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Cardiovascular Research 43 (1999) 58–66
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Assessment of the functional status of heart failure in non ischemic dilated
cardiomyopathy: an echo-dobutamine study
Ioannis A. Paraskevaidis*, Dimitrios P. Tsiapras, Stamatis Adamopoulos, Dimitrios Th. Kremastinos
2 nd Department of Cardiology, Onassis Cardiac Surgery Center, 356 Sygrou Avenue, GR-17674 Athens, Greece
Received 16 September 1998; accepted 1 December 1998
Abstract
Background: The functional status of heart failure (HF) is conventionally evaluated by peak exercise oxygen consumption (VO 2 max).
Dobutamine echocardiography can be used to evaluate myocardial reserve. The aim of this study was to estimate the functional status of
chronic HF in patients with dilated cardiomyopathy, by investigating the changes in echo-variables, as assessed by echo-dobutamine, in
relation with VO 2 max. Methods and results: A low infusion rate echo-dobutamine test (10 mg / kg / min) was performed in 30 patients
with dilated cardiomyopathy and 1 h later VO 2 max was measured. VO 2 max (ranging from 7.6 to 23 ml / kg / min, mean 14.0660.64
ml / kg / min) was correlated with the changes (values obtained after inotropic stimulation minus those obtained at baseline) in left
ventricular end-systolic diameter (r:0.80, p:0.001), in left ventricular end-systolic posterior wall thickness (r:0.73, p:0.001) and in left
ventricular heart-rate corrected mean velocity of circumferential fiber shortening (Vcfc) / end-systolic meridional wall stress ratio (r:0.64,
p:0.0001). A negative correlation was found between VO 2 max and the changes in end-systolic meridional wall stress (r: 20.76, p:0.001).
After dobutamine infusion Vcfc / systolic meridional wall stress ratio increased in patients with VO 2 max .14 ml / kg / min but decreased in
patients with VO 2 max ,14 ml / kg / min (0.000160.0001 vs 20.000260.0003 circ3cm 2 / g3s, p:0.0001). End-systolic meridional wall
stress was decreased in patients with VO 2 max .14 ml / kg / min but increased in patients with VO 2 max ,14 ml / kg / min
(2126.97634.24 vs 205.77656.71 g / cm 2 , p:0.0001). Conclusion: The changes in echo-variables assessed by echo-dobutamine are well
correlated with VO 2 max and seem to be accurate for evaluating the functional status of chronic HF in patients with dilated
cardiomyopathy.  1999 Elsevier Science B.V. All rights reserved.
Keywords: Cardiomyopathy; Contractile function; Heart failure; Inotropic agents; Transplantation
1. Introduction
Despite continuing advances in the diagnosis and
therapy of heart failure (HF) the mortality of this
syndrome remains high [1]. Although various parameters
have been used to assess the severity of congestive HF
[2,3], they have several potential limitations [4]. Recent
American Heart Association consensus reports have recommended that peak exercise oxygen consumption (VO 2
max) can be used to evaluate objectively the functional
*Corresponding author. Tel.: 130-1-9406-184 or 130-1-9393-372;
fax: 130-1-9393-373 or 130-1-9393-331.
E-mail address: [email protected] (I.A. Paraskevaidis)
status of HF [5]. Specifically, it has been suggested that, in
spite of similar left ventricular ejection fraction, patients
with VO 2 max more than 14 ml / kg / min have a far better
prognosis than those with VO 2 max less than 14 ml / kg /
min [6]. However, several groups have found no statistical
difference in survival between patients with VO 2 max
levels in the range of 10 to 14 ml / kg / min and those with
levels in the range of 14 to 18 ml / kg / min [7].
Although, several echocardiographic indexes have been
proposed as prognostic indicators in chronic HF [8,9];
these indexes represent the functional status of the heart at
rest. In patients with HF, both the response of cardiac
Time for primary review 26 days.
0008-6363 / 99 / $ – see front matter  1999 Elsevier Science B.V. All rights reserved.
PII: S0008-6363( 98 )00345-9
I. A. Paraskevaidis et al. / Cardiovascular Research 43 (1999) 58 – 66
output to exercise and VO 2 max provide valuable independent prognostic information regarding the functional
status of the failing heart [10], indicating that the ability of
the failing heart to maintain an adequate cardiac output
depends on its functional reserve.
