatedwith increased levels of inflam-matory markers and atrial biopsies in patients with AF have also

confirmed the presence of inflammation. There is evidence sup-porting a link between inflammation and AF, and some of thedrug therapies, such as the angiotensin-converting-enzyme(ACE) inhibitors, angiotensin receptor blockers (ARBs), ste-

roids, fish oils, and vitaminC, thatmight be efficacious in the pre-vention of AF bymodulating inflammatory pathways. However,randomized trial and longitudinal studies are needed to confirm

the direct relationship between AF and inflammation.The left atrial (LA) anatomy, structure, function and elec-

trophysiology is different than the right atrial (RA). Fibro-

blasts migrate selectively to the LA secreting collagen,pectin and are not excitable. Fibroblasts produce atrial fibro-sis and inhomogeneity, which are a good substrate for

arrhythmias.Recent reports by Marrouche et al., demonstrated that the

magnitude of atrial fibrosis correlates with increased risk ofAF as well as progression from paroxysmal to persistent and

permanent. Furthermore, the presence of increased fibrosis willlower the success rate of catheter ablation as well as anincrease in the risk of recurrence of AF. Marrouche et al., cat-

egorized the magnitude of atrial fibrosis to Utah 1–4. Utah 1has 0–5% fibrosis, Utah II >5–20%, Utah III >20–35%and IV >35% (Ref. 8). Kottkamp recently proposed fibrotic

atrial cardiomyopathy as the substrate for AF.10 Fig. 6 showsthe relationship between magnitude of atrial fibrosis and typesof AF as detected by delayed-enhanced MRI.

3.7. Atrial fibrillation progression

In majority of cases AF may initially present as paroxysmalform and may progress to persistent and eventually become

permanent. The rate of progression is variable and dependson many factors including magnitude of atrial remodeling,


associated structural heart disease and their progression.11 It

is unknown why in some patients it takes a few months forparoxysmal AF to become permanent and others 30 years.

3.8. Biomarkers of atrial fibrillation (see Table 1)

Certain pathophysiological markers are used to assess the riskof AF and its progression as well as the response to therapyand interventions. The most common biomarkers that are used

in clinical practice are B-type natriuretic peptide (BNP) and C-reactive protein (CRP), which predict the high risk of incidentAF, and its progression. However, most of our biomarkers are

nonspecific and overlap with other cardiac and non-cardiacconditions making their clinical utility marginal. It maybe thatin the future the biomarker scores integrated with other risk

score systems to better select high risk individuals, but to datetheir clinical appreciation is limited. Other biomarkers likeinterleukin-6 and tissue necrosis factors have been reported

and are currently under investigation in large trials.

3.9. Hypertension and atrial fibrillation

Hypertension is the most common risk factor for AF and is

present in 70–80% of patients with AF. Hypertension causesleft ventricular hypertrophy (LVH), diastolic dysfunction, leftatrial hypertrophy and fibrosis, all of which promote AF.

Long-term longitudinal studies from Framingham HeartStudy1 and Women’s Health Study revealed both high systolicand diastolic BP increase the risk of developing AF.12 Almost

one-third of AF patients with hypertension remain asymptom-atic. A combination of hypertension and AF is present in 72%of stroke patients and 82% of patients with chronic kidney dis-

ease, 77% of those with diabetes, 73% of those with CAD,71% of patients with HF, and 62% with metabolic syndrome.In addition, hypertension is seen in 49–90% of AF trials.13

LVH alone is an independent risk factor of AF recurrences.




Figure 6 Relationship between magnitude of atrial fibrosis and types of AF as detected by delayed-enhanced MRI. Courtesy of Nassir

Marrouche. (MRI: Magnetic resonance imaging, AF: Atrial fibrilation)

A

B

Figure 7 Panel A: Demonstrates the interplay between AF and

HF cycle and Panel B HF–AF cycle. (AF, atrial fibrillation; ANP,

atrial natriuretic peptide; BNP, brain natriuretic peptide; EDP,

end diastolic pressure; LAP, left atrial pressure; HF, heart failure;

LVD, left ventricular dilation). Courtesy of Alfred Bove.

6 M. Shenasa et al.

4. Heart failure and atrial fibrillation

4.1. Atrial fibrillation in patients with decreased left ventriculardysfunction

AF is the most common dysrhythmia in patients with HF andthere exists significant association between AF and HF. Both

conditions share many risk factors. AF and HF are two impor-tant emerging epidemics in medicine.14 AF causes HF and HFcauses AF (HF begets AF and AF begets HF).

