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\begin{document}

\title{Comparative analysis of the diagnostic value of several methods for the
diagnosis of patent foramen ovale}



\author[1]{Fangfang Liu}%
\author[2]{Qingyu Kong}%
\author[2]{Xiaojun Zhang}%
\author[2]{Yan Li}%
\author[2]{Shimin Liang}%
\author[2]{Shuang Han}%
\author[1]{Guishuang Li}%
\affil[1]{Shandong University Qilu Hospital}%
\affil[2]{Affiliation not available}%


\vspace{-1em}



  
  \date{June 08, 2024}


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\selectlanguage{english}
\begin{abstract}
Objective: The aim of this research was to compare the sensitivity and
positive predictive value of contrast transcranial Doppler (c-TCD),
contrast- transthoracic echocardiography (c-TTE) and contrast-
transesophageal echocardiography (c-TEE), to determine the best method
for diagnosing patent foramen ovale (PFO) and to provide a reference for
the further improvement of clinical practice. Methods: We investigated
161 patients who suffered from migraines, cryptogenic stroke, TIA, and
cerebral infarction of unknown cause. All patients underwent
transcatheter examination, and the results of the right heart
catheterization (RHC) were considered the gold standard for PFO
diagnosis. Results: The present study revealed that c-TTE with the
Valsalva maneuver had a higher sensitivity in detecting PFO related
right-to-left shunt (PFO-RLS), but it might have a higher rate of
misdetection than c-TCD. Conclusion: Patients with suspected PFO can be
examined with c-TCD first, and if positive results are obtained, then
c-TTE and c-TEE should be performed for further confirmation.%
\end{abstract}%



\sloppy


\textbf{Introduction}

In recent years, embolic strokes of undetermined source (ESUS) have
emerged as a new clinical construct for characterizing cryptogenic
stroke (CS). Most patients were young and have no medical history of
hypertension, diabetes or hyperlipidemia, and routine imaging
examination also failed to detect significant vascular
abnormalities\textsuperscript{{[}1{]}}. Currently, patent foramen ovale
(PFO) has been reported to be strongly associated with a number of
diseases, including cryptogenic stroke \textsuperscript{{[}2{]}},
transient ischemic attack (TIA)\textsuperscript{{[}3{]}}, migraine
\textsuperscript{{[}4{]}}, peripheral arterial embolism, and
decompression sickness\textsuperscript{{[}5{]}}.

Foramen ovale is a persistent fetal communication between the right and
left atrium due to incomplete closure of the atrial septum. After birth,
with the interruption of umbilical blood circulation and the
establishment of respiration, the foramen ovale closes functionally, and
complete closure generally occurs 5 to 7 months after birth. If the
foramen ovale is still unclosed in children over 3 years old, PFO can be
diagnosed. If the right atrial pressure is higher than left atrial
pressure (for example, during cough, inspiration, or the Valsalva
maneuver), blockages in the venous~system can flow to the left atrium.
Patent foramen ovale is the cause of 95 \% of paradoxical
embolisms\textsuperscript{{[}5{]}}.

There are three methods for diagnosing PFO: contrast-transcranial
doppler(c-TCD), transthoracic echocardiography (TTE), and
transesophageal echocardiography (TEE). TEE has a major role in the
diagnosis of PFO. The diagnostic sensitivity of PFO related
right-to-left shunt (PFO-RLS) with contrast transcranial Doppler (c-TCD)
is similar to that with TEE. However, c-TCD has a limited ability to
differentiate cardiac from pulmonary RLS. The use of contrast
echocardiography was first reported by Gramiak\textsuperscript{{[}6{]}}.
Currently, contrast transthoracic echocardiography (c-TTE) with the
Valsalva maneuver is extensively used for the detection and
semiquantitative assessment of PFO-RLS\textsuperscript{{[}7{]}}.
However, the diagnostic criteria are not unified. Thus, the aim of this
research was to compare the sensitivity and specificity of each
examination method to determine which is the best method for diagnosing
PFO and to provide a reference for the further improvement of clinical
practice.