Dobutamine stress echocardiography is receiving increasing attention in relation to patients with coronary
artery disease [11]. Moreover, by its well known direct
positive inotropic action, it is known to increase cardiac
performance in patients with HF [12]. In this regard, it has
been suggested that dobutamine can be used in order to
evaluate myocardial reserve, which is a better descriptor of
the functional status of the heart than rest indexes or
indexes based on volumetric measurements [13]. This has
been confirmed in several subgroups of patients with
chronic heart failure due to coronary artery disease [14],
left ventricular hypertrophy [15], dilated cardiomyopathy
[16], or after cardiac transplantation [17].
The aim of this study was to estimate the functional
status of chronic HF in patients with dilated cardiomyopathy, by investigating the changes in echo-variables, assessed by echo-dobutamine, in relation with VO 2
max.
2. Methods
2.1. Study patients
Thirty one consecutive patients with documented dilated
cardiomyopathy were studied. Thirty patients (97%) 21
men and 9 women, mean age 55610 years, with good
quality M-mode and 2-dimensional echocardiography were
recruited for analysis. The cause of dilated cardiomyopathy
was idiopathic in 25 patients while an evidence of myocarditis based on clinical, ECG and echocardiographic findings, was reported in five patients. Nine patients were in
New York Heart Association functional class II, thirteen
were in class III, and eight were in class III–IV. Diagnosis
of dilated cardiomyopathy was based on the echocardiographic findings of a dilated left ventricle (left ventricular
end-diastolic diameter .60 mm) with severely affected
systolic function; fractional shortening ,20% and ejection
fraction below 35%. In no case was a significant regional
wall motion abnormality recorded by two-dimensional
echocardiography. Coronary angiography performed in all
patients revealed no coronary artery disease. All patients
were in sinus rhythm and were under digoxin, angiotensinconverting enzyme inhibitors and diuretic drugs in
adequate doses. Patients with rhythm disturbances, ischemic cardiomyopathy, more than mild valvular heart
disease, or regional wall motion abnormalities were excluded. Transthoracic echocardiography was performed
and the echocardiographic variables were measured at
baseline and after dobutamine infusion. One hour later VO 2
max was calculated. All patients gave informed consent.
59
2.2. Echocardiography
Measurements and tracings were carried out according
to the principle of the leading edge, in accordance with the
recommendations of the American Society of Echocardiography [18]. Left ventricular dimensions and wall thickness
were measured from parasternal targeted M-mode echocardiographic recordings. Care was taken to record the
largest and smallest left ventricular dimensions present
between the tips of the mitral valve leaflets and the
superior aspect of the papillary muscles. End-diastolic
diameter was taken at the Q wave of the electrocardiogram. End-systolic dimension was determined to be the
shortest distance between walls rather than at the time of
peak downward septal motion [19]. Using a HewlettPackard (Sonos 1000 or 2500) ultrasound device the
following echocardiographic variables were measured at
baseline and after the end of 10 mg / kg / min of dobutamine
infusion: (1) Left ventricular end-diastolic (LVEDD) and
end-systolic diameter (LVESD) and the derived fractional
shortening, FS5[(LVEDD2LVESD) / LVEDD]3100; (2)
maximal ventricular septum and posterior wall thickness
(PWTH) in systole(s); (3) end-systolic meridional wall
stress, calculated using the formula: systolic blood
pressure 3 LVESD 3 1.35 / 4 3 PWTHs 3 (1 1 PWTHs) /
LVESD [20] (systolic blood pressure was represented by
brachial artery systolic pressure and was measured every
minute with a cuff sphygmomanometer); Although the
above variables are easily calculated by echocardiography,
care must be taken to make accurate calculations. (4) left
ventricular heart-rate corrected mean velocity of circumferential fiber shortening (Vcfc), calculated as follows:
Vcfc5(%FS / LVET)3RR [20]. (LVET represents left ventricular ejection time in milliseconds from the opening to
the closing clicks of the aortic valve flow velocity envelope by continuous-wave Doppler imaging); (5) Vcfc /
systolic meridional wall stress ratio; (6) cardiac output,
calculated as the product of stroke volume3heart rate
(stroke volume, was calculated according to the formula:
p / 43(aortic diameter)2 3aortic velocity–time integral.