The AF–HF cycle: There exists a complex interaction andrelationship between the two diseases. Data from Framinghamstudy demonstrated that AF and HF often coexist and that

both often have an adverse effect on each other irrespectiveof which comes first (chicken or the egg). Data from multiplelongitudinal studies suggest AF increases the risk of HF by

2–3 fold, and HF also increases the likelihood of AF and pro-motes AF from paroxysmal to permanent. About one-third ofpatients with HF will develop AF (Fig. 7). The incidence of AFin patients with HF increases according to the severity of HF

and yet remains diverse. Furthermore, the prevalence of AF inHF increases according to the New York Heart Association(NYHA) Class ranging from 4% in NYHA Class I to almost

50% in NYHA Class VI. Furthermore, HF poses a significantrisk of proarrhythmia in patients treated with antiarrhythmicagents for AF. A recent trial on the use of dronedarone in

high-risk patients with AF (i.e. those with HF and reduced sys-tolic function) revealed the unexpected deleterious effect withincreased mortality in patients who received dronedarone com-

pared to a placebo.15

5. Atrial fibrillation in patients with diastolic dysfunction (AF

with preserved LV systolic function)

Diastolic dysfunction is now recognized as an independent riskfactor for incident AF. In patients with diastolic dysfunction,the most common findings are left atrial enlargement,


increased left atrial afterload and preload as well as increasedatrial wall stress and fibrosis, as they all promote occurrence ofAF.16 Diastolic dysfunctions share many etiologies with AFsuch as hypertension, cardiomyopathies, diabetes.




Table 2 Risk scheme for CHADS2 and CHADS2-VASc.

CHADS2

C Congestive HF 1 point

H Hypertension 1 point

A Age P75 yrs 1 point

D Diabetes 1 point

S2 Stroke 2 points

CHADS2-VASc

C Congestive HF 1 point

H Hypertension 1 point

A Age P75 yrs 2 points

D Diabetes 1 point

S2 Stroke 2 points

V Vascular disease 1 points

A Age P65 yrs 1 points

Sc Sex category, female 1 points


5.1. Atrial fibrillation and type II diabetes

Type II diabetes is an independent risk factor for developingAF. Diabetes has been found in 20% of patients with AFand patients with diabetes have approximately 40% greater

risk of developing AF. The exact mechanism and relationshipbetween diabetes type II and AF are not fully understoodhowever it is postulated to be due to atrial patchy amyloidin the atrium leading to atrial remodeling and fibrosis which

promotes AF.

5.2. Atrial fibrillation and hypertrophic cardiomyopathy

Hypertrophic Cardiomyopathy (HCM) is an independent riskfactor for AF and is the most common arrhythmia in patientswith HCM with a prevalence of 22%. As such patients with

HCM carry a 4–6 fold higher risk of developing AF comparedto the general population.17 AF poses an adverse outcomeeffect in patients with AF and once AF occurs in patients with

HCM the prognosis is poor. Most patients with HCM havesignificant hypertrophy, diastolic dysfunction and left atrialenlargement all of which promote occurrence of AF. Manage-ment of AF in patients with HCM is a challenge.

5.3. Atrial fibrillation and stroke

AF is found in about 25% of patients admitted with ischemic

stroke and it increases the risk of stroke by 3–6 fold. Stroke isthe most devastating complication of AF and causes death,neurological deficits, longer hospitalization and disability.

Multiple studies have demonstrated the relationship betweenAF and stroke. The Stroke Prevention in Atrial FibrillationStudy (SPAF III) data showed that up to 45% of the patients

enrolled had ECG documentation of AF.18 Stroke can occuras the first manifestation of AF. A recent study by Healyet al.,19 demonstrated that the patient with asymptomatic‘‘silent’’ AF and atrial tachyarrhythmias detected during inter-

rogation of permanent pacemakers and ICDs revealed higherincidence (50%) of stroke than those without silent AF.Fig. 8 illustrates an example of asymptomatic atrial tachycar-

dia. Another similar study (TRENDS) provided similar dataand conclusions.20 Based on the STROKESTOP trial it is

Figure 8 Example of atrial tachycardia from interrogation of an

asymptomatic (silent) AF.


recommended that patients with silent AF should be screenedfor the risk of stroke.21

Several stroke risk prediction scores have been proposed.The most widely accepted predictor is CHADS2 (CongestiveHeart Failure (CHF), hypertension, age, diabetes, stroke/tran-

sient ischemic attack). Recently CHADS2-VASC score hasbeen introduced which additionally includes age >65 years,vascular disease and female sex. CHADS2 has been validated

by several studies and CHADS2-VASC is more popular inEurope. There is a stepwise approach increase in risk ofstroke as the CHADS2 or CHADS2-VASC score increases22

(Table 2).

A simplified approach for real world cases is based on apatient’s age being over 65 years and presence of any of thestroke risk factors (CHF, hypertension, diabetes, previous

stroke/transient ischemic attack, vascular disease and femalesex), anticoagulation is recommended. Otherwise no treatmentor aspirin is the recommended management.

5.4. Post-operative atrial fibrillation

AF is the most common arrhythmia after cardiac surgery and

occurs approximately in 20–50% of patients depending on thetype of surgery. AF occurs in 30–40% of patients post

implantable device in a patient who was recurrent episodes of




8 M. Shenasa et al.

coronary artery bypass graft (CABG) and up to 60–70% ofpatients with combined CABG and valve surgery. Almost,60% of episodes of AF happen in day 2–3 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 sponta-neously in the first 24–48 h, however if it takes longer than

48 hours it increases the risk of stroke and prolongs hospital-ization and its related costs. Risk factors and predictors forpost-op AF include older age, male gender, pervious history

of AF, history of previous cardiac surgery, concomitant valvesurgery, LV dysfunction and impaired renal function. In thepostoperative period volume overload, hyper/hypotension,inflammation, 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-termmanagement with antiarrhythmic agents and antithromboticmanagement is warranted.

