Download Changes in Left Ventricular Diastolic Filling Patterns by Doppler

Changes in Left Ventricular Diastolic
Patterns by Doppler Echocardiography
Cystic Fibrosis*
Gregory
M.D.;Jarnshed
L. Johnson,
Claudine
B. Moffrtt,
R.D.,
F Kanga,
M.S.;
M.D.,
andJacqueline
F.C.C.P;
A. Noonan,
The onset of cor pulmonale
is a common
terminal
finding
in patients with cystic fibrosis.
Since Doppler
echocardiography can detect changes
in diastolic
filling patterns
prior
to the onset of either systolic dysfunction
or clinical
symptoms, we utilized
this technique
to determine
whether
detectable
changes
in left
ventricular
diastolic
ifiling
patterns
exist in patients
with cystic fibrosis.
Among
#{163}5
patients,
the proportion
of left ventricular
filling
attributable
to
atrial
contraction
was significantly
increased
when compared
with age-matched
control
individuals.
When filling
C
ystic
and
of severe
fibrosis,
characterized
infection
chronic
of the airways,
is the
lung disease
of children.
by chronic
obstruction
prognostic
cardiac
estimated
sign,
failure
being
to be the
with
rapid
common,
and
cause
of death
progression
to
cor pulmonale
in 40 percent
is
of
individuals
with cystic
fibrosis.2
Studies
performed
in individuals
with
congestive
heart
failure
have shown
that as many as one third
those
patients
who develop
signs
and symptoms
cardiac
failure
have
cause
of congestive
is abnormal
diastolic
in left ventricular
normal
systolic
heart
failure
function.3’4
diastolic
function.
of
of
The
in these
individuals
In children,
changes
filling
patterns
as measured
by pulsed
Doppler
echocardiography
have been shown
to be useful
in the assessment
of cardiac
status in the
absence
of both
clinical
symptoms
and systolic
dysfunction.5’6
geometry
tricular
have
Additionally,
changes
a quantifiable
ventricular
effect
diastolic
echocardiography
fibrosis
changes
left
induced
by the development
dilation
and hypertrophy
have
on
patterns.7
In view of these
ease of obtaining
serial data
left
in
in
filling
in a series
order
in such
to
patterns
left
determine
exist
ventricular
of right yenbeen shown
to
ventricular
findings
and
noninvasively,
patterns
of patients
whether
in these
filling
the relative
we studied
by
M.D.
were compared
with severity
of pulmonary
disease, worsening
pulmonary
disease was directly correlated
to shifts in left ventricular
filling patterns.
We conclude
that
changes
in left ventricular
patterns
of relaxation
are detectable
early in the course of cystic fibrosis
and that such
changes
are probably
progressive.
Early detection
could
lead to therapeutic
trials
designed
to improve
left ventricular
filling and delay the onset
of overt cor pulmonale.
(Chest 1991; 99:646-50)
patterns
changes
major cause
During
the
course
ofdisease
progression,
the onset
ofcor
pulmonale is common,
occurring
in up to 70 percent
of
1 The
onset
of clinical
cor pulmonale
is an
ominous
might
prognosis
then
and
be
of clinical
treatment
This
study
AND
prospectively
approved
by
the
University
of
Center institutional
review
committee
on human
There were 27 patients
with
cystic
fibrosis
entered
into
echocardiographicdata
suitable foranalysis
were obtained
research.
the study;
25 (Table
1). Informed
consent
was
obtained
from
all
subjects
and, when applicable,
their parents.
There were 13 males and 12
female patients
ranging
in age from
4 to 29 years.
Subjects
were
studied
during hospitalization
for acute pulmonary
exacerbation
of
the disease.
Following
clinical stabilization,
all patients
underwent
pulmonary
function
testing,
transcutaneous
pulse oximetry,
chest
x-ray films and simultaneous
Doppler
echocardiography
as well as
thoracic impedance
monitoring.
All data were gathered
within
as
narrow
age-
a time
frame
as possible,
and sex-matched
Doppler
echocardiography
served
as a comparison
cystic
fibrosis
usually
control
(‘Bible
and
obtained
control
In
patients
disease
chest
was
x-ray
film
21 patients,
disease
Table
cystic
plain
at
rest
1-Clinical
fibrosis,
utilizing
findings,
the
on
saturation
with
estimated
imaging
had a history
was normal
studies
did
not
or dysfunction.
clinical
and
and
with
examination
a composite
oximetry
monitoring
in patients
individuals
of cardiopulmonary
complaints.
