From January 2020 to December 2021, we enrolled 124 patients, with PFO, Sign informed consent. Those who met the inclusion and exclusion criteria were examined by TEE, c-TTE and c-TCD. Morphological characteristics and tunnel characteristics of PFO in resting and Valsalva manoeuvre were observed by TEE, Intra-atrial parameters and other indicators and RLS levels were measured and recorded.
Inclusion criteria
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Patients with unexplained migraine, paradoxical embolism or clinically suspected PFO;
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Transthoracic echocardiography found suspicious PFO, and further examination was required;
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Subjects could accept TEE examination under psychological and physiological conditions.
Exclusion criteria
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Severe pulmonary hypertension;
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Severe emphysema;
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Respiratory failure;
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Severe anemia;
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Acidosis and severe heart and kidney dysfunction;
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Acute coronary syndrome;
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The subjects cooperated poorly and were unable to complete the Valsalva manœuvre;
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With atrial septal aneurysm.
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Anesthetic allergy;
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TEE contraindications;
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Subjects were unable to undergo TEE, c-TTE and c-TCD examinations after evaluation by clinicians and sonographers.
Subject’s informed consent
Investigators should fully inform subjects who met the inclusion and exclusion criteria, or their legal representatives, of all relevant aspects of the study before proceeding with any prescribed procedures. The subject's consent to the study should be recorded. (2) The investigator should ensure that the subject signed and date the informed consent form in person. Any manipulation should be done after completing the informed consent procedure.
Baseline characteristics
Record the gender, age, BMI, left ventricular EF value, underlying diseases (hypertension, coronary heart disease, diabetes, hyperlipidemia), smoking history, drinking history, and clinical symptoms of subjects who met the inclusion and exclusion criteria (Unexplained stroke, migraine, dizziness, history of syncope, chest tightness).
TEE procedure
The subjects fasted for 6–8 h before TEE, removed the oral dentures, and performed local anesthesia on the throat surface with lidocaine hydrochloride mortar (Handan Kangye Pharmaceutical, National Medicine Approval No. H13021217). After being fully anesthetized for about 15 min, a bite protector was placed in the oral cavity of the subject. Use Philips IE Elite Color Doppler Ultrasound or Philips EPIQ 7C Color Doppler Ultrasound and Transesophageal Ultrasound Probe X7-2t, frequency 4–7 MHz. During the examination, the subjects were placed in the left lateral decubitus position, the probe was placed in the middle of the esophagus, and the views of the double atrium, superior vena cava and inferior vena cava were clearly displayed, and the angle was fine-tuned to show the complete picture of the separation of the septum secundum and septum primum. Two-dimensional and color Doppler videos of at least 3 cardiac cycles were obtained. On-machine image analysis was performed by two cardiac ultrasound specialists above the attending level. The following parameters were observed and recorded: right atrial height, left atrial height, tunnel length, septum secundum thickness, IAS mobility, PFO angle and transseptal blood flow characteristics of the PFO, as shown in Fig. 1. The length of the PFO tunnel was the maximum overlapping distance between the septum secundum and septum primum; IAS mobility distance: the measurement line was placed in the middle of the atrial septum to measure the total offset distance of the left and right atrium; PFO angle: the mid-esophageal view showed and measured the angle of the inferior vena cava and the foramen ovale flap.
c-TTE method
Agitated saline contrast (ASC) was be injected, while the subjects were in a resting state. In addition, after the right atrium was completely visualized, the amount of microbubbles in the left heart was observed within 3–5 cardiac cycles. Repeat the above steps after the left heart microbubbles disappeared, and continue to observe the number of microbubbles in the left heart cavity [11, 12]. During the process, the subjects felt discomfort and terminated the examination immediately.
c-TCD method
The RLS grade was assessed using a transcranial Doppler ultrasound system (DWL, Germany) with a bitemporal 2 MHz probe. The subject was in a semi-recumbent position, and the indwelling needle was placed in the subject's forearm superficial vein and connected to a three-way tube. The contrast agent was prepared by mixing 9 ml of normal saline and 1 ml air. Rapid bolus injection was performed, and the microbubbles signal was monitored within 10 s. Repeat the above steps in the Valsalva manoeuvre.
Diagnostic criteria
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Diagnosis of PFO by TEE: separation between the septum secundum and septum primum, visible between the primary and secondary septa blood flow signal [13].
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The c-TTE grading standard refers to Agitated Saline Contrast Echocardiography in the Identification of Intra-and Extracardiac Shunts: Connecting the Dots [12]: according to the maximum number of microbubbles appearing in the left heart cavity of a static single frame image, the degree of shunt is divided into 4 grades. Grade 0: the number of microbubbles in the left heart cavity is 0; Grade 1: the number of microbubbles is 1–9; Grade 2: the number of microbubbles is 10–30; Grade 3: the number of microbubbles is more than 30.
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The c-TCD grading standard refers to the 2000 Detection of Right-to-Left Shunt with Ultrasound Contrast Agent and Transcranial Doppler Sonography [14]. According to the number of microbubbles, it is divided into four levels: Grade 0: no microbubbles are detected; Grade 1: 1–10 microbubbles; Grade 2: more than 10 microbubbles, non-curtain; Grade 3: embolic signal Curtain or shower type.
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RoEF score: Refer to the CS risk stratification score for patients with PFO created by Dr. Ken et al. [15]. No history of hypertension (1 point), no history of diabetes (1 point), no history of stroke or TIA (1 point), no smoking history (1 point), cortical infarction (1 point), age 18–29 years (5 points), age 30–39 years (4 points), age 40–49 years (3 points), age 50–59 years (2 points), age 60–69 years (1 point), age ≥ 70 years (0 points).
Four PFO anatomical features
Referring to the study of Jun Tanaka et al. [16], the anatomical morphology of PFO observed by TEE in this study was divided into the following four types: (1) SUT: the height of the right atrial side of the PFO tunnel was similar to that of the left atrium side, there was no obvious bulge of fat particles in the tunnel, and the inside of the tunnel showed a uniform strip-shaped transseptal blood flow signal (Fig. 2); (2) GUT: fat-like thickening of septum secundum, adipose tissue-like bulges could be seen in the tunnel, causing local adhesion of septum primum and septum secundum, the tunnel was segmented and the inner diameter was generally less than 2.0 mm, and the interior was mainly dot-shaped or short-rod-shaped blood flow signals (Fig. 3); (3) right funnelform: the primary septum primum and septum secundum at the tunnel exit were not clearly separated, and the inner diameter was mostly less than 2.0 mm. The septum primum and septum secundum at the entrance were obviously separated, and the difference from the inner diameter at the exit was greater than 2.0 mm, which was narrow strip and mainly bright blood flow signals (Fig. 4); (4) the left funnelform was the opposite of the right funnelform. The inside of the tunnel was mostly dim blood flow signal, and the blood flow at the entrance was brighter (Fig. 5).
Statistical analysis
SPSS26.0 was used for statistical analysis of the data. The measurement data were tested by normality. The data conforming to the normal distribution were expressed by mean ± standard deviation, and the inter group comparison was performed by independent sample T test; The data that did not conform to the normal distribution were expressed by the median (quartile), and the Mann–Whitney U test was used for comparison between groups. Categorical enumeration data are expressed by the number of cases (percentage). The chi-square test was used for comparison between groups. Logistic regression was used to analyze the factors affecting the shunt classification of c-TCD and c-TTE. The diagnostic value of the model was analyzed by ROC curve, P < 0.05 was statistically significant.