Download Age, gender, blood pressure, and ventricular geometry influence

European Heart Journal – Cardiovascular Imaging (2013) 14, 366–373
doi:10.1093/ehjci/jes196
Age, gender, blood pressure, and ventricular
geometry influence normal 3D blood flow
characteristics in the left heart
Daniela Föll 1, Steffen Taeger 1, Christoph Bode 1, Bernd Jung 2, and Michael Markl 3,4*
1
Department of Cardiology and Angiology, University Heart Center Freiburg, Hugstetterstr.55, Freiburg 79106, Germany; 2Department of Diagnostic Radiology, Medical Physics,
Albert-Ludwigs-University Hospital Freiburg, Freiburg, Germany; 3Department of Radiology, Feinberg School of Medicine, Northwestern University, 737 N. Michigan Avenue Suite
1600, Chicago, IL 60611, USA; and 4Department of Biomedical Engineering, McCormick School of Engineering, Northwestern University, 737 N. Michigan Avenue Suite 1600,
Chicago, IL 60611, USA
Received 27 June 2012; accepted after revision 24 August 2012; online publish-ahead-of-print 21 September 2012
Aims
The aim of this study was to assess the effect of age, gender, physiological, and global cardiac function parameters on
differences in normal 3D blood flow in the left ventricle (LV) and atrium (LA) using 4D flow magnetic resonance
imaging (MRI).
.....................................................................................................................................................................................
Methods
Four-dimensional flow MRI was acquired in healthy volunteers of two age and gender groups: ,30 years (6 women,
and results
n ¼ 12) and .50 years (6 women, n ¼ 12). Systolic and early to mid-diastolic vortex flow (number of vortices, duration, area, peak velocity inside the vortex) in the LA and LV was assessed using intra-cardiac flow visualization based
on 3D particle traces and velocity vector fields. A larger number of vortices in the LA were found in young compared
with older individuals (number of diastolic vortices: 1.6 + 0.8 vs. 0.7 + 0.7, P ¼ 0.01) with higher velocities
(54 + 12 cm/s vs. 41 + 11 cm/s in systole, 47 + 13 vs. 31 + 8 cm/s in diastole, P , 0.05). Vortices in the LV base
were smaller in women compared with men (369 + 133 vs. 543 + 176 mm2, P ¼ 0.009), while vortex size was
increased in mid-ventricular locations (maximum area: 546 + 321 vs. 293 + 174 mm2, P , 0.05). Correlation analysis
revealed significant relationships (P ¼ 0.005 –0.048, correlation coefficients ¼ 0.44–0.84) between LA and LV vortex
characteristics (number, size, vortex velocities) and blood pressure as well as end-diastolic volume, LV length, and
ejection fraction.
.....................................................................................................................................................................................
Conclusions
Flow patterns in the left heart demonstrated differences related to age, gender, blood pressure, and ventricular geometry. The findings constitute a prerequisite for the understanding of the impact of cardiac disease on intra-cardiac
haemodynamics.
----------------------------------------------------------------------------------------------------------------------------------------------------------Keywords
Blood flow † 4D flow MRI † Ageing † Gender † Vortex
Introduction
Blood flow through the beating heart is complex and normal
physiological as well as pathologically altered blood flow conditions
are difficult to assess in vivo. Alterations of blood flow can carry
important consequences in congenital or valvular heart disease,
in remodelling of the left ventricle (LV) in ischaemic heart
disease or in aortic diseases.1,2
To date, a comprehensive analysis of intra-cardiac 3D flow patterns is not performed in clinical routine and only limited data on
normal atrial and ventricular flow patterns are available. Blood flow
measurements are limited to 2D Doppler echocardiography or
phase contrast magnetic resonance imaging (MRI) which acquires
flow velocities within a user-selected 2D plane.3,4 Both techniques
are limited to measurements at predefined locations and often
assess only a single velocity component of the underlying threedirectional blood flow. Routinely used phase contrast MRI or
Doppler ultrasound do not offer the possibility to measure and
visualize the temporal evolution of complex flow patterns within
a 3D volume encompassing the beating human heart.
* Corresponding author. Tel: +1 312 695 1799, Email: [email protected]
Published on behalf of the European Society of Cardiology. All rights reserved. & The Author 2012. For permissions please email: [email protected]
367
3D blood flow characteristics in the left heart
To overcome these limitations, 4D flow MRI (ECGsynchronized 3D phase contrast MRI with three-directional velocity encoding) has been applied in a number of studies for the
analysis of 3D blood flow with full volumetric coverage of the
left atrium (LA)5 and left ventricle (LV).6 – 8 Vortical flow within
the cardiac chambers has been described in healthy volunteers1,5,7 – 10 as well as in patients with cardiomyopathy,6,11 mitral
valve insufficiency,12 and after heart transplantation.13 Fourdimensional MRI data have been used for the quantification of
flow within cardiac chambers,14 through the heart valves,15 and
in pulmonary arteries in patients with Fontan circulation.1
Although it is known that age and gender alter LV myocardial
tissue properties16 and function,17,18 a systematic evaluation of
normal physiological LA and LV flow formation in relation to
age, gender, and other influencing factors such as blood pressure
or heart rate is missing. The aim of this study was to test the hypothesis that age, gender, physiological, and global cardiac function
parameters correlate with the presence and extent of left atrial and
left ventricular systolic and diastolic vortex flow patterns in healthy
volunteers.
