Clinical Investigations
Multi-Plane Mechanical Dyssynchrony in
Cardiac Resynchronization Therapy
Address for correspondence:
Christopher L. Kaufman, PhD
St. Paul Heart Clinic Department
of Research 225 Smith Ave. N.,
Suite 400 St. Paul, MN 55102
ckaufman@stphc.com;
kauf0127@umn.edu
Christopher L. Kaufman, PhD; Daniel R. Kaiser, PhD; Kevin V. Burns, BS;
Aaron S. Kelly, PhD; Alan J. Bank, MD
Department of Research, St. Paul Heart Clinic (Kaufman, Burns, Kelly, Bank), St. Paul, Minnesota;
CRDM Heart Failure Research, Medtronic Inc. (Kaiser), Minneapolis, Minnesota
Background: The aims of this study were to assess the ability of several echo measures of dyssynchrony to
predict CRT response and to characterize the global effect of CRT.
Hypothesis: We hypothesized that after CRT there would be significant reductions in mechanical dyssynchrony
in all 3 orthogonal planes of cardiac motion and that those patients with significant dyssynchrony prior to
implant would have the best echocardiographic response.
Methods: Standard echocardiograms were performed pre-CRT and post-CRT (138 ± 63d) in 70 heart failure
patients. Longitudinal dyssynchrony was calculated as the standard deviation (SD) of time to peak systolic
displacement and velocity of 12 segments from 3 apical views. Using midventricular short axis views
and speckle-tracking methods, the SD of time to peak radial and circumferential strain in 6 segments were
calculated. Cardiac resynchronization therapy echo response was defined as ≥ 15% decrease in left ventricular
end-systolic volume.
Results: Cardiac resynchronization therapy significantly improved systolic function in the longitudinal, radial,
and circumferential planes. The CRT echo response rate was 57%. Echo responders (CRTR ) had significantly
(P < .05) more dyssynchrony at baseline as compared to nonresponders (CRTNR ). Cardiac resynchronization
therapy significantly (P < .05) reduced longitudinal and radial, but not circumferential, dyssynchrony in
CRTR . Dyssynchrony was unchanged in CRTNR . Receiver-operator characteristic (ROC) curve analysis indicated
significant, but modest sensitivity and specificity for longitudinal and radial intraventricular dyssynchrony
and for interventricular dyssynchrony. Combining radial and longitudinal dyssynchrony measures improved
positive prediction of CRT response.
Conclusions: Cardiac resynchronization therapy improves left ventricular function in 3 orthogonal planes of
motion. Longitudinal, radial, and interventricular dyssynchrony modestly predict reverse remodeling.
Introduction
Cardiac resynchronization therapy (CRT) improves symptoms, functional status, left ventricular (LV) dimensions and
function, morbidity, and mortality in advanced congestive
heart failure patients.1 – 3 The primary mechanism thought
to be involved in these improvements is the enhancement
of the synchronous contraction of the LV. In early clinical
trials, QRS duration was used to measure dyssynchrony.
However, it has been suggested that mechanical dyssynchrony, as opposed to electrical dyssynchrony (wide QRS),
might be a more sensitive measure of the dysfunction
This study was funded by Medtronic, Inc., Minneapolis, MN.
Dr. Kaufman receives research grant support and honoraria
from Medtronic and Boston Scientific. Dr. Kaiser is a current
employee of Medtronic. Kevin Burns has no disclosures. Dr.
Kelly receives research support from Medtronic and Boston
Scientific. Dr. Bank receives honoraria from Medtronic, Boston
Scientific, and General Electric (ultrasound division).
Received: July 27, 2008
Accepted with revision: September 18, 2008
that is corrected by CRT and more importantly, may better predict which patients are likely to respond to the
therapy.4 – 8
Several retrospective studies have shown that either
longitudinalor radial measures of mechanical dyssynchrony
can predict which patients will respond to CRT.4 – 8
However, cardiac motion is 3-dimensional and thus, 1dimensional measurements may not accurately quantify
dyssynchronywhen used alone. Few studies have examined
multiple measures of dyssynchrony using these new
echocardiographic methods to determine which might be
best in predicting CRT response.6 – 9
The primary aim of this retrospective single-center study
was to examine CRT response prediction using measures
of dyssynchrony from 3 orthogonal planes of cardiac
motion (ie, longitudinal, radial, and circumferential) via
tissue Doppler imaging (TDI) and speckle-tracking echocardiography (STE). A secondary aim involved examining
global LV function in each respective plane of cardiac
motion.
