Download Radiation-Associated Valvular Disease

Radiation-Associated
Robert
G. Carison,
Sigurd
Normann,
Valvular Disease*
M.D.;t
William R. Mayfield, M.D.4
M.D. , Ph.D.;*
and James A. Alexander,
The
prevalence
of radiation-associated
cardiac
disease
is
due to prolonged
survival
following
mediastinal
irradiation.
Side effects of radiation
include
pericarditis,
accelerated
coronary
artery
disease,
myocardial
fibrosis
and
valvular
injury.
We evaluated
the cases of three young
patients
with evidence
ofsignificant
valvular
disease followbig mediastinal
irradiation.
One
patient
underwent
the first
reported
successful
aortic
and
mitral
valve replacement
for
radiation-associated
valvular
disease
(RAVD)
as well as
concurrent
coronary
artery revascularization.
A review of
the literature
revealed
35 reported
cases
of RAVD,
with
only one successful
case of valve replacement
that was
limited
to the aortic valve. Asymptomatic
RAVD
is diagnosed
11.5 years after mediastinal
irradiation
compared
increasing
C
ardiac
injury
after
mediastinal
irradiation
includes
acute pericarditis,”2
chronic
pericarditis
without
effusion,3’7
accelerated
arteriosclerosis
coronary
arteries,6
vular dysfunction,2’6’7’9
ities.1”#{176}’12Although
astinal
irradiation
coronary
sudden
some
causes
arteries,’6
death
have
following
been
(to our
knowledge)
symptomatic
ease
and
mitral
last two
have
identified
no
the
radiation-associated
dysfunction
bivalvular
tion-associated
valvular
three
patients
with
disease
had concurrent
coronary
artery
we describe
the first successfully
revascularization
patient
on this
conclude
and
from
asymptomatic
valvular
and Mitral
the Division
of Surgery,
Cainesville.
tSurgical
tAssistant
§Professor
Resident.
Professor
#{182}Professor
of Pathology.
and Chief,
Manuscript
received
538
of Thoracic
University
and
cCy.
The
of Florida,
College
cCy
to the
of Medicine,
ofCardiothoracic
April 18; revision accepted
Division
86
and
unilateral
node
Bypass
Artery
adrenalectomy
dissection
regions
with
with
and
and
right
of
nodal
evidence
to
descending
a diagonal
artery
De-
167
(CX)
distinct
distal
to the
inferior
mg/dl
revealed
total
valvular
posterior
and
the
first
was
noted
vessel
to
the
later
scarred
distally.
aorta,
extension
onto
the
thickened
nor adherent
There
aortic
right
but
segment
was
root,
ventricle.
to the
of
a four-
marginal
of the
of the RCA was noted
second
scarring
atherosclerotic.
thickening
The
and
evidence
underwent
Severe
of the
and
akinesis
with
LAD
of the
pulmonary
pericardium
Scarring
a normalepicardium
artery
was
with
neither
heart.
Radiation-associated
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not
of
circumflex
no
was
RCA,
arteries.
wall in the distribution
proximal
left
Apical
anterior
stenosis
The right ventricular
he
to the LAD,
coronary
appeared
in the
branch.
coronary
left
proximal
of the
was
as a child.
right
in the
were noted.
and there
months
level
ofthe
stenosis
marginal
bypass
diagonal
myocardial
artery
infarction.
fever
80 percent
percent
Three
artery
and
cCy.
triglyceride
rheumatic
stenosis
(LAD),
50
abnormalities.
coronary
of the
he experienced
myocardial
occlusion
proximal
hypokinesis
ofthe septum
was modestly
elevated
pressure
4,100
parts
4000
wall
and
having
artery
and
received
of 4,200
with
posterior
at age 22 years,
denied
80 percent
branch,
treated
one pack a day for five years; his serum
patient
coronary
dose
were
and
region
therapy,
an acute
catheterization
(RCA),
artery
a
suffered
abdominal
nodes
anterior
supraclavicular
The
a total
lymph
approximately
value was
mg/dl,
adjacent
Surgery.
July 30.
underwent
mediastinum
left
pain
appearing
of Surgery.
He
femoral
The
Cardiac
in
Surgery,
Comnanj
Irradiation
supradiaphragmatic
He smoked
cholesterol
heart disease.
Based
of the literature,
we
a continuum,
pro-
and Cardiovascular
with
Replacement
retroperitoneal
circumflex,
partment
99:538-45)
REPORTS
Mediastinal
testicle.
vessel
5From
requiring
1991;
dysfunction.
Four years after radiation
two
thickening
Valve
Follot
chest.
radia-
replacement
compromise
(Chest
CASE
aortic,
disand
of whom
valvular
hemodynamic
mild
to severe
metastasis.
Postoperatively,
he received
chemotherapy
(chlorambucil, dactinomycin,
and methotrexate)
and simultaneous
supervoltage
radiation
therapy
using
the inverted
Y format
to the mantle,
para-
disease.
