Ventricular dyssynchrony assessment using ultra-high frequency ECG technique
J Interv Card Electrophysiol
Ventricular dyssynchrony assessment using ultra-high frequency ECG technique
Pavel Jurak 0 1 2 3 4 5
Josef Halamek 0 1 2 3 4 5
Jaroslav Meluzin 0 1 2 3 4 5
Filip Plesinger 0 1 2 3 4 5
Tereza Postranecka 0 1 2 3 4 5
Jolana Lipoldova 0 1 2 3 4 5
Miroslav Novak 0 1 2 3 4 5
Vlastimil Vondra 0 1 2 3 4 5
Ivo Viscor 0 1 2 3 4 5
Ladislav Soukup 0 1 2 3 4 5
Petr Klimes 0 1 2 3 4 5
Petr Vesely 0 1 2 3 4 5
Josef Sumbera 0 1 2 3 4 5
Karel Zeman 0 1 2 3 4 5
Roshini S. Asirvatham 0 1 2 3 4 5
Jason Tri 0 1 2 3 4 5
Samuel J. Asirvatham 0 1 2 3 4 5
Pavel Leinveber 0 1 2 3 4 5
0 1st Department of Internal Medicine-Cardioangiology, St. Anne's University Hospital, Masaryk University , Brno , Czech Republic
1 International Clinical Research Center, St. Anne's University Hospital , Brno , Czech Republic
2 Institute of Scientific Instruments of the Czech Academy of Sciences , Brno , Czech Republic
3 Department of Pediatrics and Adolescent Medicine, Mayo Clinic , Rochester, MN , USA
4 Division of Cardiovascular Diseases, Department of Internal Medicine, Mayo Clinic , Rochester, MN , USA
5 Student Scholar Program, Mayo Clinic , Rochester, MN , USA
Purpose The aim of this proof-of-concept study is to introduce new high-dynamic ECG technique with potential to detect temporal-spatial distribution of ventricular electrical depolarization and to assess the level of vent ricular dyssynchrony. Methods 5-kHz 12-lead ECG data was collected. The amplitude envelopes of the QRS were computed in an ultra-high frequency band of 500-1000 Hz and were averaged (UHFQRS). UHFQRS V lead maps were compiled, and numerical descriptor identifying ventricular dyssynchrony (UHFDYS) was detected.
Ventricular dyssynchrony; Cardiac resynchronization therapy; High-frequency electrocardiography; Left bundle branch block; Depolarization
Pathological changes in the structure of cardiac ventricles
often manifest themselves in electrical activity. The clinical
12lead ECG-based criteria for left ventricle (LV) dyssynchrony
quantification and cardiac resynchronization therapy (CRT)
implementation are based primarily on the duration and
morphology of the QRS complex [
]. Unfortunately, QRS
descriptors still do not appear to be effective tools for the
diagnosis of LV dyssynchrony [
Conventional ECG diagnostic information is usually
limited to 100 Hz. Most QRS parameters including QRS duration
or morphology use frequency band below 30 Hz. Broad-band
ECG measured by high-frequency and high-resolution
monitors provide more precise QRS morphology [
information not accessible by conventional ECG. In 1981, Goldberger
et al. [
] reported the effect of myocardial infarction on
lowvoltage high frequency (HF, 150–250 Hz) potentials in the
QRS complex (HFQRS, HF-ECG). Studies dedicated to this
] have shown that HFQRS potential morphology
and amplitude reduction are modified by coronary occlusion
or infarct-induced ischemia. When compared to commonly
used ECG parameters such as the duration of the QRS
complex, ST-segment abnormalities, fragmented QRS, and
upward and downward slopes of the QRS complex [
cardiac ischemic pathology is detected with higher sensitivity
using HFQRS. However, the presented methodologies have
focused predominantly on heart ischemia (single-lead HFQRS
morphology), neglected the temporal-spatial properties
(dyssynchrony), and analyzed ECG in a limited frequency
range (up to 250 Hz) [
Here, we introduce an ultra-high frequency
electrocardiogram (UHF-ECG) technique. The higher
frequency and the dynamic range allow for more accurate
identification of the temporal distribution of electrical
depolarization in a single lead. The mutual comparison of
depolarization activation patterns in different ventricular
segments (leads) and computation of depolarization
inter-lead delays can be potentially interpreted as
2.1 Data acquisition and processing
The acquisition system BioSDA09 (M&I, Prague, CZ)
was used to record ECG signals at 5-kHz with a
dynamic range of 26 bits (3 nV resolution) and a
frequency range of 2-kHz. Measurements were performed at the
International Clinical Research Center at St. Anne’s
University Hospital, Brno, Czech Republic. The
UHFECG data was collected over 5–15 min in the resting
supine position with a standard 12-lead ECG setup.