\textbf{Materials and Methods}

\emph{Patient Population}

We investigated 161 patients (86 male, 75 female; mean age, 42.0\selectlanguage{ngerman}±15.6
years) admitted to the Departments of Neurology and Cardiology in Qilu
Hospital, Shandong University from August 2018 to July 2019 who suffered
from migraine, cryptogenic stroke, TIA, and cerebral infarction of
unknown cause, including 55 migraine, 56 cryptogenic stroke, 20 cases of
both symptoms, 19 cases of dizziness or syncope, 9 TIA cases, and 2
epilepsy cases. Exclusion~criteria: (1) Cerebral embolism due to any
cause, for example, cardiac cerebral embolism or arteriosclerosis; (2)
Contraindications for antiplatelet or anticoagulant therapy, for
example, due to severe bleeding in the past 3 months, severe
retinopathy, history of intracranial hemorrhage or other intracranial
disease; (3) Obstruction caused by inferior vena cava or pelvic venous
thrombosis, systemic or local infection, septicemia, intracardiac
thrombosis, etc.; (4) Pregnancy; (5) Concurrent
pulmonary~arterial~hypertension or PFO that cannot be closed; (6) Acute
stroke in the past 2 weeks.

The study was approved by the local ethics committee, and all patients
or their relatives provided written informed consent to participate in
this study prior to the examination.

\emph{Saline contrast preparation}

The right anterior elbow vein was selected for the placement of an
indwelling needle. The contrast agent was prepared by mixing it with 3
ml of air, 30 ml of saline solution, and 3-5 ml of the patient's blood
and intensively mixing it back and forth 20 times between two 30-ml
syringes connected by a T-branch pipe.

\emph{c-TCD Examination}

TCD was performed using the Multi-DopX4 Transcranial doppler (DWL
Electronic Systems, Sipplingen, Germany) with a 2MHz probe. Middle
cerebral artery flow was monitored through the temporal bone window at a
depth of 50-65 mm. The study was performed by a neurologist who
specialized in this technique and was blinded to the results of the
echocardiographic study. After value of the the middle cerebral artery
blood flow velocity was obtained, the contrast agent was quickly
injected via the established route of the anterior elbow vein. The
contrast agent was prepared, and right-to-left shunt was diagnosed when
TCD detected microsignals in the middle cerebral artery, in both the
resting state and during performance of the Valsalva maneuver. The
severity of the shunt was quantified as negative (no microsignals), mild
(1-20 microsignals, 1-10 per side), moderate (\selectlanguage{english}[?]20 microsignals, \selectlanguage{english}>10 per
side), or extensive (\selectlanguage{english}>30 microsignals or rain curtain-like signals)
(Figure 1).

\emph{c-TTE and c-TEE Examination}

Contrast- TTE was conducted using a GE Vivid E9 or E95 platform equipped
with a 3.7--5 MHz M5S transducer (Horten, Norway) or a Philips EPIQ7
platform equipped with a 1--5 MHz S5-1 transducer (Philips USA). All
patients were asked to remain still in the left lateral position.
Conventional 2D echocardiography was performed to acquire the standard
apical, parasternal, and subxyphoid four-chamber views. Color flow
Doppler was used to determine whether there was RLS at the foramen ovale
of the interatrial septum. First, with the patient in a resting state,
the contrast agent was mixed and injected as the same manner that was
used for c-TCD. The apical four-chamber view was maintained, and after
microbubbles filled the right atrium, observation continued to determine
whether microbubbles appeared in the left atrium. The operation was then
repeated while the patient performed the Valsalva maneuver. When the
right atrium was filled with microbubbles, the patient was instructed to
immediately perform the Valsalva maneuver. RLS was graded according to
the highest number of microbubbles observed in the left chamber in a
single frame: image-negative (no microbubbles), mild (1-10
microbubbles), moderate (11-30 microbubbles), or extensive (\selectlanguage{english}>30
microbubbles or left chamber opacification) (Figure 2). If microbubbles
appeared in the left atrium within five cardiac cycles after they are
released, RLS was primarily considered to be derived from a PFO. If
microbubbles appeared in the left atrium after more than five cardiac
cycles, RLS was assumed to originate from a pulmonary arteriovenous
malformation.

