1. ATRIAL FIBRILLATION Dr ABHAY BAJPAI
Consultant Cardiologist & Electrophysiologist
Epsom & St Helier University Hospitals NHS Trust
St George’s Hospital NHS Foundation Trust

2. Electrical system

3. What characterises AF?
AF is a rhythm disorder (arrhythmia) of the top chambers
Rapid, disorganized electrical signals in the atria
Conduction to the ventricles is limited by the AV node. AF leads to:
Irregular ventricular rate (pulse)

4. ECG tracing
Normal - Sinus rhythm
Atrial Fibrillation

5. AF Burden in England 2.4% = 1.36 million people in England have AF
Only 1.6% diagnosed – 474,000 undiagnosed!

6. AF Burden in England Prevalence increases with age
2.9% in people aged < 45
16.6% in people aged 45-65
80.5% in people aged > 65.
Greater in men vs women, 2.8% vs 2.0%.
Prevalence (%)
The Rotterdam study
Age (years)
55–59
65–69
60–64
70–74
75–79
80–84
85

7. AF Burden in England

8. Lifetime risk of developing AF
At ≥40 years of age, the remaining lifetime risk for developing AF is:
26.0% for men
23.0% for women
In the absence of previous chronic heart failure or heart attacks, the lifetime risk of AF at age ≥40 years is reduced similarly for both men and women:
16.3% for men
15.6% for women

9. Why do we develop AF? Cardiovascular conditions Metabolic conditions
High Blood pressure
Heart attacks / Angina (ischaemic heart disease)
Heart failure
Heart Valve disease
Metabolic conditions
Obesity
Diabetes mellitus
Overactive Thyroid - Hyperthyroidism
Other
Obstructive sleep apnoea syndrome – common in obese people
Pneumonia / chest infections / other lung conditions
Heart - Lung surgery
High alcohol intake
Familial
Lone AF

10. Patients with AF (millions)
AF Epidemic has begun!
Year
2.08
2.44
2.26
5.1 2 4 6 8 10 12 14 16
1990
1995
2000
2005
2010
2015
2020
2025
2030
2035
2040
2045
2050
Patients with AF (millions)
5.42
11.7
15.2
4.34
9.4
3.33
7.5
8.9
2.94
6.8
7.7
8.4
10.2
3.80
4.78
10.3
13.1
5.16
11.1
14.3
5.61
12.1
15.9
5.6
5.9
2.66
6.1
6.7
Olmsted County data, 2006
(assuming a continued increase in AF incidence)
ATRIA study data, 2000
Olmsted County data, 20061
(assuming no further increase in AF incidence)

11. Why treat AF ? Independent risk factor for stroke
Background
Why treat AF ?
Independent risk factor for stroke
Approximately 5 x increased risk1
1 in 6 strokes occur in patients with AF2
AF-related strokes are typically more severe than strokes due to other aetiologies3,4
Independent risk factor for mortality
Approximately twofold increased risk5
Independent risk factor for heart failure
Heart failure further aggravates AF, worsening overall prognosis6
AF has serious consequences
AF can result in multiple serious consequences, such as stroke, heart failure and death
AF is an independent risk factor for stroke, increasing the risk by approximately fivefold;1 one in six strokes occur in patients with AF2
Furthermore, AF-related strokes are, in general, more severe than strokes due to other aetiologies3,4 and stroke risk persists even in patients with asymptomatic AF5
AF is also an independent risk factor for mortality – conferring an approximately twofold increased risk of death6
Additionally, AF is an independent risk factor for heart failure – and heart failure can further aggravate AF, worsening overall patient prognosis7
References
Wolf PA et al. Stroke 1991;22:983–988
Fuster V et al. Circulation 2006;114:700–752;
Lin HJ et al. Stroke 1996;27:1760–1764
Jørgensen HS et al. Stroke 1996;10:1765–1769
Page RL et al. Circulation 2003;107:1141–1145
Benjamin EJ et al. Circulation 1998;98:946–952
Wang T et al. Circulation 2003;107:2920–2925
1. Wolf PA et al. Stroke 1991;22:983–988; 2. Fuster V et al. Circulation 2006;114:700–752; 3. Lin HJ et al. Stroke 1996;27:1760–1764; 4. Jørgensen HS et al. Stroke 1996;27:1765–1769;5. . Benjamin EJ et al. Circulation 1998;98:946–952; 6. Wang T et al. Circulation 2003;107:2920–2925 11