The UHF Solver and SignalPlant (ISI CAS, Brno,
] software was specifically developed for
UHFECG data processing. Stimulating peaks were removed
from the signal in patients with pacemakers. QRS
complexes were detected [
] and clustered into different
QRS morphology categories using a robust multichannel
approach capable of recognizing sinus QRS patterns as
well as irregular patterns. This technique was used to
focus the analysis primarily on the sinus (dominant)
rhythm. The amplitude envelopes were computed in a
frequency band of 500–1000 Hz using the Hilbert
transform and were averaged with an R-wave trigger and
smoothed in a 0–40 Hz passband (UHFQRS). The
stimulation peaks detection and removal and QRS
categorization are the crucial parts of UHF-ECG signal
pre-processing. The precision of signal pre-processing
substantially influences the signal-to-noise ratio in averaged
The shapes of averaged QRS complexes (Fig. 1a) of V
leads can be compared to averaged UHFQRS envelopes
(Fig. 1b) and UHFQRS maps (Fig. 1c). Each horizontal row
of the map represents the normalized shape of UHFQRS for
single V lead. The maximum in each map row (lead) is
normalized to 1 (red), while the minimum is normalized to 0
(blue). Normalization standardizes the UHFQRS to the
uniform amplitude range of 0–1. The parameter UHFDYS (Fig.
1e), defined by differences in the positions of maxima in leads
V1 and V6, is especially helpful in the numerical
identification of ventricular electrical dyssynchrony. The UHFDYS
parameter in Fig. 1 means that peak depolarization in the RV and
septum precedes peak depolarization in the LV lateral wall by
84 ms. This value is clearly identifiable from UHFQRS (Fig.
1b–e) but cannot be detected from standard (low-frequency)
QRS (Fig. 1a, d). An example of a UHFQRS map (Fig. 1c)
also demonstrates that dyssynchrony UHFDYS in V1 and V6
leads sometimes does not reflect the highest dyssynchrony. In
this case, V2 and V6 dyssynchrony (Fig. 1c, UHFDYS ALL)
is 96 ms. Therefore, both C and E images are important for
presentation of the results.
Detailed description of UHF-ECG signal processing
including comparison of different frequency ranges is available
in the Electronic Supplementary Material.
2.2 Patient selection
Initially, we have studied seven patients with
characteristic QRS complex shape. Table 1 (subjects 1–7)
presents their baseline clinical data. To assess predictive
power of UHF-ECG-derived dyssynchrony for
identification of responders to CRT, we started prospective
6month follow-up study. The baseline data of first ten
consecutive patients who completed that follow-up
interval are demonstrated in Table 1 (patients 8–17). All
patients were in sinus rhythm and did not have signs
of cardiac decompensation. CRT patients were selected
on the basis of European Society of Cardiology criteria
for CRT [
]. Two patients were implanted even if their
LVEF mildly exceeded the recommended guidelines
cutoff value of 35%. All CRT subjects underwent
UHFECG and standard transthoracic echocardiography within
24 h before CRT and at 6 months after CRT.
Pt. patient, M/F male/female, AA medication Antiarrhythmic medication, QRSd QRS duration, LVEF left ventricular ejection fraction, ESV end-systolic
volume, CAD coronary artery disease, DCM dilated cardiomyopathy, WPW sy. Wolf-Parkinson-White syndrome, VHD valvular heart disease, LBBB left
bundle branch block, RBBB right bundle branch block, RSAP right-sided accessory pathway
* Standard 2-dimensional echocardiography was used to obtain LV volumes and EF [
All subjects gave their informed consent to the
investigation. This study was approved by the local ethics committee—
The Ethics Committee at St. Anne’s Hospital, Brno,
2.3 UHFQRS physiology
potentials (AP) serves as a main UHF transmitter (Fig. 2c).
Steep cell membrane potential gradients caused by the sodium
ion current change (Phase 0 of AP) represent a unique source
of UHF oscillations. The mass of myocardium, especially the
left ventricle, defines the main location of UHF transmitters.