Methods
Study population
We included 24 healthy volunteers in two age and gender groups:
,30 years (n ¼ 12, mean 23.3 + 1.6 years, 6 women) and .50
years (n ¼ 12, 58.3 + 4.2 years, 6 women). The cut-off age was
chosen based on the assumption that a large difference between the
age-group cut-offs (20 years) would provide a clear separation of
both groups and result in an improved separation of flow characteristics given the small number of individuals in each cohort. All volunteers
were without history, symptoms, or medication of cardiovascular or
pulmonary disease, diabetes, arterial hypertension, or peripheral arterial disease. All volunteers had a normal echocardiography and ECG
findings. Written informed consent was obtained from all participants
and the study was approved by our local ethics board. The volunteers’
characteristics are summarized in Table 1.
MR imaging
All examinations were performed using a standard 12-element torso
coil (3T, Magnetom TRIO, Siemens, Erlangen, Germany). We
employed flow-sensitive MRI with volumetric 3D coverage of the
whole heart and three-directional velocity encoding (4D flow MRI)
to systematically identify and evaluate the existence and extent of characteristic flow patterns in the left heart.19 The imaging sequence consisted of a previously described, k-space segmented, rf-spoiled gradient
echo sequence with interleaved three-directional velocity encoding.1,20
Other imaging parameters were: TE ¼ 2.4 ms, TR ¼ 4.8 ms, flip
angle ¼ 78, field of view ¼ 320 × 240 mm, spatial resolution ¼ 2.5 ×
2.5 × 2.8 mm3, temporal resolution ¼ 38.4 ms, scan time 15 –
25 min, and parallel imaging with reduction factor R ¼ 2.21 Magnetic
resonance imaging acquisitions were synchronized to the heart and
breathing cycle using prospective ECG gating and adaptive diaphragm
navigator gating.20 Prospective ECG gating resulted in 4D flow data
covering about 80 – 90% of the heart cycle, i.e. including systole,
early, and mid-diastole.
Data analysis
All 4D flow data underwent pre-processing including noise masking, eddy
current correction, Maxwell corrections, and calculation of a 3D phase
contrast MR angiogram as described previously.22 – 24 To visually identify
and grade intra-cardiac flow patterns, 3D visualization was employed
(EnSight v. 8.2, CEI, Apex, NC, USA). Flow analysis included the calculation
of time-resolved 3D particle traces originating from emitter planes which
were manually placed in the pulmonary veins. The resulting traces provide
a visual representation of the temporal dynamics and spatial distribution of
3D blood flow (Figure 1). In addition, vector fields in the two- and fourchamber planes were calculated for each time point (Figures 2 and 3). In
order to identify and grade intra-atrial and intra-ventricular vortex flow,
particle traces were first used to identify vortices and their directions of
rotation. In the following, vector graphs were analysed as follows:
† Left atrium (two-chamber and four-chamber view): number, duration, maximum area, and peak velocities inside the vortex. The analysis was performed separately for both systole and early to
mid-diastole.
† Left ventricle (two-chamber and four-chamber view): peak diastolic
LV in-flow velocity and systolic and early to mid-diastolic vortex formation (number, duration, maximum area, and peak velocity inside
the vortex) at base, mid, and apex of the LV.
Vortex duration was defined as the time between the onset of
visible vortical flow to its disappearance. Vortical flow in the LA was
assessed as viewed from behind, LV flow was evaluated as viewed
from above (four-chamber view) or from the left side (two-chamber
view). If not stated otherwise, the results given in the text refer to
the analysis in two-chamber view.
Statistical analysis
All data are presented as mean + standard deviation unless stated
otherwise. Comparisons between age groups and genders were performed by unpaired Student’s t-test for normally distributed values
and the Mann– Whitney U-test for values not normally distributed.
Systolic and diastolic vortex formation in the LA and LV (number, duration, maximum area, and peak velocity inside the vortex) were correlated with physiological parameters, such as age, heart rate, and blood
pressure and with LV geometry and function. Correlations were calculated by the Pearson Product Moment for values normally distributed,
and Spearman’s test was used to calculate correlations for values not
normally distributed. The Kolmogorov – Smirnov test was used to test
for normality. A. Kruskal – Wallis one-way analysis of variance (‘on
Ranks’ for not normally and equally distributed values) followed by
the Holm– Sidack (or Dunn’s) procedure for pairwise multiple
testing was used for the comparisons between the flow characteristics
within the three levels of the LV. Statistical testing was performed using
SigmaStat for Windows Version 3.10. Two-tailed tests with P , 0.05
were considered statistically significant.
