Download Total heart volume variation throughout the cardiac cycle in humans

Am J Physiol Heart Circ Physiol 287: H243–H250, 2004.
First published March 11, 2004; 10.1152/ajpheart.01125.2003.
Total heart volume variation throughout the cardiac cycle in humans
Marcus Carlsson,1 Peter Cain,1 Catarina Holmqvist,2
Freddy Stahlberg,3 Stig Lundback,4 and Hakan Arheden1
Departments of 1Clinical Physiology, 2Radiology, and 3Radiophysics, Lund
University Hospital, Lund SE-22185; and 4Inovacor, Stockholm SE-18592, Sweden
Submitted 25 November 2003; accepted in final form 5 March 2004
cardiac volume. Investigations in humans with the use of
computed tomography (15) and MRI in ventilated patients (18)
have suggested that a volume variation of 8 –13% may occur
between diastole and systole. However, recent work (7) with
the use of high-resolution MRI found a lower volume variation
of 5% with the largest variation calculated to be at the left side
using individual chamber volume measurements at end systole
and end diastole (7).
These studies confirm the presence, but an unclear extent
and timing, of total heart volume variation throughout the
cardiac cycle at rest. Additional physiological information may
be obtained using measurements of blood flow that are easily
obtained using MRI.
Therefore, the goals of this study were to investigate the
magnitude, timing, and contributors of the total heart volume
change during the cardiac cycle in healthy humans with the use
of both the MRI-planimetric method as in earlier studies as
well as quantitative velocity mapping MRI (21). This will
allow the opportunity to explore total heart volume variation
from a structural (planimetry) and functional (flow) perspective. The use of both of these principally different techniques in
the same subjects gives the possibility to identify whether the
volume change is due to a physiological phenomena or a
measurement error inherent to the planimetric method (which
could explain the large variation between studies).
magnetic resonance imaging; left ventricle; output
MATERIALS AND METHODS
Study Population and Design
cardiac function have been
studied for centuries (27) with the knowledge acquired providing detailed insights into the fundamental physiology of this
organ. Although much of this research has concentrated on the
characteristics of the individual cardiac chambers, little is
known about total heart volume variation during the cardiac
cycle and the respective contributors to this variation. The
extent of any volume variation is not just of “academic”
concern because it reflects the efficient use of energy by the
heart; a large total volume change could result in energy loss
through displacement of surrounding tissues or induce a pendular motion of cardiac tissue and blood (11, 12, 14, 20).
In 1932, Hamilton and Rompf (11) described a relative
constancy of the total heart volume during the cardiac cycle in
frogs, turtles, and dogs. They concluded that through the
motion of the atrioventricular (AV) plane, the heart was able to
pump blood but still maintain the same volume. Subsequent
noninvasive investigations in cats (10) and dogs (12, 14) were
concordant with this initial finding of a relatively consistent
THE CHARACTERISTICS OF HUMAN
Address for reprint requests and other correspondence: M. Carlsson, Dept.
of Clinical Physiology, Lund University Hospital, Lund SE-22185, Sweden
(E-Mail: [email protected]).
http://www.ajpheart.org
Eight healthy volunteers (26 – 47 yr old, 5 men and 3 women) were
examined after approval of the local ethics committee. Subjects
underwent cardiac MRI in the supine position. Short-axis gradientecho cine imaging encompassing the entire heart from the base of the
atria to the apex of the ventricles was followed by blood flow
measurements using velocity mapping in all vessels leading into and
out of the heart. Changes in total heart volume throughout the cardiac
cycle were calculated directly by planimetry of the gradient-echo cine
images and indirectly by subtracting all of the blood flow out of the
heart (aorta and pulmonary artery) from all blood flow into the heart
(inferior and superior vena cava and the lung veins).
Magnetic Resonance Imaging
A 1.5-T MRI scanner (Magnetom Vision; Siemens, Erlangen,
Germany) with 25 mT/m maximum gradient strength and 600-␮s
gradient ramp time was used to acquire all images.
