Download Left Atrial Functional Reserve in Patients With Nonischemic Dilated

Left Atrial Functional Reserve in
Patients With Nonischemic Dilated
Cardiomyopathy*
An Echocardiographic Dobutamine Study
Ioannis A. Paraskevaidis, MD; Thomas Dodouras, MD;
Stamatis Adamopoulos, MD; and Dimitrios Th. Kremastinos, MD
Objective: To evaluate left atrial functional reserve in patients with chronic heart failure and
nonischemic dilated cardiomyopathy (DCM).
Background: Left ventricular functional status has been investigated using echocardiographic
dobutamine.
Methods: In 35 consecutive patients (29 men and 6 women; mean ⴞ SD age, 42.37 ⴞ 13.5 years),
peak oxygen consumption (V̇O2max) was measured; the day after, a low-dose dobutamine (5 to 10
␮g/kg/min, of 5 min each step) study was performed. Left atrial volumes at mitral valve opening,
onset of left atrial systole, and mitral valve closure were measured by using two-dimensional
echocardiography. Left atrial active emptying volume (LAEV) [volume at onset of atrial
systole ⴚ minimal volume] was calculated, as was left atrial active emptying fraction (LAEF):
[(volume at onset of atrial systole ⴚ minimal volume)/volume at onset of atrial systole] ⴛ 100. The
changes (values obtained after inotropic stimulation minus those obtained at baseline) of the
above-mentioned echocardiographic variables were considered as left atrial functional reserve.
Results: In the entire study group after dobutamine infusion, increases in LAEV (3.34 ⴞ 7.54 mL,
p ⴝ 0.01) and LAEF (6 ⴞ 13.2%, p ⴝ 0.01) were observed. The changes in the above-mentioned
parameters were correlated with V̇O2max values (r ⴝ 0.73 and r ⴝ 0.71, respectively; p < 0.001).
After inotropic stimulation, LAEV and LAEF were increased in patients with V̇O2max values > 14
mL/kg/min (5.62 ⴞ 7.28 mL and 10.04 ⴞ 13.13%, respectively) and decreased in patients with
V̇O2max values < 14 mL/kg/min (ⴚ 1.08 ⴞ 6.13 mL and ⴚ 1.6 ⴞ 9.9%, respectively; p ⴝ 0.01 for
both).
Conclusion: Echocardiographic dobutamine can evaluate left atrial functional reserve in patients
with nonischemic DCM.
(CHEST 2002; 122:1340 –1347)
Key words: dilated cardiomyopathy; echocardiographic dobutamine; heart failure; left atrial functional reserve
Abbreviations: DCM ⫽ dilated cardiomyopathy; LAEF ⫽ left atrial active emptying fraction; LAEV ⫽ left atrial active
emptying volume; LAVmax ⫽ left atrial maximal volume at the point of mitral valve opening; LAVmin ⫽ minimal
volume at the point of mitral valve closure; LAVp ⫽ left atrial volume at onset of atrial systole; LVEDD ⫽ left
ventricular end-diastolic diameter; LVEF ⫽ left ventricular ejection fraction; LVESD ⫽ left ventricular end-systolic
diameter; LVFS ⫽ left ventricular fractional shortening; NS ⫽ not significant; V̇o2max ⫽ peak oxygen consumption
the mechanical characteristics of the left
A lthough
ventricle have been extensively studied, left atrial
function is poorly understood despite its key role in
optimizing left ventricular function.1,2 In physiologic
investigations, the evaluation of pressure/dimension
relationship is the most accurate and representative
*From the Second Department of Cardiology, Onassis Cardiac
Surgery Center, Athens, Greece.
Manuscript received November 12, 2001; revision accepted April
16, 2002.
Correspondence to: Ioannis A. Paraskevaidis, MD, Onassis Cardiac Surgery Center, Second Department of Cardiology, 356
Syngrou Ave, 176 74 Athens, Greece; e-mail: elbee@ath.
forthnet.gr
index of the hemodynamic conditions that exist in
cardiac chambers.3,4 However, these relationships
require combined measurement of left atrial chamber pressures and dimensions. Thus, their use has
been primarily limited to invasive clinical and experimental studies.