Results
Study cohort
The clinical characteristics for all subjects are summarized in Tables 1
and 2. Older volunteers had higher systolic blood pressure (P ¼
0.01) and shorter LV length (P ¼ 0.02). Older men had higher heart
rates (P ¼ 0.01), systolic blood pressures (P ¼ 0.04), and higher LV
mass (P ¼ 0.02) compared with young men. Women had a higher
LVEF and reduced left ventricular end-diastolic volume (LVEDV),
LVESV, and LV mass compared with men (P , 0.05, Table 2).
368
Table 1
D. Föll et al.
Study cohort
Age group 1
....................................................................
All (n 5 12)
Men (n 5 6)
Women (n 5 6)
Age group 2
....................................................................
All (n 5 12)
Men (n 5 6)
Women (n 5 6)
...............................................................................................................................................................................
Age (years)
23 + 2
24 + 1
23 + 2
58 + 4*
59 + 4*
58 + 4*
Heart rate (b.p.m.)
66 + 9
61 + 5
70 + 10
67 + 6
70 + 5*
64 + 7
113 + 5
74 + 4
113 + 7
75 + 4
123 + 10*
77 + 8
128 + 9*
80 + 10
120 + 9
75 + 4
BP sys. (mmHg)
BP dia. (mmHg)
LVEF (%)
LVEDV (mL)
LVESV (mL)
LV length (mm)
LV mass (gm)
LVSV (mL)
113 + 3
72 + 4
65 + 3
64 + 2
65 + 3
65 + 4
62 + 2
68 + 3**
139 + 21
146 + 18
132 + 21
127 + 17
138 + 14
116 + 12**
49 + 9
95 + 6
52 + 8
99 + 5
45 + 8
91 + 3**
45 + 10
86 + 7*
52 + 8
90 + 7
37 + 6**
83 + 5
118 + 27
138 + 21
97 + 12**
134 + 37
174 + 7*
103 + 15**
91 + 13
94 + 12
82 + 8
86 + 6
87 + 13
78 + 8
BP, blood pressure; LVEF, ejection fraction; LVEDV, left ventricular end-diastolic volume; LVESV, left ventricular end-systolic volume; LVSV, left ventricular stroke volume. All
values are means + 1 standard deviation.
*P , 0.05 vs. age group 1.
**P , 0.05 vs. men.
Figure 1 3D visualization of diastolic left atrial and ventricular inflow characteristics with substantial vortex formation in the LA and laminar
ventricular filling with clearly separated left and right pulmonary vein flow channels. LV, left ventricle; LPV, left pulmonary veins; rPV, right pulmonary veins.
Three-dimensional particle traces
In all volunteers, vortical flow was found in the LA und LV. Systolic
and diastolic vortical flow in the LA was evident in 92% of the
young and 83% of the older volunteers (Figure 1). Most LA vortices
(81% in young and 74% in older subjects) were directed clockwise
as viewed from the back. Twenty-eight percent of the vortices in
men and only 16% in women were anti-clockwise.
(151 + 60 vs. 124 + 74 ms; P ¼ 0.055 in two-chamber view;
171 + 90 vs. 96 + 56 ms in four-chamber view, P ¼ 0.005).
Younger individuals showed an increased duration (P ¼ 0.023)
and higher velocities (P ¼ 0.012) inside the vortices in the LA for
both systole and diastole compared with the older group. Diastolic
LA vortices occurred less frequently in older volunteers (five subjects showed no vortex compared with one subject ,30 years)
(P , 0.013).
Left atrial flow
In 75% of subjects, systolic and diastolic vortex flow in the LA was
evident as shown in Figure 1 and summarized in Tables 3 for vector
plot analysis. Compared with early to mid-diastolic vortex flow,
systolic vortex flow occurred more frequently (systole vs. diastole:
2.2 + 1.0 vs. 1.1 + 0.9, P , 0.001), and had longer duration
Left ventricular flow
The results of LV flow analysis are summarized in Tables 4. The
maximum area of vortices decreased from base to apex for both
men and women. Larger vortices were found at the base
(472 + 196 vs. 299 + 112 mm2 in mid-ventricular and 214 +
3D blood flow characteristics in the left heart
369
Figure 2 Vector graph visualization of intra-cardiac blood flow in a young (A) and an old (B) healthy volunteer. The formation of diastolic
vortex flow in the LA and LV is evident and indicated by the dashed circles. Note the reduced diastolic in-flow velocities (colour coding) and
less-prominent vortex flow in the older volunteer. RV, right ventricle; Ao, aorta.
