Download Septal to Posterior Wall Motion Delay Fails to Predict

Journal of the American College of Cardiology
© 2005 by the American College of Cardiology Foundation
Published by Elsevier Inc.
Vol. 46, No. 12, 2005
ISSN 0735-1097/05/$30.00
doi:10.1016/j.jacc.2005.05.095
FOCUS ISSUE: CARDIAC RESYNCHRONIZATION THERAPY
CLINICAL RESEARCH
Resynchronization and M-Mode Echo
Septal to Posterior Wall
Motion Delay Fails to Predict Reverse
Remodeling or Clinical Improvement in
Patients Undergoing Cardiac Resynchronization Therapy
Gregory M. Marcus, MD,* Emily Rose, MD,† Esperanza M. Viloria, BS,* Jill Schafer, MS,‡
Teresa De Marco, MD, FACC,* Leslie A. Saxon, MD, FACC,§ Elyse Foster, MD, FACC,*
for the VENTAK CHF/CONTAK-CD Biventricular Pacing Study Investigators
San Francisco and Los Angeles, California; Boston, Massachusetts; and St. Paul, Minnesota
The aim of this study was to test the hypothesis that a longer septal-to-posterior wall motion
delay (SPWMD) would predict greater reverse remodeling and an improved clinical response
in heart failure patients randomized to cardiac resynchronization therapy (CRT) in the
CONTAK-CD trial.
BACKGROUND The SPWMD predicted clinical benefit with CRT in two previous studies from the same
center.
METHODS
In this retrospective analysis of the CONTAK-CD trial, SPWMD was measured from the
baseline echocardiogram of 79 heart failure patients (ejection fraction 22 ⫾ 7%, QRS
duration 159 ⫾ 27 ms, 72% ischemic, 84% male) randomized to CRT and compared with
six-month changes in echocardiographic and clinical parameters. Patients with a left
ventricular end-systolic volume index (LVESVI) reduction of at least 15% were considered
responders.
RESULTS
The feasibility and reproducibility of performing the SPWMD measurements were poor.
Larger values for SPWMD did not correlate with six-month changes in left ventricular
end-diastolic volume index (p ⫽ 0.26), LVESVI (p ⫽ 0.41), or left ventricular ejection
fraction (p ⫽ 0.36). Responders did not have a significantly different SPWMD than
non-responders (p ⫽ 0.26). The SPWMD did not correlate with measures of clinical
improvement. At a threshold of SPWMD ⬎130 ms, the test characteristics to predict reverse
remodeling or a clinical response were inadequate.
CONCLUSIONS The previous findings that SPWMD predicts reverse remodeling or clinical improvement
with CRT were not reproducible in patients randomized in the CONTAK-CD trial. (J Am
Coll Cardiol 2005;46:2208 –14) © 2005 by the American College of Cardiology Foundation
OBJECTIVES
Intraventricular conduction delay, primarily in the form of
left bundle-branch block, is present in approximately 25% of
heart failure patients (1). The resultant delayed and dyssynchronous left ventricular (LV) contraction worsens ventricular function and results in increased myocardial oxygen
demand, ventricular remodeling, and increased mortality
(2– 4).
By simultaneously stimulating the right ventricle and the
free wall of the LV, cardiac resynchronization therapy (CRT)
has been shown to decrease LV volumes and dimensions,
From *Department of Medicine, Division of Cardiology, University of California,
San Francisco, San Francisco, California; †Department of Medicine, Brigham and
Women’s Hospital, Boston, Massachusetts; ‡Guidant Corporation, St. Paul, Minnesota; and §Department of Medicine, Division of Cardiology, University of
Southern California, Los Angeles, California. Drs. DeMarco and Foster received
grants from Guidant Corporation. Dr. Saxon consults for and receives grants from
Guidant Corporation, Medtronic, and St. Jude Corporations. Ms. Schafer is an
employee of Guidant Corporation. The first two authors contributed equally to this
paper.