Contrast- TEE was performed using the same system fitted with a 2-7 MHz
multi-frequency transesophageal probe. To improve the tolerance of the
test, pharyngeal topical anesthesia was administered using tetracaine
hydrochloride gel 15 min before the examination.~The probe was pushed in
30-40 cm, rotated within 45deg--140deg to clearly display ascending aorta
root, the septum primum and the septum secundum, and to observe whether
an opened PFO existed in the two-dimensional view, measured PFO width
and length at the same time. Color Doppler was used to observe whether
there was a shunt across the PFO. Then, with the patient at rest and
performing the Valsalva maneuver, prepared saline contrast agent was
injected according to the procedure described above. To ensure maximal
diagnostic yield, a standard apical four-chamber view was performed with
the administration of contrast agents. The severity of the microbubbles
was quantified as the same way as for c-TTE (Figure 3).

\emph{Right heart catheterization and transcatheter closure}

All patients for whom~RLS was indicated underwent transcatheter
examination, and the results of the right heart catheterization~(RHC)
were regarded as the gold standard for PFO diagnosis. After localized
anesthesia with lidocaine, the femoral vein was punctured with an
intravenous cannula, and then a 6-F sheath was inserted over the
guidewire to reach the foramen ovale at the right atrium; if the
catheter could pass though the foramen ovale to reach the left atrium,
then PFO could be diagnosed. If the sheath failed to pass though the
foramen ovale, then the guidewire was exchanged for a 0.035-inch
hydrophilic wire, and if the hydrophilic wire could pass though the
foramen ovale to reach the left atrium, then PFO can also be diagnosed.
Finally, if the hydrophilic wire failed, we injected intravascular
contrast media though the catheter, and if the contrast media could not
reach the left atrium, PFO could not be diagnosed. If PFO could not be
diagnosed, then pulmonary arteriovenous fistula (PAVF) was excluded
by~pulmonary~angiography (Figure 4).

\emph{Statistical Analysis}

Qualitative variables are presented as percentages and continuous data
and expressed as the mean +- standard deviation. The chi-square test was
used to compare the sensitivity and specificity of the three methods.
A\emph{P} value of \textless{}0.05 indicated statistical significance.
All data were analyzed using SPSS software (version 18.0.1, SPSS Inc.).

\textbf{Results}

\emph{Diagnosis of PFO}

Using the results of the right heart catheterization~(RHC) as the gold
standard for PFO diagnosis, 141 of the 161 patients studied were
diagnosed with PFO, 18 patients could not be diagnosed with PFO, 2
patients were diagnosed with pulmonary arteriovenous malformation, and
the morbidity of PFO was 88.17\% (Table 1).

\emph{Diagnostic value of c-TCD}

Two patients did not accept the c-TCD~examination, right-to-left shunt
was visualized at baseline by c-TCD in 97 patients (70.28\%, 97/138).
Forty-four patients had mild~RLS (31.88\%, 44/138), 22 had moderate~RLS
(15.94\%, 22/138), 31 had extensive~RLS (22.46\%, 31/138). The Valsalva
maneuver was effective in all c-TCD studies, and RLS was identified in
128 patients (92.75\%, 128/138). Thirty-six patients had mild~RLS
(26.09\%, 36/138), 28 had moderate~RLS (20.29\%, 28/138), 64 had
extensive~RLS (46.38\%, 64/138). The difference between the baseline
measurement and measurement during the performance of the Valsalva
maneuver was statistically significant (Table 2).

\emph{Diagnostic value of c-TTE and c-TEE}

Loss of echo was identified in 12 patients (8.51\%, 12/141) by TTE.
There were 3 patients with atrium septal aneurysms and 17 with color
shunt (12.06\%, 17/141). Six patients did not agree to undergo the
c-TTE~examination, TEE bubbles were identified in 81 patients (60.00\%,
81/135) at baseline, including 41 with mild involvement (30.37\%,
41/135), 15 with moderate~involvemen (11.11\%, 15/135), 25 with
extensive~involvemen (18.52\%, 25/135). The Valsalva maneuver was
effective in all c-TTE studies, and RLS was identified 126 patients
(93.33\%, 126/135), 24 patients had mild RLS (17.78\%, 24/135), 35
patients had moderate RLS (25.93\%, 37/135), and 67 patients had
extensive RLS (49.63\%, 67/135). Eight patients did not tolerate TEE
examination, including seven with PFO and one without PFO.
Two-dimensional TEE displayed a slit-like channel \selectlanguage{english}[?]2mm between the
septum primum and the septum secundum in 119 patients (90.15\%,
119/132). Color shunt was identified in 40 patients (30.30\%, 40/132).
Two patients did not undergo c-TEE examination, and TEE bubble was
identified in 69 patients (53.08\%, 69/130) at baseline, 37 patients had
mild results (28.46\%, 37/130), 12 had moderate~results (9.23\%,
12/130), 20 had extensive~results (15.38\%, 20/130). The Valsalva
maneuver was effective in all c-TEE studies, and RLS was identified 113
patients (86.92\%, 113/130), including 32 with mild RLS (24.62\%,
32/130), 15 with moderate~RLS (11.54\%, 15/130), and 66 with
extensive~RLS (50.77\%, 66/130) (Table 2).