Impaired exercise tolerance is one of the most
common clinical manifestations in patients with left
ventricular dysfunction.5 Left atrial fractional shortening at rest reflects left ventricular filling during
exercise and therefore predicts cardiac output and
stroke volume response to exercise, and exercise
capacity.6 Exercise and left ventricular performance
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Clinical Investigations
during exercise have been shown to be mainly
dependent on left ventricular diastolic filling rather
than systolic function.6 Of note, it has been reported
that indexes of left atrial function are related to peak
aerobic capacity in patients with congestive heart
failure.7 However, none of the above-mentioned
studies have investigated left atrial response during
exercise. We have shown that left ventricular
changes induced by dobutamine infusion are well
correlated with peak oxygen consumption (V̇o2max)
and can be used to evaluate the functional status of
heart failure.8,9 In this respect, we aimed to investigate left atrial functional reserve in patients with
chronic heart failure and nonischemic dilated cardiomyopathy (DCM) using echocardiographic dobutamine.
Materials and Methods
Study Patients
Thirty-six consecutive patients with documented DCM were
studied. V̇o2max was calculated the day before the echocardiographic dobutamine study. Thirty-five patients (98%; 26 men and
9 women; mean ⫾ SD age, 42.37 ⫾ 13.5 years) with good-quality
two-dimensional echocardiography were recruited for analysis.
The cause of DCM was idiopathic in all patients assessed by a
detailed history and clinical examination, echocardiography, coronary angiography (angiographic lesions ⬍ 30% lumen stenosis
diameter), and biopsy. All patients were in New York Heart
Association functional class III. Diagnosis of DCM was based on
the echocardiographic findings of a dilated left ventricle (left
ventricular end-diastolic diameter [LVEDD] ⬎ 60 mm) with
severely affected systolic function, left ventricular fractional
shortening [LVFS] ⬍ 20%, and left ventricular ejection fraction
[LVEF] ⬍ 35%. In no case was a significant regional wall motion
abnormality recorded by two-dimensional echocardiography. All
patients were in sinus rhythm and were receiving digoxin,
angiotensin-converting enzyme inhibitors, and diuretic drugs in
adequate doses. No patients received ␤-blocker therapy because
when our study started this treatment had not yet become an
established standard. Patients with rhythm disturbances, ischemic cardiomyopathy, more-than-mild valvular heart disease, or
regional wall motion abnormalities were excluded. More specifically, patients with more-than-mild mitral regurgitation were
excluded from the study to avoid confounding echocardiographic
volumetric measurements.
Transthoracic echocardiography was performed, and the echocardiographic variables were measured at baseline and after
dobutamine infusion. In an additional 15 subjects (mean age,
34.7 ⫾ 6.3 years) with normal left ventricular size and function,
and normal left atrial size, an echocardiographic dobutamine
study was performed. All patients gave informed consent.
Echocardiography
In all patients, the ultrasound transducer was positioned at the
point of maximal cardiac impulse and angled toward the right
shoulder until an image was obtained that included all four
cardiac chambers and both mitral and tricuspid valves. Thereafter, the transducer was angled to obtained the maximal left
atrial and ventricular size while recording portions of both
www.chestjournal.org
atrioventricular valves. In the apical two-chamber view, the aortic
valve and aorta were included when outlining the left atrial cavity.
In addition, at least 80% of endocardium had to be seen and the
difference in measurements of the left atrial common axis shared
by both apical four-chamber and two-chamber views had to be
ⱕ 3 mm. Following this, digital tracing (Sonos 1000 or 2500;
Hewlett-Packard; Andover, MA) was used and left atrial volumes
were measured from apical four-chamber and two-chamber
views. The volume determinations were calculated according to
method of Dodge et al,10 using a biplane area-length formula:
V ⫽ 8A1 ⫻ A2/3␲L, where A1 and A2 represent the enclosed
area of the atrial chamber from two orthogonal views, respectively, and L is the common axis shared and directed from apex
to base. The following measurements were made at baseline and
after the end of 10 ␮g/kg/min of dobutamine infusion: (1) left
atrial maximal volume at the point of mitral valve opening
(LAVmax), and minimal volume at the point of mitral valve
closure (LAVmin). Left atrial volume at onset of atrial systole
(LAVp) was considered the volume corresponding to the onset of
the P wave in the simultaneous recorded ECG. (2) Left atrial
function was evaluated with the left atrial active emptying
volume (LAEV) [volume at onset of atrial systole ⫺ minimal
volume], and with the left atrial active emptying fraction
(LAEF): [(volume at onset of atrial systole ⫺ minimal volume)/
volume at onset of atrial systole] ⫻ 100. Total atrial reservoir
function was determined by measuring left atrial maximal
volume minus minimal volume. (3) From the parasternal
long-axis view and according to American Society of Echocardiography,11 LVEDD, left ventricular end-systolic diameter
(LVESD), and LVFS (LVEDD ⫺ LVESD/LVEDD ⫻ 100)
were calculated. LVEF was measured by using the modified
Simpson rule. The changes of the above-mentioned parameters
after dobutamine infusion were considered as indexes of left
atrial functional reserve. Changes represent values obtained after
dobutamine infusion minus those obtained at baseline. All measurements 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.
