Usefulness of Left Ventricular Systolic Dyssynchrony by Real-Time

Three-Dimensional Echocardiography to Predict Long-Term

Response to Cardiac Resynchronization Therapy
Osama I.I. Soliman, MD, PhDa,b,*, Marcel L. Geleijnse, MD, PhDa, Dominic A.M.J. Theuns, PhDa,
Bas M. van Dalen, MDa, Wim B. Vletter, MSca, Luc J. Jordaens, MD, PhDa,
Ahmed K. Metawei, MDb, Aly M. Al-Amin, MDb, and Folkert J. ten Cate, MD, PhDa
Real-time 3-dimensional echocardiography (RT3DE) allows simultaneous timing of re-
gional volumetric changes as a net result of longitudinal, radial, circumferential left
ventricular (LV) contraction, hence LV systolic dyssynchrony. We sought to examine
real-time 3-dimensional echocardiographically derived dyssynchrony for prediction of
long-term response to cardiac resynchronization therapy (CRT) in a prospective study.
Ninety consecutive patients with heart failure (mean age 60 ⴞ 12 years, 73% men, New
York Heart Association class III in 97%) underwent clinical and echocardiographic as-
sessments at baseline and at 12 months after CRT including real-time 3-dimensional
echocardiographically derived LV systolic dyssynchrony index. The systolic dyssynchrony
index (SDI) was defined as the SD of time to minimum systolic volume of the 16 LV
segments, expressed in percent RR duration. CRT response was defined as a >15%
decrease in LV end-systolic volume on real-time 3-dimensional echocardiogram. After 12
months of CRT, 68 patients (76%) were responders. Feasibility of the SDI was 94%. An
SDI >10% predicted CRT response with good sensitivity (96%), specificity (88%), positive
likelihood ratio (8), and negative likelihood ratio (0.05). Patients with an SDI >10% had
mean change (ⴚ21%, ⴚ31%, 39% vs ⴚ13%, ⴚ10%, 10%) in LV end-diastolic volume, LV
end-systolic volume, and LV ejection fraction, respectively, compared with baseline versus
patients with an SDI <10% (p <0.01). Mean acquisition and analysis duration of single-
patient RT3DE was 8 minutes (range 6 to 13). Interobserver variabilities of LV end-systolic
volume and SDI were 5% and 11%, respectively. In conclusion, RT3DE provides accurate
identification of reverse volumetric LV remodeling after CRT. From these accurate volu-
metric data, RT3DE provides more intuitive assessment of dyssynchrony and response to
CRT as a simple, reproducible, and fast technique. CRT can be individually tailored using
RT3DE and seems very effective in patients with heat failure with real-time 3-dimensional
echocardiographic evidence of dyssynchrony. © 2009 Elsevier Inc. (Am J Cardiol 2009;
103:1586 –1591)

Cardiac resynchronization therapy (CRT) is an effective
therapy for selected patients with drug-refractory heart fail-
ure (HF).1 However, the beneficial effects of CRT are chal-
lenged by significant numbers of nonresponders.1 Yet there
is no acceptable echocardiographic method to predict and
improve response rate to CRT.2 Contrary to the extensively
studied tissue Doppler imaging3 and M-mode techniques,4
real-time 3-dimensional echocardiography (RT3DE) has
been hardly examined in patients using CRT. State-of-the-
art technology allows accurate and highly reproducible as-
sessment of left ventricular (LV) volume changes over time
by RT3DE.5–7 RT3DE allows reproducible assessment of
a
Department of Cardiology, The Thoraxcenter, Erasmus Medical
Center, Rotterdam, The Netherlands; and bDepartment of Cardiology,
Al-Hussein University Hospital, Al-Azhar University, Cairo, Egypt.
Manuscript received December 31, 2008; revised manuscript received and
accepted January 31, 2009.
*Corresponding author: Tel: 31-10-703-5994; fax: 31-10-703-5498.
E-mail address: o.soliman@erasmusmc.nl (O.I.I. Soliman).