12. AF significantly impairs quality of life
Background
AF significantly impairs quality of life
Patients with AF experience significant impairments to their QoL1–3 * * * *
SF-36 mean score
AF significantly impairs quality of life
Patients with AF have significantly lower QoL, as measured by the SF-36 scale, in terms of general health, physical health, mental health and social function, compared with subjects without AF
Notably, patients with AF have been found to have numerically lower SF-36 scores than patients who had suffered a non-fatal MI
Abbreviation
SF-36, short form 36
References
Dorian P et al. J Am Coll Cardiol 2000;36:1303–1309
Van den Berg MP et al. Neth J Med 2005;63:170–174
1. Dorian P et al. J Am Coll Cardiol 2000;36:1303–1309; 2. Van den Berg MP et al. Neth J Med 2005;63:170–174
* p<0.001 compared to AF patients 12

13. Symptoms of AF Typical symptoms of AF include:
Background
Symptoms of AF
Typical symptoms of AF include:
Palpitations (a sensation of rapid irregular heartbeat)
Fatigue
Shortness of breath
Dizziness/light headedness Or Stroke
Chest pain - uncommon
Blackout - uncommon
AF may not cause any symptoms
Approximately 1/3rd of patients
Symptoms of AF
The presence of AF in patients may be indicated by certain physical symptoms; these include palpitations, fatigue/weakness, chest pain, lightheadedness, syncope and dyspnoea.1 However, a substantial number of patients remain asymptomatic; this is a particularly serious situation because these patients may be at continuous risk of stroke2
The degree to which AF remains undetected was demonstrated in a study by Israel and colleagues.2 Their aim was to determine the incidence and time course of AF recurrences in patients with a history of paroxysmal or persistent (not permanent) AF, who had been fitted with an implantable monitoring device that specifically recorded AF episodes
Patients were followed up for a mean period of 19 months (±11 months). During that period, patients were also monitored at regular intervals with standard serial ECG recordings
Out of a total of 110 patients enrolled, 50 patients had device-documented AF episodes lasting longer than 48 hours. Of these, 19 (38%) were asymptomatic and presented in normal sinus rhythm at the respective follow-up visit (i.e. no AF detected with serial ECG)
This prospective study clearly showed that in patients with recurrent AF episodes lasting longer than 48 hours, more than a third remained completely asymptomatic2
References
Fuster V et al. Circulation 2006;114:700–752
Israel CW et al. J Am Coll Cardiol 2004;43:47–52
1. Fuster V et al. Circulation 2006;114:700–752; 2. Moran PS et al. The Cochrane Collaboration, April 2013 13

14. Classification of AF Paroxysmal < 7 days , commonly < 48hrs
Persistent > 7days and < 1 year
Long standing persistent > 1year
Permanent

15. Background
Progression of AF
Progression of AF is thought to be driven by structural changes in the atria, including electrical, contractile changes, known as atrial remodelling1
First diagnosed episode of AF
Paroxysmal
(usually ≤48 hours)
Persistent
(>7 days or requires cardioversion)
Progression of AF
The progression of AF is hypothesized to be driven by structural changes in the atrium –including electrical and contractile changes – known as atrial remodelling
AF is a progressive disease; it tends to progress from paroxysmal (self-terminating, usually within 48 hours) to persistent (non-self-terminating or requiring cardioversion), long-standing persistent (lasting longer than 1 year) and eventually to permanent (accepted) AF
First-onset AF may be the first of recurrent attacks – or indeed, may already be permanent
Reference
Camm AJ et al. Eur Heart J 2010;31:2369–2429
Long-standing
persistent (>1 year)
Permanent
(accepted)
Different types of AF. The arrhythmia tends to progress from paroxysmal (self-terminating, usually <48 hours) to persistent (non-self-terminating or requiring cardioversion), long-standing persistent (lasting longer than 1 year) and eventually to permanent (accepted) AF. First-onset AF may be the first of recurrent attacks or already be deemed permanent1
1. Camm AJ et al. Eur Heart J 2010;31:2369–2429 15