Volumetric imaging. ECG-triggered gradient-echo sequences were
used to obtain cine images during end-expiratory apnea (⬃15 s). The
number of phases was determined by the R-R interval, resulting in
15–21 images per heart cycle. The typical imaging parameters were
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0363-6135/04 $5.00 Copyright © 2004 the American Physiological Society
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Carlsson, Marcus, Peter Cain, Catarina Holmqvist, Freddy
Stahlberg, Stig Lundback, and Hakan Arheden. Total heart volume variation throughout the cardiac cycle in humans. Am J Physiol
Heart Circ Physiol 287: H243–H250, 2004. First published March 11,
2004; 10.1152/ajpheart.01125.2003.—Variations in total heart volume (atria plus ventricles) during a cardiac cycle affect efficiency of
cardiac pumping. The goals of this study were to confirm the presence,
extent, and contributors of total heart volume variation during the cardiac
cycle in healthy volunteers with the use of MRI. Eight healthy volunteers
were examined by MRI at rest. Changes in total cardiac volume throughout the cardiac cycle were calculated using the following methods: 1)
planimetry derived from gradient-echo cine images and 2) flow-sensitive
sequences to quantify flow in all vessels leading to and from the heart.
The maximum total heart volume diminished during systole by 8.2 ⫾
0.8% (SEM, range 4.8 –10.6%) measured by method 1 and 8.8 ⫾ 1.0%
(SEM, range 5.6 –11.8%) by method 2 with good agreement between the
methods [difference according to Bland-Altman analysis ⫺0.6% ⫾ 1.0%
(SD), intraclass correlation coefficient ⫽ 0.999]. This decrease in volume
is predominantly explained by variation at the midcardiac level at the
widest diameter of the heart with a left-sided predominance. In the short
axis of the heart, the change of slice volume was proportional to the
end-diastolic slice volume. The present study has confirmed the presence
of total heart volume variation that predominantly occurs in the region of
atrioventricular plane movement and on the left side. The total heart
volume variation may relate to the efficiency of energy use by the heart
to minimize displacement of surrounding tissue while accounting for the
energy required to draw blood into the atria during ventricular systole.
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TOTAL HEART VOLUME VARIATION IN HUMANS
Fig. 1. Volumetric measurements of total cardiac volume. Top: long-axis
gradient echo images of the heart at end diastole (A) and end systole (B),
showing the four-chamber view of the left ventricle (LV), right ventricle (RV),
left atrium (LA), and right atrium (RA). This projection was used to align the
short-axis image planes (lines) perpendicular to the septum and parallel to the
atrioventricular (AV) plane. Bottom: corresponding short-axis gradient echo
images in end diastole (C) and end systole (D). Each short-axis view consisted
of 15–21 images, 50 ms apart, covering the cardiac cycle. The dotted line
shows how a region of interest (ROI) was drawn around the entire cardiac
structure. This was undertaken for every image frame in each imaging plane.
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Fig. 2. Measurement of blood flow with magnetic resonance imaging. For each
anatomic image (A) a corresponding phase image is obtained (B). The anatomic
image is used to identify the vessel in which flow shall be measured (in this case,
vena cava inferior). A ROI (white oval) representing the vessel and two ROIs
(black circle) in nonmoving tissue for background correction are drawn in the
anatomic image and copied to the phase image where flow is measured. The
grayscale in the phase image is directly proportional to flow velocity in each pixel
(scale bar). Darker gray means flow in one direction and lighter gray flow in the
opposite direction. The resulting absolute blood flow within the target vessel may
then be derived from the combination of velocity values from each pixel (C).
Volumetric measurements. A ROI was drawn around the pericardial border (Image software; Scion Image, Scion) of the heart in each
image of the cine-loop throughout the heart (Fig. 1, C and D). The
ROI included all structures within the pericardium: the atria, ventricles, and the roots of the aorta and pulmonary artery. The area was
multiplied by slice thickness to give the volume. The volumes of all
slices of the heart were added to identify the total heart volume at each
phase during the cardiac cycle. The percentage of total heart volume
change was calculated as maximum change divided by total heart
volume at end diastole.
Flow measurements. Two different evaluation platforms were used
(RADGOP; Context Vision, Linköping, Sweden, and Scion Image).
Each blood vessel was manually outlined in the anatomic images for
each time point with flow calculation undertaken in the corresponding
velocity-mapped images. To determine the change in heart volume,
the difference between the sums of blood flow into the heart (pulmonary and caval veins) and out of the heart (aorta and pulmonary artery
flow) was calculated over the cardiac cycle. Total heart volume
change by the flow method divided by total heart volume at end
diastole by the volumetric method gives the percentage of total heart
volume change for the flow method.