LV systolic dyssynchrony in the form of a systolic dys-
synchrony index (SDI).8 –10 The SDI has been recently
associated with acute hemodynamic improvement after
CRT.9,11 However, the long-term value of RT3DE in
CRT is not yet known. Contrary to 2-dimensional tech-
niques, RT3DE can identify “true” responders by accu-
rate LV volumetric assessment.5 Identifying patients at
high risk for nonresponse after CRT would be helpful to
decrease the number of nonresponders. Therefore, the
goals of our study were to (1) assess the incremental
value of real-time 3-dimensional echocardiographically
derived LV dyssynchrony over QRS criterion for predic-
tion of reverse LV remodeling after CRT and (2) identify
true CRT responders by accurate LV volumetric assess-
ment in patients with HF referred for CRT.
Methods
Population: The study comprised 90 consecutive pa-
tients with HF (60 ⫾ 12 years of age, 73% men) who
received CRT-D and had (1) New York Heart Association
functional class ⱖIII despite optimal drug therapy, (2) im-

0002-9149/09/$ – see front matter © 2009 Elsevier Inc. www.AJConline.org

doi:10.1016/j.amjcard.2009.01.372
 Heart Failure/RT3DE and Reverse Remodeling After CRT 1587

Table 1 Table 2
Baseline characteristics of study population (n ⫽ 90) Characteristics between responders and nonresponders
Age (yrs) 60 ⫾ 12 Variable Responders Nonresponders p Value
Men 66 (73%) (n ⫽ 68) (n ⫽ 22)
QRS duration (ms) 166 ⫾ 33
Age (yrs) 61 ⫾ 12 60 ⫾ 12 NS
New York Heart Association functional class III/IV 87/3
Men 49 (72%) 17 (77%) NS
6-min walking distance (m) 291 ⫾ 94
QRS duration (ms) 167 ⫾ 29 159 ⫾ 34 NS
Ischemic cause of HF 46 (51%)
New York Heart Association 68 19/3 NS
Amiodarone 22 (24%)
functional class III/IV
␤ blockers 72 (80%)
Ischemic cause of HF 30 (44%) 16 (73%) NS
Angiotensin-converting enzyme inhibitors/angiotensin 85 (94%)
Amiodarone 15 (22%) 7 (32%) NS
receptor blockers
Diuretics 85 (94%) ␤ lockers 58 (85%) 14 (64%) NS
Angiotensin-converting enzyme 65 (96%) 20 (91%) NS
Digitalis 32 (36%)
inhibitors/angiotensin
LV end-diastolic volume (ml) 232 ⫾ 62
receptor blockers
LV end-systolic volume (ml) 181 ⫾ 51
Diuretics 65 (96%) 20 (91%) NS
LV ejection fraction (%) 23 ⫾ 4
Digitalis 22 (32%) 10 (45%) NS
Mitral regurgitation (grade) 2.5 ⫾ 0.7
6-min walking distance (m)
SDI (%) 14 ⫾ 5
Baseline 291 ⫾ 81 290 ⫾ 115 NS
Values are presented as mean ⫾ SD or absolute number (percentage). 12 mos 406 ⫾ 71 301 ⫾ 99 0.003
Percent change 40 ⫾ 31 4 ⫾ 22 ⬍0.001
New York Heart Association
paired LV ejection fraction (⬍35%), and (3) wide QRS functional class
complex ⬎120 ms. Patients with atrial fibrillation, acute Baseline 3.0 ⫾ 0.2 3.0 ⫾ 0.4 NS
coronary syndrome, or coronary revascularization within 6 12 mos 1.6 ⫾ 0.4 2.4 ⫾ 0.5 0.003
months before CRT were excluded. Informed consent was Percent change ⫺47 ⫾ 7 ⫺20 ⫾ 3 ⬍0.001
LV end-diastolic volume (ml)
obtained from all patients and the institutional review board
Baseline 230 ⫾ 60 234 ⫾ 74 NS
approved the study. 12 mos 182 ⫾ 46 209 ⫾ 65 ⬍0.001
Protocol: This study was a prospective study aimed at Percent change ⫺21 ⫾ 7 ⫺11 ⫾ 18 0.003
enrollment of CRT candidates at our institution from No- LV end-systolic volume (ml)
Baseline 180 ⫾ 50 182 ⫾ 63 NS
vember 2005 to September 2007 and follow-up after im-
