8no-nonenonePyxaras, Stylianos A; Santangelo, Sara; Perkan, Andrea; Vitrella, Giancarlo; Rakar, Serena; Grazia, Erica Della; Salvi, Alessandro; Sinagra, GianfrancoPyxaras, Stylianos A; Santangelo, Sara; Perkan, Andrea; Vitrella, Giancarlo; Rakar, Serena; Grazia, Erica Della; Salvi, Alessandro; Sinagra, Gianfranc

Grazia, Erica Della

Perkan, Andrea

Pyxaras, Stylianos A.

Rakar, Serena

Salvi, Alessandro

Santangelo, Sara

Sinagra, Gianfranco

Vitrella, Giancarlo

SummaryAortic valve stenosis associated with angiodysplasia (Heyde's syndrome) and consequent anemia had previously been reported to benefit from surgical aortic valve replacement. In this clinical case an 89-year-old patient with chronic angiodysplasia-derived anemia, characterized by acute phases of active gastrointestinal bleeding experienced a normalization of hemoglobin values after a trans-catheter aortic valve implantation (TAVI) of a self-expandable aortic valve prosthesis (CoreValve, Medtronic Inc., Minneapolis, MN, USA). This is the first, to our knowledge, reported clinical case of remission of angiodysplasia-derived anemia after TAVI

Elsevier - Publisher Connector 

Reversal of angiodysplasia-derived anemia after transcatheter aortic valve implantation 