UHFQRS can be simply interpreted as a histogram of UHF
oscillation distribution in time (horizontal time axis) and
location (V leads). The UHF transmitters work synchronously in
the healthy heart (Fig. 2b, HEALTHY). In a dyssynchronous
left bundle branch block (LBBB) heart, the depolarization in
the RV and septum (blue color in Fig. 2b, LBBB) precedes the
depolarization in the LV lateral wall (green color).
2.4 UHFQRS and two-dimensional speckle tracking echocardiography (STE)
The main aim of cardiac resynchronization therapy is to
improve mechanical synchrony [
]. STE was used to
demonstrate the relationship of the electrical activation derived from
the UHFQRS and the initiation of mechanical contraction
(Fig. 3). STE is an angle-independent method that depicts
myocardial deformation without the influence of
extracardiac motion. Using the apical 4-chamber view, STE
enables simultaneous detection of the onset of myocardial
deformation of the septum and lateral wall. Fig. 3 demonstrates the
match between electrical and mechanical activation and LV
dyssynchrony in a patient suffering from LBBB.
The STE analysis software depicted the color-coded strain
rate map from the basal, middle, and apical segments of the
septum and left lateral wall (Fig. 3c). The onset of isovolumic
deformation of each segment was defined by the first
appearance (left margin) of the orange/red area at the
electrocardiographic QRS complex region (red arrow). The mechanical
STE septal-to-lateral asynchrony (Fig. 3c, orange horizontal
bar, 87 ms) is analogical to the electrical UHFDYS (61 ms)
and UHFDYS ALL (74 ms) asynchrony (Fig. 3a, black
horizontal bars). Similarly, the course of electrical UHFQRS
maps correspond to the course of the beginnings of
myocardial deformations of the pertinent myocardial segments.
Comparison of UHFQRS and STE has also provided a new
parameter: the time delay between electrical and mechanical
action onset (Fig. 3c, green horizontal bar). This time delay
could define a physiological link between electrical activation
and the onset of myocardial deformation in ventricles.
3.1 Typical UHFQRS patterns—Normal, RBBB, LBBB, and RV pre-excitation
Figure 4 shows examples of typical UHFQRS pattern, from
the left: a normal healthy heart, a patient with right bundle
branch block (RBBB), a patient with LBBB, and a patient
with WPW syndrome with RV pre-excitation. The UHFQRS
maps (Fig. 4c) provide a detailed overview of the
temporalspatial distribution of depolarization computed from V leads.
The UHFQRS maps demonstrate how the change in electrical
depolarization synchrony can vary across different
pathologies. Nevertheless, the description of dyssynchrony by
temporally synchronized with A and B. d V1-V6 ECG. UHFDYS and
UHFDYS ALL electrical dyssynchrony are 61 and 74 ms, respectively,—
black horizontal bars. a The time delay of mechanical motion between
the onset of myocardial deformation of the middle septum and the middle
lateral wall is 87 ms—orange horizontal bar. c. The green horizontal bar
defines delay 48 ms between the first electrical UHF activation in V2 lead
and onset of mechanical myocardial deformation of the middle septum
81 ms, patient 3—RBBB, QRSd 139 ms, patient 4—LBBB, QRSd
190 ms, and patient 5 with WPW syndrome with right lateral accessory
pathway QRSd 105 ms.
UHFQRS in leads V1 and V6 (Fig. 4b) simplifies
interpretation and allows for inter-subject computation of comparable
3.2 UHFQRS CRT response, LV pre-excitation
Table 2 demonstrates the first results of patients before and
6month after CRT. The patients No. 8–14 represent responders
with post-implantation LV ESV reduction of 10% or more and
patients No. 15–17 non-responders [
]. In our preliminary
analysis, UHF-ECG dyssynchrony with cut-off value of more
than 50 ms identified correctly all responders and
Figure 5 introduces UHFQRS CRT responses, patients 8–
12, 14 (responders), and patients 15–17 (non-responders)
from Table 2. Electrical dyssynchrony DYS, QRSd, left
ventricular ejection fraction (LVEF), and end-systolic volume
(ESV) were measured before CRT and 6-month after CRT
implantation during CRT ON. Patients 8, 9, 10, 11, and 12
represent ideal CRT recipients with significant improvement
of both LV functional parameters and electrical ventricular
synchrony. The wide QRS complex and large dyssynchrony
before CRT are changed into a narrow QRS complex with
almost no dyssynchrony - merging of blue and green V1 and
V6 depolarization patterns during CRT and narrowing of
UHFQRS maps. Patient 14 has the lowest DYS from the
responders (53 ms). Bi-ventricular stimulation creates an
alignment of electrical depolarization with slight delay in V1
lead. Patients 15, 16, and 17 shows reduced CRT effect on
ventricular synchrony. There is no significant positive change
in QRSd, LVEF, or ESV. UHFDYS before CRT is low.
