Download Electrical Conduction Disturbance Effects on Dynamic

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.2005.08.037
FOCUS ISSUE: CARDIAC RESYNCHRONIZATION THERAPY
Electrical Conduction Disturbance Effects on
Dynamic Changes of Functional Mitral Regurgitation
Shota Fukuda, MD, Richard Grimm, DO, FACC, Jong-Min Song, MD, Takashi Kihara, MD,
Masao Daimon, MD, Deborah A. Agler, RDCS, Bruce L. Wilkoff, MD, FACC, Andrea Natale, MD,
James D. Thomas, MD, FACC, Takahiro Shiota, MD, FACC
Cleveland, Ohio
The aim of this study was to investigate the relationship between dynamics of functional
mitral regurgitation (MR) and the degree of electrical conduction disturbance, and to evaluate
the impact of cardiac resynchronization therapy (CRT) on MR severity and its phasic pattern.
BACKGROUND Mechanisms of phasic changes of functional MR, which may be determined by annulus
dilation and tethering of the leaflet, remain unclear.
METHODS
Transthoracic two-dimensional echocardiography was performed in 60 patients with functional MR. A biventricular pacemaker was implanted in 19 patients. The mitral annulus area
(MAA) and the tenting area (TA) were measured from apical views. The MR volume and
fraction were assessed by the quantitative pulsed Doppler method. Instantaneous regurgitation flow rate was measured by proximal flow convergence method. A dynamic change in MR
flow rate was evaluated by frame-by-frame analysis throughout systole.
RESULTS
A phasic pattern with two peaks at early- and late-systole and decrease in mid-systole was
noticed in 57 patients. The early-systolic peak of MR was larger than the late-systolic peak
(128.4 ⫾ 64.3 ml/s vs. 73.9 ⫾ 55.1 ml/s, p ⬍ 0.001). The ratio of flow rate at these two peaks
correlated with QRS duration (r ⫽ 0.55, p ⬍ 0.001). Early-systolic flow rate reduced after
CRT (143.9 ⫾ 60.8 ml/s to 90.7 ⫾ 54.1 ml/s, p ⬍ 0.05), but late-systolic flow rate did not
(61.5 ⫾ 55.0 ml/s to 51.2 ⫾ 40.9 ml/s, p ⫽ NS). A similar pattern was observed for TA,
whereas MAA did not change after CRT.
CONCLUSIONS Biphasic pattern was found in functional MR, and the ratio of flow rate at two peaks
correlated with QRS duration. The CRT decreased regurgitation flow volume by reducing
early-systolic MR but not late-systolic MR, resulting in the change in phasic pattern of
functional MR. (J Am Coll Cardiol 2005;46:2270 – 6) © 2005 by the American College of
Cardiology Foundation
OBJECTIVES
Functional mitral regurgitation (MR) is a common and
morbid complication in patients with ischemic heart disease
or dilated cardiomyopathy, increasing long-term risk and
mortality (1– 4). Several competing geometric and hemodynamic factors may cause the functional MR: mitral annulus
dilation, tethering of the leaflet secondary to papillary
muscles dislocation, and ventricular dysfunction with reduced transmitral pressure acting to close the leaflets (5–9).
Importantly, these factors vary throughout a cardiac cycle,
leading to dynamic changes in functional MR during the
regurgitation period (10 –14). Previous studies reported that
a biphasic pattern with early- and late-systolic peaks and a
mid-systolic decrease of regurgitation flow was observed in
patients with functional MR (12,14). Although this phenomenon may have the potential to provide insights into
important aspects of mechanisms and therapeutic target of
functional MR, it is relatively ignored.
Cardiac resynchronization therapy (CRT) has been recently introduced as a complementary treatment option to
improve ventricular synchrony, resulting in increased venFrom the Department of Cardiovascular Medicine, Cleveland Clinic Foundation,
Cleveland, Ohio.
