Use of a novel fragmentation map to identify the
substrate for ventricular tachycardia in postinfarction
cardiomyopathy
Bieito Campos, MD,* Miguel E. Jauregui, MD,* Francis E. Marchlinski, MD, FHRS,†
Sanjay Dixit, MD, FHRS,† Edward P. Gerstenfeld, MS, MD, FHRS‡
From the *Electrophysiology Section, Department of Cardiology, Hospital Universitari Arnau de Vilanova,
Lleida, Spain, †Electrophysiology Section, Cardiovascular Division, Department of Medicine, Hospital of the
University of Pennsylvania, Philadelphia, Pennsylvania, and ‡Electrophysiology Section, Cardiovascular
Division, Department of Medicine, University of California San Francisco; San Francisco California.
BACKGROUND Substrate ablation is commonly performed in
patients with postinfarction cardiomyopathy and ventricular tachy-
cardia (VT). Recognition of fragmented and late potentials during
sinus rhythm is a tedious process subject to operator fatigue.
OBJECTIVE The purpose of this study was to assess the value of
automated analysis to quantify electrogram fragmentation and to
determine the relationship of fragmented regions to the VT isthmus.
METHODS Detailed left ventricular (LV) mapping was performed in
2 groups: (1) 14 patients with previous myocardial infarction and
tolerated VT and (2) 14 controls with structurally normal hearts. In
patients with VT, mid-isthmus sites were identified using entrain-
ment mapping. Sinus rhythm endocardial LV electrograms under-
went time– and frequency–domain analysis and were displayed as
fragmentation or frequency maps. The region of fractionated
electrograms and their relation to the VT isthmus sites were
determined.
RESULTS Cutoffs for abnormal electrogram fragmentation were
ventricular fractionation index Z7 and fast Fourier transform ratio
Z14%, respectively. In the time domain, LV surface area with
fractionated electrograms was significantly smaller than the total
Introduction
Entrainment mapping is the gold standard for identifying the
critical isthmus of ventricular tachycardia (VT) during ca-
theter ablation procedures. However, because the majority of
VTs are poorly tolerated, substrate modification has emerged
as a valuable technique for identifying the abnormal sub-
strate distribution and exit sites of VT in patients with ische-
mic cardiomyopathy. Such techniques involve a detailed
point-by-point acquisition of bipolar voltage information
Drs. Gerstenfeld and Marchlinski have received honoraria from Bio-
sense Webster. Address reprint requests and correspondence: Dr.
Edward P. Gerstenfeld, University of California, San Francisco, MU-East
4th Floor, 500 Parnassus Ave, San Francisco, CA 94143. E-mail address:
egerstenfeld@medicine.ucsf.edu.
1547-5271/$-see front matter B 2015 Heart Rhythm Society. All rights reserved.
scar surface area (27.3% ⫾ 7.1% vs 42.1% ⫾ 12.3%, P o.001), yet
contained 100% of VT isthmus sites. In the frequency domain, areas
of abnormal fractionation occupied 9.7% ⫾ 6.9% of total LV
surface area and included only 60% of the VT isthmus sites.
CONCLUSION Automated electrogram fractionation analysis rep-
resents an objective tool to rapidly quantify electrogram fragmen-
tation and guide substrate-based ablation of VT. Empiric ablation of
these regions may be a new strategy for substrate-guided VT
ablation.
KEYWORDS Ventricular tachycardia; Fragmentation; Mapping;
Ablation; Cardiomyopathy; Fourier transform
ABBREVIATIONS A-VFI ¼ abnormal ventricular fragmentation
index; FFT ¼ fast Fourier transform; FFTr ¼ fast Fourier transform
ratio; H-FFTr ¼ high fast Fourier transform ratio; HF-VFI ¼ highly
fragmented ventricular fragmentation index; LV ¼ left ventricle;
VFI ¼ ventricular fragmentation index; VT ¼ ventricular
tachycardia
(Heart Rhythm 2015;12:95–103) I 2015 Heart Rhythm Society. All
rights reserved.
throughout the chamber of interest and display on a
3-dimensional electroanatomic mapping system. Cutoffs
for abnormal voltage reflecting damaged myocardial tissue
or scar have been established in prior studies and are widely
accepted.1 Once the location of scar is identified, pace-
mapping around the scar border can be used to locate the
presumed exit site of the induced VT. Then, linear ablation
through these exit sites can render the VT noninducible.
Although such substrate modification techniques opened
up a new era in the ablation of poorly tolerated VT, the
efficacy in completely eliminating recurrent VT has been
limited.1–5 Therefore, other surrogates of slow conduction
within scar that might harbor a VT isthmus, such as frac-
tionated and late potentials, are also often empirically
targeted for ablation. Such sites are often manually tagged
http://dx.doi.org/10.1016/j.hrthm.2014.10.002
96
on an electroanatomic map during acquisition and then
targeted later for ablation.6,7 The detail of such maps requires
laborious acquisition, the labeling of these sites is quite
subjective, and cumulative labeling of all fractionated/late
signals depends on the number of points acquired and
operator diligence. The frustration with such detailed map-
ping has led some to advocate empiric ablation of all tissue
within the scar, a laborious process that may increase the risk
of complications and create more slow conduction through
incomplete substrate ablation.8
Therefore, in addition to display of “activation time” and
