The Anatomical Significance of the Patent Foramen Ovale by Real-time 3D
TEE in Cryptogenic Stroke and Migraine
Li Wang1, Haibo Sun3, Han Shen#2
1 Department of Cardiology, The First Affiliated Hospital of Soochow
University, Suzhou, China.
2 Department of Cardiovascular Surgery, The First Affiliated Hospital of
Soochow University, Suzhou, China.
3. Department of Ultrasound, HYGEIA Su Zhou Yong Ding Hospital.
#2.Correspondence to: Han Shen, MD, Department of Cardiovascular
Surgery, The First Affiliated Hospital of Soochow University, 899
Pinghai Road, Gusu District, Suzhou, China. Email:
shenhangongyong@126.com
Abstract:
Background:
The transesophageal echocardiogram (TEE) is the standard imaging
modality for confirming the presence or absence of patent foramen ovale.
PFO is a flap valve depending on the pressure change between the left
and right atrium, which can help determine whether to open. 3D-TEE was
shown to optimize the visualization of PFO. There is a causal
association between PFO and unexplained stroke. It seems that 3D-TEE can
present a high-risk PFO morphological feature, which seems to show more
than just being easier to open.
Methods: In total 134 consecutive patients with cryptogenic stroke or
migraine who had suspected PFO and underwent c-TCD, TTE, and c-TEE were
included in this study. TEE confirmed the PFO. The right-to-left shunt
(RLS) grade of PFO at rest and abdominal compression Valsalva maneuver
was detected by c-TEE.
Results:
The long diameter of FO (1.74±0.3 vs. 1.60±0.4, P=0.039), the short
diameter of FO (1.12±0.3 vs. 1.00±0.3, P=0.036), perimeter of FO
(4.62±0.7 vs. 4.22±1.0, P=0.026) and area (1.80±0.8 vs. 1.35±0.8,
P=0.05) of the FO were significantly larger in the larger RLS group. In
group of CS, a larger proportion of Eustachian valve or a Chiari’s
network (14.3% vs. 3.5%, P=0.036), a larger proportion of in the left
funnelform (55.1% vs. 16.3% P<0.001), a longer length of the
PFO tunnel (13.4±4.4
vs. 7.8±2.5, P<0.001), a lower IVC-PFO angle (16.4±3.4 vs.
20.3±7.7, P=0.001), a higher proportion of LA multiple exits of the
tunnel (46.9% vs. 14.3%, P<0.001). Multivariate regression
analysis showed that male gender (HR: 4.026, 95% CI:
0.883~18.361, P=0.072), age (HR: 1.076, 95% CI:
1.002~1.155, P=0.045), the left funnelform (HR:7.299, 95%
CI: 1.585~33.618, P=0.011), a longer length of the PFO
tunnel tunnel (HR: 1.843, 95% CI: 1.404~2.418,
P<0.001) and multiple exits of the tunnel of LA (HR: 8.544,
95%CI: 1.595~45.754, P=0.012) increased the risk of
cerebral infarction. The cut-off value calculated by ROC for the
diagnosis of high-risk PFO was that the length of the PFO tunnel was 12
mm and Left funnelform combined with multiple exits of left atrial
(sensitivity was 92%, specificity was 90%). The area under the curve
of combine index VS PoPE score (0.932 VS 0.736) relative to the RoPE
score was statistically significant.
Conclusions:
A larger oval fossa can be more easily activated and cause a large
right-to-left shunt. The left funnelform, a longer length of the PFO
tunnel, and multiple exits of the tunnel of LA increase the risk of CS
in anatomical of PFO respect. TEE can precisely visualize the specific
morphological characteristics of PFO. These features on TEE have a
strong correlation with CS.
Keywords: Cryptogenic stroke, Migraine contrast-TEE, Patent foramen
ovale, Real-time 3D TEE
Introduction
Patent foramen ovale (PFO) is present in approximately 25% to 30% of
the general population [1]. PFO can be found in 27.3% of all adults
and is associated with many pathological conditions, such as ischemic
stroke, paradoxical embolism, embolic stroke of undetermined source
(ESUS), migraine, cerebrovascular injury, non-cerebral paradoxical
systemic embolic events, decompression illness, and obstructive sleep
apneas [2, 3] [4]. PFO is a potential space or separation
between the septum primum and septum secundum in the anterosuperior
portion of the atrial septum [5]. The foramen remains functionally
closed as long as the LA pressure is greater than the RA pressure. In
many cases, a PFO is only functionally patent and has a tunnel-like
appearance, as the septum primum forms a flap valve [6](Figure 1).
Since PFO is a highly dynamic and complex structure, more studies are
needed to confirm the presence of PFO and to rule out pulmonary shunt
via intrapulmonary arteriovenous malformations (AVMs). Three-dimensional
transesophageal echocardiogram (TEE) is the standard imaging technique
for confirming the presence or absence of PFO [7].Previous studies
have shown that the size, length, and width (functional potential) of
PFO play a critical role in the development of migraine and ischemic
stroke. Additionally, the presence of atrial septal aneurysm (ASA),
hypermobile IAS, large RL shunt, Eustachian valve or a Chiari’s network,
and a sharp (≤10◦) angle between the inferior vena cava and the PFO flap
are associated with a high-risk PFO [6, 8-11].