128 mm2 in apical parts of the LV, P ¼ 0.002). Peak velocities
within the vortices decreased from base to apex (base 6.1 +
1.7 cm/s, mid 4.5 + 1.0 cm/s, apex 3.3 + 0.8 cm/s, P , 0.001).
The smallest numbers of vortices were found in apical parts of
the LV (0.3 + 0.4 vs. 2.0 + 0.4 in basal or 2.0 + 0.7 in midventricular segments, P , 0.001). The majority subjects presented
with two vortices in the LV base (88%) and mid-ventricular LV
(54%) irrespective of age.
Peak vortex velocities were significantly higher in the younger
compared with older volunteers in the LV base (6.9 + 1.4 vs.
5.2 + 1.6 cm/s; P ¼ 0.005) as exemplary illustrated in Figure 2. In
the mid-ventricular LV, older participants demonstrated less vortices compared with the younger individuals (in four-chamber view:
1.7 + 0.7 vs. 1.1 + 0.7, P ¼ 0.002).
Gender-related differences
At the LV base, women revealed smaller vortices (369 + 133 vs.
543 + 176 mm2, P ¼ 0.009) (Figure 3), while vortex size was
increased at the mid-ventricular location compared with men
(maximum area: 546 + 321 vs. 293 + 174 mm2, P ¼ 0.033). In
addition, apical vortices had increased duration in women compared with men (98 + 38 vs. 48 + 19 ms; P ¼ 0.038).
Correlation with physiological data, LV
function, and morphology
There was an inverse relationship between increasing age and systolic vortex velocities [correlation coefficient (CC) ¼ 20.51, P ¼
0.01] and number of diastolic vortices (CC ¼ 20.45, P ¼ 0.03) in
the LA. Furthermore, age was inversely correlated with the
maximum area (CC ¼ 20.49, P ¼ 0.02) and velocity (CC ¼
20.48, P ¼ 0.02) of basal LV vortices.
Heart rate did affect the number of diastolic LA vortices (CC ¼
20.55, P ¼ 0.007) and was also correlated with the duration
(basal: CC ¼ 20.46, P ¼ 0.03; mid-LV: CC ¼ 20.57, P ¼ 0.005)
and area (mid-LV: CC ¼ 20.45, P ¼ 0.03) of LV vortices.
Increased systolic blood pressure resulted in a larger size of diastolic LA vortices (CC ¼ 0.50, P ¼ 0.046) but reduced vortex peak
velocity (CC ¼ 20.54, P ¼ 0.03) and less basal LV vortices (CC ¼
20.44, P ¼ 0.048) with lower peak velocities (CC ¼ 0.57, P ¼
0.007). Diastolic blood pressure correlated with mid-ventricular
and apical LV vortex velocities (CC ¼ 20.74, P , 0.001, respectively, CC ¼ 20.84, P ¼ 0.03).
Left ventricular end-diastolic volume influenced the number of
LA vortices in diastole (CC ¼ 0.49, P ¼ 0.03) and LV length correlated with the number of LV vortices (mid-LV: CC ¼ 0.52, P ¼
370
D. Föll et al.
Figure 3 Vector graph visualization of intra-cardiac blood flow in a female participant (A) and a male participant (B) of the young age group.
Note the reduced diastolic vortex flow in the base of the LV in women compared with men. Vortices in the LV base and mid-ventricle are
indicated by the dashed circles. LA, left atrium; RV, right ventricle; Ao, aorta.
Table 2
Genders’ characteristics
Men (n 5 12)
Women (n 5 12)
0.04, apical: CC ¼ 20.69, P ¼ 0.003). A higher LVEF was associated with a decreased area of basal vortices (CC ¼ 20.49, P ¼
0.03) and more apical vortices (CC ¼ 0.421, P ¼ 0.05).
................................................................................
Age (years)
Heart rate (b.p.m.)
41 + 18
66 + 7
39 + 18
66 + 9
BP sys. (mmHg)
120 + 11
117 + 8
BP dia. (mmHg)
LVEF (%)
77 + 8
63 + 3*
74 + 4
66 + 3
142 + 17*
127 + 19
52 + 8*
95 + 8*
42 + 8
87 + 6
154 + 24**
100 + 14
90 + 10
85 + 12
LVEDV (mL)
LVESV (mL)
LV length (mm)
LV mass (gm)
LVSV (mL)
BP, blood pressure; LVEF, left ventricular ejection fraction; LVEDV, left ventricular
end-diastolic volume; LVESV, left ventricular end-systolic volume; LVSV, left
ventricular stroke volume. All values are means + 1 standard deviation.
*P , 0.05 vs. women.
*P , 0.001 vs. women.
Discussion
The maintenance of a stable blood flow is fundamental for human
life and the ultimate measure of adequate cardio-vascular function.
