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Am J Physiol Heart Circ Physiol 299: H364–H371, 2010.
First published May 21, 2010; doi:10.1152/ajpheart.00264.2010.
Integrated analysis of atrioventricular interactions in tetralogy of Fallot
Eugénie Riesenkampff,1 Lena Mengelkamp,1 Matthias Mueller,2 Siegfried Kropf,3 Hashim Abdul-Khaliq,2
Samir Sarikouch,4 Philipp Beerbaum,5 Roland Hetzer,6 Paul Steendijk,7 Felix Berger,1 and Titus Kuehne1,8
1
Department of Congenital Heart Disease and Pediatric Cardiology, Unit of Cardiovascular Imaging, Deutsches Herzzentrum
Berlin, Berlin; 2Department of Pediatric Cardiology, Saarland University Hospital, Homburg/Saar; 3Institute for Biometrics
and Medical Informatics, University of Magdeburg, Magdeburg; 4Department of Cardiothoracic, Transplantation and
Vascular Surgery, Hannover Medical School, Hannover, Germany; 5Division of Imaging Sciences, Kings’s College London,
BHF Centre, NIRH Biomedical Research Centre at Guy’s and St. Thomas’ NHS Foundation Trust, London, United Kingdom;
6
Department of Cardiothoracic and Vascular Surgery, Deutsches Herzzentrum Berlin, Berlin, Germany; 7Departments
of Cardiology and Cardiothoracic Surgery, Leiden University Medical Center, Leiden, The Netherlands; and 8Department
of Pediatric Cardiology, Charité Universitaetsmedizin Berlin, Berlin, Germany
Riesenkampff E, Mengelkamp L, Mueller M, Kropf S, Abdul-Khaliq
H, Sarikouch S, Beerbaum P, Hetzer R, Steendijk P, Berger F, Kuehne
T. Integrated analysis of atrioventricular interactions in tetralogy of Fallot.
Am J Physiol Heart Circ Physiol 299: H364–H371, 2010. First published
May 21, 2010; doi:10.1152/ajpheart.00264.2010.—The atria play an important role in cardiac performance. We evaluated their function and the
atrioventricular interaction in operated patients with tetralogy of
Fallot (TOF). Twenty patients who had undergone surgical repair of
TOF and seven controls were investigated. Patients had residual
pulmonary but no major tricuspid valve insufficiency. Atrial and
ventricular strain rates were obtained by echocardiographic speckle
tracking. Cine MRI-derived volumetric analysis provided atrial and
ventricular time volume and time volume change curves yielding
emptying and filling parameters. In addition, at the atrial level,
reservoir, conduit and pump function, and cyclic volume change were
calculated. At the atrioventricular valve level, tricuspid and mitral
annular plane systolic excursion (TAPSE and MAPSE, respectively)
were measured by two-dimensional echocardiography. In the patients
compared with controls, right ventricular end-diastolic volumes were
increased and biventricular ejection fraction was decreased (all P ⬍
0.05). Biventricular measures of early diastolic ventricular filling were
at control levels, but in late diastole, right ventricular filling parameters and strain rates were decreased (P ⬍ 0.001). The maximal right
atrial size was slightly but not significantly diminished, but cyclic
volume change was significantly reduced (P ⬍ 0.0001). Pump and
reservoir function were decreased (P ⬍ 0.05), and conduit function
was elevated (P ⬍ 0.001). The left atrium showed reduced reservoir
function and cyclic volume change (P ⬍ 0.05). TAPSE and MAPSE
were also decreased (P ⬍ 0.05). There were statistically significant
interdependencies between RV ejection fraction, TAPSE, and right
atrial filling and emptying parameters (all P ⬍ 0.05). In TOF patients,
moderate systolic and diastolic right ventricular dysfunction is associated with clearly impaired right atrial function. The left atrium is
affected to a lesser extent.
congenital heart disease; atrial function; magnetic resonance imaging
PROGRESSIVE RIGHT VENTRICULAR (RV) enlargement and dysfunction due to pulmonary regurgitation or obstruction across the
reconstructed outflow tract dominate the long-term outcome in
patients with surgically corrected tetralogy of Fallot (TOF) (8,
9). Recent studies (5, 22, 27) that have investigated the com-
Address for reprint requests and other correspondence: E. Riesenkampff,
Deutsches Herzzentrum Berlin, Dept. of Congenital Heart Disease and Pediatric Cardiology, Augustenburger Platz 1, Berlin D-13353, Germany (e-mail:
[email protected]).
H364
plex adaptive response of the RV to chronic overload in TOF
have provided evidence that the RV cannot be seen as one
entity. In addition, the impact of RV dysfunction on left
ventricular (LV) and atrial function must be considered (1, 12,
15, 26). In 1974, Suga (25) highlighted the role of the atria in
cardiac performance by transforming the continuous venous
return into the intermittent ventricular filling flow.