Dobutamine Infusion
Dobutamine was infused IV in two steps after establishment of
a stable hemodynamic state for each step (heart rate, BP). The
duration of each step was 5 min, and the maximal end-dose of
dobutamine infused was 10 ␮g/kg/min.12 At each step, dobutamine infusion was increased by 5 ␮g/kg/min, reaching
10 ␮g/kg/min at the second step. Every minute during the
protocol, systolic, diastolic, and hence mean arterial BP (Sirecust
888; Siemens; Erlangen, Germany), heart rate and a 12-lead
ECG were recorded.
Cardiopulmonary Exercise Testing
Exercise testing with respiratory gas exchange measurements
was performed while patients exercised on a treadmill according
to the Dargie protocol.13 Oxygen consumption, carbon dioxide
production, and respiratory exchange ratio were measured continuously during exercise using an automated gas exchange
measuring system (CPX/MAX; Medgraphics; Minneapolis, MN).
BP was measured with a mercury sphygmomanometer, and the
ECG was monitored continuously with a computer-assisted
system (Marquette Electronics; Milwaukee, WI). V̇o2max at peak
exercise was calculated as the mean of values during the last
minute of exercise.
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Statistical Analysis
All values are expressed as mean ⫾ 1 SD. A paired t test was
applied to compare variables between groups before and after
dobutamine infusion. An unpaired t test was applied to compare
variables between different groups. Correlation analysis (linear
regression analysis) was used in order to evaluate the relations
between V̇o2max values and the echocardiographic parameters.
Reproducibility (interobserver and intraobserver variability) of
our laboratory have been reported previously.8,9 A p value ⬍ 0.05
was considered statistically significant.
Results
No major side effects were reported during dobutamine infusion. The V̇o2max measured in all patients
ranged from 10 to 21.8 mL/kg/min (mean, 15 ⫾ 2.9
mL/kg/min).
Echocardiographic Measurements
The echocardiographic measurements of the normal group and the heart failure group at baseline and
after dobutamine infusion and their changes are
shown in Table 1. Systolic BP was unchanged after
low-dose dobutamine infusion (from 112.1 ⫾ 10.9 to
113.1 ⫾ 8.7 mm Hg), whereas R-R interval was
significantly decreased (from 759.4 ⫾ 50.6 to
732.3 ⫾ 57 ms, p ⫽ 0.01). After dobutamine infusion, statistically significant decreases in LAVp and
in LAVmin (both p ⬍ 0.001) were recorded, while
LAEV and LAEF were significantly increased (both
p ⬍ 0.01). LVEDD was unchanged after dobutamine infusion, whereas LVESD was significantly
decreased (⫺ 4.4 ⫾ 4.7 mm, p ⫽ 0.0001) after inotropic stimulation. LVFS and LVEF were significantly increased: 6.7 ⫾ 7.3% (p ⫽ 0.0002) and
5.8 ⫾ 3.6% (p ⫽ 0.0001), respectively. The changes
in LAEV (r ⫽ 0.73, p ⫽ 0.001), LAEF (r ⫽ 0.71,
p ⫽ 0.001), LAVmin (r ⫽ ⫺ 0.66, p ⫽ 0.001) and
LVESD (r ⫽ 0.79, p ⫽ 0.001) were highly correlated
with V̇o2max values (Fig 1).
At baseline, left ventricular inflow pattern presented an E-wave velocity of 62.3 ⫾ 9.3 cm/s and an
A-wave velocity of 42.1 ⫾ 13.9 cm/s. The ratio between the early peak transmitral flow velocity and
the late peak velocity (1.6 ⫾ 0.7) was correlated
with V̇o2max (r ⫽ ⫺0.56, p ⬍ 0.001) and with the
dobutamine-induced changes in LAEV (r ⫽ ⫺ 0.50,
p ⬍ 0.001) and in LAEF (r ⫽ ⫺ 0.54, p ⬍ 0.001).