Clin. Cardiol. 33, 2, E31 – E38 (2010)
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20529 © 2010 Wiley Periodicals, Inc.
E31
Clinical Investigations
continued
Methods
Patient Population
A total of 97 consecutive patients that received biventricular
pacemakers at our center were screened for inclusion.
A total of 27 patients were excluded for the following
reasons: previously paced in the right ventricle (n = 21),
poor quality short axis images that did not allow for
proper STE analyses (n = 3), and LV lead complications
(n = 3). Thus, the final sample included 70 patients. Of
these 70 patients, 66 (94%) met current standard criteria for
CRT. Only 4 of the 70 patients (6%) met standard criteria for
CRT with the exception of having a QRS duration less than
120 msecs. Institutional review board approval was obtained
for retrospectively examining the echocardiograms and
clinical data.
Device Implantation
Patients received either a biventricular pacemaker
(InSync III, Medtronic Inc., Minneapolis, MN) or biventricular ICD (Concerto, Medtronic Inc., Minneapolis, MN;
Contak Renewal, Boston Scientific, St. Paul, MN). Device
programming was assessed 1 day post implant and 4 to 6
weeks post implant to ensure that nearly 100% biventricular pacing was achieved. Cardiac resynchronization therapy
implants were performed using standard techniques and
exclusively transvenous lead placement. LV lead position
was chosen based on venous anatomy and accessibility.QRS
duration was determined via a 12-lead electrocardiogram on
the same day as the pre-CRT echocardiogram.
Echocardiography Protocol
Echocardiographic information was collected by trained
sonographers before implantation of the CRT device and 3
to 10 months after CRT using standard American Society
of Echocardiography criteria and commercially available
equipment (Vivid 7, GE Vingmed Ultrasound Bedford,
United Kingdom). Digital gray-scale 2D and TDI cine loops
from 1 cardiac cycle that was neither before nor after an
ectopic beat was obtained from apical 4-chamber and 2chamber, long axis, and mid-LV short axis views. Pulsed
Doppler echocardiography of transmitral, transaortic, and
transpulmonary blood flow was recorded for a minimum
of 3 beats and used to determine timing of valve opening
and closure. The difference in the time delay from the start
of aortic and pulmonic flow was calculated as a measure
of interventricular dyssynchrony (AV-PV). Left ventricular
ejection fraction (LVEF), end-diastolic volume (LVEDV),
and end-systolic volume (LVESV) were calculated using the
biplane Simpson’s method. All images were analyzed offline with commercially available software (Echopac 6.1.0,
GE Vingmed Ultrasound Bedford, United Kingdom) by the
same trained investigator, who was blinded to treatment
status (ie, pre-CRT or post-CRT) and clinical data. Cardiac
resynchronization therapy response was defined as a
E32
Clin. Cardiol. 33, 2, E31 – E38 (2010)
C.L. Kaufman et al.: Mechanical Dyssynchrony in CRT
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20529 © 2010 Wiley Periodicals, Inc.
reduction in LVESV ≥ 15% as it has previously been shown
that left ventricular remodeling (ie, echocardiographic
response) is a more powerful predictor of long-term
mortality in this patient population than changes in clinical
status (ie, New York Heart Association [NYHA] class), and
is more objective.10
Tissue Doppler Imaging
Tissue Doppler imaging was performed in 3 apical
(4-chamber, 2-chamber, and long axis) views with optimized
frame rates (80–135 frames/s, velocity range of ±16 cm/s).