The influence of different conditions on left atrial (LA)
function, such as aging (24), LV dysfunction (2, 14, 19, 23),
and aortic or mitral valve disease (6, 7), have been widely
assessed. However, data about the interaction of the RV with
the right atrium (RA) are sparse. Studies (10, 21, 28) have been
conducted that assessed components of RA function in animals
and humans with pulmonary arterial banding or pulmonary
hypertension. A study by Hui and coworkers (15) investigated
TOF patients with a focus on late atrial active emptying, the
so-called atrial kick. However, a more systematic assessment
of RA function that accounts for both filling and emptying
parameters has not yet been studied in TOF patients with RV
dysfunction. With this in mind, we designed the present study
to use an integrated approach to investigate right and left atrial
and ventricular function in TOF patients by MRI and twodimensional echocardiographic speckle tracking imaging techniques.
METHODS
Study Population
Twenty patients with previously repaired TOF without additional cardiac malformations as well as seven controls without
cardiac medical history were included in the study after random
selection from the database of the Competence Network for Congenital Heart Defects (www.kompetenznetz-ahf.de) from one center. Exclusion criteria were as follows: 1) the existence of mitral or
aortic valve insufficiency and tricuspid valve insufficiency greater
than grade I in echocardiographic studies and 2) severe stenosis
(⬎65 mmHg) of the pulmonary outflow and arteries, as assessed
morphologically and reflected by elevated RV peak systolic pressure as calculated by echocardiography via tricuspid regurgitation.
Sinus rhythm in the electrocardiogram was mandatory. This study
was approved by the institutional research ethics committee, and
written informed consent was obtained from the participants or
their guardians.
The diagnostic procedures (see below) were all done on the same
day in 11 subjects (8 patients and 3 controls). Seven subjects (3
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ATRIOVENTRICULAR INTERACTIONS IN TOF
patients and 4 controls) were studied within 1 wk; the remaining nine
patients were assessed within 1 mo.
MRI
was calculated by subtracting the minimal atrial volume from the
maximal atrial volume at middiastole. Conduit volume resulted after
subtraction of the sum of reservoir and pump volume from effective
stroke volume of the LV. The terms “systole” and “diastole” always
refer to ventricular systole and ventricular diastole.
Reservoir, conduit, and pump function were expressed as a percentage
of LV effective stroke volume. The cyclic volume change was defined as
the difference between maximal and minimal atrial volume (16, 20).
Dividing the cyclic volume change by the maximal atrial volume multiplied by 100 resulted in the total atrial filling fraction. Again, all volumes
were indexed by dividing them by the body surface area.
Atrial and ventricular time volume curves. For the four heart
chambers, time volume curves were generated by summation of the
volumes of every slice for each phase. Time volume change curves,
which were adapted from the work of Helbing et al. (13), were
generated with assessment of the following parameters.
RV AND LV FUNCTION. The following parameters were assessed:
1) early peak filling rate (in ml/s) as the maximal ventricular volume
change in early diastole; 2) early filling fraction as the ventricular
volume increase during the first third of diastole, normalized to
ventricular stroke volume; 3) late peak filling rate (in ml/s) as the
maximal ventricular volume change in late diastole; and 4) late filling
fraction as the ventricular volume increase after the onset of atrial
contraction, normalized to ventricular stroke volume.
RA AND LA FUNCTION. The following parameters were assessed:
1) early peak emptying rate (in ml/s) as the maximal atrial volume
change in early diastole; 2) early emptying fraction as the atrial
volume decrease during the first third of diastole, normalized to the
cyclic volume change; 3) late peak emptying rate (in ml/s) as the
maximal atrial volume change in late diastole; and 4) late emptying
fraction as the atrial volume decrease after the onset of atrial contraction, normalized to the cyclic volume change.
The conduit volume was calculated for each diastolic heart phase
(t) according to the following formulas:
LA conduit volume共t) 共in ml兲 ⫽ 关LV共t) ⫺ LVESV兴 ⫺
关LA Volmax ⫺ LA共t)]
RA conduit volume共t) 共in ml兲 ⫽ 关RV共t) ⫺ RVESV兴 ⫺
关RA Volmax ⫺ RA共t)] ⫺ PR共t)
where LV(t) and RV(t) indicate the LV and RV volumes at a
particular heart phase t, LVESV and RVESV are the LV and RV
end-systolic volumes, LA Volmax and RA Volmax are the maximal
volumes of the LA and RA, LA(t) and RA(t) are the LA and RA
volumes at a particular heart phase t, and PR(t) is the pulmonary
regurgitation volume during a particular heart phase t.
Heart phase t always refers to the same diastolic heart phase, and,
for each subject, the time points of maximal and minimal volumes of
the heart chambers were assessed individually.