“voltage” information on an electroanatomic map, we
hypothesized that automated display of a “fractionation
map” could be useful for guiding catheter ablation. Using
this rubric, after acquisition of a sinus rhythm voltage map, a
“fractionation map” could be displayed and all abnormal
areas targeted for ablation, thus limiting the ablated area to
that of abnormal electrograms. Therefore, we studied patents
with an postinfarction cardiomyopathy and tolerated entrain-
able VT, together with a population of patients with
idiopathic VT and normal endocardial voltage maps in order
to determine (1) cutoffs for normal and abnormal electro-
gram fractionation, (2) percentage of scar attributed to areas
of abnormal electrogram fractionation, and (3) relationship
between regions of abnormal fractionation to the VT isthmus
in patients with tolerated VT.
Methods
Study population
Detailed left ventricular (LV) electroanatomic data were
obtained from 2 groups of patients undergoing ablation of
ventricular arrhythmias: (1) patients with a history of remote
myocardial infarction and spontaneous VT, and (2) a
reference group of patients with structurally normal hearts
undergoing ablation of idiopathic ventricular premature
depolarizations or VT. All patients provided written
informed consent. All of the procedures were clinically
indicated, and data collection was approved by the human
research committee.
1. Postinfarction cardiomyopathy: Fourteen patients (13
men, mean 67 ⫾ 8 years) with a history of remote
myocardial infarction undergoing detailed endocardial
LV electroanatomic mapping and catheter ablation of
VT in whom at least 1 critical isthmus of a hemodynami-
cally tolerated and mappable monomorphic sustained VT
had been accurately identified using entrainment maneu-
vers were included in the study. In all cases, VT
terminated with ablation at the critical isthmus site.
Fractionation analysis of the electroanatomic maps was
performed offline after the procedure.
2. Reference population: Fourteen patients (10 men, mean
age 42 ⫾ 13 years) with structurally normal hearts who
underwent detailed endocardial LV mapping for catheter
ablation of idiopathic ventricular premature depolariza-
tions/VT and had normal bipolar endocardial voltage
Heart Rhythm, Vol 12, No 1, January 2015
served as the reference group to determine the reference
value of abnormal bipolar electrogram fractionation.
Absence of structural heart disease was confirmed by
transthoracic echocardiography, stress testing, and/or
coronary angiography.
Endocardial electroanatomic substrate mapping
Patients were studied in the postabsorptive state under
conscious sedation or general anesthesia. Detailed maps of
the endocardial LV surface were obtained during sinus
rhythm before radiofrequency ablation from the 28 patients
in the study using an electroanatomic mapping system
(CARTO, Biosense Webster, Diamond Bar, CA) and a
3.5-mm open irrigated-tip catheter (NaviStar ThermoCool,
Biosense Webster), which contains a 2-mm ring electrode
with a 1-mm interelectrode distance. Bipolar electrograms
(sampled at 1 kHz and bandpass filtered at 30–500 Hz) were
recorded, displayed at 200 mm/s sweep speed, and digitally
stored for offline analysis. A detailed assessment of each
electrogram was made to exclude premature or paced beats
and noisy signals. Valvular sites were identified, and intra-
cavitary and poor contact points were deleted and excluded
from the analysis. To ensure adequate sampling density and a
complete representation of voltage distribution, a fill thresh-
old r15 mm was maintained with an emphasis on fully
defining the scar and border zone of the infarcted tissue.
Normal bipolar endocardial electrogram voltage was defined
as a peak-to-peak amplitude Z1.5 mV, and “dense scar” was
defined as a peak-to-peak amplitude o0.5 mV.1 Peak-to-
peak amplitude was measured automatically. A retrograde
transaortic approach was used to access the LV endocardium
in all except 2 cases (1 in each group of patients) in whom
transseptal access was used to map the LV endocardium.
VT mapping and catheter ablation
Once the endocardial LV bipolar voltage map during sinus
rhythm was completed, ventricular programmed stimulation
applying up to 3 extrastimuli at Z2 basic cycle lengths was
performed. Induced VTs were analyzed for cycle length and
morphology using the CardioLab recording system (GE,
Houston, TX). If an induced VT was hemodynamically
tolerated, standard entrainment maneuvers were performed
by pacing from the mapping catheter at a cycle length 20–30
ms faster than the tachycardia cycle length and observing the
response to entrainment. A site was considered a VT mid-
isthmus only if it demonstrated (1) concealed fusion on all 12
ECG leads during entrainment, (2) postpacing interval within
30 ms of the VT cycle length, (3) stimulus-to-electrogram
interval within 30 ms of the electrogram–QRS interval
following entrainment, and (4) local electrogram-to-QRS
interval between 30% and 70% of the VT cycle length.
Confirmed VT isthmus sites were annotated on the map after
VT termination in sinus rhythm. Radiofrequency ablation
was performed using an open-irrigated ablation catheter
(NaviStar ThermoCool) with power of 30–50 W. For the
purpose of this analysis, only isthmus sites that resulted in
Campos et al Fragmentation Map of Postinfarction VT 97