Systolic contraction amplitude (SCA) was calculated for
each of 12 segments (6 basal, and 6 mid-LV) from the
3 apical views and defined as the amount of displacement
at the time of aortic valve closure (AVC). Global systolic
contractionamplitude(GSCA) was derived from the average
of the 12 regional systolic contraction amplitudes.7 An
example of tissue tracking (TT) and its related variables
of cardiac function and synchrony in a normal healthy
patient is depicted in Figure 1. Longitudinal dyssynchrony
was calculated as the standard deviation of time to peak
displacement for 12 segments (SDTT-12) from the 3 apical
views. Time to peak displacement was measured as the
time from mitral valve closure (MVC) to peak myocardial
displacement. Mitral valve closure was chosen as the zero
point because it marks the end of diastole of the previous
beat. Also, since QRS morphology is different pre-CRT
vs post-CRT, this provides a consistent zero reference
point between testing periods. The average peak systolic
velocity (PSVM ) occurring between aortic valve opening
(AVO) and AVC was calculated for 12 segments as an
additional measure of global LV function. A second measure
of longitudinal dyssynchrony was calculated as the standard
deviation of time to peak systolic velocity of 12 segments
(SDTVI-12 ) as previously described.8 Time to peak systolic
velocity was determined as the time from MVC to the peak
velocity occurring between AVO and AVC.
Speckle-Tracking Echocardiography
Radial and circumferential strains were determined from
midventricular short axis images of the LV using STE with
commercially available software (EchoPac, GE Medical,
Milwaukee, WI) as described by others.6 Briefly, markers
along the endocardial border of the LV are placed to provide
a region of interest including the myocardium. The LV
is divided into 6 standard segments (ie, anteroseptum,
anterior, lateral, posterior, inferior, and septum). The
software employs an algorithm that tracks speckles created
by the ultrasonic interference pattern of the myocardium.
Only segments with adequate tracking were included in
the analysis. Of the 840 segments tracked, 806 (96%) had
adequate tracking.
Speckle-tracking echocardiography allowed the calculation of peak systolic radial and circumferential strain for
Figure 1. Tissue tracking echocardiography. Example of a tissue-tracking image generated from tissue Doppler imaging in a normal healthy control. Note
the synchronous contraction of the left ventricle as peak displacement. In the heart failure population, greater dispersion in time to peak displacement is
often observed and as such is noted as being dyssynchronous.
each segment, which was defined as the peak strain at
the end of systole (AVC). The average peak systolic radial
(RAD ) and circumferential (CIRC ) strains were calculated
from 6 segments. Furthermore, times to peak radial and
circumferential strains were calculated as the times from
MVC to peak strain. The standard deviations of time to
peak radial and circumferential strain were calculated as
measures of radial (SDRAD-6 ) and circumferential (SDCIRC-6)
dyssynchrony.Examples of radial and circumferential strain
images from STE are provided in Figures 2 and 3.
Statistical Analysis
Coefficient of variability and intraclass correlations were
calculated and Bland-Altman plots11 were generated to
examine interobserver and intraobserver variability for
TDI and STE. Within patient comparisons (ie, pre-CRT
vs post-CRT) were made with dependent Student t tests.
Between-group comparisons (ie, responder vs nonresponder) were examined with an analysis of covariance model
that allowed adjustment for baseline differences. Nonparametric data (ie, NYHA class) were analyzed with the
Wilcoxon signed ranks test. Receiver-operator characteristic (ROC) curve analysis was performed to establish the
sensitivity and specificity of prespecified variables for predicting CRT response. Statistical analyses were performed
with SPSS 13.0 (SPSS Inc., Chicago, IL) and GraphPad
Prism 4 (GraphPad Software Inc., San Diego, CA). An alpha
Table 1. Reproducibility of TDI and STE Measures of LV Dyssynchrony
Mean
Difference
Coefficient
of Variation
Intraclass
Correlation
SDTT-12
0.4±9.0
12.1%
0.90
SDTVI-12
−5.8±13.8
21.5%
0.66
SDRAD-6
−0.4±7.4
13.9%
0.97
SDCIRC-6
−0.9±9.9
15.5%
0.89
SDTT-12
−3.3±13.0
14.3%
0.88
SDTVI-12
−6.0±14.1
23.5%
0.57
SDRAD-6
−0.7±9.7
17.6%
0.96
SDCIRC-6
1.6±14.7
22.1%
0.74
Variable
Intraobserver Variability
Interobserver Variability
Data are presented as mean±Standard Deviation unless otherwise
noted.
level of 0.05 was used to denote statistical significance. Data
are presented as mean±standard deviationunless otherwise
noted.