Physical
in all and, in all, routine
echocardiographic
suggest
the presence
ofany cardiac
disease
of 25
simultaneous
impedance
for data
ofthe
24 h. A group
underwent
thoracic
group
1). None
within
individuals
severity
of
pulmonary
clinical
score
based
FEV1
(Table
on
2). Among
the
Brasfield
et al#{176}
score for severity
of pulmonary
chest x-ray film ranged
from 8 to 18, oxygen
ranged
from
55
to
98
Characteristics
percent
ofPatients
and
FEy1
and
ranged
Controls
cystic
Control
Characteristics
Such
Patients
Male/female
Age (yr)
Subjects
25
25
13/12
13/12
ii
*From
the Department
of Pediatrics,
University
of Kentucky
Medical Center,
Lexington.
Manuscript
received
April 23; revision
accepted
August 20.
Reprint
requests:
Dr. Johnson,
Department
ofPed4attic
University
ofK.entucky
Medical Center, Lexington
40536
646
METHODS
detectable
patients.
in assessing
Medical
Kentucky
in
was
utility
options.
MATERIALS
Doppler
with
Filling
in
4-29
4-29
(median
BSA(mean±SD)
=
16)
1.17±0.35
Left Ventricular
Diastolic
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21625/ on 05/11/2017
Ailing Patterns
(median
=
16)
1.49±0.43
in CF (Johnson
et a!)
Table
2-Cystic
Pulmonary
Disease
Clinical
Score
FIbrOSIS
Composite
0
Fbints
1
...
Brasfield
2
>19
Table
Severity
12-19
3
4
<12
...
score
saturation
Oxygen
>95
90-95
85-90
>80
60-80
40-60
.. .
<85
(%)
FEy1,
% of
<40
...
expected
from 13 to 99 percent
patients
had
of normal.
By composite
clinical score,
greater than or equal to 7 and were believed
scores
have severe disease,
have
moderately
to
equal
4 and
eight
severe
were
had
of
scores
disease,
believed
and
5 or 6 and
six
to have
had
were
scores
clinically
mild
than
±
Filling
SD)
Inspiration
91 ± 3
(cm/s)
89 ± 4
(cm/s)
85 ± 3
78 ±3t
Normal
A velocity
(cm/s)
46±
3
47±3
Patient
A velocity
69±
5*
Normal
E/A
velocity
Patient
E/A
velocity
Normal
atrmal filling
Patient
atrial
ratio
to
*p<0.01
normal
tp<0.01
expiration
63 4*
2.06±0.14
2.06±0.
ratio
1.35±0.09
1.32±0.07
fraction
0.30±0.01
0.31
0.40±0.02*
0.39±0.02*
filling fraction
75±3
heart
rate
in
Expiration
E velocity
14
± 0.01
82±3t
102 ± 5*
110 ±5*t
vs patient.
vs inspiration.
disease.
RESULTS
Subjects
underwent
thoracic
impedance
Packard
Sonos
simultaneous
in a quiet,
monitoring
1000
Doppler
ultrasonoscope
with
echocardiography
resting
state.
and
Mean
values
derived
parameters
control
individuals
A Hewlett-
simultaneous
recording
of the electrocardiogram,
echocardiographic
data and
tracing
derived
from thoracic
impedance
monitoring
was utilized.
To ensure
detection
of maximal
flow velocities
and
minimize
the angle ofincidence,
Doppler
patterns
ofleft ventricular
inflow were obtained
from
the apical four.chamber
view with the
Doppler
sample volume placed
at the level ofthe mitral annulus.
Dopplerwaveforms
were
analyzed
from videotape
replay utilizing
and
ofLeft
Ventricular
Subjects
(mean
E velocity
Patient
pulmonary
Control
Patient
Normalheartrate
or
Normal
Normal
11
to
thought
less
Parameters
3-Doppler
Ibtients
and
display
respiratory
an on-line
internal
compared
with
microprocessor
cystic
system.
fibrosis
test. Doppler
data were
standard
linear regression
group
data
compared
the
to clinical
and by multiple
CIPITE
Normal
by
group
data were
Student
paired
variables
regression
WMCAL
by
shown
phase
Among
normal
control
subjects,
had no significant
effect
on left
filling
patterns
although
there
was,
as
expected,
a slight
ration.