12 mos 122 ⫾ 29 160 ⫾ 49 ⬍0.001
plantation for ⱖ1 year. Before CRT, a standard Doppler Percent change ⫺33 ⫾ 8 ⫺12 ⫾ 25 ⬍0.001
echocardiographic examination, including real-time 3-di- LV ejection fraction (%)
mensional echocardiographic study, was done in all pa- Baseline 23 ⫾ 4 22 ⫾ 3 NS
tients. In the next 48 hours after CRT, atrioventricular delay 12 mos 33 ⫾ 5 23 ⫾ 4 ⬍0.001
was optimized by 2-dimensional Doppler echocardiography Percent change 43 ⫾ 13 5⫾9 ⬍0.001
to provide the longest time for completion of the end- Mitral regurgitation (grade)
diastolic filling flow before LV contraction with the highest Baseline 2.5 ⫾ 0.8 2.5 ⫾ 0.9 NS
LV outflow tract velocity timed integral.12,13 Patients were 12 mos 1.9 ⫾ 0.5 2.6 ⫾ 0.9 ⬍0.001
scheduled for regular clinical follow-up and the CRT device Percent change ⫺24 ⫾ 12 4⫾2 ⬍0.001
SDI (%)
was interrogated to ensure that biventricular pacing was
Baseline 16 ⫾ 3 8⫾2 ⬍0.001
being maintained at least every 3 months. At 12 months 12 mos 7⫾2 11 ⫾ 3 ⬍0.001
after CRT implantation, all echocardiographic examinations Percent change ⫺58 ⫾ 13 38 ⫾ 38 ⬍0.001
were repeated. CRT response was defined as a ⬎15% de-
crease of LV end-systolic volume on real-time 3-dimen-
sional echocardiogram. were InSync 7272, 7279, and 7298 (Medtronic, Inc., Min-
Device implantation: As previously described,12,13 de- neapolis, Minnesota), Renewal II (Guidant, Inc., St. Paul,
vice implantation was performed preferably with a single Minnesota), and Epic HF V-339 and Atlas HF V-341 (St.
left pectoral incision, a left cephalic vein cut down, and a Jude Medical, Sylmar, California). For all patients, defibril-
left subclavian puncture. The defibrillation lead was posi- lator programming was intended to avoid inappropriate
tioned in the right ventricular apex. Transvenous implanta- therapy and therefore tailored according to clinical
tion of the CRT device was successful in 85 patients (94%). presentation.
The LV pacing lead was placed in a tributary of the coro- Doppler echocardiography: All patients were exam-
nary sinus. A posterolateral branch was used in 39 patients ined using an iE33 ultrasound system (Philips, Best, The
(43%), a lateral branch in 14 (16%), a posterior branch in 14 Netherlands) with an S5-1 transducer according to the
(16%), and an anterolateral branch in 18 (20%). In the guidelines.14,15 Degree of mitral regurgitation (grades I to
remaining 5 patients the LV lead was surgically implanted.
IV) was assessed as the midsystolic jet area versus left atrial
Adequate pacing and sensing properties of all leads and
area in the apical 4-chamber view.16
diaphragmatic stimulation with the LV pacing lead were
tested. The lowest effective defibrillation energy was as- RT3DE: Acquisition of RT3DE datasets was performed
sessed and a safety margin of ⱖ10 J was used. Devices used using an iE33 ultrasound system (Philips) equipped with an
1588 The American Journal of Cardiology (www.AJConline.org)

Figure 2. Scatterplot displays relation between the SDI by RT3DE (y axis)

and the relative change in LV end-systolic volume (x axis) after CRT.

Figure 1. Receiver operating characteristics of the SDI from RT3DE for

separation of responders from nonresponders to CRT. AUC ⫽ area under
the curve.