16. Diagnosis and monitoring of AF via ECG
Background
Diagnosis and monitoring of AF via ECG
An irregular pulse raises the clinical suspicion of AF
AF typically progresses from short, rare episodes to longer and more frequent attacks AF
Antiarrhythmic drugs
Anticoagulation
Rate control
Cardioversion
Paroxysmal
Silent
Persistent
Long-standing
persistent
Permanent
‘Upstream’ therapy of concomitant conditions
First documented
Ablation
Diagnosis and monitoring of AF via ECG
An irregular pulse always raises the suspicion of AF, but an ECG recording is necessary to actually diagnose it1
AF is considered present if any detected arrhythmia:1
Has the ECG characteristics of AF and lasts sufficiently long for a 12-lead ECG to be recorded, or
Lasts ≥30 seconds on a rhythm strip
The risk of AF-related complications is not different between short AF episodes and sustained forms of the arrhythmia2
It is therefore important to detect paroxysmal AF to prevent AF-related complications (e.g. stroke)
AF may manifest initially as an ischaemic stroke or TIA, and it is reasonable to assume that most patients experience asymptomatic, often self-terminating, arrhythmia episodes before AF is first diagnosed
ECG is not ideal for detecting early AF because it relies on AF being present at the time of monitoring
The rate of AF recurrence is 10% in the first year after the initial diagnosis, and ~5% per annum thereafter – co-morbidities and age significantly accelerate both the progression of AF and the development of complications
Abbreviation
TIA, transient ischaemic attack
Reference
Camm AJ et al. Eur Heart J 2010;31:2369–2429
Friberg L et al. Eur Heart J 2010;31:967–975
1. Camm AJ et al. Eur Heart J 2010;31:2369–2429 16

17. Valvular heart disease
Cardiovascular conditions and risk factors are important predictors of AF
Background
The Framingham Heart Study
Men (n=2,090)
Women (n=2,641)
Heart failure
4.5
5.9
Valvular heart disease
1.8
3.4
Hypertension
1.5
1.4
Cardiovascular conditions and risk factors are important predictors of AF
Cardiovascular and other medical conditions, including diabetes mellitus and hypertension, have been shown to place individuals at increased risk for developing AF1
In 1994, based on a 38-year follow-up of a cohort of 4,731 participants aged between 55 and 94 years and without a history of AF in the Framingham study, Benjamin and co­-workers reported that heart failure, valvular heart disease, hypertension, diabetes mellitus, MI and male sex were all significant predictors for AF
References
Benjamin EJ et al. JAMA 1994;271:840–844
Diabetes mellitus
1.4
1.6 MI
1.4
1.2; not significant 1 2 3 4 5 6 7 1 2 3 4 5 6 7 8 9
Odds ratio
Odds ratio
1. Benjamin EJ et al. JAMA 1994;271:840–844 17

18. Background
AF and stroke
Stroke is the most serious ongoing risk associated with AF1
In patients with AF, blood clots tend to form in the atria, particularly within the left atrial appendage, due to abnormal blood flow and pooling2
These clots may travel to the brain, causing an ischaemic stroke2
Around 20% of ischaemic strokes are caused by blood clots originating in the heart (cardioembolic); of these, AF is the most common cause3
AF and stroke
Individuals with AF are at increased risk for a number of clinically significant sequelae, such as hypertension, coronary heart disease and stroke. The most common and potentially serious of these is stroke1
Owing to the relative stasis of blood in the atria, patients with AF are predisposed to developing blood clots in the atria.2 The left atrial appendage, a muscular pouch located in the wall of the left atrium, is thought to be a common source of blood clots in patients with AF3
If a clot, or part of a clot, breaks free, it forms an embolus that can leave the left atrium of the heart and travel to the brain where it can cause an ischaemic stroke2
Approximately 20% of ischaemic strokes are a result of cardiogenic emboli (i.e. embolized blood clots that originated in the heart) and are often referred to as cardioembolic strokes; AF is the most common cause of cardiogenic emboli3
References
Wolf PA et al. Stroke 1991;22:983–988
Fuster V et al. Circulation 2006;114:700–752
Paciaroni M et al. Stroke 2007;38:423–430
1. Wolf PA et al. Stroke 1991;22:983–988; 2. Fuster V et al. Circulation 2006;114:700–752; 3. Paciaroni M et al. Stroke 2007;38:423–430 18