\emph{Diagnosis of patients without PFO}

Of the total group of 161 patients, 18 patients could not be diagnosed
with PFO. Among them, 4 (22.22\%, 4/18) patients had positive c-TCD both
at baseline and with the Valsalva maneuver, and 7 (38.89\%, 7/18)
patients had positive results only after the Valsalva maneuver was
performed. Additionally, the c-TTE results for 6 (33.33\%, 6/18)
patients were positive both at baseline and with the Valsalva maneuver,
and 7 (38.89\%, 7/18) patients were positive only after the Valsalva
maneuver was performed. The slit-like channel between the septum primum
and the septum secundum on TEE was identified in 5 (29.41\%, 5/17)
patients, and TEE bubble was identified in 4 (23.53\%, 4/17) patients
both at baseline and with the Valsalva maneuver and in 6 (35.29\%, 6/17)
patients only when the Valsalva maneuver was performed (Table 3).

\emph{Diagnostic value of the different methods}

In total, the sensitivity of c-TCD at baseline was 70.28\% (97/138):
22.46\% (31/138) for extensive cases and 38.40\% (53/138) for moderate
and extensive cases. The sensitivity of c-TCD with the Valsalva maneuver
was 92.75\% (128/138): 46.38\% (64/138) for extensive cases and 66.67\%
(92/138) for moderate and extensive cases. The sensitivity of TTE to
loss of echo was 8.51\% (12/141), and the sensitivity to color shunt was
12.06\% (17/141). The sensitivity of the total c-TTE at baseline was
60.00\% (81/135): 18.52\% (25/135) for extensive cases and 29.63\%
(40/135) for moderate and extensive cases. The sensitivity of the total
c-TTE after the Valsalva maneuver was 93.33\% (126/135): 49.63\%
(67/135) for extensive cases and 75.56\% (102/135) for moderate and
extensive cases. The sensitivity of TEE to the slit-like channel between
the septum primum and the septum secundum was 90.15\% (119/132), the
sensitivity to color shunt was 30.30\% (40/132); the sensitivity of the
total c-TEE at baseline was 53.08\% (69/130): 15.38\% (20/130) for
extensive cases and 24.62\% (32/130) for moderate and extensive cases.
The sensitivity of the c-TEE after the Valsalva maneuver was 86.92\%
(113/130): 50.77\% (66/130) for extensive cases and 62.31\% (81/130)for
moderate and extensive cases.

In the comparison among groups, there were no significant~difference
between the sensitivity of total c-TCD, c-TTE and c-TEE at baseline.
When~pairs of methods were compared, c-TCD was significantly more
sensitive than c-TEE (\emph{P} =0.004). With the Valsalva maneuver, the
sensitivity of the total c-TTE was significantly higher than that of
c-TEE (\emph{P} =0.041). For the within-group comparisons, when bubbles
were extensive in c-TTE examination at baseline, c-TTE had significantly
higher sensitivity than c-TCD (\emph{P} =0.011) and c-TEE (\emph{P}
=0.009).

The positive~predictive value of total c-TCD at baseline was 96.04\%
(97/101): 96.88\% (31/32) for extensive cases and 98.15\% (53/54) for
moderate and extensive cases. With the Valsalva maneuver, the
positive~predictive value of total c-TCD was 92.09\% (128/139): 96.97\%
(64/66) for extensive cases and 96.84\% (92/95) for moderate and
extensive cases. The~false~negative~rate~of total c-TCD was 29.71\%
(41/138) at baseline and 7.25\% (10/138) after the Valsalva maneuver.
The positive~predictive value of c-TTE at baseline was 93.10\% (81/87):
100.00\% (25/25) for extensive cases and 97.56\% (40/41) for moderate
and extensive cases. After the Valsalva maneuver, the
positive~predictive value was 90.65\% (126/139): 97.10\% (67/69) for
extensive cases and 93.58\% (102/109) for moderate and extensive cases.
The~false~negative~rate~of total c-TTE was 40.00\% (54/135) at baseline
and 6.67\% (9/135) after the Valsalva maneuver. The positive~predictive
value of c-TEE at baseline was 94.52\% (69/73): 95.24\% (20/21) for
extensive cases and 96.97\% (32/33) for moderate and extensive cases.
After the Valsalva maneuver, the positive~predictive value was 91.87\%
(113/123): 95.65\% (66/69) for extensive cases and 93.10\% (81/87) for
moderate and extensive cases. The~false~negative~rate~of total c-TEE was
46.92\% (61/130) at baseline and 13.08\% (17/130) after the Valsalva
maneuver (Table 4).