Mean ratio
increase
ofpeak
in heart
rate during
inspivelocity
offiuing
during
the
passive
phase
of diastole
filling
(E)
to peak
velocity
during
the atrial contraction
(A) phase was 2.06.
Ratio
and absolute
values
for E and A velocities
in both
both
analysis.
SCOI
Doppler
echocardiographically
ofleft
ventricular
filling in normal
and patients
with cystic fibrosis
are
in Table
3.
of respiration
ventricular
t
for
#{163}/A RATIO
VS.
0
Q
I-.
.c
2.
I.-
0
0
0
2
3
5
4
PULtIONARY
CLN$ICAL
CI1POSITE
6
DISEASE
SCOI
7
8
9
10
11
SEVERITY
ATRIAL
VS.
FLLING
FRACTiON
0
0
0
0
I’.
1. Correlation
FIGURE
for
severity
with
peak
clinical
score
in patients
fibrosis
with
left ventricular
E/A
ratio (top panel, r=0.74)
and with
cystic
velocity
left ventricularatrial
r
0
1
2
3
4
PULMONARY
5
6
DISEASE
7
SEVERITY
8
9
10
11
=
0.73).
ofcomposite
of pulmonary
Lines
are
disease
fihlingfraction
(lower panel,
regression
lines with
linear
90 percent confidence
limits for the true
ofthe dependent
variable.
CHEST/99/3/MARCH,1991
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21625/ on 05/11/2017
mean
647
Table
4-Multiple
Transmitral
Regression
Analysis
Ratio vs Heart
Clinical Score
Partial
Regression
Coefficient
(SEE)
E/A
Velocity
transmitral
Rate
and Composite
Variable
p Value
Intercept
Heart rate
(0.298)
0.001
-0.006
(0.003)
0.075
Clinicalscore
-0.106
(0.027)
0.001
2.556
Transmitral
Atrial
and
Filling
Intercept
Heartrate
Clinical score
and expiration
by others.
At end-expiration,
when
The
with
independent
Rate
0.001
(0.001)
0.033
0.022
(0.005)
0.001
are similar
with
to those
cystic
ratio
dem-
contraction
change
in
Accordingly,
comprised
of
FdA
velocity
ratio or atrial filling
flow associated
with atrial cona greater
proportion
of total dia-
stolic
flow in cystic
fibrosis
patients
control
subjects
regardless
of phase
End-expiratory
in patients
severity
composite
negative
transmitral
E/A
compared
of respiration.
flow
velocity
Table 5-Correlation
Echocardiographic
multiple
regression
of disease
severity
ofDoppler
Filling
Data in Patients
with
E/A
ratio
Ratio
ventricular
peak
peak
also
analysis
on the
Thtterns
with
Cystic
Fibrosis
Atrial
Filling
r(p)
Fraction
r(p)
ventricular
ventricular
Heartrate
(expiratory)
648
4).
cystic
size
E/A
value
ratio
of the
ventricles
ventricular
rate was
effect
or echocardiographic
systolic
correlated
and atrial
separate
fibrosis,
atrial filling
ventricle,
filling
function
with
fraction,
of pulmonary
(Table 5).
both
peak
independent
disease
severity.
Left
ventricular
found
to
be
systolic
well
performance
preserved
in
has
patients
been
with
cystic
fibrosis.
Studies
performed
utilizing
cardiac
catheterization,
two-dimensional
echocardiography
and radionuclide
angiography
have
documented
normal
left
ventricular
systolic
performance
regardless
of the
presence
of clinical
cor pulmonale
or impaired
right
ventricular
systolic
cardiac
evated
percent
function.2”#{176}”
catheterization,
mean
pulmonary
normal
left
of patients
disease
severity
however,
artery
ventricular
studied.2
Data
systolic
While
or outcome
gathered
were
in 40
with
not performed,
these
of left yenin patients
adults
with
fibrosis
and chronic
pulmonary
disease
demona significantly
lower
E to A peak velocity
ratio
and greater
atrial
matched
control
filling fraction
than
subjects,
suggesting
impairment
of left
echocardiographic
independent
signs
of such
of phase
of respiration
correlated
elde-
function,
correlations
data would
suggest
that altered
patterns
tricular
filling
may be a common
finding
with cystic fibrosis.
