1) Atrial fibrillation is the most common cardiac arrhythmia characterized by irregular electrical activity in the atria. It increases in prevalence with age and can cause complications like heart failure, stroke, and systemic embolism.
2) Management of atrial fibrillation involves rate or rhythm control as well as long-term anticoagulation to prevent thromboembolism depending on stroke risk factors. The CHA2DS2-VASc score is used to assess this risk.
3) While antiarrhythmic drugs and cardioversion can restore normal sinus rhythm, rate control is preferred for many patients. Newer anticoagulants like dabigatran and rivar
2. A Fib
• Atrial fibrillation (AF) is the most common
cardiac arrhythmia
• Prevalence increases with age - 1 in 5 people
over the age of 85 years having the condition,
compared to <1% of people younger than 60
years
• Spontaneous discharge by ectopic pacemaker
cells in large pulmonary veins @ point where
they join LA
3. Pathophysiology
• Chaotic electrical discharge in the atria of the
heart from ectopic foci
• Cause an irregular, rapid atrial contraction
• Leads to rapid ventricular conduction via AV
nodal conduction
4. Features
• RR intervals follow no repetitive pattern—
they have been labeled as “irregularly
irregular.”
• While electrical activity suggestive of P waves
is seen in some leads, there are no distinct P
waves
• ”cherche la P!”
7. Main complications :
Systemic emboli
Heart failure
• Systemic emboli are mainly to the cerebrum
are due to irregular haemodynamic flow
through the left atrium.
• Predisposes to thrombus formation
• Assoc with 16% of all strokes
8. • Atrial fibrillation also leads to loss of atrial
contraction at the end of diastole, which in
elderly people with reduced ventricular
compliance, can lead to reduced stroke
volume and thus reduced cardiac output,
predisposing to the development of heart
failure
• Atrial fibrillation is present in up to 50% of
patients with heart failure
9. Classification
• Paroxysmal: Terminates spontaneously in
less than 7 days (usually <24h)
• Persistent: Sustained greater than 7 days
and rarely terminates
spontaneously
• Permanent: Cardioversion has failed or the
restoration of sinus rhythm is
no longer possible
11. ESC, AHA & NICE
Acutely unwell with rapid ventricular rate and
acute symptoms need:
i) urgent rate control treatment via oral or IV
pharmacological intervention
and/or
i) emergency DC (electrical) cardioversion to
restore normal sinus rhythm (NSR)
12. OPD Setting
• Outpatient initiation of antiarrhythmic drug therapy
with the following agents may be considered:
• Flecainide or propafenone in patients in sinus rhythm
who have no underlying structural heart disease,
normal baseline QT intervals, and no profound
bradycardia or suspected sinus or AV node
dysfunction.
• Amiodarone or dronedarone in selected patients who
have no other risk factors for torsades de pointes (eg,
hypokalemia, hypomagnesemia) or sinus node
dysfunction or AV conduction disease. Dronedarone
and amiodarone are the only two drugs that can be
initiated in outpatients while in atrial fibrillation.
13.
14. Decision for Inpatient
• The decision to hospitalize depends upon several
factors:
i. The presence and severity of structural heart disease.
ii. The indication for treatment (eg, etiology of the
arrhythmia and type and severity of associated
symptoms). Treatment for ventricular tachycardia is
usually started in the hospital.
iii.The drug used. For example, the labeling information
for dofetilide and sotalol specify inpatient initiation,
while flecainide, propafenone, dronedarone, and
amiodarone can generally be initiated outside the
hospital in appropriate patients.
16. Reasons to not cardiovert
Circumstances in which it is reasonable to avoid cardioversion attempts in
patients with new onset AF include:
•Patients who are minimally symptomatic, particularly those with multiple comorbidities or poor
overall prognosis, where the risks of undergoing cardioversion and/or pharmacologic rhythm control
may outweigh the benefits of restoring sinus rhythm. There is no age cut-off for the restoration of sinus
rhythm, but the benefit from cardioversion begins to decline as age increases after 80.Patients with a
low likelihood of maintenance of sustained SR (see below).
•Patients with paroxysmal AF are usually not cardioverted, as the AF is often of short duration, resolves
spontaneously, and almost always.
The following factors decrease the likelihood of success of immediate
conversion as well as long-term maintenance of SR; they should be
considered when deciding whether to perform a cardioversion:
•AF has been present continuously for more than one year [1-8]
•The left atrium is markedly enlarged (atrial dimension >5.0 cm) [9-13]
•Elderly (>80 years of age) [2]
•Associated cardiovascular conditions (eg, left ventricular dysfunction) [2]
•Patients who had recurrence while taking adequate doses of appropriate antiarrhythmic drug therapy.
