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54
CARDIOVASCULAR MEDICINE
Heart 2003;89:5460
.......................
Correspondence to:
Dr C-M Yu, Department of
Medicine, Prince of Wales
Hospital, The Chinese
University of Hong Kong,
Hong Kong;
cmyua@hkucc.hku.hk
Accepted 28 August 2002
.......................
Objective: To study the possible occurrence of left ventricular (LV) systolic and diastolic asynchrony in
patients with systolic heart failure (HF) and narrow QRS complexes.
Design: Prospective study.
Setting: University teaching hospital.
Patients: 200 subjects were studied by echocardiography. 67 patients had HF and narrow QRS complexes (< 120 ms), 45 patients had HF and wide QRS complexes (> 120 ms), and 88 served as normal controls.
Interventions: Echocardiography with tissue Doppler imaging was performed using a six basal, six
mid-segmental model.
Main outcome measures: Severity and prevalence of systolic and diastolic asynchrony, as assessed
by the maximal difference in time to peak myocardial systolic contraction (TS) and early diastolic
relaxation (TE), and the standard deviation of TS (TS-SD) and of TE (TE-SD) of the 12 LV segments.
Results: The mean (SD) maximal difference in TS (controls 53 (23) ms v narrow QRS 107 (54) ms v
wide QRS 130 (51) ms, both p < 0.001 v controls) and in TS-SD (controls 17.0 (7.8) ms v narrow QRS
33.8 (16.9) ms v wide QRS 42.0 (16.5) ms, both p < 0.001 v controls) was prolonged in the narrow
QRS group compared with normal controls. Similarly, the maximal difference in TE (controls 59 (19) ms
v narrow QRS 104 (71) ms v wide QRS 148 (87) ms, both p < 0.001 v controls) and in TE-SD (controls
18.5 (5.8) ms v narrow QRS 33.3 (27.7) ms v wide QRS 48.6 (30.2) ms, both p < 0.001 v controls)
was prolonged in the narrow QRS group. The prevalence of systolic and diastolic asynchrony was 51%
and 46%, respectively, in the narrow QRS group, and 73% and 69%, respectively, in the wide QRS
group. Stepwise multiple regression analysis showed that a low mean myocardial systolic velocity from
the six basal LV segments and a large LV end systolic diameter were independent predictors of systolic
asynchrony, while a low mean myocardial early diastolic velocity and QRS complex duration were
independent predictors of diastolic asynchrony.
Conclusions: LV systolic and diastolic mechanical asynchrony is common in patients with HF with narrow QRS complexes. As QRS complex duration is not a determinant of systolic asynchrony, it implies
that assessment of intraventricular synchronicity is probably more important than QRS duration in considering cardiac resynchronisation treatment.
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55
Table 1 Clinical characteristics of patients with heart failure with narrow and wide
QRS complexes
Age (years)
Male:female (%)
QRS duration (ms)
Causes of heart failure (%)
Coronary artery disease
Dilated cardiomyopathy
Hypertension
Valve disease
Alcoholic cardiomyopathy
Diabetes mellitus (%)
Hypertension (%)
Medications (%)
ACEI
Diuretics
Aspirin
Blockers
Nitrates
Calcium antagonists
Digitalis
Lipid lowering drugs
P value
65.7 (13.2)
73:27
99 (11)
67.6 (10.4)
78:22
155 (23)
0.31
NS
NS
<0.001
70
21
6
1.5
1.5
33
50
54
40
4
0
2
39
42
6.23
NS
0.41
0.50
NS
NS
72
62
69
30
53
9
16
35
71
83
53
34
44
5
19
21
0.01
5.82
2.52
0.14
0.90
0.38
0.21
2.37
NS
0.02
NS
NS
NS
NS
NS
NS
METHODS
Patients
One hundred and twelve patients (75% men) who had been
admitted to hospital for clinical signs and symptoms of HF
and had impaired systolic function by echocardiography
(ejection fraction < 50%) were recruited. They were stabilised
by anti-HF medications and underwent elective tissue Doppler
imaging 46 weeks later. Of these, 71 had coronary artery disease, 32 had dilated cardiomyopathy, 6 had hypertensive heart
disease, 2 had alcoholic cardiomyopathy, and 1 had aortic valve
heart disease. Patients with coronary artery disease had either
previous evidence of myocardial infarction (n = 52) diagnosed by standard criteria or angiographic evidence of significant disease with or without previous percutaneous coronary
intervention (n = 19). Patients with atrial fibrillation were
excluded from the study. Among the participating patients,
QRS complexes were narrow (> 120 ms; narrow QRS group)
in 67 (60%) and prolonged (< 120 ms; wide QRS group) in 45
(40%) (table 1). The results of echocardiography were
compared with those of 88 normal healthy volunteers (62%
men, 2 = 1.31, NS v HF group). The volunteers had no history
of cardiovascular or systemic diseases and had normal physical examination, and electrocardiographic and echocardiographic findings.