Manuscript received April 11, 2005; revised manuscript received July 11, 2005,
accepted August 15, 2005.
tricular function (15–19) as well as reduced MR (18 –22). In
recent investigations of the mechanism of reduced MR after
CRT, transmitral pressure (20) and mechanical activation of
papillary muscle insertion regions (21), which determine the
severity of MR (5,6,8) and its time variation (12,14), were
altered by CRT in patients with functional MR. Decrease of
regurgitation flow after CRT might occur with concurrent
changes of its dynamics. In addition, the degree of coordination of the regional ventricular wall activation might
relate to the severity of MR and/or its phasic pattern. The
purpose of this study was therefore to investigate the
relationship between dynamics of MR and the degree of
electrical conduction disturbance, and to evaluate the impact
of CRT on the overall severity of MR and its phasic pattern.
METHODS
Study population. Seventy-four patients with functional
MR who underwent transthoracic two-dimensional echocardiography were initially enrolled in this study. The patients
with a history of cardiac surgery (n ⫽ 1), permanent atrial
fibrillation (n ⫽ 5), evident intrinsic abnormality of the
mitral valve (n ⫽ 2), and poor image quality of echocardiography (n ⫽ 6) were excluded. The final study group
JACC Vol. 46, No. 12, 2005
December 20, 2005:2270–6
Abbreviations and Acronyms
CRT ⫽ cardiac resynchronization therapy
EDV ⫽ end-diastolic volume
EF ⫽ ejection fraction
ESV ⫽ end-systolic volume
LV ⫽ left ventricle
MAA ⫽ mitral annulus area
MR ⫽ mitral regurgitation
PFC ⫽ proximal flow convergence
TA ⫽ tenting area
consisted of 60 patients (44 males, mean age 60 ⫾ 10 years).
Eighteen had idiopathic dilated cardiomyopathy, and 42 patients had a history of myocardial infarction (20 in the anterior
wall, 17 in the inferoposterior wall, and 5 in both the anterior
and inferoposterior walls). Echocardiography documented left
ventricular (LV) dysfunction in all patients with a mean LV
end-diastolic volume (EDV) of 312.4 ⫾ 126.0 ml, a mean
end-systolic volume (ESV) of 242.3 ⫾ 107.5 ml, and a mean
LV ejection fraction (EF) of 23.5 ⫾ 7.7%. The patients had
either a normal sinus rhythm (n ⫽ 58) or had a pacemakerinduced rhythm (n ⫽ 2) with a mean QRS duration of 138.5
⫾ 39.5 ms (range 74 to 222 ms) on 12-lead surface
electrocardiogram.
A biventricular pacemaker was implanted in 19 of 60
patients (15 males, mean age 64 ⫾ 9 years) according to
the recommendation of the patient’s attending physicians,
independent of the results of the present study. The mean
QRS duration was 161.6 ⫾ 33.3 ms before biventricular
pacemaker implantation, and transthoracic twodimensional echocardiography was obtained before and ⬎3
months after biventricular pacemaker implantation (241 ⫾
187 days). All patients received a biventricular pacing
system with a right ventricular apical lead and LV pacing
electrodes implanted through the coronary sinus and positioned in a LV epicardial vein (15 in a lateral position and
4 in a posterior position). The study was approved by the
ethics committee at our institution.
Transthoracic two-dimensional echocardiography. Transthoracic two-dimensional echocardiography was performed
with a Sonos 5500 (Philips Medical Systems, Andover,
Massachusetts) or a Vivid 7 (GE Medical Systems, Milwaukee, Wisconsin). The standard parasternal and apical
views with the highest possible quality were carefully selected and digitally stored for off-line analysis. The LV
EDV and ESV were obtained to calculate LV EF by using
the Simpson’s method from apical four- and two-chamber
views (23). The MR volume was calculated as the difference
between mitral and aortic stroke volumes integrated by the
quantitative pulsed Doppler method, as reported in previous
studies (3,8,21,22,24). Mitral stroke volume was determined
as the product of mitral annulus area (MAA) and the mitral
time velocity integral during diastole, and aortic stroke
volume was calculated by multiplying the LV outflow tract
area and time velocity integral at systole. The MR fraction
Fukuda et al.