Echocardiography
Fig. 1. Atrial function. Shown is an exemplary atrial time volume curve of a
control subject with assessment of atrial performance and function. Whereas
reservoir volume, pump volume, and cyclic volume change are calculated from
atrial volumes at special time points (see METHODS), the conduit volume, which
is passing the atrium without causing atrial volume change, is calculated by the
subtraction of the sum of reservoir and pump volume from the effective stroke
volume of the left ventricle (LV).
AJP-Heart Circ Physiol • VOL
Transthoracic two-dimensional speckle tracking imaging was done
at the ventricular level (apex, midsegment, and base) and atrial level
(roof, midsegment, and base) to attain the parameters of myocardial
deformation. Strain and strain rate were obtained in early diastole, late
diastole, and systole on the basis of three cardiac cycles in the apical
four chamber view (15, 17, 18). Peak strain was measured independently of aortic and pulmonary valve closure, and a mean value was
calculated from the three measuring points. Images were acquired using
a 2.5/3.5 transducer interfaced with a Vingmed System VII (GE Vingmed, Horten, Norway). Analysis was performed offline (EchoPAC 6.1.0,
GE Vingmed). To evaluate the movement of the atrioventricular plane,
maximal tricuspid and mitral annular plane systolic excursions (TAPSE
and MAPSE, respectively) were measured (3).
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MRI was performed using a 1.5-T scanner (Release 2.6, Philips
Medical Systems, Best, The Netherlands) with a cardiac surface array
coil. ECG-triggered multislice multiphase steady-state free precession
magnetic resonance images were acquired at end expiration in axial
orientation, covering the whole heart (4). The sequence parameters
were as follows: 25 phases/cardiac cycle, repetition time (TR) and
echo time (TE) ⫽ shortest, flip angle ⫽ 60°, slice thickness ⫽ 6
mm, gap ⫽ 0 mm, field of view ⫽ 280 – 400 ⫻ 220 –320 mm2, and
matrix ⫽ 140 –212 ⫻ 160 –246, resulting in a plane resolution of
1.4 ⫻ 1.4 ⫻ 6 mm3.
Blood flow was measured in the main pulmonary artery with
through-plane velocity-encoded cine MRI. The sequence parameters
were as follows: TR/TE ⫽ 5.1/3.0 ms, flip angle ⫽ 15°, and encoding
velocity ⫽ 200 – 400 cm/s (4).
Image analysis. Analysis of the cine MRI was performed using
View Forum software (release 5.1V1L2 SP3, Philips Medical Systems). For volumetric analysis, RA, RV, LA, and LV endocardial
contours were manually traced in every slice and phase of the stack of
axial cine MR images. The atrial appendages were included in the
measurement of atrial volumes. The superior and inferior caval vein,
coronary sinus, and pulmonary veins were excluded at their junction
to the atrium, and ventricular trabeculations and papillary muscles
were also excluded. To minimize interobserver variability, all tracing
was done by one experienced observer, and traces were reviewed by
a second observer.
RV and LV function. The following standard parameters were
determined for the RV and LV: end-diastolic volume (EDV), endsystolic volume (ESV), ejection fraction, and stroke volume. All
volumes were indexed by dividing them by the body surface area.
RA and LA function. The following atrial function parameters were
studied: reservoir, conduit and pump volumes and function, the cyclic
volume change, and emptying fraction. The reservoir volume was
calculated by subtracting the minimal atrial volume at middiastole
from the maximal atrial volume (Fig. 1) (16, 20). The pump volume
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ATRIOVENTRICULAR INTERACTIONS IN TOF
RESULTS
Table 1. Characteristics of the patient and control groups
No. of patients
No. of men/no. of women
Age at study inclusion, yr
Body surface area, m2
Mean heart rate, beats/min
QRS duration, ms
Pulmonary regurgitation fraction, %
RVSP, mmHg
Maximal O2 consumption, ml 䡠 min⫺1 䡠 kg⫺1
No. of previous palliations
Time from repair, yr
No. of repeated surgeries
No. of homografts/heterografts
Control Group
Patient Characteristics
20
8/12
19.5 ⫾ 8.9
1.57 ⫾ 0.29
74.4 ⫾ 12.1*
141.1 ⫾ 24.6*
31.8 ⫾ 13.4*
40.1 ⫾ 14.8
26.8 ⫾ 7.2*
10
14.6 ⫾ 5.3
4
9
7
4/3
24.6 ⫾ 8.7
1.86 ⫾ 0.28
63.4 ⫾ 9.0
92.3 ⫾ 9.5
2.06 ⫾ 1.65
N/A
34.6 ⫾ 6.7
Twenty asymptomatic patients (New York Heart Association class I, mean age: 19.5 ⫾ 8.9 yr, 8 men and 12 women, all
Caucasian) with surgically repaired TOF as well as seven
controls (mean age: 24.6 ⫾ 8.7 yr, 4 men and 3 women, all
Caucasian) were enrolled in the study (Table 1). All patients
had volume load of the RV with a mean pulmonary regurgitation fraction of 31.8 ⫾ 13.4% and mild pressure load with a
mean RV peak pressure of 40.1 ⫾ 14.8 mmHg. Patients were
studied 14.6 ⫾ 5.3 yr after TOF repair. The pulmonary regurgitation fraction differed between patients dependent on the
type of surgical repair (24.5 ⫾ 8.9% in n ⫽ 9 patients with
homograft and 36.4 ⫾ 16.9% in n ⫽ 11 patients without
homograft). This difference just failed to reach statistical
significance (P ⫽ 0.06). Nineteen patients had complete right
bundle branch block, and one patient had incomplete right
bundle branch block. Maximal O2 uptake was reduced in
patients versus controls (P ⬍ 0.05).