JC
R
t
S
G
A
C
R
I
S
t
h
W
m
m
s
w
(
f
1
dournal of Cardiology Cases (2012) 5, e128—e131
Available  online  at  www.sciencedirect.com
j ourna l ho me  p age: www.elsev ier .com/ locate / j ccase
ase Report
eversal  of  angiodysplasia-derived  anemia  after
ranscatheter  aortic  valve  implantation
tylianos  A.  Pyxaras  (MD) ∗,  Sara  Santangelo  (MD),  Andrea  Perkan  (MD),
iancarlo  Vitrella  (MD),  Serena  Rakar  (MD),  Erica  Della  Grazia  (MD),
lessandro  Salvi  (MD),  Gianfranco  Sinagra  (MD)
ardiovascular  Department,  University  Hospital  of  Trieste,  Via  Valdoni  7,  34149  Trieste,  Italy
eceived  19  August  2011;  received  in  revised  form  20  September  2011;  accepted  6  October  2011
KEYWORDS
Transcatheter  aortic
valve  implantation;
Summary  Aortic  valve  stenosis  associated  with  angiodysplasia  (Heyde’s  syndrome)  and  conse-
quent anemia  had  previously  been  reported  to  beneﬁt  from  surgical  aortic  valve  replacement.
In this  clinical  case  an  89-year-old  patient  with  chronic  angiodysplasia-derived  anemia,  char-Angiodysplasia acterized  by  acute  phases  of  active  gastrointestinal  bleeding  experienced  a  normalization  of
hemoglobin  values  after  a  trans-catheter  aortic  valve  implantation  (TAVI)  of  a  self-expandable
aortic valve  prosthesis  (CoreValve,  Medtronic  Inc.,  Minneapolis,  MN,  USA).  This  is  the  ﬁrst,  to
our knowledge,  reported  clinical  case  of  remission  of  angiodysplasia-derived  anemia  after  TAVI.
f  Car
r
a
o
c
i
C© 2011  Japanese  College  o
ntroduction
evere  aortic  valve  stenosis  can  be  complicated  by  gas-
rointestinal  angiodysplasia  (Heyde’s  syndrome)  [1],  a
emorrhagic  syndrome  associated  with  acquired  type  2A  von
illebrand  disease,  characterized  by  the  loss  of  the  largest
ultimers  of  von  Willebrand  factor  (vWF)  [2—5]. vWF  abnor-
alities  were  previously  found  to  be  directly  related  to  the
everity  of  aortic  stenosis  [6],  while  clinical  improvements
ere  reported  after  surgical  valve  replacement  [7,8].
Most  recently,  transcatheter  aortic  valve  implantation
TAVI)  has  emerged  as  an  alternative  to  surgical  aortic  valve
∗ Corresponding author. Tel.: +39 040 399 4477;
ax: +39 040 399 4153.
E-mail address: steliospyxaras@yahoo.it (S.A. Pyxaras).
A
a
i
m
h
T
a
w
878-5409/$ — see front matter © 2011 Japanese College of Cardiology.
oi:10.1016/j.jccase.2011.10.002diology.  Published  by  Elsevier  Ltd.  All  rights  reserved.
eplacement  (SAVR)  for  patients  with  symptomatic  severe
ortic  stenosis  considered  to  be  at  very  high  or  prohibitive
perative  risk  [9—14]. Currently,  there  are  no  reported
ases  of  remission  of  gastrointestinal  angiodysplasia  follow-
ng  TAVI.
ase description
n  89-year-old  female  patient  with  hypertension,  peripheral
rterial  vascular  disease,  and  previous  episodes  of  transient
schemic  attack  was  admitted  to  our  Cardiovascular  Depart-
ent  with  acute  pulmonary  edema.
During  the  previous  three  years  she  underwent  repeatedospital  admissions  for  syncope  and  exertional  angina.
ransthoracic  Doppler  echocardiography  showed  a  severe
ortic  stenosis.  SAVR  was  proposed  to  the  patient,
hich  she  refused  and  was  discharged  on  optimal  drug
 Published by Elsevier Ltd. All rights reserved.
Reversal  of  angiodysplasia-derived  anemia  after  transcatheter  aortic  valve  implantation  e129
Figure  1  Endoscopic  view  of  gastric  angiodysplasia,  hemor-
Figure  2  Implanted  CoreValve  (end  of  the  procedure  of  the
t
p
m
t
w
S
i
c
p
(
l
a
t
t
p
a
u
a
(
t
t
t
c
w
a
3
a
h
a
t
arhagic lesion.
treatment.  Moreover,  during  the  previous  year  she  was
repeatedly  admitted  to  the  Internal  Medicine  Depart-
ment  for  ematemesis  and  melena;  the  patient  underwent
an  esophagogastroduodenoscopy  during  acute  anemization
[hemoglobin  (Hb)  8.6  g/dl]  that  demonstrated  active  bleed-
ing  lesions  compatible  with  gastrointestinal  angiodysplasia
(Fig.  1).  She  underwent  a  colonoscopy,  which  also  showed