Manuscript received March 1, 2005; revised manuscript received May 8, 2005,
accepted May 15, 2005.
increase ejection fraction, and improve functional status in
some, but not all patients with severe LV systolic dysfunction, interventricular conduction delay, and symptomatic
heart failure (5,6). In previous studies, a greater degree of
electrical and mechanical dyssynchrony at baseline have
been associated with greater likelihood of improvement in
LV structure and function with CRT (7,8).
Current inclusion criteria for CRT devices use only the
QRS duration to assess dyssynchrony. Given the costs and
risks associated with CRT, identifying reliable non-invasive
measures of ventricular dyssynchrony that predict therapeutic benefit are needed to optimize patient selection.
In a non-randomized study of 20 CRT patients with predominantly non-ischemic cardiomyopathy, it was demonstrated that septal-to-posterior wall motion delay (SPWMD)
measured by M-mode echocardiography was a useful predictor of reverse remodeling (9). More recently, a study of
60 CRT patients from the same center demonstrated that
the SPWMD was useful to predict heart failure progression.
JACC Vol. 46, No. 12, 2005
December 20, 2005:2208–14
Abbreviations and Acronyms
CRT
⫽ cardiac resynchronization therapy
LV
⫽ left ventricle/ventricular
LVEDVI ⫽ left ventricular end-diastolic volume index
LVEF
⫽ left ventricular ejection fraction
LVESVI ⫽ left ventricular end-systolic volume index
NYHA ⫽ New York Heart Association
SPWMD ⫽ septal-to-posterior wall motion delay
In both studies, a longer SPWMD was associated with
greater improvement with CRT, and a SPWMD ⱖ130 ms
was found to be a useful cutoff point to predict success.
Based on these results, SPWMD has been suggested as a
screening method for patient selection for CRT. However,
the feasibility and utility of this parameter have not been
tested in a largely ischemic population in whom endocardial
excursion of either the septal or posterior wall may be
markedly diminished and therefore not clearly identifiable.
This study was designed to test the hypothesis that
SPWMD would predict greater reverse remodeling and an
improved clinical response in heart failure patients randomized to CRT in the CONTAK-CD trial.
METHODS
Subjects. The VENTAK CHF/CONTAK-CD study enrolled 581 patients from 47 investigational centers throughout the U.S. from February 1998 through December 2000.
The study was approved by the institutional review board at
each participating institution, and patients gave written
informed consent. Inclusion criteria were an indication at
the time of enrollment for an implantable cardioverter
defibrillator, symptomatic heart failure despite optimal drug
therapy, left ventricular ejection fraction (LVEF) ⱕ35%, a
QRS duration ⱖ120 ms; age ⱖ18 years, and normal sinus
node function. The exclusion criteria and study design have
been described in a previous publication (5). Originally, all
patients received a CRT device and were randomized to
CRT turned on or to CRT turned off (phase 1, n ⫽ 248).
Because of regulatory concern, the study was modified from
a crossover to a six-month parallel design in phase 2 (n ⫽
333). Of the 581 patients enrolled between the two phases,
501 were successfully implanted with the investigational
system (5). Only phase 2 patients randomized to CRT
turned on with paired baseline and six-month echo data are
included in this analysis.
Echocardiographic analysis. Two-dimensional Doppler
echocardiograms were performed at multiple investigational
sites according to a standardized protocol at baseline, three
months, and six months after randomization. For the
purposes of this study, the baseline and six-month echocardiograms were analyzed. A two-dimensionally guided (Mmode) echocardiogram at a level just below the tips of the
mitral leaflets, basal to the tips of the papillary muscles, was
used for measurement of the SPWMD as described subsequently. Left ventricular end-diastolic volumes and LV end-
Marcus et al.
SPWMD Fails to Predict CRT Outcomes
2209
systolic volumes were obtained by tracing the endocardium at
the end-diastole (maximum cavity dimension) and endsystole (frame before mitral valve opening or the minimum
cavity area) in the two-chamber and four-chamber views
and derived according to Simpson’s rule (biplane method of
discs) (10). The left ventricular end-systolic volume index
(LVESVI) and left ventricular end-diastolic volume index
(LVEDVI) are normalized for body surface area. The
LVEF was calculated as the total stroke volume divided by the
end-diastolic volume. Echocardiograms were excluded when
less than 80% of the endocardium could be visualized. Responders were defined as those who had greater than a 15%
decrease in LVESVI (9,11). Clinical improvement measures
included six-month change in peak exercise O2 consumption,
6-min walk distance, quality of life score as assessed by the
Minnesota Living with Heart Failure Questionnaire, and New
York Heart Association (NYHA) functional class.