Isolated contribution of systole to change in total heart volume. To
calculate the total heart volume change that would occur if there were
no cardiac inflows to the atria during systole, the combined volume
ejected into the aorta and pulmonary artery in systole (the ventricular
stroke volumes obtained by the flow method) was divided by the total
heart volume at end diastole obtained by the volumetric method. To
calculate how large the filling of the heart is during systole, the
combined inflows to the heart were divided by the total heart volume
at end diastole by the volumetric method. To calculate the percentage
of the stroke volumes that is secured by the heart by filling of the atria
during ventricular systole, the combined inflows during systole were
divided by the stroke volumes obtained by the flow method.
Chamber contribution to change in total heart volume. Flow
measurements were used to calculate the contribution to the heart
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the following: 100-ms repetition time (echo sharing resulting in
phases every 50 ms), 4.8-ms echo time, 30° flip angle, and 10-mm
slice thickness (edge to edge). Short-axis images (Fig. 1, C and D)
were taken from cardiac base to ventricular apex perpendicular to the
left ventricular longitudinal axis (Fig. 1, A and B). Three long-axis
images were obtained in the two-chamber, four-chamber, and the left
ventricular aortic-outflow-tract views.
Flow imaging. ECG-triggered, flow-sensitive sequences (gradientecho velocity-mapping sequences provided by the manufacturer) were
used to measure blood flow in the vessels leading from and to the
heart (the aorta, the pulmonary trunk, the superior and inferior caval
veins, and the four pulmonary veins). Flow was measured in a
perpendicular plane to the vessel. The typical imaging parameters
were the following: 30-ms repetition time, 5-ms echo time, 8-mm
slice thickness, 150 cm/s velocity encoding, and 36 – 47 images per
heart cycle. In the case of aliasing, the study was repeated with 250
cm/s velocity encoding. No images with aliasing were used for
analysis. Velocity information was acquired over one or two heart
cycles (acquisition time of 3–7 min). Accuracy and precision of this
technique has been thoroughly validated (2, 16, 26).
Figure 2 shows an example of the velocity mapping technique in an
image plane perpendicular to the inferior caval vein. The grayscale
values of each pixel in these images (Fig. 2B) are directly proportional
to velocity. Thus within a region of interest (ROI), the average blood
flow velocity for any given time point throughout the cardiac cycle
can be calculated. Knowledge of the measured area will allow calculation of absolute blood flow (average velocity ⫻ area ⫽ average
flow) (Fig. 2C). Two ROIs for background correction of field inhomogenities were drawn in stationary tissue at equal length from the vessel
investigated, as previously described (2). The average signal intensity of
these ROIs in nonmoving tissue were set to represent 0 cm/s.
TOTAL HEART VOLUME VARIATION IN HUMANS
volume change from the left and the right side of the heart. The net
volume difference between inflow and outflow to the left side of the
heart (pulmonary veins and aorta) from end diastole to end systole
was divided by the total cardiac volume difference from end diastole
to end systole. This provided the contribution of the left side (atrium
and ventricle) to the total heart volume change in percent.
Validation of short-axis measurements and interobserver variability. To validate short-axis measurements [which have proven to be the
best plane to determine left ventricular volumes (9, 19) and therefore
are commonly used in cardiac MRI], one subject was examined using
the frontal, axial, sagittal (5-mm image slice thickness), as well as the
short-axis imaging planes (10-mm image slice thickness). The variation in total heart volume was compared between each of these
imaging planes. Interobserver variability was performed by two independent observers in all subjects for volumetric measurements and in
the first four subjects for flow measurements.
Continuous variables are presented as means ⫾ SE and with the range
of the variables. The interobserver or method concordance was calculated
using the intraclass correlation coefficient (ICC) (25). Bland-Altman
analysis (5) and ICC were used to test whether the two methods used to
measure changes in total heart volume (volumetric and flow) differed.
Paired t-test was used to test whether the changes in apex base length
were significant. Pearson’s correlation was used to examine the relationship between relative contribution to total heart volume change and
starting slice volume.
RESULTS
Validation of Short-Axis Measurements and
Interobserver Variability
Good agreement (ICC 0.91) between imaging planes was
observed for total heart volume and its variation and was consistent with previous investigations of interstudy variability (4, 24).
Therefore, only one imaging plane (short axis) was used for
subsequent subjects. The interobserver variability of planimetry
measurements of total heart volume using short-axis images was
good (ICC 0.98) and consistent with earlier studies of interobserver agreement of MRI measurement (4, 6, 24). The interobserver variability of flow measurements, ICC ⬎0.99, was also
acceptable. The agreement between observers is visually demonstrated by the original data in Fig. 3 where all in- and outflows
measured by two observers in one subject is shown.
