Predicting Catheter Ablation Outcome in Persistent Atrial Fibrillation
via Multivariate Analyses of ECG Fibrillatory Wave Amplitude
A. R. Hidalgo-Mu˜noz
1
, V. Zarzoso
1
, M. Meo
2
, O. Meste
1
, D. G. Latcu
3
, I. Popescu
3
and N. Saoudi
3
1
Laboratoire I3S, UMR 7271, Universit´e Nice Sophia Antipolis, CNRS, Nice, France
2
Department of Anesthesiology, Brigham and Women’s Hospital, Harvard Medical School, Boston, MA, U.S.A.
3
Service de Cardiologie, Centre Hospitalier Princesse Grace, Monaco, Monaco
1 INTRODUCTION
Atrial fibrillation (AF) is the most common sustained
arrhythmia encountered in clinical practice. Among
the possible strategies to face AF, catheter ablation
(CA) is a well established therapy with proven effi-
cacy to maintain sinus rhythm during follow-up. The
highest rate of AF recurrence is reported to occur
during the first 6 months following ablation (Calkins
et al., 2012). Hence, an accurate selection of patients
who can really benefit from this intervention at long-
term is essential.
In this work, two multivariate approaches for se-
lecting the most relevant features linked to CA out-
come are proposed. The first one is known as logistic
regression (LR) (Indrayan, 2012). The second one is
based on a machine learning technique, named sup-
port vector machine (SVM) (Burges, 1998). The goal
of both analyses is to distinguish the AF patients more
prone to a successful CA outcome from those who are
more sensitive to arrhythmia recurrence. More specif-
ically, patients who suffer from persistent AF are con-
sidered in this study.
There are many possibilities to tackle the analy-
sis of the fibrillatory waves (f-waves) such as time or
frequency domains (Matsuo et al., 2009; Jones et al.,
2013). One of the most direct and easily interpretable
measurements obtained from the f-waves is the fibril-
latory wave amplitude (Nault et al., 2009; Meo et al.,
2013), which is the focus of the present work.
2 METHODS
2.1 Database and ECG Acquisition
Sixty-two patients (52 male, age = 61.5±10.4 years)
having persistent and long-lasting persistent
AF (Calkins et al., 2012) were recruited at the
Cardiology Department, Princess Grace Hospital,
Monaco, after giving their informed consent. One
minute standard 12-lead ECG was acquired at a
sampling rate of 977 Hz at the beginning of the CA
procedure. ECG signals were filtered by a 4th-order
zero-phase bandpass Chebyshev filter with cut-off
frequencies of 0.5 Hz and 30 Hz. For every lead of
each recorded ECG, the fibrillatory wave amplitude
was computed as in (Meo et al., 2013). Also as in
that reference, this work focused exclusively on the 8
linearly independent leads I, II, V1-V6.
All patients underwent stepwise CA (Calkins
et al., 2012), including lasso-guided circumferential
pulmonary vein (PV) disconnection, fractionated po-
tentials, non-PV triggers, roof line and mitral isthmus
line right atrial ablation. Outcome was followed up
during at least 6 months after the CA procedure. Fi-
nally, 47 patients were free from AF (success) while
15 patients had documented AF recurrences (failure).
2.2 Statistical Analysis
Normal distribution was first checked by the
Kolmogorov-Smirnov test. A U-Mann Whitney test
was performed to verify any statistically significant
differences between the groups of interest. Both the
statistical analysis and the subsequent logistic regres-
sion model were performed by using the software
SPSS version 13.0.
LR consists of a probabilistic statistical model
aimed at predicting the outcome of a categorical de-
pendent variable (success and failure after CA) based
on one or more predictor variables (features). The
next equation is an example for M predictors:
LR = log
θ
1 θ
= b
0
+ b
1
x
1
+ ... + b
M
x
M
(1)
where θ is the probability of belonging to the suc-
cess CA class, {b
0
, b
1
, ..., b
M
} are the coefficients of
the regression model and {x
1
, ..., x
M
} correspond to
the numerical values of the different features. In
our case, x
m
corresponds to the fibrillatory amplitude
R. Hidalgo-Muñoz A., Zarzoso V., Meo M., Meste O., G. Latcu D., Popescu I. and Saoudi N..
Predicting Catheter Ablation Outcome in Persistent Atrial Fibrillation via Multivariate Analyses of ECG Fibrillatory Wave Amplitude.
Copyright
c
2014 SCITEPRESS (Science and Technology Publications, Lda.)
mean value for the mth lead selected by the model
from the complete set of 8 leads. A backward elimi-
nation method that discards the least significant vari-
able at each iteration according to the Wald index was
employed (Indrayan, 2012) to keep only the most rel-
evant ECG leads.
