Download Paradigm shift in the management of Atrial Fibrillation

Overview management of
Atrial Fibrillation-the
cardiologist aspect
腦及行為科學整合課程
(Min-Forum -Summary)
跨領域教師:心臟血管科
林維祥
Outlines
• Historical review and mechanism, risk
factors of atrial fibrillation
• Impact of AF progression and benefits
of early rhythm control
• Overview of current management of
atrial fibrillation
• Take home messages
Historical review of Atrial fibrillation
AF was described for the first time in 1628
• A. « But I … have noticed , that after the
heart proper, and even the right auricle
were ceasing to beat and appeared on the
point of death, an obscure movement,
undulation / palpitation had clearly
continued in the right auricular blood itself
for as long as the blood was perceptly
imbued with warthm and spitit »
William Harvey – Exercitatio Anatomica de
Motu Cordis et Sanguinis in Animalibus
(1628)
William Harvey (1578-1657), English physician and physiologist, was
probably the first to describe « fibrillation of the auricles » in animals
AF is characterized by the presence of
multiple abnormal electrical circuits
Role of Pulmonary Vein Electrical
activity in the initiation of Atrial
fibrillation by Professor Cheung DW
• Electrical activity of the pulmonary vein and its
•
interaction with the right atrium in the guinea-pig.
J Phsyiol 1981;314:445
Pulmonary vein as an ectopic focus in digitalis-induced
arrhythmia. Nature 1981;294(5841):582
Mechanisms of Atrial Fibrillation
Ganglionic plexi
Multiple reentrant wavelets
PV and non-PV triggers
Composite of the anatomic and
arrhythmic mechanism
Multiple interacting risk factors drive
AF development and progression
Heart diseases
Pericarditis
Hypertensive
Valvular
Ischemic
Heart failure
Aging
Diabetic
Structural
remodelling
Extrinsic factors
Thyroid dysfunction
Endurance exercise
Tobacco - Illicit drugs
Sleep apnea
Alcohol
Obesity
Reentry
AF
Electrical
remodelling
Triggered activity
Autonomic
remodelling
Genetics
Mutations
Polymorphisms
Adapted from:
Camm AJ et al. Am Heart J. 2012;164(3):292-302.e1. Kirchhof P et al. Europace. 2012;14(1):8-27.
Outlines
• Historical review and mechanism, risk
factors of atrial fibrillation
• Impact of AF progression and benefits
of early rhythm control
• Overview of current management of
atrial fibrillation
• Take home messages
ESC guidelines classify AF based on
the presentation and duration of the arrhythmia
First diagnosed episode of atrial fibrillation
Paroxysmal
(usually ≤48 h)
Persistent
(>7 days or requires CV)
Long-standing
Persistent (>1 year)
Permanent
(accepted)
CV = cardioversion
Adapted from: Camm AJ et al. Europace. 2010;12:1360-420.
ACCF/AHA/HRS guidelines classify AF
based on duration and self-termination
First
detected
Persistent
"Recurrent AF"
Patient has 2 or
more episodes
(Not self-terminating)
Paroxysmal
Sustained beyond 7 days
Also includes cases of longstanding AF (e.g., greater than
1 year)
(self-terminating)
Permanent
Cardioversion has
failed or has not been
attempted
Adapted from: Fuster V et al. J Am Coll Cardiol. 2011 15;57(11):e101-98.
AF progression
Change from first detected AF or paroxysmal AF
to persistent / permanent AF
 Self-terminating >> non-self-terminating AF
Progressive atrial and ventricular remodelling and
cardiovascular events
 Atrial dilatation, fibrosis
 Tachycardiomyopathy, stroke, death
Adapted from: Camm AJ et al. Europace. 2010;12:1360-420.