Aortic diameter was measured in a two-dimensional
parasternal long axis view, just below the aortic orifice,
from the inner echo at rest only, because the aortic valve is
thought to remain constant during exercise or dobutamine
infusion [21]. Aortic velocities were measured by continuous Doppler in an apical five chamber view; (7) from 2D
echocardiography and using the modified Simpson’s rule
technique, end-diastolic and end-systolic volumes were
calculated and ejection fraction was derived [(end diastolic-end systolic volume) / end diastolic volume]3100.
Vcfc / end systolic meridional wall stress ratio was also
measured as an index of myocardial contractile reserve.
The latter index is a preload and heart rate-independent
index of contractility that incorporates afterload [15]. The
changes in the above echocardiographic variables after
dobutamine infusion were also calculated. Changes repre-
60
I. A. Paraskevaidis et al. / Cardiovascular Research 43 (1999) 58 – 66
sent the values obtained after inotropic stimulation minus
those obtained at baseline. All measurements were made at
a speed paper of 100 mm / s and represent the average of
the measurements of five consecutive beats. In all cases
echocardiograms were analyzed by two independent expert
observers. In cases of discrepancy the average was calculated and the mean value was reported.
2.3. Dobutamine infusion
Dobutamine was infused intravenously in two steps after
establishment of a stable hemodynamic state (heart rate,
blood pressure). The duration of each step was 5 min and
the maximal end dose of dobutamine infused was 10
mg / kg / min [22]. At each step dobutamine infusion was
increased by 5 mg / kg / min, reaching 10 mg / kg / min at the
second step. Every minute during the protocol, systolic,
diastolic and hence mean arterial blood pressure (Siemens,
Sirecust 888 device), heart rate and a 12-lead electrocardiogram were recorded.
2.4. Cardiopulmonary exercise testing
Exercise testing with respiratory gas exchange measurements was performed while patients exercised on a treadmill according to the Dargie protocol [23]. Oxygen consumption, carbon dioxide production and respiratory exchange ratio were measured continuously during exercise
using the Medgraphics CPX / MAX automated gas exchange measuring system, which provides the above gas
exchange data for each individual breath (which can then
be averaged over a 5 s interval). Blood pressure was
measured with a mercury sphygmomanometer and the
electrocardiogram was monitored continuously with a
computer-assisted system (Marquette Electronics Inc.).
Patients were familiar with exercise testing and they were
encouraged to exercise until symptoms forced them to
stop. All patients terminated the test because of dyspnea or
fatigue, and in all patients the gas exchange anaerobic
threshold (the point at which carbon dioxide production
increased disproportionately in relation to oxygen consumption) and a respiratory exchange ratio .1.0 were
reached. Peak oxygen consumption (ml / min / kg) at peak
exercise was calculated as the mean of values during the
last minute of exercise.
2.5. Statistical analysis
All values are expressed as mean6standard error. An
unpaired two-tailed t-test was used to compare values
between groups; a paired two-tailed t-test was used to
compare the differences between values in the same group
before and after inotropic stimulation. Linear regression
analysis was employed for the assessment of the correlation between VO 2 max and the echocardiographic measurements. To assess reproducibility (inter-and intra-ob-
server variability) root mean square differences between
duplicate determinations was performed. A p value ,0.05
was considered statistically significant.
3. Results
No major side effects were reported during dobutamine
infusion. The VO 2 max measured in all patients ranged
from 7.6 to 23 ml / kg / min (mean 14.0660.64 ml / kg / min).
3.1. Echocardiographic measurements
The echocardiographic measurements of the whole study
group at baseline and after dobutamine infusion are shown
in Table 1. The changes in the echocardiographic variables
are also reported in Table 1. After dobutamine infusion
statistically significant increases in fractional shortening
( p:0.004) and ejection fraction ( p:0.005) were observed.
Systolic blood pressure increased at borderline significance
( p:0.06), while mean blood pressure significantly decreased ( p:0.000). Heart rate, stroke volume and consequently cardiac output significantly increased ( p:0.02,
p:0.0000 and p:0.0000, respectively). Vcfc and Vcfc / endsystolic meridional wall stress significantly increased
( p:0.001 and p:0.04, respectively). The other echocardiographic variables did not change significantly after inotropic
stimulation.