Echocardiography
Standard echocardiography with Doppler studies were performed (System 5, Vingmed-General Electric, Horten, Norway). LV dimension and ejection fraction were measured by
two dimensional guided M mode echocardiography according
to the guidelines of the American Society of Echocardiography.13 Tissue Doppler imaging was performed in the
apical views (four chamber, two chamber, and long axis) for
the long axis motion of the LV as previously described.12 14 In
brief, two dimensional echocardiography with tissue Doppler
colour imaging was performed with a 2.5 or 3.5 MHz phase
array transducer. The system was set by bypassing the high
pass filter, while the low frequency Doppler shifts were input
directly into an autocorrelator.15 Gain settings, filters, and
pulse repetitive frequency were adjusted to optimise colour
saturation, and a colour Doppler frame scanning rate of 100
140 Hz was used. At least three consecutive beats were stored
and the images were digitised and analysed off line by a computer (EchoPac 6.3, Vingmed-General Electric). Myocardial
regional velocity curves were constructed from the digitised
RESULTS
There was no difference in age between the patient group as a
whole and normal controls (66 (12) v 64 (10) years, NS). The
heart rate was observed to be faster in the patient group than
in controls (73 (15) v 65 (11) beats/min, p < 0.001). However,
age and heart rate were not confounders of systolic and
diastolic asynchrony according to analysis of covariance, and
hence unadjusted p values are presented. Table 1 shows the
comparison of baseline clinical characteristics between the
narrow and wide QRS groups. The age, sex, and aetiology of
HF were not different between the two groups. The
prescription of medications was also similar except for a
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Table 2 Comparison of time to peak myocardial sustained systolic velocity (TS) (in ms) between heart failure patients
with narrow and wide QRS complexes and normal controls
Segment
1. Controls
(n=88)
2. Narrow QRS
(n=67)
3. Wide QRS
(n=45)
p Value
(1 v 2)
p Value
(1 v 3)
p Value
(2 v 3)
Basal septal
Basal anteroseptal
Basal anterior
Basal lateral
Basal posterior
Basal inferior
Mid-septal
Mid-anteroseptal
Mid-anterior
Mid-lateral
Mid-posterior
Mid-inferior
Maximal difference in TS
TS-SD
127 (19)
124 (18)
125 (26)
131 (23)
131 (25)
129 (23)
130 (28)
125 (25)
126 (29)
125 (29)
125 (25)
136 (30)
53 (23)
17.0 (7.8)
165 (40)
165 (43)
179 (56)
184 (58)
180 (50)
177 (46)
173 (45)
158 (43)
177 (55)
191 (66)
184 (55)
195 (59)
107 (54)
33.8 (16.9)
192 (52)
176 (45)
185 (43)
211 (56)
204 (50)
193 (47)
206 (62)
183 (63)
179 (51)
195 (57)
201 (60)
212 (53)
130 (51)
42.0 (16.5)
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
0.001
NS
NS
0.01
0.02
NS
0.001
0.02
NS
NS
NS
NS
0.02
0.009
Systolic asynchrony
The systolic synchronicity was impaired in patients with HF.
The maximal difference in TS was prolonged in the narrow
QRS group compared with normal controls (p < 0.001) and
was the longest in the wide QRS group (table 2, fig 1).
