Download Left Ventricular Untwisting Is an Important Determinant of Early

JACC: CARDIOVASCULAR IMAGING
VOL. 2, NO. 6, 2009
© 2009 BY THE AMERICAN COLLEGE OF CARDIOLOGY FOUNDATION
PUBLISHED BY ELSEVIER INC.
ISSN 1936-878X/09/$36.00
DOI:10.1016/j.jcmg.2009.01.015
Left Ventricular Untwisting Is an Important
Determinant of Early Diastolic Function
Andrew T. Burns, MB, BS (HONS), BMEDSCI, MD,* Andre La Gerche, MB, BS,*
David L. Prior, MBBS, PHD,*† Andrew I. MacIsaac, MBBS, MD*†
Melbourne, Victoria, Australia
O B J E C T I V E S We sought to establish the relationship between invasive measures of diastolic
function and untwisting parameters measured with speckle tracking imaging.
B A C K G R O U N D Left ventricular (LV) diastolic function is determined by early diastolic relaxation
(which creates suction gradients for LV filling) and myocardial stiffness. Assessment of LV torsion has
shown that untwisting begins before aortic valve closure and, in animals, might be an important
component of normal diastolic filling. Studies in human subjects using indirect indexes derived from
right heart catheterization have suggested a relationship between ␶ and measures of untwisting, but the
relationship between directly measured diastolic function indexes with micromanometer catheters and
untwisting parameters has not been established in human subjects.
M E T H O D S Simultaneous Millar micromanometer LV pressure and echocardiographic assessment
was performed on 18 patients (10 male, mean age 66 years) with normal systolic function and a
spectrum of diastolic function. Invasive rate of the rise of LV pressure, dp/dt minimum and ␶ were
recorded as measures of active relaxation, and the LV minimum diastolic pressure was recorded as an
index of diastolic suction. The LV stiffness constant and functional chamber stiffness were estimated
from hybrid pressure-volume loops. Echocardiographic speckle tracking imaging was used to quantify
torsion.
R E S U L T S As relaxation was impaired, (prolonged ␶) untwisting was delayed (r ⫽ 0.35, p ⬍ 0.01).
There were nonsignificant associations between reduced untwisting and longer values of ␶ and lower
dp/dt minimum. Reduction in the extent of untwisting before mitral valve opening was associated with
increased LV minimum diastolic pressure (r ⫽ ⫺0.30, p ⬍ 0.034). No relation was observed between the
LV stiffness constant (␤: r ⫽ 0.11, p ⫽ NS) or the functional LV chamber stiffness (b: r ⫽ 0.11, p ⫽ NS)
and untwisting.
C O N C L U S I O N S Untwisting parameters are related to invasive indexes of LV relaxation and
suction but not to LV stiffness. These data suggest that untwisting is an important component of early
diastolic LV filling but not later diastolic events. (J Am Coll Cardiol Img 2009;2:709 –16) © 2009 by the
American College of Cardiology Foundation
From the *Cardiac Investigation Unit and †University of Melbourne Department of Medicine, St. Vincent’s Hospital
Melbourne, Victoria, Australia. Dr. Burns is supported by a Postgraduate Research Scholarship from the National Heart
Foundation of Australia.
Manuscript received July 28, 2008; revised manuscript received December 18, 2008, accepted January 23, 2009.
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Burns et al.
Untwisting in Diastolic Function
JACC: CARDIOVASCULAR IMAGING, VOL. 2, NO. 6, 2009
JUNE 2009:709 –16
T
raditional measures of left ventricular (LV)
diastolic function have focused on relaxation
and stiffness. Early diastolic LV relaxation
creates intraventricular pressure gradients or
suction gradients that are important, because they
allow efficient LV filling without increasing left atrial
(LA) pressure (1,2), particularly during exercise (3,4).