In addition,
combined
coronary
bivalvular
with radiation-associated
experience
and a review
that RAVD
represents
gressing
(RAVD)
with
1
of the
of
artery
begins
=
radical
coexistence
aortic
that
and progresses
An 18-year-old white male subject was in good health until March
1974 when he was diagnosed
as having embryonal
cell carcinoma
reports
coronary
in the
radiation
thickening
aortic
regurgitation;
BBB
bundle
branch
block;
cGycentigray;
CXleft
circumflex
artery;
IMA
internal
mammary
artery;
LAD
left anterior
descending
artery;
LVEDPleft
ventricular
end diastolic
pressure;
MR
mitral
regurgitation;
NYHA
New
York
Heart
Association;
PAP
pulmonary
artery
pressure;
BAVD
radiation
associated
valvular
disease;
RCAright
coronary
artery
chest
we present
following
=
AR
Grafting
positions.
In this report
disease
asymptomatic
valvular
valvular
fibrosis with
surgical
intervention.
Aortic
infarction
and
young
patients
decades,
valvular
CASE
authors
disagree
that mediocclusive
disease
in the
In the
16.5 years for symptomatic
patients,
emphasizing
that
long-term
follow-up
is important
for patients
receiving
mediastinal
irradiation.
This study defines a continuum
of
with
symptomatic
fibrosis,’#{176}’2”’9
valconduction
abnormal-
acute
myocardial
occurred
in very
C.PI
F. C.
,
with or
of the
mediastinal
irradiation.8”#{176}”2
In addition,
valvular
dysfunction
following
radiation
cited
infrequently,
with only ten reported
symptomatic
has
myocardial
and
M.D.
Valvular
Disease
(Carlson
eta!)
‘
.
.“
c
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y;
Ficuiw
1. Coronary
vein
flOtlS
site
of
aortic
graft
arteriogram
leading
high-grade
to the
in case
ol)tuse
ostial
lesions
at age
32 ears,
1 demonstrating
marginal
of
the
arter)
Arrow
saphenous
vein
indicates
graft
.
at
..,
years
heart
later,
failure
proved
with
patent
saphenous
occlusion
of
diseased
secondary
to
medical
therapy
vein
the
CX.
(PAP)
months
Four
mv()cardial
mm
aortic
later,
valve
that
revealed
stenosis
dysfunction
47
mm
RCA
Hg).
(mean
=
LAD
hut
a 95
and
1 + aortic
and
a left
im-
3.
the
artery
pres-
ventricular
was
followed
end-
he
had
bs
artery
mm
disease
moderate
and
had
(Fig
2).
An
ventricular
PAP
progressed
He
AR,
left
65/30,
and
vein
then
patch
and
matted
chordae
leaflets
were
tion
aortic
with
done
Artery
noted
nodular
and exhibits
thickened.
was
focal
was
unremarkable
exhibits
valve
(Fig
dystrophic
was thickened
had
and
mitral
fibrosis
focal
with
mcdi-
stenotic
extensive
with
3).
calcifi-
and composed
calcification.
and
New
A
graft.
entire
The
a
valve.
marginal
nodules.
tissue
The
in follow-up
York
heart
Associa-
with
Radiation-
tolerance.
Reva.ccularization
Coronary
A 33-year-old
is
left
with
mitral
of the
valve
with
and
left
and
2
woman
She
underwent
a total
aontic
and
cCy
Thirteen
non-Q
wave
no
history
health
mass.
was
splenic
years
chest
cCv
(using
10 MeV
later
pain.
myocandial
the
to
portals.
Stage
was
age
hA
after
the
mantle
A right
she
of cigarette
until
diagnosed
radiotherapy
of 3,700
by Betatron
intermittent
type,
Disease
in good
supraclavicular
sclerosing
with
with
was
a night
in a Patient
and Valvular
Artery
hypercholesterolemia
the
well
1 exercise
and
movement
replacement
St Jude
fibrosis
fibrotic
course
at the
MR
incomplete
on the obtuse
the penicardium
has
valve
mitral
were
postoperative
associated
1 showing
mitral
suhvalvular
connective
class
lesion
enlargement
a 25 mm
thickened
leaflets
Histologicall);
Coronary
axis. The aortic
valve
(AV) is thickened
movement.
The
mitral
valve
(MV)
LV
left ventricle;
RV
right ventricle.
tn-
pattern.
severe
The
tendinae
he
and
and
included
markedly
atnial
performed
was
fibrous
ostial
revealed
left
a strain
valve
penicardium.
(NYHA)
CASE
she
with
with
aontic
valve
a high-grade
(ECG)
(BBB)
findings
astinum
dense
had
and restricted
angioplasty
evaluations
parasternal
restricted
Ao - aorta;
a 27-year-old
aortic valve thickening
underwent
St Jude
patient’s
of case
in
1). Photomicrograph
valve
(Masson
confirmed
block
Intraoperative
of
echocardiogram
disease
Echocardiography
hypentrophy
21 mm
vein
graft
1).
electrocardiogram
branch
cation.
2. Two-dimensional
valvular
(Fig
AR with associated
fatigue.
moderate
and
Hg
wave
non-Q
persistent
MR.
gradient,
30
a
marginal
anastomosis
bundle
to severe
mm
obtuse
aortic
Hg.