Clin. Cardiol. 33, 2, E31 – E38 (2010)
C.L. Kaufman et al.: Mechanical Dyssynchrony in CRT
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20529 © 2010 Wiley Periodicals, Inc.
E33
Clinical Investigations
continued
Figure 2. Radial strain via speckle-tracking echocardiography. Example of radial strain in a normal healthy control. It is important to note that radial strains
are denoted as positive strains due to the fact that the myocardium is thickening (final length is greater than initial length) in the radial plane during systole.
Figure 3. Circumferential strain via speckle-tracking echocardiography Example of circumferential strain in a normal healthy control. It is important to note
circumferential strains are denoted as negative due to the fact that the myocardium is thinning (final length is lesser than initial length) in the
circumferential plane during systole.
E34
Clin. Cardiol. 33, 2, E31 – E38 (2010)
C.L. Kaufman et al.: Mechanical Dyssynchrony in CRT
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20529 © 2010 Wiley Periodicals, Inc.
Results
The reproducibility data for the echocardiographic methods
of assessing LV dyssynchrony are provided in Table 1.
Baseline clinical and echocardiographic characteristics of
the 70 patients studied and classified as CRT responders
(CRTR) and nonresponders (CRTNR) are presented in
Tables 2 and 3. Patients were receiving a high percentage
of biventricular pacing (98% ± 3%) and there were no
differences between CRTR (98% ± 3%) and CRTNR (98% ±
4%) for this variable. Overall, CRT significantly improved
the clinical status of the patient sample (NYHA class
pre-CRT = 3.0 ± 0.3 vs NYHA class post-CRT = 2.3 ± 0.6,
P < .05). The change in NYHA class was significantly
greater in CRTR (−1.0 ± 0.5) as compared to CRTNR
(−0.5 ± 0.6, P < .05).
Table 2. Baseline Clinical Characteristics of CRT Responders and
Nonresponders
All (n = 70)
R (n = 40)
NR (n = 30)
54/16
33/7
21/9
67.5 ± 12.9
68.1 ± 12.8
66.7 ± 13.3
SBP (mm Hg)
116 ± 18
121 ± 17a
109 ± 18
DBP (mm Hg)
69 ± 12
71 ± 11
66 ± 13
Ischemic etiology (%)
53%
55%
50%
NYHA class II/III/VI (n)
2/63/5
1/38/1
1/25/4
QRS duration (msec)
138 ± 24
139 ± 34
136 ± 22
Global LV Function
Heart rate (bpm)
67 ± 12
67 ± 10
67 ± 13
Global LV function at baseline and after CRT is presented
in Tables 3 and 4. Overall, CRT resulted in an 8% ±7%
increase in LVEF. Global systolic contraction amplitude,
radial (RAD ), and circumferential (CIRC ) systolic function
improved following CRT. When expressed in percentages
relative to baseline values; longitudinal, radial, and
circumferential systolic function improved by 19%, 34%, and
9%, respectively.
Follow-up time (days)
138 ± 63
150 ± 65
123 ± 60
Atrial fibrillation (%)
13%
15%
10%
Diabetes (%)
27%
30%
23%
Mechanical Dyssynchrony and CRT
At baseline, longitudinal and radial, but not circumferential,
dyssynchrony was significantly greater in CRTR (Table 3) as
compared to CRTNR. The effect of CRT on measures of interventricularand intraventricularmechanical dyssynchrony is
presented in Table 4. Overall, interventricular (AV-PV) and
intraventricular longitudinal and radial (SDTT-12 , SDTVI-12 ,
and SDRAD-6 ) dyssynchrony were significantly reduced
following CRT. CRTR had significant reductions in interventricular, longitudinal (SDTT-12 and SDTVI-12 ), and radial
dyssynchrony. CRTNR had no significant changes in any
measures of interventricular or intraventricular dyssynchrony.