X3-1 transducer, with the patient in a left lateral decubitus

position. To encompass the entire left ventricle into the
RT3DE dataset, a full-volume scan was acquired from the
apical window in harmonic mode from 5 (when a wide-
angle sector of 101 ⫻ 105° was necessary) to 7 R-wave
triggered subvolumes during end-expiratory breath-hold.
The depth and angle of the ultrasound scan sector were
adjusted as minimally as possible while still encompassing Figure 3. Mean 12-month relative change in clinical and echocardiographic
the entire left ventricle. data compared with before CRT in patients with and without baseline
dyssynchrony. *p ⬍0.001; #p ⬍0.05 for patients with an SDI ⬎10% (black
Analysis of RT3DE datasets was performed on a QLAB
bars) versus patients with an SDI ⬍10% (white bars). 6MWD ⫽ 6-minute
workstation using 3D-Advanced Quantification 6.0 (Phil- walking distance; LV-EDV ⫽ LV end-diastolic volume; LV-EF ⫽ LV
ips) as described previously.7,10 In brief, this software uses ejection fraction; LV-ESV ⫽ LV end-systolic volume; NYHA ⫽ New
all voxels from RT3DE datasets to perform 3-dimensional York Heart Association.
semiautomated border detection of LV volume over 1 car-
diac cycle. Quick LV quantification starts by definition of
end-diastolic and end-systolic phases and later in any phase.
the correct apical 4-chamber view with avoidance of LV
However, in this study efforts were made to minimize sec-
foreshortening. Then, it is made sure that the intersection
ondary border editing. Once the LV endocardial border
point of the displayed horizontal and vertical lines is in the
definition is verified, the software can automatically read-
middle of the LV cavity. Subsequently, end-diastolic (larg-
just the dynamic 3-dimensional model mesh by tracking the
est LV volume) and end-systolic (smallest LV volume)
edited borders in all phases of the cardiac cycle. At this step,
phases are identified. On these 2 end-diastolic and end-
the 3-dimensional spatial and temporal information can be
systolic frames, 5 identification points are sequentially
displayed as a curve representing volume changes as a
marked: the inferoseptal, anterolateral, anterior, and inferior
function of time (volume–time curve). LV ejection fraction
mitral annuluses, and the apex (from either of the 2 orthog-
is calculated as (end-diastolic volume) ⫺ (end-systolic
onal long-axis views). After this the software automatically
volume)/end-diastolic volume ⫻ 100%.
delineates the LV endocardial border from the end-diastolic
and end-systolic phases and by sequential analysis the soft- Regional LV data: LV segmentation is performed in
ware creates an LV mathematical dynamic 3-dimensional accordance with standard recommendations according to a
model mesh that represents changes in the LV cavity. Of 17-segment model.17 To improve spatial information, the
note, the speckle-tracking feature in this software helps to software computes volumetric changes from 1,088 small
make the semiautomated endocardial border more robust. anatomic tetrahedrons of myocardial subsegments and the
From this dynamic mesh LV volumes can be calculated final volume–time curves from the 17 standard segments
from all phases of the cardiac cycle. Unsatisfactory delin- can be displayed. All dyssynchrony calculations are based
eation of the endocardial border can be manually adjusted at on the algorithm in the QLAB software, which considers the
 Heart Failure/RT3DE and Reverse Remodeling After CRT
Table 3
Sensitivity, specificity, area under the curve, and positive and negative likelihood ratios for prediction of reverse left ventricular remodeling using
systolic dyssynchrony index greater than 10%
Sensitivity (95% CI) Specificity (95% CI) AUC
96% (88–99) 88% (66–97) 0.93
AUC ⫽ area under the curve; CI ⫽ confidence interval.
standard 17-segment model for analysis. However, for prac-
tical standardization the software excludes the apical cap
from analysis.