However, previous studies used 2-dimensional imaging of TEE. Most
recently, 3D TEE has been described to improve the visualization of PFO,
its surrounding tissue rims, and surrounding structures. 3D TEE can be
used to guide percutaneous transcatheter closure of PFO [12].Using
3D TEE, this study compared the anatomical and functional
characteristics of PFO between patients with CS and those without CS to
identify high-risk PFO.
Methods:
Study population
In total, 134 consecutive patients with cryptogenic stroke or migraine
who had suspected PFO and underwent c-TCD, TTE and TEE at our
institution from 5.1.2023 to 3.1.2024 were enrolled in this study
(Supplementary Figure). These patients underwent transcatheter closure.
All patients provided written informed consent. The study was approved
by the Ethics Committee of The Affiliated Hospital of Soochow University
(No.235/2024). This study was conducted following the Declaration of
Helsinki (as revised in 2013).
The diagnosis of CS was established when patients exhibited a transient
or enduring neurological deficit and presented evidence of ischemic
lesions on cerebral MRI or CT scans, without an exact explanation of the
etiology. The diagnosis of migraine followed the criteria of the
International Headache Society [13].The classification of
right-to-left shunt (RLS) severity was as follows: the absence of
bubbles was designated as grade 0, the presence of 1-10 bubbles as grade
I or mild, 10-30 bubbles as grade II or moderate, and over 30 bubbles as
grade III or severe [14].
Contrast -TEE:
The saline contrast consisted of 1 mL air, 1 mL blood, and 8 mL saline.
Blood sample was taken using 20-gauge cannulas via the antecubital vein
because of its enhanced contrast appearance [15]. The content was
agitated between two 10-mL syringes connected with a three-way stopcock
and was injected quickly from the anterior cubital vein.
Abdominal compression Valsalva maneuver:
The examiner placed a hand on the patient ’s right upper abdomen. At
this time, the patient was in a state of abdominal relaxation. The
examiner pressed the patient ’s right upper abdominal wall
simultaneously with a spontaneous Valsalva maneuver. And check the
patient ’s abdominal muscle contraction. Next, the agitated saline
contrast was injected during the Valsalva maneuver phase. Abdominal
compression and the Valsalva maneuver were released immediately after
the opacification of the right atrium.
PFO confirmation and relevant measurements:
The presence or absence of PFO was confirmed by TEE and cardiac
catheterization. TEE (Philips 7c with an X8-2t probe) was performed
under local anesthesia. PFO was evaluated at the end of routine
examinations. Images of the interatrial septum were obtained from the
optimal imaging plane displayed by septal membrane visualization,
typically 60 to 90. The excited saline contrast was injected during the
strain phase of the Valsalva maneuver. The Valsalva maneuver was
released immediately after the opacification of the right atrium. If the
left side of the atrial septum was observed, the Valsalva maneuver was
considered effective.
The thickness of the primary septum and the secondary septum of PFO was
measured at a significantly separated perspective (Figure 2). The height
of PFO was regarded as the maximum distance between the primary septum
and the secondary septum, and the tunnel length of PFO was regarded as
the maximum overlap surface between the primary septum and the secondary
septum (Figure 3). Right funnelform shape: the primary septum and
secondary septum at the tunnel exit were not obviously separated. The
primary septum and the secondary septum at the entrance were obviously
separated (Figure 4). The left funnelform was opposite to the right
funnel form (Figure 4). Three-dimensional imaging of TEE. The red arrow
points to the exit of the PFO tunnel, single channel exit (Figure 5A),
more than one channel exit (Figure 5B). Measurement of the fossa oval in
3D-TEE (Figure 6). The presence of PFO was confirmed by actual
visualization of microbubbles passing through the compartment, which was
achieved by the separation between the septum primum and septum secundum
(Figure 7). We measured the angle between IVC and the PFO valve on the
imaging plane, showing the IVC and the atrial septum (Figure 8).
TEE
TEE evaluates atrial septum at a 0 multi-plane angle, in 15 increments.
Color Doppler at a low color Doppler scale can help identify flow
through the PFO and visualize additional defects in the atrial septum.
To capture low-speed blood flow across a small PFO, the color Doppler
scale can be slightly reduced to approximately 35-40 cm/sec.
Starting at 30-50 plane angle, the PFO was visualized adjacent to the
aorta. Rotation of the imaging plane in 15 increments should line the
imaging plane with the pathway or tunnel of the PFO. The length of the
PFO tunnel can be assessed from this point of view. The thickness of the
septum secundum can also be evaluated from this view. With the
visualization of PFO, agitated saline contrast is injected to evaluate
right-to-left shunting.
RoPE score