Atrial fibrillation

1. MECHANISMS &
MANAGEMENT OF ATRIAL
FIBRILLATION
-ROHITWALSE
SENIOR RESIDENT
DM CARDIOLOGY
SCTIMST

2. SCOPE
 INTRODUCTION
 CLASSIFICATION
 MECHANISM-
 TRIGGERS
 SUBSTRATE
 MANAGEMENT
 RECOMMENDATIONS

3. INTRODUCTION
 Definition- Supraventricular tachyarrhythmia
with uncoordinated atrial activation 
ineffective atrial contraction
 (ECG) characteristics-
1) Irregular R-R intervals
2) Absence of distinct repeating P waves and
3) Low amplitude baseline oscillations
(fibrillatory waves), f waves – 300-600 bpm

4. INTRODUCTION
 Ventricular rate during AF- 100-160 bpm
 WPW syndrome- ventricular rate > 250 bpm
 Patients with pacemaker and patients with 3rd
degree heart block with regular escape
rhythm- ventricular rhythm may be regular

5. • Onset of an irregular ventricular rhythm and an increase in
ventricular rate
Change in the ventricular response
• Loss of atrioventricular (AV) synchrony, decreased ventricular
filling time, and possibleAV valve regurgitation
Detrimental hemodynamic consequences
• Loss of effective contraction and atrial stasis.
Likelihood of sustaining a thromboembolic event
Sinus rhythm  Atrial fibrillation

6. • terminates spontaneously or with intervention within 7 days
of onset
Paroxysmal
• continuously sustained beyond 7 days, including episodes
terminated by cardioversion (drugs or electrical cardioversion)
after >_7 days
Persistent
• ContinuousAF of >12 months duration when decided to adopt
a rhythm control strategy
Long standing persistent
• Long standingAF refractory to cardioversion
Permanent
Classification of AF

7. Electrophysiology of AF
 Trigger: Rapidly firing focus that can act as an
initiator for the arrhythmia
 Substrate: Electrophysiological, mechanical and
anatomical characteristics of the atria that
sustain AF.
 Electrical remodeling – changes in properties of ion
channels
 Structural remodeling – alteration in tissue
architecture
 Macroscopic-Atrial dilatation
 Microscopic-Fibrosis
Trigger driven
disease
ParoxysmalAF
Functional
atrial substrate
PersistentAF
Structural atrial
remodelling
PermanentAF

8. Basic atrial
electrophysiology
 APD & RF are shorter in the atria (particularly
in the left atrium) compared with the
ventricular myocardium
 Regional heterogeneity within and between
the atria
 Differences in Intra-atrial ion channel
density

9. Triggers for AF
 Muscular sleeves: Extension of Left atrial
myocardium over PVs
 Muscular sleeves within the pulmonary vein (PV)
ostia are the source of the ectopic beats triggering
AF in many patients with paroxysmalAF.
 Superior PVs have longer and better-developed
myocardial sleeves than inferior PVs  most of the
ectopic foci that initiate AF are from the superior PVs
 Regional Difference of ERPs
 Distal PVs have short ERPs compared to Proximal PVs
(differences in ERP between proximal and distal PVs were
decreased after isoproterenol infusion)

10. Ectopic focus
 Paroxysmal AF
 Superior PVs > Inferior PVs
 Distal PVs > Proximal PVs

11. Non-PV triggers
 Superior vena cava
 Coronary sinus
 Left atrial appendage
 Vein of marshall
 Crista terminalis
 Left atrial posterior free
wall
 Myocardial sleeves
 Fibrosis
 P/catheter ablation procedure

12.  Ganglionated plexi, which are
conglomerations of autonomic ganglia on the
epicardial surface of the heart, may play a
role in the initiation and maintenance of AF
 Afterdepolarizations and extra-systolic
activity
 DADs
 EADs

13. DADs
 Ionic Mechanisms.
 RyR2 channel abnormally
remains open in diastole
NCX activity enhanced

14. EADs
 Strong simultaneous discharge of vagal and
sympathetic nerves (vagosympathetic
discharge)
 Vagal discharge   APD   (RP)
 Sympathetic stimulation   Ca2+ transients
  cytoplasmic free Ca2+ during AP