See page 717
Torsion, the rotation of the apex and the base of
the LV on its longitudinal axis in opposite directions, results from the contraction of the obliquely
oriented subendocardial and subepicardial helixes
(5,6). The LV untwisting results begins before
aortic valve closure and before longitudinal and
radial expansion (7). Because it is one of the earliest
events leading to LV filling, untwisting might be a
critical determinant of early diastolic function. The
quantification of LV untwisting might provide
novel insights into diastolic function (8,9),
ABBREVIATIONS
in particular the generation of intravenAND ACRONYMS
tricular pressure gradients (10).
Dong et al. (11) found, in a canine
dp/dt ⴝ rate of the rise of left
model,
a strong correlation between recoil
ventricular pressure
rate
assessed
with cardiac magnetic resoGTN ⴝ glyceryl trinitrate
nance
and
invasively
measured ␶. More
IVRT ⴝ isovolumic relaxation
recently, Wang et al. (12) showed that
time
untwisting rate was related to a time conLA ⴝ left atrial
stant of isovolumic relaxation, both paLV ⴝ left ventricle/ventricular
rameters being derived from echocardioMVO ⴝ mitral valve opening
graphic data (13) rather than invasive
STI ⴝ speckle tracking imaging
measurement. Clinical studies have shown
a consistent reduction in the magnitude
and delay in the timing of untwisting in the context
of diastolic dysfunction due to aortic stenosis (14),
hypertrophic cardiomyopathy (15), and severe LV
hypertrophy (16), supporting an important role for
untwisting in abnormal diastolic function.
Thus, the relationship between invasively measured indexes of diastolic function and torsion
parameters in human subjects is not known. We set
out to establish the relationship between parameters
of untwisting and invasive hemodynamic measures
of early and late diastolic filling in human subjects
with a range of diastolic function.
METHODS
Patient selection. Patients referred for routine coronary angiography to investigate chest pain were
invited to participate. Patients with acute coronary
syndrome, abnormal systolic function, regional wall
motion abnormality, valvular heart disease of worse
than moderate severity, atrial fibrillation, permanent pacemaker, history of coronary artery bypass
graft surgery, renal impairment (estimated glomerular filtration rate ⬍60 ml/min/1.73 m2), and abnormal QRS complex morphology on electrocardiogram were excluded. This study was undertaken
with the approval of the Human Research Ethics
Committee of St. Vincent’s Health, and written
informed consent was obtained from all subjects.
Routine echocardiographic analysis. The following
echocardiographic data were acquired at end expiratory apnea: apical 4- and 2-chamber views of the
LV; a parasternal long-axis view; and short-axis
images at level of mitral valve, the mid-ventricle,
and apex. Pulsed wave Doppler of the LV outflow
tract and mitral inflow were recorded and stored in
raw data format for offline analysis. Three cycles
were analyzed, and the results were averaged.
To calculate ejection fraction, LV end-diastolic
and end systolic volumes were measured with a
Simpson’s biplane method. Mitral inflow and tissue
Doppler velocities and the isovolumic relaxation
time (IVRT) were recorded as previously described
(17). Diastolic function was classified as abnormal
on the basis of the invasive criteria (18): ␶ ⬎48 ms
or LV end-diastolic pressure ⬎16 mm Hg or mean
LV diastolic pressure ⬎12 mm Hg. Those with
abnormal diastolic function were then classified as
having impaired relaxation or pseudonormal or
restrictive patterns of echocardiographic diastolic
filling (19). The LV mass index was calculated with
the area-length method and LV hypertrophy was
defined according to standard criteria (20): LV mass
index ⬎115 g/m2 for men and ⬎95 g/m2 for women.
