Atrial fibrillation

Topics

Mechanism of AF
Management of new onset AF
Role of TTE in AF
Anticoagulant choice

Rhythm control vs rate control in AF

Update
Update

AF + HF
Role of angiotensin inhibition

Mechanism of AF: Terminology

Trigger rapidly firing focus often arising in

pulmonary vein
Substrate mechanical/anatomical struc of the atria
where AF can occur
Substrate remodelling
Electrical remodelling
Mechanisms of cardiac arrhythmias:

Triggered activity additional depolarization's which occur

during or immediately following a cardiac depol and may
cause sustained cardiac arrhythmia
Reentry/reentrant mechanism most common mechanism
of cardiac arrhythmias and refers to presence of one or
more electrical circuits in which electrical activation
proceeds in a circular fashion to complete a elf sustain
circuit.

AF BEGETS AF

Triggers

Maintenance
of AF

AF mechanism most common triggers

1.

Myocardial tissue on pulmonary vein

1.

2.

Isolation show repetitive firing and even

presence of episodic re-entrant activation in
pulmonary veins.

Stretch increase the propensity for rapid

firing form PVs as a result of stretch sensitive
ion channels
1.

Could explain association b/w AF and mitral

regurgitation

AF not so common triggers

3. Non PV sites of rapid firing:

Tissue near pulm vein, near SVC, coronary sinus

4. Atrial flutter

Atrial flutter is a right atrial re-entry circuit, while A

fib is a left atrial issue
Elimination of atrial flutter frequently does not
eliminate the predisposition of AF

Electrical remodelling
Few minutes of paroxysmal
AF
Enhanced cellular
Ca2+
Auto protective mechanisms which
reduce Ca2+ entry

Initially, these changes

are spatially uniform
Overtime, they become
heterogeneous

Decrease in atrial
refractoriness

High rate of electrical activation

Clinical implication: these transient changes are considered
to be reason why patients revert to AF after cardioversion

Electrical modelling and Substrate

modelling combined mechanism

Maintenance of AF
1.
2.
3.
4.
5.

Electrical remodelling
Atrial remodelling
Role of ANS
Role of fibrosis
Re-enterant mechanism

AF- maintenance

Atrial remodelling

Structural changes
Fibrosis
Electrical changes refractory period
dispersion, conduction delay

Clinical implications of mechanistic model

Refractory nature of AF

After initiation of AF atrium relatively healthy

sinus rhythm can be spontaneously restored
As substrate remodels over time, AF no longer
terminates spontaneously

RF of AF

Hypertension 60-80%
Cardiovascular disease 25-30%

Cardiomyopathy
Valvular disease
CAD

NYHA II-IV 30%

Diabetes 20%
Age

Asso w/
atrial
dilatation

New Onset AF

New Onset AF: Presentation

Found incidentally i.e nil symptoms

May be symptomatic
May have precipitating factors:

Surgery
Infection
Recent MI
Thyrotoxicosis
PE
Myocarditis
Pericarditis

New onset AF: terminology

Paroxysmal AF spont revert within 7 days

Persistent AF persist >7days with continuous
AF
Long standing persistent AF more than 12
months

New onset AF: Mx

Categorise patients:

Symptomatic
Severely symptomatic
Organ failure

Cardiac active ischemia, pulmonary oedema

Renal - AKI

New onset AF: Stable - assessment

Hx:

Look though old ECG find out prvs hx of prior

supraventricular arrhythmia
RF for AF
Identify risks of stroke or bleeding

CHADS SCORE
HAS BLED

O/E

Vitals
Resp: Pul oedema?
Cardiac: fluid overload

HF changes
management:
HF can cause AF
AF can cause AF

New onset AF: Stable - assessment

ECG ischemia? Pre-excitation?

Labs: FBC, EUC, CMP, TSH

Risk of AF is increased 3x EVEN IN SUBCLINIC

HYPERTHYROIDISM:

Serum TSH <0.5 mU/L

Serum free T4 = normal

Imaging

CXR
TTE

Role of TTE in AF

Left atrial size:

Mitral valve function:

Stenosis
Regurg

Left ventricular function:

pharmacotherapy choice
Future stroke prognostication

BAATAF, SPINAF and SPAF incdience of stroke 9.3%/ year in

patients with moderate to severe left ventricular dysfunc.