LV dyssynchrony data: After calculation of time to
minimum systolic volume of each standard LV segment,
maximum dispersion, defined as the difference between the
largest and smallest time to minimum systolic volume, is
calculated. Also, the LV SDI, defined as the SD of time to
minimum systolic volume of the 16 LV segments, is calcu-
lated. The SDI is corrected for RR duration and thus dis-
played as a percentage to compensate for heart rate vari-
ability and to improve its reproducibility when repeated
during follow-up. LV dyssynchrony is considered present
if the SDI is ⬎8% (mean ⫾ 2 SDs of that in healthy
controls).10
Statistical analysis: All statistics were performed using
SPSS 16 for Windows (SPSS, Inc., Chicago, Illinois). De-
scriptive statistics for nominal data were expressed in fre-
quencies and percentages and comparisons were performed
using chi-square test or Fischer’s exact test. After checking
for normality, means and SDs were calculated for normally
distributed continuous variables. Student’s t test or Mann-
Whitney U test, when appropriate, compared baseline and
12-month data. Pearson correlation analysis was used to
compare the relation between the SDI and change of LV
end-systolic volume or LV ejection fraction after CRT.
Receiver operating characteristic curves were generated to
determine cut-off values of the SDI that were best associ-
ated with CRT response. All tests were conducted on a
2-tailed basis with the intention to accept a chance proba-
bility of 5% (p ⬍0.05). Interobserver variability and inter-
class correlation of the SDI have been reported previously
as 11% and 0.98, respectively.10
Results
Baseline data: Out of the originally enrolled 100 pa-
tients, 6 patients (6%) were excluded due to poor RT3DE
image quality and 4 patients had died during the first year
after CRT. The final study cohort included 90 patients
(mean age 60 ⫾ 12 years, 73% men). Forty-six patients
(51%) had ischemic HF and 44 patients (49%) had non-
ischemic HF. Eighty-seven patients (97%) were in New
York Heart Association class III, and 3 patients were in
New York Heart Association class IV. Baseline clinical
characteristics of the study population are presented in
Table 1.
CRT-D outcome: After 12 months of CRT, 68 patients
(76%) were responders. At 12-month follow-up, QRS du-
1589
p Value for AUC Positive Likelihood Ratio Negative Likelihood Ratio
0.0001 8 0.05
ration decreased from 166 ⫾ 33 to 122 ⫾ 34 ms (p ⬍0.001).
New York Heart Association class improved by 1 class in
77 patients (86%), and the 6-minute walking distance in-
creased from 291 ⫾ 94 to 381 ⫾ 81 m (p ⬍0.001). LV
end-diastolic volume decreased from 232 ⫾ 62 to 186 ⫾ 55
ml (p ⬍0.001), LV end-systolic volume decreased from 181 ⫾
51 to 131 ⫾ 39 ml (p ⬍0.001), and LV ejection fraction
increased from 23 ⫾ 4% to 31 ⫾ 7% (p ⬍0.001). Mean
mitral regurgitation grade decreased from 2.5 ⫾ 0.7 to 2.2 ⫾
0.8 (p ⬍0.001).
CRT responders versus nonresponders: Baseline ech-
ocardiographic characteristics were similar between re-
sponders and nonresponders except for more dyssynchrony
on real-time 3-dimensional echocardiogram (SDI 16 ⫾ 3 vs
8 ⫾ 2, p ⬍0.001). All other relevant baseline clinical char-
acteristics were similar between responders and nonre-
sponders (Table 2). Responders had a more changes (vs
values before CRT) in LV end-diastolic volume (⫺21 ⫾ 7%
vs ⫺11 ⫾ 18%, p ⫽ 0.003) LV end-systolic volume (⫺33 ⫾
8% vs ⫺12 ⫾ 25%, p ⬍0.001), LV ejection fraction (43 ⫾
13% vs 5 ⫾ 9%, p ⬍0.001), and 6-minute walking distance
(40 ⫾ 31% vs 4 ⫾ 22%, p ⬍0.001) compared with nonre-
sponders (Table 2).
Cut-off value for LV systolic dyssynchrony: Receiver
operating characteristic curve analysis yielded cut-off
values of SDI ⬎10% best associated with CRT response
(Figure 1).