The correlation between VO 2 max and the changes in
echocardiographic variables are shown in Table 2.
3.2. Response of echocardiographic variables to
dobutamine in patients with high vs those with low VO2
max
The study population was further divided in two groups;
Group I (17 patients), comprised patients with VO 2 max
more than 14 ml / kg / min (mean 16.3660.66 ml / kg / min)
and group II (13 patients) patients with VO 2 max less than
14 ml / kg / min (mean 11.160.49 ml / kg / min).
The values of the echocardiographic variables before
and after inotropic stimulation with dobutamine are shown
in Tables 3 and 4. In Table 5 are shown the significant
changes of the echocardiographic variables; in group I
posterior wall systolic thickness increased, whereas in
group II it decreased ( p:0.0001). End systolic diameter
end-systolic meridional wall stress and end-diastolic diameter decreased in group I but increased in group II
( p:0.001), ( p:0.0001), ( p:0.003), respectively. Shortening
and ejection fraction increased more in group I than in
group II ( p:0.02 for both). Vcfc increased in group I but
was unchanged in group II ( p:0.02). Vcfc / end-systolic
meridional wall stress increased in group I but decreased in
group II ( p:0.0001). After dobutamine infusion the
changes in the other echocardiographic variables were not
statistically different between the groups.
I. A. Paraskevaidis et al. / Cardiovascular Research 43 (1999) 58 – 66
61
Table 1
Echocardiographic and other measurements before and after dobutamine infusion in the whole study group (n: 30)
IVSs (cm)
PWTHs (cm)
EDD (cm)
ESD (cm)
FS (%)
2-D EF (%)
SV (ml)
CO (l / min)
SWS (g / cm 2 )
Vcfc (circ / s)
Vcfc / SWS (circ*cm 2 / g*s)
SBP (mm Hg)
MBP (mm Hg)
HR (beats / min)
Before
After
Change
p value
0.9660.03
1.2360.05
7.2260.14
6.2760.13
13.1160.47
23.0161.25
39.7861.66
3.5560.06
577.58649.56
0.4360.01
0.000960.0000
109.761.4
76.1360.89
92.4362.90
0.9960.03
1.2560.06
7.2460.16
6.1460.15
15.1460.51
28.0561.42
47.3162.28
4.3860.09
594.8658.83
0.4960.02
0.00160.0001
112.2761.36
68.4310.94
96.163.0
0.0360.03
0.00960.04
0.01760.07
20.1360.07
2.0360.64
5.0461.68
7.5461.22
0.8360.08
17.22643.37
0.0660.02
0.000260.0001
2.5361.30
2 7.760.70
3.6761.44
NS
NS
NS
NS
0.004
0.005
0.0000
0.0000
NS
0.001
0.04
NS(0.06)*
0.0000
0.02
* Borderline statistical significance. Change represents the values obtained after inotropic stimulation minus those obtained at baseline.
CO, cardiac output; EDD, end-diastolic diameter; 2D EF, ejection fraction measured by 2-dimensional echocardiography; ESD, end-systolic diameter; FS,
fractional shortening; HR, heart rate; IVSs, ventricular septum thickness in systole; PWTHs, left posterior wall thickness in systole; MBP, mean blood
pressure; SBP, systolic blood pressure; SV, stroke volume; SWS, end-systolic meridional wall stress; Vcfc, left ventricular heart-rate corrected mean
velocity of circumferential fiber shortening.
Table 2
Correlation between VO 2 max and the changes in echocardiographic variables
Variable
Cor. coef.
p value
Intercept
Slope
Std. err.
LPWT
ESD
SWS
EDD
Vcfc
Vcfc / SWS
0.73
20.80
20.76
20.72
0.37
0.64
0.001
0.001
0.001
0.001
0.04
0.0001
13.97 (13.05–14.88)
13.16 (12.32–14)
14.26 (13.38–15.13)
14.18 (13.23–15.11)
13.43 (12.03–14.82)
12.03 (10.92–13.13)
11.26
26.9
20.01
26.46
10.8
5414.50
2.43
2.13
2.33
2.5
3.33
2.77
Cor. coef.: correlation coefficient, Std. err.: standard error. The other abbreviations as in Table 1. Values in parenthesis represent the lower and upper 95%
confidence limit.