Pulmonary artery systolic pressure measured at
baseline (40.2 ⫾ 4.6 mm Hg) was not significantly
correlated with exercise capacity and with left
atrial functional reserve. Pulmonary artery systolic
pressure was calculated by using the following
formula: 4 ⫻ tricuspid regurgitation peak velocity2 ⫹ 10 mm Hg.
Atrial response to dobutamine in patients with
high vs low V̇o2max. The heart failure group was
further divided in two groups: group 1 (n ⫽ 23) comprised patients with V̇o2max values ⬎ 14 mL/kg/min
Table 1—Echocardiographic Measurements Before and After Dobutamine Infusion in the Heart Failure Group
(n ⴝ 35) and in Normal Subjects (n ⴝ 15)*
Variables
Heart failure group
LAVmax, mL
LAVp, mL
LAVmin, mL
LAEV, mL
LAEF, %
LAVmax-min, mL
LVEDD, mm
LVESD, mm
LVFS, %
LVEF, %
Normal subjects
LAVmax, mL
LAVp, mL
LAVmin, mL
LAEV, mL
LAEF, %
LAVmax-min, mL
Before
After
Change†
p Value
67.4 ⫾ 16
59.1 ⫾ 13.3
53.6 ⫾ 12.3
5.5 ⫾ 5.8
8.8 ⫾ 10.5
13.2 ⫾ 11.5
73.3 ⫾ 10.1
63.6 ⫾ 10.7
13.4 ⫾ 3.8
27.5 ⫾ 3.9
66.9 ⫾ 16.5
56.7 ⫾ 11.6
47.8 ⫾ 9.8
8.8 ⫾ 7.7
14.8 ⫾ 11.6
18.2 ⫾ 12.7
73.8 ⫾ 10.1
59.2 ⫾ 11.4
20.1 ⫾ 7.7
33.3 ⫾ 3.8
⫺0.5 ⫾ 4.9
⫺2.5 ⫾ 4.2
⫺5.8 ⫾ 7.2
3.3 ⫾ 7.5
6 ⫾ 13.2
5 ⫾ 8.3
0.5 ⫾ 3.1
⫺4.4 ⫾ 4.7
6.7 ⫾ 7.3
5.8 ⫾ 3.6
NS
0.001
0.001
0.01
0.01
0.001
NS
0.0001
0.0001
0.0001
56.6 ⫾ 1.3
47.4 ⫾ 6.6
42.7 ⫾ 7.3
4.7 ⫾ 3.1
10.1 ⫾ 6.3
13.9 ⫾ 4.1
53.8 ⫾ 5.7
41.1 ⫾ 6.7
25.8 ⫾ 2.7
15.3 ⫾ 6.7
35.9 ⫾ 10.8
28 ⫾ 6.1
⫺2.8 ⫾ 2.2‡
⫺6.3 ⫾ 3.6§
⫺16.9 ⫾ 7.7㛳
10.6 ⫾ 8.1§
25.8 ⫾ 14.1㛳
14.1 ⫾ 7.5㛳
0.001
0.001
0.001
0.001
0.001
0.001
*LAVmax-min ⫽ LVAmax minus LVAmin.
†Values obtained after inotropic stimulation min values obtained at baseline.
‡p ⬍ 0.05 for the relation between dobutamine-induced changes in normal subjects and in patients with DCM.
§p ⬍ 0.01 for the relation between dobutamine-induced changes in normal subjects and in patients with DCM.
㛳P ⬍ 0.001 for the relation between dobutamine-induced changes in normal subjects and in patients with DCM.
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Clinical Investigations
Figure 1. Correlation between V̇o2max values and LAEV (upper
panel) and LAEF (lower panel). Changes represent values after
dobutamine infusion minus those observed at baseline.
(mean, 16.6 ⫾ 2.1 mL/kg/min), and group 2 patients
(n ⫽ 12) had V̇o2max values ⬍ 14 mL/kg/min (mean,
12 ⫾ 1.2 mL/kg/min).
The values of the echocardiographic variables of
each group both before and after inotropic stimulation as well as their changes are shown in Table 2.