The results of this study demonstrate the potential of 4D flow MRI
with whole heart coverage for the detailed analysis of intra-cardiac
vortex flow. The results of our semi-quantitative analysis of flow
patterns demonstrated significant age as well as gender-related differences in intra-atrial and intra-ventricular flow patterns.
Flow characteristics in the LA have previously been analysed by
others and anti-clockwise vortex formation in the LA has been
reported before (as viewed from the front).7 In our study, previously not described vortex formation in the opposite direction
was found in 54% of the individuals mainly from blood flow originating in the upper pulmonary veins. Similar to findings in other
371
3D blood flow characteristics in the left heart
Table 3 Cumulative results of vortex analysis in the LA for the young (<30 years) and the older age group (>50 years)
analysed in the two-chamber view and in the four-chamber-view
Number
Duration (ms)
Area max. (mm2)
Vmax (cm/s)
...............................................................................................................................................................................
Analysis based on two-chamber view
Systole
,30 years (n ¼ 12)
.50 years (n ¼ 12)
Diastole
,30 years (n ¼ 12)
.50 years (n ¼ 12)
Analysis based on four-chamber view
2.2 + 1.0
178 + 63*
338 + 142
54 + 12*
2.3 + 1.1#
124 + 44
354 + 268
41 + 11
1.6 + 0.8*
134 + 88
319 + 283
47 + 13*
0.7 + 0.7
110 + 47
332 + 164
31 + 8
1.9 + 0.9
2.0 + 1.2
174 + 68#
169 + 112#
350 + 279
259 + 167
41 + 11
36 + 12
1.7 + 1.0
1.0 + 1.2
111 + 5
70 + 50
219 + 194
157 + 100
37 + 8
27 + 11
Systole
,30 years (n ¼ 12)
.50 years (n ¼ 12)
Diastole
,30 years (n ¼ 12)
.50 years (n ¼ 12)
Data represent mean values + standard deviation. Vmax, peak velocity; Area max., maximum area.
*P , 0.05 vs. older age group.
#
P , 0.05 vs. diastole (same age group).
Table 4 Cumulative results of vortex analysis in the LV for the young (<30 years) and the older age group (>50 years)
analysed in the two-chamber view and in the four-chamber view
Number
Duration (ms)
Area max. (mm2)
Vmax (cm/s)
2.1 + 0.3
2.0 + 0.4
154 + 68
116 + 52
538 + 164
406 + 206
69 + 14
52 + 16*
2.3 + 0.7
1.8 + 0.6
170 + 81
123 + 55
286 + 110
312 + 118
48 + 6
43 + 14
0.3 + 0.4
0.3 + 0.5
153 + 66
89 + 89
149 + 108
260 + 152
30 + 10
37 + 6
Base
,30 years (n ¼ 12)
1.8 + 0.4
126 + 37
473 + 200
65 + 9
.50 years (n ¼ 12)
1.9 + 0.3
131 + 55
438 + 155
52 + 10*
...............................................................................................................................................................................
Analysis based on two-chamber view
Base
,30 years (n ¼ 12)
.50 years (n ¼ 12)
Mid
,30 years (n ¼ 12)
.50 years (n ¼ 12)
Apex
,30 years (n ¼ 12)
.50 years (n ¼ 12)
Analysis based on four-chamber view
Mid
,30 years (n ¼ 12)
.50 years (n ¼ 12)
1.7 + 0.7
155 + 103
452 + 333
54 + 19
1.1 + 0.7*
130 + 89
381 + 219
43 + 14
Apex
,30 years (n ¼ 12)
0.5 + 0.7
72 + 33
152 + 51
26 + 6
.50 years (n ¼ 12)
0.5 + 0.7
84 + 50
124 + 55
28 + 8
Data represent mean values + standard deviation.
Vmax, peak velocity; Area max., maximum area.
*Significant differences between both age groups (P , 0.05).
372
studies and probably due to the more cranial location of the left
pulmonary veins, vortex formation in flow path ways originating
from the left side was more prominent.5 In contrast to a previous
study,5 we did not find a relationship between LA vortex flow duration and heart rate. In addition, we found shorter durations of LA
vortices which might be related to the higher temporal resolution
in our study.
As reported by Kilner et al.,7 the heart’s vortical flow characteristics in conjunction with the looped formation of the heart itself
seem to be fundamental for a stable blood flow, prevention of
energy losses, and optimal atrial –ventricular coupling especially
with increased heart rate under exercise. Furthermore, vortex
flow is meant to play an important role in the valves’ closure25
and in preventing blood flow stasis and thromboembolic risk.
The asymmetric vortical inflow in the cardiac chambers has been
reported in healthy volunteers using phase contrast MRI5,7 and
ultrasound vectorparticle image velocimetry.26,27 Vortices have
been described in basal LV locations at the anterior mitral leaflet
and near the posterior mitral leaflet.7,28 It is assumed that vortices
play an important role in redirecting the inflowing blood flow
towards the aortic valve.