Fig. 3. Flow of all vessels entering and leaving the heart in one
subject measured by two independent observers. The outflows
of the heart [the aorta (A) and the pulmonary artery (B)] are
more pulsatile than the inflows to the heart [cava and pulmonary veins (C–H)], which are more continuous. The graphs
show original data from one subject. Note the agreement
between the two observers.
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Statistical Analysis
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TOTAL HEART VOLUME VARIATION IN HUMANS
Table 1. Total heart volume during cardiac cycle and related parameters
Subject
Sex
Age
1
2
3
4
5
6
7
8
Means ⫾ SE
F
F
F
M
M
M
M
M
37
39
35
26
36
35
47
26
THV Change,
%Volumetric
THV Change,
%Flow
THV, ml
THV/BSA,
ml/m2
Length in
ED-ES, %
THV Change
left, %
Ejected Volume/
THV, %
Atrial Filling
in systole, %
Pulse Rate,
beats/min
4.8
10.6
6.6
9.1
10.6
6.1
8.8
9.1
8.2⫾0.8
5.6
11.8
6.6
11.8
11.1
5.3
8.9
9.4
8.8⫾1.0
618
584
667
807
715
985
956
891
778⫾55
381
368
389
384
374
442
502
426
408⫾16
⫺1
0
3
2
1
2
1
⫺2
0.9⫾0.5
63
62
56
52
66
70
57
62
61⫾2
21
30
21
26
30
18
25
22
24⫾1
73
60
69
55
62
71
64
58
64⫾2
60
57
71
67
53
61
54
53
60⫾2
Fig. 4. Total heart volume during the cardiac cycle in all eight
subjects by volumetric and flow measurements. There is a
decrease in total heart volume in the first part of the cardiac
cycle (systole) and a recovery in volume at the later part of the
cardiac cycle (diastole). The change in heart volume by the flow
measurements was set to begin at the volume of the heart
obtained from the volumetric method. Note the agreement
between the two principally different methods in both phase
and magnitude.
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THV change %volumetric, % total heart volume change during the cardiac cycle as measured by gradient echo MRI (volumetric measurement); THV change
%flow, % THV change as measured by phase-subtraction, velocity-mapping MRI; THV/BSA, THV normalized to body surface area; length in ED-ES%, mean
difference in length of the three long-axis planes from end diastole to end systole divided by the length in end diastole; THV change left%, contribution to total
change from the left ventricle and atrium; ejected volume/THV%, volume leaving the heart in systole in aorta and pulmonary artery divided by THV. Atrial filling
in systole %, percentage of the stroke volume from the ventricles that is filled into the atria during ventricular systole.
TOTAL HEART VOLUME VARIATION IN HUMANS
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Characteristics of Total Heart Volume Variation During the
Cardiac Cycle
Volume Variation According to Cardiac Chamber
The proportion of total heart volume variation was greater
on the left side of the heart, 61 ⫾ 2% (range 52–70%)
compared with the right (Table 1). The predominant volume
changes were visually observed where the heart was most
adjacent to the lungs, whereas the regional changes in volume
at the borders to the liver were less and were essentially absent
near the thoracic wall (Fig. 8B).
Change in Slice Volumes
The largest volume change during systole was located where
the diameter of the heart was largest, i.e., at the base of the
ventricles. This coincided with the region of the AV plane
movement (Figs. 1 and 6). The contribution to change in total
heart volume from each individual short-axis slice was relative
to the size of that slice (r2 ⫽ 0.43) (Fig. 7) resulting in a
proportional decrease in volume in all parts of the heart in
systole.
Notably, the epicardium of the ventricles and the pericardium are opposed (Fig. 8) at end diastole, whereas at end
systole, the epicardium of the anterobasal part of the left
ventricle is no longer opposed to the pericardium, but instead
meets the left atrial appendage. Thus the appendages can be
seen to “fill out” the volume loss resulting from ventricular
contraction.
Longitudinal Shortening of the Heart
There was only a minor change in the length of the heart,
0.9 ⫾ 0.5% (range ⫺2 to 3%; P ⫽ 0.07) from apex to base, and
the apex of the ventricles was essentially stationary (Table 1).