Systolic BP was similarly increased in both groups
(1 ⫾ 8.3 mm Hg for group 1 and 0.8 ⫾ 7.6 mm Hg
for group 2). R-R interval was similarly decreased in
both groups (⫺ 23.4 ⫾ 53.4 ms for group 1 and
⫺ 34.2 ⫾ 59.4 ms for group 2).
Dobutamine-induced changes in LAVp were
similar between groups. In contrast, LAVmin,
although similar at baseline, was decreased more
in group 1 (⫺ 7.5 ⫾ 7.7 mL) than in group 2
(⫺ 2.6 ⫾ 5 mL) [p ⫽ 0.02]. However, LAEV and
LAEF, although similar at baseline, after dobutamine infusion were increased in group 1
(5.6 ⫾ 7.3 mL and 10 ⫾ 13.1%, respectively) and
decreased in group 2 (⫺ 1.1 ⫾ 6.1 mL and
⫺ 1.6 ⫾ 9.9%, respectively) [p ⫽ 0.01 for both].
The changes in LVEDD were similar before and
after dobutamine infusion, while LVESD was
decreased in group 1 (⫺ 7.1 ⫾ 2.7 mm) and increased in group 2 (0.7 ⫾ 3.5 mm) [p ⫽ 0.0001].
LVFS and LVEF were increased more in group 1
(9.9 ⫾ 5.5% and 7.1 ⫾ 2.6%, respectively;
p ⫽ 0.001 for both) than in group 2 (0.4 ⫾ 6.1%
and 3.4 ⫾ 4.2%, respectively).
Table 2—Echocardiographic Measurements Before and After Dobutamine Infusion in Patients With V̇O2max
> 14 mL/kg/min (Group 1, n ⴝ 23) and in Patients With V̇O2max < 14 mL/kg/min (Group 2, n ⴝ 12)*
Variables
Group 1
LAVmax, mL
LAVp, mL
LAVmin, mL
LAEV, mL
LAEF, %
LAVmax-min, mL
LVEDD, mm
LVESD, mm
LVFS, %
LVEF, %
Group 2
LAVmax, mL
LAVp, mL
LAVmin, mL
LAEV, mL
LAEF, %
LAVmax-min, mL
LVEDD, mm
LVESD, mm
LVFS, %
LVEF, %
Before
After
Change†
p Value
64.9 ⫾ 17.3
56.6 ⫾ 14
50.9 ⫾ 12.4
5.6 ⫾ 5.9
9.2 ⫾ 11.2
14 ⫾ 12.6
72 ⫾ 8.5
62.6 ⫾ 9
13.5 ⫾ 3.6
27.5 ⫾ 4.1
63.6 ⫾ 17.7
54.7 ⫾ 12.5
43.4 ⫾ 8.1
11.3 ⫾ 7.9
19.2 ⫾ 11
20.3 ⫾ 13.9
71.9 ⫾ 7.7
55.3 ⫾ 9.6
23.4 ⫾ 6.4
34.6 ⫾ 3.6
⫺1.3 ⫾ 4.7
⫺1.9 ⫾ 3.8
⫺7.5 ⫾ 7.7
5.6 ⫾ 7.3
10 ⫾ 13.1
6.2 ⫾ 8.8
⫺0.08 ⫾ 3.1
⫺7.1 ⫾ 2.7
9.9 ⫾ 5.5
7.1 ⫾ 2.6
NS
0.02
0.001
0.001
0.001
0.002
NS
0.0001
0.0001
0.0001
72.2 ⫾ 12.2
64.1 ⫾ 10.8
58.8 ⫾ 10.7
5.2 ⫾ 5.8
8 ⫾ 9.5
13.3 ⫾ 9.2
75.7 ⫾ 12.6
65.9 ⫾ 13.5
13.4 ⫾ 4.5
27.4 ⫾ 3.6
73.2 ⫾ 12.2
60.4 ⫾ 9.2
56.2 ⫾ 6.8
4.2 ⫾ 4.7
6.3 ⫾ 7.2
17 ⫾ 9.9
77.4 ⫾ 13.3
66.6 ⫾ 11.4
13.8 ⫾ 5.9
30.8 ⫾ 2.9
1.1 ⫾ 5.1
⫺3.7 ⫾ 4.9
⫺2.6 ⫾ 5
⫺1.1 ⫾ 6.1
⫺1.6 ⫾ 9.9
3.7 ⫾ 7.4
1.7 ⫾ 2.8
0.7 ⫾ 3.5
0.4 ⫾ 6.1
3.4 ⫾ 4.2
NS
0.03
NS
NS
NS
NS
NS
NS
NS
0.02
*See Table 1 for expansion of abbreviation.