Speckle tracking imaging and torsion analysis. The
speckle tracking imaging (STI) algorithm and torsion analysis technique have been described in detail
previously (21,22). Briefly, offline analysis of raw
ultrasound data was performed with EchoPac PC
software (version 4.1, GE Medical Systems, Princeton, New Jersey). Speckle tracking analysis with
2-dimensional images was performed as previously
described (23) on high frame rate (50 to 90 Hz)
single-focus parasternal short-axis images at the
level of the mitral valve (mitral valve leaflets on
view) and apex (circular LV cavity with no papillary
muscle visible) (21) to generate rotation and rotation rate data. Frame by frame rotation and rotation
rate data were exported to Excel (Microsoft Corporation, Seattle, Washington), and temporal data
were normalized to the percentage duration of
systole and diastole separately as previously de-
Burns et al.
Untwisting in Diastolic Function
JACC: CARDIOVASCULAR IMAGING, VOL. 2, NO. 6, 2009
JUNE 2009:709 –16
Left ventricular torsion =
apical rotation - basal rotation
Torsion (degrees)
7.5
Tmvo
Tpeak
Apical rotation
Basal rotation
Torsion
5.0
2.5
AVC MVO
0.0
Time
-2.5
Systole
Diastole
-5.0
Recoil (%)=
Tpeak - Tmvo
x 100
Tpeak
B
Torsion velocity (deg/sec)
A
Left ventricular torsion velocity=
apical rotation rate - basal rotation rate
Peak positive torsion velocity
50
25
0
Time
-25
-50
Recoil rate (%/sec)=
Peak untwisting
velocity
Recoil
Time (Tpeak) - Time (Tmvo)
Figure 1. Torsion and Torsion Velocity Versus Time Plot
(A) Torsion versus time plot. Left ventricular torsion (black line) was calculated by subtracting basal rotation (red line) from apical rotation (orange line). Positive torsion rate (dashed line) was the slope of the torsion versus time curve from the beginning of systole to
peak torsion (Tpeak). Recoil was the percentage decrement from peak torsion to torsion at mitral valve opening (Tmvo), and recoil rate
was calculated as recoil divided by the time from Tpeak to Tmvo. (B) Torsion velocity versus time plot. Left ventricular torsion velocity
(yellow line) was calculated by subtracting basal rotation rate from apical rotation rate. Peak positive torsion velocity and peak untwisting velocity are indicated by the arrows. AVC ⫽ aortic valve closure.
scribed (24). Because apical and basal rotation data
cannot be acquired from the same cardiac cycle and
to allow comparison within and between subjects,
cubic spline interpolation (Graphpad Prism Plus software, San Diego, California) was undertaken with 300
data points for both systole and diastole. Subtraction
of the basal data from the apical data at each of the
interpolated time points was undertaken to calculate
torsion and torsion velocities (Fig. 1). Three cycles
were analyzed, and the results were averaged.
Definition of torsion parameters. Peak torsion
(Tpeak) was defined from the torsion versus time
curve and positive torsion rate as the slope from the
start of systole to peak torsion (Fig. 1A). Torsion at
the time of mitral valve opening (Tmvo) (Fig. 1)
was used to calculate the indexes recoil (Fig. 1A)
and recoil rate (recoil rate ⫽ recoil/[timeTpeak ⫺
timeTmvo]) (11). The real time of peak torsion and
mitral valve opening was used for the calculation of
recoil rate rather than normalized time. Peak positive torsion velocity and peak untwisting velocity
were defined from the torsion velocity versus time
curve (Fig. 1B). The time to peak untwisting
velocity was measured from mitral valve opening.
Simultaneous micromanometer LV pressure and echocardiography. Studies were undertaken in the cath-
eterization laboratory with the subjects in the supine position. Echocardiography was performed
with a VIVID 7 echocardiograph (GE Medical
Systems). A single-use 5-F Millar micromanometer
catheter (SPC-454D, Millar Instruments, Inc.,
Houston, Texas) was placed within the LV, and
ventricular pressures were recorded with Powerlab/
4sp recording unit (ADI Instruments, Mountain
View, California) connected to an iMac desktop
computer (Apple, Cupertino, California). The LV
pressure data were acquired with Chart 3.6.3 for
MacOS (ADI Instruments) during each of the 4
conditions. Data from 5 cycles at each condition
were analyzed and averaged. The dp/dt minimum, ␶
(25,26), and minimum LV diastolic pressure (LV
minimum pressure) (27) were recorded as invasive
measures of diastolic function.