Previous 4D flow MRI studies have demonstrated that in the
healthy heart 30% of the blood in the LVEDV passes the LV directly within one cardiac cycle in the shortest way and with least
energy losses,14 whereas this percentage of ‘direct flow’ in the
LV is strongly reduced in the failing heart.6,11 Studies with vector
particle image velocimetry also revealed altered LV vortices in
patients with systolic LV dysfunction,27 stressing the importance
of an undisturbed vortical flow for optimal cardiac function.
However, none of these studies based their findings on a systematic age- and gender-related comparison of LA and LV flow characteristics including other influencing factors such as blood
pressure or heart rate.
As we could demonstrate, ageing resulted in a reduced number
of diastolic LA vortices as well as lower velocities and durations of
systolic LA vortices. These findings could not be explained by heart
rate or LVEF, which did not differ between the age groups. Shorter
LV lengths and higher systolic blood pressures might have contributed to the reduced numbers of mid-ventricular vortices and the
reduced diastolic vortical velocities in the LA and LV base but
do not explain the other differences of LA vortical flow. It is
known that ageing alters LA29 and LV function17 due to changes
of myocardial structure and differences in Ca channel handling,
alterations in the sympathic nervous system, and a reduction in arterial compliance and endothelial function.16 In this context,
altered Doppler inflow characteristics in the LA30 and LV31 have
been described with ageing. In line with our finding of reduced
LA diastolic vortices, the inflow in the LA decreases in diastole
with increased age, whereas inflow in systole increases.30 Our
finding of reduced diastolic vortex formation in the LA and LV in
older volunteers might therefore reflect age-related diastolic dysfunction of these individuals.
Women revealed smaller vortices in the LV base and a higher
number of vortices in the mid-ventricular LV. In addition, apical
vortex formation lasted longer compared with men. Geometric
differences such as reduced LVEDV or LV length in women did
not explain these gender differences. The higher LVEF in older
D. Föll et al.
women might have contributed to smaller vortices in basal parts
in women. Similar to our findings, gender differences in LV
inflow measured by Doppler echo have been described.31
However, the increased extent of mid-ventricular vortices in
women is a previously unreported finding and might be caused
by increased vascular and ventricular stiffness in women as previously reported by Redfield et al.32
Limitations
A limitation of our study is related to the prospective ECG gating
of our 4D flow MR sequence. As a result, only data representing
about 80 –90% of the heart cycle were acquired within the RR
interval. Therefore, atrial contraction with consecutive second
filling of the LV could only be visualized in four of the older individuals despite sinus rhythm in all volunteers. It should be noted
that, as a result of prospective ECG gating, late diastole is variably
included in the results. As a result, the findings of this study need to
be interpreted with care and represent flow characteristics during
early and mid-diastole only.
A further drawback of the data analysis methodology is related
to the use of velocity vector fields from conventional two- and
three-chamber views which minimize the ‘three-dimensional’
aspect of our findings, even though these were based on threedirectional data.
Another limitation of the study is that we did only perform a
semi-quantitative analysis without evaluation of intra- and interobserver variability. In addition, no data on inter-study variability are
currently available to provide information on the test-retest reliability of cardiac 4D flow MRI and the analysis methods presented
here.
The small size of the study cohort constitutes a major limitation
and underlines the feasibility character of this study. In our current
study, we have analysed the impact of the haemodynamic state of
an individual (heart-rate, blood pressure, etc.) on the resulting
cardiac flow characteristics using correlation analysis. The small
number of volunteers might explain the significant but moderate
correlations (r ¼ 0.4 –0.8) found in our cohort between flow characteristics and cardiac function parameters, blood pressure, heart
rate, and age. The evaluation of intra-cardiac 3D blood flow in
larger cohorts is warranted to confirm our results and clarify the
degree of correlation between the haemodynamic state of an individual and the observed flow characteristics.
In addition, further studies with increased sample sizes and including patient data are essential to evaluate the influence of
cardiac disease on the flow characteristics of the left heart.
Further, an investigating of the reproducibility of the flow characteristics indices and semi-quantitative flow pattern grading used
in this study are needed. Although we did not evaluate the observer variability of the semi-quantitative flow pattern grading, previous work by our group has demonstrated the reliability of flow
pattern grading based on 4D flow MRI data. In a recent study assessing aortic flow patterns in patients with Marfan syndrome using
4D flow MRI, we found substantial inter-observer agreement
(kappa ¼ 0.7) for the visual grading of helix and vortex flow in
the ascending aorta, the aortic arch, and descending aorta.33
A further drawback is related to the relatively long 4D flow MRI
acquisition times and the effective averaging of velocity
373
3D blood flow characteristics in the left heart
measurements over many heart cycles, only flow characteristics
that occur consistently through successive beats are recorded
and analysed. The peak local velocities and numbers of vortices
identified may underestimate those occurring in real time in any
given beat. Nevertheless, our study describes the feasibility of
blood flow imaging in the healthy heart and offers new insights
into intra-cardiac blood flow characteristics.