Dyssynchrony and CRT outcome: As seen in Figure 2,
baseline SDI correlated well (y ⫽ 1.56x ⫺ 6.43, R2 ⫽
0.31, p ⬍0.0001) with a change (vs values before CRT)
in LV end-systolic volume at 12 months after CRT. There
were significant improvements in 6-minute walking dis-
tance (45 ⫾ 38% vs 5 ⫾ 25%, p ⬍0.001) in patients with
an SDI ⬎10% compared with those with an SDI ⬍10%.
Likewise, patients with an SDI ⬎10% had significant
changes in LV end-diastolic volume (⫺21 ⫾ 8% vs ⫺13 ⫾
19%, p ⫽ 0.015), LV end-systolic volume (⫺31 ⫾ 14% vs
⫺10 ⫾ 16%, p ⬍0.001), and LV ejection fraction (39 ⫾
17% vs 10 ⫾ 9%, p ⬍0.001) compared with those with an
SDI ⬍10% (Figure 3). An SDI ⬎10% yielded a sensitivity
of 0.96 and a specificity of 0.88 for separation of responders
from nonresponders. Area under the curve was 0.93 ⫾
0.027 (SEM; Figure 1). Of note, the SDI predicted CRT
response with a high positive likelihood ratio of 8 and a
minimum negative likelihood ratio of 0.05 (Table 3). Mean
acquisition and analysis duration of single-patient RT3DE
was 8 minutes (range 6 to 13). Interobserver variabilities of
LV end-systolic volume and SDI were 5% and 11%, res-
pectively.
1590 The American Journal of Cardiology (www.AJConline.org)
Discussion
The main findings of this prospective study are that (1)
RT3DE showed reverse volumetric LV remodeling in 76% of
patients with HF treated by CRT-D after 12-month follow-up
and (2) the SDI predicted reverse LV remodeling after CRT
with a high positive likelihood ratio and a minimal negative
likelihood ratio. In most CRT studies 2-dimensional echocar-
diography has been used for assessment of LV size and func-
tion before and after CRT. However, the accuracy of serial
measurements of LV volume from nonenhanced 2-dimen-
sional images is quite low compared with enhanced 2-dimen-
sional images or RT3DE.18,19 This is mainly due to geometric
assumptions of the distorted failing left ventricle and 2-dimen-
sional image plane errors. Using state-of-the-art technology
RT3DE allows accurate and highly reproducible LV volumet-
ric quantification in a quite shorter duration compared with
cardiac magnetic resonance imaging.7 This in turn is a unique
feature of RT3DE that cannot be offered by other 2-dimen-
sional echocardiographic techniques or cardiac magnetic res-
onance before and after CRT. Another important feature of
RT3DE is 3-dimensional assessment of LV systolic dyssyn-
chrony based on accurate volumetric quantification.10 Current
evidence-based guidelines20 –22 have recommended CRT for
improvement of symptoms and survival in selected patients
with impaired LV function and abnormal ventricular electrical
conduction rather than mechanical dyssynchrony (echocardi-
ography). In real practice, the question is whether the more
difficult echocardiographic dyssynchrony (1, 2, and 3 dimen-
sions) offers a significant additional benefit compared with
QRS duration. The recently published Predictors of Response
to Cardiac Resynchronization Therapy (PROSPECT) study
showed modest predictive value for 1- and 2-dimensional
echocardiographic techniques for prediction of reverse LV
remodeling after CRT.4 Of note, in 2 recent reports RT3DE
based dyssynchrony correlated well with acute hemodynamic
response after CRT.9,11 In this study, for the first time, we
investigated 3-dimensionally based dyssynchrony for predic-
tion of reverse LV remodeling after long-term CRT. In line
with major CRT randomized trials and observational studies, a
significant proportion of our study population did not show
reverse LV remodeling after CRT. Therefore, identification of
patients at low and high likelihood for reverse LV remodeling
after CRT with simple, routine, clinical, and echocardiographic
parameters seems mandatory.