Simultaneous echocardiograph and pressure recordings were obtained under 4 conditions: PreGTN ⫽ in the fasting state; GTN ⫽ at nadir of LV
pressure after sublingual glyceryl trinitrate (GTN)
administration (if the subject’s resting LV pressure
was ⬍110 mm Hg [n ⫽5], 300 ␮g of sublingual
GTN was administered; for the remainder of patients, 600 ␮g was administered); Pre-fluid ⫽ stable
hemodynamic state at least 15 min after GTN
administration; and Fluid ⫽ after rapid infusion of
750 ml normal saline (warmed to 37°C).
Pressure–volume relations. With simultaneous micromanometer pressure and echocardiographic volume data, a pressure–volume relation was plotted
from the coordinates under each of the hemodynamic conditions at minimum diastolic pressure
and end-diastolic pressure (Fig. 2). From the micromanometer pressure versus time data, enddiastolic pressure was defined as the pressure at 10%
of dp/dt maximum (28).
The LV stiffness constant, ␤, was estimated from
the slope of the linear regression equation relating
the end-diastolic pressure to volume coordinates
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Burns et al.
Untwisting in Diastolic Function
JACC: CARDIOVASCULAR IMAGING, VOL. 2, NO. 6, 2009
JUNE 2009:709 –16
LV functional chanber stiffness
LV stiffness constant
30
Pressure
712
20
10
Min diast p
End diast p
0
0
25
50
75
100
125
Volume
Figure 2. Pressure-Volume Loop Derived From Simultaneous
Micromanometer Pressure and Echocardiographic Volume
Data points for minimum diastolic pressure (squares) and end diastolic pressure (triangles) are shown under each of the 4 conditions. The linear functional chamber stiffness (orange line) and left ventricular (LV) stiffness
constant (yellow line) are shown.
under each of the conditions (Fig. 2). The functional LV chamber stiffness, b, under each condition was the linear slope of the pressure-volume
curve from minimum diastolic pressure to enddiastolic pressure (Fig. 2) (29,30).
Statistics. Normality of data was assessed with the
Kolmogorov-Smironov statistic. Where data were
not normally distributed, log transformation was
applied, and tests were performed on the log transformed data. Repeated-measures linear regression
was performed to quantify the relationship between
torsion and invasive indexes of diastolic function as
previously described (11). The commercially available statistics software SPSS (SPSS Inc., Chicago,
Illinois) was used. Data are presented as mean ⫾
SD unless otherwise specified, and p ⬍ 0.05 was
considered significant.
RESULTS
Patient characteristics. The demographic data of
the 18 patients included in the study are summaTable 1. Patient Characteristics (n ⴝ 18)
Male, n (%)
10 (56%)
Age (yrs), mean ⫾ SD (range)
65.7 ⫾ 7.6 (47–77)
Body mass index, kg/m2, mean ⫾ SD (range)
28.0 ⫾ 3.9 (22.2–36.7)
Hypertension, n (%)
Type 2 diabetes mellitus, n (%)
Heart failure
Current smoker
Hyperlipidemia, n (%)
11 (61%)
3 (17%)
0
0
9 (50%)
rized in Table 1. According to invasive criteria, 9
patients had normal diastolic function and 9
patients had abnormal diastolic function. Of the
9 patients with abnormal diastolic function by
invasive criteria, 3 had an impaired relaxation
pattern, 6 had a pseudonormal pattern, and none
had a restrictive pattern of diastolic filling by
echocardiographic criteria. Mean LV mass index
was 89.2 ⫾ 3.6 g/m2 (range 58.3 to 120.8 g/m2),
and 3 patients had LV hypertrophy. Of the eleven
hypertensive patients, 8 required 1 antihypertensive and 3 required 2 antihypertensive medications. Nine patients had angiographically smooth
coronary arteries, 3 had minor diffuse disease, 4
had single-vessel stenosis of ⬎70%, and 2 had
multivessel stenoses of ⬎70%. A pre-fluid dataset
was not collected in 3 subjects, and poor image
quality meant that torsion analysis could not be
performed on 2 subjects in the GTN dataset.