Electrical Conduction Disturbance and MR
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was then calculated as MR volume divided by mitral stroke
volume.
The MAA was estimated by the product of annulus diameters in apical four- and two-chamber views (14,21). The
tenting area (TA) of the mitral valve was measured by tracing
between the atrial surface of the leaflets and the mitral
annular plane from the apical four-chamber view (Fig. 1).
The proximal flow convergence (PFC) area of MR was
obtained from the apical views in color Doppler flow image
with the Doppler color gain carefully adjusted to maximize
signal without random noise velocities (3,12–14,20). The
setting of the color Doppler flow image was consistent
before and after CRT. The maximal radius (r) of the PFC
area was measured after a baseline shift of the color flow to
decrease the aliasing velocity (V). The MR flow rate was
then calculated as 2 ⫻ ␲ ⫻ r2 ⫻ V. A dynamic change in
the degree of MR was evaluated by frame-by-frame analysis
throughout the regurgitation period, and then images at the
timing of the maximum PFC area at early- and late-systole,
and minimum at mid-systole were separately selected for
assessing the phasic change and to calculate early/late peaks
ratio in MAA, TA, and MR flow rate (Fig. 2).
Statistical analysis. Values were expressed as mean ⫾ SD.
Comparison of echocardiographic parameters between before and after CRT were made with the paired t test.
Repeated measures analysis of variance was used to compare
among three cardiac phases (early-, mid-, and late-systole).
When differences were found, any two phases were compared using Student t test with Bonferroni correction.
One-way analysis of variance followed by post hoc with
Bonferroni test was used to compare among three subgroups
defined according to the etiology of underlying LV disease
(idiopathic dilated cardiomyopathy, or myocardial infarction with or without inferoposterior wall). Linear regression
was used for correlation of variables of interest. Multivariate
linear regression analysis was performed to identify determinant factors of MR early/late flow ratio, and the significant variables on univariate analysis were entered into
models. Differences were considered significant at p ⬍ 0.05.
Figure 1. Schema explaining echocardiographic measurements of mitral
annulus (arrow) and tenting area (oblique line) in apical four-chamber
view. LA ⫽ left atrium; LV ⫽ left ventricle; RA ⫽ right atrium; RV ⫽
right ventricle.
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JACC Vol. 46, No. 12, 2005
December 20, 2005:2270–6
Figure 2. Example images of instantaneous proximal flow convergence region (arrows) during regurgitation period with color Doppler imaging (upper).
Typical pattern of mitral regurgitation (MR) flow rate showing an increase to maximum size at early-systole, a decrease at mid-systole, and a re-increase
at late-systole or isovolumetric relaxation period (lower).
Inter-observer and intra-observer variabilities for measurement of MAA, TA, and the radius of MR flow area by
the PFC method were obtained by analysis of 10 random
images by two independent blinded observers and by the
same observer at two different time points. The results were
analyzed by both least squares fit linear regression analysis
and the Bland-Altman method (25).
RESULTS
Dynamic changes of functional MR and mitral valve
deformations. A phasic pattern with two peaks at early- and
late-systole and decrease in mid-systole was noticed in 57 of
60 patients (95%) (Fig. 2). Second peak was observed at
late-systole (n ⫽ 37) or isovolumic relaxation time (n ⫽ 20).
In the remaining three patients (5%), a peak during latesystole or isovolumetric relaxation time was not observed,
and therefore a late-systolic image was defined as image at
end-systole from electrocardiogram. In these three patients,
the etiology of LV disease was idiopathic dilated cardiomyopathy in one and inferoposterior infarction in two. The
QRS duration was 138, 144, and 222 ms, respectively.