Values are means ⫾ SD. RVSP, right ventricular (RV) systolic pressure;
N/A, not applicable. Primary surgical correction had been performed with
transannular patch (n ⫽ 9), without transannular patch (n ⫽ 2), and with
valved conduit insertion (n ⫽ 9). *Significant difference compared with data
in control subjects (P ⬍ 0.05).
Exercise Testing
Maximal O2 uptake (in ml · min⫺1 · kg body wt⫺1) was determined
by bicycle ergometry with work load increase of 20 W/min. All
subjects exercised until exhaustion.
Statistical Analysis
As the parameters of atrial and ventricular function showed an
approximately Gaussian shape in a graphical check by boxplots, they
were reported as means and SDs and compared between patients and
controls using Student’s t-test in the version for different variances.
The association of variables was investigated with Pearson’s correlation coefficient (r) including a test for the null hypothesis of independence. Computations were done with SPSS 17.0. P values of ⬍0.05
were considered as significant.
RV
As expected, the patient group had significant RV enlargement (P ⬍ 0.005; Table 2) with reduced ejection fraction (P ⬍
0.005), systolic strain rate (P ⬍ 0.05; Table 3), and global peak
strain (P ⬍ 0.001).
In early diastole, covering the first third of diastole, there
were no significant changes of ventricular filling parameters
and strain rates. However, at late diastole, starting with the
onset of atrial contraction, peak filling rate and filling fraction
were significantly diminished (P ⬍ 0.05 and P ⬍ 0.005; Table
2 and Fig. 2B). At the same time, the late diastolic strain rate
was reduced (P ⬍ 0.001; Table 3). TAPSE was significantly
Table 2. Size and function of the RV and LV
RV
LV
Control group
Patient group
Control group
Patient group
88.3 ⫾ 5.6
31.8 ⫾ 5.8
56.5 ⫾ 5.5
87.1 ⫾ 13.9
37.6 ⫾ 11.2
49.5 ⫾ 8.4*
Global parameters
End-diastolic volume, ml/body surface area
End-systolic volume, ml/body surface area
Stroke volume, ml/body surface area
Regurgitation fraction, %
Pulmonary valve
Aortic valve
Ejection fraction, %
Cardiac index, l 䡠 min⫺1 䡠 body surface area⫺1
102.0 ⫾ 17.4
45.6 ⫾ 11.1
56.8 ⫾ 7.2
135.2 ⫾ 27.9*
70.7 ⫾ 17.2*
64.4 ⫾ 12.5
2.06 ⫾ 1.65
32.7 ⫾ 14.7*
55.7 ⫾ 0.04
3.61 ⫾ 0.71
48.0 ⫾ 4.1*
4.78 ⫾ 1.22*
None
64.1 ⫾ 5.5
3.59 ⫾ 0.68
1.89 ⫾ 1.24
57.3 ⫾ 8.1*
3.66 ⫾ 0.76
EPFR, ml 䡠 s⫺1 䡠 body surface area⫺1
Early filling fraction, %
LPFR, ml 䡠 s⫺1 䡠 body surface area⫺1
Late filling fraction, %
EPFR/LPFR
226.3 ⫾ 121.3
57.1 ⫾ 17.5
134.6 ⫾ 66.4
22.7 ⫾ 6.8
2.15 ⫾ 1.50
237.8 ⫾ 71.1
41.2 ⫾ 15.5
74.6 ⫾ 48.3*
11.0 ⫾ 7.2*
10.70 ⫾ 21.41
259.7 ⫾ 108.5
65.6 ⫾ 14.3
106.6 ⫾ 40.7
16.3 ⫾ 4.9
2.9 ⫾ 1.5
266.6 ⫾ 88.6
62.7 ⫾ 21.6
73.2 ⫾ 24.2
10.1 ⫾ 3.6*
4.1 ⫾ 2.0
Filling parameters
Other parameters
TAPSE, mm
MAPSE, mm
2.75 ⫾ 0.14
1.64 ⫾ 0.3*
1.59 ⫾ 0.15
1.40 ⫾ 0.21*
Values are means ⫾ SD. LV, left ventricle; EPFR, early peak filling rate; LPFR, late peak filling rate; TAPSE, tricuspid annular plane systolic excursion;
MAPSE, mitral annular plane systolic excursion. *Significant difference compared with data in control subjects (P ⬍ 0.05).
