Study population
Between February 2019 and July 2020, we studied 75 clinically suspected PFO patients (31 men, 44 women: mean age, 45 ± 9 years) using consecutive CCTA and TEE examinations. Exclusion criteria included patients with severe coronary artery stenosis by CCTA and ASD by TEE. Clinical characteristics of the patients were collected from complete questionnaires and electronic medical records (Table 1). Of them, 56 patients had headache, 32 lacunar infarction and 25 recent stroke.
This study was approved by our medical school Institutional Review Board (IRB). Informed consent was exempted due to the retrospective study.
TEE examination
TEE examination was performed with a 6-VT real-time 3D transducer (Vivid E95, GE Medical Systems, Horten, Norway) using a standard technique. Patients underwent a comprehensive TEE study including two-dimensional imaging and color Doppler flow imaging of the PFO and agitated saline contrast test. The agitated saline contrast test was performed with 10 mL of agitated saline (a mixture of 9 mL of saline with 1mL of air) administered through an antecubital vein. The contrast test was positive by bubble visualization in the left atrium within three cardiac cycles following the Valsalva maneuver. PFO was confirmed on TEE by visualization of the gap between the septum primum and septum secundum and demonstration of interatrial shunting either by color Doppler imaging or saline contrast. Using two-dimensional imaging, we measured the tunnel length (TL) and opening diameter of the left atrial entrance (ODLAE) and right atrial entrance (ODRAE) of the PFO (Fig 1). All the TEE images were saved and analyzed later by two experienced echocardiography doctors who were blind to the clinical data.
CT scan protocol
All CT examinations were performed using 64-detector scanners (the SIEMENS dual-source CT, SOMATOM Definition system, Erlangen, Germany). Before the scan, the patients were required to fast for more than four hours. Strict breathing technique training (inhale, exhale, or breath-hold, according to the machine instructions) and heart rate control (<70/min) were used to avoid respiratory and motion artifacts that might affect image quality.
ECG monitoring was used, and venous access was established. The coronary artery calcification score was evaluated before the contrast injection. A bolus of 65-90 ml iodixanol (320 mg/ml), followed by 30-50 mL saline solution, was injected into an antecubital vein at a flow rate of 5-6 mL/s. The conventional method of contrast injection, coupled with a saline tracker to wash off the right side of the heart and assess the anatomy of the left side of the heart, allowed for PFO shunting from left-to-right to be demonstrated. The region of interest (ROI) was set in the ascending aorta, and the scan would be triggered after a delay of 4 s when the CT value reached 100 Hu.
The scan range extended from tracheal bifurcation to the cardiac diaphragmatic side. Data were acquired using retrospective electrocardiography gating with the following parameters: 64 × 0.6 mm detector collimation, 0.33 s gantry rotation time, 0.20-0.46 pitch adapted to the heart rate, 120 kVp tube voltage, and automatic tube current.
CT data analysis and measurement
Multiplanar reformations of the images (short-axis, two-chamber, and four-chamber views) were rendered and evaluated on the Carestream Vue PACS workstation (Version 11.3.6.1156, Shanghai, China). All the image series were obtained at mid-diastole, and the best series that showed the flap valve of the septum primum, PFO shunt, and its direction were selected for the measurements. Image analysis and measurement were performed independently by two radiologist with cardiovascular CT diagnosis experience. PFO was considered to be present if a contrast jet from the contrast-filled left atrium to the saline-filled right atrium toward the inferior vena cava with a tunnel-like appearance of the interarterial septum was detected. Measurement indicators included the length of the flap valve tunnel, diameters of the tunnel at the left atrium side (diameter-A), and diameters of the tunnel at the entrance into the right atrium (diameter-B) (Fig 2). The images were magnified, and each distance was measured twice.
With the four-chamber view as a reference, sagittal-oblique images perpendicular to the interatrial septum were obtained, demonstrating the channel-like appearance of the interatrial septum. FFV length, PFO tunnel diameters (diameter-A and diameter-B), and shunt existence (Fig 3) were evaluated in the sagittal oblique images. The length of FFV and the diameter-A were measured from its free margin, and diameter-B was measured at the entrance into the right atrium.
Variability analysis
The interobserver variability and accuracy of TL, ODLAE, and ODRAE of the PFO by CCTA and TEE images were initially analyzed in 20 randomly selected patients by two qualified radiologists and echocardiography experts, who were blinded to the results of the initial study. To calculate the intraobserver variability in the CCTA and TEE, imaging assessment of the PFO parameters was repeated on the same data set after a delay of at least one month by the same investigator in 20 randomly selected patients.
Statistical analysis
Statistical analysis was performed using commercially available SPSS software (Version19.0, IBM, Armonk, NY, USA). All the data were presented as mean ± standard deviation. The correlation of function parameters between CCTA and TEE imaging was tested using a paired t-test and linear regression analysis with Pearson’s correlation coefficient. Agreement of inter/intraobserver variability was determined by an inter-rater agreement (kappa), and weighted kappa (k) values were calculated (<0.40: poor agreement, 0.40-0.75: fair to good, and >0.75: excellent). The accuracy of PFO shunt contrast present on CCTA was assessed by a diagnostic test, and the sensitivity (Sen) (%), specificity (Spe) (%), accuracy (Acc) (%), negative predictive value (NPV) (%), and positive predictive value (PPV) (%) were calculated. The significance of the biases was tested using a paired 2-sided t-test. Statistical significance was demonstrated when the p-value was less than 0.05.