VT termination with ablation directed at the isthmus were

included as true isthmus sites.

Fragmentation analysis of bipolar electrograms

during sinus rhythm
The bipolar signals recorded during sinus rhythm with the
CARTO system before the ablation procedure underwent
offline fragmentation analysis using custom developed soft-
ware and implemented in the MATLAB (Mathworks Inc,
Natick, MA) environment. The CARTO system records a
2.5-second continuous bipolar electrogram at 1000-Hz
sampling frequency at each point on the electroanatomic
map. All of the electrograms recorded from the distal bipole
of the mapping catheter were digitally exported and then
imported into MATLAB for quantitative analysis. Time–
domain analysis is technically easier to implement in online
software and is not fraught with difficulties interpreting
frequency spectra and harmonics of the dominant frequen-
cies. Frequency analysis allows more automated analysis
without relying on time–domain thresholds to determine
electrogram onset/offset and amplitude/duration of a change
in slope to qualify as fractionation. Therefore, we tested both
methods to measure electrogram fractionation in sinus
rhythm.

Time–domain analysis
The bipolar signals underwent an automated time–domain
fragmentation analysis using custom developed software.
The automated ventricular fragmentation index (VFI) was
defined as the total number of deflections (ie, change in slope
from positive to negative or negative to positive), identified
for each recorded electrogram. We previously described such
an algorithm in maps of atrial fibrillation using manual
counting of electrogram deflections.9 The automated soft-
ware algorithm was implemented to make the procedure less
laborious and more uniform. The software algorithm for
deflection detection is based on the amplitude and the timing
of each signal deviation compared to the previous detected
deflection. This algorithm was optimized by meticulous and
careful visual analysis of many normal, abnormal, and highly
fragmented electrograms (Figure 1).
Reference values for VFI
We determined the reference value for abnormal ventricular
fragmentation index (A-VFI) by examining the VFI distri-
bution in the reference cohort of 14 patients with structurally
normal hearts who underwent catheter ablation of idiopathic
ventricular premature depolarizations/VT. Bipolar electro-
grams underwent offline automatic fragmentation analysis,
and the VFI for every point was calculated. Normal VFI was
defined as the value exceeded by 95% of all electrograms.
This criterion has previously been used to determine the
bipolar voltage cutoffs for scar.1 We also determined the
reference value for highly fragmented electrograms (HF-
VFI) by analyzing the distribution of abnormal electrograms
in the 14 patients with a previous myocardial infarction.
Figure 1 Time–domain analysis of bipolar electrograms. The automated
ventricular fragmentation index (VFI) was defined as the total number of
deflections identified for each recorded electrogram (EGM). Three degrees
of fractionation were defined by examining the VFI distribution in the
2 populations of the study: normal (VFI o7), abnormal (VFI Z7), and
highly fragmented (VFI Z14).
HF-VFI was defined as the value exceeded by 75% of all
abnormal electrograms in the ischemic population.
Frequency–domain analysis
We used the fast Fourier transform ratio (FFTr), previously
described by our laboratory for use in atrial fibrillation, as
another automated method for identifying abnormal areas of
electrogram fractionation and late potentials within myocar-
dial scar.9 The digital 2.5-second signals were zero padded
and underwent a 1000-point FFT (frequency resolution 0.25
Hz). The ratio of the area under the curve for the high-
frequency (Z80 Hz) to low-frequency (o80 Hz) compo-
nents of the resulting spectra was calculated as FFTr
(Figure 2). The FFTr values were manually coded back into
the electroanatomic maps (100* ratio as “local activation
time”) for display and analysis.
Reference value for abnormal FFTr
We did not use the cohort of 14 patients with structurally
normal hearts to determine the cutoff for abnormal FFTr
because normal high-voltage bipolar electrograms had too
98 Heart Rhythm, Vol 12, No 1, January 2015

