1. Atrial Fibrillation Steve McGlynn
Specialist Principal Pharmacist (Cardiology),
Greater Glasgow and Clyde
Honorary Clinical Lecture,
University of Strathclyde

3. Some types of arrhythmia
Supraventricular
Sinus Nodal
Sinus bradycardia
Sinus tachycardia
Sinus arrhythmia
Atrial
Atrial tachycardia
Atrial flutter
Atrial fibrillation
AV Nodal
AVNSVT
Heart blocks
Junctional
Ventricular
Escape rhythms
Ventricular tachycardia
Ventricular fibrillation

4. Atrial fibrillation
A heart rhythm disorder (arrhythmia). It usually involves a rapid heart rate, in which the upper heart chambers (atria) are stimulated to contract in a very disorganized and abnormal manner.
A type of supraventricular tachyarrhythmia
The most common arrhythmia

6. Aetiology Rheumatic heart disease Coronary heart disease (MI)
Hypertension
Myopericarditis
Hypertrophic cardiomyopathy
Cardiac surgery
Thyrotoxicosis
Infection
Alcohol abuse
Pulmonary embolism
Caffeine
Exercise
Lone AF

7. Incidence / Prevalence
1.7 / 1000 patients / year
3 / 1000 patients / year (>60 years)
% (overall)
2 – 4% (>60 years)
>8% (>80 years)

8. Classification New / Recent onset Paroxysmal Persistent Permanent
< 48 hours
Paroxysmal
variable duration
self terminating
Persistent
Non-self terminating
Cardiovertable
Permanent
Non-cardiovertable

9. Symptoms / Signs Breathlessness / dyspnoea Palpitations
Syncope / dizziness
Chest discomfort
Stroke / TIA
6 x risk of CVA
2 x risk of death
18 x risk of CVA if rheumatic heart disease
Irregularly irregular pulse
Atrial rate
bpm
Ventricular rate depends on degree of AV block
bpm
Peripheral rate slower (pulse deficit)

10. Investigations Electrocardiogram (ECG)
All patients
May need ambulatory monitoring
Transthoracic echocardiogram (TTE)
Establish baseline
Identify structural heart disease
Risk stratification for anti-thrombotic therapy
Transoesophogeal echocardiography (TOE)
Further valve assessment
If TTE inconclusive / difficult

11. Normal Sinus Rhythm

12. ‘Fast’ AF

13. ‘Slow’ AF

14. Atrial Flutter

15. Investigations Electrocardiogram (ECG)
All patients
May need ambulatory monitoring
Transthoracic echocardiogram (TTE)
Baseline
Structural heart disease
Risk stratification for anti-thrombotic therapy
Transoesophogeal echocardiography (TOE)
Further valve assessment
TTE inconclusive / difficult

16. Diagnosis
Based on:
ECG
Presentation
Response to treatment

17. Treatment objectives
Rhythm / rate control
Stroke prevention

18. Treatment strategies New / Recent onset Cardioversion Rhythm control
Paroxysmal
Rate control or cardioversion during paroxysm
Rhythm control if needed
Persistent
Cardioversion
Rhythm control
Peri-cardioversion thromboprophylaxis
Permanent
Rate control
Thromboprophylaxis

19. Pharmacological Options
Class Ic Anti-arrhythmics
Flecainide / Propafenone
Rhythm control
May also be pro-arrhythmic
Class II Anti-arrhythmics
Beta-blockers
Mainly rate control
Control rate during exercise and at rest
Generally first choice
Choice depends on co-morbidities
The standard classification of antiarrhythmic drugs is Vaughn-Williams. This is based on the effect of the drugs on the action potential. Digoxin is not included.
All classes have a place in the management of AF. Choice depends of type of AF, co-morbidities and other patient factors.
The Class Ic antiarrhythmics are used to restore and maintain sinus rhythm. They are, however, negatively inotropic (shouldn’t be used in heart failure) and are also pro-arrhythmic, especially if the patient has coronary heart disease.
The Class II anti-arrhythmic drugs are the beta-blockers. Mainly used for rate control, and are effective both at rest and during periods of high sympathetic tone e.g. exercise, stress. They are usually first choice unless contra-indicated, e.g. asthma, acute heart failure.

20. Class III Anti-arryhthmics
Amiodarone / Dronedarone
Mainly rhythm control
May be pro-arrhythmic
Concerns over toxicity
Class IV Anti-arryhthmics
Calcium channel blockers (verapamil / diltiazem only)
Rate control only
Alternative to beta-blockers if no heart failure
Digoxin
Does not control rate during exercise
Third choice unless others contra-indicated
The class III agents are amiodarone and dronedarone, although sotalol, a beta-blocker also has class III effects. They work by prolonging the action potential and therefore both restore and maintain sinus rhythm. Amiodarone is particularly effective but its long term use is limited by serious side effects. Dronedarone is a newer, less toxic but less effective alternative. It’s use is limited in patients with heart failure and there are now concerns about hepatotoxicity.
Intravenous amiodarone is useful to restore sinus rhythm in acute AF.
The Class IV antiarrhythmics are the calcium channel blockers verapamil and diltiazem. They are useful alternatives to beta-blockers but are contra-indicated in acute and chronic heart failure.
Digoxin has been used for hundreds of years. It is of little use in patients who are active since high sympathetic tone overcomes its effect at the AV node. Its main role is in rapid rate control in patients who also present in acute heart failure and in those patients who require long-term management but lead sedentary lifestyles.
Plasma levels need to be checked due to a narrow therapeutic index.

