trial fibrillation (AFIB) was reported to be an independent risk factor for stroke in the Framingham Study. In
patients with coronary heart disease or cardiac failure,
atrial fibrillation doubled the stroke risk in men and trebled the
risk in women.1,2) Left atrial myocardial extension on to pulmonary veins in humans by anatomic observation might be
relevant for atrial arrhythmias.3) Certain cases of AFIB may be
maintained by small re-entrant rotors that result in a hierarchical distribution of frequencies throughout the atria.4,5) Recent
advances in interventional catheter ablation and surgical pulmonary vein isolation, radical treatments have been applied in
patients with atrial flutter (AFL) and AFIB.6,7) Holma, et al reported noninvasive assessment of the atrial cycle length during
atrial fibrillation in humans.8) Sanders, et al reported spectral
analysis and frequency mapping identify localized sites of
high-frequency activity during AFIB in humans with different
distributions in paroxysmal and permanent AFIB.9,10) Determination of the features of cycle length of excitation of atrial fibrillation is important for a therapeutic strategy.
Magnetocardiography (MCG) has the potential to detect
3-dimensional (3D) electrical current density and electrical repolarization phenomena because the magnetic field is unaffected by the shape of the lungs and the torso.11,12) Previously,
we reported a 3D spectral map of the atrial fibrillation generated by 64ch cardiomagnetic fields B in the z direction using a
space filter.13) Recently, we developed a 187 channel vectorprojected ECG (187ch VP-ECG) that could evaluate 2-dimensional (2D) characteristics of recovery time dispersion and
high frequency late potentials.14-16)
We hypothesized that AF cycle length may be correlated
locally with atrial refractoriness and globally with the degree
of atrial organization. In the present study, we developed body
surface spectral maps of AFIB and AFL using 187ch VP-ECG,
and verified the significance of the accuracy by 64ch MCG.
Methods
Subjects and surgical procedure: The study subjects consisted
From the Departments of 1 Internal Medicine of Dentistry, 2 Cardiac Surgery, 3 Cardiology and 4 Radiology of Memorial Heart Center, Iwate Medical University, Iwate,
Japan.
This study was supported by a Grant-in-Aid for Scientific Research (C)(22590792) of The Ministry of Education, Culture, Sports, Science and Technology (MEXT).
Address for correspondence: Kenji Nakai, MD, Internal Medicine of Dentistry, Iwate Medical University, 19-1 Uchimaru, Morioka, Iwate 020-8505, Japan.
Received for publication July 25, 2011.
Revised and accepted November 17, 2011.
5
Int Heart J
January 2012
NAKAI, ET AL
Table. Baseline Characteristics of the Study Patients
No
ID
Name
Age
Sex
DIAG
Rhythm
HR
fQRS
MCG mF
VP-ECG mF
1
2
3
4
5
6
7
8
9
10
11
12
13
14
15
16
17
18
19
20
21
22
23
24
25
26
27
28
20061002
20061115
20070207
20071105
20060522
20060526
20060529
20060621
20060719
20061013
20061025
20061025
20061129
20061127
20061115
20061108
20061122
20070611
20070516
20070528
20070608
20070612
20070702
20070928
20071003
20071022
20080121
20080128
KY
KN
YH
AS
IS
KY
TY
TY
OE
IC
MH
MY
MY
SS
ES
YK
YN
KM
KT
KI
IY
TS
TT
ST
YS
AS
KK
HY
70
68
71
58
74
51
73
73
73
55
64
69
69
61
54
80
60
60
83
65
21
75
55
63
73
58
65
65
M
F
M
M
F
M
M
M
M
M
M
M
M
M
F
M
F
M
M
M
M
F
F
F
M
M
M
F
MR,MVP
MS
AR
AR
MR
HHD
MR
MR
MR,TR
MR,AR
MR
MR
MR
MR
MR
MR
MS
Lone AFIB
HHD
HHD
MR
MR
MR
MR,AS
MR
AR
MR
MS
AFL
AFL
AFL
AFL
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
AFIB
97
66
90
91
54
79
54
83
49
87
55
59
78
52
92
91
58
79
81
98
57
66
46
64
81
52
75
51
114
110
107
131
104
114
106
100
109
99
170
133
120
109
116
100
93
106
87
95
119
106
114
111
112
132
101
109
4.4
3.9
4.5
5.4
7.0
7.2
9.5
9.8
8.0
7.1
6.8
6.8
6.6
9.0
6.8
6.8
7.8
7.5
5.6
6.3
6.5
7.8
5.7
7.3
9.3
7.1
7.0
6.8
4.5
3.6
4.5
5.7
7.1
6.9
9.0
8.7
7.6
7.4
6.2
6.9
7.2
8.2
5.4
6.7
8.1
7.5
5.5
6.4
6.4
6.9
6.1
7.5
8.9
7.2
6.9
6.9
DIAG indicates diagnosis; HR, heart rate (beat/minutes); fQRS, filtered QRS (msec); MCG mF, mean frequency by MCG (Hz); VP-ECG mF, mean frequency by VP-ECG (Hz); MR, mitral regurgitation; MVP, mitral prolapse; AR, aortic regurgitation; HHD, hypertensive heart disease; TR, tricuspid regurgitation; MS, mitral stenosis; Lone AFIB, lone atrial fibrillation; AS, aortic stenosis; AFL, atrial flutter; and AFIB, atrial fibrillation.
