Download Effects of Flecainide and Propafenone on Systolic

Effects of Flecainide and Propafenone
on
Systolic Performance
in Subjects With
Normal Cardiac Function*
Vincenzo
Igino
Santinelli,
Oppo,
Stefania
Maione,
Giunta,
Flecainide
and
both
their
effects.
the
effects
and
are
is often
study
was
ance.
limited
(ejection
shortening
rameters
(28
normal
tolic
were
and
blood
drugs.
systolic
pressure
internal
percent
FS
(th)
oth
propafenone
and
in
a
on
selected
12 women;
structure
and
indexes
of global
[EF] and percentage
mean
did
not
diameter
in
was observed
after
(p<O.OO1),
flecainide
EF
and
(p<0.0Ol),
acetate
1C antiarrhythmic
left
and
agents
of ventricular
1
However,
other
antiarrhythmic
agents,
related
side
effects.
The
flecainide
are well known,’2
percent
after
are
thick-
are
class
effective
in the
and supraventricular
their
efficacy,
like
is often
limited
proarrhythmic
as demonstrated
tachythat of
by doseeffects
of
by the
possibility
to increase
the arrhythmic
deaths
tients
with
ventricular
ectopy
and ischemic
disease
(Cardiac
Arrhythmic
Suppressor
in paheart
3
In
addition
to the proarrhythmic
effects,
flecainide
has
been
shown
to induce
a slightly
negative
inotropic
effect
on
significant
function.’5
the left ventricle’
that becomes
in patients
with compromised
Even
if the risk of this latter
adverse
effect
for example,
*From
the
diography,
Manuscript
appears
to be small,
it is not
Haissaguerre
et a116 noted
Laboratory
of Clinical
Electrophysiology
clinically
ventricular
significant
negligible;
new-onset
and
I Clinica
Medica,
University
of Naples,
Italy.
received
April 28; revision
accepted
October
Reprint
requests:
Dr Santinelli,
Department
ofCardiology,
sity ofNaples,
80131
Naples,
Italy
1068
FS
from
37
was
percent
to 13 percent;
from
EF
65 percent
patient
after
percent
to
recorded.
moderate
to 17 percent
from
These
EF
from
reversible
58 percent
reduction
of
42
and in one
(percent
FS from
30
to 35 percent).
that both intravenous
flecainide
mild negative
inotropic
effects
and
from
to 40 percent
respectively)
propafenone
15 percent;
and
55 percent
to 35 percent,
intravenous
We conclude
none
exhibit
left
and propafeleading
to a
ventricular
sys-
tolic
performance;
however,
impairment
of systolic
pump
in some
cases,
a dramatic
function
may occur,
suggesting
careful
first-line
use of both
subjects;
finally,
the
drugs
true
as
incidence
agents
ofthis
is still unknown.
EF
of
flecainide
propafenone
that
propafenone)
also in normal
deleterious
(Chest
1993;
effect
103:1068-73)
both
decrease
PW
(p<O.00l
after
after
ventricular
both flecainide
a significant
PWex
sys[ex])
after,
randomized
Heart
rate
change
(p<O.00l)
simultaneously
(p<O.00l),
management
significantly
paleft
and
(percent
and
perform-
as monodimensional
septum
(IVS)
p<0.0l
changes
were
comparable
and promptly
reversible.
In
analyzing
individual
data,
a marked
systolic
dysfunction
was observed
in two patients
after intravenous
flecainide
percent
systolic
pump
of fractional
(15 mm)
after
or propafenone.
increase
propafenone;
ening
men
recovery
flecainide
A significant
and
and
side
wail
the early
of either
and
noninvasively
(PW) contractility
(percent
[percent
th] and systolic
excursion
in all subjects
at baseline,
immediately
thickening
assessed
and in
injection
dose-related
indices
cardiac
fraction
posterior
by
flecainide
[percent
FS]) as well
of the interventricular
ventricular
B
with
in suppressing
to evaluate
function
Echocardiographic
function
M.D.;
M.D.;
tachyarrhythmias,
performed
of intravenous
25 years)
Palma,
effective
supraventricular
left ventricular
systolic
population
of 40 subjects
age,
Arnese,
M.D.;
F. C. C. F; Mario
propafenone
efficacy
This
,
Mariarosaria
Matarazzi,
M.D.
ventricular
but
Crescenzo
;
M. D.
andAnna
, F. C. C. F;
Al. D.