Conclusions
Cardiac 4D flow MRI in a small cohort of healthy subjects demonstrated that heart rate, blood pressure, LV geometry, age, and
gender can affect intracardiac blood flow characteristics. These
findings might have the potential to improve our understanding
of physiological and pathological processes of cardiovascular function. Future studies including data on reproducibility and larger
patient cohorts are needed to assess the impact of intra-cardiac
flow patterns on cardiovascular disease and their diagnostic value
related to disease progression and therapy monitoring.
14.
15.
16.
17.
18.
19.
20.
Funding
21.
M.M. is supported by the NMH Excellence in Academic Medicine
(EAM) Program ‘Advanced Cardiovascular MRI Research Center’.
D.F. is supported by the Deutsche Forschungsgemeinschaft (DFG).
Grant # FO 507/2-1, FO 507/3-1.
22.
Conflict of interest: none declared.
23.
References
24.
1. Markl M, Geiger J, Kilner PJ, Föll D, Stiller B, Beyersdorf F et al. Time-resolved
three-dimensional magnetic resonance velocity mapping of cardiovascular flow
paths in volunteers and patients with Fontan circulation. Eur J Cardiothorac Surg
2011;39:206 –12.
2. Clough RE, Waltham M, Giese D, Taylor PR, Schaeffter T. A new imaging method
for assessment of aortic dissection using four-dimensional phase contrast magnetic resonance imaging. J Vasc Surg 2012 [Epub ahead of print].
3. Pelc NJ, Sommer FG, Li KC, Brosnan TJ, Herfkens RJ, Enzmann DR. Quantitative
magnetic resonance flow imaging. Magn Reson Q 1994;10:125 – 47.
4. Chai P, Mohiaddin R. How we perform cardiovascular magnetic resonance flow
assessment using phase-contrast velocity mapping. J Cardiovasc Magn Reson
2005;7:705 –16.
5. Fyrenius A, Wigstrom L, Ebbers T, Karlsson M, Engvall J, Bolger AF. Three dimensional flow in the human left atrium. Heart 2001;86:448 – 55.
6. Bolger AF, Heiberg E, Karlsson M, Wigstrom L, Engvall J, Sigfridsson A et al.
Transit of blood flow through the human left ventricle mapped by cardiovascular
magnetic resonance. J Cardiovasc Magn Reson 2007;9:741–7.
7. Kilner PJ, Yang GZ, Wilkes AJ, Mohiaddin RH, Firmin DN, Yacoub MH. Asymmetric redirection of flow through the heart. Nature 2000;404:759–61.
8. Kim D, Gilson WD, Kramer CM, Epstein FH. Myocardial tissue tracking with twodimensional cine displacement-encoded MR imaging: development and initial
evaluation. Radiology 2004;230:862 –71.
9. Wigstrom L, Ebbers T, Fyrenius A, Karlsson M, Engvall J, Wranne B et al. Particle
trace visualization of intracardiac flow using time-resolved 3D phase contrast MRI.
Magn Reson Med 1999;41:793 –9.
10. Fredriksson AG, Zajac J, Eriksson J, Dyverfeldt P, Bolger AF, Ebbers T et al. 4-D
blood flow in the human right ventricle. Am J Physiol Heart Circ Physiol 2011;301:
H2344 –50.
11. Carlhall CJ, Bolger A. Passing strange: flow in the failing ventricle. Circ Heart Fail
2010;3:326 –31.
12. Dyverfeldt P, Kvitting JE, Carlhall CJ, Boano G, Sigfridsson A, Hermansson U et al.
Hemodynamic aspects of mitral regurgitation assessed by generalized phasecontrast MRI. J Magn Reson Imaging 2011;33:582 –8.
13. Markl M, Geiger J, Arnold R, Stroh A, Damjanovic D, Föll D et al. Comprehensive
4-dimensional magnetic resonance flow analysis after successful heart
25.
26.
27.
28.
29.
30.
31.
32.
33.
transplantation resolves controversial intraoperative findings and reveals
complex hemodynamic alterations. Circulation 2011;123:e381 –3.
Eriksson J, Carlhall CJ, Dyverfeldt P, Engvall J, Bolger AF, Ebbers T. Semi-automatic
quantification of 4D left ventricular blood flow. J Cardiovasc Magn Reson
2010;12:9.
Roes SD, Hammer S, van der Geest RJ, Marsan NA, Bax JJ, Lamb HJ et al. Flow
assessment through four heart valves simultaneously using 3-dimensional
3-directional velocity-encoded magnetic resonance imaging with retrospective
valve tracking in healthy volunteers and patients with valvular regurgitation.