Similarly, the TS-SD was significantly prolonged in the narrow
QRS group (p < 0.001), though it was further increased in the
wide QRS group (table 2, fig 2A). When a maximal difference
of TS of > 100 ms was used to define significant systolic asynchrony, it was not found in the control group but was present
in 34 (51%) patients in the narrow QRS group and in 33 (73%)
in the wide QRS group (2 = 83.2, p < 0.001). When a TS-SD
of > 32.6 ms (+ 2 SD of normal controls) was used to define
significant systolic asynchrony, it was present in only 3 (3%)
control subjects but in 29 (43%) patients in the narrow QRS
group and in 29 (64%) in the wide QRS group (2 = 58.3,
p < 0.001). In addition, systolic asynchrony was more
prevalent in patients with wide than in those with narrow
QRS complexes by both maximal difference in TS (2 = 5.7,
p = 0.02) and in TS-SD (2 = 4.8, p = 0.03).
Table 2 shows the regional TS in individual LV segments. It
was significantly delayed in all 12 LV segments in both narrow
and wide QRS groups compared with normal controls. In
addition, it was further prolonged in some of the LV segments
in the wide QRS group compared with the narrow QRS group.
Diastolic asynchrony
Similar to systole, diastolic asynchrony was also evident in
patients with HF. The maximal difference in TE was prolonged
in the narrow QRS group (p < 0.001) and was the longest in
the wide QRS group (table 3, fig 1). In addition, TE-SD was
significantly longer in the narrow QRS group than in the normal controls (p < 0.001) and was further prolonged in the
wide QRS group (table 3, fig 2B). When a maximal difference
of TE of > 100 ms was used to define significant diastolic
asynchrony, it was not found in the normal controls but was
present in 31 patients (46%) in the narrow QRS group and 31
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57
Figure 2 Regional myocardial
velocity curves obtained by tissue
Doppler imaging at the basal septal
(yellow) and basal lateral (green)
segments. In the left hand panels the
systolic movement of the myocardium
is encoded by colour Doppler with
movement towards the probe shown
in red and that away from the probe
in blue. (A) In the normal control,
there is simultaneous peaking of
systolic contraction (SM) and early
diastolic relaxation (EM) in the basal
septal and basal lateral segments in
the apical four chamber view. Tissue
colour tracking shows systolic
contraction in red in both regions.
(B) In patients with heart failure and
normal QRS duration, there is a
dramatic reduction in the amplitude
of peak SM and peak EM in both
regions. In addition, there is delay in
reaching peak SM in the basal lateral
segment EM of 120 ms. A difference
in peak early diastolic relaxation of
60 ms is also seen. Tissue tracking in
early systole shows a delayed systolic
movement in the basal and
mid-lateral segments, shown in blue
(arrow heads).
DISCUSSION
The present study illustrates the changes in systolic and
diastolic synchronicity in patients with HF. Irrespective of QRS
duration, patients with HF could develop mechanical asynchrony in both systole and diastole. Although the condition
was more prevalent in the wide QRS group, it was not uncommon in patients with narrow QRS complexes. Among various
clinical and echocardiographic predictors of asynchrony, it was
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Table 3 Comparison of time to peak myocardial early diastolic velocity (TE) (in ms) between heart failure patients with
narrow and wide QRS complexes and normal controls
Segment
1. Controls
(n=88)
2. Narrow QRS
(n=67)
3. Wide QRS
(n=45)
p Value
(1 v 2)
p Value
(1 v 3)
p Value
(2 v 3)
Basal septal
Basal anteroseptal
Basal anterior
Basal lateral
Basal posterior
Basal inferior