AF usually progresses towards more
sustained forms as time goes by
Diagnosis
Paroxysmal
Spontaneous termination
Persistent
No spontaneous termination
AF episode
Permanent
Cannot be converted
to sinus rhythm
Sinus rhythm
 Only a small proportion of patients will remain in paroxysmal AF
over several decades (2-3% of AF patients)
Adapted from: Camm AJ et al. Europace. 2010;12:1360-420.
Prevalence of comorbidities increases
with degree of AF progression
Sanofi. Strictly confidential. Do not distribute. This information is provided for medical and
scientific purpose only. GLB.DRO.12.10.02 – 11/12
RealiseAF
Paroxysmal
Persistent
Permanent
p value
At least 1 comorbidity, %
69.3
75.7
84.8
<0.0001
Heart failure, %
32.9
44.3
55.6
<0.0001
Heart failure in class, %
<0.0001
No HF or NYHA I
72.7
62.0
50.3
NYHA II
20.0
24.3
29.5
NYHA III-IV
7.3
13.7
20.2
Left ventricular ejection fraction within
past 12 mo in %, n mean (SD)
1,975
58.5 (10.7)
1,892
54.3 (12.1)
3,481
53.3 (12.2)
<0.0001
Left ventricular hypertrophy (ECG), %
12.3
12.7
14.6
0.0117
Coronary artery disease, %
30.0
32.9
34.3
0.0009
Cerebrovascular disease, %
11.7
10.8
17.6
<0.0001
Valvular heart disease, %
16.7
21.2
35.8
<0.0001
Chronic pulmonary disease, %
9.4
8.9
12.9
<0.0001
Liver diseases, %
4.5
3.9
4.9
0.16
Chronic advanced renal failure, %
3.5
3.9
4.3
0.22
Lone AF*, %
9.3
5.3
2.0
<0.0001
* Defined as patients aged <60 y with no coronary artery disease/heart failure/valvular heart disease/chronic pulmonary
disease/venous thromboembolism/arterial hypertension.
Adapted from: Chiang CE et al. Circ Arrhythm Electrophysiol. 2012 1;5(4):632-9.
13
RecordAF: AF progression is associated
with CV events
Sanofi. Strictly confidential. Do not distribute. This information is provided for medical and
scientific purpose only. GLB.DRO.12.10.02 – 11/12
RecordAF
Progression
(n=318)
No progression
(n=1,819)
p value
67 ± 11
65 ± 12
0.0011
Gender, % female
48
47
0.9749
Family history of AF, %
8
11
0.0527
Coronary artery disease
24
18
0.0213
Stroke or TIA
11
7
0.0283
Arterial hypertension
78
69
0.0015
Heart failure
32
18
<0.0001
Valvular heart disease
19
16
0.1932
Diabetes
17
15
0.2926
Lone AF
11
22
<0.0001
Progression at one year
Age, years
Cardiovascular disease, %
 The propensity score-adjusted OR of AF progression in patients with rate
rather than rhythm control was 3.3 (95% CI 2.4-4.6, p<0.0001)
OR = odd’s ratio
Adapted from: De Vos CB et al. Am Heart J. 2012;163:887.93.
14
Euro Heart Survey: AF progression is
associated with CV events
Sanofi. Strictly confidential. Do not distribute. This information is provided for medical and
scientific purpose only. GLB.DRO.12.10.02 – 11/12
Euro Heart Survey
All
patients
n (%)
AF
progression
n (%)
No AF
progression
n (%)
1,219 (100)
178 (15)
1,041 (85)
366 (32)
86 (52)
280 (29)
<0.001
22 (2)
6 (3)
16 (2)
0.118
Coronary artery disease
72 (6)
15 (8)
57 (6)
0.168
Myocardial infarction
17 (1)
5 (3)
12 (1)
0.091
Unstable angina
44 (4)
10 (6)
34 (3)
0.130
Ischaemic stroke or TIA
31 (3)
11 (6)
20 (2)
0.003
Ischaemic stroke
20 (2)
8 (5)
12 (1)
0.005
TIA
11 (1)
3 (2)
8 (1)
0.212
40 (3)
13 (7)
27 (3)
0.005
CV outcomes at 1-year follow-up
Number of patients
Symptoms
Death
p value
Major adverse cardiovascular events
Combined mortality/stroke
Adapted from: De Vos CB et al. J Am Coll Cardiol. 2010;55:725-31.