AJP-Heart Circ Physiol • VOL
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Patient Group
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ATRIOVENTRICULAR INTERACTIONS IN TOF
Table 3. Strain rates and strain by two-dimensional echocardiographic speckle tracking imaging in the RV and LV
RV
LV
Control group
Patient group
Control group
Patient group
Ventricular strain rate, s⫺1
2.00 ⫾ 0.84
2.10 ⫾ 0.59
2.39 ⫾ 0.77
2.06 ⫾ 0.72
1.71 ⫾ 0.59
2.12 ⫾ 0.81
2.28 ⫾ 0.87
1.80 ⫾ 0.47
1.64 ⫾ 0.38
2.08 ⫾ 0.70
1.99 ⫾ 0.68
2.31 ⫾ 0.81
1.00 ⫾ 0.33
1.05 ⫾ 0.37
1.27 ⫾ 0.41
0.51 ⫾ 0.17*
0.57 ⫾ 0.24*
0.91 ⫾ 0.42
0.65 ⫾ 0.22
0.60 ⫾ 0.17
0.81 ⫾ 0.25
0.66 ⫾ 0.41
0.66 ⫾ 0.47
1.00 ⫾ 0.70
⫺1.69 ⫾ 0.41
⫺1.57 ⫾ 0.46
⫺1.85 ⫾ 0.92
⫺1.26 ⫾ 0.25*
⫺1.27 ⫾ 0.26*
⫺1.58 ⫾ 0.36
⫺1.35 ⫾ 0.49
⫺1.10 ⫾ 0.18
⫺1.49 ⫾ 0.50
⫺1.36 ⫾ 0.51
⫺1.10 ⫾ 0.29
⫺1.47 ⫾ 0.51
⫺19.5 ⫾ 2.4
⫺19.7 ⫾ 3.7
Peak strain, %
Mean
⫺26.3 ⫾ 3.2
⫺21.6 ⫾ 2.8
Values are means ⫾ SD. The early diasolic strain rate was the strain rate during the E wave in early ventricular diastole, the late diastolic strain rate was the
strain rate during the A wave in late ventricular diastole, and the systolic strain rate was the strain rate during ventricular systole. *Significant difference compared
with data in control subjects (P ⬍ 0.05).
lower in the patient group (P ⬍ 0.0001; Table 2) and correlated
with RV ejection fraction (r ⫽ 0.555, P ⬍ 0.005).
LV
The patient group had a lower ejection fraction and EDV
(P ⬍ 0.05 and P ⫽ 0.09; Table 2). The effective stroke volume
was reduced (P ⬍ 0.05), but the cardiac index was at control
levels (P ⫽ 0.83) due to a slightly elevated heart rate (P ⬍
0.05; Table 1). In early diastole, there were no significant
changes of ventricular filling parameters (Table 2 and Fig. 3B),
but the late filling fraction was significantly reduced in the
patients (P ⬍ 0.05). MAPSE was lower (P ⬍ 0.05), whereas all
other echocardiographic measurements were at control levels
(Table 3). There was no correlation between MAPSE and RV
ejection fraction (r ⫽ 0.293).
RA
Reservoir function was lower in the patient group than in the
control group (P ⬍ 0.001; Table 5), conduit function was
elevated (P ⬍ 0.001), and pump function was diminished (P ⬍
0.05). There was strong negative correlation between reservoir
and conduit function (r ⫽ ⫺0.916, P ⬍ 0.001). The maximal
size of the atrium was slightly diminished in the patient group
(P ⫽ 0.23), whereas the minimal size of the atrium was
significantly larger (P ⬍ 0.05). This resulted in a significant
decrease of the cyclic volume change (P ⬍ 0.001; Fig. 2C) and
atrial filling fraction (P ⬍ 0.001; Table 5). The latter was
significantly correlated to RV ejection fraction (r ⫽ 0.675, P ⬍
0.001) and TAPSE (r ⫽ 0.698, P ⬍ 0.001). In addition, during
atrial filling, strain and strain rates were reduced in every
segment of the RA (all P ⬍ 0.001; Table 4). Atrial emptying
was reduced in early and late diastole (P ⬍ 0.001 and P ⬍
0.05, Table 5 and Fig. 2D). The strain rate, measured close to
the tricuspid valve, was significantly lower in early and late
diastole (both P ⬍ 0.05; Table 4). The values of the other atrial
segments were at control levels.