†Values obtained after inotropic stimulation minus those obtained at baseline.
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1343
Of note, plotting the variables V̇o2max vs the
changes in LAEV and LAEF (Fig 2), we can make
the following observations. Firstly, the trend line
of the above-mentioned variables cuts the x-axis
near the value 13 mL/kg/min for V̇o2max, indicating
that we may expect an improvement in atrial contractile
reserve even for values of V̇o2max ⬍ 14 mL/kg/min.
Secondly, dobutamine-induced changes in the abovementioned variables that correspond to the range of
10 to 14 mL/kg/min of V̇o2max fall very near to the
zero line, and some of them are even positive or
negative, expressing an improvement in atrial contractile reserve.
At baseline, mitral E-wave velocity and pulmonary
systolic pressure were similar between groups
(62.4 ⫾ 9.3 cm/s and 40.1 ⫾ 5.1 mm Hg for group 1
and 62.1 ⫾ 9.9 cm/s and 40.4 ⫾ 4 mm Hg for
group 2, respectively; p ⫽ not significant [NS]).
However, mitral A wave was higher in group 1
(46.5 ⫾ 14.1 cm/s) than in group 2 (33.7 ⫾ 9.3 cm/s),
p ⬍ 0.01. The ratio between the early peak transmitral flow velocity and the late peak systolic velocity
was of borderline significance (p ⫽ 0.07), higher in
group 2 (1.9 ⫾ 0.6) than in group 1 (1.5 ⫾ 0.6).
Atrial Response to Dobutamine in Patients With
V̇O2max Values ⬎ 14 mL/kg/min
Since in the above-mentioned groups there was a
statistically significant change both in left ventricular
and left atrium functional reserve, to further investigate the role of left atrial functional status we
divided group 1 in two subgroups according to
median value of V̇o2max (15.8 mL/kg/min). Group
1a represents patients (n ⫽ 12) with V̇o2max values
above (18.2 ⫾ 1.7 mL/kg/min) the V̇o2max median
value, and group 1b represents patients (n ⫽ 11)
with V̇o2max values below (14.9 ⫾ 0.2 mL/kg/min)
the V̇o2max median value.
Interestingly, the dobutamine induced changes in
LVEDD (0.2 ⫾ 3.1 mm for subgroup 1a and
⫺ 0.4 ⫾ 3.2 mm for subgroup 1b, p ⫽ NS), LVESD
(⫺ 7.9 ⫾ 3 mm for subgroup 1a and ⫺ 6.2 ⫾ 2 mm
for subgroup 1b, p ⫽ NS), in LVFS (12 ⫾ 6.4% for
subgroup 1a and 7.2 ⫾ 3.5% for subgroup 1b,
p ⫽ NS), and LVEF (6.1 ⫾ 3.3% for subgroup 1a and
6.8 ⫾ 2.5% for subgroup 1b, p ⫽ NS) were similar
between subgroups. Moreover, the dobutamineinduced changes in LAVmax and LAVp were similar
between subgroups. However, LAEV and LAEF were
increased more in subgroup 1a (10.7 ⫾ 5.7 mL and
19 ⫾ 9.5%, respectively; p ⫽ 0.0001 for both) than in
subgroup 1b (0.09 ⫾ 3.9 mL and 0.2 ⫾ 8.7%, respectively) [Table 3, Fig 3].
Twelve-Month Follow-up
During the 12-month follow-up period, two patients from group 2 died and two patients underwent
heart transplantation. From group 1 (more specifically, subgroup 1b), one patient died during the
follow-up period.
Discussion
The results of this study suggest that after inotropic stimulation in patients with chronic heart failure
and nonischemic DCM, there is an improvement of
left atrial volumetric indexes. Importantly, this study
indicates that left atrial functional reserve, detected
by echocardiographic dobutamine, might differentiate patients with V̇o2max values ⬎ 14 mL/kg/min
higher or ⬍ 14 mL/kg/min. Interestingly, these findings also suggest that in the evolution of heart failure
in this group of patients, left atrial might precede left
ventricular contractile reserve impairment.