\textbf{Discussion}

Foramen ovale is a persistent fetal communication between the right and
left atrium caused by the incomplete closure of the atrial septum. After
birth, the foramen ovale normally closes, but the morbidity of PFO was
about 30\% \textsuperscript{{[}8{]}}. PFO normally has no obvious
symptoms, it is difficult to hear an associated heart murmur, and there
are~no~abnormalities on electrocardiogram or chest X-ray, therefore, PFO
is easy to overlook. It was recently proposed that for patients who
suffer from migraine headaches, cryptogenic stroke, TIA, and cerebral
infarction that do have acute cerebral infarction or anterior
circulation transient ischemic attack on admission, the possibility of
right-to-left shunt as a cause should be considered.

Our study assessed a large series of patients to identify the presence
of right-to-left shunt. The results demonstrated that c-TTE has better
sensitivity than c-TEE in the diagnosis of PFO both at baseline and with
the Valsalva maneuver; c-TCD performed similarly to c-TEE but maybe
produce more false positives. TEE with contrast showed similar
sensitivity to c-TCD, but had a higher probability of false-negatives,
therefor, c-TCD can be used as an effective supplement for diagnosing
PFO. TEE had the highest sensitivity of the three methods and can be
considered the gold standard. However, the results of c-TCD can only
point out the presence of right-to-left shunt and cannot exclude
extracardiac shunt, so additional measures should be used.

PFO is a three-dimensional structure that changes shape with the cardiac
cycle. Therefore, it is difficult to fully display a PFO using TEE's
two-dimensional technology, and in our results, there were some false
positive cases when we used 2D TEE images (5 cases). The use of
three-dimensional (3D) technology can solve the one-sidedness problem,
but the quality of 3D images can be poor compared to that of 2D images;
sometimes, 3D images were only used for reference
\textsuperscript{{[}9{]}}. In terms of sensitivity, total c-TTE after
the Valsalva maneuver had the highest sensitivity, especially for
extensive cases, we consider that sensitivity increased with increasing
quantities of bubbles in the left heart. Moreover, when we observed
color shunt from the slit-like channel between the septum primum and the
septum secundum on TEE, the positive~predictive value was 100.00\%;
therefor, in our daily clinical~work, the observation color shunt on TEE
is very important. However, the sensitivity of c-TEE is lower than that
of c-TTE after the Valsalva maneuver, based on our observations,
patients sometimes cannot perform the Valsalva maneuver perfectly during
TEE examination, which is the most likely reason for the reduced
sensitivity during the Valsalva maneuver. c-TCD has the greatest value
in diagnosing PFO; almost all the PFO patients had positive results on
the c-TCD examination, but c-TCD can only identify right-to-left shunt
and cannot exclude extracardiac shunt \textsuperscript{{[}10{]}}; c-TTE
and c-TEE can observe the structure of the foramen ovale and are more
convincing. The positive~predictive value can reflect the possible
prevalence rate of patients with positive results. For all the three
methods (c-TCD, c-TTE, c-TEE), when there were a large number~of bubbles
in the left heart, especially in the presence of color shunt from the
slit-like channel, the positive~predictive value was the highest.
Although c-TCD had the highest positive~predictive value, some unsolved
problems remained; for example, some bubbles can get though the
pulmonary circulation and be detected in the cerebral arteries, leading
to a false positive result. On the other hand, c-TTE and c-TEE had more
false negatives, and the rate of misdetection might be higher than that
for c-TCD. Thus, for suspected~patients, c-TCD should be performed
first; if positive results are obtained, then c-TTE and c-TEE should be
used for further confirmation.