Preoperative treatments with beta-blockers have beenshown to effectively reduce the risk of AF since inflammationplays a significant role in the genesis of post op AF. Colchicine

as well as statins is effective in prevention of thisarrhythmia.23,24.

5.5. Atrial fibrillation in athletes and during endurance exercise

AF is the most common arrhythmia seen in athletes. The inci-

dence of AF in this population depending on the type of sportranges from 5 to 10% and is most common in marathon run-ners, cyclists and cross country skiers. The mechanism(s) ofendurance exercised AF is not fully understood but maybe

related to left atrial enlargement, inflammation, remodelingand fibrosis. As well as left ventricular hypertrophy, enhancedvagal tone and sinus bradycardia, which is a physiological

response to exercise. Aside from restriction of endurance exer-cise management of AF in athletes remains the same as others,however current guidelines recommend to rule out the pres-

ence of associated conditions such as Wolff–Parkinson–Whitesyndrome, HCM and ARVD/C.25 History, physical examina-tion, ECG and treadmill test should be part of the workup.26

5.6. Genetics of atrial fibrillation

Lone AF and those occurring in patients 60 years or youngerhave a genetic background and it is important to screen

families with a history of AF in young population. FamilialAF is now a known entity and is often associated withother inherited channelopathies such as Brugada syndrome,

Long and Short QT syndrome and other sodium-channelmutations.

The most common type of genetic AF is linked to chromo-

some 4q25.27 In addition, several other genes identified havebeen to be linked to AF such as KCNQ1, KCNE2, SCN5Aand others.

Giustetto et al.28 recently reported on the prevalence of AFin large patient population with Brugada syndrome. Theresults revealed that the prevalence with AF and Flutter ishigher than the general population of the same age. Patients

who developed AF and flutter after the diagnosis of BrugadaECG are younger, have a greater prevalence of spontaneous


type 1 Brugada ECG and more often experience cardiac arrest.The prognosis is worse in this patient population compared tothose with Brugada Syndrome without AF and Flutter. At

present genetic testing is not recommended.

5.7. Novel risk factors in atrial fibrillation

Several novel risk factors have emerged in relation to AF asseen in Table 1.

5.8. Atrial fibrillation and obesity

Obesity carries a high risk of developing AF, as it shares multi-ple etiologies with other comorbidities such as hypertension,

diastolic dysfunction, diabetes type 2, sleep apnea and meta-bolic syndrome. Obesity adversely affects the response of AFto antiarrhythmic agents and catheter ablation. Thereforeaggressive lifestyle modifications should be discussed with the

patient to potentially reduce the risk of AF.29

5.9. Atrial fibrillation and obstructive sleep apnea

Obstructive sleep apnea (OSA) is a recognized independentrisk factor for AF. In particular nocturnal AF of either parox-ysmal or persistent type is often detected in patients with OSA.

Thus patients with significant OSA should be screened for therisk of AF and likewise patients with nocturnal AF should bescreened for possible sleep apnea. Appropriate management of

OSA will decrease the incidence of AF. OSA significantlydecreases the efficacy of antiarrhythmic agents as well as radio-frequency ablation of AF.30

6. Atrial fibrillation and kidney disease

Impaired renal function is now recognized among novel riskfactors for incident AF and progression of this arrhythmia.

Chronic kidney disease may be found in about 35% of patientswith AF.31 Patients with end stage renal disease and on kidneydialysis are at highest risk for developing AF. On the other

hand newly diagnosed AF doubles the mortality in patientswith end stage renal disease and those on dialysis. Further-more, chronic kidney disease is now emerging as an indepen-

dent 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 significant renal clearance such asDabigatran.

7. Management of atrial fibrillation

The goals of AF management are:

1. Prevention of recurrences and maintenance of sinusrhythm.

2. Prevention of AF complications: most importantly stroke

prevention including risk stratification for stroke.3. Prevention of HF.4. Improving quality of life.

5. Improving survival.6. Anticoagulation in AF.





7.1. Acute management of atrial fibrillation

A majority of patients with acute AF present to hospitals(emergency rooms). Acute management of AF depends onthe severity of symptoms, which often present as rapid palpita-

tions, increasing shortness of breath, chest pain, light headed-ness, and rarely syncope. If the patient is hemodynamicallycompromised, direct current cardioversion is the safest. Ifpatients are stable enough pharmacological cardioversion is

done with intravenous Procainamide, Flecainide, Ibutilide,Vernakalant or Amiodarone depending on the availability ofthese drugs34 Fig. 9.

7.2. Drug therapy for atrial fibrillation

Long-term management of AF should be individualized and

evidence based. Selection should be based according to theunderlying structural heart disease. Althoughmost trials on anti-arrhythmic drugs for AF remain unsatisfactory, antiarrhythmic

therapy remains themainstay ofAFmanagement. Two strategiesof rate control versus rhythm control have been discussed inlength elsewhere. 35 Current evidence suggests that rate controleven 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 dis-

ease and normal LV function, Class I C agents may be usedsafely. In patients with congestive HF, Amiodarone is moreeffective than Sotalol, but has more non-cardiac side effects.36

Figure 9 Indications for electrical and pharmacological cardiover

cardioversion in patients with recent-onset AF. Adopted from Camm J

Guidelines for the management of atrial fibrillation. Eur Heart J 2012;3


Dofetilide can be used in patients with reduced LV ejectionfraction37 (Fig. 10).