Vol 53
No 1
type: SQUID sensor, manufactured by Hitachi High-Technology, Co., Ltd., Tokyo). We recorded the 64ch MCG in a magnetically shielded room. A brief examination was performed in
order to guide the probe placement. Magnetic coils were
placed at precordial leads in the V1, V2, V4, and xiphoid regions. Current signals from these magnetic coils were initially
recorded at approximately 2-second intervals, followed by a
10-minute recording for each subject in the same position. The
recordings were digitized at 500 Hz and filtered with a bandpass frequency range of DC to 200 Hz. Subject interference
was removed using a matched filter.
The acquired MCG and MR images were processed by
custom software (prototype: MCG manager). The pre-processing module acquired MCG signals by noise filtration, the elimination of bad signals, and the interpolation of missing signals.
The generation of a space filter for determining the current
density from Bz magnetic fields has been reported previously.
Theoretically, the electric current and the magnetic field have a
linear relationship (B = LJ). Next, we determined the current
density by the next equation, J = L-1B. The dumped least
squares method with the Tikhonov regulation method was applied to handling signals (B) equally from the deep and shallow parts in the next equation, J = LT[LLT + I]-1B.12)
To determine the 3D heart polygons, the 3D current density was calculated from the Bz magnetic fields by applying
the space filter. The 3D heart polygons for the atrium and ventricle were determined from the magnetic field distribution.
Details of this procedure have been described previously.11,12)
The 3D spectral map of AFIB was generated using a previously reported method.12) MCG was acquired for 5 minutes
from each patient. We used a space filter to compose the 3D
current density map from the 64ch MCG data in the z direction. After high-pass filtering, the QRS complexes were subtracted using a template-matched algorithm. The resulting fibrillatory baseline signal was tapered at the edges to a 0 value
by the Hamming window. Next, we applied a 2048-point FastFourier transform (spectral resolution, 0.48 Hz) to obtain the
Figure 2. The body surface spectral map of AFIB was generated as follows: 187ch VP-ECG was acquired for 5 minutes from each patient. After
high-pass filtering (0.5 Hz), the QRS complexes were subtracted at the
zone of 50 msec from the peak R using a template-matched algorithm.
The fibrillatory baseline signal was then tapered at the edges to a 0 value
by the Hamming window. We performed spectral analysis by MEM in 4
second nonaveraged 187ch electrical current waves estimated by VPECG. Right lower panel indicates frequency feature for each minute and
2D dominant frequency map based on the power magnitude of hierarchic
frequency. Color coding indicates hierarchic dominant frequency feature,
blue; 0~5 Hz, yellow; 5~7 Hz, red; 7~10 Hz, respectively.
power spectrum of the nonaveraged 3D 64ch MCG data. Power spectral analysis allowed automatic determination of the
gradient frequency for each point acquired. We created 3D
color-coded frequency spectral maps within the heart outline
generated by the MCG, displaying low frequencies in blue and
high frequencies in red (blue represented 0~5 Hz, purple 5~7
Hz, and red 7~10 Hz).
MR images and reconstruction of the spectral map: We obtained MR images by standard techniques using a Signa Horizon LX instrument [GE Yokokawa, Tokyo]) in selected subjects (1 normal volunteer, 1 patient with common AFL, and 1
patient with AFIB) after applying a NifedipineR capsule at the
position of the precordial leads of V1, V2, V4, and the xiphoid
regions. The capsule could provide verification of the heart
outline generated by the MCG. Digital Imaging and Communications in Medicine (DICOM)-formatted MR images were
transferred to a personal computer (IBM Japan, Tokyo). A representative heart polygon of the atrium and ventricle determined by an integrated current density of the MCG was reconstructed with the silhouette on the MR images with adjustment
to the markers on the precordial position of the V1, V2, V4, and
xiphoid regions. Furthermore, the 3D power spectral map of
the common AFL was reconstructed on the MR images.
