a lifetime’s journey · wl = rp * cv. control acetylcholine functional circuits may shrink....
TRANSCRIPT
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Maurits A. Allessie
Department of Physiology
Cardiovascular Research Institute
Maastricht, The Netherlands
Atrial Fibrillation from 1973 to 2017
A Lifetime’s Journey
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1973
left atrium of the rabbit
300 different sites
in a small area of atrial muscle, containing no anatomical obstacle
the impulse can be entrapped in a circus movement
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Isolated Left Atrium ofthe Rabbit
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Runs of Rapid Repetitive Activity by a Single Premature Stimulus
5
0
0
5
0
0
5
0
0
5
0
0
5
0
016 17 18 19 20 1 2
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Focal or Reentrant?
C
BA
K
J
H
G
F ED
Allessie et al. Circ Res 1973
J
H
G
F
E
D
C
B
A
K
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First Reentrant Beat
Allessie et al. Circ Res 1973
5 mm
Basic Beat Premature Stimulus
Second Reentrant Beat
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A Ring of Microelectrodes
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Unidirectional Block and Reentry
E
D
F
G
C
H
A
B
AC
D
E
F
GH
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105 106 105 105 105 104
5 mm
Stable 'Leading Circle' Reentry
Allessie et al.
Circ Res 1978
(Ach)40
30
20
10
0100
90
80
50 60
70
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The 'Eye' of the Rotor
A12345D
1
2
3
4
5
D
A0
105 106
00
3 33
7 76
9 1010
9 1110
6362
5858
6969
6970
Allessie et al. Circ Res 1978
5 mm
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Shortening of the Wavelengthby Acetylcholine
WAVE LENGTH
WL = RP * CV
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Control Acetylcholine
Functional Circuits May Shrink
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Wijffels, Allessie et al. Circulation 1995
5 sec
20 sec
Persistent AF
Sinus Rhythm
After
24 h
After
1 week
Control
Sinus Rhythm
Burst
1995: ‘AF Begets AF’
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Pacing Interval (ms)
110
130
150
100 200 300 400 500
AERP
(ms)
Control
After 24 hours
of AF
Control
AF
Wijffels et al.
Circulation 1995
The First Days of AF…Electrical Remodeling
Mimics Acetylcholine
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Increased Number of Wavelets
Acute AF
Longstanding AF
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‘Early’ Cardioversion of Persistent AF by
Prolongation of the Remodeled Action Potential
Sinus
Rhythm
Control
AVE
0118
Blaauw et al. Circulation 2004
Persistent AF (1 Month)
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(4/5)
(3/6)
(2/6)
(0/7) (0/7) (0/7)
Pharmacological
Cardioversion
(%)
(10/10)
0
25
50
75
0 1 2 3 4 5 6
AF Duration (months)
100
After 4 Months of AF …Cardioversion No Longer Possible
Structural Remodeling!
Verheule et al. Circ AE 2010
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You are Being Told that
the Multiple Wavelets Hypothesis
is Wrong …
… and that Atrial Fibrillation is
Maintained by One or More
‘Drivers’ (Rotors)
2017
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Rotor Detection by Low-Resolution Mapping
“Rotors Have Not Been Demonstrated
to be the Drivers of Atrial Fibrillation”
Allessie & de Groot, J Physiol 2015
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Complete Epicardial Mapping of AF
within 3-4 Minutes
RA1
RA2
RA3
RA4
BBRBBL
Flex-Tape
4.8cm
1.6cm
192Electrodes
de Groot, Kik, Allessie et al.
PVRPVL
High-Resolution Mapping during Surgery
in Patients with Persistent AF
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Consecutive Wave-Maps of Persistent AF(4.8 x 1.6cm)
7 waves 6 waves 4 waves 4 waves 6 waves 7 waves
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Complete Epicardial Mapping in
60 Patients with Persistent AF:
Not a Single
Fully Rotating Wave(> 360 degrees)
was Observed
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‘Wannabe’ Reentry
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Pivoting of Waves
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Repetitive PivotingBeat 10 Beat 11 Beat 12 Beat 13
Three Times Max
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Repetitive Pivoting in 60 Patients
with Persistent AF
Median
0.01%
< 0.25%
Patients
Per
cen
tag
e o
f R
epet
itiv
e P
ivo
tin
g W
av
es (
%)
Repetitive Pivoting
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In Patients with Persistent AF:
● Rotors do NOT Exist
● Pivoting is Rare
● Repetitive Pivoting is Very Rare
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Atrial Fibrillation is Not
Perpetuated by a Rapid Stable
Source, but by the Production
of Abundant Offspring
Atrial Fibrillation is Not
Perpetuated by a Rapid Stable
Source, but by the Production
of Abundant Offspring
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Many Focal Fibrillation Waves
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Median
21%
Percentage of Focal Waves
in 60 Patients with Persistent AF
Patients
Per
cen
tag
e o
f F
oca
l W
av
es (
%)
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> 5.000/minute
What is the Source of this Amazing
Number of Focal Waves
They Appear over the Entire Atrium
(Right and Left Alike)
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30 mm
14 mm
Endocardium Epicardium
CT
VCS
VCI
RA
Cannula Incision
Simultaneous Endo-Epicardial Mapping
of Persistent AF during Cardiac Surgery
de Groot, Kik, Allessie et al. Circ AE 2016
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1624
Epi Endo
Epicardial
Breakthrough
41
Epi Endo
46
Endocardial
Breakthrough
7369
66
Epi Endo
64
Endo + Epicardial
Breakthroughs
de Groot, Kik, Allessie et al. Circ AE 2016
Direct Evidence that Focal Fibrillation Waves
Are Due to Endo-Epicardial Breakthrough
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Single Rotor ... or …
Multiple Breakthroughs?
This Is How Fibrillation Waves
Multiply Themselves!
Epi
Endo
40 35 30 30 35 40ms
0 5 10 20 25 30ms 15Allessie et al. Circ Res 1973
Rabbit
de Groot et al. Circulation 2010
Human
Focal Waves Are Bifurcation Sites
in a Double-Layer of
Dissociated Multiple Wavelets
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The High Persistence of AF is due to
a Double Layer of Dissociated Waves that
Constantly ‘Feed’ Each Other
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‘Rotor Detection’ by Low-Resolution
Mapping is False
“Ignoring the Complexities of Human AF
is like Throwing Away your Microscope
and Saying that Bacteria Don’t Exist.”
Allessie & de Groot, J Physiol 2015