Figure 2 Frequency–domain analysis of bipolar electrograms (EGM). Bipolar signals from the left ventricular endocardium underwent fast Fourier transform
(FFT) analysis (digital 2.5-second signals were zero padded and underwent a 1000-point FFT, frequency resolution 0.25 Hz). The ratio of the area under the
curve for the high-frequency (Z80 Hz) to low-frequency (o80 Hz) components of the resulting spectra was calculated as the fast Fourier transform ratio (FFTr).
A cutoff for high FFTr was defined at 14% by examining the FFTr distribution within the bipolar scar area in the postinfarction cardiomyopathy group.

many high-frequency harmonics in the frequency spectra to The χ2 test was used for comparison of dichotomous
make it meaningful. Therefore, we calculated the abnormal variables. P r.05 was considered significant.
FFTr cutoff as the fractionation value exceeded by 75% of
the electrograms in the scar area (o1.5 mV) in the group of Results
patients with postinfarction cardiomyopathy.
Patient characteristics
Baseline characteristics of the 14 patients with previous
Assessment of surface areas of abnormal myocardial infarction are given in Table 1. Mean age was
fragmented electrograms 67 ⫾ 8 years, and13 (92.9%) were men. Mean LV ejection
The surface area of the A-VFI was measured using the fraction was 34% ⫾ 7%. A total of 12 patients (85.7%) had a
surface area measurement software included in the CARTO prior inferior myocardial infarction, and 2 patients (14.3%)
system. The proportion of the VFI and HF-VFI area to the had a prior anterior myocardial infarction. An implantable
area of dense scar, total scar, and total LV endocardial cardioverter-defibrillator was present in 13 patients (92.9%).
surface area was calculated. We also measured the area of Eight patients (57.1%) were treated with antiarrhythmic
overlap between the A-VFI and HF-VFI area and the area of drugs at the time of the procedure.
scar and dense scar according to bipolar criteria. Baseline characteristics of the 14 reference patients with
structurally normal hearts are also given in Table 1. Mean
age was 42 ⫾ 13 years, and 10 (71.4%) were men. Mean LV
Correlation between A-VFI, HF-VFI, and H-FFTr areas ejection fraction was 61% ⫾ 5%, and mean LV end-diastolic
and VT circuit diameter was 48 ⫾ 5 mm.
Confirmed VT isthmus sites according to standard entrain-
Table 1 Baseline patient characteristics
ment maneuvers criteria were carefully tagged on the LV
endocardial electroanatomic map in sinus rhythm after Postinfarction Structurally
ablation terminated VT. The linear distance of the VT cardiomyopathy normal heart
isthmus site to the border of the nearest area of A-VFI, No. of patients 14 14
HF-VFI, and H-FFTr was calculated using the CARTO Male 13 (93%) 10 (71%)
software. Age (years) 67 ⫾ 8 42 ⫾ 13
Left ventricular ejection 34 ⫾ 7 61 ⫾ 5
fraction (%)
Myocardial infarction Anterior 2 (14%) —
Statistical analysis location Inferior 12 (86%)
Continuous data are expressed as mean ⫾ SD. All contin- Antiarrhythmic drug at 8 (57%) 5 (36%)
uous data were tested using the 1-sample Kolmogorov– procedure
Smirnov test against a normal distribution. Continuous Implantable cardioverter- 13 (93%) 1 (7%)
defibrillator
variables were compared using the paired Student t test.
Campos et al Fragmentation Map of Postinfarction VT 99