The SPWMD represents the delay between the motion
of the septum and the posterior wall of the LV. We adopted
the method described by Pitzalis et al. (9) and measured the
SPWMD on the M-mode echocardiogram obtained at
baseline before randomization: the maximum displacement
of the septal wall and the maximum displacement of the
posterior wall were both measured from the onset of the
QRS; the QRS to septal wall deflection value was then
subtracted from the QRS to posterior wall deflection value
to calculate the SPWMD (Fig. 1). Three measurements
were made for each parameter and then averaged. These
measurements were performed for each subject by two
independent observers for 60% of the subjects for the
primary and first observer and 47% of the subjects for the
primary and second observer. In adopting this method, we
recognize that the level of M-mode echocardiogram differs
from the original description (9): Pitzalis obtained the
M-mode at the level of the papillary muscles. In contrast,
the measurements for the present study were made at a more
basal level, representing the standard location for measuring
LV dimensions.
The ability to accurately measure SPWMD on the
M-mode tracing was highly dependent on the extent of
excursion of the septal and posterior walls. Therefore, a scale
of difficulty was created. A value of one was given if both the
septal wall and the posterior wall deflection were easily
visualized. A value of two was given if either the septal or
posterior wall displacement was difficult to visualize. A value
of three was given if both the septal and posterior wall were
difficult to visualize or if either one had no identifiable
deflection.
Operators blinded to the success of resynchronization
therapy for the individual patients performed the echocardiographic analysis of intraventricular dyssynchrony. Interobserver reliability was measured with two independent
observers compared with the primary observer.
Statistical analysis. Linear comparisons between SPWMD
and LVESVI, LVEDVI, and LVEF were made by calculating the Pearson product-moment correlation coefficient.
2210
Marcus et al.
SPWMD Fails to Predict CRT Outcomes
JACC Vol. 46, No. 12, 2005
December 20, 2005:2208–14
Figure 1. Septal wall motion delay (SWMD) was measured in M-mode by measuring from the start of the QRS to the peak of the septal wall deflection.
Posterior wall motion delay (PWMD) was measured similarly by measuring from the start of the QRS to the peak of the posterior wall deflection. The
difference between the septal wall deflection and the posterior wall deflection is the septal-to-posterior wall motion delay (SPWMD).
Differences in categorical and continuous variables between
responders and non-responders were assessed by the chisquare test or Student t test, as appropriate. In addition,
six-month change in peak exercise O2 consumption, 6-min
walk distance, quality of life score, and NYHA functional
class were correlated with all dyssynchrony parameters. To
reveal whether patients with longer baseline SPWMD
measurements experienced a significantly greater improvement in LVESVI, LVEDVI, and LVEF with CRT than
other patients, linear regressions with respect to these
variables and their effect on treatment group were performed. To be consistent with previous studies, a SPWMD
value ⱖ130 ms was used to determine the sensitivities,
specificities, and positive and negative predictive values for
six-month improvement in echocardiographic and clinical
parameters (8,9). In determining associations between patients with and without a SPWMD ⱖ130 ms and clinical
outcomes, continuous measures were calculated from a
Student t test and values for categorical measures were
calculated by a chi-square test.
Within-subjects standard deviation was calculated using
the analysis of variance between the two independent observers
and compared with the primary observer, and repeatability
of measurements was calculated by multiplying the withinsubjects standard deviation by 2.77 to account for 2 SD
from the mean and two independent measurements of the
same value (12–14).
RESULTS
Of the 333 subjects randomized to CRT in the
CONTAK-CD trial, six-month echocardiograms were available for 79 (24%) (Table 1). Compared with subjects for
whom six-month echocardiograms were not available, those
with both baseline and six-month echocardiograms had no
significant differences in regard to gender, etiology of heart
failure, QRS duration, and ejection fraction (Table 1).