8. Pharmacological therapy for rate control

The selection of pharmacological agents is dictated by apatient’s type of AF, underlying structural heart disease most

importantly degree and left ventricular dysfunction and coro-nary artery disease34 Fig. 11.

8.1. Rate versus rhythm control strategies

The rate control strategies became popular after the large scaleAFFIRM Trial: Atrial fibrillation follow up investigation of

rhythm management38–40 was published. The AFFIRM studyincluded 4060 patients, 65 years and older with AF and wererandomized into rate or rhythm control strategies. Follow up

included stroke, heart failure, hospitalization and death. Thestudy found slightly higher trends toward increased mortalityin patients with rhythm control compared to rate control(p= 0.08). This may have been due to adverse effect of antiar-

rhythmic therapy that has offset the benefit of sinus rhythm. Ina similar trial of rate control versus electrical cardioversion(RACE Trial), there was no significant difference between rate

versus rhythm control strategy.41

From these controlled randomized trials it can be concludedthat in older and less active individuals who make the majority

cases of AF, a rate control strategy with appropriate stroke riskstratification and anticoagulation therapy is acceptable.

sion, and choice of antiarrhythmic drugs for pharmacological

A, Lip GYH, De Caterina R, et al. 2012 Focused update of the ESC

3:2710–2747.




Figure 10 A and B demonstrates a simplified approach with antiarrhythmic therapy for rhythm control in patients with normal LV

systolic function (Panel A) and reduced LV systolic function (Panel B).

10 M. Shenasa et al.

A variety of rate control agents are available includingcalcium antagonist, beta-blockers and digoxin. Combinationsof beta-blockers and digoxin have been found to be mosteffective.34

In certain young active individuals who remain symptom-atic rhythm control is preferred over rate control.34

8.2. Arguements in favor of rhythm control approach

Maintenance of sinus rhythm has been associated withimprovement in quality of life, left ventricular ejection fraction

improved exercise capacity and left atrial size.42 Furthermorepatients who undergo catheter ablation and maintain sinusrhythm have significantly reduced the rate of progression to

permanent AF.


8.3. Arguements against rhythm control approach

1. Rhythm control management is often difficult to achieve.2. Antiarrhythmic drugs have a significant side effect includ-

ing proarrhythmic effect.

3. Antiarrhythmic agents are potentially contraindicated in alarge number of patients.

4. Associated structural heart disease and risk factors modu-late and reduce the response to antiarrhythmic agents and

under certain conditions have a negative effect such asHF and cardiomyopathies.

5. No evidence that maintaining sinus rhythm will improve

survival.6. Due to the high incidence of silent AF anticoagulation

needs to be continued.




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 fibrillation. Eur Heart J 2012;33:2710–2747.


8.4. Argues in favor of rate control approach

1. Rate control agents are safe and do not produce

proarrhythmia.2. Rate control even lenient rate control approach is not infe-

rior to rate control.

3. In patients with CHF large randomized trials have notshown superiority of rhythm control over rate control interms of mortality and hospitalization (Ref. University of

Ottawa pg1156, FALK).

8.5. Anticoagulation in atrial fibrillation

In view of the recent experience with NOAC we only summa-rized the comparison of the three new NOACs with Warfarin.

Oral anticoagulation either with Warfarin or NOACs is rec-ommended for most patients with AF. Stroke risk scores aremore useful for small portion of patients in which oral antico-


agulation may not be necessary. Table 3 shows the pertinentclinical and pharmacological profile of the three NOACs com-pared to Warfarin.43

The recommendation from ESC Guidelines on AF forchoice of anticoagulants in AF is shown in Fig. 12.

9. Catheter ablation of atrial fibrillation

Since the landmark report of Haissaguerre et al.44 on success-

ful ablation of triggers from pulmonary veins that eliminatedparoxysmal AF was published, a plethora of reports haveemerged (Fig. 13).

9.1. Pulmonary veins and atrial fibrillation

Electrical activity arises from pulmonary veins (PVs) that trig-

gers AF and ablation of these triggers eliminates recurrences ofAF. Many reports have confirmed these observations and PVisolation (PVI) is now the corner stone of catheter ablation of




Table 3 Comparison of warfarin to novel oral anticoagulants. Adopted and modified from Cairn JA. Canadian Journal of

Cardiology 2013;29:1165–1172.

