A rotor, the rotation center of spiral waves, has been proposed as a causal mechanism to maintain atrial fibrillation (AF) in human. However, our current understanding of the causality between rotors and spiral waves remains incomplete. One approach to improving our understanding is to determine the relationship between rotors and downward causation from the macro-scale collective behavior of spiral waves to the micro-scale behavior of individual components in a cardiac system. This downward causation is quantifiable as inter-scale information flow that can be used as a surrogate for the mechanism that maintains spiral waves. We used a numerical model of a cardiac system and generated a renormalization group with system descriptions at multiple scales. We found that transfer entropy quantified the upward and downward inter-scale information flow between micro- and macro-scale descriptions of the cardiac system with spiral waves. In addition, because the spatial profile of transfer entropy and intrinsic transfer entropy was identical, there were no synergistic effects in the system. Furthermore, inter-scale information flow significantly decreased as the description of the system became more macro-scale. Finally, downward information flow was significantly correlated with the number of rotors, but the higher numbers of rotors were not necessarily associated with higher downward information flow. This finding contradicts the concept that the rotors are the causal mechanism that maintains spiral waves, and may account for the conflicting evidence from clinical studies targeting rotors to eliminate AF.

1.
Allessie
,
M. A.
,
de Groot
,
N. M.
,
Houben
,
R. P.
,
Schotten
,
U.
,
Boersma
,
E.
,
Smeets
,
J. L.
, and
Crijns
,
H. J.
,
Circ. Arrhythm. Electrophysiol.
3
,
606
(
2010
).
2.
Aronis
,
K. N.
and
Ashikaga
,
H.
,
J. Electrocardiol.
51
,
82
(
2018
).
3.
Aronis
,
K. N.
,
Berger
,
R. D.
, and
Ashikaga
,
H.
,
Circ. Arrhythm. Electrophysiol.
10
,
e005634
(
2017
).
4.
Ashikaga
,
H.
,
Aguilar-Rodrí
,
J.
,
Gorsky
,
S.
,
Lusczek
,
E.
,
Marquitti
,
F. M. D.
,
Thompson
,
B.
,
Wu
,
D.
, and
Garland
,
J.
,
J. R. Soc. Interface
12
,
20141201
(
2015
).
5.
Ashikaga
,
H.
and
Asgari-Targhi
,
A.
,
Sci. Rep.
8
,
1967
(
2018
).
6.
Ashikaga
,
H.
and
James
,
R. G.
,
Chaos
27
,
013106
(
2017
).
7.
Benharash
,
P.
,
Buch
,
E.
,
Frank
,
P.
,
Share
,
M.
,
Tung
,
R.
,
Shivkumar
,
K.
, and
Mandapati
,
R.
,
Circ. Arrhythm. Electrophysiol.
8
,
554
(
2015
).
8.
Benjamin
,
E. J.
,
Wolf
,
P. A.
,
D’Agostino
,
R. B.
,
Silbershatz
,
H.
,
Kannel
,
W. B.
, and
Levy
,
D.
,
Circulation
98
,
946
(
1998
).
9.
Berntsen
,
R. F.
,
Håland
,
T. F.
,
Skårdal
,
R.
, and
Holm
,
T.
,
Heart Rhythm
13
,
1768
(
2016
).
10.
Bosch
,
R. F.
,
Scherer
,
C. R.
,
Rüb
N.
,
Wöhrl
,
S.
,
Steinmeyer
,
K.
,
Haase
,
H.
,
Busch
,
A. E.
,
Seipel
,
L.
, and
Kühlkamp
,
V.
,
J. Am. Coll. Cardiol.
41
,
858
(
2003
).
11.
Bossomaier
,
T.
,
Barnett
,
L.
,
Harré
,
M.
, and
Lizier
,
J. T.
,
An Introduction to Transfer Entropy: Information Flow in Complex Systems
(
Springer
,
2017
).
12.
Bray
,
M.-A.
and
Wikswo
,
J. P.
,
IEEE Trans. Biomed. Eng.
49
,
1086
(
2002
).
13.
Buch
,
E.
,
Share
,
M.
,
Tung
,
R.
,
Benharash
,
P.
,
Sharma
,
P.
,
Koneru
,
J.
,
Mandapati
,
R.
,
Ellenbogen
,
K. A.
, and
Shivkumar
,
K.
,
Heart Rhythm
13
,
636
(
2016
).
14.
Calkins
,
H.
,
Hindricks
,
G.
,
Cappato
,
R.
,
Kim
,
Y.-H.
,
Saad
,
E. B.
,
Aguinaga
,
L.
,
Akar
,
J. G.
,
Badhwar
,
V.
,
Brugada
,
J.
,
Camm
,
J.
et al.,
Heart Rhythm
14
,
e275
(
2017
).
15.