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Fig. 5. Temporal difference of cardiac inflow and outflow by flow measurements in one subject. Change in total heart volume was calculated as cumulative volume difference (C; ‚). This was done by mapping inflow and outflow
(A) and calculating the cumulative volume (B) as the sum of inflow and
outflow at each phase of the cardiac cycle. A: total flow leaving the heart (the
sum of the flows of the aorta and the pulmonary artery) is pulsatile and the total
flow entering the heart (the sum of the flows of the cava and pulmonary veins)
is more continuous. Positive values are inflow and negative values outflow. B:
there is a discrepancy in time of the cumulative values of the volume entering
and leaving the heart due to the difference in flow patterns described in A. The
cumulative curves diverge during systole and converge during diastole. This
results in a decrease in total volume in systole that returns to the presystolic
volume during diastole. C: volume difference () is negative during systole,
meaning that total heart volume (‚) decreases. When the volume difference
changes from negative to positive values the total heart volume regains its
original value.
DISCUSSION
This study has shown a variation of ⬃8% (range 5–11%) in
total heart volume between diastole and systole in healthy
individuals measured noninvasively using cine-MRI. Importantly, both the planimetric and flow-based methods independently show similar results for total heart volume variation in
each individual subject and the reproducibility of each of these
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The overall total heart volume variation during a cardiac
cycle did not differ between the volumetric and the flow
methods: 8.2 ⫾ 0.8% (range 4.8 –10.6%) versus 8.8 ⫾ 1.0%
(range 5.6 –11.8%) (Table 1). ICC was 0.999 and the difference
according to Bland-Altman analysis was ⫺0.6 ⫾ 1.0% (SD).
The magnitude and time course of the total heart volume
variation were essentially similar in all subjects (Fig. 4). It
should be noted that the investigated subjects were at rest, with
cardiac output of 6.4 ⫾ 0.3 l/min, range 4.7–7.4 l/min; cardiac
index 3.4 ⫾ 0.1 l 䡠min⫺1 䡠m⫺2, range 2.9 –3.7 l䡠min⫺1 䡠m⫺2
and low heart rates, range 53–71 beats/min.
Examination of the pattern of flow throughout the cardiac
cycle, was, however, more complex (Fig. 5). The pulsatile
pattern of the outflow in systole and the more continuous,
slightly bipolar, inflow both in diastole and systole (Fig. 5A)
resulted in a variable flow difference between outflow and
inflow over time. In systole, outflow was greater than inflow
(decrease in cardiac size), whereas the reverse was true during
diastole (Fig. 5C). These findings were reflected across the
study population with the proportion of blood ejected during
systole exceeding the filling of the atria during systole; 24 ⫾
1% (range 18 –30%) versus 15 ⫾ 1% (range 13–19%) of the
total heart volume (P ⫽ 0.001). During systole, 64 ⫾ 2%
(range 58 –73%) of the stroke volume from the ventricles was
secured by filling of the atria (Table 1).
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TOTAL HEART VOLUME VARIATION IN HUMANS
techniques was shown to be high. The variation in total heart
volume change between subjects likely demonstrates a true
physiological variation because of the concordant findings
from two independent methods. The variation arises from a
decrease in total heart volume in systole due to a discrepancy
in blood flow into and out of the heart with no significant
longitudinal shortening of the heart during this process. The
major contributor to the volume change is the region around
the AV plane movement with a leftsided predominance. For
any given cardiac MRI short-axis imaging plane, the change in
volume was essentially proportional to the starting volume in
that plane.
Earlier Studies of Total Heart Volume
Since the days of Da Vinci (27), researchers have attempted
to explain the fundamental properties of cardiac function.
Much of this work has concentrated on the mechanics of
individual chambers; however, the properties of total heart
volume and shape are less well explored.
Earlier studies undertaken in this area using animal and
human subjects have produced conflicting results regarding the
variation of cardiac volume. Some reported no variation (11),
Fig. 7. Volume change as a function of slice volume. y-Axis: heart volume
change (C) in one slice in percentage of total heart volume change in that
subject. x-Axis: heart volume (V) in one slice in percentage of total heart
volume at end diastole. The relationship is shown between the relative
contribution from a single slice to the total heart volume change (y-axis) and
the relative contribution of that slice to the total heart volume (x-axis). The
larger a slice is, the more it contributes to total heart volume change. The
relationship is essentially proportional. The equation for the regression line is:
y ⫽ 1.1x ⫺ 0.75.
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Fig. 8. Regional differences in total heart volume changes. app, Appendage.