Statistical analysis: The mean standard deviations (SD) and
the comparison of mean frequency between 187ch VP-ECG
and 64ch MCG correlation were calculated and statistical analyses were performed by an unpaired t test using GraphPad
Prism4 (San Diego, CA, USA). Samples were considered to
be statistically significant when the two-tailed P value was <
0.05.
NAKAI, ET AL
Results
The baseline characteristics and clinical courses of the
patients are shown in the Table. A 3-dimensional spectral map
on 64ch MCG in representative AFL demonstrated homogenous distribution with a frequency of 4.4 Hz around the right
atrium verified by MRI (Figure 3A). A 3-dimensional spectral
map on 64ch MCG in representative AFIB demonstrated nonhomogenous distribution with a frequency of 6.8 Hz around
the atrium verified by MRI (Figure 3B).
The average mean frequency in AFL was lower than
those in AFIB (4.6 0.9 Hz in AFL, 7.2 0.9 Hz in AFIB, P
< 0.01). Comparison of mean frequency between 187ch VPECG and 64ch MCG indicated good agreement (y =
Int Heart J
January 2012
Figure 4. Relationship of frequency between 64ch MCG and 187ch VPECG. The average mean frequency in AFL was lower than that in AFIB
(4.6 0.9 Hz in AFL, 7.2 0.9 Hz in AFIB). Comparison of mean frequency between 187ch VP-ECG and 64ch MEG demonstrated good
agreement (y = 0.86x+0.84, r2 = 0.89, P < 0.0001).
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Discussion
This study demonstrated that novel body surface spectral
mapping using 187ch VP-ECG represents a 2D spectral feature. Body surface spectral mapping demonstrated a homogenous frequency pattern in AFL, and various frequency patterns
in AFIB. Thus, novel body surface dominant frequency mapping in humans could represent a 2D hierarchical gradient of
activity of spectral features that may be related to a profile of
atrial refractoriness and organization.
Frequency mapping in AFIB - Etiology of AFIB: Schuessler, et
al19) observed that activation patterns characterized by multiple
re-entrant circuits converted to a single high-frequency re-entrant circuit that resulted in fibrillation. Certain cases of chronic AFIB are maintained by small re-entrant sources that result
in a hierarchical distribution of frequencies throughout the
atria. The rotor frequency has been found to correlate well with
the dominant frequency that is determined by spectral analysis
using optical mapping.20) Recently, Konings reported that there
were significant differences among the 3 types of pacing-induced AFIB in median intervals (174, 150, 136 milliseconds)
using optical mapping.21)
Holma, et al hypothesized noninvasive assessment of the
atrial cycle length during atrial fibrillation in man.22) They proposed a new method named Frequencyanalysis of fibrillatory
ECG (FAF-ECG) originally developed by Slocum, et al.23) In
brief, (1) an average of the time-aligned QRST complexes was
created and subtracted from the original ECG signal, and (2) a
frequency spectrum of the residual ECG signal was estimated
using FFT. Of the 12 surface ECG leads, the precordial lead V1
was chosenfor the frequency analysis. This method has, however, some important limitations as pointed out by Holma.22) A
reliable and accurate identification of the atrial spectral component is dependent on suppression of the QRST complexes.
Our algorithm is different in several ways; 1) QRS complexes were subtracted at the zone of 50 msec from the peak
R (offset) in cases with a normal QRS interval, and 70 msec
from the peak R in cases with bundle branch block, 2) frequency spectrum was estimated by 187ch VP-ECG, 3) MEM
was used for frequency analysis, and 4) body surface spectrum
mapping was displayed. A MEM approach provides a more
accurate and noise-immune mean frequency estimation than
the FFT method.24) Most importantly, body surface maps enable us to display 2D frequency distribution.
Previous studies have shown that the atrial cycle length
during AFIB was from 300 to 600 msec, which may be correlated with the dominant frequency.25) In this study, the average
dominant frequency in AFL was lower than that in AFIB (4.2
0.39 Hz in AFL, 7.1 0.2 Hz in AFIB). Interestingly, this
study revealed that body surface spectral mapping demonstrated a homogenous frequency pattern in AFL, and various frequency patterns in AFIB.
Recent studies have revealed that the global cycle length
reflects the organization of the fibrillation and, further, that the
local cycle length correlates to atrial refractoriness.5) First, it
demonstrates the feasibility of performing spectral analysis
and endocardial dominant frequency (DF) mapping in humans
to recognize relatively small DF sites with spatiotemporal stability in a 3D representation with a hierarchical gradient of activity. Second, it identifies that, in patients with paroxysmal
AF, the DF sources of activity are often localized to the PVs.
Disclosure
Dr. Nakai has a license agreement concerning software use (ECG
manager) with Fukuda Denshi Co., Ltd., Japan.
10
NAKAI, ET AL
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