In the present
study, children
and young
cystic
strated
at
do demonstrate
wedge
pressure,
to the
ventricular
clinical
chronic
pulmonary
ured at the level
did age- and
disease-related
ax’2
severity
sex-
Doppler
impairment
and were
of the
were
directly
underlying
disease.
Flow patterns
were measof the mitral annulus
in an attempt
-0.22
(0.37)
0.16
(0.52)
-0.13
(0.59)
0.22
(0.38)
to more
carefully
standardize
sample
volume
placement.
This
placement
of the
sample
volume
can
produce
a lower
peak E velocity
in comparison
with
results
found
in studies
performed
more
distally
between
the mitral
leaflet
tips.’3”4
Small
changes
in
sample
volume
location
relative
to the heart
can
-0.22
(0.37)
0.42
(0.09)
produce
dimension
ventricular
(Table
with
(0.96)
ventricular
shortening
rate
0.01
dimension/left
Left
in heart
of patients
(0.81)
dimension/BSA
Right
independent
-0.06
dimension/BSA
Right
of the
spite
score
and left ventricular
K/A
(rO.74,
p<O.000l).
While
FIA
and particularly
peak A velocity,
were related
to heart rate,
confirmed
that the effect
Left
with
with cystic fibrosis
was then compared
with
of pulmonary
disease
as estimated
by the
clinical
score (Fig 1). There was a significant
linear correlation
demonstrable
between
din-
ical severity
velocity
ratio
velocity
ratio,
was
DISCuSSION
the total diastolic
flow integral,
also was significantly
higher
in cystic
fibrosis
patients.
With inspiration,
patients
with cystic
fibrosis
demonstrated
small decreases
in peak E and A velocities
but no
fraction.
traction
group
ofleft
heart
in control
integral
of
as a fraction
the
estimates
As noted,
of the
maximal
rapid
filling
(E) velocity
A, or atrial
contraction-related,
atrial
ratio
peak left ventricular
E/A velocity
ratio and
fraction
did not correlate
with size ofeither
reported
fibrosis
with
these
data
fraction,
or area
velocity
of changes
Within
0.053
compared
atrial
filling
associated
vs Heart
peak
similar
results
(Fig 1), with worsening
disease
being
associated
with a greater
relative
contribution
of atrial
contraction
to total
diastolic
left ventricular
filling
(r = 0.73,
p<O.0005).
This effect
was also found
to be
Score
(0.058)
patients
onstrated
a similar
but elevated
peak
flow
Clinical
0.118
inspiration
previously
velocity
subjects.
Fraction
Composite
FdA
of the effect
of heart
rate (Table 4).
Comparison
oftransmitral
atrial filling fraction
with
clinical
severity
of pulmonary
disease
demonstrated
fraction
difficulties
-0.51
(0.01)
0.62
(0.01)
These
of the
changes
in
potential
annulus
in
the
the
velocity
evaluation
changes
and
Left Ventricular
are
may
curve
and
of individual
be
Diastolic
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21625/ on 05/11/2017
more
notable
produced
Ailing Pafterns
create
patients.
at the
by
level
relatively
in CF (Johnson
et a!)
minor
respiratory
or cardiac
movement.
Since
and
values
volume
overload
measured
in patients
were being compared
with those
from
matched
control
individuals,
sample
volume
location
should
not be a significant
source
of error in
displacement
septum
and
this study.
Location
should
be considered,
when
attempting
to compare
the results
dimension
ventricular
obtained
with
a more
distal
placement
sample
volume.
There
are a number
of possible
changes
in left ventricular
with cystic
fibrosis
and
filling
chronic
The
results
interplay
observed
are almost
Diminished
left
shown
to result
in a shift
suggest
the
left
atrial
are
certainly
due
acting
preload
to the
patterns
similar
to
recent
studies
to changes
in
l617
could occur as a result
and left atrial pressure
pulmonary
vascular
decreasing
be
increasing
right
expiratory
expected,
left ventricular
however,
determining
factor
patients
respiratory
with
evident.
present
Such
study.