Effect of LV mass and preload on measures of diastolic
function. As LV mass increased, ␶ was prolonged (r
⫽ 0.34, p ⬍ 0.002), and there were reductions in
peak untwisting velocity (r ⫽ 0.57, p ⬍ 0.007) but
not recoil (r ⫽ ⫺0.26, p ⫽ NS) or recoil rate (r ⫽
0.32, p ⫽ NS). As preload increased (increased
end-diastolic volume and pressure), ␶ was prolonged, but no consistent effect on untwisting
parameters was observed (Table 2).
Correlation between measures of diastolic function.
As ␶ was prolonged, the time to peak untwisting
velocity was delayed (r ⫽ 0.34, p ⬍ 0.01). There
were nonsignificant associations between reduced
recoil and longer values of ␶ and lower dp/dt
minimum (Fig. 3). No relationship was observed
between the echocardiographic IVRT and ␶ or
between IVRT and untwisting parameters.
The LV minimum diastolic pressure increased as ␶
was longer (Fig. 4A) (r ⫽ 0.67, p ⬍ 0.001) and recoil
decreased (Fig. 4B) (r ⫽ ⫺0.30, p ⬍ 0.034). No
relationship was observed between LV minimum diastolic pressure and peak untwisting velocity or recoil rate.
Relationships were observed between the magnitude of peak untwisting velocity and that of the
systolic torsion parameters peak torsion (r ⫽ ⫺0.75,
p ⬍ 0.001), positive torsion rate (r ⫽ ⫺0.60, p ⬍
0.001), and peak positive torsion velocity (r ⫽
⫺0.42, p ⬍ 0.002).
Relation between LV stiffness and untwisting indexes. No relation was observed between measures
of stiffness, the LV stiffness constant, ␤, and the
functional LV chamber stiffness, b, and the untwisting indexes recoil, recoil rate, and peak untwisting velocity (Table 3).
Burns et al.
Untwisting in Diastolic Function
JACC: CARDIOVASCULAR IMAGING, VOL. 2, NO. 6, 2009
JUNE 2009:709 –16
DISCUSSION
Table 2. Correlation Coefficients Between Measures of Preload
and Diastolic Parameters
We have shown in human subjects with invasive
measures of LV pressure that indexes of untwisting
are related to parameters of early diastolic filling but
not events happening later in diastole. Reductions
in the rate and magnitude of untwisting were
associated with worsening of diastolic relaxation
and reduced early diastolic suction. These findings
lend further weight to the hypothesis that untwisting is important in generating early diastolic LV
suction, an important component of early diastolic
filling. There was a close relationship observed between systolic and diastolic torsion parameters, suggesting that torsion might be an important mechanistic link between the phases of the cardiac cycle.
Our data are in keeping with earlier findings in a
canine model where, with cardiac magnetic resonance, Dong et al. (11) described a close relation
between recoil rate and invasively measured ␶.
Wang et al. (12) found that the untwisting rate
correlated with a time constant of isovolumic relaxation in patients with systolic LV dysfunction, but
this correlation was not maintained in patients with
preserved LV ejection fraction. This inconsistency
might be due to a failure to interpolate temporally
normalized STI data or an artefact of the method
used to derive ␶ from echocardiographic and right
heart catheterization data (13) rather than direct
invasive measurement, as we have used in this
patient group with normal ejection fraction.