Plotting the variables VO 2 max vs. the changes in
Vcfc / end-systolic meridional wall stress ratio (Fig. 1), VO 2
max vs the changes in left ventricular end systolic diameter, (Fig. 2), and VO 2 max vs the changes in left
ventricular posterior wall thickness (Fig. 3), on a scatter-
plot shows the linear relationship and in addition we can
make the following observations. Firstly, the trend line
(linear regression model) of the above variables cuts the x
axis at the value 12, 13, or 14 ml / kg / min for VO 2 max
respectively indicating that we may expect an improve-
Table 3
Echocardiographic variables before dobutamine infusion in the patients with VO 2 max .14 ml / kg / min (Group I, n:17), and in the patients with VO 2 max
,14 ml / kg / min (Group II, n:13)
IVSs (cm)
PWTHs (cm)
EDD (cm)
ESD (cm)
FS (%)
2-D EF (%)
SV (ml)
CO (l / min)
SWS (g / cm 2 )
Vcfc (circ / s)
Vcfc / SWS (circ*cm 2 / g*s)
SBP (mm Hg)
MBP (mm Hg)
HR (beats / min)
Abbreviations as in Table 1.
Group I
Group II
p value
0.9960.05
1.2260.06
7.1760.13
6.2360.12
13.1560.60
23.4361.54
42.462.59
3.6460.07
602.56680.55
0.4460.02
0.000960.0001
110.7661.61
75.9460.96
89.8864.65
0.9260.04
1.2560.07
7.2860.28
6.3360.26
13.0660.78
22.4762.14
36.3661.39
3.4560.08
544.92647.22
0.4210.03
0.000960.0001
108.3862.47
76.3861.67
95.7762.78
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
NS
62
I. A. Paraskevaidis et al. / Cardiovascular Research 43 (1999) 58 – 66
Table 4
Echocardiographic variables after dobutamine infusion in the patients with VO 2 max .14 ml / kg / min (group I, n:17), and in the patients with VO 2 max
,14 ml / kg / min (group II, n:13).
IVSs (cm)
PWTHs (cm)
EDD (cm)
ESD (cm)
FS (%)
2-D EF (%)
SV (ml)
CO (l / min)
SWS (g / cm 2 )
Vcfc (circ / s)
Vcfc / SWS (circ*cm 2 / g*s)
SBP (mm Hg)
MBP (mm Hg)
HR (beats / min)
Group I
Group II
p value
1.0460.04
1.3760.07
7.0160.16
5.8660.15
16.4860.54
31.8661.31
50.6163.58
4.5260.09
475.6677.13
0.5460.02
0.001560.0000
113.7661.98
69.3561.30
94.5365.03
0.9360.05
1.160.08
7.5260.30
6.5160.26
13.460.7
23.0662.14
43.0061.99
4.260.14
750.7673.19
0.4260.02
0.000760.0001
110.3161.70
67.2361.33
98.1562.35
NS
0.02
NS
0.03
0.001
0.001
NS
NS
0.02
0.001
0.001
NS
NS
NS
Abbreviations as in Table 1
Table 5
Statistically significant changes in echocardiographic variables in the patients with VO 2 max .14 ml / kg / min (group I, n: 17), and in the patients with VO 2
max ,14 ml / kg / min (group II, n:13)
PWTHs (cm)
EDD (cm)
ESD (cm)
FS (%)
2-D EF (%)
SWS (g / cm 2 )
Vcfc (circ / s)
Vcfc / SWS (circ*cm 2 / g*s)
Group I
Group II
p value
0.1460.04
20.1660.07
20.3760.07
3.3260.59
8.4361.53
2126.97634.24
0.1060.02
0.000660.0001
20.1660.05
0.2560.11
0.1860.09
0.3461.13
0.5962.96
205.77656.71
0.000860.04
20.000260.0001
0.0001
0.003
0.0001
0.02
0.02
0.0001
0.02
0.0001
Change represents the values obtained after inotropic stimulation minus those obtained at baseline.
Abbreviations as in Table 1.