Subjects for whom six-month echocardiograms were not
available were less likely to be taking a beta-blocker and
were less likely to have a lateral lead location.
Feasibility of the SPWMD measurements. A definitive
systolic deflection of both the septal and posterior walls was
evident in less than half of all subjects (45%). According to
the difficulty scale, the number of patients in each category
was: 1 (n ⫽ 39), 2 (n ⫽ 27), and 3 (n ⫽ 13). The level of
difficulty scale did not influence relationships between
dyssynchrony parameters and CRT benefit in any category.
Reproducibility of SPWMD measurements. There was
poor inter-observer precision of SPWMD (observer 1 with
the primary observer ⫽ 141 ms, n ⫽ 37; observer 2 with the
primary observer ⫽ 194 ms, n ⫽ 47). For example, the
within-subjects standard deviation for SPWMD between
observer 1 and the primary observer was 51 ms, yielding a
repeatability of 141 ms. These suggest that 95% of pairs of
measurements of the same echocardiographic parameter by
different observers should fall between 141 ms.
Correlations between baseline SPWMD and six-month
evidence of reverse remodeling. The reduction in LVESVI
and LVEDVI and the improvement in ejection fraction
were determined by comparing the baseline and six-month
echocardiograms. Baseline SPWMD did not correlate with
six-month changes in LVESVI (⫺0.10, p ⫽ 0.41),
LVEDVI (⫺0.14, p ⫽ 0.26), or ejection fraction (0.11, p ⫽
0.36). Correlations remained non-significant when examining the same echocardiographic parameters in patients with
and without ischemic etiologies of heart failure.
The baseline SPWMD did not significantly differ between responders (mean 77 ⫾ 141 ms, range ⫺340 ms to
312 ms) and non-responders (mean 59 ⫾ 160, range ⫺326
ms to 525 ms, p ⫽ 0.63). The lack of any relationship
between baseline SPWMD and responders persisted when
examining patients with ischemic etiologies of heart failure
alone or non-ischemic etiologies of heart failure alone. Pa-
Marcus et al.
SPWMD Fails to Predict CRT Outcomes
JACC Vol. 46, No. 12, 2005
December 20, 2005:2208–14
Table 1. Baseline Characteristics: Patients With and Without
Paired Six-Month Echocardiograms
Characteristic
Age at implant (yrs)
n
Mean ⫾ SD
Range
Gender, n (%)
Male
Female
NYHA funtional class, n (%)
II
III
IV
Concomitant medications,
n (%)
ACE or ARB
Beta-blocker
Digoxin
Diuretic
Qualifying LVEF (%)
n
Mean ⫾ SD
Range
PR interval (ms)
n
Mean ⫾ SD
Range
Qualifying QRS duration (ms)
n
Mean ⫾ SD
Range
Resting heart rate, beats/min
n
Mean ⫾ SD
Range
Systolic blood pressure
(mm Hg)
n
Mean ⫾ SD
Range
Diastolic blood pressure
(mm Hg)
n
Mean ⫾ SD
Range
Primary tachyarrhythmia,
n (%)
Monomorphic VT
Polymorphic VT
Nonsustained VT
Ventricular fibrillation
Other arrhythmias, n (%)
Paroxysmal atrial fibrillation
Atrial flutter
Conduction disorder, n (%)
LBBB
RBBB
Non-specific
Etiology of heart failure,
n (%)
Ischemic
Non-ischemic
Paired Echo No Paired Echo
p
(n ⴝ 79)
(n ⴝ 69)
Value
79
66.8 ⫾ 1.2
26.1–82.5
169
65.6 ⫾ 10.1
28.9–82.6
66 (83.5)
13 (16.5)
144 (85.2)
25 (14.8)
0.73
28 (35.4)
46 (58.2)
5 (6.3)
52 (30.8)
102 (60.4)
15 (8.9)
0.66
68 (86.1)
49 (62.0)
56 (70.9)
69 (87.3)
144 (85.2)
70 (41.4)
116 (68.6)