intestinal  angiodysplasic  lesions.  All  other  alternative  causes
of  bleeding  were  excluded.  The  patient  was  treated  with
perendoscopic  plasma  coagulation,  blood  transfusions,  and
proton-pump  inhibitors  and  the  Hb  levels  were  stabilized  at
10  g/dl  approximately.  The  blood  count  was  consistent  with
acute  anemization  superimposed  on  chronic  sideropenic
anemia.  The  platelet  count  was  normal  in  all  the  consec-
utive  determinations.  Considering  the  former  diagnosis  of
severe  aortic  stenosis,  a  Heyde’s  syndrome  diagnosis  was
made.
At  admission  in  our  department,  the  patient  had  elec-
trocardiographic  evidence  of  anteriorlateral  subepicardial
ischemia,  but  troponin  I  levels  were  normal.  Diffuse  antero-
lateral  ST  segment  alterations  were  observed  at  the
telemetric  monitoring  of  the  patient  during  angina.  Other
laboratory  exams  documented  a  Hb  value  of  11.1  g/dl,  a
platelet  count  of  166,000/mm3,  and  evidence  of  sideropenic
anemia.  B-natriuretic  peptide  was  657  pg/ml.  The  transtho-
racic  Doppler  echocardiographic  evaluation  demonstrated
a  normal  left  ventricular  (LV)  systolic  function  (LV  ejection
fraction  60%  —  Simpson  biplane  method),  a  mild  and  homo-
geneous  LV  hypertrophy  and  conﬁrmed  the  severity  of  the
aortic  stenosis  (aortic  valve  area  measured  by  continuity
equation  0.56  cm2;  mean  and  maximum  pressure  gradient
44  and  73  mmHg,  respectively).
The  patient  was  evaluated  by  our  Department  Heart  Team
(heart  surgeon—interventionist—clinical  cardiologist).  Logis-
tic  Euroscore  and  Society  of  Thoracic  Surgeons  score  were
32.2%  and  10.3%,  respectively.  Considering  the  patient’s
will  and  the  relatively  high  surgical  risk,  a  TAVI  procedure
was  proposed  and  accepted  by  the  patient.  Pre-TAVI  angio-
graphic  coronary  evaluation  demonstrated  a  proximal  and
medial  left  anterior  descending  (LAD)  artery  disease  (steno-
sis  of  60%  and  90%,  respectively),  an  anatomically  critical
h
m
sranscatheter  aortic  valve  implantation).
roximal  circumﬂex  stenosis  (80%)  and  a  70%  stenosis  of  the
edial  and  distal  segment  of  the  right  coronary  artery.
The  patient  had  no  echocardiographic  evidence  of  sys-
olic  dysfunction  and  also  kinetical  alteration  of  segmental
all  movement  were  never  observed.  Diffuse  anterolateral
T  segment  alteration  was  observed  at  the  telemetric  mon-
toring  of  the  patient  during  angina;  therefore  we  chose  a
onservative  approach  by  treating  only  the  LAD.
A  percutaneous  transcatheter  coronary  angioplasty  was
erformed  on  medial  LAD  with  bare  metal  stent  implantation
Medtronic  Driver  3  mm  ×  15  mm,  Medtronic  Inc.,  Minneapo-
is,  MN,  USA).  An  angiography  of  the  iliac  and  femoral
rteries  was  performed  after  the  end  of  the  interven-
ional  procedure,  showing  absence  of  critical  stenosis.  A
ransesophageal  bidimensional  echocardiography  was  also
erformed,  which  measured  an  aortic  annulus  of  23  mm.
A  transfemoral  approach  was  decided  on  the  basis  of  the
ngiographic  and  echocardiographic  ﬁndings.  The  patient
nderwent  balloon  aortic  valvuloplasty  and  transcatheter
ortic  valve  implantation  with  CoreValve  n.26  (Medtronic)
Fig.  2).
The  procedure  was  complicated  by  the  occlusion  of
he  left  common  femoral  artery,  which  was  successfully
reated  with  percutaneous  angioplasty  and  stent  implanta-
ion.  The  immediate  post-TAVI  echocardiography  showed  a
omplete  remission  of  the  trans-aortic  pressure  gradient,
ith  moderate  aortic  regurgitation.  The  patient  remained
symptomatic  during  the  following  days  and  was  discharged
 days  after  the  procedure.
During  follow  up,  the  patient  was  asymptomatic  for
ngina.  The  clinical  evaluation  did  not  reveal  signs  of
eart  failure.  The  aortic  regurgitation  remained  moderate