Campbell
,
D. T.
, in
Studies in the Philosophy of Biology: Reduction and Related Problems
, edited by
F. J.
Ayala
and
T.
Dobzhansky
(
Palgrave
,
1974
), pp.
179
186
.
16.
Christandl
,
M.
,
Renner
,
R.
, and
Wolf
,
S.
, in
Proceedings of the IEEE International Symposium on Information Theory
(
2003
), p.
258
.
17.
Chugh
,
S. S.
,
Havmoeller
,
R.
,
Narayanan
,
K.
,
Singh
,
D.
,
Rienstra
,
M.
,
Benjamin
,
E. J.
,
Gillum
,
R. F.
,
Kim
,
Y.-H.
,
McAnulty
,
J. H.
,
Zheng
,
Z.-J.
 et al,
Circulation
129
,
837
(
2014
).
19.
Fogoros
,
R. N.
,
Electrophysiologic Testing
(
John Wiley and Sons
,
2012
).
20.
Gianni
,
C.
,
Mohanty
,
S.
,
Di Biase
,
L.
,
Metz
,
T.
,
Trivedi
,
C.
,
Gökoğlan
,
Y.
,
Güneş
,
M. F.
,
Bai
,
R.
,
Al-Ahmad
,
A.
,
Burkhardt
,
J. D.
et al.,
Heart Rhythm
13
,
830
(
2016
).
21.
Gómez-Herrero
,
G.
,
Wu
,
W.
,
Rutanen
,
K.
,
Soriano
,
M. C.
,
Pipa
,
G.
, and
Vicente
,
R.
,
Entropy
17
,
1958
(
2015
).
22.
Goryachev
,
A.
and
Kapral
,
R.
,
Phys. Rev. Lett.
76
,
1619
(
1996
).
23.
de Groot
,
N.
,
Van Der Does
,
L.
,
Yaksh
,
A.
,
Lanters
,
E.
,
Teuwen
,
C.
,
Knops
,
P.
,
van de Woestijne
,
P.
,
Bekkers
,
J.
,
Kik
,
C.
,
Bogers
,
A.
 et al,
Circ. Arrhythm. Electrophysiol.
9
,
e003648
(
2016
).
24.
Haissaguerre
,
M.
,
Hocini
,
M.
,
Denis
,
A.
,
Shah
,
A. J.
,
Komatsu
,
Y.
,
Yamashita
,
S.
,
Daly
,
M.
,
Amraoui
,
S.
,
Zellerhoff
,
S.
,
Picat
,
M.-Q.
et al.,
Circulation
130
,
530
(
2014
).
25.
James
,
R. G.
,
Barnett
,
N.
, and
Crutchfield
,
J. P.
,
Phys. Rev. Lett.
116
,
238701
(
2016
).
26.
James
,
R. G.
,
Zakirov
,
B.
, and
Crutchfield
,
J. P.
, in American Physical Society Annual Meeting of the Far West Section, November 3–4, 2017, Merced, California (
2017
).
27.
January
,
C. T.
,
Wann
,
L. S.
,
Alpert
,
J. S.
,
Calkins
,
H.
,
Cleveland
,
J. C.
,
Cigarroa
,
J. E.
,
Conti
,
J. B.
,
Ellinor
,
P. T.
,
Ezekowitz
,
M. D.
,
Field
,
M. E.
et al.,
Circulation
130
,
e199
(
2014
).
29.
Katz
,
A. M.
,
J. Cardiovasc. Electrophysiol.
3
,
150
(
1992
).
30.
Kraskov
,
A.
,
Stö
,
H.
, and
Grassberger
,
P.
,
Phys. Rev. E
69
,
066138
(
2004
).
31.
Lee
,
S.
,
Sahadevan
,
J.
,
Khrestian
,
C. M.
,
Durand
,
D. M.
, and
Waldo
,
A. L.
,
J. Cardiovasc. Electrophysiol.
24
,
328
(
2013
).
32.
Lip
,
G. Y. H.
,
Fauchier
,
L.
,
Freedman
,
S. B.
,
Van Gelder
,
I.
,
Natale
,
A.
,
Gianni
,
C.
,
Nattel
,
S.
,
Potpara
,
T.
,
Rienstra
,
M.
,
Tse
,
H.-F.
, and
Lane
,
D. A.
,
Nat. Rev. Dis. Primers
2
,
16016
(
2016
).
33.
Lizier
,
J. T.
,
Front. Robot. AI
1
,
11
(
2014
).
34.
Lu
,
Z.
,
Scherlag
,
B. J.
,
Lin
,
J.
,
Niu
,
G.
,
Fung
,
K.-M.
,
Zhao
,
L.
,
Ghias
,
M.
,
Jackman
,
W. M.
,
Lazzara
,
R.
,
Jiang
,
H.
et al.,
Circ. Arrhythm. Electrophysiol.
1
,
184
(
2008
).