148 (87.6)
0.86
⬍0.01
0.72
0.96
79
21.9 ⫾ 6.6
9.0–35.0
169
21.1 ⫾ 6.6
5.0–35.0
0.40
79
201 ⫾ 41
90–332
145
207 ⫾ 43
88–336
0.30
79
159 ⫾ 27
121–237
147
161 ⫾ 27
120–240
0.49
79
72 ⫾ 13
49–108
169
74 ⫾ 12
43–106
0.15
79
117 ⫾ 18
83–170
168
119 ⫾ 22
79–197
0.40
79
66 ⫾ 10
31–88
168
68 ⫾ 12
36–100
0.13
44 (55.7)
8 (10.1)
19 (24.1)
8 (10.1)
104 (61.5)
8 (4.7)
39 (23.1)
18 (10.7)
0.43
13 (16.5)
4 (5.1)
30 (17.8)
6 (3.6)
0.80
0.57
47 (59.5)
8 (10.1)
24 (30.4)
86 (50.9)
27 (16.0)
56 (33.1)
0.34
57 (72.2)
22 (27.8)
110 (65.1)
59 (34.9)
0.27
0.41
2211
Table 1 Continued
Characteristic
Left anterior oblique view lead
position, n (%)
Anterior
Lateral
Posterior
Anterior-posterior view lead
position, n (%)
Apical
Basal
Mid
Paired Echo No Paired Echo
p
(n ⴝ 79)
(n ⴝ 69)
Value
16 (21.1)
54 (71.1)
6 (7.9)
50 (35.0)
73 (51.0)
20 (14.0)
0.02
9 (11.8)
7 (9.2)
60 (78.9)
18 (12.6)
14 (9.8)
111 (77.6)
0.97
ACE ⫽ angiotensin-converting enzyme; ARB ⫽ angiotensin receptor blocker;
LBBB ⫽ left bundle-branch block; LVEF ⫽ left ventricular ejection fraction; NYHA
⫽ New York Heart Association; RBBB ⫽ right bundle-branch block; VT ⫽
ventricular tachycardia.
tients with a SPWMD ⱖ130 ms did not have significantly
improved six-month changes in LVESVI, LVEDVI, or
ejection fraction compared with those with SPWMD ⬍130
ms; again, this finding was independent of heart failure
etiology. In addition, the test characteristics for a SPWMD
ⱖ130 ms to predict a responder were poor (Table 2).
Correlation between baseline SPWMD and measures of
clinical improvement. Baseline SPWMD parameters did
not significantly correlate with six-month change in oxygen
consumption (⫺0.04, p ⫽ 0.75), six-month change in
6-min walk (⫺0.06, p ⫽ 0.59), six-month change in quality
of life (0.11, p ⫽ 0.32), or six-month change in NYHA
functional class (0.06, p ⫽ 0.54). Patients with a SPWMD
ⱖ130 ms were no more likely to have six-month improvement in any of the clinical parameters (Table 3). The test
characteristics for a SPWMD ⱖ130 ms to predict an
improvement in at least one NYHA functional class were
poor (Table 2).
In the linear regression analyses, no significant interactions between SPWMD and CRT with respect to improvements in LVESVI, LVEDVI, and LVEF were found.
DISCUSSION
With respect to reverse remodeling, systolic function, and
improvements in clinical outcomes, SPWMD as determined by M-mode echocardiography did not predict a
response to CRT in this group of patients. We do not
believe that our findings bear any reflection on the validity
of the concept that true baseline LV dyssynchrony itself
might predict benefit with CRT. Instead, contrary to
previous publications, we believe our data demonstrate that
M-mode SPWMD does not provide a reliable or accurate
reflection of actual LV dyssynchrony.
Primarily, the limited feasibility of obtaining the necessary M-mode measurements in order to calculate the
SPWMD suggests that this method of screening for CRT
selection would likely not be applicable in clinical practice.
In this cohort, nearly one-half (45%) of patients had neither
a definitive septal nor posterior wall deflection visualized on
M-mode echocardiography. Twenty-seven (34%) had only
2212
Marcus et al.