Feature Warfarin Dabigatran Rivaroxaban Apixaban

Mechanism Inhibits synthesis: II, VII, IX, X Direct IIa inhibitor Direct Xa inhibitor Dirext Xa inhibitor

Prodrug No Yes No No

Dose regiment Oral Oral Oral Oral

Administration OD BID OD BID

AF dose (mg) INR 2–3 150, 110, 75 20, 15 5, 25

Food effect Yes Delays absorption Delays absorption No

Food interaction Many No No No

Bioavailability (%) 98 6.5 80–100 50

tmax (h) 72–120 0.5–2 2–4 3–4

T½ (h) 20–60 11–17 5–13 5–13

Substrate CYP 2C9, 3A4 No 3A4, 2J2 3A4

Substrate P-gp No Yes Yes Yes

Renal clearance No 85 33 27

Protein binding (%) 99 35 90–95 87–93

Monitoring INR No No No

AF trial complete Phase III (1989–1992) Phase III (2010) Phase III (2010) Phase III (2011)

Figure 12 Recommendation from ESC Guidelines on AF for the

choice of anticoagulation in AF. (NOAC : novel oral anticoag-

ulant , VKA : vitamin K antagonist) Camm JA, Lip GYH, De

Caterina R, et al. 2012 Focused update of the ESC Guidelines for

the management of atrial fibrillation. Eur Heart J 2012;33:2710–

2747. With permission.



AF. Although PV triggers are common they are not exclusive,as other sources of AF triggers exist.45 Further it has beendemonstrated that left atrial tissue extends 1–3 cm like a

‘‘sleeve’’ into the PVs and carries the same structural and elec-trical properties.46

The reason then why everyone does not get AF and only

certain individuals develop AF remains elusive of certain elec-trical and neurohormonal changes such as stretch, increasedleft atrial pressure, may promote trigger activity in PVs. It is

also assumed that there may be an electrical block betweenPVs and left atrium under normal conditions. Once therepeated firing from PVs enters the left atrium ‘‘the substrate’’initiates AF in a multiple macro-reentrant circuit either of sin-

gle or multiple rotors (see mechanism). Thus elimination oftriggers will abolish recurrences of AF in about 60% of thepatients. Failure in the remaining patients and recurrences is

most likely due to incomplete PVI and presence of the so-called gaps that often necessitate redo procedures.

9.2. Current status and results of atrial fibrillation ablation

Today catheter ablation of paroxysmal AF is commonly pre-formed generally after a failure of at least one antiarrhythmic

agent. In 2012 about 50,000 procedures were performed in theUnited States. On average the short-term success rate in highvolume experienced centers is about 60% for the first proce-dure and 71% after multiple procedures. 15–35% of patients

undergo a redo procedure.47

PVI remains the cornerstone of AF ablation, which is ofteneffective in 50–60% of patients with paroxysmal AF

(Figs. 14A and 14B).Substrate modification, i.e., left atrial and other sources are

often necessary in cases of persistent and long-lasting persis-

tent AF. In more complex cases extensive substrate modifica-tion including roofline, posterior left atrial wall ablation;ablation around the left atrial appendage may be needed.

Fig. 15A–C is from our laboratory illustrates a case of AFas detected in intracardiac electrograms from His bundle andcoronary sinus electrodes. Occasionally after termination ofAF, atrial flutter emerges may necessitate ablation at the




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 posterior–anterior 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 abla-tion to the left atrium in some cases produces left atrial tachy-

cardia/flutter at the mitral isthmus that also may requireablation of that region.

Several randomized trials have compared catheter ablationwith antiarrhythmic agents in a randomized fashion. All the


reported trials were designed to include symptomatic patientswith paroxysmal, persistent and long lasting persistent AF

who have failed at least one antiarrhythmic agent. All these tri-als have shown superiority of catheter ablation over antiar-rhythmic therapy in terms of symptom relief, recurrences,quality of life and outcome issues.




Figure 14B Electroanatomical mapping (EMA) and computerized tomography (CT) of the left pulmonary veins. LAA, left atrial

appendage. Abbreviations same as Fig. 14A above.


Experimental and clinical reports suggest that neural pelxithat lie over the junction of PVs and left atrium may serveas a source of inducing and maintain AF. High frequency stim-ulation of neural plexi in both animals and humans demon-

strated to induce AF and thus attempts to ablate neuralplexi have resulted in the elimination of AF. To date thereare no randomized trials comparing PVI with neural plexi

ablation in patients with AF.48

Thus, catheter ablation of AF in patients with paroxysmaltype with no to minimal structural heart disease may now be

considered as first line therapy and is considered reasonablein patients with paroxysmal and persistent AF.33 Fig. 17Ashows the ESC guidelines and Fig. 17B illustrates the Ameri-

can College of Cardiology, American Heart Association andHeart Rhythm Society 2014.

9.3. Perioperative anticoagulation

Based on the Meta-analysis results, 9 studies with 27,402patients, undergoing uninterrupted anticoagulation therapywith Warfarin have significantly reduced the risk of thrombo-

embolic complication without an increased risk of bleeding.49

9.4. Strategies for catheter ablation of atrial fibrillation

Different approaches for catheter ablation of AF have beenused in different centers as summarized below.

1) Anatomical approach: PV isolation, roof-lines, boxlines.

2) Substrate based approach.

Pleasej.ehj.2

� Electrogram based.

cite this article in press as: Shenasa M et al. Update on atrial fibril014.03.004

� Electrogram fractionation (Complex FractionatedAtrial Electrograms (CFAE)).50

� Neural Plexi.48

3) Etiology and mechanism based approach.