Figure 2. Dobutamine-induced changes in LAEV (upper panel)
and in LAEF (lower panel) in group 1 (n ⫽ 23 patients, white
columns) and group 2 (n ⫽ 12 patients, black columns). Dob 0
and Dob 10 represent measurements at baseline and after
dobutamine infusion of 10 ␮g/kg/min, respectively.
Left Atrial Function After Dobutamine Infusion
The hemodynamic effects of ␤-adrenergic stimulation with IV dobutamine have been extensively
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Clinical Investigations
Table 3—Echocardiographic Measurements Before and After Dobutamine Infusion in Subgroup 1a
(n ⴝ 12 patients) and in Subgroup 1b (n ⴝ 11 patients)*
Variables
Subgroup 1a
LAVmax, mL
LAVp, mL
LAVmin, mL
LAEV, mL
LAEF, %
LAVmax-min, mL
LVEDD, mm
LVESD, mm
LVFS, %
LVEF, %
Subgroup 1b
LAVmax, mL
LAVp, mL
LAVmin, mL
LAEV, mL
LAEF, %
LAVmax-min, mL
LVEDD, mm
LVESD, mm
LVFS, %
LVEF, %
Before
After
Change†
p Value
67.2 ⫾ 19.4
61 ⫾ 14.9
56.9 ⫾ 12
4.1 ⫾ 5.5
5.3 ⫾ 10.3
10.3 ⫾ 12.3
69.4 ⫾ 8.1
59.6 ⫾ 8.3
14.3 ⫾ 3
29.6 ⫾ 4.6
66 ⫾ 18.2
58.8 ⫾ 13.4
44 ⫾ 9.9
14.8 ⫾ 8.1
24.4 ⫾ 10.5
22 ⫾ 13.5
69.7 ⫾ 7.4
51.7 ⫾ 9.9
26.3 ⫾ 6.5
35.7 ⫾ 3.4
⫺1.2 ⫾ 4
⫺2.2 ⫾ 3.2
⫺12.9 ⫾ 4.7
10.7 ⫾ 5.7
19 ⫾ 9.5
11.7 ⫾ 5.8
0.2 ⫾ 3.1
⫺7.9 ⫾ 3
12 ⫾ 6.4
6.1 ⫾ 3.3
NS
0.04
0.001
0.001
0.001
0.002
NS
0.0001
0.0001
0.0001
62.4 ⫾ 15.2
51.7 ⫾ 11.7
44.4 ⫾ 9.4
7.4 ⫾ 6.1
13.4 ⫾ 11.1
18.1 ⫾ 12.1
74.7 ⫾ 8.4
65.4 ⫾ 9.1
12.6 ⫾ 3.8
26.6 ⫾ 4.9
61.1 ⫾ 17.7
50.2 ⫾ 10
42.7 ⫾ 6.1
7.4 ⫾ 5.8
13.6 ⫾ 8.9
18.4 ⫾ 14.7
74.3 ⫾ 7.6
59.3 ⫾ 7.7
20.3 ⫾ 4.7
33.4 ⫾ 3.5
⫺1.4 ⫾ 5.6
⫺1.5 ⫾ 4.4
⫺1.6 ⫾ 5.7
0.1 ⫾ 3.9
0.2 ⫾ 8.7
0.3 ⫾ 7.7
⫺0.4 ⫾ 3.2
⫺6.2 ⫾ 2
7.7 ⫾ 3.5
6.8 ⫾ 2.5
NS
NS
NS
NS
NS
NS
NS
0.0001
0.0001
0.0001
*See Table 1 for expansion of abbreviation. Subgroup 1a represents patients with V̇o2max values above and subgroup 1b patients with V̇o2max
values below group 1 V̇o2max median value (15.8 mL/kg/min).
†Values obtained after inotropic stimulation minus those obtained at baseline.
studied in animals14 and in human beings.15,16 Left
atrial function includes three phases: reservoir, conduit, and contraction. Left atrial reservoir function is
influenced by left atrial relaxation17 and stiffness,18
left ventricular contraction,19 and pulmonary circulation.20
In this study, although LAVmax was similar both
before and after dobutamine infusion, total atrial
reservoir function was increased probably as a result
of the improvement of left atrial and ventricular
contraction and left atrium stiffness.21 Contrasting
effects of dobutamine on pulmonary circulation have
been reported with some studies showing a decrease,22 no changes,23 or even an increase24 in
pulmonary artery pressure, suggesting a different
response to dobutamine on left atrial reservoir
phase.