SPWMD Fails to Predict CRT Outcomes
JACC Vol. 46, No. 12, 2005
December 20, 2005:2208–14
Table 2. Sensitivity, Specificity, and Positive and Negative Predictive Values of SPWMD ⱖ130
ms for Reverse Remodeling and Clinical Improvement
Six-Month Change
Sensitivity
Specificity
Positive Predictive
Value
Negative Predictive
Value
LVESVI reduction of at least 15%
Increase of at least one NYHA
functional class
24%
24%
66%
66%
29%
29%
61%
61%
LVESVI ⫽ left-ventricular end-systolic volume index; NYHA ⫽ New York Heart Association; SPWMD ⫽ septal-to-posterior
wall motion delay.
one of the two walls exhibiting a definite systolic excursion.
The remaining 13 patients (16%) of the cohort with
M-mode echocardiograms showed both definitive septal
and posterior wall deflections. However, as demonstrated in
Figure 2, the SPWMD measurement remained difficult
even when both septal and posterior wall deflections are well
visualized. The difficulty was further confounded by the
thinning and akinesis of infarcted segments frequently
present in many of these predominantly ischemic patients.
Given the practical limitations of obtaining these measurements, the poor inter-observer reproducibility in our study
was not surprising.
How then can the discrepancies between previous studies
and our current study be explained? Pitzalis et al. demonstrated that SPWMD predicted echocardiographic parameters of reverse remodeling in 20 patients (20% with
ischemic cardiomyopathy) undergoing CRT (9); the same
group more recently showed that SPWMD predicted clinical benefit in 60 patients (22% with ischemic cardiomyopathy) undergoing CRT (8). It is not clear if any of the
patients from the first study were included in the second,
but, at the most, all of the data supporting the use of
SPWMD as a useful predictor stems from 80 patients, 17
(21%) of whom had an ischemic cardiomyopathy. Our
cohort included 79 patients, 57 (72%) with an ischemic
cardiomyopathy. Therefore, it is possible that the different
conclusions between the studies are due to the significantly
larger number of patients with ischemic cardiomyopathies
in our patient group. Indeed, patients with ischemic cardiomyopathies may be more likely to have focal hypokinesis or
akinesis that would sufficiently perturb septal or posterior
wall motion so as to make accurate measurements of systolic
deflections difficult if not impossible. However, separate
analyses of the 22 patients with non-ischemic cardiomyopathy in our study (a number comparable to the original
study) (8) also failed to demonstrate any predictive value of
SPWMD.
As described in the Methods section, the M-mode
images in the previous studies were taken in the parasternal
short-axis view at the level of the papillary muscle (8,9),
whereas our M-mode images were taken in the parasternal
long-axis view at the tips of the mitral valve leaflets.
Although it is theoretically possible that a measurement
taken a few millimeters towards the base would make such
a significant difference, we doubt that it would rectify the
significant difficulties in identifying a definite systolic excursion in one or both walls. If such a difference were found,
this would mean that the measurement at the papillary
muscle would have to be quite precise in location, potentially limiting applicability in clinical practice. In our opinion, it is more likely that defining the complex activation
sequence of the LV using a single dimensional view is
inherently unreliable independent of the precise location of
the ultrasound beam. Moreover, because septal infarcts tend
Table 3. Difference in Six-Month Change in Clinical Response Measures by SPWMD at
Baseline
Measure
Six-month change
n
Mean ⫾ SD
Range
Six-month change
n
Mean ⫾ SD
Range
Six-month change
n
Mean ⫾ SD
Range
Six-month change
Improved
No change
Worsened
SPWMD <130 ms
SPWMD >130 ms
p Value
42
0.4 ⫾ 3.1
⫺9.5 to 8.0
21
1.2 ⫾ 2.7
⫺4.2 to 8.7
0.29
55
42 ⫾ 73
⫺91 to 229
26
41 ⫾ 102
⫺177 to 249
0.97
62
⫺7 ⫾ 21
⫺67 to 33
27
⫺10 ⫾ 20
⫺41 to 34
0.62
25 (39%)
31 (48%)
8 (13%)
8 (29%)
16 (57%)
4 (14%)
0.63
in peak VO2 (ml/kg/min)
in 6-min walk (ms)
in QOL (points)
in NYHA functional class
NYHA ⫽ New York Heart Association; QOL ⫽ quality of life; SPWMD ⫽ septal-to-posterior wall motion delay; VO2 ⫽
oxygen consumption.