15. Arrhythmic mechanisms that
sustain AF
 1. Multiple wavelet hypothesis
 2. Localized AF drivers
 Anatomical reentry
 Functional reentry
 Leading circle concept
 Spiral wave reentry / rotor concept

16. 1. Multiple wavelets
 Fibrillation is maintained by the irregular
wandering of numerous wavelets generated
by the fractionation of a wave front passing
through tissue in a state of inhomogeneity
with respect to excitability and conduction
velocity

17. 2. Localized AF drivers

18. Dimension of circuit = wavelength (WL) = RP(Refractory period) × CV (conduction velocity)
smallest circuit which can sustain functional reentry
Leading Circle Model

19. • Stability of AF according to
the leading circle concept is
determined by the number
of simultaneous re-entry
circuits that the atria can
accommodate
• When the 1) WL is short (as
a result of reduced RP or
CV) or
• 2) when the atria are
enlarged, more re-entrant
circuits can be
accommodated and AF is
more likely to maintain
itself
Why Atrial Enlargement Predisposes to AF?

20. Functional Reentry Due to Rotors/Spiral Waves
 Wavefront has a curved
or spiral form, and the
wavefront and wavetail
meet at a focal point
called a phase singularity
(PS)
 Wavefront velocity in a
rotor is not constant,
depending instead on
wavefront curvature due
to current source–sink
mismatch

21. Functional Reentry Due to Rotors/Spiral Waves
 Wavefront in close proximity to the PS is
the region of highest curvaturearea of
slowest wavefront conduction velocity
 At the PS, the wavefront curvature is so
high and conduction velocity is so slow,
that the propagating wavefront is unable
to invade a core of tissue in the centre of
the rotor
 This tissue core  effectively
unexcitable forms an area of functional
block similar to the centre of a leading
circle reentrant circuit.

22. Reentry Circuit Rotor
 A reentrant circuit in
the leading circle
model must remain
fixed in space because
the centre of the circuit
is completely
unexcitable
 A rotor is able to move
through space and, due
to constant source–
sink current mismatch
at the PS and core,
under certain
circumstances the
rotor can meander in
various complex forms
which in turn have
important effects on
rotor behavior and
sustainability

23. SUBSTRATE
 Electrical Remodelling
 Structural Remodeling
 Autonomic or Neural remodeling

24. Electrical remodeling

25. Atrial Tachycardia Remodeling
 Decrease in atrial effective refractory period (ERP)
and reduction in physiological ERP rate adaptation
 This ERP decrease reduces the wavelength, and thus
atrial tachycardia remodeling produces a substrate
favorable for AF
 Atrial tachycardia suppresses atrial myocyte
contractility, by altering Ca2+ homeostasis and
thereby causes “contractile remodeling” that may
contribute to atrial stasis and the associated
thromboembolic predisposition, as well as to AF
perpetuation

26. CHF and Atrial Structural
Remodeling
 Atrial ERP is unchanged or increased by CHF, but
local atrial conduction abnormalities occur in
association with marked fibrosis between and within
atrial muscle bundles
 Abnormalities in atrial structure and local
conduction  stabilize atrial reentry allow AF-
sustaining reentry circuits that sometimes appear to
have a stable macro-reentry pattern
 Ionic Mechanisms.
 NCX activity enhanced in CHF
 Delayed afterdepolarisation

27. Fibrosis
 Action potential shortening occurs within
about 10 days and coincides with the initial
spontaneous maintenance of AF, but that
atrial fibrosis then occurs over a period of up
to a year, coinciding with long-standing
persistence

28. Structural remodelling
 fatty infiltration
 inflammatory infiltration
 necrosis and
 amyloid deposition
 Adipose tissue has a paracrine effect through the
release of adipokines with profibrotic properties.
 It also forms barriers to wavefront conduction and
favour reentrant circuits

29. Autonomic and neural remodeling
 Increase in the density of sympathetic and
parasympathetic innervation with AF
 After MI and cardiomyopathy
 Supported by the circadian variation of the paroxysmal
AF episodes
 morning and a second rise in the evening
 fewer episodes on Saturdays
 more arrhythmias occurred during the last months of each year