35.
Mandapati
,
R.
,
Skanes
,
A.
,
Chen
,
J.
,
Berenfeld
,
O.
, and
Jalife
,
J.
,
Circulation
101
,
194
(
2000
).
36.
Maurer
,
U.
and
Wolf
,
S.
, in
Proceedings of IEEE International Symposium on Information Theory
(
IEEE
,
1997
), p.
88
.
37.
McComb
,
W. D.
,
Renormalization Methods: A Guide for Beginners
(
Oxford University Press
,
2004
).
38.
Mermin
,
N. D.
,
Rev. Mod. Phys.
51
,
591
(
1979
).
39.
Miller
,
J. M.
,
Kowal
,
R. C.
,
Swarup
,
V.
,
Daubert
,
J. P.
,
Daoud
,
E. G.
,
Day
,
J. D.
,
Ellenbogen
,
K. A.
,
Hummel
,
J. D.
,
Baykaner
,
T.
,
Krummen
,
D. E.
et al.,
J. Cardiovasc. Electrophysiol.
25
,
921
(
2014
).
40.
Moe
,
G.
and
Abildskov
,
J.
,
Am. Heart J.
58
,
59
(
1959
).
41.
Nagumo
,
J.
,
Arimoto
,
S.
, and
Yoshizawa
,
S.
,
Proc. IRE
50
,
2061
(
1962
).
42.
Narayan
,
S. M.
,
Baykaner
,
T.
,
Clopton
,
P.
,
Schricker
,
A.
,
Lalani
,
G. G.
,
Krummen
,
D. E.
,
Shivkumar
,
K.
, and
Miller
,
J. M.
,
J. Am. Coll. Cardiol.
63
,
1761
(
2014
).
43.
Narayan
,
S. M.
,
Krummen
,
D. E.
,
Shivkumar
,
K.
,
Clopton
,
P.
,
Rappel
,
W.-J.
, and
Miller
,
J. M.
,
J. Am. Coll. Cardiol.
60
,
628
(
2012
).
44.
Ott
,
A.
,
Breteler
,
M. M.
,
de Bruyne
,
M. C.
,
van Harskamp
,
F.
,
Grobbee
,
D. E.
, and
Hofman
,
A.
,
Stroke
28
,
316
(
1997
).
45.
Pertsov
,
A. M.
,
Davidenko
,
J. M.
,
Salomonsz
,
R.
,
Baxter
,
W. T.
, and
Jalife
,
J.
,
Circ. Res.
72
,
631
(
1993
).
46.
Rahman
,
F.
,
Kwan
,
G. F.
, and
Benjamin
,
E. J.
,
Nat. Rev. Cardiol.
11
,
639
(
2014
).
47.
Rogers
,
J. M.
and
McCulloch
,
A. D.
,
IEEE Trans. Biomed. Eng.
41
,
743
(
1994
).
48.
49.
Soliman
,
E. Z.
,
Safford
,
M. M.
,
Muntner
,
P.
,
Khodneva
,
Y.
,
Dawood
,
F. Z.
,
Zakai
,
N. A.
,
Thacker
,
E. L.
,
Judd
,
S.
,
Howard
,
V. J.
,
Howard
,
G.
et al.,
JAMA Intern. Med.
174
,
107
(
2014
).
50.
Umapathy
,
K.
,
Nair
,
K.
,
Masse
,
S.
,
Krishnan
,
S.
,
Rogers
,
J.
,
Nash
,
M. P.
, and
Nanthakumar
,
K.
,
Circ. Arrhythm. Electrophysiol.
3
,
105
(
2010
).
51.
Verma
,
A.
,
Jiang
,
C.-y.
,
Betts
,
T. R.
,
Chen
,
J.
,
Deisenhofer
,
I.
,
Mantovan
,
R.
,
Macle
,
L.
,
Morillo
,
C. A.
,
Haverkamp
,
W.
,
Weerasooriya
,
R.
et al.,
N. Engl. J. Med.
372
,
1812
(
2015
).
52.
Wijffels
,
M. C.
,
Kirchhof
,
C. J.
,
Dorland
,
R.
, and
Allessie
,
M. A.
,
Circulation
92
,
1954
(
1995
).
53.
Winfree
,
A. T.
,
When Time Breaks Down: The Three-Dimensional Dynamics of Electrochemical Waves and Cardiac Arrhythmias
(
Princeton University Press
,
1987
).
54.
Wolf
,
P. A.
,
Abbott
,
R. D.
, and
Kannel
,
W. B.
,
Stroke
22
,
983
(
1991
).
55.
Yue
,
L.
,
Melnyk
,
P.
,
Gaspo
,
R.
,
Wang
,
Z.
, and
Nattel
,
S.
,
Circ. Res.
84
,
776
(
1999
).

Supplementary Material

You do not currently have access to this content.