M. D.
Echocar7.
Univer-
ejection
fraction;
ex
excursion;
FS
fractional
shorten.
1VS = interventricular
septum;
LVIDd
left ventricular
end-diastolic
dimension;
LYIDs
left ventricular
endsystolic
dimension;
PW
posterior
wall; th
thickening
=
ing;
congestive
with
heart
failure
flecainide;
in
similarly,
their
overall
in a recent
experience
editorial
ment,
Benditt
et al’7 outlined
that the
of flecainide
are becoming
increasingly
com-
adverse
apparent.
effects
Propafenone
is a recently
released
antiarrhythmic
drug
that shares
many
clinical
characteristics
with
flecainide.
The overall
incidence
of cardiovascular
side
effects
during
propafenone
therapy
has been
reported
to be approximately
13 percent.
‘
These
cardiac
side
effects
usually
occur
advanced
heart
disease,
and they
dependent.
Thus,
like flecainide,
quires
patients
close monitoring
with
congestive
in patients
appear
to be
propafenone
of left ventricular
heart
failure,
during
the first weeks
of
was
designed
to compare
the
intravenously
flecainide
none
ively
The
study
40
subjects
formance
Effects
administered
on left
assessed
ventricular
systolic
by two-dimensional
was
performed
with
at
of Flecainide
rest,
normal
the
and Propafenone
majority
on Systolic
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21669/ on 05/13/2017
function
particularly
in
The present
study
inotropic
effects
of
and
propafe-
function,
noninvasechocardiography.
in a selected
cardiac
with
dose
re-
population
of
structure
and
of
required
whom
Performance
(Santinelli
per-
et a!)
antiarrhythmic
tachyarrhythmias.
therapy
because
of
NI-mode
supraventricular
and
88 percent,
Treatment
MATERIAL
AND
Once
studied
men
population
and
years;
age,
department
sion
clinical
presence
instnimental
older
did
not
trict,lar
reentry
nodal
tachycardia,
and
Treatment
for
Baseline
five
with
a 2.5
and
also
view,
was
used
thickness
apex,
the
the different
myocardial
regions
through
of the
IVS
assessment
th) and systolic
ventricle
various
and
excursion
(percent
biplane
FS)
and
pump
Echocardiograms
who
measurements
cycles.
Table
1 -Mean
blinded
expressed
Intraohserver
Values
as mean
and
cm
cm
% FS,
EF,
%
%
IVSth,
%
IVSex,
mm
PWth,
%
PWex,
by
mm
text
for abbreviations;
the
two
sets
observed
The
two
experi-
but
3.4±0.6
<0.01
42.4±7.2
32.1±10.7
<0.001
62.9±7.0
54.2±6.8
<0.001
were
for
to
observed
pressure
after
both
did not change
vice versa,
both
of LVIDs.
A
of
global
percentage
and
images
quantified
and
25
sys-
of FS,
propafenone
of the
left
in a fall
percent
of systolic
and
a decrease
of
and of23
percent
ex was reduced
to 25 percent
in
ventricle
a
func-
of about
FS
after
12
both
after propafenone,
to 32 percent
after
after
at Baseline
NS
5.2±0.2
5.0±0.4
2.9±0.4
3.3±0.5
40±5.0
33.4±7.1
60.5±5.3
18.9
52.9±15.9
<0.001
72.9±17.3
by F and
basal
values;
P on all parameters
p Value
NS
<0.01
<0.001
16.4
NS
2.9±0.8
NS
55.8±14.3
<0.001
3.8±0.8
no significant
were
1V
After
<0.001
31.2±
5.1±0.7
<0.001
vs respective
and
54±5.4
41.4±
73.1±20.4
(B)
Studied*
P
3.9±1
while
flecai-
propafenone.