1989,
Radiation-associated
man 9 years after mediastinal
irradiation
(case
demonstrates
extensive
fibrosis
of the mitral
chrome
stain, original
magnification
x 307).
The aontic
FIcuRE
‘
-,
0
percent
a diffusely
regurgitation
a pulmonary
46),
mm
January
a 20
which
revealed
artery
with
(LVEDP
Coronary
and
was 3 + MR,
moderate
with
(MR),
congestive
catheterization
descending
of22
in
infarction
ventricular
=
Fig
(LVEDP)
Recatheterization
to the
there
mild
regurgitation
hypertension
of 60/34
with
presented
Cardiac
posterior
In addition,
presstlre
he
mitral
grafts
distal
pulmonary
and
diastolic
mean
‘
the
FIceRE
sure
..:
-:#{149}lk
i
anastomosis.
Nine
(AR),
‘:
.‘
p
a saphe-
hodgkin’s
extensive
Linac
and
smoking
19 years,
3 technique,
cCy
supnaclavicular
disease,
evaluation.
2 and
3,700
or
when
to the
boost
with
para300
performed.
had
However,
infarction.
CHEST
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normal
one
Cardiac
results
ear
of
thereafter,
catheterization
I 99 I 3 I MARCH,
a
workup
she
for
had
revealed
1991
539
a
atrial
l)io)sy
thickening
interstitial
and
stitial
an(l
The
she
exhibited
C.ss:
:3
Prngres.sion
Aor-tic,
of
involvement.
her
1over
Fifte’ui
evaluation
of
with
ening
Fu
m 11 I
4 . ( oronarv
Ol)li(luI(
01)1
K(lIl’i(
rvtrogradv
()1)tuIS(
AR.
right
111
On
transfer
nuamnunarv
to
(Ibtuges
rouuarv
urtu’rv
s’er(’
urk’rv
first
now
total
mica.
;x
occi
usion
of
developed
snhsternal
the
first
ni1d
(Ilest
H(
vit1i
grafting
left
A an(1
utuutm’
using
the
1lt1)lIg11
aorta
,;s
-,,
.
:
1)’
.
-.-
.‘
.
‘
.
I;
.
-
.,
‘-
.,.
,t;
.S.
:
. There-
ther(’
.
%as
Right
-;--
:
-
LVEDP
followed
Iii)
..:.,
t!:.
11g.
mm
,
*:
has
reduction
-
.
five
,
5.
1-nUn
Nlv(x.ar(lial
sluing
1nV()CVte
(-n(locar(litIn
fication
540
irradiation
and
.
.
and
X 307).
va(uuolar
interstitiuum
and
aortic
a 45-sear-old
(‘lltflge
has
past
four
the
valve
valve
has
with
patient
thickening
and
regurgi-
around
remained
diuretics
and
20
afterload
r Disease
for
RAVD
1).
However,
has
not
be
reported
one
patient,
patient,
valve
because
the
In
mediasaortic
performed
placed
aorta
been
in
of extensive
a second
calcification.
aortic
patients
have
valvular
replacement
aortic
year,
latter
between
the
to temporarily
2).
atal
Right
ment
14
svonien
atnial
e-xt’nsive
n -eosin.
valve.
of expatient,
left
a
ventricle
a severely
bypass
valve
oe
1)iopSy
fibrosis
original
ears
Speciof the
niagni-
described
require
surgical
actually
last
disease
ofwhom
surgery
intervention
of
only
patient
received
survived
had
aortic
valve
three
underwent
less
replacement
mitral
and
valve
the
and
operative
is extremely
high
with
decades,
numerous
than
died
replace-
annuloplasty
Accordingly,
for RAVD
66
valve
a third
with
One
and
mitral
intraoperatively.
the
who
for RAVD.
had
puhlished.26’’9’2#{176}
to
reported
and
of
cases
replacement
combined
rate
the
Thus,
been
postoperatively,
‘
mortality
(heniatoxvli
in
was
descending
tality
(case
aortic
thickening
because
could
stenotic
ofle
,
in
The
p
#{149}#{149}‘
fibrosis
1fle(1iLsti0al
valve
tolerance.
Valvula
abandoned
conduit
In
FIGURE
dysp-
progressed
for
with
exercise
(Table
was
valvular
folloving
aortic
intervention
tensive
.
;
nocturnal
had
and
gradient
shortness
unchanged
valve
therapy
her
patients
valve
-
died
.
the
improved
replacement
..
,.:
,
mitral
medical
fibrosis
an
. ,,
progressive
-Associated
surgery
.,
\)
Agj.ressive
Surgical
‘
a
.
‘
.
.
..
:
1.,
-
- ,.
‘,
5\
a,-
.
echocardiography
across
normal
with
exercise.
sean1
MR.
1 +
revealed
presented
Jig during
and
thick-
a 15-mm
essentially
of tricuspid
gradient
‘
., ..
‘,
revealed
systolic
and
with
dysfunction
to 5() miii
for
penicardial
paroxysmal
worsening
ventricular
with
onset
catheterization
she
revealed
development
The
ill
..
.‘
#{149}1.,
,,
..