Top: short-axis views of the heart at end diastole (A) and end systole (B). The
pericardium in end diastole is marked with a dotted line both in A and B. A
variation of volume has occurred from diastole to systole where the epicardium
no longer opposes the dotted line in B. The level of the short-axis plane shown
is chosen where the diameter of the heart is the largest. There is a larger
volume change seen at the left-hand side than the right-hand side. At the
left-hand side, there is a volume change where the epicardium opposes the
pericardium but no volume change where the left atrial appendage opposes the
pericardium. Note that at end systole (B) due to AV plane descent the left
ventricular (LV) outflow tract can be seen where myocardium was seen at end
diastole (A). Bottom: long-axis two-chamber views of the heart at end diastole
(C) and end systole (D). The broken line indicates the epicardium of the left
ventricle at end diastole and the dotted line the epicardium at end systole. At
the basal level of the LV in end systole the epicardial border (dotted line D)
does not oppose the pericardium but the left atrial appendage (also seen in B).
The same finding can be seen for the right atrial appendage at the right
ventricle (B).
some reported a variation within the measurement error (14),
and others suggested that a variation indeed exists, although
the total heart volume variation varies between studies from 5
to 13% (7, 12, 15, 18). In 1932, Hamilton and Rompf (11) did
a study of the heart in frogs, turtles, and dogs and concluded
that the variation of total heart volume during the heart cycle
was minimal and that much of the cardiac output was generated
by movement of the AV plane. Subsequent work by Gauer (10)
expanded these initial findings by acquiring fluoroscopic ventriculograms of cat hearts and concluded that the “outside
dimensions of the heart. . .identical” between systole and diastole. Further studies by Hoffman et al. (12, 15) in dogs were
consistent with this observation with a total heart volume
variation of 5% that increased with atrial fibrillation. However,
Leithner et al. (18) demonstrated in humans a variation of up to
13% of intracavitary volumes but suggested that this could not
be considered as total heart volume and therefore was guarded
in drawing any conclusions about true total heart volume
variation. Bowman et al. (7) recently proposed that the total
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Fig. 6. Anatomic location of change in total heart volume in a typical subject.
The main part of the change in volume between diastole and systole was
located at the base of the ventricles i.e., where the diameter of the heart is
largest. A typical finding was a decrease in volume in all slices of the heart
during ventricular systole. The largest slices, and the largest contribution to
total heart volume change, were found at the midcardiac level, at the region of
the AV plane movement.
TOTAL HEART VOLUME VARIATION IN HUMANS
chamber volumes in the pericardium may be less constant than
the blood pool content. In the present study, however, we did
not find any significant difference between total heart volume
variation obtained by flow or planimetric measurements.
The variation between subjects in total heart volume change
is likely a true physiological finding because two principally
different and independent techniques (flow and planimetry)
yielded highly concordant results. This intersubject variation
may explain the differing results in total heart volume change
found in previous studies.
Physiological Relevance
Further Studies
Studies with MRI under dobutamine and/or atropine stress
would give the opportunity to tease out the effect on total heart
volume variation of higher heart rates and cardiac outputs
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discussed above. This could give new information on the
cardiac energetics in man under different physiological conditions.
Limitations
The volumetric images in this study were acquired during
end-expiratory apnea. This potentially may affect cardiac output, pulse rate, and introduce a potential “valsalva-like” effect
on the filling of the cardiac chambers. In addition, the temporal
resolution of the volumetric image sequences was 50 ms and
thus may be an undersample of the true end-diastolic and
end-systolic dimensions of the heart. Despite these potential
errors, the flow-based measurements that have a higher temporal resolution (30 – 40 frames per heart cycle) and are acquired during free breathing were in close concordance with
the volumetric measurements and therefore suggests that these
errors are likely to be small at most. It should be noted that the
volumetric images are acquired during 15–19 heartbeats per
slice and that the flow images are acquired during 256 heartbeats (or 512 when the images were obtained over two R-R
intervals). Other imaging limitations inherent to cardiac MRI
were occasionally present during this study, including the
“partial volume effect,” which results from a composite image
of 1-cm imaging planes. This effect, however, is also likely to
be small as demonstrated by the validation of the 1-cm shortaxis slice thickness with 0.5-cm slice thickness measurements
in three orthogonal planes.
In conclusion, the present study has demonstrated in humans
that total cardiac volume, during a full cardiac cycle at low
cardiac output and heart rate, diminishes 8% (range 5–11%)
during systole and predominantly occurs in the region of the
AV plane and on the left side. The total heart volume variation
may relate to the efficiency of energy use by the heart to
minimize displacement of surrounding tissues while accounting for the energy required to draw blood into the atria during
ventricular systole.