JACC Vol. 46, No. 12, 2005
December 20, 2005:2208–14
Marcus et al.
SPWMD Fails to Predict CRT Outcomes
2213
Figure 2. This figure illustrates the ambiguous nature of the septal-to-posterior wall motion delay (SPWMD) measurement even when both walls were well
visualized. It is uncertain whether the septal wall deflection should be measured at A, the first deflection, at B, the middle of the larger area of deflection,
or at point C where the maximum deflection is seen. The initial septal wall deflection is too close to the QRS to represent contraction and may reflect
posterior motion resulting from ventricular interaction. The middle of the larger area of septal wall deflection is appropriately timed while the maximum
septal wall deflection occurs in diastole.
to spare the proximal septum, basal beam angulation may
theoretically produce better results in ischemic patients.
Nevertheless, in their most recent publication, Pitzalis et al.
considered the SPWMD to have a value of 0 ms when
septal akinesis was observed, potentially biasing the results
of the study (8).
Our data, collected in a variety of echocardiography
laboratories across the U.S. and involving a majority of
ischemic cardiomyopathy patients, are more representative
of clinical practice than those acquired in a single center
with a majority of non-ischemic cardiomyopathy patients.
Tissue Doppler imaging (11,15–17), strain rate imaging
(11,17), and methods based on phase analysis (18) all show
great promise in the measurement of intraventricular dyssynchrony. One promising method for detecting and measuring dyssynchrony uses an index based on the standard
deviation of the time to peak systolic shortening in 12
myocardial segments: Yu et al. (17) have shown that a
standard deviation of 33 ms or greater predicts response to
CRT with a high degree of sensitivity and specificity . A
limitation of this method is that nearly all of the published
series have been performed with echocardiographic systems
available from a single vendor and the generalizability of
these measurements to other systems has not been proven.
In contrast, most of the current echocardiographic systems
are capable of recording pulsed tissue Doppler velocities, a
potentially useful measurement that can be used to obtain
timing differences between peak systolic velocities among
different segments. Using this technique, one study demonstrated that a septal to lateral wall delay of greater than 60
ms predicted a favorable response to CRT (15). A recog-
nized limitation of the pulsed Doppler technique is that
only one segment can be recorded in a given cardiac cycle
and may be influenced by timing shifts from beat to beat
(16). These methods remain investigational, are timeintensive, and are not currently available in the great
majority of clinical non-invasive laboratories. On the other
hand, although M-mode echocardiography is clinically
widely available and technically easy to perform, our findings suggest that it should not be used for patient selection
for CRT.
Our study demonstrates that this parameter based on
M-mode echocardiography, while attractive in its apparent
simplicity, is not adequately robust to be applied in clinical
practice. A major concern is that patients, especially those
with ischemic cardiomyopathy, will not be offered this
therapy on the basis of the previously reported studies.
Study limitations. The major limitation of this study is
that the M-mode images were not targeted to prospectively
collect these data. However, all M-mode imaging was
performed in accordance with the American Society of
Echocardiography recommendations. All centers followed a
standardized protocol, and all echocardiograms were analyzed in an experienced core laboratory.
CONCLUSIONS
Septal-to-posterior wall motion delay based on conventional
M-mode echocardiography is not adequate to predict clinical or remodeling response to CRT and therefore should
not be used to guide CRT patient selection. Because
emerging imaging techniques that provide two- and three-
2214
Marcus et al.
SPWMD Fails to Predict CRT Outcomes
dimensional measures may more accurately reflect mechanical dyssynchrony, they will likely prove superior in selecting
appropriate patients for CRT and will therefore have an
expanding role in clinical practice.
Reprint requests and correspondence: Dr. Elyse Foster, UCSF
Cardiology, M-314, 505 Parnassus Avenue, San Francisco, California 94143-0214. E-mail: [email protected].
JACC Vol. 46, No. 12, 2005
December 20, 2005:2208–14
8.
9.
10.
REFERENCES
1. Eriksson P, Hanson PO, Eriksson H, et al. Bundle-branch block in a
general male population: the study of men born 1913. Circulation
1998;98:2494 –500.
