Abstract
Purpose: There is growing evidence that paradoxical embolism through patent foramen ovale (PFO) is a cause for cryptogenic stroke. However, it is still unclear why the foramen ovale fails to close after birth. We studied whether the 3D relations between the atrial septum (AS) and the inferior vena cava (IVC) are associated with PFO. Methods: We recruited 30 patients (18–49 years) with a first-ever cryptogenic stroke and 30 age- and sex-matched stroke-free controls. Using cardiac magnetic resonance, an approach to evaluate the 3D relations between the AS and the IVC was developed. The presence of interatrial right-to-left shunt was evaluated with transesophageal echocardiography (TEE) in patients and transcranial Doppler in controls. Results: Of 30 patients, 29 underwent successful TEE, of which 12 (41%) had a shunt. Patients with a shunt had a greater mean 3D angle (γ) between the atrial septal plane and the vector from the orifice of the IVC to the middle of the AS compared with patients without a shunt (45 ± 9° vs. 36 ± 8°, p = 0.017). Of 30 controls, 12 (40%) had a shunt and a greater mean γ compared with controls without a shunt (47 ± 8° vs. 37 ± 10°, p = 0.007). In a pooled analysis, 24 (41%) of 59 subjects with a shunt had a mean γ of 46 ± 9° compared with subjects without a shunt of 37 ± 9° (p < 0.001). Conclusions: More perpendicular orientation of the atrial septal plane to the orifice of the IVC is associated with PFO, possibly by directing the IVC flow to PFO.
References
1.
Yesilot Barlas
N
, Putaala
J
, Waje-Andreassen
U
, Vassilopoulou
S
, Nardi
K
, Odier
C
, Etiology of first-ever ischaemic stroke in European young adults: the 15 cities young stroke study
. Eur J Neurol
. 2013
;20
(11
):1431
–9
.2.
Abdelghani
M
, El-Shedoudy
SAO
, Nassif
M
, Bouma
BJ
, de Winter
RJ
. Management of patients with patent foramen ovale and cryptogenic stroke: an update
. Cardiology
. 2019
;143
(1
):62
–72
. .3.
Hagen
PT
, Scholz
DG
, Edwards
WD
. Incidence and size of patent foramen ovale during the first 10 decades of life: an autopsy study of 965 normal hearts
. Mayo Clin Proc
. 1984
;59
(1
):17
–20
. .4.
Hara
H
, Virmani
R
, Ladich
E
, Mackey-Bojack
S
, Titus
J
, Reisman
M
, Patent foramen ovale: current pathology, pathophysiology, and clinical status
. J Am Coll Cardiol
. 2005
;46
(9
):1768
–76
.5.
Koutroulou
I
, Tsivgoulis
G
, Tsalikakis
D
, Karacostas
D
, Grigoriadis
N
, Karapanayiotides
T
. Epidemiology of patent foramen ovale in general population and in stroke patients: a narrative review
. Front Neurol
. 2020
;11
:281
. .6.
Clark
EB
. Pathogenetic mechanisms of congenital cardiovascular malformations revisited
. Semin Perinatol
. 1996
;20
(6
):465
–72
. .7.
Elliott
GC
, Gurtu
R
, McCollum
C
, Newman
WG
, Wang
T
. Foramen ovale closure is a process of endothelial-to-mesenchymal transition leading to fibrosis
. PLoS One
. 2014
;9
(9
):e107175
. .8.
Schuchlenz
HW
, Saurer
G
, Weihs
W
, Rehak
P
. Persisting eustachian valve in adults: relation to patent foramen ovale and cerebrovascular events
. J Am Soc Echocardiogr
. 2004
;17
(3
):231
–3
. .9.
Parikh
JD
, Kakarla
J
, Keavney
B
, O’Sullivan
JJ
, Ford
GA
, Blamire
AM
, 4D flow MRI assessment of right atrial flow patterns in the normal heart - influence of caval vein arrangement and implications for the patent foramen ovale
. PLoS One
. 2017
;12
(3
):e0173046
.10.
Salim
MA
, DiSessa
TG
, Arheart
KL
, Alpert
BS
. Contribution of superior vena caval flow to total cardiac output in children. A doppler echocardiographic study
. Circulation
. 1995
;92
(7
):1860
–5
. .11.
Mohiaddin
RH
, Wann
SL
, Underwood
R
, Firmin
DN
, Rees
S
, Longmore
DB
. Vena caval flow: assessment with cine MR velocity mapping
. Radiology
. 1990
;177
(2
):537
–41
. .12.
Ganz
W
, Tamura
K
, Marcus
HS
, Donoso
R
, Yoshida
S
, Swan
HJ
. Measurement of coronary sinus blood flow by continuous thermodilution in man
. Circulation
. 1971
;44
(2
):181
–95
. .13.
Putaala
J
, Martinez-Majander
N
, Saeed
S
, Yesilot
N
, Jakala
P
, Nerg
O
, Searching for explanations for cryptogenic stroke in the young: revealing the triggers, causes, and outcome (SECRETO): rationale and design
. Eur Stroke J
. 2017
;2
(2
):116
–25
.14.