The results sometimes were different between the resting state and the
Valsalva maneuver, and the positive rate was higher with the Valsalva
maneuver. In the resting state, RLS could not be observed in all the
patients. In some PFO patients, the foramen ovale is closed in resting
state, only under some particular~situation, for example, cough, cry,
constipation, Valsalva maneuver and so on, that's also the causes of
nervous system symptoms on PFO patients \textsuperscript{{[}11{]}}. Only
under those situations, the right atrial pressure can higher than the
left atrial transiently, the foramen ovale then opened, so we could
observe RLS. Therefore, when no bubbles were present in the left~heart,
the Valsalva maneuver was necessary, but the results were positive with
or without the Valsalva maneuver when bubbles were present in left
heart.

Pulmonary arteriovenous fistula (PAVF) is an abnormal pulmonary vascular
structure that connects a pulmonary artery to a pulmonary vein,
bypassing the normal capillary bed and resulting in an intrapulmonary
right-to-left shunt \textsuperscript{{[}12{]}}. In our study, 2 patients
were diagnosed with PVAF. At first, not much~attention was paid to this
disease; however, because the results of c-TCD, c-TTE and c-TEE were
strongly positive, we performed the transcatheter examination, and
unexpectedly, PFO could not be diagnosed. Pulmonary angiography was then
performed and the results showed that the contrast medium could get to
the pulmonary vein from the pulmonary artery, indicating that we had
previously made a diagnostic mistake. When we reviewed the examinations,
we found that the slit-like channel on TEE was not very clear, and the
bubbles seemed to come from the roof or the entrance of the pulmonary
vein; these findings could help to diagnose PVAF. Therefore,~in
conclusion, we must~consider~the following~points when diagnosing PVAF:
first, the results of c-TCD, c-TTE and c-TEE show a positive and
sometimes strong reaction; second, TEE images cannot account for the
existence of the slit-like channel, or the width of foramen ovale does
not match the quantity of bubbles; third, the bubbles seemed to come
from the roof, the entrance of pulmonary vein, and not from the foramen
ovale.

In conclusion, the present study reveals that c-TTE with the Valsalva
maneuver yields a higher sensitivity in detecting PFO-RLS, but the rate
of misdetection might be higher than that of c-TCD. Therefore,~patients
with suspected PFO, can be examined with c-TCD first, and if positive
results are obtained, then c-TTE and c-TEE should performed for further
confirmation. This procedure may be helpful for the diagnosis of patent
foramen ovale in practice.

\textbf{Funding}

The research reported in this article was supported by the technology
capture project of Shandong Province under award number 2017GGX90104.

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\selectlanguage{english}[7\selectlanguage{english}]E K Kerut,~W T Norfleet,~G D Plotnick,~T D Giles. Patent Foramen
Ovale: A Review of Associated Conditions and the Impact of Physiological
Size. J Am Coll Cardiol.~2001 Sep;38(3):613-23.

\selectlanguage{english}[8\selectlanguage{english}]Shunichi Homma,~Steven R Messe,~Tatjana Rundek,~Yee-Ping
Sun,~Jennifer Franke,~Karina Davidson,~Horst Sievert,~Ralph L
Sacco,~Marco R Di Tullio. Patent Foramen Ovale. Nat Rev Dis Primers.
2016 Jan 21; 2:15086.

\selectlanguage{english}[9\selectlanguage{english}]Miriam Shanks,~Dulka Manawadu,~Isabelle Vonder Muhll,~Khurshid
Khan,~Harald Becher,~Jonathan Choy. Detection of Patent Foramen Ovale by
3D Echocardiography. JACC Cardiovasc Imaging. 2012 Mar;5(3):329-31.

\selectlanguage{english}[10\selectlanguage{english}]Benjamin S Wessler,~David M Kent,~David E Thaler,~Robin
Ruthazer,~Jennifer S Lutz,~Joaquin Serena. The RoPE Score and
Right-to-Left Shunt Severity by Transcranial Doppler in the CODICIA
Study. Cerebrovasc Dis.~2015;40(1-2):52-8.

\selectlanguage{english}[11\selectlanguage{english}]Enfa Zhao,~Yajuan Wei,~Yafei Zhang,~Nina Zhai,~Ping Zhao,~Baomin
Liu. A Comparison of Transthroracic Echocardiograpy and Transcranial
Doppler With Contrast Agent for Detection of Patent Foramen Ovale With
or Without the Valsalva Maneuver Medicine (Baltimore).2015
Oct;94(43):e1937.