2. Grines CL, Bashore TM, Boudoulas H, et al. Functional abnormalities in isolated LBBB: the effect of interventricular asynchrony.
Circulation 1989;79:845–53.
3. Little WC, Reeves RC, Arciniegas J, et al. Mechanism of abnormal
interventricular septal motion during delayed left ventricular activation. Circulation 1982;65:1486 –91.
4. Baldasseroni S, Opasich C, Gorini M, et al., Italian Network on
Congestive Heart Failure Investigators. Left bundle-branch block is
associated with increased 1-year sudden and total mortality rate in
5,517 outpatients with congestive heart failure: a report from the
Italian network on congestive heart failure. Am Heart J 2002;143:
398 – 405.
5. Higgins SL, Hummel JD, Niazi IK, et al. Cardiac resynchronization
therapy for the treatment of heart failure in patients with intraventricular conduction delay and malignant ventricular tachyarrhythmias.
J Am Coll Cardiol 2003;42:1454 –9.
6. St. John Sutton MG, Plappert T, Abraham WT, et al. Multicenter
InSync Randomized Clinical Evaluation (MIRACLE) Study Group.
Effect of cardiac resynchronization therapy on left ventricular size and
function in chronic heart failure. Circulation 2003;107:1985–90.
7. Auricchio A, Stellbrink C, Butter C, et al. Pacing Therapies in
Congestive Heart Failure II Study Group; Guidant Heart Failure
Research Group. Clinical efficacy of cardiac resynchronization therapy
11.
12.
13.
14.
15.
16.
17.
18.
using left ventricular pacing in heart failure patients stratified by
severity of ventricular conduction delay. J Am Coll Cardiol
2003;42:2109 –16.
Pitzalis MV, Iacoviello M, Romito R, et al. Ventricular asynchrony
predicts a better outcome in patients with chronic heart failure
receiving cardiac resynchronization therapy. J Am Coll Cardiol 2005;
45:65–9.
Pitzalis MV, Iacoviello M, Romito R, et al. Cardiac resynchronization
therapy tailored by echocardiographic evaluation of ventricular asynchrony. J Am Coll Cardiol 2002;40:1615–22.
Schiller NB, Shah PM, Crawford M, et al. Recommendations for
quantitation of the left ventricle by 2-dimensional echocardiography.
American Society of Echocardiography Committee on Standards,
Subcommittee on Quantitation of Two-Dimensional Echocardiograms. J Am Soc Echocardiogr 1989;2:358 – 67.
Yu CM, Fung WH, Lin H, et al. Predictors of left ventricular reverse
remodeling after cardiac resynchronization therapy for heart failure
secondary to idiopathic dilated or ischemic cardiomyopathy. Am J
Cardiol 2002;91:684 – 8.
Bland JM, Altman DG. Statistical methods for assessing agreement
between two methods of clinical measurement. Lancet 1986;1:307–10.
Bland JM, Altman DG. Measurement error. BMJ 1996;313:744.
Bland JM, Altman DG. Measurement error and correlation coefficients. BMJ 1996;313:41–2.
Bax JJ, Marwick TH, Molhoek SG, et al. Left ventricular dyssynchrony predicts benefit of cardiac resynchronization therapy in patients
with end-stage heart failure before pacemaker implantation. Am J
Cardiol 2003;92:1238 – 40.
Bax JJ, Ansalone G, Breithardt OA, et al. Echocardiographic evaluation of cardiac resynchronization therapy: ready for routine clinical
use? A critical appraisal. J Am Coll Cardiol 2004;44:1–9.
Yu CM, Wing-Hong Fung J, Zhang Q, et al. Tissue Doppler imaging
is superior to strain rate imaging and postsystolic shortening on the
prediction of reverse remodeling in both ischemic and nonischemic
heart failure after cardiac resynchronization therapy. Circulation 2004;
110:66 –73.
Kerwin WF, Botvinick EH, O’Connell JW, et al. Ventricular contraction abnormalities in dilated cardiomyopathy: effect of biventricular pacing to correct interventricular dyssynchrony. J Am Coll Cardiol
2000;35:1221–7.