Reference value for A-VFI Conventional substrate mapping in the

A total of 1660 LV bipolar electrograms were analyzed from
the 14 reference patients with structurally normal hearts (119
⫾ 62 points per patient). Ninety-five percent of LV
endocardial bipolar signals had VFI o7 (mean 4.6 ⫾ 1.5);
therefore, VFI Z7 was defined as the VFI cutoff value for
abnormal LV endocardial electrograms.
Reference value for highly fragmented automated
fragmentation index (HF-VFI)
From the 5227 LV endocardial bipolar recordings analyzed
in the 14 patients with a history of prior myocardial
infarction, a total of 2447 exhibited A-VFI (Z7). Seventy-
five percent of these LV A-VFI recordings had VFI o14
(mean 11.6 ⫾ 5.1); therefore, we defined VFI Z14 as the
cutoff for HF-VFI.
Reference value for FFTr (H-FFTr)
From the 5227 LV endocardial bipolar recordings analyzed
in the 14 patients with a history of prior myocardial
infarction, a total of 2989 had bipolar voltage amplitude
o1.5 mV, consistent with scar according to classic criteria.
Seventy-five percent of these recordings within the LV
bipolar scar had FFTr o14% (mean 10.7 ⫾ 11.1); therefore,
we defined H-FFTr Z14% as the cutoff value for H-FFTr.
postinfarction cardiomyopathy population
The 14 patients with prior myocardial infarction and sponta-
neous VT underwent detailed endocardial LV electroanatomic
mapping (382 ⫾ 107 points sampled per patient) before
ablation. The endocardium of all patients demonstrated an
area of abnormal bipolar voltage, consistent with postinfarc-
tion scar, which occupied a mean endocardial surface area of
95.3 ⫾ 33.4 cm2 and represented 42.1% ⫾ 12.3% of the total
recorded LV geometry endocardial surface area. The dense-
scar area averaged 26.3 ⫾ 17.7cm2, which represented 27.0%
⫾ 14.5% of the scar area (o1.5 mV) and 11.3% ⫾ 7.0% of
the total recorded LV endocardial surface area.
Time–domain fractionation analysis
Areas of A-VFI (VFI Z7) were present in 14 of 14 patients
(100%) with prior myocardial infarction and occupied a
mean endocardial area of 61.6 ⫾ 19.6 cm2, which repre-
sented 27.3% ⫾ 7.1% of the total LV endocardial surface
area. The proportion of VFI area to total LV surface area was
significantly smaller than the proportion of scar surface area
to total LV surface area (27.3% ⫾ 7.1% vs 42.1% ⫾ 12.3%,
P o.001). However, 92.2% ⫾ 4.6% of the A-VFI areas
overlapped with the area of bipolar voltage scar (o1.5 mV;
Figure 3).
Areas of HF-VFI (VFI Z14) were present in 14 of the 14
patients (100%) with prior myocardial infarction and

Bipolar Voltage Fragmentation Index Bipolar Voltage

1.5 mV VFI 14 1.5 mV

0.5 mV VFI 7 0.5 mV

VT Isthmus VT Isthmus VT Isthmus

1.5 mV VFI 14 1.5 mV

0.5 mV VFI 7 0.5 mV

Figure 3 Relationship between the area of fragmented and highly fragmented electrograms and bipolar scar on the left ventricular (LV) electroanatomic map.
Inferior and left lateral views of the bipolar voltage map (A, D) show an area of low-voltage scar extending on the inferior, lateral, and anterior aspects of the LV
endocardium. Inferior and left lateral views of the ventricular fragmentation index (VFI) map (B, E) show the area of fractionated electrograms (VFI Z7, black
line) and its relationship to bipolar scar (white line). The VFI map (B, E) also shows the area of highly fractionated electrograms (VFI Z14, in purple), which is
much smaller than the bipolar scar area. The areas of highly fractionated electrograms (VFI 414) included the ventricular tachycardia (VT) isthmus site (green
tag) in this patient. The inferior and left lateral views of the bipolar voltage maps are shown again in the right panels (C, F), with the area of highly fractionated
electrograms (VFI 414) outlined in yellow.
100 Heart Rhythm, Vol 12, No 1, January 2015

Table 2 Findings from electroanatomic mapping in the postinfarction cardiomyopathy group