HASBLED

Hypertension History (Uncontrolled,

>160 mmHg systolic)
Renal Disease Dialysis, transplant, Cr
>2.6 mg/dL or >200 mol/L
Liver Disease Cirrhosis or Bilirubin >2x
Normal or AST/ALT/AP >3x Normal
Stroke History
Prior Major Bleeding or Predisposition to
Bleeding
Labile INR (Unstable/high INRs), Time in
Therapeutic Range <60%
Age > 65
Medication Usage Predisposing to
Bleeding (Antiplatelet agents, NSAIDs)
Alcohol or Drug Usage History 8
drinks/week

Score >5 9%
annual risk of
bleeding. High risk
Score 4 8.9%
annual risk of
bleeding. High risk
Score 3 5.8%
annual risk of
bleeding
Score 2 4.1%
annual risk of
bleeding moderate
risk of major
bleeding
Score 1 3.4%
annual risk of
bleeding. Low risk

CHA2Ds2 VASc score

Age

Sex

<65 = 0
67-74 = 1
>75 = 2
Male = 0, Female = 1

Hypertension =1
Stroke/TIA/Thromboemolism =2
Vascular disease hx =1
DM =1

New onset AF-Stable - Mx

Correct reversible causes

RULE OUT PRE-EXCITIATION

AV NODAL BLOCKING drugs will lead to rapid accessory

pathway conduction, increasing risk of pre-excited AF
leading to VF

1st line metoprolol, non hydrodipine CCB

2nd line - digoxin
3rd line - amiodarone

HR targets

Symptomatic HR<85
Asymptomatic - HR<110

New onset AF-Stable - Mx

1st line metoprolol, NHD CCB

2nd line digoxin

Indication:

Dilated heart failure,

in pts with AF DUE TO HEART FAILURE
Added to 1st line if BP sagging with 1st line and still in RVR

3rd line amiodarone

Indication:

1st and 2nd line fail

Poor LVEF

Caution:

Potential for pharmacological conversion and risk of

thromboembolism (TE)

1st line in stable AF pts

Beta blocker vs CCB usually depends on

consultants. Things to consider:

Beta blocker useful with:

CCB useful if:

Ventricular response increases to inappropriately high

rates during exercise
After MI
Stable angina
COPD
Asthma

Start low 25 mg BD metoprolol and titrate to

BP and HR

Rhythm vs rate control in AF

Rhythm control vs rate control in AF

AFFIRM and RACE trials

Embolic events occur with equal frequency

regardless of rate control or rhythm control
strategy

AFFIRM trial

Rate control and

anticoagulation

Statistically Significant trend

towards decrease in mortality
21.3% vs 23.8%
Patients without hx of HF and
65 years or older had a
SIGNIFICANT REDUCTION in
mortality
Less likely to require
hospitalisation 73 vs 80

Rhythm control and

warfarin left up to
discretion of investigator

Deleterious effects or
antiarrhythmic likely
contributing to increased
mortality.

No Diff b/w two groups in incidence of cardiac death,

arrythmia, or deaths due to ischemic or hemorrhagic
stroke.
No diff in functional status or QOL

RACE trial

Rate control

Significant less likely

to have a composite
index of: (17% vs
22.6)

Cardiovascular death
Admission for HF
TE event
Severe bleeding
Pacemaker
implantation
Severe SE form
antiarrhythmic dugs

Rhythm control

Higher incidence of
non fatal endpoints:

HF
TE
PM
Adverse drug effect

Rhythm control fails to reduce embolic

risk because:

It never goes away:

Doesnt take much

AF >more than 5 minutes increasing risk of TE events 6x

They have other risk factors

Even with successful cardioversion and antiarrhythmic drug

therapy recurrence of AF is 35-60% with intermittent
monitoring and 88% with continuous monitoring

Pts with nonvalvular AF (eg. Hypothyroidism, cardiac surgery)

often have predisposing factors for TE when they are in SR
these include complex aortic plaque and left ventricular
dysfunction.

SR doesnt mean no AF

Left atrium may show sinus mechanism, while atrial appendage

may display an AF contraction pattern

Rate control vs rhythm control

Rate control

Preferred in patients with heart

failure
Very elderly

Under represented in clinical

trails
AF permanent
More sensitive to proarrhtymic
effects

Rhythm control

When SR is maintained, exercise

capacity and quality of life is
improved
Failure of rate control:

Young patients

Persistent symptoms palp,

dyspnea, angina, near syncope
despite adequate rate control
Inability to achieve adequate rate
control
Who need to carry out activities
requiring optimal cardiac
performance

New diagnosis go for

cardioversion if you have the
following:

Left atrium <4.5 to 5 cm

Reversible underlying disorder

Hyperthyroidism, pericarditis, PE,

post op AF

No HTN
Normal eft ventricular systolic func.