UHFQRS maps in patients 15, 16, and 17 before and during
CRT are similar which means that there is very little effect of
CRT on electrical synchronization.
Figure 6 demonstrates effect of 20 ms LV lead
preexcitation on UHFQRS and UHFDYS. Patient 6 (Table 1)
has large electrical dyssynchrony 90 ms and QRSd 194 ms
shortened to 33 ms and 132 ms by CRT. Figure 6c depicts the
positive effect of 20 ms LV lead pre-excitation. While QRSd
remained unchanged (131 ms), there was significant reduction
of UHFDYS (23 ms). Figure 6 demonstrates the possible role
of UHFQRS method in CRT optimization when QRSd change
remains less sensitive [
3.3 UHFQRS maps and STE—electro-mechanical interpretation
Figure 7 shows examples of UHFQRS maps and STE maps.
In a healthy heart (Fig. 7a), mechanical deformation begins
synchronously in all parts of the LV, confirmed by the narrow
QRS, overlapping UHFQRS over V leads, and the single line
in the UHFQRS maps corresponding to the orange/red edge of
Figure 7b, c show the effect of biventricular pacing (patient
7). The black arrow localizes the positive shift of the onset of
deformation of the LV lateral wall and the significant
reduction in mechanical dyssynchrony in the STE. The same
positive effect can be seen in UHFQRS maps. While STE
examination requires good quality echocardiographic imaging and
cannot be performed on every patient, UHFQRS does not face
the same restrictions.
Pt. patient, QRSd QRS duration, LVEF left ventricular ejection fraction, ESV end-systolic volume. Patients No.8–14 are responders to cardiac
* Standard 2-dimensional echocardiography was used to obtain LV volumes and EF [
33 ms. c CRT ON VV delay 20 ms, QRSd remain unchanged,
preexcitation of LV lateral wall leads to further improvement of synchrony
UHFDYS 23 ms. d V1 and V6 ECG leads, CRT ON
The gold standard for detailed assessment of RV or LV
dyssynchrony is still being discussed [
]. Surface ECG
represents the oldest and most widely used method for diagnosing
pathological electrical activation of the myocardium by
comparing the shape and duration of the QRS complex in a 12-lead
ECG. Large randomized studies claim that the best criteria for
CRT candidate selection are a QRS duration of >150 ms and
true LBBB morphology of the QRS complex [
guidelines limit QRS duration to 120 ms [
]. Strauss criteria that
include a QRS duration ≥140 ms for men and ≥130 ms for
women, along with mid-QRS notching or slurring in ≥2
contiguous leads [
], currently represent the most powerful
marker for complete LBBB identification. However, ECG
represents a global view of electrical activity of the heart with no
direct information about mechanical activity.
We compared ten patients (Table 2) before CRT and
6month after CRT during CRT ON. We present ECG
parameters (QRSd, QRS morphology—Strauss criteria and
UHFQRS dyssynchrony) and echocardiographic LV
functional parameters (LVEF, ESV). Patients 8–14 show a positive
effect of CRT on LV function. The QRS morphology before
CRT meets the Strauss criteria (patients 8, 9,11,12, and 13),
and UHFQRS before CRT shows a large electrical
depolarization delay between the septum and LV lateral wall. Patient
10 does not meet Strauss criteria (no notch or slur), but has
wide QRSd and high UHFDYS. Patient 14 has the lowest
level of DYS, the shortest QRS of all responders, and does
not meet Strauss criteria. Even so, there is clear
synchronization effect (Fig. 5, p14).
Patients 15–17, classified as non-responders, have small
UHFQRS dyssynchrony (<50 ms) and narrow QRSd
(<151 ms) prior to CRT. Biventricular pacing has no effect
on QRSd and LV ESV. CRT reduces electrical dyssynchrony,
though significantly less than in responders.
Our preliminary results of ten consecutive patients who
completed 6-month follow-up suggest the potential of
UHFECG derived dyssynchrony to correctly define responders or
non-responders to CRT. Thus, UHF-ECG derived
dyssynchrony deserves attention and, considering also
advantages of UHF-ECG mentioned in the text of our paper, it may
have the potential to be one of the most significant predictors
of responsiveness to CRT.