15
AF progression is associated
with CV hospitalisations
CV hospitalisations
RecordAF1
Euro Heart Survey2
p<0.0001
Adapted from:
1. De Vos CB et al. Am Heart J. 2012;163:887-93. 2. De Vos CB et al. J Am Coll Cardiol. 2010;55:725-31.
p<0.001
Several treatment strategies are
available for AF
'Upstream' therapy of concomitant conditions
Anticoagulation
First documented
Rate control
Antiarrhythmic drugs
Ablation
cardioversion
AF
silent
paroxysmal
persistent
Long-standing
persistent
permanent
 Long-lasting AF usually renders maintenance of sinus rhythm more difficult
 It is likely that a window of opportunity to maintain sinus rhythm exists
early in the course of management of a patient with AF
Adapted from: Camm AJ et al. Europace. 2010;12:1360-420.
Overview of current
management of AF
• Pharmacologic therapy
Rate or Rhythm control
Anticoagulant therapy
Upstream therapy
• Nonpharmacologic therapy
Catheter based ablation
Electrical cardioversion
Actual treatment options in AF
Prevention of
thrombo-embolism
Rhythm control
Rate control
Prevent / Reverse
remodeling
Strategy of AF Treatment
The Vaughan-Williams classification of
anti-arrhythmic drugs
 Commonly grouped into four broad categories by Vaughan Williams
classification, based on their dominant electrophysiological effect:
Class
Channels blocked
Agents
Main Usage
I
Na+
Flecainide,
Propafenone
Rhythm Control
II
III
ß-receptors
Betablockers
Rate Control
K+
Sotalol
Amiodarone
Dofetilide
Rhythm Control
IV
Ca2+
Diltiazem
Verapamil
Rate Control
“Upstream” therapies in AF
Therapies
Possible Target
ACE inhibitors
and ARBs
Hypertension
Heart failure
Direct effects (anti-fibrotic,
antiarrhythmic?)
Aldosterone
antagonists
Hypertension, heart failure
Direct effects (anti-fibrotic,
antiarrhythmic?)
Statins
Coronary artery disease
Systemic atherosclerosis
Direct effects (antiinflammatory, antioxidant)
Corticosteroids
Anti-inflammatory effects
n-3 PUFA
(fish oil)
Lipid-lowering effects
Direct antiarrhythmic effects
Beta blockers
Reduction of BP, CHF MI, etc.
Direct antiarrhythmic effects
Savelieva I & Camm AJ. Clin Cardiol. In press
22
Atrial remodelling
Disease
Substrate
AF
Electrical Cardioversion aims at
immediate restoration of sinus rhythm
Non-pharmacologic
therapy: catheter ablation
24
Sites of 69 foci triggering
AF in 45 patients
Haissaguerre M et al. N Engl J Med 1998;339:659-666.
25
Ablation of Atrial fibrillation can only be
performed in 3% of Patients
A. PV Isolation
Make sure to complete isolation
C. PVI, Roof, CTI, Carina, SVCI
Find the residual PVP or non-PV ectopy
B. PVI, Roof line, CTI
Complete line block
D. DF and CFAE
AF substrate mapping
Choice between ablation and AADs for patients with
and without structural heart disease
www.escardio.org
Take Home Messages
• AF is a common problem that is difficult to
treat due to the complexity of underlying
mechanisms and large variability in
pathophysiology.
• New pharmacological approaches are in
active development including AAD,
upstream therapy and anti-inflammatory
agents.
• Several therapeutic options (hybrid therapy)
should be needed for individual patients.