Mid-septal
Mid-anteroseptal
Mid-anterior
Mid-lateral
Mid-posterior
Mid-inferior
Maximal difference in TE
TE-SD
515 (39)
532 (42)
526 (41)
519 (40)
519 (41)
514 (41)
534 (38)
543 (40)
540 (38)
538 (41)
538 (47)
539 (40)
59 (19)
18.5 (5.8)
556 (86)
544 (63)
545 (65)
539 (73)
531 (71)
546 (70)
545 (72)
543 (67)
545 (71)
537 (74)
545 (80)
568 (70)
104 (71)
33.3 (27.7)
559 (75)
561 (84)
541 (91)
544 (74)
558 (97)
560 (85)
556 (92)
553 (78)
521 (74)
542 (80)
547 (100)
576 (86)
147 (87)
48.6 (30.2)
0.001
NS
NS
NS
NS
0.02
NS
NS
NS
NS
NS
0.004
<0.001
<0.001
0.002
0.047
NS
NS
0.02
0.001
NS
NS
NS
NS
NS
0.007
<0.001
<0.001
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
0.001
0.002
Table 4
Correlation between systolic or diastolic asynchrony and various clinical and echocardiographic parameters
Age
Heart rate
QRS duration
Ejection fraction
Mean SM
Mean EM
LVDd
LVDs
Maximal difference in TS
TS-SD
p Value
0.12
0.14
0.11
0.60
0.60
0.50
0.55
0.61
NS
NS
NS
<0.001
<0.001
<0.001
<0.001
<0.001
0.08
0.15
0.12
0.60
0.60
0.50
0.55
0.61
Maximal difference in TE
TE-SD
p Value
p Value
p Value
NS
0.04
NS
<0.001
<0.001
<0.001
<0.001
<0.001
0.15
0.18
0.35
0.46
0.39
0.50
0.46
0.49
0.04
0.01
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
0.12
0.17
0.35
0.44
0.37
0.46
0.42
0.46
0.05
0.01
<0.001
<0.001
<0.001
<0.001
<0.001
<0.001
LVDd, left ventricular end diastolic diameter; LVDs, left ventricular end systolic diameter; Mean EM, mean myocardial early diastolic velocity from the six
basal left ventricular segments; Mean SM, mean myocardial sustained systolic velocity from the six basal left ventricular segments.
Table 5 Stepwise multiple regression analysis comparing the correlation between systolic or diastolic asynchrony and
various clinical and echocardiographic parameters
Age
Heart rate
QRS duration
Ejection fraction
Mean SM
Mean EM
LVDd
LVDs
Maximal difference in TS
TS-SD
p Value
p Value
Maximal difference in TE
0.08
0.05
0.15
0.03
8.32
0.05
0.001
12.23
NS
NS
NS
NS
0.02
NS
NS
0.009
0.04
0.04
0.13
0.03
2.67
0.04
0.03
3.89
NS
NS
NS
NS
0.02
NS
NS
0.009
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0.12
0.06
0.71
0.15
0.19
13.69
0.09
0.04
TE-SD
p Value
p Value
NS
NS
<0.001
NS
NS
<0.001
NS
NS
0.03
0.05
0.25
0.12
0.18
4.57
0.07
0.02
NS
NS
<0.001
NS
NS
<0.001
NS
NS
dynamic, clinical, or echocardiographic improvement after biventricular pacing. On the other hand, the mechanism of benefit
of biventricular pacing is attributed to the improvement of
intraventricular systolic synchrony, which was shown recently
by means of tissue Doppler imaging, where the TS-SD was
shortened and the intersegmental difference in TS was
minimised after biventricular pacing.7 9 10 Also, in patients
undergoing biventricular pacing, systolic asynchrony, but not
QRS complex duration, proved to be a better predictor of acute
haemodynamic,4 echocardiographic,8 or clinical response.7 Despite improving knowledge of systolic synchronicity in HF
patients with wide QRS complexes, it remains unclear whether
cardiac diseases may result in systolic asynchrony even in
patients with narrow QRS complexes. This study illustrates that
systolic asynchrony is a common feature in these patients. Two
59
Authors affiliations
C-M Yu, H Lin, Q Zhang, J E Sanderson, Division of Cardiology,
Department of Medicine, Prince of Wales Hospital, The Chinese
University of Hong Kong, Hong Kong
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IMAGES IN CARDIOLOGY.............................................................................
Fragile left atrial thrombus successfully treated with anticoagulants
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doi: 10.1136/heart.89.1.54
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