Fig. 1. Linear regression analysis between VO 2 max and the changes in left ventricular heart-rate corrected mean velocity of circumferential fiber
shortening / end-systolic meridional wall stress ratio (Vcf / SWS). Note that the trend line cuts the x axis at the value of 12 ml / kg / min for VO 2 max.
I. A. Paraskevaidis et al. / Cardiovascular Research 43 (1999) 58 – 66
63
Fig. 2. Linear regression analysis between VO 2 max and the changes in left ventricular end-systolic diameter (ESD). Note that the trend line cuts the x axis
at the value of 13 ml / kg / min for VO 2 max.
ment in myocardial reserve even for values of VO 2 max
less than 14 ml / kg / min. Secondly, changes in echodobutamine variables that correspond to the range of 10–
14 ml / kg / min of VO 2 max, fall very near to the zero line
and some of them are even positive or negative, expressing
an improvement in myocardial reserve.
3.4. Intra- and inter-observer variability
3.3. Ten month follow-up
4. Discussion
During the ten month follow-up, two patients from
group II died (6.6% of the whole study group) and two
patients underwent heart transplantation. All patients from
group I remained alive and none required heart transplantation.
The results of this study showed that in patients with
non ischemic dilated cardiomyopathy left ventricular
systolic performance indexes, contractility status and
stroke volume were increased after inotropic stimulation.
A correlation between VO 2 max and the changes in
Intra- and inter-observer variability of the echocardiographic measurements at baseline and after dobutamine
infusion are given in Table 6.
Fig. 3. Linear regression analysis between VO 2 max and the changes in left ventricular posterior wall thickness in systole (LPWT). Note that the trend line
cuts the x axis at the value of 14 ml / kg / min for VO 2 max.
I. A. Paraskevaidis et al. / Cardiovascular Research 43 (1999) 58 – 66
64
Table 6
Intra observer and inter observer variability
Baseline
Intra observer variability
ESD (cm)
EDD (cm)
IVSs (cm)
PWTHs (cm)
Inter observer variability
ESD (cm)
EDD (cm)
IVSs (cm)
PWTHs (cm)
After Dobutamine
RMSD
Mean
RMSD
Mean
0.10
0.13
0.04
0.05
6.27 (6.06–6.47)
7.22 (6.95–7.48)
0.96 (0.87–1.04)
1.23 (1.1–1.33)
0.11
0.16
0.03
0.05
6.14 (5.9–6.37)
7.24 (6.91–7.56)
0.99 (0.91–1.06)
1.25 (1.13–1.36)
0.16
0.17
0.05
0.07
6.27 (5.94–6.59)
7.22 (6.86–7.57)
0.96 (0.84–1.07)
1.23 (1.07–1.38)
0.18
0.23
0.05
0.08
6.14 (5.76–6.5)
7.24 (6.77–7.70)
0.99 (0.87–1.10)
1.25 (1.08–1.41)
RMSD: root mean square differences, the other abbreviations as in Table 1. Values in parenthesis represent lower and upper 95% confidence limit.
echocardiographic variables assessed by echo dobutamine
was also detected.
4.1. Echocardiographic changes during dobutamine
infusion. Possible explanations
Similarly to previous reports [14,24] we observed, that
after low dose dobutamine infusion cardiac contractility,
stroke volume, heart rate and consequently cardiac output
were increased. Although, the changes in systolic posterior
wall thickness and in left ventricular end systolic diameter
probably represent the simple easy way, to measure the
functional status of heart failure, Vcfc / end-systolic meridional wall stress ratio represents another index which
incorporates afterload. Since left ventricular afterload
increased after dobutamine infusion it seems that augmenting myocardial contractility (Vcfc and in Vcfc / end-systolic
meridional wall stress ratio) in these patients did not result
in a decrease in left ventricular internal load [16]. Vcfc
incorporates heart rate which might have variable effect on
force–frequency relationship in patients with dilated cardiomyopathy. However, in our series, heart rate did not
vary significantly between groups before and after inotropic stimulation, indicating that in low dose dobutamine
administration heart rate does not significantly influence
the contractile status of the failing heart [14,16]. Wall
stress reflects the combined effects of instantaneous
peripheral loading conditions and factors internal to the
heart [25]. The ability of the ventricle to unload itself is
crucial to the maintenance of normal myocardial mechanics since it is the wall stress that determines the overall
extent and mean velocity of fiber shortening [26]. In this
study the response of systolic meridional wall stress to
inotropic stimulation was different between the groups,
indicating that the myopathic left ventricle might have an
abnormal distribution of fiber shortening [16]. This different response of the left ventricle to inotropic stimulation
seems to represent a different stage of the same disease
process [16]. The results of this study also showed that
after dobutamine infusion there is a correlation between
peak exercise VO 2 and the changes in left posterior wall
systolic thickness, end systolic diameter, end-systolic
meridional wall stress, end diastolic diameter. Previous
reports have demonstrated that, in patients with severely
affected left ventricular systolic function, end-systolic and
end-diastolic volumes (and, consequently, in patients without wall motion abnormalities, end-systolic and end-diastolic diameter) are prognostic indexes [27]. The prognostic
value of posterior wall thickness in dilated cardiomyopathy
has also been reported [9].