Drug refractory patients may be able to be converted to SR but are less likely to maintain SR long term.
•Cardioversion with maintenance of SR is likely to be unsuccessful if the cause (thyrotoxicosis,
pericarditis, and mitral stenosis) for the AF has not been corrected prior to attempted cardioversion.
17. If haemodynamically stable and few symptoms:
• slow heart to a normal range using rate
control
• use adequate anticoagulation therapy to
prevent emboli forming
• Then long term management strategy is
chosen depending on the patient’s
circumstances
18.
19. • 1st
episode atrial fibrillation of <48 hours onset
in well patients with mild symptoms, can be
treated with pharmacological or DC
cardioversion, with IV heparin prophylaxis for
thrombus formation.
• Once NSR is restored, 4 weeks of OAC may be
necessary in a patient with an increased risk of
thrombus formation.
• This may be extended to long term OAC if risk
is significantly high.
20. • If it cannot be determined that onset is <48
hours, a transoesophageal echocardiograph may
be performed to detect the presence of a LA
thrombus.
• If none is present, immediate cardioversion may
be carried out, or 3 weeks of therapeutic OAC to
give an INR 2-3 may be carried out first before
cardioverting.
• If a thrombus is detected on TOE and is still
present after 3 weeks OAC therapy, rate control
and long term OAC is deemed to be the most
suitable treatment
21. Management of persistent/permanent
atrial fibrillation
• Traditionally been one of either rate or
rhythm management
• NICE, ESC and AHA guidelines
recommendation are for 1st
line management
are:
22. Examples of rhythm controls
(according to efficacy of cardioversion):
a) Emergency cardioversion
Flecainide (most efficient for emergency
cardioversion).
Propafenone (2nd
most efficient for em. cardioversion)
*Ibutilide.
(b) Maintenance of NSR
Amiodarone (use if structural heart disease. Delayed
pro-arrhythmic hence least efficient for emergency
cardioversion but most efficient for maintenance of
NSR, and rapid ventricular rate control).
Dofetilide (rarely used for cardioversion but
maintenance of NSR) .
Less effective for cardioversion and maintenance:
Sotalol
Dronedarone
Newer agents:
*Vernakalant.
Examples of rate controls:
Beta blockers (acute: metoprolol, propanolol,
esmolol, chronic: also **atenolol, **nadolol).
Calcium blockers (Verapamil, diltiazem).
Digoxin (use if sedentary. Controls HR at rest,
can be used in combination with BB or ?CB).
Amiodarone (best avoided due to severe side
effects, rapid ventricular control but can promote
cardioversion, consider if all the above fails).
MgSO4 (little evidence, under trials).
*IV only
** long half life so can be given OD
23.
24.
25. OAC & A Fib
• AFFIRM and RACE trial data of rate vs rhythm
control of A Fib regarding ischaemic stroke
emphasizes the need for OAC therapy in
patients being treated for atrial fibrillation.
• In AFFIRM & RACE a trend towards reduction
in ischaemic strokes in the rate control branch
of both studies was due to maintained OAC
and an INR therapeutic range of 2-3 in those
on rate therapies
27. CHADS2
• Aspirin is recommended for patients scoring 1 on
the CHADS2 score, or those in whom warfarin is
contraindicated.
• Patients scoring > 1 are recommended for
anticoagulation using warfarin
• Usually anticoagulation is recommended as long
term treatment.
• Warfarin treatment with an INR = 2-3,has been
shown to reduce the risk of stroke by 65-68%
when compared to placebo, and 32-47% when
compared to aspirin
28. • Aspirin in turn resulted in a 21% reduction in
strokes when compared to placebo.
• Warfarin & aspirin combined therapy should not
be used as it increases haemorrhage risk
significantly
• Warfarin vs combined therapy or low dose
aspirin + clopidogrel (75mg/75mg) in patients
with atrial fibrillationshowed warfarin to have a
significantly lower annual rate of mortality &
morbidity [RR 0.69 (95% C.I 0.57-0.85)].
29. • Aspirin monotherapy vs combined
Aspirin/Clopidogrel in atrial fibrillation patients when
warfarin is contraindicated showed a significant
decrease in mortality and morbidity in the
combination group [RR 0.72 (95% C.I. 0.81-0.98)] but a
significant increased risk in incidence of major bleed
(2% vs 1.3%) [RR 1.57 (95% C.I. 1.29-1.92)]
• Therefore it is reasonable to say that dual therapy of
aspirin and clopidogrel is a suitable alternative to
aspirin monotherapy in patients with atrial fibrillation
who are at high risk of stroke and in whom warfarin is
contraindicated
30. ESC Guidelines
• ESC guidelines, while acknowledging the benefit
of CHADS2 scoring system, prefer not to classify
stroke risk as “low”, “moderate” and “high”, as
risk is seen as something which is a continuum
• CHADS2 does not include many stroke risk factors,
and other ‘stroke risk modifiers’ which must also
be considered when starting OAC, such as
vascular disease and sex.