31. Demographics and
lifestyle
• Aging
• Male sex
• Cigarette
smoking
• Alcohol
consumption
• Obesity (BMI of
≥30 kg m–2)
Cardiovascular
disorders
• Hypertension
• CAD
• HF
• LVH
• Valve disease
• HCM, DCM
Other factors
• Metabolic
Syndrome
• DM
• Cerebro vascular
disease
• Hyperthyroidism
• CKD
• OSA
• COPD
• Post CABG/Valve
surgery
RISK FACTORS FOR AF

32. WHOM TO SCREEN ?
 Opportunistic screening for AF by pulse
taking or ECG rhythm strip is recommended
in patients >_65 years of age. (Class I B)

33.  ‘A’ Anticoagulation/Avoid stroke
 ‘B’ Better symptom control
 ‘C’ Cardiovascular risk factors and
concomitant diseases: detection and
management
Management:the integrated ABC
Pathway

34. ‘A’ Anticoagulation/Avoid stroke
 Stroke risk assessment
 Bleeding risk assessment
 Stroke prevention therapies
 Management of anticoagulation related bleeding risk

35.  Stroke risk
assessment
 Low risk: CHA2DS2-
VASc score of 0 in
men and 1 in
women) who do not
need any
antithrombotic
therapy
 High risk:
CHA2DS2-VASc
score of ≥1 in men
and ≥2 in women)

38. ‘B’ Better symptom control
 Rate control
 Rhythm control
 Cardioversion
 AF ablation

39. Rate control
TRIAL STRATEGY JOURNAL N; DURATION RESULTS
AFFIRMTRIAL Rate control vs
rhythm control
NEJM, 2002
(Multicentric)
2027(Rate c) vs
2033(Rhythm c)
5yrs f/u
-Mortality (p-
0.08)
-Continuous
OAC (AFSR)
RACE IITRIAL Rate control:
Lenient
(HR<110)
vs
Strict
(<80@rest;<110
during moderate
exrcise)
NEJM, 2010 311(Lenient) vs
303(Strict)
3 yr f/u
-Similar MACCE
(12.9%) -Lenient
vs
(14.9%) -Strict
(p<0.001 for non
inferiority)

43. Rhythm control
 In patients who present with an episode of
AF, more than two-thirds have spontaneous
conversion to sinus rhythm

44. Indications for rhythm
control
 Based on the currently available evidence
from RCTs, the primary indication for rhythm
control is to reduce AF-related symptoms
and improve QoL

47. CARDIOVERSION
 Acute rhythm control can be performed as an
emergency cardioversion in a haemodynamically
unstable AF patient .
 Synchronized direct current electrical
cardioversion is the preferred choice in
haemodynamically compromisedAF patients as it is
more effective than pharmacological cardioversion
and results in immediate restoration of sinus
rhythm.
 In stable patients, either pharmacological
cardioversion or electrical cardioversion can be
attempted; pharmacological cardioversion is less
effective but does not require sedation.

49. Electrical cardioversion
 Electrical cardioversion can be performed safely in sedated
patients treated with i.v. midazolam and/or propofol or
etomidate.
 BP monitoring and oximetry during the procedure should
be used routinely. Skin burns may occasionally be observed.
 Intravenous atropine or isoproterenol, or temporary
transcutaneous pacing, should be available in case of post-
cardioversion bradycardia.
 Biphasic defibrillators are standard because of their
superior efficacy compared with monophasic defibrillators.
 Anterior posterior electrode positions restore sinus rhythm
more effectively, while other reports suggest that specific
electrical pad positioning is not critically important for
successful cardioversion.

50. Pharmacological cardioversion
 Pharmacological cardioversion to sinus rhythm is
an elective procedure indicated in
haemodynamically stable patients.
 Its true efficacy is biased by the spontaneous
restoration of sinus rhythm within 48 h of
hospitalization in 76 - 83% of patients with
recent onset AF (10 - 18% within first 3 h, 55 -
66% within 24 h, and 69% within 48 h).
 Therefore, a ‘wait-and-watch’ strategy (usually
for <24 h) may be considered in patients with
recent-onset AF as a non-inferior alternative to
early cardioversion.