The correlations between invasive and untwisting
parameters in our study were weaker than those
A
Peak
Untwisting
Velocity
␶
Recoil
End-diastolic
r ⫽ 0.36
r ⫽ 0.11
r ⫽ 0.09
r ⫽ 0.05
volume
p ⬍ 0.01
p ⫽ NS
p ⫽ NS
p ⫽ NS
Recoil Rate
End-diastolic
r ⫽ 0.41
r ⫽ 0.17
r ⫽ 0.08
r ⫽ 0.15
pressure
p ⬍ 0.003
p ⫽ NS
p ⫽ NS
p ⫽ NS
reported with published animal data (11) but are
still consistent with an important role for untwisting in early diastolic function. In our study, the
method of Weiss (25) was used, which assumes that
the LV pressure decays to a zero asymptote,
whereas in the study by Dong et al. (11), a zero
pressure asymptote was not assumed. There is some
controversy about the use of a zero pressure asymptote (31); however, it has been the most commonly
used method in human studies and has established
reference values (26). In addition, Dong et al. (11)
calculated recoil with torsion at 64 ms after mitral
valve opening as a proportion of maximal torsion.
This differs slightly from the definition of recoil
used in contemporary studies employing STI
(24,32). The arbitrary time point of 64 ms does not
completely account for isovolumic relaxation, the
load independent period of negative torsion. To
reflect the changes in torsion during the isovolumic
period, an argument could be made that the torsion
at end systole should be used rather than the peak
torsion. However, in some patients, maximal tor-
B
τ
Figure 3. Recoil Versus ␶ and Recoil Versus dp/dt Minimum
Eighteen subjects underwent simultaneous Millar catheter micromanometry and echocardiography under 4 conditions: at rest (Pre-GTN)
(brown squares); after 600-␮g sublingual GTN (GTN) (red triangles); after a period of re-equilibration (Pre-fluid) (orange circles), and
after 750-ml intravenous saline bolus (Fluid) (yellow diamonds). Torsion parameters were measured with speckle tracking imaging, and
repeated measures linear regression was used to quantify relations between invasive and torsion indexes. We observed nonsignificant
associations between reduced untwisting and longer values of the time constant of isovolumic relaxation, ␶ (A), and a lower rate of the
rise of left ventricular pressure (dp/dt) minimum (B) in keeping with previous work in animal models. This supports an important role for
untwisting in early diastolic function.
713
Burns et al.
Untwisting in Diastolic Function
JACC: CARDIOVASCULAR IMAGING, VOL. 2, NO. 6, 2009
JUNE 2009:709 –16
A
B
PreGTN
GTN
Prefluid
Fluid
60
55
50
125
Recoil (%)
65
τ (ms)
714
45
r = -0.32, p < 0.005
100
75
50
40
25
35
-5
r = 0.67, p < 0.001
0
5
10
15
20
LV minimum diastolic pressure (mmHg)
-5
0
5
10
15
20
LV minimum diastolic pressure (mmHg)
Figure 4. ␶ Versus LV Minimum Diastolic Pressure and Recoil Versus LV Minimum Diastolic Pressure
Left ventricular (LV) suction is an important component of early diastolic function that allows LV filling without excessive increases in left
atrial pressure. Lower LV minimum diastolic pressure increases suction. We found that impaired suction was associated with slower isovolumic relaxation (A). As untwisting decreased, suction was also impaired (B), further evidence for an important role for untwisting in
early diastolic function.
sion occurs after end systole, and this would lead to
an inconsistency in the measurement (16). Therefore, we calculated recoil and recoil rate as the
decrement in torsion from peak to mitral valve
opening (Fig. 1).