?
s_;
has
recent
tatu)n.
and
left
of
Radiation
‘
-:
f
-,
hut
cardiac
of
referred
confirmed
stenosis
later,
catheterization
that
and
months
1)a11)itations,
elevation
tinal
,
Four
ahnornialities
ne
was
cC\
part
DISCUSSION
:
b
.
.e.-
,.,
#{149}
, :‘
,
&..
present.
posterior
hypokinesia
later.
therapy
4,000
arch,
revealed
aortic
IIB
me-
radiation
catheterization
‘ears
NIR but
stage
posterior
she
and
ventricular
.
-
-
(X
111(1 e’l)icar(Iinhll
.
‘
isclieniia.
She
right
internal
1NIA to the
())nstri(tion.
areaund
Three
AR and
having
to the
42 ears,
failure
Cardiac
arteries.
(mrdi;ic
been
MR.
generalized
muuichange(1
was
())llate’ral
and
J)isease
aortic
cC
Echocardiograph
an(l
of hr’eth,
10(1
slut’
())IIsistt-’ult
Of 1)’ri11(1i;tl
.
.
)nstratPs
of tl’
(
(Iistdl
to the
sas
HB)dvrat(’
J1 R aul
bv1)ass
(1 NI A) to t1u
ituflauiuuiuation
(‘XtU1SiV(’
thu
heart
and
cobalt
and
age
at
and
(unremarkable
extensive
with
treated
later,
inter-
thickened
as
with
amid 3,500
congestive
AR
AR.
coronary
in(licatt’s
to
artt’r
(KUlilSioll
4). There
.
arro
(listal
(I(Tfl(
1) S
hospital
large’
1 +
ant(’rior
ears
:( ;
((
(‘\i(I(’nC(’
IU)
our
arrovs
l)(’5S1
a right
arh’rv
cumrunarv
I1( A :111(1 subtotal
uuuarginal
branch
(Fig
1)1111 (11(1 E(
uuI1(Ierssent
s,as
of the
Tl-
(irclumBHex
Suuiall
.
2 sboving
urtt’r
lu’ft
( )1’ sm’mutrm
i )I1
of cus’
or’nr
thu
I)rauu(lu
filling
ilittt
P#{176}
)xjal
l’ft
111 of
nuarginal
IISV
(‘(41
of th
Vit”A
subtotul
artm’riograuuu
diagnosed
niediastinum
ears
miuuurniuurs.
was
was
biopsy
increased
and
Valvular
was
was
and
ventricular
Valves
disease
upper
change,
tolerance.
Tricuspid
wotiuan
niediastiuinni,
heart.
diastolic
and
She
to her
vacuolar
endocardiurn,
5). A left
ctirse
1 exercise
Ilodgkins
((
(Fig
Radiation-Associated
white
diastinal
the
class
sclerosing
0f4,50()
amid
postoperative
Mitral,
A 27-year-old
myocvte
vacuolar
change
The pericardium
fibrosis.
NYHA
lneolvin’
extensive
epicardium
fibrosis
moderate
patientis
(;li,uic,l
no(lnlar
the
perivascuular
i)eriascl1lar
fibrotic.
to
of
revealed
5J)e(iliieli
,,1
revealed
Si)((ifliefl
increased
mor-
a reported
percent.
three
after
reports
therapy
radiation
All together,
35 patients
five had valvular
disease
(Table
2) and
(Table
Radiation-associated
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21625/ on 05/12/2017
30 did
3). The
Valvular
mean
Disease
have
of
been
have been
sufficient
not
require
age
of the
(Car/son et a!)
Table
Case
ofSymptomatk
1-Reporte
Source
1
Warda
Radiation-induced
Age,t
Initial
yr/Sex
Diagnosis
et al’#{176}
59/M
irradiation
Dose,
Valvular
Interval,
cCy
Hodgkin’s
120
Severe
McEniery
et al’
54/M
lntervention*
Valvular
Valvular
Postoperative
Course
Surgery
AS,MR
AVR,
mitral
valve
Died
in
OR
aiinuloplasty
disease
2
Surgical
Involvement
IflO
-
Requiring
Disease
Lymphoma
348
-
Abandoned
AS,AR
AVR,
and
Survived
CABC
3
McEniery
et al’
Hodgkin’s
621M
5000
AS,AR
216
Teunporary
4
Hancock
et al
Hodgkin’s
--I
5
Lederman
6
Present
et alv
valved
Survived
conduit
disease
>3500
MR
-
Mitral
Died
valve
replacement
disease
44/M
Seminoma
4500
153
AS
Aortic
32/M
Embryonal
cell Ca
4000
162
MR,MS,AR,AS
Aortic
Ix)stPerativelY
valve
Survived
replacenuent
study
(case 1)
*A
aortic
=
MR
tAge
valve
mitral
=
at time
patients
replacement;
regurgitation;
of cardiac
years)
and
55 years
Aortic
dysfunction
present
surgery
in four
(Table
2),
RAVD.