The results of this study also showed that after
dobutamine infusion there is an improvement of left
atrial emptying, during ventricular relaxation and
diastole (left atrium conduit phase). This is in keeping with previous reports suggesting that dobutamine
infusion decreases left ventricular end-diastolic pressure in patients with normal left ventricular function,16 and increases early filling velocity15 in patients
with systolic heart failure, leading to an increase in
left atrial conduit volume.25
Dobutamine, by its well-known inotropic stimulawww.chestjournal.org
tion, acts through ␤1 and ␤2 receptors and increases
the contractility of both left atrium and left ventricle.26 In this respect, as observed in this study
following dobutamine infusion, there is an improvement in LAEV and LAEF. Additionally, and in
keeping with previous reports, LVESD, LVFS, and
LVEF are also improved. Interestingly, the results of
this study suggest that both left atrial and ventricular
contractile reserve8 can distinguish patients with
different exercise capacity (V̇o2max values ⬎ 14
mL/kg/min or ⬍ 14 mL/kg/min). Of note, it has been
reported that exercise and left ventricular performance during exercise are mainly dependent on left
ventricular diastolic filling, which to some extent is
dependent on left atrial systolic function.6 Indeed,
the results of this study suggest that there is a
different response of atrial functional reserve to
inotropic stimulation, presumably because of information transferred from a diseased ventricle to the
corresponding atrium.27 The different atrial response to dobutamine is in accordance with previous
reports showing the reduced and different contractile response of severely failing human hearts to
␤-adrenergic stimulation.28 Moreover, it has been
suggested that the same indexes of left atrial function
reported in this study are related to peak aerobic
capacity in patients with heart failure.7
Reflux of left atrial blood into the pulmonary veins
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atrial functional reserve is different, suggesting
that left atrial might precede left ventricular contractile reserve impairment.
Limitations
Various factors such as beam-angulation chamber foreshortening and improper endocardial definition may account for two-dimensional echocardiographic volumetric discrepancy. However, the
purpose of this study was not to determine the
precise left atrial volume measurements but to
measure the changes induced by dobutamine infusion. The heterogeneous contractile responses
to dobutamine observed in this study among patients with chronic heart failure have been reported previously,31 and may reflect differences in
␤1-adrenoreceptor density, which was not investigated in this study. However, it has been
suggested that the magnitude of the effects of
the drug appears to decline as heart function
deteriorates accompanied by a reduction in ␤adrenoreceptor density.32
Conclusion
Figure 3. Dobutamine-induced changes in LAEV (upper panel)
and in LAEF (lower panel) in subgroup 1a, (n ⫽ 12 patients,
white columns) and in subgroup 1b (n ⫽ 11 patients, black
columns). See Figure 2 legend for definition of abbreviations.
during atrial contraction has not been considered in
this study. In this respect, left atrial ejection fraction
might not be quite analogous to LVEF. However,
left atrial functional reserve, as assessed by echocardiographic dobutamine-induced changes, can be estimated regardless of the amount of blood ejected
into the pulmonary veins during atrial contraction.
The results of this study confirm the findings of
previous studies by showing that there is a correlation between V̇o2max and baseline left ventricular
diastolic filling pattern,29 and extend this knowledge
by demonstrating a correlation between baseline left
ventricular diastolic filling pattern and left atrial
functional reserve.
Left atrial function has received considerably
less attention than has left ventricular function
even though evidence suggests that left atrial
myopathy and failure may exist as an isolated
entity, precede left ventricular myopathy, or coexist with left ventricular myopathy and failure.30
In this study, we observed that in patients with
V̇o2max ⬎ 14 mL/kg/min, although left ventricular
contractile reserve is similar between subgroups
differentiated by the median value of V̇o2max, left
Echocardiographic dobutamine can evaluate left
atrial functional reserve in patients with chronic
heart failure and nonischemic DCM. Furthermore,
left atrial functional reserve detected by echocardiographic dobutamine may differentiate patients with
V̇o2max values ⬎ 14 mL/kg/min or ⬍ 14 mL/kg/min.
Interestingly, in this group of patients, left atrial
contractile reserve impairment might be an earlier
finding in the process of heart failure.
ACKNOWLEDGMENT: The authors thank Mrs. Polymnia
Anthopoulou for nursing assistance and Miss Eleni Binou for
secretarial assistance.
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