In these 60 patients, MR volume and fraction were
54.8 ⫾ 22.3 ml and 51.3 ⫾ 10.9%, respectively. There were
significant differences in MAA, TA, and MR flow rate
among three cardiac phases (all p ⬍ 0.001) (Fig. 3). The
MAA and TA at early-systole were significantly larger than
those at late-systole (7.23 ⫾ 1.43 cm2 vs. 6.23 ⫾ 1.26 cm2
for MAA, and 1.49 ⫾ 0.64 cm2 vs. 1.20 ⫾ 0.52 cm2 for TA,
both p ⬍ 0.01) (Fig. 3). Early-systolic peak of MR flow rate
was much larger than late-systolic peak (128.4 ⫾ 64.3 ml/s
vs. 73.9 ⫾ 55.1 ml/s, p ⬍ 0.001) with a mean value of MR
flow early/late peaks ratio of 2.50 ⫾ 1.99 (Fig. 3). Peak MR
flow rate was significantly correlated with corresponding
MAA and TA in these 60 patients (Table 1).
Relationship of MR dynamics with clinical and echocardiographic findings. By the univariate analysis, QRS duration (r ⫽ 0.55, p ⬍ 0.001), EDV (r ⫽ 0.26, p ⫽ 0.048),
and TA ratio (r ⫽ 0.31, p ⫽ 0.02) were significantly
correlated with MR flow early/late peaks ratio, whereas age
(p ⫽ 0.9), ESV (p ⫽ 0.06), EF (p ⫽ 0.5), MR volume
(p ⫽ 0.4) and fraction (p ⫽ 0.6), and MAA ratio (p ⫽ 0.6)
did not correlate (Table 2 and Fig. 4). There were no
significant differences in MR flow ratio among the patients
Figure 3. Summary of mitral annulus area (A), tenting area (B), and mitral regurgitation (MR) flow rate (C). Note decrease of these parameters during
mid-systole, followed by an increase during late-systole. These parameters at early-systolic peak were larger than those at late-systolic peak.
Fukuda et al.
Electrical Conduction Disturbance and MR
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Table 1. Correlations of MR Flow Rate With Mitral Valve
Deformations in Early- and Late-Systolic Peaks
MAA
TA
r Value
p Value
r Value
p Value
0.36
0.39
0.006
0.002
0.63
0.45
⬍0.001
⬍0.001
0.22
0.19
0.4
0.5
0.70
0.49
⬍0.001
0.03
Overall (n ⫽ 60)
Early-systolic flow
Late-systolic flow
After CRT (n ⫽ 19)
Early-systolic flow
Late-systolic flow
CRT ⫽ cardiac resynchronization therapy; MAA ⫽ mitral annulus area; MR ⫽
mitral regurgitation; TA ⫽ tenting area.
with idiopathic dilated cardiomyopathy (2.97 ⫾ 2.77),
infarction with (1.87 ⫾ 1.41) or without (2.73 ⫾ 1.61)
inferoposterior wall (p ⫽ 0.2). When all significant parameters by univariate analysis were included in the multivariate
regression analysis (QRS duration, EDV, and TA ratio),
QRS duration (p ⬍ 0.001) and TA ratio (p ⫽ 0.04) were
independent factors for MR flow ratio (Table 2). The
partial correlations were 0.48 for QRS duration and 0.29 for
TA ratio.
Both early- and late-systolic peak MR flow rates were
significantly correlated with MR volume (r ⫽ 0.67, p ⬍
0.001 and r ⫽ 0.42, p ⫽ 0.001) and fraction (r ⫽ 0.63, p ⬍
0.001 and r ⫽ 0.43, p ⫽ 0.007), respectively. However,
there were no significant correlations of MR volume (p ⫽
0.4) and fraction (p ⫽ 0.6) with the early/late flow ratio of
these two peaks.