RAVD
The
was
exhibited
agnosis
no
of
symptoms
asymptomatic
echocardiography
studies9’21’
30
of five
were
patients
symptomatic.
for diagnosis
of
These
patients
of congestive
heart
However,
the vast
percent)
with RAVD
of valvular
RAVD
dysfunction.
was primarily
of asymptomatic
RAVD
occurred
years after irradiation
compared
16.5
symptomatic
patients.
Thus,
the
required
for
years
from
interval
asymptomatic
Our
review
abnormalities
sided
for
to be
to symptomatic
identified
following
abnormalities
artery
graft;
bypass
five
35 patients
with
years
progression
valves.
iiiost
frequently
Three
cases
been
described,
No
evidence
the
literature;
aurtic
one
patient
Brosius
irradiation
stenosis;
AR
aontic
regurgitation;
percent
Left-
of
the
of
pressure
common
involving
than right with 33 (92
either
the aortic
or
abnormalities
the
have
puitnonic
abnormalities
stenosis.
was
report,
leading
noted
we
to a higher
In
in
described
occur
due
incidence
contrast,
of
unyocardial
more
frequently
to the anterior
and the position
of the right
were based
OII postmortem
on the
radiation
ventricle.m2
examinations
These
of 16
young patients
who received
more than 3,500
mediastinal
irradiation.
At an average
duration
cCy of
of 4.5
years after
was present
radiation,
valvular
endocardial
iti 80 percent
of asymptomatic
that valvular
lesions
are relatively
thickening
patients,
frequent
after radiation
but are slow to evolve
into symptomatic
valvular
disease.
This conclusion
is consistent
with an
1 1 .5-year
interval
between
radiation
and the diagnosis
valvular
in five years
disease
as well
to a symptomatic
Experimentally,
niediastinal
irradiation
in rabbits
but valvular
lesions
in animals
killed
within
70 days of
carditis
give
was more
of 36 lesions
M R were
abnormalities.
had
in this
lesions.
damage
and fibrosis
right side,
presumably
function
valvular
tricuspid
valvular
related
trauma
thickening
and
Left-sided
valve
however,
involved,
with each representing
46 percent
ofvalvular
abnormalities.
Although
only 29 percent
ofthe patients
were
symptomatic,
some
degree
of physiologic
dysin 73 percent.
pulmonic
left ventricle
left-sided
fields
results
and
physiologic
all of which
ever,
was present
regurgitation
described
with tricuspid
valve regurgitation
(case 3).
et alh2 postulated
that
valves
injured
by
are more
prone
to trauma
in the high-
ofasymptomatic
41 valvular
Aortic
lesions
and were far more common
than right-sided
abnormalities,
in contradistinction
to a previous
report
of right-sided
predominance
(pulmonic
valve).
Interestingly,
the aortic
and mitral
valves
were
equally
dysfunction
percent)
AS
of
progression
irradiation.
93
mitral
suggesting
at a
with
RAVD.
mediastinal
comprised
Diby
follow-up
pericarditis.6
diagnosis
mean age ofll.5
appears
not
the five patients
all patients
with
during
either
or evaluation
of suspected
The
was
greater
than
[13 percent]
of
mean
age
16.5 years.
usually
presented
with symptoms
failure
and had a poor prognosis.
majority
of patients
(25/35,
71
stenosis
(80 percent)
five
44
20 to 71
in the operated-
These
five patients
combined
with
who had surgery
(Table 1) constitute
symptomatic
symptomatic
coronary
(range,
(range,
patients.
This incidence
is significantly
in the nonoperated-on
patients
(four
30 patients,
x2 = 7.O p<O.Ol).
In the
requiring
CABC
Survived
stenosis,
36 years
patients.
valvular
was
was
with
for nonoperated-on
on group
centiCray;
=
mitral
=
surgery
compared
the predominant
MS
valve
CABC
diagnosis.
undergoing
to 62 years)
cCy
and
amid mitral
replacement,
as the further
condition.
induced
a panwere not noted
n’ How-
this time interval
may have been too short since
valvular
tissue
appears
relatively
resistant
to the
immediate
effects
of radiation
injury.
Over
time,
however,
suiting
cellular
in stenosis
rise
tion and
cardium
injury
of the
with
pressure-
to asymptomatic
valvular
to valvular
deformity
re-
or insufficiency.
to subvalvular
fibrosis
combined
may lead
eventually
deformity
mural
Irradiation
also
through
inflamma-
endocardium
and
can
myo-
.
CHEST
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21625/ on 05/12/2017
I 99 I 3 I MARCH,
1991
541
mediastinal
irradiation,
myocardial
ischemia
sensitizer,
dactinomycin
also
Case
1 received
chiorambucil,
methotrexate
concomitantly
with
dactinomycin,
mediastinal
and
irradia-
farction)N
The radiation
may be cardiotoxic.#{176}
tion.