Total no. of LV endocardial mapping points, per patient 382 ⫾ 107
Area of bipolar voltage scar (cm2) and proportion to total LV surface (%) 95.3 ⫾ 33.4 (42.1% ⫾ 12.3%)
Area of A-VFI (VFI Z7) (cm2) and proportion to total LV surface (%) 61.6 ⫾ 19.6.4 (27.3% ⫾ 7.1%)
Overlap of A-VFI areas to bipolar voltage scar (%) 92.2 ⫾ 4.6%
Area of highly fragmented VFI (VFI Z14) (cm2) and proportion to bipolar scar area (%) 16.4 ⫾ 12.0 (17.2% ⫾ 10.1%)
Area of high FFTr (FFTr Z14) (cm2) and proportion to bipolar scar area (%) 22. ⫾ 16.8 (23.% ⫾ 17.1%)
Isthmus included in A-VFI area (VFI Z7) 15 (100%)
Isthmus included in highly fragmented VFI area (VFI Z14) 12 (80%)
Isthmus included within 5 mm of highly fragmented VFI area (VFI Z14) 15 (100%)
Isthmus included in high FFTr area (FFTr Z14) 9 (60%)
Isthmus included within 5 mm of high FFTr area (FFTr Z14) 13 (87%)
A-VFI ¼ abnormal ventricular fragmentation index; FFTr ¼ fast Fourier transform ratio; LV ¼ left ventricle; VFI ¼ abnormal ventricular fragmentation index.

occupied a mean endocardial area of 16.4 ⫾ 12.0 cm2, which
represented 7.2% ⫾ 4.9% of total LV endocardial surface.
The area with highly fragmented electrograms represented
25.4% ⫾ 12.8% of the total A-VFI area (VFI Z7). Of the HF-
VFI areas, 98.8% ⫾ 2.9% overlapped with the areas of bipolar
voltage scar, specifically selecting small regions of highly
fragmented electrograms, which occupied 17.2% ⫾ 10.1% of
the bipolar voltage scar areas, and 81.8% ⫾ 14.2% of the HF-
VFI areas (VFI Z14) overlapped with areas of bipolar voltage
dense scar, which occupied 54.0% ⫾ 20.1% of the bipolar
voltage dense-scar areas (Table 2, and Figures 3 and 4). There
was a moderate negative correlation between electrogram
bipolar voltage amplitude and VFI (r ¼ – 0.44, P o.001).
Frequency–domain fractionation analysis
Areas of H-FFTr (FFTr Z14%) were present in 14 of the 14
patients (100%) with prior myocardial infarction and occu-
pied a mean endocardial area of 22.2 ⫾ 16.8 cm2, which
represented 9.7% ⫾ 6.9% of total LV endocardial surface.
Areas of abnormal H-FFTr specifically selected small
regions of highly fragmented electrograms, which occupied
23.8% ⫾ 17.1% of the bipolar voltage scar area (o1.5 mV);
41.0% ⫾ 22.7% of the highly fragmented FFTr areas
overlapped with the areas of bipolar voltage dense scar
(o0.5 mV), which occupied 39.1% ⫾ 31.7% of the bipolar
voltage dense-scar areas (Table 2 and Figure 5).
The size of the areas of bipolar scar specifically selected
by HF-VFI and H-FFTr were not significantly different
(17.2% ⫾ 10.1% vs 23.8% ⫾ 17.1%, respectively, P ¼.10).
Qualitatively these areas also typically overlapped.
Electrophysiologic study, VT mapping, and catheter
ablation
Programmed ventricular stimulation induced 39 different
sustained VTs in the 14 patients with prior myocardial
infarction (2.8 ⫾ 1.3 per patient, range 1–5). Thirteen VTs
required rapid termination for hemodynamic instability. The
remaining 26 VTs were hemodynamically well tolerated and
could be mapped using entrainment. A VT reentrant mid-
isthmus site was accurately identified with standard entrain-
ment maneuvers in 15 VTs (1.1 ⫾ 0.3 per patient, cycle
length 409 ⫾ 65 ms) and annotated on the electroanatomic

1.5 mV VFI 14

0.5 mV VFI 7

VT Isthmus

Figure 4 Relationship between the area of highly fragmented ventricular fragmentation index (VFI) and bipolar scar on the left ventricular (LV)
electroanatomic map. Left: Inferior view of a bipolar voltage map shows an area of scar extending on the inferior aspect of the LV endocardium. Right: Same
view of the VFI map shows the area of highly fractionated electrograms (VFI Z14, in purple, yellow line) and its relationship to bipolar scar (white line). Areas of
VFI Z14 specifically selected small regions of highly fragmented electrograms within the bipolar voltage scar (white line). All VT isthmus sites (green tags) in
the study were included within 5 mm of the highly fragmented areas (VFI Z14). VT ¼ ventricular tachycardia.
Campos et al Fragmentation Map of Postinfarction VT 101