The effect of CRT on dynamics of functional MR. In 19
patients with CRT, EDV (358.7 ⫾ 82.5 ml to 328.3 ⫾ 96.9
ml, p ⫽ 0.01) and ESV (274.8 ⫾ 74.1 ml to 248.8 ⫾ 92.0
ml, p ⫽ 0.03) were significantly reduced after CRT, whereas
EF did not change (23.7 ⫾ 7.8% to 25.3 ⫾ 9.2%, p ⫽ 0.4).
Table 3 shows the results for the measurement of MAA and
TA in early-, mid-, and late-systolic phases before and after
CRT. There were no significant differences in MAA between before and after CRT in any phase. In contrast,
early-systolic TA significantly diminished after CRT,
whereas mid- and late-systolic parameter were unchanged.
The CRT induced 27.0 ⫾ 33.3% reduction in MR
volume from 61.6 ⫾ 19.8 ml to 41.2 ⫾ 14.1 ml (p ⫽ 0.002).
Figure 4. Regression plots showing correlation of QRS duration and the
ratio of early-systolic and late-systolic peaks of mitral regurgitation (MR)
flow.
The MR fraction also decreased from 51.6 ⫾ 8.3% to
39.8 ⫾ 13.1% (p ⫽ 0.002) with 21.6 ⫾ 26.1% reduction.
Comparing instantaneous regurgitation flow among at
early-, mid-, and late-systolic phases, flow rate decreased at
early-systolic, whereas it did not change at mid- and
late-systole (Table 3). Therefore, changes of late-systolic
flow rate (⫺0.7 ⫾ 65.2%) significantly underestimated
those of MR volume (p ⫽ 0.03) and fraction (p ⫽ 0.046).
Changes after CRT in MR volume (p ⫽ 0.5) and fraction
(p ⫽ 0.1) did not significantly differ from that in earlysystolic peak flow (34.3 ⫾ 35.9%). Figure 5 illustrates
typical examples of color Doppler images before and after
CRT. The MR flow rate significantly related to corresponding TA after CRT, whereas no correlation was observed
between MR flow rate and MAA (Table 1).
Observer variability. Correlations for inter-observer and
intra-observer variability of echocardiographic measurements were r ⫽ 0.88 and r ⫽ 0.86 for MAA, r ⫽ 0.87 and
r ⫽ 0.86 for TA, and r ⫽ 0.80 and r ⫽ 0.82 for the radius
of MR PFC area, respectively. From the Bland-Altman
method, inter-observer and intra-observer variabilities were
0.84 cm2 and 0.66 cm2 for MAA, 0.29 cm2 and 0.16 cm2 for
Table 3. The Effect of CRT on Mitral Valve Deformations and
MR Flow Rate
Before CRT
After CRT
p Value
6.13 ⫾ 0.98
5.06 ⫾ 1.48
5.87 ⫾ 1.09
1.05 ⫾ 0.09
5.82 ⫾ 1.23
5.15 ⫾ 1.36
5.67 ⫾ 1.49
1.04 ⫾ 0.09
0.3
0.8
0.5
0.7
1.53 ⫾ 0.54
0.94 ⫾ 0.39
1.23 ⫾ 0.48
1.28 ⫾ 0.26
1.14 ⫾ 0.62
0.75 ⫾ 0.47
1.06 ⫾ 0.56
1.09 ⫾ 0.24
0.003
0.07
0.2
0.03
143.9 ⫾ 60.8
12.7 ⫾ 12.2
61.5 ⫾ 55.0
3.35 ⫾ 2.34
90.7 ⫾ 54.1
11.2 ⫾ 25.8
51.2 ⫾ 40.9
2.26 ⫾ 1.46
0.003
0.8
0.5
0.04
2
Table 2. The Relationships of MR Flow Ratio With Clinical
and Echocardiographic Findings
Age
QRS duration
EDV
ESV
EF
MR volume
MR fraction
MAA ratio
TA ratio
r
Univariate
p Value
0.02
0.55
0.26
0.25
0.01
0.09
0.08
0.07
0.31
0.9
⬍0.001
0.048
0.06
0.5
0.6
0.6
0.6
0.02
Multivariate
p Value
⬍0.001
0.8
0.04
EDV ⫽ end-diastolic volume; EF ⫽ ejection fraction; ESV ⫽ end-systolic volume;
MAA ⫽ mitral annulus area; MR ⫽ mitral regurgitation; TA ⫽ tenting area.