On the other hand, SVM separates the given set of
binary labeled training data with a hyperplane that is
maximally distant (Euclidean distance) from the two
classes success and failure CA outcome). Linear dis-
criminant functions define a decision hyperplane in a
multidimensional feature space as:
g(x) = w
T
x+ w
0
= 0 (2)
where w is known as the weight vector and x is the
feature vector (set of lead amplitude values). Symbol
w
0
denotes the threshold and (·)
T
the transpose op-
erator. Note that elements in vector w close to zero
have little influence on g(x) and hardly contribute to
the decision. In (Guyon et al., 2002) it was suggested
a recursive feature elimination technique (SVM-RFE)
that discards iteratively the features corresponding to
the lowest values of |w
i
|. After feature elimination,
the classifier is evaluated using a leave-one-out cross-
validation strategy. In our case, the initial feature vec-
tor x is made up of the mean fibrillatory amplitude
values computed in each of the 8 leads considered
in this study. The SVM-RFE algorithm was imple-
mented using MATLAB version R2011a.
3 RESULTS
No significant inter-class differences were found for
any of the single-lead amplitude parameters consid-
ered separately.
After applying LR by using the backward elimi-
nation method, the remaining leads were I, V1, V2
and V5. Table 1 summarizes the best results in terms
of AUC by applying univariate and multivariate ap-
proaches. The best cut-off point was θ = 0.7 yielding
83% sensitivity, 73.3% specificity and 80.6% total ac-
curacy.
The SVM-RFE algorithm ranked the leads as fol-
lows: I, V5, V2, V1, II, V4, V6 and V3 (ordered from
Table 1: Best accuracy results by the univariate contrast
with the highest AUC and the multivariate analysis after
LR backward elimination. AUC: area under the curve; IC:
AUC’s interval of confidence; p: AUC’s statistical signifi-
cance.
Analysis AUC IC p
Univariate (lead I) 0.678 0.50 to 0.85 0.039
Multivariate (θ) 0.854 0.75 to 0.96 <0.001
the most to the least relevant). The best result in terms
of accuracy is obtained by using only the three most
relevant leads (I, V5 and V2) reaching up to 82.3%
accuracy, 70% specificity and 84.6% sensitivity.
4 CONCLUSION
This work has shown that analyzing the fibrilla-
tory amplitudes measured in multiple ECG leads im-
proves the accuracy of previous CA outcome pre-
dictors based on a single lead (Nault et al., 2009).
The multivariate amplitude analysis model reaches
an AUC of up to 0.854 with four leads. Both LR
and SVM-RFE agree in pointing to I, V1, V2 and
V5 as the most discriminant leads to determine mid-
and long-term CA outcome. Along the lines of (Meo
et al., 2013), these results support the suitability of
taking into consideration the information of several
leads that are often neglected in CA outcome predic-
tion and AF analysis (Nault et al., 2009; Matsuo et al.,
2009).
ACKNOWLEDGEMENTS
Work supported in part by the French National
Research Agency under contract ANR-2010-JCJC-
0303-01 “PERSIST” and the Centre Scientifique de
Monaco. A. R. Hidalgo-Mu˜noz holds a postdoctoral
research fellowship awarded by Univ. Nice Sophia
Antipolis.
REFERENCES
Burges, C. (1998). A tutorial on support vector machines
for pattern recognition. Data Mining and Knowledge
Discovery, 2(2):121–167.
Calkins, H., Kuck, K. H., Cappato, R., Brugada, J., Camm,
A. J., et al. (2012). 2012 HRS/EHRA/ECAS expert
consensus statement on catheter and surgical ablation
of atrial fibrillation: recommendations for patient se-
lection, procedural techniques, patient management
and follow-up, definitions, endpoints, and research
trial design. Europace, 14:528–606.
Guyon, I., Weston, J., Barnhill, S., and Vapnik, V. (2002).
Gene selection for cancer classification using support
vector machines. Machine Learning, 46:389–422.
Indrayan, A. (2012). Medical Biostatistics. CRC Press.
Jones, A. R., Krummen, D. E., and Narayan, S. M. (2013).
Non-invasive identification of stable rotors and focal
sources for human atrial brillation: mechanistic clas-
sification of atrial brillation from the electrocardio-
gram. Europace, 15(9):1249–1258.
Matsuo, S., Lellouche, N., Wright, M., Bevilacqua, M.,
Knecht, S., et al. (2009). Clinical predictors of ter-
mination and clinical outcome of catheter ablation for
persistent atrial fibrillation. Journal of the American
College of Cardiology, 54(9):788–795.
Meo, M., Zarzoso, V., Meste, O., Lactu, D. G., and Saoudi,
N. (2013). Spatial variability of the 12-lead surface
ECG as a tool for noninvasive prediction of catheter
ablation outcome in persistent atrial fibrillation. IEEE
Trans. on Biomedical Engineering, 60(1):20–27.
Nault, I., Lellouche, N., Matsuo, S., Knecht, S., Wright,
M., et al. (2009). Clinical value of fibrillatory wave
amplitude on surface ECG in patients with persistent
atrial fibrillation. Journal of Interventional Cardiac
Electrophysiology, 26(1):11–19.