The
relatively
and
in-
development
rapid
development
of coronary
irradiation
and
Cases
1 and
radiation-associated
tient
developed
artery
anterior
aortic
proximal
root
sclerosis
with
showed
and
valve
tion
requiring
Coronary
Artery
has
injury.2’
chemo-
treatment
of the aortic
development
coronary
artery
was
hy-
infarction
boy 7
in a 12-year-old
years
and
after
radiation
development
anterior
thoracic
is a recognized
of occlusive
mantle
risk
coronary
of anterior-and
therapy
anterior
with
vessel
Perivascular
monly
occur
consists
muscle
media.’4
lesions
is usually
posterior-weighted
its
homogenous
the
mediastinal
may
radiodecrease
3
fibrosis
and
with
radiation
endothelial
and the
IMA
grafts
veins
they
and are less prone
are preferred
for
necessary.
myocardial
revascularization
damage
comrepair
process
of intimal
thickening
by proliferating
smooth
cells and collagen
deposition
in the intima and
In young
individuals,
intimal
and
medial
in young
advantages
of IMA grafts
were
initial
bypass
surgery
in case
grafts
were
used.
However,
better
individuals.
The
at the
vein
IMA
grafts
were
in case
used
2.
Involvement
Diffuse
interstitial
myocardial
fibrosis
finding
following
mediastinal
irradiation.’9
(96 percent)
induced
have
the
not appreciated
1 and saphenous
for revascularization
Myocardial
heart
anterior-weighted
ation-induced
is a consistent
A very high
ofdelayed-appearing
disease
occurs
in
radiation-
patients
receiving
thoracic
mantle
technique.”
fibrosis
may be significant,
individuals.’0”
Injury
to capillaries,
dently
of pericardial
constriction.
Using
echocardiography
and
irradiation
abnormality
ECG
overload
compliance
2 exhibited
cle,
to radiation
most
comradiother-
are primarily
proxispared.
Recent
use
dosing
Because
patency
rates than saphenous
to develop
arteriosclerosis,
atrial
artery
Coronary
lesions
are distributed
relative
dosimetry
with LAD
and RCA affected
monly
when anterior-weighted
mediastinal
apy is used.
The coronary
mal and the distal vessel
for
if this
becomes
mediastinal
3
factor
irradiation,
cure, to retain
revascularization
common
pairment.
after
mediastinal
radiotherapy.
Significant
coronary
artery
disease
may develop
in up to 18 percent
of patients
10 years
mediastinal
Gottdiener
et aF3 identified
or left ventricular
dysfunction
pothesized
following
reports
of myocardial
infarction
in young patients
receiving
mediastinal
irradiation.8”2
For instance,
Totterman
et al’#{176}
described
an acute
myocardial
vein
Radieven
in
arterioles,
and small intramyocardial
arteries
follows
7
Fajardo
and Stewart’8
suggest
that such injury
leads
to microcirculatory
ischemia
and fibrosis
indepen-
3).
disease
a saphenous
occluded
LAD in a
and posterior
radiIMA shielding
is
compromising
if myocardial
young
Involvement
Radiation-induced
during
incidence
and without
physvavular
dysfunc(Table
et al’5 used
corolesions
can be done without
use of these
vessels
successfully
Based
on our experience
RAVD appears
to evolve
to progressive
valve
fi-
asymptomatic
to symptomatic
surgical
of the
lesions
thickening
and subsequent
of tricuspid
regurgitation.
and a review
ofthe
literature,
from endocardial
thickening
that is initially
abnormalities
and
and
heart
disease
did not detreatment.
Yearly echocar-
progressive
leaflets
aortic
with radiation
therapy
without
therapy,
and symptomatic
velop
until 15 years after
diography
aortic
fibrosis,
calcification
calcific
been described
in association
Case 3 received
radiation
brosis
iologic
experienced
symptomatic
mediastinal
A similar
aorta.
mitral
disease,
nature
of
1, the pa-
infarction,
and
underwent
coronary
grafting
within
four years of treatment.
Ten years later, he developed
mitral
valve disease,
severe
lobal
graft to revascularize
a proximally
patient
who had received
anterior
otherapy
without
IMA shielding.’5
recommended
the progressive
disease.
In case
coronary
a myocardial
artery
bypass
management
of radiation-induced
disease
is favorable
because
the
are proximal.7”3”5
chemotherapy.
3 illustrate
heart
with minimal
lipid accumulation.
of injury,
radiation
potentiates
of atherosclerosis.3’
Operative
nary
artery
artery
disease
within
four years of mediastinal
irradiation and valvular
disease
within
nine years of therapy
in case 1 may reflect
injury induced
by both mediastinal
thickening
develop
As in other
types
may
for
radiocardiography,
an increased
in patients
Hodgldns
frequency
receiving
disease.
The
most
is left ventricular
diastolic
abnormalities
consistent
with
reflect
decreased
left
imleft
ventricular
associated
with myocardial
fibrosis.
Case
marked
fibrotic
changes
in the left ventri-
and preoperative
cardiac
catheterization
revealed
equalization
ofdiastolic
pressures
in all four chambers.
The progressive
worsening
of left ventricular
function
in case 3 illustrates
the progressive
myocardial
changes
induced
by mediastinal
irradiation.
Pericardial
involvement
Pericardial
involvement
is the
most
frequent
cause
of morbidity
and mortality
from
radiation-induced
heart disease.6
Acute
pericarditis
often presents
with
pleuritic
chest
pain, fever,
a friction
rub, and ECG
changes
percent
cGy
in the first year after
incidence
ofpericarditis
of mediastinal
irradiation
CHEST
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21625/ on 05/12/2017
irradiation.