MAA (cm )
Early-systole
Mid-systole
Late-systole
Early/late ratio
TA (cm2)
Early-systole
Mid-systole
Late-systole
Early/late ratio
MR flow rate (ml/s)
Early-systole
Mid-systole
Late-systole
Early/late ratio
CRT ⫽ cardiac resynchronization therapy; MAA ⫽ mitral annulus area; MR ⫽
mitral regurgitation; TA ⫽ tenting area.
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Electrical Conduction Disturbance and MR
JACC Vol. 46, No. 12, 2005
December 20, 2005:2270–6
Figure 5. Examples of color Doppler images before and after cardiac resynchronization therapy (CRT). Before CRT, the proximal flow convergence region
of early-systolic peak was much larger than that of late-systolic peak (A). After CRT, the opposite pattern was observed (B).
TA, and 0.07 cm and 0.07 cm for the radius of MR PFC
area, respectively.
DISCUSSION
The present study demonstrated that dynamic changes of
regurgitation flow during a cardiac cycle were associated
with QRS duration in patients with functional MR. The
phasic pattern of MR changed after CRT as a result of the
reduction of regurgitation flow in early-systole. Similar
changes were observed in tethering of the leaflet rather than
annulus size.
Phasic changes of MR flow and valve deformations. Instantaneous regurgitation flow rate of MR was not fixed
during the regurgitation period, which varied in response to
ventricular volume and shape, load conditions, and etiology
of mitral valve lesions (10 –14). In patients with rheumatic
valve disease, the flow rate was constant, but it was increased
from mid- to late-systole in patients with mitral valve
prolapse (12).
In functional MR from dilated and remodeling LV,
mitral annular enlargement, tethering of the leaflet owing to
displaced papillary muscle, and transmitral pressure were
thought to determine the severity of regurgitation flow
(5–9). These geometric and hemodynamic factors changed
throughout a cardiac cycle, leading to unique phasic variation of functional MR (12–14). Schwammenthal et al. (12),
who had measured the temporal change in regurgitation
flow with the PFC method, found a biphasic pattern with
early- and late-systolic peaks in patients with functional
MR. This initial observation has been experimentally confirmed by Shiota et al. (13) using electromagnetic flowmeters and the PFC method. Hung et al. (14) had shown that
transmitral pressure opposing tethering of the leaflet made a
stronger contribution than annulus area for dynamics of
functional MR.
The mitral deformations (tethering of the leaflet and
annulus dilation) also showed phasic pattern during a
cardiac cycle. Yiu et al. (8) demonstrated that mitral valve
tenting by tethering of the leaflet, which was determined by
displaced papillary muscles and by regional wall motion
abnormality of segments assisting papillary muscles, was the
most powerful predictor for the severity of functional MR.
In their study, early-systolic TA, which was larger than late
systolic TA, showed better correlation with the severity of
MR. On the other hand, Kaplan et al. reported that MAA
in patients with functional MR decreased from early-systole
and increased in the latter half of systole (26). They
suggested that the three-dimensional geometry of MAA
might be different between early- and late-systole. Therefore, mitral valve deformations might have different effects
on MR during these two systolic phases. Actually, we
noticed that changes of tethering of the leaflet and regurgitation flow rate after CRT were different between earlyand late-systole, indicating the differences of determinant
factors between these two peaks. However, the mechanisms
of the phasic pattern of functional MR remained unknown.