Afterload
expiratory
ventricular
that
of left
chronic
variability
pulmonary
in filling
changes
were
augmentation
also
been
the
shown
to
hypertrophy.6”9’2#{176} Hypoxemia-incould
result
in some
chronic
elevation
of afterload
in patients
but it would
be expected
that the
changes
and
the
effect
on left
be relatively
Increasing
small.
heart
in increased
A velocity
relatively
patients
control
rate
increased
with cystic
subjects
with-
ventricular
fibrosis
of these
filling
shortens
diastole
relative
to
resting
fibrosis
certainly
with cystic
magnitude
and
E velocity.2’
accounted
for some
overload
or
a combination
left ventricular
related
to right
ular dependence,
filling
might
relationship
left ventricular
of both
curvature,
in cavity
progressive
degree
radii
of
throughout
It is likely
ventricular
study
are
induced
right
ventricular
If impedance
of early
hypertrophy.
filling ultimately
is indeed
ventricular
dilatation
and
recent
evidence
would
found
to be
interventricsuggest
that
be improved
pharmacologically.’
between
right
ventricular
changes
filling patterns
in children
and
The
and
young
fibrosis
and
chronic
pulmonary
of much
further
study.
of impaired
left ventricular
filling
relatively
filling
could
young
individuals
could
be
at least
be an early
a mild
sign
leading
could
ofprogressive
in
in
myocardial
to cardiac
failure.
Intrinsic
be the result
of hypoxemia,
long-term
basis
or as intermittent,
episodes.
Analysis
ofpatterns
ofdiastolicleft
ventricular
filling
in patients
with cystic
fibrosis
and chronic
pulmonary
disease
may provide
useful
information
in the clinical
management
of these
individuals.
Follow-up
will be required
to determine
whether
the
observed
cance.
in the
present
study
have
Additionally,
analysis
relaxation,
such as isovolumic
of
the
prognostic
signifiparameters
of
time,
might
knowledge
might
be
modes
fibrosis
degree
of
into potential
Further
studies
could provide
intrinsic
myocardial
which
might
be associated
with
in left ventricular
relaxation.
alternate
and
expected
of
to provide
therapy
progressive
studies
changes
of other
relaxation
be expected
to provide
some
insight
mechanisms
for the changes
we found.
into the etiology
ofany
ofthese
changes
results
in
cor
observed
Such
a basis
patients
with
for
cystic
pulmonale.
REFERENCES
of the
pressure
with left
detailed
partly
due to intrinsic
changes
in the left ventricular
myocardium
which
would
then
lead to alterations
left ventricular
relaxation.
As such,
abnormalities
dysfunction
abnormalities
The
septal
present
geometry
estimations
changes
observed
in diastolic
filling patterns.
Statistical analysis,
however,
confirmed
an effect
of disease
severity
on patterns
of left ventricular
filling
independent
ofany
changes
attributable
to heart rate.
Right
ventricular
enlargement
due to pressure
or
volume
of
and
produce
ventricular
filling
observed
in the
to alterations
in ventricular
would
heart
rates noted
in our
compared
with those
in
right
patients.
in left
on
in
to
in our
changes
severe
a significant
should
be
While
diastole
was not performed
that a large portion
of the
diastolic
related
shown
was not correlated
in our patients,
or changes
more
hypertension
out left ventricular
duced
vasoconstriction
patterns
either
noted
systemic
distortion
a major
filling patterns
and
for the changes
with
of
cavity
in these
result
in changes
in left ventricular
has been
proposed
as a mechanism
in individuals
analysis
were
observed
has
diastole.m
filling
disease,
patterns
not
later
disease
ultimately
myocardial
changes
if preload
ventricular
It might
been
of the interventricular
ofleft
ventricular
diastolic
in end-diastole
filling
patterns
in these
intrathoracic
afterload
and
preload.
into
adults
with
cystic
disease
is deserving
Finally,
findings
disease
and impaired
right ventricular
performance.
Additionally,
the changes
associated
with chronic
respiratory
disease
could
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Multidisciplinary
Approach
The NATO-ASI
Course,
under the direction
of Dr. Dario Olivieri,
will he held at the Centro
Ettore
Majorana
for Scientific
Culture,
May 19-29 in Erice,
Italy. For information,
contact Prof
Olivieri,
Department
of Respiratory
Disease,
School
of Medicine,
University
of Parma,
Ospedale
Rasori, 43100 Parma, Italy.
650
Left Ventricular
DiastOliC
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21625/ on 05/11/2017
Ailing
Patterns
In CF (Johnson
et
a!)