• CHA2DS2VASc!
31.
32.
33. Bleed Risk assessment before start of
OAC
• HAS-BLED score assesses bleeding risk in AF
patients, with a score of ≥3 indicates ‘high
risk’.
• Cautious initial dosing and regular review of
the patient is needed following the initiation
of antithrombotic therapy, whether with
warfarin or aspirin.
35. Drug-resistant AF
• Some patients are refractory to individual antiarrhythmic agents plus an AV nodal
blocker or develop side effects on doses necessary for arrhythmia prevention.
Although some have suggested that combination antiarrhythmic drug therapy (eg, a
class IC agent with sotalol or amiodarone, often in lower doses) may be an alternative,
there are limited data to support such an approach and the patient may be exposed to
a greater risk of proarrhythmia and other side effects.
• As a result, combination antiarrhythmic drug therapy is not recommended. Such
patients can be treated with a rate control strategy or referred for nonpharmacologic
therapy to prevent recurrent AF including surgery (such as the maze operation),
radiofrequency ablation (such as pulmonary vein isolation), or an implantable atrial
defibrillator.
• Surgical approaches that are available include the maze and corridor operations as well
as radiofrequency or cryoablation. These procedures appear effective in a high
percentage of patients. However, the follow-up for many of these studies was limited
in scope and did not employ very rigorous arrhythmia surveillance.
• Long-term anticoagulant therapy is required in many patients after successful
treatment of AF with these surgical approaches.
• Patients with recurrent AF after one of these procedures may be candidates for
electrophysiology study and catheter ablation.
36. Future A Fib Mx and OACs
• Current anti-arrhythmics show no superiority
to rate control therapies due to their pro-
arrhythmic and tissue toxic side effects.
• Dronedarone is an anti-arrhythmic similar to
amiodarone but doesn’t have Iodine moiety
37. Dronedarone (Multaq)
• Dronedarone is less toxic to the body, especially to the
thyroid and pleural tissue,
• Benefit over amiodarone in people requiring long term
treatment. Dronedarone has been shown to be better
than placebo at maintaining NSR and has reduced rate
of hospital admissions
• However trials have shown that dronedarone has an
increased mortality rate in NYHA Class III/IV heart
failure when compared to amiodarone.
• Thus dronedarone is not recommended for use in
patients with severe heart failure and atrial fibrillation.
38. Future OAC therapies
• Warfarin is the anti-coagulant of choice in management of systemic
emboli risk reduction in atrial fibrillation
• Acts by inhibiting vitamin K end-glycosylation of Factor II, VII, IX and X.
• However patients on warfarin require careful INR monitoring through
frequent venepuncture and altering of dosing.
• Warfarin also interacts with a large variety of medications, thus altering
the INR profile and increasing risk of clot formation or haemorrhage.
• However:
– Cheap as chips!
– Long term use & hx known and S/Es
– Reversible (Octaplex Prothombin Complex)
– Reduced blled risk in elderly compared with newer OACs.
39.
40. Future?
• Direct thrombin and Factor X inhibitors remove the need for continued
INR sampling.
• Dabigatran (Pradaxa) is a direct thrombin inhibitor,
• Requires no INR monitoring or dose adjustments.
• Therapeutic in 4 hrs
• 2 recent large scale RCTs [26]
have shown the non-inferiority of dabigatran
vs warfarin in prevention of thromboembolus formation, with a
significantly lower rate of haemorrhagic stroke and major bleeding with
dabigatran.
• However increased GI bleed risk
• Dabigatran received FDA licensing for the prevention of embolic events in
atrial fibrillation in October 2010
• However BD dosing
• Not reversible/No antidote currently
• More suited to younger patients?
41. • Direct factor Xa inhibitors ('xabans') are a class
of OAC which act directly upon Factor X in the
coag cascade, without using antithrombin as a
mediator
• Rivaroxaban (Xarelto)
• Max inhibition of factor Xa occurs four hours
after a dose.
• Effects last 8–12 hours, but factor Xa activity
does not return to normal within 24 hours
• Once-daily dosing is possible.
• Similar qs as Dabigatran
42. A few trials
• RACE trial, AFFIRM trial – rhythm control not
superior to rate control.
• RELY trial – Dabigatran.
• ROCKET AF trial – Rivaroxaban.
• ARISTOTLE trial – Epixaban.