Figure 5 Relationship between the area of high fast Fourier transform ratio (FFTr) and bipolar scar on the left ventricular electroanatomic map. Left: Inferior
view of the bipolar voltage map shows an area of scar extending on the inferior aspect of the LV endocardium. Right: Same view of the FFTr map shows the area
of high FFTr (FFTr Z14, in purple, yellow line) and its relation to bipolar voltage scar (white line). Areas of H-FFTr specifically selected small regions of highly
fragmented electrograms within the bipolar voltage scar that included 60% of the ventricular tachycardia (VT) isthmus sites in the study. Eighty-seven percent of
VT isthmus sites in the study were included within 5 mm of the high FFTr areas.

map in sinus rhythm after VT termination. Radiofrequency
application at those sites successfully terminated the VT in
all cases and resulted in noninducibility of the targeted VT
with later programmed ventricular stimulation (Figure 6)
Relationship of VT circuit to areas of abnormal
voltage and fractionation
Of the 15 isthmus sites identified in the 14 patients with prior
myocardial infarction, all were located within the area of
bipolar voltage scar (o1.5 mV), and 11 (73.3%) were located
within the area of bipolar voltage dense scar (o0.5 mV).
All 15 of the isthmus sites (100%) were located within the
area of A-VFI (VFI Z7, Figure 3). Twelve of the 15 isthmus
sites (80%) were located within the area of HF-VFI (VFI
Z14). The mean distance of the remaining 3 isthmus sites to
the area of highly fragmented electrograms according to the
VFI criterion was 3.8 ⫾ 1.2 mm (range 2.9–4.8 mm). All 15
of the isthmus sites (100%) were located within 5 mm of the
HF-VFI area (Table 2 and Figures 3 and 4).