19. Patients with AF have an approximately fivefold increased risk of ischaemic stroke1
Background
Framingham Heart Study (N=5,070) 60
Risk ratio=4.8
p<0.001 50 40
2-year age-adjusted incidence of stroke/1,000 30
Patients with AF have an approximately fivefold increased risk of ischaemic stroke
AF is shown to substantially increase the risk of an ischaemic stroke1
The Framingham Heart Study prospectively followed men and women who were free of cardiovascular disease (including AF) at study enrolment for every 2 years for the development of cardiovascular disease2
A 34-year follow-up of this study, involving 5,070 participants, evaluated the impact of various cardiovascular conditions, including AF, on the incidence of stroke1,2
In a comparison of the 2-year age-adjusted incidence of stroke per 1,000 individuals with and without AF, those with AF were almost five times more likely to suffer an ischaemic stroke than those without AF (risk ratio=4.8, p<0.001, 2-year age-adjusted incidence of stroke: ~50/1,000 individuals with AF vs ~10/1,000 individuals without AF)1
Overall, it is estimated that ~15% of all ischaemic strokes are caused by AF2
References
Wolf PA et al. Stroke 1991;22:983–988
Wolf PA et al. Arch Intem Med 1987;147:1561–1564 20 10
Individuals
without AF
Individuals
with AF*
*Patients were untreated with antithrombotic therapy when this study was performed in line with clinical practice at the time
1. Wolf PA et al. Stroke 1991;22:983–988 19

20. AF-related stroke is preventable
Vitamin K antagonists and antiplatelet therapy for stroke prevention in AF
AF-related stroke is preventable
By preventing clot formation in the heart (thromboprophylaxis)
Blood thinning therapy reduces the risk of stroke and thromboembolism but also increases the risk of bleeding
AF-related stroke is preventable
Ischaemic strokes in patients with AF can be prevented by thromboprophylaxis – i.e. inhibition of the formation of cardiogenic thrombi
Thromboprophylaxis can be achieved by using drugs that interfere with the coagulation pathway (anticoagulants) or that inhibit platelet aggregation (antiplatelet drugs)
Although anticoagulant and antiplatelet drugs are used for thromboprophylaxis in patients with AF, anticoagulation is more effective based on clinical trials data. ASA is recommended for thromboprophylaxis in patients at low risk of stroke1–3
Both anticoagulant and antiplatelet therapy carry an increased risk of bleeding, which must be balanced against the need for thromboprophylaxis for each patient
Abbreviation
ASA, acetylsalicylic acid
References
Fuster V et al. Circulation 2006;114:700–752
Singer DE et al. Chest 2008;133:546S–592S
Camm J et al. Eur Heart J 2010;31:2369–2429
1. Fuster V et al. Circulation 2006;114:700–752; 2. Singer DE et al. Chest 2008;133:546S–592S; 3. Camm J et al. Eur Heart J 2010;31:2369–2429 20

21. Stroke risk in AF: the CHADS2 score
Clinical data
Stroke risk in AF: the CHADS2 score
Congestive heart failure 1 point
Hypertension 1 point
Age > point
Diabetes 1 point
Stroke or TIA 2 points

22. CHADS2 score correlates with stroke rate
Stroke rate per 100 patient years without antithrombotic therapy
Reference
Gage BF, et al. Validation of clinical classification schemes for predicting stroke. Results from the National Registry of Atrial Fibrillation. JAMA 2001;285:2864–2870.
CHADS2 score
Gage et al, JAMA 2001;285:2864–2870.