21. Acute AF Treatment will depend on: History of AF
Time to presentation (<> 24 hours)
Co-morbidities (CHD, CHF/LVSD etc)
Likelihood of success (History)

22. Rhythm control not feasible or safe
Rate Vs. Rhythm control
Rhythm control not feasible or safe
Beta-blocker
Verapamil
Digoxin (CHF)
Rhythm control if possible and safe
DC cardioversion (if possible)
Amiodarone (CHD or CHF/LVSD)
Flecainide (Paroxysmal AF)

23. Paroxymal AF Rhythm control* Beta-blocker Class 1c agent or sotalol
If CHD - sotalol
If LVD: Amiodarone
Dronedarone?
*May be “Pill in the pocket”
Antithrombotic therapy as per risk assessment
Aspirin mg
warfarin to INR 2-3
See later

24. Persistent AF Rhythm control Beta blocker
No structural heart disease: Class 1c* or sotalol
Structural heart disease: amiodarone
Rate control
As for permanent AF
* not if CHD present
Antithrombotic therapy as per risk assessment
Pre-cardioversion thromboprophylaxis of at least 3 weeks
If rate control, as for permanent AF

25. Permanent AF Beta blocker or Calcium channel blocker and/or Digoxin
Amiodarone?
Antithrombotic therapy as per risk assessment
Aspirin mg
Warfarin to INR 2-3
See later

26. Stroke prevention (non-rheumatic AF)

27. Stroke Risk Assessment (CHADS2)
C Chronic Heart Failure (1 point)
H Hypertension (1 point)
A Age > 75 years (1 point)
D Diabetes (1 point)
S Stroke, TIA or systemic embolisation (2 points)
Score < 2: low risk, aspirin or anticoagulant
Score ≥ 2: high risk, anticoagulant indicated
The choice of anticoagulation versus antiplatelet therapy to reduce the risk of stroke is based on the balance between the stroke risk versus the risk of a serious bleed.
The CHADS2 scoring system is commonly used to assess stroke risk. High risk patients should be offered anticoagulation unless contra-indicated.
This scoring system has been criticised because it underestimates the effect of age as well as several other factors.

28. Stroke Risk Assessment (CHA2DS2VASc)
Alternative to CHADS2
C Chronic Heart Failure (1 point)
H Hypertension (1 point)
A Age > 75 years (2 points)
D Diabetes (1 point)
S Stroke, TIA or systemic embolisation (2 points)
V vascular disease (1 point)
A Age years (1 point)
Sc Sex category (1 point if female)
THE CHADSVASc scoring system has been proposed as an alternative. It adds in the effect of co-existing vascular disease and being female. It also increases the score factor associated with age.
Under this system, more patients are eligible for anticoagulation.

29. Bleeding Risk Assessment (HAS-BLED)
1 point each for:
Hypertension
Abnormal renal/liver function (1 for each)
Stroke
Bleeding history or predisposition
Labile INR
Elderly (age over 65)
Drugs*/alcohol** concomitantly (1 for each)
*Drugs that increase bleeding, e.g. aspirin
** Alcohol excess
To assess the risk of a bleed on anticoagulation, a scoring system for bleeding has been developed.
The HAS-BLED score gives an indication of how high risk a patient is. A score of >3 is considered high risk. No definitive cut-off for avoiding anticoagulation has been defined however.
It should be noted that 3 of the criteria also appear in CHADSVASc!

30. Anticoagulants Warfarin remains standard anticoagulant at present
3 new oral anticoagulants (unlicensed for AF as of June 2011)
Dabigatran (Direct thrombin inhibitor)
Rivaroxiban (Factor Xa inhibitor)
Apixaban (Factor Xa inhibitor)
Fixed doses
No monitoring
At least as effective as warfarin
Safer than warfarin?
Much more expensive (even allowing for INR costs)
Place in therapy not clear yet
Warfarin is currently the anticoagulant of choice. This is based on the experience gained over decades of use. It does however have its limitations, mainly dose variability.
Three new oral anticoagulants have been developed. All have been shown to be either:
More effective than warfarin (high dose dabigatran)
Non-inferior to warfarin (low dose dabigatran, rivaroxaban, apixaban)
As safe as warfarin (high dose dabigatran)
Safer than warfarin (low dose dabigatran)
As of July 2011 none are licensed for AF stroke prevention. Dabigatran is likely to be approved soon and is due to be reviewed by SMC late summer 2011.
These drugs are fixed dose and do not require INR monitoring. Despite these advantages there are concerns around adherence (no monitoring, BD dosing) and safety (they are not easily reversed unlike warfarin).
They are also considerably more expensive, even allowing for no monitoring. There place has yet to be established in NHS Scotland although guidance is expected late summer/early autumn.

31. Conclusions AF is a common condition.
Patients may be unaware of its presence and are therefore at risk of a stroke
Alternative treatment strategies exist to control symptoms
Alternative treatment strategies exist to reduce the risk of stroke
Patient education and choice are central to improving the likelihood of treatment success