There
after receiving
over
a four-week
I 99 I 3 I MARCH,
1991
is a 6
4,000
pe543
mediastinal
irradiation,
myocardial
ischemia
sensitizer,
dactinomycin
also
Case
1 received
chiorambucil,
methotrexate
concomitantly
with
dactinomycin,
mediastinal
and
irradia-
farction)N
The radiation
may be cardiotoxic.#{176}
tion.
The
relatively
and
in-
development
rapid
development
of coronary
irradiation
and
Cases
1 and
radiation-associated
tient
developed
artery
anterior
aortic
proximal
root
sclerosis
with
showed
and
valve
tion
requiring
Coronary
Artery
has
injury.2’
chemo-
treatment
of the aortic
development
coronary
artery
was
hy-
infarction
boy 7
in a 12-year-old
years
and
after
radiation
development
anterior
thoracic
is a recognized
of occlusive
mantle
risk
coronary
of anterior-and
therapy
anterior
with
vessel
Perivascular
monly
occur
consists
muscle
media.’4
lesions
is usually
posterior-weighted
its
homogenous
the
mediastinal
may
radiodecrease
3
fibrosis
and
with
radiation
endothelial
and the
IMA
grafts
veins
they
and are less prone
are preferred
for
necessary.
myocardial
revascularization
damage
comrepair
process
of intimal
thickening
by proliferating
smooth
cells and collagen
deposition
in the intima and
In young
individuals,
intimal
and
medial
in young
advantages
of IMA grafts
were
initial
bypass
surgery
in case
grafts
were
used.
However,
better
individuals.
The
at the
vein
IMA
grafts
were
in case
used
2.
Involvement
Diffuse
interstitial
myocardial
fibrosis
finding
following
mediastinal
irradiation.’9
(96 percent)
induced
have
the
not appreciated
1 and saphenous
for revascularization
Myocardial
heart
anterior-weighted
ation-induced
is a consistent
A very high
ofdelayed-appearing
disease
occurs
in
radiation-
patients
receiving
thoracic
mantle
technique.”
fibrosis
may be significant,
individuals.’0”
Injury
to capillaries,
dently
of pericardial
constriction.
Using
echocardiography
and
irradiation
abnormality
ECG
overload
compliance
2 exhibited
cle,
to radiation
most
comradiother-
are primarily
proxispared.
Recent
use
dosing
Because
patency
rates than saphenous
to develop
arteriosclerosis,
atrial
artery
Coronary
lesions
are distributed
relative
dosimetry
with LAD
and RCA affected
monly
when anterior-weighted
mediastinal
apy is used.
The coronary
mal and the distal vessel
for
if this
becomes
mediastinal
3
factor
irradiation,
cure, to retain
revascularization
common
pairment.
after
mediastinal
radiotherapy.
Significant
coronary
artery
disease
may develop
in up to 18 percent
of patients
10 years
mediastinal
Gottdiener
et aF3 identified
or left ventricular
dysfunction
pothesized
following
reports
of myocardial
infarction
in young patients
receiving
mediastinal
irradiation.8”2
For instance,
Totterman
et al’#{176}
described
an acute
myocardial
vein
Radieven
in
arterioles,
and small intramyocardial
arteries
follows
7
Fajardo
and Stewart’8
suggest
that such injury
leads
to microcirculatory
ischemia
and fibrosis
indepen-
3).
disease
a saphenous
occluded
LAD in a
and posterior
radiIMA shielding
is
compromising
if myocardial
young
Involvement
Radiation-induced
during
incidence
and without
physvavular
dysfunc(Table
et al’5 used
corolesions
can be done without
use of these
vessels
successfully
Based
on our experience
RAVD appears
to evolve
to progressive
valve
fi-
asymptomatic
to symptomatic
surgical
of the
lesions
thickening
and subsequent
of tricuspid
regurgitation.
and a review
ofthe
literature,
from endocardial
thickening
that is initially
abnormalities
and
and
heart
disease
did not detreatment.
Yearly echocar-
progressive
leaflets
aortic
with radiation
therapy
without
therapy,
and symptomatic
velop
until 15 years after
diography
aortic
fibrosis,
calcification
calcific
been described
in association
Case 3 received
radiation
brosis
iologic
experienced
symptomatic
mediastinal
A similar
aorta.
mitral
disease,
nature
of
1, the pa-
infarction,
and
underwent
coronary
grafting
within
four years of treatment.
Ten years later, he developed
mitral
valve disease,
severe
lobal
graft to revascularize
a proximally
patient
who had received
anterior
otherapy
without
IMA shielding.’5
recommended
the progressive
disease.
In case
coronary
a myocardial
artery
bypass
management
of radiation-induced
disease
is favorable
because
the
are proximal.7”3”5
chemotherapy.