The Bordeaux group first reported on a stepwise approach thatis currently adopted in many centers. In this approach the proce-dure begins with PVI and according to the termination or extent

of underlying atrial remodeling a roof line followed by mitral isth-mus line, followed by anterior mitral isthmus line and inferior andposterior lateral lines that completes the left atrial box.51–53

9.5. Rotor ablation in patients with AF

Evidence from patients with AF and from experimental studieshas suggested that single or multiple rotors maybe operated inAF and elimination of rotors have terminated the AF in these

models. Recently, Narayan et al.54 have demonstrated singlerotors in human AF and ablation of these rotors have elimi-nated AF without additional ablation of the PV and other

sites. A randomized trial is currently under investigation.

9.6. Techniques for atrial fibrillation ablation

1. Radiofrequency ablation.

According to the initial report of Haissaguerre et al.,44 the

triggers were within the PVs and radiofrequency (RF) currentswere delivered within the PVs have eliminated AF. However,follow up reports showed PV stenosis have developed with

significant symptoms that in some patient interventions were

lation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/



bundle and coronary sinus.

Figure 15 (A–C) 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 fibrillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/j.ehj.2014.03.004



Figure 16 Ablation at the carvo-tricuspid isthmus that abolishes atrial flutter in the same patient as Figs. 14A and 14B. The red dots

denote the site of RF ablation.

Figure 17A ESC guidelines for catheter ablation of AF. Camm

JA, Lip GYH, De Caterina R, et al. 2012 Focused update of the

ESC Guidelines for the management of atrial fibrillation. Eur Heart

J 2012;33:2710–2747. With permission.

Figure 17B 2014 AHA/ACC/HRS Guideline for the Manage-

ment of Patients with AF: Executive Summary. January CT,

Wann S, Alpert JA, et al. J Am College Cardiol 2014.


needed to correct it by stenting. Currently, PVI around theantrum is a common practice.


10. Cryoballoon ablation

This balloon based ablation system freezes the antrum of thePVs. The cryoballoon ablation isolates PVs by freezing them

at �80�. A few randomized trials have compared RF ablationwith cryoballoon ablation techniques as seen in Fig. 18A and B.

11. Results of catheter ablation

The best results of PVI are obtained in patients with paroxys-mal AF with no structural heart disease. The acute successrate is about 57% (50–60%). The success rate of multiple





procedures without antiarrhythmic agents is at best 71% (65–77%) and multiple procedures with antiarrhythmic agents are77% (73–81%).47 The immediate 3 months are considered a

blanking period as many asymptomatic recurrences have beendetected. Weerasooriya et al.55 reported on the long-termresults after multiple catheter ablation procedures of AF hav-

ing shown that the sinus rhythm maintained at 1, 2, and5 years was 87%, 81% and 63%. However after a single pro-cedure 40%, 37% and 29% at 1, 2 and 5 years were reported.55

The associated comorbidities such as hypertension, diastolicdysfunction, heart failure, obstructive sleep apnea, obesityand impaired renal function have shown to lower the successrate of catheter ablation of AF and increase recurrences.

11.1. Outcomes of catheter ablation of atrial fibrillation

Catheter ablation of AF is taken with much enthusiasm and

the ablationists promoting that the long term outcomes ofAF 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 reduc-tion of mortality, stroke, hospitalization, and improvement inheart failure. Only the MANTRA trial demonstrates that after

2 years the quality of life was better compared to antiarrhyth-mic therapy. A very recent trial comparing antiarrhythmictherapy to radiofrequency ablation of AF as first line therapyjust 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 ofsinus rhythm, atrial remodeling is minimized and improves

the burden of AF. At present no data has demonstrated thatmaintaining sinus rhythm with catheter ablation will reducethe death rate related to AF. Recently Mont et al.58 reported

on catheter ablation vs. antiarrhythmic drug treatment of per-sistent AF: a multicenter, randomized, controlled trial (SARAstudy). The results revealed that catheter ablation was superior

to medical therapy in maintaining sinus rhythm in patientswith persistent AF during a 12-month follow up. The short-coming of this trial was that the trial was terminated prema-turely due to low patient recruitment and the primary

endpoint of the study was only recurrences of AF 24 h afterablation.

Dagres et al.,59 reported on a meta-analysis of randomized

trial that there were no mortality benefits of catheter ablationover drug therapy. Similarly two Canadian trials of AF-CHF60

Figure 18 (A) Depicts circular mapping and ablation catheter. (B) C


and the RAAFT study (first line radiofrequency ablation ver-sus antiarrhythmic drugs for atrial fibrillation treatment) didnot show mortality benefit of catheter ablation.

12. Imaging before and during AF ablation

(1) Preprocedure imaging includes transthoracic echocar-diogram, cardiac computerized tomography (CT) to

evaluate left atria and PVs geometry and its branch asseen in Fig. 19.

(2) Intraprocedural imaging includes magnetic resonance

imaging (MRI) to evaluate the degree of fibrosis, intra-cardiac echocardiography (ICE), electroanatomicalmapping, magnetic resonance imaging and direct visual-

ization of ablation lesion (currently under investigation).