AJP-Heart Circ Physiol • VOL
LA
Reservoir function was diminished (P ⬍ 0.05; Table 5), but
conduit and pump function were at control levels. The maximal
and minimal size of the atrium did not differ significantly
between patients and controls, but cyclic volume change
was decreased (P ⬍ 0.05; Table 5 and Fig. 3C). Atrial
emptying was lower in early diastole (P ⬍ 0.001; Fig. 3D)
and unchanged in late diastole. Speckle tracking imaging
revealed no significant differences between patients and
controls (Table 4).
Grouping the patients according to functional aspects or the
preceding surgical procedure revealed no major differences in the
analysis of RA and LA function parameters. In patients with
combined pressure-volume load of the RV (n ⫽ 9, mean pulmonary regurgitation fraction of 24.1 ⫾ 8.0%, mean RV peak
pressure of 54.1 ⫾ 10.0 mmHg, existing homograft in n ⫽ 8
patients) compared with those with predominant volume load (n
⫽ 11, mean pulmonary regurgitation fraction of 36.7 ⫾ 17.1%,
mean RV peak pressure of 28.6 ⫾ 3.5 mmHg), the only difference
was a decreased RA reservoir function (P ⬍ 0.05).
DISCUSSION
In patients with surgically corrected TOF, residual pulmonary insufficiency and/or stenosis of the RV outflow tract
is an important disease that requires close follow-up (9). RV
enlargement and dysfunction are typically progressive, and
the time of transition from compensated into irreversible
right heart failure remains difficult to predict. There is
evidence that alterations in LA function have an important
impact on cardiac performance (19); however, there are
little data about the interaction of the RA and RV in patients
with TOF. In the present study, we systematically assessed
right and left atrial and ventricular function in a group of
patients with pulmonary regurgitation as the leading pathophysiological characteristic. We found clearly abnormal RA
function even though RV function was only moderately impaired.
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Early diastolic strain rate
Ventricular apex
Midsegment
Ventricular base
Late diastolic strain rate
Ventricular apex
Midsegment
Ventricular base
Systolic strain rate
Ventricular apex
Midsegment
Ventricular base
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ATRIOVENTRICULAR INTERACTIONS IN TOF
In addition, our data provide new points of view on the mechanisms of atrioventricular interactions that allow us to propose
cause-and-effect chains. In the following sections, we discuss our
observations in a point-by-point manner.
Interaction of the RA and RV
Ventricular systole and atrial filling. In the patient group, the
RA cyclic volume change and filling fraction were below
Table 4. Strain rates and strain by two-dimensional echocardiographic speckle tracking imaging in the RA and LA
RA
LA
Control group
Patient group
Control group
Patient group
Atrial strain rate, s⫺1
Early emptying strain rate
Atrial base
Midsegment
Atrial roof
Late emptying strain rate
Atrial base
Midsegment
Atrial roof
Filling strain rate
Atrial base
Midsegment
Atrial roof
⫺3.52 ⫾ 1.02
⫺2.62 ⫾ 0.87
⫺2.34 ⫾ 1.06
⫺2.36 ⫾ 1.29*
⫺2.38 ⫾ 1.13
⫺2.59 ⫾ 1.17
⫺3.37 ⫾ 0.73
⫺3.25 ⫾ 0.91
⫺3.19 ⫾ 1.14
⫺2.81 ⫾ 1.08
⫺2.66 ⫾ 0.88
⫺2.61 ⫾ 0.69
⫺3.82 ⫾ 0.92
⫺2.50 ⫾ 0.44
⫺2.11 ⫾ 0.91
⫺2.76 ⫾ 1.00*
⫺2.59 ⫾ 1.01
⫺2.50 ⫾ 0.44
⫺1.43 ⫾ 0.48
⫺1.80 ⫾ 0.57
⫺2.13 ⫾ 0.80
⫺2.36 ⫾ 1.47
⫺2.20 ⫾ 1.11
⫺2.22 ⫾ 1.15
4.61 ⫾ 0.97
4.05 ⫾ 0.64
3.87 ⫾ 0.96
2.78 ⫾ 0.89*
2.64 ⫾ 0.83*
2.80 ⫾ 0.94*
2.43 ⫾ 0.84
2.26 ⫾ 0.87
2.48 ⫾ 0.69
2.41 ⫾ 0.64
2.25 ⫾ 0.82
2.26 ⫾ 0.94
52.9 ⫾ 10.3
46.3 ⫾ 12.7
Peak strain, %
Mean
96.2 ⫾ 15.8
42.4 ⫾ 10.7*
Values are means ⫾ SD. RA, right atrium; LA, left atrium. The early emptying strain rate was the strain rate during the E wave in early ventricular diastole,
the late emptying strain rate was the strain rate during the A wave in late ventricular diastole, and the filling strain rate was the strain rate during ventricular
systole. *Significant difference compared with data in control subjects (P ⬍ 0.05).