CRT Response Prediction
ROC curve analyses were performed to find the cut off
value that optimized both sensitivity and specificity for
a given prespecified predictor. Baseline QRS duration
lacked predictive value for CRT response (ROC area
under the curve [AUC] = 0.54 ± 0.07, P = .53). A cut off
of 150 msecs for QRS duration had 84% sensitivity and
32% specificity. Overall, the sensitivity and specificity of
the measures of longitudinal dyssynchrony and radial
measures of dyssynchrony were all similar (Figure 4). At
a cut off of 71 ms, SDTT-12 had a sensitivity of 71% and
specificity of 60% (AUC = 0.63 ± 0.07, P = .05). When using
a value of 44 ms as a cut off, SDTVI-12 had a sensitivity
of 69% and specificity of 62% (AUC = 0.67 ± 0.07, P =
Variable
Male/Female (n)
Age (years)
History of:
Abbreviations: bpm = beats per minute; CRT = cardiac resynchronization therapy; DBP = diastolic blood pressure; msec = milliseconds;
NR = CRT echo nonresponder; NYHA = New York Heart Association;
R = CRT echo responder; SBP = systolic blood pressure. Data are presented as mean±SD unless otherwise noted. a P < .05 for R vs NR.
.02). At a cut off of 55.3 ms, SDRAD-6 had a sensitivity
of 74% and specificity of 62% (AUC = 0.72 ± 0.06, P =
.001). Finally, at a cut off of 24 ms, the measure of
interventricular dyssynchrony, AV-PV, had a sensitivity of
73% and specificity of 64% (AUC = 0.72 ± 0.07, P = .001).
However, circumferential dyssynchrony lacked clinically
meaningful sensitivity (66%) and specificity (43%; AUC =
0.54 ± 0.07, P = .60).
When using the cut offs for CRT response generated
from ROC analyses, 19 of the 70 patients (27%) met both
the SDTT-12 and SDRAD-6 cut offs and 17 of the 70 patients
(24%) met both the SDTVI-12 and SDRAD-6 for significant
longitudinal and radial dyssynchrony. Approximately 90%
of those patients were CRT responders (Figure 5). A total
of 18 patients had neither longitudinal (SDTVI-12 ) nor radial
dyssynchrony. Of these patients, only 4 (22%) were echo
responders.
Discussion
The novel findings of this study indicate that (1) longitudinal,
radial, and interventricular dyssynchrony modestly predict
reverse remodeling to a similar degree and (2) LV function in
the longitudinal,radial, and circumferentialplanes of motion
is improved with CRT, which contributes to improved global
Clin. Cardiol. 33, 2, E31 – E38 (2010)
C.L. Kaufman et al.: Mechanical Dyssynchrony in CRT
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20529 © 2010 Wiley Periodicals, Inc.
E35
Clinical Investigations
continued
Table 3. Baseline Echocardiographic Variables in CRT Responders and
Nonresponders
All (n = 70)
R (n = 40)
NR (n = 30)
28 ± 7
29 ± 6
27 ± 7
LVESV (mL)
135 ± 48
134 ± 49
137 ± 47
LVEDV (mL)
185 ± 57
186 ± 61
184 ± 52
Mitral E/A
1.3 ± 0.9
1.3 ± 0.8
1.5 ± 1.0
Mitral E DT (msec)
215 ± 83
218 ± 88
204 ± 79
DFP (msec)
434 ± 141
400 ± 121a
477 ± 155
AV-PV (msec)
30 ± 28
38 ± 29a
18 ± 23
GSCA (mm)
4.3 ± 1.8
4.5 ± 2.0
4.1 ± 1.5
SDTT-12 (msec)
68 ± 27
72 ± 27
61 ± 28
PSVM (cm/s)
2.6 ± 0.8
2.8 ± 0.9
2.4 ± 0.7
46 ± 15
50 ± 15a
41 ± 14
14.6 ± 12.0
12.7 ± 10.4
17.5 ± 13.5
68 ± 49a
68 ± 49
68 ± 49
−10.8 ± 4.0
−10.7 ± 4.0
−10.8 ± 4.0
103 ± 47
103 ± 53
106 ± 40
Variable
LVEF (%)
SDTVI-12 (msec)
RAD (%)
SDRAD-6 (msec)
CIRC (%)
SDCIRC-6 (msec)
Abbreviations: AV-PV = aortic to pulmonic valve flow time delay; CRT =
cardiac resynchronization therapy; DFP = diastolic filling period;
CIRC = average circumferential strain; RAD = average radial strain;
GSCA = global systolic contraction amplitude; LVEF = left ventricular
ejection fraction; LVESV and LVEDV = left ventricular end-systolic and
end-diastolic volume; Mitral E/A = mitral E wave to A wave ratio;
Mitral E DT = mitral E wave deceleration time; msec = milliseconds;
NR = CRT echo nonresponder; PSVM = average peak systolic velocity;
R = CRT echo responder; SDCIRC-6 = standard deviation of time to peak
circumferential strain of 6 segments; SDRAD-6 = standard deviation of
time to peak radial strain of 6 segments; SDTT-12 = standard deviation
of time to peak displacement of 12 segments; SDTVI-12 = standard
deviation of time to peak velocity of 12 segments. Data are presented
as mean ± SD. a P<.05 for R vs NR.