Invest Radiol 2009;44:669 –75.
Lakatta EG, Levy D. Arterial and cardiac aging: major shareholders in cardiovascular disease enterprises: part II: the aging heart in health: links to heart
disease. Circulation 2003;107:346 –54.
Föll D, Jung B, Schilli E, Staehle F, Geibel A, Hennig J et al. Magnetic resonance
tissue phase mapping of myocardial motion—new insights in age and gender magnetic resonance tissue phase mapping of myocardial motion- new insights in age
and gender. Circ Cardiovasc Imaging 2010;3:54–64.
Föll D, Jung B, Staehle F, Schilli E, Bode C, Hennig J et al. Visualization of multidirectional regional left ventricular dynamics by high-temporal-resolution tissue
phase mapping. J Magn Reson Imaging 2009;29:1043 –52.
Markl M, Kilner PJ, Ebbers T. Comprehensive 4D velocity mapping of the heart
and great vessels by cardiovascular magnetic resonance. J Cardiovasc Magn
Reson 2011;13:7.
Markl M, Harloff A, Bley TA, Zaitsev M, Jung B, Weigang E et al. Time-resolved 3D
MR velocity mapping at 3T: improved navigator-gated assessment of vascular
anatomy and blood flow. J Magn Reson Imaging 2007;25:824 – 31.
Griswold MA, Jakob PM, Heidemann RM, Nittka M, Jellus V, Wang J et al. Generalized autocalibrating partially parallel acquisitions (GRAPPA). Magn Reson Med
2002;47:1202 – 10.
Walker PG, Cranney GB, Scheidegger MB, Waseleski G, Pohost GM,
Yoganathan AP. Semiautomated method for noise reduction and background
phase error correction in MR phase velocity data. J Magn Reson Imaging 1993;3:
521 –30.
Bernstein MA, Zhou XJ, Polzin JA, King KF, Ganin A, Pelc NJ et al. Concomitant
gradient terms in phase contrast MR: analysis and correction. Magn Reson Med
1998;39:300 –8.
Bock J, Kreher BW, Hennig J, Markl M. Optimized pre-processing of time-resolved
2D and 3D phase contrast MRI data. In Proceedings: 15th Scientific Meeting
International Society for Magnetic Resonance in Medicine Berlin, Germany 2007;
p. 3138.
Bellhouse BJ. Fluid mechanics of a model mitral valve and left ventricle. Cardiovasc
Res 1972;6:199 – 210.
Sengupta PP, Khandheria BK, Korinek J, Jahangir A, Yoshifuku S, Milosevic I et al.
Left ventricular isovolumic flow sequence during sinus and paced rhythms: new
insights from use of high-resolution Doppler and ultrasonic digital particle
imaging velocimetry. J Am Coll Cardiol 2007;49:899 – 908.
Hong G, Pedrizzetti G, Tonti G, Li P, Wei Z, Kim JK et al. Characterization and
quantification of vortex flow in the human left ventricle by contrast echocardiography using vector particle image velocimetry. JACC Cardiovasc Imaging 2008;1:
705 –17.
Kim WY, Walker PG, Pedersen EM, Poulsen JK, Oyre S, Houlind K et al. Left ventricular blood flow patterns in normal subjects: a quantitative analysis by threedimensional magnetic resonance velocity mapping. J Am Coll Cardiol 1995;26:
224 –38.
Germans T, Gotte MJW, Nijveldt R, Spreeuwenberg MD, Beek AM,
Bronzwaer JGF et al. Effects of aging on left atrioventricular coupling and left ventricular filling assessed using cardiac magnetic resonance imaging in healthy subjects. Am J Cardiol 2007;100:122–7.
Gentile F, Mantero A, Lippolis A, Ornaghi M, Azzollini M, Barbier P et al.
Pulmonary venous flow velocity patterns in 143 normal subjects aged 20 to 80
years old. An echo 2D colour Doppler cooperative study. Eur Heart J 1997;18:
148 –64.
Daimon M, Watanabe H, Abe Y, Hirata K, Hozumi T, Ishii K et al. Gender differences in age-related changes in left and right ventricular geometries and functions.
Echocardiography of a healthy subject group. Circ J 2011;75:2840 –6.
Redfield MM, Jacobsen SJ, Borlaug BA, Rodeheffer RJ, Kass DA. Age- and genderrelated ventricular-vascular stiffening: a community-based study. Circulation 2005;
112:2254 –62.
Geiger J, Markl M, Herzer L, Hirtler D, Loeffelbein F, Stiller B et al. Aortic flow
patterns in patients with Marfan syndrome assessed by flow-sensitive fourdimensional MRI. J Magn Reson Imaging 2012;35:594 – 600.