Impact of anticoagulation
Reduction of stroke

Multiple trials and

subsequent metaanalyses show
definite reduction of
clinical stroke in
patients with
CHADsVASc>2
But CHADsVasc 1 and
0 not well studied

Increase risk in bleeding

Annual risk of ICH in

patients with AF who are not
anticoagulated 0.2%
Annual risk of ICH in
patients with AF who are ant
coagulated 0.4%
Think twice for these
patients:

Thrombocytopenia or known
coagulopathy
Recent surgery
Prior severe bleeding while
on oral anticoag
Suspected aortic dissec
Malignant HTN

Anticoagulant choice

In general, newer anticoag preferable to warfarin

Meta-analysis of RE-LY, ROCKET AF, ARISTOTLE and

ENGAGE AF TIMI

New agents had a lower rate of haemorrhagic stroke [RR 0.49]

Aggregate Ich reduced RR0.480

Warfarin>new anticoag

Patient already on warfarin, comfortable with INR and

within therapeutic range atleast 65% of time
Unacceptable increase in cost
Severe CKD Creat CL<30 (apxiban is the exception in US)
If drug interactions:

Phenytoin
HIV protease inhibitor based antioretroviral therapy

Other anticoagulant options

Aspirin monotherapy

CHADS2=0- i.e low risk

2007 meta analysis not statistically significant risk

reduction

For CHADS2>1

Consistently and substantially less effective in reducing

TE risk in meta analysis of 6 trials.
Absolute rate increase of major bleeding was 0.9
events per 100 patient year more

Other anti-coagulant options

Aspirin + clopidogrel

ACTIVE W [RCT] (compare clopidgrel + aspirin to

warfarin)

Warfarin significantly lowered the annual rate of primary

end point which was a composite outcome of different
TE
Decrease risk of major bleeding in warfarin group

ACTIVE A (compare clopidogrel + aspirin to Asprin

alone) [for patient not candidate for warfarin]

Reduction in TE in the DAPT group [2.4% vs 3.3%

annum]
Increased incidence of bleeding [2.0% vs 1.3% annum]

Other anti-coagulant options

Asprin + Low dose warfarin for INR 1.2-1.5

SPAF III trial high risk of embolism

Specific patient groups

Short duration PAF

Duration of AF doesnt matter- anticoagulate

according to CHADSVAC score

Renal patients
Hyperthyroidism

Initially anticoag according to CHADSVASC start

treatment for hyperthyroidism if it can be
documented that nil AF for 3/12 then
anticoagulation can be cased
Expert opinion

Management of AF in patients with

heart failure

AF + HF

AF + HF go together

Framingham Heart Study 2003 [n=1407 over 47

year interval]

HF 1st 5.4%/year incidence of AF

AF 1st 3.3%/year incidence of HF

Prevalence of AF increases from 4% to 40% as

NYHA functional class increases from I to IV

AF + HF: mechanism

Tachy/brady/abrupt change in rate decreases

cardiac output
Persistent tachycardia leads to tachycardia
mediated cardiomyopathy
Loss of atrial systole

diastolic heart failure

where left ventricular filling occurs largely in late

diastole
more dependent than normal hearts on atrial
contraction

AF + HF: acute management

Cease/withold beta blockers until stabilisation

Management fluid overload
Rhythm control in young patients who can
tolerate burdens of rhythm control
Rate control:
Regardless of strategy used must
anticoagulate

AF + HF: management
Manage heart failure aspect
and stabilise

Rate control

Rhythm control

Cather Ablation

Anticoagulat
e regardless
of arm

AV nodal
ablation

AF-CHF trial

RCT- Long term rhythm control better than rate control in

pts with HF and paroxysmal AF?
1376 with LVEF <35%, HF, hx of PAF, 2 groups:

Rhythm: amiodarine, sotalol, dofetilide

Rate control: with beta blockers

Outcome at 37 months

No significant difference in primary outcome of death

No outcome of event free survival
Improvement in QOL and functional

capacity were similar in treatment

arms

Authors opinion re: AF and HF

Attempt rhythm control initially for HF patients

with AF (anti-arrythmic drugs or catheter
ablation)