13. Complication of catheter ablation

Catheter ablation of AF is now an established procedure andhas a low incidence of procedural complications in experienced

and high volume centers. Two worldwide surveys by Cappatoet al. have reported on the safety and complication of catheterablation of AF, initially in 200561 and again in 2010.62 Guptaet al.63 recently reported a systemic review of 192 studies with a

total of 83,236 patients with periprocedural complication rateof 2.6–3.2% in catheter ablation of AF.

The most common acute complications include vascular

complications including atriovenous fistula, femoral pseudoan-eurysm, stroke and TIA. PV stenosis (less often seen as PV iso-lation is preformed at the antrum of PVs), tamponade,

pericardial effusion, phrenic nerve injury, pneumothorax/hemothorax, sepsis and valve damage. However, the most dev-astating complications are death, stroke and atrioespohageual

fistula. The predictors of complications are related to the oper-ators experience, low volume centers and extent of othercomorbidities.63

Two recent reports on complications of catheter ablation of

AF have been published.64,65 The most common complicationof cryoballoon procedure is phrenic nerve palsy, which oftenresolves spontaneously however occasionally permanent dam-

age may occur. Lee et al. recently reported a low risk of majorcomplications in 500 consecutive patients who underwent PVIonly for paroxysmal AF.66 Therefore overall catheter ablation

ryoballoon ablation catheter. Image courtesy of Medtronic, Inc.




Figure 19 CT angio and Fly Thru of the LA and Pulmonary Veins. (LA : left Atrium).


of AF appears to be safe and effective in a selected patientpopulation.

14. Ablate and PACE

In patients who are not appropriate candidates of AF ablation

and adequate rate control with pharmacological agents cannotbe achieved, AV-nodal ablation and pacemaker implantationmaybe considered. In this group those with heart failure maybenefit from biventricular devices.67–69

14.1. Left atrial appendage (LAA) closure for stroke prevention

In patients who are not a candidates for antithrombotic agents

and are at risk for stroke, left atrial appendage (LAA) closureeither surgically or with implantation of devices appears rea-sonable. Currently, several devices are under investigation

and the most commonly used is the Watchman device.70 ThePROTECT-AF trial was designed to prospectively evaluatethe safety and efficacy of the Watchman device in 59 centers.

A total of 707 patients with CHADS2 score of >1 wereenrolled and in 89.5% of patients successful implantationwas achieved. The trial concluded that the LAA closure wasnot inferior to systemic anticoagulation to Warfarin.71 Other

devices such as the Lariat (SentreHeart, Inc.) is a percutaneoussuture ligation for LAA closure is also under investigation.70,72

14.2. Uncertainties in catheter ablation of AF

When catheter ablation was initially introduced for more dis-crete cases such accessory pathways and AV nodal reentrant

tachycardias.There existed a large experience in electrophysiology studies

defining the characteristics of tachycardia circuits as well as

experience obtained from surgical cases. Thus it was the bestof times; and it was the age of wisdom. However in AF abla-tion, it was the worst of the times; it was the age of foolish-ness.73 Thus in the former scenario, the procedure was more


successful (90%) with a very low complication rate. Howeverin case of AF after the Haisseguerre and colleagues landmark

report ‘‘Spontaneous initiation of atrial fibrillation by ectopicbeats originating in the pulmonary veins,’’ many centers havebegun to perform the procedure without scientific backgroundin a more complex and heterogeneous substrate.7

14.3. Should catheter ablation be the first line therapy for

patients with AF?

Controversies continue surrounding whether catheter ablationshould be offered as first line therapy in patients with paroxys-mal AF. Few studies have prospectively and in a randomized

fashion have assessed the outcome of catheter ablation ofAF as the first line therapy. The available data indicate thatthe efficacy of catheter ablation as a first line therapy is at least

equivalent74 or better56 than the first line antiarrhythmic drugtherapy. Quality of life appears to be better in the ablationgroup compared with antiarrhythmic therapy. Thus currentevidence supports the position of European Society of Cardi-

ology, AF guidelines, as first line therapy in symptomatic par-oxysmal AF appears reasonable in experienced centers.

14.4. Definition of successful procedure

The Heart Rhythm Society consensus on AF published in 2012defined success as freedom from any symptomatic or asymp-

tomatic AF of any type, atrial tachycardia or flutter longerthan 30 s, 12 months after the procedures. However for practi-cal purpose a significant reduction in AF burden as well as sig-

nificant reduction in symptomatic AF is considered a clinicalsuccess. The limitation of these definitions is however theuncertainty of duration of monitoring post ablation.

14.5. Duration of post ablation monitoring

It has been recognized that during the first 3 months post AFablation there are significant short and long term AF

recurrences. Therefore this period is arbitrarily designed as





‘‘blanking period’’ which may be due to the significant amountof tissue damage and edema that promotes AF.

14.6. Procedural end points

At present there is no uniform agreement on what is acceptedas 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 postablation protocol, i.e., burst pacing, isoproterenol infusion,adenosine–triphosphate administration etc. (5) Duration and

methods of rhythm monitoring.