23. CHA2DS2-VASc score: definition
Risk factor
Points
Congestive heart failure/LV dysfunction +1
Hypertension
Age ≥75 years +2
Diabetes mellitus
Stroke/TIA/TE
Vascular disease (MI, aortic plaque, PAD)*
Age 65–74 years
Sex category (female)
Cumulative score
Range 0−9
CHA2DS2-VASc is a newly proposed scheme that takes into account some of the risk factors (female gender and vascular disease) not included in CHADS2
In addition, this scheme takes into account that in reality age does not suddenly become a risk factor at age 75 years (1 point is awarded for age 65–74 years, 2 points are awarded for age ≥75 years)
Patients with a CHA2DS2-VASc score ≥2 (1 definitive risk factor [age≥75 or prior stroke/TIA] or 2 clinically relevant non-major risk factors) are considered to be at high risk of stroke and in need of anticoagulation
Patients at intermediate risk, i.e. with a CHA2DS2-VASc score of 1 (1 clinically relevant non-major risk factor), may be managed with either ASA or OAC, although the latter is generally preferred
In contrast patients with a CHA2DS2-VASc score of 0 (no risk factors) may not require any form of antithrombotic therapy, thus simplifying the selection of patients for anticoagulation
Abbreviations
ASA, acetylsalicylic acid (aspirin); LV, left ventricular; MI, myocardial infarction; OAC, oral anticoagulation; PAD, peripheral artery disease; TE, thromboembolism; TIA, transient ischaemic attack
References
Lip et al. Refining clinical risk stratification for predicting stroke and thromboembolism in atrial fibrillation using a novel risk factor based approach: The Euro Heart Survey on Atrial Fibrillation. Chest 2010;137:263–272.
Lip et al. Improving stroke risk stratification in atrial fibrillation. Am J Med 2010;123:484–488.
Score: 0 = low risk; 1 = intermediate risk; ≥2 = high risk
Lip et al Chest 2010;137:263–272

24. Clinical data
Blood thinning drugs
The Rat Poison ! WARFARIN

25. Warfarin significantly more effective than clopidogrel + ASA combined
Vitamin K antagonists and antiplatelet therapy for stroke prevention in AF
ACTIVE-W results: patients with AF and ≥1 additional risk factor 10
Cumulative risk of stroke
RR 1.44
ARR 1.67 p=0.0003
0.05
Clopidogrel/ASA
RR=1.72 (1.24–2.37), ARR 0.99 p=0.001 8
Warfarin
0.04
RR 1.10
ARR 0.21
p=0.53 6
5.60
0.03
Annual incidence (%)
Cumulative hazard rates
Clopidogrel + ASA 4
3.93
0.02
2.42
2.21
Warfarin 2
Warfarin significantly more effective than clopidogrel + ASA combined
ACTIVE-W results: patients with AF and ≥1 additional risk factor:
In ACTIVE-W, patients (n=6,706) with AF and ≥1 additional risk factor for stroke were randomized to receive warfarin or clopidogrel plus ASA
The additional risk factors for stroke were: age ≥75 years, previous stroke/TIA or systemic embolism, left ventricular ejection fraction <45%, peripheral arterial disease, or if aged 55–74 years, patients also had to have diabetes mellitus or previous coronary artery disease
The primary endpoint was the first occurrence of stroke, non-CNS systemic embolus, myocardial infarction or vascular death
Patients were allocated randomly to receive warfarin therapy (target INR 2.0–3.0) or clopidogrel (75 mg/day) plus ASA (75–100 mg/day) and were intended to be followed for approximately 2 years
The trial was stopped early because of clear evidence of the superiority of warfarin therapy
Patients on warfarin had 165 primary endpoint events (annual risk 3.93%) and those on clopidogrel plus ASA had 234 (annual risk 5.60%; RR=1.44; 95% CI 1.18–1.76; p=0.0003) and ARR of 1.67.
Major bleeding rates were similar in both treatment groups
It was concluded that warfarin therapy is superior to clopidogrel plus ASA for the prevention of vascular events in patients with AF at high risk of stroke
Abbreviations
CNS, central nervous system; INR, international normalized ratio; TIA, transient ischaemic attack, ARR, Absolute Risk Reduction
Reference
ACTIVE Writing Group of the ACTIVE Investigators. Lancet 2006;376:1903–1912
0.01
Primary endpoint*
Major bleeding
0.05
1.0
1.5
Years
Number at risk
Clopidogrel + ASA 3,335 3,168 2,
Warfarin 3,371 3,232 2,
*Composite of stroke, non-CNS embolism, myocardial infarction and vascular death
1. ACTIVE Writing Group of the ACTIVE Investigators et al. Lancet 2006;367:1903–1912 25