GRANTS
This study was supported by the Swedish Research Council, the Swedish
Heart and Lung Foundation, and The Medical Faculty of Lund University.
REFERENCES
1. Appleton CP. Hemodynamic determinants of Doppler pulmonary venous
flow velocity components: new insights from studies in lightly sedated
normal dogs. J Am Coll Cardiol 30: 1562–1574, 1997.
2. Arheden H, Holmqvist C, Thilen U, Hanseus K, Bjorkhem G, Pahlm
O, Laurin S, and Stahlberg F. Left-to-right cardiac shunts: comparison
of measurements obtained with MR velocity mapping and with radionuclide angiography. Radiology 211: 453– 458, 1999.
3. Bartzokis T, Lee R, Yeoh TK, Grogin H, and Schnittger I. Transesophageal echo-Doppler echocardiographic assessment of pulmonary venous
flow patterns. J Am Soc Echocardiogr 4: 457– 464, 1991.
4. Bellenger NG, Davies LC, Francis JM, Coats AJ, and Pennell DJ.
Reduction in sample size for studies of remodeling in heart failure by the
use of cardiovascular magnetic resonance. J Cardiovasc Magn Reson 2:
271–278, 2000.
5. Bland JM and Altman DG. Statistical methods for assessing agreement
between two methods of clinical measurement. Lancet 1: 307–310, 1986.
6. Bogaert JG, Bosmans HT, Rademakers FE, Bellon EP, Herregods
MC, Verschakelen JA, Van de Werf F, and Marchal GJ. Left ventricular quantification with breath-hold MR imaging: comparison with echocardiography. Magma 3: 5–12, 1995.
7. Bowman AW and Kovacs SJ. Assessment and consequences of the
constant-volume attribute of the four-chambered heart. Am J Physiol
Heart Circ Physiol 285: H2027–H2033, 2003.
287 • JULY 2004 •
www.ajpheart.org
Downloaded from http://ajpheart.physiology.org/ by 10.220.33.2 on April 28, 2017
A low total heart volume variation will lower the energy
required to move surrounding tissues during filling and emptying of the heart (12). Our qualitative visual assessment and
quantitative findings (Table 1) have shown that the largest
volume variation occurred in the region of the AV plane and
slightly more on the left-hand side and is consistent with
previously published findings (13). At higher heart rates and
cardiac output, the momentum of the blood created by the
descent of the AV plane can be used for a more rapid filling of
the expanding atria and the reverse motion of the AV plane.
Thus at higher heart rates, blood will have a higher momentum,
decreasing the requirement of outer volume change in the
surrounding tissue, which would save energy. In addition,
higher heart rates may result in a lower total heart volume
change because of a shortened diastolic phase, and this possibly could make the outflow less pulsatile, and hence, synchronize the in- and outflow (20). This could result in a lesser total
heart volume change at higher frequencies. This is in line with
the findings of Brecher (8), Nilsson et al. (22), and the conclusions of Gauer (10) that faster and smaller hearts secure
80% of their stroke volume during ventricular systole. In the
present study in humans (larger species and therefore larger
hearts and slower heart rates) 64% (range 55–73%) of the
stroke volumes from both chambers were secured into the atria
during systole (reservoir function of both atria). The reservoir
function of the left atrium in percentage of the stroke volume
of the left ventricle has previously been reported to be 38% as
assessed by Doppler echocardiography (23) and 41% as assessed by MRI (17). Thus the reservoir function of the right
atrium is higher than the left atrium. This can be visualized in
the flow curves as a more bipolar flow in the caval veins with
the highest peak in systole and a more continuous flow in the
pulmonary veins.
In Doppler examination of caval and pulmonary veins, a
similar biphasic pattern of blood flow during systole and
diastole into the heart as in the present study has been found (3)
and also alteration of cardiac filling according to heart rate (1).
At an increased heart rate, proportionally greater systolic atrial
filling over diastolic flow occurs compared with that which
occurs at lower heart rates. These findings with echocardiography are consistent with the previously stated relationship
between cardiac volume variation and heart rate, as increased
systolic atrial filling would minimize volume variation.
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H250
TOTAL HEART VOLUME VARIATION IN HUMANS
AJP-Heart Circ Physiol • VOL
18. Leithner C, Podolsky A, Globits S, Frank H, Neuhold A, Pidlich J,
Schuster E, Staudinger T, Rintelen C, Roggla M, Glogar D, and Frass
M. Magnetic-resonance-imaging of the heart during positive end-expiratory pressure ventilation in normal subjects. Crit Care Med 22: 426 – 432,
1994.