Mechanical cardiac activity can be assessed primarily by
echocardiography or magnetic resonance imaging (MRI).
Several echocardiographic methods have been clinically
utilized for the quantification of mechanical (contractile)
myocardial dyssynchrony, including M-mode echocardiography,
Doppler tissue imaging, Doppler-derived strain, and strain rate
analysis or, more recently, STE. Each of these methods has
limitations leading to modest accuracy to predict CRT
]. Lower reproducibility and temporal
resolution over 10 ms are the main drawbacks. MRI is a rapidly
developing non-invasive technique for monitoring cardiac
mechanics. It provides valuable spatial imaging of cardiac
tissues and their dynamic change. The main limitation of
MRI is its availability for routine diagnostics and its cost.
High UHFQRS temporal resolution, resulting from the
frequency band, is coupled with superior reproducibility.
Sufficient signal-to-noise ratio is obtained by averaging. The
averaging technique cannot be used in echocardiography.
Moreover, the analysis may be conducted with various types
of QRS complexes, and even irregular beats can be
If the premise that UHFQRS measures the activity of
depolarizing action potentials of myocardial contractile cells
(Phase 0 of AP) is accepted, the electrical and mechanical
activity of the ventricles can also be put into context (Figs. 3
and 7). Leclerq et al. [
] showed in a canine study that the
course of mechanical contraction (during LBBB, LV paced
only and biventricular paced states) was different from the
electrical depolarization of ventricles. However, the initial
phase of mechanical contraction corresponded with
myocardial depolarization. Kroon et al. [
] introduced a comparison
of LV electrical activation and mechanical shortening delays in
ten heart failure patients with prolonged QRSd. The
conclusion is that there are intra-individual and inter-individual
differences in depolarization time and mechanical shortening,
though overall depolarization maps strongly correlate with
time-to-peak mechanical maps. This is in agreement with
our findings about the connection between the ventricular
electrical depolarization and the initial phase of mechanical
activation. The assumption of a relationship between electrical
depolarization and mechanical activation makes the analysis
of electrical depolarization dyssynchrony by UHFQRS an
Here, we present a new technique based on limited examples.
We are aware that these preliminary results serve rather as a
demonstration of the potential of the UHFQRS method.
UHF-ECG measures and evaluates very weak voltage
potentials far below the level of microvolts. The lower signal-to-noise
ratio must be eliminated by prolongation of the measurement
time to obtain more QRS patterns to average (usually 3–5 min).
Technical limitations: We demonstrate UHFQRS in a
frequency range of 500–1000 Hz. To validate the presented
results, ECG monitors with internal sampling higher than 2 kHz
and minimal 16-bit or higher analog-digital converters are
needed. Conventional 1 kHz ECG and frequency range 150–
350 Hz seems to be sufficient to obtain basic information
about ventricular dyssynchrony.
UHFQRS is a deterministic method. In this proof-of-concept
study, the clinical operator had no access to the UHFQRS
maps and UHFQRS morphology computation.
A significant advantage of the UHFQRS method is
simplicity in application: Standard 12-lead ECG electrode
placements can be used. The UHFQRS amplitude shape and
multilead amplitude overlap can be identified and parametrized,
unlike the morphology of the QRS complex which is not
always clear (Fig. 1d, e). Moreover, irregular beats can be
analyzed and compared with sinus beats. Such analysis is
nearly impossible with echocardiographic methods.
The purpose of this study was to demonstrate the technical
feasibility and the potential ability to assess the
temporalspatial distribution of LV depolarization. UHFQRS is an
easily accessible and simple technique with the potential to
provide valuable information about myocardial electrical
dyssynchrony that could be related to the initial point of
mechanical activation. The major clinical potential of UHFQRS
may lie in more accurate identification and selection of CRT
recipients and optimization of biventricular pacing
parameters. Further retrospective and prospective studies with high
resolution ECGs will be needed to define the appropriate role
of this new technology.
Acknowledgements The research was supported by grants: Czech
Science Foundation, project GA17-13830S, ERD Fund project
FNUSA-ICRC CZ.1.05/1.1.00/02.0123, MEYS project LO1212 and
CZ.1.05/2.1.00/01.0017, and the CAS project RVO:68081731.
There was no other form of contracts or financial support. There were
no relationship with companies and industry. The research was ongoing
with no specific funding or financial investments. The PCT patent
application was submitted on December 2014: https://patentscope.wipo.int/
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