26. Non-VKA Blood thinning drugs
Clinical data
Non-VKA Blood thinning drugs
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
These drugs are not inferior to Warfarin and appear to have lesser risks of major bleeds
Less interaction with food or other drugs
No blood testing (no INR testing)
Rapid action, predictable action
Loss of action if not taken drug for hrs
No antidote yet if bleeding

27. HAS-BLED Bleeding Risk Score
Clinical data
Anticoagulation carries a risk of bleeding
CHA2DS2VASc score
versus
HAS-BLED Bleeding Risk Score
Thrombus prevention
Risk of bleeding

28. Unable to take blood thinners ?
Clinical data
Unable to take blood thinners ?
-High bleeding risk
-Drug allergy/intolerance
Left Atrial Appendage Occluder Device

29. Rate and Rhythm Control
Consider pharmacological and/or electrical rhythm control for people with Atrial Fibrillation whose symptoms continue after heart rate has been controlled or a rate-control strategy has not been successful
Electrical Cardioversion (shock treatment)
Rhythm maintaining drugs
- Beta-blocker
- Sotalol, Flecainide, Amiodarone etc
Have potential side effects
Rate controlling drugs
- Beta blockers, Digoxin, Diltiazem, etc
Note here the recommendation for using amiodarone before and for a year after electrical cardioversion. If Xarelto is used in this situation in addition, there is no need to worry about an interaction with amiodarone.
As we mentioned earlier, caution must be exercised if dabigatran is used in combination with amiodarone due to an increased risk of bleeding.
NICE AF Guideline June 2014

30. AF Ablation Invasive Frequently require General anaesthesia
Works best for Paroxysmal AF patients
(Pulmonary Vein Isolation)
Poor results if AF > 1year or large Atrium
(requires more extensive ablation)
Multiple procedures common
Invasive
Frequently require General anaesthesia
1% risk of complications overall
1: risk of fatality from procedure
Radiofrequency energy – ‘Burning’
Cryothermal energy – ‘Freezing’
Note here the recommendation for using amiodarone before and for a year after electrical cardioversion. If Xarelto is used in this situation in addition, there is no need to worry about an interaction with amiodarone.
As we mentioned earlier, caution must be exercised if dabigatran is used in combination with amiodarone due to an increased risk of bleeding.

31. AF Ablation
No evidence currently of benefit in patients who are asymptomatic
Blood thinners likely to continue longterm after ablation esp if high risk factors
No evidence that improves prognosis / mortality from AF (except if AF related heart failure)
Note here the recommendation for using amiodarone before and for a year after electrical cardioversion. If Xarelto is used in this situation in addition, there is no need to worry about an interaction with amiodarone.
As we mentioned earlier, caution must be exercised if dabigatran is used in combination with amiodarone due to an increased risk of bleeding.
NICE AF Guideline June 2014

32. Radiofrequency Ablation – ‘Burning’
St Jude Medical

34. Radiofrequency Ablation – ‘Gaps’
Courtesy Google!

35. Cryoballon Ablation – ‘Freezing’
Medtronic Inc
Picture courtesy Gammie JS et al

37. Key points AF is the commonest rhythm problem
There is considerable related morbidity and mortality
Prevalence is increasing in epidemic proportions
Significantly increases risk of stroke, esp in patients with score >1
Blood thinning agents significantly reduce stroke risk
Higher incidence in patients with common health problems & increasing age
Maintaining healthy lifestyle, controlling risk factors (eg Diabetes, BP)
significantly reduces AF occurrence
Persistent AF greater than 1 year is challenging to treat
Rate control is equally good as rhythm control in asymptomatic patients
Ablation procedures offer high success rates in paroxysmal AF.