19. Longmore DB, Klipstein RH, Underwood SR, Firmin DN, Hounsfield
GN, Watanabe M, Bland C, Fox K, Poole-Wilson PA, Rees RS,
Denison D, McNeilly AM, and Burman ED. Dimensional accuracy of
magnetic resonance in studies of the heart. Lancet 1: 1360 –1362, 1985.
20. Lundback S. Cardiac pumping and function of the ventricular septum.
Acta Physiol Scand 127: 8 –101, 1986.
21. Nayler GL, Firmin DN, and Longmore DB. Blood flow imaging by cine
magnetic resonance. J Comput Assist Tomogr 10: 715–722, 1986.
22. Nilsson NJ and Kurt K. Stromvolumpulse der herznahen Venen bei
verschiedenen Kreislaufzuständen. Zeitschrift Biologie 106: 386 –394,
1954.
23. Prioli A, Marino P, Lanzoni L, and Zardini P. Increasing degrees of left
ventricular filling impairment modulate left atrial function in humans.
Am J Cardiol 82: 756 –761, 1998.
24. Semelka RC, Tomei E, Wagner S, Mayo J, Kondo C, Suzuki J, Caputo
GR, and Higgins CB. Normal left ventricular dimensions and function:
interstudy reproducibility of measurements with cine MR imaging. Radiology 174: 763–768, 1990.
25. Shrout PE and Fleiss JL. Intraclass correlations– uses in assessing rater
reliability. Psychol Bull 86: 420 – 428, 1979.
26. Sondergaard L, Hildebrandt P, Lindvig K, Thomsen C, Stahlberg F,
Kassis E, and Henriksen O. Valve area and cardiac output in aortic
stenosis: quantification by magnetic resonance velocity mapping. Am
Heart J 126: 1156 –1164, 1993.
27. Wandt B. Long-axis contraction of the ventricles: a modern approach, but
described already by Leonardo da Vinci. J Am Soc Echocardiogr 13:
699 –706, 2000.
287 • JULY 2004 •
www.ajpheart.org
Downloaded from http://ajpheart.physiology.org/ by 10.220.33.2 on April 28, 2017
8. Brecher GA. Cardiac variations in venous return studied with a new
bristle flowmeter. Am J Physiol 176: 423– 430, 1954.
9. Chuang ML, Hibberd MG, Salton CJ, Beaudin RA, Riley MF, Parker
RA, Douglas PS, and Manning WJ. Importance of imaging method over
imaging modality in noninvasive determination of left ventricular volumes
and ejection fraction: assessment by two- and three-dimensional echocardiography and magnetic resonance imaging. J Am Coll Cardiol 35:
477– 484, 2000.
10. Gauer OH. Volume changes of the left ventricle during blood pooling and
exercise in the intact animal: their effects on left ventricular performance.
Physiol Rev 35: 143–155, 1955.
11. Hamilton WF and Rompf JH. Movement of the base of the ventricle and
the relative constancy of the cardiac volume. Am J Physiol 102: 559 –565,
1932.
12. Hoffman EA and Ritman EL. Heart-lung interaction: effect on regional
lung air content and total heart volume. Ann Biomed Eng 15: 241–257,
1987.
13. Hoffman EA and Ritman EL. Intracardiac cycle constancy of total heart
volume. Dyn Cardiovasc Imaging 1: 199 –205, 1988.
14. Hoffman EA and Ritman EL. Invariant total heart volume in the intact
thorax. Am J Physiol Heart Circ Physiol 249: H883–H890, 1985.
15. Hoffman EA, Rumberger J, Dougherty L, Reichek N, and Axel L. A
geometric view of cardiac “efficiency” (Abstract). J Am Coll Cardiol 13:
86A, 1989.
16. Hundley WG, Li HF, Hillis LD, Meshack BM, Lange RA, Willard JE,
Landau C, and Peshock RM. Quantitation of cardiac output with
velocity-encoded, phase-difference magnetic resonance imaging. Am J
Cardiol 75: 1250 –1255, 1995.
17. Jarvinen V, Kupari M, Hekali P, and Poutanen VP. Assessment of left
atrial volumes and phasic function using cine magnetic resonance imaging
in normal subjects. Am J Cardiol 73: 1135–1138, 1994.