LV function. To date, the authors are unaware of any
previous studies that have assessed global LV function in all
3 orthogonal planes of cardiac motion. Our data indicate
that the greatest improvements in global function with
CRT occur in the longitudinal and radial planes of motion.
Not surprisingly, we found the greatest improvements
in intraventricular mechanical dyssynchrony in the same
planes of motion.
Our results indicate that measures of longitudinal (from
TT and TVI) and radial intraventricular dyssynchrony and
interventricular dyssynchrony have similar sensitivity and
E36
Clin. Cardiol. 33, 2, E31 – E38 (2010)
C.L. Kaufman et al.: Mechanical Dyssynchrony in CRT
Published online in Wiley InterScience. (www.interscience.wiley.com)
DOI:10.1002/clc.20529 © 2010 Wiley Periodicals, Inc.
Table 4. Effect of CRT on LV Function and Dyssynchrony
All (n = 70)
R (n = 40)
NR (n = 30)
8 ± 7a
12 ± 7b
2±4
LVESV (mL)
−26 ± 27a
−44 ± 19b
−2 ± 11
LVEDV (mL)
−23 ±
31a
−42 ± 24b
3 ± 18
Mitral E/A
−0.1 ± 0.9
−0.5 ± 0.4
0.1 ± 0.5
7 ± 79
21 ± 79
−13 ± 96
14 ± 136
57 ± 174b
−42 ± 154
Variable
LVEF (%)
Mitral E DT (msec)
DFP (msec)
AV-PV (msec)
−20 ± 27a
−29 ±
GSCA (mm)
0.8 ± 1.6
1.5 ± 1.5
0.0 ± 1.3
SDTT-12 (msec)
−10 ± 30a
−21 ± 23b
4 ± 32
PSVM (cm/s)
0.3 ± 0.8a
0.6 ± 0.7b
0.1 ± 0.7
SDTVI-12 (msec)
−7 ± 17a
−16 ± 12b
5 ± 15
−3.3 ± 13.1
a
25b
b
−6 ± 24
RAD (%)
4.9 ± 16.3
11.1 ± 15.9
SDRAD-6 (msec)
−20 ±
68a
−57 ±
56b
28 ± 49
CIRC(%)
−1.0 ±
3.8a
−2.1 ± 3.8
0.4 ± 3.5
−14 ± 64
12 ± 67
SDCIRC-6 (msec)
a
0 ± 64
b
Abbreviations: AV-PV = aortic to pulmonic valve flow time delay;
CRT = cardiac resynchronization therapy; DFP = diastolic filling period;
CIRC = average circumferential strain; RAD = average radial strain;
GSCA = global systolic contraction amplitude; LVEF = left ventricular
ejection fraction; LVESV and LVEDV = left ventricular end-systolic and
end-diastolic volume; Mitral E/A = mitral E wave to A wave ratio;
Mitral E DT = mitral E wave deceleration time; msec = milliseconds;
NR = CRT echo nonresponder; PSVM = average peak systolic velocity;
R = CRT echo responder; SDCIRC-6 = standard deviation of time to peak
circumferential strain of 6 segments; SDRAD-6 = standard deviation of
time to peak radial strain of 6 segments; SDTT-12 = standard deviation
of time to peak displacement of 12 segments; SDTVI-12 = standard
deviation of time to peak velocity of 12 segments.
Data are post − pre (ie, a negative sign indicates a reduction) and
presented as mean ± SD.
a
P < .05 for pre-CRT vs post-CRT for overall group effect.
b
P < .05 for R vs NR.
specificity in predicting CRT response. These novel findings contradict data previously published.8 We found that
patients that met both cut off points for longitudinal and
radial dyssynchrony were very likely to be CRT responders.