51.  The choice of a specific drug is based on the type and
severity of associated heart disease, and pharmacological
cardioversion is more effective in recent onsetAF.
 Flecainide (and other class Ic agents), indicated in patients
without significant LV hypertrophy (LVH), LV systolic
dysfunction, or ischaemic heart disease, results in prompt
(3 - 5 h) and safe restoration of sinus rhythm in >50% of
patients
 While i.v. amiodarone, mainly indicated in HF patients, has
a limited and delayed effect but can slow heart rate within
12 h.
 Intravenous vernakalant is the most rapidly cardioverting
drug, including patients with mild HF and ischaemic heart
disease, and is more effective than amiodarone or
flecainide

52.  In selected outpatients with rare paroxysmal AF
episodes, a self administered oral dose of flecainide or
propafenone is slightly less effective than in-hospital
pharmacological cardioversion but may be preferred
(permitting an earlier conversion), provided that the drug
safety and efficacy has previously been established in the
hospital setting.
 An atrioventricular node-blocking drug should be
instituted in patients treated with class Ic AADs
(especially flecainide) to avoid transformation to AFL
with 1:1 conduction.

55. AF ablation
 AF catheter ablation is effective in maintaining
sinus rhythm in patients with paroxysmal and
persistent AF.
 The main clinical benefit of AF catheter ablation
is the reduction of arrhythmia-related
symptoms.
 This has been confirmed in a recent RCT showing
that the improvement in QoL was significantly
higher in the ablation vs. medical therapy group
as was the associated reduction in AF burden.

56. TRIAL STRATEGY JOURNAL N; DURATION RESULTS
APAF STUDY Circumferential
PV Ablation vs
Antiarrhythmic
Drug Therapy for
paroxysmal AF
JACC, 2006
(ITALY)
99(CPVA) vs
99(ADT)
1 yr f/u
AT free
CPVA-86% vs
ADT-22%
(p<0.001)
MANTRA PAF Catheter RFA vs
Antiarrhythmic
agents for
paroxysmal AF
NEJM, 2012
(Multicetric RCT)
146(RFA) vs
148(AAT)
2 yr f/u
Cumulative AF
burden
RFA-13%
AAT-19%
(p=0.10)
PAROXYSMAL AF

57. TRIAL STRATEGY JOURNAL N; DURATION RESULTS
CAMERA-MRI
Study
Catheter
ablation vs
Medical rate
control
AF with LV dysf
(MR based)
JACC, 2017
(Multicentric RCT)
33 catheter
ablation vs
33 medical rate
control
6 mnth f/u
EF normalised
Catheter
ablation grp-
58%
MedicalTx- 9%
(P-0.0002)
{No LGE on MRI}
CASTLE-AF Catheter
ablation vs
Medical therapy
AF with HF
(mean EF-32%)
NEJM, 2018
(Multicentric RCT)
179 Catheter
ablation vs
189 Medical
therapy
Death & HF
hospialization
Catheter –28.5%
Mx- 44.6%
(p-0.006)
AF WITH HF

58. TRIAL STRATEGY JOURNAL N; DURATION RESULTS
CABANATRIAL Catheter
ablation vs
Drug therapy
JAMA, 2019
(Multicentric RCT)
1108 catheter
ablation vs
1096 Drug
therapy
5 yrs f/u
Primary end
point
Ablation-8% vs
Drug- 9.2%
(P = 0.30)
CABANA
Subgroup
Catheter
ablation vs
Drug therapy
AF with HF
(EF<40%)
N=778(35%) Primary end
point
AF recurrence
=CV mortality or
HF hospi.

60. ‘C’ Cardiovascular
risk factors and
concomitant diseases:
detection and
management

61. LIFESTYLE
INTERVENTIONS
• Obesity and weight loss
• Alcohol and caffeine use
• Physical activity
SPECIFIC CV RISK
FACTORS/COMORBIDITI
ES
• Hypertension
• Heart failure
• Coronary artery disease
• Diabetes mellitus
• Sleep apnoea

63.  THANKYOU!