I
1.5 mV
II
III
aVR
aVL
aVF 0.5 mV

V1
V2
V3
VT Isthmus VFI 14
V4
V5
V6

ABLd
VFI 7
ABLp
RVa

Figure 6 Identification of ventricular tachycardia (VT) isthmus sites. Standard entrainment maneuvers were systematically performed to characterize the
circuit of well-tolerated mappable VT in the postinfarction cardiomyopathy patients. A site was considered a VT mid-isthmus only if it demonstrated (1)
concealed fusion on all 12 ECG leads during entrainment, (2) postpacing interval (PPI) within 30 ms of the VT cycle length (CL), (3) stimulus-to-electrogram
interval within 30 ms of the electrogram-to-QRS interval following entrainment, and (4) local electrogram-to-QRS interval between 30% and 70% of the VT CL.
102
Nine of the 15 isthmus sites (60%) were located within the
area of high FFTr (FFTr Z14%). The mean distance of the
remaining 6 isthmus sites to the area of highly fragmented
electrograms was 5.7 ⫾ 4.0 mm (range 2.2–12.2 mm).
Thirteen of the isthmus sites (87%) were located within 5
mm of the H-FFTr area (Table 2 and Figure 5).
Discussion
Substrate ablation for treatment of poorly tolerated VT
includes ablation through areas of pace-maps matching a
clinical VT and ablation of visually identified late potentials
within scar.1,6,7 However, VT recurrence rates have led some
to propose complete “scar homogenization” or empiric
ablation of the entire scar to prevent current and future
VTs.8 We have developed and automated a method for
quantifying and displaying abnormal fractionated scar elec-
trogram characteristics on an electroanatomic map. We
defined cutoffs for abnormal fractionated and highly fractio-
nated regions in the time and frequency domain based on a
normal control population. Importantly, we have shown that
the fractionated region composes roughly 60% of the total
scar surface area yet contains 100% of the mapped VT
isthmuses. This finding suggests that empiric ablation of
these automatically detected regions of electrogram fractio-
nation may be a new method for performing substrate
modification without the need to homogenize the entire scar.
From previous data we know that bipolar electrogram
amplitude tends to label larger areas as border zone
compared to late gadolinium enhancement magnetic reso-
nance imaging.10 Moreover, Zeppenfeld et al11 described the
importance of bipolar electrogram duration and fragmenta-
tion, manually determined, to better define the scar area
compared to bipolar voltage. Our current data are consistent
with these previous findings and support the potential value
of automated fractionation analysis for scar area delineation.
The study also demonstrates the ability of time–domain
fractionation analysis to specifically select, using a higher
cutoff (VFI Z14), small regions of highly fragmented
electrograms within the LV endocardial bipolar scar
(17.2% ⫾ 10.1%) that significantly correlated with critical
VT circuit components, including 80% of the VT isthmus in
the ischemic population. Even more, 100% of VT isthmus
sites were included within 5 mm of the HF-VFI areas (VFI
Z14). Fragmented and late or isolated potentials recorded
during sinus rhythm have been long recognized as a potential
marker of slowly conducting critical components during
reentrant VT, reflecting local depolarization of surviving
myocardial bundles insulated within denser scar.12 As
demonstrated in previous studies, the presence of late and
high-frequency multiple component electrograms during
baseline rhythm mapping is specific for VT circuit identi-
fication.6,7,13 Moreover, Zeppenfeld et al11 described a
highly sensitive and specific method to visually but reliably
determine electrogram number of deflections and duration,
independently of interobserver variability, and demonstrated
the usefulness of a mapping strategy based on manually
Heart Rhythm, Vol 12, No 1, January 2015
measured bipolar electrogram duration and fragmentation
during sinus rhythm for the identification of target areas for
radiofrequency ablation of VT. However, because of the
complexity of electrograms within the scar, manual deter-
mination of the number of deflections and electrogram
duration may be subjective, time consuming, and hardly
feasible during regular VT mapping and ablation procedures,
making such a technique difficult to expand to general
practice in other laboratories. Moreover, the manual labeling
of fragmented and late signals on electroanatomic maps that
currently is performed in such procedures usually is a tedious
process that also is subject to operator subjectivity. The
usefulness of automated fractionation analysis lies in its
objectivity, reproducibility, and reliability for fast electro-
gram fragmentation quantification when mapping the sub-
strate for ischemic reentrant VT.
The present study also explored the usefulness of a
frequency–domain analysis based on fast Fourier transform
(FFT) to quantify electrogram fractionation. We had already
demonstrated that signal processing using the FFTr param-
eter closely approximated a manual measure of atrial bipolar
electrogram fractionation in sinus rhythm.9 FFTr is computa-
tionally more complex than the time–domain measure, only
overlapped with 60% of the identified VT isthmus sites, and
did not perform well in areas of normal voltage because of
multiple harmonics in the frequency spectra. Therefore, the
simpler time–domain measure of fractionation should be
easier to implement.
Study limitations
This analysis focused only on mappable VTs. Although the
correlation of all the identified VT isthmuses to areas of
highly fragmented electrograms imply that they will also be
useful for targeting nonmappable unstable VTs, this requires
further prospective confirmation. We also did not attempt to
correlate additional empiric ablation targeting nontolerated
VTs performed by some operators to areas of electrogram
fractionation because of the empiric and diffuse nature of
these ablation lesions.
This was a retrospective study performed using signal
analysis after VT ablation. Reproducibility of fractionation
maps on the same patient has not been reported because, due
to the length of the VT ablation procedures and the
retrospective nature of the study, only 1 detailed voltage
map was acquired during sinus rhythm for each patient
before ablation. These findings should be confirmed pro-
spectively with an online analysis tool.
Changing the direction of depolarization can influence the
appearance of local electrograms. We did not test the
algorithm during pacing from multiple locations because of
time limitations and the retrospective nature of the study.
Finally, additional nonclinical, poorly tolerated VTs were
often induced, and empiric substrate modification was
performed by the operators after ablation of the tolerated
VTs. Because of the broad and varied nature of such
ablation, we did not attempt to correlate this with regions
Campos et al Fragmentation Map of Postinfarction VT 103

of electrogram fractionation. Whether empiric ablation of all
areas of electrogram fractionation would also address non-
tolerated VTs needs to be tested in prospective studies.
Conclusion
Automated electrogram fractionation analysis provides
useful information complementary to voltage mapping,
allowing objective and fast identification of areas of highly
fragmented signals related to critical parts of VT circuits
in patients with a previous healed myocardial infarc-
tion. Prospective evaluation of empiric ablation targeting
regions of automatically detected abnormal fractionation is
warranted.
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CLINICAL PERSPECTIVES
Catheter ablation of ventricular tachycardia (VT) can be lengthy and has only moderate success. Because the induced VT
can be rapid and poorly tolerated, ablation is often performed in sinus rhythm and includes targeting of fractionated and late
potentials. However, identification of late potentials is quite subjective and depends on the density of mapping and the
fastidiousness of the operator in labeling every late potential. We examined methods, in the time and frequency domains,
for automatically identifying late potentials and fractionated electrograms on an electroanatomic map. We found that the
time–domain method was simpler and identified 100% of the VT isthmus sites that were identified with detailed
entrainment mapping. This process could simplify the mapping process by allowing display of a VT “fractionation map” in
addition to the usual activation and voltage maps. Empiric ablation of the fractionated regions may be a simpler and more
effective approach than current substrate modification approaches, without the need to ablate the entire scar. We believe
such an approach should be tested in a prospective randomized trial of VT ablation compared to standard substrate-guided
ablation approaches.