Several 1- and 2-dimensional echocardiographic tech-
niques have been tested for prediction of CRT response. The
M-mode septal-to-posterior wall motion delay was pro-
posed, in a single-center study, as a useful predictor of
reverse remodeling23 after CRT. It is the highest temporal
resolution echocardiographic form of dyssynchrony. How-
ever, these data were not reproducible in single-center stud-
ies24 and in the multicenter PROSPECT study.4 This can be
explained by the limited feasibility, such as in patients with
large infarctions due to an akinetic septum, which lacks
clear displacement; hence, identification of maximal dis-
placement is not feasible.4,24 In addition, the latest activated
myocardial territories have varied significantly between
myocardial territories.25 Like M-mode echocardiography,
previously proposed tissue Doppler imaging dyssynchrony
failed to predict CRT outcome in a single-center study12 and
in the multicenter PROSPECT study.4 Tissue Doppler im-
aging is prone to angle-related errors and translational car-
diac and respiratory motion. In addition, in tissue Doppler
tracings in patients with poor LV function, it is difficult to
identify the peak of mechanical contraction. In addition,
interobserver variability of tissue Doppler imaging dyssyn-
chrony is high in several single-center studies26,27 and in the
multicenter PROSPECT study.4 LV contractility is a com-
plex, 3-dimensional issue including electromechanical cou-
pling, pattern of electrical activation, distribution of myo-
cardial fibers, and torsion forces on cardiac fibers. RT3DE
semiautomated analysis of LV volumes in this study allows
simultaneous assessment of time to minimum volumes from
all myocardial segments, which is the net result of longitu-
dinal, radial, and circumferential contractilities. Thus, it
allows for calculation of the temporal difference in maxi-
mum volumetric changes at 1 moment, which is the SDI.
Using a reasonable temporal resolution, such as in our
study, the SDI can discriminate CRT responders. In our
study, reverse LV remodeling was related to RT3DE de-
rived dyssynchrony. The high positive and negative likeli-
hood ratios of the SDI offer a clinical beneficial tool for
tailoring CRT therapy using RT3DE.
In the published literature, RT3DE based dyssynchrony
has been investigated in patients using CRT in only a few
studies. Our group first proposed the use of 3-dimensional
dyssynchrony from a multiplanar reconstruction (not real-
time) 3-dimeniosnal echocardiogram for guiding and opti-
mization of LV pacing lead the identification of latest acti-
vated territories.28 In their initial experience, Kapetanakis et
al8 found a significant difference in the SDI between re-
sponders and nonresponders using the same definition as in
our study. More recently, 2 different groups have found a
strong correlation between the SDI and acute hemodynamic
changes after CRT.9,11 Our study is the first to investigate
the predictive value of the SDI for reverse LV remodeling
after long-term CRT. Contrary to our study, previous inves-
tigations comprised fewer patients8 and/or shorter follow-up
duration after CRT.8,9,11 Our results confirm the initial find-
ing of previous reports that RT3DE provides more intuitive
assessment of dyssynchrony and response to CRT by a
simple, reproducible, and fast technique. Therefore, it may
be an attractive strategy to use RT3DE for assessment of
dyssynchrony and volumetric response to CRT.
RT3DE image quality can be poor. Luckily, recent im-
provements in hardware technology have been associated
with improvement in the accuracy and reproducibility of
RT3DE derived LV volumes.7 Moreover, LV opacification
can improve endocardial border definition in patients with
poor images.29 In addition, 3DE in this study was not true
real time but rather subvolumes from 4 to 7 cardiac cycles,
which may preclude full-volume acquisition in patients with
arrhythmias. However, all guideline-based CRT recipients,
such as in our study, were in sinus rhythm. Current com-
mercially available machines provide low volume rate
RT3DE datasets. However, most RT3DE datasets in our
study had ⬎20 volumes/s, which is the minimum limit
recommended by the American Society of Echocardiogra-
phy. Moreover, LV full-volume acquisition from a single
beat will be commercially available in the very near future.
Being a single-center study, there is a necessity for a mul-
 Heart Failure/RT3DE and Reverse Remodeling After CRT
ticenter study to confirm our findings. In conclusion,
RT3DE provides accurate identification of volumetric re-
verse LV remodeling after CRT. From these accurate volu-
metric data, RT3DE provides more intuitive assessment of
dyssynchrony and response to CRT as a simple, reproduc-
ible, and fast technique.
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