t  echocardiography  six  months  after  TAVI.  Serial  labora-
ory  evaluations  documented  a  normalization  of  the  Hb
t  13.3  g/dl,  no  further  acute  anemization,  and  normal
emosiderin  and  transferrin  levels.  Platelet  count  was  nor-
al  in  all  the  determinations  and  the  patient  did  not  further
uffer  from  gastrointestinal  bleeding.
e130  S.A.  Pyxaras  et  al.
Figure  3  Hemoglobin  trend,  treatment,  and  procedures.
The patient  was  on  chronic  treatment  with  aspirin,  and  also
treated  with  clopidogrel  for  one  month  after  angioplasty  with
bare metal  stent,  and  TAVI.  The  platelet  count  was  stable,
2
a
D
H
b
p
h
[
A
s
r
W
c
b
b
c
p
p
a
d
b
f
f
w
b
o
d
a
i
a
t
f
e
v
l
l
m
t
F
T
i
r
g
a
a
(
R50,000  ±  20,000/mm3.  Hb,  hemoglobin;  TAVI,  transcatheter
ortic  valve  implantation.
iscussion
eyde’s  syndrome  was  previously  deﬁned  as  the  association
etween  aortic  stenosis  and  gastrointestinal  angiodys-
lasia  [1].  Previous  studies  veriﬁed  this  association  and
ypothesized  a  causative  mechanism  implying  the  vWF
6].  Highest-molecular  multimers  of  vWF  are  cleaved  by
DAMTS-13,  a  metalloprotease,  in  the  presence  of  elevated
hear  stress,  such  as  in  aortic  stenosis  [15]. This  interaction
esults  in  the  phenotypic  expression  known  as  acquired  von
illebrand  syndrome  type  2A,  which  is  frequently  compli-
ated  by  angiodysplasic  gastrointestinal  lesions  that  could
leed  and  lead  to  severe  and  difﬁcult-to-treat  anemia.
Aortic  stenosis  and  anemia  could  determine  a  clinical
urden  potentially  characterized  by  recurrent  angina,  syn-
ope,  and  heart  failure.  These  symptoms  and  signs  are
roportionally  related  to  the  severity  of  each  of  the  two
athological  conditions  and  their  cumulative  presence  may
ct  incrementally  and  confound  diagnosis  and  treatment.
King  et  al.  [8]  reported  14  patients  with  Heyde’s  syn-
rome,  all  of  whom  had  abrupt  cessation  of  gastrointestinal
leeding  post-SAVR,  including  11  patients  needing  war-
arin  anticoagulation  for  their  mechanical  prosthesis;  at
ollow-up,  which  ranged  from  8  to  12  years,  only  1  patient
ho  underwent  aortic  valve  replacement  had  recurrent
leeding  secondary  to  excessive  anticoagulation.  More-
ver,  some  case  reports  conﬁrm  the  efﬁcacy  of  SAVR  on
etermining  the  remission  of  Heyde’s  syndrome’s  related
nemia  [7,16,17].This,  to  our  knowledge,  is  the  ﬁrst  case
n  the  literature  with  a  documented  remission  of  the
ngiodysplasia-derived  anemia  after  TAVI.  The  post-TAVI  aor-
ic  regurgitation  was  moderate  and  remained  stable  during
ollow  up.  The  post-procedural  normalization  of  the  Hb  lev-
ls  along  with  not  particularly  elevated  aortic  regurgitation
elocity  measurements  (max  2.4  m/s),  suggest  relatively
ow  levels  of  residual  shear  stress.We  acknowledge  the
imitation  that  no  evidence  of  improvement  in  the  high
olecular  weight  component  of  vWF  is  available,  along  with
he  fact  that  it  is  impossible  to  be  absolutely  certain  if  the
[igure  4  Mean  cell  volume  trend.  MCV,  mean  cell  volume;
AVI, transcatheter  aortic  valve  implantation.
mprovement  in  gastrointestinal  bleeding  and  anemia  was
elated  to  the  AVR,  natural  history,  or  to  the  other  therapies
iven  prior  to  surgery  (e.g.  endoscopic  plasma  coagulation),
lthough  the  temporal  relationship  between  TAVI  and  Hb
nd  mean  cell  volume  (MCV)  levels  suggests  this  hypothesis
Figs.  3  and  4).
eferences
[1] Heyde EC. Gastrointestinal bleeding in aortic stenosis. N Engl
J Med 1958;259:196.
[2] Warkentin TE, Moore JC, Morgan DG. Aortic stenosis and
bleeding gastrointestinal angiodysplasia: is acquired von Wille-
brand’s disease the link? Lancet 1992;340:35—7.
[3] Gill JC, Wilson AD, Endres-Brooks J, Montgomery RR. Loss
of the largest von Willebrand factor multimers from the
plasma of patients with congenital cardiac defects. Blood
1986;67:758—61.