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Fig. 2. Right atrial (RA) and right ventricular (RV) time volume (A and C) and time volume change curves (B and D) of the patient and control groups. Mean
values are shown.
ATRIOVENTRICULAR INTERACTIONS IN TOF
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control values. Cyclic volume change is thought to reflect atrial
distensibility. Previous investigators have concluded from
studies (11, 25) that were performed for the LA or RA with
normal RV systolic function that it has a positive impact on
global cardiac output. In our noninvasive study, atrial pressure
was not measured, and thus the compliance of the atria could
not be determined. However, the clearly diminished strain and
strain rates of the RA during atrial filling are indicative for
reduced atrial compliance (17). In addition, Barbier and colleagues (2) showed interdependencies among LA filling, mitral
valve plane displacement, LV ejection fraction, and atrial
filling being a strong predictor of ventricular performance.
Bazaz et al. (3) reported that the coupling of ventricular
ejection fraction and valvular plane displacement is even more
pronounced for the right side compared with the left side of the
heart, but they did not evaluate the effect on atrial function.
Our study, which was performed in a homogeneous group of
TOF patients with moderate RV dysfunction, shows a strong
coupling between RA filling, TAPSE, and RV ejection fraction. Additional research is warranted to evaluate these interdependencies in a group of TOF patients with different degrees
of RV dysfunction.
Ventricular filling and atrial emptying in the early and
middiastolic phases. In the patient group, in early diastole,
which relates to the first third of diastole, we noted normal RV
filling despite abnormal RA emptying. RV filling was delayed
AJP-Heart Circ Physiol • VOL
but otherwise unsuspicious, as indicated by early peak filling
and strain rates that were at control levels. In contrast, RA
reservoir function was substantially reduced, and atrial emptying was also slowed and delayed. One could speculate that
pulmonary regurgitation, which is highest in early diastole,
contributes to maintained early RV filling but “competes”
hydrodynamically with atrial emptying. Then, in middiastolic
phases, where pulmonary regurgitation abates, we noted in the
patient group an atrial conduit function that was delayed, and
its magnitude was clearly above control levels (Fig. 4).
The transformation of the continuous venous return into the
intermittent ventricular filling flow is one major task of the
atrium (25). This implies that conduit volumes should be low
in relation to reservoir volumes. This goes along with the
observations of Gaynor et al. (11), who reported that a low
conduit-to-reservoir ratio favors high cardiac output. In our
study of TOF patients, we noted augmented conduit but decreased reservoir volumes being associated with RV dysfunction. Again, future research is warranted to evaluate the impact
of this finding in subgroups of TOF patients with different
degrees of RV dysfunction.
Ventricular filling and atrial emptying in the late diastolic
phases. After the onset of atrial contraction, RV filling fraction
and ventricular strain rates were decreased, implying abnormal
RV filling in late diastole. These findings were associated with
simultaneously diminished RA pump function (atrial kick), as
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Fig. 3. Left atrial (LA) and LV time volume (A and C) and time volume change curves (B and D) of the patient and control groups. Mean values are shown.