Parameters
Subjects
th of the left ventricular
about
27 percent
after
B
NS
induced
t test
peformed
blood
indices
and
pVah,e
10.9
changes
rate
flecainide
be
percentage
showed
<0.001
changes
was
decrease
both
EF
EF
2.9±0.9
The
Student
Systolic
significant
of
may
the
3.9±1.1
P values.
(30 mm)
drug
injections
clearly
demonstrated
distributed
depression
of ventricular
in
nide
3.6±0.9
not
after
which
about
5.0±0.7
F and
imme-
late
significant.
in heart
function,
of
flecainide
its systolic
2.9±0.47
to drug-induced
and
± SD.
considered
1). Two-dimensional
three
patients.
5.0±0.35
refer
moni-
at baseline,
samples
drugs.
reduction
was
PW
F
p values
continuwas
drugs.
b
B
5.3±0.6
*See
was
changes
Two-Dimensional
Echocardiographic
(F) and Propafrnone
(P) in the
32.2±
and
sphygmomanometer.
(15 mm)
values
indicated)
of both
a slight
pump
systolic
agreements
and
mg/kg)
pressure
made
earls’
as mean
A p<O.O5
significant
percent
of left
of at least
ofFlecainide
18.3
data.
tolic
tion,
(percent
to the
in the
or
other
at a constant
were
arterial
were
and
(2
echocardiogram
of a standard
(when
injection
at peak
uniformly
systolic
quantified
by
value
(± SD) ofM-Mode
44.6±
ofhaseline
by moving
calculated
given
interobserver
Injection
LVDId,
drug
means
infusion,
unpaired
the
(Table
During
of overall
independently
to the
and
systemic
are expressed
and
significant
levels
The
(EF),
as indices
by
Flecainide
to the
intravenously
fenone
are reported
in Table 1. LVIDd
after both flecainide
and propafenone;
drugs
induced
a significant
increase
as
(IVS)
shortening
fraction
20
view
two-chamber
was
ECC
over
flecainide
(from
115±15
to 105±10
mm
Hg) and
propafenone
(from 1 10 ± 17 to 105 ± 12 mm Hg).
Mean
values
of echocardiographic
parameters
before and after
injection
of both flecainide
and propa-
ventricle
thickening
fractional
assumed
analyzed
were
were
cardiac
LVDIs,
after
function.
were
observers
PW
period.
crossed
RESULTS
end-
at various
identified
Both
then
were
flecainide
Analysis
No
well
contractility
systolic
ejection
left
rapidly.
ventricular
axis
septum
and
were
patieIlts
phase.
compare
to the American
scan
either
measurements
the
All values
paired
in the
as
The
were
percent
were
and
an
770
ventricular
according
all
to receive
injected
In addition,
after
Statistical
2
was
(lIP
(LVIDs)
regional
percent
(ex);
method,
ventricular
left
positions
left
of both
in all patients
discontin-
short
four-chamber
qualitatively
tored
completed,
were
atrial
performed
system
short-axis
in the
10 mm.
recorded.