Saeed
S
, Gerdts
E
, Waje-Andreassen
U
, Sinisalo
J
, Putaala
J
. Searching for explanations for cryptogenic stroke in the young: revealing the etiology, triggers, and outcome (SECRETO): echocardiography performance protocol
. Echo Res Pract
. 2019
;6
(3
):53
–61
. .15.
Schulz-Menger
J
, Bluemke
DA
, Bremerich
J
, Flamm
SD
, Fogel
MA
, Friedrich
MG
, Standardized image interpretation and post processing in cardiovascular magnetic resonance: society for cardiovascular magnetic resonance (SCMR) board of trustees task force on standardized post processing
. J Cardiovasc Magn Reson
. 2013
;15
:35
.16.
Maceira
AM
, Cosin-Sales
J
, Prasad
SK
, Pennell
DJ
. Characterization of left and right atrial function in healthy volunteers by cardiovascular magnetic resonance
. J Cardiovasc Magn Reson
. 2016
;18
(1
):64
–8
. .17.
Heiberg
E
, Sjögren
J
, Ugander
M
, Carlsson
M
, Engblom
H
, Arheden
H
. Design and validation of segment: freely available software for cardiovascular image analysis
. BMC Med Imaging
. 2010
;10
:1
. .18.
Eaton
J
, Baterman
D
, Hauberg
S
, Wehbring
R
. GNU Octave version 4.2.2 manual: a high-level interactive language for numerical computations
: GNU Octave
; 2018
. Available at: https://www.gnu.org/software/octave/doc/v4.2.2/.19.
Mosteller
RD
. Simplified calculation of body-surface area
. N Engl J Med
. 1987
;317
:1098
. .20.
Silvestry
FE
, Cohen
MS
, Armsby
LB
, Burkule
NJ
, Fleishman
CE
, Hijazi
ZM
, Guidelines for the echocardiographic assessment of atrial septal defect and patent foramen ovale: from the american society of echocardiography and society for cardiac angiography and interventions
. J Am Soc Echocardiogr
. 2015
;28
(8
):910
–58
.21.
Tsivgoulis
G
, Stamboulis
E
, Sharma
VK
, Heliopoulos
I
, Voumvourakis
K
, Teoh
HL
, Safety of transcranial Doppler ‘bubble study’ for identification of right to left shunts: an international multicentre study
. J Neurol Neurosurg Psychiatry
. 2011
;82
(11
):1206
–8
.22.
Bland
JM
, Altman
DG
. Measuring agreement in method comparison studies
. Stat Methods Med Res
. 1999
;8
(2
):135
–60
. .23.
Zanchetta
M
, Rigatelli
G
, Ho
SY
. A mystery featuring right-to-left shunting despite normal intracardiac pressure
. Chest
. 2005
;128
(2
):998
–1002
. .24.
Bertaux
G
, Eicher
JC
, Petit
A
, Dobsák
P
, Wolf
JE
. Anotomic interaction between the aortic root and the atrial septum: a prospective echocardiographic study
. J Am Soc Echocardiogr
. 2007
;20
(4
):409
–14
. .25.
Laybourn
KA
, Martin
ET
, Cooper
RA
, Holman
WL
. Platypnea and orthodeoxia: shunting associated with an aortic aneurysm
. J Thorac Cardiovasc Surg
. 1997
;113
(5
):955
–6
. .26.
Smeenk
FW
, Postmus
PE
. Interatrial right-to-left shunting developing after pulmonary resection in the absence of elevated right-sided heart pressures. Review of the literature
. Chest
. 1993
;103
(2
):528
–31
. .27.
Klepper
JI
, Seifert
F
, Lawson
WE
, Mallis
GI
, Dervan
JP
, Smaldone
G
, Intracardiac right-to-left shunting following cardiac surgery
. Am Heart J
. 1988
;116
(1 Pt 1
):189
–92
.28.
Teupe
CH
, Groenefeld
GC
. Platypnea-orthodeoxia due to osteoporosis and severe kyphosis: a rare cause for dyspnea and hypoxemia
. Heart Int
. 2011
;6
(2
):e13
. .29.
Cabanes
L
, Mas
JL
, Cohen
A
, Amarenco
P
, Cabanes
PA
, Oubary
P
, Atrial septal aneurysm and patent foramen ovale as risk factors for cryptogenic stroke in patients less than 55 years of age. A study using transesophageal echocardiography
. Stroke
. 1993
;24
(12
):1865
–73
.30.
De Castro
S
, Cartoni
D
, Fiorelli
M
, Rasura
M
, Anzini
A
, Zanette
EM
, Morphological and functional characteristics of patent foramen ovale and their embolic implications
. Stroke
. 2000
;31
(10
):2407
–13
.31.
Langholz
D
, Louie
EK
, Konstadt
SN
, Rao
TL
, Scanlon
PJ
. Transesophageal echocardiographic demonstration of distinct mechanisms for right to left shunting across a patent foramen ovale in the absence of pulmonary hypertension
. J Am Coll Cardiol
. 1991
;18
(4
):1112
–7
. .32.
Kustner
T
, Fuin
N
, Hammernik
K
, Bustin
A
, Qi
H
, Hajhosseiny
R
, CINENet: deep learning-based 3D cardiac CINE MRI reconstruction with multi-coil complex-valued 4D spatio-temporal convolutions
. Sci Rep
. 2020
;10
(1
):13710
–8
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