Myocardial contractile reserve represents the common
denominator of both Vcfc / end-systolic meridional wall
stress ratio and VO 2 max and may, therefore, explain the
correlation between these two parameters in patients with
heart failure. However, apart from central, peripheral
factors may also contribute substantially to lower VO 2 max
seen in chronic heart failure. In this respect these two
indexes may measure different aspects of heart failure,
although both of them reflect functional status of heart
failure.
Although VO 2 max ,14 ml / kg / min has been used as
an objective index of the functional status of the heart, it
has been shown to improve with vasodilator and exercise
therapy in patients with HF [28,29]. Accordingly, the
results of this study showed that the cut-off point of VO 2
max may not be 14 ml / kg / min (indeed it may be lower,
depending on other factors). This may indicate an improvement not only in functional capacity but also in prognosis.
4.2. Study limitations
(1) The heterogeneous contractile responses to
dobutamine observed in this study among patients with
chronic HF have been reported previously [16] and may
reflect differences in b1-adrenoreceptor density, which was
not investigated in this study. Although the response to
dobutamine may underestimate the contractile reserve of
the failing myocardium, the magnitude of the drug’s effect
appears to decline as left ventricular function deteriorates;
the latter is accompanied by a reduction in b-adreno-
I. A. Paraskevaidis et al. / Cardiovascular Research 43 (1999) 58 – 66
receptor density [30]. (2) Brachial arterial pressure was
used to calculate peak systolic blood pressure. Although
numerous validation studies have been performed [31], we
recognize that brachial arterial pressure is only an estimate
of left ventricular ejection pressure and not a direct
measurement. Additionally, there is a lack of synchrony of
estimates of ventricular pressure (which occurred at early
or mid ejection) and those of cavity dimensions and wall
thickness which occurred at end-ejection). However, since
the main interest of this study was to estimate wall stress
before and after inotropic stimulation, we assumed that the
method used in this study for the measurement of peak
systolic blood pressure had little influence on the final
result. Although the peak (as opposed to end-systolic)
pressure was used in this study, previous reports have
shown that this substitution is reasonable [32]. (3) Although, the most satisfactory estimates of stroke volume
are made using pulsed Doppler aortic velocities were
measured by continuous Doppler in an apical five chamber
view since the main interest of this study was the changes
in velocity time integral which occurred after inotropic
stimulation and not the absolute values.
4.3. Clinical implications
The results of this study showed that echo-dobutamine
indices could provide clinical and prognostic information
complementary to the VO 2 max value for a given patient,
since the numerical approach does not necessarily shed
light on pathophysiology and prognosis. Furthermore,
patients should be reevaluated after 6 months, since they
sometimes improve their functional capacity. There is
growing evidence that VO 2 max is influenced by non
cardiac factors, [33,34]. In this respect dobutamine echocardiography might be an alternative tool in the detection
of the functional status of the heart, especially in those
patients with VO 2 max levels between 10 and 14 ml / kg /
min.
5. Conclusion
The changes in echocardiographic variables assessed by
echo-dobutamine are well correlated with VO 2 max and
seem to be an accurate index for evaluating the functional
status of chronic HF in patients with dilated cardiomyopathy.
Acknowledgements
We thank George Tentis, PhD for assistance with
statistical analysis and Eleni Binou for her secretarial
assistance.
65
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