Echocardiographic
patients
procedure
interventricular
to assess
M-mode
was
recommendations.#{176}
and
during
were
fashion
they
(2 mg/kg)
showed
array
(PW),
after
ously
recover
34 had
was
of the
to obtain
of the
drug-free
tachycardia.
dimension
wall
a 48-h
had
and
an ectopic
Parasternal
in a standardized
base
contractility
enced
obtained.
end-systolic
posterior
transducer
ellipse
nature
was
transducer.
level
and
visualized
test,
All
MHz
systolic
the
apical
pathway;
agents
The
ageilt
myocardial
All
ventricular
drug;
diately
had an atrioven-
1 had
of a phased
of Echocardiography
between
the
3.5
or
92 percent
disease;
40 years
defect.
examination
means
ventricular
Society
was
by
(LVIDd)
left
than
exercise
antiarrhythmic
consent
midventricular
diastolic
artery
studies
as first
the
Study
manner
diastolic
left
baseline
in a single-blind
propafenone
rate
and
and
No patient
to accessory
half-lives.
informed
of
as assessed
recordings.
14 patients
a benign
echocardiographic
standard
and
1 had
all previous
at least
and
last
Echocardiographic
the
the
propafenone
Inclu-
or coronary
tachycardia,
our
because
examination
perfusion
due
1991
disease
older
study:
reentry
the
with
explained
at the
any
tachycardia
atrioventricular
AC),
detect
to
two-dimensional
thallium-201
an electrophysiologic
underwent
ECC,
(8 men
years),
17 to 56
tachycardias.
radiograph)
patients
45
from
referred
heart
hypertension
oldest
than
scintigraphy
March
echocardiographic
in the
women
ued
(12-lead
ofessential
in addition,
and
paroxysmal
cilest
of adequate
history
those
of structural
patients
varied
from
1989
the absence
and
in age
selected
echocardiography,
clinical
range
years)
of symptomatic
were
Doppler
of 40 nonconsecutive
September
episodes
criteria
by
whose
25
between
recurrent
consisted
12 women
mean
were
Protocol
randomized
The
ineastrements
METHODS
Ihtients
(28
two-dimensional
respectivel)
differences
<0.01
were
found
comparing
comparable.
CHEST
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I 103
I 4 I APRIL,
1993
1069
2A and
FIGURE
the changes
recordings
were
similar
to those
recordings
a marked
observed
in Figure
in the same subject
after
detected
(IVS = interventricular
obtained
(bottom)
it appears
still exist
B. M-mode
echocardiographic
(26-year-old
man) showing
left) in a patient
(A,
were
fiecainide
septum;
to be interesting
because
controversial
data
about
the inotropic
properties
of propafe-
before
(top)
and after (bottom)
IV propafenone
drug-induced
impairment
of systolic
function:
1A and
B. In B (right)
the echocardiographic
are shown;
only minor changes
in systolic
function
PW = posterior
wall).
The
latter
therefore,
serious
none.
In
particular,
negative
inotropic
concentrations
of propafenone
in vitro24 as well as in animal
clinical
studies
by oral
propafenone
decreased
have
effects
have been
studies;23
demonstrated
a reduction
in patients
or clearly
of
with
impaired
either
ventricular
high
recognized
in addition,
of EF
minimally
and
does
believe
not
that
unpredictable
fect ofboth
flecainide
to outline
that
in
induced
dramatic
propafenone
changes,
remaining
function.27
effect
we
caused
comparable
patients.
only
after
paired.
ofan
subclinical
experience.
in
the
First,
albeit
tion
normal
there
negative
propafenone
lion.
should
are
inotropic
on
Second,
left
both
promptly
in some
be
ventricles.
significant
effects
ventricular
drugs
reversible
young
no
emphasized
and
are
of
to induce
impairment
healthy
pump
patients
ofsystolic
with
dude
a severe
func-
this
condition
because
a
ef-
hemodynamic
observed
in all the
hand,
similar
findings
patient
with
dysfunction.
the presence
cardiomyopathy
and
related;
It is important
with
flecainidesystolic
function,
flecainide
in the
marked
systolic
permits
us to rule out
of the left ventricular
functional
in these
patients,
although
we
func-
otherwise
underlying
dose
considered
adverse
minor
our
differences
flecainide
systolic
able
in
be
hemodynamic
to those
On the other
were
observed
propafenone-induced
This observation
observations
to be
may
and propafenone.
the two patients
impairment
of
However,
other
clinical
studies
on propafenone
have found
no further
decrease
in EF in patients
whose
initial
systolic
pump
function
had been
imTwo
appear
this
as a cause
alterations
observed
cannot
definitely
ex-
a myocardial
biopsy
was
not performed.