We have shown that suction was reduced in
subjects with decreased recoil. Although LV minimum diastolic pressure is an accepted index of
suction in clinical studies (27), the gold standard
assessment involves the measurement of intraventricular pressure gradients with a triple sensor micromanometer catheter placed across the mitral
valve to record LA, basal LV, and apical LV
pressures. This technique is limited to animal models (1) and the clinical open heart surgery setting
(2). More recently, the mitral inflow propagation
velocity derived from color M-mode Doppler has
been validated as a noninvasive index of intraventricular pressure gradient (4,33). With this technique and tissue Doppler-derived measurement of
torsion, Notomi et al. (10) suggested that untwisting velocity is an important determinant of early
diastolic LV suction. Our study provides invasive
data to support this hypothesis.
The observed effect of increased LV mass on
untwisting velocity is consistent with the findings of
Table 3. Correlation Coefficients Between Invasive Measures of Stiffness
and Diastolic Torsion Parameters
Recoil
Recoil Rate
Peak
Untwisting
Velocity
LV stiffness constant
0.11
⫺0.023
⫺0.015
Functional LV stiffness
0.11
⫺0.10
⫺0.049
LV ⫽ left ventricular.
clinical studies involving patients with LV hypertrophy (14 –16). No relation was observed between
untwisting parameters and the LV stiffness constant
or the functional LV chamber stiffness. Untwisting
begins before aortic valve closure (7,10), and a lack
of correlation with late diastolic parameters of
stiffness is not unexpected. Although invasive
pressure-volume loop analysis with conductance
catheters is the gold standard to measure stiffness,
pressure-volume loops derived from simultaneous
micromanometer pressure and echocardiographic
volume are well-validated (26). The end-diastolic
pressure-volume relation is generally modeled from
conductance catheter data with nonlinear equations
(34); however, the ranges of diastolic pressure and
volume coordinates produced by the hemodynamic
manipulations in the current study could be accurately modeled with linear regression as previously
described (30,35).
The observation of close relations between systolic and diastolic torsion indexes lends weight to
the hypothesis that torsional motion results from
the buildup and release of elastic energy (10,36),
possibly in the molecule of the large elastic cardiomyocyte protein titin, which acts as a bidirectional
spring (37). Titin itself has been shown to be a
major determinant of early diastolic function
(38,39), and changes in titin isoforms have been
documented in the context of ventricular dysfunction (40). In an animal heart failure model, rapid
ventricular pacing induced a change to stiffer titin
isoforms, resulting in reduced systolic twist and
diastolic untwisting associated with reduced suction
gradients (41). Further work is required to elucidate
Burns et al.
Untwisting in Diastolic Function
JACC: CARDIOVASCULAR IMAGING, VOL. 2, NO. 6, 2009
JUNE 2009:709 –16
the role of titin in untwisting and diastolic suction
in humans.
Study limitations. Eighteen patients with normal
systolic function were assessed in this study, of
whom one-half had diastolic dysfunction on invasive criteria. The failure to reproduce the strong
correlations between invasive and torsion indexes of
diastolic function might relate to the small sample
size in our cohort and the relatively narrow dynamic
range through which the invasive parameters were
manipulated in our experiment relative to what can
be achieved in the animal model with varying
pacing modes, dobutamine, and esmolol. Although
GTN and fluid administration have some effect on
afterload, their predominant effect is on preload.
Maneuvers to specifically manipulate afterload,
such as vasopressor administration, would be of
great interest but were felt to be unwarranted in this
experiment. To elucidate the clinical utility of
measuring torsion parameters to characterize diastolic function, a larger group of systolic and diastolic heart failure patients with more severe diastolic dysfunction would need to be studied.
The advent of echocardiographic STI has enabled reproducible noninvasive quantification of
twisting motion (22,42,43). Cubic spline interpolation and normalization are mandatory to allow
accurate subtraction of apical and basal data at the
same time points (44), which makes the technique
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Acknowledgments
The authors gratefully acknowledge Mr. Don
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for their assistance with cardiac catheterization in
this study and Mr. Graham Hepworth, University
of Melbourne Statistical Consulting Centre, for
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Reprint requests and correspondence: Dr. Andrew T.
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Key Words: diastole y
echocardiography y speckle
tracking imaging y torsion y
untwisting.