\selectlanguage{english}[12\selectlanguage{english}]Ahmed Kamel Abdel Aal,~Joseph Eason,~Sherif Moawad,~Khalid
Mahmoud,~Basant Farouk Hamed,~Moustafa Omar Massoud,~Nathan
Ertel,~Andrew Gunn,~Rachel Oser,~Souheil Saddekni. Persistent Pulmonary
Arteriovenous Malformations: Percutaneous Embolotherapy. Curr Probl
Diagn Radiol. 2018 Nov;47(6):428-436.

Table 1\selectlanguage{english}:Baseline characterization of patients\selectlanguage{english}
\begin{longtable}[]{@{}ll@{}}
\toprule
Items & Cases\tabularnewline
\midrule
\endhead
Total cases & 161\tabularnewline
Male & 86\tabularnewline
Famale & 75\tabularnewline
Age(years) & 42.0\selectlanguage{ngerman}±15.6\tabularnewline
migraine & 55\tabularnewline
cryptogenic stroke (CS) & 56\tabularnewline
migraine +CS & 20\tabularnewline
TIA & 9\tabularnewline
dizzy or syncope & 19\tabularnewline
epilepsy & 2\tabularnewline
Diagnosed of PFO & 141\tabularnewline
\bottomrule
\end{longtable}

Table 2, Results of c-TCD, c-TTE and c-TEE in 141 cases\selectlanguage{english}
\begin{longtable}[]{@{}lllll@{}}
\toprule
\begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
Baseline\strut
\end{minipage} & \begin{minipage}[b]{0.17\columnwidth}\raggedright\strut
Valsalva maneuver\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
c-TCD* n=138\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
c-TCD* n=138\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
41\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
10\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
mild\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
44\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
36\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
moderate\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
22\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
28\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
extensive\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
31\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
64\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
c-TTE\# n=135\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
54\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
9\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
mild\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
mild\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
41\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
24\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
moderate\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
moderate\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
15\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
35\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
extensive\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
extensive\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
25\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
67\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TTE 2D (+), n=141\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TTE 2D (+), n=141\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TTE 2D (+), n=141\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
12\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TTE color (+), n=141\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TTE color (+), n=141\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TTE color (+), n=141\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
17\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
c-TEE\& n=130\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
c-TEE\& n=130\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
negative\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
61\strut
\end{minipage} & \begin{minipage}[t]{0.19\columnwidth}\raggedright\strut
17\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
mild\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
37\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
32\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
moderate\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
12\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
15\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
extensive\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
20\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
66\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TEE 2D (+), n=132\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TEE 2D (+), n=132\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TEE 2D (+), n=132\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
119\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TEE color (+), n=132\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TEE color (+), n=132\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
TEE color (+), n=132\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
40\strut
\end{minipage} & \begin{minipage}[t]{0.17\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

*: Two patients did not accept the c-TCD~examination; \#: Six patients
did not accept the c-TTE~examination; \&:Seven patients did not accept
the TEE~examination.

Table 3 Diagnosis of patients without PFO (18 cases)\selectlanguage{english}
\begin{longtable}[]{@{}llll@{}}
\toprule
& & Baseline & Valsalva maneuver\tabularnewline
\midrule
\endhead
c-TCD & negative & 14 & 7\tabularnewline
& mild & 3 & 8\tabularnewline
& moderate & 0 & 1\tabularnewline
& extensive & 1 & 2\tabularnewline
c-TTE & negative & 12 & 5\tabularnewline
& mild & 5 & 6\tabularnewline
& moderate & 1 & 5\tabularnewline
& extensive & 0 & 2\tabularnewline
TTE 2D (+) & TTE 2D (+) & 0 & 0\tabularnewline
TTE color (+) & TTE color (+) & 0 & 0\tabularnewline
c-TEE* & negative & 13 & 7\tabularnewline
& mild & 3 & 4\tabularnewline
& moderate & 0 & 3\tabularnewline
& extensive & 1 & 3\tabularnewline
TEE 2D (+) & TEE 2D (+) & 5 & 5\tabularnewline
TEE color (+) & TEE color (+) & 0 & 0\tabularnewline
\bottomrule
\end{longtable}

*: One of the 18 patients did not tolerate TEE.