Conversely, patients who met neither of the cut off points
were likely to be nonresponders. This corroborates data
recently published6 and suggests that there could be some
additive value to considering measures of dyssynchrony
from both of these planes of cardiac motion. Corroboration
of findings from other labs/centers is an important aspect
100
80
80
Echo responders (%)
Sensitivity
100
60
SDTT-12
40
SDTVI-12
SDRAD-6
20
60
40
20
AV-PV
0
0
20
40
60
80
0
100
Figure 4. Predicting response to cardiac resynchronization therapy with
measures of dyssynchrony. Receiver-operator characteristic curves for
intraventricular measures of dyssynchrony via (1) tissue tracking (SDTT-12 ;
black line and squares), (2) tissue velocity imaging (SDTVI-12 ; red line and
triangles), and (3) speckle-tracking radial strain (SDRAD-6 ; blue line and
circles), and interventricular measures of dyssynchrony (AV-PV; green line
and stars) for determining cardiac resynchronization therapy response.
lacking in the vast body of literature in this area of research.
Few studies have assessed the predictive capacity of echobased measures of circumferential dyssynchrony.12,13 We
found this measure to be lacking significant predictive capacity for CRT response, which might be due to the inability of
echocardiographic speckle-tracking methods to accurately
quantify this unique cardiac motion or could be due to
the level of the heart (mid-LV) at which the short axis
images were analyzed (ie, circumferential dyssynchrony
may be more important at the base or apex of the LV).
Although the longitudinal and radial dyssynchrony measures were significant predictors of CRT response, the
sensitivity and specificity were lower than what has previously been publishedby others.4,6 – 8,14 The reasons for these
discrepancies are unclear and require further study. Consistent with previous studies, in our cohort, QRS duration and
other clinical parameters lacked predictive capabilities.
This was a retrospective single-center study and thus
the results should be interpreted based on the limitations
of such a study design. The results of the only trial
to prospectively assess the predictive capacity of echo
measures of dyssynchrony on CRT response failed to show
clinically meaningful sensitivity and specificity primarily
due to high variability in the dyssynchrony measures.15
However, this trial had follow-up data on only 57% of the
patients originally enrolled, had 3 echo core laboratories,
used several ultrasound machine manufacturers, and only
utilized TDI data; which all could increase the variability
of the echo measures. In our study, we found the speckletracking measure of radial dyssynchronyto have the highest
intraclass correlation as compared to the tissue Doppler
measures of longitudinal dyssynchrony. It is possible that
6
6
100 - Specificity
&
D-
RA
&
12
T-
T
SD
SD
SD
D-
RA
SD
2
2
-1
TT
SD
6
I-1
TV
SD
D
rS
2
er
Ne
T
DT
D
rS
D-
RA
no
2
-1
-1
ith
D-
RA
no
2
-1
VI
T
SD
6
6
D-
RA
D
S
rS
I
TV
e
ith
Ne
Figure 5. Additive value of combining longitudinal and radial measures of
dyssynchrony. The percentage of responders above the cut off value for
any single measure of dyssynchrony was similar between SDTT-12 ,
SDTVI-12 , and SDRAD-6 . However, a much higher percentage of cardiac
resynchronization therapy response was observed in patients that met
the cut off values for both longitudinal (ie, SDTT-12 or SDTVI-12 ) and radial
dyssynchrony (solid bars).
the slightly better reproducibility of speckle-tracking aided
its ability to be a better predictor of outcome in our
patient cohort. Given the vast differences between our study
and PROSPECT, comparisons between the study data are
limited.
In conclusion, LV function improves in 3 orthogonal
planes, but dyssynchrony only improves in the longitudinal
and radial planes following CRT. Echocardiographic
measures of intraventricular (longitudinal and radial) and
interventricular dyssynchrony individually have modest
sensitivity and specificity on predicting echocardiographic
response to CRT. Combining measures of dyssynchrony
aids in the positive prediction of CRT response.
Acknowledgments
The authors wish to acknowledge Andrea M. Metzig, MA
for assistance with clinical data collection.
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