If Rhythm control not possible, then rate

control via definite means

Allows determination if symptom rhythm

correlation exists

AV node ablation with pacing support

No high quality evidence exists that anti

arrhythmic result in better outcome.[]but
data is older, retrospective and suspect

AF + HF: ongoing management

Rhythm control vs rate control in HF patients

AF-CHF
Catheter ablation
?cardiovert
Anti arrhythmic

Dofetilide younger patients with persevered kidney

fection
Amiodarone
Sotalol avoid in those with poor left ventricular
function preferred in young healthy and those

Rate control

Dofelitide

Class 3 anti-arrhtymic drug

DIAMON CHF Trial

1518 patients with symptomatic HF including 391

with AF at baseline
Dofetilide arm was more likely to be associated
with reversion to SR at 1 month and 1 year
HOWEVER NO DIFFERENCE IN MORTALITY
BETWEEN DOFETILIDE AND PLACEBO GORUP

AMIODARONE

When used in low doses - <400mg/day

Lack of negative inotropic effect

Low incidence of QT prolongation, but no proarrhthymia

CHF STAT trial subset analysis

103 patients with AF 51 randomly assigned to

amiodarone 52 to placebo

Amiodarone arm had lower mortality

During AF 16-20% reduction in mean ventricular rate

Issues encountered in amiodarone arm:

32% developed bradycardia required discontuion of digoxin

19% required permanent pacemaker
14% other complications hypothyroidism and neurotoxicity.

Cather ablation in patients with HF

More optimistic re: outcomes in patients with HF and AF

ARC HF 52 patients RCT catheter ablation or rate control

PABA CHF trial 81 patients with symptomatic drug resistant

AF and an LVEF <40%

Peak oxygen consumption significantly increase in ablation arm

compared with rate control
QOL and BNP significant improved in ablation arm

RCT biventricular pacing rate control or catheter ablation

rhythm control
At 6/12 catheter ablation group: better QOL, longer 6 min walk
distance, higher ejection fraction

CAMTAF trial 50 patients with persistent AF, symptomatic HF

and LVEF<50%

Cather ablation group 81% achieved SR, LVEF significantly higher

Catheter ablation in patients with HF

2014 Meta-analysis 1838 AF patients with

mean LVEF of 40%
Long term efficacy at end of follow up was
60%, fall of BNP 1187 to 657 pg/ml

Anselmino M, Matta M, DAscenzo F, et al. Catheter ablation of atrial

fibrillation in patients with left ventricular systolic dysfunction: a
systemic review and meta analysis. Circulation Arrhythmia
Electrophysiology 2015; 7:1011

AF + HF: when to cardiovert?

1st episode of AF
If after management of heart failure, patient
does not improve.

Rate control

Rate control goal:

1st line beta blocker (Carvedilol, extended

metoprolol, bisprolol)

<110
<85 at rest <110 during moderate exercise

Does not improve mortality in acute setting

CCB has been show to increase mortaltiy
Digoxin lesser effeicacy
Amiodarone significant limitation

2nd line: digoxin added to betablocker

IF decompenwsated start with digoxin
If not under contorl, then amiodarine

Angiotensin Inhibition: Mechanism

Reduction in atrial stretch

?prevention of atrial fibrosis

Prevention of electrical remodelling and direct
antiarrhythmic effects

Angiotensin Inhibition: Prevention of AF

Few RCTs which show reduced incidence of AF

TRACE trial

SOLVD trial

Chronic left ventricular dysfunc in patients with IHD. Reduced incidence

of subsequent AF at a mean follow up of 2.9 years

2010 metanalysis 26 trials

ACE and ARB significantly reduces risk of development of AF

More effective in patients with systolic heart failure
Greater in prevent recurrent AF than compared to new AF
Issues with paper:

Left ventricular dysfunc and sinus rhythm after AMI, trandopril was asso
w/ significantly reduced incidence of AF at 2 and 4 year follow up 2.8 vs
5.3 rel to placebo

Inclusion of post hoc analysis of randomist trialis performed for reasons

other than prevention of AF (eg. HF, post MI, HTN)
Hetrogeniety
Likely presence of public bias, ascertainment bias

In setting of hypertension:

2010 metanalysis found no significant reduction in risk of AF

Angiotensin Inhibition: Prevention of

recurrent AF

GISSI-AF RCT

Hx of symptomatic AF but in valsartan or

placebo
Did not prevent recurrent AF
Downside of trial only 8% had heart failure/left
ventricular dysfunc

ACTIVE I study RCT

Irbesartan or placebo
Nil difference in indience of AF on follow up