Table 4, Diagnostic value of c-TCD, c-TTE and c-TEE\selectlanguage{english}
\begin{longtable}[]{@{}lllllllll@{}}
\toprule
\begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
Baseline\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
Baseline\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
Valsalva maneuver\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
Valsalva maneuver\strut
\end{minipage} & \begin{minipage}[b]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\midrule
\endhead
\begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
Sensi(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
PPV(\%)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
FNR (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
Sensi (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
PPV (\%)\strut
\end{minipage} & \begin{minipage}[t]{0.11\columnwidth}\raggedright\strut
FNR (\%)\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
c-TCD\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
c-TCD\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Total\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
70.29**\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
96.04\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
29.71\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
92.75\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
92.09\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
7.25\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
extensive\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
22.46\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
96.88\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
56.94\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
46.38\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
96.97\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
13.51\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
moderate + extensive\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
38.40\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
98.15\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
43.62\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
66.67\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
96.84\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
9.80\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
c-TTE\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Total\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Total\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
60.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
93.10\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
40.00\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
93.33*\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
90.65\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
6.67\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
extensive\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
extensive\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
18.52\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
100\#\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
68.35\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
49.63\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
97.10\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
11.84\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
moderate + extensive\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
moderate + extensive\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
29.63\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
97.56\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
57.44\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
75.56\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
93.58\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
8.10\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TTE 2D\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TTE 2D\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TTE 2D\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
8.51\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
100\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TTE color\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TTE color\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TTE color\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
12.06\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
100\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
c-TEE\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
c-TEE\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
Total\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
53.08\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
94.52\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
46.92\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
86.92\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
91.87\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
13.08\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
extensive\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
15.38\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
95.24\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
75.30\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
50.77\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
95.65\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
20.48\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
moderate + extensive\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
24.62\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
96.97\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
65.59\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
62.31\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
93.10\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
17.35\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TEE 2D\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TEE 2D\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TEE 2D\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
90.15\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
94.17\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
9.85\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TEE color\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TEE color\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
TEE color\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
30.30\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
100\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage} & \begin{minipage}[t]{0.08\columnwidth}\raggedright\strut
\strut
\end{minipage}\tabularnewline
\bottomrule
\end{longtable}

PPV: positive predictive value; Sensi: Sensitive; FNR: false negative
rate. **:\emph{P} <0.005(0.004) vs c-TEE; *: \emph{P} <0.05(0.041) vs
c-TEE; \#: \emph{P} <0.05(0.011) vs extensive of c-TCD, (0.009) vs
extensive of c-TEE.

FIGURE 1. Quantification of the shunt by c-TCD. (A) Grade I, mild
signals. (B) Grade II, moderate signals. (C) Grade III, extensive
signals.

FIGURE 2. Quantification of the shunt by c-TTE. (A) Grade I, mild
signals. (B) Grade II, moderate signals. (C) Grade III, extensive
signals. LA: left atrium; LV: left ventricle; RA: right atrium; RV:
right ventricle.

FIGURE 3. Two-dimensional and color Doppler TEE; quantification of the
shunt by c-TTE. (A) Two-dimensional TEE displayed the slit-like channel
between the septum primum and the septum secundum. (B) Color Doppler
displayed right-to-left color shunting. (C) Grade I, mild signals. (D)
Grade II, moderate signals. (E) Grade III, extensive signals. LA: left
atrium; LV: left ventricle; RA: right atrium; RV: right ventricle.

FIGURE 4. Right heart catheterization with~angiography. (A) After
intravascular contrast media was injected though the catheter, if the
contrast media cannot reach the left atrium, PFO cannot be diagnosed. (B
\& C) If PFO cannot be diagnosed, then pulmonary arteriovenous fistula
(PAVF) is excluded by~pulmonary~angiography. (D) Pulmonary arteriography
showed PAVF.\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/c-TCD-2/c-TCD-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/c-TTE/c-TTE}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/c-TEE-2/c-TEE-2}

\end{center}
\end{figure}\selectlanguage{english}
\begin{figure}[H]
\begin{center}
\includegraphics[width=0.70\columnwidth]{figures/zy/zy}

\end{center}
\end{figure}

\selectlanguage{english}
\FloatBarrier
\end{document}