14.7. Cost of catheter ablation of atrial fibrillation

Catheter ablation is an expensive procedure with the initialcost and 5 year follow up totaling a sum of $30,000–35,000

per patient in the United States.55,79 McKenna et al.76 reportthe cost of catheter ablation in United Kingdom to be7700 - 7900 pound while Canada having a cost of $16,278.75–77

15. Future directions in catheter ablation of atrial fibrillation

Due to relatively high recurrence rates even after the blankingperiod and the need for repeated procedure, newer ablation

technologies are sought. Endoscopic navigation and visualiza-tion of the target tissue and ablation effect on the atria areunder investigation. Preliminary reports have examined the

feasibility of this method in experimental animal and the first200 patients.78

(1) Recent reports revealed that case done in communityhospitals with low volume procedures had higher com-plication rates of about 6.2%. Whereas procedures that

are performed in high volume centers with experiencedoperators had lower complication rates (3.9%).61–64

(2) Direct vision during catheter ablation to better identifythe target tissue and its effect on the atrial tissue.78,79

(3) Since radiation during the procedure is an importantissue to the patient, operator and cath lab staff, newertechnologies are emerging to use ionized radiation free

techniques such as magnetic resonance guided EP studyand 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, Dronedaroneand Ranolazine).

� Atrial channel selective (usually ‘‘relative’’).� Substrate based mapping and ablation.– Gap junction conduction.

– Fibrosis.– Inflammation.

Future AF management should focus on personalized riskfactors that better predict the best approach (pharmacologicalor nonpharmacological), identify risk and biomarkers as well


as better understanding of genetic, environmental interactionwith such complex arrhythmias. At the same time improve-ment in AF detection tools and imaging techniques of both

the heart and brain to better understand the pathophysiologyof AF, i.e., ‘‘system biology.’’ Furthermore, the burden offibrosis should be on the future agenda.

16. Future opportunities

(1) Noninvasive characterization of AF and its types maybeuseful in the identification of patient profiles.

(2) At present there are no uniform protocols for catheterablation of AF and it remains empirical. Hopefully thefuture trials will provide insights to design uniform pro-

tocols. This inconsistency maybe imparted due to thecomplexity of substrate and presence of evolving under-lying heart disease such as HF, hypertension. As such

there remain many unanswered questions like endpoints,follow-ups and definition of success, etc.

(3) Atrial selective antiarrhythmic and upstream therapywill continue to expand.

(4) Results and technology of catheter ablation of AF willexpand.

(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 ablationapproaches in paroxysmal and persistent AF, i.e.,PVI only versus PVI and substrate modification

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, hospital-

ization, stroke, death and quality of life.5. Cost-effectiveness of catheter ablation.

16.1. Future trials

(1) Catheter ablation vs. anti-arrhythmic drug therapy foratrial fibrillation trial (CABANA).80

(2) Early treatment of atrial fibrillation for stroke preven-tion trial (EAST).81

(3) Rate vs. catheter ablation rhythm control in patientswith heart failure and high-burden atrial fibrillation(RAFT-AF).82,83

(4) First line radiofrequency ablation vs. antiarrhythmicdrugs for atrial fibrillation treatment (The RAAFTStudy).84

(5) Delayed-Enhancement MRI Determinant of SuccessfulRadiofrequency Catheter Ablation of Atrial Fibrillation(DECAAF)85

17. Summary

In summary AF prevalence and incidence are increasing by age.Aggressive risk stratification and preventive measures should bepart of management. The management should focus on four

strategies: (1) Prevention of arrhythmia and progression fromparoxysmal to persistent and permanent forms, (2) strokerisk assessment and prevention of embolic complications, (3)




Figure 20 Opportunities and challenges for future AF. AF, atrial fibrillation; 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 inflammation, fibrosis and remodeling lead to AF.


Please cite this article in press as: Shenasa M et al. Update on atrial fibrillation, The Egypt Heart J (2014), http://dx.doi.org/10.1016/j.ehj.2014.03.004




arrhythmiamanagement according to the guidelines and patientunderlying structural heart disease, and (4) treatment of theunderlying causes.

Our current biomarkers for AF are nonspecific, however amultimarker approach may improve their sensitivity.Improved detection methods of AF especially after antiar-

rhythmic therapy and ablative procedures are important.Overall, trials to date have failed to show that rhythm controlapproach is superior to rate control approach in all-composite

measures, although some trials have shown that patients whomaintained sinus rhythm reported improved quality of life.

According to the recent evidence based and guidelines cath-eter ablation of AF seems reasonable in patients with paroxys-

mal AF with no to minimal structural heart disease who havefailed at least one antiarrhythmic agent. Aggressive risk mod-ification of comorbidities such as obesity sleep apnea, impaired

renal function. is necessary and should be an integral part ofAF management. Finally, Berti et al. proposed a multidisci-plinary nurse-coordinated AF program to improve detection

management and outcome of patients with AF. This approachwill begin with comprehensive risk assessment, patient educa-tion, patient centered medical care and evaluation of manage-

ment outcome.86

As AF is an evolving disease we will witness a significantparadigm shift in understanding the pathophysiology andmanagement 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. Pre-vention should be the first line of therapy. As inflammation,fibrosis and remodeling are the final common pathway of

diverse etiologies, innovative therapies should focus on fibrosisand inflammation as shown in Fig. 21.

Conflict of Interest

None.

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