[4] Veyradier A, Balian A, Wolf M, Giraud V, Montembault S, Obert
B, Dagher I, Chaput JC, Meyer D, Naveau S. Abnormal von Wille-
brand factor in bleeding angiodysplasias of the digestive tract.
Gastroenterology 2001;120:346—53.
[5] Federici AB, Rand JH, Bucciarelli P, Budde U, van Genderen PJ,
Mohri H, Meyer D, Rodeghiero F, Sadler JE. Subcommittee on
von Willebrand factor acquired von Willebrand syndrome: data
from an international registry. Thromb Haemost 2000;84:345—9
[Erratum, Thromb Haemost 2000;84:739].
[6] Vincentelli A, Susen S, Le Tourneau T, Six I, Fabre O, Juthier F,
Bauters A, Decoene C, Goudemand J, Prat A, Jude B. Acquired
von Willebrand syndrome in aortic stenosis. N Engl J Med
2003;349:343—9.
[7] Morishima A, Marui A, Shimamoto T, Saji Y, Tambara K, Nishina
T, Komeda M. Successful aortic valve replacement for Heyde
syndrome with conﬁrmed hematologic recovery. Ann Thorac
Surg 2007;83:287—8.
[8] King RM, Pluth JR, Guiliani ER. The association of unexplained
gastrointestinal bleeding with calciﬁc aortic stenosis. Ann Tho-
rac Surg 1987;44:514—6.
[9] Cribier A, Eltchaninoff H, Tron C, Bauer F, Agatiello C, Nercolini
D, Tapiero S, Litzler PY, Bessou JP, Babaliaros V. Treatment of
calciﬁc aortic stenosis with the percutaneous heart valve mid-
term follow-up from the initial feasibility studies: the French
experience. J Am Coll Cardiol 2006;47:1214—23.
10] Webb JG, Pasupati S, Humphries K, Thompson C, Altwegg L,
Moss R, Sinhal A, Carere RG, Munt B, Ricci D, Ye J, Che-
ung A, Lichtenstein SV. Percutaneous transarterial aortic valve
er  ao
[
[
[Reversal  of  angiodysplasia-derived  anemia  after  transcathet
replacement in selected high-risk patients with aortic stenosis.
Circulation 2007;116:755—63.
[11] Ye J, Cheung A, Lichtenstein SV, Altwegg LA, Wong DR, Carere
RG, Thompson CR, Moss RR, Munt B, Pasupati S, Boone RH,
Masson JB, Al Ali A, Webb JG. Transapical transcatheter aortic
valve implantation: 1-year outcome in 26 patients. J Thorac
Cardiovasc Surg 2009;137:167—73.
[12] Walther T, Simon P, Dewey T, Wimmer-Greinecker G, Falk V,
Kasimir MT, Doss M, Borger MA, Schuler G, Glogar D, Fehske
W, Wolner E, Mohr FW, Mack M. Transapical minimally invasive
aortic valve implantation multicenter experience. Circulation
2007;116:I240—5.
[13] Svensson LG, Dewey T, Kapadia S, Roselli EE, Stewart A,
Williams M, Anderson WN, Brown D, Leon M, Lytle B, Moses
J, Mack M, Tuzcu M, Smith C. United States feasibility study
of transcatheter insertion of a stented aortic valve by the left
ventricular apex. Ann Thorac Surg 2008;86:46—55.
[rtic  valve  implantation  e131
14] Grube E, Schuler G, Buellesfeld L, Gerckens U, Linke A,
Wenaweser P, Sauren B, Mohr FW, Walther T, Zickmann
B, Iversen S, Felderhoff T, Cartier R, Bonan R. Percuta-
neous aortic valve replacement for severe aortic stenosis
in high-risk patients using the second- and current third-
generation self-expanding CoreValve prosthesis. J Am Coll
Cardiol 2007;50:69—76.
15] Tsai HM. Physiologic cleavage of von Willebrand factor by a
plasma protease is dependent on its conformation and requires
calcium ion. Blood 1996;87:4235—44.
16] Warkentin TE, Moore JC, Morgan DG. Gastrointestinal
angiodysplasia and aortic stenosis. N Engl J Med 2002;347:
858—9.17] Anderson RP, McGrath K, Street A. Reversal of aortic
stenosis, bleeding gastrointestinal angiodysplasia, and von
Willebrand syndrome by aortic valve replacement. Lancet
1996;347:689—90.


Pyxaras, Stylianos A

SANTANGELO, SARA

PERKAN, ANDREA

VITRELLA, GIANCARLO

RAKAR, SERENA

SALVI, ALESSANDRO

SINAGRA, GIANFRANCO

Archivio istituzionale della ricerca - Università di Trieste

Reversal of angiodysplasia-derived anemia after transcatheter aortic valve implantation

file:///data/remote/core/dit/data/elsevier/pdf/b0f/aHR0cDovL2FwaS5lbHNldmllci5jb20vY29udGVudC9hcnRpY2xlL3BpaS9zMTg3ODU0MDkxMTAwMDc5eA==.pdf

Reversal of angiodysplasia-derived anemia after transcatheter aortic valve implantation

Abstract

Similar works

Full text

Available Versions

Elsevier - Publisher Connector

Elsevier - Publisher Connector

Archivio istituzionale della ricerca - Università di Trieste