However,
the complete
absence
of
abnormalities
in clinical
and instrumental
examination
as well as the different
responses
observed
in the same
patient
after flecainide
and propafenone
may suggest
that the drug by itself is responsible
for the observed
CHEST
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I 103
I 4 I APRIL
1993
1071
2A and
FIGURE
the changes
recordings
were
similar
to those
recordings
a marked
observed
in Figure
in the same subject
after
detected
(IVS = interventricular
obtained
(bottom)
it appears
still exist
B. M-mode
echocardiographic
(26-year-old
man) showing
left) in a patient
(A,
were
fiecainide
septum;
to be interesting
because
controversial
data
about
the inotropic
properties
of propafe-
before
(top)
and after (bottom)
IV propafenone
drug-induced
impairment
of systolic
function:
1A and
B. In B (right)
the echocardiographic
are shown;
only minor changes
in systolic
function
PW = posterior
wall).
The
latter
therefore,
serious
none.
In
particular,
negative
inotropic
concentrations
of propafenone
in vitro24 as well as in animal
clinical
studies
by oral
propafenone
decreased
have
effects
have been
studies;23
demonstrated
a reduction
in patients
or clearly
of
with
impaired
either
ventricular
high
recognized
in addition,
of EF
minimally
and
does
believe
not
that
unpredictable
fect ofboth
flecainide
to outline
that
in
induced
dramatic
propafenone
changes,
remaining
function.27
effect
we
caused
comparable
patients.
only
after
paired.
ofan
subclinical
experience.
in
the
First,
albeit
tion
normal
there
negative
propafenone
lion.
should
are
inotropic
on
Second,
left
both
promptly
in some
be
ventricles.
significant
effects
ventricular
drugs
reversible
young
no
emphasized
and
are
of
to induce
impairment
healthy
pump
patients
ofsystolic
with
dude
a severe
func-
this
condition
because
a
ef-
hemodynamic
observed
in all the
hand,
similar
findings
patient
with
dysfunction.
the presence
cardiomyopathy
and
related;
It is important
with
flecainidesystolic
function,
flecainide
in the
marked
systolic
permits
us to rule out
of the left ventricular
functional
in these
patients,
although
we
func-
otherwise
underlying
dose
considered
adverse
minor
our
differences
flecainide
systolic
able
in
be
hemodynamic
to those
On the other
were
observed
propafenone-induced
This observation
observations
to be
may
and propafenone.
the two patients
impairment
of
However,
other
clinical
studies
on propafenone
have found
no further
decrease
in EF in patients
whose
initial
systolic
pump
function
had been
imTwo
appear
this
as a cause
alterations
observed
cannot
definitely
ex-
a myocardial
biopsy
was
not performed.
However,
the complete
absence
of
abnormalities
in clinical
and instrumental
examination
as well as the different
responses
observed
in the same
patient
after flecainide
and propafenone
may suggest
that the drug by itself is responsible
for the observed
CHEST
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I 103
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1993
1071
effects.
It may
known
proarrhythmic
be
hypothesized
that,
effect12”3
like
the
well-
in
some
observed
otherwise
healthy
subjects,
flecainide
and
none
exhibit
a primary
adverse
hemodynamic
in
some
subjects
with
norma]
cardiac
The
results
of our
clinical
observations
failure
by Haissaguerre
ence with flecainide.
on the implications
type
study
agents
the clinical
as a worsening
disquieting
agents
be
like
adverse
failure
because
cautiously
only in patients
without
clinical
BL,
previous
flecainide
mandate
with heart
evidence
as first-line
failure,
of left
agents
but also
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