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ATRIOVENTRICULAR INTERACTIONS IN TOF
Table 5. Size and function of the RA and LA
RA
LA
Control group
Patient group
Control group
Patient group
Global parameters
57.3 ⫾ 9.3
22.5 ⫾ 4.9
34.9 ⫾ 5.4
61.0 ⫾ 4.2
23.0 ⫾ 1.4
19.8 ⫾ 3.2
13.7 ⫾ 4.5
41.0 ⫾ 3.4
35.2 ⫾ 5.5
23.9 ⫾ 6.3
Maximum volume, ml/body surface area
Minimum volume, ml/body surface area
Cyclic volume change, ml/body surface area
Filling fraction, %
Reservoir volume, ml/body surface area
Conduit volume, ml/body surface area
Pump volume, ml/body surface area
Reservoir function, %
Conduit function, %
Pump function (atrial kick), %
50.8 ⫾ 17.1
29.8 ⫾ 11.7*
21.1 ⫾ 6.5*
42.3 ⫾ 8.2*
12.6 ⫾ 4.3*
28.1 ⫾ 8.8*
8.7 ⫾ 2.7*
26.1 ⫾ 9.2*
56.2 ⫾ 12.6*
17.8 ⫾ 6.0*
43.8 ⫾ 10.2
18.1 ⫾ 5.0
25.6 ⫾ 6.0
58.4 ⫾ 4.5
17.7 ⫾ 3.7
28.5 ⫾ 4.9
9.9 ⫾ 3.4
31.2 ⫾ 5.4
50.6 ⫾ 9.6
17.3 ⫾ 4.4
34.6 ⫾ 9.6
15.5 ⫾ 6.2
19.2 ⫾ 5.0*
56.3 ⫾ 8.8
12.4 ⫾ 2.7*
29.9 ⫾ 7.8
7.2 ⫾ 3.0
25.5 ⫾ 6.4*
60.0 ⫾ 10.5
14.8 ⫾ 6.2
20.1 ⫾ 2.4
⫺265.1 ⫾ 73.6
58.6 ⫾ 10.1
11.03 ⫾ 4.43
⫺233.3 ⫾ 131.4
31.0 ⫾ 8.6
9.8 ⫾ 4.7*
⫺115.1 ⫾ 71.3*
48.0 ⫾ 19.9
6.30 ⫾ 3.15*
⫺102.8 ⫾ 65.9*
31.3 ⫾ 13.1
14.2 ⫾ 4.1
⫺238.4 ⫾ 101.8
58.2 ⫾ 20.1
8.4 ⫾ 3.4
⫺179.8 ⫾ 73.5
32.1 ⫾ 6.6
6.1 ⫾ 3.8
⫺110.4 ⫾ 75.0*
32.5 ⫾ 18.4*
5.5 ⫾ 2.3
⫺92.4 ⫾ 61.1*
28.7 ⫾ 12.0
Other parameters
Atrioventricular E-to-A ratio
2.00 ⫾ 0.17
1.66 ⫾ 0.51
1.90 ⫾ 0.39
2.33 ⫾ 0.70
Values are means ⫾ SD. EPER, early peak emptying rate; LPER, late peak emptying rate; E-to-A ratio, ratio of the early ventricular filling wave to late atrial
contraction filling wave. *Significant difference compared with data in control subjects (P ⬍ 0.05).
evidenced by decreased late diastolic RA emptying fraction
and strain rate. This observation is in line with several studies
(7, 15) that reported a reduced active atrial pump function in
volume-loaded ventricles. Other authors (7, 10, 28) have reported increased active atrial performance in the presence of
severe, isolated pressure loaded LVs or RVs, for example, in
the setting of pulmonary hypertension. In our selected group of
patients with only moderate pressure load of the RV in addition
to volume load, we did not see this effect of increased atrial
pump function. Although the relation between active atrial
pump function and ventricular load reported by other investigators is striking, it is not possible to explain the underlying
mechanisms on the basis of the studies performed so far. One
might speculate that atrial filling, which correlated in our study
with atrial pump function, has an impact on atrial activation.
However, systematic future research is necessary to further
evaluate this matter.
Limitations
To keep variability low, this study was conducted in
preselected TOF patients who had a homogeneous moderate
degree of RV enlargement and dysfunction. In addition, we
excluded patients with major tricuspid insufficiency, as this
will cause atrial distension and thus induce other pathophysiological mechanisms of atrial function. Therefore, the results of our study are not representative for all TOF patients.
The values for natriuretic peptides are lacking, as these were
not measured in our patients. Whether the observed abnormalities of RA function are from intrinsic causes or express
the functional response to abnormal RV function cannot be
fully determined at present. A possible intrinsic cause might
be the scar in the RA after open-heart surgery. Furthermore,
after surgery, the pericardium was left open, whereas the
intact pericardium seems to play a role in regular atrial
function (11).
Conclusions
In the TOF patients studied, moderate systolic and diastolic
RV dysfunction is already associated with impaired RA function. There is a strong coupling of RV ejection fraction,
tricuspid annular plane displacement, and RA filling. Future
studies need to systematically evaluate if RA dysfunction is a
predictor of RV failure.
ACKNOWLEDGEMENTS
The authors thank Anne Gale for editorial assistance.
GRANTS
Fig. 4. Conduit flow for one typical patient and one typical control subject. In
the patient, the conduit flow is delayed but higher in its magnitude.
AJP-Heart Circ Physiol • VOL
This work was supported by Federal Ministry of Education and Research
Grant 01EV0704 and Competence Network for Congenital Heart Defects
Grant FKZ 01G10210.
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Emptying parameters
Atrial emptying in early diastole, ml/body surface area
EPER, ml 䡠 s⫺1 䡠 body surface area⫺1
Early emptying fraction, %
Atrial emptying in late diastole, ml/body surface area
LPER, ml 䡠 s⫺1 䡠 body surface area⫺1
Late emptying fraction, %
ATRIOVENTRICULAR INTERACTIONS IN TOF
DISCLOSURES
No conflicts of interest, financial or otherwise, are declared by the author(s).
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