Maurits A. Allessie

Department of Physiology

Cardiovascular Research Institute

Maastricht, The Netherlands

Atrial Fibrillation from 1973 to 2017

A Lifetime’s Journey

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

Isolated Left Atrium ofthe Rabbit

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

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

First Reentrant Beat

Allessie et al. Circ Res 1973

5 mm

Basic Beat Premature Stimulus

Second Reentrant Beat

A Ring of Microelectrodes

Unidirectional Block and Reentry

E

D

F

G

C

H

A

B

AC

D

E

F

GH

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

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

Shortening of the Wavelengthby Acetylcholine

WAVE LENGTH

WL = RP * CV

Control Acetylcholine

Functional Circuits May Shrink

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’

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

Increased Number of Wavelets

Acute AF

Longstanding AF

‘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)

(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

You are Being Told that

the Multiple Wavelets Hypothesis

is Wrong …

… and that Atrial Fibrillation is

Maintained by One or More

‘Drivers’ (Rotors)

2017

Rotor Detection by Low-Resolution Mapping

“Rotors Have Not Been Demonstrated

to be the Drivers of Atrial Fibrillation”

Allessie & de Groot, J Physiol 2015

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

Consecutive Wave-Maps of Persistent AF(4.8 x 1.6cm)

7 waves 6 waves 4 waves 4 waves 6 waves 7 waves

Complete Epicardial Mapping in

60 Patients with Persistent AF:

Not a Single

Fully Rotating Wave(> 360 degrees)

was Observed

‘Wannabe’ Reentry

Pivoting of Waves

Repetitive PivotingBeat 10 Beat 11 Beat 12 Beat 13

Three Times Max

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

In Patients with Persistent AF:

● Rotors do NOT Exist

● Pivoting is Rare

● Repetitive Pivoting is Very Rare

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

Many Focal Fibrillation Waves

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 (

%)

> 5.000/minute

What is the Source of this Amazing

Number of Focal Waves

They Appear over the Entire Atrium

(Right and Left Alike)

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

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

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

The High Persistence of AF is due to

a Double Layer of Dissociated Waves that

Constantly ‘Feed’ Each Other

‘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