Effect of CRT on functional MR. Recent studies showed
acute beneficial effects of CRT in patients with functional
MR (20,21). Breithardt et al. (20) had reported that an
increase of transmitral pressure, generating closing force to
the leaflet, was an important factor for reduction of MR in
the first week after CRT. They found that an increase in
transmitral pressure provided decreased tethering of the
leaflet. Kanzaki et al., who measured regional mechanical
synchrony by echocardiographic strain imaging technique,
demonstrated that re-coordinated synchrony between papillary muscle insertion segments by CRT related to the
reduction of MR, whereas mitral annulus size was not
changed after CRT (21). In the present study, CRT
provided approximately a 25% reduction of functional MR
⬎3 months after pacemaker implantation. The TA decreased at early-systole, although MAA did not change
during any phases. As a consequence, in both short-term
and mid-term follow-up periods, reduction of MR after
JACC Vol. 46, No. 12, 2005
December 20, 2005:2270–6
CRT might be caused by alternation of tethering of the
leaflet rather than annulus dilation. Uncoordinated regional
LV activation in the segments attaching papillary muscles
might prevent the optimal timing and position for
coaptation of mitral valve leaflets (20,21). Additionally,
we demonstrated that regurgitation flow decreased after
CRT only in early-systole, not in late-systolic peak,
suggesting that early-systolic regurgitation flow might be
caused by severe ventricular asynchrony. The CRT might
re-coordinate regional LV activation, leading to reduction of early-systolic MR.
Study limitations. Several limitations of our study should
be mentioned. First, the number of patients was small (n ⫽
60), and CRT was performed only in 19 patients (32%) with
relatively wide QRS duration (161.6 ⫾ 33.3 ms). Nonselected and randomized studies are necessary to test the
effect of CRT on the phasic pattern of MR in patients with
narrow QRS duration. Additionally, 2 of 60 patients had
pacemaker-induced rhythm, although the mechanical ventricular asynchrony induced by pacing might be different
from the remaining patients.
Second, mitral valve deformations and PFC areas were
estimated by two-dimensional echocardiography. The imaging planes of two-dimensional echocardiography during
systole may not have been fixed at the same location of the
mitral valve orifice, although we carefully selected stable
images during image acquisition. Three-dimensional echocardiography allows us to assess these parameters more accurately without elliptic (27) or hemispheric assumptions (28).
In addition, PFC area of regurgitation flow was measured
by color two-dimensional Doppler imaging with a mean
frame rate of 22.4 ⫾ 7.2 Hz when the images were
expanded by using regional expansion selection mode. Color
M-mode imaging could provide higher temporal resolution.
However, its cursor direction might not be placed parallel to
the axis of PFC area.
Third, observer variability of echocardiography was based
on the measurement only. Reproducibility of image acquisition was not examined. Additionally, observer variability
of PFC area of MR was relatively low, and might have
affected the results in this study. However, because most
patients showed similar results on dynamic changes of MR
flow, our essential message on this matter would hold true.
Finally, the duration of the QRS complex from the
12-lead surface electrocardiogram might not be an optimal
marker to address ventricular asynchrony, although it was
used to select candidates for CRT in the previous studies
(15,16,18 –21). The electrical conduction disturbance and
mechanical ventricular asynchrony might be different, although there was a close relationship. Recently introduced
echocardiographic techniques, such as tissue Doppler imaging and strain-rate imaging, have a potential for more
accurate assessment of global and regional ventricular systolic asynchrony (29,30). Further studies may be needed to
confirm our results by using these techniques.
Fukuda et al.
Electrical Conduction Disturbance and MR
2275
Conclusions. Biphasic pattern was found in functional
MR, and the ratio of flow rate at two peaks correlated with
QRS duration. The CRT decreased regurgitation flow volume
by reducing early-systolic MR but not late-systolic MR,
resulting in the change in phasic pattern of functional MR.
Reprint requests and correspondence: Dr. Takahiro Shiota,
Department of Cardiovascular Medicine, Cleveland Clinic Foundation, 9500 Euclid Avenue, Desk F15, Cleveland, Ohio 44195.
E-mail: [email protected].
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