3 illustrate
heart
with minimal
lipid accumulation.
of injury,
radiation
potentiates
of atherosclerosis.3’
Operative
nary
artery
artery
disease
within
four years of mediastinal
irradiation and valvular
disease
within
nine years of therapy
in case 1 may reflect
injury induced
by both mediastinal
thickening
develop
As in other
types
may
for
radiocardiography,
an increased
in patients
Hodgldns
frequency
receiving
disease.
The
most
is left ventricular
diastolic
abnormalities
consistent
with
reflect
decreased
left
imleft
ventricular
associated
with myocardial
fibrosis.
Case
marked
fibrotic
changes
in the left ventri-
and preoperative
cardiac
catheterization
revealed
equalization
ofdiastolic
pressures
in all four chambers.
The progressive
worsening
of left ventricular
function
in case 3 illustrates
the progressive
myocardial
changes
induced
by mediastinal
irradiation.
Pericardial
involvement
Pericardial
involvement
is the
most
frequent
cause
of morbidity
and mortality
from
radiation-induced
heart disease.6
Acute
pericarditis
often presents
with
pleuritic
chest
pain, fever,
a friction
rub, and ECG
changes
percent
cGy
in the first year after
incidence
ofpericarditis
of mediastinal
irradiation
CHEST
Downloaded From: http://journal.publications.chestnet.org/pdfaccess.ashx?url=/data/journals/chest/21625/ on 05/12/2017
irradiation.
There
after receiving
over
a four-week
I 99 I 3 I MARCH,
1991
is a 6
4,000
pe543
riod.4 The development
ranges from 4 months
blocking
ofdelayed
to 45 years.5
techniques
have
acute
pericarditis.
fusions
varies
from
raphy
is
useful
pericardial
Improved
decreased
the
The incidence
6 to 29 percent
in
patients
with
of
early
Cardiac
tamponade
is a possible
complication,
particularly
if the effusion
develops
rapidly.
Pericardiectomy
is the treatment
of choice
for symptomatic
radiation
pericarditis,
recurrent
pericardial
and/or
Conduction
ECG
ST
have been
consisting
segment
close
to
the
was not
infarction.
is commonly
because
evident
on
the
time
of his
first
Cardiol
1983;
JM.
cases
injury.
The
with
minimal
valvular
I.
Cardiol
side.’#{176}
myocardial
mean
age
thickening
significant
at diagnosis
diac
may
potentiate
9 McEniery
WC.
Case
1 had
ultimately
progressive
required
replacement.
In
patients
valvular
combined
addition,
he
had
and
PT,
Wiernik
coronary
valve
artery
disease
that required
revascularization.
Case
2 had
asymptomatic
valvular
disease
but progressive
coronary
artery
disease
that required
revascularization
using
the IMA.
These
two
patients
illustrate
the
successful
surgical
management
of radiation-associated cardiac
disease.
Case
3 illustrates
the medical
management
of progressive
valvular
disease
involving
the aortic,
mitral,
and
illustrate
the spectrum
disease
to
placement.
received
valvular
Long-term
mediastinal
tricuspid
of RAVD
requiring
for patients
irradiation
is critical.
J
Heart
developing
mediastinum:
1969;
as review
of
77:89-95
radiation
pericarditis:
of angiocardiography
two
in diagnosis.
J
Am
MA,
disease.
J Am Coil Cardiol
Dorosti
K,
Dunsmore
BA.
Schiavone
Radiation
induced
1986; 8:239-44
WA,
Pedrick
TJ, Sheldon
et al.
Long-term
cardiovascular
evaluation
of
disease
treated
by thoracic
mantle
therapy.
Cancer Treat Rep 1982; 66:1003-13
FC III, Wailer BF, Roberts WC. Radiation
heart disease:
of 16 young
(aged 15 to 33 years) necrospy
patients
who
over 3,500
reds to the heart. Am J Med 1981; 70:519Hodgkiils
13 Annest LS, Anderson
lIP, Wei-i L, Hafermann
MD. Coronary
artery disease following mediastinal
radiation therapy. J Thorac
Cardiovasc
Surg 1983; 85:257.63
14 McReynolds
BA, Cold GL, Roberts
WC. Coronary heart disease
after
mediastinal
irradiation
for HOdgkiiiS
disease.
Am J Med
1976; 60:39-45
15 lobal SM, Hanson EL, Gensini GG. Bypass graft for coronary
arterial
stenosis
following
radiation
therapy.
Chest
1977;
71:664-
66
17
LF. Radiation
1977;
71:563-64
Burch
GE,
Sohal
induced
RS,
Sun
coronary
SC,
artery
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LoPbnte
PH
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Workshops
The La Crosse Exercise
and Health
Program,
affiliated
with the University
LaCrosse,
will present the following workshops:
Cardiac
Rehabthtation-April
8-12
Advanced
Cardiac
Rehabilitation-May
6-9
Exercise
Physiology
for Health Care Professionals,
June 10-14
Cardiac
Rehabilitation-June
17-21 and September
16-20
For information,
contact
John Porcari,
Ph.D.,
La Crosse
Exercise
and Health
Mitchell
Hall,
University
ofWisconsin-La
Crosse, La Crosse 54601
(608:785-8683).
of Wisconsin-
Program,
CHEST
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221
I 99 I 3 I MARCH,
1991
545